Cutaneous T-cell lymphoma (CTCL) is a rare disease occurring in Europe among two persons per million per year. It affects men more often than women (2:1). It is primarily a skin disease. In about 20% of patients, it becomes fatal with tumours in the skin and spreading to lymph glands. Approximately 3% of patients show a leukemic form called Sezary's syndrome, where malignant cells are present in blood with accompanying erythrodermia. CTCL is a T-lymphocyte disease occurring late in life as the average age of patients is around 66 years in Europe, Japan and the US. This article focuses on cell lines and immune surveillance in CTCL, and especially the pronounced chromosomal instability. It leads to the hypothesis that chromosomal changes is the key event linked to DNA repair deficiencies, which in a subpopulation of T cells leads to CTCL development over years.
Adult atopic eczema is often chronic and with moderate to severe disease activity commonly complicated with Staphylococcus aureus infection. The 'gold standard' therapy is emollients in combination with topical steroids whose potency depends on the location of the eczema. A combination of a steroid and an antibiotic has shown its efficacy in infected eczema. If long-term control is needed the calcineurin inhibitors, pimecrolimus and tacrolimus, have shown their efficacy. Another option is the use of UV light, where narrowband UVB seems most beneficial. Only rarely is systemic immunosuppressive treatment necessary. It is important to discuss treatment strategies with the patients to secure long-term control of the eczema.
In treatment of severe atopic dermatitis, drugs with carcinogenic potentials are used to manage the disease. We therefore analyzed whether patients having severe atopic eczema had an increased cancer risk. The study population included all individuals hospitalized in Denmark with a primary diagnosis of atopic dermatitis during 1977-1996. Follow-up was conducted in 1996 in the Danish Cancer Register. A total of 6275 persons were included. Among 2030 adult patients, an increased risk of cancer was observed, standard morbidity ratio (SMR)=1.5 (95% CI: 1.2-1.9). Half the excess cases of cancer was keratinocyte carcinomas of the skin diagnosed within the first 9 y of follow-up, SMR=2.4 (95% CI: 1.4-3.9). For men, SMR=2.7 (95%CI: 1.2-5.4). In conclusion, earlier hospitalized adult atopic dermatitis patients had an increased risk of cancer. Half the excess cases of cancer were keratinocyte carcinomas. This may be a result of a detection bias or due to the carcinogenic potentials of some of the therapies of severe atopic dermatitis.
a University of Bonn, Bonn , Germany; b University of Sheffi eld Medical School & Sheffi eld Children’s Hospital, Sheffi eld , UK; c University of Michigan Medical School, Ann Arbor, Mich. , USA; d University of Verona, Verona , Italy; e St. Johns Institute of Dermatology, St. Thomas’ Hospital, London , UK; f Dalhousie University, Halifax , Canada; g University of Münster, Münster , and h Dresden University of Technology, Dresden , Germany; i St George Hospital, University of New South Wales, Sydney , Australia; j NYU School of Medicine, New York, N.Y. , and k Northwestern University’s Feinberg School of Medicine, Chicago, Ill. , USA; l Hôpital Necker-Enfants Malades, Paris , France; m Hospital Santa Creu i Sant Pau, Barcelona , Spain; n Technical University Munich, Munich , Germany; o University Hospital, Geneva , Switzerland; p University of Kiel, Kiel , Germany; q University of Toronto, Toronto , Canada; r Medical University of Vienna, Vienna , Austria; s Central Hospital, University of Bordeaux, Bordeaux , France; t Aarhus University Hospital, Aarhus , Denmark
BACKGROUND:Three years ago, the nonablative wrinkle reduction laser (a 585-nm laser, Chromogenex V3; Chromogenex Light Technologies, Llanelli, U.K.) was developed, and there have already been several reports about its clinical effectiveness. The Chromogenex V3 laser has also been reported to be effective in treating acne and atopic dermatitis. These results suggest that the Chromogenex V3 laser has some immunological role. In this study, we investigated immunological changes elicited by laser irradiation at the ultrastructural level and by analysis of interleukin (IL)-2 and IL-4 mRNA in skin homing T lymphocytes.MATERIALS AND METHODS:Eight healthy adult volunteers (mean age 56.3 years, range 25-66 years) were recruited for this study. Ultrastructural analysis was done 3 h after the laser irradiation, as well as 1 day, 3 days, 1 week, 2 weeks, 4 weeks and 5 weeks later. IL-2 and IL-4 mRNAs in skin homing T cells cultured for 6 weeks were semiquantitatively measured using reverse transcriptase-polymerase chain reaction.RESULTS:Ultrastructural observations revealed that at 3 h after laser therapy, neutrophils, monocytes and mast cells could already be seen in the extravascular dermis. These dermal acute inflammatory changes were observed also at 1 week after laser treatment. Two weeks after laser treatment, the capillaries showed an almost normal structure. Four weeks after laser treatment, many lymphocytes and fibroblasts were observed. The numbers of these lymphocytes increased further at 5 weeks after the laser treatment. One week after the laser irradiation, all subjects were positive for IL-2 mRNA and for IL-4 mRNA. The level of IL-4 mRNA was larger compared with that of IL-2 mRNA in all subjects.CONCLUSION:The Chromogenex V3 is a 585-nm visible light laser, and it may affect the skin not only by selective photothermolysis but also by direct cutaneous immunological activation.
