Drug-Induced Skin Reactions

Drug-Induced Skin Reactions

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Drug-Induced Skin Reactions Sandra Knowles, BScPhm Date of Revision: December 2014

Pathophysiology

Approximately 6% of all hospital admissions are the result of adverse drug reactions (ADRs).1 Drug-induced skin eruptions are the most frequently observed adverse reactions to medications. 3

Table 1: Dermatologic Terminology Bulla

A vesicle greater than 0.5 cm in diameter

Desquamation

Peeling of the skin

Erythema

Abnormal redness of the skin

Exanthem

An eruptive disease

Macule

A circumscribed, flat lesion less than 0.5 cm in diameter that differs from surrounding skin because of its colour

Morbilliform

Measles-like eruption

Papule

A solid, circumscribed, elevated lesion less than 0.5 cm in diameter

Plaque

An elevated, flat lesion greater than 0.5 cm in diameter

Purpura

Impalpable (macular) unblanchable purple spots

Pustule

A vesicle or bulla (usually less than 1 cm in diameter) filled with purulent exudates

Urticaria

Hives or an eruption of itching wheals

Vesicle

Blister or a small, circumscribed, elevation of the skin filled with clear fluid less than 0.5 cm in diameter

Wheal

A transitory, elevated papule or plaque caused by edema of the skin

In the Boston Collaborative Drug Surveillance Program, the prevalence of cutaneous ADRs in hospitalized patients was 2.2%.2 The morphology of cutaneous eruptions (Table 1 and Table 3) may be broadly classified as exanthematous, urticarial, blistering or pustular. Within each of these categories, the presence of a fever or other accompanying symptoms other than itch signals a more serious reaction, which requires immediate referral to a physician (Table 2).16 15

Table 2: Clinical Features of Severe Cutaneous Drug Reactions • Fever

• Enlarged lymph nodes • Arthralgias or arthritis • Shortness of breath, wheezing, hypotension • Confluent and diffuse erythema • Facial edema or involvement of central part of face • Palpable purpura • Skin tenderness • Blisters or epidermal detachment • Mucous membrane erosions • Angioedema or swelling of tongue

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Table 3: Description of Drug Eruptions Type of eruption

Exanthematous

Urticarial

Blistering

Pustular

↓

↓

↓

↓

Fever?

Fever?

Fever?

Fever?

No

Yes

No

Yes

Simple

Drug rash with eosinophilia and systemic symptoms (DRESS) also known as drug hypersensitivity syndrome reaction

Urticaria and/or angioedema

Serum sickness-like reaction

Onset after initial exposure

7–10 days

14–21 days (up to 3 months)

Minutes to hours

Clinical features

Rash only

Fever, rash, eosinophilia, internal organ involvement (may be asymptomatic)

Common drug causes

Anticonvulsant medications, ß-lactam antibiotics, sulfonamide antibiotics 2

Treatment

Testing

No

Yes

No

Bullous fixed drug eruption

SJS, TEN

Acneiform

AGEP

7–21 days

Hours to days

7–14 days

7–21 days

Less than or equal to 10 days

Urticaria ± angio-edema

Fever, rash, arthralgias ± lymphadenopathy

Solitary erythematous macules that may blister and that recur in the same skin area after readministration of drug

Targets ± epidermal detachment, mucous membrane involvement

Atypical areas: arms, legs. No comedones

Many pustules on diffuse erythematous base. Fever. 50% have other cutaneous lesions. 25% have mucosal erosions

Allopurinol,4 anticonvulsants (barbiturates, carbamazepine, lamotrigine, phenytoin),5 dapsone, sulfonamide antibiotics

ASA,6 ACE inhibitors,7 penicillins, NSAIDs,6 opioid analgesics, radiocontrast media, sulfonamide antibiotics

Bupropion,8 cefaclor,9 minocycline,10 penicillins, rituximab,11 sulfonamide antibiotics

