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Pellagra: A revisionist approach
Pellagra: A
evisionist Approach
SAMUEL EICHOLD, M.D., MIROSLAV~ELEK, M.D. Mobile, AlabamaCLIFFORD DACSO, M.D., M.P.H. SanDego,
istory is rarely kind in its remembrances. Dimly H remembered eponyms pepper the medical literature and, with the possible exception of teaching rounds, fade once again into obscurity. Three errors characterize the history of pellagra and have been perpetuated in the medical literature. Clarification of these three misconceptions is critical to the understanding of this now rare malady and its place in the history of medicine. Francoise Thiery is commonly credited with primacy in the clinical description of pellagra. He published his account in 1755 [l], antedating the publication of Gaspar Casal(1691-1759) in 1762 [2]. Casal described the illness, known as “ma1 de rosa” at that time, and recognized its connection to the importation of maize from the New World. This connection gave another name to pellagra-Asturian leprosy-named for a region in Northern Spain where maize was consumed. Casal recognized dementia as a prominent feature of pellagra and described “Casal’s necklace,” the sunburn-like lesions present around the collars of pellagrins. There is reasonable evidence to suggest that Thiery learned about Casal’s work at the Court and published his own observations. The error of crediting Thiery with the primal observation rather than simply the earliest publication persists. Casal seems to have been there first. The disease was named by Francesco Frapolli [3] in 1775, deriving the word from pell (skin) and agra (rough). Frapolli, like Casal, attributed the illness to the consumption of maize by the poor. In the United States, pellagra was not described until the beginning of the 19th century, when the southeast part of the country was widely affected. Sydenstricker noted that this extensive disease was related to the widespread use of the milling process on corn. Because of the prominent neurologic component, many of the victims of the disorder were placed in asylums for the insane. In Alabama, George Searcy [4] described 88 cases of pellagra with a mortality rate of 60 percent. E.D. Bondurant of the Medical Department of the Medical College in Mobile, the precursor of the University of South Alabama, provided histologic support for the report. Bondurant [5] subsequently wrote, “I contributed nothing material toward the making of the diagnosis, but I did become interested in the disease.” Bondurant [6] made further observations on the neurologic manifestations of pellagra in 1910, with the report of an additional 17 cases. Bondurant recognized the disease as connected with malnutrition. He wrote From the Departmentsof Internal Medicine and Psychratry, University of South Alabama College of Medicine, Mobile, Alabama, and the Department of Medicine, University of California, San Diego School of Medicine, and the Veterans Administration Medical Center, San Diego, California. Requests for reprints should be addressed to Dr. Samuel Eichold, Department of Internal Medicine, University of South Alabama College of Medicine, 2451 Fillingim Street, Mobile, Alabama 36617. Manuscript submitted December 11, 1986, and accepted in revised form July 8, 1988. I
I
California
of “the diagnostic value of the neurasthenic complex: nervousness, irritability, depression of the spirits, change in disposition, emotional instability, intellectual sluggishness, tendency to causeless suspicion, and hypochondria. These symptoms, especially when occurring in association with ‘nervous dyspepsia,’ ‘anemia,’ emaciation, and ‘summer diarrhea,’ are, in one who has eaten much cornbread, suggestive of a possible pellagrous intoxication. In such cases,” Bondurant continued, “the further use of cornbread should be forbidden and measures looking to the upbuilding of the general health instituted. . . . [T]he action of the toxin [of pellagra] is reinforced and intensified by the general state of malnutrition, which constitutes an important feature of the malady.” This early description of the neuropsychiatric manifestations of pellagra recognized that dietary manipulation can be salutary. A further work on pellagra was published in 1912 by Bondurant [7] distinguishing the terminal dementia of pellagra from the other neurologic syndromes of the disease. Although Searcy received a posthumous citation from the Alabama Medical Association in 1940 [8], Bondurant’s contributions have generally been overlooked. A second error in the history of this disease is perpetuated. In a series of papers, Casimir Funk [g-11] associated pellagra with a vitamin-deficient