170 Garcia-Diaz, Mira, Nevado, et al

Retinal vasculitis associated with Crohn's disease

Miguel Garcia-Diaz, Maria Mira, Leticia Nevado, Antonio Galvan, Alicia Berenguer,Juan Carlos Bureo

Unidad de AparatoDigestivo, UniversityHospital InfantaCristina, University ofExtremadura,Avenida de Elvas,06080-Badajoz, SpainM Garcia DiazServicio deOftalmologiaM MiraA GalvanServicio de MedicinaInternaL NevadoA BerenguerJC Bureo

Correspondence to MiguelGarcia-Diaz, Miguel PerezCarrascosa no 2-90A,06011 -Badajoz, Spain

Accepted 21 September 1994

SummaryAlthough systemic vasculitis can be acomplication of inflammatory boweldisease at several locations (skin, eyes,brain, mesentery, and lung) the associa-tion of retinal vasculitis with Crohn'sdisease is rare. We studied a 26-year-oldwoman with biopsy-demonstrated Crohn'sdisease who developed a severe bilateralretinal arteritis and phlebitis, with acuteloss of vision.

Keywords: retinal vasculitis, Crohn's disease,inflammatory bowel disease

Introduction

Ocular disorders arising in association withCrohn's disease occur in between 4 and 6% ofcases (see box).'-4 Retinal vasculitis, however,is an uncommon complication.5`7 There hasoften been an association found between someof the systemic complications of Crohn'sdisease.'The pathogenic mechanism of retinal injury

could be either vasculitis of vessels5-7 or throm-botic occlusion of vessels."4'8 Fluoresceinangiography study is useful in diagnosis ofretinal vasculitis.57

Case report

A 26-year-old woman with a seven-year historyof Crohn's disease was admitted to the hospitalafter five months of lower left quadrantabdominal pain associated with diarrhoea withblood, vomiting, fever, and weight loss. Hertemperature at admission was 37.2°C.

Initial investigations are shown in the box. Abarium enema showed edema, ulceration,mucosal thickening and fistulas penetrating tothe vagina. Flexible colonoscopy demonstrateda segmental colitis with rectal and sigmoidinvolvement. The patient had biopsy-provenCrohn's disease. Treatment (6-methyl-prednisolone, 1 mg/kg/day, and parenteralnutrition) resulted in clinical and analyticalimprovement.

Despite the clinical and analytical improve-ment, the patient began to suffer an acute loss ofvision. On examination, the visual acuity wasfound to be: right eye 0.1, left eye 0.6. Theintraocular pressures were: right eye 13 mmHg,left eye 14 mmHg. Fundoscopy revealed scat-tered cotton-wool spots in both eyes (figure 1).One cotton-wool spot was on the right eye

Ocular manifestations of Crohn'sdisease

* 4-6% cases* uveitis* corneal ulcers, keratitis* blepharitis* episcleritis, conjunctivitis* myositis* thrombotic retinal artery occlusion

Biochemical investigations

* WBC 14.9 x 1091* neutrophil leucocytosis* haemoglobin 99 g/l* haematocrit 0.3* MCV 72.7 fl* MCH 24 pg/cell* platelets 796 x 109/1* ESR 109mm/h* liver functions normal* kidney functions normal* total serum protein 84 g/l* polyclonal immunoglobulin 36.99 g/l* ACE 54 U/I (normal 10-50)* coagulation studies normal* chest X-ray normal* hepatitis A, B, C, toxoplasma, herpes,

cytomegalovirus negative* mantoux negative* NMR imaging ofbrain normal

macula. The retinal veins were tortuous andshowed sheathing. The retina was edematousthroughout the posterior pole and intraretinalblood was observed near some vessels. Weobserved uveitis and vitritis and later,preretinal blood.

Intravenous fluorescein angiography showedprolongation of the arm-retinal transit timewith swollen optic disks which demonstrateddiffuse leakage of fluorescein. It also showedneovascularisation filling and intraretinalhaemorrhage on the posterior pole (figure 2).Cyclophosphamide (100 mg/day) and pred-

nisone (50 mg/day) was employed but onlyimprovement of the uveitis and vitritis wasobserved. The retinal vasculitis did not imp-rove.

Six weeks later, she could only count fingersat most 3 m with the right eye. The visualacuity of the left eye remained unchanged.

