Rheumatology Section, Eric Bywaters Centre, Imperial College London, 1 Department of Histopathology, Charing Cross Hospital and 2 Gastroenterology Unit, Hammersmith Hospital, London, UK
Correspondence to: W. F. Ng, Department of Rheumatology, Ealing Hospital, Uxbridge Road, Middlesex UB1 3HW, UK. E-mail: faingl{at}doctors.org.uk
SIR, Peripheral blood eosinophilia is a well-recognized finding in patients with rheumatoid arthritis (RA) and may be associated with increased disease activity or use of disease-modifying drugs [1, 2]. The relationship between tissue eosinophilia and RA is, however, unclear. We report here a case of eosinophilic enteritis (EE) in a patient with RA.
A 71-yr-old Indian woman presented with a 2-month history of worsening peripheral oedema, right iliac fossa pain and weight loss. She had two similar previous but milder episodes (4 and 6 yr before this presentation) which resolved spontaneously. She had a 10-yr history of seropositive RA and suffered from secondary Sjögren's syndrome, hypothyroidism and vitamin B12 deficiency. Her medications included sulphasalazine, methotrexate, thyroxine, Calcichew D3 and vitamin B12. She was born in East Africa, has been resident in the UK for 42 yr and visits India and the Middle East frequently. Physical examination revealed bilateral pitting oedema of the thigh and right iliac fossa tenderness. Her RA was clinically inactive with no swollen or tender joints. There was no evidence of lymphadenopathy, cardiac failure or other abnormal clinical findings.
Investigations revealed an iron deficiency anaemia (9.3 g/dl), peripheral eosinophilia (1.4 x 109/l; 17% of total white cell count), hypoalbuminaemia (17 g/dl), hypocalcaemia and hypogammaglobulinaemia. Electrolytes, transaminases, thyroxine and prothrombin time were normal. The erythrocyte sedimentation rate was 16 mm/first hour and the C-reactive protein 29 g/dl. Urinalysis revealed no active sediment or proteinuria. Analysis of tumour markers (CA-125, CA19-9, carcinoembryonic antigen, -fetoprotein) and peripheral blood gene rearrangement were negative. Three separate stool cultures and serology for parasites were negative. A small bowel follow-through study showed irregularly thickened mucosal folds in the jejunum consistent with small bowel lymphoma, hypereosinophilic syndrome, Whipple's disease or parasitic infections. Upper and lower gastrointestinal endoscopies and duodenal biopsy were normal. Enteroscopy showed patchy erythema in the jejunum but the biopsy was normal. An 111indium-labelled transferrin isotope scan demonstrated reduced retention of labelled transferrin, indicative of protein-losing enteropathy. Laparoscopy revealed a thickened proximal jejunum on palpation and a full-thickness biopsy was taken. Histology revealed a prominent mucosal and submucosal eosinophilic infiltrate accompanied by mild oedema. Small focal eosinophilic aggregates were also seen in the muscularis propria and subserosa (supplementary Figure 1; may be viewed in colour as supplementary data at Rheumatology Online). The villi were normal and no parasites were identified. There was no evidence of vasculitis or lymphoma. These features are those of EE of submucosal type. A diagnosis of protein-losing enteropathy secondary to EE was made. Her symptoms improved with frusemide, protein supplementation, calcium and vitamin D. Investigations into previous laboratory data over the last 10 yr revealed fluctuating eosinophil counts (absolute levels 0.181.4 x 109/l, corresponding to 2.317.6% of total white cell count) and this appeared to correlate with hypoalbuminaemia, implying a causal link between the two conditions. EE is an inflammatory disorder of unknown aetiology characterized by eosinophilic infiltration of the gastrointestinal tract. Any part of the gastrointestinal tract may be affected. Presenting symptoms may include abdominal pain, vomiting, diarrhoea, obstruction or malabsorption depending on the intestinal segment and the specific layer of the bowel wall involved. The clinical course of EE is usually chronic with exacerbations and remissions, as in our patient. The mainstay of treatment is corticosteroid therapy. Sodium cromoglycate, montelukast, suplatast tosilate, ketotifen and an elimination diet have also been tried with some success. Surgical intervention may be indicated for complications such as bowel obstruction or perforation. We considered the use of budesonide, which is locally effective in the gastrointestinal tract but not systemically absorbed. However, to date, this therapy has not been required.
Several aetiological factors have been proposed, including food or drug allergy, parasitic infection and infestation. Furthermore, EE may also be part of the manifestation of hypereosinophilic syndrome, vasculitides or systemic mastoidosis [1, 2]. To date, only two cases of RA and EE have been reported [3, 4]. While the association between RA and peripheral blood eosinophilia is well recognized, the link between tissue eosinophilia and RA is less well established. Eosinophilic pneumonia, eosinophilic fasciitis, hypereosinophilic syndrome and cutaneous eosinophilic vasculitis have been described in patients with RA [58]. In our patient, there was no evidence of other systemic tissue eosinophilic infiltration outside the gastrointestinal tract. Quallich et al. [9] reported a case of severe reaction to sulphasalazine with peripheral eosinophilia, granulomatous enteritis and myelotoxicity in a patient with RA. Although our patient was taking sulphasalazine, her peripheral eosinophilia predated the treatment, and hence was unlikely to be the causative agent.
In conclusion, we present a case of EE in a patient with RA. The reported association between RA and a variety of eosinophilic disorders suggests that our observation may be more than a coincidence, but represents a genuine link between these two conditions. The diverse symptomatology and the relapsingremitting course of EE results in this condition being underdiagnosed, and should be actively sought in patients with RA with unexplained abdominal symptoms or oedema.
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The authors have declared no conflicts of interest.
References
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