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Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by the formation of nodules, abscesses, and fistulae at intertriginous sites. The skin-gut axis is an area of emerging research in inflammatory skin disease and is a potential contributory factor to the pathogenesis of HS. A total of 59 patients with HS provided fecal samples and nasal and skin swabs of affected sites for analysis. A total of 30 healthy controls provided fecal samples, and 20 healthy controls provided nasal and skin swabs. We performed bacterial 16S ribosomal RNA gene amplicon sequencing on total DNA derived from the samples. Microbiome alpha diversity was significantly lower in the fecal, skin, and nasal samples of individuals with HS, which may be secondary to disease biology or related to antibiotic usage. Ruminococcus gnavus was more abundant in the fecal microbiome of individuals with HS, which is also reported in Crohn's disease, suggesting comorbidity due to shared gut microbiota alterations. Finegoldia magna was overabundant in HS skin samples relative to that in the healthy controls. It is possible that local inflammation is driven by F. magna by promoting the formation of neutrophil extracellular traps. These alterations in both the gut and skin microbiome in HS warrant further exploration, and therapeutic strategies, including fecal microbiota transplant or bacteriotherapy, could be of benefit., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease presenting with diverse manifestations ranging from nodules and abscesses to draining tunnels. Whether the underlying inflammation from lesions extends to relatively healthy-appearing adjacent perilesional and distant nonlesional skin has not been systematically evaluated., Objective: We sought to characterize lesional, perilesional, and nonlesional skin in patients with HS., Methods: Skin biopsy samples were collected under ultrasound guidance from patients with active, untreated moderate-to-severe HS. Site-matched control biopsy samples from healthy volunteers were used for comparison., Results: RNA sequencing demonstrated that HS skin clustered separately from healthy control skin, with perilesional and lesion skin clustering together and away from nonlesional skin. Immunohistochemistry analysis identified psoriasiform hyperplasia with keratin 16 positivity in both perilesional and lesional skin, with comparable levels of CD3 + , CD11c + , and neutrophil elastase-positive cellular infiltration. There was a marked upregulation of IL-17 signaling in perilesional and lesional skin. HS samples clustered on the basis of expression of lipocalin-2 (LCN2), with samples characterized by high LCN2 expression in the skin exhibiting a differing transcriptomic profile with significantly higher overall inflammation than that of skin characterized by low LCN2 levels., Conclusions: Perilesional HS skin has a transcriptomic and molecular profile comparable to that of lesional skin. HS can be grouped into 2 distinct subtypes based on molecular levels of LCN2 in the skin, with the LCN2-high subtype exhibiting an overall higher inflammatory burden and an upregulation of targetable cytokines. To our knowledge, this is the first study to characterize a unique HS subtype (and a potential endotype) that may guide future therapeutic targets., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Hidradenitis suppurativa (HS) is a chronic, recurring inflammatory dermatosis characterized by abscesses, deep-seated nodules, sinus tracts, and fibrosis in skin lesions around hair follicles of the axillary, inguinal, and anogenital regions. Whereas the exact pathogenesis remains poorly defined, clear evidence suggests that HS is a multifactorial inflammatory disease characterized by innate and adaptive immune components. Bioactive lipids are important regulators of cutaneous homeostasis, inflammation, and resolution of inflammation. Alterations in the lipid mediator profile can lead to malfunction and cutaneous inflammation. We used targeted lipidomics to analyze selected omega-3 and omega-6 polyunsaturated fatty acids in skin of patients with HS and of healthy volunteers. Lesional HS skin displayed enrichment of 5-lipoxygenase (LO)‒derived metabolites, especially leukotriene B4. In addition, 15-LO‒derived metabolites were underrepresented in HS lesions. Changes in the lipid mediator profile were accompanied by transcriptomic dysregulation of the 5-LO and 15-LO pathways. Hyperactivation of the 5-LO pathway in lesional macrophages identified these cells as potential sources of leukotriene B4, which may cause neutrophil influx and activation. Furthermore, leukotriene B4-induced mediators and pathways were elevated in HS lesions, suggesting a contribution of this proinflammatory lipid meditator to the pathophysiology of HS., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Due to its anti-hyperglycemic effect, metformin is the first-line medication for the treatment of type 2 diabetes, particularly in people who are obese. However, metformin is a drug with a very wide range of pharmacological properties and reports of its therapeutic effect on diseases including inflammation and cancer are increasing. Numerous research groups have reported that metformin has beneficial effects on a variety of inflammatory skin disorders including psoriasis, acanthosis nigricans, acne, hidradenitis suppurativa, and allergic contact dermatitis. According to these reports, in addition to the well-known action of metformin, that is, its anti-hyperglycemic effect, NF-kB inhibition and the resulting alteration to the cytokine network may be the potential targets of metformin. Its anti-hyperandrogenism effect has also been confirmed as the major action of metformin in some inflammatory skin diseases. Moreover, novel regulatory mechanisms, including autophagy and antioxidant processes, have been suggested as promising mechanisms of action for metformin in inflammatory skin disorders.

