Digestive Diseases and Sciences, Vol. 35, No. 7 (July 1990), pp. 912-915
CASE R E P O R T
Recurrent Acute Pancreatitis as a Manifestation of Wegener's Granulomatosis J A M E S A L A N K E M P , MD, S A N J E E V A R O R A , MD, and K A R I M F A W A Z , MD KEY WORDS: vasculitis; glucocorticoids; computed tomography; x-ray; cholangiopancreatography; endo-
scopic retrograde.
Although W e g e n e r ' s granulomatosis is an uncomm o n disorder, its clinical and pathological features are well k n o w n and distinct. Acute pancreatitis has not been reported as a manifestation of Wegener's granulomatosis, in spite of the demonstration of pancreatic vasculitis in a number of autopsied cases (1-3). We report a case of recurrent acute pancreatitis in association with reactivation of Wegener's granulomatosis in a patient with long-standing disease. CASE REPORT
A 57-year-old white man with a 16-year history of Wegener's granulomatosis was admitted to New England Medical Center Hospitals on February 24, 1988, because of abdominal pain and hyperamylasemia. Wegener's granulomatosis was diagnosed in May 1971 when he presented with a three-month history of bilateral serous otitis media, rhinitis, saddle nose deformity, nasopharyngitis, arthralgias, and pulmonary nodules. Biopsy of nasal and nasopharyngeal mucosa revealed necrotizing perivascular granulomata, establishing the diagnosis of Wegener's granulomatosis. He was treated with prednisone. After clinical remission was achieved, cyclophosphamide was added and the dose of prednisone was gradually reduced. He remained in remission over the ensuing years, and four years later all medicines were stopped. The patient remained well until March 1978 when he had a recurrence of pulmonary lesions, which again responded to treatment with prednisone and cyclophosphamide. These drugs were again tapered and stopped. In June 1983 there was recurrence of Wegener's granulomatosis with development of cavitary lung lesions, palpable purpura, hematuria, and deterioration of Manuscript received January 26, 1990; accepted March 7, 1990. From the Division of Gastroenterology, Department of Medicine, New England Medical Center, 750 Washington Street, Boston, MA 02111. Address for reprint requests: Sanjeev Arora, New England Medical Center, 750 Washington Street, Gastroenterology Division, Box 239, Boston, Massachusetts 02111.
912
renal function. Treatment with high-dose intravenous steroids and azathioprine resulted in complete clinical recovery. Over the next several years repeated attempts to taper the prednisone and azathioprine led to relapses of Wegener's granulomatosis, with fever, chills, subcutaneous skin nodules, and cavitary lung lesions. He responded rapidly to reinstitution of prednisone on each occasion. Azathioprine was replaced by cyclophosphamide. On January 11, 1988, while on tapering doses of 10 mg alternating with 5 mg prednisone and 150 mg cyclophosphamide daily, he presented to the New England Medical Center Hospitals with epigastric pain of 24 hr duration. Mild epigastric tenderness was present on examination. Amylase was 240 units/liter (normal < 125); aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, and alkaline phosphatase were normal. He was treated conservatively as an outpatient with resolution of pain. No change was made in the dose of prednisone or cyclophosphamide. In the following month he was hospitalized twice at another hospital for acute pancreatitis diagnosed clinically, with amylase > 800 units/liter on both occasions. Both episodes resolved after oral intake was stopped and he was given intravenous fluids. On February 24, 1988, he was admitted for evaluation of recurrent severe epigastric pain of several hours' duration. Past medical history was remarkable for a cholecystectomy for symptomatic cholelithiasis in 1968. He had worked as an office supervisor for the past 19 years. He had consumed 12-24 oz beer daily, but stopped all alcohol intake in January 1988 after the first episode of abdominal pain. There was no family history of pancreatitis and no history of abdominal trauma. Physical examination revealed moderate periumbilical and left upper quadrant tenderness, without peritoneal signs. Bowel sounds were present. Rectal examination was unremarkable and stool was guaiac negative. Amylase was 1039 units/liter and lipase 6.2 units/ml (normal limits 0-1.5). Serum AST, ALT, bilirubin, alkaline phosphatase, calcium, and triglycerides were normal. Abdominal flat plate showed no abnormal calcifications, and ultrasound of the abdomen was normal. Oral intake was withheld, and he was treated with intravenous fluids, meperidine, hydroxyzine, and ranitiDigestive Diseases and Sciences, Vol. 35, No. 7 (July 1990)
0163-2116/90/0700-0912506.00/0 9 1990 Plenum Publishing Corporation
P A N C R E A T I T I S IN W E G E N E R ' S G R A N U L O M A T O S I S
Fig 2. Chest roentgenogram with nodular infiltrate at right base (arrow).