Atopic dermatitis is a common skin disorder of unknown aetiology with peak incidence in early childhood. The disease is associated with peripheral T-cell accumulation in the skin. The thymus is a key organ of the cellular immune response early in life. We hypothesized that atopic dermatitis is associated with an unbalanced establishment of the peripheral T-lymphocyte system. This cross-sectional study was performed to compare thymus sizes in patients with atopic dermatitis and healthy controls. Thirty-seven children with current atopic dermatitis were enrolled and compared with 29 healthy controls. An interview and medical examination were performed by one doctor, an ultrasound scan was performed within 3 days of the examination, and the thymus index, a marker of thymus size, was measured. The thymus index was on average 32% higher (95% CI 3%-67%) in children with active atopic dermatitis compared with healthy controls. It declined with age in both children with atopic dermatitis and healthy controls, but the reduction in size was only significant for healthy controls. We demonstrate increased size of thymus among children with active atopic dermatitis compared with healthy controls. The larger size of thymus is compatible with increased thymic activity and emission of T lymphocytes.
A continuous cell line, Se-Ax, from a patient with Sézary syndrome has been established. The Se-Ax cell line is IL-2 dependent, requires human serum for permanent growth, and has the following phenotype: CD1-, CD2+, CD3+, CD4-, CD5-, CD8-, CD20-, CD25+; it expresses the T9, T10, and HLA-DR antigens. This cell line reveals multiple chromosome aberrations as seen in the most abundant abnormal clone in peripheral blood. Therefore, it is not unlikely that it derives from tumor cells. A putative cytotoxic cell line derived from the same patient has only weak killer-cell activity against the autologous permanent cell line: this CD8+ cytotoxic cell line has a 14q+ chromosomal marker. The fact that the patient demonstrated no natural killer-cell or activated killer-cell activity against the Se-Ax cell line may in part explain the successful establishment of the continuous cell line from bulk culture.
The prevalence of atopic dermatitis increased markedly in the period 1960s to the 1990s. Earlier findings indicate that infections acquired in early life enhance or suppress the expression of atopic disease as a result of a change in immune reactivity. Our objectives were to examine the association between measles, mumps and rubella vaccination, measles infection and the risk of atopic dermatitis. A random sample of 9,744 children were followed up from birth to 3-15 years. Their parents responded to a questionnaire including highly structured questions on atopic dermatitis, measles, mumps and rubella vaccination and measles infection. Information on parental educational level was obtained from Statistics Denmark. The cumulative incidence of atopic dermatitis at age 14 was 19.7%. The confounder adjusted incidence ratio of atopic dermatitis among measles, mumps and rubella vaccinated children versus children not subjected to measles, mumps and rubella vaccination and measles infection was 1.86 (95% CI 1.25-2.79); the incidence ratio for measles-infected children was similar. The incidence of atopic dermatitis increased after measles, mumps and rubella vaccination and measles infection, which is surprising in view of the hygiene hypothesis. We suggest further study of the possible short-term and long-term effects of virus and bacteria on the immune responses and expression of atopic disease.
Atopic dermatitis (AD) is today the most common, chronic inflammatory skin disease among children in developed countries. Its cumulative prevalence varies from 20% in northern Europe and the USA to approximately 5% in Mediterranean countries. As a chronic disease it puts a special demand on treatment. There is no curative therapy, but competent guidance on treatment principles can control the disease in most, if not all children. This article summarizes the evidence-based knowledge that relates to the treatment of atopic eczema. It also gives advice and opinions on prophylactic measures as these are the focus of interest from most parents.Learning objective This article should enable you to give advice and guidance to parents of children with AD, including what is necessary for diagnosis, what is of value and importance considering allergies and allergological investigations, allergen exposure, prophylactic measures, diets and indoor environment. Finally, you should be able to explain the diversity of treatment principles for parents.