[Differences in anatomical area-specific wound healing in hidradenitis suppurativa/acne inversa after surgery].

BACKGROUND: Hidradenitis suppurativa/acne inversa is an inflammatory, debilitating disease for which wide local excision of the affected area with secondary wound healing is considered the treatment of first choice for the inactive scarring form or after adequate anti-inflammatory medical treatment. OBJECTIVES: In this study, we aimed to assess the duration of complete secondary wound healing after surgical intervention for hidradenitis suppurativa/acne inversa. MATERIALS & METHODS: Twenty-three surgical procedures in 17 consecutive patients (eight female, nine male) were evaluated for duration of secondary wound healing at axillary or anogenital/inguinal sites. To investigate the contribution of hair follicle bulge progenitor cells in wound re-epithelialization, tissue samples of lesional and perilesional skin were analysed for expression of the stem cell marker, cytokeratin 15 (CK15), and CD200, a marker for human follicular stem cells that resides in the bulge area. RESULTS: Initial wound size did not differ significantly between surgical wounds in the axillary (mean: 30.0 cm2 ± 5.4) and anogenital/inguinal (mean: 35.3 cm2 ± 5.7) region. However, healing time to complete wound closure was almost twice as fast in the anogenital/inguinal (mean: 132 days ± 10.4) than axilla area (mean: 254 days ± 39.1; p < 0.01). The accelerated wound healing in the anogenital/inguinal region was accompanied by significantly enhanced CK15 and CD200 expression, compared to axillary wounds (p < 0.05). CONCLUSION: The anogenital/inguinal region showed significantly faster secondary wound healing after surgical intervention for hidradenitis suppurativa/acne inversa compared to axillary wounds. We suspect differences in pilosebaceous unit density and thus hair follicle progenitor cells (as mirrored by CK15 and CD200 expression) to be the main driver behind this finding.

Clinical Implementation of Biologics and Small Molecules in the Treatment of Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic, recurrent, auto-inflammatory skin disease originating from the hair follicles. The typical inflammatory nodules, abscesses, and draining sinus tracts (tunnels) are characterized by a massive influx of neutrophils, macrophages, B-cells, plasma cells, T helper (Th)1, Th17 cells and upregulation of pro-inflammatory cytokines such as IL-1, IL-17, IL-12/23, and TNF-α. Over the last decades, several clinical trials evaluated the clinical efficacy of different biologics targeting these pro-inflammatory cytokines, in particular TNF-α and IL-1. However, adalimumab is still the only registered drug for HS. This review discusses biologics and small molecules with high level of evidence for their clinical application, provides guidance on when and how to use these biologics and small molecules in clinical practice, and elaborates on the combination with medical and surgical treatment options beyond the current guidelines. Furthermore this review provides an overview of potential biologics and small molecules currently under investigation for novel targets in HS such as IL-36, C5a, Janus kinase family members, CD-40, LTA4 and CXCR1/2.

Hidradenitis suppurativa in South-East Asia and East Asia.

Hidradenitis suppurativa (HS) in South-East Asia and East Asia shows distinct clinical, environmental, physiological and likely genetic differences compared with the West. A male predominance is present, which may be due to differences in smoking habits. Involvement of the buttocks is common in East Asian patients, while the axillae are most commonly affected in South-East Asian patients. Metabolic comorbidities are prevalent in South-East Asian and East Asian HS patients. A family history of HS is less common than noted in Western populations. Asian ethnic subgroups deserve further study.

Hidradenitis suppurativa in skin of colour.

Hidradenitis suppurativa/acne inversa (HS) more prevalent and disproportionally affects African American females. Although there are limited studies in HS skin of colour populations in the USA, there is more scarcity of HS skin of colour studies in other countries, which limits the overall understanding of the disease among these patients. Herein, our overview of the 10th European Hidradenitis Suppurativa Foundation (EHSF) e.V. Conference provided a crude example of the limited number of skin of colour physicians, physician scientists and inclusion of skin of colour patients highlighting the need to increase awareness of this important issue. We summarized the epidemiology, pathogenesis, clinical picture and focused on treatment options from southeast Asia and Africa. Our outlined general recommendations for diagnosis will render better clinical care and outcomes for diverse patient populations.

