Multicentre, phase II trial on the safety and efficacy of topical tacrolimus ointment for the treatment of lichen sclerosus.

BACKGROUND: Lichen sclerosus is a chronic inflammatory autoimmune disease causing significant sclerosis, atrophy and pruritus. Treatment remains unsatisfactory, with potent corticosteroids being the most effective therapy. OBJECTIVES: To conduct a multicentre, phase II trial to assess the safety and efficacy of tacrolimus ointment 0.1% for the treatment of lichen sclerosus with a follow-up period of 18 months at 10 university and teaching hospitals in Germany and Austria. METHODS: Eighty-four patients (49 women, 32 men and three girls) aged between 5 and 85 years with long-standing, active lichen sclerosus (79 with anogenital and five with extragenital localization) were treated with topical tacrolimus ointment 0.1% twice daily for 16 weeks. Computerized analysis of the lesional area was performed. The primary endpoint was clearance of active lichen sclerosus. Secondary endpoints were time to optimal response, reduction of sclerosis and duration of remission. RESULTS: The primary endpoint (clearance of active lichen sclerosus) was reached by 43% of patients at 24 weeks of treatment. Partial resolution was reached in 34% of patients. Maximal effects occurred between week 10 and 24 of therapy. Treatment led to a significant reduction of the total lesional area (P < 0.01) and to a significant decline in the total symptom score (P < 0.005). Symptoms (e.g. itching) and findings (erythema, erosions and induration) showed significant improvement. No serious adverse events were observed. There were three (9%) recurrences during the follow-up period. CONCLUSIONS: Topical tacrolimus ointment 0.1% was safe and effective for the treatment of long-standing active lichen sclerosus.

[Acanthosis nigricans, papillomatosis mucosae and "tripe palms" in a patient with metastasized gastric carcinoma]. / Acanthosis nigricans, Papillomatosis mucosae und "tripe palms" bei einem Patienten mit metastasiertem Magenkarzinom.

HISTORY AND CLINICAL FINDINGS: A 48-year-old obese man presented with thickening, coarseness and hyperpigmentation of the skin, especially of the intertriginous areas, papillomatous to verrucous lesions of the lips and buccal oral mucosa, and hyperkeratosis of the palms ("tripe palms") and soles. He was obese, reported sleep apnea and had a history of hyperuricemia, mixed hyperlipidemia and previous myocardial infarction. He was on a maintenance dose of a proton pump inhibitor for chronic gastro-esophageal reflux. EXAMINATIONS: Immunohistochemical studies of the skin lesion revealed increased epidermal immunoreactivity for the melanocortin-1-receptor. Increased levels of tumor markers CA 19-9 (141100 U/ml), CA 72-4 (755 U/ml) and CEA (189 ng/ml) were found in the serum. Gastroscopic findings were suspicious of adenocarcinoma of the stomach: it was classified histologically as a signet-ring cell, non-mucinous adenocarcinoma. At the time of diagnosis the tumor had already metastasized to perigastric and peripancreatic lymph nodes with peritoneal carcinosis. TREATMENT AND COURSE: Since a curative resection was impossible a gastrojejunostomy was carried out. After this the patient received several courses of chemotherapy according to different schemes. Serum tumor marker levels and cutaneous signs regressed several times. CONCLUSIONS: Marked acanthosis nigricans -- especially when associated with further cutaneous markers of malignancy, e.g. mucocutaneous papillomatosis or so-called tripe palms -- calls for thorough search for malignant tumor, also if metabolic or endocrinological abnormalities co-exist. A pathogenetic role of a-melanocyte-stimulating hormone in the development of the skin changes is suggested.

Reactive perforating collagenosis associated with scabies in a diabetic.

Reactive perforating collagenosis (RPC) in adults commonly manifests in patients with diabetes mellitus. Pruritus and consequent induced scratching have been identified as the bases for the evolution of this skin disease. We present the unusual case of a 55-year-old female diabetic with characteristic umbilicated skin lesions and a long history of scabies. Histology from a crusty nodule revealed transepidermal elimination of collagen. Following antiscabietic treatment, two courses of oral doxycycline demonstrated beneficial effects in controlling the perforating skin disorder.

[Exudative erythema multiforme with transition to a toxic epidermal necrolysis after taking aceclofenac (Beofenac)]. / Erythema exsudativum multiforme mit Ubergang in eine toxische epidermale Nekrolyse nach Einnahme von Aceclofenac (Beofenac).

