M.H.A. Rustin

Efficacy of traditional Chinese herbal therapy in adult atopic dermatitis

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.

Telomere Erosion in Memory T Cells Induced by Telomerase Inhibition at the Site of Antigenic Challenge In Vivo

The extent of human memory T cell proliferation, differentiation, and telomere erosion that occurs after a single episode of immune challenge in vivo is unclear. To investigate this, we injected tuberculin purified protein derivative (PPD) into the skin of immune individuals and isolated responsive T cells from the site of antigenic challenge at different times. PPD-specific CD4+ T cells proliferated and differentiated extensively in the skin during this secondary response. Furthermore, significant telomere erosion occurred in specific T cells that respond in the skin, but not in those that are found in the blood from the same individuals. Tissue fluid obtained from the site of PPD challenge in the skin inhibited the induction of the enzyme telomerase in T cells in vitro. Antibody inhibition studies indicated that type I interferon (IFN), which was identified at high levels in the tissue fluid and by immunohistology, was responsible in part for the telomerase inhibition. Furthermore, the addition of IFN-α to PPD-stimulated CD4+ T cells directly inhibited telomerase activity in vitro. Therefore, these results suggest that the rate of telomere erosion in proliferating, antigen-specific CD4+ T cells may be accelerated by type I IFN during a secondary response in vivo.

Neuropeptides in the skin of patients with atopic dermatitis

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 neuro‐peptides 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.

Follow‐up of adult patients with atopic eczema treated with Chinese herbal therapy for 1 year

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 stop treatment 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).

Comparative effects of calcipotriol (MC903) solution and placebo (vehicle of MC903) in the treatment of psoriasis of the scalp

The efficacy and safety of calcipotriol solution in the treatment of scalp psoriasis was compared with placebo (vehicle solution), in a multicentre double‐blind, randomized, parallel‐group study of 49 adult patients. Calcipotriol solution (50 μg/ml), or placebo, was applied twice daily over a 4‐week period. At the end of the study period 60% of patients on calcipotriol showed clearance or marked improvement of their psoriasis compared with 17% on placebo. Overall assessment of treatment response showed that calcipotriol was superior to placebo in both investigator (P<0.001;95% confidence interval for difference 19.0–67.6) and patient (P<0.001; 95% confidence interval for difference 18.3–68.0) assessments. Total sign score for psoriasis (i.e. the sum of the scores for redness, thickness and scaliness) decreased by 48.9% in the calcipotriol group, and by 18.6% in the placebo group (P =0.005). Calcipotriol was significantly superior to placebo in reducing redness, thickness, scaliness and extent of psoriasis, and in the patients’assessment in reducing scalp flaking and itching.

Etanercept-induced systemic lupus erythematosus

Tumour necrosis factor (TNF) is a pro‐inflammatory cytokine with a role in the pathogenesis of a number of conditions including rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis and Crohns disease. Etanercept (Enbrel®; Immunex Corp., Seattle, WA, USA) is a recombinant soluble fusion protein of TNF‐α type II receptor and IgG which acts by blocking the action of TNF‐α. It is licensed for use in rheumatoid arthritis and juvenile chronic arthritis. A number of studies report the development of antinuclear and anti‐double‐stranded DNA antibodies in patients treated with TNF antagonists for rheumatoid arthritis. There are few reports of the development of clinical features of discoid, subacute or systemic lupus erythematosus. We present one of the first reported cases of etenercept‐induced systemic lupus erythematosus and review the literature of lupus and TNF antagonists.

The safety of tacrolimus ointment for the treatment of atopic dermatitis: a review

Tacrolimus ointment is a topical calcineurin inhibitor (TCI) that was developed specifically for the treatment of atopic dermatitis (AD). It is one of the most extensively tested dermatological products, with more than 19u2003000 patients (including approximately 7600 children) having participated in the tacrolimus ointment clinical development programme. Recent regulatory reviews have focused on the potential risk of malignancy with TCIs, based on their mode of action and the effects of systemic tacrolimus when given to transplant recipients. Studies have shown, however, that the systemic absorption of tacrolimus when applied topically is very low, with blood concentrations being below the level of quantification in most patients. Moreover, TCIs are not associated with a decrease in immunocompetence in the skin and there is no increase in the incidence of infections with long‐term treatment. More than 5·4u2003million prescriptions for tacrolimus ointment have been issued worldwide, with no evidence of an increased risk of malignancy in adults or children compared with the general population. Similarly, epidemiological studies have failed to demonstrate an increased incidence of skin cancer in patients using TCIs. The most common adverse events (AEs) that occur with tacrolimus ointment treatment are transient application‐site reactions, such as burning or pruritus. These complications are related to disease severity, and decrease in frequency over time as AD improves. The incidence of nonapplication‐site AEs does not increase with long‐term treatment, and most such events occurring in clinical trials were considered to be unrelated to therapy. Although it is important that clinicians are aware of the recent changes in product labelling, extensive clinical trials continue to show that tacrolimus ointment is well tolerated, and is generally an effective therapy for suitable patients with AD.

Association of Immunological Changes with Clinical Efficacy in Atopic Eczema Patients Treated with Traditional Chinese Herbal Therapy (Zemaphyte

The efficacy of the Chinese herbal therapy (Zemaphyte) has been well established as a treatment for atopic eczema (AE) in clinical trials. The purpose of this study was to probe the immunological changes that occurred when patients were treated with the herbs for a period of 8 weeks. This treatment decreased serum IgE complexes (p less than 0.05) but did not affect total serum IgE or CD23 expression on peripheral blood monocytes. Peripheral blood mononuclear cells from patients before and after treatment were cultured overnight with interleukin 4 and the ability of this cytokine to induce CD23 on monocytes from treated patients was found to be significantly diminished (p less than 0.01). Soluble interleukin 2 receptor and soluble vascular cell adhesion molecule were both raised in the serum of AE patients compared to control individuals. Both these parameters were decreased following treatment (p less than 0.05). All these changes coincided with improvement in erythema and surface damage scores. There was no alteration in soluble intracellular adhesion molecule or soluble CD23. The results of these investigations would suggest that this herbal treatment has the ability to target various immunological parameters which may be involved in the pathogenesis of AE.

Clinical and pathological heterogeneity in cutaneous gamma-delta T-cell lymphoma : a report of three cases and a review of the literature

Cutaneous gamma‐delta (γδ) T‐cell lympboma is rare. Eleven cases have been reported to date including four cases of mycosis fungoides (MF). two of pagetoid reticulosis and five of pleomorphic cutaneous T‐cell lymphoma (CTCL). We report three further cases of cutaneous γδ T‐cell lymphoma: one of ME. one of a pleomorpbic CTCL and one of a subcutaneous T‐cell iymphoma. Combined data suggest that although cutaneous γδ T‐cell iymphomas do not appear to comprise a single clinicopathoiogical entity, they may be associated with aggressive clinical behaviour and a poor prognosis.

Bullous eruption of systemic lupus erythematosus : A clinicopathological study of four cases

We describe the clinical, histological and immunopathological features of four female patients with the bullous eruption of systemic lupus erythemutosus (bullous SLE). Three patients had circulating anti‐basement membrane zone (BMZ) antibodies, and Western blot analysis in two cases revealed binding to type VII collagen. Immunoeiectron microscopy in one of these patients demonstrated deposition of antibody in the lamina densa and sublamina densa regions, thus sharing immunopatho‐logical features with epidermolysis bullosa acquisita (KBA). The vesiculobullous lesions developed 8 months to 6 years after the initial symptoms of SLE, and cleared promptly with dapsone treatment.