The Relationship of Lithium Carbonate to Psoriasis

The Relationship of Lithium Carbonate To Psoriasis THOMAS

N.

CARTER,

In 1949 Cade, using lithium carbonate in an experiment with guinea pigs, noticed it made them lethargic without altering consciousness.1o Serendipitously he tried to repeat the effects in manic patients and obtained similar results. Since then, it has enjoyed various levels of fame or notoriety as the case may be. At present, it is being prescribed most commonly for the control of manic episodes and seems to be of some use in prophylactically controlling mood swings. Although lithium seems to alter sodium transport in nerve and muscle cells, effecting a shift toward intraneuronal metabolism of catecholamines, no specific biochemical mechanism of lithium action in mania is known. Not unlike other clinically effective chemicals, lithium carbonate also causes various untoward effects in some patients. The side effects which have been reported include fine hand tremor, polydipsia, polyuria, weight gain, decreased thyroid function, leukocytosis. nausea, general discomfort, and cutaneous reactions. Of the cutaneous reactions reported, Callaway, et aI, cited five who developed pruritic maculopapular rash and/or ulceration of the lower anterior tibial region during the first three weeks of treatment with lithium. 9 All of these cases responded to a reduction of lithium or administration of antihistamines and steroids. O'Connell mentions that the cutaneous side effects are usually papular and erythematous, often occurring around pressure points. l l He does mention one case who had macula-papular lesions on the trunk. Most of these patients had a history of a dermatological disorder in adolescence but none since. These symptoms were transient and responded to a lower dose of lithium. In the cases he reported, steroids were not necessary. There have been no cases reported on the correlation of lithium administration and the exacerbation of psoriasis. The folFrom Veterans Administration Hospital, Topeka, Kansas. Septembe r-October 1972

M.D.

lowing case reports seem to indicate that such a causal relationship does exist. Case No.1 Mr. P. is a 41-year old, single, Jewish man who had been diagnosed as having chronic undifferentiated schizophrenia with frequent episodes of rather marked hyperactivity for approximately eighteen years during which time he has been an inpatient. He had a history of very mild pSJriasis involving the elbows and knees for approximately four years. During this period he had noticed that when he felt less disturbed his psoriasis seemed to "go away" but when he was "hot and bothered" (Le., hyperactive) it would reappear. In 1968 he was started on lithium carbonate 300 mg., b.Ld., which was increased to 600 mg., t.i.d. after one month. From that time until September, 1970, when his medicine was stopped, his psoriasis was "worse than it has ever been." The average range for the lithium carbonate serum level during that period was from 0.8-1.10 mEq/L. By October 14, 1970, the lithium carbonate level was zero. and one week later the psoriasis was negligibly present. Even though he has remained psychotic with periods of moderate hyperactivity, the psoriasis has not exacerbated since. He continued to receive the same phenothiazine dose throughout. Interestingly, he also has seborrheic dermatitis which did not appear to be affected by the lithium. Case No.2 Mr. G., a 43-year-old white man was diagnosed as having manic-depressive psychosis in 1959. His psoriasis began in February 1945 as a "dimesized lesion" on his left shin and progressed to "saucer-sized" in two months. It then decreased to a "minimal-sized patch" until 1949 at which time it spread to involve small areas of both shins and elbows. At that time he was a junior in college. He received a course of x-ray therapy for it, after which it spread more extensively; now also involving the forearms and anterior trunk moderately. Just prior to graduation the following year (while having many job interviews) the psoriasis began to involve his penis for the first time. Although it was quite widespread at this time, it did not involve his scalp and was of only moderate intensity. During 1950, after graduation, he spent a lot of time in the sun and salt water off the coast of the Gulf of Mexico, and his pscriasis markedly improved. This improvement lasted until 1959 at which time he was admitted to the TVAH for the first time. Between 1960 and 1966 he had three or four exacerbations of psoriasis lasting

