ABSTRACT
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.
Subject(s)
Mast Cells , Neutrophil Infiltration , Receptors, IgE , STAT3 Transcription Factor , Urticaria , Humans , Urticaria/immunology , Mast Cells/immunology , Receptors, IgE/genetics , Female , Adult , STAT3 Transcription Factor/metabolism , Male , Neutrophil Infiltration/immunology , Middle Aged , Skin/immunology , Skin/pathology , Sunlight/adverse effects , Cytokines/metabolism , Cytokines/immunology , Photosensitivity Disorders/immunology , Ultraviolet Rays/adverse effects , Neutrophils/immunology , Urticaria, SolarABSTRACT
Photosensitivity is a sensitivity to UV radiation (UVR) commonly found in systemic lupus erythematosus (SLE) patients who have cutaneous disease. Upon even ambient UVR exposure, patients can develop inflammatory skin lesions that can reduce the quality of life. Additionally, UVR-exposed skin lesions can be associated with systemic disease flares marked by rising autoantibody titers and worsening kidney disease. Why SLE patients are photosensitive and how skin sensitivity leads to systemic disease flares are not well understood, and treatment options are limited. In recent years, the importance of immune cell-stromal interactions in tissue function and maintenance is being increasingly recognized. In this review, we discuss SLE as an anatomic circuit and review recent findings in the pathogenesis of photosensitivity with a focus on immune cell-stromal circuitry in tissue health and disease.
Subject(s)
Lupus Erythematosus, Systemic/immunology , Photosensitivity Disorders/immunology , Skin/pathology , Animals , Autoantibodies/metabolism , Cell Communication , Humans , Immunity, CellularSubject(s)
Photosensitivity Disorders/diagnosis , Photosensitivity Disorders/therapy , Phototherapy/methods , Diagnosis, Differential , Female , Fluorescence , Humans , Lighting/adverse effects , Middle Aged , Photosensitivity Disorders/classification , Photosensitivity Disorders/immunology , Sunlight/adverse effectsABSTRACT
BACKGROUND: Galectin-3 is widely expressed in many immunocytes and epithelial cells including skin keratinocytes. Galectin-3 can regulate immunological or inflammatory processes and plays a proinflammatory role in some disease models. Galectin-3 has a role in disorders related to ultraviolet (UV) photodamage such as apoptosis, skin squamous cell carcinoma and basal cell carcinoma. However, the evidence of galectin-3 in UVB-induced skin inflammation is still limited and the underlying molecular mechanism remains elusive. OBJECTIVE: We aimed to investigate the effects of galectin-3 in human epidermal keratinocytes and in mice after UVB irradiation. METHODS: Primary human epidermal keratinocytes with galectin-3 knockdown were used as the in vitro model. ELISA, QPCR, and western blotting were applied to evaluate the released cytokine, mRNA and protein expression. Histologic analysis, measurement of erythema and transepidermal water loss (TEWL) were applied to evaluate UVB-induced skin damage in galectin-3 knockout mice. RESULTS: In UVB-irradiated human keratinocytes, galectin-3 knockdown downregulated the UVB-induced ASC crosslinking, cleavage of caspase-1, and formation of active IL-1ß. Galectin-3 knockdown also decreased UVB-induced production of reactive oxygen species, p38 phosphorylation, and COX2 expression in human keratinocytes. After four days of UVB irradiation, galectin-3 knockout mice showed reduced gross erythema, histologic features of tissue inflammation, quantified levels of erythema and TEWL compared to wild type mice. The skin tissue lysate also showed less expression of active IL-1ß and COX2 in galectin-3 knockout mice. CONCLUSION: Galectin-3 may play a positive regulatory role in UVB-induced skin inflammation.