Fig 1. Pancreatogram showing extravasation of contrast from mid-pancreatic duct filling a 2.5 x 1.5-cm cavity (arrow).
dine. He improved rapidly and was discharged with a normal serum amylase on the fourth day. The dose of prednisone was maintained at 10 mg alternating with 5 mg, but the dose of cyclophosphamide was reduced to 50 mg daily. Endoscopic retrograde cholangiopancreatography (ERCP) was performed three weeks later to identify a cause for recurrent pancreatitis. Findings included a normal bile duct and extravasation of contrast medium from the mid-pancreatic duct into a cavity measuring 2.5 • 1.5 cm (Figure 1). There were no changes suggestive of chronic pancreatitis. On March 31, 1988, epigastric pain recurred with radiation to the back and right shoulder. On presentation to New England Medical Center Hospitals, physical examination was remarkable for a temperature of 38 ~ C and marked epigastric tenderness. Amylase was 950 units/liter; AST, ALT, and alkaline phosphatase were normal. Bilirubin was 1.1 mg/dl. A chest roentgenogram revealed a new nodular infiltrate at the right base (Figure 2), which on computed tomography appeared as a 2.5-cm cavitary lesion in the right posterior basal lung (Figure 3). In addition, a 2-cm nodular soft-tissue-density mass in the apex of the right lung was seen. Computed tomography of the abdomen revealed an irregular cystic area consistent with a pseudocyst in the body of the pancreas (Figure 4), corresponding to the site of duct disruption seen on ERCP. There was diffuse swelling of the pancreas suggestive of pancreatitis. He was treated as on the previous admission. Resolution of pain and normalization of serum amylase occurred gradually, and oral intake was resumed. Two weeks after admission, severe abdominal pain recurred, accompanied by nausea and vomiting, fever, and orthostatic hypotension. Amylase was 4651 units/liter. Because of the new cavitary pulmonary lesion, it was suspected that the pancreatitis might be a rare manifestation of Wegener's Digestive Diseases and Sciences, Vol. 35, No. 7 (July 1990)
granulomatosis. Intravenous methylprednisolone, 25 mg twice a day was begun. Soon after methylprednisolone was started there was a dramatic improvement in his abdominal pain, nausea, and vomiting. Amylase normalized, and he tolerated oral intake. He continued to improve clinically and was discharged after a five-week hospitalization on a regimen of prednisone, 40 mg daily, cyclophosphamide, 50 mg daily, and ranitidine, 150 mg twice a day. A computed tomogram as an outpatient two months later revealed resolution of the changes in and around the pancreas and near resolution of the pulmonary lesions. He has now remained completely asymptomatic 14 months after discharge. DISCUSSION T h i s is, to o u r k n o w l e d g e , t h e first r e p o r t e d c a s e o f r e c u r r e n t a c u t e p a n c r e a t i t i s in a s s o c i a t i o n w i t h a
Fig 3. Computed tomogram of the chest with 2.5-cm cavitary lesion in right posterior basal lung (arrow) corresponding to nodular infiltrate seen in Figure 2.
