The effect of prostaglandin D2 on the response of human skin to histamine.

The interaction of prostaglandin D2 (PGD2) and histamine in human skin was studied by intradermal injection of the compounds alone or in combination in healthy volunteers. Responses were recorded by measurement of areas of wheal and erythema, and changes in cutaneous blood flow quantified using a laser Doppler flow meter. The effect of a near-threshold dose of PGD2 on histamine dose-response relationships and on the response to a single low dose of histamine were examined. Histamine caused dose-related increases in blood flow and in areas of wheal and erythema in human skin. Prostaglandin D2 caused dose-related increases in blood flow and erythema area, but not wheal area, in the dose range used. When the compounds were injected together, PGD2 did not potentiate the increase in blood flow and areas of wheal and erythema due to histamine. The modest augmentation of histamine response in the presence of PGD2 could be attributed to summation alone. The role of PGD2 in cutaneous disorders such as the physical urticarias, in which its release has been demonstrated, is therefore uncertain. In the amounts measured in the urticarias, it is unlikely alone to cause a significant cutaneous response; nor does it appear to act by potentiation of the response to histamine.

Mycobacterium avium-intracellulare infection associated with hairy-cell leukemia.

A 66-year-old man with hairy-cell leukemia was treated successfully with interferon alfa, with normalization of his hematologic parameters. After 2.5 months he became ill again and, following extensive investigation, Mycobacterium avium-intracellulare grew from a bone marrow specimen. Although initiation of quadruple antituberculous chemotherapy resulted in an improvement of his general condition, after two months he started to develop widespread cutaneous and subcutaneous nodules, biopsy of which showed appearances compatible with mycobacterial infection. Over the next two months the skin lesions progressed slowly so erythromycin, to which in vitro testing showed the organism to be sensitive, was added to his therapy. This resulted in a marked improvement of all skin lesions. This case is the first to be reported of disseminated atypical mycobacterial infection in a patient receiving interferon treatment for hairy-cell leukemia.

Monitoring patients on methotrexate: hepatic fibrosis not seen in patients with normal serum assays of aminoterminal peptide of type III procollagen.

BACKGROUND: The aminoterminal peptide of type III procollagen (PIIINP) is formed during the synthesis of type III collagen and can be measured in the serum. It has been used as a marker for hepatic fibrosis in patients on long-term methotrexate and it has been suggested that serial assay of PIIINP could reduce or eliminate the need for liver biopsies in these patients. OBJECTIVES: To determine whether routine use of the PIIINP assay in a cohort of patients on methotrexate would reliably identify those who were developing hepatic fibrosis and exclude those who were not, thereby reducing or eliminating the need for liver biopsies in this latter group. METHODS: Data were available from a clinical series of 38 patients on methotrexate, who had undergone a total of 70 liver biopsies and 306 PIIINP assays. Liver biopsies were graded using the Roenigk classification. RESULTS: In 34 patients, the findings on 46 liver biopsies could be compared with the results of contemporaneous PIIINP assays. Apart from two biopsies from two patients where fibrosis was no longer detected on a subsequent biopsy, all four biopsies showing fibrosis had abnormal results on over half of the associated PIIINP assays. There were no biopsies showing fibrosis where all associated PIIINP assays were normal. However, 50% of biopsies without fibrosis had at least one abnormal associated assay. In 23 patients, the results of serial PIIINP assays performed between two sequential liver biopsies were correlated with changes in the biopsy in terms of fibrosis. Data were available for 32 pairs of liver biopsies. Apart from a biopsy pair in one patient where fibrosis on the second biopsy was not detected on a third biopsy, all four biopsy pairs defined as showing deterioration had abnormal results on over half of the intervening PIIINP assays. There were no biopsy pairs showing deterioration where all intervening assay results were normal. However, 63% of stable biopsy pairs had at least one abnormal intervening assay. Two patients with nonalcoholic steatohepatitis, which manifests a pattern of fibrosis not scored under the Roenigk classification, had persistently and substantially elevated PIIINP levels. CONCLUSIONS: The data presented support the view that follow-up liver biopsies, as recommended by published guidelines, for patients on long-term low-dose methotrexate can be avoided if PIIINP levels are consistently normal. This approach would have reduced the number of patients requiring biopsy in our series by 45%. The PIIINP assay will also be helpful in the management of patients on methotrexate in whom liver biopsy is contraindicated, and in patients with nonalcoholic steatohepatitis.

Ovarian carcinoma and digital ischaemia.

A case of ovarian carcinoma presenting as digital ischaemia, with progression to gangrene, is described. The case serves as a reminder of an important association, and the potential mechanisms are reviewed.

