Drug Eruptions

Practice Essentials

Drug eruptions can mimic a wide range of dermatoses. They may be related to traditional pharmaceutical agents, biologic agents and targeted immunotherapeutic agents, food additives, and dyes.^{[1, 2, 3, 4, 5]} The morphologies are myriad and include morbilliform (see the image below), urticarial, papulosquamous, pustular, and bullous. 

View Image

Morbilliform drug eruption.

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. Medications that are known for causing cutaneous reactions include antimicrobial agents,^[6]  nonsteroidal anti-inflammatory drugs (NSAIDs), cytokines, chemotherapeutic agents, anticonvulsants, and psychotropic agents. Morbilliform eruption localized to striae has been described with clindamycin.^[7]

Signs and symptoms

The first steps in the history are as follows:

• Review the patient’s complete medication list, including prescription and over-the-counter (OTC) drugs
• Document any history of previous adverse reactions to drugs or foods
• Consider alternative etiologies (eg, viral exanthems and bacterial infections)
• Note any concurrent infections, metabolic disorders, or immunocompromise

In addition, the following should be noted and detailed:

• Interval between introduction of a drug and onset of the eruption
• Route, dose, duration, and frequency of drug administration
• Use of parenterally administered drugs (more likely to cause anaphylaxis)
• Use of topically applied drugs (more likely to induce delayed-type hypersensitivity)
• Use of multiple courses of therapy and prolonged administration (risk of allergic sensitization)
• Any improvement after drug withdrawal and any reaction with readministration

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

• Mucous membrane erosions
• Blisters
• Nikolsky sign
• Confluent erythema
• Angioedema and tongue swelling
• Palpable purpura
• Skin necrosis
• Lymphadenopathy
• High fever, dyspnea, or hypotension

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

• Acneiform
• Acral erythema (erythrodysesthesia)
• Acute generalized exanthematous pustulosis (AGEP)
• Dermatomyositislike
• Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome
• Erythema multiforme (EM), including EM minor, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap
• Erythema nodosum
• Erythroderma
• Fixed drug eruptions
• Hypersensitivity syndrome
• Leukocytoclastic vasculitis
• Lichenoid
• Lupus
• Morbilliform or exanthematous
• Pseudoporphyria^[8]
• Serum sickness and serum sickness–like
• Sweet syndrome (acute febrile neutrophilic dermatosis)
• Urticaria
• Vesiculobullous

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:

• Biopsy
• Complete blood count (CBC) with differential
• Serum chemistry studies (especially for electrolyte balance and indices of renal or hepatic function in patients with severe reactions)
• Antibody or immunoserology tests
• Direct cultures to investigate a primary infectious etiology or secondary infection
• Urinalysis, stool guaiac tests, and chest radiography for vasculitis
• Skin prick or patch testing to confirm the causative agent

See Workup for more detail.

Management

Principles of medical care are as follows:

• The ultimate goal is to identify and discontinue the offending medication if possible
• Patients can sometimes continue to be treated through morbilliform eruptions; 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, involving the administration of oral antihistamines, topical steroids, and moisturizing lotions
• Severe reactions (eg, SJS, TEN, and hypersensitivity reactions) warrant hospital admission
• TEN is best managed in a burn unit, and intravenous immunoglobulin (IVIG) may improve outcomes^{[9, 10, 11]}
• Hypersensitivity syndrome may have to be treated with liver transplantation if the offending drug is not stopped in time; treatment with systemic corticosteroids has been advocated in the acute phase; in the chronic phase, patients may require treatment for hypothyroidism or diabetes mellitus

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

• Patients with exanthematous eruptions should 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; there is also a risk of diabetes
• The prognosis for patients with TEN is guarded; scarring, blindness, and death are possible

Oncodermatology

Oncodermatology is increasing in importance as more patients are being treated with chemotherapeutic agents that modulate immune response and are associated with expected cutaneous reactions. Often, clinicians are called upon to manage drug eruptions in this setting while affected individuals are kept on the triggering therapy because of life saving or life sustaining benefits. Unusual reactions such as vitiligo may result from some medications such as cyclin dependent kinase inhibitors.^[12]

Vaccinations

DRESS syndrome has been reported after vaccination for SARS COVID-19.^[13]  Vaccinations may contribute to other types of reactions as well.

See Treatment and Medication for more detail.

• References

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:

• Type I - Immunoglobulin E (IgE)-dependent reactions, which result in urticaria, angioedema, and anaphylaxis (see the first image below)
• Type II - Cytotoxic reactions, which result in hemolysis and purpura (see the second image below)
• Type III - Immune complex reactions, which result in vasculitis, serum sickness, and urticaria
• Type IV - Delayed-type reactions with cell-mediated hypersensitivity, which result in contact dermatitis, exanthematous reactions, and photoallergic reactions

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Urticaria.

