CASE REPORTS
this approach would probably not be frequently justified. As with this patient, improvement is gradual and follows a time course similar to the decline seen in blood acetone concentrations. Clinically, it is important to recognize that the time required for recovery of these patients is measured in days, and that acetone concentrations may be useful in distinguishing acetone intoxication from other causes of central nervous system depression. REFERENCES 1. Browning EC: Ketones, chap. 8, In Toxicity and Metabolism of Industrial Solvents. New York, Elsevier Publishing Company, 1965, pp 412-420 2. Ross DS: Acute acetone intoxication involving eight male workers. Ann Occup Hyg 16:73-75, 1973 3. Gitelson S, Werczberger A, Herman JB: Coma and hyperglycemia following drinking of acetone. Diabetes 15:810-811, 1966 4. Rooth G, Ostenson S: Acetone in alveolar air and the control of diabetes. Lancet 2:1102-1105, Nov 19, 1966 5. Haggard HW, Greenberg LA, McCullough-Turner J: The physiological principles governing the action of acetone together with determination of toxicity. J Indust Hyg Toxicol 26:133-151, 1944 6. Sulway MJ, Malins JM: Acetone in diabetic ketoacidosis. Lancet 2:736-740, Oct 10, 1970 7. DiVincenzo GD, Yanno FJ, Astill BD: Exposure of man and dog to low concentrations of acetone vapor. Am Ind Hyg Asscc J 34:329-336, Aug 1973 8. Knott GD, Reece DK: MLAB: A civilized curve-fitting system, Proceedings of the Online '72 International Conference, Vol. 1. England, Brunel University, Sep 1972, pp 497-523 9. Briggs AP, Shaffer PA: Excretion of acetone from the lungs. J Biol Chem 48:413-428, 1921 10. Goldman HI, Becklake MR: Respiratory function testsNormal values at median altitudes and the prediction of normal results. Am Rev Tuber Pulm Dis 79:457-467, 1959 Refer to: Rushing JL, Hanna CJ, Selecky PA: Pancreatitis as the presenting manifestation of miliary tuberculosis. West J Med 129:432-436, Nov 1978
Pancreatitis as the Presenting Manifestation of Miliary Tuberculosis JAMES L. RUSHING, MD San Jose, California CAROL J. HANNA, MD PAUL A. SELECKY, MD Torrance, California THE CLINICAL PRESENTATION of miliary tuberculosis may take many forms. Some of these are quite nonspecific and obscure,1-3 making the diagnosis very difficult at times. Although not widely appreciated, it is not uncommon for abdominal pain to be a major clinical finding. This has been From the Departments of Medicine (Drs. Rushing and Selecky), and Pathology (Dr. Hanna), UCLA School of Medicine and Harbor General Hospital, Torrance. Dr. Rushing is now with Stanford University School of Medicine and Santa Clara Valley Medical Center, San Jose. Submitted September 28, 1977. Reprint requests to: James L. Rushing, MD, Respiratory Medicine, Santa Clara Valley Medical Center, 751 South Bascom Avenue, San Jose, CA 95128.
432
NOVEMBER 1978 * 129 * 5
attributed largely to tuberculous infiltration of the peritoneum and gastrointestinal tract.24 Pancreatitis and hyperamylasemia, however, are exceedingly rare features of miliary tuberculosis5'6 and neither has been previously reported as a presenting feature of this disease. The association of the adult respiratory distress syndrome (ARDS) and miliary tuberculosis is also an uncommon occurrence. Only six cases have been reported.7-'0 We recently cared for a patient in whom both pancreatitis and a transient episode of ARDS developed as complications of miliary tuberculosis. Because each of these conditions is a distinctly unusual feature of disseminated tuberculosis infections, we wish to report our experience.
