ALERTS, NOTICES, AND CASE

176

bosis. It is noteworthy that our patient started using an oral contraceptive only months before the diagnosis of mesenteric artery thrombosis. Asherson and colleagues recently reported that ten patients with antiphospholipid antibodies had thrombosis or other complications develop while they were taking oral contraceptives." Whether smoking contributed to the thrombosis described in this patient is uncertain. The treatment of thrombosis from antiphospholipid syndrome is anticoagulation. The importance of continuing anticoagulant therapy in patients with thrombosis and persistently high anticardiolipin antibody levels has been emphasized.28 The role of corticosteroid therapy appears to be limited, but it has been used in patients with recurrent thrombotic events despite anticoagulation and in extremely ill patients.4 29 Plasmapheresis combined with the use of cyclophosphamide has been proposed as adjunctive therapy for patients with devastating vasculopathy.29 In summary, a young woman with several manifestations of the antiphospholipid syndrome presented with jejunal and ileal infarction requiring resection of most of the small intestine. After four years' follow-up, the patient remains anticoagulated without evidence of recurrent thrombosis but with a high level of IgG anticardiolipin antibody. Measurement of antiphospholipid antibodies is indicated in the evaluation of clinical manifestations consistent with antiphospholipid syndrome, including thrombosis, recurrent fetal loss, and thrombocytopenia.

REPORTS

consecutive patients by activated partial thromboplastin time, Russell viper venom time, and anticardiolipin antibody level. Ann Intern Med 1987; 106:524-531 20. Tan EM, Cohen AS, Fries JF, et al: The 1982 revised criteria for the classifica-

tion of systemic lupus erythematosus. Arthritis Rheum 1982; 25:1271-1277 21. Cohen AJ, Philips TM, Kessler CM: Circulating coagulation inhibitors in the acquired immunodeficiency syndrome. Ann Intern Med 1986; 104:175-180 22. Carreras LO, Defreyn G, Machin SJ, et al: Arterial thrombosis, intrauterine death, and 'lupus' anticoagulant: Detection of immunoglobulin interfering with prostacyclin formation. Lancet 1981; 1:244-246 23. Angeles-Cano E, Sultan Y, Clauvel JP: Predisposing factors to thrombosis in systemic lupus erythematosus: Possible relation to endothelial cell damage. J Lab Clin Med 1979; 94:313-323 24. SanFelippo MJ, Drayna CJ: Prekallikrein inhibition associated with the lupus anticoagulant: A mechanism of thrombosis. Am J Clin Pathol 1982; 77:275-279 25. Kauffmann RH, Veltkamp JJ, Van Tilburg NH, Van Es LA: Acquired antithrombin Ill deficiency and thrombosis in the nephrotic syndrome. Am J Med 1978; 65:607-613 26. Jackson CA, Greaves M, Patterson AD, Brown CB, Preston FE: Relationship between platelet aggregation, thromboxane synthesis and albumin concentration in nephrotic syndrome. Br J Haematol 1982; 52:69-77 27. Asherson RA, Harris EN, Hughes GRV: Complications of oral contraceptives and antiphospholipid antibodies (Letter). Arthritis Rheum 1988; 31:575-576 28. Asherson RA, Chan JK, Harris EN, Gharavi AE, Hughes GRV: Anticardiolipin antibody, recurrent thrombosis, and warfarin withdrawal. Ann Rheum Dis 1985; 44:823-825 29. Ingram SB, Goodnight SH, Bennett RM: An unusual syndrome of a devastating noninflammatory vasculopathy associated with anticardiolipin antibodies: Report of two cases. Arthritis Rheum 1987; 30:1167-1172

