Early syphilis mimicking tuberculous meningoencephalitis in an HIV-positive patient

PATIENT AND METHODS

A 50-year-old British man was admitted to an infectious diseases ward with a six-week history of headache, blurred vision in the right eye, loss of balance, night sweats and weight loss. Eight years previously he had been successfully treated for tuberculosis (TB) of the right elbow joint. He gave no history of ano-genital ulceration, skin rashes or lymphadenopathy.

He had last had sexual intercourse two months earlier with his wife of 20 years. However, he had also had unprotected oral and anal sexual intercourse with three casual male partners in the preceding six months. He denied previous sexually transmitted infections and had never been tested for HIV infection.

CLINICAL FEATURES

He was apyrexial and his pupils were equal and reactive. Visual acuity and visual fields were normal. Neurological examination revealed ataxic gait with no other abnormality.

INVESTIGATIONS

Computerized tomography (CT), magnetic resonant imaging (MRI) of the head and the chest X-ray were normal. A lumbar puncture (LP) showed an opening pressure of 21 mm of water, protein 1.61 g/L (0.1–0.4), glucose 1.1 mmol/L (blood glucose 5.7 mmol/L) and white cell count of 36 cells/mm³ (mainly lymphocytes). No acid fast bacilli were seen. An HIV antibody test four days after admission proved positive, with a CD4 lymphocyte count of 172/μL (500–1500) and HIV viral load of 119,450 copies/mL.

TREATMENT AND PROGRESS

Probable tuberculous meningitis was diagnosed on the second day of admission on the basis of past history of TB, clinical symptoms and cerebrospinal fluid (CSF) findings (lymphocytosis, raised protein and greatly reduced glucose). Quadruple therapy including Isoniazid, Rifampicin, Ethambutol and Pyrazinamide was initiated.

Although polymerase chain reaction (PCR) and culture of CSF for M. tuberculosis later proved negative, the patient's condition improved within 10 days of initiation of treatment and he was discharged.

However, two days later his condition deteriorated and he was re-admitted. On examination he was apyrexial and had a generalized maculopapular skin rash.

There was no lymphadenopathy, mouth or perianal ulceration. He was confused with a Glasgow coma score of 13/15 and disorientated. Ophthalmoscopy showed blurring of the right disc margin. His gait was ataxic and he had bilateral Babinski responses. No other abnormal neurological signs were found.

INVESTIGATIONS

CT and MRI head scans were, again, normal. LP showed an opening pressure of 22 mm of water, protein 1.79 g/L, glucose 0.8 mmol/L (blood glucose 5.6 mmol/L) and cell count of >118 cells/mm³ (mainly lymphocytes). No organisms were seen. The CSF tested negative for cryptococcal antigen and M. tuberculosis by PCR. The CSF rapid plasma reagin (RPR) test was positive at 1:8 as was the Treponema pallidum particle agglutination (TPPA) test at 1:2560. Treponemal serology was positive with an RPR of 1:64, TPPA of >1:2560 and a positive T. pallidum IgM test. A diagnosis of acute syphilitic encephalitis was made within 21 days of initial admission.

RESULTS

Since the initial diagnosis was possible bacterial meningitis, the patient was treated with a seven-day course of cefotaxime 2 g intravenously six-hourly. Undoubtedly, he had neurosyphilis but with the history of previous TB and CSF findings (lymphocytosis, raised protein and greatly reduced glucose), it was very difficult to completely exclude TB. Therefore, as he was tolerating TB treatment, it was continued for six months to cover the – unlikely – possibility of dual infection. The patient made a full neurological recovery, achieving serological cure for syphilis after two months (the RPR fell from a peak of 1:64 to 1:8). The LP was repeated four months later, showing a negative RPR and a normal white cell count.

DISCUSSION

Syphilis is a sexually transmitted infection caused by the spirochaete bacterium T. pallidum. The incidence of syphilis in the UK has increased dramatically since the late 1990s, mostly in men who have sex with men. ^1–3

T. pallidum is a highly invasive organism and has been isolated in CSF in 30% of patients with primary and secondary syphilis. ⁴

Clinical neurosyphilis represents 1% of all neurological diseases in HIV-1 infected patients, ⁵ where a more fulminant course may be observed. ⁶ The major symptomatic types of neurosyphilis are parenchymatous and meningovascular. Meningovascular syphilis may manifest as an acute stroke syndrome or as a subacute illness, with a prodrome of weeks to months. ⁷ Meningovascular syphilis presenting as frank encephalitis, as in this case, is rare. ⁷

In our case neurosyphilis also mimicked TB, which occurs more commonly in HIV-positive patients. ^8,9

The recommended treatment for neurosyphilis is parenteral procaine penicillin. ¹⁰ There are less data on the efficacy of ceftriaxone. ¹⁰ Although cefotaxime has been beneficial in treating bacterial meningitis, ¹¹ we believe our case to be the first report of successfully treated early neurosyphilis using cefotaxime.

Syphilis has long been called ‘The Great Imitator’ and, as in our case, others have also reported on misdiagnosis of TB in syphilis. ¹² In this case, the previous history of TB and ‘typical’ CSF findings led to an incorrect diagnosis of tuberculous encephalitis. Since syphilis prevalence has increased significantly over the last decade, physicians should be alert to include it in their differential diagnosis.