Alavi, Afsáneh

Importance Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a substantial burden. Standardized global prevalence estimates and data on associated sociodemographic and risk factors are lacking. Objective To estimate the global prevalence of HS and study differences in prevalence by age, sex, geographical location, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), smoking status, gross domestic product (GDP), and Human Development Index (HDI). Data Sources and Study Selection Included studies were conducted using the standardized Global Hidradenitis Suppurativa Atlas methodology with finalized data collection before May 19, 2023. Studies were required to use a population-based sampling method and conduct clinical confirmation of HS diagnosis following a screening questionnaire. Data Extraction and Synthesis Data were independently extracted from relevant studies by 2 reviewers (D.B. and C.E.M.) using a standardized form. Extracted variables included geographic location, age, sex, BMI (median and BMI >30), smoking status, HS prevalence estimates (with 95% CIs), GDP, and HDI. A proportional meta-analysis using a random-effects model was conducted on the included studies. Main Outcomes and Measures The primary outcome was the point prevalence of HS, confirmed by clinical examination. Secondary outcomes included differences in HS prevalence by sex, age, BMI category, smoking status, and country-level socioeconomic indicators (GDP and HDI). All outcomes were prespecified before data analysis. Results The sample included 22 743 participants, identifying 247 patients with HS, across 25 studies in 23 countries spanning 6 continents. The median proportion of female patients with HS was 55.6%, and the median age was 34.5 years. While the prevalence estimates showed considerable inconsistency ( I 2 > 75%; τ 2 = 0.747), the overall random-effects global prevalence of HS was 0.99% (95% CI, 0.67%-1.46%). Female sex was the only factor observed to be associated with the prevalence estimates (β = 1.02; 95% CI, 1.01-1.03). Conclusions and Relevance In this meta-analysis, an estimated global prevalence of HS between 0.67% and 1.46% surpassed previous global estimates. Substantial global variations in HS prevalence were also observed. Female sex was the only factor associated with prevalence in this sample. Future studies assessing genetic, environmental, and etiological factors are warranted to explain the heterogeneity in prevalence.

ABSTRACT Background Secukinumab, a fully human, monoclonal antibody targeting interleukin‐17A, is approved for moderate‐to‐severe HS in adults. This study evaluated pharmacokinetics (PK), high‐sensitivity C‐reactive protein (hsCRP) changes, and safety of secukinumab over 52 weeks in SUNSHINE and SUNRISE Phase 3 trials. Methods An exploratory analysis of pooled Phase‐3 trials evaluated serum PK and safety of secukinumab 300 mg every 2 (SECQ2W) or 4 weeks (SECQ4W). A population PK model assessed the effects of body weight, disease severity, and baseline hsCRP on secukinumab serum concentration. Exposure–response analysis assessed the relationship between predicted PK and HS clinical response [HiSCR]. No confirmatory statistical testing was performed. Results Mean serum trough concentration at Weeks 16, 24, and 52 was ~2‐fold higher with SECQ2W vs. SECQ4W. At Week 16, exposure overlap was high, with an estimated numerical increase in HiSCR of ~3% for SECQ2W over SECQ4W. At Week 52, HiSCR levels plateaued. At Week 16, hsCRP decreased from 18.6 ± 26.3 mg/L to 12.8 ± 18.0 mg/L (SECQ2W), 15.9 ± 27.6 mg/L to 11.5 ± 18.4 mg/L (SECQ4W), and remained unchanged with placebo (14.4 ± 22.5 mg/L to 14.7 ± 23.8 mg/L); reductions were sustained through Week 52. Higher body weight, disease severity, and baseline hsCRP were associated with lower secukinumab serum concentrations. Secukinumab immunogenicity was low (< 1%), with no new safety signals. Conclusion Secukinumab serum concentrations in patients with HS varied with body weight, disease severity, and baseline hsCRP. SECQ2W may benefit certain patients. Secukinumab reduced hsCRP through Week 52. The safety profile of secukinumab was consistent with other approved indications, with no apparent dose–response relationship observed. Trial Registration NCT03713619 (Novartis study code CAIN457M2301). NCT03713632 (Novartis study code CAIN457M2302)