Acetaminophen, barbiturates, NSAIDs, sulfonamide antibiotics, tetracycline

Allopurinol,12 anticonvulsants (barbiturates, carbamazepine, lamotrigine, phenytoin), NSAIDs (especially piroxicam),13 sulfonamide antibiotics

Androgens, anticonvulsants, corticosteroids (systemic), epidermal growth factor receptor inhibitors (e.g., cetuximab, erlotinib, gefitinib), isoniazid, lithium

ß-lactam antibiotics, calcium channel blockers, quinolones, 14 macrolide antibiotics

Symptomatic therapy (e.g., antihistamines, soothing baths, topical corticosteroids)

Systemic cortico-steroids, symptomatic therapy

Symptomatic relief (e.g., antihistamines, topical corticosteroids); angioedema requires immediate therapy with epinephrine

Symptomatic treatment (including antipyretic, antihistamine); short course of oral corticosteroids in patients with severe symptoms

Symptomatic therapy (e.g., moisturizer, topical corticosteroid)

Supportive measures, intravenous immune globulin (IVIG), cyclosporine

Topical tretinoin (if drug cannot be discontinued)

Symptomatic therapy, corticosteroids if severe

Mononucleosis

CBC, liver enzymes, urinalysis, thyroid function tests

Skin test for penicillin, if suspected as causal agent

CBC, liver enzymes, urinalysis, skin biopsy

Yes

CBC, skin biopsy

Abbreviations: AGEP = acute generalized exanthematous pustulosis; CBC = complete blood count; SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis

Exanthematous Eruptions

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Simple Eruptions Exanthematous eruptions, also known as morbilliform or maculopapular eruptions, are the most common cutaneous ADRs. These eruptions have been reported to account for approximately 95% of all drug-induced cutaneous eruptions.17 They usually start as erythematous macules and papules on the trunk, become confluent and later spread symmetrically to the face and limbs; there is no evidence of blistering or pustulation. Resolution occurs with a change in colour from bright red to a brownish red. This colour change may be followed by scaling or desquamation. Pruritus is a frequent clinical symptom but is not necessarily present. Simple eruptions usually begin within 7–10 days of starting therapy and resolve within 7–14 days after discontinuation of the drug.18

Complex Exanthems Drug rash eosinophilia and systemic symptoms (DRESS), also known as the drug hypersensitivity syndrome reaction is a complex drug reaction that includes the triad of fever, skin eruption (usually exanthematous), eosinophilia and internal organ involvement such as hepatitis, nephritis or agranulocytosis, although the internal organ involvement may be asymptomatic.19 The syndrome usually begins with fever at 2–3 weeks from initial drug exposure, and patients often initially complain of malaise.16 In patients with a history of DRESS, re-exposure to the offending agent may cause development of symptoms within 1 day. DRESS is not related to dose or serum concentration of the drug. Although symptoms resolve in most patients after discontinuation of the drug, some patients develop autoimmune disease and/or production of autoantibodies after resolution of DRESS.20,21 This can include development of type 1 diabetes mellitus, autoimmune thyroid disease or lupus erythematosus. (See Photo, Hypersensitivity Syndrome Reaction.) Photo 1: DRESS (Hypersensitivity Syndrome Reaction)

Courtesy of Dr. John Sullivan

Urticarial Eruptions Simple Eruptions Urticaria, characterized by extremely pruritic red raised wheals of varying sizes and shapes, and angioedema, affecting deep dermal and subcutaneous tissues, are reversible types of edema affecting the skin. In general, individual lesions of urticaria last for less than 24 hours, although new lesions continually develop. Although many different medications can cause urticaria, angioedema or both, other causal agents are food, physical factors (e.g., cold, pressure), infections and idiopathic factors.22 In fact, medications account for only 5–10% of urticaria cases. Adverse reactions to ACE inhibitors, manifesting as angioedema, may occur within hours of starting the drug but can occur as late as 1 week to several months into therapy.23

Complex Eruptions Serum sickness-like reactions are defined by fever, rash (usually urticarial) and arthralgias occurring 1–3 weeks after drug initiation. In contrast to true serum sickness, serum sickness-like reactions are not associated with immune complex formation, vasculitis or renal lesions. (See Photo, Serum Sickness-like Reaction.) Photo 2: Serum Sickness-Like Reaction

