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OBJECTIVE Previous endocrine studies of women with acne have produced diverse results. This study was designed to seek evidence, from endocrine and genetic studies, for impaired steroid biosynthesis in patients with acne. DESIGN Adrenal stimulation tests with synthetic adrenocorticotrophic hormone (ACTH) were performed. MEASUREMENTS Steroid hormones were measured basally and 30 minutes after ACTH. The results were correlated with analysis of the steroid 21-hydroxylase gene (CYP21). PATIENTS Fifty-one consecutive female patients (mean age 27.1 years) referred with acne. RESULTS The median plasma 17-hydroxyprogesterone (17-OHP) before and 30 minutes after ACTH were 2.5 nmol/l (range 1.1-8.2) and 7.3 (2.1-17.8) nmol/l which were significantly above normal female controls (n = 11, mean age 25.6 years) at 1.5 (0.9-4.2) and 4.6 (2.6-8.4) nmol/l. Eighteen of 51 acne patients showed an abnormal 17-OHP response. The 21-hydroxylase gene (CYP21) was examined for major deletions and for three common point mutations in 31 of the patients (14 with exaggerated 17-OHP response). One patient had a deletion of CYP21 on one allele consistent with carrier status for the classical congenital adrenal hyperplasia (CAH). Five patients, one of whom had a normal 17-OHP response to Synacthen, were heterozygous for the val 281 leu mutation in exon 7 of the CYP21 and were therefore carriers for a mutation associated with late-onset CAH. One patient with a raised 17-OHP response was homozygous for the splice site mutation in intron 2 and one patient with a normal 17-OHP response was heterozygous for the mutation. None of the patients had the ile 172 asn mutation. Eight of the 31 acne patients who had CYP21 gene analysis were carriers for mutations in the 21-hydroxylase gene but only six would have been detected by an abnormal response of 17-OHP on stimulation. CONCLUSION Although alterations of the CYP21 gene were more common in acne than in controls there is a poor correlation between these events and raised steroids and acne. Factors other than mild impairment of CYP21 contribute to the variability of the clinical phenotype in hyperandrogenic states including acne.

Adult patients with severe atopic eczema who had completed a double-blind placebo-controlled crossover trial of a specific formulation of Chinese herbal therapy were offered continued therapy for 1 year. Of 31 patients who completed the original placebo-controlled study and after a washout period and 2 months of further treatment, 17 continued treatment (group 1), 11 chose not to continue treatment (group 2), one was lost to follow-up and two patients originally in group 1 decided to stoptreatment and became pregnant. At the end of the year, 12 of the patients in group 1 had greater than 90% reduction and the remaining five had greater than 60% reduction in clinical scores compared with baseline values. Clinical scores of patients in group 2 gradually deteriorated so that by the end of the year the difference between groups 1 and 2 was highly significant (P=0.005 and P=0.002 for erythema and surface damage, respectively). At the end of the year no patient in group 1 felt able to discontinue treatment permanently, but eight patients were on an alternate-day regimen by 6 months and remained on this regimen until the end of the year, and seven were able to control their eczema with a 1 in every 3 day treatment by the end of the year. The remaining two patients continued on daily treatments. Toxicology screening revealed no abnormalities in either full blood counts or biochemical parameters in any patient on continued treatment. Improvement in disease was not associated with any significant change in serum IgE level or peripheral blood lymphocyte subsets. This study has shown that Chinese herbal therapy produces a sustained remission of disease activity in patients whose atopic eczema had been unresponsive to a variety of conventional treatments. Furthermore it has suggested that withdrawal of treatment in patients whose eczema had responsed to treatment, produces a gradual relapse of the disease but to a severity less than pretreatment levels. No evidence of toxicity was observed in any patient receiving this specific formulation of Chinese herbal therapy, but we advise continued surveillance of patients receiving such therapy

A family with features of Dowling-Degos disease associated with Kitamura's reticulate acropigmentation is reported. There have been three previous reports describing the association of these two conditions. Our family extends four generations, and the proband shows some unusual features not typical of Dowling-Degos disease or Kitamura's reticulate acropigmentation.

