The role of TRPV4 channels in cutaneous epithelia.

Transient receptor potential vanilloid 4 (TRPV4) channels are multi-modally activated cation permeable channels that are expressed most organ tissues including the skin. TRPV4 is highly expressed in the skin and functions in skin resident cells such as epidermal keratinocytes, melanocytes, immune mast cells and macrophages, and cutaneous neurons. TRPV4 plays many crucial roles in skin homeostasis to affect an extensive range of processes such as temperature sensation, osmo-sensation, hair growth, cell apoptosis, skin barrier integrity, differentiation, nociception and itch. Since TRPV4 functions in a plenitude of pathological states, TRPV4 can become a versatile therapeutic target for diseases such as chronic pain, itch and skin cancer.

Visible light. Part I: Properties and cutaneous effects of visible light.

Approximately 50% of the sunlight reaching the Earth's surface is visible light (400-700 nm). Other sources of visible light include lasers, light-emitting diodes, and flash lamps. Photons from visible light are absorbed by photoreceptive chromophores (e.g., melanin, heme, and opsins), altering skin function by activating and imparting energy to chromophores. Additionally, visible light can penetrate the full thickness of the skin and induce pigmentation and erythema. Clinically, lasers and light devices are used to treat skin conditions by utilizing specific wavelengths and treatment parameters. Red and blue light from light-emitting diodes and intense pulsed light have been studied as antimicrobial and anti-inflammatory treatments for acne. Pulsed dye lasers are used to treat vascular lesions in adults and infants. Further research is necessary to determine the functional significance of visible light on skin health without confounding the influence of ultraviolet and infrared wavelengths.

Protective effect of a topical sunscreen formulation fortified with melatonin against UV-induced photodermatitis: an immunomodulatory effect via NF-κB suppression.

Objective: Melatonin and pumpkin seed oil, along with US FDA approved UV filters were incorporated into a formulation for enhancement of UV protection by exerting an antioxidant effect. The objective of this study was to assess the protective effect of this formulation against ultraviolet (UV) radiation-induced photo dermatitis in rats, which is an established model to study the aetiopathogenic mechanisms in psoriasis vulgaris, as the former exhibits the same features to those of clinical psoriasis vulgaris in humans. Materials and methods: The animals were segregated into five groups (6/group) and all received their respective formulations dermally prior to chronic UV irradiation for 28 days. The test, placebo, and standard groups; received the test, placebo, and standard formulations respectively; whereas the positive control group received only UV radiation. A normal control group was also maintained. Disease and treatment status were analyzed using various techniques by euthanizing the rats after 28 days. Results: The test formulation was able to ameliorate the UV-induced increase in skin fold, epidermal thickness, and skin edema; inhibit the reduction of hydroxyproline content and incidence of LPO within the skin tissues of exposed animals. The formulation was also able to inhibit the release of proinflammatory cytokines; IFN-γ, IL-1ß, IL-6, and TNF-α; and upregulation of NF-κB and COX-2 genes caused by chronic UV exposure. Conclusion: It can be stated that melatonin included in the newly formulated sunscreen was able to inhibit the induction of photodermatitis via immunoregulation of inflammatory cytokines along with NF-κB and COX-2 genes.

Photodermatitis for the Allergist.

PURPOSE OF REVIEW: The photodermatoses represent a group of disorders of sensitivity to light that continue to pose difficulties in diagnosis and management. Photodermatoses are of interest to allergists because many photosensitive skin disorders have immunologic underpinnings, and patients often present to clinic complaining of "allergy" to the sun. We provide a concise reference for allergists on the clinical recognition and management of photodermatitis. RECENT FINDINGS: New developments in the understanding of immunomodulatory effects of light have demonstrated normally immunosuppressive responses in the skin to light exposure, and a blunted immunosuppressive response in the pathogenesis of many photodermatoses. Vitamin D plays an important role in immunomodulation and itself may be affected by photodermatoses due to the impact of photoprotective treatment strategies on circulating vitamin D levels. The elucidation of the immunological basis of many photodermatoses may provide guidance for developing new treatment modalities. Further research is necessary to determine the optimal management of vitamin D metabolism in patients with photodermatoses.