Acquired perforating dermatosis and diabetic nephropathy--a case report and review of the literature.

A case of acquired perforating dermatosis associated with diabetic nephropathy is described. The case is unusual in that the dermatosis first developed approximately 1 year after renal transplantation rather than at a time when renal function was more severely impaired or during haemodialysis. There was a partial response to treatment with isotretinoin but the use of this drug was limited by the development of hyperlipidaemia. The relevant literature is reviewed.

Malaria: a laboratory risk.

A case is described of malaria contracted in a clinical laboratory by accidental self-inoculation with infected blood.

Relationship between skin type and erythemal response to anthralin.

Anthralin erythema dose-response curves were drawn for thirty adult patients of various skin types who had chronic plaque psoriasis. A small statistically significant difference was observed between the curves for skin types I and IV but this was not thought to be sufficient to account for the clinical impression of increased anthralin irritancy in fair-skinned subjects.

Isotretinoin in the treatment of systemic sclerosis.

Thirteen patients with systemic sclerosis were treated with isotretinoin. Nine patients completed between 6 and 14 months of treatment and all showed an improvement in the cutaneous manifestations of their disease. The drug did not appear to benefit internal organs affected by the disease. Most patients experienced the well-recognized side-effects of retinoids, which in three cases necessitated withdrawal from the study within 3 months. Serum levels of type III procollagen aminopropeptide did not show a consistent decline during treatment, despite a clinical improvement. The mode of action of the reported therapeutic effect of isotretinoin in systemic sclerosis is unclear. There may be a preferential suppression of the synthesis of type I collagen, or the drug may be acting by an unrelated mechanism.

Arachidonic acid metabolism by polymorphonuclear leukocytes in psoriasis.

The metabolism of endogenous arachidonic acid by human polymorphonuclear leukocytes (PMNL) isolated from peripheral blood has been studied in 19 patients with chronic plaque psoriasis and 19 healthy controls. Using calcium ionophore A23187 as a stimulus, the PMNL synthesized leukotriene B4 (LTB4), 6-trans-leukotriene B4, 12-epi-6-trans-LTB4, and 5-hydroxy-6,8,11,14-eicosatetraenoic acid. There was no significant difference in the amounts of the products formed between the psoriatic and control groups. The elevated levels of LTB4 that have been described in psoriatic skin may therefore be due to the PMNL infiltrate or to enhanced synthesis by another cell type. The reported increase in activity of the circulating PMNL in psoriasis does not appear to be due to increased 5-lipoxygenase activity in these cells.

Isotretinoin and curly hair.

A 46-year-old woman with systemic sclerosis was treated with isotretinoin for 1 year. She obtained considerable benefit and experienced only minor side-effects from the drug, comparable to those familiar to dermatologists in the treatment of acne. However, she noticed that her hair became pronouncedly more curly during treatment.

The metabolism of leukotriene B4 by peripheral blood polymorphonuclear leukocytes in psoriasis.

The formation of leukotriene B4 and its omega-oxidised metabolites has been compared in calcium ionophore-stimulated polymorphonuclear leukocytes, in the absence of exogenous substrate, from fourteen psoriatic subjects and thirteen healthy controls. Although there was no significant difference in the levels of leukotriene B4, the psoriatic cells synthesised significantly greater amounts of omega-oxidation products than control cells. This difference was confirmed in an experiment comparing the time course of formation of the omega-oxidation products of leukotriene B4, under similar conditions, in polymorphonuclear leukocytes from four psoriatic subjects and three healthy controls. The kinetic constants for the metabolism of exogenous leukotriene B4 by 20-hydroxylase were determined by a radiochromatographic enzyme assay in polymorphonuclear leukocytes from three patients with psoriasis and three healthy controls. No significant differences were found in the apparent Km and Vmax values. It is concluded that the increased formation of omega-oxidation products in psoriatic cells may be secondary to increased synthesis of leukotriene B4 by these cells, with consequent increased metabolism, rather than to an inherent abnormality of the 20-hydroxylase system. Further work is needed to determine the kinetics of the enzymes involved in leukotriene B4 synthesis in the psoriatic polymorphonuclear leukocyte, and also to assess the contribution of the leukotriene B4 and omega-oxidation products from polymorphonuclear leukocytes infiltrating the skin to the pathogenesis of the psoriatic lesion.

The effect of thalidomide on arachidonic acid metabolism in human polymorphonuclear leukocytes and platelets.

The effect of thalidomide on the metabolism of arachidonic acid by purified washed human platelets and polymorphonuclear leukocytes was examined. The drug was found to be without effect under the conditions used. The action of thalidomide cannot therefore be attributed to a direct inhibition of prostaglandin or leukotriene biosynthesis.

