LAS VEGAS – Someday, pharmacogenomics will advance precision psychiatry, but in the opinion of Erika L. Nurmi, MD, PhD, routine use of genetic testing to guide clinical treatment decisions is not indicated.

“It’s misleading to rely on results of genetic tests to drive clinical treatment,” Dr. Nurmi, a child and adolescent psychiatrist in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “There’s a lot of hope and promise there. But currently, we only know the tip of the iceberg about how drugs work and the genetics influencing these effects. Current testing is probably a very poor reflection of the complexity of drug effects.”

According to Dr. Nurmi, there are at least 165 Food and Drug Administration–approved drugs with pharmacogenetic information on 64 different biomarkers – 37% with CYP p450 notations. Of these, 32 psychiatric drugs have pharmacogenetic information, and most of them are dosing recommendations based on whether a patient has the variant. However, there is wide public acceptance of genetic testing in preventing the wrong drug from being used, in selecting the best drug dose, and avoiding side effects (Pharmacogenomics 2012;12[3]:197-204). “Most people have a lot of hope [for genetic testing in psychiatry],” Dr. Nurmi said. “But is the science really there? It doesn’t matter, because these companies are doing it, and you are being shown these reports from patients. Whether or not the science supports it, we’re going to have to interpret these reports and explain them to our patients – even if we don’t order them.”

Currently, she continued, clinicians practice trial and error prescribing where they might try one treatment in a class that they think that will work based on previous literature. If nothing works, they try another one. If that’s intolerable, they try a third treatment, and so on. “When we finally find the right treatment, it can take some time to get the dosing right,” Dr. Nurmi said. “So, it can take many months to get a child on the right medication. Precision treatment, on the other hand, would start off by taking a saliva or blood sample to get a printout that lets physicians know which drugs might be used with caution because they might lack efficacy at standard doses, which ones would likely have adverse effects at standard doses, and which are the best choices and what are the dosing recommendations for those choices. If we could get all the information to guide us, that would be a useful product, but right now, we don’t know enough to be able to make these determinations.”

Current evidence-based genetic testing supports a limited role for CYP2D6 and CYP2C19 genotyping because most psychiatric drugs are metabolized by those two enzymes. Poor metabolizers have two dysfunctional copies of the enzyme-encoding gene. This results in increased drug plasma levels with a potentially increased rate of adverse effects.

“Intermediate and extensive metabolizers usually have a normal phenotype, but you can also have ultrarapid metabolizers who have duplications or other enhancing mutations of the CYP gene,” Dr. Nurmi said. “This can result in lower bioavailability and possibly efficacy. Psychiatrists treat poor metabolizers and ultrarapid metabolizers all the time, because the variants are very common.” An estimated 10% of White people are poor metabolizers at the CYP2D6 gene while about 7% are ultrarapid metabolizers. At the same time, an estimated 20% of Asians, Africans, and Whites are poor metabolizers at the CYP2C19 gene. “So, you’re seeing a lot of this in your practice, and you’re probably changing dosing based on genetic differences in metabolism,” she said.

The only FDA pharmacodynamic treatment guideline is for the risk of Stevens-Johnson syndrome (SJS) with the use of carbamazepine. In a study of 44 patients with SJS, all were positive for the HLA-B*1502 variant, compared with 3% of carbamazepine-tolerant patients (Nature 2004;428[6982]:486). The frequency of carrying this variant is an estimated 1:10,000 among Whites and 1:1,000 among Asians. In 2007, the FDA recommended that patients of Asian ancestry should be screened for HLA-B*1502 prior to starting carbamazepine.

Genetic variation also predicts clinical outcome with atomoxetine use. “Most child psychiatrists I know think atomoxetine doesn’t work as a second-line nonstimulant medication for ADHD,” Dr. Nurmi said. “I’d like to convince you that why you think it doesn’t work is because of the genetics.” In a study published in 2019, Dr. Nurmi and colleagues reviewed medical literature and provided therapeutic recommendations for atomoxetine therapy based on CYP2D6 genotype (Clin Pharmacol Ther 2019 Jul;106[1]:94-102). They observed 10- to 30-fold plasma differences in drug exposure between normal metabolizers and poor metabolizers.

“Poor metabolizers therefore get more benefit, but they are also going to get more side effects,” she said. “FDA recommended doses are inadequate for normal metabolizers, so they had to make guidelines based on poor metabolizers because there would be too much risk for them at higher doses. One-third of individuals require doses above the FDA limit to achieve a therapeutic drug level.”

Dr. Nurmi warned that the existing evidence base for using these genetic tests in children “is really poor. There is no data in adults with any diagnosis other than depression, and even those studies are plagued by concerns. When you’re implementing decision support tools in your practice, the key factors are patient presentation, history and symptoms, your clinical skills, the evidence base, FDA recommendations, and patient autonomy. Appropriate incorporation of genetic data should include avoiding a medication with high toxicity (like SJS), titration planning (dose and titration speed adjustments), and choosing between medications in the same class with an indication or evidence base for the target disorder.” She added that while the benefit of current genetic testing is limited, it may help some patients feel more comfortable tolerating a medication. “For example, being able to tell someone with anxiety that their genetics suggests that they will not have side effects could be very powerful,” she said.

In a 2018 safety communication, the FDA warned the public about its concerns with companies making claims about how to use genetic test results to manage medication treatments that are not supported by recommendations in the FDA-approved drug labeling or other scientific evidence. The American Academy of Child and Adolescent Psychiatry also published a guide for patients and families.

Dr. Nurmi disclosed that she is an unpaid advisory board member for Myriad Genetics and the Tourette Association of America, a paid adviser for Teva Pharmaceuticals, and a recipient of research support from Emalex Pharmaceuticals. She has received research funding from the National Institutes Health, the International OCD Foundation, the Tourette Association of America, and the Brain & Behavior Research Foundation.

LAS VEGAS – Someday, pharmacogenomics will advance precision psychiatry, but in the opinion of Erika L. Nurmi, MD, PhD, routine use of genetic testing to guide clinical treatment decisions is not indicated.

“It’s misleading to rely on results of genetic tests to drive clinical treatment,” Dr. Nurmi, a child and adolescent psychiatrist in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “There’s a lot of hope and promise there. But currently, we only know the tip of the iceberg about how drugs work and the genetics influencing these effects. Current testing is probably a very poor reflection of the complexity of drug effects.”

According to Dr. Nurmi, there are at least 165 Food and Drug Administration–approved drugs with pharmacogenetic information on 64 different biomarkers – 37% with CYP p450 notations. Of these, 32 psychiatric drugs have pharmacogenetic information, and most of them are dosing recommendations based on whether a patient has the variant. However, there is wide public acceptance of genetic testing in preventing the wrong drug from being used, in selecting the best drug dose, and avoiding side effects (Pharmacogenomics 2012;12[3]:197-204). “Most people have a lot of hope [for genetic testing in psychiatry],” Dr. Nurmi said. “But is the science really there? It doesn’t matter, because these companies are doing it, and you are being shown these reports from patients. Whether or not the science supports it, we’re going to have to interpret these reports and explain them to our patients – even if we don’t order them.”

Currently, she continued, clinicians practice trial and error prescribing where they might try one treatment in a class that they think that will work based on previous literature. If nothing works, they try another one. If that’s intolerable, they try a third treatment, and so on. “When we finally find the right treatment, it can take some time to get the dosing right,” Dr. Nurmi said. “So, it can take many months to get a child on the right medication. Precision treatment, on the other hand, would start off by taking a saliva or blood sample to get a printout that lets physicians know which drugs might be used with caution because they might lack efficacy at standard doses, which ones would likely have adverse effects at standard doses, and which are the best choices and what are the dosing recommendations for those choices. If we could get all the information to guide us, that would be a useful product, but right now, we don’t know enough to be able to make these determinations.”

Current evidence-based genetic testing supports a limited role for CYP2D6 and CYP2C19 genotyping because most psychiatric drugs are metabolized by those two enzymes. Poor metabolizers have two dysfunctional copies of the enzyme-encoding gene. This results in increased drug plasma levels with a potentially increased rate of adverse effects.

“Intermediate and extensive metabolizers usually have a normal phenotype, but you can also have ultrarapid metabolizers who have duplications or other enhancing mutations of the CYP gene,” Dr. Nurmi said. “This can result in lower bioavailability and possibly efficacy. Psychiatrists treat poor metabolizers and ultrarapid metabolizers all the time, because the variants are very common.” An estimated 10% of White people are poor metabolizers at the CYP2D6 gene while about 7% are ultrarapid metabolizers. At the same time, an estimated 20% of Asians, Africans, and Whites are poor metabolizers at the CYP2C19 gene. “So, you’re seeing a lot of this in your practice, and you’re probably changing dosing based on genetic differences in metabolism,” she said.

The only FDA pharmacodynamic treatment guideline is for the risk of Stevens-Johnson syndrome (SJS) with the use of carbamazepine. In a study of 44 patients with SJS, all were positive for the HLA-B*1502 variant, compared with 3% of carbamazepine-tolerant patients (Nature 2004;428[6982]:486). The frequency of carrying this variant is an estimated 1:10,000 among Whites and 1:1,000 among Asians. In 2007, the FDA recommended that patients of Asian ancestry should be screened for HLA-B*1502 prior to starting carbamazepine.

Genetic variation also predicts clinical outcome with atomoxetine use. “Most child psychiatrists I know think atomoxetine doesn’t work as a second-line nonstimulant medication for ADHD,” Dr. Nurmi said. “I’d like to convince you that why you think it doesn’t work is because of the genetics.” In a study published in 2019, Dr. Nurmi and colleagues reviewed medical literature and provided therapeutic recommendations for atomoxetine therapy based on CYP2D6 genotype (Clin Pharmacol Ther 2019 Jul;106[1]:94-102). They observed 10- to 30-fold plasma differences in drug exposure between normal metabolizers and poor metabolizers.

“Poor metabolizers therefore get more benefit, but they are also going to get more side effects,” she said. “FDA recommended doses are inadequate for normal metabolizers, so they had to make guidelines based on poor metabolizers because there would be too much risk for them at higher doses. One-third of individuals require doses above the FDA limit to achieve a therapeutic drug level.”

Dr. Nurmi warned that the existing evidence base for using these genetic tests in children “is really poor. There is no data in adults with any diagnosis other than depression, and even those studies are plagued by concerns. When you’re implementing decision support tools in your practice, the key factors are patient presentation, history and symptoms, your clinical skills, the evidence base, FDA recommendations, and patient autonomy. Appropriate incorporation of genetic data should include avoiding a medication with high toxicity (like SJS), titration planning (dose and titration speed adjustments), and choosing between medications in the same class with an indication or evidence base for the target disorder.” She added that while the benefit of current genetic testing is limited, it may help some patients feel more comfortable tolerating a medication. “For example, being able to tell someone with anxiety that their genetics suggests that they will not have side effects could be very powerful,” she said.

In a 2018 safety communication, the FDA warned the public about its concerns with companies making claims about how to use genetic test results to manage medication treatments that are not supported by recommendations in the FDA-approved drug labeling or other scientific evidence. The American Academy of Child and Adolescent Psychiatry also published a guide for patients and families.

Dr. Nurmi disclosed that she is an unpaid advisory board member for Myriad Genetics and the Tourette Association of America, a paid adviser for Teva Pharmaceuticals, and a recipient of research support from Emalex Pharmaceuticals. She has received research funding from the National Institutes Health, the International OCD Foundation, the Tourette Association of America, and the Brain & Behavior Research Foundation.

LAS VEGAS – Someday, pharmacogenomics will advance precision psychiatry, but in the opinion of Erika L. Nurmi, MD, PhD, routine use of genetic testing to guide clinical treatment decisions is not indicated.

“It’s misleading to rely on results of genetic tests to drive clinical treatment,” Dr. Nurmi, a child and adolescent psychiatrist in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “There’s a lot of hope and promise there. But currently, we only know the tip of the iceberg about how drugs work and the genetics influencing these effects. Current testing is probably a very poor reflection of the complexity of drug effects.”

According to Dr. Nurmi, there are at least 165 Food and Drug Administration–approved drugs with pharmacogenetic information on 64 different biomarkers – 37% with CYP p450 notations. Of these, 32 psychiatric drugs have pharmacogenetic information, and most of them are dosing recommendations based on whether a patient has the variant. However, there is wide public acceptance of genetic testing in preventing the wrong drug from being used, in selecting the best drug dose, and avoiding side effects (Pharmacogenomics 2012;12[3]:197-204). “Most people have a lot of hope [for genetic testing in psychiatry],” Dr. Nurmi said. “But is the science really there? It doesn’t matter, because these companies are doing it, and you are being shown these reports from patients. Whether or not the science supports it, we’re going to have to interpret these reports and explain them to our patients – even if we don’t order them.”

Currently, she continued, clinicians practice trial and error prescribing where they might try one treatment in a class that they think that will work based on previous literature. If nothing works, they try another one. If that’s intolerable, they try a third treatment, and so on. “When we finally find the right treatment, it can take some time to get the dosing right,” Dr. Nurmi said. “So, it can take many months to get a child on the right medication. Precision treatment, on the other hand, would start off by taking a saliva or blood sample to get a printout that lets physicians know which drugs might be used with caution because they might lack efficacy at standard doses, which ones would likely have adverse effects at standard doses, and which are the best choices and what are the dosing recommendations for those choices. If we could get all the information to guide us, that would be a useful product, but right now, we don’t know enough to be able to make these determinations.”

Current evidence-based genetic testing supports a limited role for CYP2D6 and CYP2C19 genotyping because most psychiatric drugs are metabolized by those two enzymes. Poor metabolizers have two dysfunctional copies of the enzyme-encoding gene. This results in increased drug plasma levels with a potentially increased rate of adverse effects.

“Intermediate and extensive metabolizers usually have a normal phenotype, but you can also have ultrarapid metabolizers who have duplications or other enhancing mutations of the CYP gene,” Dr. Nurmi said. “This can result in lower bioavailability and possibly efficacy. Psychiatrists treat poor metabolizers and ultrarapid metabolizers all the time, because the variants are very common.” An estimated 10% of White people are poor metabolizers at the CYP2D6 gene while about 7% are ultrarapid metabolizers. At the same time, an estimated 20% of Asians, Africans, and Whites are poor metabolizers at the CYP2C19 gene. “So, you’re seeing a lot of this in your practice, and you’re probably changing dosing based on genetic differences in metabolism,” she said.

The only FDA pharmacodynamic treatment guideline is for the risk of Stevens-Johnson syndrome (SJS) with the use of carbamazepine. In a study of 44 patients with SJS, all were positive for the HLA-B*1502 variant, compared with 3% of carbamazepine-tolerant patients (Nature 2004;428[6982]:486). The frequency of carrying this variant is an estimated 1:10,000 among Whites and 1:1,000 among Asians. In 2007, the FDA recommended that patients of Asian ancestry should be screened for HLA-B*1502 prior to starting carbamazepine.

Genetic variation also predicts clinical outcome with atomoxetine use. “Most child psychiatrists I know think atomoxetine doesn’t work as a second-line nonstimulant medication for ADHD,” Dr. Nurmi said. “I’d like to convince you that why you think it doesn’t work is because of the genetics.” In a study published in 2019, Dr. Nurmi and colleagues reviewed medical literature and provided therapeutic recommendations for atomoxetine therapy based on CYP2D6 genotype (Clin Pharmacol Ther 2019 Jul;106[1]:94-102). They observed 10- to 30-fold plasma differences in drug exposure between normal metabolizers and poor metabolizers.

“Poor metabolizers therefore get more benefit, but they are also going to get more side effects,” she said. “FDA recommended doses are inadequate for normal metabolizers, so they had to make guidelines based on poor metabolizers because there would be too much risk for them at higher doses. One-third of individuals require doses above the FDA limit to achieve a therapeutic drug level.”

