Psoriasis localization patterns in the Swiss Psoriasis Registry (SDNTT) over 11 years: an analysis by sex and age.

Real-world data on anatomically localized psoriasis and its response to systemic therapy across different age-groups and sexes is limited. This study aimed to evaluate the severity and distribution of psoriasis over time in female and male patients receiving systemic therapies, categorized by age within the Swiss psoriasis registry (SDNTT). Patient-data was obtained over 11 years through the SDNTT. The localized Psoriasis Area and Severity Index (locPASI) of the head, trunk, upper and lower extremities was analyzed over two years following the start of systemic non-/biologic treatment. A total of 316 female and 517 male patients were analyzed. Male patients had a higher baseline locPASI for legs, trunk and arms (p < 0.001), but not for the head (p = 0.961). The locPASI for the head in younger female patients (18-40 years) had a higher score than those aged 55 + (p = 0.022) and after two years, middle aged (41-54) showed a lower score compared to younger patients (p = 0.045). Younger male patients revealed a lower score after two years of therapy in the leg- and arm-area compared to older (p = 0.018 and p = 0.048, respectively). Female patients on non-biologics had a fast initial response, converging with male patients' scores over 24 months. Over 75% locPASI reduction was observed for female head-area (81.4%), male trunk (82.7%) and legs (76.1%). Absolute locPASI ≤ 2 was achieved 3-6 months for all locations with interleukin (IL)-17, IL-12/23 and IL-23-inhibitors, except for the legs of male patients on anti-IL-17 and female patients on anti-IL-12/23 and -IL-23. After two years, male patients did not achieve a locPASI ≤ 2 for any biologic-treatment in the legs, nor for the arms on anti-TNF-α. Significant disparities in localized PASI were observed between female and male patients. The age, sex and severity of distinct localizations should be considered to optimize treatment goals.

Microenvironmental host-microbe interactions in chronic inflammatory skin diseases.

Several microbiome studies have recently demonstrated microbial dysbiosis in various chronic inflammatory skin diseases, and it is considered an important role in the pathogenesis. Although the role of skin dysbiosis in inflammatory skin diseases is debatable, the local microenvironment is considered essential concerning compositional changes and functional alterations of the skin microbiota. Indeed, various local nutrients (e.g., lipids), pH values, water, oxygen, and antimicrobial peptides may affect the level of skin dysbiosis in these skin diseases. In particular, in atopic dermatitis and hidradenitis suppurativa, significant changes in skin dysbiosis have been associated with local aberrant host immune changes. In this review, the potential pathogenic crosstalk between the host and the microbiota is reviewed in relation to the physical, chemical, and biological microenvironments of various chronic inflammatory skin diseases.

Biomarkers of systemic inflammation are associated with disease severity and metabolic syndrome in patients with hidradenitis suppurativa.

Background: Biomarkers associated with disease severity and comorbid metabolic syndrome (MetS) in patients with hidradenitis suppurativa (HS) are lacking. Objective: To identify biomarkers associated with disease severity and comorbid MetS in patients with HS. Methods: Data on hospital outpatients with HS were obtained through clinical examination and interviews. Indicators of systemic inflammation; C-reactive protein (CRP), erythrocyte sedimentation-rate (ESR), neutrophil/lymphocyte-ratio (NLR), platelet/lymphocyte-ratio (PLR), monocyte/lymphocyte-ratio (MLR), platelet/neutrophil-ratio (PNR), pan-immune-inflammation-value (PIV), and systemic-immune-inflammatory-index (SII), were calculated from blood samples. Results: Seven hundred patients were included; of those 444 (63.4%) and 256 (36.6%) were female and male, respectively, with a median age of 38.3 years (IQR = 27.9-51.0). Increasing CRP, ESR, NLR, PIV, and SII (P < .001) were significantly associated with increasing Hurley-stage and international hidradenitis suppurativa severity score system 4 (IHS4)-score in adjusted analysis. A doubling in CRP (OR 1.59 (1.36-1.85), P < .001), ESR (OR 1.39 (1.17-1.66), P < .001) and PIV (OR 1.41 (1.12-1.77) P = .002) was associated with MetS in adjusted analysis. ESR was the best estimator for severe IHS4-score (AUC = 0.72 (0.66-0.77), P < .001) and Hurley III (AUC = 0.79 (0.73-0.85), P < .001) whereas CRP was best for MetS (AUC = 0.67 (0.62-0.72), P < .001). Limitations: Patients in a hospital setting tend to have more severe disease. Conclusion: Biomarkers like CRP, ESR, and PIV measuring systemic inflammation were associated with disease severity and comorbid MetS in patients with HS.