Metastasis-induced Acute Pancreatitis SHAUN S. J. HUNG, MD BACH ARDALAN, MD

Miami, Florida

REFERENCES 1. Harris EN, Gharavi AE, Boey ML, et al: Anticardiolipin antibodies: by radioimmunoassay and association with thrombosis in systemic lupus sus. Lancet 1983; 2:1211-1214 2. Elias M, Eldor A: Thromboembolism in patients with the 'lupus' type ing anticoagulant. Arch Intern Med 1984; 144:510-515 3. Harris EN, Gharavi AE, Asherson RA, Boey ML, Hughes GRV: Cerebral infarction in systemic lupus erythematosus: Association with anticardiolipin ies. Clin Exp Rheumatol 1984; 2:47-51 4. Harris EN, Gharavi AE, Hughes GRV: Anti-phospholipid antibodies. Rheum Dis 1985; 11:591-609 5. Harris EN, Chan JKH, Asherson RA, Aber VR, Gharavi AE, Hughes GRV: Thrombosis, recurrent fetal loss, and thrombocytopenia: Predictive value of the cardiolipin antibody test. Arch Intern Med 1986; 146:2153-2156 6. Hughes GRV, Harris EN, Gharavi AE: The anticardiolipin syndrome. Rheumatol 1986; 13:486-489 7. Kalunian KC, PeterJB, Middlekauff HR, et al: Clinical significance of test for anticardiolipin antibodies in patients with systemic lupus erythematosus. Med 1988; 85:602-608 8. Asherson RA, Khamashta MA; Ordi-RosJ, et al: The 'primary' antiphospholipid syndrome: Major clinical and serological features. Medicine 1989; 9. Asherson RA, Morgan SH, Harris EN, Gharavi AE, Krausz T, Hughes Arterial occlusion causing large bowel infarction-A reflection of clotting diathesis SLE. Clin Rheumatol 1986; 5:102-106 10. Asherson RA, Mackworth-Young CG, Harris EN, Gharavi AE, Hughes GRV: Multiple venous and arterial thromboses associated with the lupus anticoagulant antibodies to cardiolipin in the absence of SLE. RheumatolInt 1985; Detection

erythemato-

circulat-

antibod-

Clin

anti-

J

a

single

J

Am

68:366-374

GRV:

in

and

5:91-93

11. Kant KS, PollakVE,Weiss MA, Glueck HI,

Miller MA,

Hess EV:

Glomerular

thrombosis in systemic lupus erythematosus: Prevalence and significance. (Baltimore) 1981; 60:71-86 12. Branch DW, Scott JR, Kochenour NK, Hershgold E: Obstetric associated with the lupus anticoagulant. N Engl J Med 1985; 13. Feinstein DI: Lupus anticoagulant, thrombosis, and fetal loss. N Engl 1985; 313:1348-1350 14. Lockshin MD, Druzin ML, GoeiS, et al: Antibody to cardiolipin as of fetal distress or death in pregnant patients with systemic lupus erythematosus. EngI J Med 1985; 313:152-156 15. Khamashta MA, Harris EN,Gharavi AE, et al: Immune mediated for thrombosis: Antiphospholipid antibody binding to platelet membranes. Dis 1988; 47:849-854 16. Asherson RA, Mayou SC, Merry P, Black MM, Hughes GRV: The

Medicine

complications

THE COMMON CAUSES of acute pancreatitis include alcoholism, biliary tract disease, trauma, surgical therapy, hyperlipidemia, hypercalcemia, and infections. In addition, acute pancreatitis can be induced by chemotherapy,12 tumor lysis,3 or tumor itself in patients with malignancy. The association of pancreatitis and pancreatic carcinoma is well recognized.

