Bronchiolitis Obliterans Associated with Polyarteritis Nodosa

Bronchiolitis Obliterans Associated with Polyarteritis Nodosa* Bruce W S. Robinson , M.D ., F.C .C .P.;and Gregory Sterrett, M.D .

FIGURE 1. Bronchoscopic views of the left main bronchus, showing

(left) tumor extension, obscuring the carina and the orifice of the

left lower lobe bronchus before HDR brachytherapy and the local situation thereafter. Following HDR (right), radical pneumonectomy could be performed.

cm intralumenal tumor length axis; specific activity iridium-192 10 Ci; 10 Gy at 1 cm from the source axis) in two sessions two weeks apart. The total duration of each bronchoscopic session was less than 15 min. On bronchoscopic evaluation four weeks after HDR, there was a significant reduction of the tumor mass (Fig 1). Biopsies and aspirates of the main carina and the proximal part of the mucosa of the left main bronchus were negative. A left pneumonectomy was carried out. The resected margin and all mediastinal lymph nodes were free of tumor (T2NOMO). No tumor recurrence has been assessed after a follow-upof 43 months. DISCUSSION

Our case documents that HDR is effective in reducing mucosal tumor infiltration. The HDR treatment prior to surgery permitted less extensive surgical resection avoiding resection of the main carina. The approach to use HDR to improve resectability in NSCLC seems especially appropriate in cases of intralumenal mucosal tumor infiltration. It may enable a less extensive surgical approach . The feasibility of this approach could be valuable in surgical candidates with limited pulmonary function . REFERENCES

Macha HN, Koch K, Stadler M, Schumacher W, Krumhaar D. New technique for treating occlusive and stenosing tumours of the trachea and main bronchi: endobrach ial irradiation by high dose Iridium-192 combined with laser canalisation. Thorax 1987; 42:511-15 2 Speiser B, Spratling L. High dose rate remote afterloading brachytherapy in the control of endobronchial carcinoma. In: Martinez AA, ed . Brachytherapy HDR and LDR: proceedings brachytherapy meeting: remote after loading: state of the art. Nucletron Columbia 1990; 10-23 3 Schray MF, McDougall JC, Martinez AA, Edmundson GK, Cortese DA. Management of malignant airway obstruction : clinical and dosimetric considerations using an iridium-192 afterloading technique in conjunction with the neodymium-YAG laser. Int J Rad Oncol Bioi Phys 1985; 11:403-09 4 Burt PA, O'Driscoll BR, Notley HM, Barker PY, Stout R. Intraluminal irradiation for the palliation of lung cancer with high-dose rate Micro Selectron. Thorax 1990; 45:765-68

Bronchiolitis obliterans with organizing pneumonia (BOOP) has not previously been described in association with polyarteritis nodosa (PAN). This report describes a patient in whom fulminant systemic PAN followed subacute onset of BOOP, with associated pulmonary arteritis. (Chest 1992; 102:309-11) HOOP = bronchiolitis obliterans with organizing pneumonia; PAN polyarteritis nodosa

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ronc h io li ti s obliterans with organizing pneumonia (BOOP) is usually not associated with any apparent cause of underlying disorder, although some cases occur after inhalation of noxious gases, recent infection, or one of the connective tissue disorders. I It has not previously been described in association with polyarteritis nodosa (PAN). This report describes a patient who presented with a systemic illness and BooP and whose underlying PAN did not become manifest until some months after the onset of his pulmonary disease. This report adds PAN to the list of associated disease processes to consider in a patient presenting with BOOP. CASE REPORT