Report of a Case The patient was a 39-year-old black man admitted with a three-week history of intermittent right upper quadrant abdominal pain and a oneweek history of fever, malaise, nausea and vomiting. The patient said that he did not use alcohol, did not smoke and had not been exposed to tuberculosis. He was told he had sarcoidosis at another hospital seven years previously-the diagnosis based on abnormal findings on a roentgenogram of the chest. No further studies were carried out, and he was not treated. His past history was otherwise noncontributory. On physical examination at admission the patient was noted to be well-developed and thin; body temperature was 39.4°C (103°F). Mild epigastric tenderness was elicited by palpation; neither organomegaly nor rebound tenderness was present. The other findings from the examination were noncontributory. A roentgenogram of the chest done at admission (Figure 1) showed bilateral hilar and right paratracheal lymph node enlargement. An electrocardiogram showed no abnormalities. A complete blood count gave the following values: hemoglobin, 14.2 grams per dl; hematocrit, 41.4 percent; leukocyte count, 4,800, with 19 percent bands, 52 percent polymorphonuclear cells, 17 percent lymphocytes and 12 percent monocytes. Analysis of urine showed 1 + protein by dipstick and up to two leukocytes per high-power field; other results were within normal limits. Electrolytes and blood urea nitrogen were normal, as were the prothrombin and partial thromboplastin times. The serum glutamic-oxaloacetic transami-
CASE REPORTS
nase (SGOT), alkaline phosphatase and total bilirubin levels were abnormal (SGOT, 520 mIU per ml [normal, 10 to 30 mIU per ml], alkaline phosphatase, 247 mlU per ml [normal, 36 to 92 mIU per ml], total bilirubin, 1.4 mg per dl [normal, 0.1 to 1.2 mg per dl]). The serum amylase value was 332 Somogyi units per dl (normal, 30 to 194 Somogyi units per dl). Skin tests showed no reaction to coccidioidin 1: 10 or purified protein derivative intermediate (5 TU) and second strength (250 TU). There was 15 mm induration to mumps antigen. The patient was treated conservatively: fluid was administered intravenously and oral intake was stopped. Temperature spikes to 40°C (1040 F) continued to occur. Bacterial cultures of blood, urine and sputum were repeatedly negative. On the ninth hospital day, the patient became dyspneic and tachypneic. Arterial blood gas studies on room air showed an arterial oxygen pressure (Pao2) of 25 mm of mercury, an arterial carbon dioxide pressure (Pacoj, 25 mm of mercury and a pH of 7.48. A roentgenogram of the chest (Figure 2) showed alveolar infiltrates with no cardiomegaly. On physical examination there was tachycardia without S3 or S4. The lungs were clear to auscultation and there was no peripheral edema or signs of volume depletion. Maximum nasal and mask oxygen supplementation failed to provide adequate oxygenation. An orotracheal tube was inserted, and the patient was placed on a volume ventilator, requiring fraction of inspired oxygen ..
(FIo2) of 1.0 for adequate oxygenation. Fiberoptic bronchoscopy was carried out and bronchial brushings were collected. Stains for routine bacteria, acid-fast, fungal and Pneumocystis organisms were negative on these specimens. The patient was begun on a regimen of methylprednisolone, 100 mg given intravenously every six hours, for treatment of the ARDS. Oral administration of isoniazid (300 mg per day) and ethambutol (25 mg per kg of body weight per day) was started but was discontinued after five days because of worsening liver function and the lack of documented tuberculosis. The steroids were tapered and discontinued over the course of one week. The arterial blood gas values and findings on a roentgenogram of the chest improved on the above regimen, and the patient was successfully extubated six days later (15th hospital day). Postextubation arterial blood gases at FIO2 of 0.3 were an arterial oxygen pressure of 66 mm of mercury, an arterial carbon dioxide pressure of 30 mm of mercury and a pH of 7.45. Despite this response, the patient continued a deteriorating course with persistent temperatures to 39.4°C (103°F), intermittent lethargy, nausea, vomiting and abdominal pain. Extensive laboratory studies failed to reveal a cause other than pancreatitis and hepatitis. The SGOT value reached a peak of 900 mIU per ml and then declined to 150 mIU per ml. Similarly, the serum bilirubin reached a peak of 9.2 mg per dl and declined to 2.6 mg per dl. The serum amylase was consis-
ell. *.--
*I..'. 12...i
..
-
.- .,
:L
F
Figure 1.-Admission roentgenogram of the chest showing bilateral hilar and right paratracheal lymph node enlargement with clear lung fields.
Figure 2.-Supine roentgenogram of the chest showing bilateral alveolar infiltrates without cardiac enlargement. THE WESTERN JOURNAL OF MEDICINE
433
CASE REPORTS
and peribronchial soft yellow-white nodules, averaging 1 mm or less in diameter, were evident. Viewed microscopically, there were small foci of acute necrosis which contained scattered polymorphonuclear leukocytes and occasional lymphocytes. The alveolar walls were edematous and were the site of a mixed acute and chronic cellular infiltrate. Numerous lipid-laden macrophages and large collections of hyaline membranes lined the air spaces, which also contained focal fresh blood (Figure 3A and 3B). In addition, there were collections of intraalveolar and intrabronchial polymorphonuclear leukocytes and fibrin. The hilar lymph nodes were notably enlarged, varying in' consistency from areas which were softly fluctuant to areas of rubbery fibrosis. The cut sections displayed caseous material. On microscopic examination these nodes showed multiple hyalinized granulomata indicating focal areas of peripheral breakdown with associated moderate mononuclear cell infiltration.