Dr. Nurmi warned that the existing evidence base for using these genetic tests in children “is really poor. There is no data in adults with any diagnosis other than depression, and even those studies are plagued by concerns. When you’re implementing decision support tools in your practice, the key factors are patient presentation, history and symptoms, your clinical skills, the evidence base, FDA recommendations, and patient autonomy. Appropriate incorporation of genetic data should include avoiding a medication with high toxicity (like SJS), titration planning (dose and titration speed adjustments), and choosing between medications in the same class with an indication or evidence base for the target disorder.” She added that while the benefit of current genetic testing is limited, it may help some patients feel more comfortable tolerating a medication. “For example, being able to tell someone with anxiety that their genetics suggests that they will not have side effects could be very powerful,” she said.

In a 2018 safety communication, the FDA warned the public about its concerns with companies making claims about how to use genetic test results to manage medication treatments that are not supported by recommendations in the FDA-approved drug labeling or other scientific evidence. The American Academy of Child and Adolescent Psychiatry also published a guide for patients and families.

Dr. Nurmi disclosed that she is an unpaid advisory board member for Myriad Genetics and the Tourette Association of America, a paid adviser for Teva Pharmaceuticals, and a recipient of research support from Emalex Pharmaceuticals. She has received research funding from the National Institutes Health, the International OCD Foundation, the Tourette Association of America, and the Brain & Behavior Research Foundation.

The Diagnosis: Bullous Pyoderma Gangrenosum

A bone marrow biopsy revealed 60% myeloblasts, leading to a diagnosis of acute myeloid leukemia (AML). A biopsy obtained from the edge of the bullous plaque demonstrated a dense dermal neutrophilic infiltrate with extravasated erythrocytes (Figure). Fite, Gram, and Grocott-Gomori methenamine-silver staining failed to reveal infectious organisms. Tissue and blood cultures were negative. Given the pathologic findings, clinical presentation including recent diagnosis of AML, and exclusion of other underlying disease processes including infection, the diagnosis of bullous pyoderma gangrenosum (PG) was made. The lesion improved with systemic steroids and treatment of the underlying AML with fludarabine and venetoclax chemotherapy.

First recognized in 1916 by French dermatologist Louis Brocq, MD, PG is a sterile neutrophilic dermatosis that predominantly affects women older than 50 years.^1,2 This disorder can develop idiopathically; secondary to trauma; or in association with systemic diseases such as inflammatory bowel disease, rheumatoid arthritis, and hematologic malignancies. The pathogenesis of PG remains unclear; however, overexpression of inflammatory cytokines may mediate its development by stimulating T cells and promoting neutrophilic chemotaxis.³

Pyoderma gangrenosum classically presents as a rapidly enlarging ulcer with cribriform scarring but manifests variably. Four variants of the disorder exist: classic ulcerative, pustular, bullous, and vegetative PG. Ulcerative PG is the most common variant. Bullous PG is associated with hematologic malignancies such as primary myelofibrosis, myelodysplastic disease, and AML. In these patients, hematologic malignancy often exists prior to the development of PG and portends a poorer prognosis. This association underscores the importance of timely diagnosis and thorough hematologic evaluation by obtaining a complete blood cell count with differential, peripheral smear, serum protein electrophoresis with immunofixation, and quantitative immunoglobulins (IgA, IgG, IgM). If any of the results are positive, prompt referral to a hematologist and bone marrow biopsy are paramount.³

The diagnosis of PG remains elusive, as no validated clinical or pathological criteria exist. Histopathologic evaluation may be nonspecific and variable depending on the subtype. Biopsy results for classic ulcerative PG may reveal a neutrophilic infiltrate with leukocytoclasia. Bullous PG may include subepidermal hemorrhagic bullae. Notably, bullous PG appears histologically similar to the superficial bullous variant of Sweet syndrome.

Sweet syndrome (also known as acute febrile neutrophilic dermatosis) is a type of neutrophilic dermatosis characterized by fever, neutrophilia, and the sudden onset of tender erythematous lesions. Variations include idiopathic, subcutaneous, and bullous Sweet syndrome, which present as plaques, nodules, or bullae, respectively.⁴ Similar to PG, Sweet syndrome can manifest in patients with hematologic malignancies. Both PG and Sweet syndrome are thought to exist along a continuum and can be considered intersecting diagnoses in the setting of leukemia or other hematologic malignancies.⁵ There have been reports of the coexistence of distinct PG and Sweet syndrome lesions on a single patient, further supporting the belief that these entities share a common pathologic mechanism.⁶ Sweet syndrome also commonly can be associated with upper respiratory infections; pregnancy; and medications, with culprits including granulocyte colony-stimulating factor, azathioprine, vemurafenib, and isotretinoin.⁷

Other differential diagnoses include brown recluse spider bite, bullous fixed drug eruption (FDE), and necrotizing fasciitis (NF). Venom from the brown recluse spider (Loxosceles reclusa) can trigger toxin-mediated hemolysis, complement-mediated erythrocyte destruction, and basement membrane zone degradation due to the synergistic effects of the toxin’s sphingomyelinase D and protease content.⁸ The inciting bite is painless. After 8 hours, the site becomes painful and pruritic and presents with peripheral erythema and central pallor. After 24 hours, the lesion blisters. The blister ruptures within 3 to 4 days, resulting in eschar formation with the subsequent development of an indurated blue ulcer with a stellate center. Ulcers can take months to heal.⁹ Based on the clinical findings in our patient, this diagnosis was less likely.

Fixed drug eruption is a localized cutaneous reaction that manifests in fixed locations minutes to days after exposure to medications such as trimethoprimsulfamethoxazole, nonsteroidal anti-inflammatory drugs, salicylates, and oral contraceptives. Commonly affected areas include the hands, legs, genitals, and trunk. Lesions initially present as well-demarcated, erythematous to violaceous, round plaques. A rarer variant manifesting as bullae also has been described. Careful consideration of the patient’s history and physical examination findings is sufficient for establishing this diagnosis; however, a punch biopsy can provide clarity. Histopathology reveals a lichenoid tissue reaction with dyskeratosis, broad epidermal necrosis, and damage to the stratum basalis. A lymphocytic perivascular infiltrate also may appear in the dermis.¹⁰ Both the clinical findings and histopathology of our case were not characteristic of FDE.

Necrotizing fasciitis is a fulminant, life-threatening, soft-tissue infection precipitated by polymicrobial flora. Early recognition of NF is difficult, as in its early stages it can mimic cellulitis. As the infection takes its course, necrosis can extend from the skin and into the subcutaneous tissue. Patients also develop fever, leukocytosis, and signs of sepsis. Histopathology demonstrates neutrophilic infiltration with bacterial invasion as well as necrosis of the superficial fascia and subepidermal edema.¹¹ Pyoderma gangrenosum previously has been reported to mimic NF; however, lack of responsiveness to antibiotic therapy would favor a diagnosis of PG over NF.¹²

Treatment of PG is driven by the extent of cutaneous involvement. In mild cases, wound care and topical therapy with corticosteroids and tacrolimus may suffice. Severe cases necessitate systemic therapy with oral corticosteroids or cyclosporine; biologic therapy also may play a role in treatment.⁴ In patients with hematologic malignancy, chemotherapy alone may partially or completely resolve the lesion; however, systemic corticosteroids commonly are included in management.³

The Diagnosis: Bullous Pyoderma Gangrenosum

A bone marrow biopsy revealed 60% myeloblasts, leading to a diagnosis of acute myeloid leukemia (AML). A biopsy obtained from the edge of the bullous plaque demonstrated a dense dermal neutrophilic infiltrate with extravasated erythrocytes (Figure). Fite, Gram, and Grocott-Gomori methenamine-silver staining failed to reveal infectious organisms. Tissue and blood cultures were negative. Given the pathologic findings, clinical presentation including recent diagnosis of AML, and exclusion of other underlying disease processes including infection, the diagnosis of bullous pyoderma gangrenosum (PG) was made. The lesion improved with systemic steroids and treatment of the underlying AML with fludarabine and venetoclax chemotherapy.

First recognized in 1916 by French dermatologist Louis Brocq, MD, PG is a sterile neutrophilic dermatosis that predominantly affects women older than 50 years.^1,2 This disorder can develop idiopathically; secondary to trauma; or in association with systemic diseases such as inflammatory bowel disease, rheumatoid arthritis, and hematologic malignancies. The pathogenesis of PG remains unclear; however, overexpression of inflammatory cytokines may mediate its development by stimulating T cells and promoting neutrophilic chemotaxis.³

Pyoderma gangrenosum classically presents as a rapidly enlarging ulcer with cribriform scarring but manifests variably. Four variants of the disorder exist: classic ulcerative, pustular, bullous, and vegetative PG. Ulcerative PG is the most common variant. Bullous PG is associated with hematologic malignancies such as primary myelofibrosis, myelodysplastic disease, and AML. In these patients, hematologic malignancy often exists prior to the development of PG and portends a poorer prognosis. This association underscores the importance of timely diagnosis and thorough hematologic evaluation by obtaining a complete blood cell count with differential, peripheral smear, serum protein electrophoresis with immunofixation, and quantitative immunoglobulins (IgA, IgG, IgM). If any of the results are positive, prompt referral to a hematologist and bone marrow biopsy are paramount.³

The diagnosis of PG remains elusive, as no validated clinical or pathological criteria exist. Histopathologic evaluation may be nonspecific and variable depending on the subtype. Biopsy results for classic ulcerative PG may reveal a neutrophilic infiltrate with leukocytoclasia. Bullous PG may include subepidermal hemorrhagic bullae. Notably, bullous PG appears histologically similar to the superficial bullous variant of Sweet syndrome.

Sweet syndrome (also known as acute febrile neutrophilic dermatosis) is a type of neutrophilic dermatosis characterized by fever, neutrophilia, and the sudden onset of tender erythematous lesions. Variations include idiopathic, subcutaneous, and bullous Sweet syndrome, which present as plaques, nodules, or bullae, respectively.⁴ Similar to PG, Sweet syndrome can manifest in patients with hematologic malignancies. Both PG and Sweet syndrome are thought to exist along a continuum and can be considered intersecting diagnoses in the setting of leukemia or other hematologic malignancies.⁵ There have been reports of the coexistence of distinct PG and Sweet syndrome lesions on a single patient, further supporting the belief that these entities share a common pathologic mechanism.⁶ Sweet syndrome also commonly can be associated with upper respiratory infections; pregnancy; and medications, with culprits including granulocyte colony-stimulating factor, azathioprine, vemurafenib, and isotretinoin.⁷

Other differential diagnoses include brown recluse spider bite, bullous fixed drug eruption (FDE), and necrotizing fasciitis (NF). Venom from the brown recluse spider (Loxosceles reclusa) can trigger toxin-mediated hemolysis, complement-mediated erythrocyte destruction, and basement membrane zone degradation due to the synergistic effects of the toxin’s sphingomyelinase D and protease content.⁸ The inciting bite is painless. After 8 hours, the site becomes painful and pruritic and presents with peripheral erythema and central pallor. After 24 hours, the lesion blisters. The blister ruptures within 3 to 4 days, resulting in eschar formation with the subsequent development of an indurated blue ulcer with a stellate center. Ulcers can take months to heal.⁹ Based on the clinical findings in our patient, this diagnosis was less likely.

Fixed drug eruption is a localized cutaneous reaction that manifests in fixed locations minutes to days after exposure to medications such as trimethoprimsulfamethoxazole, nonsteroidal anti-inflammatory drugs, salicylates, and oral contraceptives. Commonly affected areas include the hands, legs, genitals, and trunk. Lesions initially present as well-demarcated, erythematous to violaceous, round plaques. A rarer variant manifesting as bullae also has been described. Careful consideration of the patient’s history and physical examination findings is sufficient for establishing this diagnosis; however, a punch biopsy can provide clarity. Histopathology reveals a lichenoid tissue reaction with dyskeratosis, broad epidermal necrosis, and damage to the stratum basalis. A lymphocytic perivascular infiltrate also may appear in the dermis.¹⁰ Both the clinical findings and histopathology of our case were not characteristic of FDE.

Necrotizing fasciitis is a fulminant, life-threatening, soft-tissue infection precipitated by polymicrobial flora. Early recognition of NF is difficult, as in its early stages it can mimic cellulitis. As the infection takes its course, necrosis can extend from the skin and into the subcutaneous tissue. Patients also develop fever, leukocytosis, and signs of sepsis. Histopathology demonstrates neutrophilic infiltration with bacterial invasion as well as necrosis of the superficial fascia and subepidermal edema.¹¹ Pyoderma gangrenosum previously has been reported to mimic NF; however, lack of responsiveness to antibiotic therapy would favor a diagnosis of PG over NF.¹²

Treatment of PG is driven by the extent of cutaneous involvement. In mild cases, wound care and topical therapy with corticosteroids and tacrolimus may suffice. Severe cases necessitate systemic therapy with oral corticosteroids or cyclosporine; biologic therapy also may play a role in treatment.⁴ In patients with hematologic malignancy, chemotherapy alone may partially or completely resolve the lesion; however, systemic corticosteroids commonly are included in management.³

The Diagnosis: Bullous Pyoderma Gangrenosum

A bone marrow biopsy revealed 60% myeloblasts, leading to a diagnosis of acute myeloid leukemia (AML). A biopsy obtained from the edge of the bullous plaque demonstrated a dense dermal neutrophilic infiltrate with extravasated erythrocytes (Figure). Fite, Gram, and Grocott-Gomori methenamine-silver staining failed to reveal infectious organisms. Tissue and blood cultures were negative. Given the pathologic findings, clinical presentation including recent diagnosis of AML, and exclusion of other underlying disease processes including infection, the diagnosis of bullous pyoderma gangrenosum (PG) was made. The lesion improved with systemic steroids and treatment of the underlying AML with fludarabine and venetoclax chemotherapy.

First recognized in 1916 by French dermatologist Louis Brocq, MD, PG is a sterile neutrophilic dermatosis that predominantly affects women older than 50 years.^1,2 This disorder can develop idiopathically; secondary to trauma; or in association with systemic diseases such as inflammatory bowel disease, rheumatoid arthritis, and hematologic malignancies. The pathogenesis of PG remains unclear; however, overexpression of inflammatory cytokines may mediate its development by stimulating T cells and promoting neutrophilic chemotaxis.³

Pyoderma gangrenosum classically presents as a rapidly enlarging ulcer with cribriform scarring but manifests variably. Four variants of the disorder exist: classic ulcerative, pustular, bullous, and vegetative PG. Ulcerative PG is the most common variant. Bullous PG is associated with hematologic malignancies such as primary myelofibrosis, myelodysplastic disease, and AML. In these patients, hematologic malignancy often exists prior to the development of PG and portends a poorer prognosis. This association underscores the importance of timely diagnosis and thorough hematologic evaluation by obtaining a complete blood cell count with differential, peripheral smear, serum protein electrophoresis with immunofixation, and quantitative immunoglobulins (IgA, IgG, IgM). If any of the results are positive, prompt referral to a hematologist and bone marrow biopsy are paramount.³

The diagnosis of PG remains elusive, as no validated clinical or pathological criteria exist. Histopathologic evaluation may be nonspecific and variable depending on the subtype. Biopsy results for classic ulcerative PG may reveal a neutrophilic infiltrate with leukocytoclasia. Bullous PG may include subepidermal hemorrhagic bullae. Notably, bullous PG appears histologically similar to the superficial bullous variant of Sweet syndrome.

