Cristina Bulai-Livideanu

Bullous and mucous membrane pemphigoid show a mixed response to rituximab: experience in seven patients.

Editor Rituximab, a chimeric monoclonal antibody directed against the cell-surface glycoprotein CD20, was originally developed to treat B-cell malignancies. Recently, rituximab, alone or in combination with intravenous immune globulins, has been shown to induce remission in up to 86% of patients with pemphigus refractory to oral steroids. However, there is limited information regarding the efficacy and safety of rituximab in auto-immune bullous disorders other than pemphigus. Herein, we report on a retrospective study of seven patients with refractory bullous pemphigoid (BP) or mucous membrane pemphigoid (MMP) who underwent treatment with rituximab. We performed a retrospective study on patients treated with rituximab for an auto-immune bullous disease other than pemphigus. Patients were selected between August 2007 and August 2009 at Toulouse and Limoges University Hospitals. During this period, seven patients (four men and three women) had received rituximab treatment. Five had BP and two had MMP (Table 1). The decision to initiate rituximab treatment was a multidisciplinary therapeutic decision. The median age at diagnosis was 70 years (range 33–85). Most patients had a history of comorbidities, including cardiac disease (four), pulmonary disease (one), renal disorder (one) and cutaneous cancers (two). All patients had previously not responded to topical corticosteroids or to at least one systemic immunosuppressive regimen (systemic corticosteroids, methotrexate, mycophenolate mofetil, cyclophosphamide, dapsone, azathioprine, etanercept). On physical examination, all patients had cutaneous lesions and four of the seven patients had erosions of the mucous membranes: oral (three patients), genital (three patients), ocular (two patients) and nasal (one). Direct immunofluorescence showed linear IgG and complement C3 deposits at the dermoepidermal junction of perilesional skin in six patients. Using indirect immunofluorescence analysis, antibasement membrane zone antibodies were detected in the serum of five and anti-BP-180 autoantibodies were detected by ELISA (Euroimmun, Lubeck, Germany) analysis in six patients. Six patients received four infusions of rituximab at weekly intervals at a dose of 375 mg ⁄ m. In one patient with BP, four additional rituximab infusions were given 11 months after the first dose, due to relapse of the disease. All patients received concomitant immunosuppressive medications. Four patients experienced complete remission on therapy, while two patients had partial remission. The median time to improvement in skin lesions was 4 months. Four patients are still in maintained remission, but one patient relapsed after 4 months of complete remission. The average duration of follow-up was 8 months (0.25; 27). Concerning clinical adverse events, one 85year-old patient with BP suddenly died 10 days after introduction of the first infusion of rituximab. The patient had a previous history of cardiac disease (ischaemic cardiopathy, atrial fibrillation and abdominal aortic aneurysm). In this retrospective review, rituximab appears to be an interesting therapeutic option, alone or in association with other systemic immunosuppressants, to treat BP and MMP that is resistant to conventional immunosuppressive treatments. Rituximab has shown promise in several case reports and cohort studies in treating paraneoplastic pemphigus, refractory cases of pemphigus vulgaris and foliaceus. There are also case reports for other autoimmune bullous skin disorders, where rituximab therapy successfully treated four patients with MMP and nine with refractory BP (Table 2). At present, rituximab treatment may be proposed in patients with autoimmune bullous diseases who are resistant to at least two conventional treatment regimens, including systemic glucocorticosteroids and immunosuppressants. However, further studies are needed to assess the role of rituximab in autoimmune bullous diseases other than pemphigus.

Significant delay in the introduction of systemic treatment of moderate to severe psoriasis: a prospective multicentre observational study in outpatients from hospital dermatology departments in France

Background  There is a low rate of systemic treatment usage in moderate to severe psoriasis.