Subject(s)
Blood Proteins/metabolism , Galectin 3/metabolism , Galectins/metabolism , Photosensitivity Disorders/immunology , Skin/pathology , Ultraviolet Rays/adverse effects , Animals , Caspase 1/metabolism , Cells, Cultured , Cyclooxygenase 2/metabolism , Disease Models, Animal , Galectin 3/genetics , Humans , Interleukin-1beta/metabolism , Keratinocytes , Male , Mice, Knockout , Photosensitivity Disorders/pathology , Primary Cell Culture , Reactive Oxygen Species/metabolism , Skin/cytology , Skin/immunology , Skin/radiation effects , Water Loss, Insensible/radiation effectsSubject(s)
Down-Regulation/radiation effects , Photosensitivity Disorders/immunology , Tumor Necrosis Factor alpha-Induced Protein 3/metabolism , Ultraviolet Rays/adverse effects , Down-Regulation/immunology , Gene Knockdown Techniques , HaCaT Cells , Humans , Inflammation/immunology , Inflammation/pathology , NF-KappaB Inhibitor alpha/metabolism , Photosensitivity Disorders/pathology , Primary Cell Culture , Signal Transduction/immunology , Signal Transduction/radiation effects , Skin/immunology , Skin/pathology , Skin/radiation effects , Transcription Factor RelA/metabolism , Tumor Necrosis Factor alpha-Induced Protein 3/geneticsABSTRACT
Rosacea is a chronic skin disease characterized by photosensitivity, abnormal dermal vascular behavior, inflammation, and enhanced expression of the antimicrobial peptide LL-37. We observed that dermal endothelial cells in rosacea had an increased expression of VCAM1 and hypothesized that LL-37 could be responsible for this response. The digestion of double-stranded RNA from keratinocytes exposed to UVB blocked the capacity of these cells to induce adhesion molecules on dermal microvascular endothelial cells. However, a synthetic noncoding snoU1RNA was only capable of increasing adhesion molecules on endothelial cells in the presence of LL-37, suggesting that the capacity of UVB exposure to promote both double-stranded RNA and LL-37 was responsible for the endothelial response to keratinocytes. Sequencing of RNA from the endothelial cells uncovered the activation of Gene Ontology (GO) pathways relevant to the human disease, such as type I and II interferon signaling, cell-cell adhesion, leukocyte chemotaxis, and angiogenesis. Functional relevance was demonstrated as double-stranded RNA and LL-37 promoted adhesion and transmigration of monocytes across the endothelial cell monolayers. Gene knockdown of TLR3, RIGI, or IRF1 decreased monocyte adhesion in endothelial cells, confirming the role of the double-stranded RNA recognition pathways. These observations show how the expression of LL-37 can lead to enhanced sensitivity to UVB radiation in rosacea.
Subject(s)
Antimicrobial Cationic Peptides/metabolism , Immunity, Innate/immunology , Photosensitivity Disorders/immunology , Rosacea/complications , Vascular Cell Adhesion Molecule-1/metabolism , Animals , Antimicrobial Cationic Peptides/genetics , Biopsy , Cell Adhesion/immunology , Cell Line , Cell Movement/immunology , Disease Models, Animal , Endothelial Cells/metabolism , Endothelium, Vascular/cytology , Endothelium, Vascular/metabolism , Female , Gene Expression Regulation/immunology , Humans , Immunity, Innate/genetics , Keratinocytes , Mice , Mice, Transgenic , Microvessels/cytology , Microvessels/metabolism , Photosensitivity Disorders/pathology , RNA, Double-Stranded/metabolism , RNA, Small Nuclear/metabolism , Rosacea/immunology , Rosacea/pathology , Signal Transduction/genetics , Signal Transduction/immunology , Skin/blood supply , Skin/immunology , Skin/pathology , Skin/radiation effects , THP-1 Cells , Ultraviolet Rays/adverse effects , CathelicidinsSubject(s)
