Syphilis should not be overlooked in any individual, irrespective of their condition

Oriane Cellier1, Juliette Jourdan2, Lotfi Dahmane2, Véronique Perronne2, Aurélien Dinh2,3, Karim Jaffal2

1 Internal Medicine Resident, Paris-Est Créteil Université, Paris, France

2 Infectious Disease Department, Raymond-Poincaré University Hospital, AP-HP, Paris Saclay University, Garches, France

3 Université Versailles Saint Quentin Paris Saclay, Versailles, France

Corresponding author’s e-mail: orianecellier@hotmail.fr

Received: 20/05/2024
Accepted: 29/05/2024
Published: 05/08/2024

Conflicts of Interests: The Authors declare that there are no competing interests.
Patient Consent: Written consent was obtained from the patient for this article.
Acknowledgements: The authors would like to thank all the infectious disease ward and all the seniors for their assistance.
This article is licensed under a Commons Attribution Non-Commercial 4.0 License

How to cite this article: Cellier O, Jourdan J, Dahmane L, Perronne V, Dinh A, Jaffal K. Syphilis should not be overlooked in any individual, irrespective of their condition. EJCRIM 2024;11:doi:10.12890/2024_004578

ABSTRACT

Introduction: Syphilis remains a significant challenge in public health, largely because of its diverse clinical manifestations, often resulting in underdiagnosis especially among patients with neurogenic disability.
Case description: We present a case of neurosyphilis in a 63-year-old patient with a spinal cord injury. Despite syphilis being a well-established sexually transmitted infection, the exacerbation of neurological and dermatological symptoms during physical examination prompted an investigation into alternative causes beyond the patient’s pre-existing paraparesis, ultimately resulting in the diagnosis of neurosyphilis.
Conclusion: This case highlights the importance of considering syphilis as a potential diagnosis in individuals regardless of their medical history.

KEYWORDS

Neurosyphilis, tetraparetic, sexually transmitted infection, roseoliform exanthema, meningoradiculitis

LEARNING POINTS

INTRODUCTION

In recent years, there has been a resurgence of syphilis. The decline in exposure to its various manifestations has led to challenges in diagnosing a disease that was once well-recognised[1-3]. With the increasing rates of syphilis, cases of neurosyphilis have likely risen as well[4]. The global population could be contaminated, even in patients with disability. Despite some attention to this rising incidence, there remains a striking delay in diagnosis and subsequent treatment of this infectious disease[5-7]. This delay is even more pronounced when the patient does not fit the typical profile for a sexually transmitted disease.

CASE DESCRIPTION

In September 2022, a 63-year-old male with a medical history of infantile paraparesis, which had been progressively worsening over the previous four years, with hypertension and gout, presented to the department of infectious diseases. He reported a 15-day history of multiple painless, non-itchy plaques. Physical examination revealed a rash resembling roseola on the trunk and back, with erythematous-squamous papules on both arms and upper limbs, leaving behind pink scars (Fig. 1). He also exhibited spastic weakness and worsening sensory loss in the lower extremities. The patient recalled experiencing a sore throat with ulcers in the mouth, a rash on the palms of hands and feet, and inflammatory joint pain in the upper limbs without swelling. There had been a single episode of eye floaters without vision loss or pain six months prior, which resolved on its own within a few days. Since then, he noted a decline in his condition marked by weakness, pain and paraparesis of the lower extremities. The patient denied any recent travel, lived in an urban area and did not report any tick bites. Laboratory analyses including routine blood examination, liver and kidney function tests were normal. To exclude any neurological pathologies, brain and spinal MRI were performed showing only minor leukoaraiosis with no signs of neurological compression or stroke. Electromyography showed signs of bilateral axonal lesions with delayed central motor conduction to both legs compatible with myeloradiculitis. Ophthalmological evaluation was unremarkable. A complete CT-scan eliminated a deep infectious focus and neoplastic involvement. The aetiologies of roseoliform exanthema are mainly infectious, therefore a complete infectious assessment was undertaken; a cerebrospinal fluid polymerase chain reaction test ruled out Borrelia burgdorferi infection, and other possible aetiologies such as tuberculosis, herpes simplex virus 1 and 2, varicella-zoster virus, enterovirus, Epstein-Barr virus and cytomegalovirus. No evidence for vasculitis or collagen vascular disorders was found. Anti-nuclear antibodies such as ds-DNA (antibodies against single and double-stranded DNA), and autoantibodies to extractable nuclear antigens such as anti–Sjögren’s-syndrome-related antigen A or complement levels were normal.

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Figure 1. Physical examination revealed a rash resembling roseola on the trunk and back, along with erythematous-squamous papules on both arms and upper limbs, leaving behind pink scars.

The new-patient interview revealed unprotected sexual activity since beginning of 2022. Given the unprotected sexual intercourse, serological tests for HIV, hepatitis B surface antigen and anti-HCV (hepatitis C virus) were performed and came back negative. Finally, syphilis testing (reactive venereal disease research laboratory, VDRL) returned positive with an index of 1/256. Moreover, the patient tested negative for other sexually transmitted diseases such as Chlamydia trachomatis and gonorrhoea.