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PSYCHOSOMATICS four to five months each and seemingly correlated with increased emotional strain in psychotherapy. In 1967 he began taking lithium carbonate 300 mg., q.i.d. for the f:rst time and remained on it for one year. "A few months" after starting the lithium, his ps~riasis exacerbated, but he was having considerable emotional discomfort at the same time. Around the middle of 1968 he quit taking it, and his psoriasis went into remission "soon afterward." However, the emotional strain decreased, and he was receiving increased exposure to the sun at approximately the same time. Until February, 1970 his psoriasis remained in remission. At that time he was readmitted to TVAH with marked depression. On March 26 he was restarted on lithium carbonate, 300 mg., b.i.d. due to his bec:-ming manic after the depression lifted, and this was increased to 300 mg., t.i.d. after one week. In about two weeks his ps;)riasis increased greatly both in severity and extent. Due to his having "flu" in April, 1970 he discontinued the lithium for three weeks, and his psoriasis improved. Again lithium was started and, after receiving 600 mg., t.i.d. for about two weeks, his ps:-rbsis exacerbated. One week later he discontinued the med:cine (again for the "flu") for two weeks; the psoriasis again remitting. Once more he was started on lithium, and after approximately two weeks his psoriasis became much worse. Finally, in July 1970 his ward physician took him off the drug, and Mr. G. was transfered to the Medical Service where he received Methotrexate 0.6 mg. every four hours for two 10-day p~ri::ds with a 5-day interim break. Very marked remission of the psoriasis occurred. However, he began entering the manic phase about one week prior to being returned to the Psychiatric Service, so lithium was restarted at 600 mg., t.i.d. Two weeks after restarting the lithium the serum level reached greater than 0.8 mEq/L and clinically the mania subsided. At this same time the patient noticed that his psoriasis was getting worse. It continued to exacerbate for two weeks at which time the lithium was s~opped because a correlation between it and the psoriasis was suspected. During the following week his serum lithium level dropped to zero and for one additional week he took no medication. The progressive exacerbation stopped and, although the psoriasis did not go into marked remission in that period of time, the redness subsided and the scaling decreased to a minimum. Fearing that he would become manic the lithium was restarted on October 2, 1970, and, again, progressive exacerbation of his psoriasis began. This exacerbation continued until December 14, 1970 when he was transferred back to the Medical Service to receive another regimen of Methotrexate. This time he continued to receive lithium carbonate 600 mg., t.i.d. while taking Methotrexate 0.6 mg. every four hours for ten days and after a 5-day interim, 0.6 mg. every four hours for eight more days. This second regimen of Methotrexate caused negligible results on the psoriasis which was 326

actually not as severe prior to this regimen as it had been prior to the first one. The most obvious difference was that the patient had not been on lithium during the first administration of Methotrexate and was on it during the second administration. Since January, 1971 he has remained on lithium; free of mood swings. His psoriasis remained generalized and moderately severe until May and June, during which time he went to the Gulf of Mexico. There he lay in the sun one hour daily and soaked in the ocean for 15 to 30 minutes a day, allowing the salt to stay on his skin for approximately three hours afterward. A moderate remission of the psoriasis occurred, and his serum lithium level remained at 0.8 mEq/L. Case No.3 Mr. L. is a 65-year-old white man who was diagnosed as having a chronic anxiety reaction in 1958. In April 1962 he developed a "mild rash" over the midsternal area which consisted of a small patch of erythematous pruritic skin. This was not diagnosed or treated. By 1965 he had mild "crusty" patches on his elbows which were not given a diagnosis in his medical chart but for which he was given Synalar cream 0.25% which helped. In January 1966 he was seen by a dermatologist because he had developed small crusty lesions with bright red haloes on his ankles, shins, elbows, post-auricular areas, a "spot or two" on the dorsum of his hands and some on his cheeks. These were diagnosed as psoriasis, and the 2% salicylic acid and USP ammoniated mercury ointment prescribed aided him greatly. Involvement of the perianal area began in July 1967 and was treated with Synalar cream 0.25% which also helped. A f1areup occurred in August 1970 involving the shins, elbows, gluteal cleft, and inner thighs for which he again consulted a dermatologist. At that time he received intradermal Triamcinolone and Synalar cream 0.25%. Again, a rapid remission was effected. On December 30, 1970, he was started on lithium carbonate 300 mg., t.i.d. which was increased to 300 mg., q.i.d. on January 7, 1971, and to 600 mg., Li.d. on February 24. The psoriasis exacerbated to greater intensity than ever before and, for the first time, became generalized. On March 24 he was transferred to the Medical Service where he received 0.6 mg. Methotrexate q.i.d., p.o., for ten days and Synalar cream 0.25% topically. This regimen resulted in negligible results. Prior to February 24 the serum lithium level was from 0.40 to 0.55 mEq/L and since then it has ranged from 0.6 to 1.16 mEq/L (including during the Methotrexate regimen). On June 21, 1971, he was placed on Haldol, 5 mg. daily, Cogentin" 2 mg. daily and the lithium was discontinued. His serum lithium level was 0.48 mEq/L on June 22. On July 2 his serum lithium level was zero. Since June 22 his psoriasis has steadily improved. First, the redness decreased and then the scaling, with the old scales falling off. Volume XIII

