Solar urticaria involves rapid mast cell STAT3 activation and neutrophil recruitment, with FcεRI as an upstream regulator.

BACKGROUND: Solar urticaria is a rare photodermatosis characterized by rapid-onset sunlight-induced urticaria, but its pathophysiology is not well understood. OBJECTIVE: We sought to define cutaneous cellular and molecular events in the evolution of solar urticaria following its initiation by solar-simulated UV radiation (SSR) and compare with healthy controls (HC). METHODS: Cutaneous biopsy specimens were taken from unexposed skin and skin exposed to a single low (physiologic) dose of SSR at 30 minutes, 3 hours, and 24 hours after exposure in 6 patients with solar urticaria and 6 HC. Biopsy specimens were assessed by immunohistochemistry and bulk RNA-sequencing analysis. RESULTS: In solar urticaria specimens, there was enrichment of several innate immune pathways, with striking early involvement of neutrophils, which was not observed in HC. Multiple proinflammatory cytokine and chemokine genes were upregulated (including IL20, IL6, and CXCL8) or identified as upstream regulators (including TNF, IL-1ß, and IFN-γ). IgE and FcεRI were identified as upstream regulators, and phosphorylated signal transducer and activator of transcription 3 expression in mast cells was increased in solar urticaria at 30 minutes and 3 hours after SSR exposure, suggesting a mechanism of mast cell activation. Clinical resolution of solar urticaria by 24 hours mirrored resolution of inflammatory gene signature profiles. Comparison with available datasets of chronic spontaneous urticaria showed transcriptomic similarities relating to immune activation, but several transcripts were identified solely in solar urticaria, including CXCL8 and CSF2/3. CONCLUSIONS: Solar urticaria is characterized by rapid signal transducer and activator of transcription 3 activation in mast cells and involvement of multiple chemotactic and innate inflammatory pathways, with FcεRI engagement indicated as an early event.

Systematic review of the prevalence and incidence of the photodermatoses with meta-analysis of the prevalence of polymorphic light eruption.

Information about the prevalence of photodermatoses is lacking, despite their substantial impact on life quality. Our objective was to systematically review the literature to establish what is known regarding prevalence and incidence of photodermatoses. We searched Medline, CINAHL and Embase from inception to 2021 to identify original population-based studies in English literature reporting the prevalence and/or incidence of photodermatoses. Information was extracted according to geographical location and risk of bias was assessed using a 10-point risk of bias tool for prevalence studies. Primary outcome was the population prevalence of photodermatoses. Prevalence data for polymorphic light eruption (PLE) were used to calculate the global pooled prevalence of PLE. Twenty-six studies were included; 15 reported prevalence of photodermatoses based on samples of the general population and 11 on prevalence and/or incidence from national and international registry data. The general population studies involved PLE (nine studies), unspecified photosensitivity (2), actinic prurigo (2), juvenile spring eruption (1), chronic actinic dermatitis (1) and variegate porphyria (1), while registry studies reported on cutaneous porphyrias and genophotodermatoses (nine and two studies, respectively). Worldwide the prevalence of PLE between countries ranged from 0.65% (China) to 21.4% (Ireland). The pooled estimated prevalence of PLE was 10% (95% CI 6%-15%) among the general population (n = 19,287), and PLE prevalence increased with distance from the equator (r = 0.78, p < 0.001). While several photodermatoses are rare, photosensitivity can be prevalent at wide-ranging world locations, including Egypt where photosensitivity was found in 4% of children and 10% of adults. This study showed that PLE is highly prevalent in many populations and that its prevalence shows a highly significant correlation with increasing northerly or southerly latitude. Available population-based studies for photodermatoses suggest they can be prevalent at a range of world locations; more attention is required to this area.

Clinicophotobiological Characterization of Photoaggravated Atopic Dermatitis.

