Abdominal Sarcoidosis with Ascites

692

PAPOWITZ AND Ll Table l-Phyaiolo6ie

MeG~Juremerata

Observed

% Predicted

Vital capacity (L)

1.75

39

Residual volume (L)

1.54

77

Forced expiratory volume (I second, L)

0.97

25

M

M

Spirometric Data

Maximum voluntary ventilation ~m~

Differential Bronchospirometry Percent Total Right Left

Ventilation Oxygen uptake

27

73

19

81

Arterial Blood Gases Rest

Exercise

7.37

7.35

Pco, (mm Hg)

54

46

66

Po, (mm Hg)

51

52

410

pH

described two such patients. In her patients, and in the one described in this report, it is probable that an obliterative bronchiolitis early in life produced a hypoplastic lung with increased transradiancy of one side. Function was maintained at or near normal levels in the uninvolved areas until the development of diffuse chronic bronchitis in adult life. It is postulated that the resulting airway obstruction and ventilation-perfusion abnormalities led to the derangements of gas exchange, and to polycythemia, pulmonary hypertension and heart failure.

100%

7.31

o.

1 Swyer PR, James GCW: Case of unilateral pulmonary emphysema. Thorax 8:133-136, 1953 2 MacLeod WM: Abnormal transradiancy of one lung. Thorax 9:147-153, 1954 3 Domhorst AC, Heaf PJ, Semple SJG: Unilateral emphysema. Lancet 273:873-875, 1957 4 Reid L, Simon G: Unilateral lung transradiancy. Thorax 17:230-239, 1962 5 Margolin HN, Rosenberg LS, Felson B, et al: Idiopathic

Resting Diffusing Capacity*

7 ml/mm Hg/min

(Predicted: 17)

Mean Pulmonary Artery Pres81J.re (mm Hg)

Normal Observed

Occluded Right Pulmonary Artery

Resting

Exercise

<20

<20

<20

28

35

32

*Carbon Monoxide, Steady State, End-tidal CO Sampling. alveolar development is impaired; however, the number of bronchial branches is normal. Since alveolar development is usually complete by the age of eight years, the lesions are probably caused by bronchial obliteration secondary to infection prior to this age. Physiologic abnormalities7·8 are variable, but there is usually only mild to moderate ventilatory impairment and mild arterial hypoxemia in most patients with localized increased lung transradiancy. Differential bronchospirometric studies support the clinical and roentgenographic data. Diminished ventilation and little or no oxygen uptake or carbon dioxide excretion are found in the affected lobe or side.7· 9 In the patient described in this report, hypoxemia, hypercapnia, and polycythemia were present, with ensuing pulmonary hypertension and right-sided heart failure. The pulmonary hypertension at rest and exercise can be ascribed to the existence of the blood gas abnormality in the presence of a restricted pulmonary vascular bed. The failure of the pulmonary artery pressure to rise with rightsided balloon occlusion reflects the already markedly deficient right pulmonary circulation. The clinical, radiographic and spirometric manifestations encountered in the case reported herein conform to the pattern previously described. 3 • 5 The additional features mentioned in the preceding paragraph are rarely seen in the unilateral hyperlucent lung syndrome. Reid6

6 7

8 9

unilateral hyperlucent lung: Roentgenologic syndrome. Amer J Roentgenol 82:63-75, 1959 Reid L: The Pathology of Emphysema. London, LloydLuke Ltd, 1967, 144 Darke CS, Crispin AR, Snowdon BS: Unilateral lung transradiance: Physiological study. Thorax 15:74-81, 1960 Bates DV, Christie RV: Respiratory Function in Disease. Philadelphia and London, WB Saunders Company, 1964, 206 Pendharker MM, Kori RC: Unilobar hyperlucency of the lung. Arch Int Med 123:69-73, 1969

Reprint requests: Dr. Baum, VA Hospital, Miami 33125.

Abdominal Sarcoidosis with Ascites* A. Joel Papowitz, M.D.•• and John K. H. Li, M.D.t

A patient with sarcoidosis Hmited to the abdomen and productive of massive ascites is reported. The patient presented in her last month of pregnancy with a markedly distended abdomen. Laparotomy was performed when abdominal sweUing did not subside after delivery of a normal infant. Pathologic findings indicated active sarcoidosis. This is the third such case reported in tbe Hterature and the only one fUI1ber substantiated with a positive K veim test.

