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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 10  |  Issue : 2  |  Page : 105-111

Bronchus sign on HRCT thorax: presenting sign of Wegener granulomatosis with lung involvement — misdiagnosed as TB in presence of acino-nodular pattern on imaging


1 Pulmonary Medicine, MIMSR Medical College, India
2 Internal Medicine, MIMSR Medical College, Latur, India

Date of Submission02-Feb-2022
Date of Decision22-Mar-2022
Date of Acceptance28-Apr-2022
Date of Web Publication19-Dec-2022

Correspondence Address:
Shital Patil1
Pulmonary Medicine, MIMSR Medical College
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jacp.jacp_3_22

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  Abstract 


Abstract
Tuberculosis is the most common diagnosis in India in presence of constitutional symptoms such as cough, fever, and weight loss with lung parenchymal abnormality irrespective of microscopy or nucleic acid amplification test abnormalities in high TB prevalent tropical settings. Pulmonary manifestations of systemic vasculitis have very diverse involvement ranging from the nodule to consolidation. Bronchus sign is classically described in lung malignancies than Wegener disease. The acino-nodular pattern is classical of pulmonary tuberculosis, sometimes documented in fungal infections. In this case report, a 45-year-old female, presented with constitutional symptoms with lung parenchymal nodules, without mycobacterial microscopic or genome documentation, received empirical antituberculosis treatment with the progression of the disease without clinical or radiological response. Bronchoscopy workup is inconclusive and tropical screen for bacterial, fungal, TB, and malignancy was negative. Vasculitis workup was done in view of the presence of persistent fever and documented PR3-ANCA positive with very highly raised titers. We have started on steroid and cyclophosphamide and clinical response documented with near-complete resolution of shadows in 12 weeks. Pulmonary manifestations of Wegener disease are rare and underestimated and early pickup of the entity in course of illness will have a good outcome with an excellent prognosis.

Keywords: Acino-nodular masses, bronchus sign, HRCT (high resolution computerised tomography) thorax, Wegener granulomatosis


How to cite this article:
Patil1 S, Gondhali G. Bronchus sign on HRCT thorax: presenting sign of Wegener granulomatosis with lung involvement — misdiagnosed as TB in presence of acino-nodular pattern on imaging. J Assoc Chest Physicians 2022;10:105-11

How to cite this URL:
Patil1 S, Gondhali G. Bronchus sign on HRCT thorax: presenting sign of Wegener granulomatosis with lung involvement — misdiagnosed as TB in presence of acino-nodular pattern on imaging. J Assoc Chest Physicians [serial online] 2022 [cited 2023 Jan 28];10:105-11. Available from: https://www.jacpjournal.org/text.asp?2022/10/2/105/364442




  Introduction Top


Wegener granulomatosis (WG) rare systemic disease first described by German pathologist Friedrich Wegener in 1936, characterized by necrotizing, granulomatous small-vessel vasculitis that affects mainly the upper airways, lungs, and kidneys, but may affect any organ system. The most frequently affected organ is the lung, with involvement seen in more than 90% of patients with WG during the course of the disease. It is a multisystemic necrotizing vasculitis first described by German pathologist Friedrich Wegener in 1936.[1]

WG nodules may occur in a centrilobular distribution, mimicking tuberculosis, hypersensitivity pneumonitis, or an acute viral, bacterial, or fungal pneumonia.[2]


  Case Summary Top


A 45-year-old female, farmer by occupation, no addiction history, normotensive, nondiabetic, was referred to our center by a family physician for persistent fever, cough, and weight loss since 3 months of duration. She received symptomatic treatment initially with antibiotics and antipyretics and showed poor response to treatment. She was further evaluated with sputum workup as microscopy was not showing acid-fast bacilli and Gene Xpert MTB/RIF was negative for MTB genome. She received empirical antituberculosis treatment for 2 months, and poor response to treatment was the reason for her referral to our center for further workup.

