Plasma cell-directed therapies induce profound clinical and durable responses in patients with severe or relapsed/refractory scleromyxedema.

BACKGROUND: Scleromyxedema (SM) is a rare skin disorder related to monoclonal gammopathy. High dose intravenous immunoglobulins (HDIVIg) are usually used as a frontline therapy with initial efficacy. However, some patients evolve with relapse, refractory state or severe extra-cutaneous complications such as dermato-neuro syndrome (DNS) or cardiac involvement. The objective of the study is to evaluate the use of anti-plasma cell treatment in these patients in order to obtain a deep and durable dermatological and haematological response. METHODS: We report here eight patients treated with HDIVIg together with anti-plasma cell therapy including: lenalidomide and dexamethasone (n = 5); bortezomib, cyclophosphamide and dexamethasone (n = 1); daratumumab, lenalidomide and dexamethasone (n = 2). RESULTS: Combination of HDIVIg with a treatment targeting the monoclonal component led to a high level of haematological remission and drastically improved skin response with an acceptable safety profile in all patients. Moreover, HDIVIg was reduced and stopped in 4 of the 7 patients who achieved complete remission. CONCLUSIONS: The association of lenalidomide and dexamethasone with HDIVIg could improve the treatment of relapsed or severe SM.

Treatment of Eosinophilic Annular Erythema: Retrospective multicenter study and literature review.

BACKGROUND: Eosinophilic annular erythema (EAE) is a rare eosinophil-related skin disease which typically manifests with annular erythematous plaques and severe pruritus. Besides the diagnosis, the treatment of EAE is challenging since relevant published data are sparse. METHODS: The aim of this study was to assess the underlying diseases, treatments and outcomes of patients with EAE. To this end, we conducted a retrospective multicenter study and a systematic review of the MEDLINE database. RESULTS: We included 18 patients with EAE followed in 8 centers. The MEDLINE database search yielded 37 relevant publications reporting 55 cases of EAE with 106 treatment sequences. The most common and efficient treatments included topical or systemic corticosteroids, hydroxychloroquine and dapsone. In refractory patients, a combination of systemic corticosteroids with hydroxychloroquine was associated with 88% of complete clinical response. DISCUSSION: To improve the management of EAE patients, we discuss the following treatment strategy: in topical steroid-resistant patients, hydroxychloroquine can be given as first-line systemic treatment. Dapsone, hydroxychloroquine or systemic corticosteroids are second-line options to consider. Last, monoclonal antibodies or JAK inhibitors targeting type 2 inflammation could represent promising last-resort options in refractory patients.

[Association of borderline tuberculoid leprosy and tuberculosis: A case report and review of the literature]. / Association d'une lèpre borderline tuberculoïde et d'une tuberculose : un cas et revue de la littérature.

INTRODUCTION: In metropolitan France, nearly 20 new cases of leprosy are diagnosed each year. The incidence of tuberculosis in France is 8/100,000 inhabitants and there are very few accounts of association of these two mycobacteria. Herein we report a case of co-infection with borderline tuberculoid (BT) leprosy and disseminated tuberculosis diagnosed in metropolitan France. PATIENTS AND METHODS: A male subject presented with diffuse painless infiltrated erythematous plaques. The biopsy revealed perisudoral and perineural lymphohistiocytic epithelioid cell granuloma as well as acid-alcohol-fast bacilli on Ziehl staining. PCR was positive for Mycobacterium leprae, confirming the diagnosis of leprosy in the BT form. The staging examination revealed predominantly lymphocytic left pleural effusion, right-central necrotic adenopathy without histological granuloma, negative screening for BK, a positive QuantiFERON-TB™ test, and a positive intradermal tuberculin reaction. The clinical and radiological results militated in favour of disseminated tuberculosis. Combined therapy (rifampicin, isoniazid, ethambutol and pyrazinamide) together with clofazimine resulted in regression of both cutaneous and extra-cutaneous lesions. This rare co-infection combines leprosy, often present for several years, and tuberculosis (usually pulmonary) of subsequent onset. The pathophysiological hypothesis is that of cross-immunity (with anti-TB immunity protecting against subsequent leprosy and vice versa), supported by the inverse correlation of the two levels of prevalence and by the protection afforded by tuberculosis vaccination. In most cases, treatment for TB and leprosy improves both diseases. Patients presenting leprosy should be screened for latent tuberculosis in order to avoid reactivation, particularly in cases where corticosteroid treatment is being given.

[Cutaneous plasmacytosis with Darier's sign in a woman of European origin]. / Plasmocytose cutanée avec signe de Darier chez une femme d'ascendance européenne.