Hidradenitis suppurativa (HS) is a chronic skin disorder of unknown etiology that manifests as recurrent, painful lesions. Cutaneous dysbiosis and unresolved inflammation are hallmarks of active HS, but their origin and interplay remain unclear. Our metabolomic profiling of HS skin revealed an abnormal induction of the kynurenine pathway of tryptophan catabolism in dermal fibroblasts, correlating with the release of kynurenine pathway-inducing cytokines by inflammatory cell infiltrates. Notably, overactivation of the kynurenine pathway in lesional skin was associated with local and systemic depletion in tryptophan. Yet the skin microbiota normally degrades host tryptophan into indoles regulating tissue inflammation via engagement of the aryl hydrocarbon receptor (AHR). In HS skin lesions, we detected contextual defects in AHR activation coinciding with impaired production of bacteria-derived AHR agonists and decreased incidence of AHR ligand-producing bacteria in the resident flora. Dysregulation of tryptophan catabolism at the skin-microbiota interface thus provides a mechanism linking the immunological and microbiological features of HS lesions. In addition to revealing metabolic alterations in patients with HS, our study suggests that correcting AHR signaling would help restore immune homeostasis in HS skin.

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin condition characterized by painful nodules which suppurate and later develop into scar tissues followed by the development of hypodermal tracts. Although the mechanisms behind HS are not fully understood, it is known that dietary factors play important roles in flare frequency and severity. We hypothesize that the high fat diet (HFD) causes dysbiosis, systemic inflammation, and hyperhomocysteinemia (HHcy) in susceptible individuals, which subsequently elevate inflammatory cytokines such as IL-1β, IL-6, IL-17, and tumor necrosis factor alpha (TNF-α). This increase in dysbiosis-led inflammation coupled with a dysregulation of the 1-carbon metabolism results in an increase in matrix metalloproteinases MMP-2, MMP-8, and MMP-9 along with tissue matrix remodeling in the development and maintenance of the lesions and tracts. This manuscript weaves together the potential roles played by the gut microbiome, HHcy, MMPs, and the 1-carbon metabolism toward HS disease causation in susceptible individuals., (Copyright © 2020 Molnar, Mallonee, Stanisic, Homme, George, Singh and Tyagi.)