A Multicenter, Randomized, Open-Label, Controlled Study Comparing the Efficacy, Safety and Cost-Effectiveness of a Sequential Therapy with RV4104A Ointment, Ciclopiroxolamine Cream and Ciclopirox Film-Forming Solution with Amorolfine Nail Lacquer Alone in Dermatophytic Onychomycosis

Background: The efficacy of topical antifungals is controversial. Objective: To compare the efficacy and safety of a sequential (SEQ) treatment with chemical nail avulsion and topical antifungals to amorolfine nail lacquer in dermatophytic onychomycosis. Methods: This was a randomized, parallel-group, controlled study comparing a 36-week SEQ treatment with chemical nail avulsion with RV4104A ointment (class I medical device containing 40% urea) followed by ciclopirox cream for 8 weeks and ciclopirox nail lacquer for 25 weeks (SEQ group) to amorolfine nail lacquer for 36 weeks (AMO group). Patients had to have a big toenail onychomycosis, sparing the matrix. The primary efficacy criterion was complete cure at week 48. A cost-effectiveness analysis was performed. Results: A total of 142 patients were randomized. The complete cure rate at week 48 was significantly higher in the SEQ group than in the AMO group (36.6 vs. 12.7%, p = 0.001). Clinical cure at week 48 was observed in 53.5% of patients in the SEQ group versus 17% in the AMO group (p < 0.01). The cost of cure per patient was 50% lower with SEQ treatment (EUR 33) compared with amorolfine (EUR 76). Conclusion: A treatment of onychomycosis comprising chemical avulsion of the pathological nail, ciclopirox cream and nail lacquer is significantly more effective than amorolfine nail lacquer.

Botulinum Toxin A: An Effective Treatment for Linear Immunoglobulin A Bullous Dermatosis Located in the Axillae

Linear immunoglobulin A bullous dermatosis (LABD) is a rare chronic disease, but it is the most frequent auto-immune bullous disease in children (1). In this age group, the eruption is characterized by a clustered arrangement of blisters, located mainly on the lower abdomen, perineum, and perioral area (2). In adults, the eruption is polymorphic, with no specific anatomical sites, and can simulate other auto-immune bullous diseases (1). Functional symptoms vary from mild pruritus to severe burning. Histological examination reveals a dense superficial dermal infiltrate made of neutrophils and eosinophils in the form of micro-abscesses on top of papillae, together with dermo-epidermal detachment. LABD is caused by IgA auto-antibodies typically directed against a proteolytic fragment of 180-kDa bullous pemphigoid antigen (BP180) detected as a 97 or 120 kDa protein on western blotting, and/or other components of the dermal–epidermal junction (3). Direct immunofluorescence is characterized by linear IgA deposits on the basal membrane. First-line treatment for LABD is dapsone, used as monotherapy or in combination with systemic corticosteroids. For patients not responding to dapsone, sulphapyridine, immunosuppressive drugs, immunoglobulins or rituximab have been advocated (4). We report here the efficacy of botulinum toxin A (BtxA) injections for LABD located in the axillae.

Élaboration d’un référentiel d’éducation thérapeutique dans le psoriasis

INTRODUCTION Psoriasis is a chronic inflammatory skin disease which can cause significant impairment of quality of life, absenteeism at work and significant psychological distress. This justifies the elaboration of a multidisciplinary education program for patients. The objective of this work was to develop the content of a therapeutic education program in psoriasis, which may serve as a basis for teams wishing to develop psoriasis therapeutic education in their community. PATIENTS AND METHODS A group of 15 health professionals (dermatologists, dermatology nurses, and psychologist) and four psoriasis patients representatives of the psoriasis patient association (Association pour la lutte contre le psoriasis) participated in the development of this program. Health professionals all had an experience in therapeutic patient education in psoriasis through prior participation in a multicenter open pilot study, evaluating a therapeutic education program in psoriasis. Based on the previous experience, preparatory work in subteams was initiated to prepare draft objectives and content of the program. A two-day meeting was then organized to discuss in depth content of the therapeutic education program and elaborate recommendations. The meeting structure combined subteam work and plenary sessions. The following program was elaborated: two individual sessions and three group sessions. The groups have worked for two days, according to a predefined pattern: interview guide of educational diagnostic, content of collective workshops and knowledge questionnaire. All these documents were validated in plenary session. The methodology used for the development of this program followed the recommendations of the HAS in the field of chronic disease. RESULTS In the end, were retained three collective workshops, preceded by a consultation of individual educational diagnosis and knowledge questionnaire followed by an evaluation session at the end of the program. The interview guide for educational diagnosis and the knowledge basis questionnaire have been defined. Three themes of group workshops were defined: (1) understanding the disease, (2) understanding the mechanism of onset of disease and treatments available, (3) how to live with psoriasis in everyday life. For each workshop, were defined learning objectives, skills to acquire and how to get there. DISCUSSION We describe here a framework of educational therapy program in psoriasis comprising educational objectives, skills to acquire, basic disease knowledge, suitable for patients with psoriasis. The content was tailored to patient language and knowledge based on feedback from participating patients. The list of skills may be adapted to patients individual needs. This program serves primarily as a working basis for the caregiver, to standardize practices in terms of therapeutic education in psoriasis in France.

