Original Paper Received: July 21, 2014 Accepted after revision: October 31, 2014 Published online: March 24, 2015

Dermatology 2015;230:302–307 DOI: 10.1159/000369617

Clinical Aspects of Syphilis Reinfection in HIV-Infected Patients Johan Courjon a Thomas Hubiche a Nicolas Dupin b, c Philippe Alain Grange b, c Pascal Del Giudice a   

 

 

 

 

a

Unité de Maladies Infectieuses et Dermatologie, Hôpital Bonnet, Centre Hospitalier Intercommunal Fréjus Saint-Raphaël, Fréjus, b CNR Syphilis Paris, Groupe Hospitalier Cochin, AP-HP, Paris, and c UPRES-EA 1833, Laboratoire de Dermatologie, Université Paris Descartes, Paris, France  

 

Key Words Immunization · Sexually transmitted diseases · Syphilis · Sexual behavior

Abstract Background: The incidence of HIV-syphilis co-infection has risen since 2000, especially among men having sex with men (MSM). Syphilis reinfection can occur, but the clinical features of such events remain poorly characterized. Objective: To compare the cutaneous lesions seen with syphilis reinfections with those of first episodes in HIV-infected patients. Methods: In a cohort of HIV-infected patients, syphilis reinfection was established both clinically and biologically by evaluating changes in Venereal Disease Research Laboratory titers. Photographs and medical records were studied in order to determine the type of skin lesions and their quantification. Results: Among 533 HIV-infected patients, 42 (8%) experienced a first syphilis infection. Thirteen episodes of reinfection occurred in 12/42 (28%) patients, all MSM. In 78% of cases, reinfections were less symptomatic than first episodes. All patients presented classical syphilis lesions. Conclusions: We observed a high rate of reinfection, but with less severe skin manifestations during reinfection episodes. © 2015 S. Karger AG, Basel

© 2015 S. Karger AG, Basel 1018–8665/15/2304–0302$39.50/0 E-Mail [email protected] www.karger.com/drm

Introduction

In recent years, HIV-syphilis co-infection has emerged, with a particularly high prevalence in men having sex with men (MSM) [1]. Syphilis reinfection can occur. Its incidence rate has been reported to be 2.5–10% [2, 3] (over 8- and 10-year periods, respectively). In the MSM population, this rate is close to 6% within 1 year [4] or 2 years [5]. MSM status, HIV infection, black race and a history of gonorrhea or chlamydia are the factors associated with syphilis reinfection [2–5]. Obviously, syphilis reinfection raises the question of immunity against Treponema pallidum. Already during the pre-penicillin era, syphilis reinfection, such as experimental syphilis re-inoculation in man, was studied in order to characterize syphilis immunity [6, 7]. The development of an immune response during syphilis is undeniable [8]. The reason why this immunity does not always prevent reinfection could be because antibodies secreted during syphilis reinfection target a part of the T. pallidum repeat protein K (TprK), which differs in seven discrete variable regions. In rabbits, this antibody response shows a limited crossreactivity with the heterologous TprK variable region [9]. Moreover, endogenous oscillations have been observed in the incidence of syphilis over a period of 8–11 years. Johan Courjon Unité de Maladies Infectieuses et Dermatologie, Hôpital Bonnet Centre Hospitalier Intercommunal Fréjus Saint-Raphaël Avenue André Léotard, FR–83700 Fréjus (France) E-Mail johan_courjon @ hotmail.fr

Downloaded by: NYU Medical Center Library 198.143.38.97 - 6/23/2015 8:37:28 AM

 

These may be linked to partial immunity [10]. Whether this incompletely described immunity influences clinical signs remains unknown. Thus, it would be valuable to know how the skin lesions of the first episode differ from those of the reinfection. To the best of our knowledge, this has never been investigated in HIV-co-infected patients. We report herein the clinical description of 12 HIV patients presenting with syphilis reinfection and compare their clinical manifestations with those observed during the first syphilis infection.

fined as follows: sparse (+), moderate (++) and profuse (+++). When the three characteristics were the same for each episode, the reinfection was classified as identical. If the type of skin and mucosal lesions was the same, but with a different topography, or when the scale of quantification was different, the reinfection was classified as similar. When the clinical stage or type of lesions varied, reinfection was classified as different. Only patients with photographs and complete data available from medical record for each episode were considered for final comparison.