Background: Diagnosis of pyoderma gangrenosum, acne and hidradenitis suppurativa (PASH) and pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PAPASH) patients, in spite of recently identified genetic variations, is just clinical, since most patients do not share the same mutations, and the mutations themselves are not informative of the biological pathways commonly disrupted in these patients., Objective: To reveal genetic changes more closely related to PASH and PAPASH etiopathogenesis, identifying novel common pathways involved in these diseases., Methods: Cohort study on PASH (n = 4) and PAPASH (n = 1) patients conducted using whole exome sequencing (WES) approach and a novel bioinformatic pipeline aimed at discovering potentially candidate genes selected from density mutations and involved in pathways relevant to the disease., Results: WES results showed that patients presented 90 genes carrying mutations with deleterious and/or damage impact: 12 genes were in common among the 5 patients and bared 237 ns ExonVar (54 and 183 in homozygosis and heterozygosis, respectively). In the pathway enrichment analysis, only 10 genes were included, allowing us to retrieve 4 pathways shared by all patients: (1) Vitamin D metabolism, (2) keratinization, (3) formation of the cornified envelope and (4) steroid metabolism. Interestingly, all patients had vitamin D levels lower than normal, with a mean value of 10 ng/mL., Conclusion: Our findings, through a novel strategy for analysing the genetic background of syndromic HS patients, suggested that vitamin D metabolism dysfunctions seem to be crucial in PASH and PAPASH pathogenesis. Based on low vitamin D serum levels, its supplementation is envisaged., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare, (Copyright © 2020 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Background: Interleukin (IL)-26 is a signature T helper 17 cytokine described as a proinflammatory and antimicrobial mediator. So far, IL-26 has been reported in several immune-mediated inflammatory diseases, but its involvement in inflammatory skin disorders is poorly known., Objectives: To investigate the role of IL-26 in hidradenitis suppurativa (HS), through its involvement in antimicrobial activity., Methods: IL-26 was assessed in patients with HS through gene expression and protein analysis at skin and circulating levels. Ex vivo HS organ skin cultures, together with IL-26 antibody treatment, were performed to determine the IL-26 activity. Peripheral blood mononuclear cells (PBMCs) from patients with HS and healthy controls were either silenced or not with IL-26 small interfering (si)RNA in order to measure its antimicrobial, cytotoxic and phagocytic activities against Staphylococcus aureus., Results: Firstly, we observed that IL-26 is able to modulate the proinflammatory response at the immune cell level. IL-26 was increased in the plasma of patients with HS compared with healthy controls. Subsequently, we explored the bactericidal, cytotoxic and phagocytic activities of PBMCs against S. aureus in patients with HS and healthy controls. These activities were lower in patients with HS than in controls. Remarkably, the killing activities were reduced when healthy control PBMCs were transfected with IL-26 siRNA. However, the transfection did not affect the killing activity of HS PBMCs, supporting the idea that IL-26 lacks efficacy in HS., Conclusions: Our findings suggest that infection susceptibility in HS might be related to IL-26. Although the role of bacteria remains controversial in HS, this paper supports that there is a defect of antimicrobial response in these patients. What's already known about this topic? Interleukin (IL)-26 is a T helper 17 cytokine described as an antimicrobial and proinflammatory mediator. IL-26 has been reported in immune-mediated inflammatory diseases, but its involvement in inflammatory skin disorders remains unclear. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder characterized by deficiency of IL-20 and IL-22 (a close homologue of IL-26), which causes antimicrobial peptide pauperization leading to severe and recurrent skin infections. What does this study add? IL-26 plasma levels are higher in patients with HS than in healthy control individuals. The antimicrobial activity of IL-26 might be ineffective in patients with HS. What is the translational message? Cutaneous antimicrobial incompetence in HS could be related to IL-26., (© 2019 British Association of Dermatologists.)

Background: Biologics targeting inflammatory mediators can achieve clinical improvements in hidradenitis suppurativa (HS). However, their clinical efficacy shows great interpatient variability in daily practice., Objectives: To investigate the anti-inflammatory potency of a selection of currently available biologics and prednisolone for the treatment of HS in an ex vivo skin culture system using lesional HS biopsies., Methods: Lesional skin samples from 10 patients with HS and skin samples from five healthy controls were cultured ex vivo and exposed to prednisolone or biologics targeting tumour necrosis factor (TNF)-α, interleukin (IL)-17A, IL-12/23p40 or CD20 (adalimumab, infliximab, secukinumab, ustekinumab and rituximab, respectively). Real-time quantitative polymerase chain reaction and cytokine bead arrays were used to measure the inhibitory effect of the biologics on cytokines and antimicrobial peptides (AMPs)., Results: The relative mRNA expression of all tested cytokines and AMPs was significantly downregulated by all anti-inflammatory agents (P < 0·001). The protein production of the proinflammatory cytokines TNF-α, interferon γ, IL-1β, IL-6 and IL-17A was significantly inhibited by adalimumab, infliximab, ustekinumab, prednisolone (all P < 0·001) and rituximab (P = 0·0071), but not by secukinumab (P = 0·0663). On both mRNA and protein levels, adalimumab, infliximab and prednisolone reduced the levels of a broader mix of individual cytokines than secukinumab, ustekinumab and rituximab. Moreover, a significant inhibitory effect on mRNA expression levels of inflammatory markers in healthy control skin was observed only for TNF-α inhibitors (P < 0·001) and prednisolone (P = 0·0015)., Conclusions: This ex vivo study suggests that TNF-α inhibitors and prednisolone are the most powerful inhibitors of proinflammatory cytokines and AMPs in HS lesional skin, which concurs with our clinical experience in patients with HS., (© 2019 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Hidradenitis suppurativa (HS) is a rare, debilitating neutrophilic dermatosis characterized by chronic inflammation of hair follicles. Many inflammatory conditions may accompany HS., Objectives: To investigate the association of variants of the MEFV gene with a complex HS phenotype., Methods: Firstly, we identified the clinical characteristics of 119 patients with HS with a complex phenotype (Hurley stage III disease and/or additional inflammatory symptoms). Then, we searched for MEFV variants among these patients. The odds ratios (ORs) for pathogenic MEFV mutations were calculated using data from these patients with HS and 191 healthy controls., Results: The male/female ratio was higher, and the mean age of onset was earlier, in our complex HS group compared with patients with HS in general. Five of the patients with HS (4·2%) had a diagnosis of familial Mediterranean fever (FMF) with a standardized morbidity ratio of 45 [95% confidence interval (CI) 16·50-99·84, P < 0·001] when compared with the frequency of FMF in the general Turkish population. Of the patients with complex HS, 38% were positive for pathogenic variants of MEFV. The OR for carrying a pathogenic MEFV allele was 2·80 (95% CI 1·31-5·97, P < 0·001)., Conclusions: The frequency of MEFV mutations in the group of patients with complex HS was higher than that in healthy controls, suggesting that MEFV mutations may contribute to the pathogenesis of HS. Understanding the role of autoinflammation in HS is of fundamental importance for the development of novel therapies., (© 2018 British Association of Dermatologists.)

Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin disease resulting in non-healing wounds affecting body areas of high hair follicle and sweat gland density. The pathogenesis of HS is not well understood but appears to involve dysbiosis-driven aberrant activation of the innate immune system leading to excessive inflammation. Marked dysregulation of antimicrobial peptides and proteins (AMPs) in HS is observed, which may contribute to this sustained inflammation. Here, we analyzed HS skin transcriptomes from previously published studies and integrated these findings through a comparative analysis with a published wound healing data set and with immunofluorescence and qPCR analysis from new HS patient samples. Among the top differently expressed genes between lesional and non-lesional HS skin were members of the S100 family as well as dermcidin, the latter known as a sweat gland-associated AMP and one of the most downregulated genes in HS lesions. Interestingly, many genes associated with sweat gland function, such as secretoglobins and aquaporin 5, were decreased in HS lesional skin and we discovered that these genes demonstrated opposite expression profiles in healing skin. Conversely, HS lesional and wounded skin shared a common gene signature including genes encoding for S100 proteins, defensins, and genes encoding antiviral proteins. Overall, our results suggest that the pathogenesis of HS may be driven by changes in AMP expression and altered sweat gland function, and may share a similar pathology with chronic wounds., Competing Interests: ASM received research support from Silab and is now consulting for this company. This relationship does not confer any conflict of interest. This role as consultant does not alter our adherence to PLOS ONE policies on sharing data and materials.

Hidradenitis suppurativa is an inflammatory disease associated with subcutaneous nodules/abscesses that occur commonly in the axillary, inguinal, and perineal regions. We describe a case of a 64-year-old man presenting for F-FDG PET/CT for staging of a left vocal cord squamous cell carcinoma. The scan showed uptake in the left vocal cord malignancy and multiple hypermetabolic subcutaneous foci in the right axilla, right buttocks, and scalp in known locations of skin lesions related to hidradenitis suppurativa. This case illustrates an unusual inflammatory cause of F-FDG incidental uptake that should not be mistaken for metastases.

Recently, we could show that the expression levels of the key regulators of the microRNA (miRNA) maturation and transport were dysregulated in inflamed hidradenitis suppurativa (HS) tissue (Heyam et al. in Wiley Interdiscip Rev RNA 6:271-289, 2015). The RNA-induced silencing complex (RISC) is the central element of the miRNA pathway and regulates miRNA formation and function. We investigated the expression of the RISC components, namely transactivation-responsive RNA-binding protein-1 (TRBP1), TRBP2, protein activator (PACT) of the interferon-induced protein kinase R, Argonaute RISC Catalytic Component-1 (AGO1) and Component-2 (AGO2), metadherin, and staphylococcal nuclease and Tudor domain-containing-1 (SND1) in inflamed HS tissue compared to healthy and psoriatic controls by real-time reverse transcription polymerase chain reaction. Expression levels of all investigated components were significantly lower in lesional HS skin (n = 18) compared to healthy controls (n = 10). TRBP1, PACT, AGO1, AGO2, and SND1 expression levels were significantly down-regulated in lesional HS skin compared to healthy-appearing perilesional skin (n = 7). TRBP2 and SND1 expression levels were significantly lower in healthy-appearing perilesional skin compared to healthy controls. In lesional HS skin, expression levels of PACT, AGO1, and AGO2 were significantly lower compared to psoriatic skin (n = 10). In summary, our data showed that all investigated components of RISC are dysregulated in the skin of HS patients, providing support for the hypothesis that miRNAs may have a pathological role in the inflammatory pathogenesis of HS.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease defined by recurrent nodules, tunnels (sinus tracts) and scarring involving the intertriginous regions. The clinical course of HS is compatible with a biofilm-driven disease, and biofilm has been described in lesional HS skin. We therefore hypothesized that clinically unaffected HS skin would also have an increased presence of biofilm compared with that of healthy controls. We conducted a case-control study, investigating the morphology of the axillary skin microbiota. Peptide nucleic acid - fluorescence in situ hybridization probes were used in combination with confocal laser scanning microscopy. Significant differences were found in both distribution and quantity of the cutaneous microbiota in clinically non-affected axillary skin of patients with HS compared with healthy controls. Surprisingly, we detected fewer bacteria and less biofilm in patients with HS. The reduced microbiota in patients with HS may play an important role in the early course of the disease.

