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| CASE REPORT |
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| Year : 2022 | Volume
: 13
| Issue : 2 | Page : 103-109 |
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Wegener's granulomatosis mimicking like pulmonary tuberculosis and presenting as cavitating lung disease with mycetoma: A case report with review of literature
Shital Patil1, Deepak Patil2
1 Department of Pulmonary Medicine, MIMSR Medical College, Latur, Maharashtra, India
2 Department of Internal Medicine, MIMSR Medical College, Latur, Maharashtra, India
| Date of Submission | 16-Jul-2022 |
| Date of Acceptance | 12-Nov-2022 |
| Date of Web Publication | 10-Jan-2023 |
Correspondence Address:
Dr. Shital Patil
Department of Pulmonary Medicine, MIMSR Medical College, Latur, Maharashtra
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/mjmsr.mjmsr_37_22
Pulmonary tuberculosis (TB) is the most common cause of bilateral pulmonary cavities with constitutional symptoms in India being endemic and more prevalent nature of the disease, irrespective of microscopy or nucleic acid amplification test abnormalities. Pulmonary manifestations of systemic vasculitis have very diverse involvement ranging from nodule, consolidation, and cavitation. In this case report, a 45-year-old female, presented with constitutional symptoms with lung parenchymal consolidations progressed to cavitation, and started empirical anti-TB treatment without mycobacterial microscopic or genome documentation in sputum with clinical or radiological worsening. Bronchoscopy workup is inconclusive and the tropical screen for bacterial, TB, and malignancy was negative and fungal yield Aspergillus colonization. A vasculitis workup was done in the presence of clinical and radiological worsening documented PR3-antineutrophil cytoplasmic antibody positive with very highly raised titers. We have started on steroids and cyclophosphamide with antifungals and clinical response was documented with a near-complete resolution of shadows in 24 weeks.
Keywords: Cavitating lung disease, high-resolution computed tomography thorax, mycetoma, pulmonary tuberculosis, Wegener's granulomatosis
How to cite this article:
Patil S, Patil D. Wegener's granulomatosis mimicking like pulmonary tuberculosis and presenting as cavitating lung disease with mycetoma: A case report with review of literature. Muller J Med Sci Res 2022;13:103-9 |
How to cite this URL:
Patil S, Patil D. Wegener's granulomatosis mimicking like pulmonary tuberculosis and presenting as cavitating lung disease with mycetoma: A case report with review of literature. Muller J Med Sci Res [serial online] 2022 [cited 2023 May 28];13:103-9. Available from: https://www.mjmsr.net/text.asp?2022/13/2/103/367404 |
| Introduction | |  |
Wegener's granulomatosis (WG) is a 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. Wegener's granulomatosis is an uncommon multisystemic disorder of unknown aetiology with classical necrotizing granulomatous vasculitis in histopathology.[1]
WG nodules may occur in a centrilobular distribution, mimicking tuberculosis (TB), hypersensitivity pneumonitis, or acute viral, bacterial, or fungal pneumonia.[2]
| Case Report | | |
45-year-old female farmer by occupation and no addiction history, normotensive and non-diabetic, referred to our center by family physician for-ATT induced hepatitis with history of intermittent fever, cough and weight loss for 6 months of duration. She was started on symptomatic treatment initially with antibiotics and antipyretics and observed poor response to treatment. She was further evaluated with sputum microscopy and Gene Xpert MTB/RIF with inconclusive reports for AFB and MTB genome. She received empirical anti-tuberculosis treatment for 4 months and showed poor response to treatment. She was diagnosed with ATT induced hepatitis, and finally referred to our center for adverse drug reaction management and to rule out alternative diagnosis.
Further clinical details are as follows:
- Jaundice – recent onset, yellowish discoloration of eyes with nails, associated with nausea and vomiting, unable to tolerate anything by mouth, resulted in decreased urine output in the past 7 days
- Fever – for 6 months, intermittent, moderate-to-high grade without chills, and rigors associated with minimal body ache and headache
- Cough – for 4 months dry, intermittent, with minimal white sputum production
- Loss of appetite and weight loss for 6 months
- Weakness and myalgia with fatigability
- Shortness of breath on exertion in the past 2 months.