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disease with fluctuating activity that requires long-term visual documentation to evaluate disease severity and treatment response. A standardized protocol for photographing HS is critically needed. Objectives: To establish a standardized protocol for using photography to clinically document HS. Methods: We brought together a panel of international experts and used a modified Delphi process to reach consensus on statements about standardized practices for using photography to document HS in clinical practice and research settings. A 75% agreement level was prespecified as the cutoff for consensus. Results: Consensus for photographically documenting HS was developed within 6 key areas: patient preparation, background, lighting, size and reference scale, camera considerations, and patient positioning. The revised and optimized protocol includes 34 standardized reference illustrations. However, the proposed recommendations are for ideal scenarios, and their implementation may not always be practical in a clinical setting. Variations in resources may not have been captured. Conclusions: The proposed consensus-based protocol provides a standard for consistent photographic documentation of HS. This protocol may help clinicians provide better disease surveillance and patient care, and it may aid in more precise and reliable research and clinical trials for HS.

ABSTRACTBackgroundHidradenitis suppurativa (HS) is a chronic inflammatory condition. While obesity is linked to increased HS severity in adults, data on its impact in pediatric HS remain limited. This study investigates the relationships between obesity, HS severity, HS‐related comorbidities, and therapeutic management in pediatric patients.MethodsThis is a retrospective cohort analysis on patients diagnosed with HS before 18 years of age. Data were collected on disease severity, comorbidity development, and treatments. Trends were compared between HS patients with and without obesity and with healthy controls for comorbidity development.ResultsThere was no difference in disease severity using Hurley staging between patients with and without obesity (p = 0.679). Patients with obesity were more likely to be prescribed biologics (p = 0.012), but not other treatments. The risk of developing dyslipidemia, anxiety, depression, and thyroid disease was elevated in pediatric HS patients, even after controlling for BMI (p < 0.001).ConclusionsIn this study, obesity was not associated with HS disease severity in children. However, children with obesity were more likely to be prescribed biologics. HS may independently increase the risk of dyslipidemia, anxiety, depression, and thyroid disease.

ImportanceMetastatic cutaneous Crohn disease (MCD) is a rare condition for which there are currently no published diagnostic criteria. Formal MCD diagnostic criteria will expand clinical care and research by enabling future diagnostic code validation, crystallizing a more uniform disease entity for the purposes of translational research, and allowing the development of more formalized outcome measures aimed at treatment response.ObjectiveTo define a set of criteria for the diagnosis of MCD.Evidence ReviewIn this consensus statement, a panel of experts on MCD and related conditions was assembled. Their opinions were gathered regarding the clinical and histologic findings that are sufficient, necessary, and highly suggestive of MCD through serial survey. Subsequent surveys were continued until consensus was achieved. Sufficient was defined as a feature that, if noted, would enable diagnosis of MCD without any other signs, symptoms, or testing. Necessary was defined as a feature that must be present to establish a diagnosis of MCD. Highly suggestive referred to any other features that were indicative of MCD but did not qualify as sufficient or necessary to diagnose MCD.FindingsOf 24 experts invited, 19 agreed to participate, with a 79% to 100% response rate across 5 rounds conducted. Five patients were also invited to participate, but none opted to participate, citing lack of clinical expertise and time concerns. The experts were all from the US; 5 (26%) have practiced medicine for 0 to 5 years, 5 (26%) practiced for 6 to 10 years, 6 (32%) practiced for 11 to 15 years, and 3 (16%) practiced for more than 20 years. A total of 18 experts (95%) worked in an academic practice setting. There was consensus agreement that MCD could present as oral disease, genital disease, or, rarely, in another location. Consensus was achieved on 2 major and 5 minor criteria for genital/other subtypes of MCD and 5 minor criteria for oral MCD. There was consensus that, while there are some pathological findings that are highly suggestive of MCD, histologic criteria are not necessary for diagnosis.Conclusions and RelevanceA panel of experts reached consensus on the diagnostic criteria for MCD described in this study. These criteria include major and minor clinical criteria, along with histopathological criteria for the diagnosis of genital and oral MCD. This consensus is a crucial step in the diagnosis of and future treatment development for MCD, a rare and clinically understudied condition.

ABSTRACTRubinstein‐Taybi syndrome (RTS) is a rare genetic disorder featuring craniofacial abnormalities, intellectual disability, and multi‐organ involvement, including increased risk of keloid formation, pilomatricomas, and hypertrichosis. Hidradenitis suppurativa (HS), a chronic inflammatory skin condition characterized by recurrent abscess formation and draining tunnels, has never been described in a patient affected by RTS. In this report, we detail the history of a 32‐year‐old male with RTS and refractory Hurley stage III HS and discuss the important considerations and risks of managing this unique patient population.

