A Case of Granulomatosis With Polyangiitis With Pulmonary Nodules and Masses


 Background: Granulomatosis with polyangiitis (GPA) is autoimmune-mediated, necrotizing granulomatous vasculitis, primarily involving the upper and lower respiratory tract and kidneys. Pulmonary parenchymal necrosis, vasculitis, and granulomatous inflammation are the main pathological features. Pulmonary imaging visualizes various manifestations, like lung consolidation, ground-glass shadow, speckle shadow, nodules and mass shadows, cavitation, pulmonary interstitial change, pleural effusion, and multiple mediastinal lymph nodes enlargements, and stenosis or occlusion of a lobe or bronchus segment. Case presentation: We report a 53-year-old patient diagnosed with Granulomatous polyangiitis with multiple pulmonary nodules and masses, by ultrasound-guided lung mass puncture biopsy. After treatment with methylprednisolone, Mycophenolate Mofetil, compound sulfamethoxazole and cyclophosphamide, the patient's condition improved and the pulmonary lesions were better than before.Conclusions: In addition to specific infections and tumors, immunological diseases, especially granulomatous polyangiitis, should be considered when treating patients in a clinical setting with multiple pulmonary nodules and weights. Through close multidisciplinary cooperation and communication, the disease will be hopefully received timely diagnosis and early treatment, relieving pain for more patients.

We considered that the preliminary diagnosis was pulmonary in ammation or cancer. Thus, we made differential diagnoses based on the following aspects: (1) Pulmonary infection: The patient had no history of long-term hormone or broad-spectrum antibiotic use, and did not belong to the population with low immunity, had no fever, no night sweats, no cough or yellow sputum, no cough with odorous sputum, and laboratory examination showed procalcitonin, EB virus-DNA, CMV virus-DNA, fungal 1,3 D-glucan detection, fungal galactomannan detection, sputum bacteria and fungi cultivation, sputum smear with acid-fast bacilli were all negative. Therefore, we found no clear evidence of pulmonary pathogenic infection. ( However, to further clarify the diagnosis and communicate with the patients, a B-ultrasound-guided right lung biopsy was performed according to the suggestion of imaging specialists. The pathology displayed that right lung biopsy with chronic in ammation and brogenic hyperplasia. Immunohistochemical results: CD68+ (diffuse), SMA-, STAT6-, desmin-, S100-, CD34-, Bcl-2, ALK-, Ki67-, IgG-, IgG4- (Fig. 2). So, we did not think about lung cancer. According to the 2017 ACR/EULAR (American College of Rheumatology/ European Alliance against Rheumatism) granulomatous vasculitis classi cation criteria, patients with positive C-ANCA = 5 points, and patients with pulmonary imaging indications of the nodule, mass, or cavity formation = 2 points. Therefore, the patient with a total of 7 points, and a total score of 5 or more points was diagnosed with granulomatous vasculitis and treated with 80mg methylprednisolone iv drip QD, Mycophenolate Mofetil 0.5g PO bid, compound sulfamethoxazole one-piece PO TID, and cyclophosphamide 0.4g iv drip stat. After treatment for ten days, we reviewed the following indicators: White blood cell 9.25 × 10*9/L increased to 16.33 × 10*9/L, hemoglobin 103 g/L increased to 125 g/L, platelet 510 × 10*9/L decreased to 400 × 10*9/L, ESR 72 mm/H decreased to 27 mm/H, CRP 85.67 mg /L decreased to 0.87 mg /L. A reexamination of lung CT showed multiple patchy and blocky high-density shadows in both lungs, with multiple cords around them, local pleural thickening and pulling, cavities in some of the lesions, bands of slightly high-density shadows in the hollow of the left lower lobe, local bronchiectasis, and thickening of the bronchial wall. Compared with a CT from another hospital on June 15, 2018, the lesions were smaller to different degrees (Fig. 3).