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Retinal vasculitis associated with Crohn's disease 171

Figure 1 Posterior poles of both eyes: cotton-woolspots are present. A: right eye. B: left eye

Discussion

A diagnosis of retinal vasculitis is made on thebasis of sheathing of the walls of retinal vessels,haemorrhages in the retina, and late staining ofthe walls of affected vessels. Retinal vasculitishas been associated with cotton-wool spots dueto retinal ischaemia.'57

In Crohn's disease and in ulcerative colitis,the vasculitis could affect several tissues(retina,`7 skin,9 brain,'0 bowel,'""3 lung'2). Apossible pathogenic mechanism in Crohn'sdisease could be inflammatory microvascularocclusion, associated with vasculitis. In theaffected bowel, the injury is focal and it mayoccur in the absence of either macroscopic ormicroscopic disease." The pathogenicsequence ofevents in Crohn's disease might be:vascular injury, focal arteritis, fibrin depositionand arterial occlusion followed by tissue infarc-tion or neovascularisation.""',3 Granulomatousvasculitis was suggested to be the mechanism oftissue injury"3: granulomatous inflammationwas associated with focal disruption of theblood vessel walls, adherence of chronicinflammatory cells to the luminal surface of thelesion, and fibrin deposition. This pathogenicsequence was only seen in specimens fromsmall and large bowel Crohn's disease."3 How-ever, this granulomatous inflammation has notbeen observed in other tissues, althoughimmunochemical staining techniques were notused to identify vascular structures andgranulomas in these studies.9'l2

Retinal vasculitis is uncommon in Grohn'sdisease, although there are some systemicdiseases (sarcoidosis, tuberculosis, syphilis,toxoplasmosis, cytomegalovirus, herpes zoster,temporal arteritis, polyarteritis nodosum,

Figure 2 Intravenous fluorescein angiogram of botheyes after injection of fluorescein, showing prominentleakage ofthe dye from the optic disk and the new vesselsgrowing at the posterior pole. The arrows show leakageof fluorescein from the neovascularization. A: right eye.B: left eye

systemic lupus erythematosus and multiplesclerosis) which can be associated with retinalvasculitis, and there is also an idiopathic pres-entation (Eale's disease).'4 These othersystemic diseases were rejected on the basis ofnegative results in their differential diagnosis.

Retinal arterial occlusions have been des-cribed in previous reports of patients withCrohn's disease, but the authors saw noevidence of intrinsic retinal vascular disease inthe fluorescein angiography and the aetiologyof these lesions was thrombi occluding smallvessels."4 In our patient, the absence of anyprevious systemic manifestation of throm-boembolic phenomena, and the normalcoagulation studies and platelet count when theacute loss of vision began did not suggest athromboembolic phenomenon. Moreover, thefluorescein angiography of our patient demon-strated retinal vasculitis.

In our patient, the inflammatory boweldisease complication manifested as acute loss ofvision due to severe, bilateral, obliterative andproliferative retinal vasculitis in which thearteries were predominantly affected. Weobserved cotton-wool spots in her eyes suggest-ing tissue ischaemia, leakage of fluoresceinindicating haemorrhage, and neovascularisa-tion (figures 1 and 2).There are other previously reported cases

that share some similarities with our case.5~7Two involved patients with Crohn's diseasewho have optic nerve vasculitis with secondaryinvolvement of retinal vessels,6~7 and anotherwas of a patient with arterial and venous

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172 Garcia-Diaz, Mira, Nevado, et al

vasculitis.5 Papillitis, haemorrhages andsheathing of vessels was observed in thesepatients.57The treatments employed in these previous

reports have been prednisone or cyclophos-phamide plus corticosteroids. The improve-

ment of the ocular damage was limited.57 Inour case, we used cyclophosphamide plus pred-nisone, but only the uveitis and vitritis im-proved. The retinal vessel lesions did notimprove.

1 Hopkins DJ, Horan E, Burton IL, Clamp SE, De DomballFT, Goligher JC. Ocular disorders in a series of 332 patientswith Crohn's disease. Br J Ophthalmol 1974; 58: 732-7.

2 Greenstein AJ, Janowitz HD, Sachar DB. The extra-intestinal complications of Crohn's disease and ulcerativecolitis: a study of 700 patients. Medicine 1976; 55: 401-11.

3 Petrelli EA, McKinley M, Troncale FJ. Ocular manifesta-tions of inflammatory bowel disease. Ann Ophthalmol 1982;14: 356-60.

4 Schneiderman JH, Sharpe JA, Sutton DMC. Cerebral andretinal vascular complications of inflammatory boweldisease. Ann Neurol 1979; 5: 331-7.

