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Drug-Induced Photosensitivity Workup

  • Author: Alexandra Y Zhang, MD; Chief Editor: Dirk M Elston, MD  more...
 
Updated: May 31, 2016
 

Laboratory Studies

To exclude porphyria cutanea tarda, assess urine porphyrin levels, which are elevated in porphyria cutanea tarda and within the normal range in pseudoporphyria and drug-induced photosensitivity. Determine antinuclear antibody (ANA) and anti-Ro (SS-A) antibody levels.

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Other Tests

Photopatch testing is an important tool in the diagnosis of photoallergic contact dermatitis. Suspected photoallergens are applied to the back in 2 sets. One set is removed after 24 hours and irradiated with 5-10 J/cm2 UV-A. Both sets of patch tests are evaluated for a positive reaction after 48 hours. Erythema, edema, and/or vesiculation at an irradiated site indicate a positive reaction. A positive reaction at both sites is interpreted as an allergic contact dermatitis. A positive reaction at the unirradiated site with a stronger one at the irradiated site should be interpreted as both allergic dermatitis and photoallergic contact dermatitis reaction to the same compound.

Phototesting with UV-A; UV-B; and, sometimes, visible light is helpful in diagnosing photosensitivity disorders. This test is performed by treating small areas of skin on the back or inner aspect of the forearms with gradually increasing doses of light. The minimum dose of light required to produce uniform erythema over the entire irradiated site after 24 hours is called the minimum erythema dose (MED). Patients with phototoxic reactions have a reduced MED to UV-A or, in some instances UV-B.

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Histologic Findings

In acute phototoxic reactions, necrotic keratinocytes are observed. If the reaction is severe, the necrosis is panepidermal. In addition, epidermal spongiosis with dermal edema and a mixed infiltrate consisting of lymphocytes, macrophages, and neutrophils may be present. Blue-gray pigmentation associated with phototoxic reactions results from increased melanin in the dermis or deposition of the drug or its metabolites within the skin.

The histologic features of a lichen planus–like phototoxic reaction are essentially indistinguishable from idiopathic lichen planus. However, increased amounts of spongiosis and necrotic keratinocytes may be present.

The histologic features of a subacute cutaneous lupus erythematosus (SCLE) – like reaction reveal an interface dermatitis that is indistinguishable from non–drug-induced SCLE. Like porphyria cutanea tarda, pseudoporphyria causes a subepidermal blister at the level of the lamina lucida. A characteristic feature of both pseudoporphyria and porphyria cutanea tarda is festooning, which refers to the irregular configuration of the dermal papillae in the floor of the bulla.

Photoallergic reactions are histologically similar to contact dermatitis. Epidermal spongiosis with a dermal lymphocytic infiltrate is a prominent feature. However, the presence of necrotic keratinocytes is suggestive of photoallergy rather than allergic contact dermatitis.

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Contributor Information and Disclosures
Author

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.

Coauthor(s)

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.

Specialty Editor Board

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: American Medical Association, Alpha Omega Alpha, Association of Military Dermatologists, American Academy of Dermatology, American Society for Dermatologic Surgery, 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: XOMA; Biogen/IDEC; Novartis; Janssen Biotech, Abbvie, CSL pharma<br/>Received honoraria from UpToDate for author/editor; Received honoraria from JAMA Dermatology for associate editor and intermittent author; 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: Celgene; Pfizer; 3M; Johnson and Johnson; Merck; Abbott Laboratories; AbbVie; Procter and Gamble; Amgen.

Chief Editor

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.

Additional Contributors

Abdul-Ghani Kibbi, MD Professor and Chair, Department of Dermatology, American University of Beirut Medical Center, Lebanon

Disclosure: Nothing to disclose.

References
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Phototoxic reaction.
Photoallergic reaction.
Pseudoporphyria.
Subacute cutaneous lupus erythematosus exacerbated by terbinafine. Courtesy of Jeffrey P. Callen.
Table 1. Common Photosensitizing Medications
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)[4] Yes No No No No
Sulfonamides Yes No No No No
Nonsteroidal anti-inflammatory drugs[5] Ibuprofen Yes No Yes No No
Ketoprofen Yes Yes No No No
Naproxen[6] Yes No Yes Yes No
Celecoxib[7] 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)[4] No Yes Yes Yes No
HMG-CoA* reductase inhibitors Statins (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin)[8] Yes Yes Yes Yes No
Epidermal growth factor receptor inhibitors Cetuximab, panitumumab, erlotinib, gefitinib, lapatinib, vandetanib[9] Yes Yes Yes Yes No
BRAF inhibitors Vemurafenib,[1, 2, 3] sorafenib Yes No No No Yes
Photodynamic therapy prophoto-sensitizers 5-Aminolevulinic acid[10] Yes No No No No
Methyl-5-aminolevulinic acid Yes No No No No
Verteporfin[11] Yes No No No No
Photofrin[12] Yes No No No No
Neuroleptic drugs[13] Phenothiazines (chlorpromazine, fluphenazine, perazine, perphenazine, thioridazine)[14] 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
Voriconazole[15, 16, 17, 18] 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
Paclitaxel[5, 19] 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
Oral contraceptives[20, 21] No Yes No Yes No
Sunscreens[22] 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.
Table 2. Distinguishing Characteristics of Phototoxic and Photoallergic Reactions
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
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