Case Letter

To the Editor:

We report an interesting clinical case of dermatomyositis (DM) that presented with an associated malignancy (small cell lung cancer). This patient also had an unusual clinical finding of predominantly unilateral, confluent, erythematous papules on the knee, a cutaneous sign that is seldom described in the DM literature. This case serves to reinforce the classic findings and associations of DM, in addition to the uncommon manifestation of predominantly unilateral papules on the knee.

A 68-year-old woman presented with several cutaneous manifestations including the classic findings of photo distributed erythema on the arms and face, a heliotrope rash, Gottron papules, and confluent pink papules on the left knee (Figure 1). The patient also had one of the more rare manifestations of DM, flagellate erythema on the back (Figure 2). She had a history of breast cancer and was found to have metastatic small cell lung cancer at the time of the DM diagnosis.

A punch biopsy from an area of flagellate erythema on the back revealed an interface dermatitis with a superficial, perivascular, lymphocyte-predominant inflammatory infiltrate (Figure 3). Alcian blue and colloidal iron stains revealed a marked increase in papillary dermal mucin. With the characteristic changes on skin biopsy and the classic skin findings present in our patient, we felt confident diagnosing her with DM. At the time of diagnosis, the patient also was found to have metastatic small cell lung cancer, suggesting a true paraneoplastic relationship.

In 1975, Bohan and Peter¹ noted that the presence of cutaneous involvement was considered necessary for definite identification of DM. Since then, numerous dermatologic features have been identified (Figure 4),² including the characteristic findings of a heliotrope rash and Gottron papules.³ The DM literature describes knee involvement consisting of confluent pink papules^1,2,4 similar to the rash in our patient. However, a symmetric pattern of involvement typically has been described, either the macular erythematous patches of Gottron sign² or the follicular eruption and pustules of the knees described by Lister et al.⁴ Our case represents a unique dermatologic manifestation of DM that requires further research to identify its incidence given its unilaterality.

 

The association of DM and amyopathic DM with internal malignancy is well known. Bohan and Peter¹ noted an overall figure ranging from 15% to 34% with an increased frequency in patients with skin and muscle involvement.¹ Hill et al⁵ examined this link in a population-based study that identified corresponding malignancies. Specifically, they noted cancers to arise most frequently in the airway (eg, lung, trachea, bronchus), ovaries, breasts, colorectal region, and stomach.⁵ There also has been work performed to identify if certain dermatologic findings may be associated with a higher risk of malignancy.^6,7 A meta-analysis by Wang et al⁶ showed that Gottron sign did not have an association with cancer, but findings of cutaneous necrosis did have an association. It is unknown if the specific cutaneous findings in our patient, including the predominantly unilateral papules on the knee, may have been a clue to the underlying malignancy.

In summary, we believe that our patient presented with the classic manifestations of DM in addition to the curious cutaneous sign of predominantly unilateral, confluent, erythematous papules on the knee, a clinical finding that may aid in the diagnosis of DM and also may alert the clinician to a possible underlying malignancy.

To the Editor:

We report an interesting clinical case of dermatomyositis (DM) that presented with an associated malignancy (small cell lung cancer). This patient also had an unusual clinical finding of predominantly unilateral, confluent, erythematous papules on the knee, a cutaneous sign that is seldom described in the DM literature. This case serves to reinforce the classic findings and associations of DM, in addition to the uncommon manifestation of predominantly unilateral papules on the knee.

A 68-year-old woman presented with several cutaneous manifestations including the classic findings of photo distributed erythema on the arms and face, a heliotrope rash, Gottron papules, and confluent pink papules on the left knee (Figure 1). The patient also had one of the more rare manifestations of DM, flagellate erythema on the back (Figure 2). She had a history of breast cancer and was found to have metastatic small cell lung cancer at the time of the DM diagnosis.

A punch biopsy from an area of flagellate erythema on the back revealed an interface dermatitis with a superficial, perivascular, lymphocyte-predominant inflammatory infiltrate (Figure 3). Alcian blue and colloidal iron stains revealed a marked increase in papillary dermal mucin. With the characteristic changes on skin biopsy and the classic skin findings present in our patient, we felt confident diagnosing her with DM. At the time of diagnosis, the patient also was found to have metastatic small cell lung cancer, suggesting a true paraneoplastic relationship.

In 1975, Bohan and Peter¹ noted that the presence of cutaneous involvement was considered necessary for definite identification of DM. Since then, numerous dermatologic features have been identified (Figure 4),² including the characteristic findings of a heliotrope rash and Gottron papules.³ The DM literature describes knee involvement consisting of confluent pink papules^1,2,4 similar to the rash in our patient. However, a symmetric pattern of involvement typically has been described, either the macular erythematous patches of Gottron sign² or the follicular eruption and pustules of the knees described by Lister et al.⁴ Our case represents a unique dermatologic manifestation of DM that requires further research to identify its incidence given its unilaterality.

 

The association of DM and amyopathic DM with internal malignancy is well known. Bohan and Peter¹ noted an overall figure ranging from 15% to 34% with an increased frequency in patients with skin and muscle involvement.¹ Hill et al⁵ examined this link in a population-based study that identified corresponding malignancies. Specifically, they noted cancers to arise most frequently in the airway (eg, lung, trachea, bronchus), ovaries, breasts, colorectal region, and stomach.⁵ There also has been work performed to identify if certain dermatologic findings may be associated with a higher risk of malignancy.^6,7 A meta-analysis by Wang et al⁶ showed that Gottron sign did not have an association with cancer, but findings of cutaneous necrosis did have an association. It is unknown if the specific cutaneous findings in our patient, including the predominantly unilateral papules on the knee, may have been a clue to the underlying malignancy.

In summary, we believe that our patient presented with the classic manifestations of DM in addition to the curious cutaneous sign of predominantly unilateral, confluent, erythematous papules on the knee, a clinical finding that may aid in the diagnosis of DM and also may alert the clinician to a possible underlying malignancy.

To the Editor:

We report an interesting clinical case of dermatomyositis (DM) that presented with an associated malignancy (small cell lung cancer). This patient also had an unusual clinical finding of predominantly unilateral, confluent, erythematous papules on the knee, a cutaneous sign that is seldom described in the DM literature. This case serves to reinforce the classic findings and associations of DM, in addition to the uncommon manifestation of predominantly unilateral papules on the knee.

A 68-year-old woman presented with several cutaneous manifestations including the classic findings of photo distributed erythema on the arms and face, a heliotrope rash, Gottron papules, and confluent pink papules on the left knee (Figure 1). The patient also had one of the more rare manifestations of DM, flagellate erythema on the back (Figure 2). She had a history of breast cancer and was found to have metastatic small cell lung cancer at the time of the DM diagnosis.

A punch biopsy from an area of flagellate erythema on the back revealed an interface dermatitis with a superficial, perivascular, lymphocyte-predominant inflammatory infiltrate (Figure 3). Alcian blue and colloidal iron stains revealed a marked increase in papillary dermal mucin. With the characteristic changes on skin biopsy and the classic skin findings present in our patient, we felt confident diagnosing her with DM. At the time of diagnosis, the patient also was found to have metastatic small cell lung cancer, suggesting a true paraneoplastic relationship.

In 1975, Bohan and Peter¹ noted that the presence of cutaneous involvement was considered necessary for definite identification of DM. Since then, numerous dermatologic features have been identified (Figure 4),² including the characteristic findings of a heliotrope rash and Gottron papules.³ The DM literature describes knee involvement consisting of confluent pink papules^1,2,4 similar to the rash in our patient. However, a symmetric pattern of involvement typically has been described, either the macular erythematous patches of Gottron sign² or the follicular eruption and pustules of the knees described by Lister et al.⁴ Our case represents a unique dermatologic manifestation of DM that requires further research to identify its incidence given its unilaterality.

 

The association of DM and amyopathic DM with internal malignancy is well known. Bohan and Peter¹ noted an overall figure ranging from 15% to 34% with an increased frequency in patients with skin and muscle involvement.¹ Hill et al⁵ examined this link in a population-based study that identified corresponding malignancies. Specifically, they noted cancers to arise most frequently in the airway (eg, lung, trachea, bronchus), ovaries, breasts, colorectal region, and stomach.⁵ There also has been work performed to identify if certain dermatologic findings may be associated with a higher risk of malignancy.^6,7 A meta-analysis by Wang et al⁶ showed that Gottron sign did not have an association with cancer, but findings of cutaneous necrosis did have an association. It is unknown if the specific cutaneous findings in our patient, including the predominantly unilateral papules on the knee, may have been a clue to the underlying malignancy.

In summary, we believe that our patient presented with the classic manifestations of DM in addition to the curious cutaneous sign of predominantly unilateral, confluent, erythematous papules on the knee, a clinical finding that may aid in the diagnosis of DM and also may alert the clinician to a possible underlying malignancy.

To the Editor:
Kwashiorkor, or protein-calorie malnutrition, is a common issue in developing countries subject to starvation. In economically advanced nations, however, kwashiorkor is extremely rare and may appear in children placed on restrictive diets instituted by well-meaning guardians. Kwashiorkor also may occur because of gastrointestinal malabsorption. We present a unique case of kwashiorkor that revealed an underlying diagnosis of pancreatic insufficiency.

A 12-year-old girl presented to the hospital with 4 days of watery nonbloody diarrhea occurring with every feeding as well as new onset of presumed diaper dermatitis that had not responded to nystatin cream. Facial swelling also was noted the day prior to admission. Her medical history was notable for cerebral palsy secondary to nonaccidental trauma, leaving the patient nonverbal and quadriplegic. She had numerous prior admissions for sepsis with marked hypotension and more recently was diagnosed with insulin-dependent type 2 diabetes mellitus. She had never lived outside the United States and resided at home with her adoptive parents.

Physical examination revealed a nonverbal underweight girl (weight, 25 kg). Large areas of denudation with surrounding desquamated skin resembling flaking enamel paint covered the buttocks and posterior legs bilaterally (Figure). She had linear hyperpigmented patches on the dorsal hands with one superficial erosion on the left wrist. Marked periorbital edema as well as nonpitting edema of the face, arms, and legs were present.

Upon additional questioning, the patient’s adoptive parent reported a diet of formula containing 1.0 cal/mL with 200-mL feedings 3 times daily through a Geiger-Müller tube, providing a daily protein intake of approximately 17.7 g per day (0.7 g/kg per day). On the day of admission, abnormal laboratory findings included low protein and albumin levels at 4.6 g/dL (reference range, 5.7–8.2 g/dL) and 2.1 g/dL (reference range, 3.2–4.8 g/dL), respectively; an elevated aspartate aminotransferase level of 73 U/L (reference range, 10–34 U/L); and an elevated alanine aminotransferase level of 80 U/L (reference range, 10–40 U/L). Based on the patient’s characteristic clinical findings and abnormal laboratory values, a diagnosis of acute kwashiorkor was made. Although the zinc level was low at 0.29 µg/mL (reference range, 0.66–1.10 µg/mL), the patient did not have any periorificial involvement to support a diagnosis of acrodermatitis enteropathica.

Upon further workup, stool elastase was measured at less than 50 µg per gram of stool (reference range, >200 µg pancreatic elastase per gram of stool), confirming a diagnosis of severe pancreatic insufficiency. Pancreatic enzyme supplementation was initiated along with an increase in protein intake to 1.5 g/kg per day. The patient’s hospital course was complicated by respiratory distress and sepsis, leading to a prolonged hospital stay. A component of refeeding syndrome may have contributed to the patient’s respiratory distress.

 

Kwashiorkor, a form of protein malnutrition, is caused by inadequate protein intake and usually is seen in developing countries when children are weaned from breastmilk to a diet high in starch and low in protein. It is characterized by edema, growth retardation, a characteristic dermatosis, depigmentation of hair, lethargy, and irritability.¹ If left untreated, kwashiorkor can be fatal. Skin changes associated with kwashiorkor first occur in areas of friction or pressure. The skin develops patches of hyperpigmentation that subsequently desquamate in a pattern likened to flaky paint. In the current case of a nonmobile child with diarrhea, prominent involvement of the buttocks and thighs would be expected. This dermatosis does not appear in marasmus and is pathognomonic for kwashiorkor when seen in a child with edema.²

Children in the United States developing kwashiorkor secondary to severely restrictive diets has been reported.³ However, kwashiorkor also may occur due to underlying chronic malabsorptive disease. There have been rare reports of children with cystic fibrosis presenting with kwashiorkor,⁴ as well as a case of kwashiorkor secondary to underlying infantile Crohn disease.⁵

Cerebral palsy is associated with multiple different risk factors for malnutrition. Musculoskeletal deformities, oral-motor difficulties, medication side effects, limited communication skills, compromised pulmonary status, and poor muscle tone can all contribute to energy and nutrient deprivation.⁶ A 2018 study including 728 children registered into the Bangladesh Cerebral Palsy Register between January 2015 and December 2016 demonstrated that more than two-thirds were underweight (70.0%) and stunted (73.1%) and that children with tri/quadriplegic cerebral palsy presented with the highest proportion of severe malnutrition.⁷ In another report (N=142), up to 85% of children with spastic quadriplegia had severe feeding problems,⁸ making this population particularly high risk for poor nutritional status.

Pancreatic exocrine insufficiency is characterized by reduced secretion of amylase, lipase, and protease, and it may result in diarrhea, weight loss, malabsorption of essential nutrients, and malnutrition. Pancreatic exocrine insufficiency may occur in the setting of chronic pancreatitis, pancreatic surgery, and cystic fibrosis. Our patient had numerous hospitalizations for sepsis marked by hypotension, and in the absence of more typical causes, we postulate that both endocrine and exocrine pancreatic damage resulted from prolonged hypotension. A sweat chloride test was not performed, as the patient had not experienced frequent pulmonary infections or other signs of cystic fibrosis.

According to a report from the Food and Agriculture Organization of the United Nations/World Health Organization/United Nations University (FAO/WHO/UNU), protein should provide at least 10% of the total caloric intake in a child.⁹ Although the adoptive parent approximated that our patient received 12% of her daily calories in the form of protein, the amount that she absorbed in the context of pancreatic insufficiency was undoubtedly much lower.

In this case, the diagnosis of kwashiorkor led to the discovery of underlying pancreatic exocrine insufficiency. Low stool elastase confirmed the diagnosis. Because kwashiorkor is rare in developed countries, the classic signs and symptoms may go unrecognized, which can lead to delayed diagnosis and notable morbidity and mortality. New-onset edema and desquamative rash in a child, especially a child with cerebral palsy, should alert physicians to the possibility of acute kwashiorkor and prompt investigation into underlying medical issues that may have contributed to its development.

To the Editor:
Kwashiorkor, or protein-calorie malnutrition, is a common issue in developing countries subject to starvation. In economically advanced nations, however, kwashiorkor is extremely rare and may appear in children placed on restrictive diets instituted by well-meaning guardians. Kwashiorkor also may occur because of gastrointestinal malabsorption. We present a unique case of kwashiorkor that revealed an underlying diagnosis of pancreatic insufficiency.

A 12-year-old girl presented to the hospital with 4 days of watery nonbloody diarrhea occurring with every feeding as well as new onset of presumed diaper dermatitis that had not responded to nystatin cream. Facial swelling also was noted the day prior to admission. Her medical history was notable for cerebral palsy secondary to nonaccidental trauma, leaving the patient nonverbal and quadriplegic. She had numerous prior admissions for sepsis with marked hypotension and more recently was diagnosed with insulin-dependent type 2 diabetes mellitus. She had never lived outside the United States and resided at home with her adoptive parents.

Physical examination revealed a nonverbal underweight girl (weight, 25 kg). Large areas of denudation with surrounding desquamated skin resembling flaking enamel paint covered the buttocks and posterior legs bilaterally (Figure). She had linear hyperpigmented patches on the dorsal hands with one superficial erosion on the left wrist. Marked periorbital edema as well as nonpitting edema of the face, arms, and legs were present.

Upon additional questioning, the patient’s adoptive parent reported a diet of formula containing 1.0 cal/mL with 200-mL feedings 3 times daily through a Geiger-Müller tube, providing a daily protein intake of approximately 17.7 g per day (0.7 g/kg per day). On the day of admission, abnormal laboratory findings included low protein and albumin levels at 4.6 g/dL (reference range, 5.7–8.2 g/dL) and 2.1 g/dL (reference range, 3.2–4.8 g/dL), respectively; an elevated aspartate aminotransferase level of 73 U/L (reference range, 10–34 U/L); and an elevated alanine aminotransferase level of 80 U/L (reference range, 10–40 U/L). Based on the patient’s characteristic clinical findings and abnormal laboratory values, a diagnosis of acute kwashiorkor was made. Although the zinc level was low at 0.29 µg/mL (reference range, 0.66–1.10 µg/mL), the patient did not have any periorificial involvement to support a diagnosis of acrodermatitis enteropathica.

Upon further workup, stool elastase was measured at less than 50 µg per gram of stool (reference range, >200 µg pancreatic elastase per gram of stool), confirming a diagnosis of severe pancreatic insufficiency. Pancreatic enzyme supplementation was initiated along with an increase in protein intake to 1.5 g/kg per day. The patient’s hospital course was complicated by respiratory distress and sepsis, leading to a prolonged hospital stay. A component of refeeding syndrome may have contributed to the patient’s respiratory distress.