A lumbar puncture revealed clear fluid with slightly increased protein levels (525 mg/l) and 20 cells/µl, predominantly lymphocytes (79%), and monocytes (11%), with Treponema pallidum antibodies. The T. pallidum antibody levels were 1 UI/ml in the cerebrospinal fluid (CSF) and 1/256 units in the serum. A diagnosis of neurosyphilis was made, and intravenous crystallised penicillin G (24 million units/day) was administered for 14 days. After 72 hours of anti-syphilitic treatment, the patient developed an extension of cutaneous lesions on the trunk and face, consistent with a Herxheimer reaction or drug-induced allergy (Fig. 2). Topical steroids were prescribed, resulting in clinical improvement, and penicillin G treatment was continued with a favourable outcome: skin lesions disappeared, and neurological impairment decreased.

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Figure 2. After 72 hours of anti-syphilitic treatment, the patient developed an extension of cutaneous lesions on the trunk and face, consistent with a Herxheimer reaction.

Reassessment after three months of treatment revealed an improvement in the patient’s general condition, with restored motor function and regression of all skin lesions. Syphilis serological control found a decrease in the index with a VDRL of 1/4 after 6 months and 1/2 after one year.

DISCUSSION

Neurosyphilis arises from the invasion of the central nervous system by T. pallidum and can occur at any stage of syphilis[8]. The initial stage of syphilis, characterised by genital chancre, often goes unnoticed. The secondary stage typically presents with a transient roseoliform skin rash, while the subsequent asymptomatic latent stage can persist for several years. Neurological invasion occurs rapidly, affecting approximately 30% of patients during the primary stage, often without symptoms[8,9]. However, symptomatic cases – which typically arise within 12 months post-infection – often manifest as acute meningitis, frequently involving the basilar region and can lead to cerebral vessel thrombosis. Hydrocephalus accompanied by increased intracranial pressure has also been reported. Late neurological manifestations, such as tabes dorsalis and general paresis, typically arise 10–30 years after infection, but can occur earlier in immunocompromised individuals[10]. While those cases have declined since the penicillin era, physicians should remain vigilant for atypical presentations, including epilepsy, ocular symptoms, stroke and confusion, which have become more prevalent.

For a neuro-injured patient, all these symptoms can be part of their neurological stage and can be neglected or can also be caused by other irritative stimuli. Thus, neurological worsening in a neuro-injured patient must lead to discussions about a curable diagnosis before ruling on progression of the underlying disease. Faced with atypical neurological symptomatology, with a negative aetiological assessment, it is necessary to know how to investigate and discuss sexually transmitted disease and especially tertiary syphilis, which can appear a long time after the infection and be responsible for a polymorphous picture. The essential diagnostic test is a lumbar puncture, with evidence of intrathecal antibody synthesis and positive VDRL. CSF laboratory abnormalities are commonly found in individuals with early syphilis, regardless of whether they exhibit neurological signs or symptoms. No single laboratory test can definitively confirm or rule out a diagnosis of neurosyphilis. Instead, the current best practice for diagnosing neurosyphilis relies on a combination of clinical history, physical examination findings, serum antibody tests and CSF analysis.

A recent review by Hamill et al. outlines the key clinical features of both early and late (tertiary) neurosyphilis. It discusses the clinical significance of an asymptomatic patient, examines the indications for CSF examination, evaluates the performance characteristics of various CSF assays including treponemal and lipoidal antibodies, and discusses the role of imaging[11].

Clinical observations suggest that most cases of neurological invasion and CSF abnormalities in asymptomatic individuals likely either resolve or do not progress with non-neurosyphilis antibiotic regimens. Symptomatic neurosyphilis is rare, even without universal CSF examinations. There is currently no evidence to support treating neurosyphilis at any stage in individuals without clinical neurological findings. Furthermore, it remains uncertain whether treating asymptomatic neurosyphilis with IV penicillin improves long-term outcomes. According to the Centers for Disease Control and Prevention (CDC) guidelines, CSF examination should be conducted in patients with clinical signs or neurological involvement, patients with lipoidal serological titres showing a sustained fourfold increase following appropriate therapy, and patients diagnosed with gummatous or cardiovascular syphilis[12]. However, CSF examinations are not recommended for individuals presenting solely with ocular or optic signs without neurological symptoms[12]. While people living with HIV have a higher risk of neurosyphilis, the overall risk is likely small, especially in the era of antiretroviral therapy.

Treatment recommendations for neurosyphilis are largely based on case series, retrospective studies, pharmacokinetic/pharmacodynamic data and clinical experience, as opposed to robust clinical trials. The optimal duration of therapy has not been studied in a trial setting, but clinical experience suggests that 10–14 days of penicillin is usually sufficient[13]. The role of corticosteroids in neurosyphilis management is uncertain, and routine use is not recommended by the CDC[12]. Post-treatment monitoring should involve regular VDRL titre checks every three months until it becomes undetectable – a process that can take up to 24 months, particularly in people living with HIV. Finally, doxycycline taken as pre- or post-exposure prophylaxis within 72 hours of potential exposure has been shown to reduce incident syphilis by approximately 70%[14]. However, unanswered questions remain regarding potential harms, including antimicrobial resistance in sexually transmitted infections[15].

CONCLUSION

The incidence of syphilis cases is on the rise, presenting an ongoing challenge despite the availability of effective treatments, diagnostic tests and educational public health initiatives. This case serves as a reminder that due to the typically prolonged disease course, resulting from diagnostic delays and the diverse affected organ systems with their respective symptoms, syphilis is often referred to as ‘the great imitator’. This characteristic leads to significant delays in both diagnosis and subsequent treatment. While the majority of new syphilis infections are diagnosed in men who have sex with men or sex workers, our case highlights that the diagnostic of syphilis should not be disregarded in any individual, regardless of their circumstances.

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