Correspondence

Accidental Success with Carbamazepine for Psoriatic Erythroderma

N Engl J Med 1996; 335:1999-2000December 26, 1996

Article

To the Editor:

In patients infected with human immunodeficiency virus type 1 (HIV-1), immunosuppression limits the choice of drugs that may be used to treat psoriatic erythroderma. We describe a patient who had a dramatic therapeutic response to carbamazepine. This may be a new therapeutic agent for psoriasis.

The patient was a 29-year-old HIV-1–positive man with a history of plaque psoriasis, disseminated varicella–zoster virus infection, Pneumocystis carinii pneumonia, disseminated Mycobacterium avium complex infection, and a CD4+ T-cell count in peripheral blood below 10 cells per cubic millimeter. The patient's skin disease had become progressively more difficult to control. In July 1995, diffuse exfoliative erythroderma developed. At the time, his medications were acyclovir, azithromycin, ethambutol, rifampin, trimethoprim–sulfamethoxazole, fluconazole, and ranitidine. A decision was made to treat the patient with etretinate (Tegison, Hoffmann–LaRoche), starting with a dose of 20 mg per day, and increasing the dose to 40 mg per day over a two-week period.

During the first week the patient's chills and erythema disappeared and his mood improved, and by the end of two weeks there was minimal scaling of his skin. However, when the prescription was refilled, it was found that he had initially been given carbamazepine (Tegretol [Ciba–Geigy], not Tegison) and had taken 200 mg per day, later increasing the dose to 400 mg per day. The patient discontinued the medication. His skin disease flared up over the next few days. In two weeks, he again had exfoliative erythroderma. He was given carbamazepine again. After two weeks, his skin had cleared once more, except for mild scaling and xerosis. He has continued to take the medication over the past year, with no change in laboratory values and no new opportunistic infections.

Carbamazepine is a tricyclic compound related to imipramine and nortriptyline. The improvement in our patient's mood may be related to the drug's tricyclic effects. Tricyclic compounds also have local anesthetic and antihistaminic properties.1 Carbamazepine has been used for many years to treat epilepsy, trigeminal neuralgia, causalgia, some kinds of painful neuropathy, migraines, and various psychoses. Neuropathy is mentioned as a complication of carbamazepine, but if it occurs, it is mild, uncommon, and reversible. Adverse hematologic reactions to carbamazepine are rare but important, because they may lead to aplastic anemia, agranulocytosis, leukopenia, and thrombocytopenia and may be associated with a hypersensitivity syndrome consisting of dermatitis, eosinophilia, lymphadenopathy, and splenomegaly. A number of drugs interact with carbamazepine, and it induces its own metabolism, but none of the patient's medications are strongly implicated in inducing adverse drug reactions with carbamazepine.1 Furthermore, the dose of carbamazepine the patient took was not large.

The mechanisms of action of carbamazepine are still far from clear. It inhibits the uptake of norepinephrine. It also appears to block a cyclic AMP–mediated calcium influx that is associated with both the release of neuropeptides and the control of a slow potassium current.1

Psoriasis is one of a number of conditions that may be induced by psychological factors. There have been reports of the clearing of psoriatic plaques only at sites of anesthesia due to damage to sensory nerves or the sectioning of nerves.2-5 Farber et al. proposed that the release of neuropeptides from sensory nerves in the skin causes local inflammatory responses that trigger psoriasis in genetically predisposed persons.6 Although there is some variability in reports, levels of neuropeptides have been found to be increased in psoriatic skin.

The rapid response to carbamazepine, the rapid flare of psoriasis when the medication was discontinued, and the clearance of lesions when therapy was begun again are all evidence that carbamazepine was therapeutic. In addition, the patient's prolonged response without recurrence of clinical disease is also consistent with a therapeutic role for carbamazepine in psoriasis. Although the mechanism of the therapeutic effect is not known, it may involve the inhibition of neuropeptide secretion, both locally and centrally.

(The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army, the Department of the Navy, or the Department of Defense.)

Kathleen J. Smith, M.D., Col., M.C., U.S.A.
National Naval Medical Center, Bethesda, MD 20889

Henry G. Skelton, M.D.
Bethesda, MD 20817

6 References

1. 1

   Kutt H, Paris-Kutt H. Carbamazepine. In: Woodbury DM, Penry JK, Pippenger CE, eds. Antiepileptic drugs. 2nd ed. New York: Raven Press, 1982:453-547.
   

2. 2

   Farber EM, Bright RD, Nall ML. Psoriasis -- a questionnaire survey of 2144 patients. Arch Dermatol 1968;98:248-259
   CrossRef | Web of Science | Medline

3. 3

   Raychaudhuri SP, Farber EM. Are sensory nerves essential for the pathogenesis of psoriasis? J Am Acad Dermatol 1983;23:488-489
   

4. 4

   Billy AJ, Walters ET. Long-term expansion and sensitization of mechanosensory receptive fields in Aplysia support an activity-dependent model of whole-cell sensory plasticity. J Neurosci 1989;9:1254-1262
   Web of Science | Medline

5. 5

   Harvima IT, Viinamaki H, Naukkarinen A, et al. Association of cutaneous mast cells and sensory nerves with psychic stress in psoriasis. Psychother Psychosom 1993;60:168-176
   CrossRef | Web of Science | Medline

6. 6

   Farber EM, Nickoloff BJ, Recht B, Fraki JE. Stress, symmetry, and psoriasis: possible role of neuropeptides. J Am Acad Dermatol 1986;14:305-311
   CrossRef | Web of Science | Medline

Citing Articles (5)

Citing Articles

1. 1

   Nilesh Morar, Saffron A Willis-Owen, Toby Maurer, Christopher B Bunker. (2010) HIV-associated psoriasis: pathogenesis, clinical features, and management. The Lancet Infectious Diseases 10:7, 470-478
   CrossRef

2. 2

   Michael M. Jiaravuthisan, Denis Sasseville, Ronald B. Vender, Francis Murphy, Channy Y. Muhn. (2007) Psoriasis of the nail: Anatomy, pathology, clinical presentation, and a review of the literature on therapy. Journal of the American Academy of Dermatology 57:1, 1-27
   CrossRef

3. 3

   M. Lomia, T. Tchelidze, M. Pruidze. (2006) Bronchial asthma as neurogenic paroxysmal inflammatory disease: A randomized trial with carbamazepine. Respiratory Medicine 100:11, 1988-1996
   CrossRef

4. 4

   Jack L Arbiser, Baskaran Govindarajan, Traci E Battle, Rebecca Lynch, David A Frank, Masuko Ushio-Fukai, Betsy N Perry, David F Stern, G Tim Bowden, Anquan Liu, Eva Klein, Pawel J Kolodziejski, N Tony Eissa, Chowdhury F Hossain, Dale G Nagle. (2006) Carbazole Is a Naturally Occurring Inhibitor of Angiogenesis and Inflammation Isolated from Antipsoriatic Coal Tar. Journal of Investigative Dermatology 126:6, 1396-1402
   CrossRef

5. 5

   Virendra N. Sehgal, Govind Srivastava, Kabir Sardana. (2004) Erythroderma/exfoliative dermatitis: a synopsis. International Journal of Dermatology 43:1, 39-47
   CrossRef