Gut, 1984, 25, 1296-1300

Case report

Severe intestinal involvement in Wegener'sgranulomatosisS J HAWORTH AND C D PUSEY

From the Department ofMedicine, Royal Postgraduate Medical School, Hammersmith Hospital,London

SUMMARY A case of Wegener's granulomatosis is described, in which the presentation was bloodstained mucus diarrhoea. Severe ileal, caecal, and rectal involvement improved rapidly aftertreatment with cyclophosphamide, azathioprine, and prednisolone. Although intestinal disease isan uncommon feature of Wegener's granulomatosis, both in our own experience (four of 45cases) and in the literature, this diagnosis should be considered in view of the response toappropriate therapy.

Wegener's granulomatosis is a systemic vasculitis ofunknown aetiolog4', with distinct clinical and histo-logical features.1- The disease is characterised byinvolvement of the upper airways, lung and kidney,although almost any organ can be affected. Thereported incidence of gastrointestinal involvement islow and histological confirmation often lacking,although there is one well documented case withproven ileal pathology.4 We would like to report acase in which gastrointestinal symptoms were theprincipal feature at presentation.

Case report

A 43 year old woman was admitted with bloodstained mucus diarrhoea and impaired renalfunction. She had been well until 11 monthspreviously when she developed right frontal sinusitisand mouth ulcers, which resolved spontaneously.Six months later she noticed deafness, and wasfound to have bilateral impaired air conduction withsecretory otitis media; her symptoms responded toantihistamines and decongestants. Two monthsbefore admission she developed pain and swelling ofthe knees, ankles, elbows, wrists and the small jointsof the hands. In the month before admission shebecame increasingly unwell with anorexia, weightloss of 2*75 kg, and painful red eyes. Two daysAddress for correspondence: Dr S J Haworth, Renal Unit, Royal Post-graduate Medical School. Hammersmith Hospital. London W12 OHS.

Received for publication 24 January 1984

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before admission she developed profuse diarrhoea,four to five times per day, with blood and mucus.She subsequently noted a widespread blotchy rash,and a decrease in urine output. There was norelevant past medical history.On examination she was pyrexial at 37-50C, with

mild keratitis, splinter haemorrhages, extensivepurpuric lesions over the extremities and buttocks,and numerous oral ulcers (Fig. la); there was a largenecrotic perianal ulcer surrounded by purpura (Fig.lb). There was swelling and tenderness of the knees,ankles, wrists, elbows and small joints of the hands.Blood pressure was raised at 160/110 mmHg, butexamination of the heart and lungs was otherwisenormal. The abdomen was distended, but nottender. Neurological assessment was normal apartfrom bilateral conduction deafness.

Investigations showed: haemoglobin 10.5 g/dl,white cell count 26 6x109/l (80% neutrophils),platelet count 315 x 109/l, plasma creatinine 384,umol/l, serum albumin 37 g/l, alkaline phosphatase261 IU/l (30-130) and aspartate amino-transferase106 IU/1.7-40 Immunoglobulins and complementcomponents were normal; rheumatoid factor andantinuclear factor were negative. Circulatingimmune complexes were detected by rheumatoidfactor binding assay. Urine sediment containednumerous red cell casts and free red cells. Renalbiopsy showed focal necrotising glomerulonephritiswith crescents and mild tubular atrophy (Fig. 2).Stool microscopy and culture for Shigella,

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Severe intestinal involvement in Wegener's granulomatosis

Fig. 1(a) Photograph ofmouth at presentation showing labial ulceration. (b) Photograph of buttocks at presentationshowing necrotic perianal ulceration with surrounding erythema. Vasculitic skin lesions are also present.

Salmonella, and Campylobacter were negative, aswas the amoebic fluorescent antibody test.Sigmoidoscopy revealed ulcerated rectal mucosa,which bled spontaneously, but was normal beyond10 cm. Rectal biopsy showed essentially normalmucosa and submucosa, with no evidence ofvasculitis, granuloma formation of chronic inflam-matory bowel disease; there were, however, large

Fig. 2 Photomicrograph of renal biopsy showing focalnecrotising glomerulonephritis with crescentformation andmild tubular atrophy (H & E x 400 original magnification).

collections of neutrophils on the mucosal surface.Plain abdominal and chest radiographs werenormal, but sinus radiographs showed mucosalthickening in both maxillary antra with a fluidconcentration on the right. Barium meal and followthrough 10 days after admission showed anabnormal and narrowed terminal ileum and caecum(Fig. 3). Barium enema, 19 days after admissionshowed an ulcerated and ragged caecum; thesigmoid colon did not contract well, but the rectumappeared normal.