A 71-year-old nonsmoking retired carpenter presented with a four-week history of fever, sweating, anorexia, malaise, weight loss (3.2 kg), dry cough, and muscle aches without chest pain, hemoptysis, or previous pulmonary disease . He was febrile (38°C) with signs collapse/consolidation in the left upper zone only plus paninspiratory crackles at both bases. A chest roentgenogram revealed patchy left upper zone consolidation. The white cell count was 15,6OOIcu mm (80 percent neutrophils with left shift; no eosinophilia). The hemoglobin level was 11.1 gIL (normal, 13 to 18 gIL); erythrocyte sedimentation rate , 90 mmlh; platelet count, 832,OOO/cu mm. The serum albumin concentration was 29 gIL (normal, 35 to 45 gIL); alkaline phosphatase , 287 UIL (normal, 35 to 135UIL); aspartate aminotransferase, 43 UIL(normal, 6 to 42 UIL); creatinine, 87 .... rnol/L (normal, <120 ....mol/L); urea nitrogen, 6.1 mmoVL(normal, 3 to 8 mmol/L), electrolytes, normal. Urine microscopic findings were normal. Levels of serum immunoglobulins G, M, A, and E were all within normal limits, and the antinuclear factor and rheumatoid factors were both normal. Hepatitis B serologic testing was negative. The patient was treated with systemic antibiotics (erythromycin, c1indamycin, and cefotaxime) but remained well. All investigations for infective agents were negative, specifically, sputum examination (including examination for acid-fast bacilli) and serologic testing for respiratory viruses (influenza A and B; adenovirus; parainfluenza I, ·From the University Department of Medicine, University of Western Australia (Dr Robinson), and Hospital and University Pathology Services, Sir Charle s Gairdner Hospital (Dr Sterrett), Queen Elizabeth II Medical Centre, Nedlands, Western Australia.

CHEST I 102 I 1 I JULY, 1992

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FIGURE 1. Open-lung biopsy specimen display s loose fibroblastic tissue filling alveoli and bronchioles and patchy nonspecific interstitial inflammation (hematoxylin-eosin, original magnification x 96).

Figure 3. Renal tissue obtained at autopsy shows necrotizing arteritis in an arcuate artery with aneurysm formation (hematoxylin-eosin, original magnification x 240).

II , and III ; respiratory syncytial virus ; cytomegalovirus; varicella) as well as for psittacosis, Q fever, Mycoplasma, and Legionella (all performed on two separate occasions) plus Toxoplasma, Leptospira, and Brucella. The patient remained unwell, and the cough persisted. A chest roentgenogram showed progression of the left upper zone changes, with infiltration of the right middle and upper zones. Bronchoscopy revealed no endobronchial lesion, and bronchial washings, brushings, and biops y revealed no infective organisms. Bronchoalveolar lavage was markedly abnormal with elevated neutrophil proportions (SO percent; normal , <4 percent) with some elevation in eosinophil and lymphocyte proportions (2 percent and 17 percent, respectively [normal, respectively) <1 percent and <16 percent). Open lung biopsy of the right upper lobe was performed four weeks after admission. Biopsy of the right upper lobe showed severe patchy alteration of lun~ architecture by IIK>se intra-alveolar fibroblastic tissue and associated nonspecifi c chronic interstitial inflammation . Many bronchioles contained IK>IYIK>id projections of fibroblastic and inflammatory tissue, and the numbers of identifiable bronchioles were reduced (Flg 1). Small, thick-walled muscular vessels were present within damaged lung tissue. One mediumsized artery demonstrated fibrinoid necrosis of the wall and infiltration by lymphocytes, histiocytes, and neutrophils (Fig 2). This vessel was cons idered to be a pulmonary artery, rather than a bronchial artery, because of its large size in relation to the adjacent bronchiolar structure; the vessel was similar in size to other pulmonary arteries in nearby lung, whereas identifiable bronchial arteries were of smaller diameter.

Postoperatively, the patient's renal function deteriorated, the creatinine level rising to 355 ....moVL. Urinalysis demonstrated hematuria, proteinuria, and occasional hyaline and granular casts. A renal biopsy was performed. One segmental area of glomerular fibrinoid change was evident , together with a mild focal and segmental increase in glomerular mesangial cellularity, and patchy interstitial infiltration. A large arcuate artery showed severe fibrinoid necrosis of the wall. Ultrastructurally, there were no electrondense deposits. Despite treatment with systemic methylprednisolone and cyclophosphamide , the patient developed ARDS one week postoperatively and died in respiratory and renal failure. At autopsy, the lungs exhibited alveolar exudation of neutrophils and maerophages and foci of hemorrhage and necrosis . Areas of pneumonia were also present, although fihrosis and or~anizin~ changes of bronchiolitis were difficult to find. No vasculitis could he identified in multiple lung sections, and no organisms were seen with special stain s. Th e kidne ys had mottled external surfaces with hemorrhagic and infarcted areas with aneurysrnally dilated blood vessels. Multiple foci of segmental or circumferential fibrinoid necrosis were observed microscopically in med ium-sized arte ries (Fig 3), as well as patchy interstitial hemorrhage and numerous foci of ischemic necrosis. Vasculitis was confirmed microscopically in the testes, deltoid muscle , tongue, sciatic nerve, prostate gland, and adrenal glands, Fibrinous pericarditis was noted .

