Dermatology

Menter, A., A. S. Van Voorhees and S. Hsu (2021). “Pustular Psoriasis: A Narrative Review of Recent Developments in Pathophysiology and Therapeutic Options.” Dermatol Ther (Heidelb) Oct 9. [Epub ahead of print].

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Pustular psoriasis is an unusual form of psoriasis that frequently presents clinical challenges for dermatologists. The condition presents with pustules on an erythematous background and has two distinct subtypes: localized disease on the palms and soles, called palmoplantar pustulosis (PPP), and generalized pustular psoriasis (GPP). The involvement of the fingers, toes, and nails is defined as a separate localized variant, acrodermatitis continua of Hallopeau, and is now thought to be a subset of PPP. The rarity of pustular psoriasis frequently makes the correct diagnosis problematic. In addition, treatment is limited by a relative lack of evidence-based therapeutic options. Current management is often based on existing therapies for standard plaque psoriasis. However, there remains a need for treatments with high, sustained efficacy and a rapid onset of action in pustular psoriasis. Recent advances in understanding of the pathogenesis of pustular psoriasis have provided insights into potential therapies. Treatment of pustular psoriasis is generally determined by the extent and severity of disease, and recent years have seen an increasing use of newer agents, including biologic therapies. Current classes of biologic therapies with US Food and Drug Administration and European Medicines Agency approval for treatment of moderate-to-severe plaque psoriasis in the USA (and elsewhere) include tumor necrosis factor alpha inhibitors (adalimumab, certolizumab pegol, etanercept, infliximab), interleukin (IL)-17 inhibitors (brodalumab, ixekizumab, secukinumab), an IL-12/23 inhibitor (ustekinumab), and IL-23 inhibitors (guselkumab, risankizumab, tildrakizumab). Recently, specific inhibitors of the IL-36 pathway have been evaluated in GPP and PPP, including spesolimab, an IL-36 receptor inhibitor which has shown promising results in GPP. The emerging drugs for pustular psoriasis offer the possibility of rapid and effective treatment with lower toxicities than existing therapies. Further research into agents acting on the IL-36 pathway and other targeted therapies has the potential to transform the future treatment of patients with pustular psoriasis. This article reviews the clinical features of PPP and GPP, and current understanding of the genetics and immunopathology of these conditions; it also provides an update on emerging treatments.

Lewis, K., R. Dummer, A. S. Farberg, A. Guminski, N. Squittieri and M. Migden (2021). “Effects of Sonidegib Following Dose Reduction and Treatment Interruption in Patients with Advanced Basal Cell Carcinoma During 42-Month BOLT Trial.” Dermatol Ther (Heidelb) Oct 20. [Epub ahead of print].

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INTRODUCTION: Sonidegib is a Hedgehog pathway inhibitor approved to treat locally advanced basal cell carcinoma and, depending on regulatory approval, metastatic basal cell carcinoma. Results from the BOLT study demonstrated robust efficacy and continued tolerability through 42 months. This analysis evaluated the impact of sonidegib dose reductions and interruptions in patients with advanced basal cell carcinoma through 42 months. METHODS: BOLT was a randomized, double-blind, multicenter, phase 2 study. Adults with no previous Hedgehog pathway inhibitor therapy were randomized 1:2 to sonidegib 200 or 800 mg once daily. Primary endpoint was objective response rate. Dose modifications were permitted in patients unable to tolerate the dosing schedule or if a treatment-related adverse event was suspected. RESULTS: The incidence of dose interruptions was similar between the 200- and 800-mg groups (68.4% vs 65.3%, respectively). Dose reductions occurred more frequently in patients receiving sonidegib 800 mg (36.7%) than 200 mg (16.5%). Overall response rate for all patients receiving sonidegib 200 mg daily was 48.1% and was similar to those of patients without dose reduction or interruption (48.5%) and patients with at least one dose reduction or interruption (46.2%). CONCLUSION: Dose reductions and interruptions were practical and did not impact the efficacy of sonidegib. In patients with advanced basal cell carcinoma who necessitate long-term treatment, dose interruptions may be beneficial for continued treatment and disease control. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01327053.