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Oral ulcerations in patient receiving cytotoxic therapy.

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 (eg, neomycin). Sulfonamides are most frequently associated with TEN.

Although most drug eruptions are type IV hypersensitivity reactions, only a minority are IgE-dependent. That is, antibodies can be demonstrated in fewer 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
• Phototoxic dermatitis

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.

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. This reaction can be seen with penicillin therapy for syphilis, griseofulvin or ketoconazole therapy for dermatophyte infections, and diethylcarbamazine therapy for oncocerciasis. It does not constitute an indication for stopping treatment; symptoms of Jarisch-Herxheimer reactions resolve with continued drug therapy, which should be maintained until the infection is fully eradicated.

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 tanning booth. Note sharp cutoff where clothing blocked exposure.

• References

Etiology

Fibrosing reactions have been associated with a variety of chemical exposures. Nephrogenic systemic fibrosis has been associated with gadolinium contrast agents used in magnetic resonance imaging (MRI). Individuals with renal failure may have a buildup of 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:

• Amoxicillin - 5.1%
• Trimethoprim-sulfamethoxazole (TMP-SMX) - 4.7%
• Ampicillin - 4.2%
• Semisynthetic penicillin - 2.9%
• Blood (whole human) - 2.8%
• Penicillin G - 1.6%
• Cephalosporins - 1.3%
• Quinidine - 1.2%
• Gentamicin sulfate - 1%
• Packed red blood cells (RBCs) - 0.8%
• Mercurial diuretics - 0.9%
• Heparin - 0.7%

Cutaneous reaction rates in patients with HIV infection are as follows^[14] :

• Sulfasalazine - 20%
• TMP-SMX - 14.9%
• Aminopenicillins - 9.3%
• Penicillins - 3.8%
• Anticonvulsants - 3.4%
• Dapsone - 3.1%
• Penicillinase-resistant penicillins - 2.9%
• Cephalosporins - 2.7%
• Quinolones - 2.1%
• Ketoconazole - 2%
• Clindamycin - 1.8%
• Primaquine - 1.8%
• Tetracycline - 1.2%
• Pentamidine - 1%
• NSAIDs - 0.9%
• Erythromycin - 0.6%
• Zidovudine - 0.3%

Drugs that commonly cause serious reactions include the following:

• Allopurinol
• Anticonvulsants
• Bumetanide
• Captopril
• Furosemide
• NSAIDs
• Penicillamine
• Piroxicam
• Sulfa drugs
• Thiazide diuretics

Drugs unlikely to cause skin reactions include the following:

• Acetaminophen
• Aminophylline
• Aspirin
• Chlorpromazine
• Codeine
• Digoxin
• Diphenhydramine hydrochloride
• Ferrous sulfate
• Folic acid
• Meperidine
• Methyldopa
• Morphine
• Prednisone
• Prochlorperazine
• Regular insulin
• Serotonin-specific reuptake inhibitors
• Tetracycline
• Topical gels (eg, 4% tetracaine gel may cause serious cutaneous adverse reactions)^[15]
• Warfarin

Medications associated with specific types of cutaneous reactions

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 one is confronted with a new-onset eruption in a patient on multiple medications.

Acneiform

Causative agents include amoxapine, corticosteroids (see the image below), halogens, haloperidol, hormones, isoniazid, lithium, phenytoin, and trazodone.

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Steroid acne. Note pustules and absence of comedones.

Acute generalized exanthematous pustulosis

The most common causative agents include beta-lactam antibiotics and antibacterial sulfonamides,^[16]  diltiazem, antimalarials, macrolides,  mercury, quinolones, and terbinafine.

Less common causative agents include acetaminophen, allopurinol, bufexamac, buphenine, carbamazepine, carbutamide, celecoxib, chloramphenicol, clindamycin, TMP-SMX, clobazam, cyclins (eg, tetracycline), cytarabine, famotidine, furosemide, ginkgo biloba, hydrochlorothiazide, hydroxychloroquine, ibuprofen, imatinib, imipenem, isoniazid, intravenous (IV) contrast dye, lopinavir-ritonavir, mexiletine, morphine, nadoxolol, nifedipine, nystatin, olanzapine, phenytoin, pipemidic acid, piperazine, pseudoephedrine, pyrimethamine, quinidine, ranitidine, rifampicin, salbutamine, sertraline, simvastatin, streptomycin, terbinafine, thallium, vancomycin, calcium-channel blockers, angiotensin-converting enzyme (ACE) inhibitors (eg, captopril, ramipril), glyburide, and gemfibrozil.^{[17, 18]}

Alopecia

Causative agents include ACE inhibitors, allopurinol, anticoagulants, azathioprine, bromocriptine, beta blockers, cyclophosphamide, didanosine, hormones, indinavir, NSAIDs, phenytoin, methotrexate (MTX), retinoids, and valproate.

