A high prevalence of cytomegalovirus antigenaemia in patients with moderate to severe chronic plaque psoriasis: an association with systemic tumour necrosis factor α overexpression

Microbiological aspects are considered to be of pathophysiological importance in psoriasis, but there has so far been no information regarding cytomegalovirus (CMV) infection. This is of interest due to the high prevalence of latent infection in the general population, the frequent reactivation in inflammatory diseases, and the immunomodulating capacity of CMV. To detect active infection we analysed CMV antigen expression of peripheral blood mononuclear cells (PBMC) from psoriatic patients ( n  = 30) in comparison with healthy volunteers ( n  = 65). Using three monoclonal antibodies and immunocytological staining (alkaline phosphatase–antialkaline phosphatase technique), we frequently found CMV antigenaemia in psoriasis (43%) compared with healthy laboratory staff (12%, P  < 0.01) and blood donors (6%, P  < 0.001). Clearance of CMV antigenaemia was observed with antipsoriatic treatment. CMV antigenaemia was symptomless, and was associated with seropositivity for anti-CMV IgG but not IgM antibodies, indicating subclinical activation of latent infection. Serological investigations in 85 psoriatic patients gave no evidence for a higher prevalence of latent CMV infection. In psoriatic lesions, CMV DNA was only rarely detected by polymerase chain reaction. As it has been shown that tumour necrosis factor (TNF)-α can induce CMV reactivation, we determined TNF-α plasma concentrations and mRNA expression in PBMC from psoriatic patients. Elevated TNF-α levels were found and correlated with the frequency of CMV antigen-expressing PBMC, suggesting a critical role of TNF-α in CMV activation. We speculate that active, subclinical CMV infection may be of pathophysiological importance in psoriasis.     

A successful response to an outbreak of cholera in Afghanistan

Although postconflict Afghanistan has some of the worst health indicators in the world, the government is working hard to rebuild the health infrastructure, extend services to underserved areas and improve the quality of health services. An outbreak of cholera ElTor O1 that struck Kabul and spread nationwide in 2005, prompted a collaborative response from the Afghan Ministry of Public Health, partner agencies, and the system established to provide the Basic Package of Health Services, of which diarrhoeal disease control is an essential component. This response illustrates that, with good preparation, it is possible to respond to an outbreak of cholera effectively. The very low mortality rate during the outbreak (0.1%) shows how a resource-poor country can succeed in providing high-quality health services with government commitment, coordinated action by partners, proper case management and treatment and expanded access to services.     

Interleukin 10 treatment of psoriasis: clinical results of a phase 2 trial

OBJECTIVE: To determine the safety and clinical effects of interleukin 10 (IL-10) treatment of psoriasis. DESIGN AND METHODS: In an open-label phase 2 trial, 10 patients with psoriasis subcutaneously received recombinant human IL-10 over a 7-week period in a dosage of 8 microg/kg daily (n=5) or 20 microg/kg 3 times per week (n=5). Patients were followed up for an additional 5 weeks. RESULTS: The treatment was well tolerated. Antipsoriatic effects were found in all but 1 patient. A significant decrease of the psoriasis area and severity index by 55.3% +/- 11.5% (mean +/- SEM) was observed (P<.02). The antipsoriatic efficiency was confirmed by histological examination. Heterogeneity in the effectiveness was found among the patients, but seems to be independent of the dosage regimen. However, a tendency to a better response was found in the patients who received 20-microg/kg IL-10 3 times per week. Decreasing response in the delayed-type hypersensitivity reaction against recall antigens indicated immunosuppressive effects. Moderate effects on hematopoietic cells were observed. CONCLUSIONS: Our data suggest that IL-10 therapy for psoriasis is safe and possibly clinically effective. Consequently, its value in psoriasis and similar immune diseases should be further determined. Dose-finding, placebo-controlled, double-blind trials are necessary now.     

Glucocorticoid therapy-induced skin atrophy

Glucocorticoids (GCs) are highly effective for the topical treatment of inflammatory skin diseases. Their long-term use, however, is often accompanied by severe and partially irreversible adverse effects, with atrophy being the most prominent limitation. Progress in the understanding of GC-mediated molecular action as well as some advances in technologies to determine the atrophogenic potential of compounds has been made recently. It is likely that the detailed mechanisms of GC-induced skin atrophy will be discovered and in vitro models for the reliable prediction of atrophy will be established in the foreseeable future. This knowledge will not only facilitate safety profiling of established drugs but will also foster further drug discovery by improving compound characterization processes. New insights into GC modes of action will guide optimization strategies aiming at novel GC receptor ligands with improved effect/side effect profile.     

Interleukin-10 promoter polymorphism IL10.G and familial early onset psoriasis

BACKGROUND: The anti-inflammatory cytokine interleukin (IL)-10 is considered to play a major role in the pathophysiology of psoriasis, which is characterized by an IL-10 deficiency. Systemic administration of IL-10 has been shown to be an effective therapy for psoriasis. The IL-10 promoter region contains a highly polymorphic microsatellite (IL10.G) and in a recent case-control study the IL10.G13 (144 bp) allele was found to be associated with familial early onset psoriasis (type 1 psoriasis) having a susceptible effect. OBJECTIVES: As it is essential in multifactorial diseases to replicate findings before definite conclusions can be drawn, we decided to perform a follow-up study and to follow a genetic approach analysing allele transmission in families with a positive family history of psoriasis. METHODS: We studied 137 nuclear families (trio-design) comprising 456 individuals and genotyped the IL10.G marker. For comparison we also genotyped the microsatellite tn62 as a reference marker of the major psoriasis susceptibility locus on chromosome 6p21 (PSORS1). In the present study allele transmission was evaluated using the family-based association test (FBAT) and GENEHUNTER 2.0 based on the transmission/disequilibrium test. RESULTS: The G13 allele (144 bp) had a frequency of 24%, was present in 88 families and clearly showed an even transmission (FBAT, P = 0.753). In contrast, allele 3 (IL10.G9) (136 bp) had a frequency of 39%, was present in 110 families and was transmitted in 43 trios and remained untransmitted in 67 trios (FBAT, P = 0.026), thus showing preferential nontransmission. For the HLA-linked tn62-marker we obtained a P-value of 0.00027 for allele 4 in the same study group. CONCLUSIONS: In conclusion, we failed to confirm the susceptible effect of the G13 allele, but provide the first data for a protective effect of allele 3 (IL10.G9) for familial psoriasis. Our results suggest that the IL10.G polymorphism is not a major locus, but acts as a minor locus.     

Interleukin‐ und Interferontherapie in der Dermatologie

Summary: Cytokines are highly potent biologically active proteins that play an essential role in intercellular communication. They are vital to the mediation and regulation of inflammatory and specific immune reactions as well as to non immunological processes. Several cytokines are already used for the treatment of malignant, inflammatory and infectious skin diseases. This in particular includes certain interleukins (ILs) and interferons (IFNs). Whereas some cytokine therapies are already approved and well established, such as IFN‐α and IL‐2 (approved in the USA) for melanoma, others are in the early stages of development and are used in explorative trials (e.g. IL‐4 and IL‐10 in the treatment of psoriasis). It is likely that some of the new approaches currently under investigation will actually lead to both the registration of new drugs for dermatological treatment, and to supplementation of existing therapeutic options. The aim of this review is to give an overview on the current state of cytokine therapy in dermatology.