Impact of Atopic Dermatitis on Adult Women's Lives: A Survey of 1,009 French Women.

Atopic dermatitis (AD) is one of the most common inflammatory diseases, and has a higher prevalence among females in adulthood. The aim of this observational, cross-sectional, survey-based study was to evaluate the impact of AD on the daily lives of adult women patients. A scientific committee composed exclusively of women constructed a specific questionnaire in partnership with the French Eczema Association. Severity of AD was evaluated with the Patient-Oriented Eczema Measure (POEM). A sample of 1,009 adult women (mean age ± standard deviation: 41.8 ± 14.2 years) with AD was identified from a representative sample of the French population (82% response rate 1,230 women surveyed). According to the POEM, 50.64% (n = 511) of subjects were identified as having mild AD, 39.35% (n = 397) moderate AD, and 10.01% (n = 101) severe AD. Overall, 67.7% (n = 682) reported that their eczema involved a visible area (face, neck or hands), and 19.6% (n = 198) a sensual area (breasts/chest, genital area or buttocks). Of the 720 women with menstrual cycles, exacerbations of AD were reported to occur mostly before (50.6%) and during (48.3%) menstruation. A small proportion of women, 7.3% (n = 74), reported being afraid of  becoming pregnant because of their eczema. If AD involvement was in a visible area it had a greater impact on romantic relationships, sexual relationships and occupation. If AD involvement was in a sensual area it had a greater influence on romantic relationships and sexuality. Particular attention should be given to patients with localization of AD on the face, neck or hands, as they have a higher risk of social exclusion. Moreover, these results should encourage health professionals to ask patients with AD about the possible involvement of sensual areas.

Two cases of dupilumab-responsive Kimura disease.

Kimura disease (KD) is a rare, chronic angiolymphoproliferative inflammatory disease appearing to be mostly restricted to the skin and soft tissue. Cutaneous involvement of KD includes head and/or neck nodules showing suggestive histological features, frequently associated with an atopic dermatitis-like or prurigo-like presentation. KD is challenging to treat, with high rate of recurrence using current therapeutic strategies. Evidence for involvement of a T-helper type 2 (Th2) immune response in KD pathogenesis has been found in previous studies. Consequently, this study aimed to determine the efficacy and safety of dupilumab, a human monoclonal antibody that inhibits signalling of key Th2 cytokines, interleukin (IL)-4 and IL-13, within a single-centre cohort of patients with cutaneous KD. Two adults with a diagnosis of refractory (failure of at least one treatment line) cutaneous-restricted KD based on clinical, biological, histological, molecular and imaging findings received dupilumab for KD, and showed dramatic response with a good safety profile.

Cutaneous vasculitis occurring in the setting of systemic lupus erythematosus: a multicentre cohort study.

OBJECTIVES: To describe the clinical and pathological features of biopsy-proven cutaneous vasculitis (CV) associated with SLE, focusing on diagnosis classification and impact on overall SLE activity. METHODS: Retrospective multicentric cohort study including SLE patients with biopsy-proven CV identified by (i) data from pathology departments of three university hospitals and (ii) a national call for cases. SLE was defined according to 1997 revised ACR and/or 2019 ACR/EULAR criteria. CV diagnosis was confirmed histologically and classified by using the dermatological addendum of the Chapel Hill classification. SLE activity and flare severity at the time of CV diagnosis were assessed independently of vasculitis items with the SELENA-SLEDAI and SELENA-SLEDAI Flare Index. RESULTS: Overall, 39 patients were included; 35 (90%) were female. Cutaneous manifestations included mostly palpable purpura (n = 21; 54%) and urticarial lesions (n = 18; 46%); lower limbs were the most common location (n = 33; 85%). Eleven (28%) patients exhibited extracutaneous vasculitis. A higher prevalence of Sjögren's syndrome (51%) was found compared with SLE patients without CV from the French referral centre group (12%, P < 0.0001) and the Swiss SLE Cohort (11%, P < 0.0001). CV was mostly classified as urticarial vasculitis (n = 14, 36%) and cryoglobulinaemia (n = 13, 33%). Only 2 (5%) patients had no other cause than SLE to explain the CV. Sixty-one percent of patients had inactive SLE. CONCLUSION: SLE-related vasculitis seems very rare and other causes of vasculitis should be ruled out before considering this diagnosis. Moreover, in more than half of patients, CV was not associated with another sign of active SLE.

