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Drug-induced photosensitivity

Last reviewed: April 2023

Author(s): Dr Lachlan Dat Wah Lau, Dermatology Resident; Dr Mi Vu, Dermatologist; and A/Prof Laura Scardamaglia, Dermatologist, Melbourne, Australia (2023).
Previous contributors: Vanessa Ngan, Staff Writer (2006).

Reviewing dermatologist: Dr Ian Coulson

Edited by the DermNet content department


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What is drug-induced photosensitivity?

Drug-induced photosensitivity (DIP) is a common adverse drug reaction resulting in a cutaneous eruption after exposure to visible or ultraviolet (UV) radiation in patients taking topical or systemic photosensitising medications. 

There are many established and new drugs with photosensitising potential. The drug or its metabolites present within the skin absorbs UV radiation and triggers a chemical photosensitivity reaction, either phototoxic (more common) or photoallergic

Photosensitising properties are sometimes used for therapeutic purposes in photodynamic therapy and photochemotherapy.

Click here for more images of drug-induced photosensitivity

Who gets drug-induced photosensitivity?

Drug-induced photosensitivity (DIP) is not genetically inherited, and there is no known age, gender, or racial predilection to developing a photosensitising cutaneous eruption. 

DIP is generally considered to account for up to 8% of reported adverse cutaneous reactions to drugs, although it is likely underdiagnosed and underreported.

Phototoxic reactions are more common than photoallergic reactions.

What causes drug-induced photosensitivity?

Table 1. Common photosensitising agents

  Phototoxic drugs Photoallergic drugs
Antibiotics

Fluoroquinolones (eg, ciprofloxacin)

Tetracyclines (eg, doxycycline)

Sulfonamides

 

Fluoroquinolones

Dapsone

 
Antifungals

Griseofulvin

Itraconazole

Ketoconazole

Voriconazole

  Griseofulvin  
Cardiovascular and diuretic agents

Amiodarone

Atorvastatin

Diltiazem

Furosemide

Hydrochlorothiazide

Quinidine

 

Quinidine

Hydrochlorothiazide

 
Furocoumarins / psoralens eg, for PUVA (photochemotherapy)

Methoxsalen (8-methoxypsoralen)

5-methoxypsoralen

Trioxsalen

Topical psoralens    
Non-steroidal anti-inflammatory drugs (NSAIDs)

Ibuprofen

Naproxen

Piroxicam

Diclofenac

Ketoprofen

Celecoxib

Ketoprofen

Piroxicam

Diclofenac

Ketoprofen

Etofenamate

Other agents

BRAF inhibitors (eg, vemurafenib)

Oral retinoids (eg, acitretin, isotretinoin)

Phenothiazines (eg, chlorpromazine)

St John’s wort

Sulfonylureas (eg, glipizide)

Antineoplastics (eg, fluorouracil cream)

Coal tar

Photodynamic therapy agents (eg, methyl aminolevulinate)

Topical retinoids

Pyridoxine

Quinine

Sulfonylureas

Fragrances (eg, musk ambrette, 6-methylcoumarin)

Phenothiazines (eg, promethazine, chlorpromazine)

Topical sunscreen agents (eg, benzophones)

Wound cleansers (eg, chlorhexidine, hexachlorophene)

Phototoxicity

A phototoxic reaction is a non-immunologic cutaneous reaction that appears acutely within minutes to hours on sun-exposed skin after taking photosensitising medications.

Phototoxicity could theoretically occur in any patient taking photosensitising medication. However, there is a dose-dependent relationship where it frequently requires a high dose of medication or light exposure that exceeds a critical threshold. 

Phototoxic skin damage begins when the drug or its metabolite within the skin absorbs ultraviolet radiation (UVR) or visible light. Then, photochemical pathways may involve:

  • The formation of an excited triplet state where UVR causes the drug molecule to transition to a more excited and chemically unstable state by the promotion of its electrons. Subsequently, an excited triplet cascade results in a direct energy transfer to oxygen creating a singlet oxygen — ie, a reactive oxygen species (ROS).
  • An excited state drug molecule removes electrons from surrounding molecules, leading to a chain reaction of ongoing free radical formation.

The resulting oxidative stress due to the formation of ROS, and direct cellular damage caused by the free radicals, manifests as an exaggerated sunburn-like reaction. 

Photoallergy

A photoallergic reaction is an immune-mediated delayed type IV hypersensitivity reaction. The key sensitising event involves the photobinding of a drug (or its metabolite) to skin biomolecules upon exposure to UVR; this forms a photoallergen. The initial sensitisation period typically takes 7–10 days. Upon subsequent re-exposure to light, an eczematous or lichen planus-like eruption that may spread beyond sun-exposed areas occurs 24–72 hours later.

What are the clinical features of drug-induced photosensitivity? 

The clinical features of DIP depend on the specific photosensitising agent involved and the type of skin reaction it triggers (phototoxic or photoallergic).

