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Annals of the Rheumatic Diseases Nov 2018Skin inflammation and photosensitivity are common in patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE), yet little is known about...
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. 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
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) 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.
Topics: Adult; Cells, Cultured; Dendritic Cells; Epidermis; Female; Humans; Interferon Type I; Keratinocytes; Lupus Erythematosus, Cutaneous; Male; Middle Aged; Photosensitivity Disorders; RNA, Messenger; Skin; TYK2 Kinase; Up-Regulation
PubMed: 30021804
DOI: 10.1136/annrheumdis-2018-213197 -
Journal Der Deutschen Dermatologischen... Jan 2021Drug-induced photosensitivity, the development of phototoxic or photoallergic reactions due to pharmaceuticals and subsequent exposure to ultraviolet or visible light,... (Review)
Review
Drug-induced photosensitivity, the development of phototoxic or photoallergic reactions due to pharmaceuticals and subsequent exposure to ultraviolet or visible light, is an adverse effect of growing interest. This is illustrated by the broad spectrum of recent investigations on the topic, ranging from molecular mechanisms and culprit drugs through epidemiological as well as public health related issues to long-term photoaging and potential photocarcinogenic consequences. The present review summarizes the current state of knowledge on the topic while focusing on culprit drugs and long-term effects. In total, 393 different drugs or drug compounds are reported to have a photosensitizing potential, although the level of evidence regarding their ability to induce photosensitive reactions varies markedly among these agents. The pharmaceuticals of interest belong to a wide variety of drug classes. The epidemiological risk associated with the use of photosensitizers is difficult to assess due to under-reporting and geographical differences. However, the widespread use of photosensitizing drugs combined with the potential photocarcinogenic effects reported for several agents has major implications for health and safety and suggests a need for further research on the long-term effects.
Topics: Dermatitis, Photoallergic; Dermatitis, Phototoxic; Drug Eruptions; Humans; Pharmaceutical Preparations; Photosensitivity Disorders; Ultraviolet Rays
PubMed: 33491908
DOI: 10.1111/ddg.14314 -
Journal of the European Academy of... Jun 2022Drug-induced photosensitivity is associated with a wide range of anticancer treatments, including conventional chemotherapeutic agents, targeted anticancer therapies,... (Review)
Review
Drug-induced photosensitivity is associated with a wide range of anticancer treatments, including conventional chemotherapeutic agents, targeted anticancer therapies, and immune checkpoint inhibitors. These dermatologic adverse events can have a major impact on the well-being and quality of life of cancer patients, leading to dose modifications and interruption or discontinuation of anticancer treatments in severe cases. However, the heterogeneous nature of the photosensitive reactions induced by these agents, as well as the common concomitant use of other potentially photosensitizing drugs (antibiotics, voriconazole, nonsteroidal anti-inflammatory drugs, etc.), can make the diagnosis and, therefore the prevention, of these adverse events particularly challenging. The aim of this review is to describe the most characteristic forms of photosensitivity observed in patients being treated with anticancer treatments, including phototoxicity and photoallergy, and other potentially photo-induced manifestations such as UV recall, exaggerated sunburn reactions associated with treatment-related vitiligo, drug-induced cutaneous lupus erythematosus, and UV-induced hyperpigmentation. We also discuss the photosensitive reactions recently reported with new-generation targeted anticancer therapies and immune checkpoint inhibitors and highlight the importance of continued surveillance to identify photosensitizing agents, and of educating patients on the need for preventive UVA/UVB photoprotective measures.
Topics: Dermatitis, Photoallergic; Dermatitis, Phototoxic; Humans; Immune Checkpoint Inhibitors; Photosensitivity Disorders; Quality of Life
PubMed: 35738806
DOI: 10.1111/jdv.18200 -
Mutation Research Jun 2015Photosensitivity in humans can result from defects in repair of light-induced DNA lesions, from photoactivation of chemicals (including certain medications) with... (Review)
Review
Photosensitivity in humans can result from defects in repair of light-induced DNA lesions, from photoactivation of chemicals (including certain medications) with sunlight to produce toxic mediators, and by immune reactions to sunlight exposures. Deficiencies in DNA repair and the processing of damaged DNA during replication and transcription may result in mutations and genomic instability. We will review current understanding of photosensitivity to short wavelength ultraviolet light (UV) due to genetic defects in particular DNA repair pathways; deficiencies in some are characterized by an extremely high incidence of cancer in sun-exposed tissues, while in others no cancers have been reported.