913
K E M P ET AL
Fig 4. Computed tomogram of abdomen with cystic area in region of the midbody (arrow).
flare of Wegener's granulomatosis. Because of the absence of a previously reported case, there was delay in the diagnosis in this patient. Pancreatitis associated with Wegener's granulomatosis was diagnosed only on his sixth episode of pancreatitis, when new cavitary pulmonary lesions suggested a relapse in his long-standing disease. Vasculitis of pancreatic vessels has been observed histologically in a number of patients with Wegener's granulomatosis (1-4), but clinical acute pancreatitis has not been described in these reports. Acute pancreatitis may occur in other systemic vasculitides, including polyarteritis nodosa prior to therapy (5-7), as well as in the course of treated polyarteritis or Churg-Strauss vasculitis (8-10), in Henoch-Shonlein purpura (11, 12), and in systemic lupus erythematosus at presentation or during treatment (13-18). These cases of acute pancreatitis in other systemic vasculitides and the documented involvement of pancreatic vessels in Wegener's granulomatosis support our conclusion that Wegener's granulomatosis was the cause of this patient's acute pancreatitis. Attempts to identify other causes of acute pancreatitis in this patient were not successful. The limited alcohol use, lack of pancreatic calcification, and absence of changes of chronic pancreatitis by ERCP make ethanol-induced pancreatitis unlikely. Although the patient underwent cholecystectomy 20 years prior to the occurrence of pancreatitis, he had no biochemical manifestations of choledocholithiasis, and choledocholithiasis was not demonstrated by ultrasound, CT scan, or ERCP. Serum calcium and triglycerides were normal. There was
914
no support for a diagnosis of familial pancreatitis, no recent trauma or abdominal surgery, and no evidence of pancreas divisum or other proposed causes of acute pancreatitis. The patient's medications at the time of the onset of pancreatitis were cyclophosphamide and prednisone. There is no evidence to implicate cyclophosphamide as a cause of acute pancreatitis. The role of corticosteroids as a cause of acute pancreatitis is controversial (19). Many of the cases reported as acute pancreatitis with the administration of steroids are suspect because of the concurrent administration of other drugs that are recognized as causes of acute pancreatitis, such as tetracycline (20, 21), thiazides (22), azathioprine (23), or 6mercaptopurine (24). Other patients with presumed steroid-induced pancreatitis have had illnesses such as systemic lupus erythematosus or other disorders that are independently associated with acute pancreatitis (20, 23-25). Further evidence against a causal role of steroids in this case of pancreatitis is the dramatic improvement in the pancreatitis associated with an increase in glucocorticoid dose. The strongest support for the role of Wegener's granulomatosis is provided by his clinical course. Recurrent episodes of abdominal pain and hyperamylasemia began three months after a reduction in the prednisone dosage. The final moderately severe and prolonged episode followed reduction of the cyclophosphamide dose from 150 mg to 50 mg daily. During the final episode of pancreatitis, new nodular pulmonary infiltrates characteristic of active Wegener's granulomatosis were seen. Dramatic improvement in the manifestations of pancreatitis and in the pulmonary nodules occurred with an increased glucocorticoid dose. He has remained free of active Wegener's granulomatosis or acute pancreatitis 14 months after discharge. One unusual feature that may help better define the nature of this entity is the rapid recurrence of disease. During a period between January 11 and April 15, 1988, he had