Four weeks of vitamin D supplementation improves nitric oxide-mediated microvascular function in college-aged African Americans.

Reduced nitric oxide (NO)-mediated cutaneous vasodilation, secondary to increased oxidative stress, presents in young African American (AA) compared with European American (EA) adults and may be modulated by vitamin D status. We assessed cutaneous microvascular function in 18 young, healthy (21 ± 2 yr; 9 men, 9 women) subjects before (pre, 8 AA, 10 EA) 4 wk of 2,000 IU/day oral vitamin D supplementation and in 13 subjects after (post, 7 AA, 6 EA) 4 wk of 2,000 IU/day oral vitamin D supplementation. Serum vitamin D concentrations [25(OH)D] were measured at each visit. Three intradermal microdialysis fibers placed in the ventral forearm were randomized for treatment with 10 µM Tempol, 100 µM apocynin, or lactated Ringer's solution (control). Local heating (39°C) induced cutaneous vasodilation; red cell flux was measured at each site (laser-Doppler flowmetry), and cutaneous vascular conductance (CVC = flux/MAP) was expressed as a percentage of maximum (28 mM sodium nitroprusside, +43°C) for each phase of local heating. After stable elevated blood flow was attained, 15 mM NG-nitro-l-arginine methyl ester (l-NAME; NO synthase inhibitor) was perfused at all sites to quantify the NO contribution to cutaneous vasodilation (%NO), calculated as the difference between local heating and l-NAME plateaus. Serum [25(OH)D], the magnitude of the local heating response, and %NO were all lower in AAs versus EAs (P < 0.01). Tempol (P = 0.01), but not apocynin (P ≥ 0.19), improved the local heating response and %NO. Four weeks of supplementation improved serum [25(OH)D], the local heating response, and %NO in AAs (P ≤ 0.04) but not in EAs (P ≥ 0.41). Vitamin D supplementation mitigated endothelial dysfunction, an antecedent to overt cardiovascular disease (CVD), in otherwise healthy, young AA adults.NEW & NOTEWORTHY Endothelial dysfunction, an antecedent to overt cardiovascular disease (CVD), is observed earlier and more frequently in otherwise healthy African Americans (AAs) when compared with other ethnic groups. Vitamin D may modulate endothelial function, and darkened skin pigmentation increases risk of vitamin D deficiency. We show that 4 wk of 2,000 IU/day vitamin D supplementation improves microvascular responses to local heating in AAs. Ensuring adequate vitamin D status may mitigate development of cardiovascular dysfunction in this at-risk population.

Sunscreen or simulated sweat minimizes the impact of acute ultraviolet radiation on cutaneous microvascular function in healthy humans.

NEW FINDINGS: What is the central question of this study? Are ultraviolet radiation (UVR)-induced increases in skin blood flow independent of skin erythema? Does broad-spectrum UVR exposure attenuate NO-mediated cutaneous vasodilatation, and does sunscreen or sweat modulate this response? What are the main findings and their importance? Erythema and vascular responses to UVR are temporally distinct, and sunscreen prevents both responses. Exposure to UVR attenuates NO-mediated vasodilatation in the cutaneous microvasculature; sunscreen or simulated sweat on the skin attenuates this response. Sun over-exposure may elicit deleterious effects on human skin that are separate from sunburn, and sunscreen or sweat on the skin may provide protection. ABSTRACT: Exposure to ultraviolet radiation (UVR) may result in cutaneous vascular dysfunction independent of erythema (skin reddening). Two studies were designed to differentiate changes in erythema from skin vasodilatation throughout the 8 h after acute broad-spectrum UVR exposure with (+SS) or without SPF-50 sunscreen (study 1) and to examine NO-mediated cutaneous vasodilatation after acute broad-spectrum UVR exposure with or without +SS or simulated sweat (+SW) on the skin (study 2). In both studies, laser-Doppler flowmetry was used to measure red cell flux, and cutaneous vascular conductance (CVC) was calculated (CVC = flux/mean arterial pressure). In study 1, in 14 healthy adults (24 ± 4 years old; seven men and seven women), the skin erythema index and CVC were measured over two forearm sites (UVR only and UVR+SS) before, immediately after and every 2 h for 8 h post-exposure (750 mJ cm-2 ). The erythema index began to increase immediately post-UVR (P < 0.05 at 4, 6 and 8 h), but CVC did not increase above baseline for the first 4-6 h (P ≤ 0.01 at 6 and 8 h); +SS prevented both responses. In study 2, in 13 healthy adults (24 ± 4 years old; six men and seven women), three intradermal microdialysis fibres were placed in the ventral skin of the forearm [randomly assigned to UVR (450 mJ cm-2 ), UVR+SS or UVR+SW], and one fibre (non-exposed control; CON) was placed in the contralateral forearm. After UVR, a standardized local heating (42°C) protocol quantified the percentage of NO-mediated vasodilatation (%NO). The UVR attenuated %NO compared with CON (P = 0.01). The diminished %NO was prevented by +SS (P < 0.01) and +SW (P < 0.01). Acute broad-spectrum UVR attenuates NO-dependent dilatation in the cutaneous microvasculature, independent of erythema. Sunscreen protects against both inflammatory and heating-induced endothelial dysfunction, and sweat might prevent UVR-induced reductions in NO-dependent dilatation.