 

Kwashiorkor, a form of protein malnutrition, is caused by inadequate protein intake and usually is seen in developing countries when children are weaned from breastmilk to a diet high in starch and low in protein. It is characterized by edema, growth retardation, a characteristic dermatosis, depigmentation of hair, lethargy, and irritability.¹ If left untreated, kwashiorkor can be fatal. Skin changes associated with kwashiorkor first occur in areas of friction or pressure. The skin develops patches of hyperpigmentation that subsequently desquamate in a pattern likened to flaky paint. In the current case of a nonmobile child with diarrhea, prominent involvement of the buttocks and thighs would be expected. This dermatosis does not appear in marasmus and is pathognomonic for kwashiorkor when seen in a child with edema.²

Children in the United States developing kwashiorkor secondary to severely restrictive diets has been reported.³ However, kwashiorkor also may occur due to underlying chronic malabsorptive disease. There have been rare reports of children with cystic fibrosis presenting with kwashiorkor,⁴ as well as a case of kwashiorkor secondary to underlying infantile Crohn disease.⁵

Cerebral palsy is associated with multiple different risk factors for malnutrition. Musculoskeletal deformities, oral-motor difficulties, medication side effects, limited communication skills, compromised pulmonary status, and poor muscle tone can all contribute to energy and nutrient deprivation.⁶ A 2018 study including 728 children registered into the Bangladesh Cerebral Palsy Register between January 2015 and December 2016 demonstrated that more than two-thirds were underweight (70.0%) and stunted (73.1%) and that children with tri/quadriplegic cerebral palsy presented with the highest proportion of severe malnutrition.⁷ In another report (N=142), up to 85% of children with spastic quadriplegia had severe feeding problems,⁸ making this population particularly high risk for poor nutritional status.

Pancreatic exocrine insufficiency is characterized by reduced secretion of amylase, lipase, and protease, and it may result in diarrhea, weight loss, malabsorption of essential nutrients, and malnutrition. Pancreatic exocrine insufficiency may occur in the setting of chronic pancreatitis, pancreatic surgery, and cystic fibrosis. Our patient had numerous hospitalizations for sepsis marked by hypotension, and in the absence of more typical causes, we postulate that both endocrine and exocrine pancreatic damage resulted from prolonged hypotension. A sweat chloride test was not performed, as the patient had not experienced frequent pulmonary infections or other signs of cystic fibrosis.

According to a report from the Food and Agriculture Organization of the United Nations/World Health Organization/United Nations University (FAO/WHO/UNU), protein should provide at least 10% of the total caloric intake in a child.⁹ Although the adoptive parent approximated that our patient received 12% of her daily calories in the form of protein, the amount that she absorbed in the context of pancreatic insufficiency was undoubtedly much lower.

In this case, the diagnosis of kwashiorkor led to the discovery of underlying pancreatic exocrine insufficiency. Low stool elastase confirmed the diagnosis. Because kwashiorkor is rare in developed countries, the classic signs and symptoms may go unrecognized, which can lead to delayed diagnosis and notable morbidity and mortality. New-onset edema and desquamative rash in a child, especially a child with cerebral palsy, should alert physicians to the possibility of acute kwashiorkor and prompt investigation into underlying medical issues that may have contributed to its development.

To the Editor:
Kwashiorkor, or protein-calorie malnutrition, is a common issue in developing countries subject to starvation. In economically advanced nations, however, kwashiorkor is extremely rare and may appear in children placed on restrictive diets instituted by well-meaning guardians. Kwashiorkor also may occur because of gastrointestinal malabsorption. We present a unique case of kwashiorkor that revealed an underlying diagnosis of pancreatic insufficiency.

A 12-year-old girl presented to the hospital with 4 days of watery nonbloody diarrhea occurring with every feeding as well as new onset of presumed diaper dermatitis that had not responded to nystatin cream. Facial swelling also was noted the day prior to admission. Her medical history was notable for cerebral palsy secondary to nonaccidental trauma, leaving the patient nonverbal and quadriplegic. She had numerous prior admissions for sepsis with marked hypotension and more recently was diagnosed with insulin-dependent type 2 diabetes mellitus. She had never lived outside the United States and resided at home with her adoptive parents.

Physical examination revealed a nonverbal underweight girl (weight, 25 kg). Large areas of denudation with surrounding desquamated skin resembling flaking enamel paint covered the buttocks and posterior legs bilaterally (Figure). She had linear hyperpigmented patches on the dorsal hands with one superficial erosion on the left wrist. Marked periorbital edema as well as nonpitting edema of the face, arms, and legs were present.

Upon additional questioning, the patient’s adoptive parent reported a diet of formula containing 1.0 cal/mL with 200-mL feedings 3 times daily through a Geiger-Müller tube, providing a daily protein intake of approximately 17.7 g per day (0.7 g/kg per day). On the day of admission, abnormal laboratory findings included low protein and albumin levels at 4.6 g/dL (reference range, 5.7–8.2 g/dL) and 2.1 g/dL (reference range, 3.2–4.8 g/dL), respectively; an elevated aspartate aminotransferase level of 73 U/L (reference range, 10–34 U/L); and an elevated alanine aminotransferase level of 80 U/L (reference range, 10–40 U/L). Based on the patient’s characteristic clinical findings and abnormal laboratory values, a diagnosis of acute kwashiorkor was made. Although the zinc level was low at 0.29 µg/mL (reference range, 0.66–1.10 µg/mL), the patient did not have any periorificial involvement to support a diagnosis of acrodermatitis enteropathica.

Upon further workup, stool elastase was measured at less than 50 µg per gram of stool (reference range, >200 µg pancreatic elastase per gram of stool), confirming a diagnosis of severe pancreatic insufficiency. Pancreatic enzyme supplementation was initiated along with an increase in protein intake to 1.5 g/kg per day. The patient’s hospital course was complicated by respiratory distress and sepsis, leading to a prolonged hospital stay. A component of refeeding syndrome may have contributed to the patient’s respiratory distress.

 

Kwashiorkor, a form of protein malnutrition, is caused by inadequate protein intake and usually is seen in developing countries when children are weaned from breastmilk to a diet high in starch and low in protein. It is characterized by edema, growth retardation, a characteristic dermatosis, depigmentation of hair, lethargy, and irritability.¹ If left untreated, kwashiorkor can be fatal. Skin changes associated with kwashiorkor first occur in areas of friction or pressure. The skin develops patches of hyperpigmentation that subsequently desquamate in a pattern likened to flaky paint. In the current case of a nonmobile child with diarrhea, prominent involvement of the buttocks and thighs would be expected. This dermatosis does not appear in marasmus and is pathognomonic for kwashiorkor when seen in a child with edema.²

Children in the United States developing kwashiorkor secondary to severely restrictive diets has been reported.³ However, kwashiorkor also may occur due to underlying chronic malabsorptive disease. There have been rare reports of children with cystic fibrosis presenting with kwashiorkor,⁴ as well as a case of kwashiorkor secondary to underlying infantile Crohn disease.⁵

Cerebral palsy is associated with multiple different risk factors for malnutrition. Musculoskeletal deformities, oral-motor difficulties, medication side effects, limited communication skills, compromised pulmonary status, and poor muscle tone can all contribute to energy and nutrient deprivation.⁶ A 2018 study including 728 children registered into the Bangladesh Cerebral Palsy Register between January 2015 and December 2016 demonstrated that more than two-thirds were underweight (70.0%) and stunted (73.1%) and that children with tri/quadriplegic cerebral palsy presented with the highest proportion of severe malnutrition.⁷ In another report (N=142), up to 85% of children with spastic quadriplegia had severe feeding problems,⁸ making this population particularly high risk for poor nutritional status.

Pancreatic exocrine insufficiency is characterized by reduced secretion of amylase, lipase, and protease, and it may result in diarrhea, weight loss, malabsorption of essential nutrients, and malnutrition. Pancreatic exocrine insufficiency may occur in the setting of chronic pancreatitis, pancreatic surgery, and cystic fibrosis. Our patient had numerous hospitalizations for sepsis marked by hypotension, and in the absence of more typical causes, we postulate that both endocrine and exocrine pancreatic damage resulted from prolonged hypotension. A sweat chloride test was not performed, as the patient had not experienced frequent pulmonary infections or other signs of cystic fibrosis.

According to a report from the Food and Agriculture Organization of the United Nations/World Health Organization/United Nations University (FAO/WHO/UNU), protein should provide at least 10% of the total caloric intake in a child.⁹ Although the adoptive parent approximated that our patient received 12% of her daily calories in the form of protein, the amount that she absorbed in the context of pancreatic insufficiency was undoubtedly much lower.

In this case, the diagnosis of kwashiorkor led to the discovery of underlying pancreatic exocrine insufficiency. Low stool elastase confirmed the diagnosis. Because kwashiorkor is rare in developed countries, the classic signs and symptoms may go unrecognized, which can lead to delayed diagnosis and notable morbidity and mortality. New-onset edema and desquamative rash in a child, especially a child with cerebral palsy, should alert physicians to the possibility of acute kwashiorkor and prompt investigation into underlying medical issues that may have contributed to its development.

To the Editor:
A 52-year-old woman with a medical history of migraines and cervicalgia presented with lesions on the right arm, back, and right calf. The patient stated that the lesions began as small papules that had grown over 13 months, with the largest papule on the right forearm. She reported no itching, bleeding, pain, discharge, or other symptoms associated with the lesions. She had a multiple-year history of similar lesions that did not respond to treatment with antifungals, moderate-potency steroids, and other over-the-counter creams. The lesions would resolve spontaneously with scarring and subsequently recur. Prior skin biopsies were inconclusive. The patient did not report any systemic symptoms or a personal or family history of connective tissue diseases.

Physical examination revealed a 4-cm asymmetric, annular, erythematous plaque with central clearing on the right dorsal forearm with defined margins except over the distal aspect (Figure 1). She also had several 1- to 2-cm erythematous, nummular, asymmetric plaques on the right upper arm with well-defined margins. She had several lesions over the central and left sides of the upper back that were similar to the lesions on the upper arm.

Two 4-mm punch biopsies of the right dorsal forearm and left side of the upper back revealed similar histologic features with a predominantly unremarkable epidermis. The dermis revealed a lymphohistiocytic infiltrate with prominent multinucleated giant cells organized into foreign body–type granulomas that extended into the deep dermis and subcutaneous tissue (Figure 2). In the granulomatous areas, there was a near-complete loss of elastic fibers with focal elastophagocytosis highlighted with Verhoeff-van Gieson (elastin) stain (Figure 3). Grocott-Gomori methenamine-silver and Fite stains for microorganisms were negative, and there was an absence of necrobiosis, lipids, and mucin.

The histologic findings of a granulomatous dermatitis with loss of elastic fibers and elastophagocytosis in addition to the patient’s clinical presentation and history were consistent with the diagnosis of annular elastolytic giant cell granuloma (AEGCG). Infectious and other granulomatous diseases including sarcoidosis were ruled out via clinical history, unremarkable laboratory analysis (ie, complete blood cell count, chemistry panel, antinuclear antibody, urinalysis), and a normal chest radiograph. The histologic findings via the various stains were instrumental to the diagnosis. The patient was treated with fluocinonide and subsequently lost to follow-up.

Annular elastolytic giant cell granuloma is an uncommon cutaneous disease that presents with recurring annular plaques with raised erythematous borders and subsequent residual scarring.¹ O’Brien² originally described this condition in 1975 as an actinic granuloma due to similar histologic findings in areas of the patient’s sun-exposed skin. Ragaz and Ackerman³ disputed O’Brien’s² description, claiming granulomatous inflammation was a primary pathologic process and not a consequence to damaged elastotic material. In 1979, Hanke et al⁴ termed the lesions as AEGCG because he did not find a correlation to the sun-exposed areas of the patients and did not see solar elastosis.

Although AEGCG has an unclear pathogenesis, cellular immunologic reactions induced by modified function of elastic fibers’ antigenicity contribute to AEGCG formation.⁵ Therefore, environmental and host factors may play a role in its etiopathogenesis. In one study, 37% of 38 Japanese patients with AEGCG were found to have definitive or latent diabetes mellitus, raising the possible role of diabetes in the structural damage of the elastic fibers.⁶

Patients typically are middle-aged women who present clinically with red or atrophic plaques that have slightly elevated borders. They have centripetal spread with a resulting atrophic center.⁷ Clinically, the differential diagnosis of this condition includes actinic granuloma, granuloma annulare, and granuloma multiforme.⁸

Histologically, AEGCG has a granulomatous component with multinucleated giant cells in the upper and mid dermis. This component typically is distributed peripherally to a central zone that lacks elastic tissue. Elastophagocytosis, a classic finding in AEGCG, is the phagocytosis of elastic fibers that can microscopically be seen in the cytoplasm of histiocytes and multinucleated giant cells. There also is an absence of necrobiosis, lipids, mucin, and a palisading arrangement of the granulomas. These findings distinguish AEGCG from granuloma annulare and necrobiosis lipoidica, the primary histologic differential diagnoses.⁹ In addition, consideration of entities consistently exhibiting elastophagocytosis such as mid-dermal elastolysis, papillary dermal elastolysis, actinic granuloma, and granulomatous slack skin should be considered.^5,10,11

Therapy for AEGCG is broad and includes topical, intralesional, and systemic corticosteroids. Hydroxychloroquine, isotretinoin, clofazimine, dapsone, photochemotherapy, and cyclosporine also have been utilized with varying results. Other reports show improvement with surgical excision, cryotherapy, or cauterization of small lesions.^12-15

To the Editor:
A 52-year-old woman with a medical history of migraines and cervicalgia presented with lesions on the right arm, back, and right calf. The patient stated that the lesions began as small papules that had grown over 13 months, with the largest papule on the right forearm. She reported no itching, bleeding, pain, discharge, or other symptoms associated with the lesions. She had a multiple-year history of similar lesions that did not respond to treatment with antifungals, moderate-potency steroids, and other over-the-counter creams. The lesions would resolve spontaneously with scarring and subsequently recur. Prior skin biopsies were inconclusive. The patient did not report any systemic symptoms or a personal or family history of connective tissue diseases.

Physical examination revealed a 4-cm asymmetric, annular, erythematous plaque with central clearing on the right dorsal forearm with defined margins except over the distal aspect (Figure 1). She also had several 1- to 2-cm erythematous, nummular, asymmetric plaques on the right upper arm with well-defined margins. She had several lesions over the central and left sides of the upper back that were similar to the lesions on the upper arm.

Two 4-mm punch biopsies of the right dorsal forearm and left side of the upper back revealed similar histologic features with a predominantly unremarkable epidermis. The dermis revealed a lymphohistiocytic infiltrate with prominent multinucleated giant cells organized into foreign body–type granulomas that extended into the deep dermis and subcutaneous tissue (Figure 2). In the granulomatous areas, there was a near-complete loss of elastic fibers with focal elastophagocytosis highlighted with Verhoeff-van Gieson (elastin) stain (Figure 3). Grocott-Gomori methenamine-silver and Fite stains for microorganisms were negative, and there was an absence of necrobiosis, lipids, and mucin.

The histologic findings of a granulomatous dermatitis with loss of elastic fibers and elastophagocytosis in addition to the patient’s clinical presentation and history were consistent with the diagnosis of annular elastolytic giant cell granuloma (AEGCG). Infectious and other granulomatous diseases including sarcoidosis were ruled out via clinical history, unremarkable laboratory analysis (ie, complete blood cell count, chemistry panel, antinuclear antibody, urinalysis), and a normal chest radiograph. The histologic findings via the various stains were instrumental to the diagnosis. The patient was treated with fluocinonide and subsequently lost to follow-up.

Annular elastolytic giant cell granuloma is an uncommon cutaneous disease that presents with recurring annular plaques with raised erythematous borders and subsequent residual scarring.¹ O’Brien² originally described this condition in 1975 as an actinic granuloma due to similar histologic findings in areas of the patient’s sun-exposed skin. Ragaz and Ackerman³ disputed O’Brien’s² description, claiming granulomatous inflammation was a primary pathologic process and not a consequence to damaged elastotic material. In 1979, Hanke et al⁴ termed the lesions as AEGCG because he did not find a correlation to the sun-exposed areas of the patients and did not see solar elastosis.

