Granulomatosis with polyangiitis masquerading as disseminated tuberculosis in presence of bilateral lung cavities and hemorrhagic infarct

INTRODUCTION

Granulomatosis with polyangiitis (GPA) previously called as Wegener’s granulomatosis, is systemic vasculitis involving small and medium-sized vessels was first described by a German medical student in 1931 and, later German pathologist Friedrich Wegener in 1936 described the case series of “distinct form of vasculitis” in three middle age patients with small and or medium vessel vasculitis with granulomatous inflammation. Goldman and Churg, in 1954, published a review of 22 cases with this distinct small and medium vessel vasculitis with granulomatous inflammation defined as Wegener’s granulomatosis.^[1] In 2012, the classification of the modern nomenclature of systemic vasculitis was formulated at the Chapel Hill consensus conference, and Wegener’s granulomatosis was changed to GPA.^[2] Due to diverse radiological presentations, the majority of Wegner’s granulomatosis or GPA are usually misdiagnosed, and the majority of these cases receive empirical treatment. In tropical settings, GPA is misdiagnosed and usually treated as tuberculosis. In our case, we have observed that empirical anti-tuberculosis treatment (ATT) was offered in the presence of cavitating lung disease with eye and central nervous system (CNS) involvement which is misdiagnosed as disseminated tuberculosis.

CASE REPORT

In the present case, a 40-year-old female patient referred by her family physician for ATT-induced liver dysfunction and dehydration-induced renal dysfunction in the case of pulmonary tuberculosis suspect treated with empirical ATT. She is a farmer and housewife without any addictions and comorbidities, having constitutional symptoms such as fever, cough, and weight loss for 6 months. She was treated with oral and intravenous antibiotics and hospitalized in peripheral health centers. Her illness gradually worsened with a partial response to medical treatment. Due to cavitary lung disease in chest X-ray, she was labeled as a case of pulmonary tuberculosis without microbiological confirmation and documentation of mycobacterium tuberculosis (MTB) genome in cartridge-based nucleic acid amplification tests (CBNAAT) and negative sputum smear microscopy. She was treated with empirical ATT for 4 months and referred to our center for ATT-induced hepatotoxicity and dehydration due to her inability to tolerate anything by mouth. We have done high-resolution computed tomography (HRCT) thorax and documented bilateral, peripheral multifocal consolidations involving middle and lower lobes with air bronchogram consolidation with lucencies [Figure 1]. Cerebrospinal fluid (CSF) analysis done at the neurology center due to headache and revealed normal biochemistry, lymphocytosis with 10 cells, adenosine deaminase level 6 IU/L (normal range 0–10 IU/liter), and microbiological examination negative from Gram stain and Ziehl–Nelson stain. CSF CBNAAT was negative for the MTB genome. Her fundoscopic examination findings records revealed papilledema with optic atrophy due to chronic papilledema [Figure 2]. Both eyes’ fundus examination documented disc edema, cup full, pallor present, and gross vascular attenuation [Figure 3]. Magnetic resonance imaging brain imaging documented subacute non-hemorrhagic infarct right occipital lobe and deep microvascular ischemic changes [Figure 4]. Retrospectively, the patient narrated a history of crusting in the nose and throat with intermittent altered speech for 2 years.

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Figure 1:

High-resolution computed tomography (HRCT) thorax showing bilateral, peripheral consolidation.

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Figure 2:

Fundoscopic examination showing papilledema with optic atrophy.

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Figure 3:

Fundus examination showing optic disc edema, optic cup full, and pallor present with gross vascular attenuation.

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Figure 4:

Magnetic resonance imaging brain imaging showing subacute non-hemorrhagic infarct right occipital lobe and deep microvascular ischemic changes.

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During hospitalization, ATT was withheld or omitted and supportive treatment was started for renal and liver dysfunction with targets for maintenance of hemodynamic parameters such as blood pressure, urine output, and respiratory rate. Her general condition and liver functions improved. We have repeated HRCT thorax documented bilateral pulmonary cavities, randomly placed, bizarre-shaped, irregular, thin, and thick-walled at some point without fluid level. A few cavities are giant, stepladder appearance, and variegated appearance. Some cavities contain radio-opaque mass-like structures attached to one side wall, possibility of mycetoma [Figure 5].

