Successful serial plasmapheresis for solar urticaria, a case report and literature review.

BACKGROUND/PURPOSE: Amidst the emergence of new therapeutic options, traditional therapeutic plasmapheresis (TPE) used in diseases involving a toxic substance in the plasma, remains a viable alternative for cases of recalcitrant solar urticaria (SU). We emphasize the importance of documenting successful experience with repeated plasmapheresis to increase awareness amongst physicians and dermatologists regarding this effective treatment option. MATERIAL AND METHOD: We reported a case of recalcitrant SU that had not responded to a combination of H1-antihistamines, immunosuppressants, omalizumab and intravenous immunoglobulin. We introduced serial TPE, which involved two consecutive days of procedures for each course was introduced. We detailed the regimen and highlighted the clinical and objective benefits observed with multiple treatments. Additionally, we compared this to other plasmapheresis regimens and their treatment responses previously reported for solar urticaria. RESULTS: Our patient underwent serial TPE, totaling 42 procedures over five years. Following the last TPE session, phototesting showed a sustained prolongation of minimal urticating doses (MUDS), which exceeded the maximum tested doses across nearly all ultraviolet (UV) and visible light ranges, with the exception of the two short ultraviolet B (UVB) wavelengths. MUDs increased to 25 from 6 mj/cm2 at 307.5± 5nm, and to 500 from 15 mj/cm2 at 320 ± 10nm, before the initial TPE. In our review, we included five articles covering eight SU patients who received TPE. Of these, the five patients with positive intradermal tests responded particularly well immediately after treatment. However, the condition relapsed within two weeks in one patient and within two months in another. In contrast, the other three patients with negative intradermal tests, showed no significant benefits from the treatment. No serious side effects from TPE were reported amongst the patients. CONCLUSIONS: This review underscores the efficacy of serial plasmapheresis procedures in treating refractory cases of SU, high3lighting the robust results observed.

[Solar urticaria and polymorphous light eruption]. / Lichturtikaria und polymorphe Lichtdermatose.

Solar urticaria is a rare idiopathic photodermatosis. According to the current knowledge its pathogenesis is most likely based on an allergic type I reaction to an autoantigen activated by ultraviolet (UV) radiation or visible light. As many of the patients suffer from severe forms of the disease, it may therefore severely impair the quality of life of those affected. In contrast, polymorphous light eruption is a very common disease, which, according to the current data, can be interpreted as a type IV allergic reaction to a photoallergen induced by UV radiation. As the skin lesions heal despite continued sun exposure, the patients' quality of life is generally not significantly impaired. These two clinically and pathogenetically very different light dermatoses have shared diagnostics by means of light provocation and an important therapeutic option (light hardening). Herein, we present an overview of the clinical picture, pathogenesis, diagnosis and available treatment options for the above-mentioned diseases.

[An overview of porphyrias]. / Porphyrien ­ eine Übersicht.

Porphyrias are predominantly genetic metabolic disorders caused by dysregulation of specific enzymes in porphyrin-heme biosynthesis. The enzymatic dysfunction leads to formation and excretion of intermediate metabolic products in the form of porphyrins and/or their precursors δ­aminolevulinic acid and porphobilinogen, which have cyto- and tissue-toxic properties. Clinically, porphyrias are extremely diverse, with symptoms ranging from skin changes on light-exposed areas of the body to potentially life-threatening neurovisceral attacks. Biochemical tests in urine, blood and stool are used for diagnosis, which can be supplemented by molecular genetic analyses. Treatment of the various forms of porphyria is complex and often requires close interdisciplinary cooperation between different medical specialties.

Successful treatment of actinic prurigo with baricitinib in an 8-year-old child: A case report.

Actinic prurigo is a rare photodermatosis characterized by pruritic papulonodular lesions. Treatment is challenging, especially in children, as sun protection strategies need to be rigorously implemented and symptoms often persist throughout the year. Herein, we present a case of actinic prurigo in an 8-year-old patient with rapid and successful relief with baricitinib.

Sun pain and solar dysesthesia: A new challenge in clinical practice.

BACKGROUND: A few patients report intense pain and other unpleasant sensations, such as burning, dysesthesia and hyperalgesia, after even brief exposure to the sun and in the absence of any skin lesion. Sometimes they also develop systemic symptoms, such as mild fever, fatigue, faintness and fainting. As a result, these patients carefully avoid even short-term sun exposure with a consequent severe negative impact on their lives. METHODS: We have reviewed the clinical findings and the results of photobiological investigations of 10 patients who presented this clinical picture. Six of these patients were previously described by our group with the diagnosis of sun pain. We have reviewed the similarities with other previously described disorders such as solar dysesthesia and PUVA pain and have evaluated possible pathogenetic mechanisms. RESULTS: During phototesting our patients experienced intense pain in the exposed area and in the surrounding skin, without any visible lesion, even with very low sub-erythemal doses. At follow-up, five patients were diagnosed with fibromyalgia, three with a major depressive disorder, one with bipolar syndrome and one with a conversion disorder. The pathogenesis remains unclear, but the use of a psychopharmacological treatment with antidepressants improved both the neuropsychiatric symptoms and sensitivity to the sun in most subjects. CONCLUSION: For patients with pain and other severe symptoms in the absence of skin lesions and clinical and laboratory manifestations of known photodermatoses, a neuropsychiatric evaluation should be suggested.

