Evidence-Based Reviews

Drug eruptions: Is your patient’s rash dangerous or benign?

Current Psychiatry. 2008 March;7(3):43-56

References

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

2. MacMorran WS, Krahn LE. Adverse cutaneous reactions to psychotropic drugs. Psychosomatics 1997;38(5):413-22.

3. Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis, and management. Lancet 2000;356(9237):1255-9.

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

5. 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.

6. Nigen S, Knowles SR, Shear NH. Drug eruptions: approaching the diagnosis of drug-induced skin diseases. J Drugs Dermatol 2003;3:278-99.

7. 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.

8. Odom RB, James WD, Berger TG. Contact dermatitis and drug eruptions. In: Andrew’s diseases of the skin: clinical dermatology. 9th ed. Philadelphia, PA: W.B. Saunders Co.; 2000:95-145.

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

10. Breathnach SM. Adverse cutaneous reactions to drugs. Clin Med 2002;2(1):15-9.

11. du Vivier A, McKee PH, Stoughton RB. Drug and toxic eruptions of the skin. In: du Vivier A, McKee PH, Stoughton RB. Atlas of clinical dermatology. Philadelphia, PA: W.B. Saunders Co.; 1986:14.1-14.18.

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

13. Mann SC, Walker MM. Leukocytoclastic vasculitis secondary to trazodone treatment. J Am Acad Dermatol 1984;10(4):669-70.

14. Hearn R. Recognition and management of cutaneous photosensitivity. Practitioner 2005;249(1671):418-32.

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

16. Crowson AN, Brown TJ, Magro CM. Progress in the understanding of the pathology and pathogenesis of cutaneous drug eruptions. Am J Clin Dermatol 2003;4(6):407-28.

17. Remmer HI. Successful treatment of lithium-induced acne. J Clin Psychiatry 1986;47(1):48.-

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

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

20. Physicians desk reference. 61st ed. Montvale, NJ: Thomson PDR; 2007.

21. Atkin DH, Fitzpatrick RE. Laser treatment of imipramine-induced hyperpigmentation. J Am Acad Dermatol 2000;43(1 Pt 1):77-80.

22. Thompson TR, Lal S, Yassa R, Gerstein W. Resolution of chlorpromazine-induced pigmentation with haloperidol substitution. Acta Psychiatr Scand 1988;78(6):763-5.

23. Bloom D, Krishnan B, Thavundayil JX, Lal S. Resolution of chlorpromazine-induced cutaneous pigmentation following substitution with levomepromazine or other neuroleptics. Acta Psychiatr Scand 1993;87(3):223-4.

24. Mercke Y, Sheng H, Khan T, Lippmann S. Hair loss in psychopharmacology. Ann Clin Psychiatry 2000;12(1):35-42.

25. Warnock JK. Psychotropic medication and drug-related alopecia. Psychosomatics 1999;32(2):149-52.

26. Gupta AK, Knowles SR, Gupta MA, et al. Lithium therapy associated with hidradenitis suppurativa: case report and review of the dermatologic side effects of lithium. J Am Acad Dermatol 1995;32(2 part 2):382-6.

27. Osborne SF, Stafford L, Orr KD. Paroxetine-associated psoriasis. Am J Psychiatry 2002;59(12):2113.-

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

Benign rashes

© 2001-2008, DermAtlas Exanthematous reactions are the most common ACDR.¹ Erythematous macules and papules may initially present on the trunk and spread peripherally within 1 to 2 weeks of a patient’s starting psychotropic therapy (Photo 1). Lesions may become confluent and involve the mucosa, hands, and feet. Differential diagnosis includes infections, collagen vascular diseases, and more serious drug rashes.^1,5,6

