Drug eruptions are diagnosed mainly from the medical history and clinical examination. However, they can mimic a wide range of other conditions, thus delaying diagnosis (for example, in drug-induced lupus erythematosus, or the acne-like rash caused by erlotinib). A skin biopsy, blood tests or immunological tests can also be useful.

Drug reactions have characteristic timing. The typical amount of time it takes for a rash to appear after exposure to a drug can help categorize the type of reaction. For example, Acute generalized exanthematous pustulosis usually occurs within 4 days of starting the culprit drug. Drug Reaction with Eosinophilia and Systemic Symptoms usually occurs between 15 and 40 days after exposure. Toxic epidermal necrolysis and Stevens-Johnson syndrome typically occur 7–21 days after exposure. Anaphylaxis occurs within minutes. Simple exanthematous eruptions occur between 4 and 14 days after exposure.

TEN and SJS are severe cutaneous drug reactions that involve the skin and mucous membranes. To accurately diagnose this condition, a detailed drug history is crucial. Often, several drugs may be causative and allergy testing may be helpful. Sulfa drugs are well-known to induce TEN or SJS in certain people. For example, HIV patients have an increased incidence of SJS or TEN compared to the general population and have been found to express low levels of the drug metabolizing enzyme responsible for detoxifying sulfa drugs. Genetics plays an important role in predisposing certain populations to TEN and SJS. As such, there are some FDA recommended genetic screening tests available for certain drugs and ethnic populations to prevent the occurrence of a drug eruption. The most well known example is carbamezepine (an anti-convulsant used to treat seizures) hypersensitivity associated with the presence of HLA-B*5801 genetic allele in Asian populations.

DIHS is a delayed onset drug eruption, often occurring a few weeks to 3 months after initiation of a drug. Interestingly, worsening of systemic symptoms occurs 3-4 days after cessation of the offending drug. There are genetic risk alleles that are predictive of the development of DIHS for particular drugs and ethnic populations. The most important of which is abacavir (an anti-viral used in the treatment of HIV) hypersensitivity associated with the presence of the HLA-B*5701 allele in European and African population in the United States and Australians.

AGEP is often caused by antimicrobial, anti-fungal or antimalarial drugs. Diagnosis is often carried out by patch testing. This testing should be performed within one month after resolution of the rash and patch test results are interpreted at different time points: 48 hours, 72hours and even later at 96 hours and 120 hours in order to improve the sensitivity.

It is estimated that 2—3 percent of hospitalised patients are affected by a drug eruption, and that serious drug eruptions occur in around 1 in 1000 patients.

Causality assessment is used to determine the likelihood that a drug caused a suspected ADR. There are a number of different methods used to judge causation, including the Naranjo algorithm, the Venulet algorithm and the WHO causality term assessment criteria. Each have pros and cons associated with their use and most require some level of expert judgement to apply.

An ADR should not be labeled as 'certain' unless the ADR abates with a challenge-dechallenge-rechallenge protocol (stopping and starting the agent in question). The chronology of the onset of the suspected ADR is important, as another substance or factor may be implicated as a cause; co-prescribed medications and underlying psychiatric conditions may be factors in the ADR.

Assigning causality to a specific agent often proves difficult, unless the event is found during a clinical study or large databases are used. Both methods have difficulties and can be fraught with error. Even in clinical studies some ADRs may be missed as large numbers of test individuals are required to find that adverse drug reaction. Psychiatric ADRs are often missed as they are grouped together in the questionnaires used to assess the population.

Solar urticaria can be difficult to diagnose, but its presence can be confirmed by the process of phototesting. There are several forms of these tests including photopatch tests, phototests, photoprovocation tests, and laboratory tests. All of these are necessary to determine the exact infliction that the patient is suffering from. Photopatch tests are patch tests conducted when it is believed that a patient is experiencing certain symptoms due to an allergy that will only occur when in contact with sunlight. After the procedure, the patient is given a low dosage of UVA radiation.

