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Generalized Comedones, Acne, and Hidradenitis Suppurativa in a Patient with an FGFR2 Missense Mutation.

ABSTRACT: Mutations in the fibroblast growth factor-receptor gene 2 (FGFR2) gene have been implicated in numerous diseases, including nevus comedonicus (NC) and naevoid acne that have somatic missense mutations in FGFR2 in the affected tissue. A patient presented in our department with unusual, innumerable large comedones throughout his back reminiscient of NC, as well as multifocal hidradenitis suppurativa and acne. Topical and systemic treatments were unsuccessful. Whole exome sequencing of blood-derived DNA detected a germline mutation in FGFR2 that was predicted to be damaging. This could explain the multifocal and severe nature of the disease. We suggest screening other, phenotypically similar patients for FGFR2 mutations. Our findings, once confirmed independently, could indicate that therapeutic modulation of FGFR signaling in the acne tetrad could be effective.

SUBMITTER: Higgins R

PROVIDER: S-EPMC5328982 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Generalized Comedones, Acne, and Hidradenitis Suppurativa in a Patient with an FGFR2 Missense Mutation.

Higgins Rebecca R Pink Andrew A Hunger Robert R Yawalkar Nikhil N Navarini Alexander A AA

Frontiers in medicine 20170228

Mutations in the fibroblast growth factor-receptor gene 2 (FGFR2) gene have been implicated in numerous diseases, including nevus comedonicus (NC) and naevoid acne that have somatic missense mutations in FGFR2 in the affected tissue. A patient presented in our department with unusual, innumerable large comedones throughout his back reminiscient of NC, as well as multifocal hidradenitis suppurativa and acne. Topical and systemic treatments were unsuccessful. Whole exome sequencing o ...[more]

PMID: 28293556

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Project description:Despite the rapid development in hidradenitis suppurativa (HS) research, the immediate introduction of potent therapeutic compounds in clinical trials and the lack of definitive outcome measures have led to the discontinuation of potential therapeutic compound studies. HS is a solely human disease, and therefore, the search for preclinical human models has been given priority. The 3D-SeboSkin model, a co-culture of human skin explants with human SZ95 sebocytes as a feeder layer, has been shown to prevent the rapid degeneration of human skin in culture and has been validated for HS preclinical studies. In this work, the HS 3D-SeboSkin model has been employed to characterize cellular and molecular effects of the EMA- and FDA-approved biologic adalimumab. Adalimumab, a tumor necrosis factor-α inhibitor, was shown to target inflammatory cells present in HS lesions, inducing a prominent anti-inflammatory response and contributing to tissue regeneration through a wound healing mechanism. Adalimumab inhibited the lesional tissue expression of TNF-α, IL-3, IL-15, and MCP-3 and downregulated the secretion of IL-1α, IL-5, RANTES, MCP-2, TNF-α, TNF-β, TGF-β, and IFN-γ. In contrast, IL-6 was stimulated. The compound failed to modify abnormal epithelial cell differentiation present in the HS lesions. Patients with Hurley stage II lesions exhibited stronger expression of autophagy proteins in perilesional than in lesional skin. Adalimumab modified the levels of the pro-apoptotic proteins LC3A, LC3B, and p62 in an individual, patient-dependent manner. Finally, adalimumab did not modify the NFκB signal proteins in SZ95 sebocytes and NHK-19 keratinocytes, used to study this specific pathway. The administration of the validated HS 3D-SeboSkin model in ex vivo studies prior to clinical trials could elucidate the individual pathogenetic targets of therapeutic candidates and, therefore, increase the success rates of clinical studies, minimizing HS drug development costs.

Project description:Hidradenitis suppurativa (HS) leads to disfigurement and painful eruptions in terminal hair follicles of the intertriginous skin, mainly of axillary, genitofemoral, and perianal sites. It is associated with an excessive impairment of quality of life, psychiatric disorders, and sexual distress. Body image impairment has been linked to depression and anxiety and has been described for some dermatologic disorders but has not yet been investigated in patients with HS.To investigate whether body image is diminished in patients with HS and whether disease severity, age at onset, disease duration, obesity, depression, and anxiety are linked to body image impairment.This 12-month (August 1, 2009, to August 31, 2010) case-control study with a prospective, observational, cross-sectional design recruited 47 consecutive patients with HS entering a tertiary care center and 45 healthy control individuals matched for age, sex, and body mass index (BMI). One patient and 4 controls failed to complete the questionnaire and were excluded from the evaluation. Data analysis was performed from December 1, 2013, to February 15, 2014.The Frankfurt Body Concept Scale (FKKS) and the Hospital Anxiety and Depression Scale (HADS) were given to patients and controls. Correlations among FKKS, HADS, and disease features were calculated.Of the 46 patients and 41 controls included in the evaluation (mean [SD] age, 35.6 [1.6] years; 40 [46%] male and 47 [54%] female), HS significantly reduced body image (mean FKKS score, 234.2 [5.4] in patients and 276.9 [5.7] in controls; P < .001), even when controlled for BMI. A correlation was found for the extent of body image disruption and BMI (r = -0.589; P < .001), HADS-depression score (r = -0.619; P < .001), and HADS-anxiety score (r = -0.340; P = .03). No association was found for the body image score and the severity of HS, age at onset of disease, and duration of disease. The body contact subscale score was the only subscale score that was not different between patients with HS and controls.Patients with HS have major body image impairment, which might lead to depression and anxiety, disorders that have been largely acknowledged in HS. This study identified another element of the psychosocial burden of patients with HS and reveals that body image could potentially be used as an outcome measure in future studies of HS.

Project description:IntroductionHidradenitis suppurativa (HS) has a profound negative impact on patients' health-related quality of life (HRQoL). Here we summarize the evidence on HRQoL and Patient Reported Outcomes (PROs) in patients with HS in real-world settings by conducting a systematic literature review (SLR) of observational studies.MethodsData sources included MEDLINE, Embase & PsycINFO between January 1, 2010 and August 29, 2021, and conference proceedings between 2019 and 2021. Identified abstracts were reviewed and screened independently by two reviewers. Eligibility criteria included patients with HS of any severity, sample size ≥ 100, reporting PROs including HRQoL measures. Included studies were critically appraised.ResultsFifty-eight observational studies matched inclusion criteria. Dermatology Life Quality Index (DLQI) was the most commonly utilized instrument: 57% of included studies reported mean baseline DLQI scores, ranging between 8.4 and 16.9, indicating a very large impact on the patients' HRQoL. Higher scores were reported with increasing disease severity and among female patients. Pain was assessed mostly by an 11-point (0-10) numeric rating scale (NRS) with a mean baseline score ranging from 3.6 to 7.7 indicating moderate to high pain levels. There was a negative impact of HS on patients' psychological well-being, based on PRO scores related to depression and anxiety. A high proportion of sexual dysfunction was reported, with a larger impact on women than men. Work productivity and leisure activity were consistently found to be impaired in patients with HS.ConclusionsAll included studies reported a negative impact of HS on patients' lives. A diverse set of disease- and non-disease-specific PRO instruments were utilized highlighting the need for more consistent use of HS-specific validated PRO instruments to assess the impact of HS on the different aspects of patients' HRQoL to allow for data to be more meaningfully interpreted and compared in real-world settings. Patients with HS need better disease management approaches that address the observed low quality of life.

Dataset Information

Generalized Comedones, Acne, and Hidradenitis Suppurativa in a Patient with an FGFR2 Missense Mutation.

Publications

Generalized Comedones, Acne, and Hidradenitis Suppurativa in a Patient with an <i>FGFR2</i> Missense Mutation.

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