Hepatomegaly as a rare presentation of Churg–Strauss syndrome

A. N. Bennett, S. R. Sangle, W. Jan1, M. Jenner2, J. Cavenagh2, G. Hughes and D. P. D'Cruz

Lupus Research Unit, The Rayne Institute, 1 Department of Radiology, St Thomas’ Hospital, and 2 Department of Haematology, St Bartholomew's Hospital, London, UK

Correspondence to: D. P. D'Cruz, Lupus Research Unit, The Rayne Institute, St Thomas' Hospital, London SE1 7EH, UK. E-mail: david.d'cruz{at}kcl.ac.uk

SIR, A 36-yr-old Caucasian female supermarket worker presented with increasing fatigue, dry cough, wheeze, drenching night sweats and weight loss. On examination she had multiple spider naevi and gross hepatomegaly. Investigation showed abnormal liver function tests with raised alkaline phosphatase 400 IU/l (31–116) and {gamma}-glutamyl transferase 400 IU/l (0–72). Other liver function tests were normal, as were hepatitis, cytomegalovirus and human immunodeficiency virus serology. Strikingly, she had an eosinophilia of 10 x 109/l with an erythrocyte sedimentation rate (ESR) of 95 mm/1st hour (0–15) and a C-reactive protein (CRP) of 40 mg/l (0–7). Computed tomography (CT) scanning showed hepatomegaly, the left lobe of the liver displacing the stomach, and hypoattenuation suggestive of periportal oedema with an enlarged lymph node in the porta hepatis (Fig. 1a); no other lymphadenopathy was seen on whole-body CT. All tumour markers, antinuclear and mitochondrial antibodies were negative. Smooth muscle antibody was weakly positive (1:80) and thyroid antibodies were positive, with normal thyroid function. She had never left the UK, had no contact with farm animals and an extensive infection screen for parasitic and other infectious causes was negative.


Figure 1
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FIG. 1. Churg–Strauss syndrome effecting the liver (a) Pre-treatment, marked hepatomegaly with hypoattenuation suggestive of periportal oedema. (b) Post-treatment with oral prednisolone, dramatic improvement in hepatomegaly and hypoattenuation.

 
A positron emission tomography scan showed intense abnormal uptake in the liver and less specific uptake in the inframammary and bone marrow areas. A bone marrow showed reactive features with negative cytogenetics, making a myeloproliferative disorder unlikely. Two percutaneous liver biopsies and a mini-laparotomy with wedge biopsy and portal node biopsy were performed. The liver biopsies excluded lymphoma but all showed necrotizing granulomas with infiltration of eosinophils. There were no features of vasculitis or bacterial, fungal or tuberculous infections.

Churg–Strauss syndrome (CSS) was considered and a perinuclear antineutrophil cytoplasmic antibody test (p-ANCA) was weakly positive, with proteinase 3 antibodies in low titre [12 IU/ml (0–10)] but a diagnosis of hypereosinophilic syndrome (HES) was felt more likely. Diagnostic criteria for HES [1] include the presents of persistent eosinophilia of 1.5 x 109/l for longer than 6 months, lack of evidence for parasitic, allergic or other known causes of eosinophilia, and signs and symptoms of organ involvement. A significant percentage of HES patients have cryptic rearrangements of the PDGF receptor A gene, resulting in constitutive activation of this receptor with tyrosine kinase. These patients are sensitive to STI 571(Glivec), a tyrosine kinase inhibitor well known for its activity in chronic myeloid leukaemia. This patient did not have the gene rearrangement but her eosinophils were sensitive to STI 571 so she was started on 400 mg daily.

There was, however, no improvement in her symptoms or eosinophilia, so she was referred to the St Thomas’ Hospital vasculitis clinic. Here her history revealed late-onset asthma and previous recurrent sinusitis. On examination, a right-sided nasal polyp and hepatomegaly were noted but there was no neuropathy. ANCA was negative and ESR 99 mm/1st hour. The eosinophils had reduced to 2.4 x 109/l. Chest radiograph, pulmonary function tests and echocardiogram were normal. CT scan of the sinuses showed minimal soft-tissue thickening in the ethmoid sinuses on the right. The patient did not meet the Chapel Hill Consensus conference [2] definition of CSS because of the lack of necrotizing vasculitis on biopsy. However, she did meet the ACR criteria for CSS [3], having asthma, eosinophilia, sinusitis and a positive biopsy. A positive biopsy by ACR criteria contains a blood vessel with extravascular eosinophils. On the basis of these clinical features and a previously positive p-ANCA, a diagnosis of CSS syndrome was made, and therefore by definition HES was excluded. CSS is a multisystem small-vessel granulomatous vasculitis that often affects the cardiovascular, respiratory, ENT and neurological systems. It can affect the gastrointestinal system; involvement of the hepatobiliary system is very rare but is reported [4–6]. The mainstay of treatment is corticosteroids. immunosuppressants can be used in acute severe presentations or relapses, but are often required as corticosteroid-sparing agents in chronic disease.

A reducing dose of oral prednisolone was started at 20 mg daily, reducing by 2.5 mg daily every week to 7.5 mg daily. Repeat CT scan showed dramatic improvements, with a reduction in hepatomegaly and much reduced periportal hypoattenuation (Fig. 1b). Currently, on prednisolone 7.5 mg daily alone, 6 months after initial review in the vasculitis clinic she is asymptomatic. Her hepatomegaly has improved dramatically, her ANCA, liver function tests, ESR and CRP are all normal and eosinophils have reduced to 0.7 x 109/l.

The authors have declared no conflicts of interest.

References

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  2. Jennette JC, Falk RJ, Andrassy K et al. Nomenclature of systemic vasculitides: proposal of an international consensus conference. Arthritis Rheum 1994;37:187–92.[ISI][Medline]
  3. Masi AT, Hunder GG, Lie JT et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum 1990;33:1094–100.[ISI][Medline]
  4. Brooklyn TN, Prouse P, Portmann B, Ramage JK. Churg-Srauss syndrome and granulomatous cholangiopathy. Eur J Gastroenterol Hepatol 2000;12:809–11.[ISI][Medline]
  5. Gambari PF, Ostuni PA, Lazzarin P, Fassina A, Todeesco S. Eosinophilic granuloma and necrotizing vasculitis (Churg-Strauss syndrome?) involving a parotid gland, lymph nodes, liver and spleen. Scand J Rheumatol 1989;18:171–5.[ISI][Medline]
  6. Conn DL, Dickson ER, Carpenter HA. The association of Churg-Strauss vasculitis with temporal artery involvement, primary biliary cirrhosis, and polychondritis in a single patient. J Rheumatol 1982;9:744–8.[ISI][Medline]
Accepted 10 June 2005





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