UVB irradiation can cause considerable changes in the composition of cells in the skin and in cutaneous cytokine levels. We found that a single exposure of normal human skin to UVB induced an infiltration of numerous IL-4+ cells. This recruitment was detectable in the papillary dermis already 5 h after irradiation, reaching a peak at 24 h and declining gradually thereafter. The IL-4+ cells appeared in the epidermis at 24 h postradiation and reached a plateau at days 2 and 3. The number of IL-4+ cells was markedly decreased in both dermis and epidermis at day 4, and at later time points, the IL-4 expression was absent. The IL-4+ cells did not coexpress CD3 (T cells), tryptase (mast cells), CD56 (NK cells), and CD36 (macrophages). They did coexpress CD15 and CD11b, showed a clear association with elastase, and had a multilobed nucleus, indicating that UVB-induced infiltrating IL-4+ cells are neutrophils. Blister fluid from irradiated skin, but not from control skin, contained IL-4 protein as well as increased levels of IL-6, IL-8, and TNF-α. In contrast to control cultures derived from nonirradiated skin, a predominant type 2 T cell response was detected in T cells present in primary dermal cell cultures derived from UVB-exposed skin. This type 2 shift was abolished when CD15+ cells (i.e., neutrophils) were depleted from the dermal cell suspension before culturing, suggesting that neutrophils favor type 2 T cell responses in UVB-exposed skin.
Chronic activation of the inflammatory response, defined as inflammaging, is the key physio-pathological substrate for anabolic resistance, sarcopenia and frailty in older individuals. Nutrients can theoretically modulate this phenomenon. The underlying molecular mechanisms reducing the synthesis of pro-inflammatory mediators have been elucidated, particularly for vitamin D, n-3 polyunsaturated fatty acids (PUFA) and whey proteins. In this paper, we review the current evidence emerging from observational and intervention studies, performed in older individuals, either community-dwelling or hospitalized with acute disease, and evaluating the effects of intake of vitamin D, n-3 PUFA and whey proteins on inflammatory markers, such as C-Reactive Protein (CRP), interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). After the analysis, we conclude that there is sufficient evidence for an anti-inflammatory effect in aging only for n-3 PUFA intake, while the few existing intervention studies do not support a similar activity for vitamin D and whey supplements. There is need in the future of large, high-quality studies testing the effects of combined dietary interventions including the above mentioned nutrients on inflammation and health-related outcomes.
Acute, low-doses of ultraviolet (UV)-B radiation affect the immune competent cells of the skin immune system. In this study, we examined the time-dependent changes of the cutaneous T cell population in normal human volunteers following a single local exposure to UV. Solar-simulated UV radiation caused an initial decrease in intraepidermal T cell numbers, even leading to T cell depletion at day 4, whereupon a considerable infiltration of T cells in the epidermis occurred that peaked at day 14. In the dermis the number of T cells was markedly increased at days 2 (peak) and 4 after irradiation, and subsequently declined to the nonirradiated control values at day 10. Double-staining with several T cell markers showed that the T cells, infiltrating the (epi)dermis upon UV exposure, were almost exclusively CD4+ CD45RO+ T cells, expressing an alpha/beta type T cell receptor, but lacking the activation markers HLA-DR, VLA-1, and IL-2R. Application of UVB radiation resulted in similar dynamics of T cells, indicating that the UVB wavelengths within the solar-simulated UV radiation were responsible for the selective influx of CD4+ T cells. In conjunction with UVB-induced alterations in the type and function of antigen-presenting cells (i.e., Langerhans cells and macrophages), the changes of the cutaneous T cell population may also contribute to UVB-induced immunosuppression at skin level in man.
Background Few and small studies have described the management of immunomodulant/immunosuppressive therapies or phototherapy in atopic dermatitis (AD) patients during coronavirus disease 2019 (COVID‐19) pandemic. Methods A national registry, named DA‐COVID‐19 and involving 35 Italian dermatology units, was established in order to evaluate the impact of COVID‐19 pandemic on the management of adult AD patients treated with systemic immunomodulant/immunosuppressive medications or phototherapy. Demographic and clinical data were obtained at different timepoints by teledermatology during COVID‐19 pandemic, when regular visits were not allowed due to sanitary restrictions. Disease severity was assessed by both physician‐ and patient‐reported assessment scores evaluating itch intensity, sleep disturbances, and AD severity. Results A total of 1831 patients were included, with 1580/1831 (86.3%) continuing therapy during pandemic. Most patients were treated with dupilumab (86.1%, 1576/1831) that was interrupted in only 9.9% (156/1576) of cases, while systemic immunosuppressive compounds were more frequently withdrawn. Treatment interruption was due to decision of the patient, general practitioner, or dermatologist in 39.9% (114/286), 5.6% (16/286), and 30.1% (86/286) of cases, respectively. Fear of increased susceptibility to SARS‐CoV‐2 infection (24.8%, 71/286) was one of the main causes of interruption. Sixteen patients (0.9%) resulted positive to SARS‐CoV‐2 infection; 3 of them (0.2%) were hospitalized but no cases of COVID‐related death occurred. Conclusions Most AD patients continued systemic treatments during COVID pandemic and lockdown period, without high impact on disease control, particularly dupilumab‐treated patients.
