Effective rescue treatment with vemurafenib of an infant with high-risk Langerhans cell histiocytosis.

INTRODUCTION: The recently identified role of a BRAF somatic mutation in the pathophysiology of Langerhans cell histiocytosis (LCH) offers new therapeutic options. Herein we describe the case of a 10-month-old infant with refractory high-risk LCH successfully treated with vemurafenib. OBSERVATION: The patient first presented with cutaneous LCH at the age of 2 months. The disease remained undiagnosed until she was 6 months old, when it rapidly evolved to a multisystemic high-risk and life-threatening disease, refractory to 2 lines of chemotherapy. BRAFV600E mutation was found at skin biopsy, and targeted therapy with vemurafenib was started when she was 10 months old. The treatment induced a fast and sustained response, but rapid relapse occurred after treatment discontinuation, leading to resumption of treatment, once more resulting in a sustained response. CONCLUSION: Our case highlights the first-line role of dermatologists in establishing the diagnosis of LCH, especially in children, in whom the eruption may be difficult to identify, leading to delayed diagnosis. Targeted therapy with vemurafenib has recently been described in children in this indication and our results support its efficacy, highlighting the need for prolonged treatment and raising the question of maintenance therapy, as well as the necessity for large-scale and long-term studies.

[Infantile hemangioma: a new indication for propranolol? Retrospective study: a case-series of 25 infants]. / Hémangiome infantile du nourrisson: une nouvelle indication du propranolol? Etude retrospective: série de 25 cas.

BACKGROUND: In 2008, the New England Journal of Medicine reported a new indication for propranolol: treatment of complicated infantile hemangioma (IH). The objective of this study is to identify any adverse events and to measure the efficacy of propranolol in children with complicated IH, through a retrospective, observational, case-series study of 25 patients treated with propranolol at the Hôpital Universitaire des Enfants Reine Fabiola in Belgium. OBSERVATIONS: 25 patients were submitted to this therapy. The treatment was stopped prematurely for two of them, by parental fear of side effects and 48 % presented one or more adverse events; all of which were transient and rapidly controlled by adjusting the doses administered. Mean age at the start of treatment was 4,8 months. A clearly favorable response was observed in 100 % of patients at their first visit after treatment initiation ; a total response was seen in 9 patients, with subtotal and partial responses observed in 9 and 3 patients, respectively, by the end of treatment. CONCLUSION: The real efficacy of propranolol for complicated IH was confirmed by the clearly evident improvement observed in all patients and the absence of non-responders. As global tolerance was also good, propranolol can therefore be considered to be an appropriate first- line treatment for complicated IH.

[Palmoplantar neutrophilic eccrine hidradenitis with general extension in a child in remission after acute lymphoblastic leukemia]. / Hidradénite eccrine neutrophilique palmo-plantaire avec extension généralisée chez un enfant en rémission d'une leucémie aiguë lymphoblastique.

BACKGROUND: Neutrophilic eccrine hidradenitis (NEH) is a form of neutrophilic dermatitis characterized by tender erythematous and painful papules involving the trunk, extremities and face. The generalized form is associated with malignant hemopathies. The palmoplantar form occurs in children without any context of malignancy. Histology shows a neutrophilic infiltrate surrounding and infiltrating the eccrine glands associated with vacuolar degeneration and necrosis of the epithelial secretory portion. PATIENTS AND METHODS: We report the case of a 4-year-old girl with palmoplantar HEN progressing to the generalized form while in remission from acute lymphoblastic leukemia. DISCUSSION: Progression of HEN from the palmoplantar form to the generalized form has never been published previously in the literature.

[Infantile hemangioma and propranolol: a therapeutic "revolution". Literature review]. / Hémangiome infantile du nourrisson et propranolol: une "révolution" thérapeutique. Revue de la littérature.

