Drug Eruptions

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Practice Essentials

Drug eruptions can mimic a wide range of dermatoses. The morphologies are myriad and include morbilliform (see the image below), urticarial, papulosquamous, pustular, and bullous. Medications can also cause pruritus and dysesthesia without an obvious eruption. A drug-induced reaction should be considered in any patient who is taking medications and who suddenly develops a symmetric cutaneous eruption. Morbilliform eruption localized to striae has been described with clindamycin.[1]



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Morbilliform drug eruption.

Signs and symptoms

The first steps in the history are as follows:

In addition, the following should be noted and detailed:

Physical examination should address clinical features that may indicate a severe, potentially life-threatening drug reaction, including the following:

It is important to appreciate the morphology and physical features of drug eruptions, as follows:

See Clinical Presentation for more detail.

Diagnosis

With mild asymptomatic eruptions, the history and physical examination are often sufficient for diagnosis; with severe or persistent eruptions, further diagnostic testing may be required, as follows:

See Workup for more detail.

Management

Principles of medical care are as follows:

For most drug eruptions, full recovery without any complications is expected; however, the following should be noted:

See Treatment and Medication for more detail.

Background

Drug eruptions can mimic a wide range of dermatoses. The morphologies are myriad and include morbilliform (most common, see image below), urticarial, papulosquamous, pustular, and bullous. Medications can also cause pruritus and dysesthesia without an obvious eruption. Both calcium channel blockers and interferon are strongly associated with eczematous eruptions.



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Morbilliform drug eruption.

A drug-induced reaction should be considered in any patient who is taking medications and who suddenly develops a symmetric cutaneous eruption. Medications that are known for causing cutaneous reactions include antimicrobial agents,[6] nonsteroidal anti-inflammatory drugs (NSAIDs), cytokines, chemotherapeutic agents, anticonvulsants, and psychotropic agents.

Prompt identification and withdrawal of the offending agent may help limit the toxic effects associated with the drug. The decision to discontinue a potentially vital drug often presents a dilemma.

Pathophysiology

Drug eruptions may be divided into immunologically and nonimmunologically mediated reactions.

Immunologically mediated reactions

Coombs and Gell proposed four types of immunologically mediated reactions, as follows:

Th17 T cells are implicated in many drug eruptions, and sulfamethoxazole induces a T-cell switch mechanism based on the TCRVβ20-1 domain altering peptide-HLA recognition. In severe drug reactions, micro RNA-18a-5p down-regulates the expression of the antiapoptotic B-cell lymphoma/leukemia-2–like protein 10 (BCL2L10), promoting apoptosis.

Insulin and other proteins are associated with type I reactions. Penicillin, cephalosporins, sulfonamides, and rifampin are known to cause type II reactions. Quinine, salicylates, chlorpromazine, and sulfonamides can cause type III reactions. Type IV reactions, the most common mechanism of drug eruptions, are often encountered in cases of contact hypersensitivity to topical medications, such as neomycin. Sulfonamides are most frequently associated with toxic epidermal necrolysis (TEN).

Although most drug eruptions are type IV hypersensitivity reactions, only a minority are IgE-dependent. That is, antibodies can be demonstrated in less than 5% of cutaneous drug reactions. Type IV cell-mediated reactions are not dose dependent, they usually begin 7-20 days after the medication is started, they may involve blood or tissue eosinophilia, and they may recur if drugs chemically related to the causative agent are administered.

Nonimmunologically mediated reactions

Nonimmunologically mediated reactions may be classified according to the following features: accumulation, adverse effects, direct release of mast cell mediators, idiosyncratic reactions, intolerance, Jarisch-Herxheimer phenomenon, overdosage, or phototoxic dermatitis. (Symptoms of Jarisch-Herxheimer reactions disappear with continued therapy. Drug therapy should be continued until the infection is fully eradicated.)

An example of accumulation is argyria (blue-gray discoloration of skin and nails) observed with use of silver nitrate nasal sprays.

Adverse effects are normal but unwanted effects of a drug. For example, antimetabolite chemotherapeutic agents, such as cyclophosphamide, are associated with hair loss.

