Background. Oral lesions may constitute the first clinical manifestation in secondary syphilis, but detailed descriptions in HIV-infected individuals are scarce. Objective. To describe the clinical characteristics of oral secondary syphilis in HIV-infected patients and its relevance in the early diagnosis of syphilis. Methods. Twenty HIV/AIDS adult subjects with oral secondary syphilis lesions presenting at two HIV/AIDS referral centers in Mexico City (2003–2011) are described. An oral examination was performed by specialists in oral pathology and medicine; when possible, a punch biopsy was done, and Warthin-Starry stain and immunohistochemistry were completed. Intraoral herpes virus infection and erythematous candidosis were ruled out by cytological analysis. Diagnosis of oral syphilis was confirmed with positive nontreponemal test (VDRL), and, if possible, fluorescent treponemal antibody test. Results. Twenty male patients (median age 31.5, 21–59 years) with oral secondary syphilis lesions were included. Oral lesions were the first clinical sign of syphilis in 16 (80%) cases. Mucous patch was the most common oral manifestation (17, 85.5%), followed by shallow ulcers (2, 10%) and macular lesions (1, 5%). Conclusions. Due to the recent rise in HIV-syphilis coinfection, dental and medical practitioners should consider secondary syphilis in the differential diagnosis of oral lesions, particularly in HIV-infected patients. 1. Background In the USA, since 2001 a resurgence in syphilis incidence, especially among males who have sex with men (MSM), has been observed [1]. By 2004, more than a half of new cases reported of primary and secondary syphilis were estimated to occur in MSM, with a high rate of HIV coinfection [2, 3]. During 2007-2008, the total number of cases of syphilis reported to the CDC increased 13.1% [4]. The increasing incidence of syphilis reported in many studies in the last decade, especially among MSM, is clearly a marker for higher risk behavior in this population and raises concerns for a parallel increase in HIV transmission [5–8]. It has been suggested that HIV infection modifies the clinical presentation of syphilis with greater organ involvement, atypical and florid skin rashes, and more rapid progression to neurosyphilis [9–12]; consequently, the diagnosis of syphilis in HIV-infected individuals represents a challenge for care providers. A careful sexual exposure history, recognition of clinical signs and symptoms, and interpretation of diagnostic testing are crucial in this context [13]. Detailed descriptions of oral
References
[1]
K. Buchacz, J. D. Klausner, P. R. Kerndt et al., “HIV incidence among men diagnosed with early syphilis in Atlanta, San Francisco, and Los Angeles, 2004 to 2005,” Journal of Acquired Immune Deficiency Syndromes, vol. 47, no. 2, pp. 234–240, 2008.
[2]
Centers for Disease Control and Prevention (CDC), Sexually Transmitted Disease Surveillance 2004 Supplement: Syphilis Surveillance Report, Department of Health and Human Services, Atlanta, Ga, USA, 2005.
[3]
Centers for Disease Control and Prevention (CDC), “Primary and secondary syphilis—United States, 2003-2004,” Morbidity and Mortality Weekly Report, vol. 55, no. 10, pp. 269–273, 2006.
[4]
Centers for Disease Control and Prevention (CDC), Sexually Transmitted Disease Surveillance, 2008, U.S. Department of Health and Human Services, Atlanta, Ga, USA, 2009.
[5]
A. Ganesan, A. Fieberg, B. K. Agan, et al., “Results of a 25-year longitudinal analysis of the serologic incidence of syphilis in a cohort of HIV-infected patients with unrestricted access to care,” Sexually Transmitted Diseases, vol. 39, no. 6, pp. 440–448, 2012.
[6]
Centers for Disease Control and Prevention, Sexually Transmitted Disease Surveillance 2010, U.S. Department of Health and Human Services, Atlanta, Ga, USA, 2011.
[7]
V. Bremer, U. Marcus, and O. Hamouda, “Syphilis on the rise again in Germany—results from surveillance data for 2011,” Eurosurveillance, vol. 17, no. 29, p. 20222, 2012.