Further clinical details:
  1. Fever persistent, high grade without chills and rigors associated with minimal body ache and headache
  2. Cough dry, intermittent, with minimal white sputum production
  3. Loss of appetite and weight loss over 3 months
  4. Weakness and myalgia with fatigability
  5. Shortness of breath on exertion


Clinical examination documented the following:
  1. Heart rate: 100/min; respiratory rate – 26/bpm; BP – 100/70 mmHg
  2. PsO2: 91% to 94% at room air resting and 89% to 91% at room air on exertion
  3. Respiratory system examination revealed bilateral breath sounds normal and bilateral crepitations heard on both lung fields
  4. Nervous system examination: Higher functions normal, no neurological abnormality, cranial nerves normal, recent and past memory normal recall
  5. Cardiovascular and gastrointestinal systems were normal


We further asked for more history regarding the progression of the disease over the last 3 months; her husband told regarding her recurrent nasal symptoms and multiple consultations for the same. The patient disclosed that she was having nasal stuffiness without nasal discharge and she was having nasal crusting, which had increased over the last 3 months. She also told that she was having multiple throat crusting and altered voice or dysphonia that was intermittent and spontaneously recovering with saline gargles.

Laboratory examination documented the following:
  1. Hemoglobin – 8.7 gm%; total white blood cells – 24,000/mm3; polymorphs – 85%: platelet count – 490,000/uL
  2. CRP – 248 mg/L (0–6 mg/L); random blood sugar level – 134 mg%; HbA1C – 5.60%
  3. LDH – 980 IU/L (70–470 IU/L); uric acid – 3.4 mg (3.5–7.5 mg/dL)
  4. Serum electrolytes: Sodium – 138 meq/L (135–145 meq/L); potassium – 3.9 meq/L (3.5–5.5 meq/L); ionic calcium – 1.32 meq/L (1.09–1.36 meq/L)
  5. D-dimer – 193 ng/mL (<500 ng/mL)
  6. IL-6 – 1.75 pg/mL (0.00–7.00 pg/mL)
  7. Thyroid functions – normal
  8. Liver and kidney functions – normal
  9. Sputum examination for acid-fast bacilli was negative and TB Gene Xpert MTB/RIF was negative for the MTB genome.
  10. COVID-19 RT PCR test and results documented negative for SARS-CoV-2.<RL>


A chest X-ray was done and showed bilateral upper, middle, and lower zone infiltrates ([Image 1]), which have progressed over 3 months. A chest X-ray at our center showed nodular and inhomogeneous parenchymal infiltrates involving all lung fields ([Image 1]a).
Image 1 (a) Chest X-ray showing bilateral middle and lower zone infiltrates. (b) Chest X-ray showing multiple bilateral nodular and air space opacities in middle and lower zone infiltrates.

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As clinical findings and chest X-ray were suggestive of bilateral lung pathology, we performed HRCT thorax.

HRCT thorax documented ([Image 2],[Image 3],[Image 4],[Image 5],[Image 6],[Image 7],[Image 8],[Image 9],[Image 10],[Image 11],[Image 12],[Image 13]) the following:
  1. Bilateral random nodules with masses
  2. Bilateral acino-nodular masses
  3. CT bronchus sign
  4. Lung parenchymal mass with air bronchogram
  5. Lung parenchymal mass with eccentric lucencies or breakdown
  6. Consolidation with lucencies
  7. Early parenchymal GGOs (i . e., precursor of nodules)
Image 2 HRCT thorax showing left lung mass with bilateral nodules with ground glass opacities

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Image 3 HRCT thorax showing bilateral nodules and masses showing lucent bronchus inline and on outer side of opacities i . e. positive bronchus sign

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Image 4 HRCT thorax showing left lung mass with eccentric lucencies or breakdown and bilateral nodules with ground glass opacities

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Image 5 HRCT thorax showing bilateral randomly placed nodules with ground glass opacities in upper lobe with positive bronchus sign

