The Staffordshire Centre for Rheumatology, Haywood Hospital, High Lane, Burslem, Stoke-on-Trent ST6 7AG, UK
SIR, A 58-yr-old sheet metal worker presented with a 2-yr history of recurrent itchy erythematous papules, initially on the legs but later also on the arms and face. His symptoms had improved with the use of corticosteroid creams, and at the time of presentation to a dermatologist the rash had almost resolved and was not thought to be currently worth biopsying. He had a history of a non-productive cough for several months and a 3- to 4-month history of a left submandibular lymph node. He had no joint symptoms, headaches, scalp or artery tenderness. His past medical history was unremarkable and he had recently been commenced on salbutamol and corticosteroid inhalers for new-onset asthma. He was a non-smoker. There was no family history of atopy.
Clinical examination except for the lymph node was unremarkable. The submandibular lymph node was biopsied. The biopsy was initially reported as showing a very dense infiltrate of eosinophils with a reactive appearance. Muscular arteries were reported as showing occlusion by proliferating endothelial cells with early recanalization and dense infiltration by eosinophils. He was referred for rheumatological opinion with a presumed diagnosis of polyarteritis nodosa.
Clinical examination on rheumatological review revealed a normal blood pressure with normal peripheral pulses and no bruits. The temporal arteries were thought to be normal. Investigation revealed a haemoglobin concentration of 15 g/dl, a white cell count of 6.4x109/l and a platelet count 261x109/l. The erythrocyte sedimentation rate (ESR) was 3 mm/h and the C-reactive protein (CRP) concentration was 2 mg/l. He had an eosinophil count of 1.4x109/l (22%). Urea and electrolytes and liver function tests were normal. Urinalysis was negative. He had negative results for hepatitis B and C surface antibodies. Tests for RF, ANA, extractable nuclear antigen and ANCA were also negative. Serum electrophoresis was negative. Immunoglobulins were normal. Complement levels were normal. The 24-h urine collection was normal for protein level. Electrocardiogram and chest X-ray were normal.
ENT opinion was that he had normal, clinically healthy ears, nose and throat and biopsy was thought unnecessary. The lymph node did not recur and he remained well without systemic treatment.
Six months later he had itchy red eyes, which settled with topical steroid and chloramphenicol treatment, and no specific ophthalmological diagnosis was made. He developed bilateral cool knee effusion but aspiration of this revealed only a white cell count of 1000 mm3 with the occasional apatite crystals and no eosinophils. Total immunoglobulin (Ig) E level at the time was 858 kU/l (normal range 0100) with a corresponding 20% eosinophilia.
Eighteen months after rheumatological presentation he developed several transient episodes of slurred speech and paraesthesia affecting the right upper lip. He also reported swelling over the temporal blood vessels and an unsteady gait. Clinical examination showed blood pressure 140/90 with prominent temporal arteries bilaterally. ESR was 9 mm/h and CRP 2 mg/l. The level of complement C4 was high, at >43 mg/dl (normal range 942 mg/dl), and C3d activation product was raised. An electroencephalogram did not show convincing evidence for seizure disorder and computed tomography of the brain was normal.
The lymph node histology was reviewed and was reported as showing no evidence of any specific infective process or neoplasia. There was follicular hyperplasia and an expanded paracortex with an eosinophil infiltrate. The germinal centre was reactive and showed the presence of polykaryocytes. There was no follicular lysis. Immunostaining for IgE demonstrated IgE deposition on the follicular dendritic cells and staining for CD34 highlighted the vascular proliferation. There was no evidence of vasculitis and the vascular changes seen in angiolymphoid hyperplasia with eosinophilia were not present. The appearances were consistent with Kimura's disease.
Kimura's disease is a rare condition usually described in young to middle-aged Asian men. It has rarely been reported in Caucasians [1]. It is a chronic inflammatory condition of unknown origin. Clinically, its features consist of lymphadenopathy and often multiple small subcutaneous pruritic lesions. Both features usually occur in the head and neck region. Men are more commonly affected. Peripheral eosinophilia is a prominent feature and serum IgE is usually raised [2]. Extracutaneous features can include nephrotic syndrome [3, 4]. They may also include bronchial asthma [5]. The case we have described also had recent-onset asthma and an episode of knee arthropathy. Kimura's disease is probably immunologically mediated [6], although infective aetiologies have been postulated [7]. It has been postulated that Kimura's disease involves cytokines, such as GM-CSF (granulocyte macrophage colony-stimulating factor) and TNF- (tumour necrosis factor
), which activate eosinophils [8]. Suplatast tosilate, an antiallergenic agent that suppresses eosinophil infiltration in asthma, has been used in Kimura's disease [5]. The release of cytokines from mast cells may also play a role in the pathogenesis of Kimura's disease [9]. In the past it was thought to be part of a disease entity termed angiolymphoid hyperplasia with eosinophilia, but it is now thought that the two entities are separate [1, 10, 11]. Histologically, lymph nodes with discrete germinal centres and an eosinophilic infiltration occur. Some germinal centres may undergo lysis to form eosinophilic microabscesses. Immunostaining for IgE shows positive staining for dendritic cells and numerous mast cells. Fibrosis may be prominent, particularly in old lesions. [2]
The clinical course is benign, although the lesions can grow to be large and disfiguring. Surgical excision is sometimes used but the lesions can recur. Treatment is usually conservative; intralesional or oral steroids have been used but rarely lead to cure. Cyclosporin has been used in the disease [12]. Radiotherapy has also been used to treat large lesions, but again this may not be curative [2, 13]. This is the first case where a synovial effusion has been reported. Recognition of Kimura's disease is important as the management of the differential diagnoses, particularly salivary gland and parotid malignancy and connective tissue disorders, may lead to inappropriate treatment.
We thank Professor Mark Walport and Professor Kristen Henry for their helpful comments and assistance with this case.
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