tently elevated, reaching a maximum level of 920 Somogyi units per dl. Urinary diastase was 61,750 units per 24 hours at that time. Amylase/creatinine clearance ratios were determined serially throughout the patient's course and were consistently greater than 6: 1. The patient became progressively weak and lethargic, and urine output decreased. On the 28th hospital day a cardiac arrest occurred and there was no response to resuscitation efforts. After the patient's demise, the antemortem bronchial brushing cultures were reported as positive for Mycobacterium tuberculosis.
Findings at Autopsy At autopsy the lungs were heavy and diffusely firm, and had multiple areas of consolidation. The right lung weighed 1,400 grams (normal 450 grams); the left lung weighed 890 grams (normal 375 grams). Numerous small subpleural
*
;
-
*
*
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4
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,
.
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.
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.
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-
~~
Figure 3.-Photomicrographs from hematoxylin and eosin stained sections obtained at autopsy, A. Pulmonary parenchyma with acute tuberculous microabscesses and extensive hyaline membrane formation (arrows). B, Pulmonary parenchyma with alveolar septal edema, intraalveolar pulmonary macrophages (arrow), and a mixed acute and chronic inflammatory cell infiltrate. M=microabscess. C, Pancreatic acinar tissue showing an acute tuberculous microabscess (arrows). D, Liver with multiple acute tuberculous microabscesses (arrows). Note the hepatic cords and sinusoids retain normal architecture. C=central vein. (Enlarged from original magnification x 1 1O.)
434
NOVEMBER 1978 * 129 * 5
CASE REPORTS
Although the pancreas was unremarkable grossly, multiple small acute microabscesses, similar to those described in the lung, were microscopically observed affecting the acinar tissue but not the islets (Figure 3C). The liver (Figure 3D), cerebrum, retinas, heart, kidneys and prostate all had similar microabscesses. Notably, small clusters of acid-fast bacilli were found in all acute microabscesses. Comments Abdominal pain has been described as a major symptom in 7 percent to 14 percent of patients with miliary tuberculosis. This has been attributed to peritonitis, enteritis and retroperitoneal lymphadenitis," 2'4 but the presentation of this disease as pancreatitis has not been previously described. As many as 14 percent of patients with miliary tuberculosis have been reported to have pancreatic involvement at autopsy;4'6 however, no mention is made of hyperamylasemia or clinical signs of pancreatitis in these reviews. The histologic studies in our patient showed multiple microabscesses in the pancreas typical of miliary tuberculosis. Similar abscesses were present in multiple other organs, although the peritoneum, gastrointestinal tract and retroperitoneal nodes were not involved. This would indicate that the pancreas was the primary cause of abdominal pain. Other causes of pancreatitis, such as obstructed pancreatic ducts, evidence of biliary disease or a history of excessive alcohol intake, were not present. Infectious agents have been described as being a cause of acute pancreatitis in up to 20 percent of cases.7 The most common blood-borne organism is the mumps virus, although bacterial microabscesses have also been reported in the pancreas after septicemia. The subsequent destruction of the tissue surrounding these abscesses causes an outpouring of pancreatic enzymes into the bloodstream and surrounding tissues, resulting in the typical clinical and laboratory findings seen in our patient. The adult respiratory distress syndrome (ARDS) is also a rare complication of miliary tuberculoSiS.8 ARDS is characterized by progressive hypoxemia which is unresponsive to high concentrations of inspired oxygen, decreased lung compliance and diffuse alveolar infiltrates shown on roentgenograms of the chest.