The direct release of mast cell mediators is a dose-dependent phenomenon that does not involve antibodies. For example, aspirin and other NSAIDs cause a shift in leukotriene production, which triggers the release of histamine and other mast-cell mediators. Radiographic contrast material, alcohol, cytokines, opiates, cimetidine, quinine, hydralazine, atropine, vancomycin, and tubocurarine also may cause release of mast-cell mediators.

Idiosyncratic reactions are unpredictable and not explained by the pharmacologic properties of the drug. An example is the individual with infectious mononucleosis who develops a rash when given ampicillin.

Imbalance of endogenous flora may occur when antimicrobial agents preferentially suppress the growth of one species of microbe, allowing other species to grow vigorously. For example, candidiasis frequently occurs with antibiotic therapy.

Intolerance may occur in patients with altered metabolism. For example, individuals who are slow acetylators of the enzyme N -acetyltransferase are more likely than others to develop drug-induced lupus in response to procainamide.

Jarisch-Herxheimer phenomenon is a reaction due to bacterial endotoxins and microbial antigens that are liberated by the destruction of microorganisms. The reaction is characterized by fever, tender lymphadenopathy, arthralgias, transient macular or urticarial eruptions, and exacerbation of preexisting cutaneous lesions. The reaction is not an indication to stop treatment because symptoms resolve with continued therapy. This reaction can be seen with penicillin therapy for syphilis, griseofulvin or ketoconazole therapy for dermatophyte infections, and diethylcarbamazine therapy for oncocerciasis.

Overdosage is an exaggerated response to an increased amount of a medication. For example, increased doses of anticoagulants may result in purpura.

Phototoxic dermatitis is an exaggerated sunburn response caused by the formation of toxic photoproducts, such as free radicals or reactive oxygen species (see the image below).



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Phototoxic reaction after use of a tanning booth. Note sharp cutoff where clothing blocked exposure.

Etiology

Fibrosing reactions have been associated with a variety of chemical exposures. Nephrogenic systemic fibrosis has been associated with gadolinium contrast agents used for MRI studies. Individuals with renal failure may have a buildup gadolinium in the skin and other organs and may recruit CD34-positive bone marrow–derived fibrocytes into lesional areas. Toxic oil ingestion has been associated with morphea, and Texier disease has been associated with phytomenadione (vitamin-K1) injections.

Rates of reactions to commonly used drugs are as follows:

Cutaneous reaction rates in patients with HIV infection are as follows[7] :

Drugs that commonly cause serious reactions are as follows:

Drugs unlikely to cause skin reactions are as follows:

Drugs associated with specific morphologic patterns are described below. The following is a list of medications that have been reported to cause specific types of cutaneous reactions. However, not every possible type of drug eruption has been listed. In addition, exclusion of a drug from the following list does not imply that it is not the cause of a patient's eruption. A high index of suspicion must always be maintained when confronted with a new onset eruption in a patient on multiple medications. Note the following:

Psychotropic drugs associated with specific morphologic patterns are as follows[28] :

Chemotherapeutic agents associated with specific morphologic patterns are as follows:

Cutaneous reactions to targeted chemotherapy are as follows:

Cutaneous reactions to cytokine therapy are as follows[40] :

Epidemiology

United States

Drug eruptions occur in approximately 2-5% of inpatients and in greater than 1% of outpatients.

International

Drug eruptions occur in approximately 2-3% of inpatients.

Sex

Adverse cutaneous reactions to drugs are more prevalent in women than in men.

Age

Elderly patients have an increased prevalence of adverse drug reactions.

Prognosis

Most drug eruptions are mild, self-limited, and usually resolve after the offending agent has been discontinued. Even after the responsible agent is discontinued, drug eruptions may clear slowly or worsen over the next few days. The degree of eosinophilia is predictive of the severity of the drug eruption.[43, 44] The time required for total clearing may be 1-2 weeks or longer.

Severe and potentially life-threatening eruptions occur in approximately 1 in 1000 hospital patients. Mortality rates for erythema multiforme (EM) major are significantly higher. Stevens-Johnson syndrome (SJS) has a mortality rate of less than 5%, whereas the rate for TEN approaches 20-30%; most patients die from sepsis.

Patients with exanthematous eruptions should be counseled to expect mild desquamation as the rash resolves.

Patients with hypersensitivity syndrome are at risk of becoming hypothyroid, usually within the first 4-12 weeks after the reaction.

