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Pruritus associated with niacinamide
Journal of the American Academy of Dermatology
530 Correspondence
goides Cooperative Group. Cancer Treat Rep 63:701-707, 1979. 2. Ederer F, Axtell LM, Cutler SJ: Relative survival rates: A statistical methodology, National Cancer Institute Monograph No.6. Washington, DC, 1961, U. S. Government Printing Office, pp . 101-121. 3. Armitage P: Analysis of data from clinical trials . The Statistician 28:171-181,1979 .
Reply To the Editor: Whether or not there is agreement over the method of gathering data, the basic question to be asked once the diagnosis of mycosis fungoides has been made is how the disease is to be treated. Studies compiling data on large groups of patients such as ours and the ongoing work with Dr. Lamberg's group will hopefully shed some light on the answer. But since there is currently no clear-cut evidence that early aggressive therapy has significant benefits over other modalities, I would be hesitant to recommend systemic multidrug chernotherapy for a patient with one plaque of MF. WarreJ/ J. Redmond, M.D. 8044 Shoal Creek BIl'd. Austill, TX 78758
Pruritus associated with niacinamide To the Editor: A 71-year-old man presented to our office last June with the complaint of a burning to itching pruritus in a shawl distribution for a month. The present history was not really revealing. Past history revealed left inguinal and testicular causalgia since a herniorrhaphy in 1975, adult-onset diabetes with distal sensory neuropathy and drug reaction to tetracycline and penicillin, giving pruritus and "rash." Medication used was tolazomide (Tolinase) . Examination showed only six or seven l-rnrn papules in the same area, with skin lines preserved over them. The course of the investigation found that he had been taking a megavitamin (Stresstabs; Lederle Laboratories) he had forgotten to mention . It was suggested by another physician 1 month before without direct objective purpose. He discontinued it, found immediate relief from the pruritus, and then reproduced the symptoms with a rechallenge in a few days and also I to 2 months later. He also found somewhat similar sensa-
tions from 50 mg of niacin he had around the house for reasons uncertain. All laboratory examinations except the biopsy had been normal. It showed a perfect dermal tubercle with lymphocytes and plasma cells around vessels with thickened endothelium. His VDRL and fluorescent treponemal antibody test (Fl' A-ABS) were positive; lumbar puncture and neurologic consultation showed no syphilitic stigmata. Further pursuit of his problems was halted by his suicide, assumably because of his unremitting orchialgia. Two points can be gleaned from this case. The first is to illustrate yet again (especially to younger physicians like myself) that syphilis can be found in many forms and ages. The second and more practical point is that vitamins must be considered factors when sleuthing esoteric problems, e.g., pruritus. The patient had a clinically observable and reproducible adverse reaction to a multiple vitamin that contains some elements many times in excess of the presently accepted daily requirements . His reaction is presumed to be to niacinamide, which in his brand of vitamin amounted to 100 mg. While there is much clinical experience in treating hyperlipidernia with levels of nicotinic acid in the 1-6 gm range':" and also vascular dilatation in the 50-300 mg range, 1.2 th~re' is none using its amide derivative because it has neither of these effects clinically. Pruritus and flushing are frequent at the lower doses of nicotinic acid and are almost predictable in the higher doses. The B vitamins are water-soluble, but nicotinic acid has toxic effects in animals and man." There is apparently no toxicity information in man regarding niacinamide as revealed in our literature search. But Mosher," in reviewing nicotinic acid, reported that niacinamide was two to three times as toxic in mice and rats as nicotinic acid. In Physicians' Desk Reference, 1979, there are twenty-one entries under niacinamide as the generic substance without nicotinic acid, but perhaps as part of a compound with the dose range being 10 to 500 mg . Only two brands list flushing or pruritus as possible adverse reactions, one brand at 150 mg and the other at 200 mg. For nicotinic acid there are twelve entries, ranging from 50 to 500 mg. Eight list pruritus and/or flushing as possible adverse effects. Four do not. In a public information booklet on excess vitamin effects," neither the text nor the references mention any adverse reactions to niacinamide. Equally unrewarding arc the currently available dermatology texts,I.5-8 a standard pharmacology text," and a standard dietary reference."