Another test known as a phototest is the most useful in identifying solar urticaria. In this test, one centimeter segments of skin are subject to varying amounts of UVA and UVB radiation in order to determine the specific dosage of the certain form of radiation that causes the urticaria to form. When testing for its less intense form (fixed solar urticaria), phototesting should be conducted only in the areas where the hives have appeared to avoid the possibility of getting false-negative results.

A third form of testing is the photoprovocation test which is used to identify disorders instigated by sun burns. The process of this test involves exposing one area of a patient's arm to certain dosage of UVB radiation and one area on the other arm to a certain dosage of UVA radiation. The amount of radiation that the patient is exposed to is equal to that "received in an hour of midday summer sun." If the procedure produces a rash, then the patient will undergo a biopsy. Finally, there are laboratory tests which generally involve procedures such as blood, urine, and fecal biochemical tests. In some situations, a skin biopsy may be performed.

Many countries have official bodies that monitor drug safety and reactions. On an international level, the WHO runs the Uppsala Monitoring Centre, and the European Union runs the European Medicines Agency (EMEA). In the United States, the Food and Drug Administration (FDA) is responsible for monitoring post-marketing studies.

In Canada, the Marketed Health Products Directorate of Health Canada is responsible for the surveillance of marketed health products. In Australia, the Therapeutic Goods Administration (TGA) conducts postmarket monitoring of therapeutic products.

Drug allergies are attributed to "drug hypersensitivity," otherwise known as objectively reproducible symptoms or signs initiated by exposure to a drug at a dose normally tolerated by non-hypersensitive persons. Drug hypersensitivity reactions are the mediators of a drug allergy.

There are two mechanisms for a drug allergy to occur: IgE or non-IgE mediated. In IgE-mediated reactions, also known as Immunoglobulin E mediated reactions, drug allergens bind to IgE antibodies, which are attached to mast cells and basophils, resulting in IgE cross-linking, cell activation and release of preformed and newly formed mediators.

Risk factors for drug allergies can be attributed to the drug itself or the characteristics of the patient. Drug-specific risk factors include the dose, route of administration, duration of treatment, repetitive exposure to the drug, and concurrent illnesses. Host risk factors include age, sex, atopy, specific genetic polymorphisms, and inherent predisposition to react to multiple unrelated drugs (multiple drug allergy syndrome).

A drug allergy is more likely to develop with large doses and extended exposure.

Unlike most food allergies, it may be possible for the alpha-gal allergy to recede with time, as long as the person is not bitten by another tick. The recovery period can take anywhere from eight months to five years. This recovery potential is not confirmed. More research needs to be conducted to determine why some patients seem to recover and some do not.

A traditional skin prick allergy test for allergy to meat may give a false negative answer. Blood tests for IgE response indicating alpha-gal allergy have not been approved by the U.S. Food and Drug Administration (FDA), and must usually be purchased by private individuals, but are available and are in use. Determination of specific IgE to alpha-gal testing is commercially available. The highest sensitivity is observed with skin and basophil activation tests with cetuximab which is, however, limited by its high costs.

There are no laboratory or skin testing methods for testing salicylate sensitivity. Provocative challenge is one method of obtaining reliable diagnosis. Provocative challenge is intended to induce a controlled reaction as a means of confirming diagnosis. During provocative challenge, the person is given incrementally higher doses of salicylates, usually aspirin, under medical supervision, until either symptoms appear or the likelihood of symptoms appearing is ruled out.

Solar urticaria, due to its particular features, is considered to be a type of physical urticaria or light sensitivity. Physical urticaria arises from physical factors in the environment, which in the case of solar urticaria is UV radiation or light. SU may be classified based on the wavelength of the radiative energy that causes the allergic reaction; known as Harber's classification, six types have been identified in this system. Type I solar urticaria is caused by UVB (ultraviolet B) radiation, with wavelengths ranging from 290–320 nm. Type II is induced by UVA (ultraviolet A) radiation with wavelengths that can range from 320–400 nm. The wavelength range of type III and IV spans from 400 to 500 nm, while type V can be caused by UVB radiation to visible light (280–600 nm). Type VI has only been known to occur at 400 nm.

