Table of Contents   This Chapter   All Chapters

PHOTOSENSITIVITY DUE TO DRUGS AND EXTERNAL AGENTS

Photosensitivity due to systemic drugs

Etiology and pathogenesis

Many drugs can cause photosensitivity (Figs 17.37–17.40). In most cases, the mechanism is phototoxicity, which is not immunologically mediated, but other drugs cause photoallergy. For some drugs, the mechanism is either uncertain, or both major mechanisms may be involved. Some of the commoner drugs and their mechanisms of photodamage are listed in Table 17.6.

The main mechanism of phototoxicity is absorption of UVR by the drug or its metabolite(s) in vivo, to produce an ‘excited state' molecule. Return to the ground state releases various forms of energy, which damage cellular organelles and may create proinflammatory reactive oxygen molecules. Some drugs typically cause damage to cell nuclei, notably the psoralens, which intercalate between DNA strands to form photoadducts.

    Photoallergy occurs in a minority of exposed individuals and involves immunologic mechanisms. The first step is UVR conversion of the photoallergic drug or metabolite to create either a hapten or an excited state. This then binds to a carrier protein to produce the antigen, which causes a type IV hypersensitivity reaction. The clinical features of phototoxicity and photoallergy are therefore different.

Figure 17.37 Drug-induced photosensitivity due to nalidixic acid. There is a large bullous reaction.

Figure 17.38 Drug-induced photosensitivity with a rather lichenoid pattern, due to a proton pump inhibitor. Sparing of sun-shielded areas is often lost in chronic photosensitivity, but sparing of the relatively shielded fingers and sparing under a watch can be discerned in this case.

Figure 17.39(a,b) Two examples of drug-induced photosensitivity due to quinine. This is often a chronic condition that takes months to resolve. As in Figure 17.38, (a) shows sparing of the watch strap area and more obvious sparing under clothing.

Figure 17.40 (Drug-induced photosensitivity due to tetracycline, showing a recently ruptured blister and photoonycholysis (nails of the same patient are shown in fig.18.42).

Clinical features

The main clinical aspects of the two different types of reaction are listed in Table 17.7. Acute drug-induced photosensitivity, especially of the phototoxic type, is usually manifest as very discrete erythema with characteristic areas of sparing (see Figs 17.19 – 17.21). This sparing may be lost if the cause is not recognized and the eruption becomes more chronic.

    Associated photoonycholysis may occur, and appears to be particularly frequent with tetracyclines and the (now withdrawn) non-steroidal antiinflammatory drug benoxaprofen.

    Pigmentation may be a prominent feature with some photosensitizers; for example, tanning is inevitable with the therapeutic use of psoralens in PUVA. A grayish pigmentation with a photodistribution may occur without overt photosensitivity in some instances, and is usually related to long-term administration of medication. Drugs that cause pigmentation of this type include phenothiazines, amiodarone, and occasionally tetracyclines. It is also a feature of photolichenoid eruptions.

    Patients who have severe photosensitivity due to a drug develop a rash regardless of the season, but some who have milder photosensitivity may have been on the drug for many months before symptoms develop in the summer months; this is important, as it may erroneously suggest that the drug is not relevant. Some drug photosensitivity is inadvertently revealed by the therapeutic use of UVR if patients are on drugs that are uncommon photosensitizers.

    Phototests are generally positive, as most common drug photosensitivity occurs in the UVA range, and can be useful for rechallenge or for monitoring progress when the relevant drug is withdrawn. Photopatch tests may be positive if there is a photoallergic mechanism.

Differential diagnosis

This includes the following.

Treatment

The mainstay of treatment is withdrawal of the relevant drug, with physical protection, avoidance of sunlight, and use of sunscreens until symptoms remit. Topical corticosteroids and oral antihistamines have symptomatic benefit. Some photoallergic eruptions, such as those due to quinine, may persist for several months.

Photosensitivity due to external agents

Etiology and pathogenesis

A list of external photosensitizers is given in Table 17.8. As with medications used internally, these can be divided into phototoxic and photoallergic types.

Clinical features

The morphology depends to some extent on the mechanism, as for systemic phototoxicity and photoallergy. The site of application of the agent also alters the pattern. For example, the pattern caused by plants (Figs 17.41–17.44) may vary depending on the type of exposure. The typical morphology is a streaky distribution on limbs that have rubbed against a plant; sap or juices of plants and fruits may create trickles, and the spatter of psoralens on to the exposed trunk when using high-speed garden tools to cut hedgerow plants is known as strimmer (or weed whacker) dermatitis (fig.17.45). The psoralens produced by the Umbelliferae (such as hogweeds and cow parsley, fig. 17.46) typically cause an intense phototoxicity with large blisters and significant pigmentation. Therapeutic use for PUVA may also cause unusual reactions (fig. 17.44b). Compositae are discussed in the section on photosensitivity dermatitis.

    These eruptions typically occur during the summer, but some plant reactions are influenced by the growing season. Some reactions, such as those to perfume agents, may occur at other times of the year as well. Sunscreen ingredients cause particular problems, as patients expect these to be photoprotective. Except for the psoralen type, most of these reactions are photoallergic in mechanism and can be identified by photopatch testing.

Figure 17.41 Phytophotodermatitis due to psoralen in lime juice. This is a common cause of phototoxicity in warm climates where these fruit are grown.

Figure 17.42 Phytophotodermatitis. Residual pigmentation is a characteristic feature of this eruption, although blistering may cause a paler area, as shown here.

Figure 17.43 Phytophotodermatitis on the leg. The pigmentation is often in a streaky pattern where limbs have brushed against vegetation.

Figure 17.44 Pigmentation in trickles. (a) Fruit juice has trickled down the child’s fingers and leg and caused a phototoxic reaction. (b) During bath PUVA, the patient lies in a bath of dilute psoralen solution, and then has UVA exposure. This patient, unknown to nursing staff, sat in the bath and splashed the water (not very effectively) on to his back. He therefore has even pigmentation up to lower thoracic level, but trickles of pigmentation down his upper back.

Figure 17.45 Strimmer (weed whacker) dermatitis on the chest, due to psoralens in hedgerow and garden weeds. These tools create a spray of plant fragments, which leave drops of photosensitizing juice on the exposed skin of the person using them. The brown colour is characteristic, as shown in Figures 17.41–17.44. (Courtesy of Prof. N. Reynolds.)

Differential diagnosis

External causes of photosensitivity may be more difficult to diagnose, as the pattern will depend on both the site of application and the site exposed to light; additionally, some of the causes are airborne rather than deliberately applied to the skin, and others may be assumed to be protective (sunscreens). It is impossible to list all differential diagnoses that might apply, but other photodermatoses clearly need to be excluded. As the most likely sites to be affected are the face and hands, various forms of dermatitis (especially contact dermatitis), as well as photoaggravated facial dermatoses such as lupus erythematosus, may be in the differential.

Treatment

This comprises identification and avoidance of the trigger. The choice of sunscreen may be difficult for those who react to fragrances, benzophenones, or cinnamates, and may require photopatch testing the individual constituents.

PRACTICE POINTS

White/Cox: Diseases of the Skin, 2ed.(c) 2006, Elsevier Inc. All rights reserved.