state. He clearly related the illness to the consumption of overmilled corn. His paper “Prophylaxe und therapie der Pellagra im Lichte der Vitaminhiere” [12] appeared three months prior to Joseph Goldberger’s [13] classic and oft-cited monograph. Funk also correctly identified nicotinic acid in 1911 [14] but incorrectly thought that it was not a vitamin. Two decades elapsed until Elvenhjem [15] correctly identified nicotinic acid as the nutritional component that prevented pellagra. Goldberger, of course, published extensively on pellagra and is popularly credited with its conquest. Goldberger’s contributions cannot be diminished despite his not being first. The thorough investigation of the disease performed by Goldberger and his colleagues stands as a model for epidemiologists. On at least seven occasions, Goldberger and co-workers [16] exposed themselves orally and parenterally to skin and excreta derived from patients with pellagra to prove that this was not a contagious illness. Although this is not the currently recommended technique for latter-day infectious disease investigation, the courage of Goldberger and his associates is truly remarkable and deserves continuing recognition, Nonetheless, a third error in the popular history of this ancient disorder is perpetuated, and Casimir Funk should be credited with the description of the etiology of pellagra. Pellagra, like so many other diseases, has been distilled of its riches and controversy by history. It appears that Funk recognized the biochemical relations of pellagra and should be so credited. Bondurant
September 1988 The American Journal of Medicine
Volume 85
405
HISTORY
OF PELLAGRA
/ EICHOLD
ET AL
should be acknowledged for a systematic description of the neuropsychiatric manifestations of the disorder and its relationship to diet. Goldberger deserves recognition for his classic and courageous observations and experiments that caused the downturn in the epidemic curve of pellagra. There are three misconceptions in the popular history of pellagra. In addition to diarrhea, dermatitis, dementia, and death, the four D’s of pellagra that have survived in medical lore, a fifth, default, should be added to remind us that history is not always kind in its remembrances.
REFERENCES l.Thiery F: Journal de medicine, chirurgie, et pharmacie (Paris). 1755; 2: 337346. Cited in: Garrison FH. An introduction to the history of medicine, 4th ed. Philadelphia: W.B. Saunders: 1929, 368. 2. Casal G: Historia natural y medica de el principado de Asturias. Madrid, 1762. Cited in: Garrison FH. An introduction to the history of medicine, 4th ed. Philadelphia: W.B. Saunders; 1929, 367. 3. Frapolli F: Animadversiones in morbum, vulgo pelagram, Milan, 1771. Cited in: Garrison FH. An introduction to the history of medicine, 4th ed. Philadelphia: W.B. Saunders; 1929, 368.
406
September
1988
The American
Journal
of Medicine
Volume
4. Searcy GH: An epidemic of acute pellagra. JAMA 1907; 49: 37-38. 5. Bondurant ED: Pellagra, with report of nine cases. Medical Records (New York) 1909: 76: 300-304. 6. Bondurant ED: The nervous symptoms of pellagra. Gulf States Journal of Medicine and Surgery 1910; 16: 28-37. 7. Bondurant ED: Terminal states in pellagra resembling general paresis, with report of 5 cases. J Nerv Ment Dis 1912; 39: 734-738. 8. Holley HL: The history of medicine in Alabama. Mobile, Alabama: The University of Alabama Press, 1982. 9. Funk C: The etiology of the deficiency diseases: beriberi, polyneuritis in birds, epidemic dropsy, scurvy, experimental scurvy in animals, infantile scurvy, ship beriberi, pellagra. J State Med (London) 1913: 47: 389-392. 10. Funk C: Die vitamine und therapie der pellagra im lichte der vitaminlehre. Munchen Med Wchnschr 1914; 61: 698-699. 11. Funk C: Die vitamine, ihre bedeutung fur die physiologie und pathologie mit besonderer berucksichtigung der avitaminosen: beriberi, skorbut, pellagra, rachitis. Wiesbaden: JF Bergmann, 1914. (English translation: The vitamins. Translated by Dubin HE. Baltimore: Williams & Wilkins, 1922. 12. Funk C: Die vitamine und terapie der pellagra im lichte der vitamrnlehre. Munthen Med Wchnschr 1914; 61: 698-699. 13. Goldberger J: The etiology of pellagra. Public Health Reports (Washington, D.C.) 29: 1683, 1686, June 26, 1914. 14. Funk C: The chemical nature of the substance which cures polyneuritis in birds induced by a diet of polished rice. J Physiol (London) 1911; 43: 395-400. 15. Elvenhjem CA, Madden RJ, Strong FM, Wooley DM: Relation of nicotinic acid and nicotinic amide to canine black tongue. J Am Chem Sot 1937; 59: 1767-1768. 16. Terris M, ed: Goldberger on pellagra. Baton Rouge, Louisiana: State University Press, 1964.
