Hidradenitis Suppurativa Found Associated With Cytokine Storm.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease that generates multiple cytokines. Here, we present an example of the cytokines forming a cytokine storm and its effects on the patient. CASE PRESENTATION: We report the case of a 55-year-old man who had severe but stable HS. Serum samples were collected from the patient and extraordinarily elevated cytokine concentrations were identified in the patient's serum.  Conclusion: Cytokine storms may be a condition associated with HS posing additional risk to patient survival. J Drugs Dermatol. 2024;23(5):e134-e136.     doi:10.36849/JDD.7860R1e.

Interprofessional cooperation with a dermatovenerologist - specifics of hidradenitis suppurativa management in gynaecological practice.

Hidradenitis suppurativa is a chronic immune-mediated inflammatory disease that is manifested by formation of painful nodules, abscesses and suppurating fistulas, primarily in the intertriginous spaces. This painful, often under-diagnosed disease affects much more women. They are also exposed to certain specific challenges in the management of this disease, especially during menstruation or pregnancy. The treatment requires the interdisciplinary cooperation of a dermatologist, gynaecologist, obstetrician and last but not least an algesiologist and psychotherapist. Above all, early and correct diagnosis, initiation of therapy in the early stages of the disease, is a key, which also plays a fundamental role in controlling inflammatory activity, preventing complications and further prognosis.

A Comparison of Hidradenitis Suppurativa Characteristics Among Israeli Arabs and Jews: Analysis of Two Cohorts.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease involving apocrine gland-bearing regions. There is an under-representation of non-Caucasians in epidemiologic studies of HS. The characteristics of HS in Israeli Arabs have not yet been studied. OBJECTIVES: To investigate the demographic and clinical profile of HS in the Israeli Arab population. METHODS: A retrospective analysis was conducted in two cohorts of patients with HS in Israel. The patients were derived from the database of a large health management organization (n=4191, 639 Arabs; population-based) and a major tertiary medical center (n=372, 49 Arabs). Demographic and clinical data were compared between ethnic groups. RESULTS: The prevalence of HS in Israeli Arabs was found to be 0.5%, fivefold higher than in Jews. Arab patients were younger (35.3 vs. 40.5 years, P < 0.001) and mostly male (52% vs. 35.7%, P < 0.001), with lower rates of co-morbidities, including smoking (40.8% vs. 55.7%, P < 0.001), hyperlipidemia, and depression as well as a higher rate of dissecting cellulitis (10.2% vs. 1.9%, P = 0.008). HS was more severe in Arabs, but of shorter duration, with mainly axillary involvement (79.6% vs. 57.9%, P = 0.004). Treatment with hormones was more common in Jews, and with biologic agents in Arabs. CONCLUSIONS: The findings suggest a different phenotype of HS in Arabs, warranting further study.

Hidradenitis suppurativa as a potential risk factor of periodontitis: a multi-center, propensity-score-matched cohort study.

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with systemic symptoms. Periodontitis, a prevalent dental disease, shares immune-mediated inflammatory characteristics with HS. This cohort study aims to evaluate the association between HS and periodontitis. Methods: Using the TriNetX research network, a global-federated database of electronic health records, we conducted a retrospective cohort study. People being diagnosed of HS were identified and propensity score matching was performed to identify proper control group, via balancing critical covariates Within the follow-up time of 1 year, 3 year and 5 years, hazard ratios were calculated to assess the risk of periodontitis in HS patients compared to controls. Results: Within the 53,968 HS patients and the same number of matched controls, the HS patients exhibited a significantly increased risk of developing periodontitis compared to controls after 3 years of follow-up (HR: 1.64, 95% CI: 1.11, 2.44) and 5 years of follow-up (HR: 1.64, 95% CI: 1.21, 2.24) of follow-up. Sensitivity analyses supported these findings under various matching models and washout periods. While comparing with patients with psoriasis, the association between HS and periodontitis remained significant (HR: 1.73, 95% CI: 1.23, 2.44). Conclusion: The observed increased risk suggests the need for heightened awareness and potential interdisciplinary care for individuals with HS to address periodontal health.