Topics: DNA Breaks; DNA Repair; Genomic Instability; Humans; Mutation; Neoplasms, Radiation-Induced; Photosensitivity Disorders; Syndrome; Ultraviolet Rays
PubMed: 26255937
DOI: 10.1016/j.mrfmmm.2014.11.003 -
Orphanet Journal of Rare Diseases Sep 2009Erythropoietic protoporphyria (EPP) is an inherited disorder of the haem metabolic pathway characterised by accumulation of protoporphyrin in blood, erythrocytes and... (Review)
Review
Erythropoietic protoporphyria (EPP) is an inherited disorder of the haem metabolic pathway characterised by accumulation of protoporphyrin in blood, erythrocytes and tissues, and cutaneous manifestations of photosensitivity. EPP has been reported worldwide, with prevalence between 1:75,000 and 1:200,000. It usually manifests in early infancy upon the first sun exposures. EPP is characterised by cutaneous manifestations of acute painful photosensitivity with erythema and oedema, sometimes with petechiae, together with stinging and burning sensations upon exposure to sunlight, without blisters. These episodes have a variable severity depending on the exposure duration and may result in chronic permanent lesions on exposed skin. As protoporphyrin is a lipophilic molecule that is excreted by the liver, EPP patients are at risk of cholelithiasis with obstructive episodes, and chronic liver disease that might evolve to rapid acute liver failure. In most patients, EPP results from a partial deficiency of the last enzyme of the haem biosynthetic pathway, ferrochelatase, EC 4.99.1.1/FECH (encoded by the FECH gene). EPP appears to be inherited as an autosomal dominant disease, the clinical expression of which is modulated by the presence of the hypomorphic FECH IVS3-48C allele trans, but recessive inheritance with two mutated FECH alleles has also been described. In about 2% of patients, overt disease was recently shown to be caused by gain-of-function mutations in the erythroid-specific aminolevulinic acid synthase 2 (ALAS2/ALAS, EC 2.3.1.27) gene and named X-linked dominant protoporphyria. Diagnosis is established by finding increased levels of protoporphyrin in plasma and red blood cells, and detection of a plasma fluorescence peak at 634 nm. Investigations for hepatic involvement, ferrochelatase activity level, genetic analysis (FECH mutations, presence of the hypomorphic FECH IVS3-48C allele trans and ALAS2 mutations) and family studies are advisable. Differential diagnosis includes phototoxic drug reactions, hydroa vacciniforme, solar urticaria, contact dermatitis, angio-oedema and, in some cases, other types of porphyria. Management includes avoidance of exposure to light, reduction of protoporphyrin levels and prevention of progression of possible liver disease to liver failure. As the major risk in EPP patients is liver disease, a regular follow-up of hepatic involvement is essential. Sequential hepatic and bone marrow transplantation should be considered as a suitable treatment for most severe cases of EPP with hepatic involvement. EPP is a lifelong disorder whose prognosis depends on the evolution of the hepatic disease. However, photosensitivity may have a significant impact on quality of life of EPP patients.
Topics: Ferrochelatase; Humans; Photosensitivity Disorders; Protoporphyria, Erythropoietic
PubMed: 19744342
DOI: 10.1186/1750-1172-4-19 -
Photodermatology, Photoimmunology &... Feb 2013Ultraviolet radiation (UVR) is a well-known exacerbating factor for cutaneous lupus erythematosus (CLE), with photosensitivity comprising one of the American College of... (Review)
Review
BACKGROUND
Ultraviolet radiation (UVR) is a well-known exacerbating factor for cutaneous lupus erythematosus (CLE), with photosensitivity comprising one of the American College of Rheumatology (ACR) diagnostic criteria for systemic lupus erythematosus (SLE). However, discerning true photosensitivity in this population is difficult due to the broad language utilized by the ACR and the delayed-onset nature of photosensitive lupus lesions.
AIMS
The objective of this report is to provide a review of photosensitivity, photoprovocation, and phototherapy in the context of CLE patients.
METHODS
A literature review in PubMed was conducted using the terms 'ultraviolet light,' 'lupus erythematosus,' 'photoprovocation,' or 'photosensitivity.'
