Relationships between pediatric psoriasis and streptococcal infection, obesity, and genetics are discussed for their relevance to patient care.
Accumulating information about triggers for psoriasis in children, comorbidities, and genetics has implications for improving clinical care, according to dermatologists who provided updates on these topics at the annual meeting of the American Academy of Dermatology.
Dr. CordoroInciting factors for psoriasis are identified far more often in children than in adults, notes Kelly M. Cordoro, M.D., in her discussion on triggers. She is associate professor of dermatology and pediatrics, University of California, San Francisco.
Infection is probably the most common trigger for pediatric psoriasis, and it is important for dermatologists to know that streptococcal infection in particular can be a factor in difficult-to-treat psoriasis and the development and prognosis of guttate psoriasis.
“I recommend assessing any child with new onset psoriasis of any morphology - not just guttate - or an exacerbation of existing disease for streptococcal infection,” Dr. Cordoro says.
She advises swabbing not only the tonsils, but also the perianal region, and, in girls, the vulvar area if there is erythema or erosions, to obtain specimens for culture, and treating with culture-directed antibiotic therapy if the results are positive.
If the culture is negative and streptococcal infection or carriage is suspected, antistreptolysin O or anti-Deoxyribonuclease B titers can be checked, and an antistreptococcal antibiotic prescribed if the level is elevated.
Dr. Cordoro points out that the role of tonsillectomy for managing difficult to treat psoriasis in children is controversial.
“If a child is carrying streptococci in the tonsils, but also in the anogenital region, tonsillectomy may not result in remission of psoriasis,” she explains.
Not only is streptococcal infection a trigger for guttate psoriasis, but there is also evidence that it may serve as a prognostic factor.
“Mercy et al.1 found that preceding strep pharyngitis predicted guttate morphology but not disease severity, while initial guttate morphology in the absence of strep predicted progression to severe psoriasis,” she says.
The explanation for this observation may lie in genetics - the children who develop chronic psoriasis may be genetically predisposed because they are also more likely to have a positive family history of psoriasis.
“The take home message for clinicians is to consider more aggressive management and monitoring of guttate psoriasis that develops in the absence of streptococcal infection because that situation seems to portend risk of progression to more severe and chronic disease,” Dr. Cordoro says.
Understanding comorbidities associated with pediatric psoriasis is an evolving story, but available evidence points to a dose-response relationship between psoriasis severity and obesity, ie., the more obese the child, the more severe the psoriasis. Whether or not psoriasis improves when obese children lose weight is not known, although studies involving adults with psoriasis indicate loss of excess weight leads to improved response to systemic therapies.
It is also not known whether children with psoriasis, like adults, are at risk for early cardiovascular disease and cerebrovascular disease. Nevertheless, it is reasonable to expect the same relationship exists and to advocate for both weight loss and aggressive treatment to control psoriasis in children.
“The best evidence for obese children supports getting them into credible weight loss programs because it will benefit their general health and may also improve their psoriasis. Furthermore, we know that severe psoriasis represents a state of severe inflammation, and the consequences of chronic uncontrolled/untreated systemic inflammation may include cardiovascular and cerebrovascular events, which has been termed ‘the psoriatic march,’” Dr. Cordoro says.
“Managing severe psoriasis in children with appropriately aggressive systemic therapy may be an opportunity to prevent those sequelae. Unfortunately, severe pediatric psoriasis is being vastly undertreated in the United States.”
A manuscript from a multidisciplinary group called CSI: Comorbidity Screening Initiative, led by pediatric dermatologists at the University of California San Diego, has been prepared to offer clinicians guidelines for screening children for comorbidities based on available evidence and expert consensus where evidence is inadequate. Dr. Cordoro is a co-author of the document.
Dr. LiaoWilson Liao, M.D., says that understanding about the genetics of psoriasis has been rapidly expanding, and the progress in this area is creating excitement about applications for improving diagnosis and treatment.
“Genetics really does have promising potential to improve patient care, and we expect to see its impact in clinical practice in the near future,” he says. Dr. Liao is associate professor of dermatology, University of California, San Francisco.
As of February, 2016, there were 65 known psoriasis-associated genes. Many of the psoriasis-associated genes cluster to four biological pathways, of which two - TNF/NF-KB and Th17/IL23 - are targeted by biologics that are available or being developed for the treatment of psoriasis.
“It is satisfying to see this alignment between the genetic discoveries and the mechanisms of action of effective therapies,” Dr. Liao says.
Understanding the genetics of psoriasis is also providing insights about screening for comorbidities as some of the psoriasis-associated genes overlap with those linked to various autoimmune diseases (eg., celiac disease, Crohns disease, lupus, vitiligo, rheumatoid arthritis) and also to cardiovascular disease.
“This information suggests that when dermatologists see children with severe psoriasis, they should conduct a thorough history and review of systems in order to screen for other autoimmune diseases,” Dr. Liao says.
Considering the genetic connection between psoriasis and cardiovascular disease, Dr. Liao also echoes Dr. Cordoro’s advice about appropriately aggressive treatment.
“Severe psoriasis in a young child should not be treated with topicals alone. There is evidence that treating severe psoriasis aggressively in adults can reduce the risk of heart attack and stroke in adults. Perhaps it will help to prevent these serious comorbidities in children as well,” he says.
Researchers investigating psoriasis-associated genes have also uncovered relationships with certain disease patterns. Since the 1980s it was known that HLA-Cw6 positivity predicted early onset disease. More recently, additional associations have been identified between genotype and age of onset have been identified as well as associations between genotype and clinical features.
For example, age of onset with HLA-Cw6 positivity has been refined to a predilection for the 10- to 20-year-old age group, and this particular genotype has also been associated with the appearance of facial psoriasis. ERAP1 mutations also seem to be associated with psoriasis onset during the adolescent and teen years, while IL-22 gene mutations seem to be associated with prepubescent disease onset (ages 0 to 9) and the development of inverse psoriasis. IL1B gene mutations associated with psoriasis correspond with onset at age 40 and older.
Researchers harnessing the power of exome sequencing have also discovered four genes associated with pustular psoriasis - IL36RN, AP1S3, CARD14, TNIP1 - and the information has potential therapeutic implications, Dr. Liao says.
“Just as treatment of cancer has shifted to targeted therapies based on understanding of specific tumor mutations, perhaps we will find that pustular psoriasis is not all one disease and that treatment can be improved by tailoring therapies directed against the pathways affected by specific mutations.”
Disclosures: Dr. Cordoro reports no financial interests relevant to the content of this article. Dr. Liao is a research investigator for Abbvie, Janssen, Novartis, and Pfizer.
1. Mercy K, Kwasny M, Cordoro KM, Menter A, Tom WL, Korman N, et al. Clinical manifestations of pediatric psoriasis: results of a multicenter study in the United States. Pediatr Dermatol. 2013;30(4):424-428.