Infectious Disease Screening Prior to Systemic Immunomodulatory Therapy in Hidradenitis Suppurativa: Consensus Guidelines from the Asia-Pacific Hidradenitis Suppurativa Foundation.

BACKGROUND: Current infectious disease screening recommendations for hidradenitis suppurativa (HS) are adopted from recommendations in chronic plaque psoriasis. No HS-specific guidelines for infectious disease screening prior to immunomodulatory therapy have been developed. OBJECTIVES: To establish an expert Delphi consensus of recommendations regarding infectious disease screening prior to systemic immunomodulatory therapy in HS. METHODS: Participants were identified via recent publications in the field and were sent a questionnaire regarding infectious diseases encountered in the setting of HS, and opinions regarding infectious disease screening prior to various systemic immunomodulatory therapies. All questions were informed by a systematic literature review regarding infections exacerbated or precipitated by immunomodulatory therapy. Questionnaire responses were followed by round-table discussion with a core group of 8 experts followed by a final round of questionnaires resulting in achievement of consensus. RESULTS: 44 expert HS physicians from 12 countries on 5 continents participated in the development of the expert consensus recommendations. Consensus recommendations include screening for hepatitis B, hepatitis C and tuberculosis in all individuals with HS prior to therapy. All immunomodulatory therapies (biologic and systemic immunosuppressant therapy) should be preceded by infectious disease screening including patient and location specific considerations for endemic local diseases and high-risk activities and occupations. Clinical assessment has a significant role in determining the need for laboratory screening in the setting of many uncommon or tropical diseases such as leprosy, leishmaniasis and strongyloidiasis. CONCLUSIONS: The presented consensus recommendations are the first specifically developed for pre-treatment infectious disease screening in Hidradenitis Suppurativa.

Adalimumab for the Treatment of Periodontitis in a 35-Year-Old Woman with Hidradenitis Suppurativa.

Increasing evidence suggests an association between chronic inflammatory conditions and oral health. Herein, we present a case of a 35-year-old woman with concomitant hidradenitis suppurativa (HS) and periodontitis, who was treated successfully with adalimumab. After 3 months of treatment, a marked improvement was observed in her clinical scores of HS, quality of life, as well as her gingival pain and signs of inflammation. This finding calls for a closer collaboration between dermatologists and dentists to further explore the possible beneficial role of biologic therapy for chronic inflammatory skin conditions as well as periodontitis.

[Bullous skin diseases].

This review finds that topical corticosteroids and systemic corticosteroids are the mainstays of initial treatment for bullous pemphigoid and pemphigus diseases. Additional immunomodulatory therapies such as methotrexate, azathioprine and mycophenolatmofetil should be added early during treatment to minimize the adverse effects of chronic corticosteroid therapy and to augment improvement in the disease. Rituximab is a first-line immunomodulatory treatment for moderate to severe pemphigus disease.

Severe papulopustular rosacea successfully treated with a combination of oral azithromycin and isotretinoin.

Papulopustular rosacea is notoriously a challenge to treat, and treatment options are scarce. Only limited data exist on the use of azithromycin in treatment of papulopustular rosacea. However, the unique pharmacokinetics of azithromycin may have several indications in the treatment of papulopustular rosacea. We here report a case of hard-to-treat papulopustular rosacea which was successfully treated with pulsed oral azithromycin in addition to maintenance isotretinoin.

The road to biologics in patients with hidradenitis suppurativa: a nationwide drug utilization study.

