Håkan Granlund

Cyclosporin in atopic dermatitis: time to relapse and effect of intermittent therapy

The efficacy of cyclosporin (CyA) in the induction of remission in atopic dermatitis has been documented in controlled studies. However, little information is available on the duration of remission after CyA treatment. We studied the length of remission in 43 patients with severe alopic dermatitis after a 6‐week treatment period with CyA at 5 mg/kg per day. After a follow‐up of 6‐26 weeks, depending on the time‐point of relapse, a second treatment period with CyA, identical to the first, was performed. Disease activity was evaluated bi‐weekly, using six different parameters: 1, a total body disease activity score; 2, the extent of the disease; 3, the occurrence of itch; 4, the occurrence of sleep disturbance; 5, the use of topical emollients; and 6, the use of topical hydrocortisone. A significant decrease in disease activity was observed. The total body disease activity score decreased from the baseline score of 31 to 11.6 at the end of the first part and to 13.4 at the end of the second part of the study. An almost maximal response to treatment was already apparent after 2 weeks of treatment. All the other efficacy parameters studied also showed a significant response to CyA treatment. A similar response to CyA was seen when the patients were re‐treated. After both treatment periods, approximately half of the patients relapsed after 2 weeks (42% first part; 54% second part). After 6 weeks follow‐up, the relapse rates were 71 and 90%. respectively. However, after the first treatment period five patients did not relapse during the 26‐week follow‐up period; the corresponding number was two after the second treatment period. The remission obtained in these seven patients was of clinical relevance, as their mean disease activity score at the end of the follow‐up periods was only 28% (range 11–40) and 43% (both patients), respectively, of their own baseline score. In contrast with the rapid relapse of the dermatitis in the other patients after CyA was stopped, all disease parameters showed improvement when these patients were seen 1 year after the study, i.e. the mean activity score was 17.8 (58% of baseline). All seven patients who did not relapse after the first or second treatment period were still in remission after 1 year, and their mean activity score was only 32% (range 10–69) of their own baseline score. The most common side‐effects were paraesthesiae and gastrointestinal discomfort. CyA dose was reduced in two patients because of drug‐related side‐effects; treatment was stopped prematurely in one patient. The present study confirms the efficacy of CyA in atopic dermatitis. It also suggests that CyA treatment may improve the long‐term outcome of atopic dermatitis, although most patients initially relapsed a few weeks after CyA was stopped.

Long-term follow-up of eczema patients treated with cyclosporine.

Cyclosporine is efficacious in short-term treatment of various eczematous disorders. In a follow-up study we have evaluated the long-term efficacy of cyclosporine in 75 patients, who in previous studies had been treated with cyclosporine for chronic actinic dermatitis (6 patients), atopic dermatitis (42 patients) and chronic hand eczema (27 patients), 4, 2 and 1 year after the initial treatment, respectively. Three out of 6 patients with chronic actinic dermatitis showed long-term efficacy. Two years after the initial treatment with cyclosporine (5 mg/kg/day for 1-2 treatment periods of 6 weeks) for atopic dermatitis the mean disease activity was significantly lower compared to baseline (58% decrease), and compared to the time of treatment stop no significant change had occurred. Of 37 evaluable patients 35 were still in remission. One year after the initial treatment with cyclosporine (3 mg/kg/day for 6 weeks) for chronic hand eczema the mean disease activity was significantly lower than at baseline (54% decrease), and compared to the time of treatment stop no significant change had occurred. Of 27 evaluable patients 21 patients were still in remission. The study suggests that long-term remissions are possible in eczematous diseases treated with cyclosporine, even for a relatively short treatment period. It must be stressed, however, that we did not have control groups for any of the studied patient groups.

Comparison of cyclosporin A pharmacokinetics of a new microemulsion formulation and standard oral preparation in patients with psoriasis