85
evisionist Approach
SAMUEL EICHOLD, M.D., MIROSLAV~ELEK, M.D. Mobile, AlabamaCLIFFORD DACSO, M.D., M.P.H. SanDego,
istory is rarely kind in its remembrances. Dimly H remembered eponyms pepper the medical literature and, with the possible exception of teaching rounds, fade once again into obscurity. Three errors characterize the history of pellagra and have been perpetuated in the medical literature. Clarification of these three misconceptions is critical to the understanding of this now rare malady and its place in the history of medicine. Francoise Thiery is commonly credited with primacy in the clinical description of pellagra. He published his account in 1755 [l], antedating the publication of Gaspar Casal(1691-1759) in 1762 [2]. Casal described the illness, known as “ma1 de rosa” at that time, and recognized its connection to the importation of maize from the New World. This connection gave another name to pellagra-Asturian leprosy-named for a region in Northern Spain where maize was consumed. Casal recognized dementia as a prominent feature of pellagra and described “Casal’s necklace,” the sunburn-like lesions present around the collars of pellagrins. There is reasonable evidence to suggest that Thiery learned about Casal’s work at the Court and published his own observations. The error of crediting Thiery with the primal observation rather than simply the earliest publication persists. Casal seems to have been there first. The disease was named by Francesco Frapolli [3] in 1775, deriving the word from pell (skin) and agra (rough). Frapolli, like Casal, attributed the illness to the consumption of maize by the poor. In the United States, pellagra was not described until the beginning of the 19th century, when the southeast part of the country was widely affected. Sydenstricker noted that this extensive disease was related to the widespread use of the milling process on corn. Because of the prominent neurologic component, many of the victims of the disorder were placed in asylums for the insane. In Alabama, George Searcy [4] described 88 cases of pellagra with a mortality rate of 60 percent. E.D. Bondurant of the Medical Department of the Medical College in Mobile, the precursor of the University of South Alabama, provided histologic support for the report. Bondurant [5] subsequently wrote, “I contributed nothing material toward the making of the diagnosis, but I did become interested in the disease.” Bondurant [6] made further observations on the neurologic manifestations of pellagra in 1910, with the report of an additional 17 cases. Bondurant recognized the disease as connected with malnutrition. He wrote From the Departmentsof Internal Medicine and Psychratry, University of South Alabama College of Medicine, Mobile, Alabama, and the Department of Medicine, University of California, San Diego School of Medicine, and the Veterans Administration Medical Center, San Diego, California. Requests for reprints should be addressed to Dr. Samuel Eichold, Department of Internal Medicine, University of South Alabama College of Medicine, 2451 Fillingim Street, Mobile, Alabama 36617. Manuscript submitted December 11, 1986, and accepted in revised form July 8, 1988. I
I
California
of “the diagnostic value of the neurasthenic complex: nervousness, irritability, depression of the spirits, change in disposition, emotional instability, intellectual sluggishness, tendency to causeless suspicion, and hypochondria. These symptoms, especially when occurring in association with ‘nervous dyspepsia,’ ‘anemia,’ emaciation, and ‘summer diarrhea,’ are, in one who has eaten much cornbread, suggestive of a possible pellagrous intoxication. In such cases,” Bondurant continued, “the further use of cornbread should be forbidden and measures looking to the upbuilding of the general health instituted. . . . [T]he action of the toxin [of pellagra] is reinforced and intensified by the general state of malnutrition, which constitutes an important feature of the malady.” This early description of the neuropsychiatric manifestations of pellagra recognized that dietary manipulation can be salutary. A further work on pellagra was published in 1912 by Bondurant [7] distinguishing the terminal dementia of pellagra from the other neurologic syndromes of the disease. Although Searcy received a posthumous citation from the Alabama Medical Association in 1940 [8], Bondurant’s contributions have generally been overlooked. A second error in the history of this disease is perpetuated. In a series of papers, Casimir Funk [g-11] associated pellagra with a vitamin-deficient state. He clearly related the illness to the consumption of overmilled