Alopecia areata is characterized by expansion of circulating Th2/Tc2/Th22, within the skin-homing and systemic T-cell populations.

BACKGROUND: Characterizing blood profile of alopecia areata (AA) is important not only for treatment advancements, but also for possibly identifying peripheral biomarkers that will eliminate the need for scalp biopsies. We aimed to compare frequencies of skin homing (CLA+ ) vs systemic (CLA- ) "polar" CD4+ and CD8+ and activated T-cell subsets in AA vs atopic dermatitis (AD) and control blood. METHODS: Flow cytometry was used to measure IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines in CD4+ and CD8+ T cells. Inducible co-stimulator molecule (ICOS) and HLA-DR were used to define mid- and long-term T-cell activation. We compared peripheral blood from 32 moderate-to-severe AA adults with 43 moderate-to-severe AD patients and 30 age-matched controls. RESULTS: AA patients had increased CLA+ /CLA- Th2 (P < .007), CLA+ Tc2 (P = .04), and CLA+ Th22 (P < .05) frequencies than controls. Except of CLA- Tc1 cells (P = .03), IFN-γ levels were mostly similar between AA, AD, and controls (P > .1). ICOS and HLA-DR activation were significantly higher in AA than controls (P < .05). T regulatory cells were significantly decreased in AA patients than controls (P < .01) and were correlated with activated CD8+ T cells and with multiple cytokine subsets (P < .05). While Th2 and Tc2 clustered with disease severity, IFN-γ producing cells were linked with AA duration. CONCLUSIONS: Alopecia areata is accompanied by Th2/Tc2 activation in skin-homing and systemic subsets, correlating with disease severity, while IFN-γ is linked to disease chronicity. These data hint for a possible role of diverse T-cells subsets in disease pathogenesis and emphasize the systemic nature of AA supporting the need for systemic therapeutic strategies in severe patients.

Circulating CLA+ T cells in atopic dermatitis and their possible role as peripheral biomarkers.

Cutaneous lymphocyte-associated antigen (CLA+ ) T cells are specialized for skin homing and represent the main T-cell population in atopic dermatitis (AD) lesions. CLA+ is expressed on the surface of circulating CD45RO+ memory T cells and most skin-infiltrating T cells. Mechanistic studies and thus treatment advancements are limited by the need of large number of skin biopsies. Circulating CLA+ T cells may be a reliable surrogate marker of the inflammatory events occurring in the skin, and thus, the evaluation of CLA+ T cells in the blood may eliminate the need for skin biopsies. Preliminary work in AD has established that disease-associated T-cell abnormalities can be approached by either a study of skin lesions or activated CLA+ T-cell subsets in peripheral blood. Future studies in adults and children, across different skin disorders, correlating blood and skin phenotypes and determining skin-homing T-cell functional properties are needed to establish whether CLA+ memory subsets can be used as biomarkers and a substitute for skin biopsies. This review summarizes the latest advancements reached on circulating CLA+ in AD and the great potential they harbor in understanding AD mechanisms.

Patients with early-onset psoriasis achieve better results following Dead Sea climatotherapy.

BACKGROUND: Plaque psoriasis has recently been divided in two types, which differ in severity and inheritance according to the age of the patient at the onset of the disease. AIM: To compare the effect of Dead Sea climatotherapy (DSC) on these two types of disease, with early vs. late onset, and to determine the impact of this treatment on the response rate. METHODS: The files of 605 patients who were suffering from plaque psoriasis were retrieved from the database of the Research Institute at the Dead Sea (RIDS) and divided in two groups, types I and II, according to whether the age at the onset of the disease was under or over 40 years, respectively. The primary outcome for the assessment of DSC was Psoriasis Assessment of Severity Index of 95 (PASI 95), which indicates that the PASI improvement percentage reached 95%. Logistical regression was used to identify the factors that related to the observed outcome. RESULTS: By the end of the study, 74% of the patients in group 1 reached PASI 95 in comparison to 62% in group 2. The 95% confidence interval for the odds ratio (OR) of the effect in group 2 in comparison to that of group 1 was [0.31, 0.99], which implies that group 1 responded better to treatment in comparison to group 2. Cut-off values for patients who were aged 30 and 20, respectively, exhibited similar trends; 75% vs. 65% and 78% vs. 68% for groups 1 and 2, respectively. CONCLUSIONS: Efficacy rates following DSC were impressively high for plaque psoriasis patients. Contrary to our hypothesis, the treatment effect was found to inversely correlate with the age of the patient at disease onset.