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.

Risk factors of progression from discoid lupus to severe systemic lupus erythematosus: a registry-based cohort study of 164 patients.

BACKGROUND: No study has assessed the risk factors of progression from discoid lupus erythematosus (DLE) to severe systemic lupus erythematosus (sSLE) (defined as requiring hospitalization and specific treatment). OBJECTIVE: To identify the risks factors of and generate a predicting score for progression to sSLE among patients with isolated DLE or associated with systemic lupus erythematosus with mild biological abnormalities. METHODS: In this registry-based cohort study, multivariable analysis was performed using risk factors identified from literature and pruned by backward selection to identify relevant variables. The number of points was weighted proportionally to the odds ratio (OR). RESULTS: We included 30 patients with DLE who developed sSLE and 134 patients who did not. In multivariable analysis, among 12 selected variables, an age of <25 years at the time of DLE diagnosis (OR, 2.8; 95% CI, 1.1-7.0; 1 point), phototype V to VI (OR, 2.7; 95% CI, 1.1-7.0; 1 point), and antinuclear antibody titers of ≥1:320 (OR, 15; 95% CI, 3.3-67.3; 5 points) were selected to generate the score. Among the 54 patients with a score of 0 at baseline, none progressed to sSLE, whereas a score of ≥6 was associated with a risk of approximately 40%. LIMITATIONS: Retrospective design. CONCLUSION: In our cohort, an age of <25 years at the time of DLE diagnosis, phototype V to VI, and antinuclear antibody titers of ≥1:320 were risk factors for developing sSLE.

Intravenous and subcutaneous immunoglobulins-associated eczematous reactions occur with a broad range of immunoglobulin types: A French national multicenter study.

BACKGROUND: Human immunoglobulins are used for treating diverse inflammatory and autoimmune disorders. Eczema is an adverse event reported but poorly described. OBJECTIVES: To describe the clinical presentation, severity, outcome, and therapeutic management of immunoglobulin-associated eczema. METHODS: This retrospective and descriptive study included a query of the French national pharmacovigilance database, together with a national call for cases among dermatologists. RESULTS: We included 322 patients. Eczema occurred preferentially in men (78.9%) and in patients treated for neurological pathologies (76%). The clinical presentation consisted mainly of dyshidrosis (32.7%) and dry palmoplantar eczema (32.6%); 5% of cases exhibited erythroderma. Sixty-two percent of the eczema flares occurred after the first immunoglobulin course. Eczema was observed with 13 intravenous or subcutaneous immunoglobulin types and recurred in 84% of patients who maintained the same treatment and in 68% who switched the immunoglobulin type. After immunoglobulin discontinuation, 30% of patients still had persistent eczema. LIMITATIONS: Retrospective study, with possible missing data or memory bias. CONCLUSION: Immunoglobulin-associated eczema occurred with all immunoglobulin types, preferentially in patients with neurologic diseases who required prolonged immunoglobulin treatment. Recurrence was frequent, even after switching the immunoglobulin type, which can lead to a challenging therapeutic situation when immunoglobulin maintenance is required.

Multicenter prospective observational study of dupilumab-induced ocular events in atopic dermatitis patients.