Bullous pemphigoid

Causative agents include aspirin, ampicillin, D-penicillamine, captopril, chloroquine, ciprofloxacin, enalapril, etanercept,^[19]  everolimus, furosemide, ibuprofen, levofloxacin neuroleptics, penicillins, phenacetin, psoralen plus UV-A, salicylazosulfapyridine, sirolimus, sulfasalazine, and terbinafine.^[20]

Dermatomyositislike ^[21]

Causative agents include bacille Calmette-Guérin (BCG) vaccine, hydroxyurea (most common^[22] ), lovastatin, omeprazole, penicillamine, simvastatin, and tegafur.

DRESS syndrome

The most common causative agents include aromatic anticonvulsants (phenytoin, phenobarbital [phenobarbitone], carbamazepine, lamotrigine, leviteracetam), sulfonamides, and antimicrobials (dapsone, TMP-SMX, piperacillin-tazobactam, vancomycin, abacavir, nevirapine, minocycline, and doxycycline).^{[23, 24]}

Erythema nodosum

Causative agents include echinacea, halogens, oral contraceptives (most common), penicillin, sulfonamides, and tetracycline.

Erythroderma

Causative agents include allopurinol, anticonvulsants, aspirin, barbiturates, captopril, carbamazepine, cefoxitin, chloroquine, chlorpromazine, cimetidine, diltiazem, griseofulvin, lithium, nitrofurantoin, omeprazole, phenytoin, St John's wort, sulfonamides, and thalidomide.

Fixed drug eruptions

Causative agents include acetaminophen, ampicillin, anticonvulsants, aspirin/NSAIDs, barbiturates, benzodiazepines, butalbital, cetirizine, ciprofloxacin, clarithromycin, dapsone, dextromethorphan, doxycycline, fluconazole, hydroxyzine, lamotrigine, loratadine, metronidazole, oral contraceptives, penicillins, phenacetin, phenolphthalein, phenytoin, piperacillin-tazobactam,^[25] piroxicam, saquinavir, sulfonamides, tetracyclines, ticlopidine, tolmetin, vancomycin, and zolmitriptan.

Hypersensitivity syndrome

Causative agents include allopurinol, amitriptyline, carbamazepine, dapsone, lamotrigine, minocycline, NSAIDs, olanzapine, oxcarbazepine, phenobarbital, phenytoin, saquinavir, spironolactone, sulfonamides, zalcitabine, and zidovudine.

Lichenoid

Causative agents include amlodipine, antimalarials, beta blockers, captopril, diflunisal, diltiazem, enalapril, furosemide, glimepiride, gold, leflunomide, levamisole, L-thyroxine, orlistat, penicillamine, phenothiazine, pravastatin, proton pump inhibitors (PPIs), rofecoxib, salsalate, sildenafil, tetracycline, thiazides, and ursodeoxycholic acid.^[26]

Linear IgA dermatosis

Causative agents include atorvastatin, captopril, carbamazepine, diclofenac, glibenclamide, lithium, phenytoin, and vancomycin.^[27]

Lupus erythematosus

Drug-induced systemic lupus erythematosus (SLE) is most commonly associated with hydralazine, procainamide, and minocycline.^[28] Beta blockers, chlorpromazine, cimetidine, clonidine, estrogens, isoniazid, lithium, lovastatin, methyldopa, oral contraceptives, quinidine, sulfonamides, tetracyclines, and tumor necrosis factor (TNF)-α inhibitors have been reported. Drug-induced subacute cutaneous lupus erythematosus (SCLE) is most commonly associated with hydrochlorothiazide. Calcium-channel blockers, cimetidine, griseofulvin, leflunomide, terbinafine, and TNF-α inhibitors have been reported.

Morbilliform (exanthematous)

Causative agents include ACE inhibitors, allopurinol, amoxicillin, ampicillin, anticonvulsants, barbiturates, carbamazepine, cetirizine, ginkgo biloba, hydroxyzine, isoniazid, nelfinavir, NSAIDs, phenothiazine, phenytoin, quinolones, sulfonamides, thalidomide, thiazides, TMP-SMX, and zalcitabine.

Pemphigus

Causative agents include thiols and nonthiols.^[29] Thiols include captopril, D-penicillamine, gold sodium thiomalate, mercaptopropionylglycine, pyritinol, thiamazole, and thiopronine. Nonthiols include aminophenazone, aminopyrine, azapropazone, cephalosporins, heroin, hydantoin, imiquimod, indapamide, levodopa, lysine acetylsalicylate, montelukast, oxyphenbutazone, penicillins, phenobarbital, phenylbutazone, piroxicam, progesterone, propranolol, and rifampin.

Photosensitivity

Causative agents include ACE inhibitors, amiodarone, amlodipine, celecoxib, chlorpromazine, diltiazem, furosemide, griseofulvin, lovastatin, nifedipine, phenothiazine, piroxicam, quinolones, sulfonamides, tetracycline, and thiazide.