six episodes of acute pancreatitis. The initial episodes responded promptly to conservative treatment; however, subsequent relapses were successively more severe. Also important appears to be the finding that acute pancreatitis may be the only clinically apparent site of organ involvement for several months when a relapse of Wegener's granulomatosis occurs. We recommend that when a patient with documented Wegener's granulomatosis develops recurrent acute pancreatitis, relapse of the underlying disease should be Digestive Diseases and Sciences, Vol. 35, No. 7 (July 1990)
P A N C R E A T I T I S IN W E G E N E R ' S G R A N U L O M A T O S I S considered unless another obvious cause of pancreatitis is a p p a r e n t . T h i s w o u l d p r e v e n t d e l a y in t r e a t m e n t a n d p o s s i b l y a v o i d c o m p l i c a t i o n s s u c h as d u c t r u p t u r e a n d p s e u d o c y s t t h a t o c c u r r e d in o u r patient. SUMMARY We report a case of recurrent acute pancreatitis in a 5 7 - y e a r - o l d m a n w i t h r e a c t i v a t i o n o f W e g e n e r ' s granulomatosis. An association between acute pancreatitis and Wegener's granulomatosis has not been reported previously. Six episodes of abdominal p a i n a n d h y p e r a m y l a s e m i a o c c u r r e d a n d w e r e complicated by development of a pancreatic pseud o c y s t . N e w c a v i t a r y lung l e s i o n s t y p i c a l o f W e g e n e r ' s g r a n u l o m a t o s i s l e d to t r e a t m e n t w i t h i n c r e a s e d g l u c o c o r t i c o i d d o s a g e , r e s u l t i n g in r a p i d r e s o l u t i o n of the pancreatitis and pulmonary lesions. Acute pancreatitis may be a clinical manifestation of the h i s t o l o g i c p a n c r e a t i c v a s c u l i t i s o b s e r v e d in W e g e n er's granulomatosis. Reactivation of Wegener's granulomatosis should be considered when a patient with the disorder develops otherwise unexplained acute pancreatitis.
ACKNOWLEDGMENTS The authors acknowledge the kind assistance of Dr. Robert Schwartz and Marian Harvey.
REFERENCES 1. Walton EW, Leggat PO: Wegener's granulomatosis. J Clin Pathol 9:31-37, 1956 2. Fahey JL, Leonard E, Churg J, Godman G: Wegener's granulomatosis: Am J Med 17:168-179, 1954 3. Banowitch MM, Polayes SH, Charet R: Periarteritis nodosa: Report of five cases. Ann Intern Med 16:1149-1179, 1942 4. Godman GC, Churg J: Wegener's granulomatosis: Pathology and review of the literature. AMA Arch Pathol 58:533-553, 1954 5. Brown HW, Ghosh S: Polyarteritis presenting as an acute abdomen. Int Surg 51:30-35, 1969 6. Miller HG, Daley R: Clinical aspects of polyarteritis nodosa. Q J Med 15:255-283, 1946
Digestive Diseases and Sciences. Vol. 35, No. 7 (July 1990)
7. Pear BL: Radiologic recognition of extrahepatic manifestations of hepatitis B antigenemia. AJR 137:135-140, 1981 8. Guillevin L, Du LTH, Godeau P, Jais P, Wechsler B: Clinical findings and prognosis of polyarteritis nodosa and Churg-Strauss angiitis: A study of 165 patients. Br J Rheumatol 27:258-264, 1988 9. Camilleri M, Pusey CD, Chadwick VS, Rees AJ: Gastrointestinal manifestations of systemic vasculitis. Q J Med 52:141-149, 1983 10. Colton CL, Butler TJ: The surgical problem of polyarteritis nodosa. Br J Surg 54:393-396, 1967 11. Branski D, Gross V, Gross-Kieselstein E, Roll D, Abrahamov A: Pancreatitis as a complication of Henoch-Schonlein purpura. J Pediatr Gastroenterol Nutr 1:275-276, 1982 12. Garner JA: Acute pancreatitis as a complication of anaphylactoid (Henoch-Schonlein) purpura. Arch Dis Child 52:971972, 1977 13. DiVittorio G, Wees S, Koopman WJ, Ball GV: Pancreatitis in systemic lupus erythematosus. Arthritis Rheum 25:$6, 1982 14. Reynolds JC, Inman RD, Kimberly RP, Chuong JH, Kovacs JE, Walsh MB: Acute