DRUG-INDUCED RASHES:

Drugs can be toxic and teratogenic but they can also cause problems through allergic reactions. This frequently presents in the skin where just about any type of skin rash can arise (Table 23.14) although a widespread symmetrical maculopapular rash is the most common type (Fig. 23.38). 'Fixed drug eruptions' may occur where a rash evolves and resolves at a specific site. The rash is reproduced at exactly the same site after a repeated exposure.

A thorough history is of great value and always think of a drug cause for any skin condition. The use of prick-testing and patch-testing is rarely helpful and not without risk. Drug allergy can only be proven by rechallenging but this is rarely justified as it carries some risks. Rechallenging is occasionally justified for antituberculosis drugs or antiretroviral drugs but this should be carried out as an inpatient as there is a risk of anaphylaxis. Certain individuals (e.g. those with HIV infections) are more susceptible to drug rashes (Fig. 23.39).

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Table 23-14. Morphological types of drug rashes and some common causes

Maculopapular Penicillin/amoxicillin

Urticaria Penicillin, aspirin

Vasculitis Gold, hydralazine

Fixed drug rash Phenolphthalein in laxatives, tetracyclines, paracetamol

Pigmentation Minocycline (black), amiodarone (slate grey)

Lupus erythematosus Penicillamine, isoniazid

Photosensitivity Thiazides, chlopromazine, sulphonamide, amiodarone

Pustular Carbamazepine

Erythema nodosum Sulphonamide, oral contraceptive

Erythema multiforme Barbiturates

Acneiform Corticosteroids

Lichenoid Chloroquine, thiazides, gold, allopurinol

Psoriasiform Methyldopa, gold, lithium, beta-blockers

Toxic epidermal necrolysis Penicillin, co-trimoxazole, carbamazepine, NSAIDs

Pemphigus Penicillamine, ACE inhibitors

Erythroderma Gold, sulphonylureas, allopurinol







Figure 23.38 Morbilliform drug rash due to penicillin allergy.





Figure 23.39 Erythema nodosum in a patient with HIV on co-trimoxazole.

Most rashes will settle spontaneously once the offending agent is removed. The commonest culprits in a hospital setting are antibiotics and chemotherapy agents. The three most serious types of drug rashes are:

erythroderma (p. 1340)

toxic epidermal necrolysis

anticonvulsant hypersensitivity syndrome.

Toxic epidermal necrolysis is characterized by a widespread subepidermal blistering and sloughing of most of the skin. The skin may be itchy but typically takes on a burning quality. Fever and mucosal involvement are common. The internal epithelial surfaces (lung, bladder, gastrointestinal tract) are also involved. Multiorgan failure and sepsis often occur. Toxic epidermal necrolysis can be fatal even after drug withdrawal and intensive care support. Patients should be managed in intensive care or a specialized burns unit. Occlusive cutaneous dressings significantly reduce the pain. Ophthalmological assessment and oral hygiene are necessary. Specific medical treatment with steroids or ciclosporin is controversial. Intravenous immunoglobulin may be beneficial if given early in the disease.

A variant exists called Stevens-Johnson syndrome where the damage is restricted to the mucosal surfaces with milder bullous involvement of the skin.

Anticonvulsant hypersensitivity syndrome is characterized by a generalized mucocutaneous rash, fever and lymphadenopathy with variable arthralgia, pharyngitis, periorbital oedema and hepatosplenomegaly. Rarely pustulation of the skin and conjunctivitis are present. The blood may show a peripheral eosinophilia, lymphocytosis with atypical lymphocytes, and a hepatitic picture. It can progress to multiorgan failure. This reaction occurs typically 3-4 weeks into therapy. It can occur with any of the aromatic anticonvulsants (carbamazepine, phenytoin, phenobarbital, primidone and clonazepam). As they often cross-react, all these drugs must be avoided in the future. Sodium valproate is a suitable alternative. There is also potential for cross-reaction with the newer anticonvulsants vigabatrin and lamotrigine.

FURTHER READING

Baba M et al. (2003) The anticonvulsant hypersensitivity syndrome. Journal of the European Academy of Dermatology and Venereology 17: 399-401.

Breathnach SM (2002) Adverse cutaneous reactions to drugs. Clinical Medicine 2: 15-19.

Campione E et al. (2003) High-dose intravenous immunoglobulin for severe drug reactions: efficacy in toxic epidermal necrolysis. Acta Dermato-venereologica 83: 430-432.

Fiszenson-Albala F et al. (2003) A 6-month prospective survey of cutaneous drug reactions in a hospital setting. British Journal of Dermatology 149: 1018-1022.

Sullivan et al. (2001) The drug hypersensitivity syndrome. Archives of Dermatology 137: 357-364.