Bundled payment for actinic keratosis management: Pilot evaluation of developed models.

BACKGROUND: There is an opportunity to explore alternate payment models in dermatology. OBJECTIVE: To pilot 2 bundled payment models for actinic keratosis (AK) management. METHODS: A prospective cohort study was conducted during September 2013-June 2016. Consecutive patients were recruited from clinics of 5 dermatologists. Patients had to be adults, have ≥1 year of care at the department, and have a history of AK. A bundled payment strategy was prospectively piloted for 1 year and compared with costs in the prior year. RESULTS: Overall, 400 participants were enrolled, and complete data was collected for 254 participants. During the year of bundled payments, actual total annual spending on claims was $70,557, whereas model 1 and model 2 bundled payment models would have totaled $67,310 and $74,422, respectively, for the patient cohort. Patient satisfaction surveys showed no difference in the quality of care. LIMITATIONS: Single-center study and limited sample size. International Classification of Diseases 9 and 10 codes were used to identify claims and might be inaccurate. Costs were modeled rather than fully implemented. CONCLUSION: Dermatologists should be aware of bundled payment models. More work is needed to elucidate the optimal formulation of a bundled payment for AK management, including the services covered, time delimitation, and risk stratification factors.

Endothelial function is impaired in the cutaneous microcirculation of adults with psoriasis through reductions in nitric oxide-dependent vasodilation.

Psoriasis is an independent risk factor for cardiovascular disease; however, the underlying mechanisms are not fully understood. Deficits in conduit arterial function are evident in patients with psoriasis, but potential impairments in microcirculatory endothelial function remain unclear. We hypothesized that cutaneous microvascular dysfunction would be detectable in otherwise healthy individuals with psoriasis. Two intradermal microdialysis fibers were placed in (nonlesional) forearm skin of nine patients (3 men and 6 women, 39 ± 5 yr) with moderate (16 ± 2% of body surface area) plaque psoriasis and nine healthy (nonpsoriatic) control subjects (3 men and 6 women, 38 ± 5 yr) for local delivery of 1) lactated Ringer solution (control) and 2) 10 mM l-ascorbate (a nonspecific antioxidant). An index of skin blood flow was measured using laser-Doppler flowmetry during local heating (42°C). Nitric oxide (NO)-dependent vasodilation was directly quantified after perfusion of the nonspecific NO synthase inhibitor NG-nitro-l-arginine methyl ester (15 mM). A third fiber was perfused with increasing concentrations (10-10 - 10-2 M) of norepinephrine to elicit adrenoreceptor-mediated cutaneous vasoconstriction. NO-dependent vasodilation was attenuated in patients with psoriasis (57 ± 5% and 39 ± 7% maximum cutaneous vascular conductance in control subjects and adults with psoriasis, respectively, P < 0.01). l-Ascorbate did not improve NO-dependent vasodilation ( P > 0.05). There was no group difference in maximal vasoconstriction or microvascular sensitivity to norepinephrine ( P > 0.05). These data suggest that NO bioavailability is reduced in otherwise healthy individuals with psoriasis, which contributes to systemic microvascular dysfunction. NEW & NOTEWORTHY In adults with psoriasis, reduced nitric oxide bioavailability mediates impaired endothelium-dependent vasodilation, independent of increases in oxidative stress. Furthermore, the degree of psoriatic symptomology is directly related to greater reductions in nitric oxide-dependent vasodilation.

