A 53-year-old male was admitted to hospital with a twoweek history of coughing and breathlessness. Apart from a longstanding history of mild asthma he had been relatively well with respect to the respiratory tract. He had been on a skiing trip six weeks previously, without any respiratory problems. He had a past history of depression, for which he took lithium five years ago, and suffered from occasional tension headaches, for which he took simple analgesia. On examination he appeared pale and unwell. His heart rate was 90 beats/min and regular. His blood pressure measured 160/94 mmHg. The JVP was not raised. Both heart sounds were normal and the chest was clear. Abdominal examination did not reveal any abnormality. Urinalysis demonstrated blood ++ and protein ++. Investigations performed in hospital are shown.
What is the most likely diagnosis?
Hb 7 g/dl WCC 11 109/1 (neutrophils 8 109/l, lymphocytes 2 109/l, eosinophils 1 109/l) ESR 38 mm/h Sodium 134 mmol/l Potassium 4.6 mmol/l Urea 48 mmol/l Creatinine 798 mmol /l Renal ultrasound Both kidneys measured 12 cm: there was no evidence of ureteric obstruction.
a. Rapidly progressive glomerulonephritis.
b. Analgesic nephropathy.
c. Renal amyloidosis.
d. Churg–Strauss syndrome.
e. IgA nephritis.
The patient has a past history of asthma, eosinophilia and rapidly progressive glomerulonephritis. The most probable diagnosis is Churg–Strauss syndrome. The assumption that he probably has rapidly progressive glomerulonephritis is based on the fact that he was well enough to ski six weeks ago, which would be highly unlikely in a patient with endstage renal disease. The identification of normal-sized kidneys during renal ultrasonography supports acute rather than chronic renal failure (Table A). Churg–Strauss syndrome is a small-vessel multi-system vasculitis characterized by cutaneous vasculitic lesions, eosinophilia (usually <2.0 109/l), asthma (usually mild), mononeuritis or polyneuropathy and rarely glomerulonephritis (10% of cases). Gastrointestinal and cardiac involvement is recognized. Pulmonary findings dominate the clinical presentation with paroxysmal asthma attacks and presence of fleeting pulmonary infiltrates. Asthma is the cardinal feature and may be present for years before overt features of a multi-system vasculitis become apparent. Skin lesions, which include purpura and cutaneous and subcutaneous nodules, occur in up to 70% of patients. Gastrointestinal complications include mesenteric ischaemia or gastrointestinal haemorrhage. Cardiac involvement is characterized by myo-pericarditis. The diagnosis is usually clinical and supported by the presence of a necrotizing granulomatous vasculitis with extravascular eosinophilic infiltration on lung, renal or sural biopsy. The American College or Rheumatology criteria for the diagnosis of Churg–Strauss syndrome are tabulated (Table B). Serum ANCA (MPO subset) are elevated but this finding is also present in microscopic polyangitis. The prognosis of untreated CSS is poor, with a reported five-year survival rate of only 25%. Corticosteroid therapy has been reported to increase the five-year survival rate to more than 50%. In patients with acute vasculitis the combination of cyclophosphamide and prednisone is superior to prednisolone alone. Although rapidly progressive glomerulonephritis also features in the answer options section, the presence of asthma and eosinophilia make Churg–Strauss syndrome the best answer. It is worth noting however, that rapidly progressive glomerulonephritis may also rarely be
Table A Phases of Churg–Strauss syndrome: 1. The prodromal phase, which may be present for years and comprises of rhinitis, nasal polyposis and frequently asthma. 2. The eosinophilic phase, which can remit and recur for years. It is characterized by the onset of peripheral blood and tissue eosinophilia, resembling Loeffler’s syndrome, chronic eosinophilic pneumonia or eosinophilic gastroenteritis. 3. The vasculitic phase, which usually occurs in the third or fourth decades of life and is characterized by a life-threatening systemic vasculitis of small and occasionally medium-sized vessels. This phase is associated with constitutional symptoms and signs, fever and weight loss.
Table B American College of Rheumatology 1990 criteria for Churg–Strauss syndrome The presence of four or more of the manifestations below is highly indicative of Churg–Strauss syndrome: • Asthma • Eosinophilia (10% on WCC differential) • Mononeuropathy or polyneuropathy • Migratory or transient pulmonary infiltrates • Systemic vasculitis (cardiac, renal, hepatic) • Extravascular eosinophils on a biopsy including artery, arteriole or venule
Table C Causes of renal failure and eosinophilia • Rapidly progressive glomerulonephritis • Churg–Strauss syndrome • Acute tubulo-interstitial nephritis • Cholesterol micro-emboli
associated with eosinophilia. Causes of renal failure and eosinophilia are tabulated (Table C). The history of analgesia for headaches raises the possibility of analgesic nephropathy as the cause of his presentation; however, analgesic nephropathy is usually insidious and many patients present for the first time with renal failure. The majority have abnormalities on renal ultrasound scans. Analgesic nephropathy alone does not explain asthma or eosinophilia.