Efficacy and Safety of Tumour Necrosis Factor-α Antagonists for Folliculitis Decalvans: A Retrospective Case-series Pilot Study.

Folliculitis decalvans is a chronic inflammatory skin disease leading to scarring alopecia. Management of this disabling disease is difficult and no treatment is currently approved. Current knowledge regarding the pathogenesis of folliculitis decalvans suggests the benefit of using anti-tumour necrosis factor-α. This pilot study aimed to evaluate the clinical efficacy of anti-tumour necrosis factor-α for management of folliculitis decalvans. A single-centre retrospective pilot study included patients with refractory folliculitis decalvans treated by tumour necrosis factor-α inhibitors. An Investigator's Global Assessment (IGA) score was designed and validated to assess the efficacy of the therapy. Response to treatment was considered good to excellent when an IGA ≤ 2 was obtained at month 12. Eleven patients were included, with a mean time from diagnosis of folliculitis decalvans to the introduction of infliximab (n = 9) or adalimumab (n = 2) of 8.55 ± 1.26 years. Nine patients had failed on at least 2 lines of systemic therapies before starting anti-tumour necrosis factor-α. The median IGA score at baseline was 3. At the end of follow-up, 5 patients were considered responders. Overall, the safety profile of anti-tumour necrosis factor-α was good. The results suggest that the clinical benefit of anti-tumour necrosis factor-α is obtained after at least 6 months of treatment. However, further prospective studies are needed to confirm these results.

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.

Association of skin hyperpigmentation disorders with digital ulcers in systemic sclerosis: Analysis of a cohort of 239 patients.

BACKGROUND: Skin pigmentation disorders in systemic sclerosis (SSc) have been sparsely described in the literature. Nevertheless, they could be a diagnostic and/or severity marker. OBJECTIVES: To assess the association between pigmentation disorders and systemic involvement in patients with SSc. METHODS: A total of 5 patterns of skin pigmentation disorders were defined: diffuse hyperpigmentation; hyperpigmentation of sun-exposed areas; hypopigmentation of the head, neck, and/or upper part of the chest; acral hypopigmentation; and diffuse hypopigmentation. RESULTS: A total of 239 patients were included; 88 patients (36.8%) had skin pigmentation disorders as follows: diffuse hyperpigmentation and hyperpigmentation of sun-exposed areas in 38.6% (n = 34) and 27.3% (n = 24) of patients, respectively; hypopigmentation of the face, neck, and/or chest in 10.2% of patients (n = 9); diffuse hypopigmentation in 12.5% (n = 11); and acral hypopigmentation in 17% (n = 15). Diffuse hyperpigmentation was associated with diffuse SSc (P = .001), increased modified Rodnan skin score (P = .001), and shorter duration of Raynaud phenomenon (P = .002) in univariate analysis but not in multivariate analysis. Moreover, diffuse hyperpigmentation was associated with digital ulcers (P = .005), as confirmed by multivariate analysis (odds ratio, 2.96; 95% confidence interval, 1.28-6.89). LIMITATIONS: This was a single-center retrospective study of a cohort of patients with SSc. CONCLUSION: Screening for skin pigmentation disorders could be useful in the management of patients with SSc to identify those with a high risk of development of digital ulcers, which is a symptom of vascular involvement in SSc.

[DRUGS-INDUCED URTICARIA AND ANGIOEDEMA]. / Urticaire et angio-œdème induits par les medicaments. Le plus souvent non allergique et favorisés par des situations à risqué.

Drug-induced urticaria and/or angioedema is a frequent issue encountered in family medicine. A specific collection of the anamnesis and of the general context is very important to appreciate the involved mechanism, allergic or not, and potential cofactors. If in doubt about an allergic mechanism, tests will be conducted, mostly under a hospital setting. Bradykinin-mediated angioedema, so much rare than histamine-mediated one, has to be known, because it is potentially lethal. It is often iatrogenic (ACE inhibitors especially). At the end of the allergology work-up, a course of action is proposed to the patient and his family practitioner as far as the rechallenge of the drug is concerned, In case of non-allergic urticaria, much more frequent than allergy, taking the drug is possible with a premedication with antihistamines.

Omalizumab Drug Survival in Chronic Urticaria: A Retrospective Multicentric French Study.