HISTORY AND CLINICAL FINDINGS: A 75-year-old woman took aceclofenac (100 mg/day) for 15 days for long-standing arthritis. Starting with erythema of the face she developed multiple target lesions with central bullae on her neck, chest, back, including the palmoplantar region. In several areas the lesions became confluent and showed wide detachment. The mucous membranes of the eyes, mouth and genitalia also showed marked inflammation, most prominent were large erosions in the mouth. The clinical course culminated in an overall skin loss of about 15 % of the total body surface area. DIAGNOSIS, TREATMENT AND COURSE: Treatment with topical and systemic corticosteroids as well as antiseptics resulted in complete clearing of the cutaneous lesions within 4 weeks. Various analgetics, particularly the closely related diclofenac, were tolerated without any side-effects after oral intake. Re-exposition with aceclofenac was rejected due to safety reasons. CONCLUSION: This is the first report of a potentially life-threatening adverse cutaneous drug reaction after taking with aceclofenac.

Tetrazepam drug sensitivity -- usefulness of the patch test.

The muscle relaxant tetrazepam may cause severe cutaneous adverse effects. We report 4 cases of varying intensity: Stevens-Johnson syndrome, erythema-multiforme-like exanthema, maculopapular and maculo-urticarial exanthema. Patch testing with tetrazepam (10% in petrolatum) was strongly positive in the 2 patients with severe skin eruptions and weakly positive in the other 2. Oral rechallenge with tetrazepam was positive in 3 patients (1 not done). Diazepam, with a similar chemical structure to tetrazepam, was negative on patch testing and on oral challenge testing in 2 patients. Although the optimal patch test concentration of tetrazepam has still to be determined, it is a useful diagnostic tool to confirm sensitization, particularly in patients with severe bullous eruptions.

[Oral antibiotics with antiinflammatory/ immunomodulatory effects in the treatment of various dermatoses]. / Orale Antibiotika mit antiinflammatorischer/immunmodulatorischer Wirkung für die Therapie verschiedener Dermatosen.

A range of antibiotics has been shown to modify host functions apart from the antimicrobial potency. They may directly influence phagocyte and lymphocyte function, as well as chemotaxis. Effects on the generation and release of various cytokines involved in the inflammatory process have been studied both in vivo and in vitro. However, the molecular mechanisms have not been elucidated in detail. It is suggested that antibiotics can exert immunopharmacological effects on the basis of structure-activity relationships independent of their antibacterial activity. We present a collection of clinical studies and case reports dealing with the potential benefits of systemic antibiotics in the treatment of selected dermatoses which have primarily been classified as non-infectious. Generally accepted treatments such as dapsone in dermatitis herpetiformis and leukocytoclastic vasculitis or chloroquine in lupus erythematosus have not been considered. Based on existing clinical trials with a higher number of cases the following antibiotics have been shown to be effective: erythromycin in bullous pemphigoid and pityriasis rosea as well as tetracyclines in pemphigus vulgaris, bullous pemphigoid and pustulosis palmaris et plantaris. However, most reports have to be viewed critically due to the uncontrolled study design, particularly in dermatoses with a tendency to spontaneous resolution. Despite this lack of evidence-based data, it is important for the clinician to know about the potential use of antibiotics for various skin disorders as a primary treatment option or steroid-sparing therapeutic adjunct. In clinical practice the use of antibiotics depends on various factors including the severity of the disease, the patient's age, contraindications to conventional therapeutic regiments and economic considerations.

Pyodermatitis-pyostomatitis vegetans: a clinical course of two decades with response to cyclosporine and low-dose prednisolone.

Pyodermatitis-pyostomatitis vegetans is a rare, polymorphous inflammatory disorder of the skin and oral mucosa first described by Hallopeau in 1898. On the skin papules, pustules and reddish brown annular vegetating plaques develop, most frequently in the intertriginous areas. In the mouth, yellowish flat ulcerations arise, typically in the shape of "snail tracks". The association with inflammatory bowel disease is very common. An unusual case with a chronic relapsing course of 2 decades is presented. Gastrointestinal inflammation was absent. Prednisolone in high and medium doses suppressed most lesions. Various attempts with other drugs (dapsone, isotretinoin, azathioprine) to reduce the corticosteroid dose failed. This is the first report of the successful treatment of pyodermatitis-pyostomatitis vegetans with cyclosporin A, which proved to be highly effective in this regard. The unknown aetiopathology of pyodermatitis-pyostomatitis vegetans is discussed.