BACKGROUND: Prolonged systemic antibiotic treatment is often a part of management of hidradenitis suppurativa (HS). Although biologic therapies are now available, the patient's treatment journey leading to biologic therapy is unclear. OBJECTIVES: To examine treatment patterns and duration of systemic treatment use in patients with HS preceding biologic therapy. METHODS: We identified all patients with HS receiving treatment with biologics in the Danish National Patient Registry from 2010 to 2018 and extracted their entire prescription history of specific systemic treatments from the Danish National Prescription Registry since its inception in 1995. The patients' treatment journeys are graphically displayed through Sankey diagrams and box plots generated to show temporal distributions. Descriptive patient characteristics were presented as frequencies with percentages for categorical variables and as means with SDs or medians with interquartile ranges (IQRs) for continuous variables. RESULTS: A total of 225 patients with HS were included. Patients had most frequently been treated with penicillin (n = 214; 95·1%), dicloxacillin (n = 194; 86·2%), tetracycline (n = 145; 64·4%) and rifampicin/clindamycin (n = 111; 49·3%), as well as the retinoids isotretinoin and acitretin, and dapsone. Prior to biologic therapy, patients received a mean of 4·0 (SD 1·3) different systemic therapies, across a mean of 16·9 (SD 11·3) different treatment series. The mean time from first systemic therapy until biologic therapy was initiated was 15·3 (SD 5·1) years [8·2 (SD 5·9) years when excluding penicillin and dicloxacillin]. CONCLUSIONS: Patients with HS who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS. Delay in the initiation of biologic therapy may represent a missed opportunity to prevent disease progression. What is already known about this topic? The treatment journey leading to biologic therapy in patients with HS has not previously been investigated. What does this study add? Our data from 225 patients with HS illustrate that patients who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS.

Identification of Biomarkers and Critical Evaluation of Biomarker Validation in Hidradenitis Suppurativa: A Systematic Review.

IMPORTANCE: The identification and validation of biomarkers in hidradenitis suppurativa (HS) has potential to improve the understanding and management of this chronic, burdensome disease. OBJECTIVE: To systematically identify all known HS biomarkers, categorize them by biomarker type, and critically evaluate their validity according to established criteria. EVIDENCE REVIEW: Eligibility criteria for this review (PROSPERO Registration 230830) included randomized clinical trials, uncontrolled clinical trials, cohort studies, case-control studies, and other observational studies with no restrictions of patient age, sex, race or ethnicity, or language of publication up until December 31, 2020. All articles were categorized into biomarker type, defined using the US Food and Drug Administration Biomarkers, Endpoints, and other Tools (BEST) glossary. Assessment of each identified biomarker was undertaken in line with the US Food and Drug Administration and European Medicines Agency guidelines for the validation of proposed biomarkers. Assessment of the strength of overall data regarding individual biomarkers was undertaken using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. FINDINGS: A total of 3953 nonduplicate articles were screened, of which 1429 articles were retrieved based on the include/exclusion criteria applied. After full-text screen and data extraction, 106 articles were included in this review. The evidence of strength of 6 categories of biomarkers (susceptibility/risk, diagnostic, monitoring, predictive, prognostic, and pharmacodynamic/response biomarkers) was assessed using GRADE criteria. A total of 48 biomarkers were identified with a minimum GRADE rating of moderate. Only 1 diagnostic (serum IL-2R), 1 monitoring (dermal Doppler vascularity), and 2 predictive biomarkers (epithelialized tunnels and positive family history of HS) achieved a GRADE rating of high. None of the identified biomarkers had sufficient clinical validity to be recommended for routine use in the clinical setting. CONCLUSIONS AND RELEVANCE: Major barriers to the identification, validation, and introduction of routine biomarkers in the management of HS include lack of independent biomarker validation studies (especially assumption-free "omics"-based techniques); insufficient assessment of collinearity between identified or proposed biomarkers; and a lack of routine integration of biomarkers into the structure of clinical trials. International consensus among researchers, clinicians, and pharmaceutical stakeholders is required to standardize goals and methods and encourage biomarker integration into future HS clinical trials. This systematic review presents a number of priorities for near-term future research to overcome such barriers and limitations of biomarkers in HS.

