Christine Lenclud MD;(*1) Paul De V...

Christine Lenclud MD;(*1) Paul De Vuyst MD;(*1) Etienne Dupont M.D.;([unkeyable]) Michel Depierreux, M.D.;([unkeyable]) Paulette Ketelbant, M.D.;([unkeyable]) Michel Goldman, MD; Section

Anti-neutrophil-cytoplasm antibodies newly have been reported as serologic markers of Wegener's granulomatosis. We describe brace cases in which this proof appeared to be of great value in the diagnosis of Wegener's granulomatosis presenting as acute respiratory failure, a clinical setting in which it may be the no other than diagnostic test that can be safely and easily performed.

Wegener's granulomatosis is an rare disease characterized by necrotizing granulomatous lesions of the upper and lower respiratory tract, glomerulonephritis, and small canal vasculitis.[1,2] Classically, the diagnosis requires evidence of as well-as; not only-but also; not only-but; not alone-but necrotizing vasculitis and granulomas in the same or more of the affected organs,[3] the lung tissue being the best site for histologic diagnosis.

lately ANCA have been demonstrated in the sera of patients presenting with Wegener's granulomatosis. It has been allude toed that the titer of these antibodies could ponder disease activity.[4] In this article, we report brace cases of Wegener's disease presenting as acute respiratory failure with circulating ANCA.

CASE REPORTS

CASE 1

A 69-year-old woman was admitted to the hospital with a one-month history of flush productive cough with blood-streaked sputum asthenia and anorexia. A not many days before admission, she had conjunctivitis, which was treated with locally applied corticosteroids. For united year, she had complained of vertigo and headache. Physical examination showed a dullnes and inspiratory crackles at the right lung base. Initial laboratory studies were as follows: WBC 18500/cu mm with 70 percent neutrophils; ESR 105 mm/L h; fibrinogen, 750 mg/100 ml; LDH 322 U/L Other routine laboratory proofs were normal. The chest x-ray film showed an infiltrate at the right lung base. A diagnosis of infectious pneumonitis was made and erythromycin was given, 3 g daily. agricultures of blood, sputum and urine were negative. Serologic criterions for Mycoplasma, Legionella, Chlamydia, Psittaci and respiratory viruses were also negative. Fiberoptic bronchoscopy revealed a diffuse inflammatory mucosa with abundant mucopurulent and sanguinary secretions. The sputum improvements remained negative for acid-fast bacilli. flush persisted and the chest x-ray film showed extension of the infiltrate to the entire right lung field. upon the seventh hospital day, erythromycin was replaced by means of gentamicin and cefotaxime without clinical improvement. forward the 14th hospital day, she perform the operations indicated ined acute respiratory failure calling for intubation and ventilation, and acute renal failure for which iterative hemodialysis was started. Urinalysis showed microscopic hematuria and proteinuria (08 g/L) Serum electrophoresis, fulness studies for [C.sub.3], [C.sub.4] fractions and [CHsub50] were normal. Circulating immune complexe antinuclear antibodies and antiglomerular basement membrane antibodies were absent. onward day 21, she developed a coma without focal neurologic signs. The cerebral CAT scan showed significant hydrocephaly requiring ventriculoperitoneal derivation. An open-lung biopsy was done at the same time. Microscopic examination of the lung tissue showed characteristic lesions of Wegener's granulomatosis with granulomas and necrotizing vasculitis (Fig 1) At the same time the immunofluorescence criterion for autoantibodies against neutrophil cytoplasmic antigens (ANCA) was positive. This trial was performed on granulocytes prepared from healthy kindred donors by sedimentation of heparinized offspring on dextran followed by Ficoll-Hypaque gradient centrifugation. They were adjusted at 15 [10sup6]/ml in RPMI 1640 (Gibco) counterparted with 20 percent fetal calf serum solitary abode; squalids were centrifuged on glass slides by the agency of a Shandon Cytospin 2 at 1000 rpm and fixed in ethanol. After incubation with the patient's serum flourescein-conjugated goat antihuman IgG (Nordic, Tilburg, The Netherlands) was added. The serum titer, defined as the highest serum dilution giving an intracytoplasmic fluorescence, was 1:512

The patient received prednisolone and cyclophosphamide still died a few days later from septic impact caused by a Staphylococcus aureus infection originating from a central venous catheter. Postmortem examination showed pulmonary lesions similar to those described at open-lung biopsy, as well as a focal proliferative necrotizing glomerulonephritis with new moon formation. Other findings included endocarditis upon mitral and tricuspid valves and an important dilation of the brain's ventricular arrangement which was of unknown origin.

CASE 2