Sweet syndrome (also known as acute febrile neutrophilic dermatosis) is a type of neutrophilic dermatosis characterized by fever, neutrophilia, and the sudden onset of tender erythematous lesions. Variations include idiopathic, subcutaneous, and bullous Sweet syndrome, which present as plaques, nodules, or bullae, respectively.⁴ Similar to PG, Sweet syndrome can manifest in patients with hematologic malignancies. Both PG and Sweet syndrome are thought to exist along a continuum and can be considered intersecting diagnoses in the setting of leukemia or other hematologic malignancies.⁵ There have been reports of the coexistence of distinct PG and Sweet syndrome lesions on a single patient, further supporting the belief that these entities share a common pathologic mechanism.⁶ Sweet syndrome also commonly can be associated with upper respiratory infections; pregnancy; and medications, with culprits including granulocyte colony-stimulating factor, azathioprine, vemurafenib, and isotretinoin.⁷

Other differential diagnoses include brown recluse spider bite, bullous fixed drug eruption (FDE), and necrotizing fasciitis (NF). Venom from the brown recluse spider (Loxosceles reclusa) can trigger toxin-mediated hemolysis, complement-mediated erythrocyte destruction, and basement membrane zone degradation due to the synergistic effects of the toxin’s sphingomyelinase D and protease content.⁸ The inciting bite is painless. After 8 hours, the site becomes painful and pruritic and presents with peripheral erythema and central pallor. After 24 hours, the lesion blisters. The blister ruptures within 3 to 4 days, resulting in eschar formation with the subsequent development of an indurated blue ulcer with a stellate center. Ulcers can take months to heal.⁹ Based on the clinical findings in our patient, this diagnosis was less likely.

Fixed drug eruption is a localized cutaneous reaction that manifests in fixed locations minutes to days after exposure to medications such as trimethoprimsulfamethoxazole, nonsteroidal anti-inflammatory drugs, salicylates, and oral contraceptives. Commonly affected areas include the hands, legs, genitals, and trunk. Lesions initially present as well-demarcated, erythematous to violaceous, round plaques. A rarer variant manifesting as bullae also has been described. Careful consideration of the patient’s history and physical examination findings is sufficient for establishing this diagnosis; however, a punch biopsy can provide clarity. Histopathology reveals a lichenoid tissue reaction with dyskeratosis, broad epidermal necrosis, and damage to the stratum basalis. A lymphocytic perivascular infiltrate also may appear in the dermis.¹⁰ Both the clinical findings and histopathology of our case were not characteristic of FDE.

Necrotizing fasciitis is a fulminant, life-threatening, soft-tissue infection precipitated by polymicrobial flora. Early recognition of NF is difficult, as in its early stages it can mimic cellulitis. As the infection takes its course, necrosis can extend from the skin and into the subcutaneous tissue. Patients also develop fever, leukocytosis, and signs of sepsis. Histopathology demonstrates neutrophilic infiltration with bacterial invasion as well as necrosis of the superficial fascia and subepidermal edema.¹¹ Pyoderma gangrenosum previously has been reported to mimic NF; however, lack of responsiveness to antibiotic therapy would favor a diagnosis of PG over NF.¹²

Treatment of PG is driven by the extent of cutaneous involvement. In mild cases, wound care and topical therapy with corticosteroids and tacrolimus may suffice. Severe cases necessitate systemic therapy with oral corticosteroids or cyclosporine; biologic therapy also may play a role in treatment.⁴ In patients with hematologic malignancy, chemotherapy alone may partially or completely resolve the lesion; however, systemic corticosteroids commonly are included in management.³

To the Editor:

Iododerma is a rare dermatologic condition caused by exposure to iodinated contrast media, oral iodine suspensions, or topical povidone-iodine that can manifest as eruptive acneform lesions.^1-3

A 27-year-old woman in septic shock presented for worsening facial lesions that showed no improvement on broad-spectrum antibiotics, antifungals, and antivirals. She initially presented to an outside hospital with abdominal pain and underwent computed tomography (CT) with intravenous (IV) iodinated contrast; 24 hours after this imaging study, the family reported the appearance of “explosive acne overnight.” The lesions first appeared as vegetative and acneform ulcerations on the face. A second abdominal CT scan with IV contrast was performed 4 days after the initial scan, given the concern for spontaneous bacterial peritonitis. Hours after the second study, the lesions progressed to involve the buccal mucosae, tongue, mucosal airway, and distal arms and legs. She became progressively disoriented and developed an altered mentation over the course of the following week. Due to progressive facial edema, she required intubation 5 days after the second CT scan.

The patient had a medical history of end-stage renal disease secondary to crescenteric glomerulonephritis on peritoneal dialysis. Physical examination revealed numerous beefy-red, heaped-up, weepy, crusted nodules clustered on the face (Figure 1) and a few newer bullous-appearing lesions on the hands and feet. She had similar lesions involving the buccal mucosae and tongue with substantial facial edema. Infectious workup was notable for a positive skin culture growing methicillin-susceptible Staphylococcus aureus. All blood and tissue cultures as well as serologies for fungal and viral etiologies were negative. A tissue biopsy revealed necrosis with a neutrophilic infiltrate with mixed cell inflammation (Figure 2), and direct immunofluorescence was negative.

The patient initially was thought to be septic due to viral or bacterial infection. She was transferred from an outside hospital 7 days after the initial appearance of the acneform lesions, having already received IV contrast on 2 occasions within the first 48 hours of illness. Infectious disease was consulted and initiated broad-spectrum antiviral, antimicrobial, and antifungal therapy with acyclovir, linezolid, meropenem, and later micafungin without improvement. The diagnosis of iododerma ultimately was established based on the patient’s elevated urinary iodine levels with preceding iodine exposure in the context of renal failure. The preferential involvement of sebaceous areas and pathology findings were supportive of this diagnosis. Aggressive supportive measures including respiratory support, IV fluids, and dialysis were initiated. Topical iodine solutions, iodine-containing medications, and additional contrast subsequently were avoided. Despite these supportive measures, the patient died within 48 hours of admission from acute respiratory failure. Her autopsy attributed “septic complications of multifocal ulcerative cutaneous disease” as the anatomic cause of death.

Iododerma is an extremely rare neutrophilic dermatosis. The proposed mechanism of action involves a cell-mediated hypersensitivity reaction to iodine with induction of neutrophil degranulation.² There have been documented cases with exposure to oral potassium iodide supplements, amiodarone, topical povidone-iodine, and IV iodinated contrast material.^1-3 Iododerma typically presents 1 to 3 days after exposure to iodine. The most common source is IV radiocontrast. Diagnosis is based on the clinical presentation including acneform to vegetative nodular or bullous eruptions involving sebaceous areas in the context of recent iodine exposure. Elevated urinary iodine levels and histologic findings of neutrophilic infiltrate of the dermis support the diagnosis.^3,4

Although there have been reported cases of iododerma in patients with normal renal function, patients with renal failure are much more susceptible due to the decreased clearance of iodine.⁵ The plasma half-life of radiocontrast is 23 hours in patients with end-stage renal disease vs 2 hours in patients with normal kidney function.³ Dosage adjustments for renal impairment have not been well studied, and no specific guidelines exist for the prevention of iododerma in patients with renal failure.

The first step in treating iododerma is to remove the offending iodine-containing agent. In most cases, cutaneous lesions resolve in 4 to 6 weeks after discontinuation of the source of iodine; however, there have been reported fatalities in the literature secondary to pulmonary edema in patients with iododerma.^6,7 Despite the rarity and diagnostically challenging nature of iododerma, early recognition of this disease is crucial. Although our patient showed symptoms of iododerma after 1 dose of radiocontrast, she was not diagnosed at that time and received a second imaging study with contrast less than 48 hours later. These 2 consecutive exposures to iodine as well as the delayed diagnosis unfortunately resulted in rapid clinical deterioration.

The mainstay of therapy for iododerma includes avoidance of iodine-containing materials as soon as the diagnosis is suspected as well as supportive care. Patients have been successfully treated with systemic corticosteroids, with the addition of cyclosporine and hemodialysis in severe cases.³ Patients with a history of iododerma are advised to avoid iodine in their diet, in topical preparations, and in future imaging studies.⁸

To the Editor:

Iododerma is a rare dermatologic condition caused by exposure to iodinated contrast media, oral iodine suspensions, or topical povidone-iodine that can manifest as eruptive acneform lesions.^1-3

A 27-year-old woman in septic shock presented for worsening facial lesions that showed no improvement on broad-spectrum antibiotics, antifungals, and antivirals. She initially presented to an outside hospital with abdominal pain and underwent computed tomography (CT) with intravenous (IV) iodinated contrast; 24 hours after this imaging study, the family reported the appearance of “explosive acne overnight.” The lesions first appeared as vegetative and acneform ulcerations on the face. A second abdominal CT scan with IV contrast was performed 4 days after the initial scan, given the concern for spontaneous bacterial peritonitis. Hours after the second study, the lesions progressed to involve the buccal mucosae, tongue, mucosal airway, and distal arms and legs. She became progressively disoriented and developed an altered mentation over the course of the following week. Due to progressive facial edema, she required intubation 5 days after the second CT scan.

The patient had a medical history of end-stage renal disease secondary to crescenteric glomerulonephritis on peritoneal dialysis. Physical examination revealed numerous beefy-red, heaped-up, weepy, crusted nodules clustered on the face (Figure 1) and a few newer bullous-appearing lesions on the hands and feet. She had similar lesions involving the buccal mucosae and tongue with substantial facial edema. Infectious workup was notable for a positive skin culture growing methicillin-susceptible Staphylococcus aureus. All blood and tissue cultures as well as serologies for fungal and viral etiologies were negative. A tissue biopsy revealed necrosis with a neutrophilic infiltrate with mixed cell inflammation (Figure 2), and direct immunofluorescence was negative.

The patient initially was thought to be septic due to viral or bacterial infection. She was transferred from an outside hospital 7 days after the initial appearance of the acneform lesions, having already received IV contrast on 2 occasions within the first 48 hours of illness. Infectious disease was consulted and initiated broad-spectrum antiviral, antimicrobial, and antifungal therapy with acyclovir, linezolid, meropenem, and later micafungin without improvement. The diagnosis of iododerma ultimately was established based on the patient’s elevated urinary iodine levels with preceding iodine exposure in the context of renal failure. The preferential involvement of sebaceous areas and pathology findings were supportive of this diagnosis. Aggressive supportive measures including respiratory support, IV fluids, and dialysis were initiated. Topical iodine solutions, iodine-containing medications, and additional contrast subsequently were avoided. Despite these supportive measures, the patient died within 48 hours of admission from acute respiratory failure. Her autopsy attributed “septic complications of multifocal ulcerative cutaneous disease” as the anatomic cause of death.

Iododerma is an extremely rare neutrophilic dermatosis. The proposed mechanism of action involves a cell-mediated hypersensitivity reaction to iodine with induction of neutrophil degranulation.² There have been documented cases with exposure to oral potassium iodide supplements, amiodarone, topical povidone-iodine, and IV iodinated contrast material.^1-3 Iododerma typically presents 1 to 3 days after exposure to iodine. The most common source is IV radiocontrast. Diagnosis is based on the clinical presentation including acneform to vegetative nodular or bullous eruptions involving sebaceous areas in the context of recent iodine exposure. Elevated urinary iodine levels and histologic findings of neutrophilic infiltrate of the dermis support the diagnosis.^3,4

Although there have been reported cases of iododerma in patients with normal renal function, patients with renal failure are much more susceptible due to the decreased clearance of iodine.⁵ The plasma half-life of radiocontrast is 23 hours in patients with end-stage renal disease vs 2 hours in patients with normal kidney function.³ Dosage adjustments for renal impairment have not been well studied, and no specific guidelines exist for the prevention of iododerma in patients with renal failure.

The first step in treating iododerma is to remove the offending iodine-containing agent. In most cases, cutaneous lesions resolve in 4 to 6 weeks after discontinuation of the source of iodine; however, there have been reported fatalities in the literature secondary to pulmonary edema in patients with iododerma.^6,7 Despite the rarity and diagnostically challenging nature of iododerma, early recognition of this disease is crucial. Although our patient showed symptoms of iododerma after 1 dose of radiocontrast, she was not diagnosed at that time and received a second imaging study with contrast less than 48 hours later. These 2 consecutive exposures to iodine as well as the delayed diagnosis unfortunately resulted in rapid clinical deterioration.

The mainstay of therapy for iododerma includes avoidance of iodine-containing materials as soon as the diagnosis is suspected as well as supportive care. Patients have been successfully treated with systemic corticosteroids, with the addition of cyclosporine and hemodialysis in severe cases.³ Patients with a history of iododerma are advised to avoid iodine in their diet, in topical preparations, and in future imaging studies.⁸

To the Editor:

Iododerma is a rare dermatologic condition caused by exposure to iodinated contrast media, oral iodine suspensions, or topical povidone-iodine that can manifest as eruptive acneform lesions.^1-3

A 27-year-old woman in septic shock presented for worsening facial lesions that showed no improvement on broad-spectrum antibiotics, antifungals, and antivirals. She initially presented to an outside hospital with abdominal pain and underwent computed tomography (CT) with intravenous (IV) iodinated contrast; 24 hours after this imaging study, the family reported the appearance of “explosive acne overnight.” The lesions first appeared as vegetative and acneform ulcerations on the face. A second abdominal CT scan with IV contrast was performed 4 days after the initial scan, given the concern for spontaneous bacterial peritonitis. Hours after the second study, the lesions progressed to involve the buccal mucosae, tongue, mucosal airway, and distal arms and legs. She became progressively disoriented and developed an altered mentation over the course of the following week. Due to progressive facial edema, she required intubation 5 days after the second CT scan.

The patient had a medical history of end-stage renal disease secondary to crescenteric glomerulonephritis on peritoneal dialysis. Physical examination revealed numerous beefy-red, heaped-up, weepy, crusted nodules clustered on the face (Figure 1) and a few newer bullous-appearing lesions on the hands and feet. She had similar lesions involving the buccal mucosae and tongue with substantial facial edema. Infectious workup was notable for a positive skin culture growing methicillin-susceptible Staphylococcus aureus. All blood and tissue cultures as well as serologies for fungal and viral etiologies were negative. A tissue biopsy revealed necrosis with a neutrophilic infiltrate with mixed cell inflammation (Figure 2), and direct immunofluorescence was negative.

The patient initially was thought to be septic due to viral or bacterial infection. She was transferred from an outside hospital 7 days after the initial appearance of the acneform lesions, having already received IV contrast on 2 occasions within the first 48 hours of illness. Infectious disease was consulted and initiated broad-spectrum antiviral, antimicrobial, and antifungal therapy with acyclovir, linezolid, meropenem, and later micafungin without improvement. The diagnosis of iododerma ultimately was established based on the patient’s elevated urinary iodine levels with preceding iodine exposure in the context of renal failure. The preferential involvement of sebaceous areas and pathology findings were supportive of this diagnosis. Aggressive supportive measures including respiratory support, IV fluids, and dialysis were initiated. Topical iodine solutions, iodine-containing medications, and additional contrast subsequently were avoided. Despite these supportive measures, the patient died within 48 hours of admission from acute respiratory failure. Her autopsy attributed “septic complications of multifocal ulcerative cutaneous disease” as the anatomic cause of death.

Iododerma is an extremely rare neutrophilic dermatosis. The proposed mechanism of action involves a cell-mediated hypersensitivity reaction to iodine with induction of neutrophil degranulation.² There have been documented cases with exposure to oral potassium iodide supplements, amiodarone, topical povidone-iodine, and IV iodinated contrast material.^1-3 Iododerma typically presents 1 to 3 days after exposure to iodine. The most common source is IV radiocontrast. Diagnosis is based on the clinical presentation including acneform to vegetative nodular or bullous eruptions involving sebaceous areas in the context of recent iodine exposure. Elevated urinary iodine levels and histologic findings of neutrophilic infiltrate of the dermis support the diagnosis.^3,4

Although there have been reported cases of iododerma in patients with normal renal function, patients with renal failure are much more susceptible due to the decreased clearance of iodine.⁵ The plasma half-life of radiocontrast is 23 hours in patients with end-stage renal disease vs 2 hours in patients with normal kidney function.³ Dosage adjustments for renal impairment have not been well studied, and no specific guidelines exist for the prevention of iododerma in patients with renal failure.