Exanthems usually resolve within 2 weeks after the offending drug is discontinued.^1,6 Because exanthems may resolve without drug discontinuation,^1,8 you could continue treatment with the offending agent if other options are not feasible.⁹ Keep in mind, however, that exanthematous reactions may be the presenting symptom of a more serious condition, especially if associated with any of the red flags described in Table 2. If the suspect drug has been associated with a severe reaction, discontinue it permanently.⁴ Additional treatments for exanthems include corticosteroids, emollients, and oral antihistamines.^6-8

Clinical Point

Though usually benign, an exanthematous reaction may be the presenting symptom of a more serious condition

Urticaria usually is treated with antihistamines.^6,7 A histamine-1 blocker such as hydroxyzine or diphenhydramine—used exclusively or, for severe cases, in combination with a histamine-2 blocker such as ranitidine or cimetidine—may bring relief.¹ Dosage guidelines are based on the severity and distribution of the eruption. If these treatments are not effective, discontinuing the offending drug should resolve the condition.^1,4,11 Resuming the drug can result in anaphylaxis, so warn the patient to never take the offending drug again.⁴

If a patient has unstable vital signs or a rash that affects the airway—or if you believe he or she is at risk for anaphylaxis—emergent treatment is indicated.^1,6 This may include the use of epinephrine and corticosteroids.

© 2001-2008, DermAtlas Fixed drug eruptions can appear anywhere on the body as single or multiple sharply demarcated, pruritic erythematous macules (Photo 3). They may blister or cause a burning sensation; rarely, a patient may present with constitutional symptoms. Lesions might erupt hours to days after drug exposure. Although this condition usually is benign, consult a dermatologist if the patient exhibits constitutional symptoms or other red flags that may indicate a serious reaction.

Clinical Point

Discontinue the psychotropic if a patient experiences a fixed drug eruption

After you discontinue the offending drug, lesions should resolve within several weeks, although there may be residual hyperpigmentation.⁶ Depending on the severity of the eruptions, topical corticosteroids or wound care may be indicated.^6,12 Resuming the drug typically will cause the eruptions to reoccur at the same site, potentially with more lesions.^1,5-7

© 2001-2008, DermAtlas Photosensitivity describes phototoxic and photoallergic reactions. A phototoxic response resembles sunburn and is distributed in areas exposed to the sun. This can present as erythema, edema, and skin tenderness (Photo 4).

Delayed hypersensitivity response is a photoallergic reaction. This reaction may be pruritic and appear after sunlight exposure as eczematous, bullous, vesicular, or urticarial lesions 1 to 2 weeks after the drug is started. Photoallergic lesions may extend beyond sun-exposed areas. Phototesting can confirm this diagnosis.^1,5,13,14

Treat a phototoxic reaction as you would sunburn. Topical soothing agents should bring relief in 1 to 2 days.¹⁵ Instruct patients to use sunscreen and avoid the sun while taking the psychotropic.^1,15 You may need to discontinue the medication if lesions persist.¹

Managing a photoallergic response entails avoiding the sun or discontinuing the offending agent.^14,16 For both phototoxic and photoallergic reactions, consider consulting a dermatologist if the above measures do not resolve the rash.¹

Treatment options include benzoyl peroxide, antibiotics, and topical retinoids.^1,12,17 If these measures are insufficient, or if your patient finds the eruption distressing, discontinuing the offending drug usually resolves the condition.¹²

© 2001-2008, DermAtlas Pigmentation changes. Blue, gray, or brown discoloration resulting from changes in melanin deposition can affect skin, hair, and nails, particularly in sun-exposed areas (Photo 6). Consider in the differential diagnosis other conditions that causes skin pigmentation changes such as:

Clinical Point

Treat a phototoxic rash with topical soothing agents and advise patients to use sunscreen and avoid the sun

hematochromatosis
Addison’s disease.^{1,2,7,12,18-20}

Drug-related pigmentation changes usually resolve once the drug is discontinued, but resolution may take years.¹ Cosmetics may help mask skin discoloration. A dermatologic consultation may not be necessary.