Library

Notes: 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.One hundred subjects were enrolled and 65 completed 48 weeks of treatment. Withdrawals occurred due to remission (three), inadequate response (seven), protocol violations (11) and adverse events (14, of which seven were probably treatment related). Cyclosporin produced rapid and highly significant improvements in all indices of disease activity. Sixty-five subjects considered that they had shown a considerable improvement or complete clearance of disease. Most patients relapsed after cessation of treatment. but neither signs nor symptoms had returned to baseline severity 8 weeks later. Blood pressure and serum creatinine levels increased slightly. and in one subject renal impairment was a major factor contributing to withdrawal of the drug. Overall, 85 subjects rated the tolerability of cyclosporin as good or very good.The results indicate that cyclosporin has a place in the long-term treatment of severe atopic dermatitis provided that appropriate patients are selected and careful monitoring is performed.

Notes: Leukotriene synthesis may be increased in a variety of inflammatory diseases. Urinary leukotriene E4 is a stable metabolite of leukotrienes C4 and D4 which has previously been found to be increased in exacerbations of severe asthma and after antigen inhalation. Levels of urinary LTE4 in seven patients during and after a severe flare of atopic dermatitis were measured by high-performance liquid chromatography (HPLC) and radioimmunoassay (RIA). Mean urinary LTE4 levels (± SEM) were not increased during (16·7 ± 3·7pg/μmol) or after (16·9 ± 4·8 pg/μxmol) the acute exacerbation of atopic dermatitis when compared with the normal range (mean = 23·8 [95% confidence interval 19·9–28·2] pg/μmol creatinine). These findings do not provide evidence of cysteinyl leukotriene involvement in the pathogenesis of atopic dermatitis.

Notes: An in vivo method for the assessment of adrenergic reactivity has been employed to examine alpha-adrenergic and beta-adrenergic responses in atopic eczema. In a randomised, double-blind study, intradermal administration of noradrenaline (predominantly an alpha-1-adrenoceptor agonist) or salbutamol (predominantly a beta-2-adrenoceptor agonist) significantly inhibited the histamine wheal response (P 〈0.001) in atopic and control subjects. However, the responses to alpha-adrenergic or beta-adrenergic effects were similar in both groups, a finding which does not support the concept that atopy is due to impaired beta-adrenergic reactivity accompanied by enhanced alpha-adrenergic reactivity. The ability of patients with atopic eczema to respond normally to the anti-inflammatory effect of a beta-2-adrenoceptor agonist is of therapeutic interest.

Notes: Eruptive xanthomata are the characteristic cutaneous lesions of hyperlipaemia and here we describe their occurrence in a patient with familial type V hyperlipoproteinaemia associated with diabetes mellitus.

Notes: Previous studies show that oral antihistamines affect the Weal and flare response to intradermal injections of the inflammatory mediators platelet-activating factor (PAF) and bradykinin (BK). The aim of this study was to compare the effects of terfenadine (an H2-antagonist) and cimetidine (an H2-antagonist) on weal and Hare responses to PAF and BK in healthy non-atopic human volunteers. The effects of doxepin on PAF responses were investigated, as there is evidence that doxepin may have direct anti-PAF ejects in addition to its known antihisiaminic actions.

Notes: With the recent development of selective drugs acting on the kinin system and the identification of a kallikrein-like enzyme from psoriatic blister fluid, there is now much interest in the possible role of kinins in psoriasis. We have examined the time-course of the inflammatory (weal and flare) responses to intradermal kallidin (lysbradykinin) and hradykinin in normal volunteers, and have compared the dose–response effect of these agents in normal volunteers and patients with psoriasis.Initially, normal subjects (n= 5) received coded intradermal injections of 50μl normal saline containing kallidin or bradykinin (0.1, 0.5, 1.0 and 5.0μg). Weal volume, weal area and flare area were calculated at 5, 15, 30 and 60min by measuring two perpendicular diameters and change in skinfold thickness. Weal and flare measurements were subsequently made at 15 and 5 min, respectively.Patients with psoriasis (n= 9) and normal subjects (n= 10) were given intradermal injections of kallidin (0.1 and 1.0μg) and bradykinin (0.1, 0.5 and 1.0 μg) in clinically normal forearm skin, using histamine and normal saline as controls.The dose–response effects of kallidin on weal and dare responses in human skin were established in the study and compared with those of bradykinin. There was wide inter-individual variability for both agents and, although mean responses to the highest doses of kallidin and bradykinin were decreased in psoriatic skin, no significant differences were found between the psoriatic and normal group for kallidin, bradykinin or histamine.Hence, there do not appear to be any obvious altered vascular responses to kallidin or bradykinin in patients with psoriasis, despite the fact that kinins may be generated in psoriatic tissue.