Drug Survival of Biologics in Patients With Hidradenitis Suppurativa.

IMPORTANCE: Biologics are important in treating patients with hidradenitis suppurativa (HS). However, to our knowledge, data on their real-life performance and treatment patterns in HS are limited. OBJECTIVE: To examine the drug survival of biologic therapies for HS in a real-world setting. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included all patients with HS between January 1, 2005, and December 31, 2018, who were treated with biologics at the 5 academic hospital clinics where all biologic treatment for HS is conducted in Denmark. Biologics included adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, secukinumab, and ustekinumab. Data were analyzed between June 1, 2021, and June 20, 2021. MAIN OUTCOMES AND MEASURES: Drug survival was depicted through Kaplan-Meier curves, and Cox regression models were used to calculate adjusted (age, sex, previous number of biologic treatment series) hazard ratios (aHRs) with 95% CIs for the risk of treatment discontinuation. Switching patterns were visualized through a Sankey diagram. RESULTS: The study comprised 241 patients (176 women [61.8%]; total of 386 treatment series) with a mean (SD) age of 41.8 (12.6) years at initiation of first biologic therapy. There were a total of 256 (189 [73.8%] biologic naive), 66 (32 [48.5%] biologic naive), 23 (9 [39.1%] biologic naive), and 22 (9 [40.9%] biologic naive) treatment series with adalimumab, infliximab, etanercept, and ustekinumab, respectively. The median time to discontinuation was 36.0 (IQR, 21.9-63.0), 28.7 (IQR, 15.1-62.9), 26.0 (IQR, 16.9-155.9), and 17.9 weeks (IQR, 12.9-41.0) for adalimumab, infliximab, ustekinumab and etanercept, respectively. The risk of drug discontinuation was significantly higher for etanercept compared with adalimumab (aHR, 1.81; 95% CI, 1.16-2.82), infliximab (aHR, 1.77; 95% CI, 1.03-3.05), and ustekinumab (aHR, 2.49; 95% CI, 1.12-5.52), whereas no difference was observed when comparing these 3 therapies with each other. We found no significant differences in drug survival for biologic-naive vs nonnaive treatment series. Increasing C-reactive protein levels (aHR, 1.01; 95% CI, 1.00-1.03) and concomitant antibiotic treatment (aHR, 2.82; 95% CI, 1.36-5.86) were associated with the risk of discontinuing infliximab therapy. Men (aHR, 0.69; 95% CI, 0.51-0.91) had a reduced risk of discontinuing use of adalimumab. CONCLUSIONS AND RELEVANCE: In this cohort study, drug survival was comparable between adalimumab, infliximab, and ustekinumab but significantly lower for etanercept. There were no differences in drug survival among biologic-naive and nonnaive patients.

Human skin microbiota in health and disease: The cutaneous communities' interplay in equilibrium and dysbiosis: The cutaneous communities' interplay in equilibrium and dysbiosis.

Cutaneous microbial composition is driven by the microenvironment of the skin, as well as by internal and external factors. Local changes in the microenvironment can affect the configuration of the community, which may lead toward an imbalance of microbiota. Alterations in the microbial profile are common in both inflammatory skin diseases and chronic infections. A shift in balance within the microbiota, toward limited variation and a greater abundance of specific pathogens, may further worsen the pathogenicity of the diseases. These alterations may be prevented by topical treatment of probiotic solutions stimulating a balanced multispecies community. Compositional variations may further constitute potential biomarkers to predict flares or monitor efficacy during therapy. New approaches such as machine learning may contribute to this prediction of microbial alterations prior to the development of chronic infections and flares. This review provides insight into the composition and distribution of a healthy community of microorganisms in the skin and draws parallels with the community in chronic infections and chronic inflammatory skin diseases such acne vulgaris and Hidradenitis Suppurativa. We discuss the potential role of specific species in the pathogenesis and the possible prevention of disease exacerbation.