St. John's wort treatment in women bears risks beyond pharmacokinetic drug interactions.

We analyzed adverse events in a clinical phase I trial to assess dose-dependent metabolic effects of St. John's wort co-administered with rifampicin in 12 healthy volunteers. Within 3-6 days after increasing the St. John's wort dose from 300 to 600 mg TID, five of six female participants developed ambient temperature-dependent allodynia and paresthesia in sun-exposed areas (back of the hands and perioral and nasal area). Aggravation of symptoms resulted in persistence of paresthesia and phototoxic erythrodermia. None of the male participants showed any of these effects. Gender, duration of treatment, dose, and solar exposure seem to be extrinsic and host factors facilitating St. John's wort-induced neuropathy. The risk to develop this adverse effect is almost exclusively present in women.

UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling.

At our body surface, the epidermis absorbs UV radiation. UV overexposure leads to sunburn with tissue injury and pain. To understand how, we focus on TRPV4, a nonselective cation channel highly expressed in epithelial skin cells and known to function in sensory transduction, a property shared with other transient receptor potential channels. We show that following UVB exposure mice with induced Trpv4 deletions, specifically in keratinocytes, are less sensitive to noxious thermal and mechanical stimuli than control animals. Exploring the mechanism, we find that epidermal TRPV4 orchestrates UVB-evoked skin tissue damage and increased expression of the proalgesic/algogenic mediator endothelin-1. In culture, UVB causes a direct, TRPV4-dependent Ca(2+) response in keratinocytes. In mice, topical treatment with a TRPV4-selective inhibitor decreases UVB-evoked pain behavior, epidermal tissue damage, and endothelin-1 expression. In humans, sunburn enhances epidermal expression of TRPV4 and endothelin-1, underscoring the potential of keratinocyte-derived TRPV4 as a therapeutic target for UVB-induced sunburn, in particular pain.

Comparison of photodermatoses in African-Americans and Caucasians: a follow-up study.

BACKGROUND/PURPOSE: Only a few studies have compared frequencies of photodermatoses among different races and skin types. This is an extension of a study performed by Kerr and Lim and evaluates the frequency of photodermatoses in African-Americans compared with Caucasians in the same institution during an 8-year period. METHODS: Retrospective chart review was performed, including dermatology clinic charts from October 2004 to August 2012 with International Classification of Diseases, Ninth Revision diagnostic codes related to photodermatoses. RESULTS: We identified 229 patients with photodermatoses. Of these, 138 (46.6%) were African-American and 63 (42.2%) were Caucasian. Statistically significant differences in the distribution of photodermatoses in African-Americans and Caucasians, respectively, were as follows: phototoxic drug eruption (0.7% and 15.9%, P < 0.0001), phytophotodermatitis (0% and 6.3%, P = 0.009), polymorphous light eruption (PMLE) (86.2% and 54%, P < 0.0001) and porphyrias (0% and 7.9%, P = 0.003). CONCLUSION: Combined with data from Kerr and Lim, this is the largest study of photodermatoses in African-Americans to date. Congruent to former studies, photodermatoses do occur regularly in dark-skinned individuals. Overall, the frequency of photodermatoses in African-Americans and Caucasians are similar; however, PMLE occurs more commonly in African-Americans, and porphyias and phototoxicity occur more commonly in Caucasians.

Phytophotodermatitis From Lime Margaritas on a Mexico Vacation.

Phytophotodermatitis is a type of contact dermatitis that occurs upon skin exposure to certain plant chemicals, known as furocoumarins, along with simultaneous sun exposure. This case details a 34-year-old patient who presented to the office with an asymptomatic, irregularly shaped, and hyperpigmented patch located on the left inferior middle back that had been present since a recent beach vacation in Mexico. Upon gathering the history, clinicians should inquire about recent sunlight exposure while consuming and/or touching phytotoxic plant derivatives found in most citrus plants. The history should correspond with the skin examination findings and conclude that a cutaneous phytotoxic reaction had occurred when a lime margarita contacted the hand, which was subsequently rubbed onto the patient's back. This case highlights the importance of both taking a thorough history and physical examination and being aware of the broad range of skin manifestations to prevent unnecessary treatment, such as topical corticosteroids, for other skin disorders (the irregular presentation of atopic dermatitis, allergic contact dermatitis, and dermatitis unspecified) or improperly suspected child abuse in younger patient presentations.