A report of disseminated actinic granuloma: An unusually extensive presentation.

In this report, a case of disseminated actinic granuloma in a 50-year-old female with type 2 diabetes mellitus is described. This case is unique due to the unusually extensive cutaneous involvement of the face, neck, trunk, and extremities at initial presentation. The lesions were in a striking photo-distribution, highlighting ultraviolet light as an important environmental trigger for this process. Interestingly, the patient refused the recommended systemic therapy with hydroxychloroquine, despite her significant burden of skin disease. This refusal stems from an unexpected reluctance on the part of the patient to take this medication due to the publicity and media coverage of side effects associated with inappropriate prescribing of this drug during the COVID-19 pandemic, presenting a new and surprising treatment barrier that clinicians may need to overcome.

NRF2 in dermatological disorders: Pharmacological activation for protection against cutaneous photodamage and photodermatosis.

The skin barrier and its endogenous protective mechanisms cope daily with exogenous stressors, of which ultraviolet radiation (UVR) poses an imminent danger. Although the skin is able to reduce the potential damage, there is a need for comprehensive strategies for protection. This is particularly important when developing pharmacological approaches to protect against photocarcinogenesis. Activation of NRF2 has the potential to provide comprehensive and long-lasting protection due to the upregulation of numerous cytoprotective downstream effector proteins that can counteract the damaging effects of UVR. This is also applicable to photodermatosis conditions that exacerbate the damage caused by UVR. This review describes the alterations caused by UVR in normal skin and photosensitive disorders, and provides evidence to support the development of NRF2 activators as pharmacological treatments. Key natural and synthetic activators with photoprotective properties are summarized. Lastly, the gap in knowledge in research associated with photodermatosis conditions is highlighted.

Identification and biological analysis of LncSPRY4-IT1-targeted functional proteins in photoaging skin.

BACKGROUND/PURPOSE: Skin photoaging, main causes of skin aging, is induced by chronic UV irradiation. LncSPRY4-IT1, a broadly expressed lncRNA, takes part in various biological functions by combining with functional protein molecules. However, the role of LncSPRY4-IT1 in skin photoaging process has not been characterized. This study is to investigate the interacting proteins of LncSPRY4-IT1 by combining RNA pull-down, high-throughput, and bioinformatic analysis. METHODS: Human skin fibroblasts (HDFs) were exposed to 10 J/cm2 UVA irradiation, once a day for 14 days. LncSPRY4-IT1 expression was qualified via RT-PCR. In vitro RNA pull-down assays and liquid chromatography-mass spectrometry analysis were used to identify the LncSPRY4-IT1-related proteins. Functional annotation analysis and pathway enrichment were preformed via Gene Ontology and KEGG. RESULTS: LncSPRY4-IT1 expression in photoaging fibroblasts was increased 1.66 ± 0.23 folds. 181 LncSPRY4-IT1-interacting proteins in UVA-induced photoaging skin fibroblast irradiation were identified, of which 56 proteins with two or more unique peptides, 73 proteins related to RNA processing, and 5 proteins related to DNA processing. High-throughput and bioinformatic analysis showed that LncSPRY4-IT1-targeting proteins were involved in cellular process, metabolic process, biological regulation, and cell part in skin photoaging process. The KEGG revealed that LncSPRY4-IT1-targeting proteins were mainly enriched in metabolic pathways. CONCLUSION: The results of our studies illuminate how LncSPRY4-IT1 formed a LncRNA-protein regulatory network in skin photoaging mechanisms and suggest that LncSPRY4-IT1 may serve as a novel upstream intervention target for the prevention and treatment of photoaging and related skin diseases.

Porphyrin accumulation in humans with common dysfunctional variants of ABCG2, a porphyrin transporter: potential association with acquired photosensitivity.