Volume 3 Number 5 November, 1980
Correspondence
In a time in which the vogue of more vitamins means better health, and in which a certain segment of health practitioners are stressing health through "natural" (sic) methods, vitamins have to be elevated to drug status. The evidence is circumstantial for the association of the pruritus and niacinamide, but the clinically reliable reproduction of the symptomatology does suggest a causative association. Hopefully, this physician's experience wiII help to remind others to inquire about vitamin ingestion as well as birth control pills beyond what patients consider medicine in their histories.
Frank A. Bures, M.D. Winona Clinic, Ltd. Department of Dermatology 420 East Sarnia Winona, MN 55987 A note of gratitude is given to our dermatology nursing staff and dietitian in gathering some of the information.
REFERENCES I. Rook A, et al, editors: Textbook of dermatology. Oxford, 1972, Blackwell Scientific Publications, pp. 2054-2056. 2. Goodman LS, Gilman A: The pharmacological basis of therapeutics. New York, 1975, The Macmillan Co., pp. 749-56; 1554-1556. 3. Mosher LR: Nicotinic acid side effects and toxicity: A review. Am J Psychiatr 126:124-130, 1970. 4. Hypervitaminosis, Dining, Food, and Nutrition Council of Minnesota, 1979. 5. Moschella SL, et al: Dermatology. Philadelphia, 1975, W. B. Saunders Co., pp. 1246-1247. 6. Demis OJ, et al, editors: Clinical dermatology. New York, 1979, Harper & Row, Publishers, Inc. 7. Domonkos A: Andrew's Diseases of the skin. Philadelphia, 1973, W. B. Saunders Co., pp. 110,587. 8. Fitzpatrick TB, et al, editors: Dermatology in general medicine. New York, 1979, McGraw-Hili Book Co., pp. 1026-1027; 1774; 1828. 9. Schneider HA, et al: Nutritional support of medical practice. New York, 1977, Harper & Row, Publishers, Inc., pp.27-28.
Therapy of lentigo maligna and Spitz nevus To the Editor: I read with interest the Home Study Course on "Primary Melanoma of the Skin" by A. J. Sober, M.D., T. B. Fitzpatrick, M.D., and M. C. Mihm, Jr., M.D., which appeared on page 179 of the March, 1980, issue of the JOURNAL. Several comments I believe merit clarification. The authors referred to lentigo
531
maligna as a premalignant lesion, with a radial growth phase that may last from 5 to 50 years. They referred to this lesion in the absence of dermal invasion as "atypical melanocytic hyperplasia," and not melanoma. In the early part of their article they referred to this premetastatic growth phase, and suggested this "lead time" makes it possible to excise early lesions and markedly improve survival rates. They, however, did not suggest in their surgical guidelines excision or other treatment of this early phase, and therefore I wonder what their therapeutic approach is. Paradoxically, however, in their discussion of spindle cell nevi (Spitz nevi), they stated that these lesions, which previously •'would have been considered malignant, are now diagnosed as benign." Nonetheless, in these supposedly benign lesions, which most commonly occur on the face of young children and measure approximately a centimeter in diameter, the authors recommend excision with a 0.5 em to I ern margin. I wonder, in cases in which a 2-mm punch biopsy can differentiate this lesion from a malignant melanoma, if management of this lesion in a less aggressive fashion would prove medically suitable and cosmetically more acceptable.
Daniel Lowe, M.D. 240 Wharncliffe Rd., North, Suite 200 London, Ontario N6H 4P2 Canada
Reply To the Editor: Dr. Lowe raises two important questions with respect to our paper, namely, the therapy of lentigo maligna and the Spitz nevus. For lentigo maligna, we recommend where possible local excision of the lesions with 0.3 to 1.0 cm margin (range suggested by our group's surgeons). In some elderly individuals, especially those in poor health, close observation without surgery could be justified. We would not recommend superficial treatments such as dermabrasion, grenz irradiation, or cryosurgery since the atypical melanocytes of lentigo maligna often extend down the hair follicles and may not be destroyed by these relatively superficial forms of treatment. For the Spitz nevus, if one is certain that one is dealing with a benign spindle cell nevus (Spitz nevus), then no therapy is required. In cases in which clinically and histopathologically the lesion is unquestionably a compound nevus of Spitz, no one could quarrel with establishing the diagnosis with a 2-mm punch biopsy.
