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Study offers snapshot of esophageal strictures in EB patients
LAKE TAHOE, CALIF. – and direct visualization of these strictures is the preferred method of diagnosis. Those are key findings from a multicenter study that lead author Elena Pope, MD, discussed at the annual meeting of the Society for Pediatric Dermatology.
According to Dr. Pope, who heads the section of dermatology at the Hospital for Sick Children, Toronto, an estimated 10%-17% of epidermolysis bullosa (EB) patients experience strictures, with an overrepresentation in the recessive dystrophic EB subtype in up to 80% of cases. The risk increases with age. “What remains unknown is the best short- and long-term intervention to manage the strictures and predictors/associations for stricture-free episodes,” Dr. Pope said. “The objectives of the current study were to determine the prevalence and predisposing factors for strictures in EB, management options, patient outcomes, and predictors for recurrences and stricture-free intervals.”
She and her associates at seven centers worldwide collected data on 125 EB patients who experienced at least one episode of esophageal stricture. Data was analyzed descriptively and with ANOVA regression analysis for associations/predictors for recurrences/episode-free intervals.
The researchers evaluated 497 stricture events in the 125 patients. A slight female predominance was noted (53%), and the mean age of the first episode was 12.7 years, “which is a little bit older” than the age found in previously published data, Dr. Pope said. As expected, dystrophic EB patients made up most of the sample (98.4%); of these 123 patients, recessive dystrophic EB severe generalized subtype – approaching 50% – was the most common, followed by the recessive dystrophic EB severe intermediate subtype (almost 21%), the dominant dystrophic EB generalized subtype (7%), and other types of dystrophic EB (almost 26%).
The median body mass index percentile for age was 6.3, “so these were patients who were severely malnourished, probably as a result of their strictures as well as their underlying disease,” Dr. Pope said.
As expected, dysphagia was a presenting symptom in most patients (85.5%), while 29.8% presented with inability to swallow solids. The preferred method of evaluation was video fluoroscopy (57.7%), and less commonly with barium swallow (22.3%) or with clinical symptoms alone (0.1%). The mean number of strictures was 1.69; 76.7% were located in the cervical area, 56.7% were located in the thoracic area, and 9.7% were located in the abdominal area. Most patients (76%) had lesions that were 1 cm or longer in size.
Fluoroscopy guidance was the most common method of dilatation (in 45.2% of cases), followed by retrograde endoscopy was (33%), antegrade endoscopy (19.1%), and bougienage (0.1%). General anesthesia was used in most cases (87.6%), and corticosteroids were used around the dilatation in 90.4% of patients. The mean duration of medication use was about 5 days.
As for outcomes after dilatation, 92.2% of strictures completely resolved, 3.8% were partially resolved, 3.9% were not resolved, and 2.7% had complications. The median interval between dilatations was 7 months. Fluoroscopy-guided balloon dilatation was associated with the longest esophageal stricture-free duration (mean of 13.83 months vs. 8.75 months; P less than .001), followed by retrograde endoscopy (mean of 13.10 months vs. 7.85 months; P less than .001), and antegrade endoscopy (mean of 7.63 months vs. 11.46 months; P = .024). “I think this is interesting,” said Dr. Pope, who is also a professor of pediatrics at the University of Toronto. “I think the difference occurs because if you use the endoscopy, which a rigid tube, you can potentially cause more damage, and more long-term scarring.”
Another predictor of esophageal stricture-free episodes was systemic corticosteroid use (a mean of 25.28 months vs. 10.24 months; P less than .001) around the time of the dilatation procedure. “By using systemic steroids, you’re actually decreasing some of the inflammation associated with the trauma of the procedure decreasing the chances of strictures formation,” she said.
Dr. Pope recommended that future studies evaluate the benefit of periprocedural medical interventions on increasing the intervals between esophageal stricture occurrences.
The study was supported by an unrestricted grant from the Epidermolysis Bullosa Research Foundation. She reported having no financial disclosures.
LAKE TAHOE, CALIF. – and direct visualization of these strictures is the preferred method of diagnosis. Those are key findings from a multicenter study that lead author Elena Pope, MD, discussed at the annual meeting of the Society for Pediatric Dermatology.
According to Dr. Pope, who heads the section of dermatology at the Hospital for Sick Children, Toronto, an estimated 10%-17% of epidermolysis bullosa (EB) patients experience strictures, with an overrepresentation in the recessive dystrophic EB subtype in up to 80% of cases. The risk increases with age. “What remains unknown is the best short- and long-term intervention to manage the strictures and predictors/associations for stricture-free episodes,” Dr. Pope said. “The objectives of the current study were to determine the prevalence and predisposing factors for strictures in EB, management options, patient outcomes, and predictors for recurrences and stricture-free intervals.”
She and her associates at seven centers worldwide collected data on 125 EB patients who experienced at least one episode of esophageal stricture. Data was analyzed descriptively and with ANOVA regression analysis for associations/predictors for recurrences/episode-free intervals.
The researchers evaluated 497 stricture events in the 125 patients. A slight female predominance was noted (53%), and the mean age of the first episode was 12.7 years, “which is a little bit older” than the age found in previously published data, Dr. Pope said. As expected, dystrophic EB patients made up most of the sample (98.4%); of these 123 patients, recessive dystrophic EB severe generalized subtype – approaching 50% – was the most common, followed by the recessive dystrophic EB severe intermediate subtype (almost 21%), the dominant dystrophic EB generalized subtype (7%), and other types of dystrophic EB (almost 26%).
The median body mass index percentile for age was 6.3, “so these were patients who were severely malnourished, probably as a result of their strictures as well as their underlying disease,” Dr. Pope said.
As expected, dysphagia was a presenting symptom in most patients (85.5%), while 29.8% presented with inability to swallow solids. The preferred method of evaluation was video fluoroscopy (57.7%), and less commonly with barium swallow (22.3%) or with clinical symptoms alone (0.1%). The mean number of strictures was 1.69; 76.7% were located in the cervical area, 56.7% were located in the thoracic area, and 9.7% were located in the abdominal area. Most patients (76%) had lesions that were 1 cm or longer in size.
Fluoroscopy guidance was the most common method of dilatation (in 45.2% of cases), followed by retrograde endoscopy was (33%), antegrade endoscopy (19.1%), and bougienage (0.1%). General anesthesia was used in most cases (87.6%), and corticosteroids were used around the dilatation in 90.4% of patients. The mean duration of medication use was about 5 days.
As for outcomes after dilatation, 92.2% of strictures completely resolved, 3.8% were partially resolved, 3.9% were not resolved, and 2.7% had complications. The median interval between dilatations was 7 months. Fluoroscopy-guided balloon dilatation was associated with the longest esophageal stricture-free duration (mean of 13.83 months vs. 8.75 months; P less than .001), followed by retrograde endoscopy (mean of 13.10 months vs. 7.85 months; P less than .001), and antegrade endoscopy (mean of 7.63 months vs. 11.46 months; P = .024). “I think this is interesting,” said Dr. Pope, who is also a professor of pediatrics at the University of Toronto. “I think the difference occurs because if you use the endoscopy, which a rigid tube, you can potentially cause more damage, and more long-term scarring.”
Another predictor of esophageal stricture-free episodes was systemic corticosteroid use (a mean of 25.28 months vs. 10.24 months; P less than .001) around the time of the dilatation procedure. “By using systemic steroids, you’re actually decreasing some of the inflammation associated with the trauma of the procedure decreasing the chances of strictures formation,” she said.
Dr. Pope recommended that future studies evaluate the benefit of periprocedural medical interventions on increasing the intervals between esophageal stricture occurrences.
The study was supported by an unrestricted grant from the Epidermolysis Bullosa Research Foundation. She reported having no financial disclosures.
LAKE TAHOE, CALIF. – and direct visualization of these strictures is the preferred method of diagnosis. Those are key findings from a multicenter study that lead author Elena Pope, MD, discussed at the annual meeting of the Society for Pediatric Dermatology.
According to Dr. Pope, who heads the section of dermatology at the Hospital for Sick Children, Toronto, an estimated 10%-17% of epidermolysis bullosa (EB) patients experience strictures, with an overrepresentation in the recessive dystrophic EB subtype in up to 80% of cases. The risk increases with age. “What remains unknown is the best short- and long-term intervention to manage the strictures and predictors/associations for stricture-free episodes,” Dr. Pope said. “The objectives of the current study were to determine the prevalence and predisposing factors for strictures in EB, management options, patient outcomes, and predictors for recurrences and stricture-free intervals.”
She and her associates at seven centers worldwide collected data on 125 EB patients who experienced at least one episode of esophageal stricture. Data was analyzed descriptively and with ANOVA regression analysis for associations/predictors for recurrences/episode-free intervals.
The researchers evaluated 497 stricture events in the 125 patients. A slight female predominance was noted (53%), and the mean age of the first episode was 12.7 years, “which is a little bit older” than the age found in previously published data, Dr. Pope said. As expected, dystrophic EB patients made up most of the sample (98.4%); of these 123 patients, recessive dystrophic EB severe generalized subtype – approaching 50% – was the most common, followed by the recessive dystrophic EB severe intermediate subtype (almost 21%), the dominant dystrophic EB generalized subtype (7%), and other types of dystrophic EB (almost 26%).
The median body mass index percentile for age was 6.3, “so these were patients who were severely malnourished, probably as a result of their strictures as well as their underlying disease,” Dr. Pope said.
As expected, dysphagia was a presenting symptom in most patients (85.5%), while 29.8% presented with inability to swallow solids. The preferred method of evaluation was video fluoroscopy (57.7%), and less commonly with barium swallow (22.3%) or with clinical symptoms alone (0.1%). The mean number of strictures was 1.69; 76.7% were located in the cervical area, 56.7% were located in the thoracic area, and 9.7% were located in the abdominal area. Most patients (76%) had lesions that were 1 cm or longer in size.
Fluoroscopy guidance was the most common method of dilatation (in 45.2% of cases), followed by retrograde endoscopy was (33%), antegrade endoscopy (19.1%), and bougienage (0.1%). General anesthesia was used in most cases (87.6%), and corticosteroids were used around the dilatation in 90.4% of patients. The mean duration of medication use was about 5 days.
As for outcomes after dilatation, 92.2% of strictures completely resolved, 3.8% were partially resolved, 3.9% were not resolved, and 2.7% had complications. The median interval between dilatations was 7 months. Fluoroscopy-guided balloon dilatation was associated with the longest esophageal stricture-free duration (mean of 13.83 months vs. 8.75 months; P less than .001), followed by retrograde endoscopy (mean of 13.10 months vs. 7.85 months; P less than .001), and antegrade endoscopy (mean of 7.63 months vs. 11.46 months; P = .024). “I think this is interesting,” said Dr. Pope, who is also a professor of pediatrics at the University of Toronto. “I think the difference occurs because if you use the endoscopy, which a rigid tube, you can potentially cause more damage, and more long-term scarring.”
Another predictor of esophageal stricture-free episodes was systemic corticosteroid use (a mean of 25.28 months vs. 10.24 months; P less than .001) around the time of the dilatation procedure. “By using systemic steroids, you’re actually decreasing some of the inflammation associated with the trauma of the procedure decreasing the chances of strictures formation,” she said.
Dr. Pope recommended that future studies evaluate the benefit of periprocedural medical interventions on increasing the intervals between esophageal stricture occurrences.
The study was supported by an unrestricted grant from the Epidermolysis Bullosa Research Foundation. She reported having no financial disclosures.
REPORTING FROM SPD 2018
Key clinical point: Esophageal strictures are common complications of patients with severe types of epidermolysis bullosa.
Major finding: Most epidermolysis bullosa patients (85.5%) presented with dysphagia, while the preferred method of evaluation was video fluoroscopy (57.7%).
Study details: A multicenter study of 497 stricture events in 125 patients with epidermolysis bullosa.
Disclosures: The study was supported by an unrestricted grant from the Epidermolysis Bullosa Research Foundation. Dr. Pope reported having no financial disclosures.
Four syndromes suggest life-threatening PVL-positive S. aureus infection
MALMO, SWEDEN – Methicillin-resistant Staphylococcus aureus gets the blame in the Americas as the main cause of a great wave of community-acquired severe invasive staphylococcal infections in children and adolescents during the past nearly 2 decades, but many European pediatric infectious disease specialists believe that Panton-Valentine leukocidin (PVL), a frequent co-traveler with MRSA, is the true bad actor.
“The American literature focused first on MRSA, but we’ve seen very similar, very severe cases with MSSA [methicillin-susceptible S. aureus] PVL-positive and MRSA PVL-positive infections,” Pablo Rojo, MD, PhD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.
“It is only because at the beginning there were so many MRSA cases in the States that they thought that was the driver of the disease. It is still unclear. There is still a discussion. But I wanted to bring you my opinion and that of many other authors that it’s mostly PVL-associated,” added Dr. Rojo of Complutense University in Madrid.
He was senior author of a multinational European and Israeli prospective study of risk factors associated with the severity of invasive community-acquired S. aureus infections in children, with invasive infection being defined as hospitalization for an infection with S. aureus isolated from a normally sterile body site such as blood, bone, or cerebrospinal fluid, or S. aureus pneumonia. They identified 152 affected children, 17% of whom had severe community-acquired invasive S. aureus, defined by death or admission to a pediatric intensive care unit due to respiratory failure or hemodynamic instability.
The prevalence of PVL-positive S. aureus infection in the overall invasive infection group was 19%, while 8% of the isolates were MRSA. while MRSA was not associated with a significantly increased risk. The other independent risk factors for severe outcome were pneumonia, with an adjusted 13-fold increased risk, and leukopenia at admission, with an associated 18-fold risk (Clin Microbiol Infect. 2016 Jul;22[7]:643.e1-6.).
Of note, the virulence of PVL stems from the pore-forming toxin’s ability to lyse white blood cells. Because a leukocyte count is always available once a patient reaches the ED, severe leukopenia as defined by a count of less than 3,000 cells/mm3 at admission becomes a useful early marker of the likely severity of any case of S. aureus invasive disease, according to Dr. Rojo.
He highlighted four key syndromes involving severe invasive S. aureus infection in previously healthy children and adolescents that entail a high likelihood of being PVL positive and should cause physicians to run – not walk – to start appropriate empiric therapy. He also described the treatment regimen that he and other European thought leaders recommend for severe PVL-positive S. aureus invasive infections.
The microbiologic diagnosis of PVL can be made by ELISA (enzyme-linked immunoassay) to detect the toxin in an S. aureus isolate, by a rapid monoclonal antibody test, or by polymerase chain reaction to detect PVL genes in an S. aureus isolate. But don’t wait for test results to initiate treatment because these are high-mortality syndromes, he advised.
“Many people tell me, ‘My lab doesn’t have a way to diagnose PVL.’ And it’s true, it’s not available in real life at many hospitals. My message to you is that you don’t need to wait for a microbiological diagnosis or the results to come back from a sample you have sent to the reference lab in the main referral center. We can base our diagnosis and decision to treat on clinical grounds if we focus on these four very uncommon syndromes involving invasive S. aureus infection. I think if you have any child with these symptoms you have to manage them on the assumption that PVL is present,” said Dr. Rojo, principal investigator of the European Project on Invasive S. aureus Pediatric Infections.
The four key syndromes
The four syndromes are severe S. aureus pneumonia, S. aureus bone and joint infections with multiple foci, S. aureus osteomyelitis complicated by deep vein thrombosis, and invasive S. aureus infection plus shock.
- Severe S. aureus pneumonia. Investigators at Claude Bernard University in Lyon, France, have done extensive pioneering work on severe PVL-positive S. aureus invasive infections in children. In an early paper, they highlighted the characteristics that distinguish severe PVL-positive pneumonia: it typically occurs in previously healthy children and adolescents without underlying comorbid conditions, and it is often preceded by a influenza-like syndrome followed by an acute severe pneumonia with hemoptysis. Mortality was very high in this early series, with nearly half of the patients being dead within the first several days after admission (Lancet. 2002 Mar 2;359[9308]:753-9).
- Severe osteomyelitis. Investigators at Baylor College of Medicine, Houston, were among the first to observe that osteomyelitis caused by PVL-positive strains of S. aureus are associated with more severe local disease, with multiple affected areas, bigger abscesses, a greater systemic inflammatory response, and more surgeries required compared with osteomyelitis caused by PVL-negative S. aureus (Pediatrics. 2006 Feb;117[2]:433-40).
- Osteomyelitis with deep vein thrombosis. When a child hospitalized for acute hematogenous osteomyelitis due to S. aureus develops difficulty breathing, that’s a red flag for a severe PVL-positive infection involving deep vein thrombosis. Indeed, investigators at the Leeds (England) General Infirmary have reported that deep vein thrombosis in the setting of S. aureus osteomyelitis is associated with a greater than eightfold increased likelihood of a PVL-positive infection (Br J Hosp Med [Lond]. 2015 Jan;76[1]:18-24). Also, patients with PVL-positive osteomyelitis and deep vein thrombosis are prone to formation of septic emboli.
