Drug-Induced Photosensitivity
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Drug-induced photosensitivity refers to the development of cutaneous disease as a result of the combined effects of a chemical and light. [1] Exposure to either the chemical or the light alone is not sufficient to induce the disease; however, when photoactivation of the chemical occurs, one or more cutaneous manifestations may arise. These include phototoxic and photoallergic reactions, a planus lichenoides reaction, pseudoporphyria, and subacute cutaneous lupus erythematosus. Photosensitivity reactions may result from systemic medications and topically applied compounds (see Table 1 below).
UV-A–associated phototoxicity is also common with vemurafenib, [2, 3, 4] with reduced UV-A minimal erythema dose in 94% of those tested. [2]
Wavelengths within the UV-A (320-400 nm) range and, for certain compounds, within the visible range, are more likely to cause drug-induced photosensitivity reactions, although occasionally UV-B (290-320 nm) can also be responsible for such effects. UV-B wavelengths are most efficient at causing sunburn and nonmelanoma skin cancer. In patients who present with photosensitivity, it is often difficult to differentiate phototoxic from photoallergic reactions. However, they have a number of distinguishing characteristics (see Table 2 below).
Table 1. Common Photosensitizing Medications (Open Table in a new window)
Class
Medication
Photo-toxic Reaction
Photo-allergic Reaction
Lichenoid Reaction
Pseudo-porphyria
Subacute Cutaneous Lupus Erythematosus
Antibiotics
Tetracyclines (doxycycline, tetracycline)
Yes
No
Yes
Yes
No
Fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin) [5]
Yes
No
No
No
No
Sulfonamides
Yes
No
No
No
No
Nonsteroidal anti-inflammatory drugs [6]
Ibuprofen
Yes
No
Yes
No
No
Ketoprofen [7]
Yes
Yes
No
No
No
Naproxen [8]
Yes
No
Yes
Yes
No
Celecoxib [9]
No
Yes
No
Yes
No
Diuretics
Furosemide
Yes
No
No
Yes
No
Bumetanide
No
No
No
Yes
No
Hydro-chlorothiazide
Yes
No
No
No
Yes
Retinoid
Isotretinoin
Yes
No
No
No
No
Acitretin
Yes
No
No
No
No
Hypoglycemics
Sulfonylureas (glipizide, glyburide) [5]
No
Yes
Yes
Yes
No
HMG-CoA* reductase inhibitors
Statins (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin) [10]
Yes
Yes
Yes
Yes
No
Epidermal growth factor receptor inhibitors
Cetuximab, panitumumab, erlotinib, gefitinib, lapatinib, vandetanib [11]
Yes
Yes
Yes
Yes
No
Photodynamic therapy prophoto-sensitizers
5-Aminolevulinic acid [13]
Yes
No
No
No
No
Methyl-5-aminolevulinic acid
Yes
No
No
No
No
Verteporfin [14]
Yes
No
No
No
No
Photofrin [15]
Yes
No
No
No
No
Neuroleptic drugs [16]
Phenothiazines (chlorpromazine, fluphenazine, perazine, perphenazine, thioridazine) [17]
Yes
Yes
Yes
No
No
Thioxanthenes (chlorprothixene, thiothixene)
Yes
No
No
No
No
Antifungals
Terbinafine
No
No
No
No
Yes
Itraconazole
Yes
Yes
No
No
No
Yes
No
No
Yes
No
Griseofulvin
Yes
Yes
No
No
Yes
Other drugs
Para-aminobenzoic acid
Yes
Yes
No
No
No
5-Fluorouracil
Yes
Yes
Yes
Yes
No
Yes
No
No
No
Yes
Amiodarone
Yes
No
No
Yes
No
Diltiazem
Yes
No
No
No
Yes
Quinidine
Yes
Yes
Yes
No
No
Hydroxychloroquine
No
No
Yes
No
No
Coal tar
Yes
No
No
No
No
Enalapril
No
No
No
No
Yes
Dapsone
No
Yes
Yes
Yes
No
No
Yes
No
Yes
No
Sunscreens [25]
Para-aminobenzoic acid
No
Yes
No
No
No
Cinnamates
No
Yes
No
No
No
Benzophenones
No
Yes
No
No
No
Salicylates
No
Yes
No
No
No
Fragrances
Musk ambrette
No
Yes
No
No
No
6-Methylcoumarin
No
Yes
No
No
No
*3-Hydroxy-3-methylglutaryl coenzyme A.