Strober, B., D. Pariser, A. Deren-Lewis, T. J. Dickerson, M. Lebwohl and A. Menter (2021). “A Survey of Community Dermatologists Reveals the Unnecessary Impact of Trial-and-Error Behavior on the Psoriasis Biologic Treatment Paradigm.” Dermatol Ther (Heidelb) 11(5): 1851-1860.

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INTRODUCTION: In the USA, psoriasis affects approximately 3% of the population and costs more than $110 billion annually. The development of targeted biologics has revolutionized psoriasis management, but at an increasing cost. According to Joint AAD/NPF guidelines, an important need exists to identify biomarkers that can predict the appropriate biologic agent for patients. METHODS: A survey of community dermatologists was developed to address (1) significant factors influencing biologic therapy utilization in psoriasis; (2) the clinical utility of a test stratifying biologic response. RESULTS: Respondents confirmed that trial and error leads to frequent biologic switching. The survey indicated that 82% of dermatologists switch 10-30% of their patients in the first year and 98% switch intra-class for at least 50% of non-responding patients. The trial and error is due, in part, to formularies influencing the physician 77% of the time, with only 14% reporting that their first choice and the formulary alignment is greater than 75%. Compounding trial and error, 93% of the physicians report that they wait at least 12 weeks before determining non-response, in alignment with AAD/NPF guidelines. The lack of precision medicine and this trial-and-error approach result in unnecessary wasted spending and suboptimal patient outcomes. After being given an overview of Mind.Px, a dermal biomarker patch used to predict therapeutic response to a biologic class, survey participants expressed that: 93% would utilize Mind.Px results to determine first-line therapy even if this differed from initial clinical choice 100% would utilize Mind.Px if part of the prior authorization process 98% say Mind.Px would improve patient outcomes 81% reported Mind.Px would help with prior authorization process CONCLUSIONS: Surveyed dermatologists believe a test that predicts psoriasis treatment response to a class of biologic drugs would lessen trial and error, provide a tool for physicians to make more informed decisions about drug selection, improve patient outcomes, and significantly reduce wasted spending.

Dacy, N., K. Oney, K. Fiala and P. Parekh (2021). “Eosinophilic annular erythema.” Proc (Bayl Univ Med Cent) 34(5): 606-607.

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Eosinophilic annular erythema (EAE) is a rare eosinophilic dermatosis characterized by annular, erythematous papules and plaques commonly found on the trunk and the extremities. There is continued debate on whether EAE is a distinct entity or a clinical polymorphism of Well’s syndrome, but it is generally considered a separate entity based on clinical and histopathological differences. We present a case of EAE and discuss the histopathological findings.

Zaayman, M., Nguyen, P., Silfvast-Kaiser, A., Frieder, J., West, C., Tumminello, K. and Paek, S.Y. (2021). “BAPoma presenting as an incidental scalp papule: case report, literature review, and screening recommendations for BAP1 tumor predisposition syndrome.” J Dermatolog Treat Jun 23;1-6. [Epub ahead of print]. 1-6.

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OBJECTIVE: BRCA1-associated protein 1 (BAP1) tumor predisposition syndrome (BAP1-TPDS) is associated with an increased risk for aggressive cancers. BAP1-inactivated melanocytic tumors (BIMTs) are observed in 75% of BAP1-TPDS, often presenting as early as the second decade of life. These lesions may serve as a predictive marker to identify patients who carry germline BAP1 mutations and thus are at higher risk of developing associated cancers. Early diagnosis for these malignancies is crucial for curative treatment. METHODS: We report a patient who presented with an incidental scalp papule for which biopsy was consistent with a BIMT. A review of literature was conducted by accessing the PubMed database to delineate present knowledge of BIMTs, assess recommendations for screening of germline BAP1 mutations, and evaluate cancer surveillance strategies for BAP1-TPDS associated cancers. RESULTS: Consensus in literature indicates that genetic evaluation should be encouraged in patients presenting with multiple BIMTs or a new BIMT with significant family history of BAP1-TPDS related cancers. If positive for a germline BAP1 mutation, cancer surveillance should be recommended for early diagnosis and timely intervention. CONCLUSIONS: Further workup should be encouraged in patients who meet the proposed screening criteria for germline BAP1 mutations. Patients could benefit from cancer surveillance for earlier diagnosis, management, and improved outcomes.