Granulomatosis With Polyangiitis Presenting as Deep Vein Thrombosis in an Adolescent: A Rare Case Report

ABSTRACT

Granulomatosis with polyangiitis can rarely present as deep vein thrombosis in adolescents. Unexplained thrombosis in a young patient, accompanied by systemic inflammatory features, should raise suspicion for an underlying vasculitis. Early recognition and prompt initiation of immunosuppressive therapy alongside anticoagulation are crucial to prevent diagnostic delay and improve clinical outcomes.

1. Introduction

Granulomatosis with polyangiitis (GPA), previously known as Wegener's granulomatosis (WG), is a rare immune‐mediated systemic vasculitis affecting small vessels. It is pathologically defined by a distinct inflammatory response, including necrosis, granulomatous inflammation, and vasculitis [1]. It occurs equally in men and women, typically manifesting between ages 65 and 74, with an incidence of 13 cases per million person‐years [2]. It is the most frequent type of ANCA‐associated vasculitis in the pediatric population, though it remains a rare presentation in children [3].

GPA predominantly targets the airways and kidneys with its destructive inflammatory processes, but it has the potential to affect any organ system [4]. Patients with GPA have an increased risk of venous thromboembolism (VTE), though deep vein thrombosis (DVT) is rarely the initial presentation of the disease [5, 6]. The mechanisms underlying the increased risk of VTE in GPA remain unclear but are linked to systemic inflammation and disordered thrombogenesis [7]. GPA is diagnosed based on clinical presentation, ANCA serology, and histopathology, as no standardized criteria exist [8]. Management includes immunosuppressants such as cyclophosphamide, methotrexate, and corticosteroids. Without treatment, GPA is rapidly progressive with a two‐year survival rate of just 10%, but timely therapy has significantly improved long‐term outcomes [9].

This case report describes a 16‐year‐old patient who presented with DVT as the first manifestation of GPA, highlighting the importance of considering GPA in the differential diagnosis of unexplained thrombotic events in adolescents. This report follows the CARE (CAse REport) guidelines to ensure comprehensive and standardized clinical case documentation [10]. This case report has been prepared in accordance with the updated TITAN Guidelines 2025, which govern the transparent and ethical use of Artificial Intelligence in scientific writing and research [11].

2. Case History/Examination

A 16‐year‐old male presented to the otorhinolaryngology department with swelling over the right side of the nose, measuring approximately 2 × 2 cm. The lesion appeared bluish and bled upon touch. Initial diagnosis of nasal vestibulitis was made, and the patient was treated with antibiotics. However, he continued to experience systemic symptoms including intermittent fever associated with chills and rigors, with a maximum temperature recorded at 101°F and sweating during defervescence.

The patient reported multiple episodes of spontaneous epistaxis—five to six in total—often preceded by nose picking, each requiring anterior nasal packing. He also described a dry cough, a single episode of hemoptysis, and progressive hoarseness of voice. Over the past few weeks, he experienced significant malaise and unintentional weight loss, noticeable through the loosening of his clothes. Dermatologic findings included purpuric macules on the dorsum of both feet and the ears. He further developed right‐sided lower limb swelling, characterized by non‐pitting edema. There was no history suggestive of Raynaud's phenomenon, alopecia, arthralgia, hematuria, burning micturition, night sweats, headache, or neurological complaints. The patient had no known past medical illnesses and no family history of autoimmune or thrombotic disorders. There was also no recent travel, immobilization, or known exposure to infections or environmental toxins.

On examination, the patient appeared ill and underweight. His vital signs were as follows: blood pressure 100/60 mmHg, heart rate 110 bpm, respiratory rate 24/min, and oxygen saturation 92% on room air. Bilateral cervical lymphadenopathy was present with soft, non‐tender nodes measuring approximately 1 × 1 cm. Chest auscultation revealed decreased breath sounds and crepitations predominantly in the right mammary and infra‐axillary regions. Cardiovascular examination was unremarkable. The abdomen was soft and non‐tender, but splenomegaly was palpated.

3. Investigation and Diagnosis

Laboratory investigations were conducted to evaluate systemic inflammation, autoimmune markers, and renal involvement. The observed values and their corresponding normal reference ranges are summarized in Table 1.

TABLE 1.