Background: The etiology of hidradenitis suppurativa (HS) involves genetic and environmental factors. Well-established associated systemic factors are obesity, smoking, inflammation, and bacteria. Whether localized environmental factors such as friction and pressure may also play a causative role is still unclear., Objective: To describe the possible Koebner phenomenon (KP) in HS., Methods: The case notes on 14 patients with typical HS and additional HS lesions in previously uninvolved skin areas exposed to mechanical stress, e.g., on the abdomen at the level of the waistband, were reviewed with regard to the clinical characteristics of the cohort., Results: All 14 patients (7 females) were obese with a mean BMI of 35.8 (range 30.1-45.0). All patients developed additional ectopic HS lesions at the sites of friction on the convex abdomen. The ectopic lesions were clinically and histopathologically similar to HS., Conclusion: Mechanical stress factors or trauma play a role in obese patients with HS. It is suggested that these new induced lesions fit the concept of the KP. This phenomenon seems to occur in the so-called frictional furunculoid type of HS and may explain the unique distribution at certain localizations on the body of this follicular cutaneous eruption. Removal in an early stage of HS of external stress factors that can lead to the KP should be part of the treatment, especially in obese patients., (© 2017 S. Karger AG, Basel.)

Purpose: The aim of this study was to demonstrate the feasibility of a custom-made phased-array microcoil within a 400 MHz animal system for the morphological characterization of human skin tissue in correlation with histopathology., Materials and Methods: A dedicated 7-channel microcoil-based MR detector arranged in a phased-array geometry was developed to combine the advantages of both a large field of view and a high signal-to-noise ratio. Standard gradient echo sequences were adapted for the characterization of skin morphology ex vivo., Results: In this study, the feasibility of using this type of microdetector, combined with specially manufactured sample holders, to achieve high-resolution MR images of fresh and formalin-fixed, normal and hidradenitis suppurativa diseased skin was successfully demonstrated. The setup presented in this work allows reliable acquisitions of high-resolution images with in-plane resolution up to 25 × 25 μm², and 100 μm in the orthogonal direction, thereby allowing the differentiation of typical layers of the skin, sebaceous glands and hair follicle., Conclusion: This study demonstrates that MR microscopy on skin biopsies can be applied at low cost on a standard animal MR imaging system. The successful imaging of different skin structures ex vivo is a prerequisite for non-invasive, in vivo application of skin MR microscopy for accurate complementary disease diagnosis in dermatology., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This article is dermatological atlas of the morphologic presentations of Hidradenitis Suppurativa (HS). It includes: superficial abscesses (boils, furnucles, carbuncles), abscesses that are subcutaneous and suprafascial, pyogenic granulomas, cysts, painful erythematous papules and plaques, folliculitis, open ulcerations, chronic sinuses, fistulas, sinus tracts, scrotal and genital lyphedema, dermal contractures, keloids (some that are still pitted with follicular ostia), scarring, skin tags, fibrosis, anal fissures, fistulas (i.e. circinate, linear, arcuate), scarring folliculitis of the buttocks (from mild to cigarette-like scarring), condyloma like lesions in intertrigous areas, fishmouth scars, acne inversa, honey-comb scarring, cribiform scarring, tombstone comedones, and morphia-like plaques. HS can co-exist with other follicular diseases such as pilonidal cysts, dissecting cellulitis, acne conglobata, pyoderma gangrenosum, and acanthosis nigricans. In sum, the variety of presentations of HS as shown by these images supports the supposition that HS is a reaction pattern.HS is a follicular based diseased and its manifestations involve a multitude of follicular pathologies [1,2]. It is also known as acne inversa (AI) because of one manifestation that involves the formation of open comedones on areas besides the face. It is as yet unclear why HS is so protean in its manifestations. HS severity is assessed using the Hurley Staging System (Table 1). It also remains unclear why hidradentitis may remain limited to Hurley Stage 1, evolve to the more confluent (Hurley Stage 2), or progress even further to the fully confluent (Hurley Stage 3).In addition, HS can be associated with other follicular based diseases such as pilonidal cysts (PCs) of the sacrum and buttocks, dissecting cellulitis (DC), and acne conglobata (AC), which usually involves the face, chest, When HS occurs with PCs, DC, and/or AC it is referred to as the follicular occlusion triad or tetrad [2]. HS can more rarely be associated with pyoderma gagrenosum (PG) or Crohn disease (CD), other inflammatory diseases of the skin that are not follicular. The reason for this is unclear [2]. What AC, DC, HS, CD, and PG share is that they occur in bacterially rich environments. HS probably occurs with acanthosis nigricans because many HS patients are obese [2]. This concurrence seems under reported.