Adalimumab Induces a Wound Healing Profile in Patients with Hidradenitis Suppurativa by Regulating Macrophage Differentiation and Matrix Metalloproteinase Expression.

Adalimumab (ADA) is the only Food and Drug Administration‒approved treatment for moderate-to-severe hidradenitis suppurativa, whereas etanercept and certolizumab-pegol have been shown to be ineffective, suggesting that the mechanism of action of ADA is distinct in hidradenitis suppurativa and may contribute to improved wound healing. Given that macrophages (Mϕs) play pivotal roles throughout the wound healing process, an in vitro Mϕ differentiation assay was carried out to assess the impact of TNF‒anti-TNF complexes on these cells. TNF‒ADA complexes exhibited stronger inhibitory effects on inflammatory Mϕ differentiation. Moreover, RNA sequencing revealed several unique wound healing profiles for TNF‒ADA‒treated inflammatory Mϕs, which were not observed for those treated with either TNF‒etanercept or TNF‒certolizumab-pegol complexes, including the inhibition of the matrix metalloproteinase (MMP) pathway. In addition, ADA administration was found to significantly reduce the levels of inflammatory MMP-1 and MMP-9 while promoting wound-healing MMP-13 and tissue inhibitor of metalloproteinases 2 levels in the circulation of the patients with hidradenitis suppurativa who responded to treatment. Our in vitro findings show that TNF‒ADA‒treated inflammatory Mϕs exhibit a distinct profile resembling wound healing. Moreover, ADA not only differentially regulates MMP expression in patients with hidradenitis suppurativa responding to the therapy but also potentially induces a transition to a profile suggestive of wound healing.

A safety review of biologic therapies for the management of hidradenitis suppurativa and unmet needs.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic, debilitating inflammatory skin disorder characterized by nodules, abscesses, fistulae, and significant scarring in intertriginous areas rich in apocrine glands. Immunomodulator drugs, including biologics, are a mainstay of treatment for this disease. AREAS COVERED: This review details the safety profiles of various biologic therapies currently available commercially that have been tried for HS as assessed in clinical trials and observational studies. As the only Food and Drug Administration (FDA)-approved medication for the treatment of moderate-to-severe HS, adalimumab is discussed in the most detail. Additional biologic medications, including tumor necrosis factor α (TNFα) inhibitors, interleukin 1 (IL-1) inhibitors, IL-12 and IL-23 inhibitors, IL-17 inhibitors, and IL-23 inhibitors, are discussed as well. Safety concerns in special populations, including pregnant women and children, are outlined. EXPERT OPINION: Existing data support excellent short-term and long-term safety profiles for adalimumab, although caution must be taken with use in high-risk patient populations, including those with chronic infections or increased risk of malignancy. Based on their safety data for other indications, additional biologic agents appear safe in HS as well. However, further research is needed to fully understand the safety profiles of these medications in the HS population.

Métodos referidos por los pacientes para aliviar el dolor asociado a la hidradenitis supurativa / Self-Reported Pain Alleviating Methods in Patients with Hidradenitis Suppurativa

INTRODUCCIÓN: El dolor es un síntoma común e importante que afectará negativamente el bienestar y la calidad de vida de los pacientes con hidradenitis supurativa (HS). El objetivo del presente estudio fue valorar los métodos utilizados para aliviar el dolor asociado a la HS, referidos por los pacientes ambulatorios provenientes de un centro de referencia terciario. MÉTODOS: Se seleccionaron de manera consecutiva pacientes con el diagnóstico de HS. Posteriormente se les invitó a que completasen un cuestionario acerca de cuáles eran los métodos que utilizaban para aliviar el dolor asociado a la HS. Así mismo, los pacientes completaron el cuestionario del Índice de Calidad de Vida en Dermatología y la escala visual analógica acerca de las molestias generales que presentaban en relación con la HS, así como el dolor asociado a la aparición de forúnculos en el último mes. La información sobre la gravedad y la forma de presentación de la enfermedad se obtuvo mediante la anamnesis y el examen clínico. RESULTADOS: Se incluyeron un total de 134 pacientes con una edad media de 38,3 años (DE 12,8). El 32% (n = 43) tenía un estadio i, el 52% (n = 70) un estadio II y el 16% (n = 21) un estadio III de Hurley. Para lograr el alivio del dolor el 82% (n = 110) de los pacientes refirieron que habían drenado el pus de las lesiones inflamatorias usando la presión de los dedos. En comparación con los pacientes que no habían usado ningún método para aliviar el dolor, los pacientes que sí lo habían hecho tuvieron en general un mayor grado de angustia en relación con la enfermedad (7,43 [DE 2,81] frente a 5,47 [DE 3,37], p < 0,003), así como un mayor grado de dolor asociado a la presencia de forúnculos durante el último mes (6,56 [DE 3,07] frente a 4,39 [DE 3,88], p = 0,007). CONCLUSIÓN: El presente estudio demuestra que una elevada proporción de los pacientes con HS intentarán aliviar el dolor por sí mismos utilizando diversos métodos caseros y alternativos. Estos resultados reflejan la importancia del dolor en la HS y que posiblemente el manejo de este por los dermatólogos sea insuficiente