Angiolymphoid hyperplasia with eosinophilia treated with low-dose methotrexate.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon, benign disorder that presents as solitary or multiple papulonodules, located predominantly in the head and neck region. The pathogenesis of ALHE remains controversial. It has occurred following various forms of trauma or infection. The disorder is commonly regarded as an angioproliferative process accompanied by an inflammatory infiltrate that is thought to be a reactive component. ALHE may represent a T-cell lymphoproliferative disorder of a benign or low-grade malignant nature.1 Other reported cases have shown damaged arteries and veins at the base of the lesion, suggesting that an underlying arteriovenous malformation may play a role in the pathogenesis.2 Additionally, some evidence suggests that ALHE may be related to traumatic pseudoaneurysm, supporting a vascular origin.3 Multiple treatments are proposed in the dermatologic literature for ALHE. We report a case of multiple lesions on the neck treated with low-dose methotrexate.

Prevalence and risk factors for fragility fracture in systemic mastocytosis

OBJECTIVES Systemic mastocytosis (SM) is characterized by the accumulation of mast cells in tissues other than the skin. Bone involvement although frequent has not been thoroughly evaluated. Primary objective was to determine risk factors associated with fragility fractures (FF) in SM. Secondary objectives were to evaluate the ability of bone marrow tryptase (BMT) level to identify patients with FF, and to describe bone involvement in SM. METHODS We analyzed retrospectively all consecutive patients seen in our expert center, with a diagnosis of SM according to the 2001 WHO criteria, and with complete bone assessment. We collected data about lifetime fractures, types of cutaneous manifestations, degranulation symptoms, blood and BMT levels, bone mineral density assessed by densitometry and KIT mutation. We performed a univariate analysis investigating the factors associated with FF and then a logistic multivariable regression analysis. We assessed the ability of bone marrow tryptase to identify patients with FF. RESULTS Eighty-nine patients with SM were included. Thirty-six patients (40.4%) suffered from osteoporosis and twenty-five (28.1%) experienced lifetime FF. Univariate analysis identified age at diagnosis and disease onset, presence of telangiectasia macularis eruptiva perstans, digestive symptoms, mast cells activation symptoms, elevated BMT, low femoral and lumbar BMD, as associated with FF. Multivariate analysis identified elevated BMT, low femoral T score and older age at diagnosis as independently associated with FF. CONCLUSIONS Low femoral T-score, BMT level, and older age at diagnosis are markers associated with FF in SM. BMT may represent an important biomarker to predict FF in SM patients.

Surgical Treatment of Facial Basal Cell Carcinoma: Patient-Based Assessment of Clinical Outcome in a Prospective Cohort Study

Background: There are limited data on the esthetic, functional, and morphological outcomes of surgical treatment of facial basal cell carcinoma (BCC). Objective: The aim of our study was to assess the determinants of the evaluation of both the patients and the investigator of the esthetic, functional, and morphological impact of the surgical treatment of facial BCC. Methods: A prospective observational study evaluated 111 patients treated surgically for facial BCCs (n = 135 BCCs), using the Patient and Observer Scar Assessment Scale (POSAS), a validated and reliable scale designed for the evaluation of all types of scars by professionals and patients. Results: Scar assessment rated by the patients was very good. Skin aging was associated with a better surgical outcome as evaluated by POSAS (OR = 0.30, 95% CI: 0.09-0.98; p = 0.04). Conversely, histologically infiltrative or sclerosing BCC (OR = 2.33, 95% CI: 0.95-5.71; p = 0.06) was independently associated with poorer POSAS. In terms of the investigators evaluation, aging signs (protective factor: OR = 0.17, 95% CI: 0.04-0.73; p = 0.01), location on the H-zone of the face (risk factor: OR = 2.95, 95% CI: 1.07-8.15; p = 0.03), and histologically infiltrative or sclerosing BCC (risk factor: OR = 2.89, 95% CI: 1.01-8.29; p = 0.04) were independently associated with POSAS. Conclusion: Esthetic, functional, and morphological outcomes of facial BCC surgery provide high patient satisfaction overall. Taking wider margins requires specific measures to improve the surgical outcome.