Phototoxic reactions occur because of the damaging effects of light-activated compounds on cell membranes and, in some instances, DNA. By contrast, photoallergic reactions are cell-mediated immune responses to a light-activated compound. Phototoxic reactions develop in most individuals if they are exposed to sufficient amounts of light and drug. Typically, they appear as an exaggerated sunburn response, as shown in the image below.
Photoallergic reactions resemble allergic contact dermatitis, with a distribution limited to sun-exposed areas of the body. However, when the reactions are severe or prolonged, they may extend into covered areas of skin.
Table 2. Distinguishing Characteristics of Phototoxic and Photoallergic Reactions (Open Table in a new window)
Feature
Phototoxic Reaction
Photoallergic Reaction
Incidence
High
Low
Amount of agent required for photosensitivity
Large
Small
Onset of reaction after exposure to agent and light
Minutes to hours
24-72 hours
More than one exposure to agent required
No
Yes
Distribution
Sun-exposed skin only
Sun-exposed skin, may spread to unexposed areas
Clinical characteristics
Exaggerated sunburn
Dermatitis
Immunologically mediated
No
Yes; Type IV
Photoallergic reactions develop in only a minority of individuals exposed to the compound and light; they are less prevalent than phototoxic skin reactions. The amount of drug required to elicit photoallergic reactions is considerably smaller than that required for phototoxic reactions. Moreover, photoallergic reactions, as shown in the image below, are a form of cell-mediated immunity; their onset often is delayed by as long as 24-72 hours after exposure to the drug and light. By contrast, phototoxic responses often occur within minutes or hours of light exposure.
Phototoxic reactions result from direct damage to tissue caused by a photoactivated compound. Many compounds have the potential to cause phototoxicity. Most have at least one resonating double bond or an aromatic ring that can absorb radiant energy. Most compounds are activated by wavelengths within the UV-A (320-400 nm) range, although some compounds have a peak absorption within the UV-B or visible range.
In most instances, photoactivation of a compound results in the excitation of electrons from the stable singlet state to an excited triplet state. As excited-state electrons return to a more stable configuration, they transfer their energy to oxygen, leading to the formation of reactive oxygen intermediates. Reactive oxygen intermediates such as an oxygen singlet, superoxide anion, and hydrogen peroxide damage cell membranes and DNA. Signal transduction pathways that lead to the production of proinflammatory cytokines and arachidonic acid metabolites are also activated. The result is an inflammatory response that has the clinical appearance of an exaggerated sunburn reaction.
The exception to this mechanism of drug-induced phototoxicity is psoralen-induced phototoxicity. Psoralens intercalate within DNA, forming monofunctional adducts. Exposure to UV-A radiation produces bifunctional adducts within DNA. Exactly how bifunctional adducts cause photosensitivity is unknown.
Photoallergic reactions are cell-mediated immune responses in which the antigen is a light-activated drug. Photoactivation results in the development of a metabolite that can bind to protein carriers in the skin to form a complete antigen. The reaction then proceeds exactly as other cell-mediated immune responses do. Specifically, Langerhans cells and other antigen-presenting cells take up the antigen and then migrate to regional lymph nodes. In those locations, the Langerhans cells present the photoallergen to T lymphocytes that express antigen-specific receptors. The T cells become activated and proliferate, and they return to the site of photoallergen deposition. In the skin, the T cells orchestrate an inflammatory response that usually has an eczematous morphology if the photoallergen is applied topically or the characteristics of a drug eruption if the photoallergen is administered systemically.
Most phototoxic reactions result from the systemic administration of drugs. Photoallergic reactions can be caused by either topical or systemic administration of the chemical. Compounds that commonly cause phototoxic and/or photoallergic reactions are listed in Table 1 in Background.
United States
The incidence of drug-induced photosensitivity in the United States is uncertain. Phototoxic reactions are considerably more common than photoallergic reactions.
International
The incidence of drug-induced photosensitivity is unknown.
The racial incidence of drug-induced photosensitivity reactions is unknown. Photosensitivity reactions can occur in races with heavily pigmented skin.
Men are more likely to have photoallergic reactions than women.
Drug-induced photosensitivity reactions can occur in persons of any age.
In most patients, the prognosis is excellent once the offending agent is removed. However, complete resolution of the photosensitivity may take several weeks to months with some compounds. Occasionally, patients have persistent light reactivity for which the prospects for resolution are poor.
Drug-induced photosensitivity is associated with death only in rare individuals who are exposed to large amounts of sunlight after taking large doses of psoralens. Although mortality is rare, drug-induced photosensitivity can cause significant morbidity in some individuals, who must severely limit their exposure to natural or artificial light.