pancreatitis in systemic lupus erythematosus: Report of twenty cases and a review of the literature. Medicine 61:25-32, 1982 15. Eaker YE, Toskes PP: Case Report: systemic lupus erythematosus presenting initially with acute pancreatitis and a review of the literature. Am J Med Sci 297:38-41, 1989 16. Marino C, Lipstein-Kresch E: Pancreatitis in systemic lupus erythematosus. Arthritis Rheum 27:118-119, 1984 17. Giordano M, Gallo M, Chianese U, Maniera A, Tirri G: Acute pancreatitis as the initial manifestation of systemic lupus erythematosus. Z Rheumatol 45:60-63, 1986 18. Pollock V, Grove WJ, Kark RM, Muehrcke RC, Pirani CL, Steck IE: Systemic lupus erythematosus simulating acute surgical condition of the abdomen. N Engl J Med 259:258266, 1958 19. Mallory A, Kern F: Drug-induced pancreatitis: A critical review. Gastroenterology 78:813-820, 1980 20. Nelp WB: Acute pancreatitis associated with steroid therapy. Arch Intern Med 108:702-710, 1961 21. Barr HS, Wolfe OH: Pancreatic necrosis in cortisone-treated children. Lancet 1:812, 1957 22. Bourne MS, Dawson H: Acute pancreatitis complicating prednisolone therapy. Lancet 2:1209-1210, 1958 23. Riemenschneider TA, Wilson JF, Vernier RL: Glucocorticoid-induced pancreatitis in children. Pediatrics 41:428-437, 1968 24. Schrier RW, Bulger RJ: Steroid induced pancreatitis. JAMA 194:564-565, 1965 25. Cortese AF, Glen F: Hypocalcemia and tetany with steroidinduced acute pancreatitis. Arch Surg 96:119-122, 1968
915
CASE R E P O R T
Recurrent Acute Pancreatitis as a Manifestation of Wegener's Granulomatosis J A M E S A L A N K E M P , MD, S A N J E E V A R O R A , MD, and K A R I M F A W A Z , MD KEY WORDS: vasculitis; glucocorticoids; computed tomography; x-ray; cholangiopancreatography; endo-
scopic retrograde.
Although W e g e n e r ' s granulomatosis is an uncomm o n disorder, its clinical and pathological features are well k n o w n and distinct. Acute pancreatitis has not been reported as a manifestation of Wegener's granulomatosis, in spite of the demonstration of pancreatic vasculitis in a number of autopsied cases (1-3). We report a case of recurrent acute pancreatitis in association with reactivation of Wegener's granulomatosis in a patient with long-standing disease. CASE REPORT
A 57-year-old white man with a 16-year history of Wegener's granulomatosis was admitted to New England Medical Center Hospitals on February 24, 1988, because of abdominal pain and hyperamylasemia. Wegener's granulomatosis was diagnosed in May 1971 when he presented with a three-month history of bilateral serous otitis media, rhinitis, saddle nose deformity, nasopharyngitis, arthralgias, and pulmonary nodules. Biopsy of nasal and nasopharyngeal mucosa revealed necrotizing perivascular granulomata, establishing the diagnosis of Wegener's granulomatosis. He was treated with prednisone. After clinical remission was achieved, cyclophosphamide was added and the dose of prednisone was gradually reduced. He remained in remission over the ensuing years, and four years later all medicines were stopped. The patient remained well until March 1978 when he had a recurrence of pulmonary lesions, which again responded to treatment with prednisone and cyclophosphamide. These drugs were again tapered and stopped. In June 1983 there was recurrence of Wegener's granulomatosis with development of cavitary lung lesions, palpable purpura, hematuria, and deterioration of Manuscript received January 26, 1990; accepted March 7, 1990. From the Division of Gastroenterology, Department of Medicine, New England Medical Center, 750 Washington Street, Boston, MA 02111. Address for reprint requests: Sanjeev Arora, New England Medical Center, 750 Washington Street, Gastroenterology Division, Box 239, Boston, Massachusetts 02111.