BACKGROUND: Omalizumab (OMA) dramatically improves disease control and quality of life in patients with chronic urticaria (CU). OBJECTIVE: We aimed to evaluate the discontinuation patterns of OMA and their determinants in a cohort of French patients with CU. METHODS: We conducted a retrospective multicenter study in 9 French tertiary referral hospitals. All patients diagnosed with either spontaneous (CSU) and/or inducible (CIndU) CU who received at least 1 injection of OMA between 2009 and 2021 were included. We analyzed OMA drug survival and investigated possible determinants using Kaplan-Meier curves and log-rank tests. RESULTS: A total of 878 patients were included in this study; 48.8% had CSU, 10.1% CIndU, and 41.1% a combination of both. OMA was discontinued in 408 patients, but the drug was later reintroduced in 50% of them. The main reason for discontinuing treatment was the achievement of a well-controlled disease in 50% of patients. Half of the patients were still being treated with OMA 2.4 years after the initiation of treatment. Drug survival was shorter in patients with CIndU and in those with an autoimmune background. In atopic patients, OMA was discontinued earlier in patients achieving a well-controlled disease. A longer OMA drug survival was observed in patients with a longer disease duration at initiation. CONCLUSION: In French patients with CU, the drug survival of OMA appears to be longer than that observed in previous studies conducted elsewhere, highlighting discrepancies in prescription and reimbursement possibilities. Further studies are warranted to develop customized OMA treatment schemes based on individual patterns.

Discrepancies in the management of acquired cold contact urticaria: Results of a French-speaking urticaria experts questionnaire survey.

Acquired cold contact urticaria (ACU) is a putatively serious condition, because of the risk of anaphylactic shock whenever patients are massively exposed to cold atmosphere/water, raising the question of the prescription of an "emergency kit" with oral antihistamines and epinephrine auto-injector. We performed an online survey to evaluate how French-speaking urticaria experts manage ACU. According to the 2016 consensus recommendations on chronic inducible urticarias, all the participants perform at least 1 of the available provocation tests and 84.2%, 77.8%, and 88.9% prescribe on-label use of second generation anti-H1 antihistamines (2GAH1) as a first line treatment, updosed 2GAH1 as a second line treatment, and omalizumab as a third line treatment, respectively. Interestingly, 44.4% of the practitioners always prescribe a continuous background treatment, versus 11.1% prescribing only on-demand therapy. Also, 11.7% of participants always prescribe an epinephrine auto-injector, 70.6% sometimes do, and 17.6% never do. Finally, 89.5% authorize swimming under strict conditions but 36.8% and 68.4% contra-indicate other water sports and occupational cold exposure, respectively.

Assessment of liver fibrosis with transient elastography and FibroTest in patients treated with methotrexate for chronic inflammatory diseases: a case-control study.

BACKGROUND & AIMS: Although methotrexate (MTX) is used in the effective treatment of inflammatory disorders, its use is hampered by the risk of liver fibrosis. Non-invasive methods for the diagnosis of liver fibrosis, such as transient elastography (FibroScan) and FibroTest could be useful for monitoring MTX-liver toxicity. The aim of this case-control study was to determine factors associated with liver fibrosis in a large cohort of patients requiring MTX. METHODS: Consecutive adults with various benign inflammatory diseases were prospectively assessed using FibroScan and FibroTest when they were treated with MTX (cases) or before beginning treatment (controls). RESULTS: Among 518 included patients, 44 patients (8.5%) had FibroScan and/or FibroTest results suggesting severe liver fibrosis. In a multivariate analysis, factors associated with abnormal markers of liver fibrosis were the body mass index >28 kg/m(2) and high alcohol consumption. Neither long MTX duration nor cumulative doses were associated with elevated FibroScan or FibroTest results. CONCLUSIONS: Severe liver fibrosis is a rare event in patients treated with MTX and is probably unrelated to the total dose. Patients with other risk factors for liver disease should be closely monitored with non-invasive methods before and during MTX treatment.

A single cycle of rituximab for the treatment of severe pemphigus.

BACKGROUND: The combination of multiple cycles of rituximab and intravenous immune globulins has been reported to be effective in patients with severe pemphigus. The aim of this study was to assess the efficacy of a single cycle of rituximab in severe types of pemphigus. METHODS: We studied 21 patients with pemphigus whose disease had not responded to an 8-week course of 1.5 mg of prednisone per kilogram of body weight per day (corticosteroid-refractory disease), who had had at least two relapses despite doses of prednisone higher than 20 mg per day (corticosteroid-dependent disease), or who had severe contraindications to corticosteroids. The patients were treated with four weekly infusions of 375 mg of rituximab per square meter of body-surface area. The primary end point was complete remission 3 months after the end of rituximab treatment; complete remission was defined as epithelialization of all skin and mucosal lesions. RESULTS: Eighteen of 21 patients (86%; 95% confidence interval, 64 to 97%) had a complete remission at 3 months. The disease relapsed in nine patients after a mean of 18.9+/-7.9 months. After a median follow-up of 34 months, 18 patients (86%) were free of disease, including 8 who were not receiving corticosteroids; the mean prednisone dose decreased from 94.0+/-10.2 to 12.0+/-7.5 mg per day (P=0.04) in patients with corticosteroid-refractory disease and from 29.1+/-12.4 to 10.9+/-16.5 mg per day (P=0.007) in patients with corticosteroid-dependent disease. Pyelonephritis developed in one patient 12 months after rituximab treatment, and one patient died of septicemia 18 months after rituximab treatment. These patients had a profound decrease in the number of circulating B lymphocytes but normal serum levels of IgG. CONCLUSIONS: A single cycle of rituximab is an effective treatment for pemphigus. Because of its potentially severe side effects, its use should be limited to the most severe types of the disease. (ClinicalTrials.gov number, NCT00213512 [ClinicalTrials.gov].).