530 Correspondence
goides Cooperative Group. Cancer Treat Rep 63:701-707, 1979. 2. Ederer F, Axtell LM, Cutler SJ: Relative survival rates: A statistical methodology, National Cancer Institute Monograph No.6. Washington, DC, 1961, U. S. Government Printing Office, pp . 101-121. 3. Armitage P: Analysis of data from clinical trials . The Statistician 28:171-181,1979 .
Reply To the Editor: Whether or not there is agreement over the method of gathering data, the basic question to be asked once the diagnosis of mycosis fungoides has been made is how the disease is to be treated. Studies compiling data on large groups of patients such as ours and the ongoing work with Dr. Lamberg's group will hopefully shed some light on the answer. But since there is currently no clear-cut evidence that early aggressive therapy has significant benefits over other modalities, I would be hesitant to recommend systemic multidrug chernotherapy for a patient with one plaque of MF. WarreJ/ J. Redmond, M.D. 8044 Shoal Creek BIl'd. Austill, TX 78758
Pruritus associated with niacinamide To the Editor: A 71-year-old man presented to our office last June with the complaint of a burning to itching pruritus in a shawl distribution for a month. The present history was not really revealing. Past history revealed left inguinal and testicular causalgia since a herniorrhaphy in 1975, adult-onset diabetes with distal sensory neuropathy and drug reaction to tetracycline and penicillin, giving pruritus and "rash." Medication used was tolazomide (Tolinase) . Examination showed only six or seven l-rnrn papules in the same area, with skin lines preserved over them. The course of the investigation found that he had been taking a megavitamin (Stresstabs; Lederle Laboratories) he had forgotten to mention . It was suggested by another physician 1 month before without direct objective purpose. He discontinued it, found immediate relief from the pruritus, and then reproduced the symptoms with a rechallenge in a few days and also I to 2 months later. He also found somewhat similar sensa-
tions from 50 mg of niacin he had around the house for reasons uncertain. All laboratory examinations except the biopsy had been normal. It showed a perfect dermal tubercle with lymphocytes and plasma cells around vessels with thickened endothelium. His VDRL and fluorescent treponemal antibody test (Fl' A-ABS) were positive; lumbar puncture and neurologic consultation showed no syphilitic stigmata. Further pursuit of his problems was halted by his suicide, assumably because of his unremitting orchialgia. Two points can be gleaned from this case. The first is to illustrate yet again (especially to younger physicians like myself) that syphilis can be found in many forms and ages. The second and more practical point is that vitamins must be considered factors when sleuthing esoteric problems, e.g., pruritus. The patient had a clinically observable and reproducible adverse reaction to a multiple vitamin that contains some elements many times in excess of the presently accepted daily requirements . His reaction is presumed to be to niacinamide, which in his brand of vitamin amounted to 100 mg. While there is much clinical experience in treating hyperlipidernia with levels of nicotinic acid in the 1-6 gm range':" and also vascular dilatation in the 50-300 mg range, 1.2 th~re' is none using its amide derivative because it has neither of these effects clinically. Pruritus and flushing are frequent at the lower doses of nicotinic acid and are almost predictable in the higher doses. The B vitamins are water-soluble, but nicotinic acid has toxic effects in animals and man." There is apparently no toxicity information in man regarding niacinamide as revealed in our literature search. But Mosher," in reviewing nicotinic acid, reported that niacinamide was two to three times as toxic in mice and rats as nicotinic acid. In Physicians' Desk Reference, 1979, there are twenty-one entries under niacinamide as the generic substance without nicotinic acid, but perhaps as part of a compound with the dose range being 10 to 500 mg . Only two brands list flushing or pruritus as possible adverse reactions, one brand at 150 mg and the other at 200 mg. For nicotinic acid there are twelve entries, ranging from 50 to 500 mg. Eight list pruritus and/or flushing as possible adverse effects. Four do not. In a public information booklet on excess vitamin effects," neither the text nor the references mention any adverse reactions to niacinamide. Equally unrewarding arc the currently available dermatology texts,I.5-8 a standard pharmacology text," and a standard dietary reference."
