7 Clin Pathol 1992;45:823-825

Sarcoidosis: Association with small bowel diseaseand folate deficiency

S M MacRury, G McQuaker, R Morton, R Hume

AbstractA 30 year old woman with recurrentanaemia due to folate deficiency had evi-dence of sarcoid granuloma on smallbowel biopsy but was presumed to haveCrohn's disease. The diagnosis of smallbowel sarcoidosis was not seriously con-sidered until she developed systemic man-ifestations of sarcoidosis (cutaneous andpulmonary lesions) over the following 20years. Sarcoidosis of the gastrointestinaltract, particularly the small bowel, is rareand this case is unusual because bowelpathology preceded more generalisedlesions. As far as is known it is also thefirst case to be described presenting withmalabsorption of folic acid.

Department ofMedicine, SouthernGeneral Hospital,GlasgowS M MacRuryG McQuakerR HumeDepartment ofPathologyR MortonCorrespondence to:Dr S MacRury, MedicalUnit B, Southern GeneralHospital, Glasgow G51 4TF

Accepted for publication14 February 1992

Disease of the small bowel is the least commonform of gastrointestinal pathology in sar-

coidosis, and to date there have only been sixwell documented and histologically confirmedcases.`6 In most cases symptomatic smallbowel sarcoidosis developed on a backgroundof established disease, usually affecting thelungs, skin, or eyes,25 although these othermanifestations may have occurred several yearspreviously. Disseminated gastrointestinal dis-ease has also been reported in several of thesecases' 3-5 often with asymptomatic granulomasin the liver and spleen. 13 5 6 Symptoms of smallbowel disease in these patients have includedabdominal pain, diarrhoea, weight loss, and inone patient acute appendicitis.4

In some patients, malabsorption has resul-ted, and a megaloblastic anaemia due tomalabsorption of vitamin B12 has been docu-mented. This was explained by terminal ilealdisease in one patient3 and achlorhydria inanother,2 and in a third patient was attributedto achlorhydria secondary to gastric sarcoido-sis.4 These symptoms and signs may resembleCrohn's disease of the small bowel, but sarcoi-dosis of the small bowel generally tends tofollow a more benign course and responds totreatment with corticosteroids. We present a

case of sarcoidosis affecting the small bowelwhich presented with recurrent anaemia due tofolate deficiency.

Case reportA 30 year old woman who presented to theoutpatient department with a history of fatiguewas found to have a severe megaloblasticanaemia (haemoglobin 4-6 g/dl), with featuresof folate deficiency. The anaemia was thought

to be dietary in origin and she responded wellto oral supplements of folic acid, 5 mg threetimes a day, which were continued for one year.Five years later she presented again withanaemia (haemoglobin 6-3 g/dl) due to folatedeficiency. There was no history of alcoholabuse and dietary history confirmed adequateintake of all haematinics. Investigation formalabsorption, including faecal fat collection,xylose absorption test, and glucose tolerancetests yielded normal results, as did a bariummeal and small bowel follow-through x-raypicture. A small bowel biopsy specimenrevealed "sarcoid-like" granulomas in themucosa with partial villous atrophy (fig 1) anda diagnosis of low grade Crohn's disease wassuggested.The patient remained well on long term folic

acid supplementation until 10 years later whenshe presented to the dermatology clinic with anerythematous infiltrative lesion on her faceover the right mandibular area, which, whenbiopsied showed a non-caseating epithelioidgranulomatous reaction, including "nakedgranulomas", throughout the dermis. Fungiand foreign bodies were not identified and theappearances were suggestive of sarcoidosis (fig2).The Mantoux test was negative and the

Kveim test positive. The angiotensin convert-ing enzyme activity was 47 U/1 (normal range< 88 U/1). Four years later she presented witha history of upper abdominal pain and dys-pnoea. Barium meal and small bowel follow-through x-ray picture showed thickened andirregular mucosal folds in the upper jejunum.The chest x-ray picture showed bilateral pul-monary infiltrates in both midzones consistentwith sarcoidosis. There was no hilar lymphade-nopathy. A gallium scan showed active inflam-matory disease of the small bowel and lungs.Pulmonary function tests were normal. Both ofthese recent symptoms settled spontaneouslyand the patient declined further investigation.

DiscussionThere are many causes of gastrointestinalgranulomas, including tuberculosis, carci-noma, Whipple's disease and foreign bodyreactions. Both the duration of this patient'sillness and her general well-being throughoutallows most of these conditions to be excluded.The combination of the histological lesions inthe small bowel biopsy specimen, together withthe cutaneous and pulmonary lesions, suggestsa diagnosis of systemic sarcoidosis with smallbowel disease in this patient. The most likely

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MacRury, McQuaker, Morton, Hume

Figure I Small bowelbiopsy specimens showingnon-caseating granuloma(arrow) and severe partialvillous atrophy.

Figure 2 Biopsy specimenoffacial lesion showingseveral non-caseating gran-ulomata within the dermis.

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ew.Ir

alternative explanation for the intestinalpathology would be Crohn's disease. Crohn'sdisease, however, affects the entire bowel wallwhereas sarcoidosis affects only the mucosa.Thus patients with active Crohn's disease, inaddition to presenting with abdominal pain,diarrhoea, and weight loss, are prone to fistulae

and stricture formation. The absence of thesesymptoms and sequelae mitigates against diag-nosis of Crohn's disease and suggests a morebenign condition like sarcoid. The villousabnormalities described on biopsy explain thepatient's folate deficiency, but although similarchanges have been described in another patient

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Sarcoidosis: Association with small bowel disease and folate deficiency

with small bowel sarcoidosis,3 the associationbetween intestinal sarcoid and villous atrophyis unknown.