MANAGEMENT AND COURSETreatment was started with prednisolone 60 mg/day,cyclophosphamide 3 mg/kg/day and azathioprine 1mg/kg/day. On this therapy the plasma creatininefell and the arthritis and skin rash improved,although she continued to have bloody diarrhoea.Ten days after starting treatment cytotoxic agentswere stopped, because of leucopenia and thrombo-cytopenia. At this time discrete pulmonary lesionswere detected radiographically, which progressed tocavitation (Fig. 4). Investigations for pulmonaryinfection, including bronchoscopy, were negative.On day 13 she passed a mucosal cast of her colon,after which she continued to have diarrhoea butwithout blood. The large perianal ulcer had almosthealed by this time, and sigmoidoscopy revealedonly minor rectal ulceration and minimal hyper-

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Fig. 3 Barium follow through taken 10 days afterpresentation showing ragged and narrowed terminal ileumand caecum.

aemia. Six weeks after starting treatment bariummeal and follow through showed normal ileum butan irregular, contracted caecum; chest radiographchanges were resolving and renal function hadreturned to normal. Her diarrhoea had resolvedafter six months, and barium meal and enema werenormal. The patient has now been followed forthree years and remains in remission.

Discussion

The diagnosis of Wegener's granulomatosis in thispatient was based on the combination of upperairways involvement, radiological evidence of lungdisease and focal necrotising glomerulonephritis onrenal biopsy. Other clinical features were arthritis,oral and anal ulceration, keratitis and a vasculiticskin rash. Fauci's group have recently publishedtheir experience of 85 patients with Wegener'sgranulomatosis,3 and conclude that in order toestablish the diagnosis there should be clinicalevidence of disease in two of the three principle sites(upper airways, lung, and kidney), with histologicalconfirmation in at least one and preferably two sites.Earlier series (1) described advanced cases studiedat necropsy, which accounts for the frequent demon-stration of granulomatous vasculitis; this is oftenimpossible in life. As blood stained mucus diarrhoeawas the principal presenting feature, inflammatoryand infective bowel disease were considered in thedifferential diagnosis. The distribution of gutinvolvement, with rectal, caecal, and ileal disease,made ulcerative colitis unlikely. Crohn's disease wasa major possibility, but the extra-gastrointestinalmanifestations, notably severe respiratory and renalinvolvement, were against this diagnosis.Wegener reported gastrointestinal involvement in

two of his three patients;5 in one of these he-described an ulcerating necrotising process in theileum, colon and rectum with marked oedema andleucocyte infiltration of the submucosa. Goodmanand Churg's detailed pathological description ofseven patients, six studied at necropsy, does notdocument bowel involvement,l nor did thesepatients have gastrointestinal symptoms.2 Walton,reviewing 56 cases of Wegener's granulomatosis,noted that 24% of the 54 patients studied atnecropsy had evidence of bowel disease, but nogastrointestinal symptoms were detailed.6 Fauci'sreviews in 1973 (18 patients)7 and in 1983 (85patients),3 do not comment on gastrointestinalinvolvement, and other series also suggest thatbowel disease is rare or absent.Of our 45 patients with Wegener's granulo-

matosis, four had gut symptoms at presentation;'0two had abdominal pain, one had abdominal painand diarrhoea, and one had painless diarrhoea (thesubject of this report). In addition, one patient hadtransient abdominal pain and diarrhoea during arelapse of disease. The pattern of gastrointestinaldisease in our patients with various forms ofsystemic vasculitis, has recently been reviewed.11Symptoms suggestive of gastrointestinal involve-ment included abdominal pain, diarrhoea, andblood loss (Table). The incidence of gut involve-

