Adverse reactions in the skin to medications are very common and are an important cause of iatrogenic illness. Drug rashes are usually self-limiting and resolve completely upon withdrawal of the culprit medication, but a small number (<2%) can cause serious morbidity and mortality. This may not only have medicolegal and economic implications but may undermine the patient’s confidence in the prescriber and affect future adherence. Diagnosis of drug-induced skin disease may be difficult for a number of reasons:

• Almost any drug can cause any rash.
  
• Unrelated drugs can cause similar reactions.
  
• The same medication can cause a different rash in different individuals.
  
• Patients may not volunteer information about medicines that they have taken, which they deem not to be relevant (over-the-counter (OTC) preparations and complementary medicines).

The patient should be exposed fully to allow complete examination of the skin. The morphology of the rash should be described—for example, lichenoid, urticated, vasculitic, maculopapular or bullous. The distribution of the rash should be noted: Is it widespread? Limited? Acral (hands and feet)? Photo-distributed? These features will help to classify the eruption and may give a pointer as to the causative drug. Special attention should be paid to the mucosal sites—eyes, mouth, genitalia—as involvement at these sites can indicate one of the severe cutaneous adverse reaction (SCAR) syndromes. Early diagnosis of these syndromes is crucial as patients may become unwell and deteriorate quickly. Careful examination of the appendageal structures such as hair, nails and teeth should also be carried out as these can be affected by certain medications.

In most cases, careful history and examination will provide all the necessary clues to make a confident diagnosis of a drug rash. A skin biopsy can be helpful to confirm the diagnosis, but the result of this is likely to be delayed following an acute presentation, and so action based on clinical assessment will usually precede this. Exclusion of differential diagnoses such as infection may require other investigations such as blood tests (white cell counts and CRP levels). There are no consistently reproducible diagnostic tests which confirm specific drug allergy in the convalescent period; however, certain investigations such as measurement of specific IgE, patch testing, intradermal testing and in vitro tests such as lymphocyte transformation tests and cytokine release assays may be helpful. However, these investigations should be carried out by experts as their interpretation is highly specialised.

Cutaneous reactions to medications are extremely varied. They may be classified in a number of ways. Pathogenetically, drug reactions in the skin may be classified as immune-mediated or non-immune mediated. Immune-mediated rashes are the most common and include hypersensitivity reactions from types I to IV. Type I reactions (immediate reactions, usually mediated by IgE or drug-specific receptors bound to mast cells and other immune cell membranes) tend to manifest in the skin as urticaria or angio-oedema. Type II reactions (cytotoxic reactions) result in cutaneous purpura. Type III (immune complex-mediated) reactions lead to cutaneous vasculitis. Type IV delayed hypersensitivity reactions are by far the most common group of drug rashes resulting in generalized exanthems, phototoxic rashes and severe drug reactions such as toxic epidermal necrolysis (TEN).

Non-immune-mediated rashes include accumulation of medications in the skin (causing pigment changes), instability of mast cells (causing histamine release), slow acetylators (metabolism of drugs affected) and photosensitivity reactions (increased susceptibility to UV light).

However, drug reactions in the skin may also be classified clinically, and this is the approach adopted here. Drug reactions in the skin are discussed under the following headings:

1. Drugs which alter normal skin function.
   
2. Drugs which exacerbate an existing dermatosis.
   
3. Common drug-induced rashes—maculopapular exanthem, urticaria, vasculitis, lichenoid drug reaction and fixed drug eruption.
   
4. Severe drug-induced rashes—Stevens–Johnson syndrome (SJS) and TEN, acute generalised exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS).