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In an attempt to find an effective therapy for necrobiosis lipoidica, we have treated six patients with this disease with a 5-week course of systemic corticosteroids. This treatment resulted in complete cessation of disease activity in all patients and no recurrence in a mean follow-up period of 7 months; however, restitution of atrophic skin lesions could not he achieved. The therapy was well tolerated and did not pose problems, even in diabetic patients. These results strongly suggest that short-course therapy of necrobiosis lipoidica with corticosteroids is of lasting benefit to these patients and should probably be considered early in the course of their skin disease. [ABSTRACT FROM AUTHOR]

Recombinant human IFN-γ, used for treatment of melanoma and renal carcinoma, was found to induce HLA-DR expression on human keratinocytes in vivo. HLA-DR antigens bound to keratinocytes of the basal and suprabasal layers of the epidermis were observed after intramuscular or intravenous injections of 0·5 mg/kg body weight IFN-γ, 3 times a week. Keratinocyte-bound HLA-DR antigens were first observed at the beginning of the third or fourth week of treatment, but HLA-DQ and HLA-DP antigens were never detected on keratinocytes. The intracytoplasmic constant (γ) chain of the class II molecules was also not detectable within the keratinocytes. Patients who received IFN-α2 therapy, did not exhibit keratinocyte-bound HLA-DR antigens. [ABSTRACT FROM AUTHOR]

Although late recurrence of cutaneous malignant melanoma (CMM) is a known clinical phenomenon, only 12 adequately documented cases exist in the literature. We describe two female patients with CMM who developed melanoma metastases 18 years after radical excision of their primary tumours and presumed cure. Increasing numbers of reports of cases of delayed metastases of CMM might have implications for management and follow up of melanoma patients. [ABSTRACT FROM AUTHOR]

Amiodarone, used in the treatment of cardiac arrythmia, may lead to severe discolouration of sun-exposed skin. The lysosomal storage of a lipid-like material has been shown to be the morphological substrate for this cutaneous hyperpigmentation. Examination of peripheral white blood cells of amiodarone-treated patients disclosed identical lysosomal structures indicating that amiodarone treatment leads to a more generalized lysosomal storage of lipids and of amiodarone and its metabolites. [ABSTRACT FROM AUTHOR]

Presents letters to the editor referencing articles discussed in previous issues of the "British Journal of Dermatology." Chronic actinic dermatitis; Effects of lasers in psoriasis; Treatment of steatocystoma multiplex suppurativum with isotretinoin.

In patients undergoing photochemotherapy (PUVA) a selective accumulation of lipid droplets was observed within the cytoplasm of melanocytes. Keratinocytes did not develop lipid droplets. Within 2 months after clearing of psoriasis the droplets gradually vanished and did not reappear even during maintenance PUVA therapy. Increased intracellular lipid deposits are usually taken to herald cell degeneration. Since the maximum lipid accumulation coincided with the end of the clearing phase when melanin production was at its height, the intramelanocytic lipid may have been a morphological sign of over-stimulation of melanocytes, which could eventually result in melanocyte destruction. Since excess melanin may be cytotoxic for melanocytes this may explain the irreversible hypopigmentation which develops in some patients treated with PUVA. [ABSTRACT FROM AUTHOR]

Photochemotherapy (PUVA) with oral methoxsalen and UV-A was instituted in 8 patients with generalized pustular psoriasis (von Zumbusch). Complete clearing of skin lesions and of systemic symptoms was achieved in all patients. Patients who had been on systemic treatment prior to PUVA had to be treated with considerably more UV-A energy than patients who had received topical therapy alone. Seven patients were kept in complete remission by maintenance therapy for an observation period of up to i\ years. Side effects of systemic pre-PUVA treatment resolved during several months of maintenance therapy. [ABSTRACT FROM AUTHOR]

Photochemotherapy is a recently developed approach to the treatment of psoriasis (Parrish et at, 1974) which may have initiated a new era in photomedicine. It is based on the interaction of longwave ultraviolet light (UVA) and a systemically administered photoactive compound, 8-methoxy-psoralen, within the skin; hence the designation PUVA (PUVA = 8-rnethoxy-Psoralen plus UVA) (Wolff a at, 1976). As the penetration of UVA is restricted to the superficial layers of the skin and as the photoactivation of 8-methoxypsoralen occurs only under the influence of these wave-lengths (365 nm), PUVA represents a successful attempt to localize systemic chemotherapy to a diseased organ, the skin, sparing other tissues from cytotoxic effects (Parrish et. al., 1974; Wolffa al., 1975b, 1976). The dramatic effectiveness of this treatment, both in clearing psoriatic lesions and maintaining patients in a state of remission, has been demonstrated in several studies (Parrish et. al, 1974; Wolfi al., 1975a, b, 1976). The rationale of PUVA therapy is to bring psoriasis into remission by repeated, controlled photosensitization reactions which are monitored to remain within a therapeutically desired range. Since phototoxic erythema is a limiting factor, careful attention to dosimetry is essential and it is therefore the dosimetry system which is a key to both the effectiveness and safety of PUVA. The following account outlines and discusses criteria for dosimetry that have proved useful in 230 patients with severe, generalized psoriasis. [ABSTRACT FROM AUTHOR]