The prognosis for patients with TEN is guarded. Scarring, blindness, and death are possible.

Patient Education

If the responsible drug is identified, advise the patient to avoid that drug in the future. Clearly label the medical record. Advise patients to carry a card or some other form of emergency identification in their wallets that lists drug allergies and/or intolerances, especially if they have had a severe reaction.

Advise patients about drugs that are cross-reactive and about drugs that must be avoided. For example, penicillin allergy reactions have cross-reactivity with cephalosporins, phenytoin hypersensitivity syndrome has cross-reactivity with phenobarbital and carbamazepine, and sulfonamide reactions cross-react with other sulfa-containing drugs.

For patient education resources, see the Allergy Center.

History

The first step is to review the patient's complete medication list, including over-the-counter supplements. Document any history of previous adverse reactions to drugs or foods. Consider alternative etiologies, especially viral exanthems and bacterial infections. Exanthematous eruptions in children are more likely to be due to a viral infection than another infection; however, most such reactions in adults are due to medications.

Note any concurrent infections, metabolic disorders, or immunocompromise (eg, due to HIV infection, cancer, chemotherapy) because these increase the risk of drug eruptions. Immunocompromised persons have a 10-fold higher risk of developing a drug eruption than the general population. Although HIV infection causes profound anergy to other immune stimuli, the frequency of drug hypersensitivity reactions, including severe reactions (eg, TEN), is markedly increased in HIV-positive individuals. Patients with advanced HIV infection (CD4 count < 200 cells/µL) have a 10- to 50-fold increased risk of developing an exanthematous eruption to sulfamethoxazole.

Note and detail the following:

Physical Examination

Although most drug eruptions are exanthematous, different types of drug eruptions are described.

With every drug eruption, it is important to evaluate for certain clinical features that may indicate a severe, potentially life-threatening drug reaction, such as TEN or hypersensitivity syndrome. Such features include the following:

Appreciating the morphology and features of drug eruptions is important. This can help the clinician determine the causative medication and the most appropriate treatment.

Acneiform

This is characterized by inflammatory papules or pustules that have a follicular pattern. They are localized primarily on the upper body. In contrast to acne vulgaris, comedones are absent in acneiform eruptions.

Acral erythema (erythrodysesthesia)

This is a relatively common reaction to chemotherapy and is characterized by symmetric tenderness, edema, and erythema of the palms and soles. It is thought to be a direct toxic effect on the skin. Acral erythema often resolves 2-4 weeks after chemotherapy is discontinued.

Acute generalized exanthematous pustulosis (AGEP)

Acute-onset fever and generalized scarlatiniform erythema occur with many small, sterile, nonfollicular pustules. The clinical presentation is similar to pustular psoriasis, but AGEP has more marked hyperleukocytosis with neutrophilia and eosinophilia. Most cases are caused by drugs (primarily antibiotics) often in the first few days of administration. A few cases are caused by viral infections, mercury exposure, or UV radiation. AGEP resolves spontaneously and rapidly, with fever and pustules lasting 7-10 days then desquamation over a few days.

Dermatomyositis like

Cutaneous findings include dermatomyositis (eg, Gottron papules), but patients tend to lack muscle involvement, associated malignancy, and antinuclear antibodies. Improvement is usually noted after the drug is withdrawn.

DRESS (ie, drug reaction with eosinophilia and systemic symptoms) syndrome or DIHS drug-induced hypersensitivity syndrome

These are characterized by the triad of fever, skin eruption, and internal organ involvement, and they usually are associated with intake of anticonvulsant drugs.

Erythema multiforme

This includes a spectrum of diseases (eg, EM minor, EM major), as described below; however, many authorities categorize SJS and TEN as EM major and differentiate them by body surface involvement

Erythema nodosum

This is characterized by tender, red, subcutaneous nodules that typically appear on the anterior aspect of the legs. Lesions do not suppurate or become ulcerated (see the image below). It is a reactive process often secondary to infection, but it may be due to medications, especially oral contraceptives and sulfonamides.



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Erythema nodosum.

Erythroderma

This is widespread inflammation of the skin (see the image below), and it may result from an underlying skin condition, drug eruption, internal malignancy, or immunodeficiency syndrome. Lymphadenopathy is often noted, and hepatosplenomegaly, leukocytosis, eosinophilia, and anemia may be present.



