Case Discussion Chief complaints          Blood-tinged sputum for 2 months and fever, cough for 10 days        This 59-year-old male patient began to develop blood-tinged sputum in Aug 2000, but he dud not pay much attention to it. Unfortunately, fever and productive cough occurred in early October and he visited a local clinic but the symptoms persisted. He was admitted to another hospital on Oct 6, 2000. The chest radiograph showed infiltrates over bilateral lung fields ( Figure 1). Cefmetazole and gentamicin were given, and were shifted to Rocephin and Erythromycin due to persistent high fever. Repeated sputum examinations were negative for acid-fast bacilli. Because his condition did not improve, he was transferred to the emergency room of the National Taiwan University Hospital on Oct 12, 2000.       The patient was a heavy smoker for 40 years and had suffered from chronic cough for 6 months. The past history was otherwise unremarkable.       On examinations, the body temperature was 37℃, blood pressure 130/76 mm Hg, pulse rate 72 per minute, and the respiratory rate 18 per minute. His consciousness was clear. The conjunctivae were not pale and sclera was anicteric. Light reflex of the pupils was prompt and symmetric. The neck was supple without lymphadenopathy. The chest wall was symmetric and crackles could be heard over bilateral lung fields. The heart sounds were regular, without murmurs. The abdomen was flat and soft. There was no tenderness or rebound tenderness. The liver and spleen were not palpable. The extremities were movable and without cyanosis or edema. All peripheral pulses were intact.       The follow-up CxR and Chest CT scans showed multiple pneumonic patches of bilateral lung fields (Figure 2、3、4). <Lab > 1. Urinary analysis   Protein Bilirubin Urobil. RBC WBC Epith. Cast 89/10/16 30 -- 0.1 10-15 0-2 0-1 RBC 2. CBC   WBC RBC PLT HB MCV Seg. Lymph Mono. 89/10/13 20800 3.15 623 9.9 89.5 87.0 6.0   89/10/18 20900 3.22 455 10.0 91.0 90.2 3.3   89/10/20 22860 2.89 178 8.9         89/10/23 27780 2.81 39 8.2         89/10/26 40040 4.3 45 12.9         3. BCS   Alb Glo T-Bil D-Bil ALP GOT GPT BUN Cre Na K 891013 2.2 3.6 0.9   167 60 30 36 2.2 125 4.9 891019 1.0 1.6 0.9 0.6 85 116   87 2.6 139 4.9 4. Sputum Study: Date Gram's AFS Cytology 891020 Neg. Neg. Neg. 891027 Neg. Neg, Neg. 5. Clotting & DIC profiles:   PT PTT 3P FDP D-Dimer Fibrinogen Date sec sec   μg/ml μg/ml mg/dl 891018 18/12 40/38 Neg. 40-80 1.33 170 6. Blood pH/Gas 項 目: pH PCO2 PO2 HCO3 BE 日期   mmHg mmHg mEq/l mEq/l 891013 7.42 37.8 119.4 23.9 0.0 891016 7.17 71.8 49.3 24.9 -4.1 891019 7.42 43.3 58.9 27.8 3.5 7. Pleural effusion study Date WBC L:N:M Gram AFS TP Sugar LDH 10/13 1900 47:52:1 Neg Neg 3.5 119   10/23 500 31:51:18 Neg Neg 2.3 133 1770 8. Abdominal echo showed only parenchymal renal disease. 9. Viral marker: HBsAg(-), Anti-HBs(+), Anti-HCV(-) 10. Serology: ANA 1:40 Anti-basement memb. Ab(-) CRP: 20.8 mg/dl RA factor 1:10240 C3: 78.7 mg/dl C4: 9.8 mg/dl IgA 306. mg/dl IgG 1340 mg/dl IgM 64.3 mg/dl Cryoglobulin: Negative Antiphospholipid Ab: Negative Legionella Urinary Ag: Negative ANCA: PR3 (c-ANCA): 24.8 (positive) MPO (p-ANCA): 1.5 (negative) CMV Ab: 1:2 (--) 11. Blood culture: No growth 12. Bronchoscopy (89-10-19): Diffuse inflammatory mucosa. Much fresh blood and frothy sputum are noticed over both bronchial trees. There is no endobronchial lesion. Bronchoalveolar Lavage: PMN: 95.2%, macrophage: 2.6%, eosinophil: 0.4%, lymphocyte: 0.6% Hemosiderin-laden macrophage (+) Culture: No growth 13. Pathology：Lung biopsy: diffuse acute capillaritis, marked pleuritis with interstitial granuloma nodules and neutrophils infiltration. <COURSE and Treatment >       After admission, massive hemoptysis with acute respiratory failure developed on Oct 19 and the CxR lesions also deteriorated (Figure 5). He was intubated and was transferred to the MICU. Bronchoscopy showing large amount of frank bloody and frothy airway secretion from both lungs. Steroid pulse therapy (methyloprednisolon, 1000 mg/day x 3 days) and plasmaphoresis were started on Oct 21. Unfortunately, poor oxygenation persisted even under high PEEP and 100% of oxygen. Extracorporeal membrane oxygenation (ECMO) supportive system was used on Oct 22. Cyclophasphamide (750 mg/day x 1 day) was also given on Oct 25 because of deterioration of renal function and oligouria. Unfortunately, fever flared up on Oct 30 and the blood and sputum cultures yielded Acintobacter baumannii. Repeat steroid pulse therapy was continued but there was no clinical improvement. The patient passed away on Nov 2, 2000. 案例分析       本病例產生高燒，兩側之肺部浸潤、咳血，且尿中有紅血球柱體。應聯想到有可能產生肺腎症候群(pulmonary-renal syndrome)。此類疾病中包含了一些全身性之血管炎。由臨床表徵要得到確切診斷有時不太容易，需要血清學及病理之診斷輔助證據。Wegner's granulomatosis有時臨床表現並不具有典型之器官侵犯(上呼吸迫，肺及腎臟)，有時只有局部表現 (limited form)，但隨著病情進展幾乎都會侵犯肺及腎臟。本病例屬嚴重型之Wegner's granulomatosis。雖然經大量類固醇及免疫抑制劑治療仍無法改善、最終因敗血症及多器官衰竭而死亡。 