Voriconazole photosensitivity is associated with a risk of skin cancer. [26, 27] The changes that occur with long-term exposure resemble accelerated photo-aging. Acute photosensitivity occurs in 1–2% or more of patients taking voriconazole for more than 12 weeks. It appears to be UV-A induced, but it is not strictly dose-dependent. Cheilitis and facial erythema are typical initial manifestations.
Patients need to be counseled regarding the possible photosensitizing properties of both prescription and nonprescription medications. Most often, appropriate sun protection measures prevent drug-induced photosensitivity reactions.
For patient education resources, see the Burns Center, as well as Sunburn.
Ibbotson SH. Shedding light on drug photosensitivity reactions. Br J Dermatol. 2017 Apr. 176 (4):850-851. [Medline].
Gelot P, Dutartre H, Khammari A, et al. Vemurafenib: an unusual UVA-induced photosensitivity. Exp Dermatol. 2013 Apr. 22(4):297-8. [Medline].
Boussemart L, Routier E, Mateus C, et al. Prospective study of cutaneous side-effects associated with the BRAF inhibitor vemurafenib: a study of 42 patients. Ann Oncol. 2013 Jun. 24(6):1691-7. [Medline].
Lacouture ME, Duvic M, Hauschild A, et al. Analysis of dermatologic events in vemurafenib-treated patients with melanoma. Oncologist. 2013. 18(3):314-22. [Medline]. [Full Text].
Fox GN, Harrell CC, Mehregan DR. Extensive lichenoid drug eruption due to glyburide: a case report and review of the literature. Cutis. 2005 Jul. 76(1):41-5. [Medline].
Onoue S, Seto Y, Gandy G, Yamada S. Drug-induced phototoxicity; an early in vitro identification of phototoxic potential of new drug entities in drug discovery and development. Curr Drug Saf. 2009 May. 4(2):123-36. [Medline].
Loh TY, Cohen PR. Ketoprofen-induced photoallergic dermatitis. Indian J Med Res. 2016 Dec. 144 (6):803-806. [Medline].
Günes AT, Fetil E, Ilknur T, Birgin B, Ozkan S. Naproxen-induced lichen planus: report of 55 cases. Int J Dermatol. 2006 Jun. 45(6):709-12. [Medline].
Yazici AC, Baz K, Ikizoglu G, Kokturk A, Uzumlu H, Tataroglu C. Celecoxib-induced photoallergic drug eruption. Int J Dermatol. 2004 Jun. 43(6):459-61. [Medline].
Suchak R, Benson K, Swale V. Statin-induced Ro/SSa-positive subacute cutaneous lupus erythematosus. Clin Exp Dermatol. 2007 Sep. 32(5):589-91. [Medline].
Kong HH, Fine HA, Stern JB, Turner ML. Cutaneous pigmentation after photosensitivity induced by vandetanib therapy. Arch Dermatol. 2009 Aug. 145(8):923-5. [Medline].
Boada A, Carrera C, Segura S, Collgros H, Pasquali P, Bodet D, et al. Cutaneous toxicities of new treatments for melanoma. Clin Transl Oncol. 2018 May 24. [Medline].
Gupta AK, Ryder JE. Photodynamic therapy and topical aminolevulinic acid: an overview. Am J Clin Dermatol. 2003. 4(10):699-708. [Medline].
Houle JM, Strong HA. Duration of skin photosensitivity and incidence of photosensitivity reactions after administration of verteporfin. Retina. 2002 Dec. 22(6):691-7. [Medline].
Moriwaki SI, Misawa J, Yoshinari Y, Yamada I, Takigawa M, Tokura Y. Analysis of photosensitivity in Japanese cancer-bearing patients receiving photodynamic therapy with porfimer sodium (Photofrin). Photodermatol Photoimmunol Photomed. 2001 Oct. 17(5):241-3. [Medline].
Eberlein-Konig B, Bindl A, Przybilla B. Phototoxic properties of neuroleptic drugs. Dermatology. 1997. 194(2):131-5. [Medline].
Llambrich A, Lecha M. Photoinduced lichenoid reaction by thioridazine. Photodermatol Photoimmunol Photomed. 2004 Apr. 20(2):108-9. [Medline].
Dolan CK, Hall MA, Blazes DL, Norwood CW. Pseudoporphyria as a result of voriconazole use: a case report. Int J Dermatol. 2004 Oct. 43(10):768-71. [Medline].