We report a patient with phenytoin-induced pseudolymphoma mimicking cutaneous T-cell lymphoma (CTCL). Despite withdrawal of phenytoin, there was persistence of the cutaneous eruption and lymphadenopathy. Southern blot analysis of immunoglobulin and T-cell receptor genes was therefore used to assess whether there was a clonal lymphoid expansion. However, no rearrangement of the beta T-cell receptor gene or immunoglobulin heavy-chain gene was detected in tissue DNA from skin and lymph nodes. One year later the patient became asymptomatic, although he is still at risk of developing a true malignant lymphoma in the future, a condition known as pseudo-pseudolymphoma. It is suggested that genotypic studies may help in the initial diagnosis and the subsequent management of such patients.

There has been considerable interest in traditional Chinese herbal therapy (TCHT) as a new treatment for atopic dermatitis. To establish the efficacy and safety of this treatment, a daily decoction of a formula containing ten herbs that has been found to be beneficial in open studies was tested in a double-blind placebo-controlled study. 40 adult patients with longstanding, refractory, widespread, atopic dermatitis were randomised into two groups to receive 2 months' treatment of either the active formulation of herbs (TCHT) or placebo herbs, followed by a crossover to the other treatment after a 4-week washout period. The main outcome measures were extent and severity of erythema and surface damage as judged by standardised body scores. The patients' own assessments of the overall response to treatment were also sought. The geometric mean score for erythema at the end of active treatment was 12.6 (95% confidence interval [CI] 5.9 to 22.0) and at the end of the placebo phase was 113 (65 to 180). The geometric mean score for surface damage was 11.3 (5.8 to 21.8) and 111.0 (68 to 182), respectively. The 95% CI for the mean geometric ratio for the two values with active treatment was 0.04 to 0.22 for erythema (p less than 0.0005) and 0.04 to 0.27 for surface damage (p less than 0.0005). Of the 31 patients who completed the study and expressed a preference, 20 preferred that phase of the trial in which they received TCHT whereas 4 patients preferred placebo (p less than 0.02). There was a subjective improvement in itching (p less than 0.001) and sleep (p less than 0.078) during the TCHT treatment phase. No side-effects were reported by the patients although many commented on the unpalatability of the decoction. TCHT seems to benefit patients with atopic dermatitis. Palatability of the treatment needs to be improved and its safety assured.

A patient with Ehlers-Danlos syndrome type II who developed cutis laxa of the lower back in childhood is reported. Cutis laxa is an uncommon complication of Ehlers-Danlos syndrome (EDS) usually occurring in later life.' We report a patient with Ehlers-Danlos syndrome type II (mitis) who developed cutis laxa. This patient is highly unusual as the onset of cutis laxa was in childhood, and the lax skin is localized to an area across the lower back.

Two cases of reticulate acropigmentation of Dohi are reported, both patients demonstrating the typical features of this disorder. Reticulate acropigmentation of Dohi (dyschromatosis symmetrica hereditaria or symmetrical dyschromatosis of the extremities) is characterized by pigmented and depigmented macules mixed in a reticulate pattern on the extremities. It was first described in 12 patients from Japan, where it appears to be a well-established condition. Patients have been reported from Europe and a family from India has recently been described. We report two cases of reticulate acropigmentation of Dohi occurring in an Afro-Caribbean and an Indian patient, in order to alert clinicians to the possibility that this disorder may present in the UK.

We report a patient with generalized morphoea secondary to porphyria cutanea tarda, who responded to treatment with cyclosporin. The differences between the sclerodermatous skin changes seen in porphyria cutanea tarda and generalized morphoea are discussed.

We report a patient with severe psoriatic arthritis in whom the severity of both the arthritis and psoriasis fluctuated with the menstrual cycle. These features failed to improve with standard therapy, but there was a prompt response to treatment which suppressed oestrogen secretion. Such treatment should be considered in patients with disabling cyclical changes in psoriatic arthritis.

The development of pellagra in a patient treated with 5-fluorouracil for malignant disease is reported. The aetiology of pellagra in this patient is discussed, and the reasons for possible under-diagnosis of pellagra in association with malignant disease considered. We report a patient who presented with the typical skin changes of pellagra. The rash, and an associated acute deterioration in cerebral function, were exacerbated by treatment with 5-fluorouracil. The importance of considering nicotinic-acid deficiency in patients with malignant disease has not been emphasized in the literature.

We report a patient who developed a bullous-pemphigoid-like eruption associated with scabies. A subsequent recrudescence of the scabies was associated with recurrence of the bullous eruption.

