Case report of a man with HIV presenting with malignant syphilis

Keywords: endophthalmitis, histopathology, human immunodeficiency virus (HIV), monkeypox, polymerase chain reaction (PCR), skin lesion, syphilis, uveitis.

A 47-year-old gentleman of Thai background presented with a 2-week history of decreased vision bilaterally, worse on the right eye, with associated periorbital swelling and conjunctival injection. He also reported a 4-week history of a worsening right facial rash. The patient denied any other symptoms or past medical history. In terms of social history, the patient had migrated to Australia in 2007 with no recent travel and current crystal methamphetamine injecting. He also had a history of sex with other men, and in the preceding months prior to his presentation, reported unprotected anal intercourse with six to eight casual male partners.

On initial clinical evaluation, he was alert and orientated and his vitals were within normal limits. There were eroded plaques noted on the right side of the cheek (Fig. 1) which were also distributed on his right forearm. The ocular examination was concerning for right eye endophthalmitis, with the retina unable to be visualised, and an inferonasal endothelial plaque was noted (Fig. 2), as well as left eye papilloedema. There was no neck stiffness noted, and the remainder of the neurological examination was unremarkable. The cardiorespiratory examination was normal.

Fig. 1.  Eroded plaques on the right-hand side of the patient’s cheek.

Fig. 2.  Retina of the right eye was unable to be visualised, and an inferonasal endothelial plaque was noted.

A swab was sent of the right cheek lesion for microscopy and culture, as well as polymerase chain reaction (PCR) for herpes simplex virus, varicella zoster virus and syphilis. A biopsy was also performed and sent for histopathology. Laboratory investigations revealed the full blood count, liver and kidney functions were unremarkable. The erythrocyte sedimentation rate (69 mm/h) and C-reactive protein (15 mg/L) were elevated. Blood cultures were negative for aerobic and anaerobic bacteria, mycobacteria, and fungi. He was empirically commenced on treatment for presumed endogenous endophthalmitis with intravitreal and systemic therapy (oral moxifloxacin and voriconazole). There was no growth from the intravitreal tap cultures. A HIV preliminary test was positive and later confirmed by Western Blot. The CD4 count was 320 cells/μL and the HIV viral load was 60 500 copies/mL.

Chest computed tomography scanning showed a calcified granuloma within the right lung apex suspicious for prior tuberculosis exposure and a small nodule with surrounding ground glass change within the left lingula that favoured atypical infection. Following a bronchoscopy, the bronchial bacterial, fungal, acid fast bacilli culture and tuberculosis PCR were negative. The Quantiferon gold test came back positive indicating latent tuberculosis infection (TB1: 0.34, TB2: 0.35; Mitogen interferon gamma: 3.61).

The lumbar puncture cerebrospinal fluid (CSF) was india ink stain negative, with a white blood cell count of 324 × 10⁹/L with a mononuclear predominance. Brain magnetic resonance imaging demonstrated no focal intracranial pathology.

The diagnosis was confirmed by the Treponema pallidum PCR result from the skin swab and a rapid plasma reagin (RPR) titre of 1:256. The CSF later returned with the Venereal Disease Research Laboratory (VDRL) titre of 32. Histology of the punch biopsy of skin showed a mixed psoriasiform and vacuolar interface reaction accompanied by a superficial and deep dermal perivascular and periadnexal lymphoplasmacytic infiltrate dominated by plasma cells. A T. pallidum immunostain highlighted sparse intraepidermal spirochaetes (Fig. 3). Special stains for other bacteria, mycobacteria and fungi were negative. The plasma cell infiltrate was also polytypic with Kappa and Lambda in situ hybridisation stains.

Fig. 3.  Immunochemistry slide – organisms magnified. A T. pallidum immunostain highlighted sparse intraepidermal spirochaetes.

The patient was also diagnosed with right eye syphilitic uveitis and left eye syphilitic papillitis. Our patient completed treatment for neurosyphilis with 15 days of intravenous benzylpenicillin with a weaning steroid regiment with rapid improvement in symptoms. He was commenced on a Triumeq (Abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg) single tablet regime for his HIV.

On follow up 2 months later as an outpatient, his vision had returned back to normal and his skin lesions had resolved. The HIV viral load was undetectable and the RPR titre had fallen to 1:16. He was commenced on Isoniazid with pyridoxine for a planned total duration of 9 months to treat a latent tuberculosis infection.

Malignant syphilis is a rare manifestation of secondary syphilis and is commonly associated with HIV coinfection.^1,2 Also known as rupioid syphilis, this condition can be challenging to recognise as it may mimic other dermatological syndromes, such as pyoderma gangrenosum or ulcerative psoriasis. It is characterised by ulcerating, pustular skin lesions typically in the genital and facial areas, but can present anywhere on the body.³ Performing an immunohistochemical stain of a cutaneous biopsy appears to be a useful adjunct for the diagnosis of secondary syphilis.⁴ In addition, in our case, the positive result of T. pallidum PCR for the samples from skin lesions also played an important role in the diagnosis of secondary syphilis.

Ocular syphilis remains an important clinical presentation among patients with HIV infection.⁵ It can occur at any stage of syphilis and can affect any part of the eye, including the optic nerve and pupillomotor pathways. HIV co-infection appears to amplify syphilis progression through modulation of the immune response to T. pallidum and increases the likelihood of central nervous system involvement.⁶ As ocular syphilis is a great mimicker, it needs to be considered in patients with presumed endogenous endophthalmitis.⁷ Although it remains common practice to co-administer corticosteroids, as evidenced with this case, the benefit remains unclear and its role in severe ocular inflammation or macular oedema is yet to be determined.⁸

In recent times, an emerging outbreak of monkeypox infection has been documented worldwide since May 2022, now being reported in more than 30 countries including Australia.⁹ Monkeypox can present with a rash in varied forms, including macular, papular, vesicular or pustular and also is not confined to the genital regions. Although there has been a surge in media attention and increased laboratory testing to this developing orthopox epidemic, it is important to always investigate for syphilis as a cause in a patient presenting with a rash and/or vision problems. This case presented a few months prior to this outbreak and thus was not tested for monkeypox.

The rate of syphilis has been increasing in Australia and worldwide in high-income countries and also remains endemic in low-income countries.¹⁰ Due to the coronavirus disease 2019 (COVID-19) pandemic and multiple prolonged lockdowns in the state of New South Wales in Australia, the incidence of syphilis has plateaued temporarily during the past 2 years.¹¹ Following the lifting of restrictions, the incidence of syphilis and other sexually transmitted diseases would likely recover quickly, as evidenced in other countries.¹² Syphilis continues to cause morbidity and mortality and its increase in prevalence remains a public health concern.

The data that support the findings of this study are available from the corresponding author upon reasonable request.

The authors declare no conflicts of interest.

This research did not receive any specific funding.

The patient gave verbal and written consent for the case and the photos to be published in a medical journal, in print and online.