Another classification distinguishes two types. The first is a hypersensitivity caused by a reaction to photoallergens located only in people with SU; while the second is caused by photoallergens that can be found in both people with SU and people without it.

A subgroup of solar urticaria, fixed solar urticaria, has also been identified. It is a rare, less intense form of the disease with wheals (swollen areas of the skin) that affect certain, fixed areas of the body. Fixed solar urticaria is induced by a broad spectrum of radiative energy with wavelengths ranging from 300–700 nm.

Photosensitive drug reaction (or drug-induced photosensitivity) secondary to medications may cause phototoxic, photoallergic, and lichenoid reactions, and photodistributed telangiectasias, as well as pseudoporphyria.

Drugs involved include naproxen and doxycycline.

Idiosyncratic drug reactions, also known as type B reactions, are drug reactions that occur rarely and unpredictably amongst the population. This is not to be mistaken with idiopathic, which implies that the cause is not known. They frequently occur with exposure to new drugs, as they have not been fully tested and the full range of possible side-effects have not been discovered; they may also be listed as an adverse drug reaction with a drug, but are extremely rare.

Some patients have multiple-drug intolerance. Patients who have multiple idiopathic effects that are nonspecific are more likely to have anxiety and depression.

Idiosyncratic drug reactions appear to not be concentration dependent. A minimal amount of drug will cause an immune response, but it is suspected that at a low enough concentration, a drug will be less likely to initiate an immune response.

The diagnosis is based on involvement of less than 10% of the skin. It is known as TEN when more than 30% of the skin is involved and an intermediate form with 10 to 30% involvement. A positive Nikolsky's sign is helpful in the diagnosis of SJS and TEN. A skin biopsy is helpful, but not required, to establish a diagnosis of SJS and TEN.

With no particular affinity to any particular ethnic group, seen in all age groups and equally amongst males and females, the precise prevalence is not known.

Stevens–Johnson syndrome (SJS) is a milder form of toxic epidermal necrolysis (TEN). These conditions were first recognised in 1922. A classification first published in 1993, that has been adopted as a consensus definition, identifies Stevens–Johnson syndrome, toxic epidermal necrolysis, and SJS/TEN overlap. All three are part of a spectrum of severe cutaneous reactions (SCAR) which affect skin and mucous membranes. The distinction between SJS, SJS/TEN overlap, and TEN is based on the type of lesions and the amount of the body surface area with blisters and erosions. It is agreed that the most reliable method to classify EM, SJS, and TEN is based on lesion morphology and extent of epidermal detachment. Blisters and erosions cover between 3% and 10% of the body in SJS, 11–30% in SJS/TEN overlap, and over 30% in TEN. The skin pattern most commonly associated with SJS is widespread, often joined or touching (confluent), papuric spots (macules) or flat small blisters or large blisters which may also join together. These occur primarily on the torso.

SJS, TEN, and SJS/TEN overlap can be mistaken for erythema multiforme. Erythema multiforme, which is also within the SCAR spectrum, differs in clinical pattern and etiology. Although both SJS and TEN can also be caused by infections, they are most often adverse effects of medications.

An important salicylate drug is aspirin, which has a long history. Aspirin intolerance was widely known by 1975, when the understanding began to emerge that it is a pharmacological reaction, not an allergy.