Of 255 consecutive patients with pancreatic or ampullary carcinoma, significant pancreatitis by histologic criteria was present in 26.4 Metastatic lesions of the pancreas have been reported from a wide variety of primary tumors5; those associated with clinical pancreatitis are rare, however. Chowhan and Madajewicz documented a 3.3% incidence,6 and Yeung and colleagues reported a 7.5% incidence of metastasisinduced acute pancreatitis in patients with small-cell lung cancer.7 Similarly, McLatchie and Imrie reported only 7 cases due to metastasis among 360 patients with acute pancreatitis seen during a six-year period.8 The objectives of this study are to report this incidence in a county hospital and to review the literature on this disorder. Patients and Methods

313:1322-1326

J

Med

predictor

mechanism

Ann

The medical records of all patients

discharged from JackMemorial Hospital, Miami, Florida, between January 1980 and December 1987 with a diagnosis of primary nonpancreatic malignancy and acute pancreatitis were reviewed retrospectively. A histology-proven malignant disorder was son

spectrum

livedo reticularis and anticardiolipin

antibodies. Br

J Dermatol

17. Levine SR,Welch KMA: The spectrum of neurologic antiphospholipid antibodies. Arch Neurol 1987; 44:876-883 18.

Colaco CB, Elkon KB: The

lupus anticoagulant:

nuclear antibody negative lupus that is

1989;

120:215-221

disease associated

with

A disease marker in anti-

cross-reactive with

antibodies

to

double-

stranded DNA. Arthritis Rheum 1985; 28:67-74 19. Petri M, Rheinschmidt M,Whiting-O'Keefe Q, Hellmann D, Corash L: frequency of lupus anticoagulant in systemic lupus erythematosus: A study of

The

sixty

(Hung SSJ, Ardalan B: Metastasis-induced 1991 Aug; 155:176-178)

acute pancreatitis. West J Med

of Miami School of Medicine, Medicine, Kaiser Permanente Medi-

From the Department of Oncology, University Florida. Dr Hung is now with the Department of cal Center, Santa Clara, California.

Reprint manente

requests to

Shaun S.J. Hung, MD, Department of Medicine, Kaiser PerKiely Blvd, Santa Clara, CA 95051.

Medical Center, 900

THE THI

WESTERN JOURNAL OF MEDICINE

o

AUGUST 1991

o

155

o

177

2

;X: V TABLE 1.--ltdstdslHducedA6te P6ceabtids ihn:5 Men'V: 0XCause 0:8f~;ofOad '2 .. *:rt8;r,Ii stsue+ Patient Age, yr Primary Tumor A3" :'Ln r ace -:Alitop 54 Lunti adenoeareTha 74 Stomachadenocarcinoma I::nevt:f3d Nn;0 ..... Paceti,paeiol AutopsV yd cosrvtv consraie : :- -i: 1 d He;:flem0haW,cpaniiitis 3 .. 55 Hepatocellular carcinoma AutopsVi: :9E .:0 l+oe::Lostup40i0; 7.5 Liver angiosarcom:a -:Lpa*Oti*y CtvsemtiW,, |tX, m;;00 SAbdominaig;10wMa -W 5 .... 25 Diffuse large-cell lyphoma :None 'Conservative measures indudednasoigastictubesetionintravenwusfluids

adti::se

fad

:00

=

tDuration of survival was measured fthEv dinkeal o,nset of panqfti& to te ffme: of deatko**tu 1, 2, ;*d 5) or the last ftlolw-u .

needed for entry in this study. The diagnosis of acute pancreatitis was based on clinical, laboratory, and radiologic findings. Although histologic examination of the pancreas was not required for this analysis, it was made in about half of the patients. When pancreatic biopsy or necropsy was not done, the determination of the cause of pancreatitis was based on clinical and radiologic findings.