The first step in treating iododerma is to remove the offending iodine-containing agent. In most cases, cutaneous lesions resolve in 4 to 6 weeks after discontinuation of the source of iodine; however, there have been reported fatalities in the literature secondary to pulmonary edema in patients with iododerma.^6,7 Despite the rarity and diagnostically challenging nature of iododerma, early recognition of this disease is crucial. Although our patient showed symptoms of iododerma after 1 dose of radiocontrast, she was not diagnosed at that time and received a second imaging study with contrast less than 48 hours later. These 2 consecutive exposures to iodine as well as the delayed diagnosis unfortunately resulted in rapid clinical deterioration.

The mainstay of therapy for iododerma includes avoidance of iodine-containing materials as soon as the diagnosis is suspected as well as supportive care. Patients have been successfully treated with systemic corticosteroids, with the addition of cyclosporine and hemodialysis in severe cases.³ Patients with a history of iododerma are advised to avoid iodine in their diet, in topical preparations, and in future imaging studies.⁸

To the Editor:

Several mole and skin tag removal products are available online and over the counter (OTC).¹ Patients concerned with the cosmetic appearance of nevi may use these products as a do-it-yourself alternative to surgical removal. However, these products have the potential to cause harm.² Beyond the cosmetic adverse effects of skin necrosis and scar formation, these products can mask premalignant and malignant skin lesions.² Herein, we describe a patient with a family history of melanoma who developed facial and chest ulcerations with necrosis after applying an OTC mole and skin tag removal product.

A 45-year-old woman with fair skin presented to a clinic with multiple superficial ulcerations measuring approximately 1 cm in diameter with necrotic black bases and erythematous rims on the face, right side of the upper chest, and left earlobe after using the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set, an OTC mole and skin tag removal product. The patient reported using the product 24 hours prior for the cosmetic removal of multiple nevi. After applying the product, she observed that it “immediately melted [her] skin” and the areas where the product was applied “turned black.” She reported that the product was applied to the skin for no longer than 30 seconds, after which she developed the necrotic lesions (Figure). After removing the product, she applied an OTC ointment containing bacitracin, neomycin, and polymyxin B to the lesions.

The patient had no history of nonmelanoma skin cancers or atypical nevi. She had a family history of melanoma in her mother and maternal uncle. The treatment plan was aimed primarily at reducing scar formation. We advised frequent application of petroleum-based ointments for moisture and overlying silicone scar tape to protect the area from photodamage and promote wound healing. We further advocated for sun protection and the use of a physical sunscreen on the lesions as they healed. We discussed potential laser-based scar revision options in the future.

With more than 180 reviews on Amazon and almost 70% of these reviews made within the month prior to compiling this manuscript, the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set appeared to be popular; however, the product currently is unavailable on Amazon. Testimonials and before-and-after pictures advertising the product show an all-natural, safe, and effective method as an alternative to surgical removal of skin tags and nevi. The product website claims that skin tags and moles will “fall off naturally within 7 to 10 days” and the product can be used for “almost all skin types.” Users are instructed to apply the removal product and wipe it off when the skin surrounding the mole becomes swollen. The product kit also includes a repair lotion, which claims to help heal the skin after scab formation and scar development.

The ingredients listed on the product packaging are salicylic acid 25%, Melaleuca alternifolia (tea tree) leaf oil, propylene glycol, hydroxyethylcellulose, and alcohol. Salicylic acid 25% is a superficial peeling agent that penetrates the epidermis to the dermoepidermal junction. The potential side effects are mild and include superficial desquamation and epidermolysis.³ The Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set is not regulated by the US Food and Drug Administration and may contain variable concentrations of salicylic acid and other unknown compounds. Higher concentrations of salicylic acid can penetrate the full thickness of the epidermis into the papillary dermis, which can result in postinflammatory pigmentation, superficial infection, scarring, and deeper desquamation and epidermolysis.³ The product website advertises the use of only natural ingredients and an “advanced blend of concentrated natural ingredients contributing a broad spectrum of healing properties” in the formula. Although these claims are attractive to patients seeking alternatives to surgical approaches to nevi removal, the unfounded claims and unregulated ingredients may pose a threat to unsuspecting consumers.

Other OTC and “all-natural” mole removal products previously have been reported to cause harm.²Sanguinaria canadensis, also known as bloodroot, contains an alkaloid compound (sanguinarine) that has been shown to induce mitochondrial apoptosis and activation of Bcl-2 proteins in keratinocytes.⁴ Some products, such as Wart & Mole Vanish cream, may claim not to contain bloodroot specifically. However, sanguinarine can be extracted from other plants and may be listed as Argemone mexicana, Chelidonium majus, or Macleaya cordata in the ingredients list.⁵ The use of alternative medicine products such as black or yellow salve for the removal of suspected skin cancers also is not recommended because these escharotic treatments have not been proven safe or effective, and the manufacturing process for these compounds is unregulated.^6,7 Self-treatment with alternative remedies for nevi or suspected skin cancers has been associated with progression of disease and even death due to metastatic spread.²

Self-removal of moles is concerning because the nevi are masked by necrotic lesions and can no longer be assessed by dermoscopy or histopathology. Furthermore, the compounds in the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set may have unknown effects on the transformation of premalignant cells. They also may mask an underlying process for which clinically proven and effective treatments such as cryotherapy, prescription topical agents, and surgical excision are warranted. Awareness of this product and similar products is important to educate patients on the harmful effects they may cause.

To the Editor:

Several mole and skin tag removal products are available online and over the counter (OTC).¹ Patients concerned with the cosmetic appearance of nevi may use these products as a do-it-yourself alternative to surgical removal. However, these products have the potential to cause harm.² Beyond the cosmetic adverse effects of skin necrosis and scar formation, these products can mask premalignant and malignant skin lesions.² Herein, we describe a patient with a family history of melanoma who developed facial and chest ulcerations with necrosis after applying an OTC mole and skin tag removal product.

A 45-year-old woman with fair skin presented to a clinic with multiple superficial ulcerations measuring approximately 1 cm in diameter with necrotic black bases and erythematous rims on the face, right side of the upper chest, and left earlobe after using the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set, an OTC mole and skin tag removal product. The patient reported using the product 24 hours prior for the cosmetic removal of multiple nevi. After applying the product, she observed that it “immediately melted [her] skin” and the areas where the product was applied “turned black.” She reported that the product was applied to the skin for no longer than 30 seconds, after which she developed the necrotic lesions (Figure). After removing the product, she applied an OTC ointment containing bacitracin, neomycin, and polymyxin B to the lesions.

The patient had no history of nonmelanoma skin cancers or atypical nevi. She had a family history of melanoma in her mother and maternal uncle. The treatment plan was aimed primarily at reducing scar formation. We advised frequent application of petroleum-based ointments for moisture and overlying silicone scar tape to protect the area from photodamage and promote wound healing. We further advocated for sun protection and the use of a physical sunscreen on the lesions as they healed. We discussed potential laser-based scar revision options in the future.

With more than 180 reviews on Amazon and almost 70% of these reviews made within the month prior to compiling this manuscript, the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set appeared to be popular; however, the product currently is unavailable on Amazon. Testimonials and before-and-after pictures advertising the product show an all-natural, safe, and effective method as an alternative to surgical removal of skin tags and nevi. The product website claims that skin tags and moles will “fall off naturally within 7 to 10 days” and the product can be used for “almost all skin types.” Users are instructed to apply the removal product and wipe it off when the skin surrounding the mole becomes swollen. The product kit also includes a repair lotion, which claims to help heal the skin after scab formation and scar development.

The ingredients listed on the product packaging are salicylic acid 25%, Melaleuca alternifolia (tea tree) leaf oil, propylene glycol, hydroxyethylcellulose, and alcohol. Salicylic acid 25% is a superficial peeling agent that penetrates the epidermis to the dermoepidermal junction. The potential side effects are mild and include superficial desquamation and epidermolysis.³ The Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set is not regulated by the US Food and Drug Administration and may contain variable concentrations of salicylic acid and other unknown compounds. Higher concentrations of salicylic acid can penetrate the full thickness of the epidermis into the papillary dermis, which can result in postinflammatory pigmentation, superficial infection, scarring, and deeper desquamation and epidermolysis.³ The product website advertises the use of only natural ingredients and an “advanced blend of concentrated natural ingredients contributing a broad spectrum of healing properties” in the formula. Although these claims are attractive to patients seeking alternatives to surgical approaches to nevi removal, the unfounded claims and unregulated ingredients may pose a threat to unsuspecting consumers.

Other OTC and “all-natural” mole removal products previously have been reported to cause harm.²Sanguinaria canadensis, also known as bloodroot, contains an alkaloid compound (sanguinarine) that has been shown to induce mitochondrial apoptosis and activation of Bcl-2 proteins in keratinocytes.⁴ Some products, such as Wart & Mole Vanish cream, may claim not to contain bloodroot specifically. However, sanguinarine can be extracted from other plants and may be listed as Argemone mexicana, Chelidonium majus, or Macleaya cordata in the ingredients list.⁵ The use of alternative medicine products such as black or yellow salve for the removal of suspected skin cancers also is not recommended because these escharotic treatments have not been proven safe or effective, and the manufacturing process for these compounds is unregulated.^6,7 Self-treatment with alternative remedies for nevi or suspected skin cancers has been associated with progression of disease and even death due to metastatic spread.²

Self-removal of moles is concerning because the nevi are masked by necrotic lesions and can no longer be assessed by dermoscopy or histopathology. Furthermore, the compounds in the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set may have unknown effects on the transformation of premalignant cells. They also may mask an underlying process for which clinically proven and effective treatments such as cryotherapy, prescription topical agents, and surgical excision are warranted. Awareness of this product and similar products is important to educate patients on the harmful effects they may cause.

To the Editor:

Several mole and skin tag removal products are available online and over the counter (OTC).¹ Patients concerned with the cosmetic appearance of nevi may use these products as a do-it-yourself alternative to surgical removal. However, these products have the potential to cause harm.² Beyond the cosmetic adverse effects of skin necrosis and scar formation, these products can mask premalignant and malignant skin lesions.² Herein, we describe a patient with a family history of melanoma who developed facial and chest ulcerations with necrosis after applying an OTC mole and skin tag removal product.

A 45-year-old woman with fair skin presented to a clinic with multiple superficial ulcerations measuring approximately 1 cm in diameter with necrotic black bases and erythematous rims on the face, right side of the upper chest, and left earlobe after using the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set, an OTC mole and skin tag removal product. The patient reported using the product 24 hours prior for the cosmetic removal of multiple nevi. After applying the product, she observed that it “immediately melted [her] skin” and the areas where the product was applied “turned black.” She reported that the product was applied to the skin for no longer than 30 seconds, after which she developed the necrotic lesions (Figure). After removing the product, she applied an OTC ointment containing bacitracin, neomycin, and polymyxin B to the lesions.

The patient had no history of nonmelanoma skin cancers or atypical nevi. She had a family history of melanoma in her mother and maternal uncle. The treatment plan was aimed primarily at reducing scar formation. We advised frequent application of petroleum-based ointments for moisture and overlying silicone scar tape to protect the area from photodamage and promote wound healing. We further advocated for sun protection and the use of a physical sunscreen on the lesions as they healed. We discussed potential laser-based scar revision options in the future.

With more than 180 reviews on Amazon and almost 70% of these reviews made within the month prior to compiling this manuscript, the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set appeared to be popular; however, the product currently is unavailable on Amazon. Testimonials and before-and-after pictures advertising the product show an all-natural, safe, and effective method as an alternative to surgical removal of skin tags and nevi. The product website claims that skin tags and moles will “fall off naturally within 7 to 10 days” and the product can be used for “almost all skin types.” Users are instructed to apply the removal product and wipe it off when the skin surrounding the mole becomes swollen. The product kit also includes a repair lotion, which claims to help heal the skin after scab formation and scar development.

The ingredients listed on the product packaging are salicylic acid 25%, Melaleuca alternifolia (tea tree) leaf oil, propylene glycol, hydroxyethylcellulose, and alcohol. Salicylic acid 25% is a superficial peeling agent that penetrates the epidermis to the dermoepidermal junction. The potential side effects are mild and include superficial desquamation and epidermolysis.³ The Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set is not regulated by the US Food and Drug Administration and may contain variable concentrations of salicylic acid and other unknown compounds. Higher concentrations of salicylic acid can penetrate the full thickness of the epidermis into the papillary dermis, which can result in postinflammatory pigmentation, superficial infection, scarring, and deeper desquamation and epidermolysis.³ The product website advertises the use of only natural ingredients and an “advanced blend of concentrated natural ingredients contributing a broad spectrum of healing properties” in the formula. Although these claims are attractive to patients seeking alternatives to surgical approaches to nevi removal, the unfounded claims and unregulated ingredients may pose a threat to unsuspecting consumers.

Other OTC and “all-natural” mole removal products previously have been reported to cause harm.²Sanguinaria canadensis, also known as bloodroot, contains an alkaloid compound (sanguinarine) that has been shown to induce mitochondrial apoptosis and activation of Bcl-2 proteins in keratinocytes.⁴ Some products, such as Wart & Mole Vanish cream, may claim not to contain bloodroot specifically. However, sanguinarine can be extracted from other plants and may be listed as Argemone mexicana, Chelidonium majus, or Macleaya cordata in the ingredients list.⁵ The use of alternative medicine products such as black or yellow salve for the removal of suspected skin cancers also is not recommended because these escharotic treatments have not been proven safe or effective, and the manufacturing process for these compounds is unregulated.^6,7 Self-treatment with alternative remedies for nevi or suspected skin cancers has been associated with progression of disease and even death due to metastatic spread.²

Self-removal of moles is concerning because the nevi are masked by necrotic lesions and can no longer be assessed by dermoscopy or histopathology. Furthermore, the compounds in the Ariella Mole Corrector and Skin Tag Remover and Repair Lotion Set may have unknown effects on the transformation of premalignant cells. They also may mask an underlying process for which clinically proven and effective treatments such as cryotherapy, prescription topical agents, and surgical excision are warranted. Awareness of this product and similar products is important to educate patients on the harmful effects they may cause.

To the Editor:

Zinc chloride originally was used by Dr. Frederic Mohs as an in vivo tissue fixative during the early phases of Mohs micrographic surgery.¹ Although this technique has since been replaced with fresh frozen tissue fixation, zinc chloride still is found in topical preparations that are readily available to patients. Specifically, black salve describes variably composed topical preparations that share the common ingredients zinc chloride and Sanguinaria canadensis (bloodroot).² Patients self-treat with these unregulated compounds, but the majority do not have their lesions evaluated by a clinician prior to use and are unaware of the potential risks.^3-5 Products containing zinc chloride and S canadensis that are not marketed as black salve present a new problem for the dermatology community.

A 73-year-old man presented to our dermatology clinic for the focused evaluation of scaly lesions on the face and nose. At this visit, it was recommended he undergo a total-body skin examination for skin cancer screening given his age and substantial photodamage.

Physical examination revealed more than 20 superficial, 3- to 10-mm scars predominantly over the trunk. One scar over the left mid-back had a large, 1.2-cm peripheral rim of dark brown pigment that was clinically concerning for a melanocytic neoplasm. Shave removal of this lesion was performed. Histologic examination showed melanoma in situ with a central scar. The central scar spanned the depth of the dermis, and the melanocytic component was absent in this area, raising the question if prior biopsy or treatment had been performed on this lesion. During a discussion of the results with the patient, he was questioned about prior biopsy or treatment of this lesion. He reported prior use of a topical all-natural cream containing zinc chloride and S canadensis that he purchased online, which he had used to treat this lesion as well as numerous presumed moles.