Efficacy and safety of a combined pharmacological and surgical approach in patients affected by hidradenitis suppurativa: data from a retrospective real-world clinical study.

BACKGROUND: Hidradenitis suppurativa (HS) is a debilitating chronic skin disease; its therapeutic approach often requires combined medical and surgical treatment. METHODS: The aim of this study was to assess the efficacy and safety of the surgical approach combined with different pharmacological treatments, evaluating the proportion of patients achieving the hidradenitis suppurativa clinical response (HiSCR), along with the incidence of postoperative complications, and local recurrence. A retrospective study of HS patients (Hurley I-III) presenting at least one skin lesion requiring surgery was performed. Demographic and clinical data were collected (kind and anatomical location of lesion excised, type of surgical procedure). Further data included: Hurley stage and IHS4 at baseline and week 16, HiSCR at week 16 after surgery, ongoing therapy at the time of surgery (topical, systemic antibiotic, biologics), postoperative complications and local recurrence at week 16. RESULTS: Forty-two patients with female predominance (66.7%, 28/42), with a mean age of 30.3 (SD±10.5) years, were enrolled. At week 16, 53% of patients achieved HiSCR, with baseline Hurley III inversely related to HiSCR achievement (P<0.05). No increased incidence of postoperative complications was detected. Three cases of local recurrence were reported at week 16. CONCLUSIONS: The results support the efficacy and safety of the combined therapy in the management of HS; no increased risk of complications emerged among patients concomitantly treated with biologics, compared to those on conventional systemic therapy or exclusively treated with surgery.

Management of Pilonidal Disease and Hidradenitis Suppurativa.

Pilonidal disease and hidradenitis suppurativa affect healthy young adults, causing discomfort and pain that leads to loss of work productivity and should be approached in a personalized manner. Patients with pilonidal disease should engage in hair removal to the sacrococcygeal region and surgical options considered. Hidradenitis suppurativa can be a morbid and challenging disease process. Medical management with topical agents, antibiotics, and biologics should be used initially but wide local excision should be considered in severe or refractory cases of the disease.

Dermatologists' Perspectives on Biosimilars.

BACKGROUND: Biosimilars are biologic agents the Food and Drug Administration (FDA) has deemed to have no clinical difference from their reference biologics. In dermatology,  biosimilars are approved for the treatment of psoriasis and hidradenitis suppurativa. Although dermatologists are high prescribers of biologics, they are more reluctant to prescribe biosimilars than other specialists. This survey-based study sought to characterize dermatologists’ current perspectives on biosimilars.  Methods: A 27-question survey was distributed via email to dermatologists between September and October of 2022.  Results: Twenty percent of respondents would not prescribe a biosimilar for an FDA-approved indication. When asked about the greatest barriers to biosimilar adoption, 61% had concerns about biosimilar safety and efficacy, 24% reported uncertainty about state laws for interchangeability and substitutions, and 20% had concerns about biosimilar safety without concerns about efficacy. Thirty-five percent of respondents felt moderately or extremely knowledgeable about biosimilar interchangeability.  Conclusion: Biosimilars are safe and effective for treating approved dermatological conditions and may lower patient costs compared to their reference products. Patients are not always offered biosimilar therapy as an option, which may be due to unfamiliarity among dermatologists.  This survey suggests a need for more research and educational initiatives, such as modules and workshops that focus on biosimilar safety, efficacy, and interchangeability guidelines. J Drugs Dermatol. 2024;23(4):doi:10.36849/JDD.7755.

Gram-negative anaerobes elicit a robust keratinocytes immune response with potential insights into HS pathogenesis.