Although AEGCG has an unclear pathogenesis, cellular immunologic reactions induced by modified function of elastic fibers’ antigenicity contribute to AEGCG formation.⁵ Therefore, environmental and host factors may play a role in its etiopathogenesis. In one study, 37% of 38 Japanese patients with AEGCG were found to have definitive or latent diabetes mellitus, raising the possible role of diabetes in the structural damage of the elastic fibers.⁶

Patients typically are middle-aged women who present clinically with red or atrophic plaques that have slightly elevated borders. They have centripetal spread with a resulting atrophic center.⁷ Clinically, the differential diagnosis of this condition includes actinic granuloma, granuloma annulare, and granuloma multiforme.⁸

Histologically, AEGCG has a granulomatous component with multinucleated giant cells in the upper and mid dermis. This component typically is distributed peripherally to a central zone that lacks elastic tissue. Elastophagocytosis, a classic finding in AEGCG, is the phagocytosis of elastic fibers that can microscopically be seen in the cytoplasm of histiocytes and multinucleated giant cells. There also is an absence of necrobiosis, lipids, mucin, and a palisading arrangement of the granulomas. These findings distinguish AEGCG from granuloma annulare and necrobiosis lipoidica, the primary histologic differential diagnoses.⁹ In addition, consideration of entities consistently exhibiting elastophagocytosis such as mid-dermal elastolysis, papillary dermal elastolysis, actinic granuloma, and granulomatous slack skin should be considered.^5,10,11

Therapy for AEGCG is broad and includes topical, intralesional, and systemic corticosteroids. Hydroxychloroquine, isotretinoin, clofazimine, dapsone, photochemotherapy, and cyclosporine also have been utilized with varying results. Other reports show improvement with surgical excision, cryotherapy, or cauterization of small lesions.^12-15

To the Editor:
A 52-year-old woman with a medical history of migraines and cervicalgia presented with lesions on the right arm, back, and right calf. The patient stated that the lesions began as small papules that had grown over 13 months, with the largest papule on the right forearm. She reported no itching, bleeding, pain, discharge, or other symptoms associated with the lesions. She had a multiple-year history of similar lesions that did not respond to treatment with antifungals, moderate-potency steroids, and other over-the-counter creams. The lesions would resolve spontaneously with scarring and subsequently recur. Prior skin biopsies were inconclusive. The patient did not report any systemic symptoms or a personal or family history of connective tissue diseases.

Physical examination revealed a 4-cm asymmetric, annular, erythematous plaque with central clearing on the right dorsal forearm with defined margins except over the distal aspect (Figure 1). She also had several 1- to 2-cm erythematous, nummular, asymmetric plaques on the right upper arm with well-defined margins. She had several lesions over the central and left sides of the upper back that were similar to the lesions on the upper arm.

Two 4-mm punch biopsies of the right dorsal forearm and left side of the upper back revealed similar histologic features with a predominantly unremarkable epidermis. The dermis revealed a lymphohistiocytic infiltrate with prominent multinucleated giant cells organized into foreign body–type granulomas that extended into the deep dermis and subcutaneous tissue (Figure 2). In the granulomatous areas, there was a near-complete loss of elastic fibers with focal elastophagocytosis highlighted with Verhoeff-van Gieson (elastin) stain (Figure 3). Grocott-Gomori methenamine-silver and Fite stains for microorganisms were negative, and there was an absence of necrobiosis, lipids, and mucin.

The histologic findings of a granulomatous dermatitis with loss of elastic fibers and elastophagocytosis in addition to the patient’s clinical presentation and history were consistent with the diagnosis of annular elastolytic giant cell granuloma (AEGCG). Infectious and other granulomatous diseases including sarcoidosis were ruled out via clinical history, unremarkable laboratory analysis (ie, complete blood cell count, chemistry panel, antinuclear antibody, urinalysis), and a normal chest radiograph. The histologic findings via the various stains were instrumental to the diagnosis. The patient was treated with fluocinonide and subsequently lost to follow-up.

Annular elastolytic giant cell granuloma is an uncommon cutaneous disease that presents with recurring annular plaques with raised erythematous borders and subsequent residual scarring.¹ O’Brien² originally described this condition in 1975 as an actinic granuloma due to similar histologic findings in areas of the patient’s sun-exposed skin. Ragaz and Ackerman³ disputed O’Brien’s² description, claiming granulomatous inflammation was a primary pathologic process and not a consequence to damaged elastotic material. In 1979, Hanke et al⁴ termed the lesions as AEGCG because he did not find a correlation to the sun-exposed areas of the patients and did not see solar elastosis.

Although AEGCG has an unclear pathogenesis, cellular immunologic reactions induced by modified function of elastic fibers’ antigenicity contribute to AEGCG formation.⁵ Therefore, environmental and host factors may play a role in its etiopathogenesis. In one study, 37% of 38 Japanese patients with AEGCG were found to have definitive or latent diabetes mellitus, raising the possible role of diabetes in the structural damage of the elastic fibers.⁶

Patients typically are middle-aged women who present clinically with red or atrophic plaques that have slightly elevated borders. They have centripetal spread with a resulting atrophic center.⁷ Clinically, the differential diagnosis of this condition includes actinic granuloma, granuloma annulare, and granuloma multiforme.⁸

Histologically, AEGCG has a granulomatous component with multinucleated giant cells in the upper and mid dermis. This component typically is distributed peripherally to a central zone that lacks elastic tissue. Elastophagocytosis, a classic finding in AEGCG, is the phagocytosis of elastic fibers that can microscopically be seen in the cytoplasm of histiocytes and multinucleated giant cells. There also is an absence of necrobiosis, lipids, mucin, and a palisading arrangement of the granulomas. These findings distinguish AEGCG from granuloma annulare and necrobiosis lipoidica, the primary histologic differential diagnoses.⁹ In addition, consideration of entities consistently exhibiting elastophagocytosis such as mid-dermal elastolysis, papillary dermal elastolysis, actinic granuloma, and granulomatous slack skin should be considered.^5,10,11

Therapy for AEGCG is broad and includes topical, intralesional, and systemic corticosteroids. Hydroxychloroquine, isotretinoin, clofazimine, dapsone, photochemotherapy, and cyclosporine also have been utilized with varying results. Other reports show improvement with surgical excision, cryotherapy, or cauterization of small lesions.^12-15

To the Editor:

A 2-year-old boy was referred to our pediatric dermatology clinic by his pediatrician for an enlarging mass on the mid frontal scalp. The lesion had been present since birth and slowly enlarged. His parents thought the lesion was mostly asymptomatic; however, if it was irritated, the child would cry. He was otherwise healthy and had no history of skin conditions. There was no family history of skin conditions, birthmarks, or vascular malformations. On physical examination, we observed an isolated, approximately 3-cm, well-circumscribed, mobile, flesh-colored and violaceous nodule on the mid frontal scalp (Figure 1). At that time our differential diagnosis included a complex hemangioma or other vascular proliferation, nevus lipomatosis, or even a soft-tissue malignancy such as a sarcoma. Prior to biopsy, we ordered magnetic resonance imaging (MRI) to evaluate for intracranial extension of the lesion. The MRI revealed a 3.2-cm frontal midline scalp mass with complex imaging characteristics, and the radiologist gave a differential diagnosis of hemangioma, teratoma, or less likely liposarcoma (Figure 2). Fortunately, there was no evidence of central nervous system or intracranial invasion. We then proceeded with excisional biopsy, which grossly revealed a nodular, well-circumscribed, yellow mass (Figure 3). The wound was closed with primary closure. Histologically, there was a lobulated tumor with thin, well-vascularized connective tissue septa within a myxoid stroma (Figure 4A). The tumor was composed of lipocytes in varying stages of maturity without obvious nuclear atypia (Figures 4B and 4C), leading to a diagnosis of lipoblastoma.

Lipoblastoma (also known as an embryonic lipoma) is a rare variant of lipoma. It is a benign neoplasm of immature white fat cells primarily seen in children younger than 3 years. It is reportedly twice as common in boys versus girls. Lipoblastomas present as enlarging, soft, mobile, painless nodules, usually 3 to 5 cm in diameter. The extremities are the favored location, but they also have been described on the head, neck, and trunk. Additionally, mediastinal and retroperitoneal lipoblastomas have been documented.¹ The tumors may be symptomatic, particularly when involving the neck or mediastinum. In rare instances, they may present with respiratory distress.² Multiple cases of head and neck lipoblastomas have been published in the English-language literature.³ Growing evidence supports that a chromosomal breakpoint abnormality at 8q11-q13 may be implicated in the pathogenesis.⁴

Most lipoblastomas are well circumscribed, encapsulated, and limited to the subcutis. However, lipoblastomatosis is the diffuse counterpart to lipoblastoma, affecting deeper soft tissue and often infiltrating adjacent skeletal muscle.¹

Diagnosis is made by histologic evaluation. Lipoblastoma appears as immature fat cells in varying stages of maturity with septa separating them into lobules. There should not be nuclear atypia.⁵ The histologic differential diagnosis includes other adipose tumors, most chiefly myxoid liposarcoma. These tumors have a lobular pattern without prominent septae and contain nuclear atypia with atypical mitotic figures. Myxoid liposarcoma has an infiltrating pattern similar to lipoblastomatosis and has a metastatic rate up to 60%.⁶ Imaging studies such as MRI are helpful in diagnosis, particularly in head and neck or visceral cases.³ The treatment of choice of lipoblastoma is wide excision. With complete removal, tumors rarely recur. Recurrences are more common in lipoblastomatosis or with incompletely excised primary lesions.³ A 14% to 24% recurrence rate has been recognized. Cytogenic analysis of lipomatous tumors has begun to reveal translocations in chromosome 8q11-13 region breakpoint abnormalities and translocations, specifically involving the pleomorphic adenoma gene 1, PLAG1, as the oncogenic target in lipoblastoma.⁶ Identification of these molecular mutations may provide aid in differentiating histologically similar-appearing tumors in the future.

This case illustrates a rare benign childhood tumor that can be difficult to diagnose prior to histologic examination. Our patient did not fit the typical description of a lipoblastoma, as his tumor was axially located as opposed to the more common peripheral presentation. We aim to raise awareness of this diagnosis as more cases are being recognized.

To the Editor:

A 2-year-old boy was referred to our pediatric dermatology clinic by his pediatrician for an enlarging mass on the mid frontal scalp. The lesion had been present since birth and slowly enlarged. His parents thought the lesion was mostly asymptomatic; however, if it was irritated, the child would cry. He was otherwise healthy and had no history of skin conditions. There was no family history of skin conditions, birthmarks, or vascular malformations. On physical examination, we observed an isolated, approximately 3-cm, well-circumscribed, mobile, flesh-colored and violaceous nodule on the mid frontal scalp (Figure 1). At that time our differential diagnosis included a complex hemangioma or other vascular proliferation, nevus lipomatosis, or even a soft-tissue malignancy such as a sarcoma. Prior to biopsy, we ordered magnetic resonance imaging (MRI) to evaluate for intracranial extension of the lesion. The MRI revealed a 3.2-cm frontal midline scalp mass with complex imaging characteristics, and the radiologist gave a differential diagnosis of hemangioma, teratoma, or less likely liposarcoma (Figure 2). Fortunately, there was no evidence of central nervous system or intracranial invasion. We then proceeded with excisional biopsy, which grossly revealed a nodular, well-circumscribed, yellow mass (Figure 3). The wound was closed with primary closure. Histologically, there was a lobulated tumor with thin, well-vascularized connective tissue septa within a myxoid stroma (Figure 4A). The tumor was composed of lipocytes in varying stages of maturity without obvious nuclear atypia (Figures 4B and 4C), leading to a diagnosis of lipoblastoma.

Lipoblastoma (also known as an embryonic lipoma) is a rare variant of lipoma. It is a benign neoplasm of immature white fat cells primarily seen in children younger than 3 years. It is reportedly twice as common in boys versus girls. Lipoblastomas present as enlarging, soft, mobile, painless nodules, usually 3 to 5 cm in diameter. The extremities are the favored location, but they also have been described on the head, neck, and trunk. Additionally, mediastinal and retroperitoneal lipoblastomas have been documented.¹ The tumors may be symptomatic, particularly when involving the neck or mediastinum. In rare instances, they may present with respiratory distress.² Multiple cases of head and neck lipoblastomas have been published in the English-language literature.³ Growing evidence supports that a chromosomal breakpoint abnormality at 8q11-q13 may be implicated in the pathogenesis.⁴

Most lipoblastomas are well circumscribed, encapsulated, and limited to the subcutis. However, lipoblastomatosis is the diffuse counterpart to lipoblastoma, affecting deeper soft tissue and often infiltrating adjacent skeletal muscle.¹

Diagnosis is made by histologic evaluation. Lipoblastoma appears as immature fat cells in varying stages of maturity with septa separating them into lobules. There should not be nuclear atypia.⁵ The histologic differential diagnosis includes other adipose tumors, most chiefly myxoid liposarcoma. These tumors have a lobular pattern without prominent septae and contain nuclear atypia with atypical mitotic figures. Myxoid liposarcoma has an infiltrating pattern similar to lipoblastomatosis and has a metastatic rate up to 60%.⁶ Imaging studies such as MRI are helpful in diagnosis, particularly in head and neck or visceral cases.³ The treatment of choice of lipoblastoma is wide excision. With complete removal, tumors rarely recur. Recurrences are more common in lipoblastomatosis or with incompletely excised primary lesions.³ A 14% to 24% recurrence rate has been recognized. Cytogenic analysis of lipomatous tumors has begun to reveal translocations in chromosome 8q11-13 region breakpoint abnormalities and translocations, specifically involving the pleomorphic adenoma gene 1, PLAG1, as the oncogenic target in lipoblastoma.⁶ Identification of these molecular mutations may provide aid in differentiating histologically similar-appearing tumors in the future.

This case illustrates a rare benign childhood tumor that can be difficult to diagnose prior to histologic examination. Our patient did not fit the typical description of a lipoblastoma, as his tumor was axially located as opposed to the more common peripheral presentation. We aim to raise awareness of this diagnosis as more cases are being recognized.

To the Editor:

A 2-year-old boy was referred to our pediatric dermatology clinic by his pediatrician for an enlarging mass on the mid frontal scalp. The lesion had been present since birth and slowly enlarged. His parents thought the lesion was mostly asymptomatic; however, if it was irritated, the child would cry. He was otherwise healthy and had no history of skin conditions. There was no family history of skin conditions, birthmarks, or vascular malformations. On physical examination, we observed an isolated, approximately 3-cm, well-circumscribed, mobile, flesh-colored and violaceous nodule on the mid frontal scalp (Figure 1). At that time our differential diagnosis included a complex hemangioma or other vascular proliferation, nevus lipomatosis, or even a soft-tissue malignancy such as a sarcoma. Prior to biopsy, we ordered magnetic resonance imaging (MRI) to evaluate for intracranial extension of the lesion. The MRI revealed a 3.2-cm frontal midline scalp mass with complex imaging characteristics, and the radiologist gave a differential diagnosis of hemangioma, teratoma, or less likely liposarcoma (Figure 2). Fortunately, there was no evidence of central nervous system or intracranial invasion. We then proceeded with excisional biopsy, which grossly revealed a nodular, well-circumscribed, yellow mass (Figure 3). The wound was closed with primary closure. Histologically, there was a lobulated tumor with thin, well-vascularized connective tissue septa within a myxoid stroma (Figure 4A). The tumor was composed of lipocytes in varying stages of maturity without obvious nuclear atypia (Figures 4B and 4C), leading to a diagnosis of lipoblastoma.

Lipoblastoma (also known as an embryonic lipoma) is a rare variant of lipoma. It is a benign neoplasm of immature white fat cells primarily seen in children younger than 3 years. It is reportedly twice as common in boys versus girls. Lipoblastomas present as enlarging, soft, mobile, painless nodules, usually 3 to 5 cm in diameter. The extremities are the favored location, but they also have been described on the head, neck, and trunk. Additionally, mediastinal and retroperitoneal lipoblastomas have been documented.¹ The tumors may be symptomatic, particularly when involving the neck or mediastinum. In rare instances, they may present with respiratory distress.² Multiple cases of head and neck lipoblastomas have been published in the English-language literature.³ Growing evidence supports that a chromosomal breakpoint abnormality at 8q11-q13 may be implicated in the pathogenesis.⁴

Most lipoblastomas are well circumscribed, encapsulated, and limited to the subcutis. However, lipoblastomatosis is the diffuse counterpart to lipoblastoma, affecting deeper soft tissue and often infiltrating adjacent skeletal muscle.¹

Diagnosis is made by histologic evaluation. Lipoblastoma appears as immature fat cells in varying stages of maturity with septa separating them into lobules. There should not be nuclear atypia.⁵ The histologic differential diagnosis includes other adipose tumors, most chiefly myxoid liposarcoma. These tumors have a lobular pattern without prominent septae and contain nuclear atypia with atypical mitotic figures. Myxoid liposarcoma has an infiltrating pattern similar to lipoblastomatosis and has a metastatic rate up to 60%.⁶ Imaging studies such as MRI are helpful in diagnosis, particularly in head and neck or visceral cases.³ The treatment of choice of lipoblastoma is wide excision. With complete removal, tumors rarely recur. Recurrences are more common in lipoblastomatosis or with incompletely excised primary lesions.³ A 14% to 24% recurrence rate has been recognized. Cytogenic analysis of lipomatous tumors has begun to reveal translocations in chromosome 8q11-13 region breakpoint abnormalities and translocations, specifically involving the pleomorphic adenoma gene 1, PLAG1, as the oncogenic target in lipoblastoma.⁶ Identification of these molecular mutations may provide aid in differentiating histologically similar-appearing tumors in the future.

This case illustrates a rare benign childhood tumor that can be difficult to diagnose prior to histologic examination. Our patient did not fit the typical description of a lipoblastoma, as his tumor was axially located as opposed to the more common peripheral presentation. We aim to raise awareness of this diagnosis as more cases are being recognized.