The trend of at-home mole removal products containing the traditional ingredients in black salve seems to be one of rapidly shifting product availability as well as a departure from marketing items as black salve. Many prior black salve products are no longer available.⁴ The product that our patient used is a topical cream marketed as a treatment for moles and skin tags.⁶ Despite not being marketed as black salve, it does contain zinc chloride and S canadensis. The product’s website highlights these ingredients as being a safe and effective treatment for mole removal, with claims that the product will remove the mole or skin tag without irritating the surrounding skin and can be safely used anywhere on the body without scarring.⁶ A Google search at the time this article was written using the term skin tag remover revealed similar products marketed as all-natural “skin tag remover and mole corrector creams.” These similar products containing zinc chloride and S canadensis were available in the United States at the time of our initial research but have since been removed and only are available outside of the United States.⁷

Prior reports of melanoma masked by zinc chloride and S canadensis described the use of topical agents marketed as black salve. This new wave of products marketed as all-natural creams makes continued education on the available products and their associated risks necessary for clinicians. The lack of US Food and Drug Administration oversight for these products and their frequent introduction and discontinuation in the market makes keeping updated even more challenging. Because many patients self-treat without prior evaluation by a health care provider, treatment with these products can lead to a delay in diagnosis or inaccurate staging due to scars from the chemical destruction, both of which may have occurred in our patient.⁵ Until these products become regulated by the US Food and Drug Administration, it is imperative that clinicians continue to educate their patients on the lack of documented benefit and clear risks of their use as well as remain up-to-date on product trends.

To the Editor:

Zinc chloride originally was used by Dr. Frederic Mohs as an in vivo tissue fixative during the early phases of Mohs micrographic surgery.¹ Although this technique has since been replaced with fresh frozen tissue fixation, zinc chloride still is found in topical preparations that are readily available to patients. Specifically, black salve describes variably composed topical preparations that share the common ingredients zinc chloride and Sanguinaria canadensis (bloodroot).² Patients self-treat with these unregulated compounds, but the majority do not have their lesions evaluated by a clinician prior to use and are unaware of the potential risks.^3-5 Products containing zinc chloride and S canadensis that are not marketed as black salve present a new problem for the dermatology community.

A 73-year-old man presented to our dermatology clinic for the focused evaluation of scaly lesions on the face and nose. At this visit, it was recommended he undergo a total-body skin examination for skin cancer screening given his age and substantial photodamage.

Physical examination revealed more than 20 superficial, 3- to 10-mm scars predominantly over the trunk. One scar over the left mid-back had a large, 1.2-cm peripheral rim of dark brown pigment that was clinically concerning for a melanocytic neoplasm. Shave removal of this lesion was performed. Histologic examination showed melanoma in situ with a central scar. The central scar spanned the depth of the dermis, and the melanocytic component was absent in this area, raising the question if prior biopsy or treatment had been performed on this lesion. During a discussion of the results with the patient, he was questioned about prior biopsy or treatment of this lesion. He reported prior use of a topical all-natural cream containing zinc chloride and S canadensis that he purchased online, which he had used to treat this lesion as well as numerous presumed moles.

The trend of at-home mole removal products containing the traditional ingredients in black salve seems to be one of rapidly shifting product availability as well as a departure from marketing items as black salve. Many prior black salve products are no longer available.⁴ The product that our patient used is a topical cream marketed as a treatment for moles and skin tags.⁶ Despite not being marketed as black salve, it does contain zinc chloride and S canadensis. The product’s website highlights these ingredients as being a safe and effective treatment for mole removal, with claims that the product will remove the mole or skin tag without irritating the surrounding skin and can be safely used anywhere on the body without scarring.⁶ A Google search at the time this article was written using the term skin tag remover revealed similar products marketed as all-natural “skin tag remover and mole corrector creams.” These similar products containing zinc chloride and S canadensis were available in the United States at the time of our initial research but have since been removed and only are available outside of the United States.⁷

Prior reports of melanoma masked by zinc chloride and S canadensis described the use of topical agents marketed as black salve. This new wave of products marketed as all-natural creams makes continued education on the available products and their associated risks necessary for clinicians. The lack of US Food and Drug Administration oversight for these products and their frequent introduction and discontinuation in the market makes keeping updated even more challenging. Because many patients self-treat without prior evaluation by a health care provider, treatment with these products can lead to a delay in diagnosis or inaccurate staging due to scars from the chemical destruction, both of which may have occurred in our patient.⁵ Until these products become regulated by the US Food and Drug Administration, it is imperative that clinicians continue to educate their patients on the lack of documented benefit and clear risks of their use as well as remain up-to-date on product trends.

To the Editor:

Zinc chloride originally was used by Dr. Frederic Mohs as an in vivo tissue fixative during the early phases of Mohs micrographic surgery.¹ Although this technique has since been replaced with fresh frozen tissue fixation, zinc chloride still is found in topical preparations that are readily available to patients. Specifically, black salve describes variably composed topical preparations that share the common ingredients zinc chloride and Sanguinaria canadensis (bloodroot).² Patients self-treat with these unregulated compounds, but the majority do not have their lesions evaluated by a clinician prior to use and are unaware of the potential risks.^3-5 Products containing zinc chloride and S canadensis that are not marketed as black salve present a new problem for the dermatology community.

A 73-year-old man presented to our dermatology clinic for the focused evaluation of scaly lesions on the face and nose. At this visit, it was recommended he undergo a total-body skin examination for skin cancer screening given his age and substantial photodamage.

Physical examination revealed more than 20 superficial, 3- to 10-mm scars predominantly over the trunk. One scar over the left mid-back had a large, 1.2-cm peripheral rim of dark brown pigment that was clinically concerning for a melanocytic neoplasm. Shave removal of this lesion was performed. Histologic examination showed melanoma in situ with a central scar. The central scar spanned the depth of the dermis, and the melanocytic component was absent in this area, raising the question if prior biopsy or treatment had been performed on this lesion. During a discussion of the results with the patient, he was questioned about prior biopsy or treatment of this lesion. He reported prior use of a topical all-natural cream containing zinc chloride and S canadensis that he purchased online, which he had used to treat this lesion as well as numerous presumed moles.

The trend of at-home mole removal products containing the traditional ingredients in black salve seems to be one of rapidly shifting product availability as well as a departure from marketing items as black salve. Many prior black salve products are no longer available.⁴ The product that our patient used is a topical cream marketed as a treatment for moles and skin tags.⁶ Despite not being marketed as black salve, it does contain zinc chloride and S canadensis. The product’s website highlights these ingredients as being a safe and effective treatment for mole removal, with claims that the product will remove the mole or skin tag without irritating the surrounding skin and can be safely used anywhere on the body without scarring.⁶ A Google search at the time this article was written using the term skin tag remover revealed similar products marketed as all-natural “skin tag remover and mole corrector creams.” These similar products containing zinc chloride and S canadensis were available in the United States at the time of our initial research but have since been removed and only are available outside of the United States.⁷

Prior reports of melanoma masked by zinc chloride and S canadensis described the use of topical agents marketed as black salve. This new wave of products marketed as all-natural creams makes continued education on the available products and their associated risks necessary for clinicians. The lack of US Food and Drug Administration oversight for these products and their frequent introduction and discontinuation in the market makes keeping updated even more challenging. Because many patients self-treat without prior evaluation by a health care provider, treatment with these products can lead to a delay in diagnosis or inaccurate staging due to scars from the chemical destruction, both of which may have occurred in our patient.⁵ Until these products become regulated by the US Food and Drug Administration, it is imperative that clinicians continue to educate their patients on the lack of documented benefit and clear risks of their use as well as remain up-to-date on product trends.

An appeals court has upheld a family’s $9.5 million jury award after a physician left an 18-inch sponge in a patient’s abdomen that remained in her stomach for 5 years.

Carolyn Boerste underwent aortobifemoral bypass surgery at the University of Louisville (Ky.) Hospital in March 2011 to improve circulation in her lower extremities. She had a history of peripheral vascular disease, hypertension, and diabetes, which caused a wound on her toe to become infected and gangrenous, according to court records.

Courtesy Bo Bolus of Bolus Law Offices, Louisville, Ky.

During the surgery, performed by Marvin Morris, MD, the surgical team left a laparotomy sponge in Ms. Boerste’s abdomen. Because of its size, Ms. Boerste’s attorneys characterized the 18-by-18-inch object as “more like a towel,” according to court documents.

During the years that the sponge went undetected, the object eroded via transmural migration from Ms. Boerste’s abdomen into her intestine, causing diarrhea, vomiting, and nausea. In March 2015, Ms. Boerste was transferred by ambulance to an emergency department because of abdominal pain. An emergency physician ordered an abdominal CT scan, which showed the x-ray detectable sponge marker inside Ms. Boerste’s intestine, according to her complaint.

Although the radiologist called the emergency physician to advise him of the sponge marker, the information was not shared with Ms. Boerste and she was discharged from the hospital with a urinary tract infection diagnosis. The emergency physician later testified he had no memory of the call with the radiologist.

The CT scan was faxed to Ms. Boerste’s family physician. She testified that she read the report but did not mention the sponge marker to Ms. Boerste because she believed the issue had been handled by the emergency physician. Thus the sponge remained inside Ms. Boerste for another 20 months.

In November 2016, Ms. Boerste returned to the same emergency department with more intense gastrointestinal issues. Another CT scan was ordered, which revealed the sponge. The object was removed by exploratory laparotomy later that month. In her complaint, Ms. Boerste claimed that the removal surgery resulted in amputation of her leg because of wounds developed on her lower extremities while she was bedridden during recovery.

In 2017, she filed a negligence lawsuit against Dr. Morris, the hospital, and several others involved in her care. On the first day of trial in December 2019, the hospital conceded liability. The trial continued against Dr. Morris and the other defendants as to liability and damages and proceeded against the hospital as to damages.

At trial, evidence showed there was significant confusion among nurses on how to document sponge counts, according to the appellate decision. In general, nurses used a perioperative nursing record to document the surgical procedure, and that record had a place to document some but not all sponge counts required by hospital policy. The nursing record did not have a place to document sponge counts required to be recorded at every break, lunch, and shift change. Nurses also used a worksheet to track sponge counts, but that worksheet was not part of the medical record.

Dr. Morris testified that he relies on nurses regarding sponge counts, but that he also performs a visual and tactile inspection of the abdominal cavity. He acknowledged during trial that the standard of care required him to keep track of the sponges before closing. Dr. Morris also testified that the surgeon and nurses are a team, and “the entire team did not count the sponges correctly when finishing the bypass surgery,” according to the appellate decision.

After a 10-day trial, jurors found Dr. Morris and several other defendants liable. They apportioned 60% liability to the hospital, 10% to Morris, 15% to the family physician, 0% to the emergency physician, and 15% to the rehabilitation center. Ms. Boerste was awarded $9.5 million in damages and an additional $1 million in punitive damages, for a total of $10.5 million.

Dr. Morris and the hospital appealed to the Commonwealth of Kentucky Court of Appeals. As the appeal was pending, Ms. Boerste died, and her son took over the plaintiff’s role.

In their appeal, Dr. Morris and the hospital said they should be granted a new trial for a number of reasons, including that the pain and suffering award was grossly excessive and reflected improper jury sympathy, that the punitive damages award should be vacated because jurors were not properly instructed on the issue, and that the judgment against Dr. Morris should be overturned because there was no evidence he deviated from the standard of care.

The defendants also argued that they were entitled to instructions on “apportionment of fault and mitigation of damages against Boerste.” The mitigation of damages doctrine prevents an injured plaintiff from recovering unreasonable expenses associated with the injury if they could have been avoided through reasonable efforts. Specifically, attorneys for Dr. Morris emphasized that Ms. Boerste failed to follow medical advice for follow-up care, to obtain recommended podiatrist care, and to make necessary efforts to control her diabetes. Had Ms. Boerste taken more proactive steps to manage her health, leg amputation may not have been needed because the sponge may have been found during other treatment, they contended.

In its Jan. 7, 2022, opinion, the appeals court upheld the majority of the jury award. Judges wrote that Dr. Morris’ testimony alone was sufficient for the jury to determine whether he breached the standard of care, and that the defendants are not entitled to a new trial on pain and suffering damages. In addition, judges rejected mitigation of damages.  

“The fact that Boerste was a poor patient who failed to properly treat her diabetes is irrelevant,” the panel wrote in their decision. “She was a poor patient prior to the bypass surgery, and Appellants knew Boerste might ultimately need to have her lower leg amputated at the time of the bypass surgery. Therefore, we hold Appellants were not entitled to instructions on apportionment of fault or mitigation of damages.”

The appeals court, however, vacated the $1 million punitive damages award, ruling that the lower court did not give a proper instruction to the jury on punitive damages. The appeals court sent the case back to the lower court for a retrial as it pertains to punitive damages.

Attorneys for Dr. Morris and the hospital did not return messages seeking comment.

Bo Bolus, an attorney for Ms. Boerste’s family, said there will be no retrial on punitive damages, and that the plaintiff is satisfied with the outcome of the case.

“While we are pleased that Carolyn’s family and, equally importantly, her memory, now finally have closure on this extremely trying matter, our pleasure is severely tempered by the loss of Carolyn in November of last year,” Mr. Bolus said. “After having endured all she did, it is, frankly, painful for all concerned that she will not reap the reward of the jury’s verdict.”

A version of this article first appeared on Medscape.com.

An appeals court has upheld a family’s $9.5 million jury award after a physician left an 18-inch sponge in a patient’s abdomen that remained in her stomach for 5 years.

Carolyn Boerste underwent aortobifemoral bypass surgery at the University of Louisville (Ky.) Hospital in March 2011 to improve circulation in her lower extremities. She had a history of peripheral vascular disease, hypertension, and diabetes, which caused a wound on her toe to become infected and gangrenous, according to court records.

Courtesy Bo Bolus of Bolus Law Offices, Louisville, Ky.

During the surgery, performed by Marvin Morris, MD, the surgical team left a laparotomy sponge in Ms. Boerste’s abdomen. Because of its size, Ms. Boerste’s attorneys characterized the 18-by-18-inch object as “more like a towel,” according to court documents.

During the years that the sponge went undetected, the object eroded via transmural migration from Ms. Boerste’s abdomen into her intestine, causing diarrhea, vomiting, and nausea. In March 2015, Ms. Boerste was transferred by ambulance to an emergency department because of abdominal pain. An emergency physician ordered an abdominal CT scan, which showed the x-ray detectable sponge marker inside Ms. Boerste’s intestine, according to her complaint.

Although the radiologist called the emergency physician to advise him of the sponge marker, the information was not shared with Ms. Boerste and she was discharged from the hospital with a urinary tract infection diagnosis. The emergency physician later testified he had no memory of the call with the radiologist.

The CT scan was faxed to Ms. Boerste’s family physician. She testified that she read the report but did not mention the sponge marker to Ms. Boerste because she believed the issue had been handled by the emergency physician. Thus the sponge remained inside Ms. Boerste for another 20 months.

In November 2016, Ms. Boerste returned to the same emergency department with more intense gastrointestinal issues. Another CT scan was ordered, which revealed the sponge. The object was removed by exploratory laparotomy later that month. In her complaint, Ms. Boerste claimed that the removal surgery resulted in amputation of her leg because of wounds developed on her lower extremities while she was bedridden during recovery.

In 2017, she filed a negligence lawsuit against Dr. Morris, the hospital, and several others involved in her care. On the first day of trial in December 2019, the hospital conceded liability. The trial continued against Dr. Morris and the other defendants as to liability and damages and proceeded against the hospital as to damages.

At trial, evidence showed there was significant confusion among nurses on how to document sponge counts, according to the appellate decision. In general, nurses used a perioperative nursing record to document the surgical procedure, and that record had a place to document some but not all sponge counts required by hospital policy. The nursing record did not have a place to document sponge counts required to be recorded at every break, lunch, and shift change. Nurses also used a worksheet to track sponge counts, but that worksheet was not part of the medical record.

Dr. Morris testified that he relies on nurses regarding sponge counts, but that he also performs a visual and tactile inspection of the abdominal cavity. He acknowledged during trial that the standard of care required him to keep track of the sponges before closing. Dr. Morris also testified that the surgeon and nurses are a team, and “the entire team did not count the sponges correctly when finishing the bypass surgery,” according to the appellate decision.

After a 10-day trial, jurors found Dr. Morris and several other defendants liable. They apportioned 60% liability to the hospital, 10% to Morris, 15% to the family physician, 0% to the emergency physician, and 15% to the rehabilitation center. Ms. Boerste was awarded $9.5 million in damages and an additional $1 million in punitive damages, for a total of $10.5 million.