Courtesy of Dr. John Sullivan

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Blistering Eruptions Simple Eruptions Fixed drug eruptions usually appear as pruritic, erythematous, bright-red or dusky-red macules that may evolve into an edematous plaque. In some patients multiple lesions may be present. Blistering and erosion may occur on mucosal surfaces, especially the genitalia and the lips, and some patients may complain of burning or stinging on the affected skin sites. Fixed drug eruptions recur in the same skin area after readministration of the causative medication.24

Complex Eruptions Serious dermatologic eruptions include Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The typical course of TEN consists of extreme illness, including fever and malaise, with generalized tender or painful erythema of the skin followed by extensive epidermal necrosis and sloughing of any area of skin or mucous membrane leading to marked loss of fluids and electrolytes.16 It also predisposes the patient to pneumonia and septicemia. Mortality as high as 30% has been reported as a result of these complications. (See Photo, Toxic Epidermal Necrolysis.) Photo 3: Toxic Epidermal Necrolysis

Courtesy of Dr. John Sullivan

Pustular Eruptions Simple Eruptions Drug-induced acne may appear in atypical areas, such as arms and legs, and comedones are usually absent (see Photo, Acneiform Eruption). An acneiform eruption often occurs following treatment with epidermal growth factor receptor inhibitors (e.g., gefitinib, erlotinib, cetuximab). The acneiform rash is often accompanied by paronychia, dry skin and skin fissures. The eruption is dose dependent, with respect to both incidence and severity.25 Photo 4: Acneiform Eruption

Lemoine/Science Photo Library

Complex Eruptions Acute generalized exanthematous pustulosis (AGEP) is characterized by acute onset, with fever and a cutaneous eruption with nonfollicular pustules.

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Generalized desquamation occurs 2 weeks after the initial reaction. (See Photo, Acute Generalized Exanthematous Pustulosis.) Photo 5: Acute Generalized Exanthematous Pustulosis

Courtesy of Dr. John Sullivan

Other Skin Eruptions Photosensitivity

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Photosensitivity is an adverse cutaneous response to normally harmless doses of ultraviolet radiation. Ultraviolet A (UVA) rays are responsible for the majority of photosensitivity reactions. There are 2 types of photosensitivity reactions: phototoxicity and photoallergy. Phototoxicity, the more common type, refers to an increased reactivity of the skin to ultraviolet (UV) radiation. This can occur on the first exposure to a drug, is dose related and is confined to exposed areas of the skin (e.g., face, neckline, back of the hands, arms, forearms and tops of feet). It generally resembles an exaggerated sunburn. These reactions do not contraindicate continued treatment with the drug, or its reintroduction, as long as effective protection against sunlight is ensured. Drugs associated with phototoxicity include amiodarone, fluoroquinolones, methotrexate, phenothiazines and tetracyclines. See Prevention and Treatment of Sun-Induced Skin Damage, Table 1: Medications That May Cause Phototoxic Reactions. Photoallergic reactions involve the immune system and therefore require prior sensitization to the drug. Photoallergy is delayed, usually occurring within 24–48 hours of exposure. Pruritus may occur prior to the onset of the cutaneous eruption. The lesions are often eczematous (e.g., with erythema, vesicles and scaling) and may spread beyond exposed areas. Carbamazepine, chloroquine, NSAIDs, and sulfonamides have been reported to cause photoallergic reactions.

Contact Dermatitis Contact dermatitis is an inflammatory reaction of the skin that results from direct contact from a causative agent.27 Most cases of contact dermatitis are either allergic contact dermatitis (e.g., poison ivy, nickel) or irritant contact dermatitis (e.g., chemicals, hot peppers). See Atopic, Contact, and Stasis Dermatitis.