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Figure 5:

High-resolution computed tomography (HRCT) thorax bilateral peripheral, pleural-based thick-walled, irregular, variegated, and bizarre-shaped cavities with intracavitary opacities.

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A bronchoscopy was performed for a definitive diagnosis of cavitary lung disease with a negative microbiological workup. During bronchoscopy, an abnormality was documented in tracheobronchial lumens from the mainstem to segmental bronchial areas with abundant mucopurulent secretions coming out from the bronchial lumen was collected in three different aliquots and sent for bacterial, fungal, and malignancy. Bacterial, and tuberculosis workup were found inconclusive with negative CBNAAT results. We have done vasculitis workup in the presence of typical radiological patterns and bizarre-shaped peripheral lung cavities to rule out GPA. Vasculitis workup showed myeloperoxidase antineutrophil cytoplasmic antibody (ANCA) (P-ANCA) 0.92 RU/mL (normal range 0–20 RU/mL) and proteinase 3-ANCA or C-ANCA was >280 RU/mL (normal range 0–20 RU/mL).

During hospitalization, after clinical stability and general health improvement, we initiated acute GPA management protocol and started injection of Methyl prednisolone (MPS) 40 mg intravenously 3 times for 7 days, a tablet of azathioprine 50 mg 1 time daily. During the 2^nd week, azathioprine dose was increased to 100 mg for 12 weeks. Other supportive care, intravenous fluids, oral liquids, and antipyretics were given as a hospital protocol to maintain hemodynamic stability. Oral methylprednisolone tablet 48 mg was given in three divided doses, and the injection of methylprednisolone was stopped. Protocolized tapering of methylprednisolone was done over 12 weeks as a 4 mg reduction in every 1 week and a dose of 4 mg was maintained afterward. Additional treatment with Trimethoprim Sulfamethoxazole (160/800) was given as two times daily for the one month for the prevention and treatment of secondary opportunistic infections in GPA induced pulmonary cavities due to disease related and steroid induced immunosuppression. After 1 month, trimethoprim sulfamethoxazole (160/800) was given 1 time daily for3 months and decreased to 1 time per week for 2 years. We have monitored hemogram, liver, and kidney functions weekly, then monthly as a protocol to assess further steroid, and azathioprine-induced organ dysfunction.

Antifungal tablet voriconazole 200 mg 2 times daily was given for 12 weeks for resolution of fungal colonization in pulmonary cavities. We have documented complete resolution of radiological abnormality including pulmonary cavities and fungal colonization in followup HRCT thorax with satisfactory clinical response [Figure 6].

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Figure 6:

High-resolution computed tomography (HRCT) thorax normal lung parenchyma with resolution of lung parenchymal abnormalities.

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We have documented complete remission of GPA during maintenance of azathioprine 100 mg 1 time daily for 2 years with monitoring of complete hemogram, liver, and kidney functions monthly.

DISCUSSION

GPA is characterized by small and medium-sized vessel vasculitis, also called as a pulmonary-renal syndrome, with predominant otorhinolaryngological complications. The exact etiology of this multisystem disease is unknown. The possible link of ANCA was precluded in the pathophysiology of GPA. ANCA is a plausible pathway for inflammatory insult documented in GPA and complex interactions between microbial proteins and host genetics would have been documented to increase susceptibility and occurrence in selected cases. In addition, ANCA activates the proliferation of neutrophils toward the endothelium of small and mediumsized vessels with abnormal degranulation of neutrophils will cause endotheliitis and microabscesses and finally, ill-defined or poorly formed granulomas will form, which has been very well documented in histopathology.^[3]

CONCLUSION

In the present case report, we have observed clinical scenarios in GPA misdiagnosed as cavitary lung disease due to tuberculosis with CNS dissemination and failed to show clinical and radiological response to ATT. Recurrence of symptoms with the withdrawal of steroids and bronchoscopy-guided workup ruled out tuberculosis with superadded cavitary fungal infection. Vasculitis workup established GPA with systemic involvement and documented successful treatment outcome after treatment with methylprednisolone, azathioprine, and voriconazole with complete remission and radiological resolution of lung lesions.