Dr. Morris and the hospital appealed to the Commonwealth of Kentucky Court of Appeals. As the appeal was pending, Ms. Boerste died, and her son took over the plaintiff’s role.

In their appeal, Dr. Morris and the hospital said they should be granted a new trial for a number of reasons, including that the pain and suffering award was grossly excessive and reflected improper jury sympathy, that the punitive damages award should be vacated because jurors were not properly instructed on the issue, and that the judgment against Dr. Morris should be overturned because there was no evidence he deviated from the standard of care.

The defendants also argued that they were entitled to instructions on “apportionment of fault and mitigation of damages against Boerste.” The mitigation of damages doctrine prevents an injured plaintiff from recovering unreasonable expenses associated with the injury if they could have been avoided through reasonable efforts. Specifically, attorneys for Dr. Morris emphasized that Ms. Boerste failed to follow medical advice for follow-up care, to obtain recommended podiatrist care, and to make necessary efforts to control her diabetes. Had Ms. Boerste taken more proactive steps to manage her health, leg amputation may not have been needed because the sponge may have been found during other treatment, they contended.

In its Jan. 7, 2022, opinion, the appeals court upheld the majority of the jury award. Judges wrote that Dr. Morris’ testimony alone was sufficient for the jury to determine whether he breached the standard of care, and that the defendants are not entitled to a new trial on pain and suffering damages. In addition, judges rejected mitigation of damages.  

“The fact that Boerste was a poor patient who failed to properly treat her diabetes is irrelevant,” the panel wrote in their decision. “She was a poor patient prior to the bypass surgery, and Appellants knew Boerste might ultimately need to have her lower leg amputated at the time of the bypass surgery. Therefore, we hold Appellants were not entitled to instructions on apportionment of fault or mitigation of damages.”

The appeals court, however, vacated the $1 million punitive damages award, ruling that the lower court did not give a proper instruction to the jury on punitive damages. The appeals court sent the case back to the lower court for a retrial as it pertains to punitive damages.

Attorneys for Dr. Morris and the hospital did not return messages seeking comment.

Bo Bolus, an attorney for Ms. Boerste’s family, said there will be no retrial on punitive damages, and that the plaintiff is satisfied with the outcome of the case.

“While we are pleased that Carolyn’s family and, equally importantly, her memory, now finally have closure on this extremely trying matter, our pleasure is severely tempered by the loss of Carolyn in November of last year,” Mr. Bolus said. “After having endured all she did, it is, frankly, painful for all concerned that she will not reap the reward of the jury’s verdict.”

A version of this article first appeared on Medscape.com.

An appeals court has upheld a family’s $9.5 million jury award after a physician left an 18-inch sponge in a patient’s abdomen that remained in her stomach for 5 years.

Carolyn Boerste underwent aortobifemoral bypass surgery at the University of Louisville (Ky.) Hospital in March 2011 to improve circulation in her lower extremities. She had a history of peripheral vascular disease, hypertension, and diabetes, which caused a wound on her toe to become infected and gangrenous, according to court records.

Courtesy Bo Bolus of Bolus Law Offices, Louisville, Ky.

During the surgery, performed by Marvin Morris, MD, the surgical team left a laparotomy sponge in Ms. Boerste’s abdomen. Because of its size, Ms. Boerste’s attorneys characterized the 18-by-18-inch object as “more like a towel,” according to court documents.

During the years that the sponge went undetected, the object eroded via transmural migration from Ms. Boerste’s abdomen into her intestine, causing diarrhea, vomiting, and nausea. In March 2015, Ms. Boerste was transferred by ambulance to an emergency department because of abdominal pain. An emergency physician ordered an abdominal CT scan, which showed the x-ray detectable sponge marker inside Ms. Boerste’s intestine, according to her complaint.

Although the radiologist called the emergency physician to advise him of the sponge marker, the information was not shared with Ms. Boerste and she was discharged from the hospital with a urinary tract infection diagnosis. The emergency physician later testified he had no memory of the call with the radiologist.

The CT scan was faxed to Ms. Boerste’s family physician. She testified that she read the report but did not mention the sponge marker to Ms. Boerste because she believed the issue had been handled by the emergency physician. Thus the sponge remained inside Ms. Boerste for another 20 months.

In November 2016, Ms. Boerste returned to the same emergency department with more intense gastrointestinal issues. Another CT scan was ordered, which revealed the sponge. The object was removed by exploratory laparotomy later that month. In her complaint, Ms. Boerste claimed that the removal surgery resulted in amputation of her leg because of wounds developed on her lower extremities while she was bedridden during recovery.

In 2017, she filed a negligence lawsuit against Dr. Morris, the hospital, and several others involved in her care. On the first day of trial in December 2019, the hospital conceded liability. The trial continued against Dr. Morris and the other defendants as to liability and damages and proceeded against the hospital as to damages.

At trial, evidence showed there was significant confusion among nurses on how to document sponge counts, according to the appellate decision. In general, nurses used a perioperative nursing record to document the surgical procedure, and that record had a place to document some but not all sponge counts required by hospital policy. The nursing record did not have a place to document sponge counts required to be recorded at every break, lunch, and shift change. Nurses also used a worksheet to track sponge counts, but that worksheet was not part of the medical record.

Dr. Morris testified that he relies on nurses regarding sponge counts, but that he also performs a visual and tactile inspection of the abdominal cavity. He acknowledged during trial that the standard of care required him to keep track of the sponges before closing. Dr. Morris also testified that the surgeon and nurses are a team, and “the entire team did not count the sponges correctly when finishing the bypass surgery,” according to the appellate decision.

After a 10-day trial, jurors found Dr. Morris and several other defendants liable. They apportioned 60% liability to the hospital, 10% to Morris, 15% to the family physician, 0% to the emergency physician, and 15% to the rehabilitation center. Ms. Boerste was awarded $9.5 million in damages and an additional $1 million in punitive damages, for a total of $10.5 million.

Dr. Morris and the hospital appealed to the Commonwealth of Kentucky Court of Appeals. As the appeal was pending, Ms. Boerste died, and her son took over the plaintiff’s role.

In their appeal, Dr. Morris and the hospital said they should be granted a new trial for a number of reasons, including that the pain and suffering award was grossly excessive and reflected improper jury sympathy, that the punitive damages award should be vacated because jurors were not properly instructed on the issue, and that the judgment against Dr. Morris should be overturned because there was no evidence he deviated from the standard of care.

The defendants also argued that they were entitled to instructions on “apportionment of fault and mitigation of damages against Boerste.” The mitigation of damages doctrine prevents an injured plaintiff from recovering unreasonable expenses associated with the injury if they could have been avoided through reasonable efforts. Specifically, attorneys for Dr. Morris emphasized that Ms. Boerste failed to follow medical advice for follow-up care, to obtain recommended podiatrist care, and to make necessary efforts to control her diabetes. Had Ms. Boerste taken more proactive steps to manage her health, leg amputation may not have been needed because the sponge may have been found during other treatment, they contended.

In its Jan. 7, 2022, opinion, the appeals court upheld the majority of the jury award. Judges wrote that Dr. Morris’ testimony alone was sufficient for the jury to determine whether he breached the standard of care, and that the defendants are not entitled to a new trial on pain and suffering damages. In addition, judges rejected mitigation of damages.  

“The fact that Boerste was a poor patient who failed to properly treat her diabetes is irrelevant,” the panel wrote in their decision. “She was a poor patient prior to the bypass surgery, and Appellants knew Boerste might ultimately need to have her lower leg amputated at the time of the bypass surgery. Therefore, we hold Appellants were not entitled to instructions on apportionment of fault or mitigation of damages.”

The appeals court, however, vacated the $1 million punitive damages award, ruling that the lower court did not give a proper instruction to the jury on punitive damages. The appeals court sent the case back to the lower court for a retrial as it pertains to punitive damages.

Attorneys for Dr. Morris and the hospital did not return messages seeking comment.

Bo Bolus, an attorney for Ms. Boerste’s family, said there will be no retrial on punitive damages, and that the plaintiff is satisfied with the outcome of the case.

“While we are pleased that Carolyn’s family and, equally importantly, her memory, now finally have closure on this extremely trying matter, our pleasure is severely tempered by the loss of Carolyn in November of last year,” Mr. Bolus said. “After having endured all she did, it is, frankly, painful for all concerned that she will not reap the reward of the jury’s verdict.”

A version of this article first appeared on Medscape.com.

The American College of Rheumatology and the American Association of Hip and Knee Surgeons have released updated guidelines regarding whether to withhold drugs such as biologics and immunosuppressives for patients with inflammatory rheumatic disease who are scheduled to undergo elective total hip or knee replacement surgery.

The guidelines, published in a summary by the societies on Feb. 28, include revised and new recommendations about biologics and Janus kinase (JAK) inhibitors for patients with several types of inflammatory arthritis and systemic lupus erythematosus (SLE). In general, the guidelines recommend that the most powerful medications be withheld prior to surgery except for patients whose SLE is so severe that it threatens organs. They also recommend a shorter period of withholding drugs – 3 days instead of 7 – for JAK inhibitors.
 

The previous guidelines were published in 2017.

“These recommendations seek to balance flares of disease that are likely when medications are stopped vs. the risk of infection,” Susan M. Goodman, MD, a rheumatologist at the Hospital for Special Surgery, New York, and co–principal investigator of the guideline, told this news organization. “Patients and physicians may want to be either more conservative or more aggressive with their medications, depending on their personal priorities or specific medical history.”

According to Dr. Goodman, patients with inflammatory rheumatic diseases are especially likely to undergo joint replacement surgery because the conditions can damage the joints. “While the introduction of potent biologics has been linked to a decrease in surgery of soft tissues and small joints, there has been little impact on large-joint surgeries,” she said.

The risk of infection in these patients is about 50% higher than in the general population, she said. However, “it is hard to determine the magnitude of the effect of withholding medications, given the low rate of infection. In fact, using pharmaco-epidemiologic methods in large Medicare databases, no difference was seen in patients whose immunosuppressant medication infusions were close to the time of surgery compared to those patients whose medication infusions were months prior to surgery.”

The guidelines add a recommendation for the first time for apremilast (Otezla), saying that when it is administered twice daily it is okay to schedule surgery at any time.

Withholding drugs in patients with SLE

“We now recommend continuing biologics used to treat SLE – rituximab and belimumab – in patients with severe SLE but continue to recommend withholding them in less severe cases where there is little risk of organ damage,” Bryan D. Springer, MD, an orthopedic surgeon in Charlotte, N.C., first vice president of the AAHKS, and co–principal investigator of the new guidelines, told this news organization.

In severe SLE cases, the guidelines recommend timing total joint replacement surgery for 4-6 months after the latest IV dose of rituximab (Rituxan), which is given every 4-6 months. For patients taking belimumab (Benlysta), time surgery anytime when weekly subcutaneous doses are administered or at week 4 when monthly IV doses are given.

The guidelines also make recommendations regarding two new drugs for the treatment of severe SLE:

• Anifrolumab (Saphnelo): Time surgery at week 4 when IV treatment is given every 4 weeks.
• Voclosporin (Lupkynis): Continue doses when they’re given twice daily.

An ACR statement cautions that there are no published, peer-reviewed data regarding the use of these two drugs prior to total joint surgery. “The medications do increase the risk of infection,” the statement says, “and therefore their use in patients with severe SLE would merit review by the treating rheumatologist in consideration of surgery.”

Timing of stopping and restarting medication

The guidelines also recommend that certain drugs be withheld for patients with rheumatoid arthritis, ankylosing spondylitis, or any type of SLE and then “restarting the antirheumatic therapy once the wound shows evidence of healing, any sutures/staples are out, there is no significant swelling, erythema, or drainage, and there is no ongoing nonsurgical site infection, which is typically about 14 days.”

In regard to biologics, “we continue to recommend withholding biologic medications in patients with inflammatory arthritis, withholding the medication for a dosing cycle prior to surgery, and scheduling the surgery after that dose would be due,” Dr. Springer said. “For example, if a patient takes the medication every 4 weeks, the patient would withhold the dose of the medication and schedule surgery in the 5th week.”

The new recommendations for biologics suggest scheduling surgery at week 5 when the interleukin (IL)-17 inhibitor ixekizumab (Taltz) is given once every 4 weeks and at week 9 when the IL-23 inhibitor guselkumab (Tremfya) is given every 8 weeks.

The guidelines also revise the previous recommendation about tofacitinib (Xeljanz): Surgery should be scheduled on day 4 when the drug is given once or twice daily. New recommendations for fellow JAK inhibitors baricitinib (Olumiant, daily) and upadacitinib (Rinvoq, daily) are the same: Withhold for 3 days prior to surgery and perform surgery on the 4th day.

“We shortened the time between the last dose of JAK inhibitors and surgery to 3 days from 7 based on trial data demonstrating early flares when the drug was withheld, suggesting the immunosuppressant effect wears off sooner than we previously thought,” Dr. Springer said.

The guidelines caution that the recommendations for JAK inhibitors are for infection risk but do not consider the risk of cardiac events or venous thromboembolism.

In patients with nonsevere SLE, the guidelines revise the recommendations for mycophenolate mofetil (twice daily), cyclosporine (twice daily), and tacrolimus (twice daily, IV and oral). The new advice is to withhold the drugs for 1 week after last dose prior to surgery. New recommendations offer the same advice for belimumab, both IV and subcutaneous: Withhold for 1 week after last dose prior to surgery.

The board of the ACR approved the guidelines summary; the full manuscript has been submitted for peer review with an eye toward later publication in the journals Arthritis and Rheumatology and Arthritis Care and Research.

The ACR and AAHKS funded the guidelines. Dr. Goodman and Dr. Springer report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The American College of Rheumatology and the American Association of Hip and Knee Surgeons have released updated guidelines regarding whether to withhold drugs such as biologics and immunosuppressives for patients with inflammatory rheumatic disease who are scheduled to undergo elective total hip or knee replacement surgery.

The guidelines, published in a summary by the societies on Feb. 28, include revised and new recommendations about biologics and Janus kinase (JAK) inhibitors for patients with several types of inflammatory arthritis and systemic lupus erythematosus (SLE). In general, the guidelines recommend that the most powerful medications be withheld prior to surgery except for patients whose SLE is so severe that it threatens organs. They also recommend a shorter period of withholding drugs – 3 days instead of 7 – for JAK inhibitors.
 

The previous guidelines were published in 2017.

“These recommendations seek to balance flares of disease that are likely when medications are stopped vs. the risk of infection,” Susan M. Goodman, MD, a rheumatologist at the Hospital for Special Surgery, New York, and co–principal investigator of the guideline, told this news organization. “Patients and physicians may want to be either more conservative or more aggressive with their medications, depending on their personal priorities or specific medical history.”

According to Dr. Goodman, patients with inflammatory rheumatic diseases are especially likely to undergo joint replacement surgery because the conditions can damage the joints. “While the introduction of potent biologics has been linked to a decrease in surgery of soft tissues and small joints, there has been little impact on large-joint surgeries,” she said.

The risk of infection in these patients is about 50% higher than in the general population, she said. However, “it is hard to determine the magnitude of the effect of withholding medications, given the low rate of infection. In fact, using pharmaco-epidemiologic methods in large Medicare databases, no difference was seen in patients whose immunosuppressant medication infusions were close to the time of surgery compared to those patients whose medication infusions were months prior to surgery.”

The guidelines add a recommendation for the first time for apremilast (Otezla), saying that when it is administered twice daily it is okay to schedule surgery at any time.

Withholding drugs in patients with SLE

“We now recommend continuing biologics used to treat SLE – rituximab and belimumab – in patients with severe SLE but continue to recommend withholding them in less severe cases where there is little risk of organ damage,” Bryan D. Springer, MD, an orthopedic surgeon in Charlotte, N.C., first vice president of the AAHKS, and co–principal investigator of the new guidelines, told this news organization.