Pseudoporphyria

Causative agents include amiodarone, bumetanide, chlorthalidone, cyclosporine, dapsone, etretinate, 5-fluorouracil (FU), flutamide, furosemide, hydrochlorothiazide/triamterene, isotretinoin, NSAIDs (including nalidixic acid and naproxen), oral contraceptive pills, and tetracycline

Psoriasis

Causative agents include ACE inhibitors, angiotensin receptor antagonists, antimalarials, beta-blockers, bupropion, calcium channel blockers, carbamazepine, interferon (IFN) alfa, lithium, metformin, NSAIDs, terbinafine, tetracyclines, valproate sodium, and venlafaxine.^{[30, 31, 32]}

Serum sickness

Causative agents include antithymocyte globulin for bone marrow failure, human rabies vaccine, penicillin, pneumococcal vaccine (in AIDS patients), and vaccines containing horse serum derivatives.^[33]

Serum sickness–like

Causative agents include beta-lactam antibiotics,^[34] cefaclor (most common), minocycline, propranolol, streptokinase, sulfonamides, and NSAIDs.

Stevens-Johnson syndrome

Causative agents include allopurinol, anticonvulsants, aspirin/NSAIDS, barbiturates, carbamazepine, cimetidine, ciprofloxacin, codeine, didanosine, diltiazem, erythromycin, furosemide, griseofulvin, hydantoin, indinavir, nitrogen mustard, penicillin, phenothiazine, phenylbutazone, phenytoin, ramipril, rifampicin, saquinavir, sulfonamides, tetracyclines, and TMP-SMX.^{[35, 36, 37]}

Sweet syndrome

Causative agents include all-trans-retinoic acid, celecoxib, granulocyte colony-stimulating factor (G-CSF), nitrofurantoin, oral contraceptives, tetracyclines, and TMP-SMX.

Toxic epidermal necrolysis

Causative agents include alfuzosin, allopurinol, anticonvulsants, aspirin/NSAIDs, sulfadoxine-pyrimethamine, isoniazid, lamotrigine, lansoprazole, letrozole, penicillins, phenytoin, prazosin, sulfonamides, tetracyclines, thalidomide, TMP-SMX, and vancomycin.

Urticaria

Causative agents include ACE inhibitors, alendronate, aspirin/NSAIDs, blood products, cephalosporins, cetirizine, clopidogrel, dextran, didanosine, infliximab, inhaled steroids, nelfinavir, opiates, penicillin, peptide hormones, polymyxin, PPIs, radiologic contrast material, ranitidine, tetracycline, vaccines, and zidovudine.

Vasculitis

Causative agents include adalimumab, allopurinol, aspirin/NSAIDs, cimetidine, gold, hydralazine, indinavir, leflunomide, levofloxacin, minocycline, montelukast, penicillin, phenytoin, propylthiouracil, PPIs, quinolones, ramipril, sulfonamide, tetracycline, thiazides, and thioridazine.

Vesiculobullous (other)

Causative agents include ACE inhibitors, aspirin/NSAIDs, barbiturates, captopril, cephalosporins, entacapone, estrogen, furosemide, griseofulvin, influenza vaccine, penicillamine, penicillins, sertraline sulfonamides, and thiazides.

Photosensitivity reaction

Long-term use of voriconazole causes significantly increased photosensitivity, resulting in some patients developing squamous cell carcinoma (SCC)^[38] and melanoma.^[39]  Studies have shown a dose-dependent increased risk for SCC: 5.6% with each 60-day exposure at a standard dose of 200 mg twice daily. At 5 years after transplantation, voriconazole conferred an absolute risk increase of 28% for SCC.

Psychotropic drugs associated with specific cutaneous reactions

Psychotropic agents associated with particular morphologic patterns include the following^[40] :

• Alopecia - Carbamazepine, fluoxetine, lamotrigine, lithium, gabapentin, and valproic acid
• EM - Barbiturates, carbamazepine, diazepam overdose, fluoxetine, gabapentin, lithium plus trazodone concurrently, phenobarbital, risperidone, sertraline, and valproic acid
• Morbilliform (exanthematous) - Alprazolam, barbiturates, bupropion, carbamazepine, chlorpromazine, desipramine, fluoxetine, lithium, maprotiline, nefazodone, risperidone, and trazodone
• Photosensitivity - All antipsychotics, barbiturates, carbamazepine, chlorpromazine, doxepin, imipramine, thioridazine, and valproic acid
• Pigmentation - Amitriptyline, carbamazepine, chlorpromazine, clozapine, diazepam following dermabrasion, gabapentin, haloperidol, lamotrigine, perphenazine, and thioridazine
• Urticaria - Bupropion, carbamazepine, chlordiazepoxide, fluoxetine, imipramine, lamotrigine, lithium, paroxetine, and trazodone
• Vasculitis - Fluoxetine, maprotiline, paroxetine, and trazodone

Chemotherapeutic drugs associated with specific cutaneous reactions

The following is a list of chemotherapeutic agents associated with particular morphologic patterns of cutaneous reactions.