- Osteomyelitis with septic shock. The Lyon group compared outcomes in 14 pediatric patients with PVL-positive S. aureus osteomyelitis and a control group of 17 patients with PVL-negative disease. All 14 PVL-positive patients had severe sepsis and 6 of them had septic shock. In contrast, none of the controls did. Median duration of hospitalization was 46 days in the PVL-positive group, compared with 13 days in controls (Pediatr Infect Dis J. 2007 Nov;26[11]:1042-8).
Treatment
No randomized trials exist to guide treatment, but Dr. Rojo recommends the protocol utilized by the Lyon group: a bactericidal antibiotic – vancomycin or a beta-lactam – to take on the S. aureus, coupled with a ribosomally active antibiotic – clindamycin or linezolid – to suppress the PVL toxin’s virulence expression. The French group cites both in vitro and in vivo evidence that clindamycin and linezolid in their standard dosing have such an antitoxin effect (Clin Microbiol Rev. 2017 Oct;30[4]:887-917).
In addition, Dr. Rojo recommends utilizing any of the commercially available intravenous immunoglobulin (IVIG) products on the basis of work by investigators at Vanderbilt University in Nashville, Tenn., who have demonstrated that these products contain functional neutralizing antibodies against S. aureus leukocidins. This observation provides a likely explanation for anecdotal reports of improved outcomes in IVIG-treated patients with toxin-associated staphylococcal disease (Antimicrob Agents Chemother. 2017 Oct 24;61[11]. pii: e00968-17).
Challenged as to when specifically he would use IVIG in light of the global shortage of immunoglobulins, Dr. Rojo replied: “Not in every invasive S. aureus infection, but in serious infections that are PVL positive. I think if you have a child with one of these four syndromes who is in a pediatric ICU, you should use it. I mean, the mortality is around 30% in healthy children, so you would not stop from giving it. The risk of giving IVIG is very low, no side effects, so I highly recommend it for these severe cases.”
He reported having no financial conflicts.
MALMO, SWEDEN – Methicillin-resistant Staphylococcus aureus gets the blame in the Americas as the main cause of a great wave of community-acquired severe invasive staphylococcal infections in children and adolescents during the past nearly 2 decades, but many European pediatric infectious disease specialists believe that Panton-Valentine leukocidin (PVL), a frequent co-traveler with MRSA, is the true bad actor.
“The American literature focused first on MRSA, but we’ve seen very similar, very severe cases with MSSA [methicillin-susceptible S. aureus] PVL-positive and MRSA PVL-positive infections,” Pablo Rojo, MD, PhD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.
“It is only because at the beginning there were so many MRSA cases in the States that they thought that was the driver of the disease. It is still unclear. There is still a discussion. But I wanted to bring you my opinion and that of many other authors that it’s mostly PVL-associated,” added Dr. Rojo of Complutense University in Madrid.
He was senior author of a multinational European and Israeli prospective study of risk factors associated with the severity of invasive community-acquired S. aureus infections in children, with invasive infection being defined as hospitalization for an infection with S. aureus isolated from a normally sterile body site such as blood, bone, or cerebrospinal fluid, or S. aureus pneumonia. They identified 152 affected children, 17% of whom had severe community-acquired invasive S. aureus, defined by death or admission to a pediatric intensive care unit due to respiratory failure or hemodynamic instability.
The prevalence of PVL-positive S. aureus infection in the overall invasive infection group was 19%, while 8% of the isolates were MRSA. while MRSA was not associated with a significantly increased risk. The other independent risk factors for severe outcome were pneumonia, with an adjusted 13-fold increased risk, and leukopenia at admission, with an associated 18-fold risk (Clin Microbiol Infect. 2016 Jul;22[7]:643.e1-6.).
Of note, the virulence of PVL stems from the pore-forming toxin’s ability to lyse white blood cells. Because a leukocyte count is always available once a patient reaches the ED, severe leukopenia as defined by a count of less than 3,000 cells/mm3 at admission becomes a useful early marker of the likely severity of any case of S. aureus invasive disease, according to Dr. Rojo.
He highlighted four key syndromes involving severe invasive S. aureus infection in previously healthy children and adolescents that entail a high likelihood of being PVL positive and should cause physicians to run – not walk – to start appropriate empiric therapy. He also described the treatment regimen that he and other European thought leaders recommend for severe PVL-positive S. aureus invasive infections.
The microbiologic diagnosis of PVL can be made by ELISA (enzyme-linked immunoassay) to detect the toxin in an S. aureus isolate, by a rapid monoclonal antibody test, or by polymerase chain reaction to detect PVL genes in an S. aureus isolate. But don’t wait for test results to initiate treatment because these are high-mortality syndromes, he advised.
“Many people tell me, ‘My lab doesn’t have a way to diagnose PVL.’ And it’s true, it’s not available in real life at many hospitals. My message to you is that you don’t need to wait for a microbiological diagnosis or the results to come back from a sample you have sent to the reference lab in the main referral center. We can base our diagnosis and decision to treat on clinical grounds if we focus on these four very uncommon syndromes involving invasive S. aureus infection. I think if you have any child with these symptoms you have to manage them on the assumption that PVL is present,” said Dr. Rojo, principal investigator of the European Project on Invasive S. aureus Pediatric Infections.
The four key syndromes
The four syndromes are severe S. aureus pneumonia, S. aureus bone and joint infections with multiple foci, S. aureus osteomyelitis complicated by deep vein thrombosis, and invasive S. aureus infection plus shock.
- Severe S. aureus pneumonia. Investigators at Claude Bernard University in Lyon, France, have done extensive pioneering work on severe PVL-positive S. aureus invasive infections in children. In an early paper, they highlighted the characteristics that distinguish severe PVL-positive pneumonia: it typically occurs in previously healthy children and adolescents without underlying comorbid conditions, and it is often preceded by a influenza-like syndrome followed by an acute severe pneumonia with hemoptysis. Mortality was very high in this early series, with nearly half of the patients being dead within the first several days after admission (Lancet. 2002 Mar 2;359[9308]:753-9).
- Severe osteomyelitis. Investigators at Baylor College of Medicine, Houston, were among the first to observe that osteomyelitis caused by PVL-positive strains of S. aureus are associated with more severe local disease, with multiple affected areas, bigger abscesses, a greater systemic inflammatory response, and more surgeries required compared with osteomyelitis caused by PVL-negative S. aureus (Pediatrics. 2006 Feb;117[2]:433-40).
- Osteomyelitis with deep vein thrombosis. When a child hospitalized for acute hematogenous osteomyelitis due to S. aureus develops difficulty breathing, that’s a red flag for a severe PVL-positive infection involving deep vein thrombosis. Indeed, investigators at the Leeds (England) General Infirmary have reported that deep vein thrombosis in the setting of S. aureus osteomyelitis is associated with a greater than eightfold increased likelihood of a PVL-positive infection (Br J Hosp Med [Lond]. 2015 Jan;76[1]:18-24). Also, patients with PVL-positive osteomyelitis and deep vein thrombosis are prone to formation of septic emboli.
- Osteomyelitis with septic shock. The Lyon group compared outcomes in 14 pediatric patients with PVL-positive S. aureus osteomyelitis and a control group of 17 patients with PVL-negative disease. All 14 PVL-positive patients had severe sepsis and 6 of them had septic shock. In contrast, none of the controls did. Median duration of hospitalization was 46 days in the PVL-positive group, compared with 13 days in controls (Pediatr Infect Dis J. 2007 Nov;26[11]:1042-8).
Treatment
No randomized trials exist to guide treatment, but Dr. Rojo recommends the protocol utilized by the Lyon group: a bactericidal antibiotic – vancomycin or a beta-lactam – to take on the S. aureus, coupled with a ribosomally active antibiotic – clindamycin or linezolid – to suppress the PVL toxin’s virulence expression. The French group cites both in vitro and in vivo evidence that clindamycin and linezolid in their standard dosing have such an antitoxin effect (Clin Microbiol Rev. 2017 Oct;30[4]:887-917).
In addition, Dr. Rojo recommends utilizing any of the commercially available intravenous immunoglobulin (IVIG) products on the basis of work by investigators at Vanderbilt University in Nashville, Tenn., who have demonstrated that these products contain functional neutralizing antibodies against S. aureus leukocidins. This observation provides a likely explanation for anecdotal reports of improved outcomes in IVIG-treated patients with toxin-associated staphylococcal disease (Antimicrob Agents Chemother. 2017 Oct 24;61[11]. pii: e00968-17).
Challenged as to when specifically he would use IVIG in light of the global shortage of immunoglobulins, Dr. Rojo replied: “Not in every invasive S. aureus infection, but in serious infections that are PVL positive. I think if you have a child with one of these four syndromes who is in a pediatric ICU, you should use it. I mean, the mortality is around 30% in healthy children, so you would not stop from giving it. The risk of giving IVIG is very low, no side effects, so I highly recommend it for these severe cases.”
He reported having no financial conflicts.
MALMO, SWEDEN – Methicillin-resistant Staphylococcus aureus gets the blame in the Americas as the main cause of a great wave of community-acquired severe invasive staphylococcal infections in children and adolescents during the past nearly 2 decades, but many European pediatric infectious disease specialists believe that Panton-Valentine leukocidin (PVL), a frequent co-traveler with MRSA, is the true bad actor.
“The American literature focused first on MRSA, but we’ve seen very similar, very severe cases with MSSA [methicillin-susceptible S. aureus] PVL-positive and MRSA PVL-positive infections,” Pablo Rojo, MD, PhD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.
“It is only because at the beginning there were so many MRSA cases in the States that they thought that was the driver of the disease. It is still unclear. There is still a discussion. But I wanted to bring you my opinion and that of many other authors that it’s mostly PVL-associated,” added Dr. Rojo of Complutense University in Madrid.
He was senior author of a multinational European and Israeli prospective study of risk factors associated with the severity of invasive community-acquired S. aureus infections in children, with invasive infection being defined as hospitalization for an infection with S. aureus isolated from a normally sterile body site such as blood, bone, or cerebrospinal fluid, or S. aureus pneumonia. They identified 152 affected children, 17% of whom had severe community-acquired invasive S. aureus, defined by death or admission to a pediatric intensive care unit due to respiratory failure or hemodynamic instability.
The prevalence of PVL-positive S. aureus infection in the overall invasive infection group was 19%, while 8% of the isolates were MRSA. while MRSA was not associated with a significantly increased risk. The other independent risk factors for severe outcome were pneumonia, with an adjusted 13-fold increased risk, and leukopenia at admission, with an associated 18-fold risk (Clin Microbiol Infect. 2016 Jul;22[7]:643.e1-6.).
Of note, the virulence of PVL stems from the pore-forming toxin’s ability to lyse white blood cells. Because a leukocyte count is always available once a patient reaches the ED, severe leukopenia as defined by a count of less than 3,000 cells/mm3 at admission becomes a useful early marker of the likely severity of any case of S. aureus invasive disease, according to Dr. Rojo.
He highlighted four key syndromes involving severe invasive S. aureus infection in previously healthy children and adolescents that entail a high likelihood of being PVL positive and should cause physicians to run – not walk – to start appropriate empiric therapy. He also described the treatment regimen that he and other European thought leaders recommend for severe PVL-positive S. aureus invasive infections.
The microbiologic diagnosis of PVL can be made by ELISA (enzyme-linked immunoassay) to detect the toxin in an S. aureus isolate, by a rapid monoclonal antibody test, or by polymerase chain reaction to detect PVL genes in an S. aureus isolate. But don’t wait for test results to initiate treatment because these are high-mortality syndromes, he advised.
“Many people tell me, ‘My lab doesn’t have a way to diagnose PVL.’ And it’s true, it’s not available in real life at many hospitals. My message to you is that you don’t need to wait for a microbiological diagnosis or the results to come back from a sample you have sent to the reference lab in the main referral center. We can base our diagnosis and decision to treat on clinical grounds if we focus on these four very uncommon syndromes involving invasive S. aureus infection. I think if you have any child with these symptoms you have to manage them on the assumption that PVL is present,” said Dr. Rojo, principal investigator of the European Project on Invasive S. aureus Pediatric Infections.
The four key syndromes
The four syndromes are severe S. aureus pneumonia, S. aureus bone and joint infections with multiple foci, S. aureus osteomyelitis complicated by deep vein thrombosis, and invasive S. aureus infection plus shock.
- Severe S. aureus pneumonia. Investigators at Claude Bernard University in Lyon, France, have done extensive pioneering work on severe PVL-positive S. aureus invasive infections in children. In an early paper, they highlighted the characteristics that distinguish severe PVL-positive pneumonia: it typically occurs in previously healthy children and adolescents without underlying comorbid conditions, and it is often preceded by a influenza-like syndrome followed by an acute severe pneumonia with hemoptysis. Mortality was very high in this early series, with nearly half of the patients being dead within the first several days after admission (Lancet. 2002 Mar 2;359[9308]:753-9).
- Severe osteomyelitis. Investigators at Baylor College of Medicine, Houston, were among the first to observe that osteomyelitis caused by PVL-positive strains of S. aureus are associated with more severe local disease, with multiple affected areas, bigger abscesses, a greater systemic inflammatory response, and more surgeries required compared with osteomyelitis caused by PVL-negative S. aureus (Pediatrics. 2006 Feb;117[2]:433-40).
- Osteomyelitis with deep vein thrombosis. When a child hospitalized for acute hematogenous osteomyelitis due to S. aureus develops difficulty breathing, that’s a red flag for a severe PVL-positive infection involving deep vein thrombosis. Indeed, investigators at the Leeds (England) General Infirmary have reported that deep vein thrombosis in the setting of S. aureus osteomyelitis is associated with a greater than eightfold increased likelihood of a PVL-positive infection (Br J Hosp Med [Lond]. 2015 Jan;76[1]:18-24). Also, patients with PVL-positive osteomyelitis and deep vein thrombosis are prone to formation of septic emboli.
- Osteomyelitis with septic shock. The Lyon group compared outcomes in 14 pediatric patients with PVL-positive S. aureus osteomyelitis and a control group of 17 patients with PVL-negative disease. All 14 PVL-positive patients had severe sepsis and 6 of them had septic shock. In contrast, none of the controls did. Median duration of hospitalization was 46 days in the PVL-positive group, compared with 13 days in controls (Pediatr Infect Dis J. 2007 Nov;26[11]:1042-8).
Treatment
No randomized trials exist to guide treatment, but Dr. Rojo recommends the protocol utilized by the Lyon group: a bactericidal antibiotic – vancomycin or a beta-lactam – to take on the S. aureus, coupled with a ribosomally active antibiotic – clindamycin or linezolid – to suppress the PVL toxin’s virulence expression. The French group cites both in vitro and in vivo evidence that clindamycin and linezolid in their standard dosing have such an antitoxin effect (Clin Microbiol Rev. 2017 Oct;30[4]:887-917).
In addition, Dr. Rojo recommends utilizing any of the commercially available intravenous immunoglobulin (IVIG) products on the basis of work by investigators at Vanderbilt University in Nashville, Tenn., who have demonstrated that these products contain functional neutralizing antibodies against S. aureus leukocidins. This observation provides a likely explanation for anecdotal reports of improved outcomes in IVIG-treated patients with toxin-associated staphylococcal disease (Antimicrob Agents Chemother. 2017 Oct 24;61[11]. pii: e00968-17).
Challenged as to when specifically he would use IVIG in light of the global shortage of immunoglobulins, Dr. Rojo replied: “Not in every invasive S. aureus infection, but in serious infections that are PVL positive. I think if you have a child with one of these four syndromes who is in a pediatric ICU, you should use it. I mean, the mortality is around 30% in healthy children, so you would not stop from giving it. The risk of giving IVIG is very low, no side effects, so I highly recommend it for these severe cases.”
He reported having no financial conflicts.
EXPERT ANALYSIS FROM ESPID 2018
Adult CCSs report financial hardships
Health-related financial hardship is common among adult survivors of childhood cancer, according to a study published in the Journal of the National Cancer Institute.
Researchers analyzed more than 2800 long-term childhood cancer survivors (CCSs) and found that 65% had financial challenges related to their cancer diagnosis.
“These findings suggest primary care doctors and oncologists should routinely screen childhood cancer survivors for possible financial hardship,” said I-Chan Huang, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
Specifically, Dr Huang recommends that healthcare providers routinely ask CCSs if they are unable to purchase medications, ever skip appointments for economic reasons, or worry about how to pay their medical bills.
For this study, Dr Huang and his colleagues analyzed data from 2811 CCSs. The subjects had a mean age of 31.8 (range, 18 to 65) and were a mean of 23.6 years from cancer diagnosis. Most (57.8%) had been diagnosed with hematologic malignancies, 32.0% with solid tumors, and 10.1% with central nervous system malignancies.
