Gut, 1975,16, 230-234

Lipodystrophy, pancreatitis, and eosinophiliaP. M. SMITH, M. E. MORGANS, C. G. CLARK, AND J. E. LENNARD-JONES,AND OLAFUR GUNNLAUGSSON, AND TOMAS A. JONASSON

From University College Hospital, London, England, and St Josefsspitalinn, Reykjavik, Iceland

SUMMARY Two patients suffering from partial lipodystrophy, pancreatitis, and recurrent eosino-philia are described. In one patient the duodenum and the terminal ileum were narrowed, theappearances suggesting eosinophilic gastroenteritis: bilateral hydronephrosis was also presentwithout ureteric obstruction. An association between lipodystrophy and renal disease is recognized;it is possible that there is also an association between lipodystrophy and pancreatitis, and eosino-philia with or without an intestinal lesion may be a further association.

Partial lipodystrophy is an unusual condition ofunknown aetiology, sometimes familial, primarilyaffecting young females. There is progressive loss offat from the subcutaneous tissues, usually starting inthe face and gradually extending distally to the levelof the knees. Many cases have been associated withrenal disease (Eisenger, Shortland, and Moorhead,1972), while some have hepatomegaly, mentalretardation, or diabetes (Senior and Gellis, 1964).We wish to report two patients with partial lipo-dystrophy and pancreatitis, both of whom hadrecurrent eosinophilia, and one of whom probablyhad eosinophilic gastroenteritis.

Case 1

S.O.'G., a 27-year-old housewife, first presentedwhen aged 5 years with thinning of the face and twoyears later partial lipodystrophy was recognized.There was no family history of this complaint.Subcutaneous loss of fat gradually extended overthe next 10 years to involve the trunk, body, arms,and upper thighs.At the age of9 years recurrent attacks ofabdominal

pain, vomiting, and diarrhoea led to laparotomy.A clearly demarcated length of swollen and con-gested terminal ileum 15 cm long was found, with afew enlarged mesenteric glands. The attacks per-sisted and at a second laparotomy a year later thefindings were identical. Three months later anelevated urinary diastase level of 500 Wohlegemuthunits/ml was recorded during an attack of abdominalpain.

Received for publication 18 December 1974.

During the next two years attacks of vomitingdiarrhoea, and abdominal pain led to five furtheradmissions to hospital. On two of these occasionsthe urinary diastase level was raised (200 and 500Wohlegemuth units/ml). An intravenous pyelogramdone during this period because of dysuria showedbilateral non-obstructive hydronephrosis with anapparently normal thickness of renal cortex. At theage of 15 years, transient glycosuria was notedthough an oral glucose tolerance test was normal.The serum amylase was elevated at 480 Somogyiunits/100 ml. Following further attacks ofabdominalpain a third laparotomy at the age of 16 years led tothe finding of a thickened, hard pancreas.During the next three years abdominal symptoms

led to four further hospital admissions, the onlyabnormal findings being raised white cell counts ofbetween 10 000 and 14 000/c mm. On one occasionan eosinophilia of 10% was noted. At the age of 19barium studies showed narrowing of the terminalileum and a provisional diagnosis of Crohn'sdisease was made. A fourth laparotomy, however,revealed no evidence of this.Her symptoms persisted, and at the age of 24

years barium studies demonstrated the presence of aduodenal stricture together with narrowing andapparent mucosal swelling of the terminal ileum(fig 1). Investigations also showed an elevatedleucocyte count of 16 200/c mm (88% neutrophils),a faecal fat excretion of 15 g/day, and an abnormalglucose tolerance test. Because of the two abnormalareas in the small bowel, a fifth laparotomy wasperformed at which the duodenum and the last 30cm ofterminal ileum looked swollen and oedematous.Duodenal and ileal biopsies showed an increase in

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Lipodystrophy, pancreatitis, and eosinophilia

Fig 2 Loss ofsubcutaneousfatover the arms,face, trunk, andupper part ofthe thighs (case1).