The Effectiveness and Safety of Dupilumab for the Treatment of Recalcitrant Chronic Actinic Dermatitis: A Case Series.

Background: Although dupilumab is an effective treatment approach for chronic actinic dermatitis (CAD) in some cases, its effectiveness and safety in CAD have not been sufficiently assessed. Purpose: Evaluation of the effectiveness and safety of dupilumab in patients with recalcitrant CAD was performed. Methods: We retrospectively reviewed the medical records of CAD patients treated with dupilumab. Data regarding demographics were collected, and disease severity scores were assessed using the following: Clinical Severity Score of CAD (CSS-CAD), Atopic Dermatitis Control Tool (ADCT), Dermatology Life Quality Index (DLQI), and Numeric Rating Scale (NRS)-itch scores. Results: After 12 weeks of treatment, there was a significant decrease in disease severity scores of 16 CAD patients. Only one patient achieved a good response and most of the patients (62.5%, 10/16) had no significant symptom improvement after 4 weeks of treatment. However, after 12 weeks of treatment, 43.75% (7/16) of the patients reached excellent response (>75% improvement of CSS-CAD), 31.25% (5/16) good response (50%-75% improvement of CSS-CAD), 6.25% (1/16) partial response (25%-50% improvement of CSS-CAD), and only 18.75% (3/16) no response (<25% improvement of CSS-CAD). One patient complained of injection site reaction at the first injection. Conclusion: This study supports dupilumab as an effective and safe treatment option for patients with recalcitrant CAD. Patients may require at least 4 weeks of treatment before the partial response is noted.

HIV-associated photodermatitis in African populations.

Photosensitive dermatoses are seen in 5% of HIV-infected persons. These include drug- and chemical-induced photoallergic and phototoxic reactions, chronic actinic dermatitis of HIV, photo lichenoid drug eruptions, and porphyria. Data on photodermatitis in HIV are limited to case reports and series. The pathogenesis is not completely understood and includes a th2 phenotype in HIV which results in impaired barrier function and resultant allergen sensitisation as well as immune dysregulation. The objective of this manuscript is to review the literature on the clinical phenotype, pathogenesis, role of photo and patch testing, outcomes, and treatment of photodermatitis in HIV in an African population.

Variable Presentations of Photodermatoses - A Case Series.

Photodermatoses represent a broad spectrum of skin diseases caused because of exposure to ultraviolet radiation. It is categorized mainly as idiopathic photosensitive disorders, drug or chemical induced photosensitivity reactions, DNA repair-deficiency photodermatoses and photoaggravated dermatoses. Despite being under the photodermatoses umbrella, the pathophysiology of each type of photodermatoses varies. We reported 4 cases of photodermatoses including azathioprine induced pellagra, adult onset actinic prurigo, and photoallergic contact dermatitis due to NSAIDs and cutting fluids. Photoprotection with the usage of photoprotective clothing, broad-spectrum sunscreen application and avoidance of photosensitizing drugs and chemicals are crucial.

A Case Study of Photosensitivity Associated with Anaplasma spp. Infection in Cattle.

Anaplasma infection has not previously been reported as a cause of photosensitization. This case presents a five-year-old Holstein cow in her fifth month of gestation with skin injury of nonpigmented areas clearly delimited from adjacent unaffected pigmented skin. Specific lesions included alopecia, localized oedema, desquamation erythema, serous exudation, thick detached skin, fissures, crusting, and necrosis, indicating photodermatitis. Hematological abnormalities were leukocytosis with neutrophilia and normocytic hypochromic anemia. Based on a hemoparasitic examination of blood smears, the organism Anaplasma spp. was observed within the red blood cells. Biochemical analyses revealed increased serum liver enzyme activity associated with hepatocellular damage and cholestasis. This cow was RT-PCR positive for Anaplasma spp. infection. After treatment with oxytetracycline started, its condition improved within 24 h, and it recovered completely within 30 days. In this case, the underlying pathogenic mechanism of Anaplasma spp. infection facilitated the impairment of bile flow and liver function, resulting in hepatogenous photosensitization.

