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.

The culprit can be both a prescription drug or an over-the-counter medication.

Examples of common drugs causing drug eruptions are antibiotics and other antimicrobial drugs, sulfa drugs, nonsteroidal anti-inflammatory drugs (NSAIDs), biopharmaceuticals, chemotherapy agents, anticonvulsants, and psychotropic drugs. Common examples include photodermatitis due to local NSAIDs (such as piroxicam) or due to antibiotics (such as minocycline), fixed drug eruption due to acetaminophen or NSAIDs (Ibuprofen), and the rash following ampicillin in cases of mononucleosis.

Certain drugs are less likely to cause drug eruptions (rates estimated to be ≤3 per 1000 patients exposed). These include: digoxin, aluminum hydroxide, multivitamins, acetaminophen, bisacodyl, aspirin, thiamine, prednisone, atropine, codeine, hydrochlorothiazide, morphine, insulin, warfarin, and spironolactone.

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.

In the United States, only about 4% of patients with photosensitive disorders are reported to have been diagnosed with solar urticaria. Internationally, the number is slightly larger at 5.3%. Solar urticaria may occur in all races but studies monitoring 135 African Americans and 110 Caucasians with photodermatoses found that 2.2% of the African Americans had SU and 8% of the Caucasians had the disease showing that Caucasians have a better chance of getting the disease. Globably 3.1 per 100,000 people are affected and females are more likely to be affected than males. The age ranges anywhere from 5–70 years old, but the average age is 35 and cases have been reported with children that are still in infancy. Solar urticaria accounts for less than one percent of the many documented urticaria cases. To put that into a better perspective, since its first documented case in Japan in 1916, over one hundred other instances of the disease have been reported.

Solar urticaria is an immunoglobulin E-mediated hypersensitivity that can be introduced through primary or secondary factors, or induced by exogenous photosensitization. Primary SU is believed to be a type I hypersensitivity (a mild to severe reaction to an antigen including anaphylaxis) in which an antigen, or substance provoking an immune response, is "induced by UV or visible radiation." Secondary SU can occur when a person comes into contact with chemicals such as tar, pitch, and dyes. People who use drugs such as benoxaprofen or patients with erythropoietic protoporphyria may also contract this secondary form. These items that cause this photosensitivity are exogenous photosensitizers because they are outside of the body and cause it to have a greater sensitivity to light.

Also, there have been a few unorthodox (unusual) causes of solar urticaria. For those susceptible to visible light, white T-shirts may increase the chances of experiencing an outbreak. In one case, doctors found that the white T-shirt absorbed UVA radiation from the sun and transformed it into visible light which caused the reaction. Another patient was being treated with the antibiotic tetracycline for a separate dermatological disorder and broke out in hives when exposed to the sun, the first case to implicate tetracycline as a solar urticaria inducing agent.

It is not yet known what specific agent in the body brings about the allergic reaction to the radiation. When patients with SU were injected with an irradiated autologous serum, many developed urticaria within the area of injection. When people who did not have SU were injected, they did not demonstrate similar symptoms. This indicates that the reaction is only a characteristic of the patients with solar urticaria and that it is not phototoxic. It is possible that this photoallergen is located on the binding sites of IgE that are found on the surface of mast cells. The photoallergen is believed to begin its configuration through the absorption of radiation by a chromophore. The molecule, because of the radiation, is transformed resulting in the formation of a new photoallergen.

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.

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.

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.

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.

When a medication causes an allergic reaction, it is called an allergen. The following is a short list of the most common drug allergens:

- Antibiotics

- Penicillin

- Sulfa drugs

- Tetracycline

- Analgesics

- Codeine

- Non-steroidal anti-inflammatory drugs (NSAIDs)

- Antiseizure

- Phenytoin

- Carbamazepine

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

Insect bites and stings occur when an insect is agitated and seeks to defend itself through its natural defense mechanisms, or when an insect seeks to feed off the bitten person. Some insects inject formic acid, which can cause an immediate skin reaction often resulting in redness and swelling in the injured area. Stings from fire ants, bees, wasps and hornets are usually painful, and may stimulate a dangerous allergic reaction called anaphylaxis for at-risk patients, and some wasps can also have a powerful bite along with a sting. Bites from mosquitoes and fleas are more likely to cause itching than pain.

The skin reaction to insect bites and stings usually lasts for up to a few days. However, in some cases the local reaction can last for up to two years. These bites are sometimes misdiagnosed as other types of benign or cancerous lesions.

Drug-induced pruritus is itchiness of the skin caused by medication, a pruritic reaction that is generalized.

The second most common cause of SJS and TEN is infection, particularly in children. This includes upper respiratory infections, otitis media, pharyngitis, and Epstein-Barr virus, Mycoplasma pneumoniae and cytomegalovirus infections. The routine use of medicines such as antibiotics, antipyretics and analgesics to manage infections can make it difficult to identify if cases were caused by the infection or medicines taken.

Viral diseases reported to cause SJS include: herpes simplex virus (debated), AIDS, coxsackievirus, influenza, hepatitis, and mumps.

In pediatric cases, Epstein-Barr virus and enteroviruses have been associated with SJS.

Recent upper respiratory tract infections have been reported by more than half of patients with SJS.

