Evidence-Based Reviews

Drug eruptions: 6 dangerous rashes

Current Psychiatry. 2008 April;7(4):101-109

References

1. Warnock JK, Skonicki J. Drug eruptions: Is your patient’s rash serious or benign? Current Psychiatry 2008;7(3):42-56.

2. Kimyai-Asadi A, Harris JC, Nousari HC. Critical overview: adverse cutaneous reactions to psychotropic medications. J Clin Psychiatry 1999;60(10):714-25.

3. Knowles SR, Shapiro LE, Shear NH. Anticonvulsant hypersensitivity syndrome: incidence, prevention, and management. Drug Saf 1999;21(6):489-501.

4. Trileptal [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2007.

5. Hirsch LJ, Weintraub DB, Buchsbaum R, et al. Predictors of lamotrigine-associated rash. Epilepsia 2006;47(2):318-22.

6. Warnock CA, Azadian AG. Cross-sensitivity between paroxetine and sertraline. Ann Pharmacother 2002;36(4):631-3.

7. Babu KS, Belgi G. Management of cutaneous drug reactions. Curr Allergy Asthma Rep 2002;2(1):26-33.

8. Olfson M, Wilner MT. A family case history of fluoxetine-induced skin reactions. J Nerv Ment Dis 1991;179(8):504-5.

9. Wong IC, Mawer GE, Sander JW. Factors influencing the incidence of lamotrigine-related skin rash. Ann Pharmacother 1999;33(10):1037-42.

10. Chadwick D, Shaw MDM, Foy P, et al. Serum anticonvulsant concentrations and the risk of drug induced skin eruptions. J Neurol Neurosurg Psychiatry 1984;47(6):642-4.

11. Lamictal [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2007.

12. Warnock JK, Morris DW. Adverse cutaneous reactions to mood stabilizers. Am J Clin Dermatol 2003;4(1):21-30.

13. Warnock JK, Morris DW. Adverse cutaneous reactions to antidepressants. Am J Clin Dermatol 2002;3(5):329-39.

14. Warnock JK, Morris DW. Adverse cutaneous reactions to antipsychotics. Am J Clin Dermatol 2002;3(9):629-36.

15. Moore DE. Drug-induced cutaneous photosensitivity: incidence, mechanism, prevention, and management. Drug Saf 2002;25(5):345-72.

16. Shear NH, Knowles SR, Sullivan JR, Shapiro L. Cutaneous reactions to drugs. In: Freedburg IM, Eisen AZ, Wolff K, et al, eds. Fitzpatrick’s dermatology in general medicine. 6th ed. New York, NY: McGraw-Hill; 2003:1330-7.

17. Chosidow OM, Stern RS, Wintroub BU. Cutaneous drug reactions. In: Kasper DL, Braunwald E, Fauci AS, et al, eds. Harrisons’s principles of internal medicine. 16th ed. New York, NY: McGraw-Hill; 2005:318-24.

18. Brushan M, Craven N. Erythema multiforme. In: Lebwohl MG, Heymann WR, Berth-Jones J, Coulson I, eds.Treatment of skin disease: comprehensive therapeutic strategies. London, UK: Mosby; 2002:196-9.

19. Al-Joani KA, Fedele S, Porter SR. Erythema multiforme and related disorders. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103(5):642-54.

20. Wolf R, Orion E, Marcos B, Matz H. Life-threatening acute adverse cutaneous drug reactions. Clin Dermatol 2005;23(2):171-81.

21. Pereira FA, Mudgil AV, Rosmarin DM. Toxic epidermal necrolysis. J Am Acad Dermatol 2007;56(2):181-200.

22. Rojeau JC, Stern RS. Medical progress: severe adverse cutaneous reactions to drugs. N Engl J Med 1994;331(19):1272-85.

23. Bastuji-Garin S, Rzany B, Stern R, et al. Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme. Arch Dermatol 1993;129(1):92-6.

24. Craven N. Toxic epidermal necrolysis and Stevens-Johnson syndrome. In: Lebwohl MG, Heymann WR, Berth-Jones J, Coulson I, eds. Treatment of skin disease: comprehensive therapeutic strategies. London, UK: Mosby; 2002:633-6.

25. Chave TA, Mortimer NJ, Sladden MJ, et al. Toxic epidermal necrolysis: current evidence, practical management and future directions. Br J Dermatol 2005;153(2):241-53.

26. Bachot N, Roujeau JC. Differential diagnosis of severe cutaneous drug eruptions. Am J Clin Dermatol 2003;4(8):561-72.

27. Knowles SR, Shear NH. Recognition and management of severe cutaneous drug reactions. Dermatol Clin 2007;25(2):245-53.

28. Callen JP. Leukocytoclastic vasculitis. In: Lebwohl MG, Heymann WR, Berth-Jones J, Coulson I, eds. Treatment of skin disease: comprehensive therapeutic strategies. London, UK: Mosby; 2002:340-3.

29. Berth-Jones J. Erythroderma. In: Lebwohl MG, Heymann WR, Berth-Jones J, Coulson I, eds. Treatment of skin disease: comprehensive therapeutic strategies. London, UK: Mosby; 2002:205-8.