All subjects had been treated at St. Jude and enrolled in the St. Jude LIFE study. Participants return to St. Jude periodically for several days of clinical and functional assessments. Data for this study were collected during the CCSs’ first St. Jude LIFE evaluations.
Assessing hardship
The researchers measured 3 types of financial hardship—material, psychological, and coping/behavioral.
About 1 in 5 CCSs (22.4%) reported material financial hardship. In other words, their cancer had an impact on their financial situation.
More than half of CCSs (51.1%) reported psychological hardship—concern about their ability to pay for medical expenses.
And 33% of CCSs reported coping/behavioral hardship—an inability to see a doctor or go to the hospital due to finances.
Roughly 65% of CCSs reported at least 1 type of financial hardship.
All 3 types of hardship were significantly associated with somatization (all P<0.001), anxiety (all P<0.001), depression (all P<0.001), suicidal thoughts (all P<0.05), and difficulty in retirement planning (all P<0.001).
Furthermore, CCSs who reported financial hardship had significantly lower health-related quality of life (P<0.001 for all 3 domains), sensation abnormality (all P<0.001), pulmonary symptoms (all P<0.05), and cardiac symptoms (all P<0.05).
Predicting hardship
Intensive cancer treatment, chronic health conditions, second cancers, age at the time of study evaluation, education level, and annual household income were all significantly associated with a greater risk of financial hardship.
CCSs age 40 and older had an increased risk of psychological and coping/behavioral hardship (P<0.001 for both domains).
CCSs with an annual household income of less than $40,000 had an increased risk of material, psychological, and coping/behavioral hardship, compared to CCSs with an income of $80,000 or more (P<0.001 for all domains).
CCSs who did not obtain a high school diploma had an increased risk of material (P<0.001), psychological (P<0.01), and coping/behavioral hardship (P<0.001) compared to college graduates.
CCSs who received cancer treatments associated with a high-risk disease burden (vs low-risk) had an increased risk of material (P=0.01) and psychological (P=0.004) hardship.
Health conditions associated with material financial hardship included grade 2-4 myocardial infarction (P<0.001), peripheral neuropathy (P<0.001), subsequent neoplasm (P<0.001), seizure (P=0.007), reproductive disorders (P=0.01), stroke (P=0.02), amputation (P=0.02), upper gastrointestinal disease (P=0.04), and hearing loss (P=0.05).
Grade 2-4 myocardial infarction and reproductive disorders were significantly associated with psychological financial hardship (P=0.02 for both).
“Severe late effects that emerge early in life and disrupt education and training opportunities are a double hit for survivors,” Dr Huang said. “These health problems decrease the survivors’ earning mobility and financial security later in life. The phenomenon leaves them at risk for poor health and psychological outcomes compared to healthier survivors.”
Health-related financial hardship is common among adult survivors of childhood cancer, according to a study published in the Journal of the National Cancer Institute.
Researchers analyzed more than 2800 long-term childhood cancer survivors (CCSs) and found that 65% had financial challenges related to their cancer diagnosis.
“These findings suggest primary care doctors and oncologists should routinely screen childhood cancer survivors for possible financial hardship,” said I-Chan Huang, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
Specifically, Dr Huang recommends that healthcare providers routinely ask CCSs if they are unable to purchase medications, ever skip appointments for economic reasons, or worry about how to pay their medical bills.
For this study, Dr Huang and his colleagues analyzed data from 2811 CCSs. The subjects had a mean age of 31.8 (range, 18 to 65) and were a mean of 23.6 years from cancer diagnosis. Most (57.8%) had been diagnosed with hematologic malignancies, 32.0% with solid tumors, and 10.1% with central nervous system malignancies.
All subjects had been treated at St. Jude and enrolled in the St. Jude LIFE study. Participants return to St. Jude periodically for several days of clinical and functional assessments. Data for this study were collected during the CCSs’ first St. Jude LIFE evaluations.
Assessing hardship
The researchers measured 3 types of financial hardship—material, psychological, and coping/behavioral.
About 1 in 5 CCSs (22.4%) reported material financial hardship. In other words, their cancer had an impact on their financial situation.
More than half of CCSs (51.1%) reported psychological hardship—concern about their ability to pay for medical expenses.
And 33% of CCSs reported coping/behavioral hardship—an inability to see a doctor or go to the hospital due to finances.
Roughly 65% of CCSs reported at least 1 type of financial hardship.
All 3 types of hardship were significantly associated with somatization (all P<0.001), anxiety (all P<0.001), depression (all P<0.001), suicidal thoughts (all P<0.05), and difficulty in retirement planning (all P<0.001).
Furthermore, CCSs who reported financial hardship had significantly lower health-related quality of life (P<0.001 for all 3 domains), sensation abnormality (all P<0.001), pulmonary symptoms (all P<0.05), and cardiac symptoms (all P<0.05).
Predicting hardship
Intensive cancer treatment, chronic health conditions, second cancers, age at the time of study evaluation, education level, and annual household income were all significantly associated with a greater risk of financial hardship.
CCSs age 40 and older had an increased risk of psychological and coping/behavioral hardship (P<0.001 for both domains).
CCSs with an annual household income of less than $40,000 had an increased risk of material, psychological, and coping/behavioral hardship, compared to CCSs with an income of $80,000 or more (P<0.001 for all domains).
CCSs who did not obtain a high school diploma had an increased risk of material (P<0.001), psychological (P<0.01), and coping/behavioral hardship (P<0.001) compared to college graduates.
CCSs who received cancer treatments associated with a high-risk disease burden (vs low-risk) had an increased risk of material (P=0.01) and psychological (P=0.004) hardship.
Health conditions associated with material financial hardship included grade 2-4 myocardial infarction (P<0.001), peripheral neuropathy (P<0.001), subsequent neoplasm (P<0.001), seizure (P=0.007), reproductive disorders (P=0.01), stroke (P=0.02), amputation (P=0.02), upper gastrointestinal disease (P=0.04), and hearing loss (P=0.05).
Grade 2-4 myocardial infarction and reproductive disorders were significantly associated with psychological financial hardship (P=0.02 for both).
“Severe late effects that emerge early in life and disrupt education and training opportunities are a double hit for survivors,” Dr Huang said. “These health problems decrease the survivors’ earning mobility and financial security later in life. The phenomenon leaves them at risk for poor health and psychological outcomes compared to healthier survivors.”
Health-related financial hardship is common among adult survivors of childhood cancer, according to a study published in the Journal of the National Cancer Institute.
Researchers analyzed more than 2800 long-term childhood cancer survivors (CCSs) and found that 65% had financial challenges related to their cancer diagnosis.
“These findings suggest primary care doctors and oncologists should routinely screen childhood cancer survivors for possible financial hardship,” said I-Chan Huang, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
Specifically, Dr Huang recommends that healthcare providers routinely ask CCSs if they are unable to purchase medications, ever skip appointments for economic reasons, or worry about how to pay their medical bills.
For this study, Dr Huang and his colleagues analyzed data from 2811 CCSs. The subjects had a mean age of 31.8 (range, 18 to 65) and were a mean of 23.6 years from cancer diagnosis. Most (57.8%) had been diagnosed with hematologic malignancies, 32.0% with solid tumors, and 10.1% with central nervous system malignancies.
All subjects had been treated at St. Jude and enrolled in the St. Jude LIFE study. Participants return to St. Jude periodically for several days of clinical and functional assessments. Data for this study were collected during the CCSs’ first St. Jude LIFE evaluations.
Assessing hardship
The researchers measured 3 types of financial hardship—material, psychological, and coping/behavioral.
About 1 in 5 CCSs (22.4%) reported material financial hardship. In other words, their cancer had an impact on their financial situation.
More than half of CCSs (51.1%) reported psychological hardship—concern about their ability to pay for medical expenses.
And 33% of CCSs reported coping/behavioral hardship—an inability to see a doctor or go to the hospital due to finances.
Roughly 65% of CCSs reported at least 1 type of financial hardship.
All 3 types of hardship were significantly associated with somatization (all P<0.001), anxiety (all P<0.001), depression (all P<0.001), suicidal thoughts (all P<0.05), and difficulty in retirement planning (all P<0.001).
Furthermore, CCSs who reported financial hardship had significantly lower health-related quality of life (P<0.001 for all 3 domains), sensation abnormality (all P<0.001), pulmonary symptoms (all P<0.05), and cardiac symptoms (all P<0.05).
Predicting hardship
Intensive cancer treatment, chronic health conditions, second cancers, age at the time of study evaluation, education level, and annual household income were all significantly associated with a greater risk of financial hardship.
CCSs age 40 and older had an increased risk of psychological and coping/behavioral hardship (P<0.001 for both domains).
CCSs with an annual household income of less than $40,000 had an increased risk of material, psychological, and coping/behavioral hardship, compared to CCSs with an income of $80,000 or more (P<0.001 for all domains).
CCSs who did not obtain a high school diploma had an increased risk of material (P<0.001), psychological (P<0.01), and coping/behavioral hardship (P<0.001) compared to college graduates.
CCSs who received cancer treatments associated with a high-risk disease burden (vs low-risk) had an increased risk of material (P=0.01) and psychological (P=0.004) hardship.
Health conditions associated with material financial hardship included grade 2-4 myocardial infarction (P<0.001), peripheral neuropathy (P<0.001), subsequent neoplasm (P<0.001), seizure (P=0.007), reproductive disorders (P=0.01), stroke (P=0.02), amputation (P=0.02), upper gastrointestinal disease (P=0.04), and hearing loss (P=0.05).
Grade 2-4 myocardial infarction and reproductive disorders were significantly associated with psychological financial hardship (P=0.02 for both).
“Severe late effects that emerge early in life and disrupt education and training opportunities are a double hit for survivors,” Dr Huang said. “These health problems decrease the survivors’ earning mobility and financial security later in life. The phenomenon leaves them at risk for poor health and psychological outcomes compared to healthier survivors.”
ED key to reducing pediatric asthma x-rays
ATLANTA – but accomplishing this goal takes more than a new clinical practice guideline, according to a quality improvement team at the Monroe Carell Jr. Children’s Hospital at Vanderbilt University, Nashville, Tenn.
The team eventually reduced the chest x-ray rate for pediatric asthma exacerbations from 30% to 15% without increasing 3-day all-cause readmissions, but it took some sleuthing in the ED and good relations with staff. “We were way out in left field when we started this. Working in silos is never ideal,” said senior project member David Johnson, MD, a pediatric hospitalist and assistant professor of pediatrics at Vanderbilt.
It’s been known for a while that chest x-rays are almost always a waste of time and money for asthma exacerbations, and national guidelines recommend against them. X-rays don’t improve outcomes and needlessly expose children to radiation.
In 2014, some of the providers at Vanderbilt, which has about 1,700 asthma encounters a year, realized that the institution’s 30% x-ray rate was a problem. The quality improvement team hoped a new guideline would address the issue, but that didn’t happen. “We roll out clinical practice guidelines” from on high, “and think people will magically change their behavior,” but they don’t, Dr. Johnson said at the annual Pediatric Hospital Medicine meeting.
The guideline was not being fully implemented. So the team asked the ED what was the standard procedure for a child presenting with asthma exacerbation. It turned out that the ED had a dyspnea order set that the team ”had no idea existed.” Chest x-rays were at the top of the list; next came blood gases, ventilation-perfusion scans, and leg Dopplers, he said.
The investigators tried to get rid of the whole order set but were unsuccessful. The ED department did, however, let the team eliminate chest x-rays in the default order set in July 2015. That helped, but more changes were needed.
The next conversation was to figure out why x-rays were being ordered in the first place. ED staff said they were worried about missing something, especially pneumonia. They also thought they were helping hospitalists by getting x-rays before sending kids to the ward even though, in reality, it didn’t matter whether x-rays were done a few hours later on the floor. ED providers also said that ill-appearing children often got better after a few hours but were kept back from discharge because x-ray results were still pending and that sometimes these results revealed problems at 3 a.m. that had nothing to do with why the patients were in the ED but still required a work-up.
This discussion opened a door. The ED staff didn’t want to order unnecessary x-rays, either. That led to talks about letting kids declare themselves a bit before x-rays were ordered. ED staff liked the idea, so the guidelines were updated in early 2016 to say that chest x-rays should only be ordered if there is persistent severe respiratory distress with hypoxia, there are focal findings that don’t improve after 12 hours of treatment, or there were concerns for pneumomediastinum or collapsed lung. The updated guidelines were posted in work areas and brought home by resident education. A reminder was added to the electronic medical record system that popped up when someone tried to order a chest x-ray for an child with asthma.
It worked. Chest x-ray rates in asthma fell to 15%, and have remained there since.
“We gave them permission to take their foot off the throttle and wait a little bit, and we don’t have more kids bouncing back from reduced x-rays.” The approach is “probably generalizable everywhere,” Dr. Johnson said.
It was essential that an ED fellow, Caroline Watnick, MD, led the effort and eventually bridged the gap between hospitalists and ED providers. In the end, “the change wasn’t something from the outside,” Dr. Johnson said.
There was no industry funding, and Dr. Johnson didn’t have any disclosures. The Pediatric Hospital Medicine meeting is sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.
ATLANTA – but accomplishing this goal takes more than a new clinical practice guideline, according to a quality improvement team at the Monroe Carell Jr. Children’s Hospital at Vanderbilt University, Nashville, Tenn.
The team eventually reduced the chest x-ray rate for pediatric asthma exacerbations from 30% to 15% without increasing 3-day all-cause readmissions, but it took some sleuthing in the ED and good relations with staff. “We were way out in left field when we started this. Working in silos is never ideal,” said senior project member David Johnson, MD, a pediatric hospitalist and assistant professor of pediatrics at Vanderbilt.
It’s been known for a while that chest x-rays are almost always a waste of time and money for asthma exacerbations, and national guidelines recommend against them. X-rays don’t improve outcomes and needlessly expose children to radiation.
In 2014, some of the providers at Vanderbilt, which has about 1,700 asthma encounters a year, realized that the institution’s 30% x-ray rate was a problem. The quality improvement team hoped a new guideline would address the issue, but that didn’t happen. “We roll out clinical practice guidelines” from on high, “and think people will magically change their behavior,” but they don’t, Dr. Johnson said at the annual Pediatric Hospital Medicine meeting.
The guideline was not being fully implemented. So the team asked the ED what was the standard procedure for a child presenting with asthma exacerbation. It turned out that the ED had a dyspnea order set that the team ”had no idea existed.” Chest x-rays were at the top of the list; next came blood gases, ventilation-perfusion scans, and leg Dopplers, he said.
The investigators tried to get rid of the whole order set but were unsuccessful. The ED department did, however, let the team eliminate chest x-rays in the default order set in July 2015. That helped, but more changes were needed.
The next conversation was to figure out why x-rays were being ordered in the first place. ED staff said they were worried about missing something, especially pneumonia. They also thought they were helping hospitalists by getting x-rays before sending kids to the ward even though, in reality, it didn’t matter whether x-rays were done a few hours later on the floor. ED providers also said that ill-appearing children often got better after a few hours but were kept back from discharge because x-ray results were still pending and that sometimes these results revealed problems at 3 a.m. that had nothing to do with why the patients were in the ED but still required a work-up.
This discussion opened a door. The ED staff didn’t want to order unnecessary x-rays, either. That led to talks about letting kids declare themselves a bit before x-rays were ordered. ED staff liked the idea, so the guidelines were updated in early 2016 to say that chest x-rays should only be ordered if there is persistent severe respiratory distress with hypoxia, there are focal findings that don’t improve after 12 hours of treatment, or there were concerns for pneumomediastinum or collapsed lung. The updated guidelines were posted in work areas and brought home by resident education. A reminder was added to the electronic medical record system that popped up when someone tried to order a chest x-ray for an child with asthma.
It worked. Chest x-ray rates in asthma fell to 15%, and have remained there since.
“We gave them permission to take their foot off the throttle and wait a little bit, and we don’t have more kids bouncing back from reduced x-rays.” The approach is “probably generalizable everywhere,” Dr. Johnson said.
It was essential that an ED fellow, Caroline Watnick, MD, led the effort and eventually bridged the gap between hospitalists and ED providers. In the end, “the change wasn’t something from the outside,” Dr. Johnson said.
There was no industry funding, and Dr. Johnson didn’t have any disclosures. The Pediatric Hospital Medicine meeting is sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.
ATLANTA – but accomplishing this goal takes more than a new clinical practice guideline, according to a quality improvement team at the Monroe Carell Jr. Children’s Hospital at Vanderbilt University, Nashville, Tenn.
The team eventually reduced the chest x-ray rate for pediatric asthma exacerbations from 30% to 15% without increasing 3-day all-cause readmissions, but it took some sleuthing in the ED and good relations with staff. “We were way out in left field when we started this. Working in silos is never ideal,” said senior project member David Johnson, MD, a pediatric hospitalist and assistant professor of pediatrics at Vanderbilt.