To the Editor:

Disseminated cryptococcosis is a well-known opportunistic infection in patients with advanced human immunodeficiency virus (HIV) infection, but it is not frequently seen as a primary infection of the skin in immunocompetent hosts. We report a case of primary cutaneous cryptococcosis (PCC) of the lower legs in an immunocompetent Iraq War veteran.

A 28-year-old female service member presented to the dermatology clinic with progressively enlarging plaquelike lesions on the shins of 6 months’ duration. The patient had resided and worked as a deployed soldier in the lower level of a bullet hole–laden, pigeon-infested observation tower in southern Iraq 9 months prior to the current presentation. During her 7-month deployment, she reported daily exposure to pigeon excreta on equipment and frequently sustained superficial abrasions and lacerations to the legs due to the cramped and hazardous working environment. The patient noticed intensely pruritic, bugbitelike papular lesions on the shins and calves 1 month after residing in the observation tower. She sought medical treatment and was given hydrocortisone cream 1% and calamine lotion for a presumed irritant dermatitis. Over the ensuing 3 months, the pruritus worsened, and the primary lesions coalesced into annular erythematous plaques (Figure).

After returning to the United States, the patient presented again for medical care and was given ketoconazole cream 1% for presumed tinea corporis, which resulted in no improvement. A dermatologic consultation and evaluation ensued with subsequent microbial workup showing no bacterial growth on wound culture and no fungal elements on a potassium hydroxide preparation. Hematoxylin and eosin, periodic acid–Schiff, and Grocott-Gomori methenamine-silver staining did not demonstrate any organisms. Tissue cultures for bacteria and acid-fast bacilli showed no growth. A fungal tissue culture ultimately confirmed the presence of Cryptococcus neoformans. A lumbar puncture showed no evidence of Cryptococcus on DNA probe testing. Serologic testing for HIV was negative, and brain magnetic resonance imaging showed no lesions. Sputum culture and staining showed no fungal elements, and a chest radiograph was normal. A diagnosis of PCC was made and therapy with oral fluconazole 200 mg twice daily was initiated, with the intention of completing a 6-month course. During the treatment, the pruritus resolved within 3 weeks and the lesions involuted over 3 months. From the time of onset of the lesions throughout treatment, the patient showed no pulmonary, neurologic, or other systemic symptoms. She currently is healthy with no evidence of recurrence.

Primary cutaneous cryptococcosis mainly affects individuals with underlying immunosuppression, most commonly due to advanced HIV, prolonged treatment with immunosuppressive medications, or organ transplantation.¹ The most common route of inoculation is by inhalation of Cryptococcus spores with subsequent hematogenous dissemination.² Primary cutaneous cryptococcosis with skin lesions and no concomitant systemic involvement has rarely been reported, and when encountered, it usually is associated with environments that predispose patients to skin wounds with simultaneous exposure to soil or vegetative debris contaminated with bird excreta.³ Primary cutaneous cryptococcosis can present in a myriad of ways, including papules, nodules, plaques, and even necrotizing fasciitis–like skin lesions.^4,5 This variable presentation often creates clinical confusion and diagnostic delay; therefore, a high index of suspicion is required for timely diagnosis.

Due to the worldwide deployment of US military service members, exotic cutaneous infectious diseases such as PCC may be encountered in dermatology practice. Prompt clinical and histologic diagnosis is imperative to assess for systemic disease and avoid cutaneous spread and morbidity in US service members and travelers returning home from the Middle East.

To the Editor:

Disseminated cryptococcosis is a well-known opportunistic infection in patients with advanced human immunodeficiency virus (HIV) infection, but it is not frequently seen as a primary infection of the skin in immunocompetent hosts. We report a case of primary cutaneous cryptococcosis (PCC) of the lower legs in an immunocompetent Iraq War veteran.

A 28-year-old female service member presented to the dermatology clinic with progressively enlarging plaquelike lesions on the shins of 6 months’ duration. The patient had resided and worked as a deployed soldier in the lower level of a bullet hole–laden, pigeon-infested observation tower in southern Iraq 9 months prior to the current presentation. During her 7-month deployment, she reported daily exposure to pigeon excreta on equipment and frequently sustained superficial abrasions and lacerations to the legs due to the cramped and hazardous working environment. The patient noticed intensely pruritic, bugbitelike papular lesions on the shins and calves 1 month after residing in the observation tower. She sought medical treatment and was given hydrocortisone cream 1% and calamine lotion for a presumed irritant dermatitis. Over the ensuing 3 months, the pruritus worsened, and the primary lesions coalesced into annular erythematous plaques (Figure).

After returning to the United States, the patient presented again for medical care and was given ketoconazole cream 1% for presumed tinea corporis, which resulted in no improvement. A dermatologic consultation and evaluation ensued with subsequent microbial workup showing no bacterial growth on wound culture and no fungal elements on a potassium hydroxide preparation. Hematoxylin and eosin, periodic acid–Schiff, and Grocott-Gomori methenamine-silver staining did not demonstrate any organisms. Tissue cultures for bacteria and acid-fast bacilli showed no growth. A fungal tissue culture ultimately confirmed the presence of Cryptococcus neoformans. A lumbar puncture showed no evidence of Cryptococcus on DNA probe testing. Serologic testing for HIV was negative, and brain magnetic resonance imaging showed no lesions. Sputum culture and staining showed no fungal elements, and a chest radiograph was normal. A diagnosis of PCC was made and therapy with oral fluconazole 200 mg twice daily was initiated, with the intention of completing a 6-month course. During the treatment, the pruritus resolved within 3 weeks and the lesions involuted over 3 months. From the time of onset of the lesions throughout treatment, the patient showed no pulmonary, neurologic, or other systemic symptoms. She currently is healthy with no evidence of recurrence.

Primary cutaneous cryptococcosis mainly affects individuals with underlying immunosuppression, most commonly due to advanced HIV, prolonged treatment with immunosuppressive medications, or organ transplantation.¹ The most common route of inoculation is by inhalation of Cryptococcus spores with subsequent hematogenous dissemination.² Primary cutaneous cryptococcosis with skin lesions and no concomitant systemic involvement has rarely been reported, and when encountered, it usually is associated with environments that predispose patients to skin wounds with simultaneous exposure to soil or vegetative debris contaminated with bird excreta.³ Primary cutaneous cryptococcosis can present in a myriad of ways, including papules, nodules, plaques, and even necrotizing fasciitis–like skin lesions.^4,5 This variable presentation often creates clinical confusion and diagnostic delay; therefore, a high index of suspicion is required for timely diagnosis.

Due to the worldwide deployment of US military service members, exotic cutaneous infectious diseases such as PCC may be encountered in dermatology practice. Prompt clinical and histologic diagnosis is imperative to assess for systemic disease and avoid cutaneous spread and morbidity in US service members and travelers returning home from the Middle East.

To the Editor:

Disseminated cryptococcosis is a well-known opportunistic infection in patients with advanced human immunodeficiency virus (HIV) infection, but it is not frequently seen as a primary infection of the skin in immunocompetent hosts. We report a case of primary cutaneous cryptococcosis (PCC) of the lower legs in an immunocompetent Iraq War veteran.

A 28-year-old female service member presented to the dermatology clinic with progressively enlarging plaquelike lesions on the shins of 6 months’ duration. The patient had resided and worked as a deployed soldier in the lower level of a bullet hole–laden, pigeon-infested observation tower in southern Iraq 9 months prior to the current presentation. During her 7-month deployment, she reported daily exposure to pigeon excreta on equipment and frequently sustained superficial abrasions and lacerations to the legs due to the cramped and hazardous working environment. The patient noticed intensely pruritic, bugbitelike papular lesions on the shins and calves 1 month after residing in the observation tower. She sought medical treatment and was given hydrocortisone cream 1% and calamine lotion for a presumed irritant dermatitis. Over the ensuing 3 months, the pruritus worsened, and the primary lesions coalesced into annular erythematous plaques (Figure).

After returning to the United States, the patient presented again for medical care and was given ketoconazole cream 1% for presumed tinea corporis, which resulted in no improvement. A dermatologic consultation and evaluation ensued with subsequent microbial workup showing no bacterial growth on wound culture and no fungal elements on a potassium hydroxide preparation. Hematoxylin and eosin, periodic acid–Schiff, and Grocott-Gomori methenamine-silver staining did not demonstrate any organisms. Tissue cultures for bacteria and acid-fast bacilli showed no growth. A fungal tissue culture ultimately confirmed the presence of Cryptococcus neoformans. A lumbar puncture showed no evidence of Cryptococcus on DNA probe testing. Serologic testing for HIV was negative, and brain magnetic resonance imaging showed no lesions. Sputum culture and staining showed no fungal elements, and a chest radiograph was normal. A diagnosis of PCC was made and therapy with oral fluconazole 200 mg twice daily was initiated, with the intention of completing a 6-month course. During the treatment, the pruritus resolved within 3 weeks and the lesions involuted over 3 months. From the time of onset of the lesions throughout treatment, the patient showed no pulmonary, neurologic, or other systemic symptoms. She currently is healthy with no evidence of recurrence.

Primary cutaneous cryptococcosis mainly affects individuals with underlying immunosuppression, most commonly due to advanced HIV, prolonged treatment with immunosuppressive medications, or organ transplantation.¹ The most common route of inoculation is by inhalation of Cryptococcus spores with subsequent hematogenous dissemination.² Primary cutaneous cryptococcosis with skin lesions and no concomitant systemic involvement has rarely been reported, and when encountered, it usually is associated with environments that predispose patients to skin wounds with simultaneous exposure to soil or vegetative debris contaminated with bird excreta.³ Primary cutaneous cryptococcosis can present in a myriad of ways, including papules, nodules, plaques, and even necrotizing fasciitis–like skin lesions.^4,5 This variable presentation often creates clinical confusion and diagnostic delay; therefore, a high index of suspicion is required for timely diagnosis.

Due to the worldwide deployment of US military service members, exotic cutaneous infectious diseases such as PCC may be encountered in dermatology practice. Prompt clinical and histologic diagnosis is imperative to assess for systemic disease and avoid cutaneous spread and morbidity in US service members and travelers returning home from the Middle East.

To the Editor:

A 22-year-old Somali woman presented to our institution with oral lesions of 2 years’ duration. The lesions started as small papules in the corners of the mouth that gradually continued to spread to the mucosal lips and gums. The lesions did not drain any material. The patient reported that they were not painful and had not regressed. She was concerned about the cosmetic appearance of the lesions. The patient believed the lesions had developed from working in a chicken factory and was concerned that they appeared possibly due to contact with a substance in the factory. Additionally, she noted that her voice had become hoarse. She was otherwise healthy and denied any sexual contact or ever having a blood transfusion.

Physical examination revealed 10 to 15 flesh-colored papules measuring 2 to 3 mm in diameter on the vermilion, mucosal surfaces of the lips, and upper and lower gingivae (Figure 1). No lesions were seen on the hard and soft palate, tongue, buccal mucosa, or posterior pharynx.

Skin biopsy of the left lower mucosal lip revealed parakeratosis, acanthosis, superficial koilocytes, and atypical keratinocytes with frequent mitoses (Figures 2A–2C). In situ hybridization testing for human papillomavirus (HPV) was negative for low-risk types 6 and 11 but positive for high-risk types 16 and 18 (Figure 2D). Laboratory investigations including complete blood cell count, electrolyte panel, and liver function studies were normal, and serum was negative for syphilis and human immunodeficiency virus antibodies.

The combined clinical and histologic findings were diagnostic of oral bowenoid papulosis. Gynecologic evaluation showed that the patient had undergone female circumcision, and she had a normal Papanicolaou test. The patient was referred to both the ear, nose, and throat clinic as well as the dermatologic surgery department to discuss treatment options, but she was lost to follow-up.

Bowenoid papulosis is triggered by HPV infection and manifests clinically as solitary or multiple verrucous papules and plaques that are usually located on the genitalia.¹ Only a few cases of bowenoid papulosis have been reported in the oral cavity.^1-5 Because this disease is sexually transmitted, the mean age of onset of bowenoid papulosis is 31 years.² There is a small risk (2%–3%) of developing invasive carcinoma in bowenoid papulosis.^1-3,6 Most lesions are associated with HPV type 16; however, bowenoid papulosis also has been associated with HPV types 18, 31, 32, 35, and 39.²

Some investigators consider bowenoid papulosis and Bowen disease (a type of squamous cell carcinoma [SCC] in situ) to be histologically identical^1,6; however, some histologic differences have been reported.^1-3,6 Bowenoid papulosis has more dilated and tortuous dermal capillaries and less atypia and dyskeratosis than Bowen disease.^1,6 In contrast to bowenoid papulosis, Bowen disease is characterized clinically as well-defined scaly plaques on sun-exposed areas of the skin in older adults. Invasive SCC can be seen in 5% of skin lesions and 30% of penile lesions associated with Bowen disease.² Risk factors for Bowen disease include sun exposure; arsenic poisoning; and infection with HPV types 2, 16, 18, 31, 33, 52, and 67.^1,6

Oral bowenoid papulosis is rare. A PubMed search of articles indexed for MEDLINE using the term oral bowenoid papulosis yielded 7 additional cases, which are summarized in the Table. In 1987 Lookingbill et al² described one of the first reported cases of oral disease in a 33-year-old immunosuppressed man receiving prednisone therapy for systemic lupus erythematosus who had both mouth and genital lesions. All lesions were positive for HPV type 16. The patient subsequently developed SCC of the tongue.² Since then, 7 other cases of oral bowenoid papulosis have been described including the current case.^1,3-5 Four (57%) cases in total were associated with immunosuppression and genital lesions.^2-5

The risk for progression of oral bowenoid papulosis to invasive SCC is not known. Our search yielded only 1 case of this occurrence.²

Two of 3 cases of solitary lip lesions in oral bowenoid papulosis were treated with surgical excision.¹ Other treatment options include CO₂ laser therapy, cryotherapy, 5-fluorouracil, bleomycin, intralesional interferon alfa, and imiquimod.^1-3,5,6

Our case represents a rare report of oral bowenoid papulosis. Recognition of this unusual presentation is important for the diagnosis and management of this disease.

To the Editor:

A 22-year-old Somali woman presented to our institution with oral lesions of 2 years’ duration. The lesions started as small papules in the corners of the mouth that gradually continued to spread to the mucosal lips and gums. The lesions did not drain any material. The patient reported that they were not painful and had not regressed. She was concerned about the cosmetic appearance of the lesions. The patient believed the lesions had developed from working in a chicken factory and was concerned that they appeared possibly due to contact with a substance in the factory. Additionally, she noted that her voice had become hoarse. She was otherwise healthy and denied any sexual contact or ever having a blood transfusion.

Physical examination revealed 10 to 15 flesh-colored papules measuring 2 to 3 mm in diameter on the vermilion, mucosal surfaces of the lips, and upper and lower gingivae (Figure 1). No lesions were seen on the hard and soft palate, tongue, buccal mucosa, or posterior pharynx.

Skin biopsy of the left lower mucosal lip revealed parakeratosis, acanthosis, superficial koilocytes, and atypical keratinocytes with frequent mitoses (Figures 2A–2C). In situ hybridization testing for human papillomavirus (HPV) was negative for low-risk types 6 and 11 but positive for high-risk types 16 and 18 (Figure 2D). Laboratory investigations including complete blood cell count, electrolyte panel, and liver function studies were normal, and serum was negative for syphilis and human immunodeficiency virus antibodies.

The combined clinical and histologic findings were diagnostic of oral bowenoid papulosis. Gynecologic evaluation showed that the patient had undergone female circumcision, and she had a normal Papanicolaou test. The patient was referred to both the ear, nose, and throat clinic as well as the dermatologic surgery department to discuss treatment options, but she was lost to follow-up.

Bowenoid papulosis is triggered by HPV infection and manifests clinically as solitary or multiple verrucous papules and plaques that are usually located on the genitalia.¹ Only a few cases of bowenoid papulosis have been reported in the oral cavity.^1-5 Because this disease is sexually transmitted, the mean age of onset of bowenoid papulosis is 31 years.² There is a small risk (2%–3%) of developing invasive carcinoma in bowenoid papulosis.^1-3,6 Most lesions are associated with HPV type 16; however, bowenoid papulosis also has been associated with HPV types 18, 31, 32, 35, and 39.²

Some investigators consider bowenoid papulosis and Bowen disease (a type of squamous cell carcinoma [SCC] in situ) to be histologically identical^1,6; however, some histologic differences have been reported.^1-3,6 Bowenoid papulosis has more dilated and tortuous dermal capillaries and less atypia and dyskeratosis than Bowen disease.^1,6 In contrast to bowenoid papulosis, Bowen disease is characterized clinically as well-defined scaly plaques on sun-exposed areas of the skin in older adults. Invasive SCC can be seen in 5% of skin lesions and 30% of penile lesions associated with Bowen disease.² Risk factors for Bowen disease include sun exposure; arsenic poisoning; and infection with HPV types 2, 16, 18, 31, 33, 52, and 67.^1,6

Oral bowenoid papulosis is rare. A PubMed search of articles indexed for MEDLINE using the term oral bowenoid papulosis yielded 7 additional cases, which are summarized in the Table. In 1987 Lookingbill et al² described one of the first reported cases of oral disease in a 33-year-old immunosuppressed man receiving prednisone therapy for systemic lupus erythematosus who had both mouth and genital lesions. All lesions were positive for HPV type 16. The patient subsequently developed SCC of the tongue.² Since then, 7 other cases of oral bowenoid papulosis have been described including the current case.^1,3-5 Four (57%) cases in total were associated with immunosuppression and genital lesions.^2-5

The risk for progression of oral bowenoid papulosis to invasive SCC is not known. Our search yielded only 1 case of this occurrence.²

Two of 3 cases of solitary lip lesions in oral bowenoid papulosis were treated with surgical excision.¹ Other treatment options include CO₂ laser therapy, cryotherapy, 5-fluorouracil, bleomycin, intralesional interferon alfa, and imiquimod.^1-3,5,6

Our case represents a rare report of oral bowenoid papulosis. Recognition of this unusual presentation is important for the diagnosis and management of this disease.

