Compared burden of psoriasis, atopic dermatitis, hidradenitis suppurativa and chronic urticaria: baseline characteristics of the patients included in the OMCCI cohort, a French, prospective multicentre study of chronic inflammatory dermatoses.

INTRODUCTION: Chronic inflammatory dermatoses (CIDs) can significantly affect patients' lives. The Observatory of Chronic Inflammatory Skin Diseases (OMCCI) cohort was initiated to quantify the impact and disease evolution of four CID over 4 years' follow-up; at least 1,000 patients per CID are planned to be enrolled. To present baseline characteristics of patients included in the OMCCI cohort between December 2020 and September 2022. METHODS: This French, prospective, multicentre registry included adult patients treated in daily practice for moderate-to-severe psoriasis (PS), atopic dermatitis (AD), hidradenitis suppurativa (HS) or chronic urticaria (CU) starting or modifying a systemic treatment. At the inclusion visit and then every 6 months during 4 years, patient-reported outcomes and data on these diseases and their treatments are recorded. RESULTS: A total of 2,058 patients from 24 centers were included: 1,137 PS, 413 AD, 301 HS, and 207 CU. Of these, 1,950 patients started or changed systemic treatment and 108 reduced the dose of existing systemic treatment. Disease impact was qualified as debilitating by 80.1% (PS), 90.5% (AD), 90.5% (HS), and 89.4% (CU), affecting daily, family, and professional life. According to the SF-12 Survey, the impact of all four diseases was borderline pathological for physical health and severe for mental health. At inclusion, 20.4% of patients were receiving a conventional systemic or biologic treatment. After the first visit this percentage raised to 83.3%. During the 6 months preceding study inclusion, 17.7% (PS), 27.9% (AD), 43.1% (HS), and 43.6% (CU) of patients missed work due to their illness, and 26.3% of patients with HS had been admitted to hospital (vs. 8.1%, 5.8%, and 13% of patients with PS, AD, or CU, respectively). CONCLUSION: These CIDs (especially HS) had a major impact on all aspects of patients' quality of life. The low baseline use of systemic drugs and the high burden of these CIDs suggests that these agents are underused. Long-term and dynamic evaluation of the changes brought by the initiation or optimization of these treatments on the evolution of patients' lives will be studied prospectively during the 4-year follow-up of the OMCCI.

Evolution of dupilumab-associated conjunctivitis in patients with atopic dermatitis after switching dupilumab to tralokinumab or Janus kinase inhibitors (RESO-ADOC study).

BACKGROUND: Clinical trials and real-life data have reported an increased incidence of conjunctivitis in patients treated with dupilumab for their atopic dermatitis (AD). Although mostly mild in severity, in some cases conjunctivitis will appear or increase after dupilumab initiation, which can lead to dupilumab discontinuation. OBJECTIVES: (1) To describe the characteristics of patients developing conjunctivitis requiring discontinuation of dupilumab; and (2) to analyse the factors associated with a complete conjunctivitis improvement after dupilumab discontinuation and a switch to tralokinumab or Janus kinase inhibitors. METHODS: This was a multicentre retrospective cohort study that included all patients with AD treated with dupilumab who developed conjunctivitis leading to dupilumab discontinuation and switching to tralokinumab or Janus kinase inhibitors in daily practice. Data on patients, their AD and conjunctivitis were analysed at the inclusion visit (corresponding to discontinuation of dupilumab and the institution of new AD treatment), at visit 2 (3-6 months after inclusion) and at visit 3 (corresponding to the last medical visit). RESULTS: After multivariate analysis, the only factors associated with a complete resolution of dupilumab-associated conjunctivitis at visit 2 and/or visit 3 were conjunctivitis duration (OR 8.98, 95% CI 1.47-55) (p = 0.018), personal history of asthma (OR 10.66, 95% CI 1.82-62.63) (p = 0.009) and switching from dupilumab to Janus kinase inhibitors (OR 17.11, 95% CI 2.94-99.66) (p = 0.002). CONCLUSIONS: Although uncommon, severe dupilumab-associated conjunctivitis is more frequent in daily life compared to its incidence in the dupilumab pivotal trials. In these cases, our study suggests that a rapid switch to another molecule, particularly a Janus kinase inhibitor, should be considered.

Anti-SAE autoantibody in dermatomyositis: original comparative study and review of the literature.