Fig 1 Abnormal appearances of the duodenum,jejunum, and terminal ileum (case 1).

goblet cells and eosinophils in an otherwise normalmucosa. There were scattered eosinophils in themuscularis mucosa, with slight fibrous thickeningof the subserosa and cuffing of the subserosalarterioles with polymorphs and eosinophils. Noevidence of Crohn's disease could be found.At the age of 27 years a transient episode of

obstructive jaundice occurred and lasted for threeweeks; an eosinophilia was again recorded (1050and 1320/c mm). The patient had by now becomedependent on analgesics because of constant severeepigastric and left hypochondrial pain whichradiated through to the back. She passed up to fourpale, bulky, and offensive stools daily, and had lost13 kg in weight in the preceding three months. Shealso complained of repeated attacks of dysuria. Herappearance was classical of partial lipodystrophy(fig 2). A diagnosis of chronic pancreatitis wasconfirmed by the findings of pancreatic calcificationon radiographs, steatorrhoea, a diabetic glucosetolerance test, no uptake of 75Se-selenomethionineon a pancreatic scan, and very little recovery of theisotope from the duodenum at two hours (Youngs,Agnew, Levin, and Bouchier, 1971). Plasma amylaseand calcium were normal; there was slight generalizedaminoaciduria. The fasting plasma cholesterol,triglyceride, and lipoprotein levels were normal

with a normal electrophoretic strip. Fasting growthhormone levels were raised. The plasma alkalinephosphatase was raised to 25 KA units/100 ml butliver function tests were otherwise normal and aliver biopsy was normal. A suction mucosal biopsyfrom the descending duodenum was normal. Anintravenous pyelogram again showed bilateral non-obstructive hydronephrosis (fig 3). A micturatingcystogram did not demonstrate ureteric reflux, butthe bladder capacity was reduced and its wall was

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Smith, Morganis, Clark, and Lennard-Jones, and Gunnlaugsson and Jonasson

Fig 3 Bilateral hydronephrosis with dilatation of theureters but no evidence of ureteric obstruction (case 1).

thickened and irregular; biopsy of the bladdermucosa was normal. Plasma immunoelectrophoresisshowed an increase in IgG; no thyroid or gastricautoantibodies were detected.The incapacitating pain was ascribed to chronic

pancreatitis and subtotal pancreatectomy wasadvised. At laparotomy, the pancreas was hard andnodular, especially the head of the gland around thecommon bile duct which was dilated and thickened;subtotal pancreatectomy was performed. Adhesionswere present around the duodenum, the wall ofwhich was not thickened, and the terminal ileumwhich was a little dilated proximally. The excisedtissue showed dilatation of the main pancreaticduct and almost total replacement of pancreaticexocrine glands by fibrosis.The pain in the back and left upper quadrant of

the abdomen was relieved by the operation andanalgesics were successfully withdrawn. Diabeticcontrol proved difficult at one stage due to anacquired resistance to beef insulin (200 units/day),but sensitivity to pork insulin was normal (30 units/day).Some pain in the right upper abdomen persisted

after operation and about two years later this painbecame impossible to relieve with simple analgesics.

Failure to control persistent and severe pain made itnecessary to attempt removal of the remainingpancreatic tissue. Dense adhesions were presentaround the duodenum and pancreatic remnant;the head of the pancreas with the duodenal loopwas excised with great difficulty and with damageto the portal vein. The operation was followed byuncontrollable, fatal haemorrhage. Histologicalexamination of the duodenum and ampulla of Vatershowed epithelial hyperplasia and chronic inflam-mation with numerous eosinophils in some areas.The pancreatic tissue was chronically inflamed andfibrosed; eosinophils were present in the inflam-matory exudate but were much less prominent thanin the gut. Permission for necropsy was refused.

Case 2

S.H., a woman of 23 years, was normal until the ageof 5 years but photographs taken then showed aprogressive loss of facial subcutaneous fat over thenext three years. She presented the typical pictureof partial lipodystrophy with absence of sub-cutaneous fat over the face (fig 4), arms, and trunk.On the upper part of the thighs fat was absent buton the lateral side of the left thigh the subcutaneousfat was slightly increased; the subcutaneous fat overthe legs below the knees was normal. Musculardevelopment, particularly of the legs, was wellmarked. There was no family history suggestinglipodystrophy.At the age of 8 years, she was first admitted to

hospital with an acute episode of abdominal pain,though there was a history of similar attacks of painduring the previous year or two. At laparotomy thepancreas was oedematous, fat necrosis of theomentum was observed and confirmed by biopsy,no abnormality was found in the small intestine.