Of the numerous factors invoked as causes of ARDS, increased capillary permeability is prominent.9 The postulated mechanisms leading to this abnormality in miliary tuberculosis include (1) the presence of large numbers of mycobacteria in t-he pulmonary circulation producing damage to capillary endothelial cells; (2) platelet-fibrin microemboli in the pulmonary capillaries inducing endothelial injury; (3) a hypersensitivity reaction to the mycobacteria resulting in endothelial damage.8 Huseby and Hudson8 noted that five of the six reported cases of ARDS due to tuberculosis had disseminated intravascular coagulation, suggesting to them that microembolization of fibrin-platelet aggregates played an important role in the pathogenesis of the syndrome. In our patient, however, disseminated intravascular coagulation never developed. The possibility exists that in this patient ARDS may have been a result of pancreatitis, which has been associated with increased pulmonary capillary permeability.'0 However, it is important to note in this regard that the ARDS improved while the pancreatitis remained unchanged. Likewise, cultures of bronchial brushings obtained while the patient had clinical and roentgenologic evidence of ARDS later grew M. tuberculosis. This suggests to us that the mycobacteria in the pulmonary parenchyma were important in the pathogenesis of the ARDS. The fact that the syndrome cleared with minimal antituberculosis therapy and administration of steroids in high doses favors the role of a hypersensitivity or immune reaction. Miliary tuberculosis is generally a curable disease. The need for a high index of suspicion and early diagnosis is obvious. Our experience with this patient documents that pancreatitis and the adult respiratory distress syndrome may be manifestations of miliary tuberculosis. Their unexplained presence in an appropriate clinical setting should raise the suspicion of miliary tuberculosis and biopsy specimens of appropriate accessible organs (such as liver, bone marrow and lung) should be obtained."
Summary A patient who presented with pancreatitis was found at postmortem examination to have unsuspected acute miliary tuberculosis with extensive involvement of the lungs and the pancreas. Also the adult respiratory distress syndrome deTHE WESTERN JOURNAL OF MEDICINE
435
CASE REPORTS
veloped transiently during the course of disease. Either entity may be a manifestation of miliary tuberculosis; their unexplained occurrence should raise suspicion of this disease. REFERENCES 1. Munt PW: Miliary tuberculosis in the chemotherapy era with a clinical review in 69 American adults. Medicine 51:139-155, 1962 2. Sahn SA, Neff TA: Miliary tuberculosis. Am J Med 56:495504, 1974 3. Proudfoot AT, Akhtar AJ, Douglas AC, et al: Miliary tuberculosis in adults. Br Med J 2:273-276, 1969 4. Gelb AF. Leffler C, Brewin A, et al: Miliary tuberculosis. Am Rev Resp Dis 108:1327-1333. 1973
5. Biehl JP: Miliary tuberculosis: A review of sixty-eight adult patients admitted to a municipal general hospital. Am Rev Tuber-
culosis 77:605-622, 1958
6. Auerbach 0: Acute generalized miliary tuberculosis. Am J Path 20:121-136, 1944 7. Blumenthal HT, Probstein JG. Pancreatitis. Springfield, IL, Charles C Thomas, 1959, p 16 8. Huseby JS, Hudson LD: Miliary tuberculosis and adult respiratory distress syndrome. Ann Intern Med 85:609-611, 1976 9. Robin ED, Cross CE, Zellis R: Pulmonary edema. N Engl J Med 288:292-304, 1973 10. Murray JF: Mechanisms of acute respiratory failure. Am Rev Resp Dis 115:1071-1078, 1977 11. Grieco MH, Chinel H: Acute disseminated tuberculosis as a diagnostic problem-A clinical study based on twenty-eight cases. Am Rev Resp Dis 109:554-560, 1974
Advantages of Transplantation Over Dialysis for End-Stage Kidney Disease A PATIENT ON HEMODIALYSIS is not by any means a well patient. And there are advantages to transplantation. The patient on chronic dialysis generally runs a hematocrit of 17 percent to 20 percent, and he looks and acts and feels like he has a hematocrit of 17 percent to 20 percent. He has an extraordinarily restricted diet. The transplant patient's hematocrit improves, and his diet is almost completely liberalized in most instances. The transplant patient is not tied to that dialysis machine and the rigid three-times-a-week schedule either in a unit or in his home. Every dialysis patient has secondary hyperparathyroidism. His vitamin D metabolism is off, his calcium metabolism suffers, and they all have thinned bones and can get into serious complications. That disease is generally reversed with transplantation. There is an overall improvement in the general condition. Children who suffer renal failure and go onto dialysis do not grow; they do not enter puberty, and it is extremely gratifying to see a child grow and reach puberty after a successful transplantation. There is tremendous financial advantage to all of us, because we all pay for this program, and it is much more economical to use transplantation in a patient than to carry out chronic dialysis. -CHARLES T. FITTS, MD, Charleston, South Carolina Extracted from Audio-Digest Surgery, Volume 25, Number 10 in the Audio-Digest Foundation's subscription series of taperecorded programs. For subscription information: 1577 E. Chevy Chase Drive, Glendale, CA 91206.