Cell culture experiments using haematoporphyrin photosensitized bovine hoof fibroblasts and long-wave uv-irradiation revealed two distinct and separable patterns of lethal photosensitization according to two different sensitization procedures; (1) Photosensitization of cell membranes by short exposure (5 min) of cells to haematoporphyrin. (2) Cytoplasmic photosensitization elicited by a 2 h exposure of cells to haematoporphyrin. Cell membrane photosensitization was reversible by incubation of cells in serum which removed surface bound haematoporphyrin; cytoplasmic photosensitization was irreversible. Beta-carotene was tested in these two systems and the following results were obtained: (1) Preincubation of bovine hoof fibroblasts in β-carotene protects from lethal haematoporphyrin photosensitization. (2) Protection with β-carotene is achieved against both types of photosensitization. (3) The protective effect of β-carotene depends upon the duration of pretreatment, reaching a maximum after 7 days. (4) β-carotene protection is maintained even after trypsinization of bovine hoof fibroblasts and withdrawal of β-carotene from the medium for 24 h or more. (5) Haematoporphyrin sensitized bovine hoof fibroblasts show a distinct pattern of red fluorescence for each type of photosensitization. Incubation of bovine hoof fibroblasts in β-carotene prior to haematoporphyrin photosensitization results in a pronounced reduction of red fluorescence. Some of these data indicate that β-carotene acts, at least in cell membrane photosensitization, at the level of the cell membrane into which it appears to be incorporated. [ABSTRACT FROM AUTHOR]

The immediate response of erythropoietic protoporphyria (EPP) skin to long-wave ultraviolet radiation (UVR) was studied with the electron microscope. The main finding was severe vascular injury. This was confined to the superficial vessels of the dermis and consisted of endothelial cell degeneration and a pronounced leakage of vascular contents. In contrast, the epidermis showed no abnormalities. Short-wave UV irradiation of EPP skin resulted in epidermal changes typical for the usual sunburn reaction and spared the dermal blood vessels. The following conclusions are drawn: (i) Endothelial cells are the primary cellular target for the photodynamic reaction in EN'. (ii) The fibrillar material, characteristic for chronic El'? lesions, originates from the vessels and vascular contents. (iii) The multilayered basement membranes observed in such lesions reflect multiple consecutive reparative processes that follow endothelial injuries. [ABSTRACT FROM AUTHOR]

The heavily pigmented but otherwise normal appearing skin of a patient with diffuse melanosis secondary to metastatic malignant melanoma was examined by electron microscopy and electron microscopic cytochemistry. The findings indicate that the slate-blue colour of this melanosis is due, for the most part, to melanosomes derived from melanoma cells that have spread to and throughout the skin of the patient. The dissemination of individual, discrete tumour cells within the patient's: dermis represents a unique form of single cell metastasization. [ABSTRACT FROM AUTHOR]

Human studies using oral cyclosporin A (CyA; Sandimmun®) therapy for psoriasis have been in progress for nearly 9 years. Cumulative data of the clinical effects of this therapy in 1000 patients have been collected, and are derived from multiple open and controlled studies. The efficacy of this treatment in psoriasis is well recognized, and the relative safety of up to 2 years of therapy is also established, provided that the guidelines are observed. However, there is concern regarding the longterm safety of CyA treatment of psoriasis as experience is still limited. Careful monitoring of all CyA-treated patients is therefore mandatory, and CyA should only be used by dermatologists who have expertise in its use. During treatment, co-operation with an experienced nephrologist is strongly recommended. [ABSTRACT FROM AUTHOR]

A tan induced by 8-methoxypsoralen-long wave ultraviolet light has proved an effective photo-protective sunscreen in 5 patients with long wave ultraviolet light-induced polymorphic light eruption. [ABSTRACT FROM AUTHOR]

Presents the foreword to the June 2, 1990 issue of the "British Journal of Dermatology."