Lymphoproliferative Disorders/pathology , Skin Diseases/pathology , Skin/radiation effects , Sunlight/adverse effects , Administration, Oral , Antiviral Agents/administration & dosage , Antiviral Agents/therapeutic use , Biopsy , Drug Therapy, Combination , Female , Ganciclovir/administration & dosage , Ganciclovir/therapeutic use , Herpesvirus 4, Human/drug effects , Herpesvirus 4, Human/genetics , Humans , Hydroa Vacciniforme/diagnosis , Hydroa Vacciniforme/immunology , Hydroa Vacciniforme/pathology , Hydroa Vacciniforme/virology , Injections, Subcutaneous , Interferon-alpha/administration & dosage , Interferon-alpha/therapeutic use , Lymphoproliferative Disorders/metabolism , Lymphoproliferative Disorders/virology , Photosensitivity Disorders/diagnosis , Photosensitivity Disorders/immunology , Photosensitivity Disorders/pathology , Photosensitivity Disorders/virology , Skin/pathology , Skin Diseases/diagnosis , Skin Diseases/immunology , Skin Diseases/virology , Treatment Outcome , Young AdultSubject(s)
Lupus Erythematosus, Discoid/complications , Photosensitivity Disorders/diagnosis , Skin/pathology , Sunlight/adverse effects , Atrophy/diagnosis , Atrophy/etiology , Atrophy/pathology , Biopsy , Face , Female , Humans , Lupus Erythematosus, Discoid/immunology , Lupus Erythematosus, Discoid/pathology , Photosensitivity Disorders/immunology , Photosensitivity Disorders/pathology , Skin/immunology , Skin/radiation effects , Young AdultABSTRACT
Cytotoxic T lymphocytes (CTLs) are key players in fighting cancer, and their induction is a major focus in the design of therapeutic vaccines. Yet, therapeutic vaccine efficacy is limited, in part due to the suboptimal vaccine processing by antigen-presenting cells (APCs). Such processing typically takes place via the MHC class II pathway for CD4 T-cell activation and MHC class I pathway for activation of CD8 CTLs. We show that a combination of skin photochemical treatment and immunization, so-called photochemical internalization (PCI) facilitated CTL activation due to the photochemical adjuvant effect induced by photosensitizer, oxygen, and light. Mice were immunized intradermally with antigen and photosensitizer, followed by controlled light exposure. PCI-treated mice showed strong activation of CD8 T cells, with improved IFN-γ production and cytotoxicity, as compared to mice immunized without parallel PCI treatment. Surprisingly, the CD8 T-cell effector functions were not impaired in MHC class II- or CD4 T-cell-deficient mice. Moreover, PCI-based vaccination caused tumor regression independent of MHC class II or CD4 T cells presence in melanoma bearing mice. Together, the data demonstrate that PCI can act as a powerful adjuvant in cancer vaccines, even in hosts with impaired T-helper functions.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Neoplasms/immunology , Photosensitivity Disorders/immunology , T-Lymphocytes, Helper-Inducer/immunology , Animals , Cancer Vaccines/immunology , Cell Line, Tumor , Cytotoxicity, Immunologic/immunology , Female , Immunization/methods , Interferon-gamma/immunology , Lymphocyte Activation/immunology , Melanoma/immunology , Mice , Mice, Inbred C57BL , Photosensitizing Agents/immunology , T-Lymphocytes, Cytotoxic/immunology , Vaccination/methodsSubject(s)
Interleukins/metabolism , Photosensitivity Disorders/immunology , Skin/pathology , Adolescent , Adult , Aged , Aged, 80 and over , CD11b Antigen/metabolism , Case-Control Studies , Child , Dermatitis, Atopic/immunology , Dermatitis, Atopic/pathology , Female , Humans , Male , Middle Aged , Photosensitivity Disorders/pathology , Psoriasis/immunology , Psoriasis/pathology , Skin/cytology , Skin/immunology , Skin Neoplasms/immunology , Skin Neoplasms/pathology , Young AdultABSTRACT
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.