436
NOVEMBER 1978 * 129 * 5
this approach would probably not be frequently justified. As with this patient, improvement is gradual and follows a time course similar to the decline seen in blood acetone concentrations. Clinically, it is important to recognize that the time required for recovery of these patients is measured in days, and that acetone concentrations may be useful in distinguishing acetone intoxication from other causes of central nervous system depression. REFERENCES 1. Browning EC: Ketones, chap. 8, In Toxicity and Metabolism of Industrial Solvents. New York, Elsevier Publishing Company, 1965, pp 412-420 2. Ross DS: Acute acetone intoxication involving eight male workers. Ann Occup Hyg 16:73-75, 1973 3. Gitelson S, Werczberger A, Herman JB: Coma and hyperglycemia following drinking of acetone. Diabetes 15:810-811, 1966 4. Rooth G, Ostenson S: Acetone in alveolar air and the control of diabetes. Lancet 2:1102-1105, Nov 19, 1966 5. Haggard HW, Greenberg LA, McCullough-Turner J: The physiological principles governing the action of acetone together with determination of toxicity. J Indust Hyg Toxicol 26:133-151, 1944 6. Sulway MJ, Malins JM: Acetone in diabetic ketoacidosis. Lancet 2:736-740, Oct 10, 1970 7. DiVincenzo GD, Yanno FJ, Astill BD: Exposure of man and dog to low concentrations of acetone vapor. Am Ind Hyg Asscc J 34:329-336, Aug 1973 8. Knott GD, Reece DK: MLAB: A civilized curve-fitting system, Proceedings of the Online '72 International Conference, Vol. 1. England, Brunel University, Sep 1972, pp 497-523 9. Briggs AP, Shaffer PA: Excretion of acetone from the lungs. J Biol Chem 48:413-428, 1921 10. Goldman HI, Becklake MR: Respiratory function testsNormal values at median altitudes and the prediction of normal results. Am Rev Tuber Pulm Dis 79:457-467, 1959 Refer to: Rushing JL, Hanna CJ, Selecky PA: Pancreatitis as the presenting manifestation of miliary tuberculosis. West J Med 129:432-436, Nov 1978
Pancreatitis as the Presenting Manifestation of Miliary Tuberculosis JAMES L. RUSHING, MD San Jose, California CAROL J. HANNA, MD PAUL A. SELECKY, MD Torrance, California THE CLINICAL PRESENTATION of miliary tuberculosis may take many forms. Some of these are quite nonspecific and obscure,1-3 making the diagnosis very difficult at times. Although not widely appreciated, it is not uncommon for abdominal pain to be a major clinical finding. This has been From the Departments of Medicine (Drs. Rushing and Selecky), and Pathology (Dr. Hanna), UCLA School of Medicine and Harbor General Hospital, Torrance. Dr. Rushing is now with Stanford University School of Medicine and Santa Clara Valley Medical Center, San Jose. Submitted September 28, 1977. Reprint requests to: James L. Rushing, MD, Respiratory Medicine, Santa Clara Valley Medical Center, 751 South Bascom Avenue, San Jose, CA 95128.
432
NOVEMBER 1978 * 129 * 5
attributed largely to tuberculous infiltration of the peritoneum and gastrointestinal tract.24 Pancreatitis and hyperamylasemia, however, are exceedingly rare features of miliary tuberculosis5'6 and neither has been previously reported as a presenting feature of this disease. The association of the adult respiratory distress syndrome (ARDS) and miliary tuberculosis is also an uncommon occurrence. Only six cases have been reported.7-'0 We recently cared for a patient in whom both pancreatitis and a transient episode of ARDS developed as complications of miliary tuberculosis. Because each of these conditions is a distinctly unusual feature of disseminated tuberculosis infections, we wish to report our experience.