OBJECTIVE: Among specific autoantibodies in DM, the anti-small ubiquitin-like modifier activating enzyme (SAE) antibody is rare. We aim to describe the clinical characteristics, cancer prevalence, and muscle pathology of anti-SAE-positive DM. METHODS: Patients with a diagnosis of DM and sera positive for the anti-SAE antibody were recruited from 19 centres in this retrospective observational study. The available muscular biopsies were reviewed. We conducted a comparison with anti-SAE-negative DM and a review of the literature. RESULTS: Of the patients in the study (n = 49), 84% were women. Skin involvement was typical in 96% of patients, with 10% having calcinosis, 18% ulceration and 12% necrosis; 35% presented with a widespread skin rash. Muscular disease affected 84% of patients, with mild weakness [Medical Research Council (MRC) scale 4 (3, 5)], although 39% of patients had dysphagia. Muscular biopsies showed typical DM lesions. Interstitial lung disease was found in 21% of patients, mainly with organizing pneumonia pattern, and 26% of patients showed dyspnoea. Cancer-associated myositis was diagnosed in 16% of patients and was responsible for the majority of deaths, its prevalence being five times that of the general population. IVIG therapy was administered to 51% of the patients during the course of the disease. Comparison with anti-SAE-negative DM (n = 85) showed less and milder muscle weakness (P = 0.02 and P = 0.006, respectively), lower creatinine kinase levels (P < 0.0001) and less dyspnoea (P = 0.003). CONCLUSION: Anti-SAE positive DM is a rare subgroup associated with typical skin features but a potentially diffuse rash, a mild myopathy. Interstitial lung disease defines an organizing pneumonia pattern. Cancer associated DM prevalence is five times that of the general population. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT04637672.

Impact of Baricitinib on Patients' Quality of Life after One Year of Treatment for Atopic Dermatitis in Real-World Practice: Results of the Observatory of Chronic Inflammatory Skin Diseases Registry.

The efficacy and safety of baricitinib for treatment of atopic dermatitis have been demonstrated in clinical trials; however, very few real-life studies have been published to date. The Observatory of Chronic Inflammatory Skin Diseases (OMCCI) registry was initiated to prospectively determine the long-term impairment caused by chronic inflammatory dermatoses on patients' lives. The study included 88 patients starting baricitinib for treatment of atopic dermatitis. Clinical evaluation and patient-reported outcomes were recorded at baseline and after 6 and 12 months. After 6 months and 1 year of follow-up, 65 and 47 patients, respectively, were still being treated with baricitinib. Treatment failure was the main reason for discontinuation. Only 1 patient stopped baricitinib because of a side-effect. After 1 year of follow-up, the mean Eczema Area and Severity Index score decreased significantly from 20.7 to 6.4; the percentage of patients with severe atopic dermatitis decreased from 42.9% to 6.5% and a significant improvement in most patient-reported outcomes was noted. There was no difference in terms of efficacy whether or not patients were previously treated with dupilumab. The results remained stable after 6 and 12 months of treatment, which suggests a sustained efficacy of the treatment in patients who initially responded well.

Impact of the COVID-19 Pandemic on Chronic Inflammatory Dermatoses: Mixed Messages Regarding the Dermatologist's Point of View and the Patient's Concerns.

is missing (Short communication).

Effectiveness and Safety of Anti-interleukin-17 Therapies in Elderly Patients with Psoriasis.

Anti-interleukin-17 agents have recently been developed for the treatment of psoriasis. This study evaluated the tolerance and effectiveness of anti-interleukin-17 agents for psoriasis in elderly patients in daily practice. A multicentre, retrospective study was performed, involving psoriatic patients aged ≥65 years who had received an anti-interleukin-17 agent, including secukinumab, ixekizumab or brodalumab. A total of 114 patients were included: 72 received secukinumab, 35 ixekizumab, and 7 brodalumab. Treatment was stopped in 32 patients (28.9%), because of relapses in 14 patients (41.2%), primary failures in 11 patients (32.4%), or adverse events in 7 patients (20.6%). The 3 most frequently reported adverse events were injection site reactions (n = 4), oral candidiasis (n = 3), and influenza-like illness (n = 3). Regarding effectiveness, 80 patients (70%) reached a Physician Global Assessment score of 0/1, 6 months after treatment initiation. In conclusion, anti-interleukin-17 therapy appears to be an effective and safe therapeutic option for psoriasis treatment in patients aged ≥ 65 years.

Effectiveness and safety of dupilumab for the treatment of atopic dermatitis in a real-life French multicenter adult cohort.

