Chronic febrile respiratory illness with acino-nodular consolidations as presenting feature of granulomatosis with polyangiitis: A case report with review of literature

Shital Patil; Gajanan Gondhali; Deepak Patil

doi:10.4103/japt.japt_24_22

CASE REPORT

Year : 2022 | Volume : 5 | Issue : 3 | Page : 116-120

Chronic febrile respiratory illness with acino-nodular consolidations as presenting feature of granulomatosis with polyangiitis: A case report with review of literature

Shital Patil¹, Gajanan Gondhali², 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	03-Aug-2022
Date of Decision	01-Nov-2022
Date of Acceptance	08-Dec-2022
Date of Web Publication	01-Mar-2023

Correspondence Address:
Prof. Shital Patil
Department of Pulmonary Medicine, MIMSR Medical College, Latur, Maharashtra
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/japt.japt_24_22

Abstract

Pulmonary tuberculosis (TB) is the most common cause for chronic febrile respiratory illness with constitutional symptoms in India being endemic and more prevalent in the nature of disease. Acino-nodular consolidations are documented in infective, inflammatory, autoimmune, and systemic vasculitis with pulmonary involvement. Pulmonary manifestations of systemic vasculitis have very diverse involvement ranging from nodule, consolidation, and cavitation. In this case report, a 40-year male, presented with constitutional symptoms such as persistent fever, anorexia, and minimal dry cough lung parenchymal consolidations. Patients' symptoms progressed over 4 months with poor response to empirical anti-TB treatment without mycobacterial microscopic or genome documentation in sputum. Bronchoscopy workups were inconclusive and tropical screens for bacterial, fungal, TB, and malignancy were negative. Clinical-radiological worsening and acinonodular masses with cavitation guide us to work for vasculitis panel and documented proteinase 3-antineutrophil cytoplasmic antibody positive with very highly raised titers. We have started on steroids with cyclophosphamide and observed excellent clinical and radiological response in 24 weeks.

Keywords: Acino-nodular consolidations granulomatosis with polyangiitis, C-antineutrophil cytoplasmic antibody, chronic febrile respiratory illness, tuberculosis

How to cite this article:
Patil S, Gondhali G, Patil D. Chronic febrile respiratory illness with acino-nodular consolidations as presenting feature of granulomatosis with polyangiitis: A case report with review of literature. J Assoc Pulmonologist Tamilnadu 2022;5:116-20

How to cite this URL:
Patil S, Gondhali G, Patil D. Chronic febrile respiratory illness with acino-nodular consolidations as presenting feature of granulomatosis with polyangiitis: A case report with review of literature. J Assoc Pulmonologist Tamilnadu [serial online] 2022 [cited 2023 Mar 21];5:116-20. Available from: https://www.japt.in//text.asp?2022/5/3/116/370809

Introduction

Wegener's granulomatosis (WG) or granulomatosis with polyangiitis (GPA) 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 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 (TB), hypersensitivity pneumonitis, or acute viral, bacterial, or fungal pneumonia.^[2]

Case Report

A 40-year-old male, a farmer by occupation, no addiction history, normotensive, nondiabetic, referred to our center by a family physician with a history of persistent fever, minimal dry cough, and weight loss for 4 months of duration, received symptomatic treatment initially with antibiotics and antipyretics shown poor response to treatment, further evaluated with sputum workup as microscopy was not showing acid-fast bacilli and GeneXpert Mycobacterium TB (MTB/RIF was negative for MTB genome, received empirical anti-TB treatment (ATT) for 4 months, poor response to treatment and developed drug-induced hepatitis and was the reason for referral to our center for further workup.

Further clinical details:

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 4 months, intermittent initially progressed to persistent type and transiently responding to antipyretics. Fever was moderate-to-high grade without chills and rigors associated with minimal body ache and headache
Cough – for 2 months dry, intermittent, with minimal white sputum production
Loss of appetite and weight loss over 2 months
Weakness and myalgia with fatigability for 2 months
Shortness of breath on exertion in the last 2 months.

Clinical examination documented as follows:

Restless, dry oral mucosa, pallor, and febrile.

Heart rate – 118/min, respiratory rate: 26/bpm, and BP – 90/60 mmHg.

