Insights from γ-Secretase: Functional Genetics of Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is a chronic, relapsing, and remitting inflammatory disease of the skin with significant heritability and racial disposition. The pathogenesis of HS remains enigmatic, but occlusion of the terminal hair follicle and dysregulation of the local innate immune response may contribute to pathogenesis. Genetic predisposition might also contribute to disease susceptibility and phenotypic heterogeneity because mutations in γ-secretase have been found to underlie a minor but characteristic subset of patients with HS. In this review, we synthesized the current data on γ-secretase in HS, evaluated its importance in the context of disease pathobiology, and discussed avenues of future studies

Surgical procedures for hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that can have a considerable social and psychosocial impact in patients with skin of color. The lesions are difficult to treat and often present with notable frustration for both patients and physicians. Although current treatment ladders can delay procedures and surgical intervention, some believe that surgery should be introduced earlier in the management of HS. In this article, we review current surgical procedures for the management of HS. It is imperative that dermatologists are informed about the different techniques available for treating this disease to determine the best route to care for their patients

Polymorphic light eruption sine eruptione: A variant of polymorphous light eruption

Polymorphous light eruption (PMLE) is the most common immunologically-mediated photodermatosis; it usually presents as a pruritic, papular eruption in sun-exposed regions of the skin hours to days after sun exposure. Several variants of PMLE have been described, manifesting with varying morphologies but with photosensitivity as a common etiology. Polymorphic light eruption sine eruptione (PLESE), a rare variant presenting as sun-induced pruritus without cutaneous eruption, has been reported in a single cohort of seven patients in 1988. We report a case of a 62-year-old white female who developed PLESE

Adalimumab-induced lupus in a patient with hidradenitis suppurativa

Anti-tumor necrosis factor (TNF) agents are used to treat various inflammatory disorders, such as rheumatoid arthritis, irritable bowel disease, and hidradenitis suppurativa (HS). A known side effect of these agents is the development of autoimmunity with the formation of antinuclear antibodies and/or anti-dsDNA antibodies. Although patients sometimes develop these antibodies, they rarely exhibit clinical manifestations. If symptoms do develop, the diagnosis of anti-TNF induced lupus (ATIL) should be considered. We describe a case of adalimumab-induced lupus in a patient with hidradenitis suppurativa.https://scholarlycommons.henryford.com/merf2019caserpt/1127/thumbnail.jp

Patient-reported outcomes in hidradenitis suppurativa: A review

Hidradenitis suppurativa, also known as acne inversa, is a chronic recurrent inflammatory disease of the skin making management challenging and continuously evolving. A large number of modalities exist aimed at quantifying the efficacy of treatment in studies on hidradenitis suppurativa. Both physician-reported and patient-reported outcomes are used as endpoints in these studies; however, the vast majority of the modalities used to survey these reported outcomes lack validation and congruence between studies. Heterogeneity of outcome measures and lack of standardization from study to study make it difficult to design future hidradenitis suppurativa trials and to compare results. This high variability between studies further contributes to the lack of high- quality evidence available to guide clinical management decisions of this inflammatory skin disease. Therefore this review aims to assess the modalities frequently used to assess patient- reported treatment outcomes in hidradenitis suppurativa. Patient-reported outcomes in hidradenitis suppurativa include outcomes regarding symptoms and disease progression, measures of treatment satisfaction, quality of life surveys, impairment of function, pain, and patient-reported outcomes combined with physician-reported outcomes. Nearly all surveys demonstrate significant heterogeneity, lack standardization, and many are not validated or constructed specifically for the assessment of hidradenitis suppurativa. Yet patient-reported outcomes on symptoms and disease severity, treatment satisfaction, and quality of life are instrumental in evaluating hidradenitis suppurativa treatment efficacy in clinical trials. As such, standardization and validation of patient- reported outcome instruments are essential for comparability among studies and improved quality of evidence

Insights from γ-Secretase: Functional Genetics of Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is a chronic, relapsing, and remitting inflammatory disease of the skin with significant heritability and racial disposition. The pathogenesis of HS remains enigmatic, but occlusion of the terminal hair follicle and dysregulation of the local innate immune response may contribute to pathogenesis. Genetic predisposition might also contribute to disease susceptibility and phenotypic heterogeneity because mutations in γ-secretase have been found to underlie a minor but characteristic subset of patients with HS. In this review, we synthesized the current data on γ-secretase in HS, evaluated its importance in the context of disease pathobiology, and discussed avenues of future studies

222 Whole-blood immune profile in hidradenitis suppurativa

Hidradenitis suppurativa (HS), a chronic inflammatory skin condition with a multifactorial etiology, has a complex cutaneous immune reaction localized around the hair follicles in intertriginous skin. HS pathogenesis remains enigmatic, although some hypotheses have been proposed. Increasing evidence of the association between HS and other inflammatory conditions (e.g. inflammatory bowel disease) and cardiovascular disease suggests that patients with HS have underlying systemic inflammation. To date, few studies have sought to understand the systemic changes that occur in the immune system of HS patients. One recent study performed bulk RNA-sequencing on peripheral blood mononuclear and showed minor differences in transcriptomes of peripheral blood mononuclear cells, but bulk RNA-sequencing does not have the capacity to identify specific changes in cellular subsets. To determine whether specific systemic changes occur in HS patients we performed CyTOF using a standardized panel that identifies 37 immune cell subpopulations in whole blood. We analyzed whole blood samples from 8 HS and 7 healthy controls. Compared to healthy controls, HS patients had an increased frequency of plasmablasts and a decreased frequency of CD66b- neutrophils. Furthermore, marked differences in monocyte subclasses showed a shift from classical monocytes (CD14+ CD16-) towards intermediate (CD14+ CD16+) and non-classical subsets (CD14dim CD16+) in HS. We also identified a large population of CDR45RO+ CCR6+ CD38+ intermediate monocytes in HS, which was largely absent in healthy controls. Taken together our results support previous studies highlighting the role of neutrophils and B cells in HS pathogenesis, and identify newly discovered monocyte dynamics in peripheral blood of HS patients further supporting widespread inflammation as a feature of HS