CASE PRESENTATION
A 14-year-old transgender male presented with 1 month of worsening intermittent pleuritic chest pain, 2–3 weeks after an upper respiratory infection. A review of systems revealed mild fatigue, low appetite and mild frontal headache without red flags. Examination revealed left-sided ptosis, persistent tachycardia (max 125 bpm), pulsus paradoxus, distant heart sounds and decreased air entry at lung bases. No pericardial rub. C-reactive protein (CRP) 201.9 mg/L (high). Blood count showed microcytic anaemia (haemoglobin 77 g/L). Serum electrolytes, creatinine, urinalysis, liver enzymes and coagulation profile were normal. Troponin 4 ng/L (high). Echocardiogram showed significant pericardial effusion with right atrial collapse. Chest x-ray revealed small pleural effusions (Figure 1). Urgent pericardiocentesis was performed, and Naproxen was started for presumed viral pericarditis.
Figure 1.
Chest x-ray showing an enlarged cardiac silhouette with small bilateral pleural effusions on the anterior (a) and lateral (b) views.
Rheumatology was consulted after limited improvement on Naproxen and a negative infectious workup (including tuberculosis). Ophthalmic exam showed inflammatory dacryoadenitis. CT orbit revealed a left lacrimal mass (Figure 2). Biopsy showed scar tissue with few plasma cells, no granulomas or eosinophils, and negative IgG4 staining. Chest CT showed non-specific ground-glass opacities and mild diffuse interlobular septal thickening. Pulmonary function test (PFT) showed a mixed obstructive-restrictive pattern. Serum ANA and IgG4 normal. Myeloperoxidase (MPO)-ANCA was strongly positive >134 U/L, informing diagnosis and management.
Figure 2.
CT orbit showing a left lacrimal gland mass on coronal (a) and transverse (b) views, indicated by arrows.
DISCUSSION
The diagnosis of ANCA-associated vasculitis (AAV) was made on post-admit day 16, based on the positive MPO-ANCA, chest imaging and retro-orbital mass. Multiple specialties (Cardiology, Respirology, Immunology and Ophthalmology) were consulted prior to this to rule out more common causes of the patient’s symptoms. Paediatric AAV is a rare childhood vasculitis characterized by inflammation of small blood vessels. The underlying pathophysiology involves genetic and environmental factors. The formation of autoantibodies against neutrophil proteins, notably leukocyte proteinase 3 (PR3)-ANCA and MPO-ANCA, activate neutrophils leading to vascular inflammation. AAV is classified into subtypes based on clinical features, the pattern of autoantibody elevation and biopsy findings. It includes granulomatosis with polyangiitis (GPA, formerly known as Wegener’s granulomatosis); microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA) (1).
The most common paediatric AAV is GPA, which typically presents with constitutional symptoms (malaise, fever, weight loss), renal impairment (proteinuria, haematuria, hypertension, biopsy-proven glomerulonephritis) and/or pulmonary manifestations (cough, alveolar haemorrhage, haemoptysis and/or parenchymal lung disease including cavitation, nodules or infiltrates) (1). ENT/upper airway involvement (recurrent epistaxis, chronic sinusitis, oral/nasal ulcers, nasal septal defect, hearing loss or mastoiditis) and laryngotracheobronchial involvement (subglottic, tracheal or bronchial stenosis) can also be part of the clinical presentation (1). PR3-ANCA is highly associated with GPA (80% to 90%) (1). However, 20% to 30% of GPA cases present with MPO-ANCA positivity, demonstrating that ANCA antibody type is not limited to one type of AAV (1).