Photosensitivity is a skin reaction disorder mediated by phototoxic and/or photoallergic mechanisms. The accumulation of porphyrins is generally considered to induce phototoxicity. ATP-binding cassette subfamily G member 2 (ABCG2) has been identified as a transporter of porphyrins and its common variants-p.Gln126Ter (rs72552713) and p.Gln141Lys (rs2231142)-reportedly decrease the function of porphyrin transport in vitro; however, the physiological importance of ABCG2 as a porphyrin transporter remains to be fully elucidated. We herein investigated whether ABCG2 dysfunction could lead to porphyrin accumulation and photosensitivity in Japanese subjects, and found it to be significantly correlated with erythrocyte protoporphyrin levels (P = 0.012). This appears to be the first clinical finding of ABCG2 dysfunction-associated protoporphyrin accumulation in humans. We divided the patients into a chronic actinic dermatosis (CAD) group and a non-CAD group. CAD was diagnosed based on the criteria of reduced minimal erythema doses to ultraviolet B (UVB) and/or ultraviolet A (UVA). The non-CAD group was composed of patients who exhibited normal reactions to UVB and UVA on phototesting, but had histories of recurrent erythema/papules on sun-exposed areas. Estimated ABCG2 function according to ABCG2 genotypes in the non-CAD group was significantly lower than in the general Japanese population (P = 0.045). In contrast, no difference was found in ABCG2 function between the CAD group and the general population, suggesting that ABCG2 dysfunction might be a genetic factor in non-CAD patients with clinical photosensitivity. In this context, genetic dysfunction of ABCG2 might be an overlooked pathological etiology of "photosensitivity of unknown cause."

In vitro Assessment of Solar Filters for Erythropoietic Protoporphyria in the Action Spectrum of Protoporphyrin IX.

Introduction: Subjects with erythropoietic protoporphyria rely on broad-spectrum sunscreens with high sun protection factor, which is not informative on efficacy in the absorption spectrum of protoporphyrin IX, spanning visible radiation and peaking around 408 nm. Photoactivation of protoporphyrin IX is responsible for painful skin photosensitivity in erythropoietic protoporphyria. The authors assessed the protective efficacy of six sunscreens in vitro in the absorption spectrum of protoporphyrin IX. Method: Transmittance measurements were performed in the 300-850 nm wavelengths on samples of six photoprotective products applied to polymethyl methacrylate plates. Porphyrin protection factor was calculated in the 300-700 nm region to provide a measurement for the efficacy of each product based on the action spectrum of protoporphyrin IX. Results: Product A showed the highest porphyrin protection factor among tested products with a median value of 4.22. Product A is a sunscreen containing organic filters, titanium dioxide and synthetic iron oxides, pigmentary grade active ingredients that absorb visible radiation. Other products showed inefficient protection in the visible, with transmittance between 75 and 95% at 500 nm. The low porphyrin protection factor of inorganic filter product B was attributed to particle micronization, as declared by the manufacturer. Conclusion: Adding porphyrin protection factor to sunscreen labeling could help patients with erythropoietic protoporphyria and other photosensitivity disorders identify products tailored on their specific needs. The development of sunscreens providing protection from visible radiation and excellent cosmetical tolerability could improve the lifestyle of patients with erythropoietic protoporphyria.

Juvenile spring eruption among soldiers: A report of a large outbreak.

Juvenile spring eruption is a rare photodermatosis characterised by papules and vesicles appeared on the helix of the ears. A combination of environmental factors including sunlight and cold has been postulated in the pathogenesis. Herein, 58 soldiers with juvenile spring eruption from a single military unit are reported and the characteristics of other reported outbreaks among soldiers are reviewed. [Correction added on 14th November 2020, after first online publication: "The last sentence of the abstract section has been revised."].

Hydroa Vacciniforme and Hydroa Vacciniforme-Like Lymphoproliferative Disorder: A Spectrum of Disease Phenotypes Associated with Ultraviolet Irradiation and Chronic Epstein-Barr Virus Infection.

Hydroa vacciniforme (HV) is a rare form of photosensitivity disorder in children and is frequently associated with Epstein-Barr virus (EBV) infection, whereas HV-like lymphoproliferative disorders (HVLPD) describe a spectrum of EBV-associated T-cell or natural killer (NK)-cell lymphoproliferations with HV-like cutaneous manifestations, including EBV-positive HV, atypical HV, and HV-like lymphoma. Classic HV occurs in childhood with papulovesicules on sun-exposed areas, which is usually induced by sunlight and ultraviolet irradiation, and mostly resolves by early adult life. Unlike classic HV, atypical or severe HV manifests itself as recurrent papulovesicular eruptions in sun-exposed and sun-protected areas associated occasionally with facial edema, fever, lymphadenopathy, oculomucosal lesions, gastrointestinal involvement, and hepatosplenomegaly. Notably, atypical or severe HV may progress to EBV-associated systemic T-cell or natural killer (NK)-cell lymphoma after a chronic course. Although rare in the United States and Europe, atypical or severe HV and HV-like lymphoma are predominantly reported in children from Asia and Latin America with high EBV DNA levels, low numbers of NK cells, and T cell clones in the blood. In comparison with the conservative treatment used for patients with classic HV, systemic therapy such as immunomodulatory agents is recommended as the first-line therapy for patients with atypical or severe HV. This review aims to provide an integrated overview of current evidence and knowledge of HV and HVLPD to elucidate the pathophysiology, practical issues, environmental factors, and the impact of EBV infection.