912
renal function. Treatment with high-dose intravenous steroids and azathioprine resulted in complete clinical recovery. Over the next several years repeated attempts to taper the prednisone and azathioprine led to relapses of Wegener's granulomatosis, with fever, chills, subcutaneous skin nodules, and cavitary lung lesions. He responded rapidly to reinstitution of prednisone on each occasion. Azathioprine was replaced by cyclophosphamide. On January 11, 1988, while on tapering doses of 10 mg alternating with 5 mg prednisone and 150 mg cyclophosphamide daily, he presented to the New England Medical Center Hospitals with epigastric pain of 24 hr duration. Mild epigastric tenderness was present on examination. Amylase was 240 units/liter (normal < 125); aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, and alkaline phosphatase were normal. He was treated conservatively as an outpatient with resolution of pain. No change was made in the dose of prednisone or cyclophosphamide. In the following month he was hospitalized twice at another hospital for acute pancreatitis diagnosed clinically, with amylase > 800 units/liter on both occasions. Both episodes resolved after oral intake was stopped and he was given intravenous fluids. On February 24, 1988, he was admitted for evaluation of recurrent severe epigastric pain of several hours' duration. Past medical history was remarkable for a cholecystectomy for symptomatic cholelithiasis in 1968. He had worked as an office supervisor for the past 19 years. He had consumed 12-24 oz beer daily, but stopped all alcohol intake in January 1988 after the first episode of abdominal pain. There was no family history of pancreatitis and no history of abdominal trauma. Physical examination revealed moderate periumbilical and left upper quadrant tenderness, without peritoneal signs. Bowel sounds were present. Rectal examination was unremarkable and stool was guaiac negative. Amylase was 1039 units/liter and lipase 6.2 units/ml (normal limits 0-1.5). Serum AST, ALT, bilirubin, alkaline phosphatase, calcium, and triglycerides were normal. Abdominal flat plate showed no abnormal calcifications, and ultrasound of the abdomen was normal. Oral intake was withheld, and he was treated with intravenous fluids, meperidine, hydroxyzine, and ranitiDigestive Diseases and Sciences, Vol. 35, No. 7 (July 1990)
0163-2116/90/0700-0912506.00/0 9 1990 Plenum Publishing Corporation
P A N C R E A T I T I S IN W E G E N E R ' S G R A N U L O M A T O S I S
Fig 2. Chest roentgenogram with nodular infiltrate at right base (arrow).
Fig 1. Pancreatogram showing extravasation of contrast from mid-pancreatic duct filling a 2.5 x 1.5-cm cavity (arrow).
dine. He improved rapidly and was discharged with a normal serum amylase on the fourth day. The dose of prednisone was maintained at 10 mg alternating with 5 mg, but the dose of cyclophosphamide was reduced to 50 mg daily. Endoscopic retrograde cholangiopancreatography (ERCP) was performed three weeks later to identify a cause for recurrent pancreatitis. Findings included a normal bile duct and extravasation of contrast medium from the mid-pancreatic duct into a cavity measuring 2.5 • 1.5 cm (Figure 1). There were no changes suggestive of chronic pancreatitis. On March 31, 1988, epigastric pain recurred with radiation to the back and right shoulder. On presentation to New England Medical Center Hospitals, physical examination was remarkable for a temperature of 38 ~ C and marked epigastric tenderness. Amylase was 950 units/liter; AST, ALT, and alkaline phosphatase were normal. Bilirubin was 1.1 mg/dl. A chest roentgenogram revealed a new nodular infiltrate at the right base (Figure 2), which on computed tomography appeared as a 2.5-cm cavitary lesion in the right posterior basal lung (Figure 3). In addition, a 2-cm nodular soft-tissue-density mass in the apex of the right lung was seen. Computed tomography of the abdomen revealed an irregular cystic area consistent with a pseudocyst in the body of the pancreas (Figure 4), corresponding to the site of duct disruption seen on ERCP. There was diffuse swelling of the pancreas suggestive of pancreatitis. He was treated as on the previous admission. Resolution of pain and normalization of serum amylase occurred gradually, and oral intake was resumed. Two weeks after admission, severe abdominal pain recurred, accompanied by nausea and vomiting, fever, and orthostatic hypotension. Amylase was 4651 units/liter. Because of the new cavitary pulmonary lesion, it was suspected that the pancreatitis might be a rare manifestation of Wegener's Digestive Diseases and Sciences, Vol. 35, No. 7 (July 1990)