INTRODUCTION: Cutaneous plasmacytosis is a rare skin condition first described in 1976 and it is seen mainly in patients of Asian descent. Patients usually present with multiple reddish-brown macules and nodules chiefly on the trunk and face, with clusters of well-differentiated plasma cells in the dermis. The aetiopathogenesis and nosological features of this entity remain obscure. We report herein a case of cutaneous plasmacytosis in a European middle-aged woman with presence of Darier's sign. PATIENTS AND METHODS: A 56-year-old woman of European descent presented with asymptomatic hyperpigmented patches affecting the dorsal aspect of her trunk for at least two years. Darier's sign was present in some episodes. Cutaneous biopsy showed a moderately dense interstitial and perivascular infiltrate containing numerous well-differentiated mature plasma cells affecting the entire dermal surface. Kappa and lambda immunochemistry demonstrated polyclonal plasma cell infiltrates with absence of light-chain restriction. Immunohistochemical examination was negative for HHV-8 and Treponema pallidum spirochetes. Laboratory findings revealed hypergammaglobulinaemia with no monoclonal bands being detected on immunofixation. A diagnosis of cutaneous plasmacytosis was made. In the absence of systemic involvement initial management consisted of clinical surveillance. DISCUSSION: The characteristic clinico-pathological features of CP allowed diagnosis of this skin condition in our patient, although it is very rarely reported in patients of European descent. The main differential diagnoses were ruled out, namely plasmacytic infiltrates related to infections and marginal B-cell lymphoma.

Distinctive cutaneous and systemic features associated with specific antimyositis antibodies in adults with dermatomyositis: a prospective multicentric study of 117 patients.

BACKGROUND: Identification of myositis-specific autoantibodies (MSAs) for dermatomyositis (DM) could allow the characterization of an antibody-associated clinical phenotype. OBJECTIVE: We sought to define the clinical phenotype of DM and the risk of cancer, interstitial lung disease (ILD) and calcinosis based on MSA. METHODS: A 3.5-year multicentre prospective study of adult DM patients was conducted to determine the clinical phenotype associated with MSAs and the presence of cancer, ILD and calcinosis. RESULTS: MSAs were detected in 47.1% of 117 included patients. Patients with antimelanoma differentiation-associated protein-5 antibodies (13.7%) had significantly more palmar violaceous macules/papules [odds ratio (OR) 9.9], mechanic's hands (OR 8), cutaneous necrosis (OR 3.2), articular involvement (OR 15.2) and a higher risk of ILD (OR 25.3). Patients with antitranscriptional intermediary factor-1 antibodies (11.1%), antinuclear matrix protein-2 antibodies (6.8%) and antiaminoacyl-transfer RNA synthetase (5.1%) had, respectively, significantly more poikiloderma (OR 5.9), calcinosis (OR 9.8) and articular involvement (OR 15.2). Cutaneous necrosis was the only clinical manifestation significantly associated with cancer (OR 3.1). CONCLUSION: Recognition of the adult DM phenotype associated with MSAs would allow more accurate appraisal of the risk of cancer, ILD and calcinosis.

[What's new in internal medecine?] / Quoi de neuf en médecine interne ?

Answering the question « what's new in internal medecine in 2016? ¼ is very challenging. We used 3 methods of article selection to reduce the selection bias: 3 authors, a systematic review of the articles discussed in the weekly bibliographic meeting of our unit (Dermatology department, Saint-Louis Hospital, Paris, France) and a selection of the best articles by several internal medecine practitioners in Paris. Eleven « hot topics ¼ were analyzed: i/lowering cholesterol level but not blood blessure has a significant impact on cardiovascular morbi-mortality in cardiovascular intermediate risk patients; ii/the « treat to treat target ¼ is efficient in psoriatic arthritis; iii/ a genotype/ phenotype correlation favors the separation of ileal Crohn's disease, colonic Crohn's disease and ulcerative colitis; iv/ tocilizumab treatment (anti-IL-6 monoclonal antibody ) is very efficient in giant cell arteritis and slightly efficient in systemic sclerosis; v/ combination therapy using methotrexate plus steroids compared with steroids alone becomes the « gold standard ¼ treatment for juvenile dermatomyositis; vi/ dupilumab treatment (antibody blocking IL-4 and IL-13 receptors) is not only efficient in atopic dermatitis but also in asthma; vii/ think of eosinophilic oesophagitis in a patient with atopic dermatitis and dypshagia or food impaction; viii/ genetic A2 protein dysfunction induces NF-kB hyperactivation and an autoinflammatory disorder with features similar to Behcet's disease; ix/ no new biotherapies have shown high efficacy in systemic lupus erythematosus; x/ nanoparticles loaded with autoantigens induce Tregs and Bregs and may be a promising therapeutic option to treat auto-immune disease in the future; xi/ ipilimumab treatment (anti-CTLA4 antibody, immune checkpoint inhibitor) may induce complete remission in acute myeloid leukemia patients relapsing after haematological stem cell transplantation. Year 2016 is full of great discoveries in internal medicine keeping the dermatologist brain fully open minded.