Drug-Induced Photosensitivity Workup

Author: Alexandra Y Zhang, MD; Chief Editor: Dirk M Elston, MD more...

Updated: Apr 4, 2012

What would you like to print?

Laboratory Studies
Other Tests
Histologic Findings
Show All

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.

Other Tests

Photopatch testing is an important tool in the diagnosis of photoallergic contact dermatitis. Note the following:

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. Note the following:

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.

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.

Proceed to Treatment & Management

Contributor Information and Disclosures

Author

Alexandra Y Zhang, MD Assistant Professor, Department of Dermatology, University of Pittsburgh

Alexandra Y Zhang, MD is a member of the following medical societies: American Academy of Dermatology, Dermatology Foundation, and Women's Dermatologic Society

Disclosure: Nothing to disclose.

Coauthor(s)

Craig A Elmets, MD Professor and Chair, Department of Dermatology, Director, 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, and Society for Investigative Dermatology

Disclosure: Palomar Medical Technologies Stock None; Astellas Consulting fee Review panel membership; Massachusetts Medical Society Salary Employment; Abbott Laboratories Grant/research funds Independent contractor; UpToDate Salary Employment; Biogen Grant/research funds Independent contractor; Clinuvel Independent contractor; Covan Basilea Pharmaceutical Grant/research funds Independent contractor; ISDIN None Consulting; TenX BIopharma Grant/research funds Independent contractor

Specialty Editor Board

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

Disclosure: Nothing to disclose.

David F Butler, MD Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and 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, and American College of Rheumatology

Disclosure: Amgen Honoraria Consulting; Celgene Honoraria Safety Monitoring Committee

Catherine M Quirk, MD Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

References

Fox GN, Harrell CC, Mehregan DR. Extensive lichenoid drug eruption due to glyburide: a case report and review of the literature. Cutis. Jul 2005;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. May 2009;4(2):123-36. [Medline].
Günes AT, Fetil E, Ilknur T, Birgin B, Ozkan S. Naproxen-induced lichen planus: report of 55 cases. Int J Dermatol. Jun 2006;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. Jun 2004;43(6):459-61. [Medline].
Suchak R, Benson K, Swale V. Statin-induced Ro/SSa-positive subacute cutaneous lupus erythematosus. Clin Exp Dermatol. Sep 2007;32(5):589-91. [Medline].
Kong HH, Fine HA, Stern JB, Turner ML. Cutaneous pigmentation after photosensitivity induced by vandetanib therapy. Arch Dermatol. Aug 2009;145(8):923-5. [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. Dec 2002;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. Oct 2001;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. Apr 2004;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. Oct 2004;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. Mar 2009;15(3):370-6. [Medline].
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. May 2005;52(5 Suppl 1):S81-5. [Medline].
Rubenstein M, Levy ML, Metry D. Voriconazole-induced retinoid-like photosensitivity in children. Pediatr Dermatol. Nov-Dec 2004;21(6):675-8. [Medline].
Cohen PR. Photodistributed erythema multiforme: paclitaxel-related, photosensitive conditions in patients with cancer. J Drugs Dermatol. Jan 2009;8(1):61-4. [Medline].
Morison WL. Solar urticaria due to progesterone compounds in oral contraceptives. Photodermatol Photoimmunol Photomed. Jun 2003;19(3):155-6. [Medline].
Silver EA, Silver AH, Silver DS, McCalmont TH. Pseudoporphyria induced by oral contraceptive pills. Arch Dermatol. Feb 2003;139(2):227-8. [Medline].
Gonzalez E, Gonzalez S. Drug photosensitivity, idiopathic photodermatoses, and sunscreens. J Am Acad Dermatol. Dec 1996;35(6):871-85; quiz 886-7. [Medline].
Ellgehausen P, Elsner P, Burg G. Drug-induced lichen planus. Clin Dermatol. May-Jun 1998;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. Jul 1985;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. Sep 2001;137(9):1196-8. [Medline].
Allen JE. Drug-induced photosensitivity. Clin Pharm. Aug 1993;12(8):580-7. [Medline].
Gould JW, Mercurio MG, Elmets CA. Cutaneous photosensitivity diseases induced by exogenous agents. J Am Acad Dermatol. Oct 1995;33(4):551-73; quiz 574-6. [Medline].
Hrabovsky SL, Elmets CA. Pathogenesis, characteristics, diagnosis, and treatment of pseudoporphyria. Curr Opin in Dermatol. 1996;3:105-10.

Phototoxic reaction.

Photoallergic reaction.

Pseudoporphyria.

Subacute cutaneous lupus erythematosus exacerbated by terbinafine. Courtesy of Jeffrey P. Callen.

Table 1. Common Photosensitizing Medications

Class	Medication	Phototoxic Reaction	Photoallergic Reaction	Lichenoid Reaction	Pseudoporphyria	Subacute Cutaneous Lupus Erythematosus
Antibiotics	Tetracyclines (doxycycline, tetracycline)	Yes	No	Yes	Yes	No
	Fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin)^[1]	Yes	No	No	No	No
	Sulfonamides	Yes	No	No	No	No
Nonsteroidal anti-inflammatory drugs^[2]	Ibuprofen	Yes	No	Yes	No	No
	Ketoprofen	Yes	Yes	No	No	No
	Naproxen^[3]	Yes	No	Yes	Yes	No
	Celecoxib^[4]	No	Yes	No	Yes	No
Diuretics	Furosemide	Yes	No	No	Yes	No
	Bumetanide	No	No	No	Yes	No
	Hydrochlorothiazide	Yes	No	No	No	Yes
Retinoid	Isotretinoin	Yes	No	No	No	No
Retinoid	Acitretin	Yes	No	No	No	No
Hypoglycemics	Sulfonylureas (glipizide, glyburide)^[1]	No	Yes	Yes	Yes	No
HMG-CoA* reductase inhibitors	Statins (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin)^[5]	Yes	Yes	Yes	Yes	No
Epidermal growth factor receptor inhibitors	Cetuximab, panitumumab, erlotinib, gefitinib, lapatinib, vandetanib^[6]	Yes	Yes	Yes	Yes	No
Photodynamic therapy prophotosensitizers	5-Aminolevulinic acid^[7]	Yes	No	No	No	No
	Methyl-5-aminolevulinic acid	Yes	No	No	No	No
	Verteporfin^[8]	Yes	No	No	No	No
	Photofrin^[9]	Yes	No	No	No	No
Neuroleptic drugs^[10]	Phenothiazines (chlorpromazine, fluphenazine, perazine, perphenazine, thioridazine)^[11]	Yes	Yes	Yes	No	No
Neuroleptic drugs^[10]	Thioxanthenes (chlorprothixene, thiothixene)	Yes	No	No	No	No
Antifungals	Terbinafine	No	No	No	No	Yes
	Itraconazole	Yes	Yes	No	No	No
	Voriconazole^{[12, 13, 14, 15]}	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^{[2, 16]}	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^{[17, 18]}	No	Yes	No	Yes	No
Sunscreens^[19]	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
Fragrances	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

View Table List

Read more about Drug-Induced Photosensitivity on Medscape