Lymph-Node Bacilliform Bodies Resembling Those of Whipple's Disease in a Patient without Intestinal Involvement CHARLES M. MANSBACH II, M.D.; JOHN D. SHELBURNE, M.D., Ph.D.; ROBERT D. STEVENS, Ph.D.; and WILLIAM O. DOBBINS III, M.D.; Durham,
A 38-year-old man developed symptoms of arthralgias and arthritis, lymphadenopathy, and weight loss. An axillary lymph-node biopsy was done in the diagnostic study; a periodic acid Schiff stain, done for evidence of fungal infection, showed periodic acid Schiff reagent-positive macrophages. Electron microscopy showed the typical morphologic features of the bacilliform bodies associated with Whipple's disease to be present in the macrophages of the lymph node. The patient had no intestinal symptoms. The absorption of a variety of substrates was found to be normal. Nine intestinal biopsies showed no organisms similar to those found in his lymph node. On tetracycline therapy, he symptomatically improved. The findings raise the question of the route of infection in Whipple's disease and point up the usefulness of periodic acid Schiff staining of lymph-node biopsies.
W H I P P L E ' S DISEASE usually affects middle-aged or older
men and often begins with arthralgias (1). Diarrhea, weight loss, and abdominal pain appear later during the course of the illness (2). In all previously reported patients, the hallmark of the disease, diastase resistant periodic acid Schiff-positive macrophages, has been found in the intestinal mucosa irrespective of the presence (2) or absence (3-5) of bowel symptomatology. In contrast, we present a patient in whom multiple small-bowel biopsies showed no diagnostic macrophages, although he had other symptoms and signs of Whipple's disease. Case Report The patient was a 38-year-old married white male logger who was first admitted to the Durham Veterans Administration Hospital on 4 December 1975 for evaluation of a 3-year history of arthritis. The arthritis was symmetrical and involved primarily the shoulders, but also the neck, elbows, metacarpal-phalangeal joints, knees, ankles, and metatarsal-phalangeal joints. There was a 4-month history of lymphadenopathy and night sweats. He had lost 3.18 kg [7 lbs] and complained of moderate fatiga• From the Durham Veterans Administration Hospital; Durham, North Carolina; Division of Gastroenterology, Department of Medicine, and the Department of Pathology, Duke University Medical Center; Durham, North Carolina; and the Division of Gastroenterology, George Washington University Medical Center; Washington, D . C . 5 4
Annals of Internal Medicine 8 9 : 6 4 - 6 6 , 1 9 7 8
Downloaded from https://annals.org by Tulane University user on 01/21/2019
North Carolina
bility and malaise. There were no abdominal complaints or diarrhea. He presented as a thin white man in no acute distress; temperature, 37 °C. A 2/6 systolic ejection murmur and diffuse lymphadenopathy ( l x l to 1 x 2 cm) were the only abnormalities found. There were no objective joint changes. Laboratory findings: hemoglobin, 14.5 g/dl; leukocytes, 13 600/mm3; albumin, 5.0 g/dl; globulins, 3.4 g/dl; cholesterol, 204 mg/dl; alkaline phosphatase, 130 IU; and calcium, 9.1 mg/dl. Serologic tests for febrile agglutinins, brucella, toxoplasmosis; mononucleosis spot test, systemic lupus erythematosis preparation, fluorescent antinuclear antibody, hepatitis B surface antigen, latex fixation, and Coombs' tests were all negative or had normal titers. Roentgenograms of all joints, including the sacroiliac, were normal. The serum complement had a hemolytic complement titer of 71 (normal, 22 to 84). Purified protein derivative and histoplasmosis skin tests were nonreactive. Biopsies of both left and right axillary lymph nodes were originally interpreted as containing noncaseating granulomata, but later review of periodic acid Schiff stains of the lymph-node biopsies showed a fine-to-moderate periodic acid Schiff-positive, diastase-resistant granularity in epitheliod histiocytes. Special stains for acid-fast bacilli, fungi, and bacteria were negative; culture of the left axillary node grew Propionibacterium avidum. On 22 December 1975, the patient developed a painful right wrist, which was swollen, warm, and tender. Joint aspiration showed 96 000 leukocytes/mm3; with 92% polymorphonuclear neutrophils. No crystals were seen and cultures were negative. The patient was thought to have sarcoidosis and was discharged on 23 December 1975; ibuprofen was prescribed. Because of the finding of periodic acid Schiff-positive macrophages, electron microscopy was done on both lymph nodes. This showed numerous rod-shaped bacilliform bodies within macrophages (Figure 1). These bacilliform bodies were approximately 0.2 jmm wide and 2.0 jmm long in both biopsies. Because of this new