It’s been known for a while that chest x-rays are almost always a waste of time and money for asthma exacerbations, and national guidelines recommend against them. X-rays don’t improve outcomes and needlessly expose children to radiation.
In 2014, some of the providers at Vanderbilt, which has about 1,700 asthma encounters a year, realized that the institution’s 30% x-ray rate was a problem. The quality improvement team hoped a new guideline would address the issue, but that didn’t happen. “We roll out clinical practice guidelines” from on high, “and think people will magically change their behavior,” but they don’t, Dr. Johnson said at the annual Pediatric Hospital Medicine meeting.
The guideline was not being fully implemented. So the team asked the ED what was the standard procedure for a child presenting with asthma exacerbation. It turned out that the ED had a dyspnea order set that the team ”had no idea existed.” Chest x-rays were at the top of the list; next came blood gases, ventilation-perfusion scans, and leg Dopplers, he said.
The investigators tried to get rid of the whole order set but were unsuccessful. The ED department did, however, let the team eliminate chest x-rays in the default order set in July 2015. That helped, but more changes were needed.
The next conversation was to figure out why x-rays were being ordered in the first place. ED staff said they were worried about missing something, especially pneumonia. They also thought they were helping hospitalists by getting x-rays before sending kids to the ward even though, in reality, it didn’t matter whether x-rays were done a few hours later on the floor. ED providers also said that ill-appearing children often got better after a few hours but were kept back from discharge because x-ray results were still pending and that sometimes these results revealed problems at 3 a.m. that had nothing to do with why the patients were in the ED but still required a work-up.
This discussion opened a door. The ED staff didn’t want to order unnecessary x-rays, either. That led to talks about letting kids declare themselves a bit before x-rays were ordered. ED staff liked the idea, so the guidelines were updated in early 2016 to say that chest x-rays should only be ordered if there is persistent severe respiratory distress with hypoxia, there are focal findings that don’t improve after 12 hours of treatment, or there were concerns for pneumomediastinum or collapsed lung. The updated guidelines were posted in work areas and brought home by resident education. A reminder was added to the electronic medical record system that popped up when someone tried to order a chest x-ray for an child with asthma.
It worked. Chest x-ray rates in asthma fell to 15%, and have remained there since.
“We gave them permission to take their foot off the throttle and wait a little bit, and we don’t have more kids bouncing back from reduced x-rays.” The approach is “probably generalizable everywhere,” Dr. Johnson said.
It was essential that an ED fellow, Caroline Watnick, MD, led the effort and eventually bridged the gap between hospitalists and ED providers. In the end, “the change wasn’t something from the outside,” Dr. Johnson said.
There was no industry funding, and Dr. Johnson didn’t have any disclosures. The Pediatric Hospital Medicine meeting is sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.
REPORTING FROM PHM 2018
Key clinical point: Reduction of chest x-rays for routine pediatric asthma exacerbations in the ED can be accomplished with a team effort.
Major finding: A team project reduced x-rays for pediatric asthma exacerbations from 30% to 15% without increasing 3-day, all-cause readmissions.
Study details: Pre/post quality improvement analysis of asthma encounters in the Monroe Carell Jr. Children’s Hospital, Nashville, Tenn., starting in 2014.
Disclosures: There was no industry funding, and the presenter didn’t have any disclosures.
Foster cultural competence when examining hair, scalp of ethnic patients
LAKE TAHOE, CALIF. – The way Susan C. Taylor, MD, sees it,
At the annual meeting of the Society for Pediatric Dermatology, Dr. Taylor, a dermatologist at the University of Pennsylvania, Philadelphia, defined culturally competent care as a patient-centered approach in which clinicians establish a rapport with the patient and the caregiver. “It’s important that we ask the right questions,” she said. “In doing so, we have to be familiar with common hair care practices. It’s important that we respect our patients’ values, their goals, their health needs, and, of course, their cultural background. Finally, we have to engage in shared decision making. That’s where we can improve compliance and lead to an overall very satisfactory patient visit.”
To illustrate this point, she discussed the case of a four-year-old black female with a 9-month history of bad dandruff. The child’s mother reports thick flakes that never go away. She takes pride in caring for her daughter’s hair, and shampoos it every two weeks. “She tells me that during the 2.5 hours that it takes her on Saturdays to shampoo, detangle, and comb her daughter’s hair, which she then braids or cornrows and adorns with barrettes or balls, it is a great bonding experience for the two of them,” Dr. Taylor said. “The flakes are temporarily better after she ‘greases’ her daughter’s scalp, but after 2-3 days, they are back.”
In a case like this, Dr. Taylor recommends asking the parent or caregiver to join you while you examine the scalp. This way, the focus becomes the child’s scalp, and the parent is not just staring at your expressions. “The child also observes the pediatric dermatologist and parent/caregiver working together as a team,” she said. “You also want to ask the parent to remove the hair adornments. This makes the child feel more comfortable. It also allows you to observe how the hair is being managed. Are the adornments being removed gently? Is there aggressive pulling of the hair when they take out the braids? Is the child visibly wincing in pain? If the latter two happen this is a teachable moment. You can point out, ‘It looks like Susie is in pain. Let’s do it a little more gently. That might prevent further hair breakage.’ ”
The differential diagnosis of a scaly pediatric scalp includes infrequent shampooing, seborrheic dermatitis, tinea capitis, atopic dermatitis, psoriasis, and sebopsoriasis. The type of hairstyle also factors in. For example, cornrows are a popular hair styling option among ethnic patients. “These are very popular and very time consuming and may lead to infrequent shampooing,” she said. “If they’re put in very tightly or if they have beads or other adornments, it can lead to traction alopecia.” Twists, meanwhile, can create tension on the hair, while puffs can cause traction alopecia if they’re pulled too tightly. “Although dreadlocks are more common among adolescents, we’re seeing them more commonly in young children,” she said. “They can be very long and wavy and lead to traction alopecia.”
The time required to shampoo, detangle, and style tightly coiled African American hair can be significant. For example, in children with cornrows or braids with extensions, Dr. Taylor said that it might require 30 minutes to as long as 2 or 3 hours to remove their current hairstyle, followed by shampooing and conditioning. “Detangling can take at least 15 minutes. In tightly coiled African American hair, studies have demonstrated that detangling while the hair is wet is best, because you have fewer forces on that comb and the hair is less likely to break, as opposed to detangling when the hair is dry. After the wet hair is detangled and the conditioner is rinsed out, a leave-in conditioner is often applied. Then the hair is detangled again, which can take up to an hour, followed by styling, which can take 1-3 hours. That gives you some insight as to why there can often be infrequent shampooing.”
The recommended frequency of shampooing depends on the hairstyle selected. Many children with braids and extensions will have those braids and extensions taken out every six to 12 weeks, “but that doesn’t mean that the scalp can’t be shampooed,” Dr. Taylor said. “The scalp should be shampooed more often. Economics and socioeconomic status play into the frequency of shampooing. For example, if a parent or a caregiver sends a child to a hair stylist, that can range in price from $45 to $65 or more. Time also factors in. In the black community in particular, it’s a ritual on a Saturday to get your hair done. If the parent or caregiver works on weekends, that’s going to impact the frequency of shampooing.”
Dr. Taylor underscored the importance of framing the history-taking process to avoid common pitfall questions like “Do you wash the child’s hair every day or every other day?” or “Do you use dandruff shampoo every day?” It is important to remember that “the parent’s inherent perception is of a doctor who does not have my hair probably does not understand my hair or my child’s hair,” she said. “It’s unlikely that you’re going to find a parent who shampoos their child’s hair every day or every other day. Maybe once a week, probably biweekly. It’s important to ask culturally competent questions.”
She also advises against asking about shampooing when you’re examining the child’s hair, “because there’s going to be the perception that you may think the scalp is dirty,” Dr. Taylor explained. “You probably want to ask that when gathering the history of present illness. The culturally competent question is going to be, ‘Do you wash her/his hair weekly, every other week, monthly, or does it depend on the hair style?’ ”
Body language is also important. “Don’t lean in from afar when examining the patient,” she said. “Get up close and touch the child’s hair.” If you choose to wear surgical gloves for the exam “don’t hold your hands in the surgical scrub position,” she recommended. “Hold your hands in a more neutral position. I think it’s important to touch the hair.”
Referring back to the 4-year-old black child with bad dandruff, she said that a diagnosis of seborrheic dermatitis is unlikely since that condition usually occurs during puberty. “You should have a high index of suspicion for tinea capitis,” she said. “If the patient has occipital lymphadenopathy plus scaling of the scalp or alopecia, that’s enough to presumptively treat for tinea capitis. There are studies that support that.”
For established tinea capitis, Dr. Taylor advises parents to wash barrettes and other hair adornments in hot soapy water or in the dishwasher. She also recommends disposal of hair oil, pomade, and grease and shampooing the child’s hair with ketoconazole and use a conditioner to decrease household and patient spread, which decreases transmissible fungal spores. “There’s a misperception that the application of hair oils and grease can increase the rate of tinea capitis,” she noted. “That’s not true. However, if hair grease and hair oil is applied to the scalp within one week of culture, it could produce a false negative culture.”
For established seborrheic dermatitis, antifungal shampoos including ketoconazole, ciclopirox, and selenium sulfide may be too drying for ethnic hair, “which already has a propensity to break,” she said. “Instead, we recommend a 5-10 minute scalp contact time with the shampoo and avoid contact with strands of hair. Shampoo hair strands with a conditioning shampoo followed by a conditioner to limit hair breakage. We suggest once weekly or biweekly shampooing.”
Dr. Taylor disclosed that she has advisory board and/or investigator relationships with Aclaris Therapeutics, Allergan, Beiersdorf, Croma Pharmaceuticals, Galderma, Isdin, Johnson & Johnson, and Unilever. She also acknowledged Candrice R. Heath, MD, a dermatologist based in Newark, Delaware, for her assistance with the presentation content.
dbrunk@mdedge.com
LAKE TAHOE, CALIF. – The way Susan C. Taylor, MD, sees it,
At the annual meeting of the Society for Pediatric Dermatology, Dr. Taylor, a dermatologist at the University of Pennsylvania, Philadelphia, defined culturally competent care as a patient-centered approach in which clinicians establish a rapport with the patient and the caregiver. “It’s important that we ask the right questions,” she said. “In doing so, we have to be familiar with common hair care practices. It’s important that we respect our patients’ values, their goals, their health needs, and, of course, their cultural background. Finally, we have to engage in shared decision making. That’s where we can improve compliance and lead to an overall very satisfactory patient visit.”
To illustrate this point, she discussed the case of a four-year-old black female with a 9-month history of bad dandruff. The child’s mother reports thick flakes that never go away. She takes pride in caring for her daughter’s hair, and shampoos it every two weeks. “She tells me that during the 2.5 hours that it takes her on Saturdays to shampoo, detangle, and comb her daughter’s hair, which she then braids or cornrows and adorns with barrettes or balls, it is a great bonding experience for the two of them,” Dr. Taylor said. “The flakes are temporarily better after she ‘greases’ her daughter’s scalp, but after 2-3 days, they are back.”
In a case like this, Dr. Taylor recommends asking the parent or caregiver to join you while you examine the scalp. This way, the focus becomes the child’s scalp, and the parent is not just staring at your expressions. “The child also observes the pediatric dermatologist and parent/caregiver working together as a team,” she said. “You also want to ask the parent to remove the hair adornments. This makes the child feel more comfortable. It also allows you to observe how the hair is being managed. Are the adornments being removed gently? Is there aggressive pulling of the hair when they take out the braids? Is the child visibly wincing in pain? If the latter two happen this is a teachable moment. You can point out, ‘It looks like Susie is in pain. Let’s do it a little more gently. That might prevent further hair breakage.’ ”
The differential diagnosis of a scaly pediatric scalp includes infrequent shampooing, seborrheic dermatitis, tinea capitis, atopic dermatitis, psoriasis, and sebopsoriasis. The type of hairstyle also factors in. For example, cornrows are a popular hair styling option among ethnic patients. “These are very popular and very time consuming and may lead to infrequent shampooing,” she said. “If they’re put in very tightly or if they have beads or other adornments, it can lead to traction alopecia.” Twists, meanwhile, can create tension on the hair, while puffs can cause traction alopecia if they’re pulled too tightly. “Although dreadlocks are more common among adolescents, we’re seeing them more commonly in young children,” she said. “They can be very long and wavy and lead to traction alopecia.”
The time required to shampoo, detangle, and style tightly coiled African American hair can be significant. For example, in children with cornrows or braids with extensions, Dr. Taylor said that it might require 30 minutes to as long as 2 or 3 hours to remove their current hairstyle, followed by shampooing and conditioning. “Detangling can take at least 15 minutes. In tightly coiled African American hair, studies have demonstrated that detangling while the hair is wet is best, because you have fewer forces on that comb and the hair is less likely to break, as opposed to detangling when the hair is dry. After the wet hair is detangled and the conditioner is rinsed out, a leave-in conditioner is often applied. Then the hair is detangled again, which can take up to an hour, followed by styling, which can take 1-3 hours. That gives you some insight as to why there can often be infrequent shampooing.”
The recommended frequency of shampooing depends on the hairstyle selected. Many children with braids and extensions will have those braids and extensions taken out every six to 12 weeks, “but that doesn’t mean that the scalp can’t be shampooed,” Dr. Taylor said. “The scalp should be shampooed more often. Economics and socioeconomic status play into the frequency of shampooing. For example, if a parent or a caregiver sends a child to a hair stylist, that can range in price from $45 to $65 or more. Time also factors in. In the black community in particular, it’s a ritual on a Saturday to get your hair done. If the parent or caregiver works on weekends, that’s going to impact the frequency of shampooing.”
Dr. Taylor underscored the importance of framing the history-taking process to avoid common pitfall questions like “Do you wash the child’s hair every day or every other day?” or “Do you use dandruff shampoo every day?” It is important to remember that “the parent’s inherent perception is of a doctor who does not have my hair probably does not understand my hair or my child’s hair,” she said. “It’s unlikely that you’re going to find a parent who shampoos their child’s hair every day or every other day. Maybe once a week, probably biweekly. It’s important to ask culturally competent questions.”
She also advises against asking about shampooing when you’re examining the child’s hair, “because there’s going to be the perception that you may think the scalp is dirty,” Dr. Taylor explained. “You probably want to ask that when gathering the history of present illness. The culturally competent question is going to be, ‘Do you wash her/his hair weekly, every other week, monthly, or does it depend on the hair style?’ ”
Body language is also important. “Don’t lean in from afar when examining the patient,” she said. “Get up close and touch the child’s hair.” If you choose to wear surgical gloves for the exam “don’t hold your hands in the surgical scrub position,” she recommended. “Hold your hands in a more neutral position. I think it’s important to touch the hair.”
Referring back to the 4-year-old black child with bad dandruff, she said that a diagnosis of seborrheic dermatitis is unlikely since that condition usually occurs during puberty. “You should have a high index of suspicion for tinea capitis,” she said. “If the patient has occipital lymphadenopathy plus scaling of the scalp or alopecia, that’s enough to presumptively treat for tinea capitis. There are studies that support that.”
For established tinea capitis, Dr. Taylor advises parents to wash barrettes and other hair adornments in hot soapy water or in the dishwasher. She also recommends disposal of hair oil, pomade, and grease and shampooing the child’s hair with ketoconazole and use a conditioner to decrease household and patient spread, which decreases transmissible fungal spores. “There’s a misperception that the application of hair oils and grease can increase the rate of tinea capitis,” she noted. “That’s not true. However, if hair grease and hair oil is applied to the scalp within one week of culture, it could produce a false negative culture.”
For established seborrheic dermatitis, antifungal shampoos including ketoconazole, ciclopirox, and selenium sulfide may be too drying for ethnic hair, “which already has a propensity to break,” she said. “Instead, we recommend a 5-10 minute scalp contact time with the shampoo and avoid contact with strands of hair. Shampoo hair strands with a conditioning shampoo followed by a conditioner to limit hair breakage. We suggest once weekly or biweekly shampooing.”
Dr. Taylor disclosed that she has advisory board and/or investigator relationships with Aclaris Therapeutics, Allergan, Beiersdorf, Croma Pharmaceuticals, Galderma, Isdin, Johnson & Johnson, and Unilever. She also acknowledged Candrice R. Heath, MD, a dermatologist based in Newark, Delaware, for her assistance with the presentation content.
dbrunk@mdedge.com
LAKE TAHOE, CALIF. – The way Susan C. Taylor, MD, sees it,
At the annual meeting of the Society for Pediatric Dermatology, Dr. Taylor, a dermatologist at the University of Pennsylvania, Philadelphia, defined culturally competent care as a patient-centered approach in which clinicians establish a rapport with the patient and the caregiver. “It’s important that we ask the right questions,” she said. “In doing so, we have to be familiar with common hair care practices. It’s important that we respect our patients’ values, their goals, their health needs, and, of course, their cultural background. Finally, we have to engage in shared decision making. That’s where we can improve compliance and lead to an overall very satisfactory patient visit.”