PsO2: 91%–94% at room air resting and 89%–91% at room air on exertion.

Respiratory system examination revealed – bilateral breath sounds normal, adventitious sounds as crepitation's heard over the right interscapular and intrascapular area.

Nervous system examination – higher functions normal, no neurological abnormality, cranial nerves normal, recent and past memory normal recall.

Cardiovascular and gastrointestinal systems were normal.

We have assessed past records of hospitalization as follows:

Chest X-ray was done and showed right middle zone inhomogeneous opacification [Figure 1] and high-resolution computed tomography imaging [Figure 2], [Figure 3], [Figure 4], [Figure 5] done before hospitalization were showing right middle lobe and lower lobe acino-nodular consolidations.

Figure 1: Chest X-ray PA. PA = Posteroanterior

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Figure 2: HRCT thorax showing right middle lobe consolidations

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Figure 3: HRCT thorax showing multifocal ground glass opacities and consolidations in right lower lobe

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Figure 4: HRCT thorax showing consolidations in right middle lobe

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Figure 5: HRCT thorax showing acinonodular consolidations in right middle lobe

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Sputum examination for acid-fast bacilli was negative and TB GeneXpert MTB/RIF was negative for the MTB genome.

High-resolution computed tomography findings were documented as follows:

Right middle lobe pleural-based airspace opacity with ground-glass opacity [Figure 2]
Right lower lobe acino-nodular mass with feeding vessel and pleural-based airspace opacity with ground-glass opacity [Figure 3]
Right lower lobe pleural-based airspace opacity with feeding vessel and ground-glass opacity with consolidation [Figure 4]
Right middle lobe pleural-based consolidation with central lucency or cavitation [Figure 5]
Right lower lobe pleural-based acino-nodular mass with feeding vessel [Figure 5].

The patient had received empirical ATT as per weight band with isoniazid, rifampicin, pyrazinamide, and ethambutol for 2 months for febrile chronic respiratory illness with acino-nodular opacities. He tolerated ATT well and showed significant improvement on symptoms for a shorter duration. After completion of the intensive phase, he was shifted to the continuation phase with isoniazid, rifampicin, and ethambutol. He tolerated for 2 weeks and started on the reappearance of symptoms such as cough, fever, and anorexia, for which referred to our center for further workup in line to rule out multidrug-resistant TB. We have documented ATT-induced adverse drug reactions after laboratory workup in presence of significant anorexia and jaundice.

We, further ask for more history regarding the progression of the disease over the past 4 months, his wife told him regarding recurrent nasal symptoms and multiple consultations for the same. The patient was having nasal stuffiness without nasal discharge and nasal crusting which was increased over the past 3 months.

Laboratory examination documented as follows:

Hemoglobin – 9.0 gm%, total white blood cells – 21000/mm³, polymorphs – 85%, and platelet count – 490000/μL
Kidney function test – Serum (Sr) creatinine – 1.1 mg/dl (0.6–1.2 mg/dl) and blood urea – 28 mg/dl (10–40 mg/dl)
Liver function tests – Sr bilirubin – 14 mg/dl (06–1.2 mg/dl), indirect – 10.4, and direct – 3.6
Sr alanine aminotransferase – 1786 IU/L Sr aspartate aminotransferase – 1921 IU/L
Sr proteins – Total 6.8 gm%, albumin – 3.8 and globulin – 3.0
Sr alkaline phosphatase – 190 IU/L
C-reactive protein – 281 mg/L (0–6 mg/L) and random blood sugar level – 110 mg%
Lactate dehydrogenase – 1080 IU/L (70–470 IU/L) and uric acid – 3.4 mg (3.5–7.5 mg/dL)
Pro-BNP (brain 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)
Interleukin-6 – 9.75 pg/ml (0.00–7.00 pg/ml).

Thyroid functions – Normal

COVID-19 RT-PCR (Real-Time Reverse Transcription Polymerase Chain reaction) test and results documented negative for SARS-CoV-2. We have stopped ATT, a supportive treatment for liver dysfunctions, with intravenous fluids for dehydration and shock. 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 the right main stem bronchial lumen with increased rugosity in segmental bronchial openings without any evidence of endobronchial growth or any gross endoscopically visible submucosal or peribronchial 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 is suggestive of acute inflammation and negative for malignant cells.