A

scites as a manifestation of sarcoidosis is a distinct rarity. When present, it is usually the result of either congestive heart failure or portal hypertension, both of which are the end stages of severe organ involvement with sarcoidosis. We have been treating a patient

0

°From the Departments of Medicine and Pathology, Montefiore-Morrisania Hospital Affiliation, Bronx, New ~ork. °Fellow in Pulmonary Diseases, Montefiore Hospital and Medical Center. tDirector of Pathology, Montefiore-Morrisania Hospital Af. filiation.

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693

ABDOMINAL SARCOIDOSIS WITH ASCITES who had ascites secondary to peritoneal involvement with sarcoid granulomas. This is the third such .case reported in the literature. CASE REPORT

On May 13, 1967, a 28-year-old Negro woman in the ninth month of pregnancy was admitted to Morrisania City Hospital with the tentative diagnosis of polyhydramnios. In the seventh month, because of ankle edema, she was given a diuretic and placed on a low salt diet. She responded with a 17 pound weight loss in two weeks. At 38 weeks of gestation, increasing abdominal distention was noted; she had difficulty in walking, sitting and lying down. The day after admission the patient went into spontaneous labor and delivered a normal full term baby; however, her abdominal girth did not diminish after delivery. Physical examination showed a well-developed, well-nourished woman in no distress, but with a grossly distended abdomen. The vital signs were normal. Examination of the head was within normal limits. There was no venous distention in the neck and no adenopathy was present. The lungs were clear to percussion and auscultation. The heart was not enlarged and P2 was not accentuated. No murmur, rub or gallop was heard. The abdomen was markedly distended and taut and a fluid wave was present. The liver and spleen were neither palpable nor ballotable. There was no peripheral edema. Laboratory studies included a normal white blood cell count and hematocrit of 33 percent. The urinalysis was normal. The blood urea nitrogen (BUN), fasting blood sugar and electrolytes were within normal limits. Liver function studies included serum transaminase (SCOT) of 25; alkaline phosphatase 25 King-Armstrong units (normal limit 17), cephalin flocculation 3+; thymol turbidity 10.8; and a total bilirubin 0.7 mg percent. The total protein was 7.2 gm percent of which the albumin was 2.7 gm percent and the globulins 4.5 gm percent. Serum protein electrophoresis showed albumin 38 percent, alpha 1 6 percent, alpha 2 12 percent, beta 14 percent and gamma 30 percent. The serum calcium was 8.9 mg percent. Chest roentgenogram (Fig 1 ) was within normal limits; an abdominal film showed diffuse haziness, compatible with ascites. An intravenous pyelogram disclosed no abnormalities of the genitourinary system. The uterus was noted to be of normal post-partum size. PPD second strength was negative. Histoplasmin and mumps skin tests gave negative results. Laparotomy was performed on the tenth post-partum day.

FIGURE 1. Normal chest roentgenogram. covered with gray spots, 2 to 8 mm in diameter; these appeared to be within and beneath the capsule. The spleen was extremely firm, with a gray-brown cut surface which lacked the normal follicular architecture; no red pulp could be scraped off. A series of frozen sections during the surgery ruled out the presence of tumor and showed the presence of granulomatous inflammation. Sections showed granulomata in various stages of evolution in every tissue examined. The spleen was virtually replaced by granulomata and consequent fibrosis, while the other tissues showed scattered, discrete foci with little fibrosis. The involvement of the liver and pancreas was minimal; in the mesentery, omentum and lymph nodes, a variable and moderate number of granulomata were present. Most of the granulomata were of recent development, having plump, large, epithelioid cells, often with foamy cytoplasm. Multinucleated giant cells were a constant finding, as well as small numbers of lymphocytes. Small areas of fibrinoid change were present, hut caseous necrosis was not seen in any of the organs examined. The granulomata were present at the peritoneal surface of the omentum (Fig 2) and at the

Surgical Findings Ten liters of serous fluid were present and an enlarged spleen, with many sub-capsular small nodules, was removed. Small white nodules were also present on the greater omentum, mesentery and pancreas. The remainder of the peritoneal surface and the liver were grossly uninvolved. The portal vein pressure was 13 em of water. Pathologic Findings The tissues removed included the spleen, the tail of the pancreas, several portal lymph nodes and a wedge of liver. Gray nodules, 2 to 5 mm in diameter, were present on the surface of the omentum and peritoneum covering the tail of the pancreas. The lymph nodes measured up to 1 em in diameter. The spleen weighed 800 gm and its surface was

CHEST, VOL. 59, NO. 6, JUNE 1971

FIGURE 2. Typical serosal nodule found in this patient. The protruding nodule is composed of many active epithelioid granulomata without necrosis.