Summary A 25-year-old man suffering form acute myeloid leukaemia developed a solitary lesion on the upper abdominal wall 6 months after receiving an autologous bone marrow transplant. These lesion was a chloroma and proved to be the only evidence of clinical relapse. This is the first reported case of this rare condition occurring following bone marrow transplantation.

Eosinophilic pustular folliculitis is a rare condition which is being increasingly reported in HIV-positive patients. Many therapies have been used to treat this condition. We report the first successful use of the H1 antihistamine cetirizine to treat the condition and postulate that the specific antieosinophilic action of this drug may explain the beneficial clinical effect seen in our patient.

Background. Seborrheic dernnatitis (SD) is a frequent complication of infection with the human immunodeficiency virus (HIV). Most studies examining the cause of SD have concentrated on the roles of Pityrosporum ovale and sebaceous lipids. Previous studies of skin surface lipid from patients with SD have produced conflicting results, with some authors reporting an abnormal lipid composition and others finding little or no abnormality. Methods. The composition of skin surface lipid was studied in 15 HIV-positive and 10 HIV-negative men with SD, in 14 HIV-positive men without SD, and in 16 unaffected controls. Total lipids were extracted from unaffected forehead skin into petroleum ether and separated into lipid classes by thin layer chromatography. The lipid classes were quantitated by densitometry after charring with sulfuric acid. Results. Patients, HIV-positive with SD, had significantly lower proportions of free fatty acid (FFA) and higher levels of triglyceride than normal controls. Patients, HIV-positive without SD, had a significantly increased proportion of FFA compared to HIV-positive patients with SD. Patients with SD, both HIV-positive and HIV-negative, had a similar pattern of skin surface lipid. Levels of FFA were lower and those of triglyceride higher than in the patients unaffected by SD, whether HIV-positive or not. There was no significant difference found between groups in free cholesterol, wax esters, and squalene. Conclusions. Abnormalities of skin surface lipid composition may play a part in the development of SD in both HIV-positive and HIV-negative men.

There is increasing evidence that neuropeptides may be involved in the pathogenesis of atopic dermatitis (AD). This study examines whether neuropeptide distribution in the skin of patients with AD differs from normal controls. The distribution and density of several neuropeptides were examined in lesional and non-lesional skin of AD patients (n = 5) and in normal controls (n = 4) using indirect immunofluorescence and image analysis. Cholinergic innervation was studied using cholinesterase histochemistry. Staining with the general neuronal marker protein gene product 9 x 5 showed a subepidermal network of nerves with fibres penetrating the epidermis, and nerves around blood vessels, sweat glands and hair follicles. Image analysis of nerves around sweat glands showed a significantly higher nerve density in non-lesional compared with both normal controls and lesional skin (P < 0.05); lesional compared with control skin showed no significant difference. In the epidermis the density of nerves was not significantly greater in non-lesional compared with lesional skin and controls. Calcitonin gene-related peptide immunoreactivity was similar in all subjects except in three of the AD patients, where more nerves appeared to penetrate the epidermis. Substance P immunoreactivity in the papillary dermis was seen in all AD patients but no controls. Vasoactive intestinal polypeptide and neuropeptide Y staining were similar in all groups. Acetylcholinesterase-positive nerves were found around sweat glands in all subjects, the staining being greatest in non-lesional and least in lesional skin. Occasional nerves were seen in the papillary dermis in lesional skin of two out of the four patients. We have demonstrated quantitative differences in nerve growth in clinically normal skin of AD patients, and altered cutaneous neuropeptide expression in these patients which may contribute to the pathogenesis of AD. The cause of atopic dermatitis (AD) has not been fully established but it is believed that there is a complex interaction between genetic susceptibility, precipitating environmental factors and disordered immune responsiveness. There is increasing evidence that neuropeptides may be involved in the pathogenesis of AD. Exacerbations of the disease can be provoked by stress, scratching and sweating which may be the result of neurogenic inflammation. One of the first features of an exacerbation is flushing of the affected skin and pruritus. Several neuropeptides that have been identified in human skin are potent inducers of vasodilation and may induce pruritus. Substance P (SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) all cause vasodilation when injected intradermally, and SP and CGRP have been shown to be mediators of the weal and flare reaction. Spantide, a competitive antagonist of SP, has been shown to inhibit immediate and delayed-type hypersensitivity reactions. Part of these responses may be due to release of histamine and indeed elevated concentrations of histamine have been found in vivo in the skin and plasma of patients with AD. In this study the distribution and density of several neuropeptides were examined in lesional and nonlesional skin of AD patients and in normal controls using indirect immunofluorescence and image analysis. Cholinergic innervation was studied using cholinesterase histochemistry. Because many afferent fibres do not express CGRP or SP, the general neuronal marker protein gene product (PGP 9 x 5) was used to assess the overall nerve supply to the skin.

