Hyperlactataemia and hepatic steatosis: mitochondrial toxicity of nucleoside reverse transcriptase inhibitors.(Statistical Data Included)

Case presentation (Dr B Peters)

A 40 year old heterosexual black African man presented to the accident and emergency department with a 4 minute episode of loss of consciousness with associated incontinence. On inquiry, he gave a 1 month's history of left sided headache, weight loss, fever, and a right axillary swelling. He had a medical history of recurrent malaria, typhoid as a child, drainage of groin abscess in 1999, and severe acne. An HIV antibody test had been negative in 1993. On admission he was taking ciprofloxacin 500 mg twice daily, prescribed by a primary care physician as treatment for the axillary infection; he had recently completed a course of isotretinoin as treatment for acne. He worked as a delivery driver, drank no alcohol, and was a non-smoker. He had been resident in the United Kingdom for 7 years.

On examination he was pyrexial, temperature 38.5[degree]C, had oral candida, severe acne, and a 4 cm diameter infected sebaceous cyst in the right axilla. There was no lymphadenopathy and examination of the respiratory, cardiovascular, abdominal, and nervous systems was normal.

Investigations on admission to hospital included a computed tomograph (CT) scan of the head (with contrast) which showed a single ring enhancing lesion in the left basal ganglia with surrounding oedema and mid-line shift. A diagnosis of cerebral toxoplasmosis was made. Subsequently, an FDG PET (positron emission tomography) scan and cranial magnetic resonance image (MRI) supported this diagnosis. Other investigations showed HIV-1 antibodies detected, cytomegalovirus IgG positive, DAT negative, Toxoplasma gondii IgG> 1:1024, serum cryptococcal latex agglutination (CRAG) negative, CD+ T lymphocyte count 4 cells X [10.sup.6]/l, HIV viral load 190 000 copies/ml, hepatitis A IgM and IgG negative, hepatitis B surface antigen negative, hepatitis C IgG negative. Urea and electrolytes were normal as was a full blood count. Liver function tests showed normal bilirubin and alkaline phosphatase, the AST was 66 (normal range = 0-55) IU/1 and [gamma]GT = 137 (normal range = 0-72) IU/l.

What would your initial management plan be?

Discussant (Dr R Miller)

I would begin empirical therapy for cerebral toxoplasmosis, based on the findings of cranial imaging and the high titre of anti-toxoplasma antibodies. Although in many case series, single lesions are more likely to be due to lymphoma, [1] here you have the additional evidence from FDG PET scanning to support the diagnosis of toxoplasmosis. The assessment of response to empirical therapy would be based on clinical defervescence, neurological improvement, and reduction in size of the lesion on repeat cranial imaging. The treatment regimen of first choice would be sulphadiazine with pyrimethamine and folinic acid. I would avoid using dexamethasone, unless the patient was obtunded or had signs of raised intracranial pressure (bradycardia, widened pulse pressure, CheyneStokes…