Bronchocentric granulomatosis : Clinical course illustrated by serial computerized tomography of the chest

Bronchocentric granulomato.,is is a pathological process characterized by granulomatous inflammation in conducting airways. i\ ca.,c of bronchoccntric granulomatosi s of unknown etiology in a previou.,ly well 24-year-old female is reported. The variable and often rluctuating course of this entity and its response to corticosteroids is demonstrated by serial computerized tomography nr the chest. The patho logy, etiology and therapy ofbronchoccntric gran ulomatosis is reviewed.

Granulomatose bronchocentrique: Evolution clinique illustree par tom odcnsitomctrie thoracique en serie RESUME : La granulomatose bronchocentrique est un process us pathologique caracteri se par une inflammation granulornateuse des cond uits ae riens.Un cas Jc granulomatose bronchocentriq ue J 'etiol ogie incon nue chez une femme de 24 ans auparavan t en bonne sante est signalc.L'evolution de cellc maladie souvent variable et ineertainc.et sa reponse aux cort icostero't'J es, est de mont rec par tomodens itomet rie thoraci4 uc en serie.La pathol ogic .l 'e tiologie l'l le traite menl Jc la granulomatose brnnchocentriquc sont examines.ticnt s.Thc radiographic appeara nce of BCG is diverse and no patte rn appears to he pathognomonic.Features on plain chest rad iographs do not consistently corre late with disease presentalion (3).To our knowledge the appearance of BCG on co111p11tcriLcd to111ography (CT) or the chest has not been descrihcd .
We report a patient with BCG for which no cause could he iden tified.CT or the chest was used to follow her clinical course and guide therapeutic decisions.
As the resu lt of our experience with this ratient we he lieve that CT may he a uscl'ul tool to follow the comse or this rathological process.

CASE REPORT
A 24-year-old fe male was ret'c1Ted for assessment or fluctuating fatigue.low grade fever.anorex ia and nonproductive cough associated with t'leeting alveolar opacities ovn the previous six months.There was no history or hc moptysis .She wa., treated intermittently with oral antihiotics !'or rresumcd infection without obvious hcncfit.She was previously well and had no personal or family history or asthma.She had 110 exposure to animals or occupational agents.She was a nonsmoker and had no hu111a11 immunoddiciency vi rus risk factors.Apart from intermittent use uf antihiotics over the previous months, she was taking no medication at the time of assessment.Her phvsical examination was normal.Her white hlood cl'II count w:~s elevated ( 17.0X 10 9 /L) with a prominent neutrophilia ( 13.(iXI o'J/L) without cosinophilia and her hemoglohin was 95 g/L with normal red hlood cell indices.Tia: sL•dimentalion rate was elevated to 43 nun/h.Urinalysis wa., normal.Chest radiograph revealed hi lateral, patchy, hasilar ,iirspacc di sease (Figure I).There was 110 evidence or airflow obstruction.and her clil'f'using capacity, corrected !'or hemoglohin, was normal.A CT scan of the chest demonstrated impressive basilar nodules some of which had cavitated (Figure I ).13rnnchoscopy with transhronchial hiopsy and hronchoalveolar lavage were noncontribuwry including cultures for fungi and bacteria.Open lung hiopsy showed airway centred ulcerative disease associated with acute neutrorhil-dominant inllammation admixed with a definite granulomatous component (Figure 2).There was no evidence or a primary vasrnlitis.Eosinophils were present hut did not predominate.Periodic-acid Schill.Ziehl-Neelson and silver methenamine stains as well as c ulture or tissue did not reveal any pathogens.These features were indicative of BCG.A search for an etiology was unrewarding.The patient had no history or asthma and scrum immunoglohulin E and aspcrgil-Jus prccipitins were not elevated.Rheumatoid factor.antinuclear antibodies.cumplemcnt studies and antineutrophil cytoplasmic antihudies (ANCA) were negative.
During convalescence from surgery all or her symptoms improved without specit'ic therapy.A follow -up CT scan one month later demonstrated that the parenchymal opacities were resolving and nu areas or cavitation cuuld be identified (Figure 3 ).Five months later she complained or right-sided pleurilic chest pain in the region or her surgery.A chest radiograph performed at this time appeared unchanged from her postoperative examinations.;\limited high resolution CT examination through the region of her pain was performed.Owing to a change in scan technique ( 1.:i mm versus 10 mm collimation) and patient positioning.subsequent CT scan (middle).w111c 0(11'/iiclt /1111/ rn1•i1111n/ (bottom / f111Tmi') levels wen: not identical lu those ohtained previously.Hmvevcr, a section obtained al approximately the same level as the initial study (Figure 3) and accom panying rnts did demonstrate recurrence u1• the lung nndulcs.Therapy cunsisting of daily prednisone 40 rng orally was initiated.
Her symptoms subsequently improved over two weeks.Prednisonc was decreased slowly uver one-and-a-hall' months