BACKGROUND: Although ocular adverse events are frequent in AD patients treated with dupilumab, their characterization remains limited due to a lack of prospective studies with a systematic ophthalmological examination. OBJECTIVE: To examine the incidence, characteristics and risk factors of dupilumab-induced ocular adverse events. METHODS: A prospective, multicenter, and real-life study in adult AD patients treated with dupilumab. RESULTS: At baseline, 27 out of 181 patients (14.9%) had conjunctivitis. At week 16 (W16), 25 out of 27 had improved their conjunctivitis and 2 remained stable and 34 out of 181 patients (18.7%) had dupilumab-induced blepharoconjunctivitis: either de novo (n = 32) or worsening of underlying blepharoconjunctivitis (n = 2). Most events (27/34; 79.4%) were moderate. A multivariate analysis showed that head and neck AD (OR = 7.254; 95%CI [1.938-30.07]; p = 0.004), erythroderma (OR = 5.635; 95%CI [1.635-21.50]; p = 0.007) and the presence of dry eye syndrome at baseline (OR = 3.51; 95%CI [3.158-13.90]; p = 0.031) were independent factors associated with dupilumab-induced blepharoconjunctivitis. LIMITATIONS: Our follow-up period was 16 weeks and some late-onset time effects may still occur. CONCLUSION: This study showed that most dupilumab-induced blepharoconjunctivitis cases are de novo. AD severity and conjunctivitis at baseline were not found to be associated risk factors in this study.

Use of biologics to treat relapsing and/or refractory polyarteritis nodosa: data from a European collaborative study.

OBJECTIVES: To describe the effectiveness and safety of biologics for the treatment of relapsing and/or refractory polyarteritis nodosa (PAN). METHODS: A retrospective European collaborative study was conducted in patients with PAN who received biologics for relapsing and/or refractory disease. RESULTS: Forty-two patients with PAN received a total of 53 biologic courses, including TNF-α blockers in 15 cases, rituximab (RTX) in 18 cases, tocilizumab (TCZ) in 10 cases and other biologics in 10 cases. TNF-α blockers and TCZ were mainly used for refractory diseases whereas RTX was mainly initiated for relapsing disease. After a median follow-up of 29 (8-50) months, remission, partial response, treatment failure and treatment discontinuation due to severe adverse events occurred in, respectively, 40%, 13%, 40% and 7% of patients receiving TNF-α blockers, 50%, none, 30% and 20% of TCZ recipients, and 33%, 11%, 56% and none of the RTX recipients. No remission was noted in patients treated with other biologics. Severe adverse events were observed in 14 (28%) patients without significant differences between the three biologics, leading to early biologics discontinuation in only three cases. CONCLUSION: These results suggest that TCZ may be effective in relapsing and/or refractory PAN. Our data warrant further study to confirm these findings.

Plasma cell-directed therapies in monoclonal gammopathy-associated scleromyxedema.

Scleromyxedema is a rare skin and systemic mucinosis that is usually associated with monoclonal gammopathy (MG). In this French multicenter retrospective study of 33 patients, we investigated the clinical and therapeutic features of MG-associated scleromyxedema. Skin molecular signatures were analyzed using a transcriptomic approach. Skin symptoms included papular eruptions (100%), sclerodermoid features (91%), and leonine facies (39%). MG involved an immunoglobulin G isotype in all patients, with a predominant λ light chain (73%). Associated hematologic malignancies were diagnosed in 4 of 33 patients (12%) (smoldering myeloma, n = 2; chronic lymphoid leukemia, n = 1; and refractory cytopenia with multilineage dysplasia, n = 1). Carpal tunnel syndrome (33%), arthralgia (25%), and dermato-neuro syndrome (DNS) (18%) were the most common systemic complications. One patient with mucinous cardiopathy died of acute heart failure. High-dose IV immunoglobulin (HDIVig), alone or in combination with steroids, appeared to be quite effective in nonsevere cases (clinical complete response achieved in 13/31 patients). Plasma cell-directed therapies using lenalidomide and/or bortezomib with dexamethasone and HDIVig led to a significant improvement in severe cases (HDIVig refractory or cases with central nervous system or cardiac involvement). The emergency treatment of DNS with combined plasmapheresis, HDIVig, and high-dose corticosteroids induced the complete remission of neurological symptoms in 4 of 5 patients. Quantitative reverse-transcriptase polymerase chain reaction analysis of 6 scleromyxedema skin samples showed significantly higher profibrotic pathway levels (transforming growth factor ß and collagen-1) than in healthy skin. Prospective studies targeting plasma cell clones and/or fibrotic pathways are warranted for long-term scleromyxedema management.

