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         CASE REPORT Year : 2023  |  Volume : 69  |  Issue : 4  |  Page : 227-230

Neurosyphilis in a young man having HIV infection, blurring of vision and skin rash

JV Pagaddu, JC Valencia
Department of Medicine, Cagayan Valley Medical Center, Tuguegarao City, Cagayan, Philippines

Date of Submission13-Jun-2022Date of Decision17-Sep-2022Date of Acceptance29-Nov-2022Date of Web Publication10-May-2023

Correspondence Address:
Dr. J V Pagaddu
Department of Medicine, Cagayan Valley Medical Center, Tuguegarao City, Cagayan
Philippines

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jpgm.jpgm_484_22

We report a 22-year-old homosexual man, a known case of HIV-1 infection but non-compliant to medications, who presented with a 5-month history of progressive painless non-pruritic coin-shaped skin lesions and recent gradual bilateral blurring of vision. His history divulged a primary syphilitic event 1 year prior to the present clinical manifestations. Investigation led to the diagnosis of neurosyphilis with ocular involvement with concurrent signs of secondary syphilis. Treatment with aqueous crystalline penicillin G, ophthalmic steroid and tropicamide drops, and topical emollients resulted in significant clinical improvement of ocular symptoms and skin lesions. The diagnosis of neurosyphilis requires a high degree of clinical suspicion and should be included in the differential diagnosis of unexplained ocular symptoms, particularly in men who have sex with men and HIV-infected patients. This is necessary for the early diagnosis, appropriate management, and good outcome of these patients.

Keywords: HIV, neurosyphilis, ocular syphilis, secondary syphilis

How to cite this article:
Pagaddu J V, Valencia J C. Neurosyphilis in a young man having HIV infection, blurring of vision and skin rash. J Postgrad Med 2023;69:227-30
 :: Introduction 

Syphilis is a sexually transmitted disease (STD) and a multi-system chronic infection caused by Treponema pallidum.[1] Over the past decades, the incidence of syphilis has been significantly reduced because of the advent of antibiotic treatment. Nonetheless, it is still an important cause of STD in developing countries because of the increasing incidence of AIDS and HIV seropositivity.[2]

The natural history of syphilis classically progresses into three symptomatic stages (primary, secondary, and tertiary) and two asymptomatic stages (early and late latent). Primary syphilis infection presents with ulcers or chancre at the infection site. Secondary syphilis manifests as, but not limited to, skin rash, mucocutaneous lesions, and lymphadenopathy. Tertiary syphilis appears 10–30 years after the initial infection and comprises gummas and cardiovascular syphilis. Asymptomatic individuals with syphilis detected by serologic testing are said to have latent infections.[3]

Neurosyphilis is the syphilitic infection of the central nervous system (CNS) identified at any stage of syphilis. During the pre-antibiotic era, its occurrence was said to be common. However, with the advent of penicillin, its incidence has markedly decreased. However, in this modern era, it is more frequently seen in HIV-infected patients, particularly those who are not taking anti-retroviral medications or those with low CD4 + cell count.[4] Neurosyphilis is rarely seen in clinical practice in developing countries, such as the Philippines. In fact, its clinical features have not yet been thoroughly evaluated in Southeast Asia.[5]

Neurosyphilis is classified as early and late syphilis. Early stages of neurosyphilis involve the cerebrospinal fluid (CSF), meninges, and vascular structures. On the other hand, the late stage of neurosyphilis involves the cerebral tissue and spinal cord parenchyma. Therefore, the clinical picture of neurosyphilis is non-specific and may manifest with many different symptoms.[6] A rare clinical manifestation and an early form of neurosyphilis is ocular involvement. This may occur at any stage of infection and may serve as the only clinical manifestation.[6] The appearance of ocular syphilis is rare in the primary stage but may be seen in the secondary stage. On the other hand, ocular syphilis is more frequently seen in latent syphilis and the tertiary stage.[7]

We report an HIV-positive patient who sought medical attention because of gradual bilateral blurring of vision associated with progressive skin lesions.

 :: Case Report 

A 22-year-old homosexual man, a known case of HIV-1 infection but non-compliant to medications, presented to the emergency room with a 5-month history of painless, non-pruritic coin-shaped skin lesions that started on the right upper chest area and neck and progressively appeared over the genital area and on the upper and lower extremities. Two months before admission, the skin lesions had already involved the palms and soles. He also started to have eye redness and progressive blurring of vision. He consulted a dermatologist and an eye specialist. He was prescribed with topical anti-fungal and ophthalmic solutions, which afforded him no relief. In the following month, his condition progressed and worsened, with loss of vision in the right eye.