finding, the patient was recalled for admission on 13 January, 1976, with Whipple's disease the suspected diagnosis. The intervening history was unremarkable and the laboratory examination unchanged. His right wrist inflammation had subsided, and his systolic ejection murmur had resolved. The patient underwent the following tests of intestinal function: D-xylose absorption, 6 g recovered in the urine 5 h after a 25-g oral dose; Schilling test, 19% of the orally administered (57Co) Vitamin B12 recovered in the urine in 24 h; chemical fat balance, 3 g of fat excreted per day on a 100-g daily oral intake; (,4C) cholate half life in the enterohepatic space, 2 days (normal) (6) with a normal rate of conversion to secondary bile acids and a normal ratio of glycine-to-taurine bile-acid conjugates (6). A culture of his small-bowel contents showed 1 X 10* micrococcus/ml. Six intestinal biopsies from the proximal jejunum and duodenum were obtained using a hydraulic biopsy instrument (7). Five of these biopsies were examined microscopically (see below); only one periodic acid Schiff-positive macrophage was A 1 Q 7 Q
A m n r i / ^ o n P n l l a a a r\4 D h u e i / > i a n e
seen. One biopsy was cultured bacteriologically (8) and grew out a streptococcus. The patient was referred to Dr. Dobbins for an independent assessment, at which time four additional small-bowel biopsies were obtained (3 February 1976); one was processed for light and one for electron microscopy. Two biopsies were obtained for culture (8) and were examined at 9 and 42 days of culture by both light and electron microscopy. Immunologic evaluation showed positive intradermal tests to Tricophyton and Candida albicans, normal responses to lymphocyte mitogens, normal mixed-lymphocyte culture responses, and normal immunoglobulin levels, but a decreased number of T-cell rosettes. After these investigations, the patient was returned to the Durham Veterans Administration Hospital where tetracycline, 250 mg four times a day, was begun. He returned in July 1976. His lymphadenopathy had resolved to one fourth its original size. He had gained 2.72 kg [6 lbs]. A left epitrochliar lymph node was removed. It showed only moderate cortical hyperplasia. No granulomas or periodic acid Schiff-positive histiocytes were seen. No organisms could be found by electron microscopyIntestinal Biopsies A total of 9 intestinal biopsies were prepared for histologic examination; four were processed for light microscopy and five for transmission electron microscopy. All biopsies were examined at light microscopy, and those prepared for light microscopy were stained with the peri-
odic acid Schiff stain. At light microscopy, the villi were found to be slightly shortened. The most remarkable finding was a modest infiltration of the epithelial cells by lymphocytes. In no instance, in all nine biopsies, were foamy macrophages characteristic of Whipple's disease (2) identified. Only one periodic acid Schiff-positive macrophage was seen in appropriately stained sections, which is within the range of normal. Approximately 34 electron micrographs, prepared in two different laboratories, were obtained from four biopsies (two cultured and two not cultured). N o organisms were identified that in any way resembled those found in Whipple's disease. Discussion
The diagnosis of Whipple's disease in this case rests on the peripheral lymph-node biopsy findings. There were multiple periodic acid Schiff-positive macrophages in the lymph nodes from both axillae. More important was the finding of .bacilliform bodies within the macrophages at electron microscopy. These bacteria were identical structurally (they were small, rod-shaped bacilli) to electron micrographs of bacteria found in various organs of previous cases of Whipple's disease (2, 8-13). The three organisms cultured from the patient do not resemble the bacil-
Figure 1A. The periodic acid Schiff-positive cytoplasmic granules are visible (arrows) in this small collection of macrophages in the patient's left axillary lymph node. (Periodic acid Schiff-stained paraffin section; original magnification x 1 0 0 0 . ) B. Numerous rod-shaped bacilliform bodies are seen within the cytoplasm of this macrophage (Original magnification, x 13 7 5 0 . ) C. At high magnification both the cell wall and the cytoplasmic membrane are visualized. (Original magnification, x 1 3 9 2 0 0 . ) Mansbach et al. • Lymph-Node Bacilliform Bodies
Downloaded from https://annals.org by Tulane University user on 01/21/2019
65