Acneiform

Associated agents include cetuximab,^[41] dactinomycin, erlotinib,^[41] fluoxymesterone, gefitinib, medroxyprogesterone, and vinblastine.^[42]

Acral erythema (erythrodysesthesia)

Associated agents include capecitabine, cisplatin, clofarabine, cyclophosphamide, cytarabine, docetaxel, doxorubicin, fluorouracil, gemcitabine, MTX, tegafur, and vinorelbine.

Alopecia

All classes of chemotherapeutic agents are associated with alopecia (see the first image below). Commonly associations include alkylating agents, anthracyclines, bleomycin, doxorubicin, hydroxyurea, MTX, mitomycin, mitoxantrone, vinblastine, and vincristine. Coadministration of busulfan and cyclophosphamide can cause permanent hair loss. Nilotinib is a potent and selective bcr-abl kinase inhibitor used to treat imatinib-resistant chronic myeloid leukemia. Clinically, pink/fleshy perifollicular papules with diffuse alopecia may be seen (see the second image below), without follicular dropout. Histologically, it can demonstrate scarring or nonscarring alopecia with mixed features (see the third image below).^{[43, 44]}

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Male-pattern diffuse hair loss.

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Pink/fleshy perifollicular papules with diffuse alopecia.

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Horizontal section shows perifollicular fibrosis consistent with scarring alopecia.

Erythema multiforme

Associated agents include busulfan, chlorambucil, cyclophosphamide, diethylstilbestrol (DES), etoposide, hydroxyurea, mechlorethamine, MTX, mitomycin C, mitotane, paclitaxel, and suramin.

Erythema nodosum

Associated agents include busulfan, DES, and imatinib.

Fixed drug eruptions

Associated agents include dacarbazine, hydroxyurea, paclitaxel, and procarbazine.

Hyperpigmentation

Associated agents include bischloroethylnitrosourea (BCNU; carmustine), bleomycin, busulfan, brequinar, cisplatin, cyclophosphamide, dactinomycin, daunorubicin, docetaxel, doxorubicin, fluorouracil, fotemustine, hydroxyurea, ifosfamide, MTX, mithramycin, mitoxantrone, nitrogen mustard, procarbazine, tegafur, thiotepa, and vinorelbine.

Lichenoid

Associated agents include hydroxyurea, imatinib, and tegafur.

Lupus

Associated agents include aminoglutethimide, DES, hydroxyurea, leuprolide, and tegafur.

Morbilliform (exanthematous)

Associated agents include bleomycin, carboplatin, cis-dichloro-trans-dihydroxy-bis-isopropylamine platinum (CHIP), chlorambucil, cytarabine, docetaxel, DES, doxorubicin, etoposide, 5-FU, hydroxyurea, MTX, mitomycin C, mitotane, mitoxantrone, paclitaxel, pentostatin, procarbazine, suramin, and thiotepa.

Toxic epidermal necrolysis

Associated agents include asparaginase, bleomycin, chlorambucil, cladribine, cytarabine, doxorubicin, 5-FU, MTX, plicamycin, procarbazine, and suramin.

Urticaria

Associated agents include amsacrine, bleomycin, busulfan, carboplatin, chlorambucil, cisplatin, cyclophosphamide, cytarabine, daunorubicin, diaziquone, didemnin, DES, docetaxel, doxorubicin, epirubicin, etoposide, 5-FU, mechlorethamine, melphalan, MTX, mitomycin C, mitotane, mitoxantrone, paclitaxel, pentostatin, procarbazine, teniposide, thiotepa, trimetrexate, vincristine, and zinostatin.^[45]

Vasculitis

Associated agents include busulfan, cyclophosphamide, cytarabine, hexamethylene bisacetamide (HMBA), hydroxyurea, imatinib, levamisole, 6-mercaptopurine (MP), MTX, mitoxantrone, rituximab, and tamoxifen.

Cutaneous reactions caused by targeted chemotherapy agents

The following is a list of cutaneous reactions to targeted chemotherapy agents.

Epidermal growth factor receptor inhibitors

These agents (eg, gefitinib, cetuximab, erlotinib^[46] ) can give rise to abnormal scalp, face hair, or eyelash growth; anaphylactic infusion reaction (cetuximab); papules and annular plaques; paronychia with or without pyogenic granulomas; telangiectasias; and xerosis.^[47]  (See the images below.)

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Paronychia.

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Papules and annular plaques.

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Superficial and middermal perivascular infiltrate of lymphocytes and eosinophils. Foci of extravasation of erythrocytes.