[8]
D. Li, Y. Jia, Y. Ruan et al., “Correlates of incident infections for HIV, syphilis, and hepatitis B virus in A cohort of men who have sex with men in Beijing,” AIDS Patient Care and STDs, vol. 24, no. 9, pp. 595–602, 2010.
[9]
G. Karp, F. Schlaeffer, A. Jotkowitz, and K. Riesenberg, “Syphilis and HIV co-infection,” European Journal of Internal Medicine, vol. 20, no. 1, pp. 9–13, 2009.
[10]
N. M. Zetola and J. D. Klausner, “Syphilis and HIV infection: an update,” Clinical Infectious Diseases, vol. 44, no. 9, pp. 1222–1228, 2007.
[11]
G. Pialoux, S. Vimon, A. Moulignier, M. Buteux, B. Abraham, and P. Bonnard, “Effect of HIV infection on the course of syphilis,” AIDS Reviews, vol. 10, no. 2, pp. 85–92, 2008.
[12]
W. A. Lynn and S. Lightman, “Syphilis and HIV: a dangerous combination,” Lancet Infectious Diseases, vol. 4, no. 7, pp. 456–466, 2004.
[13]
N. M. Zetola, J. Engelman, T. P. Jensen, and J. D. Klausner, “Syphilis in the United States: an update for clinicians with an emphasis on HIV coinfection,” Mayo Clinic Proceedings, vol. 82, no. 9, pp. 1091–1102, 2007.
[14]
K. L. Ortega, N. P. M. Rezende, and M. H. C. G. Magalh？es, “Diagnosing secondary syphilis in a patient with HIV,” British Journal of Oral and Maxillofacial Surgery, vol. 47, no. 2, pp. 169–170, 2009.
[15]
J. Dalmau, M. Alegre, M. A. Sambeat, E. Roé, L. Peramiquel, and A. Alomar, “Syphilitic nodules on the tongue,” Journal of the American Academy of Dermatology, vol. 54, no. 2, pp. S59–S60, 2006.
[16]
O. Baniandrés Rodríguez, O. Nieto Perea, L. Moya Alonso, R. Carrillo Gijón, and A. Harto Casta？o, “Nodular secondary syphilis in a HIV patient mimicking cutaneous lymphoma,” Anales de Medicina Interna, vol. 21, no. 5, pp. 241–243, 2004.
[17]
K. L. Ortega, N. P. Rezende, F. Watanuki, N. Soares De Araujo, and M. H. C. G. Magalhaes, “Secondary syphilis in an HIV positive patient,” Medicina Oral, vol. 9, no. 1, pp. 33–38, 2004.
[18]
M. J. Romero-Jiménez, I. Suárez Lozano, J. M. Fajardo Picó, and B. Barón Franco, “Malignant syphilis in patient with human immunodeficiency virus (HIV): case report and literature review,” Anales de Medicina Interna, vol. 20, no. 7, pp. 373–376, 2003.
[19]
S. Y. Lu and H. L. Eng, “Secondary syphilis-related oral ulcers: report of four cases,” Chang Gung Medical Journal, vol. 25, no. 10, pp. 683–688, 2002.
[20]
R. Czerninski, A. Pikovski, K. Meir, N. Casap, A. E. Moses, and A. Maly, “Oral syphilis lesions—a diagnostic approach and histologic characteristics of secondary stage,” Quintessence International, vol. 42, no. 10, pp. 883–889, 2011.
[21]
K. Ikenberg, E. Springer, W. Br？uninger et al., “Oropharyngeal lesions and cervical lymphadenopathy: syphilis is a differential diagnosis that is still relevant,” Journal of Clinical Pathology, vol. 63, no. 8, pp. 731–736, 2010.
[22]
M. D. Mignogna, G. Fortuna, S. Leuci, C. Mignogna, and M. Delfino, “Secondary syphilis mimicking pemphigus vulgaris,” Journal of the European Academy of Dermatology and Venereology, vol. 23, no. 4, pp. 479–480, 2009.
[23]
G. L. Murrell, “Secondary syphilis oral ulcer,” Otolaryngology-Head and Neck Surgery, vol. 140, no. 6, pp. 942–943, 2009.