30. Woodall TG, Spielvogel RL. Erythema nodosum. In: Lebwohl MG, Heymann WR, Berth-Jones J, Coulson I, eds. Treatment of skin disease: comprehensive therapeutic strategies. London, UK: Mosby; 2002:200-2.

31. Schwartz RA, Nervi SJ. Erythema nodosum: a sign of systemic disease. Am Fam Physician 2007;75(5):695-700.

As described in part 1 of this article, general strategies for identifying and treating potential ACDRs include identifying the lesion by taking a history and performing a physical examination (Box). Look for “red flags” that indicate a potentially serious reaction:

constitutional symptoms (fever, sore throat, malaise, arthralgia, lymphadenopathy, cough)
facial involvement
mucous membrane involvement
skin tenderness or blistering, particularly if there is full-thickness epidermal detachment
purpura.^16,17

Clinical Point

As the prescriber, you are responsible for ensuring that a patient with a serious rash gets emergent referral and treatment

If you suspect your patient may have a serious ACDR such as those described below, immediately discontinue the psychotropic (Table 3). Consult with a dermatologist and other specialists as appropriate, and arrange hospitalization. Although a patient with a serious ACDR typically will require hospitalization and interventions that are beyond the scope of a psychiatrist’s practice, as the prescriber you are responsible for ensuring that the patient gets an emergent referral and treatment.

Table 3

Managing a serious rash

Discontinue the offending drug immediately
Consult with a dermatologist and other specialists
Hospitalize the patient if indicated for supportive care
Report the case to the FDA and the drug manufacturer if the eruption is atypical or uncommon

Erythema multiforme (EM) may appear as symmetric erythematous target or iris-like papules and vesicobullous eruptions that present on the extremities and palmoplantar surfaces within days of starting drug therapy (Photo 1). Fever and malaise may accompany this reaction. Mucous membrane involvement is typically mild and limited to oral mucosa, but ocular mucosa also may be affected. Severe EM can cause blindness.

© 2001-2008, DermAtlas
Erythema multiforme: Erythematous target or iris-like papules and vesicobullous eruptions that present on extremities and palmoplantar surfaces. The patient might present with detachment of the epidermis from the dermis. If this consider SJS spectrum disease (see below).^2,13,18,19

Because EM may be a harbinger of a more severe skin reaction, consult a dermatologist and—if the rash involves the eyes—an ophthalmologist.¹² Antihistamines and topical corticosteroids may be used to treat EM.¹⁸ Depending on the severity of the reaction, hospitalization might be indicated.

Stevens-Johnson syndrome/toxic epidermal necrolysis (TEN) are considered a spectrum of reactive skin disorders; TEN is the more severe variant. Patients may present with a prodrome of fever, cough, and malaise. Oral lesions—such as mucosal blistering (Photo 2)—may precede skin lesions. Look for widespread distribution of flat, atypical target lesions characterized by blisters on purpuric macules.² Compared with EM, SJS/TEN lesions are more far-reaching, and the more extensive mucous membrane involvement can affect the mouth, esophagus, and genitalia. Ocular involvement might lead to blindness.^20-23

© 2001-2008, DermAtlas
Stevens-Johnson syndrome/toxic epidermal necrosis: Mucosal blistering, widespread flat skin lesions, and epidermal detachment. Epidermal detachment also may be widespread. SJS and TEN are differentiated by the extent of skin detachment:

10% to 30% detachment is SJS/TEN
>30% is TEN.²

Arrange for the patient with signs of SJS/TEN to be admitted to an ICU or burn unit.²⁰ There, clinicians will implement aggressive supportive measures such as temperature control, nutritional support, fluid balance, and pain management.^2,24 Treatments for SJS/TEN include hemofiltration, IV immunoglobulin, plasmapheresis, and cyclosporine. Corticosteroids are not recommended.²⁵

Clinical Point

Hypersensitivity syndrome can present like a benign condition, so consider the diagnosis when assessing any rash

Advise patients who have had TEN to alert relatives that they also may be at increased risk of an ACDR to the offending drug.²² Because SJS/TEN can cause blindness, an ophthalmologist typically will be involved in the patient’s care.²⁰

Hypersensitivity syndrome—known as drug rash with eosinophilia and systemic symptoms (DRESS)—is a potentially life-threatening syndrome that presents as a triad of fever, rash, and internal organ involvement.²⁶ These symptoms typically present 2 to 6 weeks after the patient starts the offending drug.

Early symptoms may include fever, malaise, pharyngitis, and lymphadenopathy.² Cutaneous manifestations range from relatively benign exanthematous eruptions to more serious eruptions such as erythroderma or TEN.

Laboratory findings might show abnormalities of the liver, kidneys, lungs, or thyroid. Atypical lymphocytes and eosinophilia may be present.

Because hypersensitivity syndrome may present like a benign condition, consider the diagnosis when assessing any drug rash, particularly if the patient is receiving an anticonvulsant.^20,22,27 Appropriate, timely care may be best delivered in an inpatient setting, so hospitalization might be indicated. Laboratory tests to assess organ function may include complete blood count (CBC), urine analysis (UA), creatinine, liver function tests, and thyroid stimulating hormone (TSH).

Clinical Point

Laboratory tests to assess internal organ involvement are indicated for any patient you suspect might have vasculitis