A 7.5-year-old previously healthy female of mixed Caucasian-Middle Eastern descent presented to the emergency department with unilateral mandibular swelling and neck pain on passive movement. She had been prescribed erythromycin for 3 days of pharyngitis and 1 day of fever. She did not have hoarseness, drooling, or respiratory distress. There was no recent travel, TB exposure, or animal contact. Her father had recently been treated for a streptococcal pharyngitis; otherwise there were no ill contacts. 
Past medical history was unremarkable. She was fully immunized. 
On examination she looked well. She was febrile at 38.2 C; the rest of her vital signs were normal. She had soft tissue swelling along the left mandible extending down the neck. She had mild left cervical adenopathy that was tender to palpation. She was unable to fully flex and rotate her neck due to pain. The remainder of the examination was unremarkable. Complete blood count revealed leukocytosis (29.7 x 109/L) with neutrophilia (26.34 x 109/L), normal hemoglobin (118 g/L), and thrombocytosis (466 x 109/L). CRP and ESR were elevated at 77 mg/L and 47 mm/hr, respectively. Electrolytes, renal function, and amylase were normal. Lateral neck X-ray revealed mild thickening of the prevertebral soft tissues. She was diagnosed with cervical adenitis and admitted for antibiotic therapy. 
After admission, she clinically deteriorated. She had daily fevers and the edema increased and spread to the right mandible and anterior chest wall. On day 5 she developed a pruritic papular erythematous rash over her chin, neck, chest, and back. She had palmar erythema and erythematous papules on the dorsum of both feet. On day 8 she developed arthralgias of the left knee and ankles, bilateral calf pain, localized bone pain over the diaphysis of her right tibia, and pain over the dorsum of both feet. She had bilateral ankle effusions and was unable to weight bear. 
Her clinical course was further complicated by acute renal failure, presumed to be secondary to combined vancomycin, and NSAID nephrotoxicity. She also had an episode of hematemesis, mild hepatitis, and coagulopathy.
ESR, CRP, and platelet count were persistently elevated, indicative of an extensive inflammatory process. Bacterial cultures of blood, throat (Group A Strep), and lymph node aspirate were negative. Serology for CMV, EBV, HHV-6, hepatitis A, B and C, and Toxoplasmosis were negative. Antistreptolysin O titre was elevated (643 IU/mL), suggesting a poststreptococcal phenomenon. IgG titre to Bartonella henselae was elevated at 1 : 320, of unclear significance. ANCA, ANA, ENA, and dsDNA were all negative. An echocardiogram showed normal cardiac anatomy and function. Ultrasound and CT of the neck and chest demonstrated moderate lymph node enlargement and soft tissue edema, but no abscess or lymphatic mass. Bronchoscopy revealed 50% pharyngeal narrowing and was complicated by acute upper airway compromise that improved with oral dexamethasone 0.3 mg/kg. Ultrasound of her lower extremities was negative for deep vein thrombosis but demonstrated left knee effusion. A skin biopsy of a vasculitic lesion from the anterior chest wall revealed septal panniculitis with leukocytoclastic vasculitis involving the small- and medium- sized blood vessels consistent with cPAN. No granulomas or microorganisms were seen (Figure 1). 
Her treatments included prolonged intravenous antibiotics with no effect (cefazolin days 1 to 3, cefuroxime and clindamycin days 3 to 5, vancomycin days 5 to 13, pipercillin-tazobactam days 5 to 18). IVIg (2 g/kg) was given (on day 11) for possible atypical Kawasaki disease without effect. Her hematemesis and coagulopathy responded to pantoprazole and vitamin K. After review of the skin biopsy results, she was treated with pulse doses of intravenous methylprednisolone (30 mg/kg/day) (days 13 to 15), then moderate dose oral prednisone 1 mg/kg/day. Her rash, edema, and arthritis quickly responded to corticosteroids. On day 21 she was discharged on oral prednisone. 
Her fever, rash, and leg pain recurred when prednisone was tapered. NSAIDs were initially helpful, but she soon required admission for intravenous analgesia. On examination she was febrile and hypertensive. She had polyarthritis. Her neurologic exam revealed spastic catch at both ankles with diminished strength (4 - 4 + /5) in hip flexion and extension, and knee extension. Gower's sign was positive. Cerebellar exam was normal but on gait testing she toe-walked and was unable to perform tandem gait. Skin examination revealed palmar and palatal erythema. She had livedo reticularis and subcutaneous nodules on her arms and legs.
Nerve conduction studies demonstrated diminished amplitude of the left peroneal and right median motors; diminished conduction velocity of the tibial motors bilaterally; and absent F response in the left peroneal motor. These findings were compatible with mononeuritis multiplex. MRI of the spine and renal angiogram were normal. She was treated with pulse doses of intravenous methylprednisolone (30 mg/kg), intravenous cyclophosphamide (500 mg/m2), IVIg (2 g/kg), naproxen, gabapentin, and amlodipine. Her symptoms improved, and she was discharged on day 8, on high dose oral prednisone, monthly cyclophosphamide infusions (1000 g/m2), naproxen and gabapentin.
She was maintained on monthly infusions of cyclophosphamide (1 g/m2) and methylprednisolone and was able to slowly wean gabapentin, naproxen, and oral prednisone. After 8 months, cyclophosphamide infusions were stretched to every 2 months. However, she had a flare of her disease that necessitated admission to hospital. After a 10th dose of cyclophosphamide she was started on subcutaneous methotrexate 0.5 mg/kg weekly and cyclophosphamide was discontinued to minimize cumulative cyclophosphamide exposure. After 1 month, because of persistent symptoms, methotrexate was increased to 0.75 mg/kg and monthly Infliximab (5 mg/kg) infusions were started. Infliximab was increased to 10 mg/kg/dose q 4 weeks, and she was maintained on moderate dose prednisone, methotrexate, and naproxen. She remained corticosteroid dependent and had a flare of her arthritis, rash, fever, and mononeuritis multiplex with weaning of prednisone below 0.5 mg/kg/day. After 8 doses of infliximab she remained corticosteroid-dependent and a decision was made to stop infliximab and start rituximab. Our patient did not have any positive autoantibodies and rituximab was chosen as it has been reported to be of benefit in recalcitrant pediatric vasculitides. She received rituximab (375 mg/m2) and cyclophosphamide (500 mg/m2) at days 1 and 15. She has done well since receiving rituximab and has tolerated weaning of prednisone.