Report of a Case The patient was a 39-year-old black man admitted with a three-week history of intermittent right upper quadrant abdominal pain and a oneweek history of fever, malaise, nausea and vomiting. The patient said that he did not use alcohol, did not smoke and had not been exposed to tuberculosis. He was told he had sarcoidosis at another hospital seven years previously-the diagnosis based on abnormal findings on a roentgenogram of the chest. No further studies were carried out, and he was not treated. His past history was otherwise noncontributory. On physical examination at admission the patient was noted to be well-developed and thin; body temperature was 39.4°C (103°F). Mild epigastric tenderness was elicited by palpation; neither organomegaly nor rebound tenderness was present. The other findings from the examination were noncontributory. A roentgenogram of the chest done at admission (Figure 1) showed bilateral hilar and right paratracheal lymph node enlargement. An electrocardiogram showed no abnormalities. A complete blood count gave the following values: hemoglobin, 14.2 grams per dl; hematocrit, 41.4 percent; leukocyte count, 4,800, with 19 percent bands, 52 percent polymorphonuclear cells, 17 percent lymphocytes and 12 percent monocytes. Analysis of urine showed 1 + protein by dipstick and up to two leukocytes per high-power field; other results were within normal limits. Electrolytes and blood urea nitrogen were normal, as were the prothrombin and partial thromboplastin times. The serum glutamic-oxaloacetic transami-
CASE REPORTS
nase (SGOT), alkaline phosphatase and total bilirubin levels were abnormal (SGOT, 520 mIU per ml [normal, 10 to 30 mIU per ml], alkaline phosphatase, 247 mlU per ml [normal, 36 to 92 mIU per ml], total bilirubin, 1.4 mg per dl [normal, 0.1 to 1.2 mg per dl]). The serum amylase value was 332 Somogyi units per dl (normal, 30 to 194 Somogyi units per dl). Skin tests showed no reaction to coccidioidin 1: 10 or purified protein derivative intermediate (5 TU) and second strength (250 TU). There was 15 mm induration to mumps antigen. The patient was treated conservatively: fluid was administered intravenously and oral intake was stopped. Temperature spikes to 40°C (1040 F) continued to occur. Bacterial cultures of blood, urine and sputum were repeatedly negative. On the ninth hospital day, the patient became dyspneic and tachypneic. Arterial blood gas studies on room air showed an arterial oxygen pressure (Pao2) of 25 mm of mercury, an arterial carbon dioxide pressure (Pacoj, 25 mm of mercury and a pH of 7.48. A roentgenogram of the chest (Figure 2) showed alveolar infiltrates with no cardiomegaly. On physical examination there was tachycardia without S3 or S4. The lungs were clear to auscultation and there was no peripheral edema or signs of volume depletion. Maximum nasal and mask oxygen supplementation failed to provide adequate oxygenation. An orotracheal tube was inserted, and the patient was placed on a volume ventilator, requiring fraction of inspired oxygen ..
(FIo2) of 1.0 for adequate oxygenation. Fiberoptic bronchoscopy was carried out and bronchial brushings were collected. Stains for routine bacteria, acid-fast, fungal and Pneumocystis organisms were negative on these specimens. The patient was begun on a regimen of methylprednisolone, 100 mg given intravenously every six hours, for treatment of the ARDS. Oral administration of isoniazid (300 mg per day) and ethambutol (25 mg per kg of body weight per day) was started but was discontinued after five days because of worsening liver function and the lack of documented tuberculosis. The steroids were tapered and discontinued over the course of one week. The arterial blood gas values and findings on a roentgenogram of the chest improved on the above regimen, and the patient was successfully extubated six days later (15th hospital day). Postextubation arterial blood gases at FIO2 of 0.3 were an arterial oxygen pressure of 66 mm of mercury, an arterial carbon dioxide pressure of 30 mm of mercury and a pH of 7.45. Despite this response, the patient continued a deteriorating course with persistent temperatures to 39.4°C (103°F), intermittent lethargy, nausea, vomiting and abdominal pain. Extensive laboratory studies failed to reveal a cause other than pancreatitis and hepatitis. The SGOT value reached a peak of 900 mIU per ml and then declined to 150 mIU per ml. Similarly, the serum bilirubin reached a peak of 9.2 mg per dl and declined to 2.6 mg per dl. The serum amylase was consis-
ell. *.--
*I..'. 12...i
..
-
.- .,
:L
F
Figure 1.-Admission roentgenogram of the chest showing bilateral hilar and right paratracheal lymph node enlargement with clear lung fields.
Figure 2.-Supine roentgenogram of the chest showing bilateral alveolar infiltrates without cardiac enlargement. THE WESTERN JOURNAL OF MEDICINE
433
CASE REPORTS
and peribronchial soft yellow-white nodules, averaging 1 mm or less in diameter, were evident. Viewed microscopically, there were small foci of acute necrosis which contained scattered polymorphonuclear leukocytes and occasional lymphocytes. The alveolar walls were edematous and were the site of a mixed acute and chronic cellular infiltrate. Numerous lipid-laden macrophages and large collections of hyaline membranes lined the air spaces, which also contained focal fresh blood (Figure 3A and 3B). In addition, there were collections of intraalveolar and intrabronchial polymorphonuclear leukocytes and fibrin. The hilar lymph nodes were notably enlarged, varying in' consistency from areas which were softly fluctuant to areas of rubbery fibrosis. The cut sections displayed caseous material. On microscopic examination these nodes showed multiple hyalinized granulomata indicating focal areas of peripheral breakdown with associated moderate mononuclear cell infiltration.
tently elevated, reaching a maximum level of 920 Somogyi units per dl. Urinary diastase was 61,750 units per 24 hours at that time. Amylase/creatinine clearance ratios were determined serially throughout the patient's course and were consistently greater than 6: 1. The patient became progressively weak and lethargic, and urine output decreased. On the 28th hospital day a cardiac arrest occurred and there was no response to resuscitation efforts. After the patient's demise, the antemortem bronchial brushing cultures were reported as positive for Mycobacterium tuberculosis.