Sorafenib

Sorafenib, a multikinase inhibitor, can cause hand-foot skin reaction, facial and scalp eruption, scalp dysesthesia, subungual splinter hemorrhages, alopecia, body hair loss, stomatitis, nipple hyperkeratosis or pain, and eruptive facial cysts.^[48]

Vemurafenib

Vemurafenib is a systemic medication approved by the Food and Drug Administration (FDA) for the treatment of metastatic melanoma. It selectively targets a specific BRAF mutation, V600E, in melanoma cells that allows unchecked proliferation of malignant cells. An unintended consequence of this medication has been the development of SCCs and keratoacanthomas in approximately one fourth of patients receiving the drug. The development of nonmalignant milia in a patient treated with vemurafenib has been reported.^[49]  (See the images below.)

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Numerous milia in patient treated with vemurafenib.

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Dilated infundibular cyst.

Ipilimumab and vemurafenib each improve the overall survival of patients with metastatic melanoma. Patients with stage IV melanoma harboring a BRAF V600E mutation treated with vemurafenib after receiving ipilimumab can develop a pruritic grade 3 (severe) maculopapular reaction within 6-8 days after the start of treatment with vemurafenib.^[50]

Tamoxifen

Tamoxifen, an antiestrogenic agent, has been widely used as adjuvant hormonal therapy in the treatment of breast cancer. Distinctive cutaneous eruptions present clinically as papules and plaques and histopathologically are characterized by squamous metaplasia of eccrine ductal epithelium. The condition has varied etiologies and can occur as a drug reaction, with chemotherapeutic drugs being frequently implicated.^[51]

Cytokine agents causing cutaneous reactions

Cutaneous reactions to cytokine therapy include the following^[52] :

• Erythropoietin - Abnormal hair growth, localized rash, palpebral edema, and widespread eczema
• G-CSF - Exacerbation of preexisting psoriasis, leukocytoclastic, localized erythema, localized pruritus, Sweet syndrome, and vasculitis
• Granulocyte macrophage colony-stimulating factor (GM-CSF) - Alopecia, epidermolysis, exacerbation of vasculitis, exfoliative dermatitis, flushing, localized erythema, localized wheals, maculopapular eruptions, pruritus, purpura, and urticaria
• IFN alfa - Alopecia, anasarca, cutaneous vascular lesions, eosinophilic fasciitis, exacerbation of preexisting herpes labialis, facial erythema, fixed drug eruption, hyperpigmentation, nummular eczema, paraneoplastic pemphigus, pruritus, psoriasis, sarcoidosis, SLE, urticaria, and xerostomia
• IFN beta - Fatal pemphigus vulgaris (when used in combination with interleukin (IL)-2, localized reactions (common), and urticaria
• IFN gamma - Increased relapses in melanoma and localized inflammation
• IL-1α - Mucositis, phlebitis, Shwartzman reaction, and xerostomia
• IL-1β - Erythema at surgical wound sites, phlebitis, and rash
• IL-2 - Blisters, cutaneous ulcers, desquamation, erythema, erythema nodosum, erythroderma, exacerbation of autoimmune skin disorders, flushing, hypersensitivity to iodine contrast material, necrosis, pruritus, telogen effluvium, TEN, and urticaria
• IL-3 - Facial flushing, hemorrhagic rash, thrombophlebitis, and urticaria
• IL-4 - Facial and peripheral edema, Grover disease, and papular rash
• IL-6 - Diffuse erythematous scaling macules and papules
• TNF-α antagonists can also cause Sweet-like hypersensitivity reactions and neutrophilic eccrine hidradenitis in addition to pustular folliculitis, psoriasis, interface dermatitis, lupus, vasculitis, and palmoplantar pustulosis^[53]
• IL-12 and IL-23 monoclonal antibodies^[54] - Injection-site reactions

• References

Epidemiology

In the United States, drug eruptions occur in approximately 2-5% of inpatients and in more than 1% of outpatients. Internationally, drug eruptions occur in approximately 2-3% of inpatients.

Elderly patients have an increased incidence of adverse drug reactions. Adverse cutaneous reactions to drugs are more common in women than in men.

• References

Prognosis

Most drug eruptions are mild and self-limited, and they typically resolve after the offending agent has been discontinued. Even after the responsible agent is discontinued, however, drug eruptions may be slow to clear or may worsen over the following few days. The degree of eosinophilia is predictive of the severity of the drug eruption.^{[55, 56]} 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. Drug therapy complications account for roughly 19% of adverse events in hospitalized patients, making them the most common type; they account for 3% of disabling injuries during hospitalization. ^[57] Mortality figures for EM major are significantly higher. SJS has a mortality of less than 5%, whereas the mortality 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.