Infantile hemangioma (IH) is the most common benign vascular tumour affecting children. Most infantile hemangiomas are self-limiting, but some require specific treatment. Propranolol has been proposed for the treatment of infantile hemangiomas. The aim of this study is to explore the mechanism of action of propranolol for the treatment of infantile hemangiomas and to demonstrate its safety and efficacy through a review of the literature. The non cardioselective bêta-blocker propranolol has been used in a pediatric setting for 40 years and, since 2008, has a new indication. A clearly significant improvement has been observed in the condition of children with complicated IH (10%) treated with propranolol. This new indication has been widely described in the international literature. Various explanations have been put forward for the mechanism of action including a vasoconstrictor, antiangiogenic and apoptotic effect of propranolol on the different cells making up an IH. Overall tolerance is good and the efficacy markedly superior to that of any other treatments used for this purpose. In conclusion, with its good tolerance profile and superior efficacy versus all the other available therapies, propranolol can be considered to be a first-line treatment for complicated IH.

[Hereditary epidermolysis bullosa: clinical and ultrastructural analysis of 21 cases]. / Epidermolyses bulleuses héréditaires: etude clinique et ultrastructurale de 21 cas.

Hereditary epidermolysis bullosa (HEB) constitute a genodermatosis group with variable clinical severity. The aim of the study was to confront the diagnosis established by electron microscopy (EM), with the clinical presentation and evolution, genetic analysis and immunofluorescence, and to observe if there was concordance. Biopsies diagnosed as HEB in the last 15 years, were retrieved from the database of the C.H.U. Saint-Pierre EM lab. Each corresponding medical file was reviewed and the following data were recorded: date of birth, sex, age, age at biopsy, ultrastructural characteristics, degree of certainty regarding the EM diagnosis, family history, clinical lesions and their evolution as well as other diagnostic tests performed. 21 patients, aged 1 day to 26 year old were included. A HEB simplex was diagnosed in 10 cases, a junctional EBH in 5 cases and a dystrophic HEB in 6 cases. Immunofluorescence was requested in 4 cases. 7 patients benefited from a genetic analysis. Physical examination revealed hyperpigmented spots in 1 case. A patient with dystrophic HEB had a family history of symptoms restricted to the nails. 4 patients died. In conclusion, the accurate clinical diagnosis of the HEB sub-type is difficult because of the symptomatology heterogeneity. EM remains the gold standard for diagnosis even if immunofluorescence and genetic analysis should be more systematically considered.

[Atopic dermatitis]. / Dermatite atopique.

Atopic dermatitis is a common chronic inflammatory skin disease. It is a disease mostly of childhood, but also of adult life. The classical course of childhood eczema shows improvement in 80% of the cases. The pathogenesis of the disease is now better understood but the world wide prevalence of atopic dermatitis has increased two to threefold over the past 30 years. Atopic dermatitis affects considerably quality of life as well in children as in adults. Important clues in the understanding of the pathogenesis of the disease are genetic factors, skin barrier dysfunction and immune dysregulation. Triggers of atopic dermatitis are well identified: food and airborne allergens, contact allergens, skin microorganisms, irritants and psychological stress. Concerning therapy, the different topical and systemic options are described, as well as the importance of therapeutic education.

[Granulomatous skin disease in an immunocompromised child]. / Granulomatose cutanée chez un enfant immunodéficient.

BACKGROUND: The development of systemic and/or cutaneous granulomas associated with immunodeficiency is well established, particularly with common variable immunodeficiency (CVID). We report the case of an immunocompromised child presenting with cutaneous granulomas, predominantly on the face. PATIENTS AND METHODS: A boy aged 6 years and 9 months presenting complex and incompletely defined immunodeficiency presented with gradually worsening cutaneous lesions of granulomatous aspect on his face and right foot. Extensive laboratory tests showed no infectious or neoplastic processes. Biopsies of the lesions confirmed the presence of granulomas. Systemic corticosteroids produced no satisfying improvement and were changed to anti-TNFα. The lesions had completely disappeared after 6 months. Treatment was continued for 6 months, with no relapse 6 months after discontinuation. CONCLUSION: The originality of our case lies in the presentation of cutaneous granulomas, appearing in the context of an undefined immunodeficiency other than CVID, as well as in the therapeutic aspect, with the successful use of biotherapies in such a clinical setting.