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Image 6 HRCT thorax showing bilateral randomly placed nodules with ground glass opacities in upper lobes, more on right side with positive bronchus sign

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Image 7 HRCT thorax showing bilateral randomly placed nodules with ground glass opacities in lower lobes, and nodular consolidation in right side lower lobe

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Image 8 HRCT thorax showing bilateral randomly placed nodules with ground glass opacities in lower lobes with positive bronhus sign

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Image 9 HRCT thorax showing bilateral randomly placed nodules with ground glass opacities in upper lobes with positive bronhus sign

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Image 10 HRCT thorax showing bilateral randomly placed nodules with perinodular ground glass opacities in upper lobes with positive bronhus sign

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Image 11 HRCT thorax showing bilateral randomly placed nodules with perinodular ground glass opacities in upper lobes with positive bronhus sign

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Image 12 HRCT thorax showing bilateral randomly placed nodules with perinodular ground glass opacities in lower lobes with positive bronhus sign

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Image 13 Chest X-ray showing near complete resolution of parenchymal abnormalities.

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As HRCT showed lung parenchymal abnormality with predominant acino-nodular masses bilaterally, we performed fiberoptic video-bronchoscopy as sputum examination was inconclusive.

Bronchoscopy examination revealed hyperemic mucosa at the lower trachea, carina, and purulent secretions coming out from bilateral main stem bronchial lumens, increased rugosity in segmental bronchial openings, no evidence of endobronchial growth, gross visible abnormality, and no evidence of submucosal or peribronchial abnormality. BAL was collected after 100 mL saline instillation and four aliquots were sent for cytology, Gene Xpert, and bacterial and fungal culture.

BAL cytology suggestive of acute inflammation, negative for malignant cell

BAL AFB – negative

BAL Gene Xpert MTB/RIF – negative

BAL bacterial culture – no growth

BAL fungal culture – no growth

As tropical workup was negative and there was no evidence of malignancy as probable etiology for bronchus sign, we sent a blood sample for vasculitis workup.

MPO-ANCA (C-ANCA) – 0.86 RU/mL (normal range 0–20 RU/mL)

PR3-ANACA (P-ANCA) – >200 RU/mL (normal range 0–20 RU/mL)

We stopped antituberculosis treatment, started injection methylprednisolone 40 mg IV TDS, cyclophosphamide at a dose of 50 mg OD, increased to 100 mg in the second week and 150 mg OD in the third week, and continued for 12 weeks, antipyretics for fever control, adequate oral liquids with intravenous fluids, and maintained hydration with kidney functions and liver functions tests monitoring. After 1 week, injectable methylprednisolone was shifted to oral and the dose decreased from 40 mg TDS to oral 48 mg and tapered over 12 weeks.

We added Trimethoprim Sulphomethaxazole (160/800) BD for 1 month and then OD for 1 month and once in week for 48 weeks. Strict monitoring of hemogram, renal, and liver function tests was done weekly for the first month and then monthly for 3 months till near-complete resolution of lung parenchymal opacity ([Image 13]) was documented with satisfactory clinical response.

After 3 months, we continued oral disease-modifying agents as methylprednisolone 4 mg daily with cyclophosphamide 100 mg daily was continued for additional 12 weeks and then methylprednisolone alternate day for 1 year and cyclophosphamide stopped after 1 year. Methylprednisolone 4 mg one tablet per week with Trimethoprim Sulphomethaxazole (160/800) one tablet per week continued for additional 48 weeks. We documented complete remission of lung manifestation after 3 months and maintained with disease-modifying agents till 2 years and maintained for an additional year without medicines.