Disseminated cutaneous lymphoid hyperplasia of 12 years' duration triggered by vaccination.

Vaccine-induced cutaneous lymphoid hyperplasia (CLH) is rare. Its natural evolution is not well known, nor is its treatment. We report a case of B-cell CLH with secondary dissemination that occurred following vaccination. The symptoms lasted 12 years and were efficiently treated by thalidomide. A 17-year-old girl presented CLH which had begun at the age of 8 at the site of hepatitis B vaccination. The lesions progressively enlarged and disseminated far from the injection sites. There was no spontaneous remission. Cyclins and hydroxychloroquine were inefficient. Thalidomide treatment finally led to complete remission. Aluminium hydroxide is used as adjuvant in the majority of vaccinations. In this case, occurrence of lesions far from the injection site of the vaccine suggested that it was not the only cause and that CLH may occur in other localizations after a vaccination. Furthermore, the diagnosis of CLH should not be excluded in front of such a prolonged course, and we underline the potential efficacy of thalidomide.

A three-year-analysis of fixed drug eruptions in hospital settings in France.

Fixed drug eruption (FDE) is one of the most typical cutaneous drug adverse reactions. This localized drug-induced reaction is characterized by its relapse at the same sites. Few large series of FDE are reported. The aim of this study was to retrospectively collect and analyse well informed cases observed in a hospital setting. This study involved 17 academic clinical centers. A French nation-wide retrospective multicentric study was carried out on a 3-year-period from 2005 to 2007 by collecting data in seventeen departments of dermatology in France. Diagnosis of FDE was based essentially on clinical findings, at times confirmed by pathological data and patch-testing. Records were reviewed for demographics, causative drugs, localization, severity, and patch-tests, when available. Fifty nine cases were analysed. Patients were 59-years-old on average, with a female predilection. The most common drug was paracetamol, followed by the non-steroidal anti inflammatory drugs. The time between drug intake and skin symptoms was, on average, two days. Beside these classical characteristics, some original findings were found including, a frequent non pigmentation course and a sex-dependent pattern of distribution. Women often had lesions on the hands and feet, and men on the genitalia. Given the fact that skin pigmentation is an inconstant feature of FDE, its French name (erythème pigmenté fixe) should be reconsidered. The sex-dependent distribution could help our understanding of the pathophysiology of fixed drug eruption.

Efficacy and safety of oral alitretinoin as treatment for chronic hand eczema in France: a real-life open-label study.

BACKGROUND: Chronic hand eczema is an inflammatory dermatosis that results in a significant psychological and socio-economic burden. Alitretinoin (AL) is indicated in adults with severe chronic hand eczema (sCHE) unresponsive to potent topical corticosteroids. OBJECTIVES: To assess AL effectiveness and safety in patients with sCHE under real-life conditions based on a prospective observational study in France (2010-2014). MATERIALS & METHODS: Clinical severity was assessed using Physician Global Assessment (PGA) and Modified Total Lesion Symptom Score (mTLSS) and quality of life by Skindex and visual analogue scales. Patients were treated with AL for 12-24 weeks and followed for 24 months. Responders were patients with clear/almost clear skin based on PGA at the end of treatment and the primary outcome was remission (clear, almost clear, or mild skin) at one and two years after treatment. RESULTS: A total of 394 patients with severe or moderate PGA were included in the study by 109 dermatologists. AL treatment duration was 5.4 ± 4.1 months (mean ± SD) and 112/274 patients evaluated at the end of treatment were responders. Of the 112 responders, 41/51 evaluable patients were in remission after one year and 36/46 after two years. At the end of treatment, Skindex improved from 48.8 ± 18.1% to 27.1 ± 23.2%. Among the 112 responders, 68/84 did not relapse (mTLSS increased >75% from baseline). The most common adverse events were headache (24%) and dyslipidaemia (4%). CONCLUSIONS: This study supports a positive benefit/risk profile for AL for sCHE patients unresponsive to topical corticosteroids.