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Erythroderma.

Fixed drug eruptions

Lesions recur in the same area when the offending drug is given (see the image below). Circular, violaceous, edematous plaques that resolve with macular hyperpigmentation is characteristic. Lesions occur 30 minutes to 8 hours after drug administration. Perioral and periorbital lesions may occur, but the hands, feet, and genitalia are the most common locations.



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Fixed drug eruption.

Hypersensitivity syndrome

This is a potentially life-threatening complex of symptoms often caused by anticonvulsants. Patients have fever, sore throat, rash, lymphadenopathy, hepatitis, nephritis, and leukocytosis with eosinophilia. It usually begins within 1-3 weeks after a new drug is started, but it may develop 3 months or later into therapy. Aromatic anticonvulsant drugs cross-react (ie, phenytoin, phenobarbital, carbamazepine); valproic acid is a safe alternative.

Leukocytoclastic vasculitis

This is the most common severe drug eruption seen in clinical practice (see the image below). It is characterized by blanching erythematous macules quickly followed by palpable purpura. Fever, myalgias, arthritis, and abdominal pain may be present. It typically appears 7-21 days after the onset of drug therapy, and a laboratory evaluation to exclude internal involvement is mandatory.



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Vasculitic reaction on the legs.

Lichenoid

This reaction appears similar to lichen planus and may be severely pruritic (see the image below). The eruption may include eczematous or psoriasiform papules.



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Lichen planus on the neck.

Lupus

Drug-induced systemic lupus erythematosus (SLE) produces symptoms identical to those of SLE, but skin findings are uncommon. Lesions are also identical to drug-induced subacute cutaneous lupus erythematosus (SCLE), which is characterized by annular, psoriasiform, nonscarring lesions in a photodistributed pattern.

Morbilliform or exanthematous

This is the most common pattern of drug eruptions; it is the quintessential drug rash. Exanthem is typically symmetric, with confluent erythematous macules and papules that spare the palms and soles. It typically develops within 2 weeks after the onset of therapy.

Pseudoporphyria [2]

While largely a drug-induced condition, it can also occur with use of tanning beds and hemodialysis. Patients have blistering and skin fragility that is clinically and pathologically (see the image below) identical to that of porphyria cutanea tarda, but hypertrichosis and sclerodermoid changes are absent and urine and serum porphyrin levels are normal. Treatment is sun protection and withdrawal of the medication.



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Confluent necrosis of the epidermis in toxic epidermal necrolysis.

Serum sickness and serum sickness–like

These are type III hypersensitivity reactions mediated by the deposition of immune complexes in small vessels, activation of complement, and recruitment of granulocytes. Cutaneous signs typically begin with erythema on the sides of the fingers, hands, and toes and progress to a widespread eruption (most often morbilliform or urticarial). Viscera may be involved, and fever, arthralgia, and arthritis are common. Serum sickness–like reactions have a clinical presentation similar to that of serum sickness reactions, without the immune complex deposition. Renal involvement is rare. Serum sickness–like reactions usually occur with antibiotic therapy, especially with cefaclor.

Sweet syndrome (acute febrile neutrophilic dermatosis)

Tender erythematous papules and plaques occur most often on the face, neck, upper trunk, and extremities. The surface of the lesions may become vesicular or pustular. Systemic findings are common and include fever (most often), arthritis, arthralgias, conjunctivitis, episcleritis, and oral ulcers. Laboratory evaluation usually reveals an elevated sedimentation rate, neutrophilia, and leukocytosis. Sweet syndrome often occurs in association with cancers, inflammatory disorders, pregnancy, and medication use.

Urticaria

This usually occurs as small wheals that may coalesce or may have cyclical or gyrate forms. Lesions usually appear shortly after the start of drug therapy and resolve rapidly when the drug is withdrawn (see the image below). Giant urticaria is easily mistaken for EM.



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Perivascular mixed inflammatory infiltrate with eosinophils characteristic of drug-induced urticaria.