Hidradenitis Suppurativa (HS) is a chronic autoinflammatory skin disease with activated keratinocytes, tunnel formation and a complex immune infiltrate in tissue. The HS microbiome is polymicrobial with an abundance of commensal gram-positive facultative (GPs) Staphylococcus species and gram-negative anaerobic (GNA) bacteria like Prevotella, Fusobacterium and Porphyromonas with increasing predominance of GNAs with disease severity. We sought to define the keratinocyte response to bacteria commonly isolated from HS lesions to probe pathogenic relationships between HS and the microbiome. Type strains of Prevotella nigrescens, Prevotella melaninogenica, Prevotella intermedia, Prevotella asaccharolytica, Fusobacterium nucleatum, as well as Staphylococcus aureus and the normal skin commensal Staphylococcus epidermidis were heat-killed and co-incubated with normal human keratinocytes. RNA was collected and analysed using RNAseq and RT-qPCR. The supernatant was collected from cell culture for protein quantification. Transcriptomic profiles between HS clinical samples and stimulated keratinocytes were compared. Co-staining of patient HS frozen sections was used to localize bacteria in lesions. A mouse intradermal injection model was used to investigate early immune recruitment. TLR4 and JAK inhibitors were used to investigate mechanistic avenues of bacterial response inhibition. GNAs, especially F. nucleatum, stimulated vastly higher CXCL8, IL17C, CCL20, IL6, TNF and IL36γ transcription in normal skin keratinocytes than the GPs S. epidermidis and S. aureus. Using RNAseq, we found that F. nucleatum (and Prevotella) strongly induced the IL-17 pathway in keratinocytes and overlapped with transcriptome profiles of HS patient clinical samples. Bacteria were juxtaposed to activated keratinocytes in vivo, and F. nucleatum strongly recruited murine neutrophil and macrophage migration. Both the TLR4 and pan-JAK inhibitors reduced cytokine production. Detailed transcriptomic profiling of healthy skin keratinocytes exposed to GNAs prevalent in HS revealed a potent, extensive inflammatory response vastly stronger than GPs. GNAs stimulated HS-relevant genes, including many genes in the IL-17 response pathway, and were significantly associated with HS tissue transcriptomes. The close association of activated keratinocytes with bacteria in HS lesions and innate infiltration in murine skin cemented GNA pathogenic potential. These novel mechanistic insights could drive future targeted therapies.

An evaluation of secukinumab for the treatment of moderate-to-severe hidradenitis suppurativa.

INTRODUCTION: Until recently, biological therapy for hidradenitis suppurativa was limited to anti-tumor necrosis factor (TNF) blockade with adalimumab (ADA). However, not all patients respond to treatment with ADA. This highlighted the need for more therapeutic options. Interleukin (IL)-17/T-helper 17 (Th17) axis may play an important role in the pathophysiology of HS. Recently, the IL-17A inhibitor secukinumab, which targets IL-17A specifically and prevents it from interacting with the IL-17 receptor, has been FDA-approved for HS. AREAS COVERED: Secukinumab, represents a novel therapeutic strategy in HS management. An overview of structural and pharmacological characteristics is provided. Described efficacy in clinical trials and case reports and safety data from is presented. EXPERT OPINION: As response to anti-TNFas is lost over time, secukinumab has provided an alternative HS treatment option in clinical practice. Overall, secukinumab has shown good efficacy and a favorable side effect profile in HS clinical trials but may be avoided in patients with inflammatory bowel disease. Long-term and real-life data on the use of secukinumab are essential for improving decision-making in HS therapy.

Increased cancer incidence among patients with hidradenitis suppurativa - a Danish nationwide register study 1977-2017.

BACKGROUND: The chronic, inflammatory skin disease hidradenitis suppurativa (HS) (prevalence: 0.5%-1%, diagnostic delay: 7-10 years) primarily arises in younger adults and frequently coincides with autoimmune comorbidities and unhealthy life-styles (smoking and obesity). These factors are known to increase cancer risk, but despite this, information on cancer occurrence among HS patients is scarce. MATERIALS AND METHODS: A nationwide retrospective register-based study assessing relative risk of cancer - overall and by anatomical site - following HS diagnosis expressed as standardized incidence ratios (SIRs), which is ratios between observed cases among all Danes diagnosed with HS since 1977 and expected cases based on cancer incidence rates of the entire Danish population during the same period. RESULTS: Participants consisted of a cohort of 13,919 Danes with HS, who during an average of 14.2 years of follow-up developed a total of 1,193 incident cancers, corresponding to a 40% increased risk (SIR = 1.4, 95% CI: 1.3 to 1.4, p < 0.001). Increased risks were observed for cancers of the respiratory system, oral cavity and pharynx, digestive organs and peritoneum, urinary tract, and the lymphatic tissues. INTERPRETATION: These findings underline an unmet need for health monitoring, lifestyle interventions and cancer screening if and when relevant.