lus found in Whipple's disease and were considered to be contaminants. For these reasons, and because of his favorable clinical response to tetracycline, we believe that this patient has a variant of Whipple's disease (that is, without intestinal involvement). However, it is possible that the patient had a primary lymph-node disorder caused by bacilliform bodies that resemble structurally those seen in Whipple's disease. In previously published cases, even those without intestinal complaints (3-5), periodic acid Schiff-positive macrophages have been easily demonstrable in the small intestine, either at biopsy or autopsy. Recently, however, Moorthy, Nolley, and Hermos (14) have reported a case in which only two of four duodenal biopsies contained small foci of macrophages that stained with periodic acid Schiff reagent, indicating that intestinal involvement in Whipple's disease may be patchy in distribution. In our case, nine biopsies were done in two different laboratories; two biopsies processed for electron microscopy were examined separately by the two laboratories. Only one periodic acid Schiff reagent-positive macrophage was found, which we consider to be normal; two other macrophages, seen at electron microscopy, did not contain bacillary bodies. Appropriate cultures (8) of two biopsies for Whipple's organisms were nonrevealing. We did not biopsy the ileum, but in no instance has ileal involvement been described without concomitant proximal intestinal disease (15). In addition, the patient had normal ileal function, as judged by vitamin B12 absorption and (14C) cholic-acid turnover. Abnormalities in bile-acid kinetics have been previously described in Whipple's disease (16). Our patient was originally thought to have sarcoidosis. This confusion has occurred previously in other patients, and in one instance, the typical foamy macrophages apparently did not stain with the periodic acid Schiff reagent (17). Despite this one case (17), it is suggested that lymph-node biopsies, especially biopsies done for diagnostic purposes, be routinely stained with periodic acid Schiff reagent. This patient serves to point up two important speculates concerning Whipple's disease. First, this condition does not always first affect the small intestine with later spread to other organs systems, suggesting a route of infection other than the small bowel. This is in part substantiated by our previous observations that the Whipple's bacilliform bodies appeared to be more degenerate in the intestinal epithelial cells than in the underlying lamina propria (9). It was suggested that these bacteria were migrating toward, rather than from, the lumen of the intestine. Second, this patient's illness has implications in regard to evaluation of other patients with unexplained, nonde-
66
July 1978 • Annals of Internal Medicine • Volume 89 • Number 1
Downloaded from https://annals.org by Tulane University user on 01/21/2019
forming arthritis or arthralgias. These symptoms may appear 10 years or more before the onset of recognizable Whipple's disease. Such patients should have lymph-node biopsies, stained with the periodic acid Schiff reagent, if lymphadenopathy is present. A small-bowel biopsy in such patients may not yield the diagnosis, The reasonable possibility of a diagnosis of Whipple's disease is always worth pursuing, because this is a treatable disease when appropriate antibiotics are used. Finally, this case shows the value of electron microscopy of lymph nodes. Without this modality, the diagnosis in this case may not have been suggested. ACKNOWLEDGMENTS: Grant support: in part by the Electron Microscopy Laboratory, Veterans Administration Hospital, Durham, North Carolina, and the Medical Research Service of the Veterans Administration. • Requests for reprints should be addressed to Charles M. Mansbach II, M.D.; Veterans Administration Hospital; 508 Fulton Street; Durham, N C 27705. Received 21 November 1977; revision accepted 31 March 1978.
References 1. WHIPPLE GH: A hitherto undescribed disease characterized anatomically by deposits of fat and fatty acids in the intestinal and mesenteric tissues. Johns Hopkins Med J 18:382-391, 1907 2. MAIZEL H, RUFFIN JM, DOBBINS WO: Whipple's disease: a review of
19 patients from one hospital and a review of the literature since 1950. Medicine (Baltimore) 49:175-205, 1970 3. CAUGHEY DE, BYWATERS EGL: The arthritis of Whipple's syndrome. Ann Rheum Dis22:in-M5, 1963 4. LEMPERT P, T O M MI, CUMMINGS JN: Encephalopathy in Whipple's
disease. Neurology 12:65-71, 1962 5. BECKER FF, W I T T E MH, TESLER MA, D U M O N T AE: Intestinal lipo-
dystrophy (Whipple's disease). JAMA 194:559-561, 1965 6. GARBUTT JT, KENNEY TJ: Effect of cholestyramine on bile acid metabolism in normal man. / Clin Invest 51:2781-2789, 1972 7. FLICK AL, QUINTON WE, RUBIN CE: A peroral hydraulic biopsy tube for multiple sampling at any level of the gastrointestinal tract. Gastroenterology 40:120-126, 1961 8. CLANCY RL, TOMKINS WAF, MUCKLE TJ, RICHARDSON H, R A W L S
9. 10. 11.