Arachidonic acid metabolism by peripheral blood cells in psoriasis.

The metabolism of arachidonic acid by mixed suspensions of leukocytes and platelets prepared from peripheral blood has been studied in 20 patients with psoriasis and 21 healthy controls. A lipoxygenase-derived product, identified as 12,20-dihydroxy-5,8,10,14-eicosatetraenoic acid was formed in increased amounts by the cell suspension from the psoriatic patients. This product results from the metabolism of platelet-derived 12-hydroxy-5,8,10,14-eicosatetraenoic acid by the polymorphonuclear leukocyte 20-hydroxylase enzyme. By contrast, synthesis of the cyclo-oxygenase products 12-hydroxy-5,8,10-heptadecatrienoic acid and thromboxane B2 was diminished. Benoxaprofen, which is known to be beneficial in psoriasis, diminished the levels of 12,20-dihydroxy-5,8,10,14-eicosatetraenoic acid formed in vitro.

Isotretinoin and lung function in systemic sclerosis.

During an open prospective study of the synthetic retinoid isotretinoin in ten patients with systemic sclerosis, one patient developed an eosinophilic pleural effusion and two patients were noticed to have asymptomatic deterioration in pulmonary function tests. The pulmonary function of all treated patients was then compared retrospectively with a similar control group of patients not treated with isotretinoin. There was a significantly greater decrease in the 1-s forced expiratory volume and transfer coefficient in the patients with systemic sclerosis being treated with isotretinoin in comparison to the untreated control patients. Studies of lung function in patients treated with isotretinoin for other indications are required.

Minor skin surgery. Are prophylactic antibiotics ever needed for curettage?

Curettage of skin lesions was not followed by bacteraemia in 22 patients. The risk of bacterial endocarditis after curettage and other minor skin surgery is small but should not be overlooked in those with a prosthetic heart valve, a history of other cardiac surgery, a previous episode of infective endocarditis, drug addiction, diabetes, alcoholism, immunosuppression, or renal failure--especially where the skin lesion might be infected.

The effects of dietary supplementation with fish oil in patients with psoriasis.

Ten patients with psoriasis resistant to conventional topical treatment were given dietary supplements of fish oil, providing approximately 12 g of eicosapentaenoic acid daily for a period of at least 6 weeks. In eight patients there was a modest improvement in their psoriasis, the principal effects being a diminution of erythema and scaling. The dietary treatment resulted in a substantial inhibition of leukotriene B4 production by the peripheral blood polymorphonuclear leukocytes in vitro. The discrepancy between the high degree of inhibition of leukotriene B4 synthesis and the modest therapeutic effect suggests that leukotriene B4 is not the only mediator involved in the development of the psoriatic lesion. Furthermore, the in vivo cutaneous levels of leukotriene B4 might not have been inhibited to the same extent as the polymorphonuclear leukocyte levels in vitro. Further studies on the use of fish oil supplements, both on their own and in conjunction with other forms of treatment in psoriasis are warranted. It will also be important to determine whether the altered profile of 5-lipoxygenase products found in the blood is also seen in the skin.

Azathioprine treatment in chronic actinic dermatitis: a double-blind controlled trial with monitoring of exposure to ultraviolet radiation.

Oral azathioprine was compared with placebo in a double-blind controlled trial of therapy in chronic actinic dermatitis (CAD), a rare eczematous photodermatosis. Eighteen severely affected patients were randomly allocated to azathioprine 50 mg t.d.s. or placebo over a 2-year period. Severity of itch and rash were assessed weekly by each patient on a visual analogue scale and overall clinical status monthly by a medical observer. Monitoring of patient ultraviolet radiation (UVR) exposure was undertaken throughout treatment by polysulphone film lapel-badge dosimetry. Five of 8 patients treated with azathioprine but none of 10 placebo patients achieved remission within 6 months. One patient could not tolerate treatment because of gastrointestinal effects. No haematological or hepatic abnormality was noted. The marked improvement in clinical status of actively treated patients (P less than 0.02, Fisher's exact test), led to early termination of the trial. Oral azathioprine therapy is an effective and usually well tolerated treatment in chronic actinic dermatitis.

Thalidomide in severe orogenital ulceration.

Thalidomide was given to 15 patients with severe orogenital ulceration (OGU). 4 patients underwent a double-blind controlled trial with glutethimide as placebo and 11 were treated openly. Treatment with thalidomide produced complete resolution of ulcers in 14 and significant improvement in the remaining patient. No peripheral neuropathies developed. Patients did not respond to glutethimide. Thalidomide is an effective treatment for severe OGU. Adequate contraceptive measures should be taken during treatment.