Vesicular syphilid in a seropositive patient

Introduction

Syphilis is an sexually transmitted infection (STI) with a multitude of presentations. Vesicobullous lesions, though commonly found in congenital syphilis, are rarely encountered in the secondary stage of acquired syphilis. Only four cases of vesicobullous secondary syphilis have been reported in the literature to date to the best of our knowledge. We report this unusual case to emphasize that physicians should be aware of this rare presentation and must maintain a high index of suspicion.

Case report

A 45-year-old man presented with sudden onset of asymptomatic erythematous lesions over the body for the past four days. He related the onset of the eruption to paracetamol he had taken one day before. A history of sexual contact with a commercial sex worker 7–8 months back was obtained, but patient denied any lesions including ulcers over the genitalia in the past. There was no history of blood transfusion or chronic illness.

On examination, the patient appeared healthy and well-nourished. Erythematous papules (Figures 1(a), (b)) of size 2 × 2 mm to 5 × 5 mm were present over whole body including the palms and soles along with several vesicles over back (Figure 1(c)). Mucosal surfaces were spared. Based on clinical findings, differential diagnoses considered included drug eruption, pityriasis lichenoides et varioliformis acuta (PLEVA), pityriasis rosea and secondary syphilis. Since the patient refused skin biopsy, other appropriate investigations were undertaken and the patient was started on a short course of oral steroids and was called for follow-up after three days. OPEN IN VIEWER

Three days later, vesicular lesions had crusted and there was no improvement in the other lesions. His reports revealed positive serology for HIV-1 and for syphilis with a positive VDRL test at a dilution of 1:256 (Trepolipin, Tulip diagnostics, Goa, India). Oral steroids were discontinued and a biopsy was taken from a papule on the back, with his consent, which on H&E staining revealed mild acanthosis and dense dermal infiltrate composed of lymphocytes, plasma cells and a few histiocytes (Figure 2). For confirmation of syphilis, the Treponema pallidum haemagglutination (TPHA) test was performed and was positive. Further investigations revealed his CD4 cell count was 78 cells/µL, CD4:CD8 ratio was 0.36 and CSF-VDRL test was negative. HIV RNA testing was not available at our clinic. Both VDRL and HIV tests performed on his spouse were non-reactive. Based on the clinical, laboratory and histopathological findings, a diagnosis of secondary syphilis coexisting with HIV was made. Three doses of benzathine penicillin (2.4 million units each) were administered intramuscularly at weekly intervals along with antiretroviral therapy (ART; tenofovir 300 mg once a day, stavudine 40 mg twice a day, efavirenz 600 mg once a day). The patient and his wife were given appropriate counseling regarding various aspects of HIV and STIs. At one-week post treatment follow-up, almost all skin lesions had resolved. At 6 months follow-up visit, the patient was asymptomatic, his VDRL titre was 1:32 with CD4 count 240 cells/µL. During this period, he had a single episode of fever for which he took paracetamol; this did not result in any eruption. OPEN IN VIEWER

Discussion

Syphilis is a disease with extremely variable presentations. The eruptions of secondary syphilis can morphologically be either macular, papular, papulosquamous, pustular, vesicular or follicular. ¹ In a 20-year retrospective study, 40% of syphilitic rashes were macular, 40% maculopapular and 10% papular. ² However, no case of vesicular syphilid was reported in the study. Few cases of vesicular^3–6 or pustular^2,7 syphilids are reported in the literature. These have been thought to occur commonly in debilitated patients but this view has been contradicted by many reports.^4–7

We considered drug rash as the first possibility since morphology was consistent with the diagnosis and the patient reported sudden onset of lesions after drug intake. Therefore, a short course of oral steroids was prescribed. Unfortunately, due to patient’s refusal for skin biopsy on the first visit, histological characteristics of vesicles could not be studied. However, the possibility of drug rash is unlikely since the patient did not report any similar lesions after taking the same brand of paracetamol at a later date.

Syphilis in HIV patients poses a diagnostic dilemma because of a higher rate of altered clinical presentation and false positive as well as negative serological tests. ⁸ Failure of the nontreponemal test titre to decline even after appropriate treatment poses difficulty in assessing treatment response. ⁸ Moreover, severe ocular manifestations, an accelerated natural course of syphilis as well as neurosyphilis may be associated with HIV infection. ⁸

Syphilis, through genital ulcer disease, may increase the risk of HIV transmission. All patients presenting with an STI should be offered HIV testing and given advice on HIV prevention. ⁸ It has also been reported that syphilis, like many other acute infections, causes a transient decrease in the CD4 cell count that resolves after the infection is treated. ⁹ This might explain the fact that our patient previously remained asymptomatic despite a CD4 cell count of 78/µL at the time of his presentation. This increased to 240 cells/µL after six months of ART, which showed an appropriate immunologic response to therapy.

There is an increased prevalence of neurosyphilis in HIV-positive patients with untreated syphilis (23.5%) compared to HIV-negative patients (10%), ⁸ more so if the CD4 count is ≤350 cells/µL. ¹⁰ This has led some authorities to recommend lumbar puncture in all HIV-positive patients irrespective of the stage of syphilis. ⁸ Therefore, we performed lumbar puncture in our patient to exclude neurosyphilis. However, this view is debated and CDC asserts that unless neurologic symptoms are present, CSF examination in HIV co-infected patients has not been associated with improved clinical outcomes. ¹¹

A more aggressive disease course ⁸ and a reduced efficacy of standard therapy has been reported for early syphilis in HIV-positive patients. ¹² Therefore, at our clinic, three doses of benzathine penicillin are administered in all HIV-positive syphilis patients with normal CSF findings. However, this view is controversial and CDC recommends a single dose of intramuscular benzathine penicillin for treating early syphilis in HIV-positive patients. ¹¹ HIV-infected persons should be evaluated clinically and serologically for treatment failure at 3, 6, 9, 12 and 24 months after therapy. CSF examination and retreatment should be strongly considered if nontreponemal test titres do not decrease fourfold within 6–12 months of therapy. ¹¹ Our patient’s VDRL titer decreased from 1:256 to 1:32 at the end of six months, which indicates an appropriate response to therapy. We are reporting this case because of the rarity of a vesicular eruption in secondary syphilis. Furthermore, in syphilis patients with coexisting HIV infection, early diagnosis and treatment is essential to prevent various disease complications and to minimize transmission of the infection.