Patient Assessment

Information about the assessment of patients with possible drug-induced skin reactions can also be found in Figure 1. The patient with a drug eruption often requires a referral to a physician. Although the rash may be self-limiting and only require nonprescription treatment, the patient may require alternative therapy (e.g., a patient develops a nonspecific maculopapular rash 7 days after starting lamotrigine for a seizure disorder, the lamotrigine is discontinued and now an alternative drug is needed for the seizure disorder). Many drug eruptions are more complex in that they are also associated with systemic signs. A patient who develops any systemic symptoms such as malaise, fever or shortness of breath, requires immediate referral to a physician since this may signal a more serious reaction.28 Since many skin diseases mimic drug reactions, it is important to carefully evaluate other causes of the cutaneous eruption. For example, guttate psoriasis may develop in a person being treated with penicillin for streptococcal infection, but the skin lesions are those of psoriasis and not a drug reaction. Differential diagnoses often include viral exanthems (e.g., infectious mononucleosis, rubella or roseola), bacterial infections, Kawasaki disease, collagen vascular disease and neoplasia. Disease states can also act as cofactors in the development of a cutaneous eruption. For example, patients with infectious mononucleosis who are also taking ampicillin or amoxicillin are at an increased risk for developing an exanthematous eruption compared to other patients (60–100% versus 3–7%, respectively). As well, between 44%–83% of HIV-infected individuals experience some form of adverse reactions associated with sulfamethoxazole-trimethoprim, whereas these events occur in less than 10% of the general population.29 Cutaneous reactions to drugs frequently occur in complicated clinical scenarios that may include exposure to multiple agents, in which case a timeline should be developed. It is important that a detailed history be obtained for evaluation of an adverse drug reaction. This includes dosage, rechallenge and dechallenge, and onset of reaction. A history of prior exposure to the drug and related compounds is also important. If a patient has become sensitized to a drug they have received previously, on re-exposure to that drug the rash may appear sooner. New drugs initiated within the preceding 6 weeks are potential causative agents, as are drugs that have been used intermittently, including nonprescription preparations and herbal and naturopathic remedies.30 Although excipients do not cause ADRs in most individuals, there are isolated case reports of excipients causing skin reactions.31 The final step in the assessment of a patient with a cutaneous eruption is to determine the probability that each possible drug may have caused the reaction. A cutaneous eruption is commonly mislabelled as a drug reaction. This misdiagnosis may unnecessarily limit the future use of a particular medication or any related compound. It is important to document the possible drug reaction in the patient's medical and pharmacy records to ensure that future therapies are not

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pharmacologically and/or chemically related to the suspect drug. Figure 1: Assessment of Patients with Possible Drug-induced Skin Reactions

a Examples of underlying diseases include infectious mononucleosis and ampicillin-related reactions; HIV and sulfamethoxazole-trimethoprim; infectious etiologies, e.g., viral skin rash, bacterial infections. b At this point perform a literature search to determine if this reaction has been reported in association with this drug.

Goals of Therapy

Attempt to determine causality of the drug eruption

Control symptoms associated with the drug eruption (e.g., pruritus)

Provide patient education about drugs to avoid and those which can be used in the future

For patients with photosensitivity reactions, provide information regarding preventive measures (e.g., avoiding UV radiation, wearing broad-spectrum sunscreen)

Report all unexpected or serious ADRs or reactions to recently marketed drugs to Health Canada, through the Canada Vigilance Program or through one of the Canada Vigilance Regional Offices.

Nonpharmacologic Therapy

Many drug-induced skin eruptions, such as urticaria, are often pruritic. Dry skin and overheating can exacerbate pruritus. Overbathing, hot water, harsh soaps and bubble bath preparations dry and irritate the skin and should be avoided.32 A simple physical measure is cooling the skin by tepid showering. Four tablespoons of baking soda in the bath may also help to relieve pruritus associated with urticaria. Tap water compresses can be used on blistering lesions. To compress, moisten gauze or other thin cloth in warm tap water and apply for 20 minutes 4–6 times daily. Alternatively, the compresses can be applied intermittently, 1 minute on – 1 minute off for 20 minutes. Oral lesions can be treated with warm water or saline rinses. Avoidance of factors that may enhance pruritus, such as wearing of tight elasticized apparel or coarse woolen fabrics, is also important.