His history revealed that 1 year prior to the present clinical manifestation, he noted a single, small, round, reddish, firm, and painless skin lesion on his penis that resolved spontaneously. We hypothesize that the lesion was a syphilitic chancre, a primary manifestation of the infection. A previous fundus photograph performed 2 months prior to his present hospitalization, had revealed hazy media in the right eye and an essentially normal fundus finding in the left eye [Figure 1].

Figure 1: Fundus photograph of the right and left eyes performed 2 months prior to hospitalization: (a) right eye showing hazy media and distinct disc borders; (b) left eye showing clear media and distinct disc borders

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There was no history of fever, hearing loss, seizures, headache, change in behavior, nausea, vomiting, dysuria, or any penile discharge.

His social and sexual history was significant. He had a history of multiple male sexual partners. He practiced unprotected anal sex occasionally and was a smoker for two pack years.

On physical examination, he had multiple erythematous to hyper-pigmented plaques with scaling, some with hyperkeratosis over the extremities including palms and soles [Figure 2]. There were also multiple erythematous maculopapular scaly lesions on both testicles and hypo-pigmented plaques with scaling over the penile shaft. On neurologic examination, he was oriented to three spheres. There was relative afferent pupillary defect in the right eye. There were no meningeal signs or focal neurological deficits. Other systems examination was normal.

His latest CD4+ count was 131 cells/uL (normal value: 500 to 1,500 cells/uL), whereas the viral load (HIV-1) was 128,000 copies/mL (normal value: <40–10,000 copies/mL). Blood investigations revealed normal complete blood count, creatinine, ALT, AST and electrolytes. Hepatitis B and C serology was non-reactive. Chest radiography and computed tomography of the brain showed no significant abnormalities.

An incision biopsy of the skin lesion was performed, and histopathological findings revealed inflammatory cells, mostly lymphocytes with some plasma cells, with a note of acanthosis and hyperkeratosis [Figure 3]. With a background of HIV infection and the presence of skin lesions affecting especially the palmoplantar areas, the diagnosis of secondary syphilis was highly suspected. To confirm this diagnosis, a syphilis reverse sequence screening algorithm was employed. Rapid syphilis test (similar to EIA) was reactive, and treponema pallidum particle agglutination (TPPA) assay was positive (+4). However, Venereal Disease Research Laboratories (VDRL) test was non-reactive. During this time syphilis was still considered, although the VDRL test was negative, because of the high index of suspicion.

Figure 3: Histopathological findings of the skin lesions revealed inflammatory cells, mostly lymphocytes with some plasma cells, with acanthosis and hyperkeratosis

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Neurosyphilis must be ruled out in HIV-seropositive patients who have a CD4+ cell count ≤350 cells/uL with concomitant secondary syphilis presenting with visual impairment. Lumbar puncture was therefore performed, and CSF specimen was sent to laboratory for analysis. CSF analysis revealed absent RBC (normal value: 0 cells/uL), 16 WBC/uL (normal value: 0–3 cells/uL) with mononuclear predominance at 94%, glucose of 2.5 mmol/L (normal value: 2.5–3.5 mmol/L), and protein of 43 mg/dL (normal value: 18–45 mg/dL). CSF VDRL was reactive. With this result, a final diagnosis of neurosyphilis was established.

Treatment was initiated with aqueous crystalline penicillin G 4 million units IV every 4 hours for 14 days, ophthalmic prednisone and tropicamide drops for the affected eyes, and 10% urea lotion to affected skin lesions. During the hospital course, his ocular symptoms and skin lesions [Figure 2] improved within 5–7 days. After completion of antibiotics, the patient improved and was subsequently discharged.

 :: Discussion 

Syphilis can have protean clinical manifestations.[1] The natural history of syphilis progresses through well-characterized stages, which needs to be recognized to avoid devastating consequences.[8]

In a surveillance performed by the Centers for Disease Control and Prevention (CDC) in 2011, it was noted that the incidence of primary and secondary syphilis has increased significantly over the past 11 years.[9] This was evidently seen in the MSM (men who have sex with men) population and was attributed to the high rates of coexisting HIV infection and high-risk behaviors in this population.[8] It is thought that syphilis and HIV have a symbiotic interaction. Several studies suggest that HIV transmission is facilitated by syphilis by either increasing the expression of CCR5 receptors or inducing the expression of the HIV-1 gene in the human monocytes.[10] On the other hand, an underlying HIV infection modifies the natural history of syphilitic infection. As such, this leads to unusual and more aggressive clinical presentations and earlier neurologic involvement.[8]