Glucocorticoids for acute urticaria: study protocol for a double-blind non-inferiority randomised controlled trial.

INTRODUCTION: This study protocol describes a trial designed to investigate whether antihistamine alone in patients with acute urticaria does not increase the 7-day Urticaria Activity Score (UAS7) in comparison with an association of antihistamine and glucocorticoids and reduces short-term relapses and chronic-induced urticaria. METHODS AND ANALYSIS: This is a prospective, double-blind, parallel-group, multicentre non-inferiority randomised controlled trial. Two-hundred and forty patients with acute urticaria admitted to emergency department will be randomised in a 1:1 ratio to receive levocetirizine or an association of levocetirizine and prednisone. Randomisation will be stratified by centre. The primary outcome will be the UAS7 at day 7. The secondary outcomes will encompass recurrence of hives and/or itch at day 7; occurrence of spontaneous hives or itch for >6 weeks; patients with angioedema at day 7, and 2, 6, 12 and 24 weeks; new emergency visits for acute urticaria recurrences at days 7 and 14, and 3 months; Dermatology Life Quality Index at days 7 and 14, and 3 and 6 months; and Chronic Urticaria Quality of Life Questionnaire at 6 weeks. ETHICS AND DISSEMINATION: The protocol has been approved by the Comité de Protection des PersonnesSud-Méditerranée II and will be carried out in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. A steering committee will oversee the progress of the study. Findings will be disseminated through national and international scientific conferences and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03545464.

Large International Validation of ABSIS and PDAI Pemphigus Severity Scores.

The Pemphigus Disease Area Index (PDAI) and Autoimmune Bullous Skin Disorder Intensity-Score (ABSIS) scores have been proposed to provide an objective measure of pemphigus activity. These scores have been evaluated only on already treated patients mainly with mild to moderate activity. The objective was to assess the interrater reliability of ABSIS and PDAI scores and their correlation with other severity markers in a large international study. Consecutive patients with newly diagnosed pemphigus were enrolled in 31 centers. Severity scores were recorded during a 24-month period by the same two blinded investigators. Serum was collected at each visit for ELISA measurement of anti-desmoglein antibodies. The intraclass correlation coefficient (ICC) and Spearman rank correlation coefficient were calculated. A total of 116 patients with pemphigus vulgaris (n = 84) or pemphigus foliaceus (n = 32) were included. At baseline, the ABSIS and PDAI ICCs were 0.90 (95% confidence interval [CI] = 0.85-0.93), and 0.91(95% CI = 0.87-0.94), respectively. The ICCs for PDAI were higher in moderate and extensive pemphigus (ICC = 0.82, 95% CI = 0.63-0.92 and ICC = 0.80, 95% CI = 0.62-0.90, respectively) than in patients with intermediate (significant) extent (ICC = 0.50, 95% CI = 0.27-0.68). Conversely, the ICCs for ABSIS were lower in patients with moderate extent (ICC = 0.44, 95% CI = 0.004-0.74) than in those with intermediate or extensive forms, (ICC = 0.69, 95% CI = 0.51-0.81 and ICC = 0.75, 95% CI = 0.51-0.88, respectively). During patients' follow-up, the ICCs of both ABSIS and PDAI scores remained higher than 0.70. ABSIS and PDAI skin (r = 0.71 and r = 0.75) but not mucosal (r = 0.32 and r = 0.37) subscores were correlated with the evolution of anti-DSG1 and anti-DSG3 ELISA values, respectively. ABSIS and PDAI scores are robust tools to accurately assess pemphigus activity.

Treatment of polyarteritis nodosa with tocilizumab: a new therapeutic approach?

We describe the effect of interleukin 6 (IL-6) blockade using tocilizumab (TCZ) for inducing and maintaining remission of refractory polyarteritis nodosa (PAN). Three patients with refractory PAN defined according to the American College of Rheumatology criteria were treated with TCZ infusions (8 mg/kg) on a monthly basis. All of them had severe cutaneous and articular involvement with elevated biological inflammatory markers. One suffered from a neuritis multiplex and one from renal and digestive damage. All three patients were dependent on high doses of glucocorticoids (above 0.5 mg/kg) and two of them were resistant to immunosuppressive drugs. All patients achieved and maintained clinical response and normalisation of the inflammation acute-phase proteins after a few weeks of treatment with TCZ. Prednisolone could be reduced by an average of 41-13 mg/day. These first case reports suggest that IL-6 blockade using TCZ could be a therapeutic alternative to induce remission in patients with polyarteritis nodosa resistant or intolerant to the reference treatment.