Pharmacologic Therapy

Table 4 addresses pharmacologic management of drug-induced skin reactions. Both traditional H1-blocking antihistamines and newer nonsedating antihistamines are effective in the treatment of pruritus associated with urticaria.33 (See Allergic Rhinitis for adult and pediatric doses of nonprescription oral antihistamines.) The addition of H2-blocking antihistamines (e.g., ranitidine, famotidine) has been used in some patients with chronic urticaria with some initial benefit;33 patients with acute drug-induced urticaria do not generally require additional therapy with H2-blocking antihistamines. Patients whose symptoms do not improve within 5–7 days should be referred to a physician. The use of topical

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antihistamines, such as those containing diphenhydramine, is not recommended due to risk of allergic contact dermatitis as well as increased systemic absorption when applied to open lesions. Patients with urticarial lesions should avoid NSAIDs or ASA since these agents may exacerbate urticaria; they are common causes of drug-induced urticaria. Discontinuation of the offending drug is considered paramount in the management of patients with cutaneous eruptions. However, in some cases the drug may be continued and the reaction “treated through.”34 This decision is influenced by the severity and probable course of the reaction, disease for which the drug was prescribed, ease or difficulty with which the reaction can be managed and the availability of chemically unrelated drugs with similar pharmacologic properties.35 Bathing with colloidal oatmeal bath preparations is helpful for pruritus. Unscented moisture cream or white petrolatum should be applied to the skin while it is slightly damp to retard water evaporation. Topical agents may be kept in a refrigerator because the physical cooling enhances their antipruritic effect. Topical cream or lotion astringents, such as plain calamine lotion or zinc oxide cream, can also be used. The use of cooling salves such as menthol 0.25–0.5% or camphor 0.25–0.5% cream may be helpful although they may occasionally be irritating. Another local treatment is half-strength hydrogen peroxide rinses for oral lesions. Counsel patients with photosensitivity reactions to stay out of the sun until the reaction resolves, or to wear sunscreen and protective clothing. Exposed areas should be covered with a sunscreen that protects in the UVA range with a minimum SPF of 15–30. (See Prevention and Treatment of Sun-Induced Skin Damage for a further discussion of sunscreens.) Mild to moderate phototoxic reactions can be managed as ordinary sunburn (e.g., oral analgesics, cooling compresses or baths, emollient lotions).26 Topical corticosteroids are often used in the management of patients with drug-induced skin eruptions. Hydrocortisone 0.5%, a weak topical corticosteroid, is available without a prescription in ointment, cream or lotion. Moderately potent clobetasone butyrate 0.05% cream is also available without a prescription. Ointments are more occlusive and are preferred for dry or scaly lesions, whereas creams are used in moist areas since they are more drying. Lotions are useful for the scalp and other hairy areas or for application to large body areas. Adults and children 2 years of age and older can apply hydrocortisone sparingly, with gentle massage, onto the affected area up to 3 or 4 times a day. Clobetasone butyrate is limited to patients 12 years and older for no more than 7 days of continuous treatment. It should not be used on the face or intertriginous folds, whereas hydrocortisone may be used on these areas. If the skin lesions persist or worsen after 5–7 days of nonprescription topical corticosteroid therapy, the patient should seek the advice of a physician. Table 4: Nonprescription Pharmacologic Therapy of Drug-induced Skin Reactions

For product selection, consult Compendium of Products for Minor Ailments. Analgesic Products: Internal Analgesics and Antipyretics; Cough, Cold and Allergy Products; Skin Care Products: Dermatitis and Dry Skin, and First Aid. Class

Drug

Dose

Comments

Antihistamines, H1 blocking

diphenhydramine, loratadine, cetirizine, others

See Allergic Rhinitis

Patients whose symptoms do not improve within 5–7 days should be referred to a physician.

Bath emollients

colloidal oatmeal

Add to bath water as needed

Apply unscented moisture cream or white petrolatum to the skin while it is still slightly damp to avoid water evaporation.