RESULTS
Self-patient reporting of photosensitivity and the broad definition of photosensitivity have led to the wide range of photosensitivity rates in CLE patients. Photoprovocation testing provides a more objective method to measure photosensitivity, but even these trials demonstrate significant differences due to protocol variations. Despite UVR's deleterious effect on lupus patients, ultraviolet A (UVA)-1 may have therapeutic benefits as shown by observations on murine models and human lupus subjects.
CONCLUSIONS
Accurately discerning photosensitivity has diagnostic implications for SLE and provides motivation for greater patient adherence to photoprotective methods.
Topics: Animals; Disease Models, Animal; Humans; Lupus Erythematosus, Cutaneous; Mice; Photosensitivity Disorders; Ultraviolet Rays
PubMed: 23281691
DOI: 10.1111/phpp.12018 -
Journal of Immunology (Baltimore, Md. :... Jan 2021Photosensitivity is a sensitivity to UV radiation (UVR) commonly found in systemic lupus erythematosus (SLE) patients who have cutaneous disease. Upon even ambient UVR... (Review)
Review
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.
Topics: Animals; Autoantibodies; Cell Communication; Humans; Immunity, Cellular; Lupus Erythematosus, Systemic; Photosensitivity Disorders; Skin
PubMed: 33397744
DOI: 10.4049/jimmunol.2000905 -
American Family Physician Jun 2021
Topics: Adult; Citrus; Fruit and Vegetable Juices; Furocoumarins; Humans; Hyperpigmentation; Photosensitivity Disorders
PubMed: 34060790
DOI: No ID Found -
The Indian Journal of Medical Research Dec 2016Drug-induced photosensitivity reactions are significant adverse effects. Ketoprofen is one of the most common drugs that can cause skin rash in sun-exposed areas.... (Review)
Review
Drug-induced photosensitivity reactions are significant adverse effects. Ketoprofen is one of the most common drugs that can cause skin rash in sun-exposed areas. Non-steroidal anti-inflammatory drugs (NSAIDs), such as ketoprofen, are often used for a variety of symptoms, including pain and fever. An understanding of the presentation and clinical course of ketoprofen-induced photosensitivity is necessary to correctly diagnose and manage this condition. Ketoprofen-induced photosensitivity reactions usually present as photoallergic dermatitis, which is a cell-mediated immune process. The benzophenone moiety in ketoprofen plays a major role in ketoprofen's ability to act as a photosensitizer. Several agents, such as fenofibrate and octocrylene have been found to be associated with aggravation of ketoprofen-induced photoallergic dermatitis or cross-photosensitization, and these reactions result from structural similarities with ketoprofen. Treatment of ketoprofen-induced photoallergic dermatitis includes discontinuation of ketoprofen, topical or systemic corticosteroids and avoidance of sun exposure and agents known to exacerbate dermatitis. In conclusion, photoallergic dermatitis is a significant adverse effect of ketoprofen. Some agents known to worsen dermatitis may be found in sun protection products (notably, octocrylene in sunscreen). Educating the patient to avoid these products is critical to treatment. Since NSAIDs, such as ketoprofen, are used commonly for a variety of illnesses, drug-induced photoallergic dermatitis should be high on the differential in individuals using these medications who present with acute onset of a rash in sun-exposed areas.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Dermatitis, Photoallergic; Exanthema; Humans; Ketoprofen; Photosensitivity Disorders; Sunscreening Agents
PubMed: 28474616
DOI: 10.4103/ijmr.IJMR_626_16 -
Acta Bio-medica : Atenei Parmensis Jan 2019Adverse reactions to drugs are not frequent in childhood. Cutaneous reactions are the most frequent in this age group. Mild cutaneous reactions are immediate or delayed... (Review)
Review
Adverse reactions to drugs are not frequent in childhood. Cutaneous reactions are the most frequent in this age group. Mild cutaneous reactions are immediate or delayed adverse reactions that do not seriously compromise the clinical condition of children. The patients usually early improve and recover the state of health. Although it is difficult to define the prevalence accurately, we could affirm that the rate adverse reaction to drugs are often over estimated by both the families and the physicians. Therefore, children may be prone to loss of school days and inappropriate or sub-optimal treatments. However, the identification of a true adverse reaction to drugs allows adequate treatment and alert to further exposure to harmful drugs.
Topics: Drug Eruptions; Exanthema; Humans; Photosensitivity Disorders; Urticaria
PubMed: 30830060
DOI: 10.23750/abm.v90i3-S.8159