Primary Photosensitization by Chamaecrista serpens in Santa Inês Sheep.

This study aimed to clarify the type of photosensitization induced by C. serpens and to verify if the plant remains toxic after being collected and stored. Eight crossbred sheep, aged between 6 and 36 months, were divided into three groups (G1 to G3). Over 30 days, daily, G1 received an exclusive diet of C. serpens, and G2 and G3 received 10 g/kg/BW and 20 g/kg/BW, respectively. Two other sheep were used as controls (CG). Before administration, the plant had been harvested every 15 days. Liver biopsies and blood samples were taken from all sheep on day zero and weekly. All sheep that received the plant developed clinical signs of photosensitization, and no changes were observed in the serum activities of AST and GGT. On day 30, all sheep except Ov1 from G1 and Ov7 were euthanized and necropsied. All sheep that received the plant developed clinical signs. Macroscopic or histologic lesions were not observed in the liver. Ov 1 recovered 13 days after the end of ingestion. These results demonstrated that C. serpens causes primary photosensitization. It is advisable to avoid grazing on pastures invaded by the plant or to remove them from the pastures immediately after observing the first signs.

Assessing the frequency of adverse reactions induced by melanin-containing formulations used for the management of solar dermatitis.

BACKGROUND: Melanin from different sources is widely used by many manufacturers to produce cosmetics and sunscreens. Research data show a wide spectrum of biological activities of melanin including the protection against UV radiation and oxidants. According to the research evidence, the topical use of melanin is more effective against inflammation than the hydrocortisone. The most common side effects of topical melanin ointment are local itching, burning, and moderate hyperemia. AIM OF THE STUDY: The purpose of this work is to describe the adverse outcomes of melanin-containing formulas in patients with solar dermatitis, and to compare the frequency of adverse reactions with data from different research reports. METHODS: A Pharmacovigilance questionnaire was developed to assess potential adverse events attributable to the use of melanin ointment. We used a modified survey tool created by Jaber and coauthors. This survey of melanin application documents validated reports of adverse events manifested by objective skin changes. MEDLINE (Ovid); MEDLINE In-Process Citations & Daily Update (Ovid); PubMed (NLM) (Internet); Embase (Ovid); and Cochrane Database of Systematic Reviews were searched for the evidence on adverse reactions of topical melanin application. RESULTS: The responses documented in this survey show reliability and safety of melanin formula used for the photoprotection and treatment of solar dermatitis. Most symptoms encountered in those using melanin were consistent with exposure to excessive amount (more than 4 times per day) of the compound applied topically. Of the total 534 survey responses received, 74% reported no adverse events. A total of 140 completed adverse event reports. Melanin ointment was being administered for the indications of photo injury (burns) in 75%, photodermatitis in 18%, and solar eczematous dermatitis in 7% of patients. Data were compared with rates from other reports. CONCLUSION: We have no evidence that the chemical structure of melanin varies with currently available products, used locally or in other countries, nor that any such variability played any role in the events reported here. Further studies are required to compare the adverse events of topical melanin formulas containing melanins of different origin.

Use of hydroxychloroquine in dermatology: A multicenter retrospective study in Korea.

Despite the expanding clinical application of hydroxychloroquine in dermatology, the overall data on hydroxychloroquine use among dermatologists are limited. With retrospective review of the medical records of the 790 patients who were prescribed hydroxychloroquine, we classified the diagnoses into 12 disease categories, the lupus erythematosus group being the largest. The lupus erythematosus group had the longest prescription duration (median, 6.2 months), whereas the photodermatitis group had a significantly shorter prescription duration (median, 0.5 months). The overall good response rate was 77.1%. The photodermatitis group had the best response (88.7%), followed by the lupus panniculitis (85.1%) and lichen planus (84.4%). In conclusion, hydroxychloroquine has proven utility for various inflammatory skin diseases, including but not limited to cutaneous lupus erythematosus.

Clearance of Chronic Actinic Dermatitis With Dupilumab Therapy in Chinese Patients: A Case Series.