5 Duker JS, Brown GC, Brooks L. Retinal vasculitis inCrohn's disease. Am J Ophthalmol 1987; 103: 664-8.

6 Sedwick LA, Klingele TC, Burde RM, Behrens MM. Opticneuritis in inflammatory bowel disease. J Clin Neuro Oph-thalmol 1984; 4: 3-6.

7 Macoul KI. Ocular changes in granulomatus ileocolitis.Arch Ophthalmol 1970; 84: 95-7.

8 Novotny DA, Rubin RJ, Slezak FA, Porter JA. Arterialthromboembolic complications of inflammatory boweldisease. Dis Colon Rectum 1992; 35: 193-6.

9 Wackers FJ, Tytgat GN, Vreeken J. Necrotizing vasculitisand ulcerative colitis. BMJ 1974; 4: 83-4.

10 Nelson JN, Barron MM, Riggs JE, Gutmann L, SchochetSS. Cerebral vasculitis and ulcerative colitis. Neurology1986; 36: 719-21.

11 Wakefield AJ, Dhillon AP, Rowles PM, et al. Pathogenesisof Crohn's disease: multifocal gastrointestinal infarction.Lancet 1989; 2: 1057-62.

12 Collins WJ, Bendig DW, Taylor WF. Pulmonary vasculitiscomplicating childhood ulcerative colitis. Gastroenterology1979; 77: 1091-3.

13 Wakefield AJ, Sankey EA, Dhillon AP, et al. Granulomatousvasculitis in Crohn's disease. Gastroenterology 1991; 100:1279-87.

14 Jampol LM, Isenberg SJ, Goldberg MF. Occlusive retinalarteriolitis with neovascularization. Am J Ophthalmol 1976;81: 583-9.

Occult small bowel adenocarcinoma complicatingCrohn's disease: a report of three cases

CD Gillen, CA Wilson, RS Walmsley, DSA Sanders, ST O'Dwyer, RN Allan

Queen ElizabethHospital, Edgbaston,Birmingham, UKCD GillenRS WalmsleyST O'DwyerRN AllanDepartment ofHistopathologyCA WilsonDSA Sanders

Correspondence toDr CD Gillen,Queen Elizabeth Hospital,Edgbaston, BirminghamB15 2TH, UK

Accepted 4 October 1994

SummaryThree patients with Crohn's disease aredescribed who were treated by ileal resec-tion for intestinal obstruction. Histo-logical examination ofthe resected speci-men in each case established the diagnosisof adenocarcinoma of the small intestinecomplicating Crohn's disease. This diag-nosis should be considered in patientswith longstanding macroscopic Crohn'sdisease who present with severe or recur-rent symptoms. The diagnosis may not beapparent on routine radiological examin-ation or even macroscopically at laparo-tomy.

Keywords: Crohn's disease, small bowel, adenocar-cinoma

Introduction

The increased risk of colorectal cancer inextensive Crohn's colitis is well recognised," 2and is of the same order as the risk in ulcerativecolitis.' Small bowel adenocarcinoma compli-cating Crohn's disease is uncommon but wellrecognised. Sixty one cases were published inthe literature to 19824 and 60 cases have beensummarised in a series of publications subse-quently,5-'4 a total of 121 examples in all. It isthus an important complication to consider inthe management of patients with longstandingmacroscopic small bowel Crohn's disease. In

this paper we describe three examples ofadenocarcinoma of the ileum complicatingCrohn's disease which were only apparent onhistological examination of the resected speci-mens.

Case reports

Case 1A diagnosis of ileal Crohn's disease in thiswhite man, born in June 1949, was establishedon radiological examination in 1969. He hadfurther abdominal symptoms in 1975 whenradiological studies confirmed the changes ofterminal ileal Crohn's disease with a localisedileocaecal fistula. He re-presented in July 1992with a three month history of right-sidedcolicky abdominal pain, nausea, intermittentconstipation and 10 kg weight loss. Furtherradiological assessment confirmed an irregular8 cm of terminal ileum with abnormal mucosaand several areas of narrowing with mucosalirregularity adjacent to the ileo-caecal valve. Atlaparotomy the appearance macroscopicallywas described as typical of Crohn's disease andhe was treated by distal ileal resection. Theresected specimen comprised an 11 cm lengthof small bowel with a 4 cm diameter ulceratedarea with some transmural thickening. Therewere three distinct areas of mucosal irregu-larity. Macroscopically, the changes were con-sidered typical of Crohn's disease. However,histological examination revealed a moderatelywell differentiated adenocarcinoma, extending

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