Vesiculobullous

These reactions can resemble pemphigus, bullous pemphigoid, linear immunoglobulin A (IgA) dermatosis, dermatitis herpetiformis, herpes gestationis, or cicatricial pemphigoid. Most causative drugs have a thiol group, disulfide bonds, or sulfur-containing rings that are metabolized to thiol forms. Thiol-induced pemphigus tends to resemble pemphigus foliaceus or pemphigus erythematosus; nonthiol eruptions may resemble pemphigus vulgaris or pemphigus vegetans. Mucosal findings may be most common with nonthiol drugs. Results from direct and indirect immunofluorescence may be positive in persons with drug-induced pemphigus and bullous pemphigoid. Eruptions usually resolve after the inducing drug is discontinued, but D-penicillamine–induced pemphigus may take months to resolve and corticosteroids are often needed.

(Also see the Pill Identifier tool.)

Laboratory Studies

History and physical examination are often sufficient for diagnosing mild asymptomatic eruptions. Severe or persistent eruptions may require further diagnostic testing.

Much research is directed at identifying laboratory techniques that can establish a diagnosis of a drug eruption. In current practice, most of these techniques are still too early in development for routine clinical use. Diagnostic tools for the assessment of allergic rashes usually still depend on challenges to identify causative agents.[45]

Biopsy can be helpful in confirming the diagnosis of a drug eruption (eg, by showing eosinophils in morbilliform eruptions or numerous neutrophils without vasculitis in persons with Sweet syndrome).

CBC count with differential may show leukopenia, thrombocytopenia, and eosinophilia in patients with serious drug eruptions.

Serum chemistry studies may be useful. Liver involvement leading to death can occur in persons with hypersensitivity syndromes. Special attention should be paid to the electrolyte balance and renal and/or hepatic function indices in patients with severe reactions such as SJS, TEN, or vasculitis.

Antibody and/or immunoserology tests may be ordered. Antihistone antibodies are noted in persons with drug-induced SLE, whereas anti-Ro/SS-A antibodies are most common in persons with drug-induced SCLE.

Direct cultures may be needed to investigate a primary infectious etiology or secondary infection.

Urinalysis, stool guaiac tests, and chest radiography are important for patients with vasculitis.

Imaging Studies

Chest radiography, along with urinalysis and stool guaiac tests, is important for patients with vasculitis.

Other Tests

Rechallenge tests by means of skin prick or patch testing to confirm the causative agent is of limited value. Skin tests may be hazardous to patients who have had severe reactions. With the possible exception of acute generalized exanthematous pustulosis (AGEP), patch tests have a low sensitivity and specificity and are not useful.[46]

Histologic Findings

In some cases, biopsy may be helpful in establishing a diagnosis of a drug reaction.

Histopathology of an exanthematous drug eruption may show both superficial and deep perivascular inflammatory cell infiltrates. Eosinophils in the infiltrate suggest such a drug eruption (see the image below).



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Superficial perivascular inflammatory infiltrate with numerous eosinophils characteristic of an exanthematous drug eruption.

In patients with Sweet syndrome, biopsy reveals edema of the superficial dermis and a dense infiltrate of neutrophils. Leukocytoclasia may be present, but vasculitis is absent.

Histopathology of TEN shows subepidermal split, full-thickness epidermal necrosis and a sparse perivascular lymphocytic infiltrate (see the image below).



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Confluent necrosis of the epidermis in toxic epidermal necrolysis.

Medical Care

The ultimate goal is always to discontinue the offending medication if possible. Individuals with drug eruptions are often the most ill patients taking the most medications, many of which are essential for their survival. However, all nonessential medications should be limited. Once the offending drug has been identified, it should be promptly discontinued. Knowledge of the common eruption inducing–medications may help in identifying the offending drug.

Patients can possibly continue to be treated through morbilliform eruptions (ie, continue medication even in patients with a rash). The eruption often resolves, especially if the individual is being treated with antihistamines. Most authorities believe that exanthematous drug eruptions are not a precursor to severe reactions, such as TEN. Nevertheless, all patients with severe morbilliform eruptions should be monitored for mucous membrane lesions, blistering, and skin sloughing.

Treatment of a drug eruption depends on the specific type of reaction. Therapy for exanthematous drug eruptions is supportive in nature. First-generation antihistamines are used 24 h/d. Mild topical steroids (eg, hydrocortisone, desonide) and moisturizing lotions are also used, especially during the late desquamative phase.