Astringents

calamine lotion, zinc oxide

Cooling salves

menthol- or camphorcontaining salves

0.25–5% in various bases

May occasionally be irritating. Store in refrigerator as physical cooling enhances their effect.

Skin antiseptic

hydrogen peroxide

Half-strength rinses

Useful for oral lesions.

Topical corticosteroids

hydrocortisone 0.5%

0.5% cream/ointment/lotion sparingly with gentle massage up to 3–4 times daily

Cream: useful in moist areas (due to possible drying effect) Ointment: preferred for dry or scaly lesions

Store in refrigerator as physical cooling enhances antipruritic effect.

Lotion: useful for scalp and other hairy areas or for application to large body areas

Patients whose symptoms do not improve within 5–7 days should be referred to a physician. Topical corticosteroids

clobetasone butyrate 0.05%

0.05% cream sparingly twice daily for up to 7 days

Total dose applied should not exceed 15 g/wk in adults. For use in adults and children aged 12 y and older.

Analgesics

acetaminophen, ibuprofen, naproxen

See Prevention and Treatment of Sun-Induced Skin Damage

Useful for treatment of mild to moderate phototoxic reactions that can be managed as for ordinary sunburn. Avoid ASA and NSAIDs in urticarial lesions.

Emollient lotions

unscented moisture creams or white petrolatum

See Prevention and Treatment of Sun-Induced Skin Damage

After bathing, apply unscented moisture cream or white petrolatum to the skin while it is still slightly damp to avoid water evaporation. Useful for treatment of mild to moderate phototoxic reactions that can be managed as for ordinary sunburn.

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Monitoring of Therapy

Pharmacists can provide symptomatic therapy for patients with drug-induced skin lesions. After discontinuation of the offending medication, most drug-induced cutaneous eruptions will resolve in 5–7 days. However, for patients with serious drug-induced reactions, symptoms generally begin to abate within days, but this may vary from weeks to months. Many patients require a referral to a physician; some patients may require a change in therapy, drug testing or follow-up (e.g., measurement of liver function tests). Any patient who has a fever or other accompanying symptoms such as malaise should seek the advice of a physician.

Advice for the Patient

Provide the patient with information regarding the adverse drug reaction. This includes the drug involved in the reaction (if known), the patient's predisposition to possible recurrence on exposure to the drug, potential cross-reaction to other drugs (e.g., ASA and NSAIDs) and genetic predisposition of family members, if applicable. No genetic basis has been found for most adverse drug reactions, including penicillin-allergic reactions. However, for serious reactions such as DRESS, serum sickness-like reactions to cefaclor and serious dermatologic reactions (e.g., SJS and TEN), the risk in first-degree relatives of patients who have had reactions is substantially higher, and counselling family members is a crucial part of the management process. Studies have shown that genetic susceptibility may also increase the risk of developing SJS/TEN. In a Han Chinese population, HLA-B*1502 was strongly associated with carbamazepine-induced Stevens-Johnson syndrome.36 In response to these studies, the US Food and Drug Administration (FDA) and Health Canada recommend genetic screening for patients of Asian ancestry before initiation of carbamazepine therapy, and avoidance of carbamazepine in patients who test positive.37 In addition, advise the patient to enroll in the Medic Alert program.

Suggested Readings

Cotliar J. Approach to the patient with a suspected drug eruption. Semin Cutan Med Surg 2007;26:147-54. Mockenhaupt M. Severe drug-induced skin reactions: clinical pattern, diagnostics and therapy. J Dtsch Dermatol Ges 2009;7:142-60.