Summary of laboratory investigations with corresponding reference ranges.

Test	Observed value	Normal value	Interpretation
Erythrocyte sedimentation rate (ESR)	120 mm/h	0–20 mm/h (males)	Elevated—suggests inflammation
High‐sensitivity C‐reactive protein (hs‐CRP)	247 mg/L	< 3 mg/L	Markedly elevated—active inflammation
Procalcitonin	0.76 ng/mL	< 0.05 ng/mL	Mildly elevated—possible systemic inflammation or infection
c‐ANCA (PR3‐ANCA)	Positive	Negative	Positive—supports diagnosis of GPA
p‐ANCA	Negative	Negative	Normal
ANA (antinuclear antibody)	Negative	Negative	Normal—rules out SLE
24‐Hour urine protein	1.16 g/24 h	< 150 mg/24 h	Proteinuria—suggests renal involvement

Urinalysis revealed microscopic hematuria with red blood cell casts, suggestive of active glomerulonephritis.

The computed tomography (CT) scan was done which revealed multi‐regional abnormalities. Head and neck findings included a deviated nasal septum with bony spur, right maxillary sinusitis, and bilateral mastoiditis. Extensive lymphadenopathy was noted in the pretracheal, paratracheal, and para‐aortical regions (largest 15 × 9 mm, right paratracheal) and bilateral level II and I regions (largest 12 × 8 mm). In the chest, patchy consolidation with surrounding ground glass opacities was evident in bilateral lung fields, predominantly on the right side (Figure 1a). A hypodense filling defect in the left subclavian vein, suggestive of acute thrombosis, was also identified (Figure 1b). Abdominal imaging showed hepatomegaly (approximately 20 cm craniocaudally) and splenomegaly (13.7 cm).

FIGURE 1.

(a) Axial contrast‐enhanced CT image of the upper thorax demonstrating a hypodense intraluminal filling defect within the left subclavian vein, consistent with acute thrombosis, along with adjacent right upper lobe pulmonary infiltrates. (b) Axial CT image of the lungs showing bilateral patchy consolidation, ground‐glass opacities, and nodular infiltrates, predominantly involving the right lung, suggestive of inflammatory pulmonary involvement in GPA.

A punch biopsy was obtained from the left nasal septum. The gross specimen consisted of four gray‐white soft tissue fragments measuring a total of 0.9 × 0.3 cm, all of which were submitted for histological examination. Microscopically, the tissue sections demonstrated areas of fibrinoid necrosis and well‐formed granulomas composed of histiocytes, as well as prominent multinucleated giant cells (as shown in Figure 2). Numerous blood vessels of variable calibers exhibited fibrinoid necrosis and were surrounded by a dense inflammatory infiltrate comprising neutrophils, lymphocytes, and eosinophils. Karyorrhectic debris was also observed, indicating ongoing necrotic inflammation. Special stains, including PAS and AFB, were negative for fungal elements and acid‐fast bacilli, respectively.

FIGURE 2.

Photomicrograph of nasal septal biopsy showing well‐formed granulomas composed of epithelioid histiocytes and multinucleated giant cells, with areas of fibrinoid necrosis and surrounding inflammatory infiltrate, consistent with necrotizing granulomatous vasculitis (PAS stain, ×100).

These histopathological features were consistent with necrotizing granulomatous inflammation with vasculitis, strongly supporting a diagnosis of GPA.

Based on the patient's clinical presentation, histopathological findings of necrotizing granulomatous inflammation with vasculitis, radiologic evidence of multisystem involvement, and a positive serologic profile for c‐ANCA and PR3, a diagnosis of GPA was established. Differential diagnoses were systematically evaluated and excluded. Microscopic polyangiitis (MPA) was considered unlikely due to the absence of granulomatous inflammation and negative p‐ANCA. Eosinophilic granulomatosis with polyangiitis (EGPA) was ruled out given the absence of asthma, peripheral eosinophilia, and allergic features. Systemic lupus erythematosus (SLE) was excluded based on a negative ANA and the lack of hallmark clinical manifestations such as malar rash, arthritis, or neuropsychiatric involvement. Additionally, infective endocarditis and tuberculosis were ruled out by negative blood and sputum cultures, absence of cardiac murmurs or vegetations on auscultation, and a negative acid‐fast bacilli (AFB) stain.