Patel AR, Turner ML, Baird K, et al. Voriconazole-induced phototoxicity masquerading as chronic graft-versus-host disease of the skin in allogeneic hematopoietic cell transplant recipients. Biol Blood Marrow Transplant. 2009 Mar. 15(3):370-6. [Medline]. [Full Text].
Racette AJ, Roenigk HH Jr, Hansen R, Mendelson D, Park A. Photoaging and phototoxicity from long-term voriconazole treatment in a 15-year-old girl. J Am Acad Dermatol. 2005 May. 52(5 Suppl 1):S81-5. [Medline].
Rubenstein M, Levy ML, Metry D. Voriconazole-induced retinoid-like photosensitivity in children. Pediatr Dermatol. 2004 Nov-Dec. 21(6):675-8. [Medline].
Cohen PR. Photodistributed erythema multiforme: paclitaxel-related, photosensitive conditions in patients with cancer. J Drugs Dermatol. 2009 Jan. 8(1):61-4. [Medline].
Morison WL. Solar urticaria due to progesterone compounds in oral contraceptives. Photodermatol Photoimmunol Photomed. 2003 Jun. 19(3):155-6. [Medline].
Silver EA, Silver AH, Silver DS, McCalmont TH. Pseudoporphyria induced by oral contraceptive pills. Arch Dermatol. 2003 Feb. 139(2):227-8. [Medline].
Gonzalez E, Gonzalez S. Drug photosensitivity, idiopathic photodermatoses, and sunscreens. J Am Acad Dermatol. 1996 Dec. 35(6):871-85; quiz 886-7. [Medline].
Hansford JR, Cole C, Blyth CC, Gottardo NG. Idiosyncratic nature of voriconazole photosensitivity in children undergoing cancer therapy. J Antimicrob Chemother. 2012 Jul. 67(7):1807-9. [Medline].
Haylett AK, Felton S, Denning DW, Rhodes LE. Voriconazole-induced photosensitivity: photobiological assessment of a case series of 12 patients. Br J Dermatol. 2013 Jan. 168(1):179-85. [Medline].
Ellgehausen P, Elsner P, Burg G. Drug-induced lichen planus. Clin Dermatol. 1998 May-Jun. 16(3):325-32. [Medline].
Reed BR, Huff JC, Jones SK, Orton PW, Lee LA, Norris DA. Subacute cutaneous lupus erythematosus associated with hydrochlorothiazide therapy. Ann Intern Med. 1985 Jul. 103(1):49-51. [Medline].
Callen JP, Hughes AP, Kulp-Shorten C. Subacute cutaneous lupus erythematosus induced or exacerbated by terbinafine: a report of 5 cases. Arch Dermatol. 2001 Sep. 137(9):1196-8. [Medline].
Willis ZI, Boyd AS, Di Pentima MC. Phototoxicity, Pseudoporphyria, and Photo-onycholysis Due to Voriconazole in a Pediatric Patient With Leukemia and Invasive Aspergillosis. J Pediatric Infect Dis Soc. 2015 Jun. 4 (2):e22-4. [Medline].
Class
Medication
Photo-toxic Reaction
Photo-allergic Reaction
Lichenoid Reaction
Pseudo-porphyria
Subacute Cutaneous Lupus Erythematosus
Antibiotics
Tetracyclines (doxycycline, tetracycline)
Yes
No
Yes
Yes
No
Fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin) [5]
Yes
No
No
No
No
Sulfonamides
Yes
No
No
No
No
Nonsteroidal anti-inflammatory drugs [6]
Ibuprofen
Yes
No
Yes
No
No
Ketoprofen [7]
Yes
Yes
No
No
No
Naproxen [8]
Yes
No
Yes
Yes
No
Celecoxib [9]
No
Yes
No
Yes
No
Diuretics
Furosemide
Yes
No
No
Yes
No
Bumetanide
No
No
No
Yes
No
Hydro-chlorothiazide
Yes
No
No
No
Yes
Retinoid
Isotretinoin
Yes
No
No
No
No
Acitretin
Yes
No
No
No
No
Hypoglycemics
Sulfonylureas (glipizide, glyburide) [5]
No
Yes
Yes
Yes
No
HMG-CoA* reductase inhibitors
Statins (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin) [10]
Yes
Yes
Yes
Yes
No
Epidermal growth factor receptor inhibitors
Cetuximab, panitumumab, erlotinib, gefitinib, lapatinib, vandetanib [11]
Yes
Yes
Yes
Yes
No
Photodynamic therapy prophoto-sensitizers
5-Aminolevulinic acid [13]
Yes
No
No
No
No
Methyl-5-aminolevulinic acid
Yes
No
No
No
No
Verteporfin [14]
Yes
No
No
No
No
Photofrin [15]
Yes
No
No
No
No
Neuroleptic drugs [16]
Phenothiazines (chlorpromazine, fluphenazine, perazine, perphenazine, thioridazine) [17]
Yes
Yes
Yes
No
No
Thioxanthenes (chlorprothixene, thiothixene)
Yes
No
No
No
No
Antifungals
Terbinafine
