The patient was a ten-year-old boy who had been referred to children's medical center as a pediatric center of excellence for diagnostic and therapeutic evaluation due to persistent fever associated with upper respiratory infection symptoms and lower limb pain. In the previous medical center, he was treated with antibiotic as bacterial pneumonia that resulted in poor clinical response. After which, antituberculosis regimen was initiated mainly based on endemic region ethnicity for the mycobacterium and cavitary pulmonary lesion on radiographic studies. He also had an episode of perforated otitis media with effusion (OME) with additional mastoiditis receiving ventilation tube as the treatment. Alongside the disease course, he experienced antibiotic-resistant sinusitis for 2 months requiring surgical treatment. By this point, the diagnosing team focused on immunologic work up; hence, his recurrent infections which revealed our child had a competent immune system. It is noteworthy that the patient and his family reside in a different city than our clinic so not all the therapy happened under our supervision.
After 6 months, he was referred to Children's Medical Center, Pediatric Center of Excellence in Tehran as a tertiary referral center for more diagnostic evaluation and treatment. There was no arthritis in the lower extremity examination, but due to the difference in lower limb size, an evaluation for thrombosis was performed that was suggestive of deep vein thrombosis (DVT). Due to prolonged fever and increased inflammatory markers such as elevated erythrocyte sedimentation rate (ESR = 105), C-reactive protein (CRP = 95), leukocytosis (WBC = 17,600), and thrombocytosis (Plt = 635,000), pediatrics rheumatologists were consulted for the possibility of rheumatologic diseases and collagen vascular disorder. Transthoracic echocardiography was performed showing diffuse ectasia and dilation with huge aneurysm in the left anterior descending artery (LAD) with the size of 14 mm (Figure 1). Although, there was no other clinical signs in favor of Kawasaki disease other than prolonged fever, due to the high inflammatory markers and age of patient and the possibility of atypical neglected atypical Kawasaki disease or other rare vasculitis.
Other positive findings include antinuclear antibody (ANA) with titer of 1/640 and coarse speckled pattern in indirect immune fluorescent assay (IIF) and antineutrophil cytoplasmic antibodies (ANCAs) with perinuclear pattern. Regarding thrombosis, an assessment for antiphospholipid antibodies and antiphospholipid syndrome was performed, which was negative. Serum immunoglobulins, complements, and nitroblue tetrazolium were normal.
Finally, based on the history of severe upper airway infection, pulmonary cavitary lesion, saddle nose (Figure 2), elevated ESR and CRP, positive ANA and ANCA with perinuclear pattern (P-ANCA), granulomatosis with polyangiitis (Wegener granulomatosis) was diagnosed for this patient. Initial treatment as induction therapy was methylprednisolone pulse (30 mg/kg/day for 3 days/monthly) and cyclophosphamide pulse 750 mg/m2/monthly for 6-month duration. Oral medication was administered with prednisolone (1/mg/kg/day) and mycophenolate mofetil (1,200 mg/m2/day). An additional aspirin (5 mg/kg) plus warfarin (0.1 mg/kg) was administered to prevent further thrombotic events by maintaining the INR level at the range of 2-3.
On a follow-up, transthoracic and transesophageal echocardiographic evaluation, large circular nonorganized thrombosis occupying the majority of the aneurysm was noted that was confirmed by CT angiography despite the anticoagulation prophylaxis (Figure 3). To target the thrombosis, high dose of methylprednisolone and 10 mg/kg of heparin were applied initially, then warfarin was added subsequently to maintain INR level at 3-4. In interventional cardiology consult suggested medical therapy without any intervention due to high risk thrombotic complications.
In a longtime follow-up, he is under maintenance therapy for GPA (with low-dose prednisolone, mycophenolate mofetil, and antithrombotic therapy for 1.5 years without any flare up of underlying disease, but serial transthoracic echocardiography showed minimal improvement in the size of aneurism and thrombosis).