Digestive Diseases and Sciences, VoL 40, No. 3 (March 1995). pp, 525-527

L E T T E R TO T H E E D I T O R

ASEPTIC SYSTEMIC ABSCESSES PRECEDING DIAGNOSIS OF CROHN'S DISEASE BY

THREE YEARS

To The Editor," Extraintestinal manifestations occur in 24% of pa-

tients with Crohn's disease (1). They may precede, be concomitant with, or postdate the diagnosis, and so may reveal the inflammatory bowel disease in some cases. We report a systemic involvement of Crohn's disease that has not been previously described: mul- tiple aseptic organ abscesses.

A 25-year-old man was admitted in June 1988 because of abdominal pain, weight loss, and persis- tent fever for two months. He had no past medical history. Laboratory data revealed 20 × 109 white blood cells/liter with 83% neutrophils and 60 mm first hour erythrocyte sedimentation rate (ESR). MicroN- ologic tests found no evidence of infection. HIV serology was negative. Abdominal echography and CT scan showed spleen abscesses (Figure la). Echo- cardiography, small bowel barium meal, and colonos- copy were normal. An empiric double antibiotic ther- apy was initiated without improvement. The patient was splenectomized, and the symptoms disappeared. Abscesses contained altered polymorphonuclear neu- trophil (PMN) leukocytes with histiocytes at the bor- ders. No microorganism was found on direct exami- nation and cultures.

In March 1989, he developed fever, episcleritis, and painful erythematous indurated plaques on the chest, forearms, and thighs. The white blood cell count was 45 × 10L~/liter with 85% neutrophils. First-hour ESR was 95 mm and C-reactive protein 150 rag/liter (nor- mal < 6). After temporary improvement with broad- spectrum antibiotics, symptoms reappeared accompa- nied by abdominal pain. CT scan revealed hepatic defects and necrotic mesenteric lymphadenopathy. No subphrenic abscess was found at laparotomy. Cul- tures of liver and lymph node tissues failed to dem- onstrate any infection. The skin biopsy resulted in the diagnosis of Sweet's syndrome. Despite a treatment with teicoplanin, the patient remained febrile. Potas- sium iodide was administered (900 mg/day). Three days later, the patient was afebrile; cutaneous lesions and CT scan findings improved dramatically. The ESR decreased but PMN leukocytosis persisted (18 x 109/liter). Potassium iodide was stopped in September 1989. Ten days later, however, abdominal pain and

fever had recurred. Pancreatic abscesses and abdom- inal lymphadenopathy were found on CT scan (Fig- ure lb). A percutaneous aspiration of a mesenteric lymph node was performed and revealed altered neu- trophils without any microorganism. Evaluation of PMN leukocyte phagocytosis was normal and no anti- neutrophil antibodies were found. The HLA pheno- type was A3 A33~14 B 3 5 ~ r l Dr2. Plasma interleu- kin-l/3 (IL-1/3) and IL-6 concentrations were 0 and 201 pg/ml respectively (normal < 10). Bone marrow biopsy found neither myeloproliferative disorder nor infection on culture. Colchicine (2 mg/day) was given successfully for seven months but was stopped in May 1990 because of diarrhea. The patient had a relapse after a week; new symptoms of headaches and right chest pain appeared. Cerebrospinal fluid examination showed a white cell count of 87 × 10~'/liter (mainly PMN leukocytes) with 0.70 g/liter protein; bacteriol- ogy was negative. Brain and chest CT scans revealed a right frontal abscess and an abscess of the lower lobe of the right lung (Figure lc). Prednisone (1 mg/kg daily) was given after three pulses of methyl- prednisolone (240 mg per pulse), and this resulted in a rapid resolution of the symptoms. A right hemipa- resia with aphasia appeared in June 1990 (prednisone 25 mg/day). Cerebral CT scan and magnetic reso- nance imaging showed bilateral capsulolenticular ab- scesses (Figure ld). Control chest x-ray and CT scan found bilateral alveolar opacities predominantly in the middle and lower zones of the right lung. Results of bronchoatveolar lavage were unremarkable. Diag- nosis of bronchiolitis obliterans organizing pneumo- nia was suspected (lung biopsy was not performed). Intravenous methylprednisolone was given first and then prednisone dosage was increased to 60 mg daily. Monthly intravenous cyctophosphamide (700 mg/m 2) was added. Neurological symptoms improved and prednisone was gradually decreased.

