Prevalence of ocular disease during dupilumab treatment for atopic dermatitis: a bicentric retrospective comparative cohort study.

BACKGROUND: Dupilumab is the first human monoclonal antibody approved for the treatment of atopic dermatitis (AD). Clinical trials have reported an increase of ocular side effects in patients who receive dupilumab, with a prevalence of 5-37%. OBJECTIVE: To compare the prevalence of ocular disease between AD patients receiving dupilumab treatment and AD reference group and to study the profile of the patients who developed ocular disease secondary to dupilumab treatment. METHODS: Efficacy outcomes were collected both at baseline and at month 4 (M4). Presence of ocular disease was recorded at M4. RESULTS: Data from 100 patients were examined. At M4, ocular disease was significantly more frequent in the dupilumab group (36% vs. 10%, P = 0.002). Severe allergic conjunctivitis and blepharitis were significantly more frequent in the dupilumab group (30% vs. 4%, P < 0.001, and 22% vs. 2%, P = 0.004, respectively). Six of 18 patients permanently discontinued therapy. CONCLUSION: This study observed a prevalence of 36% of ocular disease in AD patients treated with dupilumab. Additional studies are required to confirm the risk factors we found for dupilumab-associated ocular disease and to identify new ones. Consultation with an ophthalmologist before the introduction of dupilumab might limit the occurrence of complications.

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.

Methylisothiazolinone allergic contact dermatitis: Assessment of relapses in 139 patients after avoidance advice.

BACKGROUND: Methylisothiazolinone (MI) is a preservative that is responsible for an epidemic of allergic contact dermatitis (ACD). Few studies have been published on the prognosis of patients with MI-induced ACD. OBJECTIVES: To evaluate relapses of MI-induced ACD and difficulties in avoiding MI in patients who had received avoidance advice. METHODS: A retrospective study of patients with MI-induced ACD diagnosed in two specialized dermato-allergology units between 2010 and 2015 was performed. The median follow-up was 3 years. RESULTS: Relapses were observed in 64% of 139 included patients, and were severe in 18%. Rinse-off cosmetics were responsible for the largest proportion of relapses (27%). The median time to relapse was 5 months. Sixty-nine per cent of relapses were on the hands, and 29% were on the face. Risk factors for relapsing were hand eczema and a personal history of atopy. The main difficulties encountered in the avoidance strategy were hidden sources of MI, the lack of labelling on industrial products, the complexity of cosmetic labelling, and remembering the name of the allergen. CONCLUSION: MI-induced ACD has a poor prognosis. Its high rate of relapse is mainly attributable to the difficulties of avoidance. Management needs to be improved. Specialized follow-up in the year following diagnosis is essential to educate patients.

Nicorandil-induced ulcerations: a 10-year observational study of all cases spontaneously reported to the French pharmacovigilance network.

Nicorandil-induced ulcers remain often poorly recognised, with a late diagnosis and an inadequate management. We aimed to provide a clinical overview of the 148 spontaneously reported cases of nicorandil-induced ulcers to the French pharmacovigilance network between 2005 and 2014 and to complete this picture with worldwide published cases over the same period. Spontaneously reported nicorandil-induced ulcers were mainly mucosal (oral and anal) with a previous trauma in 23·0% of patients, revealed by a severe complication in 12·8% of cases. The mean cumulative dose of nicorandil was higher in serious cases. The median delay between the start of nicorandil use and the onset of the ulcer was 23·4 months, and after the ulcer was diagnosed, the median time to incriminate nicorandil was still 3·3 months, being shorter for mucosal ulcerations than for cutaneous ulcerations (5·2 versus 14·0 months, P = 0·001). The anatomic distribution in the 199 published cases differed slightly, but delays were similar. The hypothesis of mechanism becomes more precise, leaving no doubt about the necessity to discontinue the treatment. Practitioners need to be aware that nicorandil-induced ulcers can occur in many locations, possibly multiple and complicated, and should be simply managed by discontinuing treatment with no further reintroduction of nicorandil.