12.
WE: Isolation and characterization of an aetiological agent in Whipple's disease. Br Med 7 3:568-570, 1975 DOBBINS WO, RUFFIN JM: A light and electron-microscopic study of bacterial invasion in Whipple's disease. Am J Pathol 51:225-242, 1967 SCHOCHET SS, LAMPERT PW: Granulomatous encephalitis in Whipple's disease. Acta Neuropathol (Bed) 13:1-11, 1969 MORNINGSTAR WA: Whipple's Disease: an example of the value of the electron microscope in diagnosis, follow-up, and correlation of a pathologic process. Hum Pathol 6:443-454, 1975 LIE JT, DAVIS JS: Pancarditis in Whipple's disease. Electronmicroscopic demonstration of intracardiac bacillary bodies. Am J Clin Pathol 66:22-30, 1976
13. H A W K I N S CF, FARR M, MORRIS CJ, HOARE AM, WILLIAMSON N:
Detection by electron microscope of rod-shaped organisms in synovial membrane from a patient with the arthritis of Whipple's Disease. Ann Rheum Dis 35:502-509, 1976 14. MOORTHY S, NOLLEY G, HERMOS J A: Whipple's disease with minimal intestinal involvement. Gut 18:152-155, 1977 15. ENZINGER FM, HELWIG EB: Whipple's disease. Virchows Arch [Pathol AnatJ 336:238-269, 1963 16. G A R B U T T JT, WILKINS RM, LACK L, TYOR MP: Bacterial modification
of taurocholate during enterohepatic recirculation in normal man and patients with small intestine disease. Gastroenterology 59:553-566, 1970 17. RODARTE JR, GARRISON CO, HOLLEY KE, F O N T ANA RS: Whipple's
disease simulating sarcoidosis. Arch Intern Med 129:479-482, 1972
A 38-year-old man developed symptoms of arthralgias and arthritis, lymphadenopathy, and weight loss. An axillary lymph-node biopsy was done in the diagnostic study; a periodic acid Schiff stain, done for evidence of fungal infection, showed periodic acid Schiff reagent-positive macrophages. Electron microscopy showed the typical morphologic features of the bacilliform bodies associated with Whipple's disease to be present in the macrophages of the lymph node. The patient had no intestinal symptoms. The absorption of a variety of substrates was found to be normal. Nine intestinal biopsies showed no organisms similar to those found in his lymph node. On tetracycline therapy, he symptomatically improved. The findings raise the question of the route of infection in Whipple's disease and point up the usefulness of periodic acid Schiff staining of lymph-node biopsies.