  Discussion Top


WG was first described by German pathologist Dr Friedrich Wegener as rhinogenic granulomatosis in 1936 and is an uncommon vasculitis of small and medium-sized arteries. WG, which is an angiogenic and multiple systems necrotizing disease involving the upper and lower respiratory tract and kidneys, is affected by a number of factors, including heredity, infection, the immune system, and the environment, and diagnosis is typically confirmed via clinic and laboratory examinations.[3]

Pulmonary involvement ranges from subclinical changes evidenced by chest CT or bronchoalveolar lavage fluid to devastating hemoptysis.[4] The most common respiratory symptoms include cough, mild dyspnea, hemoptysis, and pleuritic chest pain.[4]

Lung nodules are the most common manifestation of WG and occur in approximately 40–70% of patients. Nodules are usually multiple and bilateral and occur without a zonal predilection. The size of WG nodules varies, most commonly measuring between 2 and 4 cm but ranging from a few millimeters to 10 cm.[5]

Cavitation occurs in approximately 25% of nodules larger than 2 cm; the walls of the cavities may be thin or thick and nodular. WG nodules and cavities may be easily mistaken for metastases, lung abscesses, or septic infarcts. As with any lung cavity, those occurring in WG may become secondarily infected, in which case gas-liquid levels may develop. Hemorrhage may occur around nodules and manifests on high-resolution CT as ground-glass opacity surrounding the consolidated nodule, referred to as the halo sign.[6],[7]

Lung consolidation and ground-glass opacity often occur in approximately 30% of patients with active WG and are usually the result of hemorrhage. When present in isolation, lung consolidation is often initially attributed to pneumonia, and WG may be diagnosed when consolidation persists despite appropriate treatment. Arteriolar involvement with WG may present as mosaic attenuation or tree-in-bud opacities.[8],[9]

Positive bronchus sign:[10] On chest CT images, the positive bronchus sign consists of an air-filled bronchus – seen as a tubular hypo-attenuation area – oriented toward a peripheral nodular formation. In 1988, Naidich et al.[11] highlighted the importance of the positive bronchus sign inside a peripheral nodule: prior to a possible bronchoscopy, this finding would be predictive of a diagnostic result of the examination itself. A clear explanation of this radiological sign was reported in the literature by Singh in 1998.[12] The hypoattenuation area may extend into the nodule – producing an air bronchogram. The bronchus sign is not found in all types of lesions, more frequently seen in masses (≥3 cm) and in those with spiculated margins. Several studies have shown that this sign is more often associated with malignant lesions and, in particular, with pulmonary adenocarcinoma with lepidic pattern and adenocarcinoma. The relationship between the affected bronchus and the mass, however, may present variants. Tsuboi et al.[13] have described four types: (1) the bronchus reaches the nodule and undergoes an interruption, (2) the bronchus arrives at the nodule and continues inside it, (3) the bronchus is compressed by the tumor, maintaining the intact mucosa, and (4) the bronchus is obstructed due to the submucosal spread of the tumor, causing an irregular thinning of the same. The description of the relationship between bronchus and lesion plays an important role in the diagnostic planning since in the first two types biopsy is indicated; in the other two cases, better results are obtained using transbronchial aspiration.[10]

In the present case report, bronchus sign with acino-nodular masses with air bronchogram with partially caveating nodules, that is, most of the radiological patterns of pulmonary involvement of WG, was present.


  Key learning points from this case report Top


  1. Pulmonary tuberculosis is the most common cause of bilateral pulmonary acino-nodular lesions on HRCT thorax due to its high prevalence and endemic nature of disease.
  2. Although the acino-nodular pattern is well described in pulmonary tuberculosis, other etiological reasons for similar findings are lung metastasis and systemic vasculitis.
  3. Bronchus sign is commonly documented in lung malignancy, pulmonary tuberculosis, and WG with bilateral nodules.
  4. Constitutional symptoms such as cough, fever, and weight loss with lung abnormality on HRTC thorax may mislead toward empirical treatment without documentation on microscopy and nucleic acid amplification tests.
  5. Persistent symptoms and poor response to antituberculosis treatment are a clinical clue toward ruling out other etiological factors for similar syndromic presentation. Upper airway symptoms such as nasal crusting and dysphonia were important defining pointers toward WG workup.
  6. Steroids are the cornerstone of treatment of WG with lung involvement and shown excellent response to steroids with addition of cyclophosphamide. Renal workup should be actively sought in all cases before initiation of cyclophosphamide treatment as many cases may document abnormality during the course of treatment.
  7. We recommend that all cases of constitutional symptoms with negative workup for tropical diseases screened including tuberculosis should undergo a prompt evaluation to rule out underlying systemic vasculitis as an etiological factor.
  8. WG is a treatable condition irrespective of lung involvement and has a good prognosis if renal function tests are normal.
  9. Pulmonary manifestations of Wegener disease is rare and underestimated and early pickup of the entity in course of illness will have a good outcome with an excellent prognosis.