BACKGROUND: Dupilumab is the first biologic available to treat atopic dermatitis (AD). Its effectiveness and safety were demonstrated in clinical trials. OBJECTIVE: We sought to assess the effectiveness and safety of dupilumab in adults with AD in a real-life French multicenter retrospective cohort. METHODS: We included patients treated during March 2017-April 2018. Efficacy outcomes, including Scoring Atopic Dermatitis (SCORAD) and Eczema Area and Severity Index (EASI) scores, were collected at baseline and 3 months when available. Adverse events (AEs) were recorded at follow-up. RESULTS: We included 241 patients. The median ± interquartile range (IQR) follow-up time was 3.8 ± 3.7 months. A ≥75% improvement in SCORAD was achieved in 27 of 163 (16.6%) patients, and a ≥75% improvement in EASI was achieved in 40 of 82 (48.8%) patients. The median SCORAD and EASI scores at 3 months were significantly lower than those at baseline (SCORAD ± IQR, 25 ± 21 vs 56 ± 27.4, P < 10-9 and EASI ± IQR, 4.1 ± 6.8 vs 17.9 ± 15.4, P < 10-9, respectively). Conjunctivitis was reported in 84 of 241 (38.2%) patients. The proportion with eosinophilia (>500 cells/mm3) during follow-up (57%) was higher than that at baseline (33.7%) (n = 172, P < 10-6). Dupilumab was stopped in 42 cases; 27 patients stopped because of AEs. LIMITATIONS: No control group, missing data. CONCLUSION: This real-life study demonstrated a similar dupilumab effectiveness as that seen in clinical trials, but it also revealed a higher frequency of conjunctivitis and eosinophilia.

Clinical Profile of Methotrexate-resistant Juvenile Localised Scleroderma.

Methotrexate has demonstrated its efficiency for the treatment of juvenile localized scleroderma but some patients may be resistant. The aim of our study was to define the profile of such patients. We performed an observational retrospective multicenter study between 2007 and 2016 and included all children seen in the French Paediatric Dermatology and Rheumatology departments with active localized scleroderma treated by methotrexate for a minimum of 4 months. Metho-trexate efficacy was assessed clinically and/or by imaging between the fourth to twelfth months of treatment. A total of 57 patients were included. Metho-trexate dosage ranged from 7 to 15 mg/m2/week. Only 4 patients were resistant. No common features could be identified between these 4 patients. Children with localized scleroderma are rarely resistant to metho-trexate and we did not identify a clinical profile for those resistant patients.

Socioeconomic Inequalities and Severity of Plaque Psoriasis at a First Consultation in Dermatology Centers.

Psoriasis has major physical, psychological, and social impacts: its management should not be restricted by individual financial considerations in Western countries as these have well-structured health systems and social/insurance coverage. We investigated if the socioeconomic characteristics of patients were associated with severity of psoriasis and access to healthcare. In a cross-sectional study, we included 903 patients with psoriasis that were consulting for the first time. We showed that low educational level was associated with severity of disease in multivariate analyses. Moreover, patients of lower class and lower educational level, with severe psoriasis, had seen fewer physicians and had less frequently received a systemic treatment. Thus, physicians need to be vigilante of patients with a low socioeconomic status. Both low socioeconomic status and less access to dermatologists are associated with clinical severity of psoriasis at a first consultation.

Granulomatosis with polyangiitis: endoscopic management of tracheobronchial stenosis: results from a multicentre experience.

OBJECTIVES: Tracheobronchial stenosis (TBS) is noted in 12-23% of patients with granulomatosis with polyangiitis (GPA), and includes subglottic stenosis and bronchial stenosis. We aimed to analyse the endoscopic management of TBS in GPA and to identify factors associated with the efficacy of endoscopic interventions. METHODS: We conducted a French nationwide retrospective study that included 47 patients with GPA-related TBS. RESULTS: Compared with patients without TBS, those with TBS were younger, more frequently female and had less frequent kidney, ocular and gastrointestinal involvement and mononeuritis multiplex. Endoscopic procedures included 137 tracheal and 50 bronchial interventions, mainly endoscopic dilatation, local steroid injection and conservative laser surgery, and less frequently stenting. After the first endoscopic procedure, the cumulative incidence of endoscopic treatment failure was 49% at 1 year, 70% at 2 years and 80% at 5 years. Factors significantly associated with a higher cumulative incidence of treatment failure were a shorter time from GPA diagnosis to endoscopic procedure [hazard ratio (HR) 1.08 (95% CI 1.01, 1.14); P = 0.01] and a bronchial stenosis [HR 1.96 (95% CI 1.28, 3.00); P = 0.002]. A prednisone dose ≥30 mg/day at the time of the procedure was associated with a lower cumulative incidence of treatment failure [HR 0.53 (95% CI 0.31, 0.89); P = 0.02]. CONCLUSION: TBS represents severe and refractory manifestations with a high rate of restenosis. High-dose systemic CSs at the time of the procedure and increased time from GPA diagnosis to bronchoscopic intervention are associated with a better event-free survival. In contrast, bronchial stenoses are associated with a higher rate of restenosis than subglottic stenosis.

Relationship between cutaneous polyarteritis nodosa (cPAN) and macular lymphocytic arteritis (MLA): Blinded histologic assessment of 35 cPAN cases.