Results

We conducted a monocentric retrospective study between January 2002 and December 2010 in a cohort of HIV-infected patients at a secondary care hospital (Centre Hospitalier Intercommunal Fréjus Saint-Raphaël, France) where a specific dermatological examination is performed at each quarterly consultation. In addition, patients may be examined at any time during their follow-up in case of any clinical manifestation of HIV-related diseases. As part of the clinical examination, all skin lesions are photographed with the oral consent of patients. Since 2002, all HIV patients have had a syphilis screening with Venereal Disease Research Laboratory (VDRL) tests and T. pallidum hemagglutination assay every 6 months. In our department, since 2000, syphilis is systematically reported to the French Institute for Public Health (Institut de veille sanitaire, InVS). HIV patients with a syphilis infection reported to the InVS during the study period were included. Syphilis reinfection was defined according to the CDC guidelines [11]: (i) the patient had received treatment for a prior case of primary or secondary syphilis and had responded to treatment by at least a four-fold decline in VDRL titers, (ii) the patient had new seroreactivity or a four-fold increase in VDRL titers after treatment of the prior infection, (iii) the patient had a clinical history consistent with a repeat infection, including clinical symptoms consistent with syphilis and/or plausible sexual exposure. Those patients who failed to show a four-fold decline of VDRL titers within 6 months of therapy for primary or secondary syphilis were classified as treatment failures and were not considered as cases of reinfection. All patients were treated in our institution. Since 2010, in addition to serological tests, specific T. pallidum nested polymerase chain reaction (nPCR) amplifying the tpp47 gene of T. pallidum on swabs from skin lesions and in blood was performed by the French National Reference Center of Syphilis (Paris) using the method previously reported [12]. With the help of medical records and using a standardized form, the following data were recorded: duration of HIV infection at the first episode, sexual orientation, HIV viral load and CD4 T cell count at each episode, clinical stage of syphilis, time interval between infections and treatment for each episode of syphilis. Photographs and medical records were accurately analyzed in order to determine three characteristics of the dermatological manifestations: the type of skin and mucosal lesions (syphilitic roseola, papular syphilides, mucous patch, intertrigo, plaques fauchées, chancre), anatomical site and quantification. The quantification of the extension of the lesions during secondary stage syphilis was de-

Syphilis Reinfection

During the study period, 533 HIV-infected patients were followed in our institution, including 33% MSM. A first episode of syphilis was reported in 42 (8%) patients. Among these patients, 38 (90%) were MSM. Twelve patients (28%), all MSM, with a mean age of 35 years (range 27–45) at the first episode, had a syphilis reinfection. One patient had three episodes of syphilis during the study period. The patients’ characteristics are presented in table 1. All patients were treated by highly active antiretroviral therapy. The median CD4 T cell count was 377/mm3 (range 163–1,000) and 534/mm3 (range 253–1,400) at the first and second episodes, respectively. The median duration before reinfection was 24 months (range 8–72). Disease stage at diagnosis, clinical manifestations and VDRL titers for each patient are presented in table 2. One patient (No. 8) was diagnosed with syphilis in 2002 but was HIVnegative at that time. All the other patients experienced syphilis episodes during HIV infection. There were no atypical clinical manifestations of syphilis either during the first episode or during reinfection. All episodes responded well to standard treatment. 25 syphilitic episodes were recorded, with 20 symptomatic ones (15 photographed) and 5 latent ones. Photographs of lesions in patients with symptoms at each episode are presented in figure 1. In four patients, the syphilis stage was obtained from the medical record but, as no clinical photographs were available, they were not considered for final analysis. For 8 patients with a total of 9 syphilitic reinfection episodes (patient No. 11 had 2 reinfections), complete clinical data, including photographs, were available: 1 episode (11.1%) was classified as identical, 3 (33.3%) as similar and 5 (55.6%) as different. Among those 8 patients, 7 of the 9 reinfection episodes (78%) were considered less symptomatic compared to the initial one: patients 1, 2 and 6 had reinfection at the same stage (secondary) with fewer lesions, and patients 5, 7, 11 (second reinfection) and 12 had reinfection at an early latent stage after a first symptomatic episode. Dermatology 2015;230:302–307 DOI: 10.1159/000369617

303

Downloaded by: NYU Medical Center Library 198.143.38.97 - 6/23/2015 8:37:28 AM

Patients and Methods

Table 1. Patient characteristics

CD4 (cells/mm3)/viral load (copies/ml)

Patient No.

Duration of HIV infection, yearsa

1st episode

2nd episode

1 2 3 4 5 6 7 8c 9 10 11 12

4