Subject(s)
Melatonin/pharmacology , NF-kappa B/antagonists & inhibitors , Photosensitivity Disorders/prevention & control , Skin/drug effects , Sunscreening Agents/pharmacology , Ultraviolet Rays , Animals , Antioxidants/metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Combinations , Male , Melatonin/administration & dosage , NF-kappa B/genetics , Photosensitivity Disorders/immunology , Photosensitivity Disorders/pathology , Psoriasis/etiology , Psoriasis/immunology , Psoriasis/prevention & control , Rats, Wistar , Skin/immunology , Skin/pathology , Sunscreening Agents/administration & dosageABSTRACT
UVB-induced skin damage is attributable to reactive oxygen species, which are triggered by intracellular Ca2+ signals. However, exactly how the reactive oxygen species are triggered by intracellular Ca2+ upon UVB irradiation remains obscure. Here, we show that UVB induces Ca2+ signals via sequential generation of the following Ca2+ messengers: inositol 1,4,5-trisphosphate, nicotinic acid adenine dinucleotide phosphate, and cyclic ADP-ribose. UVB induced H2O2 production through NADPH oxidase 4 activation, which is downstream to inositol 1,4,5-trisphosphate and nicotinic acid adenine dinucleotide phosphate. H2O2 derived from NADPH oxidase 4 activated CD38 to produce cyclic ADP-ribose. UVB first evoked the pannexin channel to release ATP, which acts on P2X7 receptor to generate inositol 1,4,5-trisphosphate. Inhibitors of these messengers, as well as antioxidants, blocked UVB-induced Ca2+ signals and IL-1ß secretion in keratinocytes. Furthermore, ablation of CD38 and NADPH oxidase 4 protected against UVB-induced inflammation and IL-1ß secretion in the murine epidermis. These results show that UVB induces IL-1ß secretion through cross-talk between Ca2+ and reactive oxygen species, providing insight towards potential targets against UVB-induced inflammation.
Subject(s)
Calcium Signaling/immunology , Epidermis/radiation effects , Interleukin-1beta/metabolism , Ultraviolet Rays/adverse effects , ADP-ribosyl Cyclase 1/antagonists & inhibitors , ADP-ribosyl Cyclase 1/genetics , ADP-ribosyl Cyclase 1/metabolism , Animals , Antioxidants/pharmacology , Calcium/metabolism , Calcium Signaling/drug effects , Calcium Signaling/radiation effects , Carcinogenesis/immunology , Carcinogenesis/radiation effects , Cations, Divalent/metabolism , Cell Line , Epidermis/immunology , Epidermis/metabolism , Humans , Interleukin-1beta/immunology , Membrane Glycoproteins/antagonists & inhibitors , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Mice , Mice, Knockout , Models, Animal , NADPH Oxidase 4/antagonists & inhibitors , NADPH Oxidase 4/genetics , NADPH Oxidase 4/metabolism , Photosensitivity Disorders/etiology , Photosensitivity Disorders/immunology , Primary Cell Culture , Reactive Oxygen Species/immunology , Reactive Oxygen Species/metabolism , Skin Aging/immunology , Skin Aging/radiation effectsABSTRACT
Ultraviolet (UV) light is an important environmental trigger for systemic lupus erythematosus (SLE) patients, yet the mechanisms by which UV light impacts disease are not fully known. This review covers evidence in both human and murine systems for the impacts of UV light on DNA damage, apoptosis, autoantigen exposure, cytokine production, inflammatory cell recruitment, and systemic flare induction. In addition, the role of the circadian clock is discussed. Evidence is compared in healthy individuals and SLE patients as well as in wild-type and lupus-prone mice. Further research is needed into the effects of UV light on cutaneous and systemic immune responses to understand how to prevent UV-light mediated lupus flares.