The present case was diagnosed with secondary syphilis and was noted to have some degree of visual disturbances. Ocular syphilis may occur at any stage of infection and may serve as the only clinical manifestation.[6] The appearance of ocular syphilis is rare in the primary stage but may be seen in the secondary stage. On the other hand, ocular syphilis is more frequently seen in latent syphilis and the tertiary stage.[7] The differential diagnosis for neurosyphilis with ocular involvement is broad. Because syphilis comprises only a small proportion of all cases of ocular infection, delays in establishing the correct diagnosis are common.[8]

It has been observed that HIV-positive patients tend to have earlier ocular involvement than HIV-negative patients. Also, in the setting of untreated HIV, syphilitic involvement of the eye is frequently bilateral. Also, in HIV-positive patients, the risk of neurosyphilis is increased in those with lower peripheral CD4+ T cell counts, detectable plasma HIV RNA, and/or no anti-retroviral therapy. This is evident in the case being reported. The presence of ocular involvement, his non-compliance with anti-retroviral medications, and his low CD4+ T cell count (131 cells/uL) made us suspect neurosyphilis.[8]

The diagnostic testing for syphilis includes non-treponemal and treponemal serologic tests. Treponemal tests, such as FTA-ABS and enzyme immunoassay, are more specific and sensitive for later-stage syphilis. However, these tests are laborious and expensive. Non-treponemal tests, on the other hand, are used to test the reactivity of a patient's serum to cardiolipin-cholesterol-lecithin reagent. These tests include RPR and VDRL, which are non-specific, and false positive results are quite common. Nonetheless, these tests are used for screening because of their low cost and ease of performance.[11] During secondary syphilis, all tests should be reactive. In the present case, both EIA and TP-PA were reactive; however, VDRL was non-reactive. This unusual result may be attributed to prozone phenomenon. In agglutination reaction, this pertains to a zone of high antibody concentrations within which no reaction ensues. This phenomenon may be because of simply disproportionately high antibody titers, which is usually seen in secondary syphilis or with HIV co-infection.[12]

In addition to serologic testing, a lumbar puncture should be performed with CSF analysis when neurosyphilis or ocular involvement is suspected. CSF analysis may reveal a lymphocytic pleocytosis or increased protein level, but these findings may also be present in HIV-positive patients without syphilis. The diagnosis of neurosyphilis depends on a combination of CSF tests (CSF cell count or protein and a reactive CSF-VDRL) in the presence of reactive serologic test results and neurologic signs and symptoms.[3] These criteria for the diagnosis of neurosyphilis were fulfilled by the present patient. A positive CSF VDRL is highly specific for neurosyphilis. In a patient with neurologic signs or symptoms, a reactive CSF-VDRL (in the absence of blood contamination) is considered diagnostic of neurosyphilis.[3] The present patient's CSF VDRL was reactive which confirmed the diagnosis of neurosyphilis.

The management of ocular syphilis is similar to that of neurosyphilis. There are two treatment options. The first line of treatment includes a continuous infusion of intravenous aqueous crystalline penicillin G for 10–14 days. An alternative treatment regimen is an IM procaine penicillin once daily plus oral probenecid four times daily, both for 10–14 days.[3] Continued surveillance post treatment is essential in order to identify relapse or re-infection.[11] Historically, surveillance has been performed through serial lumbar punctures every 6 months until the cell count has normalized, with re-treatment if the CSF is not normal after 2 years.[3] More recent data suggest that serial serum RPR titers correlate with CSF titers, which predicts treatment success, and probably obviates the need for serial lumbar punctures.[8]

In this modern era, the resurgence of neurosyphilis is increasing, particularly among MSM. Neurosyphilis, especially its atypical forms, remains a diagnostic challenge. This present case highlights that it is important to include neurosyphilis in the differential diagnosis of unexplained ocular symptoms, particularly in MSM and HIV-infected patients. This is necessary for the early diagnosis, appropriate management, and good outcome of afflicted patients.

Declaration of patient consent

The authors certify that appropriate patient consent was obtained.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflict of interest.

 

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    5.Jamora RD, Dellosa MA, Collantes ME. A 24-year review of neurosyphilis in the Philippines. Philippine J Microbiol Infect Dis 2007;36:19-24.  
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    9.Centers for Disease Control and Prevention (CDC). Syphilis. 2011 Sexually Transmitted Diseases Surveillance. Atlanta: U.S. Department of Health and Human Services; 2012.  
    10.Sellati TJ, Wilkinson DA, Sheffield JS, Koup RA, Radolf JD, Norgard MV. Virulent Treponema pallidum, lipoprotein, and synthetic lipopeptides induce CCR5 on human monocytes and enhance their susceptibility to infection by human immunodeficiency virus type 1. J Infect Dis 2000;181:283-93.  
    11.Collis TK, Celum CL. The clinical manifestations and treatment of sexually transmitted diseases in human immunodeficiency virus-positive men. Clin Infect Dis 2001;32:611-22.  
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