ABSTRACTBackgroundDrug‐induced hypersensitivity syndrome (DiHS), or drug reaction with eosinophilia and systemic symptoms (DRESS), is a delayed and severe immune response to certain medications. We investigated vancomycin‐induced DiHS/DRESS, notable for frequent and severe organ involvement, to describe its specific histopathology and the correlations between histopathologic and clinical findings.MethodsA retrospective review was conducted to identify patients between 2006 and 2022 who received vancomycin, had archived skin biopsy specimens, and were scored as having probable or definite DiHS/DRESS. Clinical features were retrospectively collected, and biopsy specimens were reviewed by a board‐certified dermatopathologist. A subset of histopathologic and clinical features was analyzed for statistical correlation.ResultsTwenty‐three patients met the inclusion criteria. Most biopsy specimens (87%) showed an eczematous reaction pattern; 17 (74%) showed a secondary reaction pattern. Spongiosis (87%) and neutrophilic infiltration (91%) were common epidermal characteristics. The dermal inflammatory infiltrate was frequently superficial (87%) and consistently included plasma cells (96%). Eosinophils were present in the dermis in 70% of cases. Parakeratosis negatively correlated with liver involvement and positively correlated with desquamative rash. Epidermal lymphocytes were negatively correlated with the RegiSCAR score.ConclusionsVancomycin‐associated DiHS/DRESS histopathology was characterized by a frequent eczematous reaction pattern, multiple coexisting reaction patterns, and epidermal neutrophilic infiltration.

Abstract Background The SUNSHINE and SUNRISE phase III trials demonstrated sustained clinical efficacy of secukinumab in patients with moderate-to-severe hidradenitis suppurativa (HS) through 52 weeks. Patients completing the core trials could enter a 4-year extension trial. Objectives To evaluate the long-term efficacy, safety/tolerability and maintenance of clinical response to secukinumab through week 104 in the extension trial. Methods Patients with a hidradenitis suppurativa (HS) clinical response (HiSCR) at week 52 of the core trials (extension trial baseline visit) entered a randomized withdrawal period. HiSCR responders receiving subcutaneous secukinumab 300 mg every 2 or 4 weeks (SECQ2W/SECQ4W) through week 52 in the core trials were randomized 2 : 1 to continue secukinumab (SECQ2W-R-Q2W or SECQ4W-R-Q4W) or receive placebo (SECQ2W-R-PBO or SECQ4W-R-PBO) through week 104. The primary endpoint was time to loss of response (LOR; newly defined for this trial) through week 104 in week 52 HiSCR responders (SECQ2W-R-Q2W vs. SECQ2W-R-PBO and SECQ4W-R-Q4W vs. SECQ4W-R-PBO). Time to LOR was tested at 1.25% (one-sided) for each comparison (one-sided familywise alpha of 2.5%) through week 104. If LOR was met, patients could remain in the trial on open-label secukinumab treatment. Additional endpoints included safety and HiSCR. The trial was registered with ClinicalTrials.gov (NCT04179175). Results Overall, 84.3% of patients who completed the core trials entered the extension trial; 55.9% were week 52 HiSCR responders. The primary endpoint was not met for either secukinumab dosing regimen. The estimated risk reduction for LOR was 13% (SECQ2W-R-Q2W vs. SECQ2W-R-PBO; one-sided P = 0.25) and 30% (SECQ4W-R-Q4W vs. SECQ4W-R-PBO; one-sided P = 0.04). The median time to LOR was numerically longer in the secukinumab arms vs. placebo {SECQ2W-R-Q2W [283 days; 95% confidence interval (CI) 176, –] vs. SECQ2W-R-PBO [239 days; 95% CI 120, –]; SECQ4W-R-Q4W [365 days 95% CI 225, –] vs. SECQ4W-R-PBO [171 days; 95% CI 113–337]}. In week 52 HiSCR responders reporting LOR, 44% (SECQ2W-R-Q2W), 58% (SECQ2W-R-PBO), 40% (SECQ4W-R-Q4W) and 34% (SECQ4W-R-PBO) were achieving HiSCR at the time of LOR. Overall, the safety of secukinumab was consistent with the core trials. Conclusions The primary endpoint of this trial was not met. HiSCR was maintained in many patients at the time of LOR. The safety of secukinumab was consistent with the previously characterized safety profile in the core trials.