To illustrate this point, she discussed the case of a four-year-old black female with a 9-month history of bad dandruff. The child’s mother reports thick flakes that never go away. She takes pride in caring for her daughter’s hair, and shampoos it every two weeks. “She tells me that during the 2.5 hours that it takes her on Saturdays to shampoo, detangle, and comb her daughter’s hair, which she then braids or cornrows and adorns with barrettes or balls, it is a great bonding experience for the two of them,” Dr. Taylor said. “The flakes are temporarily better after she ‘greases’ her daughter’s scalp, but after 2-3 days, they are back.”
In a case like this, Dr. Taylor recommends asking the parent or caregiver to join you while you examine the scalp. This way, the focus becomes the child’s scalp, and the parent is not just staring at your expressions. “The child also observes the pediatric dermatologist and parent/caregiver working together as a team,” she said. “You also want to ask the parent to remove the hair adornments. This makes the child feel more comfortable. It also allows you to observe how the hair is being managed. Are the adornments being removed gently? Is there aggressive pulling of the hair when they take out the braids? Is the child visibly wincing in pain? If the latter two happen this is a teachable moment. You can point out, ‘It looks like Susie is in pain. Let’s do it a little more gently. That might prevent further hair breakage.’ ”
The differential diagnosis of a scaly pediatric scalp includes infrequent shampooing, seborrheic dermatitis, tinea capitis, atopic dermatitis, psoriasis, and sebopsoriasis. The type of hairstyle also factors in. For example, cornrows are a popular hair styling option among ethnic patients. “These are very popular and very time consuming and may lead to infrequent shampooing,” she said. “If they’re put in very tightly or if they have beads or other adornments, it can lead to traction alopecia.” Twists, meanwhile, can create tension on the hair, while puffs can cause traction alopecia if they’re pulled too tightly. “Although dreadlocks are more common among adolescents, we’re seeing them more commonly in young children,” she said. “They can be very long and wavy and lead to traction alopecia.”
The time required to shampoo, detangle, and style tightly coiled African American hair can be significant. For example, in children with cornrows or braids with extensions, Dr. Taylor said that it might require 30 minutes to as long as 2 or 3 hours to remove their current hairstyle, followed by shampooing and conditioning. “Detangling can take at least 15 minutes. In tightly coiled African American hair, studies have demonstrated that detangling while the hair is wet is best, because you have fewer forces on that comb and the hair is less likely to break, as opposed to detangling when the hair is dry. After the wet hair is detangled and the conditioner is rinsed out, a leave-in conditioner is often applied. Then the hair is detangled again, which can take up to an hour, followed by styling, which can take 1-3 hours. That gives you some insight as to why there can often be infrequent shampooing.”
The recommended frequency of shampooing depends on the hairstyle selected. Many children with braids and extensions will have those braids and extensions taken out every six to 12 weeks, “but that doesn’t mean that the scalp can’t be shampooed,” Dr. Taylor said. “The scalp should be shampooed more often. Economics and socioeconomic status play into the frequency of shampooing. For example, if a parent or a caregiver sends a child to a hair stylist, that can range in price from $45 to $65 or more. Time also factors in. In the black community in particular, it’s a ritual on a Saturday to get your hair done. If the parent or caregiver works on weekends, that’s going to impact the frequency of shampooing.”
Dr. Taylor underscored the importance of framing the history-taking process to avoid common pitfall questions like “Do you wash the child’s hair every day or every other day?” or “Do you use dandruff shampoo every day?” It is important to remember that “the parent’s inherent perception is of a doctor who does not have my hair probably does not understand my hair or my child’s hair,” she said. “It’s unlikely that you’re going to find a parent who shampoos their child’s hair every day or every other day. Maybe once a week, probably biweekly. It’s important to ask culturally competent questions.”
She also advises against asking about shampooing when you’re examining the child’s hair, “because there’s going to be the perception that you may think the scalp is dirty,” Dr. Taylor explained. “You probably want to ask that when gathering the history of present illness. The culturally competent question is going to be, ‘Do you wash her/his hair weekly, every other week, monthly, or does it depend on the hair style?’ ”
Body language is also important. “Don’t lean in from afar when examining the patient,” she said. “Get up close and touch the child’s hair.” If you choose to wear surgical gloves for the exam “don’t hold your hands in the surgical scrub position,” she recommended. “Hold your hands in a more neutral position. I think it’s important to touch the hair.”
Referring back to the 4-year-old black child with bad dandruff, she said that a diagnosis of seborrheic dermatitis is unlikely since that condition usually occurs during puberty. “You should have a high index of suspicion for tinea capitis,” she said. “If the patient has occipital lymphadenopathy plus scaling of the scalp or alopecia, that’s enough to presumptively treat for tinea capitis. There are studies that support that.”
For established tinea capitis, Dr. Taylor advises parents to wash barrettes and other hair adornments in hot soapy water or in the dishwasher. She also recommends disposal of hair oil, pomade, and grease and shampooing the child’s hair with ketoconazole and use a conditioner to decrease household and patient spread, which decreases transmissible fungal spores. “There’s a misperception that the application of hair oils and grease can increase the rate of tinea capitis,” she noted. “That’s not true. However, if hair grease and hair oil is applied to the scalp within one week of culture, it could produce a false negative culture.”
For established seborrheic dermatitis, antifungal shampoos including ketoconazole, ciclopirox, and selenium sulfide may be too drying for ethnic hair, “which already has a propensity to break,” she said. “Instead, we recommend a 5-10 minute scalp contact time with the shampoo and avoid contact with strands of hair. Shampoo hair strands with a conditioning shampoo followed by a conditioner to limit hair breakage. We suggest once weekly or biweekly shampooing.”
Dr. Taylor disclosed that she has advisory board and/or investigator relationships with Aclaris Therapeutics, Allergan, Beiersdorf, Croma Pharmaceuticals, Galderma, Isdin, Johnson & Johnson, and Unilever. She also acknowledged Candrice R. Heath, MD, a dermatologist based in Newark, Delaware, for her assistance with the presentation content.
dbrunk@mdedge.com
EXPERT ANALYSIS FROM THE SPD ANNUAL MEETING
Study supports meningococcal B vaccine in children with rare diseases
A new study, the first of its kind, provided support for guidelines suggesting that the capsular meningococcal B vaccine be given to children with three rare conditions that boost infection risk.
For children with terminal chain complement deficiencies or who are undergoing treatment with eculizumab, “it is important that these patients are identified, receive education about sepsis management plans, and are prescribed prophylactic antibiotics according to local guidelines, along with vaccination, to provide every chance for them to be protected against this deadly disease,” the researchers wrote in Pediatrics.
While some countries suggest that the vaccine be given to all healthy infants, U.S. guidelines advise that the vaccine be given to preteenagers, teenagers, and adults who are considered at special risk. These include those with terminal chain complement deficiencies, who are believed to be up to 10,000 times more likely than healthy children to develop invasive meningococcal disease, and those who take eculizumab (Soliris). The risk groups recommended for vaccinations also include those with asplenia and splenic dysfunction, although their excess risk, if any, is unknown.
The new study of the capsular group meningococcal B vaccine, led by Federico Martinón-Torres, PhD, of the Hospital Clinico Universitario de Santiago de Compostela, Spain, adds to previous research that confirmed the effectiveness of vaccinating complement-deficient patients with capsular group A, C, W, and Y meningococcal vaccines.
For the open-label, phase 3b study, researchers in Italy, Spain, Poland, and Russia gave two doses of the vaccine 2 months apart to 239 children aged 2-17 years with an average age of 10 years. Nearly all were white, and 45% were female.
A total of 40 children had complement deficiency, 112 had asplenia or splenic dysfunction, and 87 children in the control group also received the vaccine.
Following vaccination, the percentages of children with exogenous complement serum bactericidal activity titers greater than or equal to 1:5 to the four test strains were similar in the healthy children and those with asplenia/splenic dysfunction. “It is reasonable to expect that this vaccine will be as effective in children with asplenia or splenic deficiency as in children in the control category,” the researchers wrote.
However, these levels were lower in the complement-deficient children, particularly in those with terminal chain complement deficiency and those who took eculizumab.
The proportions of children with exogenous complement serum bactericidal activity titers greater than or equal to 1:5 against the four test strains were 87% (H44/76), 95% (5/99), 68% (NZ98/254), and 73% (M10713) in complement-deficient children, compared with 98%, 99%, 83%, and 99%, respectively, in the healthy controls.
“Ongoing surveillance for vaccine failures is required to determine the significance of the trend to reduced immune response in children with terminal chain complement deficiencies or undergoing treatment with eculizumab,” the researchers wrote.
Eculizumab’s manufacturer has noted the risk of serious meningococcal infections and warned physicians to “immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risk of developing a meningococcal infection,” according to the website.
The study was funded by Novartis Vaccines and Diagnostics (now GlaxoSmithKline Biologicals). Some of the study authors reported various disclosures, including financial relationships with Novartis and GlaxoSmithKline outside the submitted work. Dr. Kaplan reported no relevant financial disclosures.
SOURCE: Martinón-Torres F et al. Pediatrics. 2018 Aug 1. doi: 10.1542/peds.2017-4250.
The Centers for Disease Control and Prevention reported an annual average of 792 cases of meningococcal disease and 98 deaths in the United States from 2006 to 2015 with serotype B isolates causing the highest numbers of cases. In a recent development, two vaccines against this strain have become available in the United States in the past 3 years for people aged 10-25 years. But officials don’t recommend their routine use, instead, guidelines suggest they be given to those at high risk only.
There’s a gap in knowledge because vaccine researchers didn’t include people with complement deficiency (either congenital or related to eculizumab), asplenia, or splenic dysfunction in studies that led to approval. Now, the new study offers reassuring findings regarding the latter two conditions, as bactericidal antibody responses were equal to those in healthy controls.
The findings regarding complement deficiency aren’t surprising, and suggest that vaccine strength in children with the condition only reached the levels in healthy children when an exogenous complement was added.
The study supports guidelines suggesting antibiotic prophylaxis in patients receiving eculizumab even if they already underwent meningococcal vaccination. It’s not clear if this approach also will be effective in those with congenital complement deficiencies (except for complement component 6 deficiency).
It is hoped that surveillance studies will show that use of serogroup B vaccines will prevent invasive meningococcal infections in these high-risk populations for which they are recommended.
Sheldon L. Kaplan, MD, is a pediatrician at Baylor College of Medicine and Texas Children’s Hospital, both in Houston. These comments are summarized from an editorial accompanying the article by Martinón-Torres et al. (Pediatrics. 2018 Aug 1. doi: 10.1542/peds.2018-0554).
The Centers for Disease Control and Prevention reported an annual average of 792 cases of meningococcal disease and 98 deaths in the United States from 2006 to 2015 with serotype B isolates causing the highest numbers of cases. In a recent development, two vaccines against this strain have become available in the United States in the past 3 years for people aged 10-25 years. But officials don’t recommend their routine use, instead, guidelines suggest they be given to those at high risk only.
There’s a gap in knowledge because vaccine researchers didn’t include people with complement deficiency (either congenital or related to eculizumab), asplenia, or splenic dysfunction in studies that led to approval. Now, the new study offers reassuring findings regarding the latter two conditions, as bactericidal antibody responses were equal to those in healthy controls.
The findings regarding complement deficiency aren’t surprising, and suggest that vaccine strength in children with the condition only reached the levels in healthy children when an exogenous complement was added.
The study supports guidelines suggesting antibiotic prophylaxis in patients receiving eculizumab even if they already underwent meningococcal vaccination. It’s not clear if this approach also will be effective in those with congenital complement deficiencies (except for complement component 6 deficiency).
It is hoped that surveillance studies will show that use of serogroup B vaccines will prevent invasive meningococcal infections in these high-risk populations for which they are recommended.
Sheldon L. Kaplan, MD, is a pediatrician at Baylor College of Medicine and Texas Children’s Hospital, both in Houston. These comments are summarized from an editorial accompanying the article by Martinón-Torres et al. (Pediatrics. 2018 Aug 1. doi: 10.1542/peds.2018-0554).
The Centers for Disease Control and Prevention reported an annual average of 792 cases of meningococcal disease and 98 deaths in the United States from 2006 to 2015 with serotype B isolates causing the highest numbers of cases. In a recent development, two vaccines against this strain have become available in the United States in the past 3 years for people aged 10-25 years. But officials don’t recommend their routine use, instead, guidelines suggest they be given to those at high risk only.
There’s a gap in knowledge because vaccine researchers didn’t include people with complement deficiency (either congenital or related to eculizumab), asplenia, or splenic dysfunction in studies that led to approval. Now, the new study offers reassuring findings regarding the latter two conditions, as bactericidal antibody responses were equal to those in healthy controls.
The findings regarding complement deficiency aren’t surprising, and suggest that vaccine strength in children with the condition only reached the levels in healthy children when an exogenous complement was added.
The study supports guidelines suggesting antibiotic prophylaxis in patients receiving eculizumab even if they already underwent meningococcal vaccination. It’s not clear if this approach also will be effective in those with congenital complement deficiencies (except for complement component 6 deficiency).
It is hoped that surveillance studies will show that use of serogroup B vaccines will prevent invasive meningococcal infections in these high-risk populations for which they are recommended.
Sheldon L. Kaplan, MD, is a pediatrician at Baylor College of Medicine and Texas Children’s Hospital, both in Houston. These comments are summarized from an editorial accompanying the article by Martinón-Torres et al. (Pediatrics. 2018 Aug 1. doi: 10.1542/peds.2018-0554).
A new study, the first of its kind, provided support for guidelines suggesting that the capsular meningococcal B vaccine be given to children with three rare conditions that boost infection risk.
For children with terminal chain complement deficiencies or who are undergoing treatment with eculizumab, “it is important that these patients are identified, receive education about sepsis management plans, and are prescribed prophylactic antibiotics according to local guidelines, along with vaccination, to provide every chance for them to be protected against this deadly disease,” the researchers wrote in Pediatrics.
While some countries suggest that the vaccine be given to all healthy infants, U.S. guidelines advise that the vaccine be given to preteenagers, teenagers, and adults who are considered at special risk. These include those with terminal chain complement deficiencies, who are believed to be up to 10,000 times more likely than healthy children to develop invasive meningococcal disease, and those who take eculizumab (Soliris). The risk groups recommended for vaccinations also include those with asplenia and splenic dysfunction, although their excess risk, if any, is unknown.
The new study of the capsular group meningococcal B vaccine, led by Federico Martinón-Torres, PhD, of the Hospital Clinico Universitario de Santiago de Compostela, Spain, adds to previous research that confirmed the effectiveness of vaccinating complement-deficient patients with capsular group A, C, W, and Y meningococcal vaccines.
For the open-label, phase 3b study, researchers in Italy, Spain, Poland, and Russia gave two doses of the vaccine 2 months apart to 239 children aged 2-17 years with an average age of 10 years. Nearly all were white, and 45% were female.
A total of 40 children had complement deficiency, 112 had asplenia or splenic dysfunction, and 87 children in the control group also received the vaccine.
Following vaccination, the percentages of children with exogenous complement serum bactericidal activity titers greater than or equal to 1:5 to the four test strains were similar in the healthy children and those with asplenia/splenic dysfunction. “It is reasonable to expect that this vaccine will be as effective in children with asplenia or splenic deficiency as in children in the control category,” the researchers wrote.
However, these levels were lower in the complement-deficient children, particularly in those with terminal chain complement deficiency and those who took eculizumab.
The proportions of children with exogenous complement serum bactericidal activity titers greater than or equal to 1:5 against the four test strains were 87% (H44/76), 95% (5/99), 68% (NZ98/254), and 73% (M10713) in complement-deficient children, compared with 98%, 99%, 83%, and 99%, respectively, in the healthy controls.
“Ongoing surveillance for vaccine failures is required to determine the significance of the trend to reduced immune response in children with terminal chain complement deficiencies or undergoing treatment with eculizumab,” the researchers wrote.
Eculizumab’s manufacturer has noted the risk of serious meningococcal infections and warned physicians to “immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risk of developing a meningococcal infection,” according to the website.
The study was funded by Novartis Vaccines and Diagnostics (now GlaxoSmithKline Biologicals). Some of the study authors reported various disclosures, including financial relationships with Novartis and GlaxoSmithKline outside the submitted work. Dr. Kaplan reported no relevant financial disclosures.
SOURCE: Martinón-Torres F et al. Pediatrics. 2018 Aug 1. doi: 10.1542/peds.2017-4250.
A new study, the first of its kind, provided support for guidelines suggesting that the capsular meningococcal B vaccine be given to children with three rare conditions that boost infection risk.
For children with terminal chain complement deficiencies or who are undergoing treatment with eculizumab, “it is important that these patients are identified, receive education about sepsis management plans, and are prescribed prophylactic antibiotics according to local guidelines, along with vaccination, to provide every chance for them to be protected against this deadly disease,” the researchers wrote in Pediatrics.