Discussion And Conclusions:
Almost all GPA patients present with either upper airway or lower respiratory tract lesions (3). Types of GPA pulmonary lesions fall within a broad spectrum (3). The most commonly detected lesion types were nodules and masses, which most widely measured between 20-40 mm, varied in size, and buds may be located in all areas and are usually multiple and bilateral (4). Consolidation and thickening of the bronchial wall were also observed, including cavitation, necrosis, speculation, and invasion of the ssure, pleura, or diaphragm (4-6).
The process of pathetic necrosis is fundamental to the development of extravascular and vascular lesions (7). The microscopic hallmark of GPA is a triad of parenchymal disease, vasculitis, and granulomatous in ammation (5,8,9). Low power views of necrosis identi ed large areas with geographic decay that appeared basophilic, termed "blue necrosis." High power views of these necrotic zones showed microabscesses with neutrophilic and nuclear debris. The vasculitis of GPA impacts small vessels under 5 mm in diameter, including arterioles, venules, and capillaries. The vessel walls frequently exhibit chronic in ammatory in ltrates, neutrophil, brinoid, transmural necrosis, and granulomas (5).
GPA treatment includes remission-induction therapy and maintenance therapy. For remission-induction therapy, all cases require an initial prednisone dose of 1 mg/kg/d for 2 to 4 weeks, with a remissioninduction time of approximately 3-6 months. Severe cases (The Five-Factor Score, FFS ≥ 1 point), especially those with renal and pulmonary involvement requiring hyper oxygen or mechanical ventilation, can be given methylprednisolone 7.5-15 mg/kg/d for 1-3 days at initial treatment (10,11).
Cyclophosphamide, combined with GC, has been used since the 1970s to control severe vasculitis and maybe the rst choice for induction. The cyclophosphamide dose is 0.5-0.7 g/m2 body surface area, or 15mg/kg intravenous impingement, and administered at day 0, 14, 28, and once every three weeks after that until the disease was in remission. Patients aged > 65 years will receive a xed dose of 500mg per dose. Combined with sodium, methamphetamine can reduce bladder toxicity. The oral dose is 1-3 mg/kg/d, or 200mg QOD for 3-6 months, and 1mg/kg/day after stabilization for 1 or several years (10)(11)(12). CD20 monoclonal antibodies have been used since 2011 to induce remission and treat severe, recurrent vasculitis. The treatment dose is 375 mg/m2/ week for four weeks, or 1g every two weeks, for four weeks. RAVE (Rituximab in anti-neutrophil Cytoplasmic Antibody Associated with Vasculitis) tests show that Rituximab is not superior to cyclophosphamide when considering induction of remission. The main adverse reactions included anaphylaxis, infection, decreased immunoglobulin G (IgG) and immunoglobulin M during infusion (10)(11)(12).
In severe alveolar hemorrhage requiring mechanical ventilation, plasmapheresis contributes to the restoration of organ state and function. As adjuvant therapy for GC or CTX, enhanced plasmapheresis is feasible at the initial stage of induction, that is, one time per day for seven days, 2-3 L of plasma per exchange, after which the interval time extended (10)(11)(12).
Maintenance therapy lasts for 12 to 24 months. After pulse therapy of glucocorticoids, the dose should be reduced to 0.5-1 mg/kg/d for at least four weeks, gradually reduced to 12.5-20 mg/d for three months after that, and reduced to 5mg/d for six months. As for other drugs, including Mycophenolate Model, Azathioprine, Methotrexate, Le unomide, or Rituximab for maintenance therapy (10)(11)(12).
Furthermore, GPA patients should take compound sulfamethoxazole (2-6 tablets/d) regularly to prevent pneumocystis carinii pneumonia. Long-term use can reduce GPA recurrence and prolong survival.
The leading causes of recurrence were improper dosage or course of GC and cytotoxic drugs, co-infection, and signi cant stress.
Thus, we report a rare case of Granulomatous polyangiitis with multiple pulmonary nodules and masses like lung cancer as well as infection, which showed a good response after immunosuppressive therapy. Therefore, respiratory specialist and oncologists should be aware of the possibility of GPA when diagnosing patients with multiple pulmonary lesions.

Declarations:
Ethical Approval and Consent to participate This study was approved by the Review Board for Shandong Provincial Hospital A liated to Shandong First Medical University, in Jinan, P.R.China.

Consent for publication
Written informed consent was obtained from the patient for publication of this case report and accompanying images.

Availability of supporting data
The dataset supporting the conclusions of this article is included within the article.

Competing interests
The authors declare that they have no competing interests.  Compared with pulmonary CT of June 15, 2018, the lesions were smaller in different degrees.