Volume 3 Number 5 November, 1980
Correspondence
In a time in which the vogue of more vitamins means better health, and in which a certain segment of health practitioners are stressing health through "natural" (sic) methods, vitamins have to be elevated to drug status. The evidence is circumstantial for the association of the pruritus and niacinamide, but the clinically reliable reproduction of the symptomatology does suggest a causative association. Hopefully, this physician's experience wiII help to remind others to inquire about vitamin ingestion as well as birth control pills beyond what patients consider medicine in their histories.
Frank A. Bures, M.D. Winona Clinic, Ltd. Department of Dermatology 420 East Sarnia Winona, MN 55987 A note of gratitude is given to our dermatology nursing staff and dietitian in gathering some of the information.
REFERENCES I. Rook A, et al, editors: Textbook of dermatology. Oxford, 1972, Blackwell Scientific Publications, pp. 2054-2056. 2. Goodman LS, Gilman A: The pharmacological basis of therapeutics. New York, 1975, The Macmillan Co., pp. 749-56; 1554-1556. 3. Mosher LR: Nicotinic acid side effects and toxicity: A review. Am J Psychiatr 126:124-130, 1970. 4. Hypervitaminosis, Dining, Food, and Nutrition Council of Minnesota, 1979. 5. Moschella SL, et al: Dermatology. Philadelphia, 1975, W. B. Saunders Co., pp. 1246-1247. 6. Demis OJ, et al, editors: Clinical dermatology. New York, 1979, Harper & Row, Publishers, Inc. 7. Domonkos A: Andrew's Diseases of the skin. Philadelphia, 1973, W. B. Saunders Co., pp. 110,587. 8. Fitzpatrick TB, et al, editors: Dermatology in general medicine. New York, 1979, McGraw-Hili Book Co., pp. 1026-1027; 1774; 1828. 9. Schneider HA, et al: Nutritional support of medical practice. New York, 1977, Harper & Row, Publishers, Inc., pp.27-28.
Therapy of lentigo maligna and Spitz nevus To the Editor: I read with interest the Home Study Course on "Primary Melanoma of the Skin" by A. J. Sober, M.D., T. B. Fitzpatrick, M.D., and M. C. Mihm, Jr., M.D., which appeared on page 179 of the March, 1980, issue of the JOURNAL. Several comments I believe merit clarification. The authors referred to lentigo
531
maligna as a premalignant lesion, with a radial growth phase that may last from 5 to 50 years. They referred to this lesion in the absence of dermal invasion as "atypical melanocytic hyperplasia," and not melanoma. In the early part of their article they referred to this premetastatic growth phase, and suggested this "lead time" makes it possible to excise early lesions and markedly improve survival rates. They, however, did not suggest in their surgical guidelines excision or other treatment of this early phase, and therefore I wonder what their therapeutic approach is. Paradoxically, however, in their discussion of spindle cell nevi (Spitz nevi), they stated that these lesions, which previously •'would have been considered malignant, are now diagnosed as benign." Nonetheless, in these supposedly benign lesions, which most commonly occur on the face of young children and measure approximately a centimeter in diameter, the authors recommend excision with a 0.5 em to I ern margin. I wonder, in cases in which a 2-mm punch biopsy can differentiate this lesion from a malignant melanoma, if management of this lesion in a less aggressive fashion would prove medically suitable and cosmetically more acceptable.
Daniel Lowe, M.D. 240 Wharncliffe Rd., North, Suite 200 London, Ontario N6H 4P2 Canada
Reply To the Editor: Dr. Lowe raises two important questions with respect to our paper, namely, the therapy of lentigo maligna and the Spitz nevus. For lentigo maligna, we recommend where possible local excision of the lesions with 0.3 to 1.0 cm margin (range suggested by our group's surgeons). In some elderly individuals, especially those in poor health, close observation without surgery could be justified. We would not recommend superficial treatments such as dermabrasion, grenz irradiation, or cryosurgery since the atypical melanocytes of lentigo maligna often extend down the hair follicles and may not be destroyed by these relatively superficial forms of treatment. For the Spitz nevus, if one is certain that one is dealing with a benign spindle cell nevus (Spitz nevus), then no therapy is required. In cases in which clinically and histopathologically the lesion is unquestionably a compound nevus of Spitz, no one could quarrel with establishing the diagnosis with a 2-mm punch biopsy.