In severe SLE cases, the guidelines recommend timing total joint replacement surgery for 4-6 months after the latest IV dose of rituximab (Rituxan), which is given every 4-6 months. For patients taking belimumab (Benlysta), time surgery anytime when weekly subcutaneous doses are administered or at week 4 when monthly IV doses are given.

The guidelines also make recommendations regarding two new drugs for the treatment of severe SLE:

• Anifrolumab (Saphnelo): Time surgery at week 4 when IV treatment is given every 4 weeks.
• Voclosporin (Lupkynis): Continue doses when they’re given twice daily.

An ACR statement cautions that there are no published, peer-reviewed data regarding the use of these two drugs prior to total joint surgery. “The medications do increase the risk of infection,” the statement says, “and therefore their use in patients with severe SLE would merit review by the treating rheumatologist in consideration of surgery.”

Timing of stopping and restarting medication

The guidelines also recommend that certain drugs be withheld for patients with rheumatoid arthritis, ankylosing spondylitis, or any type of SLE and then “restarting the antirheumatic therapy once the wound shows evidence of healing, any sutures/staples are out, there is no significant swelling, erythema, or drainage, and there is no ongoing nonsurgical site infection, which is typically about 14 days.”

In regard to biologics, “we continue to recommend withholding biologic medications in patients with inflammatory arthritis, withholding the medication for a dosing cycle prior to surgery, and scheduling the surgery after that dose would be due,” Dr. Springer said. “For example, if a patient takes the medication every 4 weeks, the patient would withhold the dose of the medication and schedule surgery in the 5th week.”

The new recommendations for biologics suggest scheduling surgery at week 5 when the interleukin (IL)-17 inhibitor ixekizumab (Taltz) is given once every 4 weeks and at week 9 when the IL-23 inhibitor guselkumab (Tremfya) is given every 8 weeks.

The guidelines also revise the previous recommendation about tofacitinib (Xeljanz): Surgery should be scheduled on day 4 when the drug is given once or twice daily. New recommendations for fellow JAK inhibitors baricitinib (Olumiant, daily) and upadacitinib (Rinvoq, daily) are the same: Withhold for 3 days prior to surgery and perform surgery on the 4th day.

“We shortened the time between the last dose of JAK inhibitors and surgery to 3 days from 7 based on trial data demonstrating early flares when the drug was withheld, suggesting the immunosuppressant effect wears off sooner than we previously thought,” Dr. Springer said.

The guidelines caution that the recommendations for JAK inhibitors are for infection risk but do not consider the risk of cardiac events or venous thromboembolism.

In patients with nonsevere SLE, the guidelines revise the recommendations for mycophenolate mofetil (twice daily), cyclosporine (twice daily), and tacrolimus (twice daily, IV and oral). The new advice is to withhold the drugs for 1 week after last dose prior to surgery. New recommendations offer the same advice for belimumab, both IV and subcutaneous: Withhold for 1 week after last dose prior to surgery.

The board of the ACR approved the guidelines summary; the full manuscript has been submitted for peer review with an eye toward later publication in the journals Arthritis and Rheumatology and Arthritis Care and Research.

The ACR and AAHKS funded the guidelines. Dr. Goodman and Dr. Springer report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The American College of Rheumatology and the American Association of Hip and Knee Surgeons have released updated guidelines regarding whether to withhold drugs such as biologics and immunosuppressives for patients with inflammatory rheumatic disease who are scheduled to undergo elective total hip or knee replacement surgery.

The guidelines, published in a summary by the societies on Feb. 28, include revised and new recommendations about biologics and Janus kinase (JAK) inhibitors for patients with several types of inflammatory arthritis and systemic lupus erythematosus (SLE). In general, the guidelines recommend that the most powerful medications be withheld prior to surgery except for patients whose SLE is so severe that it threatens organs. They also recommend a shorter period of withholding drugs – 3 days instead of 7 – for JAK inhibitors.
 

The previous guidelines were published in 2017.

“These recommendations seek to balance flares of disease that are likely when medications are stopped vs. the risk of infection,” Susan M. Goodman, MD, a rheumatologist at the Hospital for Special Surgery, New York, and co–principal investigator of the guideline, told this news organization. “Patients and physicians may want to be either more conservative or more aggressive with their medications, depending on their personal priorities or specific medical history.”

According to Dr. Goodman, patients with inflammatory rheumatic diseases are especially likely to undergo joint replacement surgery because the conditions can damage the joints. “While the introduction of potent biologics has been linked to a decrease in surgery of soft tissues and small joints, there has been little impact on large-joint surgeries,” she said.

The risk of infection in these patients is about 50% higher than in the general population, she said. However, “it is hard to determine the magnitude of the effect of withholding medications, given the low rate of infection. In fact, using pharmaco-epidemiologic methods in large Medicare databases, no difference was seen in patients whose immunosuppressant medication infusions were close to the time of surgery compared to those patients whose medication infusions were months prior to surgery.”

The guidelines add a recommendation for the first time for apremilast (Otezla), saying that when it is administered twice daily it is okay to schedule surgery at any time.

Withholding drugs in patients with SLE

“We now recommend continuing biologics used to treat SLE – rituximab and belimumab – in patients with severe SLE but continue to recommend withholding them in less severe cases where there is little risk of organ damage,” Bryan D. Springer, MD, an orthopedic surgeon in Charlotte, N.C., first vice president of the AAHKS, and co–principal investigator of the new guidelines, told this news organization.

In severe SLE cases, the guidelines recommend timing total joint replacement surgery for 4-6 months after the latest IV dose of rituximab (Rituxan), which is given every 4-6 months. For patients taking belimumab (Benlysta), time surgery anytime when weekly subcutaneous doses are administered or at week 4 when monthly IV doses are given.

The guidelines also make recommendations regarding two new drugs for the treatment of severe SLE:

• Anifrolumab (Saphnelo): Time surgery at week 4 when IV treatment is given every 4 weeks.
• Voclosporin (Lupkynis): Continue doses when they’re given twice daily.

An ACR statement cautions that there are no published, peer-reviewed data regarding the use of these two drugs prior to total joint surgery. “The medications do increase the risk of infection,” the statement says, “and therefore their use in patients with severe SLE would merit review by the treating rheumatologist in consideration of surgery.”

Timing of stopping and restarting medication

The guidelines also recommend that certain drugs be withheld for patients with rheumatoid arthritis, ankylosing spondylitis, or any type of SLE and then “restarting the antirheumatic therapy once the wound shows evidence of healing, any sutures/staples are out, there is no significant swelling, erythema, or drainage, and there is no ongoing nonsurgical site infection, which is typically about 14 days.”

In regard to biologics, “we continue to recommend withholding biologic medications in patients with inflammatory arthritis, withholding the medication for a dosing cycle prior to surgery, and scheduling the surgery after that dose would be due,” Dr. Springer said. “For example, if a patient takes the medication every 4 weeks, the patient would withhold the dose of the medication and schedule surgery in the 5th week.”

The new recommendations for biologics suggest scheduling surgery at week 5 when the interleukin (IL)-17 inhibitor ixekizumab (Taltz) is given once every 4 weeks and at week 9 when the IL-23 inhibitor guselkumab (Tremfya) is given every 8 weeks.

The guidelines also revise the previous recommendation about tofacitinib (Xeljanz): Surgery should be scheduled on day 4 when the drug is given once or twice daily. New recommendations for fellow JAK inhibitors baricitinib (Olumiant, daily) and upadacitinib (Rinvoq, daily) are the same: Withhold for 3 days prior to surgery and perform surgery on the 4th day.

“We shortened the time between the last dose of JAK inhibitors and surgery to 3 days from 7 based on trial data demonstrating early flares when the drug was withheld, suggesting the immunosuppressant effect wears off sooner than we previously thought,” Dr. Springer said.

The guidelines caution that the recommendations for JAK inhibitors are for infection risk but do not consider the risk of cardiac events or venous thromboembolism.

In patients with nonsevere SLE, the guidelines revise the recommendations for mycophenolate mofetil (twice daily), cyclosporine (twice daily), and tacrolimus (twice daily, IV and oral). The new advice is to withhold the drugs for 1 week after last dose prior to surgery. New recommendations offer the same advice for belimumab, both IV and subcutaneous: Withhold for 1 week after last dose prior to surgery.

The board of the ACR approved the guidelines summary; the full manuscript has been submitted for peer review with an eye toward later publication in the journals Arthritis and Rheumatology and Arthritis Care and Research.

The ACR and AAHKS funded the guidelines. Dr. Goodman and Dr. Springer report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The COVID-19 pandemic continues to take a toll on the happiness, wellness, and lifestyles of many segments of the population, but especially those in the health care field, including gastroenterologists.

The newly released Medscape Gastroenterologist Lifestyle, Happiness & Burnout Report 2022 explores gastroenterologists’ level of happiness in their personal and professional lives and how they maintain their mental and physical health.

Prior to the global pandemic, 8 in 10 (80%) gastroenterologists said they were “very” or “somewhat” happy outside of work, similar to physicians overall (81%).

But as the pandemic has worn on, feelings have shifted, and there are clear signs of stress and strain on those in the health care field.

Now, the percentage of gastroenterologists who say they are currently “very” or “somewhat” happy outside of work has dropped to 60%, about the same as physicians overall (59%).
 

Buried in paperwork

In 2021’s report, 42% of gastroenterologists reported burnout; that’s risen to 47% this year.

When it comes to burnout, gastroenterologists remain in the middle range of burned-out physicians.

Perhaps not surprising given the challenges of the COVID-19 pandemic, burnout rates are highest among emergency medicine and critical care specialists.

About half of gastroenterologists (52%) report being more burned out now than during the initial quarantine months of the pandemic, similar to physicians overall (55%). About 4 in 10 (39%) said their burnout was the same.

Female gastroenterologists report burnout at a greater rate than their male colleagues – 57% versus 46%.

“There’s no question that women have reported far more role strain during the pandemic than men,” said Carol A. Bernstein, MD, a psychiatrist at Montefiore Health System and professor and vice chair for faculty development and well-being at Albert Einstein College of Medicine, New York.

“Often women assumed more of the childcare and home-schooling responsibilities in their households. As [a] result, we know that more women dropped out of the workforce. Also, past studies indicate that women are more likely to report feelings of burnout than men,” Dr. Bernstein noted.

The volume of bureaucratic tasks is the main driver of gastroenterologist burnout, similar to that for physicians overall. Lack of respect from colleagues and more time devoted to electronic health records were also selected as major factors in this year’s report.

Gastroenterologists’ top ways to quell burnout are reducing their hours on the job (24%), changing workflow or staffing to ease their workload (23%), and taking advantage of meditation or other stress-reduction methods (18%) – similar to physicians overall.

Roughly one-third (34%) of gastroenterologists feel that their personality type contributes to their burnout, similar to physicians overall. Six in 10 gastroenterologists (60%) say burnout affects their relationships, similar to physicians overall (68%).
 

Seeking better work-life balance

More than half of gastroenterologists (57%) said they are willing to take a cut in pay in order to achieve a better work-life balance or have more free time – similar among physicians overall (55%).

About 16% of gastroenterologists reported clinical depression (severe depression lasting some time and not caused by grief), while 71% reported colloquial depression (feeling down, blue, sad).

About half (53%) of depressed gastroenterologists said their depression does not have an impact on relationships with patients.

Among those who saw an impact, the major behaviors they reported included being easily exasperated with patients (44%) and feeling less motivated to take patient notes carefully (20%).

To maintain well-being, gastroenterologists often choose to spend their time with their loved ones (59%), do the things they enjoy (58%), exercise (57%), get plenty of sleep (42%), and eat right (35%).

Perhaps not surprisingly, more gastroenterologists were happy with their work-life balance before the pandemic than now (70% vs. 44%). The same holds for physicians overall.

Before the pandemic, 22% of gastroenterologists reported being unhappy with their work-life balance. That has risen to 39% this year.

Most gastroenterologists are currently in a committed relationship, with 90% either married or living with a partner, a somewhat higher percentage than physicians overall (83%).

About 83% of gastroenterologists say they are in a “very good” or “good” marriage. This is down somewhat from the 2021 report (89%).

Nearly 6 in 10 gastroenterologists have partners who do not work in medicine. This is similar to the proportion among all physicians.

Findings from Medscape’s latest happiness, wellness, and lifestyle survey are based on 13,069 Medscape member physicians (61% male) practicing in the United States who completed an online survey conducted between June 29, 2021, and Sept. 26, 2021. Most respondents were between 35 and 64 years old.

A version of this article first appeared on Medscape.com.

The COVID-19 pandemic continues to take a toll on the happiness, wellness, and lifestyles of many segments of the population, but especially those in the health care field, including gastroenterologists.

The newly released Medscape Gastroenterologist Lifestyle, Happiness & Burnout Report 2022 explores gastroenterologists’ level of happiness in their personal and professional lives and how they maintain their mental and physical health.

Prior to the global pandemic, 8 in 10 (80%) gastroenterologists said they were “very” or “somewhat” happy outside of work, similar to physicians overall (81%).

But as the pandemic has worn on, feelings have shifted, and there are clear signs of stress and strain on those in the health care field.

Now, the percentage of gastroenterologists who say they are currently “very” or “somewhat” happy outside of work has dropped to 60%, about the same as physicians overall (59%).
 

Buried in paperwork

In 2021’s report, 42% of gastroenterologists reported burnout; that’s risen to 47% this year.

When it comes to burnout, gastroenterologists remain in the middle range of burned-out physicians.

Perhaps not surprising given the challenges of the COVID-19 pandemic, burnout rates are highest among emergency medicine and critical care specialists.

About half of gastroenterologists (52%) report being more burned out now than during the initial quarantine months of the pandemic, similar to physicians overall (55%). About 4 in 10 (39%) said their burnout was the same.

Female gastroenterologists report burnout at a greater rate than their male colleagues – 57% versus 46%.

“There’s no question that women have reported far more role strain during the pandemic than men,” said Carol A. Bernstein, MD, a psychiatrist at Montefiore Health System and professor and vice chair for faculty development and well-being at Albert Einstein College of Medicine, New York.

“Often women assumed more of the childcare and home-schooling responsibilities in their households. As [a] result, we know that more women dropped out of the workforce. Also, past studies indicate that women are more likely to report feelings of burnout than men,” Dr. Bernstein noted.

The volume of bureaucratic tasks is the main driver of gastroenterologist burnout, similar to that for physicians overall. Lack of respect from colleagues and more time devoted to electronic health records were also selected as major factors in this year’s report.

Gastroenterologists’ top ways to quell burnout are reducing their hours on the job (24%), changing workflow or staffing to ease their workload (23%), and taking advantage of meditation or other stress-reduction methods (18%) – similar to physicians overall.

Roughly one-third (34%) of gastroenterologists feel that their personality type contributes to their burnout, similar to physicians overall. Six in 10 gastroenterologists (60%) say burnout affects their relationships, similar to physicians overall (68%).
 

Seeking better work-life balance

More than half of gastroenterologists (57%) said they are willing to take a cut in pay in order to achieve a better work-life balance or have more free time – similar among physicians overall (55%).

About 16% of gastroenterologists reported clinical depression (severe depression lasting some time and not caused by grief), while 71% reported colloquial depression (feeling down, blue, sad).

About half (53%) of depressed gastroenterologists said their depression does not have an impact on relationships with patients.

Among those who saw an impact, the major behaviors they reported included being easily exasperated with patients (44%) and feeling less motivated to take patient notes carefully (20%).

To maintain well-being, gastroenterologists often choose to spend their time with their loved ones (59%), do the things they enjoy (58%), exercise (57%), get plenty of sleep (42%), and eat right (35%).

Perhaps not surprisingly, more gastroenterologists were happy with their work-life balance before the pandemic than now (70% vs. 44%). The same holds for physicians overall.

Before the pandemic, 22% of gastroenterologists reported being unhappy with their work-life balance. That has risen to 39% this year.

