The three most important gaps in current understanding of psoriasis are the need to fully elucidate the genetic underpinnings of the disease, delineate in more detail its natural history and prognostic factors, and better characterize and treat its associated comorbidities, according to an article in the Journal of the American Academy of Dermatology.
The academy recently issued guidelines for the management of psoriasis and psoriatic arthritis, which included a section concerning the most prominent deficiencies in knowledge about the disease. In the current article (J. Am. Acad. Dermatol. 2014;70:146-67), the expert panel that wrote the guidelines now details some of those gaps and suggests how future research should address them.
Advances in genetic research have allowed considerable progress in our understanding of the pathogenesis of psoriasis, including the identification of genetic susceptibility regions and nucleotide polymorphisms that are significantly associated with immune pathways, skin barrier function, and epidermal proliferation. Future research should "explore whether the genetic basis of psoriasis stems from a primary defect in immunologic function, a defect in keratinocyte function, or a complex interaction of both," wrote Dr. Caitriona Ryan of the Psoriasis Research Center, Baylor University Medical Center, Dallas, and her associates on the expert panel.
In particular, genetic research should help elucidate the correlation between psoriasis genotype and phenotype, determining whether psoriasis and psoriatic arthritis are genetically distinct diseases, as well as the genetic differences underlying guttate, erythrodermic, inverse, palmoplantar, and pustular forms of the disease.
Immunologic studies are needed to define the roles of various inflammatory cells in patients’ skin and blood, and to assist the development of targeted immunotherapies that will correct immunologic dysfunction without causing adverse immunosuppression. Similarly, the role of angiogenesis and the vascular bed in the pathogenesis of psoriasis requires more research attention, because topical or systemic inhibition of this process appears to be beneficial.
Additionally, the environmental factors that predispose to the development of psoriasis or contribute to disease exacerbations are still poorly defined. Research into lifestyle factors and the role of bacterial and viral infections should be especially revealing, Dr. Ryan and her associates said.
Research to determine the prevalence and natural history of psoriasis across different populations also is critical. Robust, long-term, prospective epidemiology studies at the population level are key.
Several subpopulations of psoriasis patients also deserve special attention. There is a dearth of both clinical and basic scientific data on pediatric psoriasis, when children are the very patients most likely to suffer the adverse psychosocial effects of psoriasis and the most vulnerable to the adverse physical and developmental effects of treatments, the investigators noted.
Women who are pregnant or breastfeeding constitute another important subgroup of psoriasis patients. Studies are urgently needed to examine the effects of the disease itself and of its therapies on pregnancy outcomes. Similarly, the elderly are a subgroup of patients that requires special attention to adverse medication effects, because they have a high prevalence of comorbid conditions, greater use of concomitant medications, diminished renal function, and age-related changes in pharmacokinetics and pharmacodynamics.
Finally, future research must more closely examine several comorbidities now known to accompany psoriasis, including diabetes, obesity, the metabolic syndrome, and, most importantly, cardiovascular disease.
Severe psoriasis now should be considered an independent cardiovascular risk factor. "As physicians, it is our responsibility to counsel patients with psoriasis regarding the increased risk of cardiometabolic conditions and the need for lifestyle modifications, including smoking cessation, weight reduction, and regular screening for diabetes and hypertension," Dr. Ryan and her colleagues said.
Determining whether systemic treatment of psoriasis mitigates cardiometabolic risk, especially if it entails newer biologic agents, also is important, they added.
Psychological comorbidities should not be overlooked. Patients with psoriasis are known to have high rates of anxiety, depression, and alexithymia—the inability to recognize or discuss feelings or emotional states. Relaxation techniques, meditation, and cognitive-behavioral therapy have shown efficacy and need further assessment.
Sexual functioning also should be studied in greater detail, since psoriasis can have a significant impact on sexuality, particularly if the disease affects the genitals.
Dr. Ryan reported ties to Janssen-Cilag, Pfizer, Galderma, and Abbott, and her associates reported ties to numerous industry sources.