NSAID or nonsteroidal anti-inflammatory drug hypersensitivity reactions encompasses a broad range of allergic or allergic-like symptoms that occur within minutes to hours after ingesting aspirin or other NSAID nonsteroidal anti-inflammatory drugs. Hypersensitivity drug reactions differ from drug toxicity reactions in that drug toxicity reactions result from the pharmacological action of a drug, are dose-related, and can occur in any treated individual (see nonsteroidal anti-inflammatory drugs section on adverse reactions for NSAID-induced toxic reactions); hypersensitivity reactions are idiosyncratic reactions to a drug. Although the term NSAID was introduced to signal a comparatively low risk of adverse effects, NSAIDs do evoke a broad range of hypersensitivity syndromes. These syndromes have recently been classified by the European Academy of Allergy and Clinical Immunology Task Force on NSAIDs Hypersensitivity. The classification organizes the hypersensitivity reactions to NSAIDs into the following five categories:

- 1) NSAIDs-exacerbated respiratory disease (NERD) is an acute (immediate to several hours) exacerbation of bronchoconstriction and other symptoms of asthma (see aspirin-induced asthma) in individuals with a history of asthma and/or nasal congestion, rhinorrhea or other symptoms of rhinitis and sinusitis in individuals with a history of rhinosinusitis after ingestion of various NSAIDs, particularly those that act by inhibiting the COX-1 enzyme. NERD does not appear to be due to a true allergic reaction to NSAIDs but rather at least in part to the more direct effects of these drugs to promote the production and/or release of certain mediators of allergy. That is, inhibition of cellular COX activity deprives tissues of its anti-inflammatory product(s), particularly prostaglandin E2 while concurrently shuttling its substrate, arachidonic acid, into other metabolizing enzymes, particularly 5-lipoxygenase (ALOX5) to overproduce pro-inflammatory leukotriene and 5-Hydroxyicosatetraenoic acid metabolites and 15-lipoxygenase (ALOX15) to overproduce pro-inflammatory 15-Hydroxyicosatetraenoic acid metabolites, including eoxins; the condition is also associated with a reduction in the anti-inflammatory metabolite, lipoxin A4, and increases in certain pro-allergic chemokines such as eotaxin-2 and CCL7.

- 2) NSAIDs-exacerbated cutaneous disease (NECD) is an acute exacerbation of wheals and/or angioedema in individuals with a history of chronic urticaria. NECD also appears due to the non-allergic action of NSAIDs in inhibiting the production of COX anti-inflammatory metabolites while promoting the production 5-lipoxygenase and 15-lipoxygenase pro-inflammatory metabolites and the overproduction of certain pro-allergic chemokines, e.g. eotaxin-1, eotaxin-2, RANTES, and interleukin-5.

- 3) NSAIDs-induced urticarial disease (NEUD) is the acute development of wheals and/or angioedema in individuals with no history of chronic NSAIDs-induced urticaria or related diseases. The mechanism behind NEUD is unknown but may be due to the non-allergic action of NSAIDs in promoting the production and/or release of allergy mediators.

- 4) Single NSAID-induced urticarial/angioedema or anaphylaxis (SNIUAA) is the acute development of urticarial, angioedema, or anaphylaxis in response to a single type of NSAID and/or a single group of NSAIDs with a similar structure but not to other structurally unrelated NSAIDs in individuals with no history of underlying relevant chronic diseases. SNIUAA is due to a true IgE-mediated allergy reaction.

- 5 Single NSAID-induced delayed reactions (SNIDR) are a set of delayed onset (usually more than 24 hour) reactions to NSAIDs. SNIDR are most commonly skin reactions that may be relatively mild moderately severe such as maculopapular rash, fixed drug eruptions, photosensitivity reactions, delayed urticaria, and contact dermatitis or extremely severe such as the DRESS syndrome, acute generalized exanthematous pustulosis, the Stevens–Johnson syndrome, and toxic epidermal necrolysis (also termed Lyell's syndrome). SNIDR result from the drug-specific stimulation of CD4+ T lymphocytes and CD8+ cytotoxic T cells to elicit a delayed type hypersensitivity reaction.

In adverse drug reactions involving overdoses, the toxic effect is simply an extension of the pharmacological effect (Type A adverse drug reactions). On the other hand, clinical symptoms of idiosyncratic drug reactions (Type B adverse drug reactions) are different from the pharmacological effect of the drug.