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Allen SD, Harvey CJ. Imaging of Wegener’s granulomatosis. Br J Radiol 2007;80:757–5.  Back to cited text no. 1
    
2.
Lohrmann C, Uhl M, Kotter E, Burger D, Ghanem N, Langer M. Pulmonary manifestations of Wegener granulomatosis: CT findings in 57 patients and a review of the literature. Eur J Radiol 2005; 53:471–7.  Back to cited text no. 2
    
3.
Wegener F. Über eine eigenartige rhinogene Granulomatose mit besonderer Beteilgung des Arteriensytems und den Nieren. Beitr Pathol Anat Allg Pathol 1939;102:36–68.  Back to cited text no. 3
    
4.
Thickett DR, Richter AG, Nathani N, Perkins GD, Harper L. Pulmonary manifestations of anti-neutrophil cytoplasmic antibody (ANCA)-positive vasculitis. Rheumatology 2006; 45:261–8.  Back to cited text no. 4
    
5.
Armstrong P, Wilson AG, Dee P, Hansell DM. Imaging of Diseases of the Chest. 3rd ed. London, UK: Mosby International Limited; 2000.  Back to cited text no. 5
    
6.
Kim Y, Lee KS, Jung KJ, Han J, Kim JS, Suh JS. Halo sign on high-resolution CT: findings in spectrum of pulmonary diseases with pathologic correlation. J Comput Assist Tomogr 1999;23:622–6.  Back to cited text no. 6
    
7.
Farrelly CA. Wegener’s granulomatosis: a radiological review of the pulmonary manifestations at initial presentation and during relapse. Clin Radiol 1982;33:545–51.  Back to cited text no. 7
    
8.
Farrelly CA. Wegener’s granulomatosis: a radiological review of the pulmonary manifestations at initial presentation and during relapse. Clin Radiol 1982;33:545–51.  Back to cited text no. 8
    
9.
Hansell DM. Small-vessel diseases of the lung: CT–pathologic correlates. Radiology 2002;225: 639–53.  Back to cited text no. 9
    
10.
Chiarenza A., Esposto Ultimo L. et al. Chest imaging using signs, symbols, and naturalistic images: a practical guide for radiologists and non-radiologists. Insights Imaging 2019;10:114. https://doi.org/10.1186/s13244-019-0789-4  Back to cited text no. 10
    
11.
Naidich DP, Sussman R, Kutcher WL, Aranda CP, Garay SM, Ettenger NA. Solitary pulmonary nodules. CT-bronchoscopic correlation. Chest 1988;93:595–598.  Back to cited text no. 11
    
12.
Singh SP. The positive bronchus sign. Radiology 1998;209:251–252. https://doi.org/10.1148/radiology.209.1.9769839  Back to cited text no. 12
    
13.
Tsuboi E, Ikeda S, Tajima M, Shimosato Y, Ishikawa S. Transbronchial biopsy smear for diagnosis of peripheral pulmonary nodules and masses. Cancer 1967;20:687–698.  Back to cited text no. 13
    


    Figures

  [Image 1], [Image 2], [Image 3], [Image 4], [Image 5], [Image 6], [Image 7], [Image 8], [Image 9], [Image 10], [Image 11], [Image 12], [Image 13]



 

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