Results A total of 28 patients were discharged with the diagnosis of primary nonpancreatic malignancy and acute pancreatitis during the eight-year period. Six patients were excluded from analysis because medical records were not available in three cases and no tissue diagnosis of malignancy was made in the other three. The causes of acute pancreatitis in the remaining 22 patients include metastasis (5 patients), alcoholism (4), abdominal operation (3), cholelithiasis (2), infection (2), L-asparaginase (1), and idiopathic (5). Four of the five patients with metastasis-induced pancreatitis (Table 1) had microscopic evidence of pancreatic (patients 2, 3, and 4) or peripancreatic (patients 1, 2, and 4) invasion by tumor, and no other etiologic factors of acute pancreatitis could be identified. Although the fifth patient with non-Hodgkin's lymphoma did not have a histology-proven pancreatic metastasis, the clinical and radiologic findings and a partial response to abdominal irradiation are consistent with a lymphomatous process. Report of a Case The patient was a 25-year-old man admitted for epigastric and periumbilical pain radiating to the back for two weeks. Eleven months before admission, he was diagnosed with stage II diffuse large-cell lymphoma in the neck and mediastinum and received chemotherapy consisting of cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone, bleomycin sulfate, and methotrexate. Because the disease in the chest continued to progress, he underwent thoracic irradiation, 15 grays (1,500 rads) in ten fractions, one month before admission. There was no history of alcohol abuse. On physical examination his abdomen was soft but diffusely tender. Laboratory tests elicited the following values: leukocyte count, 9.3 x 109 per liter (9,300 per il); blood urea nitrogen, 1.4 mmol per liter (4 mg per dl); creatinine, 62 itmol per liter (0.7 mg per dl); calcium, 2.27 mmol per liter (9.1 mg per dl); and amylase, 260 units per liter (normal 30 to 110). The results of liver function tests were all within normal limits. A computed tomographic scan ofthe chest and abdomen showed a left mediastinal mass, periaortic and inguinal lymphadenopathy, and an extensive and lobulated mass in the celiac and peripancreatic regions inseparable

0

VW(ptient A0

0

from the head of the pancreas. After conservative management, he was discharged five days later with an amylase level of 196 units per liter. Two weeks after discharge, the patient was readmitted with similar symptoms and signs, and the serum amylase level was 244 units per liter. He was treated with abdominal irradiation, 20 Gy in 20 fractions. When radiotherapy was completed, the abdominal pain was partially relieved and the amylase level was 33 units per liter, but he died three weeks later because of progressive lymphoma. An autopsy was not done.

Discussion Metastasis-induced acute pancreatitis is a rare occurrence, and over an eight-year period, we saw only five such cases in a hospital serving the Dade County, Florida, area. Metastases, however, accounted for 5 (23%) of the 22 incidents of acute pancreatitis in patients with primary nonpancreatic malignancy. In all, 29 other cases of this disorder have been reported in the English literature, and these tumors include bronchogenic carcinoma (12 patients),6 -3 lymphoma (10),14-22 gastric carcinoma (5),8 melanoma (1),23 and anaplastic carcinoma of the tonsil (1).8 Two of our patients (3 and 4) had hepatocellular carcinoma-induced and hepatic angiosarcoma-induced pancreatitis, respectively, which have not previously been reported. The mechanisms of this disorder include pancreatic ductal obstruction or rupture following either direct tumor invasion or peripancreatic lymph node involvement and vascular compromise by neoplastic destruction or encasement of pancreatic vessels.7 It may be the presenting feature of a malignant neoplasm6.8.9'113,15-22 or the first evidence of metastasis10'23 or recurrence.714 Distinguishing between acute pancreatitis due to metastasis and acute pancreatitis of other causes could be difficult because the clinical presentations are similar in many respects and laboratory tests are not of much use in the differential diagnosis. Neither abdominal ultrasonography nor computed tomographic scan is definitive because metastases may be extensive or associated with secondary pancreatitis and pancreatitis of other causes could be focal. Unless clinical and radiologic findings clearly indicate the presence of pancreatic or peripancreatic metastases, a histologic diagnosis may be needed if clinical pancreatitis has not resolved after conservative management and antitumor therapy is contemplated. Percutaneous fine-needle aspiration of the pancreas is a useful procedure with a sensitivity ranging from 48% 24 to 85% ,25 and the risk and discomfort are minimal. Normal findings do not rule out the presence of metastases, however. If effective therapy exists, such as in the cases of lymphoma, an exploratory laparotomy for tissue diagnosis remains justified.

