Your Diagnosis, Please
A previously healthy 12-year-old Hispanic girl was admitted to the hospital in February 2017 with persistent headaches and intermittent fevers. She had been evaluated in the emergency department 1 week earlier for headaches of 8 days duration but had no focal neurological findings. She was given a “migraine cocktail” consisting of diphenhydramine, ketorolac and prochlorperazine and was discharged home. She continued to have headaches and developed intermittent fevers to 37.8–38.3°C during the following week and had episodes of nausea and vomiting. Headaches were severe, involving the entire head, and were associated with photophobia and phonophobia. She had no recent upper respiratory tract infection or sore throat. She denied recent travel or contact with animals or sick people, including those with known tuberculosis.
On admission, she had a temperature of 37.8°C, pulse of 116 beats/min, respiratory rate of 20 breaths/min and blood pressure of 99/49 mm Hg. She was alert and oriented. Physical examination was normal except for neck stiffness and positive Kernig’s and Brudzinski’s signs. Ophthalmological examination was normal with no papilledema.
Her white blood cell count was 5.4 × 103/mm3 (60% neutrophils, 28% lymphocytes, 3% atypical lymphocytes and 9% monocytes), hemoglobin was 14.7 g/dL, hematocrit was 44.7% and platelet count was 181 × 103/mm3. Her serum electrolytes were normal. Lumbar puncture revealed elevated opening pressure of 32 mm H2O. Cerebrospinal fluid (CSF) contained 2272 white blood cells (94% lymphocytes and 6% monocytes) with glucose of 29 mg/dL (concomitant serum glucose was 92 mg/dL) and protein of 360 mg/dL. CSF Gram stain showed no organisms. Intravenous ceftriaxone, vancomycin and acyclovir were started.
CSF bacterial cultures were negative. CSF polymerase chain reaction for herpes simplex virus 1, 2, EBV, cytomegalovirus and enterovirus were negative. Acid-fast bacilli stain on CSF, mycobacterial and fungal cultures, and pan–polymerase chain reaction tests for bacteria, mycobacteria and fungi on CSF (University of Washington Molecular laboratory) were all negative. Serum antibodies for Toxoplasma, Bartonella henselae, Borrelia burgdorferi, human immunodeficiency virus I and II were negative. Epstein Barr virus serology and Mycoplasma serology were consistent with past infection. Interferon-gamma release assay was indeterminate, but tuberculin skin test and chest radiograph were negative.
Magnetic resonance imaging (MRI) of the brain showed complete opacification of the left mastoid air cells with restriction on diffusion-weighted imaging. Serial examinations failed to demonstrate any mastoid swelling, redness or tenderness, but because of MRI findings, the patient underwent myringotomy and tympanostomy tube placement bilaterally. Clear fluid, drained from the left ear, had negative Gram stain and negative bacterial culture. Mycobacterial and fungal cultures of the fluid were also negative. Intravenous acyclovir was discontinued after 48 hours, but vancomycin and ceftriaxone were continued.
After 3 days of hospitalization, her headache and fevers improved. On day 5, she developed worsening abdominal pain associated with nausea, vomiting and poor appetite. Laboratory studies showed elevated liver (alanine aminotransferase of 118 U/L) and pancreatic (lipase of 285 U/L) enzymes. Computed tomography scan of the abdomen revealed mild hepatosplenomegaly and changes suggestive of enterocolitis.
On hospital day 9, the patient developed new fever spikes up to 39.7°C. Over the next several days, her appetite and abdominal pain improved gradually, but she continued to have an elevated lipase level. A repeat MRI of the brain on hospital day 14 revealed persistent unchanged opacification of the left mastoid. Ceftriaxone was continued for another week and vancomycin was discontinued. Mastoid biopsy was performed and histopathology showed fibrovascular papillary tissue with cystic structures likely representing a congenital lesion.
An additional laboratory test was subsequently performed that revealed the diagnosis.
For Denouement see P. 652.