FIGURE 2. Open-lung biopsy specimen shows necrotizing arteritis involving a medium-sized pulmonary artery (hematoxylin-eosin, original magnification x 240).

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DISCUSSION

The features of a systemic illness associated with patchy pulmonary consolidation, after exclusion of pulmonary infection, and the open-lung biopsy findings confirmed a diagnosis ofBOOP. This condition has a distinctive histologic pattern of subacute lung reaction to injury characterized by patchy lung involvement , intra-alveolar fibroblastic tissue, polypoid projections of fibroblastic and inflammatory tissue within bronchioles, bronchiolar destruction and disappearance, and a variable degree of interstitial inflammation and fibrosis.J.7,Il,'2 In most cases, there is no known precipitating event. The cryptogenic fonn of BOOP usually presents clinicall y as a severe subacute illness over several months with dyspnea, fever, and patchy or interstitial bilateral lung shadow ing. 1.3 Diagnosis is usually made at open-lung biopsy. Recognition of the pattern histologically and distinction from other fibrosing lung processes, in particular usual interstitial pneumonitis, is important, since most cases of Bronchiolitis Obliterans and PoIyerterilis Nodosa (Robinson. Slerrett)

cryptogenic BooP will respond to corticosteroid therapy and often resolve completely Some patients suffer progressive lung impairment and death. High-dose corticosteroids and cyclophosphamide failed to prevent progression of this patient's pulmonary or renal disease, suggesting that despite the subacute onset of his condition, the disease process in both organs accelerated rapidly at the end of his clinical course. The sequence of histologic changes was that of BooP followed by the development of florid PAN of the classic type, apart from one focus of necrotizing vasculitis in a medium-sized pulmonary artery. Although the lung exhibited one focus of necrotizing vasculitis, further vasculitis was not evident in lung at autopsy despite florid vasculitis elsewhere. The pathogenetic processes underlying the various forms of bronchiolitis obliterans are unknown. It has been suggested that, when associated with connective tissue diseases, heart-lung transplantation, and perhaps viral infection, the disease represents an autoimmune process whereby the host immune system responds to airway epithelial cell class II antigen expression induced by gamma Interferon.P-" Spontaneous gamma interferon production by cells obtained at bronchoalveoIar lavage was measured in this patient as part of another study and was very high (320 unitsll()6 cells in 24 h [normal individuals release slO unitsll()6cells in 24 h]);14.15 this finding is consistent with the above hypothesis. The failure to respond to treatment is a little unusual for BOO~ although death from progressive disease has been well described.'> This patient clearly had a very aggressive form of the disease. This report describes an association between BOOP and PAN, which suggests that similar pathogenetic mechanisms may be present in some patients with these disorders. Also, since BOOP can clearly precede the clinical manifestations of PAN, awareness of these facts may lead to careful monitoring for PAN and therefore to earlier therapy REFERENCES