[Pruritus: diagnostic strategy and therapeutic approach]. / Le prurit: stratégie diagnostique et approche thérapeutique.

Pruritus, defined as an abnormal cutaneous sensation that will provoke the desire to scratch, is the leading symptom of cutaneous disorders. However, some pruritus will be the only sign of several internal pathologies. More than hundreds etiologies are possibles. That is why a diagnostic algorithm is necessary for an optimal care and to define which investigations to make. This algorithm will distinguish localized pruritus and diffuse pruritus. The presence of specifics cutaneous lesions will be constitute a great help for making diagnosis.

Oral ulceration: an unusual manifestation of Churg-Strauss syndrome.

Churg-Strauss Syndrome (CSS) is a relatively rare entity characterized by asthma, transient pulmonary infiltrates, eosinophilia and systemic vasculitis. Oral ulceration is a possible clinical manifestation of some systemic vasculitides, such as Wegener's granulomatosis (WG) or giant cell arteritis, but has never been reported with Churg-Strauss syndrome. We report the first observation of a palatine ulceration in a 15-year-old girl with Churg-Strauss syndrome.

[Dermo-cosmetics and prevention of skin aging]. / Dermo-cosmétiques et prevention du vieillissement cutané.

Skin aging is the result of the addition of intrinsic aging (chronological aging) and extrinsic aging induced by environmental factors among whose ultraviolet radiation plays a predominant role (actinic aging). The physiopathological mechanisms of skin aging are well better known. UV radiations act either directly on DNA either through the formation of free radicals. The skin aging is characterized by the decline of numerous skin functions. Its clinical presentation is accentuated in UV exposed-skin. To struggle against skin aging is first of all to prevent it by means of an efficient photoprotection, an adequate general life style and preventive treatments as alpha-hydroxyacids, retinoids and antioxidants.

The prevalence of positive reactions in the atopy patch test with aeroallergens and food allergens in subjects with atopic eczema: a European multicenter study.

BACKGROUND: The atopy patch test (APT) was proposed to evaluate IgE-mediated sensitizations in patients with atopic eczema (AE). OBJECTIVE: The prevalence and agreement with clinical history and specific IgE (sIgE) of positive APT reactions was investigated in six European countries using a standardized method. METHODS: A total of 314 patients with AE in remission were tested in 12 study centers on clinically uninvolved, non-abraded back skin with 200 index of reactivity (IR)/g of house dust mite Dermatophagoides pteronyssinus, cat dander, grass, and birch pollen allergen extracts with defined major allergen contents in petrolatum. Extracts of egg white, celery and wheat flour with defined protein content were also patch tested. APT values were evaluated at 24, 48, and 72 h according to the European Task Force on Atopic Dermatitis (ETFAD) guidelines. In addition, skin-prick test (SPT) and sIgE and a detailed history on allergen-induced eczema flares were obtained. RESULTS: Previous eczema flares, after contact with specific allergens, were reported in 1% (celery) to 34% (D. pteronyssinus) of patients. The frequency of clear-cut positive APT reactions ranged from 39% with D. pteronyssinus to 9% with celery. All ETFAD intensities occured after 48 and 72 h. Positive SPT (16-57%) and elevated sIgE (19-59%) results were more frequent. Clear-cut positive APT with all SPT and sIgE testing negative was seen in 7% of the patients, whereas a positive APT without SPT or sIgE for the respective allergen was seen in 17% of the patients. APT, SPT and sIgE results showed significant agreement with history for grass pollen and egg white (two-sided Pr > /Z/ < or = 0.01). In addition, SPT and sIgE showed significant agreement with history for the other aeroallergens. With regard to clinical history, the APT had a higher specificity (64-91% depending on the allergen) than SPT (50-85%) or sIgE (52-85%). Positive APT were associated with longer duration of eczema flares and showed regional differences. In 10 non-atopic controls, no positive APT reaction was seen. CONCLUSION: Aeroallergens and food allergens are able to elicit eczematous skin reactions after epicutaneous application. As no gold standard for aeroallergen provocation in AE exists, the relevance of aeroallergens for AE flares may be evaluated by APT in addition to SPT and sIgE. The data may contribute to the international standardization of the APT.