To the Editor:

A 22-year-old Somali woman presented to our institution with oral lesions of 2 years’ duration. The lesions started as small papules in the corners of the mouth that gradually continued to spread to the mucosal lips and gums. The lesions did not drain any material. The patient reported that they were not painful and had not regressed. She was concerned about the cosmetic appearance of the lesions. The patient believed the lesions had developed from working in a chicken factory and was concerned that they appeared possibly due to contact with a substance in the factory. Additionally, she noted that her voice had become hoarse. She was otherwise healthy and denied any sexual contact or ever having a blood transfusion.

Physical examination revealed 10 to 15 flesh-colored papules measuring 2 to 3 mm in diameter on the vermilion, mucosal surfaces of the lips, and upper and lower gingivae (Figure 1). No lesions were seen on the hard and soft palate, tongue, buccal mucosa, or posterior pharynx.

Skin biopsy of the left lower mucosal lip revealed parakeratosis, acanthosis, superficial koilocytes, and atypical keratinocytes with frequent mitoses (Figures 2A–2C). In situ hybridization testing for human papillomavirus (HPV) was negative for low-risk types 6 and 11 but positive for high-risk types 16 and 18 (Figure 2D). Laboratory investigations including complete blood cell count, electrolyte panel, and liver function studies were normal, and serum was negative for syphilis and human immunodeficiency virus antibodies.

The combined clinical and histologic findings were diagnostic of oral bowenoid papulosis. Gynecologic evaluation showed that the patient had undergone female circumcision, and she had a normal Papanicolaou test. The patient was referred to both the ear, nose, and throat clinic as well as the dermatologic surgery department to discuss treatment options, but she was lost to follow-up.

Bowenoid papulosis is triggered by HPV infection and manifests clinically as solitary or multiple verrucous papules and plaques that are usually located on the genitalia.¹ Only a few cases of bowenoid papulosis have been reported in the oral cavity.^1-5 Because this disease is sexually transmitted, the mean age of onset of bowenoid papulosis is 31 years.² There is a small risk (2%–3%) of developing invasive carcinoma in bowenoid papulosis.^1-3,6 Most lesions are associated with HPV type 16; however, bowenoid papulosis also has been associated with HPV types 18, 31, 32, 35, and 39.²

Some investigators consider bowenoid papulosis and Bowen disease (a type of squamous cell carcinoma [SCC] in situ) to be histologically identical^1,6; however, some histologic differences have been reported.^1-3,6 Bowenoid papulosis has more dilated and tortuous dermal capillaries and less atypia and dyskeratosis than Bowen disease.^1,6 In contrast to bowenoid papulosis, Bowen disease is characterized clinically as well-defined scaly plaques on sun-exposed areas of the skin in older adults. Invasive SCC can be seen in 5% of skin lesions and 30% of penile lesions associated with Bowen disease.² Risk factors for Bowen disease include sun exposure; arsenic poisoning; and infection with HPV types 2, 16, 18, 31, 33, 52, and 67.^1,6

Oral bowenoid papulosis is rare. A PubMed search of articles indexed for MEDLINE using the term oral bowenoid papulosis yielded 7 additional cases, which are summarized in the Table. In 1987 Lookingbill et al² described one of the first reported cases of oral disease in a 33-year-old immunosuppressed man receiving prednisone therapy for systemic lupus erythematosus who had both mouth and genital lesions. All lesions were positive for HPV type 16. The patient subsequently developed SCC of the tongue.² Since then, 7 other cases of oral bowenoid papulosis have been described including the current case.^1,3-5 Four (57%) cases in total were associated with immunosuppression and genital lesions.^2-5

The risk for progression of oral bowenoid papulosis to invasive SCC is not known. Our search yielded only 1 case of this occurrence.²

Two of 3 cases of solitary lip lesions in oral bowenoid papulosis were treated with surgical excision.¹ Other treatment options include CO₂ laser therapy, cryotherapy, 5-fluorouracil, bleomycin, intralesional interferon alfa, and imiquimod.^1-3,5,6

Our case represents a rare report of oral bowenoid papulosis. Recognition of this unusual presentation is important for the diagnosis and management of this disease.

To the Editor:

Gemcitabine is a nucleoside analogue used to treat a variety of solid and hematologic malignancies. Cutaneous toxicities include radiation recall dermatitis and erysipelaslike reactions that occur in areas not previously treated with radiation. Often referred to as pseudocellulitis, these reactions generally have been reported in areas of lymphedema in patients with solid malignancies.^1-6 Herein, we report a rare case of gemcitabine-induced pseudocellulitis on the legs in a patient with a history of hematologic malignancy and total body irradiation (TBI).

A 61-year-old woman with history of peripheral T-cell lymphoma presented to the emergency department at our institution with acute-onset redness, tenderness, and swelling of the legs that was concerning for cellulitis. The patient’s history was notable for receiving gemcitabine 1000 mg/m² for treatment of refractory lymphoma (12 and 4 days prior to presentation) as well as lymphedema of the legs. Her complete treatment course included multiple rounds of chemotherapy and matched unrelated donor nonmyeloablative allogeneic stem cell transplantation with a single dose of TBI at 200 cGy at our institution. Her transplant was complicated only by mild cutaneous graft-versus-host disease, which resolved with prednisone and tacrolimus.

On physical examination, the patient was afebrile with symmetric erythema and induration extending from the bilateral knees to the dorsal feet. A complete blood cell count was notable for a white blood cell count of 5400/µL (reference range, 4500–11,000/µL) and a platelet count of 96,000/µL (reference range, 150,000–400,000/µL). Plain film radiographs of the bilateral ankles were remarkable only for moderate subcutaneous edema. She received vancomycin in the emergency department and was admitted to the oncology service. Blood cultures drawn on admission were negative. Dermatology was consulted on admission, and a diagnosis of pseudocellulitis was made in conjunction with oncology (Figure). Antibiotics were held, and the patient was treated symptomatically with ibuprofen and was discharged 1 day after admission. The reaction resolved after 1 week with the use of diphenhydramine, nonsteroidal anti-inflammatory drugs, and compression. The patient was not rechallenged with gemcitabine.

Gemcitabine-induced pseudocellulitis is a rare cutaneous side effect of gemcitabine therapy. Reported cases have suggested key characteristics of pseudocellulitis (Table). The reaction is characterized by localized erythema, edema, and tenderness of the skin, with onset generally 48 hours to 1 week after receiving gemcitabine.^1-6 Lymphedema appears to be a risk factor.^1,3-5 Six cases (including the current case) demonstrated confinement of these findings to areas of prior lymphedema.^1,4,6 Infectious workup is negative, and rechallenging with gemcitabine likely will reproduce the reaction. Unlike radiation recall dermatitis, there is no prior localized radiation exposure.

Our patient had a history of hematologic malignancy and a one-time low-dose TBI of 200 cGy, unlike the other reported cases described in the Table. It is difficult to attribute our patient’s localized eruption to radiation recall given the history of TBI. The clinical examination, laboratory findings, and time frame of the reaction were consistent with gemcitabine-induced pseudocellulitis.

It is important to be aware of pseudocellulitis as a possible complication of gemcitabine therapy in patients without history of localized radiation. Early recognition of pseudocellulitis may prevent unnecessary exposure to broad-spectrum antibiotics. Patients’ temperature, white blood cell count, clinical examination, and potentially ancillary studies (eg, vascular studies, inflammatory markers) should be reviewed carefully to determine whether there is an infectious or alternate etiology. In patients with known prior lymphedema, it may be beneficial to educate clinicians and patients alike about this potential adverse effect of gemcitabine and the high likelihood of recurrence on re-exposure.

To the Editor:

Gemcitabine is a nucleoside analogue used to treat a variety of solid and hematologic malignancies. Cutaneous toxicities include radiation recall dermatitis and erysipelaslike reactions that occur in areas not previously treated with radiation. Often referred to as pseudocellulitis, these reactions generally have been reported in areas of lymphedema in patients with solid malignancies.^1-6 Herein, we report a rare case of gemcitabine-induced pseudocellulitis on the legs in a patient with a history of hematologic malignancy and total body irradiation (TBI).

A 61-year-old woman with history of peripheral T-cell lymphoma presented to the emergency department at our institution with acute-onset redness, tenderness, and swelling of the legs that was concerning for cellulitis. The patient’s history was notable for receiving gemcitabine 1000 mg/m² for treatment of refractory lymphoma (12 and 4 days prior to presentation) as well as lymphedema of the legs. Her complete treatment course included multiple rounds of chemotherapy and matched unrelated donor nonmyeloablative allogeneic stem cell transplantation with a single dose of TBI at 200 cGy at our institution. Her transplant was complicated only by mild cutaneous graft-versus-host disease, which resolved with prednisone and tacrolimus.

On physical examination, the patient was afebrile with symmetric erythema and induration extending from the bilateral knees to the dorsal feet. A complete blood cell count was notable for a white blood cell count of 5400/µL (reference range, 4500–11,000/µL) and a platelet count of 96,000/µL (reference range, 150,000–400,000/µL). Plain film radiographs of the bilateral ankles were remarkable only for moderate subcutaneous edema. She received vancomycin in the emergency department and was admitted to the oncology service. Blood cultures drawn on admission were negative. Dermatology was consulted on admission, and a diagnosis of pseudocellulitis was made in conjunction with oncology (Figure). Antibiotics were held, and the patient was treated symptomatically with ibuprofen and was discharged 1 day after admission. The reaction resolved after 1 week with the use of diphenhydramine, nonsteroidal anti-inflammatory drugs, and compression. The patient was not rechallenged with gemcitabine.

Gemcitabine-induced pseudocellulitis is a rare cutaneous side effect of gemcitabine therapy. Reported cases have suggested key characteristics of pseudocellulitis (Table). The reaction is characterized by localized erythema, edema, and tenderness of the skin, with onset generally 48 hours to 1 week after receiving gemcitabine.^1-6 Lymphedema appears to be a risk factor.^1,3-5 Six cases (including the current case) demonstrated confinement of these findings to areas of prior lymphedema.^1,4,6 Infectious workup is negative, and rechallenging with gemcitabine likely will reproduce the reaction. Unlike radiation recall dermatitis, there is no prior localized radiation exposure.

Our patient had a history of hematologic malignancy and a one-time low-dose TBI of 200 cGy, unlike the other reported cases described in the Table. It is difficult to attribute our patient’s localized eruption to radiation recall given the history of TBI. The clinical examination, laboratory findings, and time frame of the reaction were consistent with gemcitabine-induced pseudocellulitis.

It is important to be aware of pseudocellulitis as a possible complication of gemcitabine therapy in patients without history of localized radiation. Early recognition of pseudocellulitis may prevent unnecessary exposure to broad-spectrum antibiotics. Patients’ temperature, white blood cell count, clinical examination, and potentially ancillary studies (eg, vascular studies, inflammatory markers) should be reviewed carefully to determine whether there is an infectious or alternate etiology. In patients with known prior lymphedema, it may be beneficial to educate clinicians and patients alike about this potential adverse effect of gemcitabine and the high likelihood of recurrence on re-exposure.

To the Editor:

Gemcitabine is a nucleoside analogue used to treat a variety of solid and hematologic malignancies. Cutaneous toxicities include radiation recall dermatitis and erysipelaslike reactions that occur in areas not previously treated with radiation. Often referred to as pseudocellulitis, these reactions generally have been reported in areas of lymphedema in patients with solid malignancies.^1-6 Herein, we report a rare case of gemcitabine-induced pseudocellulitis on the legs in a patient with a history of hematologic malignancy and total body irradiation (TBI).

A 61-year-old woman with history of peripheral T-cell lymphoma presented to the emergency department at our institution with acute-onset redness, tenderness, and swelling of the legs that was concerning for cellulitis. The patient’s history was notable for receiving gemcitabine 1000 mg/m² for treatment of refractory lymphoma (12 and 4 days prior to presentation) as well as lymphedema of the legs. Her complete treatment course included multiple rounds of chemotherapy and matched unrelated donor nonmyeloablative allogeneic stem cell transplantation with a single dose of TBI at 200 cGy at our institution. Her transplant was complicated only by mild cutaneous graft-versus-host disease, which resolved with prednisone and tacrolimus.

On physical examination, the patient was afebrile with symmetric erythema and induration extending from the bilateral knees to the dorsal feet. A complete blood cell count was notable for a white blood cell count of 5400/µL (reference range, 4500–11,000/µL) and a platelet count of 96,000/µL (reference range, 150,000–400,000/µL). Plain film radiographs of the bilateral ankles were remarkable only for moderate subcutaneous edema. She received vancomycin in the emergency department and was admitted to the oncology service. Blood cultures drawn on admission were negative. Dermatology was consulted on admission, and a diagnosis of pseudocellulitis was made in conjunction with oncology (Figure). Antibiotics were held, and the patient was treated symptomatically with ibuprofen and was discharged 1 day after admission. The reaction resolved after 1 week with the use of diphenhydramine, nonsteroidal anti-inflammatory drugs, and compression. The patient was not rechallenged with gemcitabine.

Gemcitabine-induced pseudocellulitis is a rare cutaneous side effect of gemcitabine therapy. Reported cases have suggested key characteristics of pseudocellulitis (Table). The reaction is characterized by localized erythema, edema, and tenderness of the skin, with onset generally 48 hours to 1 week after receiving gemcitabine.^1-6 Lymphedema appears to be a risk factor.^1,3-5 Six cases (including the current case) demonstrated confinement of these findings to areas of prior lymphedema.^1,4,6 Infectious workup is negative, and rechallenging with gemcitabine likely will reproduce the reaction. Unlike radiation recall dermatitis, there is no prior localized radiation exposure.

Our patient had a history of hematologic malignancy and a one-time low-dose TBI of 200 cGy, unlike the other reported cases described in the Table. It is difficult to attribute our patient’s localized eruption to radiation recall given the history of TBI. The clinical examination, laboratory findings, and time frame of the reaction were consistent with gemcitabine-induced pseudocellulitis.

It is important to be aware of pseudocellulitis as a possible complication of gemcitabine therapy in patients without history of localized radiation. Early recognition of pseudocellulitis may prevent unnecessary exposure to broad-spectrum antibiotics. Patients’ temperature, white blood cell count, clinical examination, and potentially ancillary studies (eg, vascular studies, inflammatory markers) should be reviewed carefully to determine whether there is an infectious or alternate etiology. In patients with known prior lymphedema, it may be beneficial to educate clinicians and patients alike about this potential adverse effect of gemcitabine and the high likelihood of recurrence on re-exposure.

To the Editor:

A 58-year-old woman with a history of hyperprolactinemia and gastrointestinal angiodysplasia presented to the dermatology department with a generalized skin rash of 3 weeks’ duration. She did not have a history of toxic habits. She had a history of chronic hepatitis C virus (HCV) genotype 1b (IL-28B locus) with severe hepatic fibrosis (stage 4) as assessed by ultrasound-based elastography. Due to lack of response, plasma HCV RNA was still detectable at week 12 of pegylated interferon and ribavirin (RIB) therapy, and triple therapy with pegylated interferon, RIB, and telaprevir was initiated.

Two months later, she was admitted to the hospital after developing a generalized cutaneous rash that covered 90% of the body surface area (BSA) along with fever (temperature, 38.5°C). Laboratory blood tests showed an elevated absolute eosinophil count (2000 cells/µL [reference range, 0–500 cells/µL]), anemia (hemoglobin, 6.5 g/dL [reference range, 12–16 g/dL]), thrombocytopenia (26×10³/µL [reference range, 150–400×10³/µL]), and altered liver function tests (serum alanine aminotransferase, 60 U/L [reference range, 0–45 U/L]; aspartate aminotransferase, 80 U/L [reference range, 0–40 U/L]). Plasma HCV RNA was undetectable at this visit. On physical examination a generalized exanthema with coalescing plaques was observed, as well as crusted vesicles covering the arms, legs, chest, abdomen, and back. Palmoplantar papules (Figure, A) and facial swelling (Figure, B) also were present. A skin biopsy specimen taken from a papule on the left arm showed superficial perivascular lymphocytic infiltration with dermal edema. These findings were consistent with a diagnosis of DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome. Application of the Adverse Drug Reaction Probability Scale¹ in our patient (total score of 5) suggested that DRESS syndrome was a moderate adverse event likely related to the use of telaprevir.