DISCUSSION
Lie.bow (4) characterized BCG as a necrotizing granulomatous inllammation centred on peripheral airways.He included BCG with the classificatiull of four fom1s of angiitis: classical Wegener's granuiomatosis; limited Wegener's; lymphomatoid granulomatosis; and necrotizing sarcoiu granulomatosis.However, BCG differs from these (it her diseases as it is not primarily angiocentriL• and uoes not involve extrapulmona1y sites.Katzenstein and colleagues (5) reviewed BCG and identified two groups of patients baseu on clinical and pathological findings in n patients.T he first cornpriscJ asthmatics in whom peripheral eosinuphilia and a sensitivity to aspergillus were observed.On examination ()f lung sections the lesions exhibited tissue cosinophilia in audition to granulomatous inflammation.Scattereu fungal hyphae could oftL•n be seen in the intraluminal exudate.In this group of patients BCG appears to represent a form of allergic bronchopulmonary aspergillosis and to be an inflammatory response to inhaled antigen (5).The seconu and larger group comprised nonasthmatie patients.
Eosinophiiia was absent and the airway-centred infiltrates were predominantly neutrophilic.Proximal obstruction with sustained inflammation and Jistentiun of uistal airways was commonly ohserved, anu this pathological appearance has been postulated to he a requirement for the development of' BCG ( I).In this regard, BCG likely represents the lung' s  11i.,w1e' 1111' 11m!t,l,,s again ,lisa1111e(l/"/'cl (bottom) limitL'U in fla mmatory response to a wiJc variety or inJurio us agents.As cmphasi1.cdhy Myers anJ Kalzenstcin (6), in this group or patients infectious causes nceJ to he care ful ly exdudeJ by appropriate cultures and tissue stains.In one stuJy of solitary necrotizing granulomas of the lung, 27'/o ol patients with tuherculosis hall bronchocentric granulrnnas identified (7).In aduition to tuberculosis.BCG has been reported in patients wit h hisloplasmosis.aspcrgillosis and echi nm:occu s inkL•tion (6.X.\Jl.BCG may also occur in patient s with scrnpositiw and seronegativc arthropathiL•s ( 10-12).
To add to tht: difficult y. BCG may be confused wit h Wegencr' s gra nulomalosi s.Reports or Wegcnc r' s granulomatosis de mo nst rating a relative •bronc hncc ntric • Jistrihution that predominated nver the associated angiitis have been described ( 13).Thus, the presence or primary vascular involvement needs lo he sought and the pr('.senceor ANCA excluded.Patients in whom Ihl cause including inl1:ction cou Id be idcnl i l'ied ha vc been reported and represented 2.'i'k, of Kaltenslicn and co-worker's patient population.
Our patient had no evidence or asthma or demonstrable sensitivity tu aspergillus.Despite apprnpriale staining and rnlturing of lung tissue and bronchualveular lavage samples, nu infectiou s et iology could be identified.Furthermore she had nn clinical or serological evidence or a collage n vascular disease nor evidence hislolugically lo support the diagnosis uf 'hronchoccntric' Wcgener's.Thus our patient appears lo have BCG or undefined etiology.
i\ variety of radiugraphic appearanL'L' S have been descrihed in BCG (3).Multiple, or more commonly Slllitary mass lesions, cavitating masses, alveolar filling and reticulorwcl ular patterns arc reported.Scallered nudules resembling metastasis have been scL• n in up lo .1:'i'/ior cases (.\..J.).An upper lobe d istribution appears lo predominate.Hilar lymph node enlargeme nt is infrequent.Hence.no radiographic pattern appears tu he specific for any etiology.\Ve are unaware or any description or the use nr CT in diag1Hlsing or following patients with BCG.In thi s patient.the initial CT appearance was dramatic and disproporti onate lo the radiographic appearance and her symptoms.Su bsequent llares in her illness were not accompanied hy any notable changes in her chest radiograph .CT scanning, however, was use ful in demonstrating regions of new pare nchymal disease.The superiority o f CT lo plain radiography has been descri hL•d in a varicty ol' diffuse lung disctscs.Mathieson cl al ( 14) dc111onstrated that. in the selling or diffuse interstitial lung disease, radi o logists ' level of diagnostic cunl'idcncl' and acrn racy was significantly greater for CT compared with chest radiography.CT scanning may also aid in dcrinin g tlK rnurse and progno.is of diffuse lu ng disease.In one study examining CT appea rances before and after therapy in pa tients with sarcoiclosis.ground-• glass, nodular.and interl obular sq1tal thickening correlated with potentially reversible disease.while cystic airspaces and architectural dis1ur1ion currclated with progressive or irreversible disease ( I)).In the present patient CT assislL•d in making therapeuti c dec isions and in l'ullowing her response to therapy .Importantl y. \Ve were able tu reduce the amount of radiation exposure by limiting CT imaging tu small rL•g ions of the chest and usin g 1.5 mm collimation scans as opposed lo IO mm collimation scans.In this regard CT scanning may he a more useful tool than chest radiography for assess ing activity or this pathologic cnl il y.
This patient also highli ghts the variable cuursc and response to trealmcnl in patients with BCG of unknown etiology.These patients often have sponlanCllUS remissions lw;ting mo nths to yea rs, making a.\Sessmcnts or response to therapy difficult.We arc conridcnl that the eorticoslcroids administered following her second flare wert: rL•sponsihiL'.for her clinical and radiographic improvc111enl.We base this assumption on the obscrvaliun that a return in her symptoms and parL•nchy111al densities paral leled attempts lo dccrc:1sc her duse of prednisone.In addition Ill curtinhtcroicb.cycltiphosphamicle, a1.atltiuprine and surgery (ror .single mass IL•sions) have been repo rted as being successful in cases wherL' infec ti ou s causes have been reliably excluded (:'i, !()).There are no prospecti ve in terventiunal studies for idiupalhic BCG and therape uti c claims arc l i mi lL'd tu case repurts.W c suggest that CT scanning may represent a usdul tool l'lir tile carL' lll' patients with BCG.pul111onary fibrosis u1111plicatcd by aspergilloma and hronchocentric gran ulomalosis.Thorax 1989:4-4:676-7.