W H I P P L E ' S DISEASE usually affects middle-aged or older
men and often begins with arthralgias (1). Diarrhea, weight loss, and abdominal pain appear later during the course of the illness (2). In all previously reported patients, the hallmark of the disease, diastase resistant periodic acid Schiff-positive macrophages, has been found in the intestinal mucosa irrespective of the presence (2) or absence (3-5) of bowel symptomatology. In contrast, we present a patient in whom multiple small-bowel biopsies showed no diagnostic macrophages, although he had other symptoms and signs of Whipple's disease. Case Report The patient was a 38-year-old married white male logger who was first admitted to the Durham Veterans Administration Hospital on 4 December 1975 for evaluation of a 3-year history of arthritis. The arthritis was symmetrical and involved primarily the shoulders, but also the neck, elbows, metacarpal-phalangeal joints, knees, ankles, and metatarsal-phalangeal joints. There was a 4-month history of lymphadenopathy and night sweats. He had lost 3.18 kg [7 lbs] and complained of moderate fatiga• From the Durham Veterans Administration Hospital; Durham, North Carolina; Division of Gastroenterology, Department of Medicine, and the Department of Pathology, Duke University Medical Center; Durham, North Carolina; and the Division of Gastroenterology, George Washington University Medical Center; Washington, D . C . 5 4
Annals of Internal Medicine 8 9 : 6 4 - 6 6 , 1 9 7 8
Downloaded from https://annals.org by Tulane University user on 01/21/2019
North Carolina
bility and malaise. There were no abdominal complaints or diarrhea. He presented as a thin white man in no acute distress; temperature, 37 °C. A 2/6 systolic ejection murmur and diffuse lymphadenopathy ( l x l to 1 x 2 cm) were the only abnormalities found. There were no objective joint changes. Laboratory findings: hemoglobin, 14.5 g/dl; leukocytes, 13 600/mm3; albumin, 5.0 g/dl; globulins, 3.4 g/dl; cholesterol, 204 mg/dl; alkaline phosphatase, 130 IU; and calcium, 9.1 mg/dl. Serologic tests for febrile agglutinins, brucella, toxoplasmosis; mononucleosis spot test, systemic lupus erythematosis preparation, fluorescent antinuclear antibody, hepatitis B surface antigen, latex fixation, and Coombs' tests were all negative or had normal titers. Roentgenograms of all joints, including the sacroiliac, were normal. The serum complement had a hemolytic complement titer of 71 (normal, 22 to 84). Purified protein derivative and histoplasmosis skin tests were nonreactive. Biopsies of both left and right axillary lymph nodes were originally interpreted as containing noncaseating granulomata, but later review of periodic acid Schiff stains of the lymph-node biopsies showed a fine-to-moderate periodic acid Schiff-positive, diastase-resistant granularity in epitheliod histiocytes. Special stains for acid-fast bacilli, fungi, and bacteria were negative; culture of the left axillary node grew Propionibacterium avidum. On 22 December 1975, the patient developed a painful right wrist, which was swollen, warm, and tender. Joint aspiration showed 96 000 leukocytes/mm3; with 92% polymorphonuclear neutrophils. No crystals were seen and cultures were negative. The patient was thought to have sarcoidosis and was discharged on 23 December 1975; ibuprofen was prescribed. Because of the finding of periodic acid Schiff-positive macrophages, electron microscopy was done on both lymph nodes. This showed numerous rod-shaped bacilliform bodies within macrophages (Figure 1). These bacilliform bodies were approximately 0.2 jmm wide and 2.0 jmm long in both biopsies. Because of this new finding, the patient was recalled for admission on 13 January, 1976, with Whipple's disease the suspected diagnosis. The intervening history was unremarkable and the laboratory examination unchanged. His right wrist inflammation had subsided, and his systolic ejection murmur had resolved. The patient underwent the following tests of intestinal function: D-xylose absorption, 6 g recovered in the urine 5 h after a 25-g oral dose; Schilling test, 19% of the orally administered (57Co) Vitamin B12 recovered in the urine in 24 h; chemical fat balance, 3 g of fat excreted per day on a 100-g daily oral intake; (,4C) cholate half life in the enterohepatic space, 2 days (normal) (6) with a normal rate of conversion to secondary bile acids and a normal ratio of glycine-to-taurine bile-acid conjugates (6). A culture of his small-bowel contents showed 1 X 10* micrococcus/ml. Six intestinal biopsies from the proximal jejunum and duodenum were obtained using a hydraulic biopsy instrument (7). Five of these biopsies were examined microscopically (see below); only one periodic acid Schiff-positive macrophage was A 1 Q 7 Q
A m n r i / ^ o n P n l l a a a r\4 D h u e i / > i a n e
seen. One biopsy was cultured bacteriologically (8) and grew out a streptococcus. The patient was referred to Dr. Dobbins for an independent assessment, at which time four additional small-bowel biopsies were obtained (3 February 1976); one was processed for light and one for electron microscopy. Two biopsies were obtained for culture (8) and were examined at 9 and 42 days of culture by both light and electron microscopy. Immunologic evaluation showed positive intradermal tests to Tricophyton and Candida albicans, normal responses to lymphocyte mitogens, normal mixed-lymphocyte culture responses, and normal immunoglobulin levels, but a decreased number of T-cell rosettes. After these investigations, the patient was returned to the Durham Veterans Administration Hospital where tetracycline, 250 mg four times a day, was begun. He returned in July 1976. His lymphadenopathy had resolved to one fourth its original size. He had gained 2.72 kg [6 lbs]. A left epitrochliar lymph node was removed. It showed only moderate cortical hyperplasia. No granulomas or periodic acid Schiff-positive histiocytes were seen. No organisms could be found by electron microscopyIntestinal Biopsies A total of 9 intestinal biopsies were prepared for histologic examination; four were processed for light microscopy and five for transmission electron microscopy. All biopsies were examined at light microscopy, and those prepared for light microscopy were stained with the peri-
