B.R. Allen

Double-blind, controlled, crossover study of cyclosporin in adults with severe refractory atopic dermatitis

A few patients remain severely affected by atopic dermatitis into adult life despite treatment with systemic steroids, azathioprine, and photochemotherapy. 33 patients took part in a double-blind, placebo-controlled, crossover study to assess the efficacy and safety of cyclosporin (5 mg/kg per day) in adults with severe refractory atopic dermatitis. Treatments were given for eight weeks each with one group (n = 16) receiving placebo followed by cyclosporin and another (n = 17) receiving cyclosporin and then placebo. Disease activity, extent of disease, sleep and itch, topical steroid use, and adverse events were assessed every two weeks. Both extent and activity of dermatitis were significantly improved (p less than 0.001) as were subjective measures of disease. 20 patients receiving cyclosporin reported adverse events compared with 8 taking placebo, although no patient required withdrawal from the study. Cyclosporin therapy led to an increase in the mean serum urea, creatinine, and bilirubin concentrations, although only the rise in bilirubin was significant (p = 0.001). Our results confirm that cyclosporin is a safe and effective short-term treatment for severe, refractory atopic dermatitis.

Cyclosporin greatly improves the quality of life of adults with severe atopic dermatitis. A randomized, double-blind, placebo-controlled trial.

A multicentre, randomized, double‐blind, controlled crossover clinical trial was conducted on 33 patients with severe refractory atopic dermatitis, to determine the effects of cyciosporin (5 mg/kg/day) on their health‐related quality of life. Treatments were administered for 8‐week periods. One group (n=16) received placebo followed by cyclosporin, and the other (n=17) received cyclosporin and then placebo. Health‐related quality of life was assessed at o, 8 and 16 weeks using a general measure, the United Kingdom Sickness Impact Profile (UKSIP), an eczema‐specibic measure, the Eczema Disability Index (EDI), and a global 5‐point rating scale of overall health (very good to very poor). In addition, clinical assessments (i.e. extent and activity of disease) were made by the investigators.

Long-term efficacy and safety of cyclosporin in severe adult atopic dermatitis.

A prospective, open, multicentre study was performed to investigate the efficacy and safety of longterm treatment with cyclosporin in adults with severe atopic dermatitis. Subjects were treated for a maximum of 48 weeks. For the first 8 weeks, cyclosporin was administered at 2.5 mg/kg per day. The dose was then adjusted according to response. Disease activity was monitored using the six‐area. six‐sign score and the proportion of skin involved. Pruritus and sleep disturbance were assessed using four‐point scales. Response was further evaluated on a five‐point scale. Adverse events. blood pressure and serum biochemistry were monitored. Tolerability was assessed on a five‐point scale.

Selective activation of circulating CD4+ lymphocytes in severe adult atopic dermatitis

Summary An analysis of peripheral blood lymphocyte subsets and their expression of activation markers was performed using flow cytometry in 12 adult patients with severe atopic dermatitis, and compared with 14 normal individuals. Repeated measurements were made over an 8‐week period during which disease activity was also assessed.

The effect of treatment on plasma uroporphyrin levels in cutaneous hepatic porphyria

Seven patients undergoing treatment for cutaneous hepatic porphyria had serial measurements of their plasma uroporphyrin. In each case there was a progressive fall during treatment but even in remission the levels did not return to normal. There was a significant correlation between urinary and plasma uroporphyrin concentrations.