Severe reactions, such as SJS, TEN, and hypersensitivity reactions, warrant hospital admission. TEN is best managed in a burn unit with special attention given to electrolyte balance and signs of secondary infection. Because adhesions can develop and result in blindness, evaluation by an ophthalmologist is mandatory. In addition, mounting evidence indicates that intravenous immunoglobulin (IVIG) may improve outcomes for TEN patients.[3, 4, 5]

Hypersensitivity syndrome, a systemic reaction characterized by fever, sore throat, rash, and internal organ involvement, is potentially life threatening. Timely recognition of the syndrome and immediate discontinuation of the anticonvulsant or other offending drug are crucial. Patients may require liver transplantation if the drug is not stopped in time. Treatment with systemic corticosteroids has been advocated.

Medication Summary

Therapy for most drug eruptions is mainly supportive in nature. Morbilliform eruptions are treated with oral antihistamines and topical steroids. IVIG is currently the most common agent used to treat TEN. Cyclosporine may also have a role in the treatment of TEN. Prednisone may be used in the treatment of hypersensitivity syndrome with heart and lung involvement, severe serum sickness–like reaction, and Sweet syndrome.

Hydroxyzine HCl (Anxanil, Atarax, Atozine, Durrax, Vistaril)

Clinical Context:  Hydroxyzine antagonizes H1 receptors in the periphery. It may suppress histamine activity in the subcortical CNS. Hydroxyzine is available as 10-, 25-, 50-, or 100-mg tablets.

Diphenhydramine HCl (Benadryl, Benylin, Diphen, AllerMax)

Clinical Context:  Diphenhydramine is used for symptomatic relief of allergic symptoms caused by the release of histamine in immune reactions.

Class Summary

These agents antagonize H1 receptors and block release of histamine. They provide symptomatic relief of pruritus and help improve eruptions.

Loratadine (Claritin)

Clinical Context:  Loratadine selectively inhibits peripheral histamine H1 receptors.

Class Summary

These agents cause less, if any, drowsiness than first-generation agents.

Desonide

Clinical Context:  Desonide is for inflammatory dermatoses responsive to steroids; it decreases inflammation by suppressing the migration of PMN leukocytes and reversing capillary permeability.

Prednisone (Deltasone, Orasone, Sterapred)

Clinical Context:  Prednisone is an immunosuppressant for the treatment of immune disorders; it may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity; it is available in 2.5-, 5-, 10-, 20-, or 50-mg tablets.

Class Summary

Topical agents provide symptomatic relief of pruritus. Systemic steroids are used in persons with hypersensitivity syndrome, severe serum sickness–like reactions, and Sweet syndrome.

Intravenous immunoglobulin (Gammagard, Gamimune)

Clinical Context:  Intravenous immunoglobulin is a blood product prepared from the pooled plasma of healthy donors. The following features are possibly relevant to efficacy: neutralization of circulating myelin antibodies through anti-idiotypic antibodies; down-regulation of proinflammatory cytokines, including IFN-gamma; blockade of Fc receptors on macrophages; suppression of inducer T and B cells and augmentation of T-suppressor cells; blockade of complement cascade; promotion of remyelination; and 10% increase in CSF IgG.

Class Summary

These agents are used to treat TEN.