[Acariasis and domestic animals]. / Acarioses et animaux domestiques.

Various parasitic dermatoses in man can find their origin in domestic animals. Acariasis are skin zoonoses which are not well known by the dermatologists and general practitioners. Due to different ectoparasite mites, the acariasis always cause prurigo in man but different areas of the body are involved. The treatment of the domestic animals usually allows the cure of the owner's skin disease.

[Antihistamines]. / Les antihistaminiques.

The H1-receptor antagonists (H1-antihistamines) are among the most widely used medications in the world. We review the molecular basis of action, pharmacology, efficacy in allergic disorders (rhinoconjunctivitis, asthma, urticaria, atopic dermatitis) and adverse effects. Special advices are given for the young children, the elderly, in case of liver or renal insufficiency and during pregnancy and breast-feeding.

[Particular aspects of ulcers in children]. / Aspects particuliers des ulcères chez l'enfant.

Leg ulcers of juvenile onset are uncommon. The infectious origin is fairly frequent but the presence of leg ulcers in children should prompt an investigation into possible underlying causes especially hemangioma, vasculitis, inborn errors of metabolism (i.e. prolidase deficiency), hemoglobinopathies, occult spinal dysraphism and immunodeficiencies. Bacteriological investigations are essential and a skin biopsy specimen may be able to differentiate some of these disorders.

[Physiopathology of bedsores]. / Physiopathologie des escarres.

Pressure is the primary pathogenic factor in the development of decubitus ulcers. Other major factors are shearing forces, friction and moisture. Significant intrinsic risk factors are immobility, age-related diseases, nutritional status, medications and smoking. The morbidity and mortality related to the complications of pressure sores are quite significant. Prevention is essential and is best achieved by identification of high risk patients. The therapeutic approach is based on the grade of pressure ulcer.

Eosinophilic pustular folliculitis in three atopic children with hypersensitivity to Dermatophagoides pteronyssinus.

Three children will be described who present recurrent episodes of pruritic papulopustular follicular lesions on the face, the extremities and the trunk. The episodes lasted for 1-3 months with intermittent remission. Each flare was accompanied by hypereosinophilia and an increased total IgE titer. RAST and prick tests were positive for Dermatophagoides pteronyssinus (DPT). Laboratory tests disclosed no infectious or parasitic etiology. Histological examination showed eosinophilic pustular folliculitis (EPF) in each of the 3 cases. The lesions responded well to topical corticosteroids. The aim of this article is to underline the importance of hypersensitivity reactions (in these particular cases to DPT) in the pathogenesis of EPF.

[Pruritus in children]. / Le prurit de l'enfant.

Itching is usually manifested by scratching. It is lacking before three months of age. The practitioner must determine whether itching is generalised or localised and whether a skin disease is present. The main skin diseases responsible for generalised itching are scabies, atopic dermatitis, urticaria and papular urticaria. When itching is localised, contact dermatitis or pediculosis are usually responsible. Diagnosis rests on careful analysis of symptoms. In patients without skin lesions, an external cause (irritation, environment) or an internal cause (cholestasis, chronic uraemia, lymphoma, drug and psychological problems) should be considered. Therapy should be causal when possible. If not, antihistaminic drugs should be used.