Crohn's disease and sarcoidosis have com-mon systemic manifestations, and the mostfrequently occurring cutaneous lesion to beassociated with both conditions is erythemanodosum. However, cutaneous granulomas dooccur in Crohn's disease, though rarely inareas which are not a direct extension from thegastrointestinal tract or of skin apposition.7Respiratory tract disease, in the form ofbronchial granulomas, has been reported inCrohn's disease but in the affected patientsthere was no other evidence of lung disease.8

Coexistent Crohn's disease and sarcoidosishas been reported in a few patients,9 andbecause of their histological and immuno-logical similarities it has been postulated thatthey may represent an overlapping syndromeof granuloma formation due to a generalisedhost response to various aetiological agents.However, the existence of non-progressivesmall bowel disease over two decades, togetherwith a positive Kveim test, is much morecompatible with sarcoidosis than Crohn's dis-ease. Io

Given the protean nature of sarcoidosis, thegenerally benign course, and the occurrence ofasymptomatic lesions it could be that intestinal

disease is commoner than previously thought.Patients with sarcoidosis who present withpersistent diarrhoea, malabsorption, or folatedeficiency should be investigated for intestinalsarcoidosis, and the diagnosis should be con-sidered in patients with small bowel pathologywho later develop manifestations of systemicsarcoidosis.

1 Miyamoto C, Nomura S, Kudo E, HamamotoY An autopsycase of sarcoidosis in the intestinal canal. Bug Osaka MedSchool 1972;18:48-55.

2 Clague RB. Sarcoidosis or Crohn's disease? Br Med J1972;3:804.

3 Sprague R, Harper P, McLain S, Trainer T, Beeken W.Disseminated gastrointestinal sarcoidosis. Case reportand review of the literature. Gastroenerorgy1984;87:421-5.

4 Tinker MA, Viswanathan B, Laufer H, Margolis IB. Acuteappendicitis and pernicious anemia as complications ofgastrointestinal sarcoidosis. Am J Gastrterol1984;79:868-72.

5 Bulger K, O'Riordan M, Purdy S, O'Brien J, Lennon J.Gastrointestinal sarcoidosis resembling Crohn's disease.Am J Gastroenterol 1988;83:1415-7.

6 Rauf A, Davis P, Levendoglu H. Sarcoidosis of the smallintestine. Am J Gastroenterol 1988;83:187-9.

7 James DG. Miscellaneous involvement. In: James DG,Williams WJ, eds. Sarcoidosis and other granulomatousdisorders. Problems in internal medicine. Vol 24. Philadelphia:W B Saunders, 1985:145-62.

8 Tweedie JH, McCann BG. Metastatic Crohn's disease ofthigh and forearm. Gut 1984;25:213-14.

9 Lemann M, Messing B, D'Agay F, Modigliani R. Crohn'sdisease with respiratory tract involvement. Gut1987;28: 1669-72.

10 Siltzbach LE, Vieria LOBD, Topilsky M, Janowitz HD. Isthere Kveim responsiveness in Crohn's disease? Lancet1971 ;ii:634-5.

J Clin Pathol 1992;45:825-827

Immunoperoxidase techniques and histology inthe diagnosis of rhabdomyolysis related acuterenal failure

P N Cooper, J Tapson, A R Morley

Department ofHistopathology, RoyalVictoria Infirmary,Newcastle upon TyneP N CooperA R MorleyDepartment of RenalMedicine, FreemanHospital, Newcastleupon TyneJ TapsonCorrespondence to:Dr P N Cooper,Department of Pathology,Royal Victoria Infirmary,Queen Victoria Road,Newcastle upon Tyne,NEI 4LPAccepted for publication24 February 1992

AbstractA case ofrhabdomyolysis associated acuterenal failure (RM-ARF) occurring as aresult of strenuous exercise is presented.Diagnostic renal biopsy was performed.The histological appearances, combinedwith immunoperoxidase staining for myo-globin, allowed a positive diagnosis ofRM-ARF to be made and excluded thepossibility of glomerulonephritis. Thepatient recovered completely after astormy clinical course.

Rhabdomyolysis can be the result of manydiverse factors including direct muscle injury,excessive muscle activity, ischaemia, immuno-logical disease, metabolic disorders, drugs,toxins, infection and genetic disorders. In twolarge series rhabdomyolysis associated acuterenal failure (RM-ARF) represented between

5% and 8-6% of cases of acute renal fail-ure. l 2

In the absence of trauma the clinical symp-toms and signs of muscle damage are unreli-able2 3 and diagnosis depends on finding raisedserum creatine phosphokinase (CPK) activityand o-toluidine positive urine and goldencoloured granular casts on microscopicalexamination of the urine. The prognosis ofRM-ARF is good provided prompt treatmentis given.We report a case of exertion related RM-

ARF in a 17 year old soldier who developedRM-ARF following exercise.

Case reportA 17 year old private collapsed after runningfor 7-5 miles wearing army boots and a fullbackpack on a day in October during which thetemperature reached a maximum of 13-90C.

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