30 December 2008

Dear Editor,


Not previously documented within paediatrics, we describe Wegener's granulomatosis (WG) with severe cardiac involvement in a 14-year-old Caucasian girl. Diagnosis of WG followed a 3-week history of fever, weight loss, rash, polyarthritis, cough, dyspnoea, post-nasal drip and epistaxis. High resolution computerised tomography (HRCT) revealed patchy consolidation, nodular opacities and ground glass changes, with restrictive pattern on lung function tests. Inflammatory markers were elevated, renal function impaired and cANCA PR3 positive (59.5 units). Skin biopsy showed small vessel vasculitis. Renal biopsy revealed crescentic glomerulonephritis, consistent with WG. Echocardiography was normal.

Management included pulsed methylprednisolone, oral prednisolone and intravenous cyclophosphamide. After 3 months of treatment, poor prognostic features persisted including low haemoglobin (Hb 9–10 g/dL), elevated ESR (40 mm/h), persistently positive cANCA, increasing proteinuria (ACR 200 mg/mm Cr) and transiently raised plasma creatinine (144 umol/L). In view of this, cyclophosphamide was replaced with rituximab (given as two intravenous pulses 2 weeks apart, with cyclophosphamide and methylprednisolone) followed by maintenance mycophenolate mofetil. This resulted in a clinical response and negative ANCA.

Three months post-rituximab, the patient developed a dry cough, dyspnoea on exertion and unilateral sensorineural hearing loss. ANCA, CD19 and CD20 remained negative. Bronchoscopy and echocardiography were normal. HRCT was static, but transfer factor reduced to 50% predicted. Daily pulsed methylprednisolone was given, proceeded by high-dose broad-spectrum intravenous antibiotics. Rapid deterioration followed with fever, fleeting vasculitic rash, increasing respiratory distress and oxygen requirement. There was no infection evident on blood cultures, pleural fluid samples or lung biopsy. Fresh blood in alveoli suggested pulmonary haemorrhage. Renal function declined rapidly (creatinine 170 umol/L) and continuous veno-venous haemofiltration commenced. Repeat echocardiogram revealed left ventricular dilatation, moderate mitral regurgitation and significantly impaired left ventricular function (fractional shortening 15–17%). Findings suggested acute myocarditis with impaired left ventricular function and associated pulmonary hypertension. Inotropic support was commenced.

With evidence of active disease without infection, treatment of underlying vasculitis was intensified using infliximab (6 mg/kg) and daily plasmapheresis. Despite this, the patient deteriorated with sudden ventricular fibrillation/ventricular tachycardia, converting to broad complex rhythm with no output. Heart failure secondary to WG, complicated by multi-system organ failure, was implicated as cause of death. A post-mortem examination was not carried out.

Paediatric WG typically presents with constitutional features, renal, pulmonary, ear, nose and throat involvement. Comparison of adult and paediatric cohorts demonstrate broadly similar organ involvement although cardiovascular complications are not described in paediatric WG.1 In adult series, cardiac complications include valvular thickening, regurgitation or prolapse, left ventricular global systolic dysfunction, regional wall motion abnormalities, pericardial effusion, left ventricular aneurysm and a large intracardiac mass.2,3 Frequently clinically silent, cardiac involvement is associated with increased morbidity and mortality.3

Standard treatment of WG (prednisolone and cyclophosphamide) produces remission rates of 85–91%, with 60% relapse rate, and risk of chronic organ damage.4 Poor prognostic features include renal involvement, initial lung involvement, cardiac involvement, positive baseline ANCA and persistently elevated ANCA.4 Relapse rate can be decreased by intensive treatment within the first 6 months of disease,4 prompting change of therapy in this patient when poor prognostic factors persisted. Case series and open label trials document impressive response to rituximab, including two prospective studies with complete response in 9/10 and 10/10 patients, respectively.5,6

This case demonstrates the existence of cardiac involvement in paediatric WG, associated with a poor prognosis. During the course of this 14-year-old girl's illness, treatment was intensified in response to the persistence of poor prognostic factors for disease. Despite this, this patient sadly died. Although a post-mortem was not carried out, the temporal existence of myocarditis associated with clinical deterioration in the absence of infection, suggests that the presence of cardiac involvement was instrumental in this girl's collapse and death.

It is important to consider the possibility of sub-clinical cardiac disease in paediatric WG. Recognition of cardiac involvement should prompt aggressive treatment, although optimum management remains unclear.


  1. Top of page
  2. Acknowledgements
  3. References

The authors would like to thank the patient's family for allowing us to publish this article.

We would also like to thank Dr Gordan Gladman, Consultant Cardiologist Royal Liverpool Children's Hospital, for his help with this report.


  1. Top of page
  2. Acknowledgements
  3. References