Hidradenitis suppurativa is a chronic skin condition, characterized clinically by painful, recurrent, deep- seated nodules and suppuration, and histologically by hyper-trophic scarring of apocrine gland bearing skin and sinus tracts. The overall consequence of the disease is considerable tissue remodelling and the underlying alterations in innate immunity are poorly understood. The aim of this study was to evaluate the expression of human beta-defensin 2, tumour necrosis factor (TNF)-α and matrix metalloproteinase-2 in skin lesions of patients with hidradenitis suppurativa. A total of 14 skin samples from patients and 2 skin samples from healthy volunteers were evaluated by immunohistochemistry. Human beta-defensin 2 was negative in 12/14 specimens. Elevated expression of metalloproteinase-2 was observed in keratinocytes, fibroblasts and inflammatory cells in dermis, sweat glands, hair follicles and sinus tracts, suggesting a key role for hidradenitis suppurativa pathogenesis. Decreased human beta-defensin 2 in the presence of inflammatory (TNF-α-containing) cells suggests a decreased innate immunity in hidradenitis suppurativa-affected skin.

Background: Current insight into the histopathological course of events during disease progression in hidradenitis suppurativa (HS) is fragmentary., Objectives: To identify histological alterations and leucocyte subsets in normal-appearing perilesional skin, and early and chronic HS lesions., Methods: In this observational study we examined eight perilesional skin samples, and six early and 10 chronic prototypic HS lesions, as well as skin samples from four healthy donors using in situ immunostaining., Results: Perilesional skin showed mild psoriasiform hyperplasia and follicular plugging as well as a low-grade influx of tryptase-positive mast cells, CD3+ T cells, CD138+ plasma cells and factor XIIIa+ dendritic cells. In early HS lesions, neutrophilic abscess formation and influx of mainly macrophages, monocytes and dendritic cells predominated. In chronic disease, the infiltrate expanded with markedly increased frequencies of CD20+ and CD79a+ B cells and CD138+ plasma cells. As in early lesions, free keratin fibres were detected in the dermis and within giant cells. Single detached keratinocytes and strands of follicular epithelium were observed in the dermis, the latter frequently expressing Ki67, indicative of active proliferation., Conclusions: Psoriasiform hyperplasia, follicular plugging and low-grade leucocytic infiltration are already present in normal-appearing perilesional skin. Keratin fibres in the dermis are associated with clinical disease. Early lesions are characterized by neutrophilic abscess formation and influx of mainly histiocytes, and chronic lesions mainly by expansion of B cells and plasma cells in 'pseudo' follicles. Proliferating strands of follicular epithelium may initiate fistula formation. Mast cells are increased in all stages of HS including perilesional skin., (© 2011 The Authors. BJD © 2011 British Association of Dermatologists.)

Hidradenitis suppurativa is a chronic skin disease, characterized by painful, deep-seated inflamed lesions, mainly in areas bearing apocrine sweat glands, most commonly the axillary and inguinal regions. Pain leads to mechanical problems, and bacterial growth in the lesions produces a foul-smelling discharge, which reduces the quality of life. In this type of hidradenitis the infection occurs around hair follicles and sebaceous glands, in contrast to what the name would suggest (hidradenitis = sweat-gland inflammation); hidradenitis suppurativa can, therefore be regarded more as a form of acne. The aetiology of hidradenitis is still unknown, but associated factors are smoking, obesity and familial predisposition.The syndrome can take a severe and disabling course. It is worthwhile implementing aggressive treatment at an early stage. Tumour necrosis factor-alpha inhibitors are now employed in the treatment of severe and treatment-resistant forms of hidradenitis suppurativa; under certain conditions this treatment will be reimbursed by the health insurance company. This development means that there are more treatment possibilities in hidradenitis than there were 5 years ago. The best results are achieved with a combination of antibiotic, anti-inflammatory and surgical treatment, tailored to the patient's individual situation.