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L:.. Day 16.a

Fig. 4(a) and (b) Chest radiographs taken 16 and 34 days after presentation, showing distinct opacities in both mid zonesdeveloping into thin walled cavities.

ment was higher in patients with classical poly-arteritis nodosa and microscopic polyarteritis than inthose with Wegener's granulomatosis, but nodistinct clinical features were observed in thedifferent types of vasculitis.The treatment of bowel disease in patients with

Wegener's granulomatosis is as for the underlyingvasculitis. Cyclophosphamide, combined withprednisolone, has had a major impact on thedisease.3 7 Our treatment regimen also includes

Table Gastrointestinal involvement in patients withsystemic vasculitis

With GIinvolve-

Disease Patient ment Abdominalgroup (no) (no) pain Diarrhoea Bleeding

Polyarteritisnodosa 8 4 3 2 3Microscopicpolyarteritis 17 9 8 4 3Churg-Strausssyndrome 4 1 0 1 1Wegener'sgranulomatosis 45 4 3 2 1

Data from reference i1, but including nine additional patients withWegener's granulomatosis.

azathioprine, 'i) and the effects of plasma exchangeare being investigated. The response to treatment isusually dramatic, with rapid improvement incutaneous, joint and muscle involvement. Recoveryof renal function usually occurs within one to fourweeks; gastrointestinal features resolve over asimilar period, although surgical intervention maybe required for the complications of bowel perfora-tion,12 infarction of the gall bladder ,3 and persistenthaemorrhage.4 Long term remission of the diseasecan be maintained with cyclophosphamide,3 7 orazathioprine combined with low doseprednisolone.10Although uncommon, intestinal involvement may

be a major feature of Wegener's granulomatosis,and this diagnosis should be considered in patientspresenting with bowel symptoms accompanied byevidence of systemic vasculitis. The importance ofmaking the diagnosis is shown in this report, asappropriate treatment can result in rapid resolutionof the disease.

We would like to thank Dr A J Rees for permissionto report this case, Professor D J Evans for thephotomicrographs, Dr N Bowley for the radio-graphs, and Miss Sue Goodwin for typing themanuscript.

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References

1 Goodman GC, Churg J. Wegener's granulomatosis:pathology and review of the literature. Arch Pathol1954; 58: 533-53.

2 Fahey JL, Leonard E, Churg J, Goodman GC.Wegener's granulomatosis. Am J Med 1954; 17: 168-79.

3 Fauci AS, Haynes BF, Katz P, Wolff SM. Wegener'sGranulomatosis: prospective clinical and therapeuticexperience with 85 patients for 21 years. Ann InternMed 1983; 98: 76-85.

4 Carrington CB, Liebow AA. Limited forms of angiitisand Granulomatosis of Wegener's type. Am J Med1966; 41: 497-527.

5 Wegener F. Uber eine eigenartige rhinogene Granulo-matose mit besonderer, Beteiligung des Arterien-systems und der Nieren. Beitr Path Anat 1939; 102:36-68

6 Walton EW. Giant cell granuloma of the respiratory

tract (Wegener's granulomatosis). Br Med J 1958; 2:265-70.

7 Fauci AS, Wolff SM. Wegener's granulomatosis:studies in eighteen patients and a review of theliterature. Medicine (Baltimore) 1973; 52: 535-61.

8 Brandwein S, Esdaile J, Danoff D, Tammerbaum H.Wegener's granulomatosis. Clinical features andoutcome in 13 patients. Arch Intern Med 1983; 143:476-9.

9 Illum P, Thorling K. Wegener's granulomatosis -longterm results of treatment. Ann Otol 1981; 90:231-5.

10 Haworth SJ. Renal involvement in Wegener's Granulo-matosis. The Hammersmith experience. In: D'AmicoG ed. Nephrology '83 Wichtig Editore: Milan. 1983.

11 Camilleri M, Pusey CD, Chadwick VS, Rees AJ.Gastrointestinal manifestations of systemic vasculitis.Q J Med 1983; 52: 141-9.

12 McNabb WR, Lennox MS, Wedzicha JA. Smallintestinal perforation in Wegener's granulomatosis.Postgrad Med J 1982; 58: 123-5.

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