Findings at Autopsy At autopsy the lungs were heavy and diffusely firm, and had multiple areas of consolidation. The right lung weighed 1,400 grams (normal 450 grams); the left lung weighed 890 grams (normal 375 grams). Numerous small subpleural
*
;
-
*
*
X; Fs,bS
X SA..4l
4
*
,
U:z -#t o@ f sw,$-S w sI *. ;
*5
.*4
.'
4
A VnA
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,
.
wkr
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*
-~
.
-' **0 ... .'
~
-,, W~
~
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4.4*,01 ~~~~~~4
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.
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Figure 3.-Photomicrographs from hematoxylin and eosin stained sections obtained at autopsy, A. Pulmonary parenchyma with acute tuberculous microabscesses and extensive hyaline membrane formation (arrows). B, Pulmonary parenchyma with alveolar septal edema, intraalveolar pulmonary macrophages (arrow), and a mixed acute and chronic inflammatory cell infiltrate. M=microabscess. C, Pancreatic acinar tissue showing an acute tuberculous microabscess (arrows). D, Liver with multiple acute tuberculous microabscesses (arrows). Note the hepatic cords and sinusoids retain normal architecture. C=central vein. (Enlarged from original magnification x 1 1O.)
434
NOVEMBER 1978 * 129 * 5
CASE REPORTS
Although the pancreas was unremarkable grossly, multiple small acute microabscesses, similar to those described in the lung, were microscopically observed affecting the acinar tissue but not the islets (Figure 3C). The liver (Figure 3D), cerebrum, retinas, heart, kidneys and prostate all had similar microabscesses. Notably, small clusters of acid-fast bacilli were found in all acute microabscesses. Comments Abdominal pain has been described as a major symptom in 7 percent to 14 percent of patients with miliary tuberculosis. This has been attributed to peritonitis, enteritis and retroperitoneal lymphadenitis," 2'4 but the presentation of this disease as pancreatitis has not been previously described. As many as 14 percent of patients with miliary tuberculosis have been reported to have pancreatic involvement at autopsy;4'6 however, no mention is made of hyperamylasemia or clinical signs of pancreatitis in these reviews. The histologic studies in our patient showed multiple microabscesses in the pancreas typical of miliary tuberculosis. Similar abscesses were present in multiple other organs, although the peritoneum, gastrointestinal tract and retroperitoneal nodes were not involved. This would indicate that the pancreas was the primary cause of abdominal pain. Other causes of pancreatitis, such as obstructed pancreatic ducts, evidence of biliary disease or a history of excessive alcohol intake, were not present. Infectious agents have been described as being a cause of acute pancreatitis in up to 20 percent of cases.7 The most common blood-borne organism is the mumps virus, although bacterial microabscesses have also been reported in the pancreas after septicemia. The subsequent destruction of the tissue surrounding these abscesses causes an outpouring of pancreatic enzymes into the bloodstream and surrounding tissues, resulting in the typical clinical and laboratory findings seen in our patient. The adult respiratory distress syndrome (ARDS) is also a rare complication of miliary tuberculoSiS.8 ARDS is characterized by progressive hypoxemia which is unresponsive to high concentrations of inspired oxygen, decreased lung compliance and diffuse alveolar infiltrates shown on roentgenograms of the chest.