After diagnosis of DRESS syndrome, telaprevir was discontinued, and the doses of RIB and pegylated interferon were reduced to 200 mg and 180 µg weekly, respectively. Laboratory test values including liver function tests normalized within 3 weeks and remained normal on follow-up. Plasma HCV RNA continued to be undetectable.

Hepatitis C virus is relatively common with an incidence of 3% worldwide.² It may present as an acute hepatitis or, more frequently, as asymptomatic chronic hepatitis. The acute process is self-limited and rarely causes hepatic failure. It usually leads to a chronic infection, which can result in cirrhosis, hepatocellular carcinoma, and the need for liver transplantation. The aim of treatment is eradication of HCV RNA, which is predicted by the attainment of a sustained virologic response. The latter is defined by the absence of HCV RNA by a polymerase chain reaction within 3 to 6 months after cessation of treatment.

Treatment of chronic HCV was based on the combination of pegylated interferon alfa-2a or -2b with RIB until 2015. Guidelines for the diagnosis and management of HCV infection have been published by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America.² These guidelines include new protease inhibitors, telaprevir and boceprevir, in the therapeutic approach of these patients. The main limitation of both drugs is the cutaneous toxicity.

Factors to be considered when treating HCV include viral genotype, if the patient is naïve or pretreated, the degree of fibrosis, established cirrhosis, and the treatment response. For patients with genotype 1,² as in our case, combination therapy with 3 drugs is recommended: pegylated interferon 180 µg subcutaneous injection weekly, RIB 15 mg/kg daily, and telaprevir 2250 mg or boceprevir 2400 mg daily. Triple therapy has been shown to achieve a successful response in 75% of naïve patients and in 50% of patients refractory to standard therapy.³

Telaprevir is an NS3/4A protease inhibitor approved by the US Food and Drug Administration and the European Medicines Agency for treatment of chronic HCV infection in naïve patients and in those unresponsive to double therapy. In phase 2 clinical trials, 41% to 61% of patients treated with telaprevir developed cutaneous reactions, of which 5% to 8% required cessation of treatment.⁴ The predicting risk factors for developing a secondary rash to telaprevir include age older than 45 years, body mass index less than 30, Caucasian ethnicity, and receiving HCV therapy for the first time.⁴

This cutaneous side effect is managed depending on the extension of the lesions, the presence of systemic symptoms, and laboratory abnormalities.⁵ Therefore, the severity of the skin reaction can be divided into 4 stages^4,5: (1) grade I or mild, defined as a localized rash with no systemic signs or mucosal involvement; (2) grade II or moderate, a maximum of 50% BSA involvement without epidermal detachment, and inflammation of the mucous membranes may be present without ulcers, as well as systemic symptoms such as fever, arthralgia, or eosinophilia; (3) grade III or severe, skin lesions affecting more than 50% BSA or less if any of the following lesions are present: vesicles or blisters, ulcers, epidermal detachment, palpable purpura, or erythema that does not blanch under pressure; (4) grade IV or life-threatening, when the clinical picture is consistent with acute generalized exanthematous pustulosis, DRESS syndrome, toxic epidermal necrolysis, or Stevens-Johnson syndrome.

DRESS syndrome is a condition clinically characterized by a generalized skin rash, facial angioedema, high fever, lymph node enlargement, and leukocytosis with eosinophilia or atypical lymphocytosis, along with abnormal renal and hepatic function tests. Cutaneous histopathologic examination may be unspecific, though atypical lymphocytes with a marked epidermotropism mimicking fungoid mycosis also have been described.⁶ In addition, human herpesvirus 6 serology may be negative, despite infection with this herpesvirus subtype having been associated with the development of DRESS syndrome. The pathophysiologic mechanism of DRESS syndrome is not completely understood; however, one theory ascribes an immunologic activation due to drug metabolite formation as the main mechanism.¹

Eleven patients⁷ with possible DRESS syndrome have been reported in clinical trials (less than 5% of the total of patients), with an addition of 1 more by Montaudié et al.⁸ No notable differences were found between telaprevir levels in these patients with respect to those of the control group.

For the management of DRESS syndrome, the occurrence of early signs of a severe acute skin reaction requires the immediate cessation of the drug, telaprevir in this case. The withdrawal of the dual therapy will depend on the short-term clinical course, according to the general condition of the patient, as well as the analytical abnormalities observed.⁹

In conclusion, telaprevir is a promising novel therapy for the treatment of HCV infection, but its cutaneous side effects still need to be properly established.

To the Editor:

A 58-year-old woman with a history of hyperprolactinemia and gastrointestinal angiodysplasia presented to the dermatology department with a generalized skin rash of 3 weeks’ duration. She did not have a history of toxic habits. She had a history of chronic hepatitis C virus (HCV) genotype 1b (IL-28B locus) with severe hepatic fibrosis (stage 4) as assessed by ultrasound-based elastography. Due to lack of response, plasma HCV RNA was still detectable at week 12 of pegylated interferon and ribavirin (RIB) therapy, and triple therapy with pegylated interferon, RIB, and telaprevir was initiated.

Two months later, she was admitted to the hospital after developing a generalized cutaneous rash that covered 90% of the body surface area (BSA) along with fever (temperature, 38.5°C). Laboratory blood tests showed an elevated absolute eosinophil count (2000 cells/µL [reference range, 0–500 cells/µL]), anemia (hemoglobin, 6.5 g/dL [reference range, 12–16 g/dL]), thrombocytopenia (26×10³/µL [reference range, 150–400×10³/µL]), and altered liver function tests (serum alanine aminotransferase, 60 U/L [reference range, 0–45 U/L]; aspartate aminotransferase, 80 U/L [reference range, 0–40 U/L]). Plasma HCV RNA was undetectable at this visit. On physical examination a generalized exanthema with coalescing plaques was observed, as well as crusted vesicles covering the arms, legs, chest, abdomen, and back. Palmoplantar papules (Figure, A) and facial swelling (Figure, B) also were present. A skin biopsy specimen taken from a papule on the left arm showed superficial perivascular lymphocytic infiltration with dermal edema. These findings were consistent with a diagnosis of DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome. Application of the Adverse Drug Reaction Probability Scale¹ in our patient (total score of 5) suggested that DRESS syndrome was a moderate adverse event likely related to the use of telaprevir.

After diagnosis of DRESS syndrome, telaprevir was discontinued, and the doses of RIB and pegylated interferon were reduced to 200 mg and 180 µg weekly, respectively. Laboratory test values including liver function tests normalized within 3 weeks and remained normal on follow-up. Plasma HCV RNA continued to be undetectable.

Hepatitis C virus is relatively common with an incidence of 3% worldwide.² It may present as an acute hepatitis or, more frequently, as asymptomatic chronic hepatitis. The acute process is self-limited and rarely causes hepatic failure. It usually leads to a chronic infection, which can result in cirrhosis, hepatocellular carcinoma, and the need for liver transplantation. The aim of treatment is eradication of HCV RNA, which is predicted by the attainment of a sustained virologic response. The latter is defined by the absence of HCV RNA by a polymerase chain reaction within 3 to 6 months after cessation of treatment.

Treatment of chronic HCV was based on the combination of pegylated interferon alfa-2a or -2b with RIB until 2015. Guidelines for the diagnosis and management of HCV infection have been published by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America.² These guidelines include new protease inhibitors, telaprevir and boceprevir, in the therapeutic approach of these patients. The main limitation of both drugs is the cutaneous toxicity.

Factors to be considered when treating HCV include viral genotype, if the patient is naïve or pretreated, the degree of fibrosis, established cirrhosis, and the treatment response. For patients with genotype 1,² as in our case, combination therapy with 3 drugs is recommended: pegylated interferon 180 µg subcutaneous injection weekly, RIB 15 mg/kg daily, and telaprevir 2250 mg or boceprevir 2400 mg daily. Triple therapy has been shown to achieve a successful response in 75% of naïve patients and in 50% of patients refractory to standard therapy.³

Telaprevir is an NS3/4A protease inhibitor approved by the US Food and Drug Administration and the European Medicines Agency for treatment of chronic HCV infection in naïve patients and in those unresponsive to double therapy. In phase 2 clinical trials, 41% to 61% of patients treated with telaprevir developed cutaneous reactions, of which 5% to 8% required cessation of treatment.⁴ The predicting risk factors for developing a secondary rash to telaprevir include age older than 45 years, body mass index less than 30, Caucasian ethnicity, and receiving HCV therapy for the first time.⁴

This cutaneous side effect is managed depending on the extension of the lesions, the presence of systemic symptoms, and laboratory abnormalities.⁵ Therefore, the severity of the skin reaction can be divided into 4 stages^4,5: (1) grade I or mild, defined as a localized rash with no systemic signs or mucosal involvement; (2) grade II or moderate, a maximum of 50% BSA involvement without epidermal detachment, and inflammation of the mucous membranes may be present without ulcers, as well as systemic symptoms such as fever, arthralgia, or eosinophilia; (3) grade III or severe, skin lesions affecting more than 50% BSA or less if any of the following lesions are present: vesicles or blisters, ulcers, epidermal detachment, palpable purpura, or erythema that does not blanch under pressure; (4) grade IV or life-threatening, when the clinical picture is consistent with acute generalized exanthematous pustulosis, DRESS syndrome, toxic epidermal necrolysis, or Stevens-Johnson syndrome.

DRESS syndrome is a condition clinically characterized by a generalized skin rash, facial angioedema, high fever, lymph node enlargement, and leukocytosis with eosinophilia or atypical lymphocytosis, along with abnormal renal and hepatic function tests. Cutaneous histopathologic examination may be unspecific, though atypical lymphocytes with a marked epidermotropism mimicking fungoid mycosis also have been described.⁶ In addition, human herpesvirus 6 serology may be negative, despite infection with this herpesvirus subtype having been associated with the development of DRESS syndrome. The pathophysiologic mechanism of DRESS syndrome is not completely understood; however, one theory ascribes an immunologic activation due to drug metabolite formation as the main mechanism.¹

Eleven patients⁷ with possible DRESS syndrome have been reported in clinical trials (less than 5% of the total of patients), with an addition of 1 more by Montaudié et al.⁸ No notable differences were found between telaprevir levels in these patients with respect to those of the control group.

For the management of DRESS syndrome, the occurrence of early signs of a severe acute skin reaction requires the immediate cessation of the drug, telaprevir in this case. The withdrawal of the dual therapy will depend on the short-term clinical course, according to the general condition of the patient, as well as the analytical abnormalities observed.⁹

In conclusion, telaprevir is a promising novel therapy for the treatment of HCV infection, but its cutaneous side effects still need to be properly established.

To the Editor:

A 58-year-old woman with a history of hyperprolactinemia and gastrointestinal angiodysplasia presented to the dermatology department with a generalized skin rash of 3 weeks’ duration. She did not have a history of toxic habits. She had a history of chronic hepatitis C virus (HCV) genotype 1b (IL-28B locus) with severe hepatic fibrosis (stage 4) as assessed by ultrasound-based elastography. Due to lack of response, plasma HCV RNA was still detectable at week 12 of pegylated interferon and ribavirin (RIB) therapy, and triple therapy with pegylated interferon, RIB, and telaprevir was initiated.

Two months later, she was admitted to the hospital after developing a generalized cutaneous rash that covered 90% of the body surface area (BSA) along with fever (temperature, 38.5°C). Laboratory blood tests showed an elevated absolute eosinophil count (2000 cells/µL [reference range, 0–500 cells/µL]), anemia (hemoglobin, 6.5 g/dL [reference range, 12–16 g/dL]), thrombocytopenia (26×10³/µL [reference range, 150–400×10³/µL]), and altered liver function tests (serum alanine aminotransferase, 60 U/L [reference range, 0–45 U/L]; aspartate aminotransferase, 80 U/L [reference range, 0–40 U/L]). Plasma HCV RNA was undetectable at this visit. On physical examination a generalized exanthema with coalescing plaques was observed, as well as crusted vesicles covering the arms, legs, chest, abdomen, and back. Palmoplantar papules (Figure, A) and facial swelling (Figure, B) also were present. A skin biopsy specimen taken from a papule on the left arm showed superficial perivascular lymphocytic infiltration with dermal edema. These findings were consistent with a diagnosis of DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome. Application of the Adverse Drug Reaction Probability Scale¹ in our patient (total score of 5) suggested that DRESS syndrome was a moderate adverse event likely related to the use of telaprevir.

After diagnosis of DRESS syndrome, telaprevir was discontinued, and the doses of RIB and pegylated interferon were reduced to 200 mg and 180 µg weekly, respectively. Laboratory test values including liver function tests normalized within 3 weeks and remained normal on follow-up. Plasma HCV RNA continued to be undetectable.

Hepatitis C virus is relatively common with an incidence of 3% worldwide.² It may present as an acute hepatitis or, more frequently, as asymptomatic chronic hepatitis. The acute process is self-limited and rarely causes hepatic failure. It usually leads to a chronic infection, which can result in cirrhosis, hepatocellular carcinoma, and the need for liver transplantation. The aim of treatment is eradication of HCV RNA, which is predicted by the attainment of a sustained virologic response. The latter is defined by the absence of HCV RNA by a polymerase chain reaction within 3 to 6 months after cessation of treatment.

Treatment of chronic HCV was based on the combination of pegylated interferon alfa-2a or -2b with RIB until 2015. Guidelines for the diagnosis and management of HCV infection have been published by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America.² These guidelines include new protease inhibitors, telaprevir and boceprevir, in the therapeutic approach of these patients. The main limitation of both drugs is the cutaneous toxicity.

Factors to be considered when treating HCV include viral genotype, if the patient is naïve or pretreated, the degree of fibrosis, established cirrhosis, and the treatment response. For patients with genotype 1,² as in our case, combination therapy with 3 drugs is recommended: pegylated interferon 180 µg subcutaneous injection weekly, RIB 15 mg/kg daily, and telaprevir 2250 mg or boceprevir 2400 mg daily. Triple therapy has been shown to achieve a successful response in 75% of naïve patients and in 50% of patients refractory to standard therapy.³

Telaprevir is an NS3/4A protease inhibitor approved by the US Food and Drug Administration and the European Medicines Agency for treatment of chronic HCV infection in naïve patients and in those unresponsive to double therapy. In phase 2 clinical trials, 41% to 61% of patients treated with telaprevir developed cutaneous reactions, of which 5% to 8% required cessation of treatment.⁴ The predicting risk factors for developing a secondary rash to telaprevir include age older than 45 years, body mass index less than 30, Caucasian ethnicity, and receiving HCV therapy for the first time.⁴

This cutaneous side effect is managed depending on the extension of the lesions, the presence of systemic symptoms, and laboratory abnormalities.⁵ Therefore, the severity of the skin reaction can be divided into 4 stages^4,5: (1) grade I or mild, defined as a localized rash with no systemic signs or mucosal involvement; (2) grade II or moderate, a maximum of 50% BSA involvement without epidermal detachment, and inflammation of the mucous membranes may be present without ulcers, as well as systemic symptoms such as fever, arthralgia, or eosinophilia; (3) grade III or severe, skin lesions affecting more than 50% BSA or less if any of the following lesions are present: vesicles or blisters, ulcers, epidermal detachment, palpable purpura, or erythema that does not blanch under pressure; (4) grade IV or life-threatening, when the clinical picture is consistent with acute generalized exanthematous pustulosis, DRESS syndrome, toxic epidermal necrolysis, or Stevens-Johnson syndrome.

DRESS syndrome is a condition clinically characterized by a generalized skin rash, facial angioedema, high fever, lymph node enlargement, and leukocytosis with eosinophilia or atypical lymphocytosis, along with abnormal renal and hepatic function tests. Cutaneous histopathologic examination may be unspecific, though atypical lymphocytes with a marked epidermotropism mimicking fungoid mycosis also have been described.⁶ In addition, human herpesvirus 6 serology may be negative, despite infection with this herpesvirus subtype having been associated with the development of DRESS syndrome. The pathophysiologic mechanism of DRESS syndrome is not completely understood; however, one theory ascribes an immunologic activation due to drug metabolite formation as the main mechanism.¹

Eleven patients⁷ with possible DRESS syndrome have been reported in clinical trials (less than 5% of the total of patients), with an addition of 1 more by Montaudié et al.⁸ No notable differences were found between telaprevir levels in these patients with respect to those of the control group.

For the management of DRESS syndrome, the occurrence of early signs of a severe acute skin reaction requires the immediate cessation of the drug, telaprevir in this case. The withdrawal of the dual therapy will depend on the short-term clinical course, according to the general condition of the patient, as well as the analytical abnormalities observed.⁹

In conclusion, telaprevir is a promising novel therapy for the treatment of HCV infection, but its cutaneous side effects still need to be properly established.