• References

Patient Education

If the responsible drug is identified, the patient should be advised to avoid that drug in the future. The medical record should be clearly labeled. Patients should be encouraged to carry a card or some other form of emergency identification in their wallets that lists drug allergies or intolerances, especially if they have had a severe reaction.

Patients should be educated 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.

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History

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

Any concurrent infections, metabolic disorders, or immunocompromise (eg, from HIV infection, cancer, or chemotherapy) should be noted 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, toxic epidermal necrolysis [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.

The following should be noted in detail:

• All prescription and OTC drugs, including topical agents, vitamins,  herbal and homeopathic remedies, vaccinations, and implants or procedures associated with medicinal agents
• Interval between the introduction of a drug and the onset of the eruption
• Route, dose, duration, and frequency of drug administration
• Use of parenterally administered drugs, which are more likely to cause anaphylaxis than oral agents are
• Use of topically applied drugs, which are more likely than other drugs to induce delayed-type hypersensitivity reactions
• Use of multiple courses of therapy and prolonged administration of a drug, which can cause allergic sensitization
• Any improvement after drug withdrawal and any reaction with readministration

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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:

• Mucous membrane erosions
• Blisters - These herald a severe drug eruption
• Nikolsky sign - Epidermis sloughs with lateral pressure; this indicates a serious eruption that may constitute a medical emergency
• Confluent erythema
• Angioedema and tongue swelling
• Palpable purpura
• Skin necrosis (see the image below)
• Lymphadenopathy
• High fever, dyspnea, or hypotension

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Warfarin necrosis involving leg.

It is vital to appreciating the morphology and features of drug eruptions; doing so can help the clinician identify the causative medication and determine 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

In 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 that of 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 ultraviolet (UV) radiation. AGEP resolves spontaneously and rapidly, with fever and pustules lasting 7-10 days, followed by desquamation over a few days.

Dermatomyositislike

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 and DIHS

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and drug-induced hypersensitivity syndrome (DIHS) 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

Erythema multiforme (EM) includes a spectrum of diseases (ie, EM minor and EM major), as described below; however, many authorities have categorized Stevens-Johnson syndrome (SJS) and TEN as forms of EM major and have differentiated them on the basis of body surface involvement.

Erythema multiforme minor

Overall, this is a mild disease; patients are generally healthy. It is characterized by target lesions distributed predominantly on the extremities (see the images below). Mucous membrane involvement may occur but is not severe. Patients with EM minor recover fully, but relapses are common. Most cases are due to infection with herpes simplex virus (HSV), and treatment and prophylaxis with acyclovir are helpful.

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Erythema multiforme.

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Target lesions of erythema multiforme.

Stevens-Johnson syndrome

This is characterized by widespread skin involvement, large and atypical targetoid lesions, significant mucous membrane involvement, constitutional symptoms, and sloughing of 10% of the skin. SJS can be caused by drugs and infections (especially those due to Mycoplasma pneumoniae). (See the image below.)

View Image

Stevens-Johnson syndrome.

Stevens-Johnson syndrome/toxic epidermal necrolysis overlap

Epidermal detachment involves 10-30% of body surface area.

Toxic epidermal necrolysis

This is a severe skin reaction in which a prodrome of painful skin (not unlike sunburn) is quickly followed by rapid, widespread full-thickness skin sloughing. (See the image below.) It typically affects 30% or more of the total body surface area (TBSA). Secondary infection and sepsis are major concerns, and pneumonia may develop from aspiration of sloughed mucosa. Most cases are due to drugs. The risk of TEN is 1000-fold higher in HIV-positive patients than in the general population.

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Toxic epidermal necrolysis.

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 that is often secondary to infection, but it may also be caused by 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.

View Image

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 are a characteristic feature. Lesions occur 30 minutes to 8 hours after drug administration. Perioral and periorbital lesions may occur, but the most common locations are the hands, feet, and genitalia.

View Image

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. The syndrome usually begins within 1-3 weeks after a new drug is started, but in some cases, it may not develop until 3 months into therapy or even later. Aromatic anticonvulsant drugs (eg, phenytoin, phenobarbital, and carbamazepine) cross-react; 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 that are 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.

View Image

Vasculitic reaction on 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.

View Image

Lichen planus on neck.

Lupus

Drug-induced systemic lupus erythematosus (SLE) produces symptoms identical to those of classic 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

Although this is largely a drug-induced condition, it can also occur with the use of tanning beds and hemodialysis.^[8]  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 consists of sun protection and withdrawal of the medication.

View Image

Confluent necrosis of epidermis in toxic epidermal necrolysis.

Serum sickness and serum sickness–like

Serum sickness reactions 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. These reactions usually occur in conjunction 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 erythrocyte sedimentation rate (ESR), 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.)

• References

Complications

The diagnosis and management of adverse reactions attributable to cancer therapies is a rapidly growing and evolving area. The side effects of conventional cytotoxic chemotherapies are extensive and include mucositis, alopecia, pigmentary changes, and changes attributable to cytopenias.