Cyclosporin A (CyA) is a potent immunosuppressive drug which has shown efficacy in various skin disorders. The bioavailability of the oral CyA formulation (Sandimmun) is approximately 30%. showing high interpatient and intrapatient variability. The steady‐state pharmacokinetics, efficacy and tolerability of CyA in two formulations: commercial Sandimmun soft gelatin capsules (CyA‐SGC) and a newer oral formulation (sandimmun Neoral: CyA‐NOF), were compared in an open prospective study with a crossover between the two treatments in 19 patients with psoriasis. Each patient received a twice‐daily treatment of CyA with a clinically effective dose of 2‐5 mg/kg per day. The individual dosages were kept unchanged for at least 2 weeks before study entry and over the 42‐day course of the study. At entry. patients were switched to CyA‐NOF for 4 weeks and then back to CyA‐SGC for another 2 weeks. Pharmacokinetic profiles were assessed at steady‐state on day 14 while the patients were on CyA‐NOF, and on day 42 while on CyA‐SGC. Switching from CYA‐SGC to CyA‐NOF using 1:1 dose conversion resulted in an increased absorption of the drug. On average there was a 61% increase in maximum drug concentration (Cmax) and a 32% increase in the area under the steady‐state blood concentration‐time curve (AUC): Cmin was comparable in the two formulations. The increases in Cmax and AUC were associated with some increase in tthe clinical efficacy of the treatment. The number of adverse events reported by the patients and observed by the investigators were increased during CyA‐NoF: the mean serum creatinine levels were not affected. An increased and a more consistent and predictable absorption of CyA is achieved with the new oral microemulsion formulation.

Realtime teleconsultations versus face-to-face consultations in dermatology: immediate and six-month outcome

We evaluated the outcome of both realtime teleconsultations and face-to-face consultations in dermatology. Forty-six patients were enrolled in an open controlled study. Twenty-nine patients (60%) answered the questionnaire sent to them after six months. Over the six-month follow-up, similar proportions of the two patient groups had visited a general practitioner or a specialist in the consulting hospital. At follow-up, overall patient satisfaction with the consultation, measured on a linear analogue scale (0–10), had fallen only slightly and to the same extent after both types of consultation, that is by 1.2 (SD 3.7) after realtime teleconsultations and by 1.4 (SD 4.5) after face-to-face consultations. The proportions of patients who would prefer the same mode of consultation for their next appointment had decreased from 83% to 50% in the realtime teleconsultation group and from 83% to 62% in the face-to-face consultation group. However, in neither group was the change significant. The study suggests that patient satisfaction with teleconsultation is well preserved after six months.

Treatment of lichenified atopic eczema with tacrolimus ointment.

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Treatment of Childhood Eczema

Eczema in childhood is almost always atopic eczema, a common disease with huge impact on the quality of life of the child and family. Although atopic eczema constitutes part of the atopic syndrome, avoidance of allergens is never enough for disease control.Treatment of eczema in childhood has the same components as in adults. Emollients constitute the preventive background therapy in all stages of eczema, and topical corticosteroids are still the mainstay of treatment. Infectious exacerbation may require the use of a short course of topical or systemic antimicrobials. UV phototherapy should be considered as an adjunctive treatment to assist topical corticosteroids after an acute exacerbation of the disease. Cyclosporine can also be used in the treatment of childhood eczema in severe cases. Maternal allergen avoidance for disease prevention, oral antihistamines, Chinese herbs, dietary restriction in established atopic eczema, homeopathy, house-dust mite reduction, massage therapy, hypnotherapy, evening primrose oil, emollients, and topical coal tar are other temporarily used treatment modalities, without, however, firm evidence of efficacy from proper controlled trials. Calcineurin inhibitors constitute a new generation of drugs for both adult and childhood eczema already marketed in some countries. It is postulated that they will replace topical corticosteroids as first-line treatment of eczema.

Use of the Newer Immunosuppressive Agents in Dermatology

SummaryImmune mechanisms play a central role in various diseases such as eczema and psoriasis, and in the past treatment tended to involve corticosteroids and cytostatic drugs. Organ transplantation has stimulated the development of newer immunosuppressants, some of which have also been found to be efficacious in the inflammatory dermatoses.The best studied such immunosuppressant is cyclosporin, which has shown efficacy especially in psoriasis and atopic dermatitis. The major limiting factor in the use of cyclosporin is its adverse effects, especially nephrotoxicity and hypertension. Therefore the risk: benefit ratio should always be considered before initiation of cyclosporin therapy, and the patient should be carefully followed for such adverse effects.Tacrolimus seems to share the efficacy and most of the adverse effects of cyclosporin when used systemically, presumably because of its similar intracellular mechanism of action. Unlike cyclosporin, tacrolimus is efficacious topically, which may allow lower systemic adverse effects to be combined with higher local efficacy.Other newer immunosuppressants include sirolimus (rapamycin) and monoclonal antibodies. Their use in dermatology is still in the research phase, and no conclusions about their clinical potential can yet be made.