Subject(s)
Lupus Erythematosus, Systemic/immunology , Photosensitivity Disorders/immunology , Ultraviolet Rays/adverse effects , Animals , Apoptosis/drug effects , Autoimmunity/drug effects , Circadian Clocks , Cytokines/metabolism , DNA Damage/radiation effects , Disease Models, Animal , Humans , Inflammation Mediators/metabolism , MiceABSTRACT
Although immune responses are essential to protect the body from infection, they can also harm tissues. Certain tissues and organs, including the eye, constitute specialized microenvironments that locally inhibit immune reactivity. Dedicator of cytokinesis protein 2 (DOCK2) is a Rac-specific guanine nucleotide exchange factor (GEF) that is predominantly found in hematopoietic cells. DOCK2 plays a key role in immune surveillance because it is essential for the activation and migration of leukocytes. DOCK2 mutations cause severe immunodeficiency in humans. We found that DOCK2-mediated Rac activation and leukocyte migration were effectively inhibited by cholesterol sulfate (CS), but not by cholesterol or other sulfated steroids. CS bound to the catalytic domain of DOCK2 and suppressed its GEF activity. Mass spectrometric quantification revealed that CS was most abundantly produced in the Harderian gland, which provides the lipids that form the oily layer of the tear film. Sulfation of cholesterol is mediated by the sulfotransferases SULT2B1b and, to a lesser extent, SULT2B1a, which are produced from the same gene through alternative splicing. By genetically inactivating Sult2b1, we showed that the lack of CS in mice augmented ultraviolet- and antigen-induced ocular surface inflammation, which was suppressed by administration of eye drops containing CS. Thus, CS is a naturally occurring DOCK2 inhibitor and contributes to the generation of the immunosuppressive microenvironment in the eye.
Subject(s)
Cholesterol Esters/metabolism , Eye/immunology , GTPase-Activating Proteins/antagonists & inhibitors , Immune Evasion , Keratitis/prevention & control , Photosensitivity Disorders/prevention & control , Animals , Disease Models, Animal , Eye/drug effects , Eye/metabolism , GTPase-Activating Proteins/genetics , GTPase-Activating Proteins/metabolism , Guanine Nucleotide Exchange Factors , Keratitis/etiology , Keratitis/immunology , Keratitis/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Photosensitivity Disorders/etiology , Photosensitivity Disorders/immunology , Photosensitivity Disorders/metabolism , Serine Proteinase Inhibitors/pharmacology , Sulfotransferases/physiologyABSTRACT
OBJECTIVE: Skin inflammation and photosensitivity are common in patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE), yet little is known about the mechanisms that regulate these traits. Here we investigate the role of interferon kappa (IFN-κ) in regulation of type I interferon (IFN) and photosensitive responses and examine its dysregulation in lupus skin. METHODS: mRNA expression of type I IFN genes was analysed from microarray data of CLE lesions and healthy control skin. Similar expression in cultured primary keratinocytes, fibroblasts and endothelial cells was analysed via RNA-seq. IFNK knock-out (KO) keratinocytes were generated using CRISPR/Cas9. Keratinocytes stably overexpressing IFN-κ were created via G418 selection of transfected cells. IFN responses were assessed via phosphorylation of STAT1 and STAT2 and qRT-PCR for IFN-regulated genes. Ultraviolet B-mediated apoptosis was analysed via TUNEL staining. In vivo protein expression was assessed via immunofluorescent staining of normal and CLE lesional skin. RESULTS: IFNK is one of two type I IFNs significantly increased (1.5-fold change, false discovery rate (FDR) q<0.001) in lesional CLE skin. Gene ontology (GO) analysis showed that type I IFN responses were enriched (FDR=6.8×10-04) in keratinocytes not in fibroblast and endothelial cells, and this epithelial-derived IFN-κ is responsible for maintaining baseline type I IFN responses in healthy skin. Increased levels of IFN-κ, such as seen in SLE, amplify and accelerate responsiveness of epithelia to IFN-α and increase keratinocyte sensitivity to UV irradiation. Notably, KO of IFN-κ or inhibition of IFN signalling with baricitinib abrogates UVB-induced apoptosis. CONCLUSION: Collectively, our data identify IFN-κ as a critical IFN in CLE pathology via promotion of enhanced IFN responses and photosensitivity. IFN-κ is a potential novel target for UVB prophylaxis and CLE-directed therapy.