While some countries suggest that the vaccine be given to all healthy infants, U.S. guidelines advise that the vaccine be given to preteenagers, teenagers, and adults who are considered at special risk. These include those with terminal chain complement deficiencies, who are believed to be up to 10,000 times more likely than healthy children to develop invasive meningococcal disease, and those who take eculizumab (Soliris). The risk groups recommended for vaccinations also include those with asplenia and splenic dysfunction, although their excess risk, if any, is unknown.
The new study of the capsular group meningococcal B vaccine, led by Federico Martinón-Torres, PhD, of the Hospital Clinico Universitario de Santiago de Compostela, Spain, adds to previous research that confirmed the effectiveness of vaccinating complement-deficient patients with capsular group A, C, W, and Y meningococcal vaccines.
For the open-label, phase 3b study, researchers in Italy, Spain, Poland, and Russia gave two doses of the vaccine 2 months apart to 239 children aged 2-17 years with an average age of 10 years. Nearly all were white, and 45% were female.
A total of 40 children had complement deficiency, 112 had asplenia or splenic dysfunction, and 87 children in the control group also received the vaccine.
Following vaccination, the percentages of children with exogenous complement serum bactericidal activity titers greater than or equal to 1:5 to the four test strains were similar in the healthy children and those with asplenia/splenic dysfunction. “It is reasonable to expect that this vaccine will be as effective in children with asplenia or splenic deficiency as in children in the control category,” the researchers wrote.
However, these levels were lower in the complement-deficient children, particularly in those with terminal chain complement deficiency and those who took eculizumab.
The proportions of children with exogenous complement serum bactericidal activity titers greater than or equal to 1:5 against the four test strains were 87% (H44/76), 95% (5/99), 68% (NZ98/254), and 73% (M10713) in complement-deficient children, compared with 98%, 99%, 83%, and 99%, respectively, in the healthy controls.
“Ongoing surveillance for vaccine failures is required to determine the significance of the trend to reduced immune response in children with terminal chain complement deficiencies or undergoing treatment with eculizumab,” the researchers wrote.
Eculizumab’s manufacturer has noted the risk of serious meningococcal infections and warned physicians to “immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risk of developing a meningococcal infection,” according to the website.
The study was funded by Novartis Vaccines and Diagnostics (now GlaxoSmithKline Biologicals). Some of the study authors reported various disclosures, including financial relationships with Novartis and GlaxoSmithKline outside the submitted work. Dr. Kaplan reported no relevant financial disclosures.
SOURCE: Martinón-Torres F et al. Pediatrics. 2018 Aug 1. doi: 10.1542/peds.2017-4250.
FROM PEDIATRICS
Key clinical point: The meningococcal B vaccine retained its strength in kids with two rare immunosuppressive diseases, but may be weaker in a third group.
Major finding: The vaccine’s effectiveness was roughly the same in healthy controls and in those with asplenia and splenic dysfunction, but it dipped in those with complement deficiency.
Study details: An open-label, multicenter analysis of children aged 2-17 years who received two doses over 2 months.
Disclosures: The study was funded by Novartis Vaccines and Diagnostics (now GlaxoSmithKline Biologicals). Some of the study authors reported various disclosures, including financial relationships with Novartis and GlaxoSmithKline outside the submitted work. Dr. Kaplan reported no relevant financial disclosures.
Source: Martinón-Torres F et al. Pediatrics. 2018 Aug 1. doi: 10.1542/peds.2017-4250.
CHMP announces 2 opinions on blinatumomab
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has released 2 new opinions regarding blinatumomab (Blincyto).
The CHMP recommended expanding the approved use of blinatumomab to include pediatric patients, but the committee also recommended against approving blinatumomab to treat patients with minimal residual disease (MRD).
Blinatumomab is already approved by the European Commission (EC) as monotherapy for adults with Philadelphia chromosome-negative (Ph-), CD19-positive, relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
Now, the CHMP has recommended expanding this use to include blinatumomab as monotherapy for patients age 1 and older with Ph-, CD19-positive, relapsed/refractory BCP-ALL. These patients must have at least 2 prior therapies or have relapsed after allogeneic hematopoietic stem cell transplant.
This recommendation was supported by data from Study ‘205. Results from this phase 1/2 study were published in the Journal of Clinical Oncology in 2016.
The CHMP has also recommended against approving blinatumomab to treat BCP-ALL patients with MRD.
This decision was influenced by data from the BLAST study. Results from this phase 2 study were published in Blood earlier this year.
The CHMP noted that, although blinatumomab helped clear away residual cells in many patients in the BLAST trial, there is no strong evidence that this leads to improved survival.
Given the uncertainty, the CHMP was of the opinion that the benefits of blinatumomab do not outweigh its risks in MRD-positive BCP-ALL patients.
Amgen, the company developing and marketing blinatumomab, can request a re-examination of the CHMP’s opinion within 15 days of receiving it.
The CHMP’s recommendations are reviewed by the EC, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.
The EC usually makes a decision within 67 days of CHMP recommendations.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has released 2 new opinions regarding blinatumomab (Blincyto).
The CHMP recommended expanding the approved use of blinatumomab to include pediatric patients, but the committee also recommended against approving blinatumomab to treat patients with minimal residual disease (MRD).
Blinatumomab is already approved by the European Commission (EC) as monotherapy for adults with Philadelphia chromosome-negative (Ph-), CD19-positive, relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
Now, the CHMP has recommended expanding this use to include blinatumomab as monotherapy for patients age 1 and older with Ph-, CD19-positive, relapsed/refractory BCP-ALL. These patients must have at least 2 prior therapies or have relapsed after allogeneic hematopoietic stem cell transplant.
This recommendation was supported by data from Study ‘205. Results from this phase 1/2 study were published in the Journal of Clinical Oncology in 2016.
The CHMP has also recommended against approving blinatumomab to treat BCP-ALL patients with MRD.
This decision was influenced by data from the BLAST study. Results from this phase 2 study were published in Blood earlier this year.
The CHMP noted that, although blinatumomab helped clear away residual cells in many patients in the BLAST trial, there is no strong evidence that this leads to improved survival.
Given the uncertainty, the CHMP was of the opinion that the benefits of blinatumomab do not outweigh its risks in MRD-positive BCP-ALL patients.
Amgen, the company developing and marketing blinatumomab, can request a re-examination of the CHMP’s opinion within 15 days of receiving it.
The CHMP’s recommendations are reviewed by the EC, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.
The EC usually makes a decision within 67 days of CHMP recommendations.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has released 2 new opinions regarding blinatumomab (Blincyto).
The CHMP recommended expanding the approved use of blinatumomab to include pediatric patients, but the committee also recommended against approving blinatumomab to treat patients with minimal residual disease (MRD).
Blinatumomab is already approved by the European Commission (EC) as monotherapy for adults with Philadelphia chromosome-negative (Ph-), CD19-positive, relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
Now, the CHMP has recommended expanding this use to include blinatumomab as monotherapy for patients age 1 and older with Ph-, CD19-positive, relapsed/refractory BCP-ALL. These patients must have at least 2 prior therapies or have relapsed after allogeneic hematopoietic stem cell transplant.
This recommendation was supported by data from Study ‘205. Results from this phase 1/2 study were published in the Journal of Clinical Oncology in 2016.
The CHMP has also recommended against approving blinatumomab to treat BCP-ALL patients with MRD.
This decision was influenced by data from the BLAST study. Results from this phase 2 study were published in Blood earlier this year.
The CHMP noted that, although blinatumomab helped clear away residual cells in many patients in the BLAST trial, there is no strong evidence that this leads to improved survival.
Given the uncertainty, the CHMP was of the opinion that the benefits of blinatumomab do not outweigh its risks in MRD-positive BCP-ALL patients.
Amgen, the company developing and marketing blinatumomab, can request a re-examination of the CHMP’s opinion within 15 days of receiving it.
The CHMP’s recommendations are reviewed by the EC, which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.
The EC usually makes a decision within 67 days of CHMP recommendations.
Promoting a child’s resilience
As an inpatient child psychiatrist, I see children with some of the most difficult emotional and behavioral issues. And among them, children with adverse childhood experiences (ACE) make up a significant portion. But early childhood adversity is common not just among children who present to the hospital. In the landmark ACE study, which was an ongoing collaboration between Kaiser Permanente and the Centers for Disease Control and Prevention to assess impact of ACEs on various health outcomes, 40% percent of the participants reported experiencing two or more ACEs.1 Subsequent studies have shown even higher numbers. The study by Copeland et al. on traumatic events based on the Great Smokey Mountains Study showed that more than two-thirds of children reported at least one traumatic event by the age of 16 years.2
The significance of this finding cannot be overstated. It is clear that the cumulative incidences of ACEs are associated with poorer health outcomes in a graded dose-response relationship. Those exposed are at great risk of developing PTSD, ADHD, mood disorders, anxiety disorders, and substance use disorder.3 Furthermore, they also are at risk for developing asthma, obesity, ischemic heart disease, diabetes, chronic obstructive pulmonary disease, autoimmune disease, and sexually transmitted disease.4 They have lower quality of life, use more health care services, and die nearly 20 years younger.5
Currently, the biology of adverse childhood experiences is being elucidated. The deleterious effects of chronically elevated cortisol leading to smaller hippocampal volume through atrophy, neurotoxicity, and disruption of neurogenesis has been demonstrated in adults, but children and adolescents have been found to have reduced medial and posterior corpus callosum.6-10 Other alterations include changes in EEG activity, and dysregulation of the sympathetic nervous system.11-13 New systems or neuropeptides that could potentially be beneficial in the treatment of trauma include tempering down of the locus coeruleus–norepinephrine system, the anxiolytic effect of neuropeptide Y, and brain-derived neurotrophic factor.14,15
Despite all the progress, the treatment for trauma remains imperfect. Depending on the presenting symptoms, stimulants, alpha-agonists (guanfacine or clonidine), alpha-1 blocker, and/or SSRIs all could be a good first step. Medication could reduce the burden of some of the symptoms, but its effects are limited. During the 1970s, researchers started noticing that some children were able to thrive despite substantial risk factors for mental illness. This led to research identifying individual and environmental factors that could be protective against ACEs.
So, what is resilience? It is the development of positive adaptations in the context of significant adversity.16 But this ability is not purely incumbent on the child. The individual characteristics that lead to resilience such as internal locus of control, optimism, and determination also are dependent on their environment. As such, it is a complex dynamic interplay of genetics, temperament, experience, and environmental supports. As much as the environment can affect resilience, this gives us opportunities to help the child be more resilient, perhaps before an adverse event happens.
One, emphasize the family! A strong family relationship is among the most robust predictor of resilient adaptation. Early experiences and attachments will shape the lens through which people view their subsequent relationships and place them on probabilistic trajectories of “relatively good or bad adaptation.”17 And just what constitutes “good parenting”? The authoritative parenting style that balances appropriate controls and warmth with consistency and responsiveness generally lead to better outcomes.18 Other important features include reasonable limit-setting, monitoring, and containment.19, 20 Clinicians with expertise in one of the parent-coaching manuals (i.e., “Helping the Noncompliant Child,” by McMahon and Forehand; and “Your Defiant Child: Eight Steps to Better Behavior,” by Barkley and Benton and others) can be helpful in answering parenting questions whether individually or in the group setting.
In addition, parental mental health issues also can adversely affect family relationships. Based on previous studies, mothers who suffer from depression have more difficulty being responsive and warm to their child.21 They are often times more punitive and less consistent. Children of mothers with depression are at risk for internalizing, externalizing, and general psychopathology.22 Mothers with history of ACEs are less able to modulate stress and model coping skills. As such, it can be just as important to screen the parents for mental health issues and refer to the appropriate clinician.
Two, community supports also can facilitate development of resilience. Studies have shown participants in the Big Brothers and Big Sisters programs of America exhibit more positive behavior such as better academic behaviors, better relationships with family and friends, and decreased substance use.23 Furthermore, studies on minority students (African American and Hispanic) suggest improved relationship with teachers led to less behavioral problems and improved social competence. Religious affiliations and other social supports can serve similar purposes as well.24
Three, keep in mind the malleability of the child. Many child attributes are dependent on environmental influences and resilience should focus more on what adults can do to bolster the child’s own efforts.
Dr. Chung is a child and adolescent psychiatrist at the University of Vermont Medical Center, Burlington, and practices at Champlain Valley Physician’s Hospital in Plattsburgh, N.Y. Email him at pdnews@mdedge.com.
References
1. Am J Prev Med. 1998 May;14(4):245-58.
2. Arch Gen Psychiatry. 2007 May;64(5):577-84.
3. Eur Arch Psychiatry Clin Neurosci. 2006 Apr;256(3):174-86.
4. Am J Prev Med. 1998 May;14(4):245-58.
5. Pediatr Res. 2016 Jan;79(1-2):227-33.
6. Prog Neuropsychopharmacol Biol Psychiatry. 2010 Oct 1;34(7):1181-8.
7. Brain Res. 1992 Aug 21;588(2):341-5.
8. J Neurosci. 1985 May;5(5):1222-7.
9. J Comp Neurol. 1996 May 20;369(1):56-63.
10. Biol Psychiatry. 2002 Dec 1;52(11):1066-78.
11. J Neuropsychiatry Clin Neurosci. 1998 Summer;10(3):298-307.
12. Biol Psychiatry. 2002 Apr 1;51(7):575-82.
13. Brain Res. 2009 Oct 13;1293:13-23.
14. Neuropeptides. 2016 Apr;56:19-24.
15. Cell. 2007 Oct 19;131(2):391-404.
16. Child Dev. 2000; 71(3): 543-62.
17. Lewis’s Child and Adolescent Psychiatry: A Comprehensive Textbook, 4th ed. (Baltimore: Lippincott Williams & Wilkins, 2007)
18. Early Hum Dev. 2010 Nov;86(11):689-93.
19. Clin Child Fam Psychol Rev. 1998 Mar;1(1):61-75.
20. Dev Psychopathol. 2003 Winter;15(1):95-117.
21. Clin Psychol Rev. 2000 Aug;20(5):561-92.
22. Clin Child Fam Psychol Rev. 2011 Mar;14(1):1-27.
23. “Making a Difference: An Impact Study of Big Brothers Big Sisters,” (Philadelphia: Public/Private Ventures, 1995).
24. Child Dev. 2003 Nov-Dec;74(6):1682-96.
As an inpatient child psychiatrist, I see children with some of the most difficult emotional and behavioral issues. And among them, children with adverse childhood experiences (ACE) make up a significant portion. But early childhood adversity is common not just among children who present to the hospital. In the landmark ACE study, which was an ongoing collaboration between Kaiser Permanente and the Centers for Disease Control and Prevention to assess impact of ACEs on various health outcomes, 40% percent of the participants reported experiencing two or more ACEs.1 Subsequent studies have shown even higher numbers. The study by Copeland et al. on traumatic events based on the Great Smokey Mountains Study showed that more than two-thirds of children reported at least one traumatic event by the age of 16 years.2
The significance of this finding cannot be overstated. It is clear that the cumulative incidences of ACEs are associated with poorer health outcomes in a graded dose-response relationship. Those exposed are at great risk of developing PTSD, ADHD, mood disorders, anxiety disorders, and substance use disorder.3 Furthermore, they also are at risk for developing asthma, obesity, ischemic heart disease, diabetes, chronic obstructive pulmonary disease, autoimmune disease, and sexually transmitted disease.4 They have lower quality of life, use more health care services, and die nearly 20 years younger.5
Currently, the biology of adverse childhood experiences is being elucidated. The deleterious effects of chronically elevated cortisol leading to smaller hippocampal volume through atrophy, neurotoxicity, and disruption of neurogenesis has been demonstrated in adults, but children and adolescents have been found to have reduced medial and posterior corpus callosum.6-10 Other alterations include changes in EEG activity, and dysregulation of the sympathetic nervous system.11-13 New systems or neuropeptides that could potentially be beneficial in the treatment of trauma include tempering down of the locus coeruleus–norepinephrine system, the anxiolytic effect of neuropeptide Y, and brain-derived neurotrophic factor.14,15
Despite all the progress, the treatment for trauma remains imperfect. Depending on the presenting symptoms, stimulants, alpha-agonists (guanfacine or clonidine), alpha-1 blocker, and/or SSRIs all could be a good first step. Medication could reduce the burden of some of the symptoms, but its effects are limited. During the 1970s, researchers started noticing that some children were able to thrive despite substantial risk factors for mental illness. This led to research identifying individual and environmental factors that could be protective against ACEs.
So, what is resilience? It is the development of positive adaptations in the context of significant adversity.16 But this ability is not purely incumbent on the child. The individual characteristics that lead to resilience such as internal locus of control, optimism, and determination also are dependent on their environment. As such, it is a complex dynamic interplay of genetics, temperament, experience, and environmental supports. As much as the environment can affect resilience, this gives us opportunities to help the child be more resilient, perhaps before an adverse event happens.
