Photosensitivity reactions, drug-induced

The word dermatitis denotes an inflammatory erythematous rash. The disorders discussed in this chapter include contact dermatitis, seborrheic dermatitis, diaper dermatitis, and atopic dermatitis. Drug-induced skin disorders have been associated with most commonly used medications and may present as maculopapular eruptions, fixed-drug eruptions, and photosensitivity reactions. 

Morliere, P. (1986) Drug-induced photosensitivity phototoxic and photoallergic reactions-a few molecular aspects, Biochemie 68, 849-855. 

Drug-induced photosensitivity reactions are divided into phototoxicity (a nonimmunologic reaction) and photoallergic reactions (an immunologic reaction). The latter form is far less common. Medications associated with photosensitivity reactions include fluoroquinolones, nonsteroidal antiinflammatory drugs, phenothiazines, antihistamines, estrogens, progestins, sulfonamides, sulfonylureas, thiazide diuretics, and tricyclic antidepressants. 

In a review of photopatch-testing in 2390 patients with rashes that were confined to sun-exposed areas, about 70% of 4374 positive reactions were classified as photo-induced reactions, of which 222 (5%) were photoaUergic reactions (6). NSAIDs, disinfectants, and phenothiazines were the main photoallergens. Photosensitive reactions to antimicrobial drugs, including topical agents, have been reviewed (7). 

Some solvents are able to filter parts of the optical spectrum — an effect that may provide some protection of the dissolved or suspended drug. However, absorption of photons may lead to formation of free radicals from solvent molecules, resulting in chain reactions that are well documented for unsaturated fats and oils (Florence and Attwood, 1998). Drugs dissolved or suspended in such vehicles may participate in the free radical chain reactions, leading to photosensitized decomposition of the drug induced by the solvent. 

Minocycline has better gastrointestinal absorption than tetracycline and may be less photosensitizing than either tetracycline or doxycycline. Side effects of minocycline include dizziness and hyperpigmentation of the skin and mucosa, serum-sickness-like reactions, and drug-induced lupus erythematosus. With all the tetracyclines, vaginal candidiasis is a common complication that is readily treated with local administration of antifungal drugs. 

Harber LC, Bickers DR (1989) Drug induced photosensitivity (phototoxic and photoallergic drug reactions). In Photosensitivity diseases principles of diagnosis and treatment, 2nd edn. Decker, Toronto, pp 160-202 Hare PJ (1951) A case of occupational iron pigmentation of the skin. Br J Dermatol 63 63-66... 

Table 3. Common drugs inducing photosensitivity to a systemic agent or photodrug reaction [33]...

Photodecarboxylation of 2-(3-benzoyl)phenylpropionate, the ketoprofen anion, was studied in water by time-resolved, laser-induced optoacoustic spectroscopy (LIOAS). The various transient species involved in the title reaction were identified and their Hfetimes measured. The intrinsic photoreactivity of the 2-benzoylthiophene chromophore of the photosensitizing drug, tiaprofenic acid, was also studied. The observed photoprocesses account readily for the biological photosensitization reactions such as membrane damage and protein modification. The transient photochemistry in photodecarboxylation of rufloxacin (a fluoroquinolone antibacterial drug), fenofibric acid (used in the treatment of hyperlipidemia), and tohnetin has also been reported. 

Figure 19.1 Mechanisms involved in sunlight-induced phototoxicity of drugs. Type 1 photosensitization (electron transfer) mainly generates singlet oxygen Oj", whereas type 2 reaction (energy transfer) leads to adduct formation or singlet oxygen...

UV exposure is known to induce photosensitive responses in humans. Photosensitivity is an adverse reaction that occurs when a chemical or drug is applied to the skin or taken internally at the same time that one is exposed to UV. Not all people are photosensitive to the same agents. Two distinct responses are observed phototoxic and photoallergic reactions. 

For example, tetracycline (506), a broad-spectrum antibiotic, and its derivatives are known to induce phototoxic or photoallergic reactions that involve photosensitization of biomolecules by the drug or the formation of one or more photoproducts and their subsequent photoreactions.1383 Singlet oxygen is probably involved. 

Harber, L. C., Bickers, D. R., Dmg Induced Photosensitivity (Phototoxic and Photoallergic Drug Reactions). In Harber, L. C., Bickers, D. R. (eds), Photosensitivity Diseases. Principles of Diagnosis and Treatment, 2nd edn, Marcel Decker, Toronto, 1986, pp. 160 202. 

Quinacrine, which is tricyclic and highly lipophilic, will easily penetrate cell membranes but hardly diffuse through the hydrophilic vitreous cavity. It also forms a stable complex with melanin and will therefore be retained in the RPE. Quinacrine must be considered a potent photosensitizer in the retina due to the absorption maximum of this drug in the visible region of the spectrum (Table 10.1). The more hydrophilic compounds chloroquine and hydroxychloroquine will more easily be transported to the lens. They are known to accumulate in the eye and induce toxic reactions. Primaquine is not likely to be distributed to the eye to any extent due to low distribution volume and fast elimination. 

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