The aim of this study was to investigate the presence and density of the nerve fibre-marker protein gene product 9.5 (PGP 9.5), with immunohistochemistry, in skin from patients with hidradenitis suppurativa (HS). Punch biopsies were obtained from 16 patients; 10 with involvement of the groin and six with axillary disease. Specimens were taken from HS lesions in the groin or axilla, clinically non-involved skin and from 12 healthy control subjects. Coded slides were observed in the microscope and PGP 9.5 positive nerve fibre profiles (profiles) as well as PGP 9.5 positive cells (cells) were counted. The overall impression was that the median number of profiles was decreased in lesional epidermis, yet statistically significant only in the groin (p = 0.0014). The median number of profiles in dermis was significantly decreased in lesional skin of the axilla, whereas in the groin there were contradictory findings with significantly increased number of profiles in upper dermis and non-significant in mid and lower dermis. The number of cells with strong immunofluorescence was few or absent in epidermis, but increased in dermis in the lesional skin. This difference was statistically significant throughout the dermis in specimens from the groin (p < 0.01) and showed the same trend, although not significant, in the axilla. The PGP 9.5 immunofluorescent cells were not yet further investigated, so it is not exactly known what cell type they represent. In conclusion, despite several study limitations, the findings indicate that PGP 9.5 positive nerve fibres could be involved in the pathogenesis of HS. Both regarding the profiles and the cells, further studies remain to show if these differences are primary events, or secondary to e g chronic inflammation, which is considered a major issue of HS.

Hidradenitis suppurativa (HS)--a rather common, very chronic and debilitating inflammatory skin appendage disorder with a notoriously underestimated burden of disease--has long been a playground for the high priests of nomenclature: Ask a bunch of eminent dermatologists and skin pathologists to publicly share their thoughts on what causes HS, and they will soon get entrenched in a heated debate on whether this historical term is a despicable misnomer. Fortunately, the recently founded Hidradenitis Suppurativa Foundation (HSF; http://www.hs-foundation.org), to which EXP DERMATOL serves as home journal, has broken with this unproductive tradition and has encouraged publication of the current CONTROVERSIES feature. This is exclusively devoted to discussing the pathobiology of this chronic neutrophilic folliculitis of unknown origin. Although traces of terminological bickering remain visible, it does the HS experts in our virtual debate room credit that they engage in a constructive and comprehensive dissection of potential pathogenesis pathways that may culminate in the clinical picture we know under the competing terms HS or acne inversa. These experts sketch more often complementary than mutually exclusive pathogenesis scenarios, and the outlines of a conceivable consensus on the many open pathobiology questions begin to emerge in these CONTROVERSIES. Hopefully, this heralds a welcome new tradition: to get to the molecular heart of HS pathogenesis, which can only be achieved by a renaissance of solid basic HS research, as the key to developing more effective HS therapy.

Clear-cell acanthoma (CCA) has been reported to be a benign epidermal neoplasm; however, several authors have suggested alternative differentiation as well as other nosologic categories, including a reactive dermatosis. Fourteen CCAs, ten tricholemmomas, and seven cases of psoriasis were reviewed with conventional microscopy, periodic acid-Schiff stains, and immunohistochemical stains. Twelve of fourteen (86%) CCAs were associated with underlying or adjacent conditions. The CCAs stained immunohistochemically in a pattern similar to normal epidermis and psoriasis. Tricholemmomas stained in a distinctly different pattern with MNF116 and NGFR/p75. These cases demonstrate CCA in settings that reflect chronic inflammation, primarily scars and stasis dermatitis, and with an immunophenotype that parallels psoriasis. These findings support the contention that CCA does not show outer follicular sheath (tricholemmal) differentiation. Furthermore, these cases lend additional support to the contention that CCA represents a psoriasiform reaction pattern, which, in appropriately taken biopsies, usually has a demonstrable associated condition. Nonetheless, the precise nosology of this phenomenon has yet to be elucidated completely.

