Idiopathic hypereosinophilic syndrome in a patient with long-standing rheumatoid arthritis: a case report

K. Chaudhuri, S. Dubey and G. Zaphiropoulos

Department of Rheumatology, Walsgrave Hospital, Clifford Bridge Road, Coventry CV2 2DX, UK

SIR, We would like to report the case of a patient with long-standing rheumatoid arthritis (RA) who developed the idiopathic hypereosinophilic syndrome (HES). HES is characterized by sustained blood eosinophilia, multiorgan involvement and absence of other causes for eosinophilia, these criteria being first defined in 1975 [1]. We report a patient who had seropositive erosive RA for 10 yr before developing HES. There was some initial delay in diagnosis as the eosinophilia was considered to have been induced by gold therapy. It was not until she developed multiorgan complications that the diagnosis of HES became apparent.

A 55-yr-old female was diagnosed as having RA in 1988. Over the next 10 yr she was treated with a succession of second-line agents, including sulphasalazine, D-penicillamine and methotrexate, and in 1993 she was started on intramuscular gold injections. In January 1998, after 5 yr on gold therapy, she developed an urticarial rash on the chest and arms, associated with peripheral blood eosinophilia of around 1.7x109/l (normal <0.3x109/l). A skin biopsy of the rash showed an eosinophilic infiltrate considered to be probably induced by parenteral gold therapy, which was discontinued. The patient exhibited a moderately raised erythrocyte sedimentation rate and C-reactive protein concentration and positive rheumatoid factor (>1600 IU/l). The rash resolved, only to recur after 2 months despite the cessation of gold therapy.

The patient started feeling lethargic and experienced night sweats, but overall her joint disease was not clinically active. The eosinophil count remained in the range of 1.5–4.5x109/l. At the end of June 1998, she was admitted as an emergency with a right-sided hemiparesis fever, atrial fibrillation and left ventricular failure. Blood cultures were negative but a small vegetation was seen on the mitral valve on transoesophageal echocardiography. A brain CT scan showed patchy deep-matter ischaemia but no focal infarct. She was treated initially with intravenous antibiotics and was later given anticoagulation treatment by the admitting team. The eosinophil count had increased to 20.5x109/l at the time of admission. The autoimmune profile remained normal, stool cultures were negative for ova and parasites, bone marrow examination showed overproduction of eosinophils, and cell markers for a clonal pathology were negative. A diagnosis of HES was made on the following criteria: (i) sustained eosinophilia of >1500/mm3; (ii) the absence of other causes of eosinophilia; and (iii) multiorgan involvement. Oral prednisolone at 40 mg/day produced a dramatic response in the eosinophil count, as shown in Fig. 1Go as well as clinically. Attempts to reduce the steroid dose, however, resulted in an almost instantaneous rise in eosinophil count. Over the next 6 months she had a number of complications: a deep-seated sacral ulcer followed by methicillin-resistant staphylococcal (MRSA) septicaemia; a transudative pleural effusion with secondary pyothorax, requiring prolonged antibiotic therapy and pleural drainage; an episode of autoimmune haemolytic anaemia with the presence of cold agglutinins. Eosinophil counts rose when the prednisolone dose went below 30 mg/day and resolved spontaneously with increase in dose. Her illness was further compounded by profound depression. Cyclosporin was added to her regime to achieve some steroid-sparing effect. Repeat echocardiogram showed no evidence of vegetations and good ventricular function. She remains stable 2 yr later on cyclosporin and has been weaned off prednisolone. Her eosinophil count is in the range 0.5–0.9x109/l.



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FIG. 1.  Graph showing the variation in eosinophil count x109/l over a 20-month period. Arrows indicate points where steroids were being reduced.

 
We have described a case of HES developing in a patient with RA after a period of 10 yr. The diagnosis of idiopathic HES is one of exclusion [1]. With regard to the pattern of systemic involvement, some organs, such as the heart, lungs, skin, nervous system and spleen, are more commonly involved than others. In RA patients, persistent eosinophilia can be due to the rheumatoid disease itself and is often associated with very active disease, with extra-articular features including rheumatoid nodules, vasculitis, neuritis, pulmonary fibrosis and cutaneous infarction [2, 3]. Eosinophil counts in these patients may range from 20 to 89% of the total white cell count. Our patient had mild to moderate activity of joint disease and a moderate increase in eosinophil count initially until she developed the stroke. Another possible explanation for the raised eosinophil count in this patient is the ongoing gold therapy. Eosinophilia has been reported to occur in approximately 5% of gold-treated patients but varies from 0–40% in different reports [4]. It is generally transient and usually of no significance, but it can be the first sign of impending toxicity affecting other organ systems. There is usually resolution of eosinophilia in almost all patients on stopping gold therapy (if it is drug-related). This did not happen in our patient, who went on to develop other organ involvement despite remaining off gold therapy for 6 months. There was no evidence of parasitic infestation, although extensive serological screening was not done.

Rheumatological manifestations of HES are infrequent. There have been five previous reports of HES associated with an inflammatory joint disease mimicking RA [48]. A further case describes the development of HES after a short duration of RA, the patient dying soon after [9]. Tay [10] has described 10 patients from Singapore with acute polyarthritis and marked hypereosinophilia of unknown aetiology, to which he attached the label ‘eosinophilic arthritis’.

This is the first case report in the UK of HES developing in a patient with long-standing RA treated successfully with a combination of steroids and cyclosporin. When peripheral blood eosinophilia was observed in association with a skin rash, it was initially attributed to the ongoing gold therapy, thus delaying the search for other causes of persistent eosinophilia. The subsequent diagnosis of HES explained the multiorgan involvement as manifested by the stroke, heart valve, vegetation and pleural effusion. The eosinophilia proved very sensitive to steroids and she tolerated cyclosporin well. Other therapeutic options, including alkylating agents and {alpha}-interferon, were not considered at the time because of ongoing problems with sepsis.

Notes

Correspondence to: K. Chaudhuri. Back

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Accepted 22 August 2001