Twelve-year analysis of severe cases of drug reaction with eosinophilia and systemic symptoms: a cause of unpredictable multiorgan failure.

BACKGROUND: Factors implicated in the severity of drug reaction with eosinophilia and systemic symptoms (DRESS) have not been identified. We retrospectively describe and analyze severe cases of DRESS defined by history of intensive care unit admission and death due to DRESS. OBSERVATIONS: Of 15 patients retrospectively recruited in France, 14 were admitted to the intensive care unit and 3 died. The culprit drugs were already known to cause or trigger DRESS: allopurinol, minocycline hydrochloride, anticonvulsants, sulfonamides, and antibiotics. Visceral involvement with severe manifestations responsible for intensive care unit admission or death was variable and often multiple (pneumonitis, hepatitis, renal failure, encephalitis, hemophagocytosis, cardiac failure, and pancytopenia) and resulted in multiorgan failure in 11 patients. These severe complications sometimes developed late in DRESS. Human herpesvirus 6 infection was demonstrated in 6 of 7 patients. In addition, human herpesvirus 6 infection was demonstrated in involved viscera in 2 patients. CONCLUSIONS: Severe DRESS is rare. Some specificities of visceral involvement were associated with allopurinol and minocycline. However, visceral involvement comprising multiorgan failure seemed to be unpredictable. Better knowledge of DRESS is necessary to propose specific and prompt treatment. Early demonstration of human herpesvirus 6 reactivation could be considered a prognostic factor for identifying patients at higher risk and, hence, needs to be evaluated.

Methotrexate for the treatment of adult atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease mediated by allergen-specific T cells which are recruited and activated in lesional skin. Methotrexate (MTX) is an old systemic agent used at low dosage for the treatment of psoriasis, another T cell-mediated skin disorder. Since MTX has been shown to improve the clinical symptoms of eczema in a model of antigen-specific dermatitis in mice, we postulated that it could be an effective treatment of AD. In the present open retrospective study, we report our results on the treatment of moderate to severe AD by MTX. Twenty patients (17 to 68-years-old) with low responses to routine therapies were treated (three months to 2 1/2 years) with a weekly dose of MTX ranging from 7.5 to 25 mg. The evaluation was made on physician's global assessment after 3 months of MTX use, and showed that 75% (15/20) of patients improved after 3 months of MTX use, among which 13/20 with an improvement>70%. The beginning of improvement was observed between the fourth and the eighth week after MTX was initiated. Tolerance was good. However, nausea and increase of liver enzymes were observed in 5 patients and required discontinuation of MTX in 2 patients. In conclusion, MTX seems to be an effective and safe treatment of AD. Placebo-controlled clinical trials are needed to confirm our observations and to define more precisely the effectiveness and safety of MTX in adult AD.

Pathophysiology of urticaria.

Urticaria is dermal edema resulting from vascular dilatation and leakage of fluid into the skin in response to molecules released from mast cells. The major preformed mediator histamine produces a prototypic, short-lived urticaria. However, the clinical spectrum and pattern of lesions indicate that other molecules, including prostaglandins, leukotrienes, cytokines, and chemokines, produced at different times after mast cell activation contribute to the polymorphism of this symptom and the variable evolution of this disease. It is a common practice to distinguish immunological and nonimmunological urticaria. Immunological urticaria is a hypersensitivity reaction mediated by antibodies and/or T-cells that results in mast cell activation. Although immunoglobulin (Ig)E-mediated type I hypersensitivity (HS) was long postulated to be the major immunological pathway associated with mast cell activation, interaction between IgE-bound mast cells and allergens is unlikely to be the mechanism by which urticaria develops in most patients. It is now well established that urticaria may result from the binding of IgG auto-antibodies to IgE and/or to the receptor for IgE molecules on mast cells, thus corresponding to a type II HS reaction. These auto-immune urticarias represent up to 50% of patients with chronic urticaria. Mast cell activation can also result from type III HS through the binding of circulating immune complexes to mast cell-expressing Fc receptors for IgG and IgM. Finally, under certain circumstances, T-cells can induce activation of mast cells, as well as histamine release (type IV HS). Nonimmunological urticarias result from mast cell activation through membrane receptors involved in innate immunity (e.g., complement, Toll-like, cytokine/chemokine, opioid) or by direct toxicity of xenobiotics (haptens, drugs). In conclusion, urticaria may result from different pathophysiological mechanisms that explain the great heterogeneity of clinical symptoms and the variable responses to treatment.

[How to understand psoriasis?]. / Comment comprendre le psoriasis?

Recent advances in the treatment of psoriasis have led to improve understanding in the pathogenesis of the disease. Skin lesions are scaling erythematous plaques. Although initially considered as a disease of epidermal cells, it is now widely accepted that the epidermal abnormalities, which are characteristic of the disease, are secondary to the development of a skin inflammation. Psoriasis is an autoimmune disease due to the activation in the skin of antigen-specific T cells leading to release of cytokines that results in proliferation of keratinocytes. However, the autoantigen(s) is (are) yet unknown. Several new biological treatments have been developed, which target specific steps in the pathophysiology of the disease.