corn. His paper “Prophylaxe und therapie der Pellagra im Lichte der Vitaminhiere” [12] appeared three months prior to Joseph Goldberger’s [13] classic and oft-cited monograph. Funk also correctly identified nicotinic acid in 1911 [14] but incorrectly thought that it was not a vitamin. Two decades elapsed until Elvenhjem [15] correctly identified nicotinic acid as the nutritional component that prevented pellagra. Goldberger, of course, published extensively on pellagra and is popularly credited with its conquest. Goldberger’s contributions cannot be diminished despite his not being first. The thorough investigation of the disease performed by Goldberger and his colleagues stands as a model for epidemiologists. On at least seven occasions, Goldberger and co-workers [16] exposed themselves orally and parenterally to skin and excreta derived from patients with pellagra to prove that this was not a contagious illness. Although this is not the currently recommended technique for latter-day infectious disease investigation, the courage of Goldberger and his associates is truly remarkable and deserves continuing recognition, Nonetheless, a third error in the popular history of this ancient disorder is perpetuated, and Casimir Funk should be credited with the description of the etiology of pellagra. Pellagra, like so many other diseases, has been distilled of its riches and controversy by history. It appears that Funk recognized the biochemical relations of pellagra and should be so credited. Bondurant
September 1988 The American Journal of Medicine
Volume 85
405
HISTORY
OF PELLAGRA
/ EICHOLD
ET AL
should be acknowledged for a systematic description of the neuropsychiatric manifestations of the disorder and its relationship to diet. Goldberger deserves recognition for his classic and courageous observations and experiments that caused the downturn in the epidemic curve of pellagra. There are three misconceptions in the popular history of pellagra. In addition to diarrhea, dermatitis, dementia, and death, the four D’s of pellagra that have survived in medical lore, a fifth, default, should be added to remind us that history is not always kind in its remembrances.
REFERENCES l.Thiery F: Journal de medicine, chirurgie, et pharmacie (Paris). 1755; 2: 337346. Cited in: Garrison FH. An introduction to the history of medicine, 4th ed. Philadelphia: W.B. Saunders: 1929, 368. 2. Casal G: Historia natural y medica de el principado de Asturias. Madrid, 1762. Cited in: Garrison FH. An introduction to the history of medicine, 4th ed. Philadelphia: W.B. Saunders; 1929, 367. 3. Frapolli F: Animadversiones in morbum, vulgo pelagram, Milan, 1771. Cited in: Garrison FH. An introduction to the history of medicine, 4th ed. Philadelphia: W.B. Saunders; 1929, 368.
406
September
1988
The American
Journal
of Medicine
Volume
4. Searcy GH: An epidemic of acute pellagra. JAMA 1907; 49: 37-38. 5. Bondurant ED: Pellagra, with report of nine cases. Medical Records (New York) 1909: 76: 300-304. 6. Bondurant ED: The nervous symptoms of pellagra. Gulf States Journal of Medicine and Surgery 1910; 16: 28-37. 7. Bondurant ED: Terminal states in pellagra resembling general paresis, with report of 5 cases. J Nerv Ment Dis 1912; 39: 734-738. 8. Holley HL: The history of medicine in Alabama. Mobile, Alabama: The University of Alabama Press, 1982. 9. Funk C: The etiology of the deficiency diseases: beriberi, polyneuritis in birds, epidemic dropsy, scurvy, experimental scurvy in animals, infantile scurvy, ship beriberi, pellagra. J State Med (London) 1913: 47: 389-392. 10. Funk C: Die vitamine und therapie der pellagra im lichte der vitaminlehre. Munchen Med Wchnschr 1914; 61: 698-699. 11. Funk C: Die vitamine, ihre bedeutung fur die physiologie und pathologie mit besonderer berucksichtigung der avitaminosen: beriberi, skorbut, pellagra, rachitis. Wiesbaden: JF Bergmann, 1914. (English translation: The vitamins. Translated by Dubin HE. Baltimore: Williams & Wilkins, 1922. 12. Funk C: Die vitamine und terapie der pellagra im lichte der vitamrnlehre. Munthen Med Wchnschr 1914; 61: 698-699. 13. Goldberger J: The etiology of pellagra. Public Health Reports (Washington, D.C.) 29: 1683, 1686, June 26, 1914. 14. Funk C: The chemical nature of the substance which cures polyneuritis in birds induced by a diet of polished rice. J Physiol (London) 1911; 43: 395-400. 15. Elvenhjem CA, Madden RJ, Strong FM, Wooley DM: Relation of nicotinic acid and nicotinic amide to canine black tongue. J Am Chem Sot 1937; 59: 1767-1768. 16. Terris M, ed: Goldberger on pellagra. Baton Rouge, Louisiana: State University Press, 1964.
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