Table 2. Clinical features of drug-induced phototoxicity and photoallergy

Phototoxicity Photoallergy
  • Develops within minutes to hours
  • Develops within 24 to 72 hours
  • Affected skin resembles an exaggerated sunburn-type reaction
  • Affected skin resembles an eczematous eruption
  • Characterised by erythema, oedema, a burning and stinging sensation, with vesicles and bullae in severe reactions
  • Characterised by erythema, pruritus, and vesicles, and may have secondary features of serous discharge and crusting
  • Involvement of sun-exposed skin; common locations include the face, neck, V-shaped area on upper chest, legs, forearms, and back of the hands
  • Classically spares the nasolabial folds or areas covered by clothing (may reveal sharp lines of demarcation where clothing provides photoprotection)
  • Rash primarily affects sun-exposed skin but may spread to involve areas not exposed to sunlight
  • Self-limiting upon discontinuing the medication; resolution is spontaneous with desquamation and hyperpigmentation
  • Usually self-limiting upon discontinuing the medication
  • More chronic than phototoxic eruptions

Click here for drug-induced photosensitivity images

How do clinical features vary in differing types of skin?

Phototoxicity is more commonly observed in individuals with lighter skin types. It is believed that increased melanin pigment provides protection due to its antioxidant properties against free radicals. The only known exception is a diltiazem-associated photodistributed hyperpigmentation reaction that is more commonly seen in patients with darker skin types.

Photoallergic reactions occur equally across different skin types. 

What are the complications of drug-induced photosensitivity?

  • Secondary skin infection.
  • Postinflammatory hyperpigmentation.
  • DIP can limit the ability to participate in outdoor activities, negatively impacting physical and mental well-being.
  • Uncommonly, chronic photoallergic contact dermatitis can cause persistent photosensitivity even after ceasing the photosensitising medication.
  • A possible complication of photosensitising medications is photocarcinogenesis. This remains a subject of controversy; mechanisms are unclear and under investigation. 

How is drug-induced photosensitivity diagnosed?

DIP is a clinical diagnosis that can be supported with reproducibility on phototesting.

Table 3. Diagnostic clues for drug-induced photosensitivity

History
  • Exposure to both photosensitising medication and visible or ultraviolet (UV) radiation, with temporal onset of the cutaneous eruption.
  • Phototoxicity is often caused by systemic drugs while photoallergy is typically caused by topical agents.
Examination
  • Phototoxic-damaged skin often reveals sharp lines of demarcation against areas protected by clothing.
  • These lines may be less defined and even extend to affect photoprotected skin in photoallergic eruptions.
Investigations

What is the differential diagnosis for drug-induced photosensitivity?

What is the treatment for drug-induced photosensitivity?

General measures

Specific measures

  • Identify and cease the suspected photosensitising medication.
  • Potent topical corticosteroids.
  • Systemic corticosteroids (in severe or persistent cases).
  • Oral antihistamines for symptomatic relief.
  • If the causative medication is necessary, dose reduction or the amount of UV exposure may alleviate phototoxic effects (latter not applicable for photoallergic reactions).

How do you prevent drug-induced photosensitivity?

Discontinuing the photosensitising medication and sun protection remain the mainstay preventative measures for DIP.

What is the outcome for drug-induced photosensitivity?

DIP often resolves upon ceasing the causative photosensitising medication, although postinflammatory hyperpigmentation may persist in phototoxic reactions. In cases when discontinuing the medication is not an option, symptom control with strict sun protection can effectively manage DIP symptoms. 

Uncommonly, in photoallergic contact dermatitis, chronic exposure to photosensitising drugs can lead to photosensitivity that persists for months or years after the medication has been ceased.

The role of photosensitising medications in photocarcinogenesis is debated and not yet fully elucidated.

Click here for drug-induced photosensitivity images

 

Bibliography

  • Alrashidi A, Rhodes LE, Sharif JC, et al. Systemic drug photosensitivity: Culprits, impact and investigation in 122 patients. Photodermatol Photoimmunol Photomed. 2020;36(6):441–451. doi: 10.1111/phpp.12583. Journal
  • Gutierrez D, Gaulding JV, Motta Beltran AF, et al. Photodermatoses in skin of colour. J Eur Acad Dermatol Venereol. 2018;32(11):1879–1886. doi: 10.1111/jdv.15115. Journal
  • Hofmann GA, Weber B. Drug‐induced photosensitivity: culprit Drugs, potential mechanisms and clinical consequences. J Dtsch Dermatol Ges. 2021;19(1):19–29. doi: 10.1111/ddg.14314. Journal
  • Kowalska J, Rok J, Rzepka Z, Wrześniok D. Drug-induced photosensitivity: From light and chemistry to biological reactions and clinical symptoms. Pharmaceuticals (Basel). 2021;14(8):723. doi: 10.3390/ph14080723. Journal
  • Montgomery S, Worswick S. Photosensitizing drug reactions. Clin Dermatol. 2022;40(1):57–63. doi: 10.1016/j.clindermatol.2021.08.014. Journal

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