Recurrent attacks of abdominal pain occurredduring the next 15 years, with admission to hospitalon 14 occasions. Between attacks the patient waswell. Repeated investigations showed a normalbiliary system, liver and pancreatic function tests.The serum amylase was elevated during acuteattacks of pain. Eosinophilia was noted (maximumrecorded 3500/c mm) on at least eight occasionsduring admission to hospital, but normal eosinophilcounts were observed during periods of good health.No evidence of parasitic infestation was found.

After a particularly severe attack of pancreatitisat the age of 23 years the pancreas was reinvesti-gated to determine whether or not surgical explora-tion should be undertaken. Tests of pancreaticfunction, including glucose tolerance, faecal fat, andmeasurement of tryptic activity in duodenal juice(Lundh test), gave normal results. Growth hormone

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Lipodystrophy, pancreatitis, and eosinophilia

Fig 4 Typical facial appearance of lipodystrophy(case 2).

and insulin levels during a glucose tolerance testwere normal. Blood lipid studies showed normalfasting cholesterol, triglyceride, and lipoproteinlevels with a normal electrophoretic strip. Coeliacangiography demonstrated normal vasculature ofthe pancreas. At duodenoscopy (Dr P. B. Cotton)the stomach, the first two parts of the duodenumand ampulla of Vater appeared normal, as werebiopsies obtained from the duodenal bulb and thirdpart of the duodenum. Retrograde cholangio-pancreatography demonstrated normal calibre ofthe main pancreatic duct and the ducts in the head,with minimal irregularity of some of the branchducts of the tail. There was delay in pancreatic ductemptying and some contrast remained 12 minutesafter injection.

In the absence of structural change, there did notappear to be any clear indication for surgicaltreatment and conservative treatment was con-tinued. Since eosinophilic gastroenteritis usuallyresponds to corticosteroid therapy this treatmentwas tried during three attacks of pain associatedwith raised plasma amylase and eosinophilia. Therewas no definite benefit or change in the eosinophilcount.

Later that year a single attack of left renal painoccurred. An intravenous pyelogram showed no

excretion of dye by the left kidney, though excretionhad been normal previously. Left retrogradepyelography demonstrated dilatation of the leftpelvis but no calculus was visible. Intravenouspyelography nine months later was within normallimits.

Discussion

There is little doubt that these two patients showedthe changes of partial lipodystrophy, as described bySenior and Gellis (1964). The diagnosis of chronicpancreatitis in case 1 and recurrent acute pancreatitisin case 2 was established by examination of thepancreas and by appropriate investigations.

Recurrent eosinophilia was noted in both patientsand in case 2 was associated with episodes ofpancreatitis. In case 1, a diagnosis of eosinophilicgastroenteritis is likely with narrowing of the duo-denum and terminal ileum, and infiltration of the gutwall by eosinophils. No lesion of the gut has beendemonstrated in case 2.

Partial lipodystrophy is commonly associatedwith renal disease (Eisenger et al, 1972), usually aform of glomerulonephritis, but in three of the 14patients with this association described by Seniorand Gellis (1964) there was bilateral hydronephrosisand hydroureter without obstruction, as in case 1,and they refer to four other reported cases. Oneexample of bladder involvement in association witheosinophilic gastroenteritis has been described(Burhenne and Carbone, 1966), the thickenedbladder wall being infiltrated with eosinophils. Incase 1, the bladder wall appeared thickened onradiographs but cystoscopy and mucosal biopsyshowed normal appearances.No association between partial lipodystrophy and

pancreatitis is recognized, though Boucher, Cohen,Frankel, Stuart Mason, and Broadley (1973) havedescribed a woman of 26 years with partial lipo-dystrophy who had a typical attack of acutepancreatitis at the age of 21, and another patientwith partial lipodystrophy and recurrent pancreatitisis known (Senior, personal communication).