Depression As a Potential Contributing Factor in Hidradenitis Suppurativa and Associated Racial Gaps.

The etiology of hidradenitis suppurativa (HS)-a chronic, relapsing, inflammatory disorder-is multifactorial, encompassing lifestyle, microbiota, hormonal status, and genetic and environmental factors. These factors propagate the production of deep-seated inflammatory nodules seen in HS through aberrant immune response activation and inflammation. The high prevalence of depression in individuals with HS and its association with systemic inflammation increases the likelihood that depression also may be a contributing etiology to HS. Because depression frequently has been discovered as a concomitant diagnosis in patients with HS, we hypothesize that there is a common susceptibility to depression in patients with HS, which we investigated through a literature search of articles published from 2000 to 2022 involving depression and HS.

Impact of Ketogenic and Low-Glycemic Diets on Inflammatory Skin Conditions.

Diet plays an emerging role in dermatologic therapy. The ketogenic and low-glycemic diets have potential anti-inflammatory and metabolic effects, making them attractive for treating inflammatory skin conditions. We provide an overview of the current evidence on the effects of ketogenic and low-glycemic diets on inflammatory skin conditions including acne, psoriasis, seborrheic dermatitis (SD), atopic dermatitis (AD), and hidradenitis suppurativa (HS). We conclude that low-glycemic diets show promise for treating acne, while the evidence for ketogenic diets in treating other inflammatory skin conditions is limited. Randomized clinical trials are needed to explore the efficacy of these diets as stand-alone or adjunctive treatments for inflammatory skin conditions.

An Update on Current Clinical Management and Emerging Treatments in Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a severe, debilitating, chronic inflammatory skin disease characterized by recurrent painful nodules, abscesses and draining sinus tracts in intertriginous areas. While this condition appears to stem from follicular unit dysfunction, its cause is multifactorial and the exact pathogenesis has yet to be fully elucidated. These factors make treatment selection challenging and contribute to variable therapeutic response among affected patients. Typical regimens consist of a combination of medical and surgical modalities, tailored to individual responses. However, HS is often refractory to traditional treatments, prompting the need for newer and more effective therapies. Herein, we review current and emerging HS therapies.

Risk of Keratitis and Keratopathy in Hidradenitis Suppurativa Patients: A Global Federated Health Network Analysis.

BACKGROUND/AIM: Hidradenitis suppurativa (HS) is linked to immune dysregulation and systemic inflammation. While previous studies indicate a higher prevalence of ocular manifestations in HS, the specific risk of keratopathy and keratitis remains unclear. The primary aim of this study was to assess the risk of keratitis and keratopathy in individuals with HS. PATIENTS AND METHODS: In this retrospective cohort study conducted with data from the TriNetX database, 53,716 patients with HS were matched to an equivalent number of non-HS controls using propensity score matching. The study covered the period from January 1st, 2005, to December 31st, 2017. Hazard ratios and their respective 95% confidence intervals (CIs), were computed to evaluate the occurrences of keratitis and keratopathy over a 5-year duration in patients with HS, compared to non-HS controls. RESULTS: HS was associated with a 1.52 times higher risk of keratitis over a 5-year period (95%CI=1.24-1.86) and a 1.47 times higher risk of keratopathy (95%CI=1.18-1.84). These risks remained consistent in sensitivity analyses. The elevated risk of keratitis was observed across both sexes. However, the risk of keratopathy was significantly higher in women with HS (HR=1.61, 95%CI=1.24-2.10) and individuals aged 18-64 years (HR=1.32, 95%CI=1.04-1.68). CONCLUSION: HS was linked to an elevated risk of both keratitis and keratopathy over a 5-year period. Ophthalmologic manifestations are recommended to be considered in HS standard care.