Clinical and molecular epidemiology of erythropoietic protoporphyria in Italy.

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare inherited disease associated with heme metabolism, characterized by severe life-long photosensitivity and liver involvement. OBJECTIVE: To provide epidemiological data of EPP in Italy. MATERIALS & METHODS: Prospective/retrospective data of EPP patients were collected by an Italian network of porphyria specialist centres (Gruppo Italiano Porfiria, GrIP) over a 20-year period (1996-2017). RESULTS: In total, 179 patients (79 females) with a clinical and biochemical diagnosis of EPP were assessed, revealing a prevalence of 3.15 cases per million persons and an incidence of 0.13 cases per million persons/year. Incidence significantly increased after 2009 (due to the availability of alfa-melanotide, which effectively limits skin photosensitivity). Mean age at diagnosis was 28 years, with only 22 patients (12.2%) diagnosed ≤10 years old. Gene mutations were assessed in 173 (96.6%) patients; most (164; 91.3%) were FECH mutations on one allele in association with the hypomorphic variant, c.315-48C, on the other (classic EPP), and nine (5.2%) were ALAS2 mutations (X-linked EPP). Only one case of autosomal recessive EPP was observed. Of the 42 different FECH mutations, 15 are novel, three mutations collectively accounted for 45.9% (75/164) of the mutations (c.215dupT [27.2%], c.901_902delTG [11.5%] and c.67 + 5G > A [7.2%]), and frameshift mutations were prevalent (33.3%). A form of light protection was used by 109/179 (60.8%) patients, and 100 (56%) had at least one α-melanotide implant. Three cases of severe acute liver involvement, requiring OLT, were observed. CONCLUSION: These data define, for the first time, the clinical and molecular epidemiology of EPP in Italy.

Health-related quality of life in porphyria cutanea tarda: a cross-sectional registry based study.

BACKGROUND: Porphyria cutanea tarda (PCT) is a rare, photosensitive disease characterized by skin fragility and blistering on sun-exposed areas. There is little previous research on how this condition affects health-related quality of life (HRQoL) and to the best of our knowledge this is the largest sample of PCT patients surveyed about their HRQoL. The aims of this study were to describe HRQoL, symptoms, susceptibility factors, disease activity and treatment in patients with PCT, and investigate the associations between these factors. METHODS: This is a cross-sectional, retrospective study based on patient-reported outcome and laboratory data. The Norwegian Porphyria Centre diagnoses all patients with PCT in Norway, all of whom are invited to participate in the Norwegian Porphyria Registry. Between December 2013-2015, 111 patients received a postal questionnaire and invitation to participate. RESULTS: Sixty-eight persons responded, with seven being excluded due to prolonged response time or missing information, resulting in 61 participants in the final analyses (55%). Median age was 60 years and 33 were female. We found a moderate negative relationship between the type and localisation of PCT symptoms and both mental (r = -.354 p < 0.01) and physical (r = -.441, p < 0.01) aspects of HRQoL. Participants who had started treatment when answering the questionnaire reported significantly better physical functioning and less bodily pain than those who had not started treatment. We did not observe an association between biochemical markers of disease activity and symptoms or HRQoL. Itching, a symptom that has received little attention in PCT was reported by 59% of the participants. CONCLUSIONS: Our results show that reduced HRQoL is associated with more symptoms and not having started treatment. PCT is a rare disease, and there is a need for the development of best-practice guidelines to facilitate good patient care.

Dermatitis actínica crónica / Chronic actinic dermatitis

RESUMEN La dermatitis actínica crónica (DAC) - dermatitis por fotosensibilidad, reacción solar persistente o su variante extrema el reticuloide actínico- es una fotodermatosis crónica, propia del adulto más frecuente en el sexo masculino provocada por rayos ultravioletas (UVB), (UVA) y luz visible. El diagnóstico es clínico, caracterizado por placas eccematosas y liquenificadas pruriginosas en aéreas expuestas al sol. Se cree que el DAC se debe a la fotosensibilización secundaria de un antígeno endógeno de la piel.

ABSTRACT Chronic actinic dermatitis (ACD) - photosensitivity dermatitis, persistent solar reaction or its extreme variant actinic reticuloid - is a chronic photodermatosis, typical of the adult male caused by ultraviolet (UVB), (UVA) and visible light. The diagnosis suggested by clinical researchers, characterized by eczematous and lichenified pruritic plaques in areas exposed to the sun. It is believed that DAC is due to the secondary photosensitization of an endogenous skin antigen.