The proposed mechanism of most idiosyncratic drug reactions is immune-mediated toxicity. To create an immune response, a foreign molecule must be present that antibodies can bind to (i.e. the antigen) and cellular damage must exist. Very often, drugs will not be immunogenic because they are too small to induce immune response. However, a drug can cause an immune response if the drug binds a larger molecule. Some unaltered drugs, such as penicillin, will bind avidly to proteins. Others must be bioactivated into a toxic compound that will in turn bind to proteins. The second criterion of cellular damage can come either from a toxic drug/drug metabolite, or from an injury or infection.

These will sensitize the immune system to the drug and cause a response.

Idiosyncratic reactions fall conventionally under toxicology.

The primary treatment strategy is to eliminate or discontinue the offensive agent. Supportive therapy, such as ice packs, may be provided to get the body temperature within physiologic range. In severe cases, when the fever is high enough (generally at or above ~104° F or 40° C), aggressive cooling such as an ice bath and pharmacologic therapy such as benzodiazepines may be deemed appropriate.

Prophylaxis and treatment with an anti-inflammatory agent may stop progression of the reaction. Oral aspirin or ibuprofen every four hours for a day or 60 mg of prednisone orally or intravenously has been used as an adjunctive treatment . However, steroids are generally of no benefit. Patients must be closely monitored for the potential complications (collapse and shock) and may require IV fluids to maintain adequate blood pressure. If available, meptazinol, an opioid analgesic of the mixed agonist/antagonist type, should be administered to reduce the severity of the reaction. Anti TNF-a may also be effective.

Anticonvulsant/sulfonamide hypersensitivity syndrome is a potentially serious hypersensitivity reaction that can be seen with drugs with an aromatic amine chemical structure, such as aromatic anticonvulsants (e.g. diphenylhydantoin, phenobarbital, phenytoin, carbamazepine, lamotrigine), sulfonamides, or other drugs with an aromatic amine (procainamide). Cross-reactivity should not occur between drugs with an aromatic amine and drugs without an aromatic amine (e.g., sulfonylureas, thiazide diuretics, furosemide, and acetazolamide); therefore, these drugs can be safely used in the future.

The hypersensitivity syndrome is characterized by a skin eruption that is initially morbilliform. The rash may also be a severe Stevens-Johnson syndrome or toxic epidermal necrolysis. Systemic manifestations occur at the time of skin manifestations and include eosinophilia, hepatitis, and interstitial nephritis. However, a subgroup of patients may become hypothyroid as part of an autoimmune thyroiditis up to 2 months after the initiation of symptoms.

This kind of adverse drug reaction is caused by the accumulation of toxic metabolites; it is not the result of an IgE-mediated reaction. The risk of first-degree relatives’ developing the same hypersensitivity reaction is higher than in the general population.

As this syndrome can present secondary to multiple anticonvulsants, the general term "anticonvulsant hypersensitivity syndrome" is favored over the original descriptive term "dilantin hypersensitivity syndrome."

The treatment is (1) stop the offending drug (antibiotics), (2) symptomatic (fever), and (3) for complications (hepatitis).

Other rashes that occur in a widespread distribution can look like an id reaction. These include atopic dermatitis, contact dermatitis, dyshidrosis, photodermatitis, scabies and drug eruptions.

Bullous drug reaction (also known as a "bullous drug eruption", "generalized bullous fixed drug eruption", and "multilocular bullous fixed drug eruption") most commonly refers to a drug reaction in the erythema multiforme group. These are uncommon reactions to medications, with an incidence of 0.4 to 1.2 per million person-years for toxic epidermal necrolysis and 1.2 to 6.0 per million person-years for Stevens–Johnson syndrome. The primary skin lesions are large erythemas (faintly discernible even after confluence), most often irregularly distributed and of a characteristic purplish-livid color, at times with flaccid blisters.