ALERTS, NOTICES, AND CASE REPORTS

178

When acute pancreatitis develops in a patient with primary nonpancreatic malignancy, conservative measures such as nasogastric tube suction, intravenous fluids, and the use of analgesics may be used first, and occasionally the pancreatitis may subside in a few days.8'5l' If clinical pancreatitis persists and a histologic diagnosis of pancreatic metastases has been made, systemic chemotherapy or abdominal irradiation should be considered in patients with small-cell carcinoma or lymphoma. Yeung and colleagues reported the cases of three patients with metastasis-induced acute pancreatitis associated with small-cell lung cancer, and clinical pancreatitis resolved completely two days, one week, and four weeks, respectively, after combination chemotherapy was instituted.7 Levine and Danovitch reported the case of a patient with bronchogenic carcinoma-induced pancreatitis that did not respond to abdominal irradiation, whereas abdominal irradiation provided palliation in one of our patients with lymphoma (patient 5). Acute pancreatitis due to metastasis seems to be an ominous prognostic sign in patients with primary nonpancreatic malignancy. Among those patients with survival data documented,6-13.16'17'21'22 the vast majority died within six months after the diagnosis of acute pancreatitis. Only two patients with non-Hodgkin's lymphoma survived for more than six months. 16'17 REFERENCES 1. Mallory A, Kern F: Drug-induced pancreatitis. A critical review. Gastroenterology 1980; 78:813-820 2. Socinski MA, Garnick MB: Acute pancreatitis associated with chemotherapy for germ cell tumors in two patients. Ann Intern Med 1988; 108:567-568 3. Spiegel RJ, Magrath IT: Tumor lysis pancreatitis. Med Pediatr Oncol 1979; 7:169-172 4. Gambill EE: Pancreatitis associated with pancreatic carcinoma: A study of 26 cases. Mayo Clin Proc 1971; 46:174-177 5. Roland CF, van Heerden JA: Nonpancreatic primary tumors with metastasis to the pancreas. Surg Gynecol Obstet 1989; 168:345-347 6. Chowhan NM, Madajewicz S: Management of metastases-induced acute pancreatitis in small cell carcinoma of the lung. Cancer 1990; 65:1445-1448 7. Yeung KY, Haidak DJ, Brown JA, Anderson D: Metastasis-induced acute pancreatitis in small cell bronchogenic carcinoma. Arch Intern Med 1979; 139:552-554 8. McLatchie GR, Imrie CW: Acute pancreatitis associated with tumor metastases in the pancreas. Digestion 1981; 21:13-17 9. Niccolini DG, Graham JH, Banks PA: Tumor-induced acute pancreatitis. Gastroenterology 1976; 71:142-145 10. Levine M, Danovitch SH: Metastatic carcinoma to the pancreas, another cause for acute pancreatitis. Am J Gastroenterol 1973; 60:290-294 11. Schmitt JK: Pancreatitis and diabetes mellitus with metastatic pulmonary oatcell carcinoma (Letter). Ann Intern Med 1985; 103:638-639 12. Hall M, Bundred NJ, Hall AW: Oat cell carcinoma of the bronchus and acute pancreatitis. Eur J Surg Oncol 1987; 13:371-372 13. Noseda A, Gangji D, Cremer M: Acute pancreatitis as presenting symptom and sole manifestation of small cell lung carcinoma. Dig Dis Sci 1987; 32:327-331 14. Francis IR, Glazer GM: Burkitt's lymphoma of the pancreas presenting as acute pancreatitis. J Comput Assist Tomogr 1982; 6:395-397 15. Cameron-Strange A: Acute pancreatitis associated with lymphosarcoma. Br J Surg 1983; 70:444 16. Freed JS, Dreiling DA, Reiner MA: Non-Hodgkin's lymphoma of the pancreas producing acute pancreatitis and pancreatic abscess. Mt Sinai J Med 1983; 50:424-427 17. Anderson JH, Morran CG, Anderson JR, Carter DC: Acute pancreatitis and non-Hodgkin's lymphoma. Postgrad Med J 1987; 63:137-139 18. Halline A, Lerios M, Melissas J, Segal I, Grieve TP: Primary lymphoma of the small bowel with obstructive jaundice and pancreatitis-A case report. S Afr Med J 1987; 72:61-62 19. Wan YL, Chen WJ, Huang SC, Lee TY, Tsai CC: Solitary hepatic Burkitt lymphoma presenting as acute pancreatitis. Pediatr Radiol 1988; 18:160 20. Liang R: Acute pancreatitis due to Hodgkin's disease in a patient with systemic lupus erythematosus. Aust NZ J Med 1988; 18:812-813 21. Kotwall CA, Brow JR, Keith RG: Lymphoma pancreatitis: A real entity. Can J Surg 1989; 32:375-377 22. Moosa MR, Segal I: Tumor-associated acute pancreatitis (Letter). J Clin Gastroenterol 1984; 6:188 23. Gatchell FG, Minor D: Malignant melanoma of the eye, metastatic after 29 years: A case report. J Okla State Med Assoc 1972; 65:211-214 24. Alpern GA, Dekker A: Fine needle aspiration cytology of the pancreas: An analysis of its use in 52 patients. Acta Cytol 1985; 29:873-878 25. Bognel C, Rougier P, Leclere J, Duvillard P, Charpentier P, Prade M: Fine needle aspiration of the liver and pancreas with ultrasound guidance. Acta Cytol 1988; 32:22-26