How are drug eruptions characterized?What should be the initial focus of history in suspected drug eruptions?What should be included in the medication history of suspected drug eruptions?Which clinical features should be the focus of the physical exam for drug eruptions?Which morphologies and physical features are characteristic of drug eruptions>?What is the role of lab testing in the diagnosis of drug eruptions?What are the principles for medical management of drug eruptions?Which conditions may complicate the recovery of drug eruptions?What are the common morphologies of drug eruptions?Which medications may cause drug eruptions?How does withdrawal of medication affect a drug eruption?What are the two types of reactions in drug eruptions?What are the types of immunologically mediated drug eruptions?What is the role of th17 T cells in the pathophysiology of drug eruptions?Which agents are associated with specific types of drug eruptions?What is the role of antibodies in the pathogenesis of type IV drug eruptions?Which features are used to classify nonimmunologically mediated drug eruptions?What is the significance of argyria in drug eruptions?What are adverse effects in nonimmunologically mediated drug eruptions?What is the role of direct release mast cell mediators in the pathophysiology of drug eruptions?What is an example of idiosyncratic reactions in nonimmunologically mediated drug eruptions?What is the role of imbalance of endogenous flora in the pathophysiology of drug eruptions?What is the role of intolerance in the pathophysiology of drug eruptions?What is the Jarisch-Herxheimer phenomenon in the pathophysiology of drug eruptions?What is the role of overdosage in the pathophysiology of drug eruptions?What is the role of phototoxic dermatitis in the pathophysiology of drug eruptions?What are possible etiologies of fibrosing drug eruptions?What are the rates of drug eruptions for commonly used medications?What are the rates of drug eruptions in patients with HIV infection?Which medications commonly cause serious drug eruptions?Which medications are unlikely to cause drug eruptions?Which medications are associated with specific morphologic patterns in drug eruptions?Which psychotropic agents are associated with specific morphologic patterns in drug eruptions?Which chemotherapeutic agents are associated with specific morphologic patterns in drug eruptions?What are the cutaneous reactions of targeted chemotherapy agents?What are the cutaneous reactions to cytokine therapy agents?What is the prevalence of drug eruptions in the US?What is the global prevalence of drug eruptions?How does the prevalence of drug eruptions vary among males and females?Which age group is at highest risk for drug eruptions?What is the prognosis of drug eruptions?What is the incidence of life-threatening drug eruptions?What is the prognosis of exanthematous drug eruptions?What is a possible complication of drug eruptions with hypersensitivity syndrome?What is the prognosis of drug eruptions in patients with TEN?What is included in patient education following a drug eruption?What is included in patient education to prevent drug eruptions?What should be the focus of patient history in drug eruptions?What should be included in the medication history of suspected drug eruptions?What are the signs and symptoms of potentially severe or life-threatening drug eruptions?What are morphological features that can help determine the causative medication for drug eruptions?What are the differential diagnoses for Drug Eruptions?What is the role of lab studies in the workup of drug eruptions?What is the role of biopsies in the workup of drug eruptions?What is the role of CBC count in the workup of drug eruptions?What is the role of serum chemistry studies in the workup of drug eruptions?What is the role of antibody and immunoserology tests in the workup of drug eruptions?What is the role of direct cultures in the workup of drug eruptions?What is the role of urinalysis, stool guaiac tests, and chest radiography in the workup of drug eruptions?What is the role of imaging studies in the workup of drug eruptions?What is the role of skin testing in the workup of drug eruptions?Which histologic findings suggest drug eruption?Which histologic findings help differentiate Sweet syndrome from drug eruptions?Which histologic findings indicate TEN in drug eruptions?What is the goal of medical care for drug eruptions?How is drug eruption managed in patients who must continue taking the causative medication?What are the treatment options for drug eruption?What is included in medical care of severe drug eruptions?Which medications are used in the treatment of drug eruptions?Which medications in the drug class First-generation antihistamines are used in the treatment of Drug Eruptions?Which medications in the drug class Second-generation antihistamines, nonsedating are used in the treatment of Drug Eruptions?Which medications in the drug class Corticosteroids are used in the treatment of Drug Eruptions?Which medications in the drug class Immunoglobulins are used in the treatment of Drug Eruptions?

Author

Jonathan E Blume, MD, Instructor in Clinical Dermatology, Columbia University College of Physicians and Surgeons; Dermatologist, Westwood Dermatology and Dermatologic Surgery Group PA

Disclosure: Nothing to disclose.

Coauthor(s)

Liaqat Ali, MD, Assistant Professor, Department of Dermatology, Wayne State University School of Medicine; Dermatopathologist, Pinkus Dermatopathology Laboratory, Monroe, MI

Disclosure: Nothing to disclose.

Michelle Ehrlich, MD, Director of Cosmetic Dermatology and Surgery Residency Program, Harbor-UCLA Medical Center; Clinical Instructor, Department of Dermatology, University of California, Los Angeles, David Geffen School of Medicine

Disclosure: Nothing to disclose.

Thomas N Helm, MD, Clinical Professor of Dermatology and Pathology, University of Buffalo, State University of New York School of Medicine and Biomedical Sciences; Director, Buffalo Medical Group Dermatopathology Laboratory

Disclosure: Nothing to disclose.