To the Editor:

Mycetoma is a noncontagious chronic infection of the skin and subcutaneous tissue caused by exogenous fungi or bacteria that can involve deeper structures such as the fasciae, muscles, and bones. Clinically it is characterized by increased swelling of the affected area, fibrosis, nodules, tumefaction, formation of draining sinuses, and abscesses that drain pus-containing grains through fistulae.¹ The initiation of the infection is related to local trauma and can involve muscle, underlying bone, and adjacent organs. The feet are the most commonly affected region, and the incubation period is variable. Patients rarely report prior trauma to the affected area and only seek medical consultation when the nodules and draining sinuses become evident. The etiopathogenesis of mycetoma is associated with aerobic actinomycetes (ie, Nocardia, Actinomadura, Streptomyces), known as actinomycetoma, and fungal infections, known as eumycetomas.¹

We report the case of a 57-year-old Albanian man who was referred to the outpatient clinic of our dermatology department for diagnosis and treatment of a chronic, suppurative, subcutaneous infection on the right foot presenting as abscesses and draining sinuses. The patient was a farmer and reported that the condition appeared 4 years prior following a laceration he sustained while at work. Dermatologic examination revealed local tumefaction, fistulated nodules, and abscesses discharging a serohemorrhagic fluid on the right foot (Figure 1). Perilesional erythema and subcutaneous swelling were evident. There was no regional lymph­adenopathy. Standard laboratory examination was normal. Radiography of the right foot showed no osteolytic lesions or evidence of osteomyelitis.

A skin biopsy from a lesion on the right foot was performed, and identification of the possible etiologic agent was based on direct microscopic examination of the granules, culture isolation of the agent, and fungal microscopic morphology.² Granules were studied under direct examination with potassium hydroxide solution 20% and showed septate branching hyphae (Figure 2). The culture produced colonies that were white, yellow, and brown. Colonies were comprised of dense mycelium with melanin pigment and were grown at 37°C. A lactose tolerance test was positive.² Therefore, the strain was identified as Madurella mycetomatis, and a diagnosis of eumycetoma pedis was made.

The patient was hospitalized for 2 weeks and treated with intravenous fluconazole, then treatment with oral itraconazole 200 mg once daily was initiated. At 4-month follow-up, he had self-discontinued treatment but demonstrated partial improvement of the tumefaction, healing of sinus tracts, and functional recovery of the right foot.

One year following the initial presentation, the patient’s clinical condition worsened (Figure 3A). Radiography of the right foot showed osteolytic lesions on bones in the right foot (Figure 3B), and a repeat culture showed the presence of Staphylococcus aureus; thus, treatment with itraconazole 200 mg once daily along with antibiotics (cefuroxime and gentamicin) was started immediately. Surgical treatment was recommended, but the patient refused treatment.

Mycetomas are rare in Albania but are common in countries of tropical and subtropical regions. Known as “Madura foot” by the native people, mycetoma was recognized as a disease entity in 1842.¹ In 1860, Carter³ (who established the fungal etiology of this disorder) first proposed the term mycetoma and further proposed the terms melanoid mycetoma and ochroid mycetoma in an attempt to classify the disease into 2 varieties on the basis of the black or pale-colored granules (ie, grains, sclerotia) on histology produced by the etiologic agents.^2-4

Clinical features of eumycetoma include lesions with clear margins, few sinuses, black grains, slow progression, and long-term involvement of bone. The grains represent an aggregate of hyphae produced by fungi; thus, the characteristic feature of eumycetoma is the formation of large granules that can involve bone.¹ A critical diagnostic step is to distinguish between eumycetoma and actinomycetoma. If possible, it is important to culture the organism because treatment varies depending on the cause of the infection.

Fungal identification is crucial in the diagnosis of mycetoma. In our case, diagnosis of eumycetoma pedis was based on clinical examination and detection of fungal species by microscopic examination and culture. The color of small granules (black grains) is a parameter used to identify different pathogens on histology but is not sufficient for diagnosis.⁵ The examination by potassium hydroxide preparation is helpful to identify the hyphae; however, culture is necessary.²

Therapeutic management of eumycetoma needs a combined strategy that includes systemic treatment and surgical therapy. Eumycetomas generally are more difficult to treat then actinomycetomas. Some authors recommend a high dose of amphotericin B as the treatment of choice for eumycetoma,^6,7 but there are some that emphasize that amphotericin B is partially effective.^8,9 There also is evidence in the literature of resistance of eumycetoma to ketoconazole treatment^10,11 and successful treatment with fluconazole and itraconazole.^10-13 For this reason, we treated our patient with the latter agents. In cases of osteolysis, amputation often is required.

In conclusion, eumycetoma pedis is a rare deep fungal infection that can cause considerable morbidity. Patients should be well educated about this condition and be made aware of the risk of environmental exposure (eg, contact of broken skin with contaminated soil and water) and the need to wear protective footwear in potentially contaminated environments. Early diagnosis, correct treatment, and regular follow-up can reduce the risk of osteolytic complications and increase the possibility of complete recovery.

To the Editor:

Mycetoma is a noncontagious chronic infection of the skin and subcutaneous tissue caused by exogenous fungi or bacteria that can involve deeper structures such as the fasciae, muscles, and bones. Clinically it is characterized by increased swelling of the affected area, fibrosis, nodules, tumefaction, formation of draining sinuses, and abscesses that drain pus-containing grains through fistulae.¹ The initiation of the infection is related to local trauma and can involve muscle, underlying bone, and adjacent organs. The feet are the most commonly affected region, and the incubation period is variable. Patients rarely report prior trauma to the affected area and only seek medical consultation when the nodules and draining sinuses become evident. The etiopathogenesis of mycetoma is associated with aerobic actinomycetes (ie, Nocardia, Actinomadura, Streptomyces), known as actinomycetoma, and fungal infections, known as eumycetomas.¹

We report the case of a 57-year-old Albanian man who was referred to the outpatient clinic of our dermatology department for diagnosis and treatment of a chronic, suppurative, subcutaneous infection on the right foot presenting as abscesses and draining sinuses. The patient was a farmer and reported that the condition appeared 4 years prior following a laceration he sustained while at work. Dermatologic examination revealed local tumefaction, fistulated nodules, and abscesses discharging a serohemorrhagic fluid on the right foot (Figure 1). Perilesional erythema and subcutaneous swelling were evident. There was no regional lymph­adenopathy. Standard laboratory examination was normal. Radiography of the right foot showed no osteolytic lesions or evidence of osteomyelitis.

A skin biopsy from a lesion on the right foot was performed, and identification of the possible etiologic agent was based on direct microscopic examination of the granules, culture isolation of the agent, and fungal microscopic morphology.² Granules were studied under direct examination with potassium hydroxide solution 20% and showed septate branching hyphae (Figure 2). The culture produced colonies that were white, yellow, and brown. Colonies were comprised of dense mycelium with melanin pigment and were grown at 37°C. A lactose tolerance test was positive.² Therefore, the strain was identified as Madurella mycetomatis, and a diagnosis of eumycetoma pedis was made.

The patient was hospitalized for 2 weeks and treated with intravenous fluconazole, then treatment with oral itraconazole 200 mg once daily was initiated. At 4-month follow-up, he had self-discontinued treatment but demonstrated partial improvement of the tumefaction, healing of sinus tracts, and functional recovery of the right foot.

One year following the initial presentation, the patient’s clinical condition worsened (Figure 3A). Radiography of the right foot showed osteolytic lesions on bones in the right foot (Figure 3B), and a repeat culture showed the presence of Staphylococcus aureus; thus, treatment with itraconazole 200 mg once daily along with antibiotics (cefuroxime and gentamicin) was started immediately. Surgical treatment was recommended, but the patient refused treatment.

Mycetomas are rare in Albania but are common in countries of tropical and subtropical regions. Known as “Madura foot” by the native people, mycetoma was recognized as a disease entity in 1842.¹ In 1860, Carter³ (who established the fungal etiology of this disorder) first proposed the term mycetoma and further proposed the terms melanoid mycetoma and ochroid mycetoma in an attempt to classify the disease into 2 varieties on the basis of the black or pale-colored granules (ie, grains, sclerotia) on histology produced by the etiologic agents.^2-4

Clinical features of eumycetoma include lesions with clear margins, few sinuses, black grains, slow progression, and long-term involvement of bone. The grains represent an aggregate of hyphae produced by fungi; thus, the characteristic feature of eumycetoma is the formation of large granules that can involve bone.¹ A critical diagnostic step is to distinguish between eumycetoma and actinomycetoma. If possible, it is important to culture the organism because treatment varies depending on the cause of the infection.

Fungal identification is crucial in the diagnosis of mycetoma. In our case, diagnosis of eumycetoma pedis was based on clinical examination and detection of fungal species by microscopic examination and culture. The color of small granules (black grains) is a parameter used to identify different pathogens on histology but is not sufficient for diagnosis.⁵ The examination by potassium hydroxide preparation is helpful to identify the hyphae; however, culture is necessary.²

Therapeutic management of eumycetoma needs a combined strategy that includes systemic treatment and surgical therapy. Eumycetomas generally are more difficult to treat then actinomycetomas. Some authors recommend a high dose of amphotericin B as the treatment of choice for eumycetoma,^6,7 but there are some that emphasize that amphotericin B is partially effective.^8,9 There also is evidence in the literature of resistance of eumycetoma to ketoconazole treatment^10,11 and successful treatment with fluconazole and itraconazole.^10-13 For this reason, we treated our patient with the latter agents. In cases of osteolysis, amputation often is required.

In conclusion, eumycetoma pedis is a rare deep fungal infection that can cause considerable morbidity. Patients should be well educated about this condition and be made aware of the risk of environmental exposure (eg, contact of broken skin with contaminated soil and water) and the need to wear protective footwear in potentially contaminated environments. Early diagnosis, correct treatment, and regular follow-up can reduce the risk of osteolytic complications and increase the possibility of complete recovery.

To the Editor:

Mycetoma is a noncontagious chronic infection of the skin and subcutaneous tissue caused by exogenous fungi or bacteria that can involve deeper structures such as the fasciae, muscles, and bones. Clinically it is characterized by increased swelling of the affected area, fibrosis, nodules, tumefaction, formation of draining sinuses, and abscesses that drain pus-containing grains through fistulae.¹ The initiation of the infection is related to local trauma and can involve muscle, underlying bone, and adjacent organs. The feet are the most commonly affected region, and the incubation period is variable. Patients rarely report prior trauma to the affected area and only seek medical consultation when the nodules and draining sinuses become evident. The etiopathogenesis of mycetoma is associated with aerobic actinomycetes (ie, Nocardia, Actinomadura, Streptomyces), known as actinomycetoma, and fungal infections, known as eumycetomas.¹

We report the case of a 57-year-old Albanian man who was referred to the outpatient clinic of our dermatology department for diagnosis and treatment of a chronic, suppurative, subcutaneous infection on the right foot presenting as abscesses and draining sinuses. The patient was a farmer and reported that the condition appeared 4 years prior following a laceration he sustained while at work. Dermatologic examination revealed local tumefaction, fistulated nodules, and abscesses discharging a serohemorrhagic fluid on the right foot (Figure 1). Perilesional erythema and subcutaneous swelling were evident. There was no regional lymph­adenopathy. Standard laboratory examination was normal. Radiography of the right foot showed no osteolytic lesions or evidence of osteomyelitis.

A skin biopsy from a lesion on the right foot was performed, and identification of the possible etiologic agent was based on direct microscopic examination of the granules, culture isolation of the agent, and fungal microscopic morphology.² Granules were studied under direct examination with potassium hydroxide solution 20% and showed septate branching hyphae (Figure 2). The culture produced colonies that were white, yellow, and brown. Colonies were comprised of dense mycelium with melanin pigment and were grown at 37°C. A lactose tolerance test was positive.² Therefore, the strain was identified as Madurella mycetomatis, and a diagnosis of eumycetoma pedis was made.

The patient was hospitalized for 2 weeks and treated with intravenous fluconazole, then treatment with oral itraconazole 200 mg once daily was initiated. At 4-month follow-up, he had self-discontinued treatment but demonstrated partial improvement of the tumefaction, healing of sinus tracts, and functional recovery of the right foot.

One year following the initial presentation, the patient’s clinical condition worsened (Figure 3A). Radiography of the right foot showed osteolytic lesions on bones in the right foot (Figure 3B), and a repeat culture showed the presence of Staphylococcus aureus; thus, treatment with itraconazole 200 mg once daily along with antibiotics (cefuroxime and gentamicin) was started immediately. Surgical treatment was recommended, but the patient refused treatment.

Mycetomas are rare in Albania but are common in countries of tropical and subtropical regions. Known as “Madura foot” by the native people, mycetoma was recognized as a disease entity in 1842.¹ In 1860, Carter³ (who established the fungal etiology of this disorder) first proposed the term mycetoma and further proposed the terms melanoid mycetoma and ochroid mycetoma in an attempt to classify the disease into 2 varieties on the basis of the black or pale-colored granules (ie, grains, sclerotia) on histology produced by the etiologic agents.^2-4

Clinical features of eumycetoma include lesions with clear margins, few sinuses, black grains, slow progression, and long-term involvement of bone. The grains represent an aggregate of hyphae produced by fungi; thus, the characteristic feature of eumycetoma is the formation of large granules that can involve bone.¹ A critical diagnostic step is to distinguish between eumycetoma and actinomycetoma. If possible, it is important to culture the organism because treatment varies depending on the cause of the infection.

Fungal identification is crucial in the diagnosis of mycetoma. In our case, diagnosis of eumycetoma pedis was based on clinical examination and detection of fungal species by microscopic examination and culture. The color of small granules (black grains) is a parameter used to identify different pathogens on histology but is not sufficient for diagnosis.⁵ The examination by potassium hydroxide preparation is helpful to identify the hyphae; however, culture is necessary.²

Therapeutic management of eumycetoma needs a combined strategy that includes systemic treatment and surgical therapy. Eumycetomas generally are more difficult to treat then actinomycetomas. Some authors recommend a high dose of amphotericin B as the treatment of choice for eumycetoma,^6,7 but there are some that emphasize that amphotericin B is partially effective.^8,9 There also is evidence in the literature of resistance of eumycetoma to ketoconazole treatment^10,11 and successful treatment with fluconazole and itraconazole.^10-13 For this reason, we treated our patient with the latter agents. In cases of osteolysis, amputation often is required.

In conclusion, eumycetoma pedis is a rare deep fungal infection that can cause considerable morbidity. Patients should be well educated about this condition and be made aware of the risk of environmental exposure (eg, contact of broken skin with contaminated soil and water) and the need to wear protective footwear in potentially contaminated environments. Early diagnosis, correct treatment, and regular follow-up can reduce the risk of osteolytic complications and increase the possibility of complete recovery.

To the Editor:

Postirradiation morphea (PIM) is a rare but well-documented phenomenon that primarily occurs in breast cancer patients who have received radiation therapy; however, it also has been reported in patients who have received radiation therapy for lymphoma as well as endocervical, endometrial, and gastric carcinomas.¹ Importantly, clinicians must be able to recognize and differentiate this condition from other causes of new-onset induration and erythema of the breast, such as cancer recurrence, a new primary malignancy, or inflammatory etiologies (eg, radiation or contact dermatitis). Typically, PIM presents months to years after radiation therapy as an erythematous patch within the irradiated area that progressively becomes indurated. We report an unusual case of PIM with a reticulated appearance occurring 3 weeks after radiotherapy, chemotherapy, and surgery for an infiltrating ductal carcinoma of the left breast.

A 62-year-old woman presented to the dermatology department with a stage IIA, lymph node–negative, estrogen and progesterone receptor–negative, human epidermal growth factor receptor 2–negative infiltrating ductal carcinoma of the left breast. She was treated with a partial mastectomy of the left breast followed by external beam radiotherapy to the entire left breast in combination with chemotherapy (doxorubicin, cyclophosphamide, paclitaxel). The patient received 15 fractions of 270 cGy (4050 cGy total) with a weekly 600-cGy boost over 21 days without any complications.

Three weeks after finishing radiation therapy, the patient developed redness and swelling of the left breast that did not encompass the entire radiation field. There was no associated pain or pruritus. She was treated by her surgical oncologist with topical calendula and 3 courses of cephalexin for suspected mastitis with only modest improvement, then was referred to dermatology 3 months later.

At the initial dermatology evaluation, the patient reported little improvement after antibiotics and topical calendula. On physical examination, there were erythematous, reticulated, dusky, indurated patches on the entire left breast. The area of most pronounced induration surrounded the surgical scar on the left superior breast. Punch biopsy for hematoxylin and eosin staining and tissue cultures was obtained at this appointment. The patient was started on doxycycline 100 mg twice daily and was instructed to apply triamcinolone ointment 0.1% twice daily to the affected area. After 1 month of therapy, she reported slight improvement in the degree of erythema with this regimen, but the involved area continued to extend outside of the radiation field to the central chest wall and medial right breast (Figure 1). Two additional biopsies—one from the central chest and another from the right breast—were then taken over the course of 4 months, given the consistently inconclusive clinicopathologic nature and failure of the eruption to respond to antibiotics plus topical corticosteroids.

Punch biopsy from the central chest revealed a sparse perivascular infiltrate comprised predominantly of lymphocytes with occasional eosinophils (Figure 2). There were foci suggestive of early dermal sclerosis, an increased number of small blood vessels in the dermis, and scattered enlarged fibroblasts. Metastatic carcinoma was not identified. Although the histologic findings were not entirely specific, the changes were most suggestive of PIM, for which the patient was started on pentoxifylline (400 mg 3 times daily) and oral vitamin E supplementation (400 IU daily). At subsequent follow-up appointments, she showed markedly decreased skin erythema and induration.