LITHIUM RELATIONSHIP TO DISCUSSION

Because of the vagueness and variability of the relationship between psoriasis and emotional disturbances,i,8 postulating a correlation between a method of treatment for one and the exacerbation of the other must necessarily seem tenuous. III Psoriasis afflicts from one to two per cent of all people with white skin at sometime during their life. l In a study based on 223 psychotic patients with skin disease in nine hospitals, Wittkower, et aI, found 12% of the patients diagnosed as having manic-depressive psychosis to also have psoriasis. 2 None of the patients are said to have been on lithium treatment and, of the few case histories he cited, the severity of the psoriasis was directly proportional to the severity of the psychosis. In the cases cited here, their psoriasis got worse as they improved mentally on lithium. Case number two had very significant remission of his psoriasis with the first regimen of Methotrexate (while off lithium) but rapid and severe recurrence occurred approximately one week after the cessation of the Methotrexate and restarting lithium. This was also at the time the lithium was becoming again clinically effective. Roenigk, Jr., et al, have found that flareups of psoriasis following the cessation of Methotrexate usually do not occur until after three to four weeks. 5 Of further significance was the failure of the second regimen in Case number two and the regimen in Case number three (while both remained on clinically effective dosages of lithium) to effect any appreciable change in the state of their psoriasis. Also, topical medications of various types failed to have their "pre-lithium" antipsoriatic effects after lithium was started with the exception of the inner thigh involvement in Case number three. The action of Methotrexate in aiding psoriasis is believed to be through the inhibition of folate reductase thus preventing the formation of tetrahydrofolate which is the necessary co-enzyme for the formation of thymidine, one of the bases needed for desoxynucleic acid formation. G Therefore, the overall effect is to inhibit the rapidly dividing epithelial cells in psoriasis. It seems that in some way lithium blocks that action. Case number two did get September-October 1972

PSORIASI~CARTER

relief from "sunlight and sea water" in spite of maintaining a serum lithium level of 0.84 mEq/L. That sunlight is therapeutically effective in psoriasis is well known.! SUMMARY

Three cases are reported which indicate a possible causal relationship between lithium carbonate treatment and the exacerbation of psoriasis. Although no definite conclusion can be made, it does point to a need for research in this area. Reprint requests to Dr. Carter, Menninger Foundation, Box 829, Topeka, Kansas 66601. BIBLIOGRAPHY I. Pillsbury, Donald M., W. B. Shelley and A. M. Kligman. A Manual of Cutaneous Medicine. Saunders, 1964, pp. 212-23. 2. Wittkower, Eric and Brian Russell. Emotional Factors ill Skin Diseases. Chapter 6 "The Skin and Psychoses," 1953, pp. 190-203. 3. Greenspan, K., R. Green and J. Durell. "Retention and Distribution Patterns of Lithium, a Pharmacological Tool in Studying the Pathophysiology of Manic-Depressive Psychosis," Am. J. of Psych., 125:4, Octobec 1968, p. 512. 4. Bunney, W. E., Jr., F. K. Goodwin, J. M. Davis, and J. A. Fawcett. "A Behavorial-Biochernica1 Study of Lithium Treatment," Am. J. of Psych., 125:4, October 1968, p. 499. 5. Roenigk, H. H., Jr., W. F. Bergfeld, R. St. Jacques, F. J. Owens, and W. A. Hawk. "Hepatotoxity of Methotrexate in the Treatment of Psoriasis," Arch. Derm., 103:3, 1971, 250-61. 6. Halprin, K. M., K. Fukui, and A. Ohkawara. "Blocd Levels of Methotrexate and the Treatment cf Psoriasis," Arch. Derm., 103:3, March, 1971. 7. Farber, E. M., R. D. Bright and M. L. NaIl. "Psoriasis. A Questionnaire Survey of 2,144 Patients," Arch. Derm., 98, September 1968,249-59. 8. Goldsmith, L. A., M. Fisher, and J. Wacks. "Psychological Characteristics of Psoriatics. Implications for Management," Arch. Derm., 100, July-December 1969, 674-76. 9. Callaway, C. L., H. C. Hendrie and E. D. Luby. "Cutanecus Conditions Observed in Patients During Treatment with Lithium, Amer.. J. of Psych., 124:Part 2, February 8, 1968. 1124-5. 10. Cade, J. F. J. "Lithium Salts in the Treatment of Psychotic Excitement," Med J. of Australia, 36, September 3, 1949, 349-52. II. O'Connell, R. A. "Lithium's Site of Action: Clues from Side Effects," Compo Psychiatry, 12:3, May 1971,224-29. 327