Correspondence

Diltiazem and Subacute Cutaneous Lupus Erythematosus–Like Lesions

N Engl J Med 1995; 333:1429November 23, 1995

Article

To the Editor:

Calcium-channel blockers are associated with rashes, including light-induced and lichenoid eruptions. An association with lupus erythematosus has been reported, although the patient and the nature of the lesion were not described.1

In four patients (two men and two women, 76 to 81 years old) subacute lupus erythematosus–like eruptions developed during treatment with diltiazem. All four had light-induced eruptions and positive tests for antinuclear antibodies, with antibodies to Ro in three patients and to La in two. None of the patients had marked extracutaneous disease. Diltiazem had been used for an average of 2.5 years before the development of lesions. The drug was discontinued in all four patients, in all of whom the lesions resolved.

Skin-biopsy specimens were examined by light microscopy and direct immunofluorescence for IgG, IgA, IgM, C3, C1q, and fibrin. Indirect immunofluorescence to detect the presence of the C5b-9 membranolytic attack complex was performed in specimens from two of the patients. Light microscopy showed features suggestive of subacute lupus erythematosus.2 Immunofluorescence revealed intense particulate deposition of IgG and C5b-9 in keratinocytes, a pattern closely correlated with a diagnosis of subacute lupus erythematosus.2,3

The drugs most frequently associated with drug-induced lupus erythematosus are chlorpromazine, hydralazine, procainamide, and quinidine. As compared with idiopathic disease, drug-induced lupus erythematosus is associated with a lower incidence of skin lesions and a higher incidence of pulmonary manifestations. Two distinctive serologic profiles have been recognized. Antihistone antibodies are correlated with the ingestion of chlorpromazine and hydralazine, and antibodies to the histone–DNA complex (H2a–H2b–DNA) with the ingestion of procainamide and quinidine.

Diltiazem was thought to have caused the eruptions because of its prior ingestion, the resolution of the skin lesions after the cessation of therapy, and the fact that it was the sole prescribed drug in all but one patient, who for five years had also received metoprolol, a drug not known to cause a subacute lupus erythematosus–like eruption.

A.N. Crowson, M.D.
Misericordia General Hospital, Winnipeg, MB R3C 1A2, Canada

C.M. Magro, M.D.
Beth Israel Hospital, Boston, MA 02215

3 References

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   Stern R, Khalsa JH. Cutaneous adverse reactions associated with calcium channel blockers. Arch Intern Med 1989;149:829-832
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   Magro CM, Crowson AN, Regauer S, Harrist TJ. The use of antibody C5b-9 as an adjunct to the lupus band test. Lab Invest 1994;70:47A-47A abstract.
   Web of Science

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   Crowson AN, Magro CM. Deposition of membrane attack complex in cutaneous lesions of lupus erythematosus. J Am Acad Dermatol 1994;31:515-516
   CrossRef | Web of Science | Medline

Citing Articles (13)

Citing Articles

1. 1

   S. M. Breathnach. 2010. Drug Reactions. , 1-177.
   CrossRef

2. 2

   S. M. Breathnach. 2010. , 1.
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3. 3

   Hildamari Justiniano, Alma C Berlingeri-Ramos, Jorge L Sánchez. (2008) Pattern Analysis of Drug-Induced Skin Diseases. The American Journal of Dermatopathology 30:4, 352-369
   CrossRef

4. 4

   Jeffrey P Callen. (2006) Cutaneous lupus erythematosus: A personal approach to management. Australasian Journal of Dermatology 47:1, 13-27
   CrossRef

5. 5

   A Neil Crowson, Tricia J Brown, Cynthia M Magro. (2003) Progress in the Understanding of the Pathology and Pathogenesis of Cutaneous Drug Eruptions. American Journal of Clinical Dermatology 4:6, 407-428
   CrossRef

6. 6

   A. Neil Crowson, Cynthia Magro. (2001) The cutaneous pathology of lupus erythematosus: a review. Journal of Cutaneous Pathology 28:1, 1-23
   CrossRef

7. 7

   Cynthia M. Magro, A. Neil Crowson. (2000) Necrotizing eosinophilic folliculitis as a manifestation of the atopic diathesis. International Journal of Dermatology 39:9, 672-677
   CrossRef

8. 8

   A. N. Crowson, C. M. Magro. (1999) Lichenoid and subacute cutaneous lupus erythematosus-like dermatitis associated with antihistamine therapy. Journal of Cutaneous Pathology 26:2, 95-100
   CrossRef

9. 9

   C. M. Magro, A. N. Crowson. (1999) Pseudoporphyria associated with Relafen therapy*. Journal of Cutaneous Pathology 26:1, 42-47
   CrossRef

10. 10

    A.Neil Crowson, Cynthia M Magro. (1997) Subacute cutaneous lupus erythematosus arising in the setting of calcium channel blocker therapy. Human Pathology 28:1, 67-73
    CrossRef

11. 11

    Marco Pahor, Jack M Guralnik, Luigi Ferrucci, Maria-Chiara Corti, Marcel E Salive, James R Cerhan, Robert B Wallace, Richard J Havlik. (1996) Calcium-channel blockade and incidence of cancer in aged populations. The Lancet 348:9026, 493-497
    CrossRef

12. 12

    Cynthia M Magro, A.Neil Crowson. (1996) Drug-induced immune dysregulation as a cause of atypical cutaneous lymphoid infiltrates: A hypothesis. Human Pathology 27:2, 125-132
    CrossRef

13. 13

    &NA;. (1995) Diltiazem. Reactions Weekly &NA;:579, 6
    CrossRef