BACKGROUND: Pain is a common, important symptom negatively affecting the well-being and quality of life of patients with hidradenitis suppurativa (HS). The aim of this study was to examine self-reported pain alleviating methods among outpatients attending a tertiary referral center. METHODS: Consecutive patients with HS were invited to complete a questionnaire regarding their self-reported pain alleviating methods for HS associated pain. Additionally, the patients filled out the Dermatology Life Quality Index questionnaire and a visual analog scale for overall distress related to HS and for boil-associated pain in the past month. Information on disease severity and onset was obtained by interview and clinical examination. RESULTS: A total of 134 patients with a mean age of 38.3 years (SD 12.8) participated; 32% (n = 43) had Hurley stage i, 52% (n = 70) had Hurley stage ii, and 16% (n = 21) had Hurley stage III. Overall, to achieve pain relief, 82% (n = 110) of the patients had previously drained pus from the lesions by manual pressure. Compared to patients who did not alleviate pain, patients who attempted to alleviate pain had a higher mean overall disease related distress score (7.43 [SD 2.81] vs. 5.47 [SD 3.37], P < .003), and a higher boil-associated pain score in the past month (6.56 [SD 3.07] vs. 4.39 [SD 3.88], P = .007). CONCLUSION: This study demonstrates that a large proportion of HS patients attempt to alleviate pain through various alternative and homespun methods. These results may reflect a major role of pain in HS and its potential insufficient management by dermatologists

Characterization and Management of Inflammatory Eye Disease in Patients with Hidradenitis Suppurativa.

Purpose: To assess the spectrum and treatment outcomes of inflammatory eye disease (IED) in subjects with hidradenitis suppurativa (HS).Methods: We conducted a single center retrospective chart review of 236 patients with HS seen for ophthalmic examination between 2013 and 2018.Results: Of 236 subjects with HS, 22 subjects (9.3%) were found to have IED. Seven of 22 subjects had more than one IED diagnosis. Anterior uveitis was the most common type of IED (40.9% of subjects with IED). Episcleritis, optic neuritis, keratitis, scleritis, intermediate and posterior uveitis, trochleitis, and dacryoadenitis were also observed. Of subjects with HS and IED, 59.1% did not have any other inflammatory or autoimmune disease that could explain the etiology of their IED. Eleven patients with IED were treated with systemic immunosuppression, with IED as the principal factor directing treatment in three patients.Conclusions: IED may be independently associated with HS and may benefit from systemic immunosuppression.

Mechanical forces and Hidradenitis Suppurativa.

The mechanism by which inflammatory skin disease forms localized patterns of lesions is poorly understood. Hidradenitis suppurtiva (HS) is strikingly located to intertriginous areas. These areas are subject to considerable mechanical stress (friction, pressure and shear forces). Koebner phenomenon (KP) describes the appearance of typical skin lesions of a pre-existing dermatosis on previously clear skin following trauma, such as friction, pressure and more often penetrating injury with subsequent scarring. Striae distensae (SD) are a form of dermal scarring and can be considered as a form of inflammation-driven dermal disarray. Ectopic HS lesions may occur as KP due to trauma and locally increased susceptibility consisting of either altered mechanical qualities or inflammation. SD and mechanical stress may thus provide a model for the development of lesions. In the absence of an (animal) model or experiment, two patients are described who show HS (-like) lesions along co-localized with SD. The suggested two-hits model may be necessary for the development of KP in HS, that is that the general susceptibility, conferred by obesity, requires a local susceptibility factor to result in ectopic lesions. Ultimately, if ectopic HS lesions are considered true HS lesions it may be speculated that similar interaction occurs in the naturally stressed skin areas offering a possible explanation of the localized pattern of the disease.