Drug reaction with eosinophilia and systemic symptoms syndrome (DRESS) syndrome associated with azithromycin presenting like septic shock: a case report.
In this retrospective case series, acitretin was a moderately effective, well-tolerated treatment in children with moderate to severe plaque psoriasis. Given the small number of patients, statements about long-term safety are not possible.
four of them) or by RCM alone (evaluation performed by six of them) 1 year before and results were compared with the previous study. Mean sensitivity, specificity and overall diagnostic accuracy (ACC) and 95% CI were calculated for the specific diagnosis of different facial lesions (Table 1). As expected, considering the evaluation of the seven experts, the combination dermoscopy/RCM had a higher mean ACC for both malignant tumour (including LM/LMM) and LM/LMM of the face (84%, CI 80-89 and 84%, CI 79-89, respectively) than the two imaging techniques alone (74%, CI 68-80 for dermoscopy vs. 80%, CI 75-85 for RCM in case of LM/LMM and 75%, CI 68-80 for dermoscopy vs. 80%, CI 74-85 for RCM in case of malignant tumour). Notably, ACC increased for each investigator. The superiority of the ACC of the combination dermoscopy/RCM on the single imaging techniques for LM/LMM was also observed when comparing the current data to the results obtained in the previous study by all the 21 investigators. Considering all evaluations, the ACC increased from dermoscopy to RCM and to dermoscopy plus RCM. According to the CI, the combination dermoscopy/RCM improved both mean sensitivity and mean specificity of RCM alone for LM/LMM, whereas it highly improved mean sensitivity of dermoscopy alone but not its mean specificity (sensitivity of 65% CI 57-73, 82% CI 76-89 and 85% CI 80-91 and specificity of 88% CI 82-95, 77% CI 68-86 and 83% CI 75-91 for dermoscopy, RCM, and dermoscopy plus RCM, respectively). As already discussed, this fact was probably related to the presence of hyper-reflective dendritic Langerhans cells under RCM mistaken for neoplastic melanocytes in the epidermis of most misdiagnosed benign lesions. 9 Concerning the facial lesions other than LM/LMM, we also observed an increase in ACC with the combination dermoscopy/RCM (Table 1). In conclusion, this study shows that the integration of dermoscopy and RCM increases the ACC of both these techniques used alone for facial tumours. More in-depth studies should be carried out, even using machine learning techniques, for optimal integration of dermoscopic data with RCM data, in order to increase ACC by reducing possible false positives induced by the RCM examination. This study received the approval from the Ethical Committee of the University Hospital of Saint-Etienne (Institutional review board number 672016/CHUSTE).
We have prospectively evaluated psoriatic arthritis (PsA) patients for (1) seropositivity for former viral infections and seroconversion and (2) efficacy of cyclosporine A (CsA) alone or in combination with other immunosuppressants in a time period of 12 months. Screening included HBV antibodies and antigens, HCV antibodies and RNA, HSV 1-2, HZV, EBV, and CMV IgG, and IgM, HHV-6 DNA, and HIV 1-2 antibodies. PsA was evaluated by the Psoriasis Area Severity Index (PASI), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and the Visual Analogue Scale (VAS). At baseline, 126 (56%) out of 225 evaluable patients had 2 or more seropositivities indicative of former infections, and 31 patients (13.8%) presented seropositivity for HCV, HBV, HSV-1 and -2, HHV-6, EBV, or parvovirus infection; one of them, positive for HBAg, was treated with lamivudine, while the remaining 30 received no specific treatment. None of the 31 patients developed virus reactivation. A reduction (P < 0.001) of PASI, BASDAI, and VAS scores was observed at 6 and 12 months. The treatment of PsA with CsA as monotherapy or in combination was safe and effective. In vitro experiments and clinical findings, including those from our study, suggest that CsA as monotherapy or in combination with biologics might be the treatment of choice in PsA HCV-positive patients.
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