Sustained improvement in urticaria pigmentosa and pruritus in a case of indolent systemic mastocytosis treated with cladribine.

Systemic mastocytosis (SM) is a myeloproliferative disorder, characterized by a clonal proliferation of abnormal mast cells accumulating in internal organs and sometimes in the skin, leading to cutaneous and systemic symptoms. Mutations within the gene KIT, which encodes the receptor tyrosine kinase (KIT) on mast cells, is found in most patients with SM. We report a case of a 62-year-old woman presenting with a pruritic rash on her limbs and trunk. Several years later she developed gastrointestinal symptoms, associated with raised serum tryptase. Skin and bone marrow biopsies confirmed a diagnosis of SM, initially presenting with urticaria pigmentosa. Responses to multiple therapies, including potent topical steroids, oral antihistamines, phototherapy and the tyrosine kinase inhibitor, nilotinib, were inadequate. Treatment with cladribine (2-chlorodeoxyadenosine) produced a marked and sustained reduction in her symptoms and serum tryptase level.

Changes in CD23 expression of blood and skin in atopic eczema after Chinese herbal therapy.

BACKGROUND: Aberrant expression of CD23 (low affinity IgE receptor) on cells of the monocyte/macrophage series in peripheral blood and lesional skin of patients with atopic eczema has been demonstrated. It is not known whether this abnormality results from a fundamental systemic problem of the monocytes of these patients or reflects local changes to cell populations within the skin tissues. OBJECTIVES: This study was designed to determine whether this aberrant expression was caused by local cutaneous influences on mature cells or fundamental changes in monocyte differentiation. The possible relationship between these aberrations and clinical severity was also investigated by repeating these immunopathological studies after a course of efficacious treatment with Chinese herbal therapy (CHT). METHODS: Peripheral blood mononuclear cells were obtained from patients with atopic eczema before, and after 8 weeks of treatment. Efficacy of CHT was quantified on clinical grounds. Monocytes were isolated by adherence to plastic and cultured for up to 7 days. Samples were harvested at 2, 5 and 7 days of culture and cytospins prepared. Immunocytochemical staining to identify phenotypic subsets was performed on the monocytes at time 0 and on maturing cells from culture. This immunocytology was quantified using computerized image analysis equipment to determine the emergence of macrophage subsets and their level of CD23 expression. Biopsies were taken from lesional skin before and after treatment and immunohistology was performed on cryostat sections to determine the number of antigen presenting cells expressing CD23 as well as the level of expression of these molecules. RESULTS: The results showed that increased numbers of monocytes from patients with atopic eczema express CD23 at day 0 and that cultured monocytes from these patients differentiate faster during the 7 day culture period as compared to normal controls. Efficacious treatment did not affect the number of peripheral blood monocytes expressing CD23. However, treatment did lead to a significant decrease in the number of CD23+ mature macrophages in the skin as well as a reduction in the level of expression of this moiety. These results demonstrate that changes in clinical severity are more closely related to the expression of CD23 on mature antigen presenting cells in lesional skin rather than to differentiating peripheral blood monocyte CD23 expression. CONCLUSIONS: These results suggests that local factors within lesional skin govern the accumulation and the expression of CD23 on mature macrophages and that these factors may be more relevant to the pathogenesis of the disease than aberrations in CD23 expression that may occur systemically.

Modulation by Chinese herbal therapy of immune mechanisms in the skin of patients with atopic eczema.

Ten patients with atopic eczema (AE) received treatment with Chinese herbal therapy (CHT; Zemaphyte) for 2 months. The severity of the eczema was recorded and skin biopsies were taken from lesional (L) and non-lesional (NL) skin before and after treatment. The skin biopsies were stained to detect T-cell subsets (CD4, CD8, CD45Ro and CD25), macrophage subsets (RFD7), dendritic cells (RFD1). Langerhans cells (CD1), HLA-DR, low-affinity IgE receptors (CD23) and high-affinity IgE receptors (15A5, 22H7). A quantitative assessment of the numbers of positively stained cells was made. Monoclonal antibody binding specifically to CD23(Fc epsilon RII) was used, in combination with cell subset monoclonal antibodies to quantify the cellular distribution of CD23 antigen in the skin. Following 2 months of treatment with CHT, erythema was reduced by 53%. There was also a significant reduction in HLA-DR expression. The numbers of RFD1 + CD23 +, RFD7 + CD23 +, CD1 + CD23+ and CD25 + cells in lesional skin decreased significantly after treatment (RFD1 + CD23 + from 0.39 to 0.21, RFD7 + CD23 + from 0.29 to 0.16. CD1 + CD23 + from 0.24 to 0.09, CD25 + from 0.84 to 0.31 in epidermis and from 1.62 to 0.94 in dermis (mean cells numbers per unit area). No significant change in cell numbers in NL skin or expression of Fc epsilon RI in either L or NL samples was observed after treatment. This study confirms that CHT is clinically efficacious and that clinical improvement is associated with a significant reduction in antigen-presenting cells expressing CD23.

Efficacy of traditional Chinese herbal therapy in vitro. A model system for atopic eczema: inhibition of CD23 expression on blood monocytes.

Recently, there has been growing interest in the use of traditional Chinese herbal therapy (TCHT) decoctions for the treatment of atopic eczema (AE). The mode of action of this treatment is still unknown, and in order to investigate this we have analysed the effect of an extract of these herbs (TCHTE) on interleukin 4 (IL-4)-induced CD23 expression on peripheral blood monocytes from non-atopic subjects. We found that TCHTE inhibited CD23 expression up to 60% (P < 0.001), whereas the placebo extract had no significant effect on CD23 expression. This inhibition was dose-dependent, and TCHTE was effective at a concentration of 250 micrograms/ml (P = 0.001). If TCHTE or placebo was added after IL-4, the action of TCHTE could still be seen at 12 h. This inhibition was not due to cell death, as peripheral blood mononuclear cells (PBMCs) cultured with TCHTE or placebo at a concentration used in these experiments had a similar viability to control cultures. Down-regulation of the low affinity receptors for IgE on antigen-presenting cells in patients with AE may contribute to the benefit observed following treatment with TCHT.

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). 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.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

The treatment of chilblains with nifedipine: the results of a pilot study, a double-blind placebo-controlled randomized study and a long-term open trial.

A pilot study, a double-blind placebo-controlled randomised study and a long term open trial have indicated that nifedipine is effective in the treatment of perniosis. At a dose of 20 mg to 60 mg daily, nifedipine significantly reduced the time to clearance of existing lesions and prevented the development of new chilblains. Nifedipine also reduced the pain, soreness and irritation of the lesions. A comparison of the pre- and post-treatment skin biopsies showed resolution of the dermal oedema and diminution of the perivascular infiltrate. An increase in cutaneous blood flow following administration of nifedipine suggests that the vasodilator action of this drug may be important in its action.

Acute sacral epidural abscess following local anaesthetic injection.

Spinal epidural abscesses are uncommon infections of the central nervous system. Delay in making the diagnosis increases the morbidity and mortality because irreversible neurological damage occurs during this time. We report a 45-year-old male who developed an acute sacral epidural abscess following a local anaesthetic injection given for the relief of low back pain. We believe this is the first documented case of a local anaesthetic injection causing an acute sacral epidural abscess.