Specialty Editors

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Disclosure: Nothing to disclose.

Jeffrey P Callen, MD, Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine

Disclosure: Received honoraria from UpToDate for author/editor; Received royalty from Elsevier for book author/editor; Received dividends from trust accounts, but I do not control these accounts, and have directed our managers to divest pharmaceutical stocks as is fiscally prudent from Stock holdings in various trust accounts include some pharmaceutical companies and device makers for i inherited these trust accounts; for: Allergen; Celgene; Pfizer; 3M; Johnson and Johnson; Merck; Abbott Laboratories; AbbVie; Procter and Gamble; Amgen.

Chief Editor

Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Neil Shear, MD, Professor and Chief of Dermatology, Professor of Medicine, Pediatrics and Pharmacology, University of Toronto Faculty of Medicine; Head of Dermatology, Sunnybrook Women's College Health Sciences Center and Women's College Hospital, Canada

Disclosure: Nothing to disclose.

Acknowledgements

Charles Camisa, MD Head of Clinical Dermatology, Vice-Chair, Department of Dermatology, Cleveland Clinic Foundation

Charles Camisa, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

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Morbilliform drug eruption.

Morbilliform drug eruption.

Urticaria.

Oral ulcerations in a patient receiving cytotoxic therapy.

Phototoxic reaction after use of a tanning booth. Note sharp cutoff where clothing blocked exposure.

Steroid acne. Note pustules and absence of comedones.

Male-pattern diffuse hair loss.

Pink/fleshy perifollicular papules with diffuse alopecia.

Horizontal section shows perifollicular fibrosis consistent with scarring alopecia.

Paronychia.

Papules and annular plaques.

Superficial and mid-dermal perivascular infiltrate of lymphocytes and eosinophils. Foci of extravasation of erythrocytes.

Numerous milia in a patient treated with vemurafenib.

Dilated infundibular cyst.

Warfarin (Coumadin) necrosis involving the leg.

Erythema multiforme.

Target lesions of erythema multiforme.

Toxic epidermal necrolysis.

Stevens-Johnson syndrome.

Erythema nodosum.

Erythroderma.

Fixed drug eruption.

Vasculitic reaction on the legs.

Lichen planus on the neck.

Confluent necrosis of the epidermis in toxic epidermal necrolysis.

Perivascular mixed inflammatory infiltrate with eosinophils characteristic of drug-induced urticaria.

Superficial perivascular inflammatory infiltrate with numerous eosinophils characteristic of an exanthematous drug eruption.

Confluent necrosis of the epidermis in toxic epidermal necrolysis.

Morbilliform drug eruption.

Warfarin (Coumadin) necrosis involving the leg.

Toxic epidermal necrolysis.

Stevens-Johnson syndrome.

Erythroderma.

Erythema multiforme.

Fixed drug eruption.

Fixed drug eruption involving the penis.

Oral ulcerations in a patient receiving cytotoxic therapy.

Phototoxic reaction after use of a tanning booth. Note sharp cutoff where clothing blocked exposure.

Vasculitic reaction on the legs.

Lichen planus on the neck.

Steroid acne. Note pustules and absence of comedones.

Drug reaction to hydroxychloroquine (Plaquenil).

Urticaria.

Erythema nodosum.

Confluent necrosis of the epidermis in toxic epidermal necrolysis.

Perivascular mixed inflammatory infiltrate with eosinophils characteristic of drug-induced urticaria.

Biopsy of pseudoporphyria shows a subepidermal blister with little to no inflammation.

Confluent necrosis of the epidermis in toxic epidermal necrolysis.

Superficial perivascular inflammatory infiltrate with numerous eosinophils characteristic of an exanthematous drug eruption.

Target lesions of erythema multiforme.

Papules and annular plaques.

Superficial and mid-dermal perivascular infiltrate of lymphocytes and eosinophils. Foci of extravasation of erythrocytes.

Numerous milia in a patient treated with vemurafenib.

Dilated infundibular cyst.

Paronychia.

Male-pattern diffuse hair loss.

Pink/fleshy perifollicular papules with diffuse alopecia.

Horizontal section shows perifollicular fibrosis consistent with scarring alopecia.