Psoriasis and palmoplantar pustulosis associated with tumor necrosis factor-α inhibitors: the Mayo Clinic experience, 1998 to 2010.

BACKGROUND: Tumor necrosis factor (TNF)-α antagonists have been associated with the induction of de novo or worsening psoriasis. OBJECTIVE: We sought to retrospectively examine the clinical characteristics and outcomes of patients with psoriasis associated with anti-TNF-α therapy. METHODS: We performed a retrospective review of patients with new-onset or worsening psoriasis during TNF-α inhibitor therapy between 1998 and 2010. RESULTS: Of the 56 patients (mean age at psoriasis onset, 48.1 years), 41 (73%) were female. In all, 22 patients (39%) had Crohn's disease and 14 (25%) had rheumatoid arthritis. Thirty patients (54%) were treated with infliximab, 19 (34%) with adalimumab, and 7 (12%) with etanercept. New-onset or worsening psoriasis occurred after a mean treatment duration of 17.1 months. Plaque psoriasis (n = 27), palmoplantar pustulosis (n = 25), scalp psoriasis (n = 12), generalized pustular psoriasis (n = 7), erythrodermic psoriasis (n = 2), and inverse psoriasis (n = 2) were the cutaneous presentations. Among the 39 patients for whom full treatment response data were available, 33 (85%) had a complete or partial response; combined response rates (complete and partial) were slightly higher among those who discontinued anti-TNF-α therapy (16 of 17 patients [94%]) than among those who continued anti-TNF-α therapy (17 of 22 patients [77%]). LIMITATIONS: Retrospective nature, possible referral bias, and lack of complete follow-up for some patients are limitations. CONCLUSION: Although some patients sufficiently controlled their psoriasis while continuing anti-TNF-α therapy, those who discontinued therapy achieved higher rates of complete response. Further studies should explore the efficacy and safety of switching to an alternative anti-TNF-α agent.

Metastatic Hürthle cell carcinoma of the thyroid presenting as ulcerated scrotum nodules.

Cutaneous metastasis from Hürthle cell carcinoma of the thyroid is an extremely rare phenomenon. As far as we can determine, there has been only a single case documented. Our patient, a 68-year old man with a history of Hürthle cell carcinoma of the thyroid, had cutaneous nodules in the scrotum and right chin. Histologic and immunohistochemical examinations confirmed the diagnosis of metastatic Hürthle cell carcinoma of the thyroid. To the best of our knowledge, this is the first reported case of scrotal skin metastasis. This case emphasizes the importance of thorough clinicopathologic correlation for any patient with a malignant scrotal cutaneous neoplasm with Hürthle cell or oncocytic differentiation.

Reactive nonsexually related acute genital ulcers: review of cases evaluated at Mayo Clinic.

BACKGROUND: Reactive nonsexually related acute genital ulcers (RNSRAGU) occur in pubertal girls after an acute systemic infection. OBJECTIVE: We sought to characterize RNSRAGU by reviewing the medical records of patients with this disorder. METHODS: We searched our medical index database from 1997 to 2007 for RNSRAGU cases. Questionnaires were mailed to identified patients. RESULTS: The study included 10 patients; 5 responded to the questionnaire. The mean age at onset was 11.5 years. Vulvar ulcers were preceded by viral gastroenteritis (n = 3), viral upper respiratory tract infection (n = 3), streptococcal pharyngitis (n = 1), influenza (n = 1), and other nonspecific febrile illnesses (n = 2). Seven patients had oral involvement also; 6 had at least one recurrence; and 3 were hospitalized for pain control. Analgesics and topical corticosteroids were the most common treatments. Ulcerations resolved within several weeks in all patients. LIMITATIONS: Retrospective study design, small study size, and 50% questionnaire response rate are limitations. CONCLUSIONS: Although rare, RNSRAGU should be considered when genital ulceration follows an acute systemic illness.