[CIS PIDD] [cis-pidd] Coxsackie B encephalitis in pt with CVID?

[Monica Lawrence]

A 28-year-old female patient with CVID was recently seen at the University of Virginia for encephalitis, initially diagnosed as toxoplasmosis, but later determined on autopsy to have been due to coxsackie B virus. This patient was status post splenectomy and status post rituximab therapy for  autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura. We are interested to know if anyone has seen another case of coxsackie B encephalitis in CVID, particularly in a patient status post splenectomy and rituximab and, if yes, if you would be interested in putting together a case series.  We are aware of publications on coxsackie A/B encephalitis in XLA, but not CVID patients.

The detailed case is as follows. 

A 28-year-old Caucasian female, presented to the University of Virginia Hospital, after a 4-month progressive encephalopathy. She has a medical history notable for a previous diagnosis of Evan’s syndrome complicated by idiopathic thrombocytopenic purpura and autoimmune hemolytic anemia. She was treated with danazol and steroids, which was discontinued due to increasing CK. She received IVIG and rituximab for severe ITP between 2001 and 2004. In 2008 she underwent splenectomy, with pneumococcal and meningococcal vaccines pre-operatively. She had recently started intravenous immunoglobulin therapy within a month prior to her starting to develop symptoms of cognitive decline.

She had previously been hospitalized for serious infections including Influenza with concurrent facial Pseudomonal cellulitis and for Pneumococcal sepsis requiring intensive care unit admission. In 2012, she was admitted for presumed viral meningitis at another hospital and since then she had developed persistent bilateral sensorineural hearing loss. Her most recent admission was for cognitive decline with persistent fevers that had been occurring since she had started IVIG. Her steady decline in cognitive function included decreased ability to form new memories, poor recall, childlike behavior, clumsiness, somnolence, and a tremor. On admission, her exam was pertinent for right sided dysmetria and hyperreflexia, narrow-based hesitant gait and a bilateral intentional tremor. Given her immunocompromised state, there was concern for a neurodegenerative process from IVIG versus an central nervous infectious process, and a brain MRI was obtained which demonstrated white matter changes concerning for encephalitis, as there were signal abnormalities in the subcortical white matter and cortex, bilaterally at the vertex, insula, anterior and mesial bilateral temporal lobes, pons and the cerebellum, but no focal lesions. She had a lumbar puncture that showed an opening pressure of 23.5 mmHg, 8 white blood cells/μL (89% lymphocytes), 4 red blood cells/μL, protein 44 mg/dl, and glucose 53 mg/dl. CSF lactate was 1.9mmol/L; Cryptococcus antigen was negative as was CSF gram stain. HSV, Lyme, HHV-6, EBV, VZV, VDRL, JC virus, and CMV were negative. Flow cytometry of the CSF demonstrated a paucity of B-cells (expected in CVID) but no aberrancy in the T-cell population. EEG demonstrated no epileptiform discharges. She was discharged but given the lack of improvement in her clinical symptoms she was readmitted for stereotactic brain biopsy. The Cortex, insula, uncus and subcortical area were biopsied. All specimens on pathology demonstrated meningo-encephalitis with a restricted B-cell population. She had a repeat lumbar puncture for Toxoplasma PCR, HSV PCR, Enterovirus PCR, EBV PCR, JC PCR, CMV and HHV-6 PCR all of which were negative. However, her Toxoplasma IgG antibody was positive at 14 IU/ml and her immunohistochemical stain was positive for Toxoplasma concerning for cerebral toxoplasmosis. She was empirically treated with Pyremethamine 50 mg PO daily, Sulfadiazine 4 grams daily in 4 divided doses as well as Leucovorin 25 mg PO daily in the interim. She was discharged to a skilled nursing facility at that time. 

She presented to the emergency department one week after discharge with worsening mental status. Her father noted that the week prior she had begun to walk with a "frankenstein-like" gait. She had also experienced episodes of incontinence. Physical exam on admission revealed erythematous auditory canals, abdominal distention with tympany, with grimacing upon suprapubic palpation, tremors. She was awake, alert, and moving all extremities spontaneously. She responded to most simple commands. A morbilliform rash was noted on the lower extremities bilaterally, sparing the soles of the feet. A rash on her chest and abdomen was erythematous, blanching, and confluent. A repeat lumbar puncture showed an opening pressure of 7 mmHg, 17 white blood cells/μL (82% lymphocytes), 120 red blood cells/μL, protein 51 mg/dl, glucose 49 mg/dl, and CSF lactate of 2.1 mmol/L.

She was admitted to the ICU at that time. Her sulfadiazine was stopped out of concern for a sulfa drug allergy and she was started on clindamycin 600 mg IV q6h. Another EEG was obtained and showed drowsiness, alpha activity attenuated and was replaced by diffusely distributed theta and delta activities, interpreted as normal for her mental state. She became verbal on hospital day 3 and was transferred to the floor shortly thereafter. She began having fevers, tremors, and worsening of mental status, and was transferred back to the MICU four days later, on hospital day 7. She was started on vancomycin and cefepime for coverage of HCAP. Her lack of clinical improvement prompted a change to sulfadiazine, and a desensitization protocol was begun. Infectious workup remained negative throughout her second hospitalization. She was ultimately transferred to palliative care and died after two months of hospitalization. 

Thank you,

Monica G. Lawrence, MD
Assistant Professor of Medicine
Department of Medicine
Division of Asthma,Allergy & Immunology
University of Virginia
PO Box 801355
Charlottesville, VA 22908
434-243-6811
ml4nz at virginia.edu








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