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Aciclovir/ceftriaxone/ustekinumab Meningococcal-meningitis, herpes-simplex-virus-2 meningitis following off-label use and fever: case report

A 60-year-old man developed meningococcal meningitis and herpes-simplex-virus-2 (HSV-2) meningitis during off-label treatment with ustekinumab for pityriasis rubra pilaris (PRP). He also developed fever during treatment with aciclovir and ceftriaxone [not all dosages, duration of treatments to reaction onsets and outcomes stated]. The man was urgently transferred from a rural hospital to an emergency department for suspected CNS infection necessitating intensive care treatment in a higher-level tertiary hospital. He had acute onset of fever up to 38.5°C accompanied by neck stiffness, vomiting, rigor and confusion lasting for 3 days. He had initially presented to the ED of a rural hospital, where he was considered for a lumbar puncture because of marked nuchal rigidity. He received an IV dose of ceftriaxone within the first hour of medical contact. His mental status rapidly deteriorated and he was intubated for airway protection. He was then transferred to another hospital a few hours post intubation. During current admission, the evaluation of his prior history revealed, a 10-year history of PRP and bilateral saphenectomy for venous insufficiency of the lower extremities. He also had frequent episodes of herpes simplex virus infections since childhood. His PRP had been managed with acitretin and unspecified topical steroids initially. Because of repeated skin lesion relapses even after 6 years of treatment, his dermatologist had decided to start off-label treatment with SC injections of ustekinumab 45mg at week 0 and week 4 and every 12 weeks thereafter for PRP. His pre-treatment tests were negative for pre-treatment tests including latent mycobacterium tuberculosis infection, human immunodeficiency virus (HIV) and viral hepatitis (HBV, HCV). He had received his last injection of ustekinumab 40 days prior to the presentation. At the time of current presentation to the hospital, he was intubated, under mechanical ventilation and was haemodynamically stable. Because of high clinical suspicion of CNS infection and apparent immunosuppression, he was given empiric broad-spectrum antibiotics, and IV ampicillin/sulbactam, vancomycin and aciclovir [acyclovir] were added to ceftriaxone treatment. As part of the hospital protocol, blood tests were repeated, which revealed increased white blood cell count and C-reactive protein (CRP), as well as a normocytic normochromic anaemia and thrombocytopenia. He was transferred to the hospital’s intensive care unit (ICU), where a lumbar puncture was performed. CSF examination showed 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). Gram stain showed presence of gram-negative diplococci, while PCR examination detected both Neisseria meningitidis serogroup B and HSV-2. Thus, meningococcal meningitis and HSV-2 meningitis were confirmed. During his stay