Chronic actinic dermatitis (CAD) is a rare chronic immunological photo-dermatosis resulting in pruritic eczematous eruption on sun-exposed skin to ultraviolet (UV) light. The disease mechanism may include a delay-type hypersensitivity reaction to an endogenous photo-induced antigen, postulated to be UVR-altered DNA, but the exact pathophysiology is unknown. Minimum erythema dosing and patch testing are diagnostic tools of CAD. There are limited safe and effective treatment options for CAD. Herein, a case series of three patients with severe recalcitrant CAD is presented after being treated with dupilumab off-label. The patients in this study had persistent severe disease and taken the first-line management plan, which consists of topical calcineurin inhibitors (TCI), topical corticosteroids (TCS), and strict photoprotection. However, the above treatment options were not able to control the symptoms. The patients were treated with dupilumab 600 mg first dose, 300 mg biweekly subcutaneously (SC), and hydroxychloroquine. Dupilumab showed excellent clinical benefits, including safe and well-tolerated in chronic actinic dermatitis. Further studies are required to be carried out before being applied in clinical practice.

Hepatogenous photosensitization in ruminants and horses caused by the ingestion of Chamaecrista serpens in Brazil.

This study aimed to describe the first reports of outbreaks of hepatogenous photosensitization in cattle, sheep, and horses caused by spontaneous ingestion of Chamaecrista serpens, as well as to reproduce poisoning in sheep experimentally. Eleven photodermatitis outbreaks of unknown cause occurred in cattle, sheep and horses on nine farms in the semiarid region of Bahia, northeastern Brazil, between July 2017 and July 2020. Cutaneous lesions of photosensitization initiated until one week after the animals were introduced in paddocks invaded by the plant at the beginning of the rainy season. The photosensitive skin lesions were progressive and consisted of hyperemia, edema, ulcerative-crusted lesions with necrosis, especially in non-pigmented skin areas. The lesions in young animals were more severe. The animals avoided the sun and exhibited hyporexia, weight loss, restlessness, irritability, and severe itching. An experimental study was made using seven sheep, and resulted in photodermatitis, similar to that observed in the natural poisoning, seven days after the beginning of plant ingestion. Two sheep were reserved for the control group. Serum biochemistry changes indicated liver injury caused by the plant. Skin biopsies and liver biopsy guided by ultrasound were performed. The one sheep that had more pronounced skin lesions was euthanized and necropsied. At the necropsy, the liver was enlarged, diffusely pale, and firm, with an evident lobular pattern and an empty gallbladder. Histopathology revealed similar skin and liver lesions in samples from biopsies and the necropsy. There was a marked disorganization of the cords of hepatocytes associated with degenerative necrotic changes on the liver. The cutaneous injuries included orthokeratotic hyperkeratosis, hypergranulosis, acanthosis, and extensive areas of epidermic necrosis and ulceration. Three sheep were protected from sunlight and the lesions regressed within 45 days after the plant's consumption ceased. In conclusion, C. serpens causes hepatogenous photosensitization in ruminants and horses, and should be included in the list of differential diagnoses in cases of photosensitive dermatitis.

Five Cases of Phytophotodermatitis Caused by Fig Leaves and Relevant Literature Review.

Phytophotodermatitis is a condition caused by sequential exposure to photosensitizing substances present in plants followed by ultraviolet light. Several plants (e.g., limes, celery, fig, and wild parsnip) contain furocoumarin compounds (psoralens). It is important for dermatologists to be aware of phytophotodermatitis because it may be misdiagnosed as cellulitis, tinea, or allergic contact dermatitis. We present five patients with a sharply defined erythematous swollen patch with bullae on both feet. They described soaking their feet in a fig leaves decoction to treat their underlying dermatologic diseases. Within 24 hours, all patients had a burning sensation in their feet, and erythema and edema had developed on the feet dorsa with exception of the portion of the skin covered by the sandals. Histopathologic examinations revealed sub-epithelial blisters with intensive epidermal necrosis. Phytophotodermatitis was ultimately diagnosed and, after several days, the patients' skin lesions began to recover upon treatment with systemic and topical corticosteroids. Unfortunately, since there are no studies providing sufficient evidence on the benefits of fig leaves, they should be used with caution.