Macrolactam immunomodulators for topical treatment of inflammatory skin diseases.

The immunomodulatory macrolactams provide an alternative to glucocorticosteroids for the topical treatment of atopic dermatitis and other inflammatory dermatoses. Tacrolimus (FK506), as well as the newer ascomycin derivative ASM 981 (pimecrolimus), penetrate the inflamed epidermis and are suitable for topical therapy. Both substances inhibit the transcription of proinflammatory cytokine genes such as interleukin 2, which are dependent on the nuclear factor NF-AT. They block the catalytic function of calcineurin, which leads to the inhibition of the transport of the cytoplasmic component of NF-AT to the cell nucleus. Multicenter, randomized, double-blind clinical trials with topical formulations have shown the efficacy of both substances in moderate to severe atopic dermatitis. A review is presented of the biochemical and cell biologic properties, mode of action, pharmacokinetic data, side effects, results of the clinical trials, and further indications for tacrolimus and ASM 981, along with an overview of the related substances cyclosporine and sirolimus (rapamycin).

[Bullous scabies and scabies-triggered bullous pemphigoid]. / Bullöse Skabies und durch Skabiesbefall getriggertes bullöses Pemphigoid.

Two patients were admitted to our hospital with tense blisters on an erythematous base, typical for bullous pemphigoid. In both patients an infestation with Sarcoptes scabiei was diagnosed by dermatoscopy as well as histological examination. In one patient the clinical diagnosis of bullous pemphigoid could be confirmed by immunofluorescence microscopy, histopathology and a clinical relapse of bullous pemphigoid without scabies infestation. In the other patient no evidence for an autoantibody-mediated autoimmune blistering disease was found. We postulate that bullous scabies could develop after long persistency of the parasites leading to a specific immune response with activation of T helper type 2 (Th2) cells causing high levels of the cytokine interleukin 5 and then consecutively eosinophilia. Secretion of proteolytic enzymes near the basal membrane zone might explain the development of intraepidermal, often suprabasal blisters. In contrast, in the first patient the scabies infestation might have triggered a flare up of the underlying autoimmune disease. Comparison of our two patients demonstrates two entities: bullous pemphigoid triggered by scabies as a Koebner phenomenon and a bullous subtype of scabies mimicking bullous pemphigoid. Therefore both, scabies infestation triggering bullous pemphigoid and bullous pemphigoid-like scabies should be included in the differential diagnosis of vesicles, tense blisters and erythema, especially at an early clinical stage.

[Immunosuppressive macrolides and their use in dermatology]. / Immunsuppressive Makrolide und ihr Einsatz in der Dermatologie.

The immunosuppressive macrolides are a novel class of antiinflammatory substances, which could supplant glucocorticosteroids for the topical treatment of some chronic inflammatory skin diseases. Cyclosporine A (CyA), well known from transplantation medicine for years, is licensed in Germany for oral treatment of psoriasis and atopic dermatitis but is not suitable for topical therapy. Tacrolimus (FK506) penetrates the inflamed epidermis and is regarded as the key immunosuppressive macrolide. Clinical trials have demonstrated the efficacy of FK506 ointment for atopic dermatitis, many case reports have been published regarding other inflammatory skin diseases. The ascomycin derivative ASM 981 has many of the properties of FK506 but less data is available at present. Sirolimus (Rapamycin) is structurally related to FK506 but has other biological effects since its molecular actions involve different biochemical pathways. A review of the biochemical and cellular properties, mode of action, therapeutic efficacy and unwanted side effects, as well as data from clinical trials and status of licensing, is given for the respective drugs.