694

PAPOWITZ AND L1

FIGURE 3. The site of the Kveim test shows a large, active granuloma in the mid-dermis. pancreatic tail. The histology in the spleen was different, in that the lesions were older and large areas were composed of an interweaving network of brightly eosinophilic material that stained as for fibrin by Masson's trichrome stain. Stains for acid-fast bacilli and fungi were negative. Subsequent Course

Because of the rare occurrence of ascites secondary to sarcoidosis it was initially felt that the patient had tuberculous peritonitis and she was started on para-aminosalicylic acid (PAS), isoniazed (INH) and streptomycin. At the time of discharge, 23 days after admission, the patient had a slight reaccumulation of her ascites. Six weeks later, there was no evidence of ascites on physical examination. At this time the Kveim test implanted just before discharge was found to be positive ( Fig 3) and cultures of the spleen, mesentery and liver were still negative for mycobacteria. Streptomycin and PAS were discontinued; INH, 100 mg three times per day, was continued for one year. At the most recent examination, 30 months after discharge, the patient had no evidence of recurrence of he!" ascites. Chest roentgenogram was normal. The complete blood count was normal and her hematocrit was 40 percent. Her liver function studies showed a total protein of 8.4 gm percent with an albumin of 4.4 gm percent and globulins of 4.0 gm percent. The SGOT, the lactic dehydrogenase ( LDH) and the alkaline phosphatase were normal. DISCUSSION

The occurrence of ascites in a patient with sarcoidosis is virtually always secondary to either severe liver involvement1·3 or congestive heart failure. 4 Porter3 de-

scribed four patients with massive hepatic involvement, three of whom had ascites. Hypoproteinemia is a necessary adjunct to the portal hypertension before ascitic fluid collects. 5 Although the serum albumin in this patient was decreased at 2.7 gm/100 ml, the portal pressure was normal and the combination of the two was insufficient to produce ascites. Physical findings and laboratory studies eliminated the possibility of other causes of ascites, such as congestive heart failure, constrictive pericarditis and nephrosis. Serosal surfaces have shown particular resistance to involvement with the granulomas. Longcope and Freiman1 state that with the exception of the pleura and pericardium, " . . . the serous surfaces of the body cavities appear as though almost immune to the disease." Involvement of both the pericardium and the pleura they attribute to local extension from the myocardium and lung, respectively. Pleural sarcoid with effusions and pericardia! sarcoid 7 have been described. Involvement of the peritoneum with various processes may result in the formation of ascites. Malignant and tuberculous peritoneal diseases are the most common offenders. Malignancy was not present and tuberculosis could well be ruled out by the lack of positive cultures, the negative skin tests and the absence of acid-fast organisms on histologic sections. Becker and Coleman, 8 Robinson and Emst9 and Montanus 10 have reported cases of peritoneal sarcoidosis without ascites. Two of these cases9,to were associated with granulomatous involvement of abdominal surgical incisions and may have extended from them to involve the peritoneum. The third case described by Becker and Colemans had an abdominal scar, but also had splenic involvement indicating more diffuse disease. There have been only two well-documented case studies which indicate that ascites resulted solely from peritoneal involvement with sarcoidosis. Becker and Colemans described a 39-yeai"-old Negro woman who presented with massive ascites. The patient had generalized sarcoidosis with hilar adenopathy, skin, liver and spleen involvement. As in our patient, laparotomy was done to differentiate between an ovarian cyst and ascites. At operation, grayish white nodules were found throughout the peritoneum and on the serosal surfaces. The patient died four years later with cor pulmonale. At postmortem, there was no evidence of residual peritoneal sarcoid. In 1962, Wong and Rosen 11 reported a case of peritoneal sarcoid in a 24-year-old man. His first presentation was for parotid gland swelling. The ascites appeared two years later and at operation numerous hard, white nodules studded the peritoneum and the serosal surfaces of the stomach and small and large bowel. The pancreas was infiltrated with similar nodules. Ascites recurred postoperatively and was only controllable with prednisone. Our patient is unique in that she presented with ascites and was found to have active sarcoidosis limited to the abdomen. The complete regression of sarcoidosis in this woman is compatible with the natural history of the disease. One-third of the 311 patients with sarcoido-