Of the numerous factors invoked as causes of ARDS, increased capillary permeability is prominent.9 The postulated mechanisms leading to this abnormality in miliary tuberculosis include (1) the presence of large numbers of mycobacteria in t-he pulmonary circulation producing damage to capillary endothelial cells; (2) platelet-fibrin microemboli in the pulmonary capillaries inducing endothelial injury; (3) a hypersensitivity reaction to the mycobacteria resulting in endothelial damage.8 Huseby and Hudson8 noted that five of the six reported cases of ARDS due to tuberculosis had disseminated intravascular coagulation, suggesting to them that microembolization of fibrin-platelet aggregates played an important role in the pathogenesis of the syndrome. In our patient, however, disseminated intravascular coagulation never developed. The possibility exists that in this patient ARDS may have been a result of pancreatitis, which has been associated with increased pulmonary capillary permeability.'0 However, it is important to note in this regard that the ARDS improved while the pancreatitis remained unchanged. Likewise, cultures of bronchial brushings obtained while the patient had clinical and roentgenologic evidence of ARDS later grew M. tuberculosis. This suggests to us that the mycobacteria in the pulmonary parenchyma were important in the pathogenesis of the ARDS. The fact that the syndrome cleared with minimal antituberculosis therapy and administration of steroids in high doses favors the role of a hypersensitivity or immune reaction. Miliary tuberculosis is generally a curable disease. The need for a high index of suspicion and early diagnosis is obvious. Our experience with this patient documents that pancreatitis and the adult respiratory distress syndrome may be manifestations of miliary tuberculosis. Their unexplained presence in an appropriate clinical setting should raise the suspicion of miliary tuberculosis and biopsy specimens of appropriate accessible organs (such as liver, bone marrow and lung) should be obtained."
Summary A patient who presented with pancreatitis was found at postmortem examination to have unsuspected acute miliary tuberculosis with extensive involvement of the lungs and the pancreas. Also the adult respiratory distress syndrome deTHE WESTERN JOURNAL OF MEDICINE
435
CASE REPORTS
veloped transiently during the course of disease. Either entity may be a manifestation of miliary tuberculosis; their unexplained occurrence should raise suspicion of this disease. REFERENCES 1. Munt PW: Miliary tuberculosis in the chemotherapy era with a clinical review in 69 American adults. Medicine 51:139-155, 1962 2. Sahn SA, Neff TA: Miliary tuberculosis. Am J Med 56:495504, 1974 3. Proudfoot AT, Akhtar AJ, Douglas AC, et al: Miliary tuberculosis in adults. Br Med J 2:273-276, 1969 4. Gelb AF. Leffler C, Brewin A, et al: Miliary tuberculosis. Am Rev Resp Dis 108:1327-1333. 1973
5. Biehl JP: Miliary tuberculosis: A review of sixty-eight adult patients admitted to a municipal general hospital. Am Rev Tuber-
culosis 77:605-622, 1958
6. Auerbach 0: Acute generalized miliary tuberculosis. Am J Path 20:121-136, 1944 7. Blumenthal HT, Probstein JG. Pancreatitis. Springfield, IL, Charles C Thomas, 1959, p 16 8. Huseby JS, Hudson LD: Miliary tuberculosis and adult respiratory distress syndrome. Ann Intern Med 85:609-611, 1976 9. Robin ED, Cross CE, Zellis R: Pulmonary edema. N Engl J Med 288:292-304, 1973 10. Murray JF: Mechanisms of acute respiratory failure. Am Rev Resp Dis 115:1071-1078, 1977 11. Grieco MH, Chinel H: Acute disseminated tuberculosis as a diagnostic problem-A clinical study based on twenty-eight cases. Am Rev Resp Dis 109:554-560, 1974
Advantages of Transplantation Over Dialysis for End-Stage Kidney Disease A PATIENT ON HEMODIALYSIS is not by any means a well patient. And there are advantages to transplantation. The patient on chronic dialysis generally runs a hematocrit of 17 percent to 20 percent, and he looks and acts and feels like he has a hematocrit of 17 percent to 20 percent. He has an extraordinarily restricted diet. The transplant patient's hematocrit improves, and his diet is almost completely liberalized in most instances. The transplant patient is not tied to that dialysis machine and the rigid three-times-a-week schedule either in a unit or in his home. Every dialysis patient has secondary hyperparathyroidism. His vitamin D metabolism is off, his calcium metabolism suffers, and they all have thinned bones and can get into serious complications. That disease is generally reversed with transplantation. There is an overall improvement in the general condition. Children who suffer renal failure and go onto dialysis do not grow; they do not enter puberty, and it is extremely gratifying to see a child grow and reach puberty after a successful transplantation. There is tremendous financial advantage to all of us, because we all pay for this program, and it is much more economical to use transplantation in a patient than to carry out chronic dialysis. -CHARLES T. FITTS, MD, Charleston, South Carolina Extracted from Audio-Digest Surgery, Volume 25, Number 10 in the Audio-Digest Foundation's subscription series of taperecorded programs. For subscription information: 1577 E. Chevy Chase Drive, Glendale, CA 91206.
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