Self-Reported Pain Alleviating Methods in Patients with Hidradenitis Suppurativa. / Métodos referidos por los pacientes para aliviar el dolor asociado a la hidradenitis supurativa.

BACKGROUND: Pain is a common, important symptom negatively affecting the well-being and quality of life of patients with hidradenitis suppurativa (HS). The aim of this study was to examine self-reported pain alleviating methods among outpatients attending a tertiary referral center. METHODS: Consecutive patients with HS were invited to complete a questionnaire regarding their self-reported pain alleviating methods for HS associated pain. Additionally, the patients filled out the Dermatology Life Quality Index questionnaire and a visual analog scale for overall distress related to HS and for boil-associated pain in the past month. Information on disease severity and onset was obtained by interview and clinical examination. RESULTS: A total of 134 patients with a mean age of 38.3 years (SD 12.8) participated; 32% (n=43) had Hurley stage i, 52% (n=70) had Hurley stage ii, and 16% (n=21) had Hurley stage iii. Overall, to achieve pain relief, 82% (n=110) of the patients had previously drained pus from the lesions by manual pressure. Compared to patients who did not alleviate pain, patients who attempted to alleviate pain had a higher mean overall disease related distress score (7.43 [SD 2.81] vs. 5.47 [SD 3.37], P<.003), and a higher boil-associated pain score in the past month (6.56 [SD 3.07] vs. 4.39 [SD 3.88], P=.007). CONCLUSION: This study demonstrates that a large proportion of HS patients attempt to alleviate pain through various alternative and homespun methods. These results may reflect a major role of pain in HS and its potential insufficient management by dermatologists.

Phenotypes and Pathophysiology of Syndromic Hidradenitis Suppurativa: Different Faces of the Same Disease? A Systematic Review.

BACKGROUND: There is growing evidence that (certain) hidradenitis suppurativa (HS) comorbidities comprise syndromes including HS as a key cutaneous manifestation. These apparently autoinflammatory syndromes and their diagnostic delay might have detrimental effects on affected patients. METHODS: A systematic review was performed on the databases MEDLINE, EMBASE, and CENTRAL utilizing a standardized extraction form according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Sixty-four eligible articles on syndromic HS were retrieved. The identified syndromes included already described ones (pyoderma gangrenosum-acne-suppurative hidradenitis, pyogenic arthritis-pyoderma gangrenosum-acne-suppurative hidradenitis, psoriatic arthritis-pyoderma gangrenosum-acne-suppurative hidradenitis, pyoderma gangrenosum-acne vulgaris-hidradenitis suppurativa-ankylosing spondylitis, synovitis-acne-pustulosis-hyperostosis-osteitis) and further novel symptom constellations. Cutaneous signs, including HS lesions, usually precede signs from other organs. The cutaneous signs of a considerable proportion of patients appear refractory to conventional treatment, and monotherapy with biologics does not suffice to sustain remission. CONCLUSION: The results are subsequently discussed with focus on the pathophysiology and treatment of the detected syndromes. The dermatologist's role in the precise diagnosis and early treatment administration of HS is pivotal. The purpose of the treatment should be the effective prevention or delay of the autoinflammatory march and its irreversible consequences.

Obesidad y piel / Obesity and skin

Introduction: Obesity is a growing global health problem; it may even be one of the worst public health issues. In Chile, 34.4% of the population is obese, therefore, is it important for clinicians to be aware of all the consequences of obesity. In this review, we will address the relation of four main dermatologic conditions with obesity: psoriasis, hidradenitis suppurativa, acanthosis nigricans and malignant melanoma. Material and methods: Search in pubmed for obesity and psoriasis, hidradenitis suppurativa, acanthosis nigricans and malignant melanoma. Results: Obesity has a direct impact in the prevalence and severity of psoriasis, hidradenitis suppurativa, acanthosis nigricans. The reduction on body weight has proven to reduce severity of psoriasis and hidradenitis suppurativa. Obese patients with psoriasis have a higher risk on adverse effects due to medication and less effectiveness of biological medications. Acanthosis nigricans is a clinical indicator of insulin resistance and a risk predictor for those with greater risk to develop diabetes in the future. The relationship between obesity and malignant melanoma is not clear and needs further research. Conclusion: Obesity is increasing, dermatologist will face this condition more frequently, it has a great impact over psoriasis, hidradenitis suppurativa, acanthosis nigricans and malignant melanoma, thus it should be considered in treatment decisions. (AU)

Physical symptoms and psychosocial problems associated with hidradenitis suppurativa: correlation with Hurley stage.