LEAD AND THE SKIN

The physical and chemical properties of lead ensure that, provided supplies are not exhausted, it will have a future in technology to match its 6000 year past. No doubt too the persisting proximity of man and metal will continue to give rise to problems of toxicity. Much work was done in the first half of this century to recognize and remove the more obvious sources of lead poisoning. Thus strict criteria are now laid down as to the maximum quantity of lead which may be contained in food, drinking water, paint for interior use and lead glazes; polyethylene and copper are used for plumbing, and even church roofs are more likely to be made of bitumenized felt than lead. In industry too, protective measures have resulted in florid lead poisoning becoming rare, although occasional accidents, such as those at Avonmouth, do occur (Windeyer, 1972). There is, however, no room for complacency especially in view of the steadily increasing usage of lead. In 1940 the total United States consumption was 782 thousand tons and in 1968 1318 thousand tons (New York Academy of Sciences, 1972). The bulk of the increase has been used in petrol additives (50 to 262 thousand tons) and storage batteries (220 to 513 thousand tons) with a drop in the amount used as white lead in paint (from 66 to 6 thousand tons). Attention has recently turned to the possibility of prolonged exposure to low doses of lead causing morbidity in the absence of the classical clinical features of poisoning. Every failed membership candidate knows that the Roman empire collapsed because the Romans drank acid wine from lead cups (Gilfillan, 1965); are we declining because we ingest some of the 100 thousand tons of lead puffed each year into the atmosphere of the Northern Hemisphere in the exhaust fumes of motor cars (Murozumi, Chow & Patterson, 1969) ? The problem of airborne lead has been subject to intensive study (National Academy of Sciences, 1972) and the whole topic of lead poisoning has recently been reviewed in the informative monograph by Waldron & Stofen (1974). Lead is absorbed mostly through the lungs and gastrointestinal tract. Some is also absorbed through the skin but with inorganic compounds the amount is small. Sussman (1922) estimated that 100-200/(g of lead could penetrate i m^ of skin per day but with the alkyl compounds used in petrol to prevent premature ignition the amount is much greater. Shortly after the most widely used compound, tetraethyl lead (TEL), was first manufactured cases of toxicity began to occur; 139 cases being reported in 17 months, thirteen of them fatal. As a result manufacture was forbidden until attention to plant design produced greater safety (Hunter, 1969). Eldridge (1924) showed that significant absorption could occur through the skin; an observation which has been adequately confirmed (Kehoe, 1927; Kehoe & Thamann, 1931; Laug & Kunze, 1948). The hazard to those handling leaded petrol in a normal manner is probably small, (Kehoe, Thamann & Cholak, 1936) mainly because 95% of a dose applied to the open skin surface evaporates (Laug & Kunze, 1948). Cases of poisoning have been reported in inadequately protected workers cleaning storage tanks in which leaded fuel has been stored (Beattie, Moore & Goldberg, 1972). Laug & Kunze (1948) studied the absorption of lead from various compounds painted on the shaved skin of rats and used the lead content of the kidneys as an index of absorption. Following TEL application there was a hundredfold increase and after lead acetate a threefold increase. Scarifying the skin enhanced absorption. Martindale (1967) lists twenty two preparations containing lead, twenty for application to the skin surface and one, blended with cows milk, for infusion into the rectum. Many are used for their

21) Partial lipodystrophy

MARKOWITZ, S.S., MCDONALD, C.J., FETHIERE, W. & KERZNER, M.S. (1972) Occupational acro-osteolysis. Archives of Dermatology, 106, 219. MEYERSON, L .B. & MEIER, G.C, (1972) Cutaneous lesions in acro-osteolysis Archives of Dermatology, 106,224. KEWIN HARRIS, D . & ADAMS, W . G . F . (t967) Acro-ostcolysis occurring in men engaged in polymerization of vinyl chloride. British Medica! Journal, iii, 712.

(7) Maffucci'S Syndrome

D.G., male, aged 31 years. Hospital case no. 17-71-92. History. He has had gross nail dystrophy of fingers and toes since the age of 11. In addition he complains of recurrent inflammation of the eyes. There is no family history, his general health is good and he is on no drugs. He works as an electrician. Examination. There is gross dystrophy of all nails. His palms and soles are hyperkeratotic. There is reticulate erythema with some atrophy especially of the light exposed areas of the face and arms. He has periodic inflammation of the conjunctivae and there are keratotic lesions of the buccal mucosa.

Activated peripheral blood T lymphocytes in atopic dermatitis

In vitro studies have demonstrated that prostacyclin (PGI2) is the most powerful antiplateiet/ antithrombotic drug. Short-term infusion of a stable analogue of PGI2 (iloprost [I]) has been recommended for the treatment of Raynauds phenomenon in patients with severe systemic sclerosis. Intravenous infusion of [I] was given to 10 such patients, according to manufacturers recommendations, on 3 consecutive days, for 8 h starting at a rate of 05 ng/kg/min and increasing by 05 ng/kg/min every 15 min to a maximimi of 20 ng/kg/min. The thrombotic status of patients was assessed by a new technique (haemostatometry) which allows measurement of platelet function such as shear-induced haemostasis and thrombus formation on collagen fibres from a non-anticoagulated venous blood sample. Coagulation of the blood was also monitored. Haemostatometry was perfonned before the infusion, 4 h after its commencement on the third day and i h after completion of the infusion. There was a complete lack of any antiplateiet effect on haemostasis and thrombus formation on collagen of [I] during and immediately after the infusion. Conversely, platelet hyperreactivity and enhanced coagulation were observed during the infusion. In vitro, a potent antiplateiet effect with greatly prolonged coagulation was observed in the i 6-80 ng/ml range of [I], which is 25-125 times higher than that achieved in the blood of patients. Enhanced platelet reactivity and coagulation was observed in vitro at the concentration which corresponds to the peak plasma level of [I] in patients. Thus our study, using the recommended dose of [I], failed to show any antiplateiet effect, but demonstrated a risk of thrombotic complication, due to the previously undetected effect of low dose of [I] on platelets and the coagulation system.