Clinical examination documented as follows:
- Restless, dry oral mucosa, pedal edema-pitting type, pallor, and febrile
- Heart rate – 130/min, respiratory rate: 26/bpm, and blood pressure – 80/60 mmHg
- PsO2: 91%–94% at room air resting and 89%–91% at room air on exertion
- Respiratory system examination revealed – bilateral breath sounds normal, bilateral crepitation's heard on both lung fields
- Nervous system examination – higher functions normal, no neurological abnormality, cranial nerves normal, and recent and past memory normal recall
- Cardiovascular and gastrointestinal systems were normal.
We have assessed records of hospitalization as follows:
Chest X-ray was done and showed bilateral lower lobe inhomogeneous opacification [Figure 1] and inhomogeneous opacification with cavitation seen in the right paracradiac region in the lower zone [Figure 2]. | Figure 1: Chest X-ray posteroanterior view showing bilateral lower zone inhomogeneous opacities
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 | Figure 2: Chest X-ray posteroanterior view showing inhomogeneous opacities with cavitations in the right paracradiac region
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Laboratory examination documented as follows:
- Hemoglobin – 11.7 g%, total white blood cells – 6000/mm3, polymorphs – 70%, and platelet count – 390,000/uL
- C-reactive protein [CRP] – 165 mg/L (0–6 mg/L), random blood sugar level – 134 mg%, and HbA1C – 5.60%
- Lactate dehydrogenase (LDH) – 880 IU/L (70–470 IU/L) and uric acid – 3.4 mg (3.5–7.5 mg/dL)
- Serum electrolytes: Sodium – 132 mEq/L (135–145 mEq/L), potassium – 3.9 mEq/L (3.5–5.5 mEq/L), and ionic calcium – 1.32 mEq/L (1.09–1.36 mEq/L)
- D-dimer – 560 ng/ml (<500 ng/ml)
- Interleukin-6 (IL-6) – 1.75 pg/ml (0.00–7.00 pg/ml)
- Thyroid functions – normal
- Liver and kidney functions – normal.
Sputum examination for AFB was negative and TB GeneXpert MTB/RIF was negative for the MTB genome.
High-resolution computed tomography (HRCT) of the thorax is suggestive of:
- Bilateral, peripheral multifocal consolidations [Figure 3] and [Figure 4] involving
- Middle and lower lobes [Figure 5] with
- Consolidation with air bronchogram [Figure 5] and [Figure 6]
- Consolidation with lucencies [Figure 3], [Figure 4], [Figure 5], [Figure 6].
 | Figure 3: High-resolution computed tomography of the thorax showing bilateral, peripheral, multifocal consolidations.
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 | Figure 4: High-resolution computed tomography of the thorax showing bilateral, peripheral, multifocal consolidations in middle and lower lobe
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 | Figure 5: High-resolution computed tomography of the thorax showing bilateral, peripheral, multifocal consolidations with cavitations in lower lobes
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 | Figure 6: High-resolution computed tomography of the thorax showing bilateral, peripheral, pleural based consolidations in lower lobes
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As she was started on empirical ATT for lung parenchymal opacities as per weight band with isoniazid, rifampicin, pyrazinamide, and ethambutol for 2 months, she tolerated well and showed significant improvement in symptoms for a shorter duration. After completion of an intensive phase, she was shifted to the continuation phase with isoniazid, rifampicin, and ethambutol without steroids; she tolerated for 2 weeks and started on the reappearance of symptoms such as cough, fever, and anorexia; we have evaluated for other diagnosis or ATT-induced adverse drug reactions due to significant anorexia and jaundice.
Laboratory examination documented as:
- Hemoglobin – 8.7 g%, total white blood cells – 21,000/mm3, polymorphs – 85%, and platelet count – 490,000/μL
- KFT: Serum (Sr) creatinine – 2.8 mg/dl (0.6–1.2 mg/dl) and blood urea – 87 mg/dl (10–40 mg/dl)
- Urine proteins – 1+ (380 mg/dl)
- Liver function tests: Sr bilirubin – 12 mg/dl (0.6–1.2 mg/dl): indirect – 8.4 and direct – 3.6
- Sr alanine aminotransferase – 1681 IU/L and Sr aspartate aminotransferase – 1980 IU/L
- Sr proteins – Total 6.8 g%: albumin – 3.8 and globulin – 3.0
- Sr alkaline phosphatase – 190 IU/L
- CRP – 249 mg/L (0–6 mg/L) and random blood sugar level – 110 mg%
- LDH – 980 IU/L (70–470 IU/L) and uric acid – 3.4 mg (3.5–7.5 mg/dL)
- Pro-BNP (NT-proB-type Natriuretic Peptide) – 96 pg/ml (<125 pg/ml)
- Serum electrolytes: Sodium – 138 mEq/L (135–145 mEq/L), potassium – 5.9 mEq/L (3.5–5.5 mEq/L), and ionic calcium – 1.26 mEq/L (1.09–1.36 mEq/L)
- D-dimer – 450 ng/ml (<500 ng/ml)
- IL-6 – 1.75 pg/ml (0.00–7.00 pg/ml)
- Thyroid functions – normal
- COVID-19 reverse transcription-polymerase chain reaction test and results documented negative for SARS-CoV-2.