Efficacy and safety of treatments in cutaneous polyarteritis nodosa: A French observational retrospective study.

BACKGROUND: Cutaneous polyarteritis nodosa is a form of medium-sized vessel vasculitis. Despite a disabling and prolonged course, data on treatment efficacy and safety remain scarce. OBJECTIVES: We aimed to describe treatment efficacy and safety in patients with cutaneous polyarteritis nodosa. METHODS: This multicenter retrospective, observational study, recorded clinical and biologic data together with treatments received. The primary outcome was the rate of complete response at month 3. Secondary outcomes assessed drug survival and safety. RESULTS: We included 68 patients who received a median of 2 therapeutic lines (interquartile range, 1-3). Overall, complete response was achieved in 13 of 42 (31%) patients with colchicine, 4 of 17 (23%) with dapsone, 11 of 25 (44%) with glucocorticoids (GCs) alone, 1 of 9 (11%) with nonsteroidal anti-inflammatory drugs, 11 of 13 (84%) with GCs+azathioprine, and 7 of 15 (47%) with GCs+methotrexate. GCs+azathioprine had the best drug survival (median duration, 29.5 months; interquartile range, 19.5-36.0). Response at month 3 was decreased with peripheral neurologic involvement (odds ratio, 0.19; 95% confidence interval, 0.03-0.81; P = .04). Overall, the rate of treatment-related adverse events was 18%, which led to the discontinuation of treatment in 7% of patients. LIMITATION: Retrospective study. CONCLUSION: Colchicine seems to confer good benefit-risk balance in cutaneous polyarteritis nodosa without peripheral sensory neuropathy. GCs+azathioprine seem the best treatment in the event of relapse.

Biopsy-proven kidney involvement in hypocomplementemic urticarial vasculitis.

BACKGROUND: Hypocomplementemic urticarial vasculitis (HUV) is a rare systemic vasculitis. We aimed to describe the kidney involvement of HUV in a multicenter national cohort with an extended follow-up. METHODS: All patients with HUV (international Schwartz criteria) with a biopsy-proven kidney involvement, identified through a survey of the French Vasculitis Study Group (FVSG), were included. A systematic literature review on kidney involvement of HUV was performed. RESULTS: Twelve patients were included, among whom 8 had positive anti-C1q antibodies. All presented with proteinuria, from mild to nephrotic, and 8 displayed acute kidney injury (AKI), requiring temporary haemodialysis in 2. Kidney biopsy showed membrano-proliferative glomerulonephritis (MPGN) in 8 patients, pauci-immune crescentic GN or necrotizing vasculitis in 3 patients (with a mild to severe interstitial inflammation), and an isolated interstitial nephritis in 1 patient. C1q deposits were observed in the glomeruli (n = 6), tubules (n = 4) or renal arterioles (n = 3) of 8 patients. All patients received corticosteroids, and 9 were also treated with immunosuppressants or apheresis. After a mean follow-up of 8.9 years, 6 patients had a preserved renal function, but 2 patients had developed stage 3-4 chronic kidney disease (CKD) and 4 patients had reached end-stage kidney disease (ESKD), among whom 1 had received a kidney transplant. CONCLUSION: Renal involvement of HUV can be responsible for severe AKI, CKD and ESRD. It is not always associated with circulating anti-C1q antibodies. Kidney biopsy shows mostly MPGN or crescentic GN, with frequent C1q deposits in the glomeruli, tubules or arterioles.

Persistent deficiency of mucosal-associated invariant T cells during dermatomyositis.