Morphea, also known as localized scleroderma, is an inflammatory skin condition characterized by sclerosis of the dermis and subcutis leading to scarlike tissue formation. Worldwide incidence ranges from 0.4 to 2.7 cases per 100,000 individuals with a predilection for white women.² Unlike systemic scleroderma, morphea patients lack Raynaud phenomenon and visceral involvement.^3,4

There are several clinical subtypes of morphea, including plaque, linear, generalized, and pansclerotic morphea. Lesions may vary in appearance based on configuration, stage of development, and depth of involvement.⁴ During the earliest phases, morphea lesions are asymptomatic, asymmetrically distributed, erythematous to violaceous patches or subtly indurated plaques expanding centrifugally with a lilac ring. Central sclerosis with loss of follicles and sweat glands is a later finding associated with advanced disease. Moreover, some reports of early-stage morphea have suggested a reticulated or geographic vascular morphology that may be misdiagnosed for other conditions such as a port-wine stain.⁵

Local skin exposures have long been hypothesized to contribute to development of morphea, including infection, especially Borrelia burgdorferi; trauma; chronic venous insufficiency; cosmetic surgery; medications; and exposure to toxic cooking oils, silicones, silica, pesticides, organic solvents, and vinyl chloride.^2,6,7

Radiation therapy is an often overlooked cause of morphea. It was first described in 1905 but then rarely discussed until a 1989 case series of 9 patients, 7 of whom had received irradiation for breast cancer.^8,9 Today, the increasing popularity of lumpectomy plus radiation therapy for treatment of early-stage breast cancer has led to a rise in PIM incidence.¹⁰Estimates have indicated an incidence among previously irradiated breast cancer patients as high as 1 in 500 individuals, appreciably higher than that seen in the general population.¹¹ Tissue changes occur as early as weeks or as late as 32 years after radiation treatment and are commonly mistaken for mastitis, such as in our case, as well as radiation dermatitis, radiation fibrosis, or malignant conditions.^1,11

In contrast to other radiation-induced skin conditions, development of PIM is independent of the presence or absence of adjuvant chemotherapy, type of radiation therapy, or the total radiation dose or fractionation number, with reported doses ranging from less than 20.0 Gy to up to 59.4 Gy and dose fractions ranging from 10 to 30. In 20% to 30% of cases, PIM extends beyond the radiation field, sometimes involving distant sites never exposed to high-energy rays.^1,10,11 This observation suggests a mechanism reliant on more widespread cascade rather than solely local tissue damage.

Prominent culture-negative, lymphoplasmacytic inflammation is another important diagnostic clue. Radiation dermatitis and fibrosis do not have the marked erythematous to violaceous hue seen in early morphea plaques. This color seen in early morphea plaques may be intense enough and in a geographic pattern, emulating a vascular lesion. However, a PubMed search of articles indexed for MEDLINE using the terms reticulate radiation morphea and livedo radiation morphea yielded no reports linking the reticulate erythema seen in our patient with early PIM. It is important to note that the histopathology findings in our patient were not entirely specific, and although there were some background changes that may have represented a sequela of radiation to the area (ie, the enlarged fibroblasts and increased number of vessels), there were foci suggestive of early sclerosing dermatitis. With clinical correlation, including the extension beyond the radiation field, these changes were best interpreted as early PIM. Therefore, our case demonstrated a novel presentation of a frequently underrecognized trigger for morphea. Although we favored a diagnosis of PIM, a fibrosing chronic radiation dermatitis could not be entirely excluded based on the clinical and histologic features.

There is no standardized treatment of PIM, but traditional therapies for morphea may provide some benefit. Several randomized controlled clinical trials have shown success with pentoxifylline and oral vitamin E supplementation to treat or prevent radiation-induced breast fibrosis.¹² Extrapolating from this data, our patient was started on this combination therapy and showed marked improvement in skin color and texture.

To the Editor:

Postirradiation morphea (PIM) is a rare but well-documented phenomenon that primarily occurs in breast cancer patients who have received radiation therapy; however, it also has been reported in patients who have received radiation therapy for lymphoma as well as endocervical, endometrial, and gastric carcinomas.¹ Importantly, clinicians must be able to recognize and differentiate this condition from other causes of new-onset induration and erythema of the breast, such as cancer recurrence, a new primary malignancy, or inflammatory etiologies (eg, radiation or contact dermatitis). Typically, PIM presents months to years after radiation therapy as an erythematous patch within the irradiated area that progressively becomes indurated. We report an unusual case of PIM with a reticulated appearance occurring 3 weeks after radiotherapy, chemotherapy, and surgery for an infiltrating ductal carcinoma of the left breast.

A 62-year-old woman presented to the dermatology department with a stage IIA, lymph node–negative, estrogen and progesterone receptor–negative, human epidermal growth factor receptor 2–negative infiltrating ductal carcinoma of the left breast. She was treated with a partial mastectomy of the left breast followed by external beam radiotherapy to the entire left breast in combination with chemotherapy (doxorubicin, cyclophosphamide, paclitaxel). The patient received 15 fractions of 270 cGy (4050 cGy total) with a weekly 600-cGy boost over 21 days without any complications.

Three weeks after finishing radiation therapy, the patient developed redness and swelling of the left breast that did not encompass the entire radiation field. There was no associated pain or pruritus. She was treated by her surgical oncologist with topical calendula and 3 courses of cephalexin for suspected mastitis with only modest improvement, then was referred to dermatology 3 months later.

At the initial dermatology evaluation, the patient reported little improvement after antibiotics and topical calendula. On physical examination, there were erythematous, reticulated, dusky, indurated patches on the entire left breast. The area of most pronounced induration surrounded the surgical scar on the left superior breast. Punch biopsy for hematoxylin and eosin staining and tissue cultures was obtained at this appointment. The patient was started on doxycycline 100 mg twice daily and was instructed to apply triamcinolone ointment 0.1% twice daily to the affected area. After 1 month of therapy, she reported slight improvement in the degree of erythema with this regimen, but the involved area continued to extend outside of the radiation field to the central chest wall and medial right breast (Figure 1). Two additional biopsies—one from the central chest and another from the right breast—were then taken over the course of 4 months, given the consistently inconclusive clinicopathologic nature and failure of the eruption to respond to antibiotics plus topical corticosteroids.

Punch biopsy from the central chest revealed a sparse perivascular infiltrate comprised predominantly of lymphocytes with occasional eosinophils (Figure 2). There were foci suggestive of early dermal sclerosis, an increased number of small blood vessels in the dermis, and scattered enlarged fibroblasts. Metastatic carcinoma was not identified. Although the histologic findings were not entirely specific, the changes were most suggestive of PIM, for which the patient was started on pentoxifylline (400 mg 3 times daily) and oral vitamin E supplementation (400 IU daily). At subsequent follow-up appointments, she showed markedly decreased skin erythema and induration.

Morphea, also known as localized scleroderma, is an inflammatory skin condition characterized by sclerosis of the dermis and subcutis leading to scarlike tissue formation. Worldwide incidence ranges from 0.4 to 2.7 cases per 100,000 individuals with a predilection for white women.² Unlike systemic scleroderma, morphea patients lack Raynaud phenomenon and visceral involvement.^3,4

There are several clinical subtypes of morphea, including plaque, linear, generalized, and pansclerotic morphea. Lesions may vary in appearance based on configuration, stage of development, and depth of involvement.⁴ During the earliest phases, morphea lesions are asymptomatic, asymmetrically distributed, erythematous to violaceous patches or subtly indurated plaques expanding centrifugally with a lilac ring. Central sclerosis with loss of follicles and sweat glands is a later finding associated with advanced disease. Moreover, some reports of early-stage morphea have suggested a reticulated or geographic vascular morphology that may be misdiagnosed for other conditions such as a port-wine stain.⁵

Local skin exposures have long been hypothesized to contribute to development of morphea, including infection, especially Borrelia burgdorferi; trauma; chronic venous insufficiency; cosmetic surgery; medications; and exposure to toxic cooking oils, silicones, silica, pesticides, organic solvents, and vinyl chloride.^2,6,7

Radiation therapy is an often overlooked cause of morphea. It was first described in 1905 but then rarely discussed until a 1989 case series of 9 patients, 7 of whom had received irradiation for breast cancer.^8,9 Today, the increasing popularity of lumpectomy plus radiation therapy for treatment of early-stage breast cancer has led to a rise in PIM incidence.¹⁰Estimates have indicated an incidence among previously irradiated breast cancer patients as high as 1 in 500 individuals, appreciably higher than that seen in the general population.¹¹ Tissue changes occur as early as weeks or as late as 32 years after radiation treatment and are commonly mistaken for mastitis, such as in our case, as well as radiation dermatitis, radiation fibrosis, or malignant conditions.^1,11

In contrast to other radiation-induced skin conditions, development of PIM is independent of the presence or absence of adjuvant chemotherapy, type of radiation therapy, or the total radiation dose or fractionation number, with reported doses ranging from less than 20.0 Gy to up to 59.4 Gy and dose fractions ranging from 10 to 30. In 20% to 30% of cases, PIM extends beyond the radiation field, sometimes involving distant sites never exposed to high-energy rays.^1,10,11 This observation suggests a mechanism reliant on more widespread cascade rather than solely local tissue damage.

Prominent culture-negative, lymphoplasmacytic inflammation is another important diagnostic clue. Radiation dermatitis and fibrosis do not have the marked erythematous to violaceous hue seen in early morphea plaques. This color seen in early morphea plaques may be intense enough and in a geographic pattern, emulating a vascular lesion. However, a PubMed search of articles indexed for MEDLINE using the terms reticulate radiation morphea and livedo radiation morphea yielded no reports linking the reticulate erythema seen in our patient with early PIM. It is important to note that the histopathology findings in our patient were not entirely specific, and although there were some background changes that may have represented a sequela of radiation to the area (ie, the enlarged fibroblasts and increased number of vessels), there were foci suggestive of early sclerosing dermatitis. With clinical correlation, including the extension beyond the radiation field, these changes were best interpreted as early PIM. Therefore, our case demonstrated a novel presentation of a frequently underrecognized trigger for morphea. Although we favored a diagnosis of PIM, a fibrosing chronic radiation dermatitis could not be entirely excluded based on the clinical and histologic features.

There is no standardized treatment of PIM, but traditional therapies for morphea may provide some benefit. Several randomized controlled clinical trials have shown success with pentoxifylline and oral vitamin E supplementation to treat or prevent radiation-induced breast fibrosis.¹² Extrapolating from this data, our patient was started on this combination therapy and showed marked improvement in skin color and texture.

To the Editor:

Postirradiation morphea (PIM) is a rare but well-documented phenomenon that primarily occurs in breast cancer patients who have received radiation therapy; however, it also has been reported in patients who have received radiation therapy for lymphoma as well as endocervical, endometrial, and gastric carcinomas.¹ Importantly, clinicians must be able to recognize and differentiate this condition from other causes of new-onset induration and erythema of the breast, such as cancer recurrence, a new primary malignancy, or inflammatory etiologies (eg, radiation or contact dermatitis). Typically, PIM presents months to years after radiation therapy as an erythematous patch within the irradiated area that progressively becomes indurated. We report an unusual case of PIM with a reticulated appearance occurring 3 weeks after radiotherapy, chemotherapy, and surgery for an infiltrating ductal carcinoma of the left breast.

A 62-year-old woman presented to the dermatology department with a stage IIA, lymph node–negative, estrogen and progesterone receptor–negative, human epidermal growth factor receptor 2–negative infiltrating ductal carcinoma of the left breast. She was treated with a partial mastectomy of the left breast followed by external beam radiotherapy to the entire left breast in combination with chemotherapy (doxorubicin, cyclophosphamide, paclitaxel). The patient received 15 fractions of 270 cGy (4050 cGy total) with a weekly 600-cGy boost over 21 days without any complications.

Three weeks after finishing radiation therapy, the patient developed redness and swelling of the left breast that did not encompass the entire radiation field. There was no associated pain or pruritus. She was treated by her surgical oncologist with topical calendula and 3 courses of cephalexin for suspected mastitis with only modest improvement, then was referred to dermatology 3 months later.

At the initial dermatology evaluation, the patient reported little improvement after antibiotics and topical calendula. On physical examination, there were erythematous, reticulated, dusky, indurated patches on the entire left breast. The area of most pronounced induration surrounded the surgical scar on the left superior breast. Punch biopsy for hematoxylin and eosin staining and tissue cultures was obtained at this appointment. The patient was started on doxycycline 100 mg twice daily and was instructed to apply triamcinolone ointment 0.1% twice daily to the affected area. After 1 month of therapy, she reported slight improvement in the degree of erythema with this regimen, but the involved area continued to extend outside of the radiation field to the central chest wall and medial right breast (Figure 1). Two additional biopsies—one from the central chest and another from the right breast—were then taken over the course of 4 months, given the consistently inconclusive clinicopathologic nature and failure of the eruption to respond to antibiotics plus topical corticosteroids.

Punch biopsy from the central chest revealed a sparse perivascular infiltrate comprised predominantly of lymphocytes with occasional eosinophils (Figure 2). There were foci suggestive of early dermal sclerosis, an increased number of small blood vessels in the dermis, and scattered enlarged fibroblasts. Metastatic carcinoma was not identified. Although the histologic findings were not entirely specific, the changes were most suggestive of PIM, for which the patient was started on pentoxifylline (400 mg 3 times daily) and oral vitamin E supplementation (400 IU daily). At subsequent follow-up appointments, she showed markedly decreased skin erythema and induration.

Morphea, also known as localized scleroderma, is an inflammatory skin condition characterized by sclerosis of the dermis and subcutis leading to scarlike tissue formation. Worldwide incidence ranges from 0.4 to 2.7 cases per 100,000 individuals with a predilection for white women.² Unlike systemic scleroderma, morphea patients lack Raynaud phenomenon and visceral involvement.^3,4

There are several clinical subtypes of morphea, including plaque, linear, generalized, and pansclerotic morphea. Lesions may vary in appearance based on configuration, stage of development, and depth of involvement.⁴ During the earliest phases, morphea lesions are asymptomatic, asymmetrically distributed, erythematous to violaceous patches or subtly indurated plaques expanding centrifugally with a lilac ring. Central sclerosis with loss of follicles and sweat glands is a later finding associated with advanced disease. Moreover, some reports of early-stage morphea have suggested a reticulated or geographic vascular morphology that may be misdiagnosed for other conditions such as a port-wine stain.⁵

Local skin exposures have long been hypothesized to contribute to development of morphea, including infection, especially Borrelia burgdorferi; trauma; chronic venous insufficiency; cosmetic surgery; medications; and exposure to toxic cooking oils, silicones, silica, pesticides, organic solvents, and vinyl chloride.^2,6,7

Radiation therapy is an often overlooked cause of morphea. It was first described in 1905 but then rarely discussed until a 1989 case series of 9 patients, 7 of whom had received irradiation for breast cancer.^8,9 Today, the increasing popularity of lumpectomy plus radiation therapy for treatment of early-stage breast cancer has led to a rise in PIM incidence.¹⁰Estimates have indicated an incidence among previously irradiated breast cancer patients as high as 1 in 500 individuals, appreciably higher than that seen in the general population.¹¹ Tissue changes occur as early as weeks or as late as 32 years after radiation treatment and are commonly mistaken for mastitis, such as in our case, as well as radiation dermatitis, radiation fibrosis, or malignant conditions.^1,11

In contrast to other radiation-induced skin conditions, development of PIM is independent of the presence or absence of adjuvant chemotherapy, type of radiation therapy, or the total radiation dose or fractionation number, with reported doses ranging from less than 20.0 Gy to up to 59.4 Gy and dose fractions ranging from 10 to 30. In 20% to 30% of cases, PIM extends beyond the radiation field, sometimes involving distant sites never exposed to high-energy rays.^1,10,11 This observation suggests a mechanism reliant on more widespread cascade rather than solely local tissue damage.

Prominent culture-negative, lymphoplasmacytic inflammation is another important diagnostic clue. Radiation dermatitis and fibrosis do not have the marked erythematous to violaceous hue seen in early morphea plaques. This color seen in early morphea plaques may be intense enough and in a geographic pattern, emulating a vascular lesion. However, a PubMed search of articles indexed for MEDLINE using the terms reticulate radiation morphea and livedo radiation morphea yielded no reports linking the reticulate erythema seen in our patient with early PIM. It is important to note that the histopathology findings in our patient were not entirely specific, and although there were some background changes that may have represented a sequela of radiation to the area (ie, the enlarged fibroblasts and increased number of vessels), there were foci suggestive of early sclerosing dermatitis. With clinical correlation, including the extension beyond the radiation field, these changes were best interpreted as early PIM. Therefore, our case demonstrated a novel presentation of a frequently underrecognized trigger for morphea. Although we favored a diagnosis of PIM, a fibrosing chronic radiation dermatitis could not be entirely excluded based on the clinical and histologic features.

There is no standardized treatment of PIM, but traditional therapies for morphea may provide some benefit. Several randomized controlled clinical trials have shown success with pentoxifylline and oral vitamin E supplementation to treat or prevent radiation-induced breast fibrosis.¹² Extrapolating from this data, our patient was started on this combination therapy and showed marked improvement in skin color and texture.