odic acid Schiff stain. At light microscopy, the villi were found to be slightly shortened. The most remarkable finding was a modest infiltration of the epithelial cells by lymphocytes. In no instance, in all nine biopsies, were foamy macrophages characteristic of Whipple's disease (2) identified. Only one periodic acid Schiff-positive macrophage was seen in appropriately stained sections, which is within the range of normal. Approximately 34 electron micrographs, prepared in two different laboratories, were obtained from four biopsies (two cultured and two not cultured). N o organisms were identified that in any way resembled those found in Whipple's disease. Discussion
The diagnosis of Whipple's disease in this case rests on the peripheral lymph-node biopsy findings. There were multiple periodic acid Schiff-positive macrophages in the lymph nodes from both axillae. More important was the finding of .bacilliform bodies within the macrophages at electron microscopy. These bacteria were identical structurally (they were small, rod-shaped bacilli) to electron micrographs of bacteria found in various organs of previous cases of Whipple's disease (2, 8-13). The three organisms cultured from the patient do not resemble the bacil-
Figure 1A. The periodic acid Schiff-positive cytoplasmic granules are visible (arrows) in this small collection of macrophages in the patient's left axillary lymph node. (Periodic acid Schiff-stained paraffin section; original magnification x 1 0 0 0 . ) B. Numerous rod-shaped bacilliform bodies are seen within the cytoplasm of this macrophage (Original magnification, x 13 7 5 0 . ) C. At high magnification both the cell wall and the cytoplasmic membrane are visualized. (Original magnification, x 1 3 9 2 0 0 . ) Mansbach et al. • Lymph-Node Bacilliform Bodies
Downloaded from https://annals.org by Tulane University user on 01/21/2019
65
lus found in Whipple's disease and were considered to be contaminants. For these reasons, and because of his favorable clinical response to tetracycline, we believe that this patient has a variant of Whipple's disease (that is, without intestinal involvement). However, it is possible that the patient had a primary lymph-node disorder caused by bacilliform bodies that resemble structurally those seen in Whipple's disease. In previously published cases, even those without intestinal complaints (3-5), periodic acid Schiff-positive macrophages have been easily demonstrable in the small intestine, either at biopsy or autopsy. Recently, however, Moorthy, Nolley, and Hermos (14) have reported a case in which only two of four duodenal biopsies contained small foci of macrophages that stained with periodic acid Schiff reagent, indicating that intestinal involvement in Whipple's disease may be patchy in distribution. In our case, nine biopsies were done in two different laboratories; two biopsies processed for electron microscopy were examined separately by the two laboratories. Only one periodic acid Schiff reagent-positive macrophage was found, which we consider to be normal; two other macrophages, seen at electron microscopy, did not contain bacillary bodies. Appropriate cultures (8) of two biopsies for Whipple's organisms were nonrevealing. We did not biopsy the ileum, but in no instance has ileal involvement been described without concomitant proximal intestinal disease (15). In addition, the patient had normal ileal function, as judged by vitamin B12 absorption and (14C) cholic-acid turnover. Abnormalities in bile-acid kinetics have been previously described in Whipple's disease (16). Our patient was originally thought to have sarcoidosis. This confusion has occurred previously in other patients, and in one instance, the typical foamy macrophages apparently did not stain with the periodic acid Schiff reagent (17). Despite this one case (17), it is suggested that lymph-node biopsies, especially biopsies done for diagnostic purposes, be routinely stained with periodic acid Schiff reagent. This patient serves to point up two important speculates concerning Whipple's disease. First, this condition does not always first affect the small intestine with later spread to other organs systems, suggesting a route of infection other than the small bowel. This is in part substantiated by our previous observations that the Whipple's bacilliform bodies appeared to be more degenerate in the intestinal epithelial cells than in the underlying lamina propria (9). It was suggested that these bacteria were migrating toward, rather than from, the lumen of the intestine. Second, this patient's illness has implications in regard to evaluation of other patients with unexplained, nonde-
66
July 1978 • Annals of Internal Medicine • Volume 89 • Number 1
Downloaded from https://annals.org by Tulane University user on 01/21/2019
forming arthritis or arthralgias. These symptoms may appear 10 years or more before the onset of recognizable Whipple's disease. Such patients should have lymph-node biopsies, stained with the periodic acid Schiff reagent, if lymphadenopathy is present. A small-bowel biopsy in such patients may not yield the diagnosis, The reasonable possibility of a diagnosis of Whipple's disease is always worth pursuing, because this is a treatable disease when appropriate antibiotics are used. Finally, this case shows the value of electron microscopy of lymph nodes. Without this modality, the diagnosis in this case may not have been suggested. ACKNOWLEDGMENTS: Grant support: in part by the Electron Microscopy Laboratory, Veterans Administration Hospital, Durham, North Carolina, and the Medical Research Service of the Veterans Administration. • Requests for reprints should be addressed to Charles M. Mansbach II, M.D.; Veterans Administration Hospital; 508 Fulton Street; Durham, N C 27705. Received 21 November 1977; revision accepted 31 March 1978.