Subject(s)
Epidermis/immunology , Interferon Type I/biosynthesis , Lupus Erythematosus, Cutaneous/complications , Photosensitivity Disorders/etiology , Adult , Cells, Cultured , Dendritic Cells/immunology , Female , Humans , Interferon Type I/genetics , Interferon Type I/immunology , Keratinocytes/immunology , Lupus Erythematosus, Cutaneous/immunology , Male , Middle Aged , Photosensitivity Disorders/immunology , RNA, Messenger/genetics , Skin/immunology , TYK2 Kinase/immunology , Up-Regulation/immunologyABSTRACT
BACKGROUND: Photoaggravated allergic contact dermatitis caused by methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI) and MI has been reported. OBJECTIVES: To describe the clinical characteristics and results of (photo)patch tests and photo-tests of 10 patients in Belgium and France suffering from photoaggravated contact dermatitis caused by MI. PATIENTS AND METHODS: Five men and five women, with a median age of 49.5 years, were investigated between January 2012 and February 2017 because of suspected photoaggravated contact dermatitis. Patch tests, photopatch tests and/or photo-tests were performed. RESULTS: Seven patients had positive patch test reactions to both MCI/MI and MI, whereas 3 patients had positive patch test reactions only to MI. In most cases, MI was the (strong) primary sensitizer. Photopatch tests with MCI/MI and/or MI gave stronger reactions than patch tests with these derivatives, indicating photoaggravation. Sensitization probably took place from cosmetics and work-related biocides, whereas elicitation of dermatitis was remarkably often related to airborne exposure to MI present in paints or industrial biocides. Four patients suffered from transient photosensitivity. CONCLUSION: Photoaggravated allergic contact dermatitis and transient photosensitivity caused by MI is a peculiar clinical presentation of allergic contact dermatitis caused by this preservative, and should be considered in daily clinical practice.
Subject(s)
Dermatitis, Allergic Contact/diagnosis , Photosensitivity Disorders/complications , Thiazoles/immunology , Adult , Allergens/pharmacology , Belgium , Cohort Studies , Cosmetics/adverse effects , Cosmetics/chemistry , Dermatitis, Allergic Contact/epidemiology , Dermatitis, Allergic Contact/etiology , Female , France , Humans , Incidence , Male , Middle Aged , Patch Tests/methods , Photosensitivity Disorders/immunology , Prognosis , Retrospective Studies , Severity of Illness IndexABSTRACT
El eritema polimorfo solar es la fotodermatosis más frecuente y suele aparecer en primavera con la primera exposición intensa al sol. Sus manifestaciones cutáneas son variadas y el diagnóstico se basa en la clínica junto al antecedente de exposición solar. En los casos leves, la fotoprotección suele ser suficiente para el control de la enfermedad, pero en formas más graves se requieren otras terapéuticas, como corticoides, antihistamínicos, o fototerapia, que genera una "fotoadaptación" de las áreas de piel afectadas. Presentamos un caso típico de erupción polimorfa solar que respondió de forma adecuada a medidas de fotoprotección. (AU)
The polymorphic solar eruption is the most frequent photodermatosis, and usually appears in spring with the first intense exposure to the sun. It has multiple cutaneous manifestations, and its diagnosis is based on the clinic and the antecedent of solar exposition. In mild cases, photoprotection is usually enough to control the disease, but in more severe forms, other therapies are required, such as corticosteroids, antihistamines, or phototherapy to generate a "photo-adaptation" of the affected skin areas. We present a typical case of polymorphic solar eruption that responded adequately to photoprotection measurements. (AU)
Subject(s)