One, emphasize the family! A strong family relationship is among the most robust predictor of resilient adaptation. Early experiences and attachments will shape the lens through which people view their subsequent relationships and place them on probabilistic trajectories of “relatively good or bad adaptation.”17 And just what constitutes “good parenting”? The authoritative parenting style that balances appropriate controls and warmth with consistency and responsiveness generally lead to better outcomes.18 Other important features include reasonable limit-setting, monitoring, and containment.19, 20 Clinicians with expertise in one of the parent-coaching manuals (i.e., “Helping the Noncompliant Child,” by McMahon and Forehand; and “Your Defiant Child: Eight Steps to Better Behavior,” by Barkley and Benton and others) can be helpful in answering parenting questions whether individually or in the group setting.
In addition, parental mental health issues also can adversely affect family relationships. Based on previous studies, mothers who suffer from depression have more difficulty being responsive and warm to their child.21 They are often times more punitive and less consistent. Children of mothers with depression are at risk for internalizing, externalizing, and general psychopathology.22 Mothers with history of ACEs are less able to modulate stress and model coping skills. As such, it can be just as important to screen the parents for mental health issues and refer to the appropriate clinician.
Two, community supports also can facilitate development of resilience. Studies have shown participants in the Big Brothers and Big Sisters programs of America exhibit more positive behavior such as better academic behaviors, better relationships with family and friends, and decreased substance use.23 Furthermore, studies on minority students (African American and Hispanic) suggest improved relationship with teachers led to less behavioral problems and improved social competence. Religious affiliations and other social supports can serve similar purposes as well.24
Three, keep in mind the malleability of the child. Many child attributes are dependent on environmental influences and resilience should focus more on what adults can do to bolster the child’s own efforts.
Dr. Chung is a child and adolescent psychiatrist at the University of Vermont Medical Center, Burlington, and practices at Champlain Valley Physician’s Hospital in Plattsburgh, N.Y. Email him at pdnews@mdedge.com.
References
1. Am J Prev Med. 1998 May;14(4):245-58.
2. Arch Gen Psychiatry. 2007 May;64(5):577-84.
3. Eur Arch Psychiatry Clin Neurosci. 2006 Apr;256(3):174-86.
4. Am J Prev Med. 1998 May;14(4):245-58.
5. Pediatr Res. 2016 Jan;79(1-2):227-33.
6. Prog Neuropsychopharmacol Biol Psychiatry. 2010 Oct 1;34(7):1181-8.
7. Brain Res. 1992 Aug 21;588(2):341-5.
8. J Neurosci. 1985 May;5(5):1222-7.
9. J Comp Neurol. 1996 May 20;369(1):56-63.
10. Biol Psychiatry. 2002 Dec 1;52(11):1066-78.
11. J Neuropsychiatry Clin Neurosci. 1998 Summer;10(3):298-307.
12. Biol Psychiatry. 2002 Apr 1;51(7):575-82.
13. Brain Res. 2009 Oct 13;1293:13-23.
14. Neuropeptides. 2016 Apr;56:19-24.
15. Cell. 2007 Oct 19;131(2):391-404.
16. Child Dev. 2000; 71(3): 543-62.
17. Lewis’s Child and Adolescent Psychiatry: A Comprehensive Textbook, 4th ed. (Baltimore: Lippincott Williams & Wilkins, 2007)
18. Early Hum Dev. 2010 Nov;86(11):689-93.
19. Clin Child Fam Psychol Rev. 1998 Mar;1(1):61-75.
20. Dev Psychopathol. 2003 Winter;15(1):95-117.
21. Clin Psychol Rev. 2000 Aug;20(5):561-92.
22. Clin Child Fam Psychol Rev. 2011 Mar;14(1):1-27.
23. “Making a Difference: An Impact Study of Big Brothers Big Sisters,” (Philadelphia: Public/Private Ventures, 1995).
24. Child Dev. 2003 Nov-Dec;74(6):1682-96.
As an inpatient child psychiatrist, I see children with some of the most difficult emotional and behavioral issues. And among them, children with adverse childhood experiences (ACE) make up a significant portion. But early childhood adversity is common not just among children who present to the hospital. In the landmark ACE study, which was an ongoing collaboration between Kaiser Permanente and the Centers for Disease Control and Prevention to assess impact of ACEs on various health outcomes, 40% percent of the participants reported experiencing two or more ACEs.1 Subsequent studies have shown even higher numbers. The study by Copeland et al. on traumatic events based on the Great Smokey Mountains Study showed that more than two-thirds of children reported at least one traumatic event by the age of 16 years.2
The significance of this finding cannot be overstated. It is clear that the cumulative incidences of ACEs are associated with poorer health outcomes in a graded dose-response relationship. Those exposed are at great risk of developing PTSD, ADHD, mood disorders, anxiety disorders, and substance use disorder.3 Furthermore, they also are at risk for developing asthma, obesity, ischemic heart disease, diabetes, chronic obstructive pulmonary disease, autoimmune disease, and sexually transmitted disease.4 They have lower quality of life, use more health care services, and die nearly 20 years younger.5
Currently, the biology of adverse childhood experiences is being elucidated. The deleterious effects of chronically elevated cortisol leading to smaller hippocampal volume through atrophy, neurotoxicity, and disruption of neurogenesis has been demonstrated in adults, but children and adolescents have been found to have reduced medial and posterior corpus callosum.6-10 Other alterations include changes in EEG activity, and dysregulation of the sympathetic nervous system.11-13 New systems or neuropeptides that could potentially be beneficial in the treatment of trauma include tempering down of the locus coeruleus–norepinephrine system, the anxiolytic effect of neuropeptide Y, and brain-derived neurotrophic factor.14,15
Despite all the progress, the treatment for trauma remains imperfect. Depending on the presenting symptoms, stimulants, alpha-agonists (guanfacine or clonidine), alpha-1 blocker, and/or SSRIs all could be a good first step. Medication could reduce the burden of some of the symptoms, but its effects are limited. During the 1970s, researchers started noticing that some children were able to thrive despite substantial risk factors for mental illness. This led to research identifying individual and environmental factors that could be protective against ACEs.
So, what is resilience? It is the development of positive adaptations in the context of significant adversity.16 But this ability is not purely incumbent on the child. The individual characteristics that lead to resilience such as internal locus of control, optimism, and determination also are dependent on their environment. As such, it is a complex dynamic interplay of genetics, temperament, experience, and environmental supports. As much as the environment can affect resilience, this gives us opportunities to help the child be more resilient, perhaps before an adverse event happens.
One, emphasize the family! A strong family relationship is among the most robust predictor of resilient adaptation. Early experiences and attachments will shape the lens through which people view their subsequent relationships and place them on probabilistic trajectories of “relatively good or bad adaptation.”17 And just what constitutes “good parenting”? The authoritative parenting style that balances appropriate controls and warmth with consistency and responsiveness generally lead to better outcomes.18 Other important features include reasonable limit-setting, monitoring, and containment.19, 20 Clinicians with expertise in one of the parent-coaching manuals (i.e., “Helping the Noncompliant Child,” by McMahon and Forehand; and “Your Defiant Child: Eight Steps to Better Behavior,” by Barkley and Benton and others) can be helpful in answering parenting questions whether individually or in the group setting.
In addition, parental mental health issues also can adversely affect family relationships. Based on previous studies, mothers who suffer from depression have more difficulty being responsive and warm to their child.21 They are often times more punitive and less consistent. Children of mothers with depression are at risk for internalizing, externalizing, and general psychopathology.22 Mothers with history of ACEs are less able to modulate stress and model coping skills. As such, it can be just as important to screen the parents for mental health issues and refer to the appropriate clinician.
Two, community supports also can facilitate development of resilience. Studies have shown participants in the Big Brothers and Big Sisters programs of America exhibit more positive behavior such as better academic behaviors, better relationships with family and friends, and decreased substance use.23 Furthermore, studies on minority students (African American and Hispanic) suggest improved relationship with teachers led to less behavioral problems and improved social competence. Religious affiliations and other social supports can serve similar purposes as well.24
Three, keep in mind the malleability of the child. Many child attributes are dependent on environmental influences and resilience should focus more on what adults can do to bolster the child’s own efforts.
Dr. Chung is a child and adolescent psychiatrist at the University of Vermont Medical Center, Burlington, and practices at Champlain Valley Physician’s Hospital in Plattsburgh, N.Y. Email him at pdnews@mdedge.com.
References
1. Am J Prev Med. 1998 May;14(4):245-58.
2. Arch Gen Psychiatry. 2007 May;64(5):577-84.
3. Eur Arch Psychiatry Clin Neurosci. 2006 Apr;256(3):174-86.
4. Am J Prev Med. 1998 May;14(4):245-58.
5. Pediatr Res. 2016 Jan;79(1-2):227-33.
6. Prog Neuropsychopharmacol Biol Psychiatry. 2010 Oct 1;34(7):1181-8.
7. Brain Res. 1992 Aug 21;588(2):341-5.
8. J Neurosci. 1985 May;5(5):1222-7.
9. J Comp Neurol. 1996 May 20;369(1):56-63.
10. Biol Psychiatry. 2002 Dec 1;52(11):1066-78.
11. J Neuropsychiatry Clin Neurosci. 1998 Summer;10(3):298-307.
12. Biol Psychiatry. 2002 Apr 1;51(7):575-82.
13. Brain Res. 2009 Oct 13;1293:13-23.
14. Neuropeptides. 2016 Apr;56:19-24.
15. Cell. 2007 Oct 19;131(2):391-404.
16. Child Dev. 2000; 71(3): 543-62.
17. Lewis’s Child and Adolescent Psychiatry: A Comprehensive Textbook, 4th ed. (Baltimore: Lippincott Williams & Wilkins, 2007)
18. Early Hum Dev. 2010 Nov;86(11):689-93.
19. Clin Child Fam Psychol Rev. 1998 Mar;1(1):61-75.
20. Dev Psychopathol. 2003 Winter;15(1):95-117.
21. Clin Psychol Rev. 2000 Aug;20(5):561-92.
22. Clin Child Fam Psychol Rev. 2011 Mar;14(1):1-27.
23. “Making a Difference: An Impact Study of Big Brothers Big Sisters,” (Philadelphia: Public/Private Ventures, 1995).
24. Child Dev. 2003 Nov-Dec;74(6):1682-96.
DTPa-HBV-IPV/Hib in infancy maintains lasting immune memory against HBV in teens
MALMO, SWEDEN – Four doses of hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus/Haemophilus influenza type b vaccine given in infancy provides reassuringly long-lasting immune memory against hepatitis B among 14- to 15-year-olds, Tino F. Schwarz, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
He presented the fourth and final study in a series evaluating the antibody persistence and immune memory against hepatitis B (HBV) in recipients of the complete four-dose series of hexavalent DTPa-HBV-IPV/Hib vaccine in infancy. Because exposure to HBV can increase during adolescence, it was essential to determine whether antibody persistence is maintained, explained Dr. Schwarz of Juliusspital Hospital in Wurzburg, Germany.
“As expected, we saw a decrease in anti-HBs [hepatitis B surface antigen] antibody levels over the years, with persistent seroprotection in 85% of children at age 4-5 years, 72% at 7-8 years, 61% at 12-13 years, and now 54% of adolescents at 14-15 years. But we could demonstrate a very strong anamnestic response in the trial. This is good information. It clearly shows that, in patients who are exposed to hepatitis B, we can certainly guarantee that they are protected. It’s a good result for public health. The vaccine is a very robust vaccine which induces a very strong response over the years. It can be boosted, but from an immunologic point of view it is not required,” he said.
The multicenter study included 268 adolescents aged 14-15 years who had received the four-dose hexavalent vaccine series in infancy. Their antibody persistence against anti-HBs was measured, then measured once again 1 month after receiving a challenge dose of monovalent HBV vaccine.
Prechallenge, 105 of the teens were seronegative, 144 were seroprotected as defined by an anti-HBs concentration of at least 10 mIU/mL, and 19 had low seropositivity marked by an antibody level of 6 to less than 10 mIU/mL. Yet 1 month after the booster, which was intended to mimic the impact of real-world exposure to HBV, 83% of the initially seronegative subjects had an anti-HBs concentration of 10 mIU/mL or more, and 67% of them had a level of at least 100 mIU/mL.
“We saw a clear fantastic anamnestic response,” Dr. Schwarz declared.
Overall, 93% of study participants seroconverted, and 87% of them had anti-HBs titers of 100 mIU/mL, “which is the level we’d like to achieve in vaccinees,” he observed.
The booster monovalent HBV vaccine was well tolerated, with one-third of subjects complaining of mild local injection site pain and 30% noting fatigue. But in response to a question posed by session chair Ronald de Groot, MD, emeritus professor of pediatrics at Radboud University in Nijmegen, the Netherlands, Dr. Schwarz said these study results indicate there’s no need for routine boosting in healthy adolescents such as those in the trial. Immunocompromised individuals might be a different story, but they weren’t investigated.
But what about in physicians and surgeons, where protection against HBV infection is essential? Dr. de Groot asked.
“In Germany, we require a titer of 100 mIU/mL or more in medical staff, but we’re quite alone in Europe. Other countries do not require booster vaccination for medical staff. The data we’ve shown here is quite reassuring: If you get exposed, you in effect get a booster. It’s complicated to test surgeons in their offices; better to just rely on the anamnestic response that we’ve demonstrated,” Dr. Schwarz replied.
He reported serving as a consultant to GlaxoSmithKline, which funded the study, as well as to Pfizer and Sanofi Pasteur.
MALMO, SWEDEN – Four doses of hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus/Haemophilus influenza type b vaccine given in infancy provides reassuringly long-lasting immune memory against hepatitis B among 14- to 15-year-olds, Tino F. Schwarz, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
He presented the fourth and final study in a series evaluating the antibody persistence and immune memory against hepatitis B (HBV) in recipients of the complete four-dose series of hexavalent DTPa-HBV-IPV/Hib vaccine in infancy. Because exposure to HBV can increase during adolescence, it was essential to determine whether antibody persistence is maintained, explained Dr. Schwarz of Juliusspital Hospital in Wurzburg, Germany.
“As expected, we saw a decrease in anti-HBs [hepatitis B surface antigen] antibody levels over the years, with persistent seroprotection in 85% of children at age 4-5 years, 72% at 7-8 years, 61% at 12-13 years, and now 54% of adolescents at 14-15 years. But we could demonstrate a very strong anamnestic response in the trial. This is good information. It clearly shows that, in patients who are exposed to hepatitis B, we can certainly guarantee that they are protected. It’s a good result for public health. The vaccine is a very robust vaccine which induces a very strong response over the years. It can be boosted, but from an immunologic point of view it is not required,” he said.
The multicenter study included 268 adolescents aged 14-15 years who had received the four-dose hexavalent vaccine series in infancy. Their antibody persistence against anti-HBs was measured, then measured once again 1 month after receiving a challenge dose of monovalent HBV vaccine.
Prechallenge, 105 of the teens were seronegative, 144 were seroprotected as defined by an anti-HBs concentration of at least 10 mIU/mL, and 19 had low seropositivity marked by an antibody level of 6 to less than 10 mIU/mL. Yet 1 month after the booster, which was intended to mimic the impact of real-world exposure to HBV, 83% of the initially seronegative subjects had an anti-HBs concentration of 10 mIU/mL or more, and 67% of them had a level of at least 100 mIU/mL.
“We saw a clear fantastic anamnestic response,” Dr. Schwarz declared.
Overall, 93% of study participants seroconverted, and 87% of them had anti-HBs titers of 100 mIU/mL, “which is the level we’d like to achieve in vaccinees,” he observed.
The booster monovalent HBV vaccine was well tolerated, with one-third of subjects complaining of mild local injection site pain and 30% noting fatigue. But in response to a question posed by session chair Ronald de Groot, MD, emeritus professor of pediatrics at Radboud University in Nijmegen, the Netherlands, Dr. Schwarz said these study results indicate there’s no need for routine boosting in healthy adolescents such as those in the trial. Immunocompromised individuals might be a different story, but they weren’t investigated.
But what about in physicians and surgeons, where protection against HBV infection is essential? Dr. de Groot asked.
“In Germany, we require a titer of 100 mIU/mL or more in medical staff, but we’re quite alone in Europe. Other countries do not require booster vaccination for medical staff. The data we’ve shown here is quite reassuring: If you get exposed, you in effect get a booster. It’s complicated to test surgeons in their offices; better to just rely on the anamnestic response that we’ve demonstrated,” Dr. Schwarz replied.
He reported serving as a consultant to GlaxoSmithKline, which funded the study, as well as to Pfizer and Sanofi Pasteur.