Chest X-ray suggestive of bilateral lung pathology predominantly cavities with inhomogeneous infiltrates in bilateral lower zones [Figure 7] | Figure 7: Chest X-ray posteroanterior view showing inhomogeneous opacities with cavitations in bilateral lower zones
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We further ask for more history regarding the progression of disease over the past 3 months, her husband told her regarding 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 was increased over the past 3 months; she also told that she was having multiple throats crusting and altered voice or dysphonia which was intermittent and spontaneously recovering with saline gargles.
We performed HRCT thorax and documented as follows [Figure 8], [Figure 9], [Figure 10]: | Figure 8: High-resolution computed tomography of the thorax showing bilateral, multifocal, irregular, variegated cavities
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 | Figure 9: High-resolution computed tomography of the thorax showing bilateral, multifocal, irregular, variegated cavities with opace or radiodense fungal elements
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 | Figure 10: High-resolution computed tomography saggital section shwoing layered, irregular cavities with fungal elements
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- Bilateral, multiple, peripheral, and pleural-based thick-walled cavities with few cavities containing radiopaque mass inside [Figure 8]
- Bilateral, multiple, peripheral, and pleural-based thick-walled single and giant cavities with few cavities containing radiopaque mass inside with variegated appearance [Figure 9]
- Bilateral, multiple, peripheral, and pleural-based thick-walled single and giant overlapping cavities "stepladder pattern" with few cavities containing radiopaque mass inside with variegated appearance [Figure 10].
We have stopped anti-tuberculosis treatment and started supportive treatment for liver and renal dysfunctions with intravenous fluids for dehydration and shock as per gastroenterologists and nephrologist opinion. They suggested a treatment protocol for 'pre-renal syndrome'. Her general health, liver and kidney dysfunctions were improved in two weeks. After clinical stability, we have decided on bronchoscopy to rule out tropical etiology.
Bronchoscopy examination revealed hyperemic mucosa at the lower trachea, carina, and purulent secretions coming out from bilateral main stem bronchial lumens. There were increased rugosity in segmental bronchial openings and no evidence of endobronchial growth or gross visible abnormality. Bronchoalveolar lavage (BAL) was collected after 100 ml saline instillation and four aliquots were sent for cytology, GeneXpert, and bacterial and fungal culture.
- BAL cytology suggestive of acute inflammation and negative for malignant cell
- BAL AFB – negative and GeneXpert MTB/RIF – negative
- BAL bacterial culture – no growth
- Fungal culture – Aspergillus species
- As the tropical workup was negative and no evidence of malignancy as a probable etiology for bronchus sign, we sent a blood sample for vasculitis workup.
MPO (myleoperoxidase)- antineurtophil cytoplasmic antibody (ANCA) (P-ANCA) – 0.86 RU/ml (normal range 0–20 RU/ml)
PR3-ANCA (proteinase 3 antineutrophil cytoplasmic antibody) or C-ANCA- >200 RU/ml (normal range 0–20 RU/ml)
A nephrologist consultation was taken for renal involvement and decided to wait and watch for renal functions, and plan for a biopsy in follow-up. We have done a renal biopsy at a 3-month follow-up and microscopy showed normal histology.
We have started injection methylprednisolone 40 mg IV TDS and oral cyclophosphamide 50 mg OD and gradually increased to 100 mg in the second week which was continued till 12 weeks. We have treated symptomatically with antipyretics for fever control and maintained hydration with adequate oral liquids and intravenous fluids. Strict monitoring of hemogram, Renal and Liver function tests were done weekly for the first month and then monthly till 24 months. Tablet voriconazole was started at 200 mg BD for 12 weeks and documented significant improvement in lung cavities. After 1 week, injectable methylprednisolone has been shifted to oral and dose decrease from 40 mg TDS to oral 48 mg and tapered over 24 weeks.
