Erythromelalgia

Abstract

Topiramate is an anti-convulsant often used off-label for the treatment of several conditions, including obesity and schizophrenia. This case report describes palmar erythema as a side effect in a patient using topiramate for paranoid schizophrenia.

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Background

We report palmar erythema in a patient using topiramate. The patient was a 34-year-old man hospitalized for paranoid schizophrenia. He was previously hospitalized elsewhere where he started topiramate 50 mg daily. He took topiramate for 5 days prior to discharge. A day later, he was rehospitalized at our facility due to violent behavior. On admission, psychiatrists noted intense palmar erythema. The patient had a medical history significant for asthma, obesity, and paranoid schizophrenia. His long-standing medications included an albuterol inhaler, risperidone 4 mg daily, and haloperidol 5 mg three times per day. He had no known drug allergies.

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Upon dermatological examination, his palms displayed erythematous plaques with collarettes of scale and fingertip exfoliation, extending approximately one centimeter above the wrist (Figure 1). The topiramate was discontinued and the patient was prescribed fluocinolone ointment 0.05% twice per day and diphenhydramine 25 mg as needed for pruritus. He refused biopsy and fungal and mineral oil preparations. His rash completely resolved over the next four days. His palms remained flesh color for the six-week duration of his hospitalization.

Discussion

Topiramate was approved as an anticonvulsant medication in the United States in 1996. It has found a variety of off-label uses including the promotion of weight loss (1) and the treatment of schizophrenia (2). Side effects frequently caused by topiramate include cognitive impairment, word-finding difficulties, and bodyweight loss, and less commonly renal calculi, hepatotoxicity, and ocular pathology such as glaucoma (3). It is felt to have special utility in obese patients with neurological and psychological problems because it promotes weight loss.

The Physicians' Desk Reference notes that topiramate can cause acneiform eruptions, alopecia, drug- induced pigmentation, exanthematous reaction, hyperhidrosis, hypertrichosis, hair texture change, lichenoid eruption, photosensitivity, and fixed drug eruptions (4). Hypohidrosis related to the administration of topiramate to children has been reported (5). Four patients with epilepsy developed pruritus after the addition of topiramate to their anticonvulsant regimens (6). These cases suggest that topiramate's side effects are potentiated by its use with other medications. Interestingly, a report notes that combination topiramate and valproic acid in three children caused apathy and elevated blood ammonia levels in all three children; hypothermia in two, increased liver transaminases in one, and thrombocytopenia in one (7).

As a cutaneous reaction pattern, acral erythema usually occurs in the context of chemotherapy with such agents as methotrexate, docetaxel, cisplatin, cytosine arabinoside, hydroxyurea, etoposide 5-fluorouracil, folinic acid, alpha-interferon, cyclophosphamide, vincristine, doxorubicin, prednisolone, and granulocyte-colony stimulating factor, tegafur (8), and some other medications such as didanosine and quinolones. Some think that this is a direct toxic effect of these agents, which are concentrated by the large number of sweat glands underlying the palmar region. The instant rash differed from acral erythema because it was pruritic rather than painful.

Red palms can be a sign of systemic disease or a normal variant. Red palms can occur with systemic diseases such as sarcoidosis, parvovirus B-19, tuberculosis, non-Hodgkin's lymphoma, eccrine squamous syringometaplasia, acute graft vs. host disease, and HIV. A condition also manifesting with palmar erythema is erythromelalgia, which involves paroxysmal vasodilation and red, intensely painful feet or hands, which is thought to be a syndrome of dysfunctional vascular dynamics. Specifically, postganglionic sympathetic dysfunction and denervation hypersensitivity may play a pathogenetic role in primary erythromelalgia, whereas local neurogenic as well as endothelial function is unaffected (9).

Our case seems to underlie the fact that toprimate's side effects especially its cutaneous side effects--occur when it used with other medications. It is possible that the combinations of topiramate with antipsychotic and anticonvulsant medications further alter neural thresholds in a fashion as to effect the sensation of itch (as in our report and the previous report of 4 cases of pruritus) and palmar erythema in a fashion similar to erythromelalgia. A non-immunogenic basis for the palmar erythema is suggested by a lack of exanthema on other body areas. The neural effects of topiramate might account for its efficacy in treating psoriasis (10), a disease in which the importance of neural function continues to be defined. As a skin biopsy was not performed in this case due to patient preference, we can not report the histopathology of this case. It is our conclusion, however, that the etiology of the instant palmar erythema is likely neural in origin, relates to the concomitant uses of other neurotropic agents, and does not have an immunologic basis. Topiramate continues to be a promising anticonvulsant agent with minimal cutaneous side effects.

References:

1. Chengappa KN, et al. Changes in body weight and body mass index among psychiatric patients receiving lithium, valproate, or topiramate: an open-label, nonrandomized chart review. Clin Ther 2002; 24: 1576-84.

2. Hosak L, Libiger J. Antiepileptic drugs in schizophrenia: a review. Eur Psychiatry 2002; 17:371-8.

3. Wong IC, Lhatoo SD. Adverse reactions to new anticonvulsant drugs. Drug Saf 2000; 23:35-56.

4. Physicians' Desk Reference. 55th ed. Montvale (NJ): Medical Economics. 2001.

5. Arcas J. Ferrer T. Roche MC. Martinez-Bermejo A, Lopez-Martin V. Hypohidrosis related to the administration of topiramate to children. Epilepsia 2001; 42:1363-5.

6. Ochoa JG. Pruritus, a rare but troublesome adverse reaction of topiramate. Epilepsia 2000; 41(Suppl. 7):122.

7. Longin E, et al. Topiramate enhances the risk of valproate-associated side effects in three children. Epilepsia 2002; 43:451-4.

8. Komamura H, et al. Three cases of chemotherapy-induced acral erythema. J Dermatol 1995; 22:116-21.

9. Mork C, Kalgaard OM, Kvernebo K. Impaired neurogenic control of skin perfusion in erythromelalgia. J Invest Dermatol 2002; 118:699-703.

10. Ryback R. Topiramate in the treatment of psoriasis: a pilot study. Br J Dermatol; 147:130-3.

NOAH SCHEINFELD MD JD, CANDICE SPAHN MD

DEPARTMENT OF DERMATOLOGY, ST LUKE'S-ROOSEVELT HOSPITAL CENTER NEW YORK, NEW YORK

ADDRESS FOR CORRESPONDENCE:

Noah Scheinfeld MD

Department of Dermatology

St. Luke's-Roosevelt Hospital Center

1090 Amsterdam Ave Suite 11 D

NYC NY 10025

Phone: (212) 523-3888

Fax: (212) 523-3808

E-mail: Scheinfeld@earthlink.net

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