Delphinidin diminishes in vitro interferon-γ and interleukin-17 producing cells in patients with psoriatic disease.

The anthocyanidin delphinidin reduces psoriasiform lesions and inflammatory mediators in human cell culture systems. Its role in psoriatic disease has not yet been investigated. We assessed delphinidin's in vitro immunomodulatory effect on ex vivo stimulated peripheral blood mononuclear cells (PBMCs) from 50 individuals [26 with psoriasis, 10 with psoriatic arthritis (PsA) and 14 healthy controls (HCs)]. Cells were either left untreated or stimulated with PMA plus ionomycin in the presence or absence of delphinidin. Intracellular production of interferon-γ (IFNγ), interleukin-17A (IL-17A), and interleukin-10 (IL-10) was measured flow cytometrically. Delphinidin dose-dependently reduced IFNγ+ T cells from patients and HCs. The mean IFNγ decrease in CD4+ T subpopulations was 42.5 ± 28% for psoriasis patients, 51.8 ± 21.5% for PsA patients and 49 ± 17% for HCs (p < 0.001 for all). Similarly, IFNγ reduction in CD8+ T cells was 34 ± 21.6% for psoriasis patients, 47.1 ± 22.8% for PsA and 44.8 ± 14.3% for HCs (P < 0.001 for all). An inhibitory effect of delphinidin was also noted in IFNγ producing NKs and NKTs from psoriasis individuals. Delphinidin also significantly decreased IL-17+ CD4+ T cells in all tested subjects, with marginal effect on the increase of IL-10-producing T regulatory subsets. In conclusion, delphinidin exerts a profound in vitro anti-inflammatory effect in psoriasis and psoriatic arthritis by inhibiting IFNγ+ innate and adaptive cells and T helper (Th) 17 cells. If this effect is also exerted in vivo, delphinidin may be regarded as a nutraceutical with immunosuppressive potential.

Effectiveness of Autologous Whole-Blood Injections in Patients with Refractory Chronic Spontaneous Urticaria.

BACKGROUND: Nonsedating antihistamines are the treatment of choice for chronic spontaneous urticaria (CSU), while omalizumab and immunosuppressants have also been approved as an add-on treatment. Autologous whole-blood injection (AWBI) has been used in previous studies with ambiguous results. The aim of our study was to evaluate changes in the Urticaria Activity Score (UAS7), Dermatology Life Quality Index (DLQI), and Chronic Urticaria Quality of Life (CU-Q2oL) score, and also the association of serologic markers with disease severity measures after AWBI. METHODS: In this observational study, AWBIs were performed (8 courses on a weekly basis) in adults with refractory CSU, who refused an add-on treatment with either omalizumab or immunosuppressants. UAS7, DLQI, and CU-Q2oL questionnaires and serum concentrations of total IgE, C-reactive protein (CRP), and D-dimer were evaluated before and after the intervention. RESULTS: Nineteen patients (12 females; mean age 54 ± 20.8 years) completed the protocol. Following AWBI, significant improvements in the UAS7 (34.26 ± 8.04 vs. 12.52 ± 10.83, p < 0.001), DLQI (11.63 ± 5.51 vs. 3.47 ± 2.85, p < 0.001), and CU-Q2oL score (32.97 ± 18.71 vs. 10.94 ± 7.71, p < 0.001) were recorded. A negative correlation between the baseline D-dimer levels and UAS7 and DLQI variations (p = 0.002 and p = 0.001, respectively) was noted. D-dimer levels ≥292 ng/mL have been associated with poor responsiveness (sensitivity 75%; specificity 83.3%). No correlation with either total immunoglobulin E or CRP levels was observed. CONCLUSION: AWBI appears to be a safe, alternative, add-on therapeutic option in refractory CSU, particularly in patients with low plasma levels of D-dimer.

Multidisciplinary lymphedema treatment program.

Lymphedema is an underrecognized and undertreated condition that requires a multidisciplinary approach in an individualized program that will address the special needs of each patient. In an ideal setting of an outpatient management program the team should be composed of a vascular surgeon, a dermatologist, a physiotherapist, a dietician, a psychologist, a social worker, and an office employee, working together in the assessment and management of all aspects of lymphedema. All treatment strategies and actions taken should ultimately focus on the improvement of the quality of life of patients suffering from lymphedema and on the prevention of lymphedema in high-risk patients.

Increased HIF-1 alpha immunostaining in psoriasis compared to psoriasiform dermatitides.

BACKGROUND: Expression of hypoxia inducible factor 1 (HIF-1) alpha can be linked to inflammation through reciprocal interactions with several cytokines. This finding is in accordance with the previously noted HIF-1 alpha overexpression in psoriatic lesional keratinocytes. METHODS: In this study we have employed a carefully selected panel of antibodies and quantitative morphometric analysis to compare HIF-1 alpha immunoreactivity in psoriatic biopsy samples vs. that in samples obtained from psoriasiform dermatitides. RESULTS: We found statistically significant HIF-1 alpha overexpression in psoriasis. Furthermore, we observed a previously unreported preferential localization of immunoreactive keratinocytes in the immediate vicinity of inflamed and elongated papillae. This pattern of immunoreactivity may partially account for the observed increase of HIF-1 alpha immunostaining in psoriasis. CONCLUSIONS: Overall, our findings imply that possible novel therapeutic intervention(s) on the HIF-1 alpha pathway may offer another approach in controlling the inflammatory activity of psoriatic lesions.