We have added trimethoprim-sulfamethoxazole (160/800) BD for 1 month and then OD for 1 month and once a week for 48 weeks. Strict monitoring of hemogram and renal and liver function tests were done weekly for 1st month and then monthly for 12 months, till near-complete resolution of lung cavities and lung parenchymal abnormalities [Figure 11], [Figure 12], [Figure 13], [Figure 14] were documented with satisfactory clinical response. | Figure 12: High-resolution computed tomography of the thorax showing normal lung parenchyma middle lobes
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 | Figure 13: High-resolution computed tomography of the thorax showing normal lung parenchyma upper lobes
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 | Figure 14: High-resolution computed tomography of the thorax showing normal lung parenchyma lower lobes
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After 6 months, we have continued oral disease-modifying agents as methylprednisolone 4 mg daily with cyclophosphamide 100 mg daily continued for additional 24 weeks and then methylprednisolone alternate day for 1 year and cyclophosphamide stopped after 1 year. Methylprednisolone 4 mg one tablet per week with trimethoprim-sulfamethoxazole (160/800) one tablet per week continued for additional 24 weeks. We have documented complete remission of lung manifestation after 3 months and maintained with disease-modifying agents till 18 months.
| Discussion | | |
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 multisystemic 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 through the clinic and laboratory examinations.[3]
Pulmonary involvement ranges from subclinical changes evidenced by chest CT or BAL 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 cm 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 HRCT 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.[7],[8]
In present case report, we have documented clinical scenario in Granulomatosis with Polyangiitis (GPA) mimicked as pulmonary tuberculosis and shown partial response to ATT. Clinical-radiological worsening with cavitations and negative microbiological workup for tuberculosis had given clue to workup towards other causes for similar presentation. Vasculitis workup diagnosed as case of Granulomatosis with Polyangiitis (GPA) with systemic involvement. We have documented improvement in clinical and radiological manifestations with systemic steroids and cyclophosphamide. We have treated as per the standard protocol and documented satisfactory treatment outcomes.
Key learning points from this case report are as follows:
- Pulmonary TB is the most common cause of bilateral pulmonary cavities with constitutional symptoms in India being endemic and more prevalent nature of disease
- Although bilateral pulmonary cavities with constitutional symptoms are well described in pulmonary TB, other etiological reasons for similar findings are lung and other tropical infections such as fungal and vasculitis with lung involvement
- Persistent symptoms and poor response to ATT is a clinical clue toward to rule out other etiological factors for similar syndromic presentation. Upper airway symptoms such as nasal crusting and dysphonia were important defining pointers toward WG workup
- Constitutional symptoms such as cough, fever, and weight loss with lung abnormality on HRCT of the thorax may mislead toward empirical treatment without documentation on microscopy and nucleic acid amplification tests
- Steroids are the cornerstone of treatment of WG with lung involvement shown excellent response to steroids with cyclophosphamide and renal workup should be actively sought in all cases before initiation of treatment as many cases may document abnormality during the course of treatment
- We recommend, all cases of constitutional symptoms with negative workup for tropical disease screen including TB should undergo a prompt evaluation to rule out underlying systemic vasculitis as an etiological factor
- WG is a treatable condition irrespective of lung involvement and has good prognosis if renal function tests are normal
- Pulmonary manifestations of Wegner's disease are rare and underestimated, and early pickup of the entity in course of illness will have good outcome with an excellent prognosis.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Allen SD, Harvey CJ. Imaging of Wegener's granulomatosis. Br J Radiol 2007;80:757-65.  |
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| 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. |
| 4. | Thickett DR, Richter AG, Nathani N, Perkins GD, Harper L. Pulmonary manifestations of Anti-Neutrophil Cytoplasmic Antibody (ANCA)-positive vasculitis. Rheumatology (Oxford) 2006;45:261-8. |
| 5. | Armstrong P, Wilson AG, Dee P, Hansell DM. Imaging of Diseases of the Chest. 3 rd ed. London, UK: Mosby International Limited; 2000. |
| 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. |
| 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. |
| 8. | Hansell DM. Small-vessel diseases of the lung: CT-pathologic correlates. Radiology 2002;225:639-53. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13], [Figure 14]
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