Importance: Photoaggravated atopic dermatitis (PAD) is estimated to affect 1.4% to 16% of patients with AD but remains poorly characterized with limited published data. Objective: To provide detailed clinical and photobiological characterization of PAD. Design, Setting, and Participants: This case series study used cross-sectional data collected from 120 consecutive patients diagnosed with PAD from January 2015 to October 2019 at a tertiary center referral unit for photobiology. Main Outcomes and Measures: Routinely collected standardized clinical and photobiological data were analyzed using descriptive statistics, and regression analysis explored associations between demographic and clinical data. Results: Of 869 patients who underwent photoinvestigation, 120 (14%) were diagnosed with PAD (69 female [58%]; median age, 45 [IQR, 31-61] years; range, 5-83 years; skin phototypes [SPTs] I-VI). Of these patients, 104 (87%) were adults. All patients had a history of AD, and most (62 of 104 [60%]) presented with sunlight-provoked or photodistributed eczema; median age at photosensitivity onset was 37 years (range, 1-72 years). Past-year Dermatology Life Quality Index score was greater than 10 for 80 of 103 adults (78%), and 82 of 119 (69%) had vitamin D (25-hydroxyvitamin D) level insufficiency or deficiency (<20 ng/mL; to convert ng/mL to nmol/L, multiply by 2.496). Broadband UV radiation provocation test results were positive for 112 patients (93%). In 28 patients (23%) with abnormal monochromator phototest findings, sensitivity occurred to UV-A, UV-B, and/or visible light, and UV-A of 350 ± 10 nm was the most prevalent wavelength. Photopatch test reactions were positive for 18 patients (15%). Patients with SPTs V to VI (31 [26%]) vs SPTs I to IV (89 [74%]) were younger at photosensitivity onset (median age, 24 years [IQR, 15-37 years] vs 40 years [IQR, 25-55 years]; P = .003), were more likely to be female (23 [74%] vs 46 [52%]; P = .03), and had a lower vitamin D status and a higher frequency of abnormal monochromator phototest findings. Conclusions and Relevance: In this case series study, PAD affected patients with different ages and SPTs and was associated with substantially impaired quality of life. The findings suggest that confirming PAD through phototesting may provide better personalized care for patients through identification of provoking wavelengths, relevant photocontact allergies, and appropriate photoprotection advice.

Severely photosensitive psoriasis: a phenotypically defined patient subset.

A subset of patients with chronic plaque psoriasis exhibits severely photosensitive psoriasis (PP) with a pronounced seasonal pattern, but the pathomechanism is not understood. We performed two related studies; first, a detailed clinical characterization of PP, and second, a controlled investigation exploring the underlying pathomechanisms through the assessment of disease onset after photoprovocation. Patients with PP (n=20) showed striking female predominance (19F:1M), very low mean age of psoriasis onset (11 years, range 2-24), family history of psoriasis (13/20), a strong HLA-Cw*0602 association (16/17), and a rapid abnormal clinical response to broadband UVA, comprising erythema+/-scaling plaques (17/20). Subsequently, patients with PP (n=10), non-PP (n=9), and healthy volunteers (n=11) were challenged with low-dose broadband UVA on 3 consecutive days, and serial biopsies were taken after 6 hours to 7 days and from unchallenged skin. Histological changes consistent with early psoriasis occurred in 4 of 10 PP patients, but in neither of the control groups, with significant dermal infiltration by neutrophils, CD4+, CD8+, and CD45RO+ cells at 24 h, accompanied by acanthosis. Thus, a phenotypically distinct subset of psoriasis has been characterized. In contrast with earlier assumptions, UV can provoke psoriasiform features rapidly de novo; a role for memory effector T cells is supported in the early phase.

Profuse congenital milia in a family.

Milia are keratin containing dermal cysts and are seen very frequently in neonates. They generally resolve spontaneously within the first few months of life. However, the presence of congenital milia may also be associated with a number of inherited disorders. We present a family with congenital milia and no other associated abnormalities in whom the milia were profuse and more persistent than usual. A number of inherited disorders which may be associated with the presence of milia are also discussed.