Diffuse hyperpigmentation can be seen in busulfan therapy. Flagellate serpentine pigmentation can be seen with ifosfamide, docetaxel, and other agents in addition to bleomycin. Taxanes are strongly associated with onycholysis and paronychia.   

Targeted therapies such as epidermal growth factor receptor (EGFR) inhibitors often trigger papulopustular reactions. Inhibitors of KIT and BCR-ABL are associated with exanthems, hypopigmentation, and hand-foot reactions. Mammalian target of rapamycin (mTOR) inhibitors (eg, everolimus, rapamycin, and sirolimus) are associated with stomatitis. 

Some adverse effects may be helpful in predicting a beneficial clinical effect and good prognosis. Accurately documenting adverse reactions in a uniform manner is therefore of great importance. 

The National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) are used to document and grade toxic effects of oncologic treatments. More information can be found here.

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Laboratory Studies

History and physical examination are often sufficient for diagnosing mild asymptomatic eruptions. For diagnosing severe or persistent eruptions,  further diagnostic testing may be required.

A considerable amount of research has been directed toward identifying laboratory techniques that can establish the diagnosis of a drug eruption. At present, most of these techniques are not yet ready for routine clinical use. Diagnostic tools for the assessment of allergic rashes usually still depend on challenges to identify causative agents.^[58]

A complete blood count (CBC) 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 to renal and/or hepatic function indices in patients with severe reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or vasculitis.

Antibody or immunoserology tests may be ordered. Antihistone antibodies are noted in persons with drug-induced systemic lupus erythematosus (SLE), whereas anti-Ro/SS-A antibodies are most common in persons with drug-induced subacute cutaneous lupus erythematosus (SCLE).

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

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

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Imaging Studies

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

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Other Tests

Rechallenge testing by means of skin prick or patch tests 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 in the workup of drug eruptions.^[59]

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Procedures

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). Drug eruptions are associated with a wide range of histologic findings, and immunomodulating medications can alter the histologic picture.^[60]

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Histologic Findings

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).

View Image

Superficial perivascular inflammatory infiltrate with numerous eosinophils characteristic of 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).

View Image

Confluent necrosis of epidermis in toxic epidermal necrolysis.

• References

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.

In some cases, patients can continue to be treated through morbilliform eruptions (ie, keep taking medication even in the presence of 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 toxic epidermal necrolysis (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 hours a day. Mild topical steroids (eg, hydrocortisone, desonide) and moisturizing lotions are also used, especially during the late desquamative phase.

Severe reactions, such as Stevens-Johnson syndrome (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, there is evidence to indicate that intravenous immunoglobulin (IVIG) may improve outcomes for TEN patients.^{[9, 10, 11]}  Cyclosporine may also have a role in the treatment of TEN.

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 discontinuance of the anticonvulsant or other offending drug are crucial. If the drug is not stopped in time, patients may require liver transplantation. Treatment with systemic corticosteroids (eg, prednisone) has been advocated.

Oncodermatology

Many reactions can be managed symptomatically, but they should be monitored closely. Life-threatening reactions such as TEN, SJS, and drug rash with eosinophilia and systemic symptoms (DRESS) can begin as an innocuous-appearing macular exanthem. Stopping therapy immediately in those situations may be critical, along with a careful discussion with the oncology team regarding risks and benefits.

Acneiform eruptions due to epidermal growth factor receptor (EGFR) inhibitors respond to tetracyclines. Topical products containing retinoic acid, benzoyl peroxide, or salicylic acid are contraindicated.^[61]

A current and thorough review provides useful specifics for certain reaction patterns.^[61]

• References

Desonide (Desonate, DesOwen, Tridesilon)

• Dosing, Interactions, etc.

Clinical Context: 

• References

Hydrocortisone topical (AlaCort, AlaScalpt, Aquanil)

• Dosing, Interactions, etc.

Clinical Context: 

• References

Prednisone (Deltasone, Prednisone Intensol, Rayos)

• Dosing, Interactions, etc.

Clinical Context: 

• References

Hydroxyzine (Vistaril)

• Dosing, Interactions, etc.

Clinical Context: 

• References

Diphenhydramine (Alka-Seltzer Plus Allergy, Benadryl, Benadryl Allergy Dye-Free LiquiGels)

• Dosing, Interactions, etc.

Clinical Context: 

• References

Loratadine (Alavert, Claritin, Claritin RediTabs)

• Dosing, Interactions, etc.

Clinical Context: 

• References

Immune globulin IV (IGIV) (Alyglo, Asceniv, Bivigam)

• Dosing, Interactions, etc.

Clinical Context: 

• References

Cyclosporine (Gengraf, Neoral, Sandimmune)

• Dosing, Interactions, etc.

Clinical Context: 

• References