Mania presenting as a VZV encephalitis in the context of HIV

Background

Varicella zoster virus (VZV), also known as human herpesvirus type 3, is a virus in the α-herpesvirus family commonly associated with chicken pox and shingles. Neurological complications of VZV include encephalitis, a life-threatening condition with significant morbidity and mortality. People living with HIV infection are at greater risk, especially those with lower CD4 counts, and hence greater degrees of immunosuppression. Often, patients present with a fever, headache, focal neurological signs and focal seizures, but neuropsychiatric symptoms are also common (ie, hallucinations, psychosis and personality changes).1 2 It is extremely rare for mania to be the only symptom on presentation.

Herein, we report the presentation of mania secondary to VZV encephalitis in a newly diagnosed HIV-positive patient. To date, we are unaware of any similarly reported cases. It is important to raise awareness of atypical HIV presentations to facilitate prompt HIV diagnosis and start appropriate treatment to improve long-term outcomes for these patients.

Case presentation

A 31-year-old heterosexual Caucasian man with no history of psychiatric illness presented to general practice with a 2-week history of hypomania. He was reported to be erratic, irritable and verbally aggressive, with grandiose ideas and pressured speech. He was initially amenable to short-term home treatment under the psychiatric intensive team. He started taking olanzapine 10 mg once nightly and clonazepam 1 mg three times per day in the community.

After an unsuccessful period of home treatment (6 days), he was admitted under Section 2 of the Mental Health Act, to an acute psychiatric inpatient ward. On physical examination, the patient was alert, afebrile and comfortable at rest (pulse 102 beats/min and regular rhythm, blood pressure 124/81 mm Hg, respiratory rate 19 breaths/min). He was noted to have oral candidiasis. Admission bloods showed a mild pancytopenia, with haemoglobin (Hb) 126 g/L, white cell count (WCC) 3.2×10⁹/L, neutrophils 1.86, lymphocytes 0.86 and platelets 119×10⁹/L. He was started on nystatin 100 000 four times per day. He continued olanzapine 15 mg once nightly and clonazepam 1 mg three times per day, with sodium valproate 500 mg two times per day added as a mood stabiliser.

Repeated bloods 7 days later showed worsening markers, with Hb 119 g/L, WCC 2.2×10⁹/L, neutrophils 1.08, lymphocytes 0.69 and platelets 101×10⁹/L. The oral candidiasis was improving. However, he had also developed a fungal toenail infection. He was referred to haematology, and a blood film showed normochromic, normocytic red cells, a few macrocytes and marked rouleaux formation. It was suggested that the mild leucopenia and neutropenia could be due to either the drug therapy, specifically olanzapine, or a result of the acute illness.

Further tests were requested and a viral screen was performed, including an HIV test that was positive. A CT head was normal. At this point, the patient developed a vesicular, erythematous rash in the right T11 dermatome. It was typical of shingles, and he started taking oral aciclovir 800 mg 5 times per day with pneumocystis pneumonia prophylaxis co-trimoxazole 480 mg one time per day (OD). Of note, on direct questioning, he reported three similar episodes of shingles over the past 3 years.

The patient’s sexual history revealed he had a regular female partner for 12 years and they had two young children. He had travelled to Thailand, Canada and Sweden 10 years ago, where he had had unprotected sex with several female partners. Since, he has only had sex with his regular partner. Shortly after the patient was informed of his diagnosis, his regular partner tested HIV negative.

Baseline tests for the patient showed CD4+ lymphocyte count 63 cells/mm³ (9%), viral load 1 550 000 copies/mL, human leukocyte antigen (HLA) B5701 negative and resistance test: E138A mutation, low-level resistance to non-nucleoside reverse-transcriptase inhibitors.

Investigations

In light of the HIV diagnosis and low CD4 count, an organic cause to the hypomanic episode was sought. An MRI brain was requested and reported as normal. An urgent lumbar puncture was performed: cerebrospinal fluid (CSF) clear and colourless, WCC 247×10⁹/L (95% lymphocytes, 5% polymorphs), glucose 2.8, protein 1.29, red cells 37×10¹²/L, gram stain and culture negative, Indian ink stain negative, acid-fast bacilli negative and subsequent tuberculosis culture negative, syphilis PCR and Treponema pallidum particle agglutination assay negative and cryptococcal antigen negative. A presumptive diagnosis of mania secondary to VZV encephalitis was made while awaiting viral multiplex PCR results on the CSF. Subsequent results showed VZV PCR was positive in the CSF and negative for herpes simplex virus, cytomegalovirus, Epstein-Barr virus and John-Cunningham virus.

Differential diagnosis

Clearly, it is salutatory to consider other differential diagnosis, including vasculitis. This patient had an MRI head that was reported as normal (as above), with no overt evidence of vasculitis. We would consider this a reasonable way to investigate for this differential, and hence further vascular-specific imaging (eg, MRA, computed tomography angiogram (CTA) or conventional angiography) was not indicated. Moreover, an MRI can show a typical ventriculitis but did not show in this case. We do, however, recognise this as a limitation.

Treatment

The patient was transferred to the infectious disease unit of the nearest teaching hospital where he was treated with intravenous aciclovir 10 mg/kg for 21 days, followed by secondary VZV prophylaxis with valganciclovir 1 g three times per day later reducing to OD. He started antiretroviral therapy with abacavir, lamivudine and dolutegravir as a fixed dose combination of one pill OD. Psychiatric medications were continued as above. He improved clinically and was discharged to home after finishing his intravenous aciclovir.

Outcome and follow-up

His psychiatric symptoms completely resolved 2 months after discharge from hospital and all his psychiatric medications were slowly reduced and then stopped under the care of the psychiatric team. After 3 months of antiretroviral therapy, his HIV load had reduced from 1 550 000 copies/mL to 190 copies/mL and his CD4 count increased from 63 cells/mm³ to 173 cells/mm³ (16%).

Unfortunately, his female partner subsequently tested HIV positive at follow-up. Her first HIV test was performed 4 weeks after last sexual intercourse and was negative; the second test was performed 6 weeks later and was positive. This was consistent with HIV seroconversion, and the HIV avidity test confirmed she had contracted the virus within the last 4 months.