The patient was admitted and managed as a case of systemic vasculitis. Immunosuppressive therapy was initiated with intravenous hydrocortisone and cyclophosphamide. Due to the presence of deep vein and subclavian vein thrombosis, anticoagulation was started with oral rivaroxaban. Over the hospital course, the patient showed significant clinical improvement, including resolution of fever, stabilization of respiratory symptoms, and improvement in cutaneous and systemic signs.

4. Outcome and Follow‐Up

On discharge, the patient was prescribed a tapering course of oral corticosteroids in conjunction with maintenance immunosuppressive therapy, along with continued oral anticoagulation to manage the thrombotic complication. At three‐month follow‐up, the patient demonstrated marked clinical improvement with resolution of fever, epistaxis, and respiratory symptoms, and continued to do well under regular outpatient monitoring. To provide a clearer clinical overview, Table 2 outlines the timeline of symptom progression, diagnostic workup, and therapeutic interventions.

TABLE 2.

Chronological timeline of symptom onset, diagnostic investigations, therapeutic interventions, and clinical outcomes during hospitalization and follow‐up.

Time period	Symptoms/events	Investigations	Interventions
2–3 weeks before presentation	Intermittent fever, malaise, weight loss	—	—
1–2 weeks before presentation	Recurrent epistaxis (5–6 episodes), nasal swelling, dry cough, hoarseness of voice	Initial clinical examination	Treated as nasal vestibulitis with antibiotics
Days before admission	Hemoptysis (single episode), purpuric skin lesions, progressive right lower limb swelling (non‐pitting), worsening fatigue	—	—
Day of hospital presentation	Fever, breathlessness, cervical lymphadenopathy; O2 saturation 92%	CBC, ESR, CRP, ANCA panel, renal profile, procalcitonin	Supportive care initiated
Hospital day 1–3	Persistent respiratory symptoms, limb swelling	CT chest/neck/abdomen: bilateral lung infiltrates, sinusitis, mastoiditis, Hepatosplenomega ly, left subclavian vein thrombosis	Oxygen supplementation; continued monitoring
Hospital day 3–5	Systemic symptoms ongoing	Nasal biopsy: necrotizing granulomatous inflammation with vasculitis	IV hydrocortisone; IV cyclophospham ide
Hospital day 5–7	Gradual improvement in fever and respiratory status	Coagulation profile; Doppler/CT confirming DVT	Oral rivaroxaban started
Discharge	Stabilized respiratory symptoms; improved limb swelling	Repeat labs showing decreased inflammatory markers	Tapering oral corticosteroids; maintenance immunosuppressants; continued anticoagulation
3‐month follow‐up	Sustained improvement; no epistaxis; resolved respiratory symptoms; improved exercise tolerance	Follow‐up labs: normalizing inflammatory markers; stable clinical examination	Continued maintenance therapy and anticoagulation

5. Clinical Discussion

GPA is a systemic, small‐vessel vasculitis characterized by noncaseating granulomatous inflammation and multisystem involvement [2]. Genetic predisposition plays a role in its pathogenesis, particularly through dysregulation of proteinase 3 (PR3) activity. Under normal physiological conditions, α1‐antitrypsin inhibits PR3 to prevent excessive inflammatory damage.

However, mutations in the SERPINA1 gene, especially the Z allele, or increased expression of the PRTN3 gene (which encodes PR3), may result in elevated levels of free PR3 in circulation. This excess PR3 can trigger the production of anti‐PR3 ANCA, initiating an autoimmune response and promoting proteolytic injury to blood vessels [12]. The immunopathological hallmark of GPA is the breakdown of immune tolerance in T and B lymphocytes toward neutrophilic antigens, particularly PR3 or myeloperoxidase (MPO) [13].

While the exact mechanism of VTE in systemic vasculitis remains unclear, PR3 antibodies [7], commonly seen in GPA, may contribute, as observed in this case. These antibodies interact with plasminogen and, in vitro, have been shown to slow fibrinolysis, leading to prolonged clot persistence [14]. Furthermore, the systemic inflammatory milieu of GPA promotes a prothrombotic state through endothelial dysfunction and imbalance in coagulation pathways, compounding the risk of thrombotic events such as DVT, as observed in this case [15]. This patient's multisystem involvement, early thrombotic event, and presentation in a resource‐limited, overcrowded tertiary‐care setting highlight the challenges families face in timely diagnosis and management.