Most gastroenterologists are currently in a committed relationship, with 90% either married or living with a partner, a somewhat higher percentage than physicians overall (83%).

About 83% of gastroenterologists say they are in a “very good” or “good” marriage. This is down somewhat from the 2021 report (89%).

Nearly 6 in 10 gastroenterologists have partners who do not work in medicine. This is similar to the proportion among all physicians.

Findings from Medscape’s latest happiness, wellness, and lifestyle survey are based on 13,069 Medscape member physicians (61% male) practicing in the United States who completed an online survey conducted between June 29, 2021, and Sept. 26, 2021. Most respondents were between 35 and 64 years old.

A version of this article first appeared on Medscape.com.

The COVID-19 pandemic continues to take a toll on the happiness, wellness, and lifestyles of many segments of the population, but especially those in the health care field, including gastroenterologists.

The newly released Medscape Gastroenterologist Lifestyle, Happiness & Burnout Report 2022 explores gastroenterologists’ level of happiness in their personal and professional lives and how they maintain their mental and physical health.

Prior to the global pandemic, 8 in 10 (80%) gastroenterologists said they were “very” or “somewhat” happy outside of work, similar to physicians overall (81%).

But as the pandemic has worn on, feelings have shifted, and there are clear signs of stress and strain on those in the health care field.

Now, the percentage of gastroenterologists who say they are currently “very” or “somewhat” happy outside of work has dropped to 60%, about the same as physicians overall (59%).
 

Buried in paperwork

In 2021’s report, 42% of gastroenterologists reported burnout; that’s risen to 47% this year.

When it comes to burnout, gastroenterologists remain in the middle range of burned-out physicians.

Perhaps not surprising given the challenges of the COVID-19 pandemic, burnout rates are highest among emergency medicine and critical care specialists.

About half of gastroenterologists (52%) report being more burned out now than during the initial quarantine months of the pandemic, similar to physicians overall (55%). About 4 in 10 (39%) said their burnout was the same.

Female gastroenterologists report burnout at a greater rate than their male colleagues – 57% versus 46%.

“There’s no question that women have reported far more role strain during the pandemic than men,” said Carol A. Bernstein, MD, a psychiatrist at Montefiore Health System and professor and vice chair for faculty development and well-being at Albert Einstein College of Medicine, New York.

“Often women assumed more of the childcare and home-schooling responsibilities in their households. As [a] result, we know that more women dropped out of the workforce. Also, past studies indicate that women are more likely to report feelings of burnout than men,” Dr. Bernstein noted.

The volume of bureaucratic tasks is the main driver of gastroenterologist burnout, similar to that for physicians overall. Lack of respect from colleagues and more time devoted to electronic health records were also selected as major factors in this year’s report.

Gastroenterologists’ top ways to quell burnout are reducing their hours on the job (24%), changing workflow or staffing to ease their workload (23%), and taking advantage of meditation or other stress-reduction methods (18%) – similar to physicians overall.

Roughly one-third (34%) of gastroenterologists feel that their personality type contributes to their burnout, similar to physicians overall. Six in 10 gastroenterologists (60%) say burnout affects their relationships, similar to physicians overall (68%).
 

Seeking better work-life balance

More than half of gastroenterologists (57%) said they are willing to take a cut in pay in order to achieve a better work-life balance or have more free time – similar among physicians overall (55%).

About 16% of gastroenterologists reported clinical depression (severe depression lasting some time and not caused by grief), while 71% reported colloquial depression (feeling down, blue, sad).

About half (53%) of depressed gastroenterologists said their depression does not have an impact on relationships with patients.

Among those who saw an impact, the major behaviors they reported included being easily exasperated with patients (44%) and feeling less motivated to take patient notes carefully (20%).

To maintain well-being, gastroenterologists often choose to spend their time with their loved ones (59%), do the things they enjoy (58%), exercise (57%), get plenty of sleep (42%), and eat right (35%).

Perhaps not surprisingly, more gastroenterologists were happy with their work-life balance before the pandemic than now (70% vs. 44%). The same holds for physicians overall.

Before the pandemic, 22% of gastroenterologists reported being unhappy with their work-life balance. That has risen to 39% this year.

Most gastroenterologists are currently in a committed relationship, with 90% either married or living with a partner, a somewhat higher percentage than physicians overall (83%).

About 83% of gastroenterologists say they are in a “very good” or “good” marriage. This is down somewhat from the 2021 report (89%).

Nearly 6 in 10 gastroenterologists have partners who do not work in medicine. This is similar to the proportion among all physicians.

Findings from Medscape’s latest happiness, wellness, and lifestyle survey are based on 13,069 Medscape member physicians (61% male) practicing in the United States who completed an online survey conducted between June 29, 2021, and Sept. 26, 2021. Most respondents were between 35 and 64 years old.

A version of this article first appeared on Medscape.com.

The prevalence of metabolic syndrome varies according to how it is defined, but approximately 30% of psoriatic arthritis (PsA) patients met the criteria in a cohort study of 724 individuals, as did approximately 23%-63% of patients across multiple studies, investigators from Spain report.

Previous studies of people with PsA in particular suggest they are at an increased risk of cardiovascular disease and have a higher prevalence of metabolic syndrome, prompting recommendations on cardiovascular risk management for patients with PsA, wrote the authors, Ana Urruticoechea-Arana, MD, of the department of rheumatology, Hospital Can Misses, Ibiza, Spain, and colleagues.

However, assessing the prevalence of metabolic syndrome remains a challenge because the definition varies across studies, they noted.

For a more thorough assessment of the prevalence of metabolic syndrome in this population, the researchers conducted a study using two sources: a systematic literature review of 18 studies published up to March 2019, and data on patients with PsA enrolled in the CARMA (Spanish Cardiovascular in Rheumatology) project, a longitudinal cohort observational study of adults with inflammatory diseases in Spain. The findings were published March 1 in the Journal of Clinical Rheumatology.

The literature review included a total of a total of 2,452 patients with PsA, with a mean age between 42 and 59 years, and a mean disease duration ranging from 3 to 14 years.

The definitions of metabolic syndrome varied; the most common was the definition from the National Cholesterol Education Program (NECP ATP III). Other definitions used in the studies included those issued by the International Diabetes Federation, the World Health Organization, and the American Heart Association.

Across these studies, the rate of metabolic syndrome ranged from 23.5% to 62.9%. Prevalence was similar between men and women. One study that included patients with a PsA disease duration of only 3 years showed a prevalence of 38%, similar to the average prevalence overall. Another study showed a significantly higher prevalence of metabolic syndrome in patients with PsA and cutaneous psoriasis, compared with those without psoriasis (40.8% vs. 13.16%; P = .006).

The CARMA study included 724 patients with PsA; 45.4% were women and 21.8% were smokers. The mean age of the population in this study was 51 years, and the mean disease duration was 9 years. Overall, 222 patients (30.7%) met at least three criteria for metabolic syndrome, based on the NCEP ATP III definition. The most common abnormal findings for traditional cardiovascular risk factors in the CARMA cohort were high blood pressure (66.8%), hyperglycemia (42.6%), and hypertriglyceridemia (30.6%).

Despite the variation in prevalence of metabolic syndrome, depending on the definition used, the authors wrote, “It can be stated that the rate of [metabolic syndrome] in patients with PsA is in general very high, especially if we take into account the mean age of patients included in the studies.”

“These findings support the hypotheses that this increase in the inflammatory pathway in PsA may contribute a higher risk of cardiovascular events and [metabolic syndrome] in patients with PsA than patients with psoriasis alone, the risk being even higher in severe PsA,” and that insulin resistance, metabolic syndrome, and atherosclerotic events “may have a common inflammatory basis,” the researchers wrote in their discussion of the results.

The study findings were limited by several factors, most importantly the variation in definitions of metabolic syndrome in the literature review, which limits the generalizability of the results, the researchers said. Limitations of the CARMA study include the focus only on patients who were being cared for in hospitals, which might yield an overestimation of metabolic syndrome, they added.

However, the results support findings from previous studies and highlight the need for proper assessment of body weight and cardiovascular risk factors in patients with PsA at the onset of disease, they said.

“Furthermore, it is necessary to conduct more research to standardize (and modify as appropriate) the definition of [metabolic syndrome] and establish the best strategy for managing it in these patients,” they concluded.

The study was funded by an independent grant from UCB Pharma. One author disclosed receiving grants from Pfizer, Abbvie, Novartis, Roche, UCB, Sanofi, BMS, Lilly, MSD, and Janssen. Lead author Dr. Urruticoechea-Arana and the other authors had no disclosures.

The prevalence of metabolic syndrome varies according to how it is defined, but approximately 30% of psoriatic arthritis (PsA) patients met the criteria in a cohort study of 724 individuals, as did approximately 23%-63% of patients across multiple studies, investigators from Spain report.

Previous studies of people with PsA in particular suggest they are at an increased risk of cardiovascular disease and have a higher prevalence of metabolic syndrome, prompting recommendations on cardiovascular risk management for patients with PsA, wrote the authors, Ana Urruticoechea-Arana, MD, of the department of rheumatology, Hospital Can Misses, Ibiza, Spain, and colleagues.

However, assessing the prevalence of metabolic syndrome remains a challenge because the definition varies across studies, they noted.

For a more thorough assessment of the prevalence of metabolic syndrome in this population, the researchers conducted a study using two sources: a systematic literature review of 18 studies published up to March 2019, and data on patients with PsA enrolled in the CARMA (Spanish Cardiovascular in Rheumatology) project, a longitudinal cohort observational study of adults with inflammatory diseases in Spain. The findings were published March 1 in the Journal of Clinical Rheumatology.

The literature review included a total of a total of 2,452 patients with PsA, with a mean age between 42 and 59 years, and a mean disease duration ranging from 3 to 14 years.

The definitions of metabolic syndrome varied; the most common was the definition from the National Cholesterol Education Program (NECP ATP III). Other definitions used in the studies included those issued by the International Diabetes Federation, the World Health Organization, and the American Heart Association.

Across these studies, the rate of metabolic syndrome ranged from 23.5% to 62.9%. Prevalence was similar between men and women. One study that included patients with a PsA disease duration of only 3 years showed a prevalence of 38%, similar to the average prevalence overall. Another study showed a significantly higher prevalence of metabolic syndrome in patients with PsA and cutaneous psoriasis, compared with those without psoriasis (40.8% vs. 13.16%; P = .006).

The CARMA study included 724 patients with PsA; 45.4% were women and 21.8% were smokers. The mean age of the population in this study was 51 years, and the mean disease duration was 9 years. Overall, 222 patients (30.7%) met at least three criteria for metabolic syndrome, based on the NCEP ATP III definition. The most common abnormal findings for traditional cardiovascular risk factors in the CARMA cohort were high blood pressure (66.8%), hyperglycemia (42.6%), and hypertriglyceridemia (30.6%).

Despite the variation in prevalence of metabolic syndrome, depending on the definition used, the authors wrote, “It can be stated that the rate of [metabolic syndrome] in patients with PsA is in general very high, especially if we take into account the mean age of patients included in the studies.”

“These findings support the hypotheses that this increase in the inflammatory pathway in PsA may contribute a higher risk of cardiovascular events and [metabolic syndrome] in patients with PsA than patients with psoriasis alone, the risk being even higher in severe PsA,” and that insulin resistance, metabolic syndrome, and atherosclerotic events “may have a common inflammatory basis,” the researchers wrote in their discussion of the results.

The study findings were limited by several factors, most importantly the variation in definitions of metabolic syndrome in the literature review, which limits the generalizability of the results, the researchers said. Limitations of the CARMA study include the focus only on patients who were being cared for in hospitals, which might yield an overestimation of metabolic syndrome, they added.

However, the results support findings from previous studies and highlight the need for proper assessment of body weight and cardiovascular risk factors in patients with PsA at the onset of disease, they said.

“Furthermore, it is necessary to conduct more research to standardize (and modify as appropriate) the definition of [metabolic syndrome] and establish the best strategy for managing it in these patients,” they concluded.

The study was funded by an independent grant from UCB Pharma. One author disclosed receiving grants from Pfizer, Abbvie, Novartis, Roche, UCB, Sanofi, BMS, Lilly, MSD, and Janssen. Lead author Dr. Urruticoechea-Arana and the other authors had no disclosures.

The prevalence of metabolic syndrome varies according to how it is defined, but approximately 30% of psoriatic arthritis (PsA) patients met the criteria in a cohort study of 724 individuals, as did approximately 23%-63% of patients across multiple studies, investigators from Spain report.

Previous studies of people with PsA in particular suggest they are at an increased risk of cardiovascular disease and have a higher prevalence of metabolic syndrome, prompting recommendations on cardiovascular risk management for patients with PsA, wrote the authors, Ana Urruticoechea-Arana, MD, of the department of rheumatology, Hospital Can Misses, Ibiza, Spain, and colleagues.

However, assessing the prevalence of metabolic syndrome remains a challenge because the definition varies across studies, they noted.

For a more thorough assessment of the prevalence of metabolic syndrome in this population, the researchers conducted a study using two sources: a systematic literature review of 18 studies published up to March 2019, and data on patients with PsA enrolled in the CARMA (Spanish Cardiovascular in Rheumatology) project, a longitudinal cohort observational study of adults with inflammatory diseases in Spain. The findings were published March 1 in the Journal of Clinical Rheumatology.

The literature review included a total of a total of 2,452 patients with PsA, with a mean age between 42 and 59 years, and a mean disease duration ranging from 3 to 14 years.

The definitions of metabolic syndrome varied; the most common was the definition from the National Cholesterol Education Program (NECP ATP III). Other definitions used in the studies included those issued by the International Diabetes Federation, the World Health Organization, and the American Heart Association.

Across these studies, the rate of metabolic syndrome ranged from 23.5% to 62.9%. Prevalence was similar between men and women. One study that included patients with a PsA disease duration of only 3 years showed a prevalence of 38%, similar to the average prevalence overall. Another study showed a significantly higher prevalence of metabolic syndrome in patients with PsA and cutaneous psoriasis, compared with those without psoriasis (40.8% vs. 13.16%; P = .006).

The CARMA study included 724 patients with PsA; 45.4% were women and 21.8% were smokers. The mean age of the population in this study was 51 years, and the mean disease duration was 9 years. Overall, 222 patients (30.7%) met at least three criteria for metabolic syndrome, based on the NCEP ATP III definition. The most common abnormal findings for traditional cardiovascular risk factors in the CARMA cohort were high blood pressure (66.8%), hyperglycemia (42.6%), and hypertriglyceridemia (30.6%).

Despite the variation in prevalence of metabolic syndrome, depending on the definition used, the authors wrote, “It can be stated that the rate of [metabolic syndrome] in patients with PsA is in general very high, especially if we take into account the mean age of patients included in the studies.”

“These findings support the hypotheses that this increase in the inflammatory pathway in PsA may contribute a higher risk of cardiovascular events and [metabolic syndrome] in patients with PsA than patients with psoriasis alone, the risk being even higher in severe PsA,” and that insulin resistance, metabolic syndrome, and atherosclerotic events “may have a common inflammatory basis,” the researchers wrote in their discussion of the results.

The study findings were limited by several factors, most importantly the variation in definitions of metabolic syndrome in the literature review, which limits the generalizability of the results, the researchers said. Limitations of the CARMA study include the focus only on patients who were being cared for in hospitals, which might yield an overestimation of metabolic syndrome, they added.

However, the results support findings from previous studies and highlight the need for proper assessment of body weight and cardiovascular risk factors in patients with PsA at the onset of disease, they said.

“Furthermore, it is necessary to conduct more research to standardize (and modify as appropriate) the definition of [metabolic syndrome] and establish the best strategy for managing it in these patients,” they concluded.

The study was funded by an independent grant from UCB Pharma. One author disclosed receiving grants from Pfizer, Abbvie, Novartis, Roche, UCB, Sanofi, BMS, Lilly, MSD, and Janssen. Lead author Dr. Urruticoechea-Arana and the other authors had no disclosures.