References 1. Pirmohamed M, James S, Meakin S et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18,820 patients. BMJ 2004;329:15-9. 2. Bigby M, Jick S, Jick H et al. Drug-induced cutaneous reactions. A report from the Boston Collaborative Drug Surveillance Program on 15,438 consecutive inpatients, 1975 to 1982. JAMA 1986;256:3358-63. 3. Segal AR, Doherty KM, Leggott J et al. Cutaneous reactions to drugs in children. Pediatrics 2007;120:e1082-96. 4. Lee HY, Ariyasinghe JT, Thirumoorthy T. Allopurinol hypersensitivity syndrome: a preventable severe cutaneous adverse reaction? Singapore Med J 2008;49:384-7. 5. Knowles SR, Dewhurst N, Shear NH. Anticonvulsant hypersensitivity syndrome: an update. Expert Opin Drug Saf 2012;11:767-78. 6. Knowles SR, Drucker AM, Weber EA et al. Management options for patients with aspirin and nonsteroidal antiinflammatory drug sensitivity. Ann Pharmacother 2007;41:1191-200. 7. Dykewicz MS. Cough and angioedema from angiotenin-converting enzyme inhibitors: new insights into mechanisms and management. Curr Opin Allergy Clin Immunol 2004;4:267-70. 8. McCollom RA, Elbe DH, Ritchie AH. Bupropion-induced serum sickness-like reaction. Ann Pharmacother 2000;34:471-3. 9. Kearns GL, Wheeler JG, Childress SH et al. Serum sickness-like reactions to cefaclor: role of hepatic metabolism and individual susceptibility. J Pediatr 1994;125:805-11. 10. Knowles SR, Shapiro L, Shear NH. Serious adverse reactions induced by minocycline. Report of 13 patients and review of the literature. Arch Dermatol 1996;132:934-9. 11. Todd DJ, Helfgott SM. Serum sickness following treatment with rituximab. J Rheumatol 2007;34:430-3. 12. Halevy S, Ghislain PD, Mockenhaupt M et al. Allopurinol is the most common cause of Stevens-Johnson syndrome and toxic epidermal necrolysis in Europe and Israel. J Am Acad Dermatol 2007;58:25-32. 13. Mockenhaupt M, Viboud C, Dunant A et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. J Invest Dermatol 2008;128:35-44. 14. Sidoroff A, Dunant A, Viboud C et al. Risk factors for acute generalized exanthematous pustulosis (AGEP)-results of a multinational case control study (EuroSCAR). Br J Dermatol 2007;157:989-96. 15. Roujeau JC, Stern RS. Severe adverse cutaneous reactions to drugs. N Engl J Med 1994;331:1272-85. 16. Mockenhaupt M. Severe drug-induced skin reactions: clinical pattern, diagnostics and therapy. J Dtsch Dermatol Ges 2009;7:142-60. 17. Gerson D, Sriganeshan V, Alexis JB. Cutaneous drug eruptions: a 5-year experience. J Am Acad Dermatol 2008;59:995-9. 18. Stern RS. Clinical practice. Exanthematous drug eruptions. N Engl J Med 2012;366:2492-501. 19. Cacoub P, Musette P, Descamps V et al. The DRESS syndrome: a literature review. Am J Med 2011;124:588-97. 20. Kano Y, Ishida T, Hirahara K et al. Visceral involvements and long-term sequelae in drug-induced hypersensitivity syndrome. Med Clin North Am 2010;94:743-59. 21. Brown RJ, Rother KI, Artman H et al. Minocycline-induced drug hypersensitivity syndrome followed by multiple autoimmune sequelae. Arch Dermatol 2009;145:63-6. 22. Lipozencic J, Wolf R. Life-threatening severe allergic reactions: urticaria, angioedema, and anaphylaxis. Clin Dermatol 2005;23:193-205. 23. Pavletic AJ. Late angio-edema in patients taking angiotensin-converting-enzyme inhibitors. Lancet 2002;360:493-4. 24. Lee AY. Fixed drug eruptions. Incidence, recognition, and avoidance. Am J Clin Dermatol 2000;1:277-85. 25. Wu PA, Balagula Y, Lacouture, ME et al. Prophylaxis and treatment of dermatologic adverse events from epidermal growth factor receptor inhibitors. Curr Opin Oncol 2011;23:343-51. 26. Moore DE. Drug-induced cutaneous photosensitivity: incidence, mechanism, prevention and management. Drug Saf 2002;25:345-72. 27. Wolff K, Johnson R, Suurmond D. Contact dermatitis. In: Wolff K, Johnson RA, eds. Fitzpatrick's color atlas and synopsis of clinical dermatology. 5th ed. New York: McGraw-Hill; 2005. 28. Cotliar J. Approach to the patient with a suspected drug eruption. Semin Cutan Med Surg 2007;26:147-54. 29. Davis CM, Shearer WT. Diagnosis and management of HIV drug hypersensitivity. J Allergy Clin Immunol 2008;121:826-32.