SCORAD 75: a new metric for assessing treatment outcomes in atopic dermatitis.

OBJECTIVE: The scoring atopic dermatitis (SCORAD) is a well-established severity-scoring tool for atopic dermatitis (AD). Dead Sea climatotherapy (DSC) is a natural selective balneo-phototherapy utilized for many years to treat severe AD. The study's goal was to evaluate the impact of DSC on AD patients through assessment of SCORAD scores and to identify parameters associated with greater improvement. METHODS: The files of 78 European patients (37 male patients and 41 female patients, mean age 37.8 years) with AD undergoing DSC were included in this retrospective study. Three sub-groups were delineated based on disease severity (as determined using the SCORAD). Demographic and clinical parameters as well as treatment characteristics--maximal and cumulative sun exposure doses--were recorded. SCORAD values were again recorded for assessment of treatment response. SCORAD 75 was defined as ≥75% decrease in SCORAD values following therapy. Statistical analysis including logistic regression models was used in multivariable analysis. RESULTS: After an average of 30 days of treatment, mean SCORAD values dropped from 50.5 to 11 (76.7%, P<0.001). 64.1% of all patients, regardless of sub-group, reached SCORAD 75, whereas 78.9% of patients with severe disease achieved this result. In a multivariate logistic regression, factors associated with achieving SCORAD 75 were maximal sun exposure, family history of AD and age at disease onset (P=0.002, P=0.009 and P=0.040 respectively). CONCLUSION: Dead Sea climatotherapy is a particularly effective treatment method for the sub-population of adults with severe AD. The SCORAD 75 can be useful for defining sub-populations in which treatment is more likely to be successful.

Dead Sea climatotherapy for vitiligo: a retrospective study of 436 patients.

BACKGROUND: Vitiligo is an acquired idiopathic skin disorder characterized by depigmented macules and patches. Despite many therapies available today, treatment of vitiligo remains a challenge. Preliminary reports cite encouraging results for Dead Sea Climatotherapy (DSC) in vitiligo patients. OBJECTIVE: To evaluate the efficacy of DSC in 436 patients suffering from vitiligo. METHODS: Files of 436 vitiligo patients, who were treated by DSC between the years 1997 and 2005 at the Deutsches Medizinisches Zentrum (DMZ) Medical Center, were retrieved for analysis. Climatotherapy, including gradually increased sun exposure following a sea bath, was administered in accordance with a computer-designed protocol. Age at vitiligo onset, skin phototype, skin involvement, duration of disease, as well as timing and duration of DSC were recorded. Logistic regression was used to estimate the effect of each one of the parameters analysed on the treatment's success. RESULTS: Following treatment, 3.9% of patients demonstrated total or significant repigmentation (defined by more than 50% repigmentation in more than 50% of the lesions); 81.4% showed good repigmentation; 13.1% showed no repigmentation but their vitiligo spots were pink-colored and 1.6% appeared not to be affected at all by DSC. Patient response to the treatment was inversely proportional to the size of the affected area. A negative correlation was found between duration of the vitiligo and the clinical short-term response to DSC. In addition, the longer the stay at the Dead Sea the better was the result. CONCLUSION: Climatotherapy at the Dead Sea is an effective treatment modality for vitiligo. Disease duration and severity, as well as length of treatment, were the main factors found to favourably influence the clinical response.