An intubated 60-year-old man was urgently transferred by air from a rural hospital to our emergency department as a possible case of CNS infection necessitating intensive care treatment in a higher-level tertiary hospital. The patient's history showed acute onset of fever up to 38.5 C accompanied by rigor, neck stiffness, vomiting and confusion lasting 3 days. He had initially presented to the emergency department of a rural hospital, where he underwent basic laboratory evaluation. An emergent computed tomography (CT) brain scan did not demonstrate any abnormal findings. The patient was considered for a lumbar puncture due to marked nuchal rigidity. Since the blood tests revealed a mild increase in INR and the rural hospital lacked neurosurgical facilities, cerebrospinal fluid (CSF) examination was temporarily postponed and the patient was administered an intravenous dose of ceftriaxone within the first hour of medical contact. The patient's mental status rapidly deteriorated and it was decided to intubate him for airway protection. The patient was then admitted to our hospital a few hours after intubation. The patient had a 10-year history of PRP, a bilateral saphenectomy 10 years previously for venous insufficiency of the lower extremities, and frequent episodes of herpes simplex virus infections (herpes labialis) since childhood. He quit smoking several years ago and drinks alcohol only on rare social occasions. The patient's PRP was initially managed with acitretin and topical steroids. After 6 years of treatment and because of repeated skin lesion relapses, the patient's dermatologist decided to escalate treatment with the addition of subcutaneous injections of ustekinumab 45 mg at week 0 and week 4 and every 12 weeks thereafter. The patient had regular medical check-ups every 6 months, with no abnormal findings in the most recent laboratory work-up (Table 1) 2 months previously.
Additionally, pre-treatment tests for latent mycobacterium tuberculosis infection, viral hepatitis (HBV, HCV) and human immunodeficiency virus (HIV) were all negative. The patient had received his last injection of ustekinumab 40 days previously and was not on any additional medication.
At presentation to our hospital, the patient was intubated, under mechanical ventilation and haemodynamically stable. The clinical examination revealed mild nuchal rigidity, with no rash or signs of increased intracranial pressure. His pupils were of equal and normal size, and reactive to light. The rest of the examination was unremarkable. A repeat CT of the brain showed no changes compared with the baseline imaging obtained a few hours previously. Due to high clinical suspicion of CNS infection and apparent immunosuppression, the patient was given empiric broad-spectrum antibiotics, adding intravenous ampicillin/sulbactam, vancomycin and acyclovir to ceftriaxone. The admission electrocardiogram showed a normal sinus rhythm with 1:1 atrioventricular conduction, while a supine chest x-ray showed the tracheal tube in the correct place with no signs of lung infiltrates or cardiac silhouette abnormalities. The admission arterial blood gas analysis (on FiO2 100%, respiratory rate 16/min, tidal volume 500 ml and positive end-expiratory pressure 5 cm H2O) showed pH 7.42, pCO2 40.6 mmHg, pO2 350 mmHg, HCO3 26 mmol/l, lactic acid 1.2 mmol/l, and SO2 100%. As part of our hospital protocol, blood tests were repeated and revealed an increase in white blood cell count and in C-reactive protein (CRP), as well as a normocytic normochromic anaemia and thrombocytopenia. INR was 0.96 (Table 2). The patient was transferred to our hospital's intensive care unit (ICU), where a lumbar puncture was performed. CSF examination revealed 5.440/mm3 cells with polymorphonuclear predominance, low glucose 18 mg/dl (blood glucose was 120 mg/dl) and high protein levels (477 mg/dl) (Table 3). Gram stain revealed gram-negative diplococci, while PCR examination identified both Neisseria meningitidis serogroup B and HSV-2. During his stay in the ICU, the patient presented persistent euvolemic hyponatremia that was attributed to inappropriate secretion of antidiuretic hormone (SIADH) due to the CNS infection.
The patient progressively improved over the following days, displaying normalization of inflammatory markers and hyponatremia. After 5 days of intensive care treatment, the patient was successfully weaned from the endotracheal tube and transferred to our internal medicine ward for further management. At that point, he was haemodynamically stable and afebrile. Apart from slight confusion, the patient's progress was initially uncomplicated while he was on ceftriaxone and acyclovir. However, on day 4 of his stay in our ward, he started to exhibit spiking fevers up to 38.5 C. Over the following 3 days he displayed abnormally elevating liver function tests (transferase enzymes) in combination with persistent fever but no new signs or symptoms. After infectious specialist team consultation and negative blood and urine cultures, we decided to stop intravenous antibiotics. Two days later, the patient became afebrile and his liver function tests returned to normal, suggesting the fever was caused by drugs. Thorough imaging analysis was requested (CT of the brain, chest and abdomen) but results were unremarkable. After 3 weeks of hospitalization, the patient was discharged ambulatory, afebrile and restored back to his previous excellent health. Our recommendation to his treating dermatologist was to halt ustekinumab for PRP. The patient was strongly advised to get vaccinated with pneumococcal (PCV-13, PPSV-23) and inactivated influenza vaccines as well as with meningococcal group B and groups A, C, W135 and Y vaccines. Follow-up in the patient's local hospital 1 month later showed an unremarkable clinical examination and normal blood tests.