Melanin distribution from the dermal–epidermal junction to the stratum corneum: non-invasive in vivo assessment by fluorescence and Raman microspectroscopy

The fate of melanin in the epidermis is of great interest due to its involvement in numerous physiological and pathological processes in the skin. Melanin localization can be assessed ex vivo and in vivo using its distinctive optical properties. Melanin exhibits a characteristic Raman spectrum band shape and discernible near-infrared excited (NIR) fluorescence. However, a detailed analysis of the capabilities of depth-resolved confocal Raman and fluorescence microspectroscopy in the evaluation of melanin distribution in the human skin is lacking. Here we demonstrate how the fraction of melanin at different depths in the human skin in vivo can be estimated from its Raman spectra (bands at 1,380 and 1,570 cm−1) using several procedures including a simple ratiometric approach, spectral decomposition and non-negative matrix factorization. The depth profiles of matrix factorization components specific to melanin, collagen and natural moisturizing factor provide information about their localization in the skin. The depth profile of the collagen-related matrix factorization component allows for precise determination of the dermal–epidermal junction, i.e. the epidermal thickness. Spectral features of fluorescence background originating from melanin were found to correlate with relative intensities of the melanin Raman bands. We also hypothesized that NIR fluorescence in the skin is not originated solely from melanin, and the possible impact of oxidized species should be taken into account. The ratio of melanin-related Raman bands at 1,380 and 1,570 cm−1 could be related to melanin molecular organization. The proposed combined analysis of the Raman scattering signal and NIR fluorescence could be a useful tool for rapid non-invasive in vivo diagnostics of melanin-related processes in the human skin

Urticarial Vasculitis Differs from Chronic Spontaneous Urticaria in Time to Diagnosis, Clinical Presentation, and Need for Anti-Inflammatory Treatment: An International Prospective UCARE Study.

Background: Chronic spontaneous urticaria (CSU) and urticarial vasculitis (UV) share several clinical features including the occurrence of wheals. As of yet, the criteria for differentiating the 2 disorders are not clearly defined. Objective: Here, we aimed to identify differences, similarities, and the likelihood for specific clinical features in patients with UV versus those with CSU. Methods: Across 10 Urticaria Centers of Reference and Excellence, 106 patients with skin biopsy–confirmed UV and 126 patients with CSU were prospectively recruited to complete a questionnaire on the clinical features, course, and response to treatment of their disease. Results: As compared with CSU, patients with UV more often experienced postinflammatory skin hyperpigmentation, wheals of ≥24-hour duration, eye inflammation, and fever (6.9, 4.0, 3.6, and 2.4 times, respectively). Clinical features that increased the risk for UV diagnosis when present at the onset of disease included wheals of ≥24-hour duration (7.3-fold), pain of the skin (7.0-fold), postinflammatory hyperpigmentation (4.1-fold), and fatigue (3.1-fold). The diagnostic delay was markedly longer for normocomplementemic UV as compared with hypocomplementemic UV and CSU (21 vs 5 vs 6 months, respectively). Oral corticosteroids and omalizumab were the most effective treatments in patients with UV and CSU, respectively. Patients with UV showed a higher need for immunosuppressive and anti-inflammatory therapies than patients with CSU. Conclusions: Long wheal duration, skin pain and hyperpigmentation, and systemic symptoms point to UV rather than CSU as the underlying disease and should prompt further diagnostic workup including a skin biopsy

Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination:Results of the UCARE COVAC-CU study

Background: Concern about disease exacerbations and fear of reactions after coronavirus disease 2019 (COVID-19) vaccinations are common in chronic urticaria (CU) patients and may lead to vaccine hesitancy.Objective: We assessed the frequency and risk factors of CU exacerbation and adverse reactions in CU patients after COVID-19 vaccination. Methods: COVAC-CU is an international multicenter study of Urticaria Centers of Reference and Excellence (UCAREs) that retrospectively evaluated the effects of COVID-19 vaccination in CU patients aged ≥18 years and vaccinated with ≥1 dose of any COVID-19 vaccine. We evaluated CU exacerbations and severe allergic reactions as well as other adverse events associated with COVID-19 vaccinations and their association with various CU parameters. Results: Across 2769 COVID-19–vaccinated CU patients, most (90%) received at least 2 COVID-19 vaccine doses, and most patients received CU treatment and had well-controlled disease. The rate of COVID-19 vaccination–induced CU exacerbation was 9%. Of 223 patients with CU exacerbation after the first dose, 53.4% experienced recurrence of CU exacerbation after the second dose. CU exacerbation most often started &lt;48 hours after vaccination (59.2%), lasted for a few weeks or less (70%), and was treated mainly with antihistamines (70.3%). Factors that increased the risk for COVID-19 vaccination–induced CU exacerbation included female sex, disease duration shorter than 24 months, having chronic spontaneous versus inducible urticaria, receipt of adenovirus viral vector vaccine, having nonsteroidal anti-inflammatory drug/aspirin intolerance, and having concerns about getting vaccinated; receiving omalizumab treatment and Latino/Hispanic ethnicity lowered the risk. First-dose vaccine–related adverse effects, most commonly local reactions, fever, fatigue, and muscle pain, were reported by 43.5% of CU patients. Seven patients reported severe allergic reactions. Conclusions: COVID-19 vaccination leads to disease exacerbation in only a small number of CU patients and is generally well tolerated.</p