1 Epler GR, Colby ~ McLoud TC, Carrington CB, Gaensler EA. Bronchiolitis obliterans organizing pneumonia. N Eng) J Med 1985; 312:152-58 2 Guerry-Force ML, Muller NL, Wright JL, Wiggs B, Coppin C, Pare PD, et ale A comparison of bronchiolitis obliterans with organizing pneumonia, usual interstitial pneumonia, and small airways disease. Am Rev Respir Dis 1987; 135:705-12 3 Muller NL, Guerry-Force ML, Staples CA, Wright JL, Wiggs B, Coppin C, et ale Differential diagnosis of bronchiolitis obliterans with organizing pneumonia and usual interstitial pneumonia: clinical, functional and radiologic findings. Radiology 1987; 162:151-56 4 Katzenstein AL, Myers JL, Prophet WD, Corley LS, Shin MS. Bronchiolitis obliterans and usual interstitial pneumonia. Am J Surg Patholl986; 10:373-81 5 Herzog CA, Miller RR, Hoidal JR. Bronchiolitis and rheumatoid arthritis. Am Rev Respir Dis 1981; 124:636-39 6 Kinney ~ Angelillo VA. Bronchiolitis in systemic lupus erythematosus. Chest 1982; 82:646-49 7 Geddes DM, Corrin B, Brewerton DA, Davies RJ, TurnerWarwick M. Progressive airway obliteration in adults and its association with rheumatoid disease. Q J Med 1977; 46:427-44 8 Epler GR, Snider GL, Gaensler EA, Cathcart ES, FitzGerald MX, Carrington CB. Bronchiolitis and bronchitis in connective

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tissue disease: a possible relationship to the use of penicillamine. JAMA1979; 242:528-32 Murphy KC, Atkins CJ, Offer RC, Hogg JC, Stein "B. Obliterative bronchiolitis in two rheumatoid arthritis patients treated with penicillamine. Arthritis Rheum 1981; 24:557-60 Homma H, Yamanaka A, Tanimoto S, Tamura M, Chijimatsu Y, Kira S, et al. Diffuse panbronchiolitis: a disease of the transitional zone of the lung. Chest 1983; 83:63-9 Schwarz MI, Matthay RA, Sahn SA, Stanford RE, Mannorstein RL, Scheinhorn DJ. Interstitial lung disease in polymyositis and dermatomyositis: analysisofsixcases and review of the literature. Medicine (Baltimore) 1976; 55:89-104. Theodore J, Lemiston N. Lung transplantation comes of age. N Eng) J Med 1990; 322:772-74 Burke CM, Glanville AR, Theodore J, Robin ED. Lung immunogenicity, rejection, and obliterative bronchiolitis. Chest 1987; 92:547-49 Halloran PF, Wadgymar A, Autenried E The regulation of expression of major histocompatibility complex products. Transplantation 1986; 41:413-20 Robinson BWS, McLemore TL, Crystal RG. Gamma interferon is spontaneously produced by lung T-Iymphocytes and alveolar macrophages in patients with pulmonary sarcoidosis. J Clin Invest 1985; 75:1488-95

Bilateral Proximal Pulmonary Artery Aneurysms Simulating Hilar Adenopathy· Hecla Girgis, M.D., F.C.c.~;t Michael Millet; M.D., F.C.C.~;t

Mani s. Kaouru, M.D., F.C.C.f?;t and David Spizamy, M.D.+

Proximal pulmonary artery aneurysms (PAAs) are rare. Most are associated with secondary pulmonary hypertension or a variety of rare systemic disorders. An asymptomatic adult patient presented with bilateral hilar enlargement on a routine chest roentgenogram. Computed tomography of the chest revealed 5 em bilateral proximal PAAs with a normal pulmonary trunk. The clinician should consider proximal PAA in the differential diagnosis of hilar enlargement. (Chat 1992; 102:311-13) DcoNA = speci6c diffusing capacity; PAA = pulmonary artery aneurysm; PT = pulmonary arterial trunk

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ilateral hilar enlargement is a relatively frequent roentgenographic pattern. In almost all cases, bilateral hilar enlargement is due to enlarged hilar lymph nodes or hilar vessels. Bilateral hiIar adenopathy is typically seen with either benign granulomatous disease (sarcoid and infection) or malignant disease. Vascular causes for bilateral hilar enlargement are far less common. The majority of proximal PAAs, those involving the pulmonary trunk and/or major divisions, are associated with pulmonary hypertension, either primary or secondary to a number of cardiopulmonary disorders.'? Isolated proximal PAAs in the absence of predisposing conditions are particularly unusual. 4 Also, all *From the tDivision of Pulmonary and Critical Care Medicine and iDivision of Diagnostic Radiol~ Henry Ford Hospital, Detroit. Reprint requests: Dr. Kavuru, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland 44195 CHEST I 102 I 1 I JUL"f, 1992

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