Notes: The tricyclic antidepressant, doxepin, is known to have H1 and H2 antihistaminic effects. Recently, 5% doxepin cream has been marketed in the U.S.A. for treatment of eczematous dermatoses. We investigated the effects of topical doxepin treatment on histamine-, substance P-and prostaglandin E2-(PGE2) induced responses in the skin of normal and atopic subjects. We compared the effects of topical doxepin with those of the oral antihistamine terfenadine. The weal volume and flare area responses to histamine were significantly reduced by treatment with topical doxepin or oral terfenadine in both normal and atopic subjects (P〈0·05). The mean ±SEM percentage reduction in flare area for 10μ/site of histamine in non-atopics and atopics was 48±8% and 60±17% with terfenadine, and 54 ± 12% and 81 ± 4% with topical doxepin, respectively. The mean percentage reduction in weal volume for the same dose of histamine in non-atopics and atopics was 70 ± 9% and 63 ± 16% with terfenadine, and 96 ± 2% and 89 ± 6% with topical doxepin, respectively. The flare but not the weal response to substance P was inhibited by both treatments in all subjects (P〈0·05). The mean ±SEM percentage reduction in flare area for 200 pmol/site of substance P in non-atopics and atopics was 53 ± 10% and 73 ±4% with terfenadine, and 74 ± 7% and 75 ± 4% with topical doxepin, respectively. The cutaneous responses to PGE2 were not affected by either drug. The inhibitory effects of doxepin were as great as those of terfenadine, and doxepin had a significantly greater effect than terfenadine in inhibiting the weal response to histamine and flare response to substance P in normal volunteers (P〈0·05). There was no significant difference between atopics and non-atopics in the percentage reduction of cutaneous responses by oral terfenadine or topical doxepin. Marked sedation occurred in three of the first 10 subjects treated with topical doxepin, necessitating a reduction in dosage for the remaining six subjects. In summary, topical doxepin was as effective as, and sometimes more effective than, a standard dose of oral terfenadine in the inhibition of histamine-induced and axon-reflex-mediated cutaneous responses. The marked sedative effect may limit its clinical use in some patients.

Notes: A working party of 13 dermatologists, two family practitioners and a paediatrician was assembled, with the aim of developing a minimum list of reliable discriminators for atopic dermatitis. Each physician was asked to select 10 consecutive new cases of unequivocal mild to moderate atopic dermatitis and 10 controls with other inflammatory dermatoses. Each subject was examined by two independent observers, who were blind to the clinical diagnosis and study aim, with regard to 31 clinically useful diagnostic features for atopic dermatitis. Two hundred and twenty-four patients were studied (120 cases and 102 controls). Using the key physician's clinical diagnosis as a gold standard, the sensitivity and specificity of each of the 31 diagnostic criteria were tested. Using multiple logistic regression techniques, a minimum set of diagnostic criteria for atopic dermatitis was derived. These were: history of flexural involvement, history of a dry skin, onset under the age of 2, personal history of asthma, history of a pruritic skin condition, and visible flexural dermatitis. Adjustment for age, sex, region, social class and ethnic group did not alter the choice of final criteria. The discriminatory value of these criteria was also satisfactory when tested against a further sample of 150 patients drawn from the community, who did not have skin disease.

Notes: Summary We report two patients with minocycline-induced pigmentation of the sclerae. Cutaneous pigtnentution is a well-recognized complication of minocycline therapy, but only live cases of pigimentation of the sclerae have been described previously. These five patients have a number of features in common with the two reported here. We propose that these patients represent the most severe end of the spectrum of minocycline-induced cutaneous changes. Patients should be warned about the possibility of the occurrence of pigmentary changes before starting therapy.

Notes: In a randomized, double-blind, placebo-controlled study, treatment of atopic dermatitis with salbutamol ointment (1% salbutamol base in white soft paraffin) b.d. for 2 weeks resulted in a decreased clinical score for redness (P 〈 0.05). No marked clinical improvement was observed, however, following treatment with either salbutamol ointment or salbutamol slow-release spandets. Some degree of systemic absorption occurred in two out of seven patients treated with salbutamol ointment, as demonstrated by urinary salbutamol levels.