P2.M256: The “Missing Link” In A Case Of Mastoiditis

Introduction: Granulomatosis with Polyangiitis (GPA) is an inflammatory disorder causing necrotizing vasculitis most commonly affecting arteries of the upper and lower respiratory tracts and kidneys. GPA is likely due to anti-neutrophil-cytoplasmic-antibody (ANCA) reactions with proteinase 3 (PR3), an enzyme in neutrophil granulocytes, that lead to de-granulation and damage to surrounding endothelial cells.

Case Description: A 13-year-old male with a history of Gilbert syndrome, recurrent otitis media, recent bilateral tympanostomy tubes, left mastoidectomy, and left middle ear biopsy, was transferred from an outside hospital (OSH) with 2 weeks of fever, headache, dysphagia, dry cough, and 17-pound weight loss. Physical exam was remarkable for a thin, ill-appearing teenage male with tachycardia, mild hypertension, drooling, and strained voice due to pain. Patient also noted to have a high arched palate and incision behind left ear post recent surgery. Exam was otherwise normal. Workup was initiated at an OSH and continued after admission (Table). Pertinent findings included mild posterior oropharynx erythema on flexible laryngoscopy. Gross pathology of middle ear and mastoid biopsy showed a “rubbery” material. Computed tomographies showed sinus opacification (Figure A) and dense lung hilum, multiple scattered nodules, and cavitary lesions (Figure B). ANCA titers were elevated at 1:160. A lung nodule biopsy was positive for C-ANCA and PR3 with giant cells and granulomas. Although initial urinalysis (UA) was normal, repeat UA showed 2+ hemoglobin and 26-50 red blood cells. The urine protein to creatinine ratio was 0.445. A diagnosis of GPA was made using the 2008 EULAR Classification Criteria for Childhood GPA as the patient had a positive C-ANCA, upper airway and renal involvement, and histopathology showing granulomatous inflammation. At 5 months post-discharge, our patient has completed 4 doses of Rituximab and continues to require daily prednisolone and azathioprine. He continues to have headaches and flairs of coughing. He is closely followed by Otolaryngology, Neurology, and Rheumatology.

Discussion: ANCA associated vasculitidies (AAV) are rare in the pediatric population with peak incidence of GPA occurring in adults aged 40-60. Compared to adult-onset AAV, pediatric AAV has a female predominance and median age at diagnosis of 12-14 years. GPA often presents with non-specific symptoms such as fever, malaise, weight loss, myalgias, and arthralgias. When lesions involve the ears, nose, and throat, symptoms can include rhinosinusitis, hearing loss, otitis media, and mastoiditis. Lung involvement often presents with cough and hemoptysis. Once identified, GPA is treated with glucocorticoids and additional immunosuppressive therapy based on organ involvement. Delay in initiation of immunosuppressive therapy is associated with high mortality.

Conclusion: Although rare in children, providers should consider GPA in pediatric patients with persistent symptoms involving the upper and lower respiratory tracts or kidneys, as early treatment leads to improved outcomes.