The patient developed an anal fistula in June 1991 after 10 pulses of cyclophosphamide and while pred- nisone dosage was 30 rag/day. Histological examina- tion of the fistula showed epithetioid granulomas and giant cells without any microorganism. Colonoscopy revealed colonic and ileocecal ulcerations with histo- logical features typical of Crohn's disease. Plasma IL-6 concentration was 68 pg/ml and IL-1/3 was not detected. Prednisone was continued associated with mesalazine (2 g/day orally); the patient gradually im- proved, and the anal fistula resolved. Cyclophospha-

525 Digestive Diseases and Sciences, VoL 40, No. 3 (March t995) II1h3.211 fl/o5/O30{MI5255(}7,51)lo © 1995 Plenum Publishing Corporalion

LETTER TO THE EDITOR

Fig 1. Computed tomography scan of abdomen showing (a) spleen defects and (b) necrotic mesenteric lymphadenopathy. Chest CT scan showing an abscess of the right lung (c). Cerebral CT scan showing a left capsulolenticular abscess (d).

mide was stopped in September 1991 and colchicine ( 1 m~day) was reintroduced. Plasma IL-6 concentra- tion was 62 pg/ml and IL-lf3 remained undetected. Eighteen months later, the patient was still receiving prednisone (15 rag/day), colchicine, and mesalazine and had suffered no relapses.

In this case, late clinical and histological features were typical of Crohn's disease. Abscesses appeared amicrobial since microbiological analyses were always negative, phagocytosis and bacterial killing were nor- mal, and antibiotics failed to alter the course of the disease, whereas immunosuppressors or drugs active on PMN leukocyte chemotaxis were effective. There was some evidence for a relationship between aseptic abscesses and Crohn's disease. Sweet's syndrome is a neutrophilic dermatosis (ND) and bronchiolitis oblit- erans organizing pneumonia (BOOP) is a cryptogenic pneumonia. Antibiotics are not effective in treating these syndromes, but both respond dramatically to

corticosteroids (2, 3). ND is exceptionally associated with Crohn's disease or BOOP (4, 5). Cryptogenic organizing pneumonitis has only been found in ulcer- ative colitis (6). Systemic aseptic abscesses have been described in ND (7); an abnormal recruitment of PMN leukocytes outside the bowel could be impli- cated in the pathophysiology of this disorder. It could be mediated by cytokines such IL-1, IL-6, and IL-8 that have been implicated in the pathogenesis of inflammatory bowel disease (8-12). In this case re- port, interleukin plasma concentrations were ana- lyzed in 1993 on samples stored at different stages of the disease. IL-6 levels were increased when the pa- tient developed abscesses and when Crohn's disease was discovered. In contrast, IL-t¢3 was undetectable at these times. These data suggest a decrease in IL-1/3 production, an inhibition of this cytokine, or a high binding to specific receptors, which might play some role in the formation of abscesses. Systemic aseptic

526 Digestive Diseasz, s and Sciences, kbL 4(I, No, 3 (March 1905]

LETTER TO THE EDITOR

abscesses may be a feature of Crohn's disease and even precede its intestinal manifestations. This un- usual feature responds dramatically to steroids and immunosuppressive agents.

MARC ANDRE, M D

OLIVIER AUMAITRE, M D

JEAN-CLAUDE MARCHEIX, M D

Department of Internal Medicine CHRU Nord, BPt45

63020 Ctermont-Ferrand Ced¢r Z France JEAN-CHARLES PmTTE, MD

Department of Internal Medicine Hopital de la Pitie

83 Bd. de l'Hopital 75651 Palqs Cedex 13, France

ACKNOWLEDGMENTS

We thank Professor Galanaud and Doctor Portier (Unit6 INSERM; U131 d'Immunologie et Immunopathologie virale; 132, rue des Carnets; 92140 Clamart, France) for determination of interleukin concentrations.

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2. Su WPD, Liu HNH. Diagnostic criteria for Sweefs syndrome.

Cutis 37:167-174, 1986 3. Epler GR: Bronchiolitis obliterans organizing pneumonia:

Definition and clinical features. Chest 102(suppl 1):2S-6S, 1992

4. Kemmett D, Gawkrodger D J, Wilson G, Hunter JAA: Sweet's syndrome in Crohn's disease. Br Med J 297:1513-1514, 1988

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6. Camus P. Piard F, Ashcroft T, Gal AA, Colby TV: The lung in inflammatory bowel disease. Medicine 72:151-I83, 1993

7. Dallot A, Decazes JM, Drouault Y, et al: Subcorneal pustular dermatosis (Sneddon-Wilkinson disease) with amicrobial lymph node suppuration and aseptic spleen abscesses. Br J Dermatol 119:803-807, 1988

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10. Mahida YR, Ceska M, Effenberger F, Kurlak L, Lindley I, Hawkey CJ: Enhanced synthesis of neutrophil-activating peptide-1/interleukin-8 in active ulcerative colitis. Clin Sci 82:273-275, 1992

11. Mazlam MZ, Hodgson HJF: Peripheral blood monocyte cyto- kine production and acute phase response in inflammatory bowel disease. Gut 33:773-778, 1992

12. Stevens C, Walz G, Singaram C, Lipman ML, Zanker B, Muggia A, Antonioli D, Peppercorn MA, Strom TB: Tumor necrosis factor-m interleukin-l/3, and interleukin-6 expression in inflammatory bowel disease. Dig Dis Sci 37:818-826, 1992

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