Bacterial infections linked to SJS include group A beta-hemolytic streptococci, diphtheria, brucellosis, lymphogranuloma venereum, mycobacteria, "Mycoplasma pneumoniae", rickettsial infections, tularemia, and typhoid.

Fungal infections with coccidioidomycosis, dermatophytosis, and histoplasmosis are also considered possible causes. Malaria and trichomoniasis, protozoal infections, have also been reported as causes.

The histomorphologic appearance of insect bites is usually characterized by a wedge-shaped superficial dermal perivascular infiltrate consisting of abundant lymphocytes and scattered eosinophils. This appearance is non-specific, i.e. it may be seen in a number of conditions including:

- Drug reactions,

- Urticarial reactions,

- Prevesicular early stage of bullous pemphigoid, and

- HIV related dermatoses.

AGEP is an acute febrile drug eruption characterized by numerous small, primarily non-follicular, sterile pustules, arising within large areas of red swollen skin.

The eruption follows a self-limiting course and will end before a week provided the causative agent (e.g. medication) is discarded. It is accompanied by fever, a high number of neutrophils and eosinophils in the blood, liver inflammation, and sometimes by facial swelling. The mortality rate is about 5% and the differential diagnosis includes Stevens–Johnson syndrome (SJS). Contrary to SJS, in AGEP, mucosa are not affected, which means that there are no blisters in the mouth or vagina.

Lipoproteins released from treatment of "Treponema pallidum" infections are believed to induce the Jarisch-Herxheimer reaction. The Herxheimer reaction has shown an increase in inflammatory cytokines during the period of exacerbation, including tumor necrosis factor alpha, interleukin-6 and interleukin-8.

Although SJS can be caused by viral infections and malignancies, the main cause is medications. A leading cause appears to be the use of antibiotics, particularly sulfa drugs. Between 100 and 200 different drugs may be associated with SJS. No reliable test exists to establish a link between a particular drug and SJS for an individual case. Determining what drug is the cause is based on the time interval between first use of the drug and the beginning of the skin reaction. Drugs discontinued more than 1 month prior to onset of mucocutaneous physical findings are highly unlikely to cause SJS and TEN. SJS and TEN most often begin between 4 and 28 days after culprit drug administration. A published algorithm (ALDEN) to assess drug causality gives structured assistance in identifying the responsible medication.

SJS may be caused by adverse effects of the drugs vancomycin, allopurinol, valproate, levofloxacin, diclofenac, etravirine, isotretinoin, fluconazole, valdecoxib, sitagliptin, oseltamivir, penicillins, barbiturates, sulfonamides, phenytoin, azithromycin, oxcarbazepine, zonisamide, modafinil, lamotrigine, nevirapine, pyrimethamine, ibuprofen, ethosuximide, carbamazepine, bupropion, telaprevir, and nystatin.

Medications that have traditionally been known to lead to SJS, erythema multiforme, and toxic epidermal necrolysis include sulfonamide antibiotics, penicillin antibiotics, cefixime (antibiotic), barbiturates (sedatives), lamotrigine, phenytoin (e.g., Dilantin) (anticonvulsants) and trimethoprim. Combining lamotrigine with sodium valproate increases the risk of SJS.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a rare cause of SJS in adults; the risk is higher for older patients, women, and those initiating treatment. Typically, the symptoms of drug-induced SJS arise within a week of starting the medication. Similar to NSAIDs, paracetamol (acetaminophen) has also caused rare cases of SJS. People with systemic lupus erythematosus or HIV infections are more susceptible to drug-induced SJS.

Fixed drug reactions are common and so named because they recur at the same site with each exposure to a particular medication. Medications inducing fixed drug eruptions are usually those taken intermittently.

Drugs causing fixed drug eruptions:

1. Fluconazole

2. Ciprofloxacin

3. Doxycycline

4. Clarithromycin

5. NSAIDs

6. Trimethoprim

7. Cotrimoxazole

8. Phenytoin

9. Cetirizine

10. Pseudoephedrine

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.

Erythroderma (also known as "Exfoliative dermatitis," "Dermatitis exfoliativa") is an inflammatory skin disease with erythema and scaling that affects nearly the entire cutaneous surface.

In ICD-10, a distinction is made between "exfoliative dermatitis" at L26, and "erythroderma" at L53.9.

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.

As research better explains the biochemistry of drug use, fewer ADRs are Type B and more are Type A. Common mechanisms are:

- Abnormal pharmacokinetics due to

- genetic factors

- comorbid disease states

- Synergistic effects between either

- a drug and a disease

- two drugs

Erythroderma is generalized exfoliative dermatitis, which involves 90% or more of the patient's skin. The most common cause of erythroderma is exacerbation of an underlying skin disease, such as psoriasis, contact dermatitis, seborrheic dermatitis, lichen planus, pityriasis rubra pilaris or a drug reaction. Primary erythroderma is less frequent and is usually seen in cases of cutaneous T-cell lymphoma, in particular in Sézary's disease.

The most common causes of exfoliative dermatitis are best remembered by the mnemonic device ID-SCALP. The causes and their frequencies are as follows:

- Idiopathic - 30%

- Drug allergy - 28%

- Lymphoma and leukemia - 14%

- Atopic dermatitis - 10%

- Psoriasis - 8%

- Contact dermatitis - 3%

- Seborrheic dermatitis - 2%

Differential diagnosis in patients with erythroderma may be difficult.

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."