BACKGROUND: Cutaneous polyarteritis nodosa (cPAN) is a skin medium vessel neutrophilic arteritis with livedo, nodules, and ulcerations. Macular lymphocytic arteritis (MLA) is a small arteritis with erythematous or pigmented macules and typical histologic features (a lymphocytic infiltrate, concentric fibrin ring, no disruption of the internal elastic lamina). OBJECTIVE: We sought to assess the frequency of clinical and histologic features of MLA in patients with cPAN. METHODS: This was a monocentric retrospective analysis of patients given the diagnosis of cPAN with blinded assessment of skin biopsy specimens. RESULTS: All 35 patients included had an infiltrated livedo, nodules, or both. Ulceration was rare. Erythematous or pigmented lesions were present in 54% of patients. Predominantly lymphocytic arteritis, a paucity of neutrophils, concentric fibrin ring, and absence of internal lamina elastic disruption were present in 60%, 20%, 18%, and 23% of patients, respectively. Median follow-up was 11 years. None of the patients had systemic involvement, and 57% had a complete remission. The incidence of complete remission was not different between patients having a predominant lymphocyte infiltrate or few neutrophils. LIMITATIONS: This was a retrospective, monocentric study without a control group of patients with MLA. CONCLUSIONS: Our data do not favor the classification of cPAN and MLA as distinct entities.

Psychometric validation of a patient-reported outcome questionnaire (Qualipsosex) assessing the impact of psoriasis and psoriatic arthritis on patient perception of sexuality.

ABSTRACT: Psoriasis (Pso) and psoriatic arthritis (PsA) frequently have a negative impact on patients' sexual health. We have developed a specific questionnaire assessing the impact of Pso and PsA on patient perception of sexuality: the QualipsoSex Questionnaire (QSQ). The aim of the present study was to further validate this questionnaire by checking its psychometric properties including validity, reliability, and responsiveness.A cross sectional observational study with a longitudinal component for responsiveness and test-retest reliability was performed in 12 centers in France including 7 dermatologists and 5 rheumatologists. Psychometric properties were examined according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) check-list.At baseline, 114 patients had Pso and 35 patients had PsA including 17 peripheral arthritis, 4 axial disease, 13 patients with both axial disease and peripheral arthritis and one patient with an undifferentiated phenotype. The mean Pso Area and Severity Index score was 12.5. Genital organs were involved in 44.7% of Pso cases. Internal consistency, construct validity, and reliability were good with Cronbach's α coefficient, measure of sampling adequacy and intraclass correlation coefficient respectively at 0.87, 0.84, and 0.93. The QSQ also demonstrated acceptable sensitivity to change.The QSQ has demonstrated good psychometric properties fulfilling the validation process relative to the recommendations of the COSMIN check list. The QSQ is simple to score and may hopefully be valuable in clinical practice and in clinical trials.

UBA1 Variations in Neutrophilic Dermatosis Skin Lesions of Patients With VEXAS Syndrome.

IMPORTANCE: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently described severe adult-onset autoinflammatory disease that is associated with myeloid lineage-restricted ubiquitin-activating enzyme 1 (UBA1) somatic variations that primarily affect the skin (Sweet syndrome), cartilage, and bone marrow. Skin symptoms have been poorly described. OBJECTIVE: To better describe clinical and pathological skin manifestations and their pathophysiology in VEXAS syndrome. DESIGN, SETTING, AND PARTICIPANTS: This multicenter retrospective case series study of clinical and histological features of 8 patients with VEXAS syndrome and skin involvement was conducted in France from December 2007 to March 2021, with molecular data obtained from March to April 2022. Any UBA1 variations were detected by Sanger or next-generation sequencing that was performed on bone marrow and formalin-fixed paraffin-embedded tissue sections of skin lesion biopsies. RESULTS: All 8 patients were men, and the median age at symptom onset was 65.5 years (interquartile range, 54-76 years). All patients had neutrophilic dermatosis skin lesions, including tender red or violaceous papules, sometimes edematous, without fever, arthralgia, recurrence or pathergy, inflammatory edematous papules on the neck and trunk (sometimes umbilicated), and firm erythematous purpuric or pigmented infiltrated plaques and nodules. Three patients had livedo racemosa. The infiltrates were perivascular and consisted of mature neutrophils with leukocytoclasia, which were admixed with myeloperoxidase-positive CD163-positive myeloid cells with indented nuclei and lymphoid cells in all cases. A sequencing analysis of paired bone marrow samples and skin lesion biopsies identified the same loss-of-function UBA1 variation in both samples for all patients. CONCLUSIONS AND RELEVANCE: This case series study describes the different clinical presentations of skin lesions found in VEXAS syndrome, which is characterized histologically by neutrophilic dermatosis. The findings suggested that the dermal infiltrates seen in VEXAS skin lesions are derived from the pathological myeloid clone. This suggests that using therapies that target the pathological clone may be effective in the long-term management of the disease.