References 1. WHIPPLE GH: A hitherto undescribed disease characterized anatomically by deposits of fat and fatty acids in the intestinal and mesenteric tissues. Johns Hopkins Med J 18:382-391, 1907 2. MAIZEL H, RUFFIN JM, DOBBINS WO: Whipple's disease: a review of
19 patients from one hospital and a review of the literature since 1950. Medicine (Baltimore) 49:175-205, 1970 3. CAUGHEY DE, BYWATERS EGL: The arthritis of Whipple's syndrome. Ann Rheum Dis22:in-M5, 1963 4. LEMPERT P, T O M MI, CUMMINGS JN: Encephalopathy in Whipple's
disease. Neurology 12:65-71, 1962 5. BECKER FF, W I T T E MH, TESLER MA, D U M O N T AE: Intestinal lipo-
dystrophy (Whipple's disease). JAMA 194:559-561, 1965 6. GARBUTT JT, KENNEY TJ: Effect of cholestyramine on bile acid metabolism in normal man. / Clin Invest 51:2781-2789, 1972 7. FLICK AL, QUINTON WE, RUBIN CE: A peroral hydraulic biopsy tube for multiple sampling at any level of the gastrointestinal tract. Gastroenterology 40:120-126, 1961 8. CLANCY RL, TOMKINS WAF, MUCKLE TJ, RICHARDSON H, R A W L S
9. 10. 11.
12.
WE: Isolation and characterization of an aetiological agent in Whipple's disease. Br Med 7 3:568-570, 1975 DOBBINS WO, RUFFIN JM: A light and electron-microscopic study of bacterial invasion in Whipple's disease. Am J Pathol 51:225-242, 1967 SCHOCHET SS, LAMPERT PW: Granulomatous encephalitis in Whipple's disease. Acta Neuropathol (Bed) 13:1-11, 1969 MORNINGSTAR WA: Whipple's Disease: an example of the value of the electron microscope in diagnosis, follow-up, and correlation of a pathologic process. Hum Pathol 6:443-454, 1975 LIE JT, DAVIS JS: Pancarditis in Whipple's disease. Electronmicroscopic demonstration of intracardiac bacillary bodies. Am J Clin Pathol 66:22-30, 1976
13. H A W K I N S CF, FARR M, MORRIS CJ, HOARE AM, WILLIAMSON N:
Detection by electron microscope of rod-shaped organisms in synovial membrane from a patient with the arthritis of Whipple's Disease. Ann Rheum Dis 35:502-509, 1976 14. MOORTHY S, NOLLEY G, HERMOS J A: Whipple's disease with minimal intestinal involvement. Gut 18:152-155, 1977 15. ENZINGER FM, HELWIG EB: Whipple's disease. Virchows Arch [Pathol AnatJ 336:238-269, 1963 16. G A R B U T T JT, WILKINS RM, LACK L, TYOR MP: Bacterial modification
of taurocholate during enterohepatic recirculation in normal man and patients with small intestine disease. Gastroenterology 59:553-566, 1970 17. RODARTE JR, GARRISON CO, HOLLEY KE, F O N T ANA RS: Whipple's
disease simulating sarcoidosis. Arch Intern Med 129:479-482, 1972