CHEST, VOL. 59, NO. 6, JUNE 1971

695

ABDOMINAL SARCOIDOSIS WITH ASCITES sis studied by Siltzbach 12 made complete recoveries. Although pregnancy appears to have a favorable effect on the course of sarcoidosis, ta the disease appears to have been exacerbated during this pregnancy. There can be little doubt that this patient had active sarcoidosis. In addition to the characteristic histology of the biopsy specimens, a positive reaction to a Kveim test was obtained. False positive reactions to this test are distinctly rare.t4 Granulomatous involvement of the peritoneum in our patient was present on histologic section and as in the two previous cases8 •11 must be the pathophysiologic process responsible for the accumulation of the ascites. ACKNOWLEDGMENT: The authors gratefully acknowledge the assistance of Dr. Spencer Koerner in the preparation of this case report.

1 Longcope WT, Freiman DC: A study of sarcoidosis. Medicine 31:1-132, 1952 2 MinoRA, Frelick RW, Murphy AI, et al: Severe systemic sarcoidosis with ascites and splenomegaly. Delaware Med J 20:65-75, 1948

3 Porter GH: Hepatic sarcoidosis. Arch Int Med 108:483495, 1961 4 Cowdell RH1 Sarcoidosis with special reference to diagnosis and prognosis. Quart J Med 23:29-55, 1954 5 Sherlock S: Disease of the Liver and Biliary System. Philadelphia, F. A. Davis Company, 1968 6 Berte SJ, Pfotenhauer MA: Massive pleural effusion in sarcoidosis. Amer Rev Resp Dis 86:261-264, 1962 7 Shiff AD, Blatt CJ, Colp C: Recurrent pericardia! effusion secondary to sarcoidosis of the pericardium. New Er.g J Med 281:141-143, 1969 8 Becker WF, Coleman WO: Surgical significance of abdominal sarcoidosis. Ann Surg 153:987-995, 1961 9 Robinson EK, Ernst RW: Boeck's sarcoid of the peritoneal cavity. Surgery 36:986-991, 1954 10 Montanus WP: Boeck's sarcoid. J Med 19:76-78, 1938 11 Wong M, Rosen SW: Ascites in sarcoidosis due to peritoneal involvement. Ann Int Med 57:277-280, 1962 12 Siltzbach LE: Sarcoidosis: Clinical features and management. Med Clin No Amer 51:483-502, 1967 13 Scadding JG: Sarcoidosis. London, Eyre and Spottiswoode, 1967 14 Siltzbach LE: The Kveim test in sarcoidosis. JAMA 178:476-482, 1961 Reprint requests: Dr. Li, Morrisania City Hospital, Bronx 10452.

ANNOUNCEMENTS Tuberculosis Today The Center for Disease Control, Atlanta (Department of Health Education and Welfare, Public Health Service) will present a five-day course, "Tuberculosis Today" on the following dates: July 2630; September 20-24; December 6-10. The course is designed primarily for physicians, nurses and other health workers. There is no registration fee. For further information, write: Phyllis Q. Edwards, M.D., Chief, Tuberculosis Branch, State and Community Services Division, Center for Disease Control, Atlanta 30333.

Conference on Extra-corporeal Technology The Ninth International Conference on Extra-cor-

CHEST, VOL. 59, NO. 6, JUNE 1971

poreal Technology will be held July 15-17 at the St. Paul Hilton Hotel, St. Paul, Minnesota. The conference is sponsored by the American Society of Extracorporeal Technology, Minnesota Heart Association, and Upper Midwest Kidney Foundation. Information is available from Mr. Edward C. Berger, Executive Director, American Society of Extra-corporeal Technology, 287 East Sixth Street, St. Paul55101.

Symposium on Pulmonary Diseases The 24th Annual Symposium on Pulmonary Diseases will be held at Fitzsimons General Hospital, Denver, September 13-17. Contact LTC Roald A. Nelson, MC Chief, Pulmonary Disease Service and Program Director, Fitzsimons General Hospital, Denver 80240.