Tariq A. Mian ( PMRC Research Centre, Jinnah Postgraduate Medical Centre, Karachi, Pakistan. )
Sarwar J. Zuberi ( PMRC Research Centre, Jinnah Postgraduate Medical Centre, Karachi, Pakistan. )
Chronic relapsing pancreatitis occurring in a familial fashion was first described by Comfort and Steinberg in 1952 and uptil 1975 over 20 families with more than 100 established cases of pancreatitis have been reported in the literature. A report of two sisters suffering from pancreatitis with pancreatic lithiasis is being presented.
Case I. Propositus, a married female aged 33 years, presented during an attack of epigastric pain and vomiting on 15-8-1979. She gave history of similar attacks, lasting for 3-4 days 3nd radiating to back, from the age of 10 years. Pain was occasionally accompanied by water-brash and vomiting which transiently relieved the pain. There are rumbling sounds in the abdomen at times. She passes 2-3 semisolid stools per day which are often "fatty" but develops constipation for a few days prior to the episode of abdominal pain. She gave history of passage of worms in the stool in childhood. When given a laxative at night for the preparation of oral cholecystogram in 1972, she passed a number of milky white, smooth, rounded stones in the stool next morning. They measured 275 upto 1 cm in diameter and were described by the patient as "some parasite is laying eggs in her abdomen". At that time she was diagnosed, at another hospital, as a case of chronic relapsing pancreatitis with pancreatic lithiasis.
On examination, she had an ill-defined epigastric mass and mild tenderness in left iliac fossa. Her investigations at that time revealed a Hb of 12.6 G%, and a normal total and differential leucocyte count, total bilirubin was 8.0 mg%, S.G.P.T. 40 umole/L, Alkaline phosphatase 50 umole/L, serum calcium 10 mEq/L, Inorganic phosphorus 4.1 mg%, serum amylase 100 S.U., glucose tolerance test showed fasting blood sugar 80 mg% and at half an hour intervals 120, 185, 165, 150 and 140 mg%. Fecal fat estimation on three consecutive days was 6.2, 5.9 and 6.0 Gram per 24 hours each. Orar cholecystogram revealed a normally functioning gall-bladder and multiple, round opacities in a horizontal line in the pancreatic region which were more dense and larger than those in the previous rentgenograms as shown in the accompanying figure.
Her previous investigations which were carried out to determine the cause of abdominal pain are as follows. In 1967, when 21 years old, an I.V.P. revealed normally functioning kidneys and no calcifications in the pancreatic region. In 1972, these were Hb 12.3 G%, T.L.C. 10,000/cmm, Urine for Salkowitch test was negative, serum amylase 100 S.U., serum calcium 8.3 mEq/L and 7.5 mEq/L on two occasions, serum inorganic phosphorus 2.6 mg% ,alkaline phosphatase 30 .0 Babson units and fasting blood glucose 80 mg%. Oral cholecystogram and Barium meal were normal except for horizontal pancreatic calcifications.
Her father had diabetes and mother is hypertensive but there is no history of abdominal pain in both. She has two sons of 12 years and 5 years of age and one daughter of 7 years of age. At present all the three are symptom free.
Case II. 17 years old sister of the propositus started having attacks of epigastric pain 3 years back. Pain is usually moderate and relieved by spasmolytics and during the attack of pain she develops vomiting. Vomitus contains "oily droplets". There is no history of steator-rhoea or diarrhoea. She is not diabetic. Her total serum lipids were slightly raised. Plain X-ray abdomen shows a horizontal row of pancreatic calculi similar to that of the propositus.
Distinguishing features of the previously reported families have been described in the accompanying table. Chronic relapsing pancreatitis is different from that of the non-hereditary type in that many members of a family are affected, age of onset is lower, disease is inherited as autosomal dominant gene and the pancreatic calcification is quite common in this type of pancreatitis. Although the initial report of Comfort and Steinberg (1952) showed an increased female preponderance (5 out of 6 were females) compared to a male/female ratio of 6:1 in non-hereditary pancreatitis, later reports have revealed no significant preponderance of either sex.
In the present family, nothing can be definitely said about the hereditary pattern of the disease because of the smallness of the family, involvement of only two members of the family and young age of the offsprings of the propositus who have not yet shown any manifestations of the disease. Familial, but not necessarily hereditary, occurrances of chronic relapsing pancreatitis have previously been described (Jackson, 1958; Beall et al., 1960; Poulscn, 1950). Alcohol, hyperlipaemia and cholelithiasis were described by Gross and Comfort (1957) to be unimportant factors in the etiology of this condition. The occurrance of abdominal pain suggesting pancreatitis has been reported during convalascence from measles (Gross et al., 1962) mumps (Gross and Comfort, 1957; Zelman, 1944) and scarlet fever (Veghelyi, 1949), the explanation of which is still not clearly understood. Various associated conditions, with an unexplained significance, have been reported in a few families with hereditary pancreatitis. These included aminoaciduria, particularly of lysine and cystine (Comfort and Steinberg, 1952; Gross and Comfort, 1957; Gross et al., 1962; Cornet et al., 1962; Carey and Fitzgerald, 1968) hypercalcaemia (Carey and Fitzgerald, 1968), gastrointestinal bleeding (Sibert, 1975) and pleural effusions (Cornet et al., 1962; Nash, 1971). Another feature of the hereditary pancreatitits is the increased incidence of pancreatic calcifications (Logan et al., 1968) suggesting increased possibility of pancreatic cancer in these cases. Paulino et al (1960) found that only 24% of the patients with non-hereditary chronic pancreatitis exhibited calcifications and the carcinoma of pancreas appeared in 25% of the patients but never in the absence of calcific pancreatitis. The number of so far reported pancreatic cancers, as shown in the table,
has not been found to be as high as was anticipated in this condition. The pancreatic calculi appear to be the result and not the cause of this disease because a variable time lapse has been observed between the initial attack of abdominal pain and the appearance of the stones (Comfort and Steinberg, 1952). In our case the propositus developed the calculi after more than eleven years of the onset of symptoms whereas her sister had them only after three years of the initial attack of pain. It is emphasised that this condition should also be considered in differential diagnosis of recurrent attacks of unexplained abdominal pain when other features of the disease are found even in the absence of pancreatic calculi.
The exact inherited defect has not yet been completely understood although several hypotheses have previously been suggested like an inborn metabolic defect (Gross and Comfort, 1957), abnormal embryological defect affecting the anatomical arrangement of pancreatic ducts Nash, 1971), hypertrophy of sphincter of Oddi Roebechek, 1967) congenital hyperplasia of sphincter of Oddi and congenital ectasia of pancreatic ducts (Whitten et al., 1968) and dilatation and ectasia of the pancreatic ductules as evidenced on surgery (Cornet et al., 1962).
Treatment of this condition is either palliative, by alleviating pain with spasmolytics or opiates, replacement of exocrine enzymes and controlling diabetes if present, or surgical which in various series consisted of sphincterotomy (Roebechek, 1967), side to side pancreaticoje-junostomy (Sato and Saitoh, 1974) and total pancreatoetomy with insulin and enzyme replacement therapy (Whitten et al., 1968), depending upon the state of pancrease at the time of surgery.
Acknowledgement: Referral of the case by Dr. Naeem-ul-Haque of Seventh Day Adventist Hospital and secretarial help of Mr. Laeeq Ahmed is gratefully acknowledged.
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