Our patient did not present with classic features of GPA, MPA or EGPA, nor did he fulfil EULAR/PRINTO/PRES classification criteria for paediatric AAV (no renal, ENT or upper airway involvement, inconclusive chest CT for GPA), making diagnosis more challenging. Furthermore, the retro-orbital mass seen on the CT scan showed features suggestive of inflammation but without granulomas or necrotizing vasculitis, as would be typical in AAV. However, the biopsy was reviewed by an adult pathologist who agreed that the sample was non-diagnostic, but that given the clinical picture, classic histopathology was likely present in a non-sampled region. In combination with the positive MPO-ANCA antibodies, this inflammatory retro-orbital mass served as a ‘surrogate marker’ supporting a diagnosis of AAV, unclassifiable subtype, according to the European Medicines Agency classification algorithm (1).
Our patient presented with pericarditis, which is rare in GPA but well-described in EGPA (2). Worldwide, most pericarditis is idiopathic and presumed to be viral. Bacterial causes, including tuberculosis, are rare in developed countries. Important rheumatologic causes of pericarditis in children include systemic juvenile idiopathic arthritis (sJIA) and systemic lupus erythematosus (SLE). In our case, no persistent fever, rash or arthritis typical of sJIA were observed, nor were there clinical features or serological markers indicative of SLE.
Our patient received pulsed steroids followed by oral prednisone and IV rituximab for induction therapy (1000 mg on week 0, and week 2) with improvement in his CRP, ptosis and dyspnoea. We considered using cyclophosphamide as an alternative induction agent, but this was not pursued after discussion with the patient and his parent based on implications for fertility in a transgender male adolescent. Now 1 year after diagnosis, the patient has received two of three maintenance doses of IV rituximab (500 mg every 6 months). He continues to do well with normal inflammatory markers, PFT, and eye exam with no end-organ damage. Following his third maintenance rituximab dose, he will be trialled off therapy.
Rheumatic causes of pericarditis should be considered when there is multisystem involvement, elevated inflammatory markers and common causes have been ruled out. A thorough review of systems, physical exam and concurrent investigation of presenting complaints is invaluable. Early involvement of subspecialty services with expertise in diagnosis and management of AAV is critical for prognosis to prevent end-organ damage.
CLINICAL PEARLS
Rheumatologic causes of pericarditis, such as SJIA, SLE and AAV, should be considered when there is evidence of multisystem involvement and infection has been ruled out.
Vasculitis, while rare, should be considered in patients presenting with multisystem involvement. A thorough review of systems on history, comprehensive physical examination, and investigations to screen for multiorgan involvement is critical in the evaluation of vasculitis.
Early identification and treatment of vasculitis is imperative to prevent end-organ damage and may require collaboration with multiple subspecialties.
ACKNOWLEDGEMENTS
The authors would like to thank the patient and his parent for providing consent to publish this case.
Contributor Information
Ashleigh India Nazareth, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Shamma Alzaabi, Division of Pediatric Rheumatology, British Columbia Children’s Hospital, Vancouver, British Columbia, Canada.
Mercedes Chan, Division of Pediatric Rheumatology, British Columbia Children’s Hospital, Vancouver, British Columbia, Canada.
INFORMED CONSENT
Informed consent for this case report was obtained from the patient and his parent, and documented in the patient’s medical chart.
FUNDING
There were no sources of funding for this research.
POTENTIAL CONFLICTS OF INTEREST
All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
REFERENCES
- 1. Cabral DA, Canter DL, Muscal E, et al. ; ARChiVe Investigators Network within the PedVas Initiative. Comparing presenting clinical features in 48 children with microscopic polyangiitis to 183 children who have granulomatosis with polyangiitis (Wegener’s): an ARChiVe Cohort Study. Arthritis Rheumatol 2016;68(10):2514–26. doi: https://doi.org/ 10.1002/art.39729. Available from: https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/art.39729 [cited 2023 Sep 26]. [DOI] [PubMed] [Google Scholar]
- 2. Thompson GE, Bourne MH Jr, Casal Moura M, et al. Pleuritis and pericarditis in antineutrophil cytoplasmic autoantibody-associated vasculitis. Chest 2021;160(2):572–81. doi: https://doi.org/ 10.1016/j.chest.2021.02.049. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0012369221004499 [cited 2023 Sep 6]. [DOI] [PubMed] [Google Scholar]