Besides our two patients, one other patient withlipodystrophy, recurrent abdominal pain, andeosinophilia has been described (Boucher et al, 1973;Boucher, B. J., and Wright, J. T., personal com-munication, 1974). This boy presented with a historyof abdominal pain and vomiting at the age of 14years. He was noted to have eosinophilia (1200-2200/c mm). Barium meals were normal and laparotomyone year later showed lack of intraabdominal fat asthe only abnormality. Total lipodystrophy wasdiagnosed two years after he was first seen and bythis time the eosinophil count had fallen to about

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234 Smith, Morgans, Clark, and Lennard-Jones, and Gunnlaugsson and Jonasson

500/c mm. A gastric mucosal biopsy contained. noexcess eosinophils; plasma amylase was not raised.There were no urinary symptoms and an intravenouspyelogram was not performed. Corticosteroidtreatment was given; by the age of 21 years thepatient was well and not receiving treatment.There is possibly an association between pancre-

atitis and eosinophilia (Juniper, 1955) and a singlepatient with a long history of eosinophilic gastro-enteritis and terminal pancreatitis has been recorded(Weisberg and Crosson, 1973).The pancreatitis in case 1 could have been due to

involvement of the pancreatic duct in duodenaldisease. It is of interest that in a recently reportedseries of 10 patients with Crohn's disease involvingthe duodenum, three had associated pancreatitis(Legge, Hoffman, and Carlson, 1971). This explana-tion cannot account for the pancreatitis in case 2nor in another patient whose duodenum was normal(Senior, personal communication). Pancreatitisis known to be associated with hyperlipoprotein-aemia (types I and V) but this was not present in ourtwo patients, nor in the patient described by Boucheret al (1973). Eosinophilia is frequently associatedwith allergic disorders such as asthma or urticaria,and a high proportion of patients with eosinophilicgastroenteritis have such a tendency (Klein,Hargrove, Sleisenger, and Jeffries, 1970; Leinbachand Rubin, 1970). Case 1 developed resistance tobeef insulin but we observed no other immunologicaldisorders. It is tempting to speculate that therecurrent eosinophilia in case 2 is associated withoedema of the pancreatic ducts or acini.The aetiology of lipodystrophy is unknownthough

an abnormality of B-adrenergic receptors in der-matomes of part or all of the body leading toincreased lipolysis has been suggested (Boucher et al,

197-3). An abrorniality of B-receptors in the pan-creatic islets has also been postulated by the sameauthors to account for an increased secretion ofinsulin in some patients. Any links between lipo-dystrophy, pancreatitis, and eosinophilia are obscure.

We are grateful to the surgeons and the PathologyDepartment of the Elizabeth Garrett AndersonHospital for giving us access to their records, toDr E. E. Davies and Dr P. M. Sutton who providedinvaluable assistance with the histology, and DrP. B. Cotton who performed the ampullary can-nulation in case 2.

References

Boucher, B. J., Cohen, R. D., Frankel, R. J., Stuart Mason, A., andBroadley, G. (1973). Partial and total lipodystrophy: changesin circulating sugar, free fatty acids, insulin and growthhormone following the administration of glucose and ofinsulin. Clin. Endocr., 2, 111-126.

Burhenne, H. J., and Carbone, J. V. (1966). Eosinophilic (allergic)gastroenteritis. Amer. J. Roentgenol., 96, 332-338.

Eisinger, A. J., Shortland, J. R., and Moorhead, P. J. (1972). Ronaldisease in partial lipodystrophy. Quart. J. Med., 41, 343-362.

Juniper, K., Jr. (1955). Chronic relapsing pancreatitis with associatedmarked eosinophilia and pleural effusion. Amer. J. Med., 19,648-651.

Klein, N. C., Hargrove, R. L., Sleisenger, M. H., and Jeffries, G. H.(1970). Eosinophilic gastroenteritis. Medicine (Baltimore), 49,299-319.

Legge, D. A., Hoffman, N. N., and Carlson, H. C. (1971). Pancreatitisas a complication of regional enteritis of the duodenum.Gastroenterology, 61, 834-837.

Leinbach, G. E., and Rubin, C. E. (1970). Eosinophilic gastroenteritis:a simple reaction to food allergens. Gastroenterology, 59,874-889.

Senior, B., and Gellis, S. S. (1964). The syndromes of total lipo-dystrophy and of partial lipodystrophy. Pediatrics, 33, 593-612.

Weisberg, S.C., andCrosson, J. T. (1973). Eosinophilicgastroenteritis:report of a case of 32 years' duration. Amer. J. dig. Dis., 18,1005-1014

Youngs, G. R., Agnew, J. E., Levin, G. E., and Bouchier, I. A. D.(1971). Radioselenium in duodenal aspirate as an assessmentof pancreatic exocrine function. Brit. med. J., 2, 252-255.

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