• Medication adverse effects and chemical toxic effects should be taken into account: E.g. ANCA-associated vasculitis after treatment with D-penicillamine / propylthiouracil or Goodpasture-like syndrome after hydrocarbon exposure (e.g. organic solvents, fuels, paints, glues and motor exhausts).

The crucial question in the present case was to differentiate between infectious versus immunological causes since both entities require specific therapeutic strategies.

Therefore, vigorous efforts were made to exclude underlying infection: multiple blood, urine, and bronchoalveolar cultures were drawn and an empiric antimicrobiological therapy with imipenem and ciprofloxacin was begun. However, all microbiological specimens remained sterile and moreover, there were no positive results from microbiological antigen or antibody testing.

A key finding was revealed by reviewing the medical history: the patient used to complain about arthralgias (asymmetric oligoarthritis) and bloody nasal discharge for three months before admission.

The urinary sediment was microscopically examined. It revealed numerous dysmorphic erythrocytes and red cell casts.

Figure 3

Dysmorphic erythrocytes in urinary sediment

Subsequently, a kidney biopsy was performed:

Figure 4

Section of a renal biopsy specimen with a single glomerulum (original magnification 400):

Glomerulonephritis with extracapillary proliferation and crescent formation (arrow)

[Histology courtesy of Professor Gröne, German Cancer Research Center, Heidelberg]

The renal biopsy showed a pauci-immune, focal and segmental glomerulonephritis with crescent formation.

An immunological laboratory testing was performed, revealing a high antineutrophil cytoplasmic autoantibody (ANCA) titer of 1:320. The PR3-ANCA was 19kU/L (normal range <5). The ANA and anti-GBM antibody testing were negative.

Question 4

Diagnosis: Wegener`s Granulomatosis

Transbronchial lung biopsy and nasal biopsy could not confirm granulomatous inflammation .

It is worth mentioning, that the detection of ANCA by assays specific for proteinase 3 (PR3) and myeloperoxidase (MPO) are highly specific for WG, MPA, and CSS. Therefore, they are valuable tools to distinguish these patients from those with various pulmonary diseases or multi-organ dysfunction (9) .

An immunosuppressive therapy with oral cyclophosphamide (3mg per kg body weight per day) and prednisolone (500 mg i.v. for three days, afterwards 1mg per kg BW per day orally) was begun on day two after referral. The clinical picture of the patient rapidly improved:

On day 7 after referral the mechanical ventilation could be stopped, the last hemodialysis therapy was performed on day 8, and the patient was discharged from the ICU on day 10. He was discharged from hospital in clinically complete remission 4 weeks later. At that time serum creatinine fell towards levels between 3.5 and 4.5 mg/dL.

Wegener`s granulomatosis may take a fulminant, life-threatening course. In pulmonary-renal syndrome, it is mandatory to have a comprehensive lists of differential diagnoses in mind, however ANCA-associated vasculitis should be on top of it. The present case and two previously published cases clearly elucidate the fact, that the initiation of immunosuppression early enough may rapidly reverse even dramatic and life-threatening courses of WG requiring ECMO therapy (10;11).

Acknowledgement:

We are indebted to Professor Hermann-Josef Gröne and Dr Eva Kiss (German Cancer Research Center, Heidelberg) for providing the renal histology of the patient.