granulomatosis. Intravenous methylprednisolone, 25 mg twice a day was begun. Soon after methylprednisolone was started there was a dramatic improvement in his abdominal pain, nausea, and vomiting. Amylase normalized, and he tolerated oral intake. He continued to improve clinically and was discharged after a five-week hospitalization on a regimen of prednisone, 40 mg daily, cyclophosphamide, 50 mg daily, and ranitidine, 150 mg twice a day. A computed tomogram as an outpatient two months later revealed resolution of the changes in and around the pancreas and near resolution of the pulmonary lesions. He has now remained completely asymptomatic 14 months after discharge. DISCUSSION T h i s is, to o u r k n o w l e d g e , t h e first r e p o r t e d c a s e o f r e c u r r e n t a c u t e p a n c r e a t i t i s in a s s o c i a t i o n w i t h a
Fig 3. Computed tomogram of the chest with 2.5-cm cavitary lesion in right posterior basal lung (arrow) corresponding to nodular infiltrate seen in Figure 2.
913
K E M P ET AL
Fig 4. Computed tomogram of abdomen with cystic area in region of the midbody (arrow).
flare of Wegener's granulomatosis. Because of the absence of a previously reported case, there was delay in the diagnosis in this patient. Pancreatitis associated with Wegener's granulomatosis was diagnosed only on his sixth episode of pancreatitis, when new cavitary pulmonary lesions suggested a relapse in his long-standing disease. Vasculitis of pancreatic vessels has been observed histologically in a number of patients with Wegener's granulomatosis (1-4), but clinical acute pancreatitis has not been described in these reports. Acute pancreatitis may occur in other systemic vasculitides, including polyarteritis nodosa prior to therapy (5-7), as well as in the course of treated polyarteritis or Churg-Strauss vasculitis (8-10), in Henoch-Shonlein purpura (11, 12), and in systemic lupus erythematosus at presentation or during treatment (13-18). These cases of acute pancreatitis in other systemic vasculitides and the documented involvement of pancreatic vessels in Wegener's granulomatosis support our conclusion that Wegener's granulomatosis was the cause of this patient's acute pancreatitis. Attempts to identify other causes of acute pancreatitis in this patient were not successful. The limited alcohol use, lack of pancreatic calcification, and absence of changes of chronic pancreatitis by ERCP make ethanol-induced pancreatitis unlikely. Although the patient underwent cholecystectomy 20 years prior to the occurrence of pancreatitis, he had no biochemical manifestations of choledocholithiasis, and choledocholithiasis was not demonstrated by ultrasound, CT scan, or ERCP. Serum calcium and triglycerides were normal. There was
914
no support for a diagnosis of familial pancreatitis, no recent trauma or abdominal surgery, and no evidence of pancreas divisum or other proposed causes of acute pancreatitis. The patient's medications at the time of the onset of pancreatitis were cyclophosphamide and prednisone. There is no evidence to implicate cyclophosphamide as a cause of acute pancreatitis. The role of corticosteroids as a cause of acute pancreatitis is controversial (19). Many of the cases reported as acute pancreatitis with the administration of steroids are suspect because of the concurrent administration of other drugs that are recognized as causes of acute pancreatitis, such as tetracycline (20, 21), thiazides (22), azathioprine (23), or 6mercaptopurine (24). Other patients with presumed steroid-induced pancreatitis have had illnesses such as systemic lupus erythematosus or other disorders that are independently associated with acute pancreatitis (20, 23-25). Further evidence against a causal role of steroids in this case of pancreatitis is the dramatic improvement in the pancreatitis associated with an increase in glucocorticoid dose. The strongest support for the role of Wegener's granulomatosis is provided by his clinical course. Recurrent episodes of abdominal pain and hyperamylasemia began three months after a reduction in the prednisone dosage. The final moderately severe and prolonged episode followed reduction of the cyclophosphamide dose from 150 mg to 50 mg daily. During the final episode of pancreatitis, new nodular pulmonary infiltrates characteristic of active Wegener's granulomatosis were seen. Dramatic improvement in the manifestations of pancreatitis and in the pulmonary nodules occurred with an increased glucocorticoid dose. He has remained free of active Wegener's granulomatosis or acute pancreatitis 14 months after discharge. One unusual feature that may help better define the nature of this entity is the rapid recurrence of disease. During a period between January 11 and April 15, 1988, he had six episodes of acute pancreatitis. The initial episodes responded promptly to conservative treatment; however, subsequent relapses were successively more severe. Also important appears to be the finding that acute pancreatitis may be the only clinically apparent site of organ involvement for several months when a relapse of Wegener's granulomatosis occurs. We recommend that when a patient with documented Wegener's granulomatosis develops recurrent acute pancreatitis, relapse of the underlying disease should be Digestive Diseases and Sciences, Vol. 35, No. 7 (July 1990)
P A N C R E A T I T I S IN W E G E N E R ' S G R A N U L O M A T O S I S considered unless another obvious cause of pancreatitis is a p p a r e n t . T h i s w o u l d p r e v e n t d e l a y in t r e a t m e n t a n d p o s s i b l y a v o i d c o m p l i c a t i o n s s u c h as d u c t r u p t u r e a n d p s e u d o c y s t t h a t o c c u r r e d in o u r patient. SUMMARY We report a case of recurrent acute pancreatitis in a 5 7 - y e a r - o l d m a n w i t h r e a c t i v a t i o n o f W e g e n e r ' s granulomatosis. An association between acute pancreatitis and Wegener's granulomatosis has not been reported previously. Six episodes of abdominal p a i n a n d h y p e r a m y l a s e m i a o c c u r r e d a n d w e r e complicated by development of a pancreatic pseud o c y s t . N e w c a v i t a r y lung l e s i o n s t y p i c a l o f W e g e n e r ' s g r a n u l o m a t o s i s l e d to t r e a t m e n t w i t h i n c r e a s e d g l u c o c o r t i c o i d d o s a g e , r e s u l t i n g in r a p i d r e s o l u t i o n of the pancreatitis and pulmonary lesions. Acute pancreatitis may be a clinical manifestation of the h i s t o l o g i c p a n c r e a t i c v a s c u l i t i s o b s e r v e d in W e g e n er's granulomatosis. Reactivation of Wegener's granulomatosis should be considered when a patient with the disorder develops otherwise unexplained acute pancreatitis.
ACKNOWLEDGMENTS The authors acknowledge the kind assistance of Dr. Robert Schwartz and Marian Harvey.
REFERENCES 1. Walton EW, Leggat PO: Wegener's granulomatosis. J Clin Pathol 9:31-37, 1956 2. Fahey JL, Leonard E, Churg J, Godman G: Wegener's granulomatosis: Am J Med 17:168-179, 1954 3. Banowitch MM, Polayes SH, Charet R: Periarteritis nodosa: Report of five cases. Ann Intern Med 16:1149-1179, 1942 4. Godman GC, Churg J: Wegener's granulomatosis: Pathology and review of the literature. AMA Arch Pathol 58:533-553, 1954 5. Brown HW, Ghosh S: Polyarteritis presenting as an acute abdomen. Int Surg 51:30-35, 1969 6. Miller HG, Daley R: Clinical aspects of polyarteritis nodosa. Q J Med 15:255-283, 1946
Digestive Diseases and Sciences. Vol. 35, No. 7 (July 1990)
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