While pediatric patients exhibit symptoms similar to adults, the frequency of organ involvement varies [16]. It commonly presents with upper airway involvement (82%), nephropathy (65%), respiratory disease (61%), and musculoskeletal symptoms (55%), with fever and fatigue in 73% of cases [17]. The patient's sudden decline suggests an infectious complication, which is common, severe, and a leading cause of death in vasculitis, with pediatric GPA mortality typically under 5%–10% [18, 19].

Despite advances in diagnostic methodologies, the identification of an optimal diagnostic tool for GPA remains a subject of ongoing investigation. While various classification criteria exist, the European League Against Rheumatism (EULAR), Pediatric Rheumatology International Trials Organization (PRINTO), and Pediatric Rheumatology European Society (PRES) criteria have demonstrated enhanced sensitivity in classifying pediatric vasculitis, including GPA. In this case, the patient fulfilled all criteria outlined by the EULAR/PRINTO/PRES classification system, reinforcing its utility in the diagnostic process [20]. Ultrasound is the first‐line imaging modality for diagnosing proximal DVT, as it accurately evaluates thrombus size, chronicity, and occlusion, guiding appropriate medical or interventional management [21].

Early diagnosis is crucial for prognosis, as immunosuppressive therapy can induce remission and reduce morbidity [1]. The current standard of care for patients. diagnosed with GPA involves a combination of glucocorticoids and cyclophosphamide, which has proven highly effective in controlling disease activity in the majority of ANCA‐associated vasculitis cases [22]. In cases where DVT is present, concurrent anticoagulation therapy is indicated unless contraindications exist, as it mitigates the risk of thromboembolic complications and promotes vascular patency [23, 24]. In this case, the patient was managed accordingly, receiving immunosuppressive therapy along with oral rivaroxaban for DVT treatment.

Thrombophilia screening, including inherited and acquired prothrombotic disorders, could not be performed due to resource limitations, which represents a limitation of this report. Another limitation of this report is the relatively short follow‐up duration of the patient. GPA is a relapsing disease with long‐term systemic consequences; therefore, extended follow‐up is essential to assess sustained remission, renal recovery, and relapse risk.

6. Patient Perspective

The patient and his family were anxious during the initial phase of illness, as it involved multiple visits with evolving symptoms that created a lot of confusion. They felt difficulties navigating a busy tertiary‐care facility where waiting hours were long and consultations were a bit brief, often leaving them without a sense of the patient's condition. The sudden appearance of symptoms like limb swelling and respiratory involvement further increased their anxiety, as they had never heard of systemic vasculitis before. A definitive diagnosis brought clarity, and they were reassured once the treatment plan was explained in simple terms. The family believed that explanation and follow‐up were important features in helping them cope with the demands of managing a rare disease in a busy clinical environment.

7. Conclusion

GPA may present with atypical manifestations such as DVT in adolescents. This case highlights that unexplained venous thromboembolism, particularly when accompanied by constitutional or ENT symptoms, should prompt evaluation for systemic vasculitis, even in the absence of advanced renal failure at presentation. Early recognition enables timely immunosuppressive therapy and may prevent irreversible organ damage.

Author Contributions

Bishal Budha: conceptualization, data curation. Aron Shrestha: conceptualization, data curation, validation, visualization, writing – original draft, writing – review and editing. Satish Bajracharya: formal analysis, investigation. Dhiraj Poudel: methodology. Bishweshar Joshi: methodology, project administration. Pujan Pandey: investigation, methodology. Rajan Budha: resources, software. Sadikshya Pandey: resources, software. Bishal Panthi: resources, software.

Funding

The authors have nothing to report.

Disclosure

All the authors declare that the information provided here is accurate to the best of our knowledge.

Ethics Statement

This work follows the Helsinki Declaration. Since this is a case report, our Institutional Review Board, has waived the requirement for ethical approval.

Consent

Written informed consent was obtained from the patient for publication of this manuscript and accompanying images. A copy of the written consent is available for review by the. Editor‐in‐Chief of this journal.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The datasets used during this study will be available from the corresponding author upon reasonable request.