A Complicated Case of an Immunocompetent Patient with Disseminated Nocardiosis
Forty-two year-old Hispanic male presented with severe and constant bilateral lower extremity pain for 3 weeks, located at the upper thighs with radiation down the legs. He also complained of a non-radiating severe, frontal, throbbing headache for one week, associated with occasional episodes of diplopia, without a stiff neck or photophobia. Four days prior he developed bilateral lower extremity weakness and could not walk or stand on his own. Other complaints included nausea, vomiting and a low-grade fever of 37.7°C. No recent travel abroad or sick contacts. He had no medical problems or previous surgical interventions. He admitted to a 20 pack year history of smoking and chronic alcohol intake of four 8 oz cans of beer every day for the last twenty years. He currently worked as a construction worker. All vital signs were stable on admission and within normal range. Physical examination demonstrated somnolent but arousable patient in no acute distress. The complete neurological and lung examination were unremarkable except hypereflexia of the right brachioradialis and right biceps and a decrease of muscle strength of bilateral lower extremities. All other body systems of physical examination were unremarkable.\nInitial laboratory work up () was remarkable for mild hyponatremia, mild transaminase elevation and hyperbilirubinemia. The ammonia level was in the upper normal range. Urinalysis, urine toxicology screen and alcohol level, hepatitis serology panel and HIV were negative. Chest x-ray on admission was unremarkable. Computer tomography (CT) of the brain () on admission revealed multiple intraaxial hyperdense lesions with surrounding vasogenic edema in the frontal, parietal and left temporal lobes. Hematogenous spread was suggested by the presence of several lesions at the gray-white junction. Chest-CT () on admission demonstrated bilateral cavitary nodules in the lung and right hilar lymphadenopathy. Our differential diagnosis included metastatic versus infectious etiology. We therefore started the patient on empiric antibiotics of vancomycin 1 gram every 12 hours, ceftriaxone 2 grams every 12 hours, and dexamethasone 6mg IV every 8 hours for cerebral edema. We then proceeded to obtain a MRI of the brain () which revealed multiple bilateral supratentorial and infratentorial rim enhancing lesions involving the subcortical gray-white matter interface, superficial and deep white matter tracts, brainstem and cerebellum associated with vasogenic edema. These findings were more likely associated with an infectious etiology causing septic emboli. The initial blood and urine cultures on admission were negative.\nThe pulmonary service was consulted on the second hospital day for bronchoscopy for bronchoalveloar lavage (BAL). Bronchoscopy revealed normal airway anatomy with diffusely erythematous mucosa and clear secretions. BAL was obtained from the left upper lobe and cytology report had no significant findings. The BAL cultures were negative for fungal, bacteria and mycobacteria. AFB stain was performed on the BAL and was also negative. The infectious disease service was also consulted on the second hospital day and recommended a PPD, Quaniferon Gold, coccidiodies serology, aspergillus antigen, toxoplasma IgG antibody, serum crytococcal antigen and a lumbar puncture for cerebrospinal fluid (CSF) analysis. All of the stated lab tests were negative. Cerebrospinal fluid analysis () was elevated WBC count, suggesting an infectious etiology. No evidence of vegetations was noted on echocardiogram. Due to the unclear etiology of the lung and brain lesions, neurosurgery was consulted for a brain biopsy. The neurosurgeon suggested that brain biopsy would not be possible considering the small size and depth of the lesions. By the tenth hospital day the mental status of the patient deteriorated to the point that he was now disoriented to time and place but oriented to person. By the twelfth hospital day the patient developed weakness of the left upper extremity and an unsteady antalgic gait. Then on the next day, he also developed right upper extremity weakness, ptosis and right lower facial weakness. Cardiothoracic surgery was consulted for video-assisted thoracoscopic surgery with biopsy of cavitary lung lesions but the location of the lesion was unsuitable for the surgical access. Eventually, the GCS of the patient decreased to 7, he was bradycardic and had complete right sided paralysis with a positive right side babinski.\nHe was subsequently transferred to the medical intensive care unit (MICU) for further monitoring and cardiopulmonary support. The repeat head-CT with contrast revealed multiple ring enhancing lesions involving both cerebral, basal ganglia and brainstem. There was no evidence for acute intracranial hemorrhage, herniation, mass effect or midline shift. The infectious disease service decided to start the patient on amphotericin B 450 mg (5 mg/kg) IV every 24 hours and advised us to continue the same antibiotics and dexamethasone. On the nineteenth hospital day the patient became tachycardic (HR: 120-130’s) and desaturated to <80%, hence he was intubated and placed on mechanical ventilation support. The infectious disease consult service recommended albendazole 15 mg/kg/day through the naso-gastric-tube every 12 hours for probable neurocysticercosis, and then to initiate toxoplasmosis therapy despite negative test result. This therapy included pyrimethamine 200 mg PO (1 dose) then 75 mg/day plus sulfadiazine 1.5 g PO every 6 hours plus leukovorin 20 mg PO every 24 hours. Despite our best efforts, the patient remained tachycardic and begun to spike fevers ranging from 38.7°C to 39°C. Considering the worsening of his clinical status we continued to advocate the attempt for a tissue biopsy in order to help us guide in the diagnosis and treatment but to no avail. The patient continued to deteriorate, did not respond and subsequently expired on the twentieth hospital day after the family withdrew care.\nAutopsy was subsequently performed two days later. Macroscopic findings of respiratory system included bilateral serosanguineous pleural effusions and a lung abscess at the right hilum. The microscopic examination of the right hilum abscess showed foci of necrosis with acute inflammation and microabscess formation. The macroscopic findings of the brain revealed multiple bilateral cavities present in the white matter throughout the entire cerebrum, and also present throughout the basal ganglia, midbrain, substantia nigra and right lobe of the cerebellum. Microscopic examination findings showed foci of acute inflammation and microabscess formation. Grocott methena mine silver (GMS), grain stain and Fite’s stain of the right hilum abscess and brain abscesses both revealed numerous gram positive branching rods, morphologically consistent with nocardia. Tissue samples from the brain abscess lesions and lung cavitary lesions were sent for cultures and subsequently grew nocardia species. PCR analysis revealed nocardia wallacei species with resistance to ceftriaxone, levofloxacin, aminoglycosides (amikacin) and to sulfonamides (trimethoprim-sulfamethoxazole – TMP-SMX). However, this species of nocardia was sensitive to imipenem. The final autopsy diagnosis revealed nocardia pneumonitis and encephalitis. The cause of death was stated as systemic nocadiosis (nocardia pneumonitis and encephalitis).