MALMO, SWEDEN – Four doses of hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus/Haemophilus influenza type b vaccine given in infancy provides reassuringly long-lasting immune memory against hepatitis B among 14- to 15-year-olds, Tino F. Schwarz, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
He presented the fourth and final study in a series evaluating the antibody persistence and immune memory against hepatitis B (HBV) in recipients of the complete four-dose series of hexavalent DTPa-HBV-IPV/Hib vaccine in infancy. Because exposure to HBV can increase during adolescence, it was essential to determine whether antibody persistence is maintained, explained Dr. Schwarz of Juliusspital Hospital in Wurzburg, Germany.
“As expected, we saw a decrease in anti-HBs [hepatitis B surface antigen] antibody levels over the years, with persistent seroprotection in 85% of children at age 4-5 years, 72% at 7-8 years, 61% at 12-13 years, and now 54% of adolescents at 14-15 years. But we could demonstrate a very strong anamnestic response in the trial. This is good information. It clearly shows that, in patients who are exposed to hepatitis B, we can certainly guarantee that they are protected. It’s a good result for public health. The vaccine is a very robust vaccine which induces a very strong response over the years. It can be boosted, but from an immunologic point of view it is not required,” he said.
The multicenter study included 268 adolescents aged 14-15 years who had received the four-dose hexavalent vaccine series in infancy. Their antibody persistence against anti-HBs was measured, then measured once again 1 month after receiving a challenge dose of monovalent HBV vaccine.
Prechallenge, 105 of the teens were seronegative, 144 were seroprotected as defined by an anti-HBs concentration of at least 10 mIU/mL, and 19 had low seropositivity marked by an antibody level of 6 to less than 10 mIU/mL. Yet 1 month after the booster, which was intended to mimic the impact of real-world exposure to HBV, 83% of the initially seronegative subjects had an anti-HBs concentration of 10 mIU/mL or more, and 67% of them had a level of at least 100 mIU/mL.
“We saw a clear fantastic anamnestic response,” Dr. Schwarz declared.
Overall, 93% of study participants seroconverted, and 87% of them had anti-HBs titers of 100 mIU/mL, “which is the level we’d like to achieve in vaccinees,” he observed.
The booster monovalent HBV vaccine was well tolerated, with one-third of subjects complaining of mild local injection site pain and 30% noting fatigue. But in response to a question posed by session chair Ronald de Groot, MD, emeritus professor of pediatrics at Radboud University in Nijmegen, the Netherlands, Dr. Schwarz said these study results indicate there’s no need for routine boosting in healthy adolescents such as those in the trial. Immunocompromised individuals might be a different story, but they weren’t investigated.
But what about in physicians and surgeons, where protection against HBV infection is essential? Dr. de Groot asked.
“In Germany, we require a titer of 100 mIU/mL or more in medical staff, but we’re quite alone in Europe. Other countries do not require booster vaccination for medical staff. The data we’ve shown here is quite reassuring: If you get exposed, you in effect get a booster. It’s complicated to test surgeons in their offices; better to just rely on the anamnestic response that we’ve demonstrated,” Dr. Schwarz replied.
He reported serving as a consultant to GlaxoSmithKline, which funded the study, as well as to Pfizer and Sanofi Pasteur.
REPORTING FROM ESPID 2018
Key clinical point:
Major finding: Ninety-three percent of recipients of four doses of hexavalent DTPa-HBV-IPV/Hib vaccine in infancy were seroprotected against HBV at age 14-15 years.
Study details: This was a prospective study of antibody persistence and immune memory in 268 teens aged 14-15 before and 1 month after receiving a booster challenge HBV monovalent vaccine.
Disclosures: The presenter reported serving as a consultant to GlaxoSmithKline, which funded the study, as well as to Pfizer and Sanofi Pasteur.
What is your diagnosis?
Laboratory work revealed a normal CBC and differential, an elevated C-reactive protein (CRP) and sedimentation rate (ESR), negative antistreptolysin O (ASO) titers, negative pregnancy test, a normal urinalysis, and negative blood, throat, and urine cultures. A chest x-ray also was negative as well as angiotensin-converting enzyme (ACE) levels. Tuberculosis interferon-gamma release essay was negative.
The patient was diagnosed with erythema nodosum (EN), based on physical exam and history of the lesions. In her particular case, infectious causes including streptococcus infection, tuberculosis, and coccidioidomycosis were ruled out. There were no x-ray findings that suggested sarcoidosis and her ACE level was within normal limits. The pregnancy test also was negative. Given her recent start on OCs, this was thought to be the cause of the lesions.
She was treated with elevation, compression stockings, and NSAIDs and discontinuation of OCs. The lesions resolved after 6 weeks leaving bruiselike patches (erythema contusiformis).
EN is a delayed-type hypersensitivity reaction, causing inflammation on the fat (panniculitis) most commonly on the shins, but it can also occur on the arms, face, neck, and thighs. It is the most common type of panniculitis and is usually seen more often in women from the second to fourth decade of life. Erythematous tender nodules in crops commonly located on the shins are the characteristic physical finding. Systemic symptoms can occur including fever, malaise, and joint pain. The lesions usually last up to 6-8 weeks and may leave bruiselike patches or postinflammatory hyperpigmentation that can take months to improve.1
The diagnosis of EN usually is made by physical examination and natural history. In unusual severe cases or lesions in atypical locations, a skin biopsy is indicated. Histologic examination of one of the lesions reveals a septal panniculitis without vasculitis. Miescher’s radial granulomas (grouped macrophages around neutrophils or septa-like spaces) often are present and are a characteristic feature of EN.
EN can be triggered by different types of infections such as streptococcus, mycoplasma, tuberculosis, or bacterial gastroenteritis; medications such as OCs, sulfonamides, iodides, penicillin, or bromides; medical conditions that include inflammatory bowel disease, pregnancy, or sarcoidosis; or neutrophilic dermatosis and malignancy such as leukemia and Hodgkin disease.2,3 A third of the cases are idiopathic. In children, streptococcal infections are responsible for most cases of EN.4
Recommended work-up to investigate possible triggers includes a CBC with differential, sedimentation rate, CRP, ASO titers or anti-DNase B titers, tuberculin skin test or interferon-gamma TB test and a chest X ray. If there are any other symptoms, physical signs, or risk factors are present for the other not so common causes, further ancillary testing may be warranted.
Erythematous nodules and papules on the shin in children are commonly caused by arthropod bites also known as papular urticaria. These lesions are pruritic rather than tender and usually respond to topical corticosteroids and oral antihistamines. Subcutaneous bacterial, fungal, or atypical mycobacterial infections can present with tender nodules that can ulcerate and drain on the shins, feet, or any other body part. These patients may have a history of immunodeficiency and usually systemic symptoms of infection are present. Cutaneous polyarteritis nodosa (PAN) also can present with tender nodules on the legs but these lesions usually necrose and ulcerate and may be associated with livedo racemosa, a transient or persistent, blotchy, reddish-blue to purple, netlike cyanotic pattern. On pathology, PAN presents with necrotizing medium vessel vasculitis. Malignant nodules also can occur on the shin. Pathology will show atypical cells. Other forms of panniculitis, such as erythema induratum and pancreatic panniculitis, can present with tender nodules but these lesions usually occur on the calves and ulcerate.
Management of EN starts with treating the underlying infection or stopping the causative medication. Initial measures include bed rest, leg elevation, compression bandages, and NSAIDs. Potassium iodide is a very effective therapy as it may control the symptoms within 24 hours. When there is no response to the above, or the patient has severe symptoms, a short course of systemic glucocorticoids can be started. Other medications for recalcitrant or recurrent lesions include colchicine, dapsone, or hydroxychloroquine.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
References
1. Panniculitis, in “Dermatology,” 3rd ed. (Philadelphia: Elsevier Saunders, 2012, p. 1641).
2. Arthritis Rheum. 2000 Mar;43(3):584-92.
3. J Clin Oncol. 2007 Sep 1;25(25):4011-2.
4. Turk J Pediatr. 2014 Mar-Apr;56(2):144-9.
Laboratory work revealed a normal CBC and differential, an elevated C-reactive protein (CRP) and sedimentation rate (ESR), negative antistreptolysin O (ASO) titers, negative pregnancy test, a normal urinalysis, and negative blood, throat, and urine cultures. A chest x-ray also was negative as well as angiotensin-converting enzyme (ACE) levels. Tuberculosis interferon-gamma release essay was negative.
The patient was diagnosed with erythema nodosum (EN), based on physical exam and history of the lesions. In her particular case, infectious causes including streptococcus infection, tuberculosis, and coccidioidomycosis were ruled out. There were no x-ray findings that suggested sarcoidosis and her ACE level was within normal limits. The pregnancy test also was negative. Given her recent start on OCs, this was thought to be the cause of the lesions.
She was treated with elevation, compression stockings, and NSAIDs and discontinuation of OCs. The lesions resolved after 6 weeks leaving bruiselike patches (erythema contusiformis).
EN is a delayed-type hypersensitivity reaction, causing inflammation on the fat (panniculitis) most commonly on the shins, but it can also occur on the arms, face, neck, and thighs. It is the most common type of panniculitis and is usually seen more often in women from the second to fourth decade of life. Erythematous tender nodules in crops commonly located on the shins are the characteristic physical finding. Systemic symptoms can occur including fever, malaise, and joint pain. The lesions usually last up to 6-8 weeks and may leave bruiselike patches or postinflammatory hyperpigmentation that can take months to improve.1
The diagnosis of EN usually is made by physical examination and natural history. In unusual severe cases or lesions in atypical locations, a skin biopsy is indicated. Histologic examination of one of the lesions reveals a septal panniculitis without vasculitis. Miescher’s radial granulomas (grouped macrophages around neutrophils or septa-like spaces) often are present and are a characteristic feature of EN.
EN can be triggered by different types of infections such as streptococcus, mycoplasma, tuberculosis, or bacterial gastroenteritis; medications such as OCs, sulfonamides, iodides, penicillin, or bromides; medical conditions that include inflammatory bowel disease, pregnancy, or sarcoidosis; or neutrophilic dermatosis and malignancy such as leukemia and Hodgkin disease.2,3 A third of the cases are idiopathic. In children, streptococcal infections are responsible for most cases of EN.4
Recommended work-up to investigate possible triggers includes a CBC with differential, sedimentation rate, CRP, ASO titers or anti-DNase B titers, tuberculin skin test or interferon-gamma TB test and a chest X ray. If there are any other symptoms, physical signs, or risk factors are present for the other not so common causes, further ancillary testing may be warranted.
Erythematous nodules and papules on the shin in children are commonly caused by arthropod bites also known as papular urticaria. These lesions are pruritic rather than tender and usually respond to topical corticosteroids and oral antihistamines. Subcutaneous bacterial, fungal, or atypical mycobacterial infections can present with tender nodules that can ulcerate and drain on the shins, feet, or any other body part. These patients may have a history of immunodeficiency and usually systemic symptoms of infection are present. Cutaneous polyarteritis nodosa (PAN) also can present with tender nodules on the legs but these lesions usually necrose and ulcerate and may be associated with livedo racemosa, a transient or persistent, blotchy, reddish-blue to purple, netlike cyanotic pattern. On pathology, PAN presents with necrotizing medium vessel vasculitis. Malignant nodules also can occur on the shin. Pathology will show atypical cells. Other forms of panniculitis, such as erythema induratum and pancreatic panniculitis, can present with tender nodules but these lesions usually occur on the calves and ulcerate.
Management of EN starts with treating the underlying infection or stopping the causative medication. Initial measures include bed rest, leg elevation, compression bandages, and NSAIDs. Potassium iodide is a very effective therapy as it may control the symptoms within 24 hours. When there is no response to the above, or the patient has severe symptoms, a short course of systemic glucocorticoids can be started. Other medications for recalcitrant or recurrent lesions include colchicine, dapsone, or hydroxychloroquine.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
References
1. Panniculitis, in “Dermatology,” 3rd ed. (Philadelphia: Elsevier Saunders, 2012, p. 1641).
2. Arthritis Rheum. 2000 Mar;43(3):584-92.
3. J Clin Oncol. 2007 Sep 1;25(25):4011-2.
4. Turk J Pediatr. 2014 Mar-Apr;56(2):144-9.
Laboratory work revealed a normal CBC and differential, an elevated C-reactive protein (CRP) and sedimentation rate (ESR), negative antistreptolysin O (ASO) titers, negative pregnancy test, a normal urinalysis, and negative blood, throat, and urine cultures. A chest x-ray also was negative as well as angiotensin-converting enzyme (ACE) levels. Tuberculosis interferon-gamma release essay was negative.
The patient was diagnosed with erythema nodosum (EN), based on physical exam and history of the lesions. In her particular case, infectious causes including streptococcus infection, tuberculosis, and coccidioidomycosis were ruled out. There were no x-ray findings that suggested sarcoidosis and her ACE level was within normal limits. The pregnancy test also was negative. Given her recent start on OCs, this was thought to be the cause of the lesions.
She was treated with elevation, compression stockings, and NSAIDs and discontinuation of OCs. The lesions resolved after 6 weeks leaving bruiselike patches (erythema contusiformis).
EN is a delayed-type hypersensitivity reaction, causing inflammation on the fat (panniculitis) most commonly on the shins, but it can also occur on the arms, face, neck, and thighs. It is the most common type of panniculitis and is usually seen more often in women from the second to fourth decade of life. Erythematous tender nodules in crops commonly located on the shins are the characteristic physical finding. Systemic symptoms can occur including fever, malaise, and joint pain. The lesions usually last up to 6-8 weeks and may leave bruiselike patches or postinflammatory hyperpigmentation that can take months to improve.1
The diagnosis of EN usually is made by physical examination and natural history. In unusual severe cases or lesions in atypical locations, a skin biopsy is indicated. Histologic examination of one of the lesions reveals a septal panniculitis without vasculitis. Miescher’s radial granulomas (grouped macrophages around neutrophils or septa-like spaces) often are present and are a characteristic feature of EN.
EN can be triggered by different types of infections such as streptococcus, mycoplasma, tuberculosis, or bacterial gastroenteritis; medications such as OCs, sulfonamides, iodides, penicillin, or bromides; medical conditions that include inflammatory bowel disease, pregnancy, or sarcoidosis; or neutrophilic dermatosis and malignancy such as leukemia and Hodgkin disease.2,3 A third of the cases are idiopathic. In children, streptococcal infections are responsible for most cases of EN.4
Recommended work-up to investigate possible triggers includes a CBC with differential, sedimentation rate, CRP, ASO titers or anti-DNase B titers, tuberculin skin test or interferon-gamma TB test and a chest X ray. If there are any other symptoms, physical signs, or risk factors are present for the other not so common causes, further ancillary testing may be warranted.
Erythematous nodules and papules on the shin in children are commonly caused by arthropod bites also known as papular urticaria. These lesions are pruritic rather than tender and usually respond to topical corticosteroids and oral antihistamines. Subcutaneous bacterial, fungal, or atypical mycobacterial infections can present with tender nodules that can ulcerate and drain on the shins, feet, or any other body part. These patients may have a history of immunodeficiency and usually systemic symptoms of infection are present. Cutaneous polyarteritis nodosa (PAN) also can present with tender nodules on the legs but these lesions usually necrose and ulcerate and may be associated with livedo racemosa, a transient or persistent, blotchy, reddish-blue to purple, netlike cyanotic pattern. On pathology, PAN presents with necrotizing medium vessel vasculitis. Malignant nodules also can occur on the shin. Pathology will show atypical cells. Other forms of panniculitis, such as erythema induratum and pancreatic panniculitis, can present with tender nodules but these lesions usually occur on the calves and ulcerate.
Management of EN starts with treating the underlying infection or stopping the causative medication. Initial measures include bed rest, leg elevation, compression bandages, and NSAIDs. Potassium iodide is a very effective therapy as it may control the symptoms within 24 hours. When there is no response to the above, or the patient has severe symptoms, a short course of systemic glucocorticoids can be started. Other medications for recalcitrant or recurrent lesions include colchicine, dapsone, or hydroxychloroquine.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
References
1. Panniculitis, in “Dermatology,” 3rd ed. (Philadelphia: Elsevier Saunders, 2012, p. 1641).
2. Arthritis Rheum. 2000 Mar;43(3):584-92.
3. J Clin Oncol. 2007 Sep 1;25(25):4011-2.
4. Turk J Pediatr. 2014 Mar-Apr;56(2):144-9.
A 16-year-old female came to the dermatology clinic for acne follow-up. She reported some improvement on her acne since she started taking OCs. She also had been using benzoyl peroxide and tretinoin on her face. In addition to the acne, she also wanted us to check some tender bumps she had been getting on her shins after she came back from a camping trip. Initially she thought they were bug bites, but the lesions were getting larger, more tender, and not improving with diphenhydramine.
The physical exam did not reveal acute distress. She was afebrile. On skin examination, she had comedones, papules and scars on her face, chest, and back. On her shins there were several erythematous tender nodules and plaques. There was no edema on her legs and pulses were present.