Spontaneous Intracranial Hypotension An Uncommon and Underrecognized Cause of Headache MICHAEL B. JACOBS, MD PHILIP H. WASSERSTEIN, MD Stanford, California

ALTHOUGH WELL DESCRIBED in the neurologic literature,`13 spontaneous intracranial hypotension (also called primary intracranial hypotension, primary cerebrospinal fluid hypotension, spontaneous hypoliquorrhea, and a number of other names) is generally not mentioned in reviews of headache diagnosis and treatment in the internal medicine literature.46 We report a case of this headache disorder and review its

characteristics, pathogenesis, and treatment. Report of a Case The patient, a 25-year-old woman with an unremarkable medical history, suddenly had moderate occipital and posterior cervical discomfort. She felt nauseated, vomited, and took a nap. On rising she had severe cervico-occipital pain"the worst I ever felt in my life"-whenever she tried to sit or stand. When she lay down, she felt perfectly well, but she was essentially unable to stand or sit. There was no history of fever or head trauma. The results of a general physical examination and the neurologic examination were within normal limits. A complete blood count with differential leukocyte count was normal. Magnetic resonance imaging (MRI) of the head showed the tips of the cerebellar tonsils to be within the foramen magnum. A lumbar puncture was done with the patient in the lateral decubitus position. The opening pressure was 20 mm of cerebrospinal fluid (CSF). The CSF flowed from the needle slowly, but the flow rate increased with a Valsalva maneuver. The fluid was acellular, and protein and glucose concentrations were normal. No imaging study was done to look for an extradural CSF leak. Treatment included a five-day course of corticosteroids, a high-salt diet, salt tablet supplements, and extra oral fluids. The headache was decreased at two weeks and gone in eight weeks. Discussion

Headache is an extremely common outpatient problem with an extensive differential diagnosis. Most headaches, particularly in young people, are not the result of intracranial disease but are considered to represent tension or vascular

headache, particularly if the headaches

are chronic. The most common vascular headache is the common migraine; less common types include classic migraine, cluster headache, cough headache, exertional headache, and coitusassociated headache. New-onset and acute headaches raise

(Jacobs MB, Wasserstein PH: Spontaneous intracranial hypotension-An uncommon and underrecognized cause of headache. West J Med 1991 Aug;

155:178-180) From the Departments of Medicine (Dr Jacobs) and Neurology (Dr Wasserstein), Stanford University Medical Center, Stanford, California. Reprint requests to Michael B. Jacobs, MD, Department of Medicine, Stanford University Medical Center, Stanford, CA 94305-5235.