BAL acid-fast bacillus – negative and GeneXpert MTB/RIF – negative
BAL bacterial culture – no growth
Fungal culture – no growth.

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 – antineutrophil cytoplasmic antibody (ANCA) and (P-ANCA) – 0.86 RU/ml (normal range 0–20 RU/ml)
Proteinase 3 (PR3) – ANCA and (C-ANCA) – >200 RU/ml (normal range 0-20 RU/ml).

Treatment was initiated with injection methylprednisolone 40 mg IV TDS, cyclophosphamide at a dose of 50 mg OD, increased to 100 mg in 3^rd 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 has been shifted to oral and the dose decreased from 40 mg TDS (three times in a day) to oral 48 mg and tapered over 24 weeks. We have added trimethoprim-sulphamethoxazole (160/800) two times for 1 month then one time daily for 1 month and once in a week for 48 weeks. Strict monitoring of hemogram, renal and liver function tests were done as weekly for 1^st month and then monthly for 12 months, till near-complete resolution of lung cavities and lung parenchymal abnormalities [Figure 6] and [Figure 7] were documented with satisfactory clinical response.

Figure 6: HRCT thorax showing normal lung parenchyma in bilateral upper lobes

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Figure 7: HRCT thorax showing complete resolution of acinonodular consolidation with normal lung parenchyma in bilateral lower lobes

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After 6 months, we continued oral disease-modifying agents such 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-sulphamethoxazole (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 multiple system 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 clinic and laboratory examinations.^[3]

Pulmonary involvement ranges from subclinical changes evidenced by chest computed tomography (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 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 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.^[7],[8]

One of the modifications that are anticipated in the 2011 Chapel Hill Consensus Conference (CHCC) nomenclature is a recommended change from the diagnostic term “WG” to “GPA,” which has already been advocated by some of the 2011 CHCC participants.^[9],[10] This is justified both on the general rule that diagnostic terms with eponyms are less effective than more descriptive terms that refer to one or more distinctive features of a disease and, in the specific instance of WG, on the evidence that Dr. Friedrich Wegener was a member of the Nazi party before and during World War II.^[11]

Unexplained fever and increasing leukocytosis were significant features of our patient's presentation and course. In one retrospective survey, fever was described as the first symptom in 33% of patients.^[12] Occasionally, GPA can present with protracted fever without localizing signs, as in our patient, although this is uncommon. Pyrexia of unknown origin is most commonly secondary to infectious disease. Fever secondary to occult collagen vascular disease is less common.^[13],[14] In a retrospective cohort of 857 patients, 16% had a fever due to collagen vascular disease. Only 0.3% of the entire cohort had a fever secondary to GPA.^[15] Our patient's fever resolved completely after the first dose of methylprednisolone.

In the present case report, chronic febrile respiratory illness with acinonodular opacities with positive feeding vessel signs has offered empirical ATT for possible pulmonary TB. We have performed bronchoscopy due to partial response to ATT with clinical and radiological worsening. Bronchoscopy-guided BAL workup ruled out TB and other causes for lung parenchymal lesions. We have diagnosed with case GPA by documenting significantly raised PR3-ANCA (C-ANCA) titers. We have treated as per standard protocol and documented satisfactory treatment outcomes.

Key learning points from this case report are as follows:

Pulmonary TB is the most common cause for chronic febrile respiratory illness with constitutional symptoms in India due to its endemic and more prevalent natural disease
Although acinonodular masses with constitutional symptoms are well described in pulmonary TB, other etiological reasons for similar findings are lung other tropical infections like fungal and vasculitis with lung involvement
Vasculitis workup is a must in presence of acino-nodular opacities which are topographically pleural based and with positive feeding vessel sign
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 like nasal crusting and dysphonia were important defining pointers toward GPA workup
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
Steroids are a cornerstone of treatment of GPA 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 diseases screen including TB should undergo a prompt evaluation to rule out underlying systemic vasculitis as the etiological factor
GPA is a treatable condition irrespective of lung involvement and has a good prognosis if renal function tests are normal
Pulmonary manifestations of GPA are rare and underestimated and early pickup of the entity in course of illness will have a good outcome with an excellent prognosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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