Summary Three patients with AIDS are described with atypical manifestations of cutaneous herpes simplex virus infection. This infection should be considered in the immuno-suppressed patient with persistent or bizarre cutaneous ulceration despite negative virological cultures, and in the acutely ill patient with a generalized rash.

We report a patient who developed urticaria, angio-oedema and polyarthropathy secondary to the hypocomplementaemic urticarial vasculitis syndrome, a year prior to the onset of ulcerative colitis. Ten years later, primary sclerosing cholangitis and the antiphospholipid syndrome developed concomitantly. We believe this patient represents only the second reported case of idiopathic systemic lupus erythematosus (SLE) occurring in association with ulcerative colitis.

The pathogenesis of pruritus in patients undergoing chronic haemodialysis is unknown. Dryness of the skin is common in uraemic patients, and a correlation between xerosis and pruritus has been reported. Transepidermal water loss (TEWL) is a measure of cutaneous barrier function and also reflects skin water content. In this study the transepidermal water loss was measured at four sites pre- and postdialysis in 20 subjects undergoing chronic haemodialysis and in 16 healthy controls. Patients were weighed before and after dialysis and blood was taken for measurement of urea, creatinine, calcium, magnesium, phosphate and haemoglobin. All patients had parathyroid hormone measured within 3 months of the assessment. There was no significant difference in TEWL between patients and controls, with control values in general being between pre- and postdialysis rates of TEWL, and no correlation between TEWL and the presence or absence of pruritus. There was no significant differences between the pruritic and non-pruritic patients for any of the biochemical markers measured. Finally there was no significant correlation between the percentage water loss and TEWL. These findings indicate that pruritus of chronic haemodialysis is not related to abnormalities of cutaneous permeability.

A 1-year-old boy developed bullous pemphigoid. Immunoblotting, which has not been previously reported in childhood pemphigoid, showed the serum reacted to a 190 kDa band only. Bullous pemphigoid is rare in infancy and childhood with only 40 cases previously reported. A brief review of the literature is given and treatment of childhood bullous pemphigoid is discussed.

Summary Neutrophilic eccrine hidradenitis (NEH) is an eruption most commonly seen in patients undergoing chemotherapy, and is characterized histologically by a neutrophilic infiltrate around the eccrine coils, with associated necrosis of the sweat coils. The rash usually affects the trunk and extremities, and the morphology of the lesions is very variable. We describe a patient with neutrophilic eccrine hidradenitis who presented with symmetrical, erythematous. swollen ears, a manifestation of NEH which has not been previously reported.

An unusual case of systemic sclerosis occurring in a patient exposed to the vinyl chloride monomer (VCM) is presented. The dermatological aspects of vinyl chloride disease (VCD) are outlined and the mechanisms of pathogenesis discussed.

We describe a case of PLEVA in an asymptomatic, human immunodeficiency virus (HIV) positive patient. This association has not been previously described. The possible mechanisms involved are discussed.

Three patients with Crohn's disease who developed the clinical features of hidradenitis suppurativa (HS) are reported. To our knowledge this association has not been previously described. These cases illustrate the similarity between cutaneous Crohn's and ano-genital HS once chronic and established.

Summary A patient with a unique urticated annular erythema associated with Sjogren's syndrome and some features of systemic lupus erythematosus (SLE) is reported. There has been one previous report of a similar eruption occurring in a patient with Sjogren's syndrome.1

Summary Carcinoma of the pancreas has been associated with both cicatricial and bullous pemphigoid.1,2 We report a case of a 53-year-old man with cicatricial pemphigoid who died within months of the diagnosis from metastattc pancreatic-carcinoma. All three reported cases were complicated by venous thrombosis, a well recognized but uncommon feature of pancreatic cancer.