No
No
No
No
Yes
Itraconazole
Yes
Yes
No
No
No
Yes
No
No
Yes
No
Griseofulvin
Yes
Yes
No
No
Yes
Other drugs
Para-aminobenzoic acid
Yes
Yes
No
No
No
5-Fluorouracil
Yes
Yes
Yes
Yes
No
Yes
No
No
No
Yes
Amiodarone
Yes
No
No
Yes
No
Diltiazem
Yes
No
No
No
Yes
Quinidine
Yes
Yes
Yes
No
No
Hydroxychloroquine
No
No
Yes
No
No
Coal tar
Yes
No
No
No
No
Enalapril
No
No
No
No
Yes
Dapsone
No
Yes
Yes
Yes
No
No
Yes
No
Yes
No
Sunscreens [25]
Para-aminobenzoic acid
No
Yes
No
No
No
Cinnamates
No
Yes
No
No
No
Benzophenones
No
Yes
No
No
No
Salicylates
No
Yes
No
No
No
Fragrances
Musk ambrette
No
Yes
No
No
No
6-Methylcoumarin
No
Yes
No
No
No
*3-Hydroxy-3-methylglutaryl coenzyme A.
Feature
Phototoxic Reaction
Photoallergic Reaction
Incidence
High
Low
Amount of agent required for photosensitivity
Large
Small
Onset of reaction after exposure to agent and light
Minutes to hours
24-72 hours
More than one exposure to agent required
No
Yes
Distribution
Sun-exposed skin only
Sun-exposed skin, may spread to unexposed areas
Clinical characteristics
Exaggerated sunburn
Dermatitis
Immunologically mediated
No
Yes; Type IV
Alexandra Y Zhang, MD Staff Physician, Dermatology and Plastic Institute, Cleveland Clinic Foundation
Alexandra Y Zhang, MD is a member of the following medical societies: American Academy of Dermatology, Women’s Dermatologic Society, Dermatology Foundation
Disclosure: Nothing to disclose.
Craig A Elmets, MD Professor and Chair, Department of Dermatology, Director, Chemoprevention Program Director, Comprehensive Cancer Center, UAB Skin Diseases Research Center, University of Alabama at Birmingham School of Medicine
Craig A Elmets, MD is a member of the following medical societies: American Academy of Dermatology, American Association of Immunologists, American College of Physicians, American Federation for Medical Research, Society for Investigative Dermatology
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: University of Alabama at Birmingham; University of Alabama Health Services Foundation<br/>Serve(d) as a speaker or a member of a speakers bureau for: Ferndale Laboratories<br/>Received research grant from: NIH, Veterans Administration, California Grape Assn<br/>Received consulting fee from Astellas for review panel membership; Received salary from Massachusetts Medical Society for employment; Received salary from UpToDate for employment. for: Astellas.
David F Butler, MD Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, Association of Military Dermatologists, American Academy of Dermatology, American Society for MOHS Surgery, Phi Beta Kappa
Disclosure: Nothing to disclose.
Jeffrey P Callen, MD Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine
Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, American College of Rheumatology
Disclosure: Received income in an amount equal to or greater than $250 from: Lilly; Amgen <br/>Received honoraria from UpToDate for author/editor; Received honoraria from JAMA Dermatology for associate editor; Received royalty from Elsevier for book author/editor; Received dividends from trust accounts, but I do not control these accounts, and have directed our managers to divest pharmaceutical stocks as is fiscally prudent from Stock holdings in various trust accounts include some pharmaceutical companies and device makers for i inherited these trust accounts; for: Allergen; Celgene; Pfizer; 3M; Johnson and Johnson; Merck; Abbott Laboratories; AbbVie; Procter and Gamble; Amgen.
Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.
Abdul-Ghani Kibbi, MD Professor and Chair, Department of Dermatology, American University of Beirut Medical Center, Lebanon
Disclosure: Nothing to disclose.
Drug-Induced Photosensitivity
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