OBJECTIVES: Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that are important for antibacterial immunity and may have regulatory roles. MAIT cells are decreased during SLE. However, their frequencies and phenotype have not been investigated in DM. We studied MAIT cell frequencies and phenotype in DM patients with active and inactive disease (after treatment). METHODS: Peripheral blood flow cytometry analysis of MAIT cells was compared between DM (n = 22), SLE (n = 10), psoriasis (n = 7) and atopic dermatitis (n = 5) patients, and healthy controls (n = 19). RESULTS: A dramatic decrease of circulating MAIT cell frequency was observed in active DM and SLE patients compared with healthy controls and other inflammatory skin diseases [active DM: median = 0.25% (interquartile range 0.19-0.6%), P < 0.0001; active SLE: median = 0.61 (0.55-0.77), P < 0.0001 vs healthy controls: 2.32% (1.18-4.45%)]. MAIT cells from active DM patients had an abnormal phenotype including increased expression of CD25 and cytotoxic T-lymphocyte-associated protein 4 that correlated with their low frequency in the blood. CONCLUSION: In DM, peripheral blood MAIT cells are dramatically reduced and have an activated/exhausted phenotype that may be linked to increased activation-induced cell death.

Risk factors for death and survival in paraneoplastic pemphigus associated with hematologic malignancies in adults.

BACKGROUND: Paraneoplastic pemphigus (PNP) occurs more often in patients with hematologic malignancies (HMs) than in patients with solid cancer. Lung bronchiolitis obliterans (BO) is a severe complication of PNP. OBJECTIVE: To determine the precise clinical and biologic features of HM-associated PNP and identify factors associated with mortality and survival. METHODS: Systematic review of previously described cases of PNP associated with HMs. RESULTS: A total of 144 patients were included. The HMs were non-Hodgkin lymphoma (52.78%), chronic lymphocytic leukemia (22.92%), Castleman disease (18.60%), and other underlying hematologic malignancy (5.70%). The mortality rate was 57%, and most deaths occurred within the first year after the diagnosis of PNP. Multivariate analysis showed that (1) the presence of antienvoplakin antibodies and BO were significantly associated with death, and (2) a toxic epidermal necrolysis-like clinical pattern, bullous pemphigoid-like clinical pattern, and BO were significantly associated with decreased survival. LIMITATION: Only case reports with sufficient mortality data were included. CONCLUSION: PNP associated with HM has a high mortality rate. The toxic epidermal necrolysis-like and BO-associated forms are independent survival factors in PNP associated with HMs.

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.

Efficacy and safety of etanercept for postoperative pyoderma gangrenosum after infliximab serum sickness.

Non-peristomal postoperative pyoderma gangrenosum (PPG) is a rare subtype of pyoderma gangrenosum that occurs in the early postoperative period at surgical incisions, most commonly after breast surgery. Early diagnosis and treatment is essential to prevent severe scaring. TNF-alpha inhibitor infliximab was reported to be efficient in treatment of PPG refractory to systemic corticosteroids. However infliximab can be not well tolerated. We report the first case of etanercept efficacy in post-plastic breast surgery pyoderma gangrenosum after infliximab serum sickness.

Changing antimalarial agents after inefficacy or intolerance in patients with cutaneous lupus erythematosus: A multicenter observational study.

BACKGROUND: Changing from one antimalarial (AM) agent to another is often recommended in cutaneous lupus erythematosus (CLE) when the first AM agent is ineffective or poorly tolerated. OBJECTIVE: To evaluate the effect on cutaneous response of a switch from hydroxychloroquine to chloroquine, or the reverse, after failure of the first AM agent. METHODS: We conducted a retrospective observational study between 1997 and September 2015. The overall cutaneous response rate and reasons for failure of the switch were assessed for up to 48 months. Kaplan-Meier survival curves were used to assess the risk for failure of the second AM agent. RESULTS: A total of 64 patients with CLE (78% were women) were included; for 48 patients, the switch was for inefficacy, and for 16, it was for adverse events. Median follow-up was 42 months (range, 3-171). Of the patients changed because of inefficacy, 56% were responders at month 3; however, the response decreased over time, with a median duration before failure of the second AM agent of 9 months (95% confidence interval, 6-24). For patients switched because of adverse events, the second AM agent was well tolerated in 69% of cases. LIMITATIONS: Retrospective design and subjective evaluation of cutaneous response. CONCLUSION: A change of AM agent should be considered in patients with CLE when the first AM agent is ineffective or poorly tolerated.