In recent years, the physiological role of non-neuronal acetylcholine (ACh) and its receptors (AChR) in epidermal physiology has been under intense investigation. However, little is known about the role of the non-neuronal cholinergic system in inflammatory skin diseases. We chose the clinically nicotine-dependent skin disease hidradenitis suppurativa (HS) as model to study the influence of long term nicotine ingestion on epidermal morphology and AChR expression. HS is a chronic inflammatory, disabling disease of unknown pathogenesis emerging from the pilosebaceous unit of the intertriginous areas. In order to correlate our findings to specific nicotine effects, we used the organotypical coculture system (OTC) and raised artificial epidermis in the presence of nicotine. After 12 days in culture control OTC showed a mature epithelium, while nicotine treated OTCs were significantly thicker. Using immunofluorescence analysis, nicotine treated OTCs produced significantly stronger immunoreactivity (IR) for the alpha3, M(3) and M(5) AChR antisera than control. In contrast, the alpha7 nAChR antiserum showed a slightly reduced IR in the granular layer and the alpha9 nAChR IR retracted to the lower suprabasal layers. In HS epidermis we found the strongest IR for all AChR around the follicular infundibulum while in the sinus epithelia it was only weak. In contrast to the nicotine treated OTC, the alpha7 nAChR IR in the hyperplastic HS epidermis was clearly extended to all living layers. Altogether we provide first hints for a causative role of the non-neuronal cholinergic system in the pathogenesis of HS by promoting infundibular epithelial hyperplasia and thus follicular plugging.

HS is a chronic, debilitating inflammatory dermatosis that is often refractory to treatment. Many medical therapies have been tried and some show efficacy. The introduction of new immunosuppressive medications has revolutionized the treatment of psoriasis in dermatology. These therapies have the potential to powerfully abort the molecular signals driving inflammation in HS and perhaps even induce a remission. This may offer patients an alternative to radical excisional surgery. However, more studies are needed to evaluate the long-term effects of these medications, particularly in light of their association with an increased risk of malignancy and infection. Evaluation of treatment efficacy has been hindered by a lack of uniform standards to track treatment response. The classic clinical classification system has limitations but is a useful scheme to guide selection of treatments. Further laboratory studies may be warranted, depending on the clinical presentation (Box 3). While there are many approaches to treating HS, the authors offer an algorithm based on disease severity (Fig. 9). It is important to address many patient-oriented concerns, such as the pain, dampness, and smell associated with draining sinuses. Communication with the patient about expectations is important to direct treatment. Often a multidisciplinary approach involving dermatology, plastic surgery, gynecology, and urology may be necessary to diagnose and treat the disease. Both medical and surgical options should be explored before embarking on therapy.

In 14 cases of hidradenitis suppurativa, cytokeratin (CK) expression was studied immunohistochemically, using six antikeratin antibodies against CK1, CK10, CK14, CK16, CK17 and CK19, respectively. The draining sinus tract epithelium of hidradenitis suppurativa lesions was divided into three components: infundibular-like keratinized epithelium (type A), non-infundibular keratinized epithelium (type B), and non-keratinized epithelium (type C). In type A samples, CK17 (which is found in normal infundibulum) was not detected, suggesting fragility of this epithelial type. Keratin expression in types B and C epithelia was similar to that observed in the outer root sheath in normal hair follicles. Our results suggest that the draining sinus epithelium may possess characteristics of fragility, undifferentiation and hyperproliferation, as shown with CK expression.

The pathogenesis of hidradenitis suppurativa (HS) has given rise to controversy about whether the central pathogenetic feature is an apocrine follicular occlusion (with subsequent bacterial infection) or it is a folliculitis with secondary involvement of both apocrine and eccrine sweat glands. Most previous concepts have focused on apocrine gland involvement. A prospective study of 27 consecutive patients (39 biopsies) was performed to investigate the immune-histological findings in early, newly formed lesions. Most of them were examined within 3 days of clinical onset. Histopathological findings showed that the initial lesion is an occluding spongiform infundibulo-folliculitis. Furthermore, it was found that T cells predominated in the lymphocytic cell population. A high percentage of HLA-DR positive lymphocytes was found in an inverse relationship with Leu-8 positive lymphocytes. Additionally, a sharp decline in the T-helper/suppressor ratio was observed after the initiation. These results reveal that the primary event in HS is an infundibulofolliculitis with secondary involvement of apocrine glands. Acne inversa would be a more appropriate name.