A 79-year-old man of Egyptian descent presented to the emergency department (ED) with complaints of chronic frontal headaches worsening over the last 2 weeks. The patient had a past medical history of hypertension, insulin-dependent diabetes mellitus, prostate cancer status-post prostatectomy, and osteoarthritis. He denied any history of steroid use or any chemotherapy. He denied recent travel. He had immigrated to the USA from Egypt eleven years before. He denied smoking, alcohol, or illicit drug use. He denied any allergies.
The history goes back one year prior when he began experiencing intermittent frontal headaches. Initially he underwent ophthalmologic evaluation which was normal. His symptoms progressed over the following months. He was evaluated several times in the ED during this time but workup was unrevealing. His headache had dramatically worsened 2 weeks ago accompanied by fever, malaise, nausea, vomiting and decreased appetite. He went to his primary medical doctor and was started on clarithromycin as an outpatient for the treatment of presumed otitis media. The symptoms did not improve after 5 days of antibiotics and the patient came to the ED.
Vital signs in the ED were temperature of 100.4°F, pulse of 106 bpm, blood pressure 159/64 mmHg, and 18 breaths/min. Physical examination was notable for bilateral tenderness over the maxillary and frontal sinuses. There was no nuchal rigidity and the extra-ocular muscles were intact. The rest of the physical exam was unremarkable. A complete blood count revealed a white blood cell count of 7700 cells/mm3; hemoglobin of 15 mg/dL; and platelet count of 182,000/mm3. The erythrocyte sedimentation rate (ESR) was 1. The basic metabolic panel was within normal limits. Initial chest x-ray revealed no acute infiltrates. Computed tomography of the head showed complete opacification of the sphenoid sinuses with loss of adjacent walls in the region of the spheno-ethmoidal recesses showing aggressive chronic sinusitis. Computed tomography of the maxillofacial sinuses revealed pansinusitis with complete opacification of bilateral sphenoid sinuses and thickening of the sphenoid sinuses consistent with chronic sinusitis. Magnetic Resonance Imaging (MRI) of the head confirmed the findings of the CT scans. Magnetic Resonance Angiogram (MRA) was also performed which ruled out the presence any aneurysm or stenosis in the CNS vasculature. Magnetic Resonance Venography (MRV) was also performed for the presence of cavernous sinus thrombosis, which was negative. For CT Scan on admission showing opacification of the sphenoid sinuses see Figure .
CT Scan on admission showing opacification of the sphenoid sinuses.
Lumbar puncture was done which showed a clear, colorless CSF with RBC count of 136/mm3 and WBC count of 8/mm3. The differential comprised of 80% neutrophils, 10% lymphocytes and 10% monocytes. The CSF chemistry revealed glucose of 70 mg/dl (serum level: 164 mg/dl); protein of 154 mg/dl; and chloride of 125 mg/dl. Gram staining, culture and India ink stain of the CSF were all negative. Based upon these findings, notably the presence of neutrophils in the CSF, a diagnosis of possible bacterial meningitis was made and the patient was started on intravenous vancomycin, ceftriaxone, as well as acyclovir, and was admitted.
While on the medical ward, the patient continued to have persistent headaches. An EEG was conducted and showed no evidence of encephalopathy or epileptiform activity. Interim blood cultures were negative for growth. Fungal blood cultures were also negative. Serum crytptococcal antigen and Lyme antibodies were unremarkable. To further aide with the diagnosis, the otorhinolaryngology service was consulted. Subsequently, he underwent endoscopic drainage of the sphenoid sinuses, which removed a significant amount of yellow, mucopurulent material. The specimen was sent to pathology for analysis. The patient reported a dramatic improvement of the headaches after the procedure and was afebrile. He was discharged home on clindamycin and ciprofloxacin, in addition to his routine medications.
In the interim two days, the pathology report of the sinus specimen was completed and was significant for marked chronic sinusitis with large collections of septate, branching fungi. Fungal stains identified the organisms most consistent with Aspergillus species, present focally within the soft tissue of the sinuses. No organisms were specifically seen invading blood vessels. Further fungal cultures for species identification were not carried out. The patient was contacted at home and advised to return to the hospital for treatment of fungal sinusitis. He returned and was started on antifungal therapy with intravenous liposomal amphoterecin B (L-AMB), 500 mg every 24 hours. After a few days of receiving L-AMB, he developed acute renal failure. As a result, L-AMB was switched to intravenous voriconazole 500 mg every 12 hours times 2 doses and then 300 mg every 24 hours. Following this, he began experiencing visual hallucinations, likely due to the antifungal azole. Over the next several days, the patient reported feeling better and subsequently he was discharged on oral voriconazole 200 mg every 12 hours for three weeks. The patient was assessed at follow-up at the end of the three weeks. The patient reported improvement in symptoms gradually over time and a repeat CT scans of the head and sinuses showed clearance of the sinuses. For specimen from sphenoid sinus fixed with H & E stain showing fungal hyphae see Figure . See Figure for Specimen from sphenoid sinus fixed with PAS stain demonstrating aspergillus.
Specimen from sphenoid sinus fixed with H & E stain showing fungal hyphae.
Specimen from sphenoid sinus fixed with PAS stain demonstrating aspergillus.
Two months later, the patient returned to the ED with severe frontal headache for the previous ten days. He also experienced diminished vision of his left eye. Jaw claudication, photophobia, and nausea were also reported. Further questioning revealed that the patient had gone to another medical institution and was discharged on oral prednisone for presumed temporal arteritis. Blood work was obtained; the patient was started on intravenous dexamethasone and admitted for additional workup. The ESR was 38.
On the medical floor, the patient continued to complain of relentless, worsening headache now associated with bilateral vision diminishment. He was assessed by the neurology and ophthalmology services. The steroid dose was increased. During the following afternoon, the patient was found unresponsive. The patient had no corneal reflexes, no response to noxious stimuli, and fixed, dilated, non-reactive pupils bilaterally. He had no doll's eyes movements. A stroke code protocol was initiated and the patient was intubated for airway protection. Emergent CT scan of the head showed diffuse subarachnoid hemorrhage with a left temporal lobe hematoma and extensive intraventricular hemorrhage. The patient was transferred to the ICU for further management. A repeat CT scan of the head 24 hours later indicated increase in size of the subarachnoid hemorrhage and acute ischemic changes in the distribution of the left middle cerebral artery. The critical condition of the patient did not allow for evaluation with MRI/MRA studies or neurosurgical intervention. Despite aggressive supportive care, the patient expired five days later. An autopsy request was declined by the patient's family.