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30. Lim YL, Thirumoorthy T. Serious cutaneous adverse reactions to traditional Chinese medicines. Singapore Med J 2005;46:714-7. 31. Caliskaner Z, Ozturk S, Karaayvaz M. Not all adverse drug reactions originate from active component: coloring agent-induced skin eruption in a patient treated with rifampicin. Allergy 2003;58:1077-9. 32. Tan JK. Pruritus. In: Repchinsky C, ed. Therapeutic choices. 6th ed. Ottawa: Canadian Pharmacists Association; 2011. p. 1202-13. 33. Deacock SJ. An approach to the patient with urticaria. Clin Exp Immunol 2008;153:151-61. 34. Valeyrie-Allanore L, Sassolas B, Roujeau JC. Drug-induced skin, nail and hair disorders. Drug Saf 2007;30:1011-30. 35. Drake LA, Dinehart SM, Farmer ER et al. Guidelines of care for cutaneous adverse drug reactions. American Academy of Dermatology. J Am Acad Dermatol 1996;35:458-61. 36. Chung WH, Hung SI, Hong HS et al. Medical genetics: a marker for Stevens-Johnson syndrome. Nature 2004;428:486. 37. Health Canada. Patients of Asian ancestry using epilepsy drug carbamazepine may be at increased risk of serious skin reactions. Ottawa: Health Canada; 2008. Available from: www.healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2008/13283a-eng.php. Accessed October 30, 2014.

Skin Reactions to Medications — What You Need to Know

Skin rashes may be caused by infections or other diseases. However, some rashes can be caused by an allergic reaction to a prescribed medicine.

You should stop taking the suspected medicine right away. The rash may continue to get worse for one to two days. It should begin to get better after five to seven days. See your doctor if: the rash does not improve or gets worse

you have a fever or feel like you have the flu (loss of appetite, nausea).

What should you do if you have a bad reaction to a medicine?

Contact your doctor or pharmacist to inform them about your rash. Find out about other medicines that may cause a similar reaction. If you see a new doctor or pharmacist, be sure to tell them about your reaction. Consider registering in the Medic Alert program.

How can you treat the rash? For rashes that are itchy:

Cool the skin with a lukewarm shower several times a day. You can also try a bath, adding an oatmeal bath preparation or four tablespoons of baking soda to the water.

Ask your doctor or pharmacist for advice about creams or lotions to relieve the itch. Ointments can be used for dry areas and creams are recommended for moist areas. Lotions are useful for the scalp and other hairy areas. Examples of nonprescription products are: plain calamine lotion or zinc oxide cream hydrocortisone 0.5% cream, ointment or lotion. Follow the directions on the package or ask the pharmacist for advice on how to use these products. moisturizing cream (use an unscented form)

Keep creams and ointments in the refrigerator. The coolness will help control the itch. Avoid tight clothing or rough fabrics.

Avoid getting your body overheated. Dress lightly.

Check with your pharmacist to see whether you can take an antihistamine to relieve the itching. Some antihistamines may interfere with other medicines or medical conditions. Use of antihistamines in creams is not recommended.

CPhA assumes no responsibility for or liability in connection with the use of this information. For clinical use only and not intended for for use by patients. Once printed there is no quarantee the information is up-to-date. [Printed on: 03-03-2016 05:45 AM] RxTx, Compendium of Therapeutics for Minor Ailments © Canadian Pharmacists Association, 2016. All rights reserved

03-Mar-16 5:45 AM