繼續教育考題 1. (D) Which description below about Wegner’s granulomatosis is WRONG? A Is a form of noninfectious necrotizing systemic vasculitis B The disease may present with limited organ involvement but ultimately may involve the skin, paranasal sinuses, nasal septum, lungs, kidneys and other organs. C The blood vessel walls damage probably results from abnormal immune reactions (circulating immune complexes). D Only occurs in patients over 60 years of age 2. (C) Which of the following organ/system is NOT commonly involved in Wegener's granulomatosis (the classic “Wegener's triad”)? A The upper airways B Lungs C The pituitary glands D The kidney 3. (D) Which of the following descriptions of Wegener's granulomatosis is true? A Wegener's granulomatosis is a distinct form of systemic vasculitis B Wegener's granulomatosis and microscopic polyangiitis generally involve small and medium sized blood vessels C Other vasculitis such as polyarteritis nodosa, Takayasu arteritis and giant-cell arteritis usually involve medium or large sized blood vessels D All of the above 4. (D) Which of the following descriptions of the pulmonary manifestations of Wegener's granulomatosis is WRONG? A Pulmonary symptoms are present in the majority of patients B Symptoms included cough, dyspnea, hemoptysis, andpleuritic chest pain. C Common chest x-ray findings were infiltrates and/or nodules, which are often bilateral and cavitary D This disease will not involve the tracheobronchial tree 5. (D) Which of the following descriptions of the renal manifestations of Wegener's granulomatosis is(are) true? A Renal abnormalities are eventually present in most patients B Glomerulonephritis, if present, may be asymptomatic. C Biopsy may show focal necrotizing glomerulitis D All of the above 6. (D) Which of the following description of the concept of "limited Wegner's granulomatosis" is WRONG ? A The manifestations of Wegner's granulomatosis are quite variable and many patients do not manifest the classic "Wegener's triad" B There exists a subset of patients without renal involvement, who have been considered to have "limited" Wegner's granulomatosis C "Limited" disease often eventually progresses to involve the kidney D None of the above 7. (D) Which of the following finding is among the three major (diagnostic) pathological features of Wegener's granulomatosis? A parenchymal necrosis B vasculitis C granulomatous inflammation D All of the above 8. (C) Common laboratory features of active Wegener's granulomatosis prior to treatment don't  include A Leukocytosis, B Anemia C Normal ESR D Proteinuria 9. (D) Which of the following is NOT true for ANCAs ? A A group of autoantibodies directed against various cytoplasmic constituents of neutrophils B Can be divided into perinuclear (p-ANCA), cytoplasmic (c-ANCA), and atypical (a-ANCA) based on staining patterns C c-ANCA are detected in more than 90% of patients with active classic Weger’s granulomatosis and in 67 to 86% of patients with "limited" disease D c-ANCA is not detectable in other vasculitis 10. (D) About the current treatment of Wegener's granulomatosis, which description is WRONG ? A High dose prednisone (1 mg/kg) and cyclophosphamide (2 mg/kg) can be initiated simultaneously B In exceptionally ill patients, such as diffuse pulmonary hemorrhage or rapid progressive glomerulonephritis, a pulse of methylprednisolone (1 g, IV, daily for 3 days) and 3-4 mg/kg of cyclophosphamide for several days can be used C Cyclophosphamide should be continued for a prolonged period (at least 1 yr) after clinical remission, D If untreated, patients may recover spontaneously from the disease

答案解說 答案解說: 1.(D) Target patients: Females 3:2 over males; any age, but 30s to 40s most commonly # American College of Rheumatology Classification Criteria for Wegener's Granulomatosis: (a) Nasal or oral inflammation; (b) Abnormal chest radiograph; (c) Urinary sediment; (d) Granulomatous inflammation on biopsy 2 (C ) Pituitary gland 少 involve 3.(D) 所有敘述皆正確 4.(D) Tracheobronchial involvement with subglottic stenosis, ulcerating tracheobronchitis with or without inflammatory pseudotumors, tracheal or bronchial stenosis are also not uncommon 5.(D) 所有敘述皆正確 Kidney involvement in Wegner's granulomatosis: glomerulonephritis (80-90% of patients develop; and is the major life threatening problem: blood, protein and pus in the urine; later, decline in kidney function 6.(D ) 所有敘述皆正確 7.(D ) Histopathologic features of WG. (A) Represents geographic areas of parenchymal necrosis. (B) Vasculitis. (C) Presence of giant cells or granulomatous inflammation. 8.(C ) Elevated ESR。 9.(D ) C-ANCA is usually directed against proteinase-3 and less often bactericidal permeability increasing protein (BPI). C-ANCA may be present in a minority of patients with microscopic polyarteritis nodosa, pauci-immune necrotizing glomerulonephritis, and undifferentiated systemic necrotizing vasculitis, diseases with many of the same features as WG. C-ANCA may also occur in patients with unrelated nonvasculitic disorders such as amebiasis and occasional cases of pulmonary infection. 10.(D ) If untreated the generalized form of the disease is usually fatal, with greater than 90% mortality within 2 years of disease onset. With the advent of cytotoxic therapy greater than 90% of patients have long-term remissions. Top of Page