Background: A multicentre, centrally randomized, open-labelled study with temozolomide and interferon (IFN)-alpha 2b was carried out to study the therapeutic effect in patients with metastatic melanoma stage IV., Objectives: The response rate, efficacy, side-effects, reasons for discontinuation of therapy and survival rate of 47 patients treated with temozolomide in combination with two different dosing regimens of IFN-alpha 2b were documented., Patients/methods: Twenty-nine male and 18 female patients (mean age 57.6 years, range 34-74) were centrally randomized to two different arms: 20 patients received a treatment schedule with temozolomide 150 mg m(-2) on days 1-5 orally every 28 days in combination with IFN-alpha 2b 10 MIU m(-2) every other day and 27 patients received temozolomide 150 mg m(-2) on days 1-5 every 28 days in combination with IFN-alpha 2b in a fixed dose of 10 MIU every other day., Results: We observed an overall response rate of 27.6% comprising five complete remissions (10.6%: one patient group A, four patients group B), in two of these five patients at the last follow-up in the study (4.3%, both in group B); and eight partial remissions (17%: six patients in group A, two patients in group B), in three of these eight patients at the last follow-up in the study (6.4%, two patients in group A, one patient in group B). Three patients showed stable disease (6.4%: one patient in group A, two patients in group B). Mean survival was 14.5 months [95% confidence interval (CI) 10-19] with no significant differences between treatment groups. However, there was a significant correlation with response after three cycles (log rank test, P < 0.03). Within the 32 patients who completed at least three cycles of therapy, seven patients (three in group A and four in group B) with a partial or complete response showed a significantly better mean survival of 30.6 months (95% CI 19.1-42) compared with 25 patients who did not respond (13.7 months 95% CI 9.2-18.3). In total, patients with at least one complete remission showed the longest survival (37.1 months 95% CI 26.3-47.9), followed by patients with at least one partial response (17.4 95% CI 10.9-23.9). Major side-effects of the treatment were nausea, vomiting, headache, leucopenia, thrombopenia, elevation of liver function parameters and neurological symptoms. In five patients, the side-effects led to a discontinuation of treatment: neurological symptoms (two patients), sepsis (one patient), brain haemorrhage (one patient) and exanthema (one patient). There were no treatment-related deaths., Conclusions: The combination of temozolomide and IFN-alpha 2b can easily be administered and shows tolerable toxicity. When an objective response occurs after three cycles, it indicates a significant survival advantage.

An 8-year-old boy with hereditary angio-oedema was treated with danazol under close endocrinological supervision. The boy's C1 esterase inhibitor (C1inh) and C4 levels increased rapidly to near normal values under a daily dose of 400 mg and were maintained at about 50% of the normal by maintenance doses of 200 mg danazol every other day. Throughout the entire treatment period (11 months) the boy has been maintained free from attacks of angio-oedema. No hormonal imbalance was detected in the follow-up period. Our results indicate that danazol should be suitable for the treatment of HAE not only in adults but also in prepubescent children.

To determine the significance of circulating immune complexes in dermatitis herpetiformis, serum samples from thirty patients with active disease were tested by a C1q binding radioassay, while serum samples from twenty-one of these patients were tested by a monoclonal rheumatoid factor (mRF) inhibition radioassay. By direct immunofluorescence, all patients demonstrated typical IgA deposition in dermal papillae. Using the C1q binding assay, only seven of forty-two serum samples had elevated C1q binding activity, while by the mRF inhibition assay, thirteen of twenty-five samples had elevated immune complex levels. Nine of these latter thirteen positive serum samples, however, were minimally elevated. Thus, IgG and/or IgM containing immune complexes are infrequently present, or at very low levels, in sera of patients with active dermatitis herpetiformis.

5-Methoxypsoralen (5-MOP, Bergapten) was evaluated as a potential photosensitizing drug in oral photochemotherapy of psoriasis. Treatment results indicate that (1) 5-MOP is as effective as, and in high doses more effective than, 8-methoxypsoralen in clearing psoriatic lesions; (2) therapeutic doses of 5-MOP do not lead to erythema; the acute side-effects of 8-MOP PUVA therapy--erythema, blistering, pruritus--are thus avoided; (3) even high doses of 5-MOP are not followed by nausea. 5-MOP PUVA therapy thus represents a real alternative to 8-MOP PUVA, its advantages over 8-MOP PUVA being greater safety and patient acceptance.

Skin biopsies of 243 patients treated with photochemotherapy (PUVA) for 1--4 years were examined histologically. Two hundred and six patients were examined retrospectively after total cumulative UV-A doses of 579 . 6 +/- 598 . 0 J/cm2 (mean +/- s.d.). An eosinophilic homogenization and a reduction of elastic fibres at the dermo--epidermal junction, and an increase of dermal macrophages were found as possible abnormalities. However, except for the increase of melanophages there was no statistically significant correlation between the incidence of these changes, the total UV-A dose applied and the skin type of the patients. Neither were such correlations found in thirty-seven patients biopsies twice after 394 . 8 +/- 267 . 6 J/cm2 and 808 . 5 +/- 458 . 9 J/cm2 (mean +/- s.d.), respectively. Studies with direct immunofluorescence techniques revealed no immunoglobulin deposits in PUVA treated skin in fifty-six patients after 469 . 2 +/- 370 . 2 J/cm2; antinuclear antibodies were observed in 4 . 6% of 129 patients after 169 J/cm2 (mean); in 11% of fifty-three patients reexamined after 381 J/cm2 (mean) and in 13 . 6% of twenty-two patients reexamined a second time after 643 J/cm2 (mean). Thirteen out of a total of 572 patients developed a peculiar mottling of skin in areas previously overdosed by PUVA. Subepidermal homogenization and reduction of elastic fibres were found in 45% of the patients, indicating that these changes indeed are a consequence of PUVA. Nuclear and cellular irregularities were found in 45% of the biopsies and 63% showed a disturbed epidermal architecture, but no carcinomas were observed. PUVA-induced mottling was reversible in 31%, partially reversible in 15%, but continued to be present in 54%.