BACKGROUND: Quality of life (QOL) in hidradenitis suppurativa (HS) patients is negatively impacted by physical and psychosocial problems. The aim of this study was to investigate the frequency and severity of HS-specific symptoms and to correlate these with disease severity. Methods We analyzed medical record data from 145 patients seen in an academic HS specialty clinic between August 2009 to March 2018. Results Hurley stage III patients had significantly higher mean Dermatology Life Quality Index (DLQI) scores (20.2) compared to patients with Hurley stage I (11.3) and II (13.9), (P<0.001 and P=0.001, respectively). More than 75% of patients reported physical symptoms of drainage, irritation, pain, itching, bleeding, and odor. There were associated psychosocial problems of embarrassment and self-consciousness. Symptom severity was most strongly correlated with disease severity for odor (correlation coefficient 0.4, P<0.001), difficulty moving arms (0.323, P<0.001), negative impact on job/school (0.303, P<0.001), and negative impact on relationships (0.298, P<0.001). Conclusion Our results highlight the significant burden of HS and the need for a more comprehensive, HS-specific evaluation tool to better assess the QOL of this patient population. Limitations A small cohort in a single academic center.

[Endocrinological mechanisms in the pathophysiology of hidradenitis suppurativa]. / Endokrine Mechanismen bei der Pathophysiologie der Hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic, recurrent cutaneous disease of the terminal hair follicle which manifests with deep-seated, painful nodules, abscesses, and sinus tract formation. The pathophysiology of the disease includes among various factors also dermatoendocrinologic variables: Correlations with metabolic syndrome, obesity, sex steroid hormones, and the improvement after antiandrogen therapy are some of the key points presented in this review. Hormonal treatment of HS can be an effective and inexpensive alternative or add-on therapy to classic HS treatments, especially in cases where antibiotics and/or biologics are ineffective or contraindicated.

Metabolic, pharmacokinetic, and toxicological issues of biologic therapies currently used in the treatment of hidradenitis suppurativa.

INTRODUCTION: Hidradenitis suppurativa is a chronic, relapsing, debilitating inflammatory dermatologic disease of the terminal hair follicles at intertriginous sites clinically characterized by painful inflammatory nodules, abscesses, draining sinus tracts, and dermal fibrosis. The management of hidradenitis suppurativa is a challenge and usually consists of both medical and surgical approaches, which must often be combined for best outcome. The introduction of biological therapies, specifically TNFα-inhibitors such as adalimumab, has profoundly changed the therapeutic armamentarium of the disease. AREAS COVERED: The PubMed database was searched using combinations of the following keywords: hidradentis suppurativa, biologic therapy, TNF-α inhibitors, adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, adverse effects, pharmacodynamics, pharmacology, adverse events, pharmacokinetics, drug interaction. This article reviews and updates the chemistry, pharmacokinetics, mechanism of action, adverse effects, drug interactions of on-label and off-label use of TNF-α inhibitors in HS. EXPERT OPINION: Biologic agents, particularly adalimumab, exhibit clinical efficacy in patients with hidradenitis suppurativa. Careful patient selection and close monitoring during treatment are mandatory to provide safe and effective use of the TNF-α inhibitor. Familiarity with biologic agents is crucial because these agents could become a consolidated treatment option in the clinician's therapeutic approaches.

Evaluation of Cardiovascular Risk in Hidradenitis Suppurativa Patients Using Heart Rate Variability (HRV) Analysis.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with elevated prevalence of comorbidities, especially metabolic and cardiovascular diseases. We used a tool called Heart Rate Variability (HRV) in order to assess the correlation between HS and alterations of the sympathetic-vagal equilibrium in the autonomic cardiovascular regulation system. We found increased sympathetic activity, associated with a higher risk of cardiovascular disease. HS, according to our results, is an independent cardiovascular risk factor.