Humans , Female , Adult , Photosensitivity Disorders/diagnosis , Sunlight/adverse effects , Erythema/diagnosis , Phototherapy , Photosensitivity Disorders/immunology , Photosensitivity Disorders/pathology , Quality of Life , Seasons , Sunscreening Agents/therapeutic use , Azathioprine/therapeutic use , Thalidomide/therapeutic use , Ultraviolet Rays/adverse effects , Ultraviolet Therapy , Adrenal Cortex Hormones/therapeutic use , Cholecalciferol/therapeutic use , Erythema/etiology , Erythema/immunology , Erythema/pathology , Histamine Antagonists/therapeutic use , Antimalarials/therapeutic useABSTRACT
Polymorphous light eruption (PLE) is the commonest immuno-mediated photodermatosis. It occurs after solar or artificial UV-light exposure and affects only the sun-exposed areas with preference of the V-area of the chest, of arms and forearms, legs, upper part of the back, and rarely the face. The lesions are itching or burning, and vary morphologically from erythema to papules, vesico-papules and occasionally blisters, plaques, sometimes erythema multiforme-like, insect bite-like wheals and purpura. The clinical manifestations befall within a few hours to days from light exposure, last a few days, and subside in about a week without sequelae. Its diagnosis is based on history, morphology and phototests. PLE is considered as a delayed hypersensitivity response to newly UV induced, but still unidentified, antigen(s). Usually, MED is normal, but the provocative phototests with UVA or UVB reproduce the spontaneous lesions in about 50% of the patients. Broad spectrum sunscreens and antioxidants, photohardening with PUVA or narrow band UVB may be beneficial to prevent the disease. Therapy is based mainly on topical or systemic corticosteroids.
Subject(s)
Hypersensitivity, Delayed/etiology , Photosensitivity Disorders/etiology , Skin/radiation effects , Sunlight/adverse effects , Ultraviolet Rays/adverse effects , Adrenal Cortex Hormones/therapeutic use , Animals , Antioxidants/therapeutic use , Humans , Hypersensitivity, Delayed/diagnosis , Hypersensitivity, Delayed/immunology , Hypersensitivity, Delayed/prevention & control , PUVA Therapy , Photosensitivity Disorders/diagnosis , Photosensitivity Disorders/immunology , Photosensitivity Disorders/prevention & control , Risk Factors , Skin/immunology , Skin/pathology , Sunscreening Agents/therapeutic use , Treatment OutcomeABSTRACT
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.
Subject(s)
Photosensitivity Disorders/diagnosis , Allergists , Humans , Photosensitivity Disorders/etiology , Photosensitivity Disorders/immunology , Vitamin D/immunologyABSTRACT
INTRODUCTION: Polymorphic light eruption (PLE) is a common idiopathic photodermatosis that typically presents with pruritic papular or papulovesicular lesions on sun-exposed skin between spring and autumn. In many subjects PLE is mild, and can usually be prevented by the use of broad-spectrum topical sunscreens and a gradual increase in sunlight exposure. However, in some individuals, sunlight exposure results in florid PLE and they often benefit from prophylactic desensitization treatment using phototherapy in early spring, an artificial method that induces a "hardening" phenomenon. OBJECTIVE: To describe and evaluate the efficacy of a short desensitization protocol, based on a one-month-treatment, administered twice a week with narrow band UVB in subjects with severe polymorphic light eruption (PLE). METHODS: A retrospective, open planned and non-randomized study to assess the efficacy of UVB phototherapy in prevention of polymorphic light eruption. RESULTS: Fifteen subjects diagnosed with severe PLE were treated with the standard protocol in our Photobiology Unit between 2014 and 2015. The effect of hardening was sustained during follow up in 87.5% of desensitization treatments. A statistically significant association (p<0.05) between the years of duration of the PLE and the response to treatment was found. CONCLUSIONS: The effect of hardening was maintained in the vast majority of subjects, obtaining a good benefit with no PLE episodes during all the summer. We demonstrate that our standard protocol is effective, and produces a successful outcome for the majority of PLE subjects. Our protocol is shorter than those currently applied, being favourable both for the patient and the physician.