[24]
D. Compilato, S. Amato, and G. Campisi, “Resurgence of syphilis: a diagnosis based on unusual oral mucosa lesions,” Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology, vol. 108, no. 3, pp. e45–e49, 2009.
[25]
M. Carlesimo, E. Palese, E. Mari et al., “Isolated oral erosions: an unusual manifestation of secondary syphilis,” Dermatology Online Journal, vol. 14, no. 2, p. 23, 2008.
[26]
M. Hayes, D. White, and A. Richards, “Secondary syphilis presenting as atypical oral ulceration—a case report,” Dental Update, vol. 35, no. 7, pp. 465–467, 2008.
[27]
J. E. Herrero-gonzález, M. E. P. Amer, M. F. Farrés, A. T. Abelló, C. Barranco, and R. M. Pujol, “Syphilitic mucous patches: the resurgence of an old classic,” International Journal of Dermatology, vol. 47, no. 12, pp. 1281–1283, 2008.
[28]
A. Stepanova and W. C. Marsch, “Plaques opalines. A rare form of secondary syphilis of the oral mucous membrane,” Hautarzt, vol. 57, no. 6, pp. 514–517, 2006.
[29]
H. Hua, Z. M. Yan, R. T. Shi, Y. Gao, and Y. Y. Xu, “Clinical and pathological analysis of oral manifestations of 40 patients with secondary syphilis,” Zhonghua Kou Qiang Yi Xue Za Zhi, vol. 40, no. 5, pp. 376–378, 2005.
[30]
A. Paz and I. Potasman, “Oral lesions as the sole presenting symptom of secondary syphilis,” Travel Medicine and Infectious Disease, vol. 2, no. 1, pp. 37–39, 2004.
[31]
C. Aquilina, R. Viraben, and P. Denis, “Secondary syphilis simulating oral hairy leukoplakia,” Journal of the American Academy of Dermatology, vol. 49, no. 4, pp. 749–751, 2003.
[32]
A. Christen, H. E. Killer, B. Stamm, and P. Itin, “Secundary syphilis with ocular manifestation and oral ulceration,” Schweizerische Rundschau fur Medizin-Praxis, vol. 92, no. 9, pp. 397–402, 2003.
[33]
S. Dave, D. V. Gopinath, and D. M. Thappa, “Nodular secondary syphilis,” Dermatology Online Journal, vol. 9, no. 1, p. 9, 2003.
[34]
A. Ulmer and G. Fierlbeck, “Images in clinical medicine. Oral manifestations of secondary syphilis,” The New England Journal of Medicine, vol. 347, no. 21, p. 1677, 2002.
[35]
G. Ficarra and R. Carlos, “Syphilis: the renaissance of an old disease with oral implications,” Head and Neck Pathology, vol. 3, no. 3, pp. 195–206, 2009.
[36]
J. C. Le？o, L. A. Gueiros, and S. R. Porter, “Oral manifestations of syphilis,” Clinics, vol. 61, no. 2, pp. 161–166, 2006.
[37]
E. Schneider, S. Whitmore, K. M. Glynn, K. Dominguez, A. Mitsch, and M. T. McKenna, “Revised surveillance case definitions for HIV infection among adults, adolescents, and children aged <18 months and for HIV infection and AIDS among children aged 18 months to <13 years—United States, 2008,” Morbidity and Mortality Weekly Report, vol. 57, no. 10, pp. 1–12, 2008.
[38]
R. Adolf, F. Bercht, M. L. Aronis, L. W. Lunardi, M. Schechter, and E. Sprinz, “Prevalence and risk factors associated with syphilis in a cohort of HIV positive individuals in Brazil,” AIDS Care, vol. 24, pp. 252–258, 2012.
[39]
M. C. Thurnheer, R. Weber, L. Toutous-Trellu et al., “Occurrence, risk factors, diagnosis and treatment of syphilis in the prospective observational Swiss HIV Cohort Study,” AIDS, vol. 24, no. 12, pp. 1907–1916, 2010.
[40]
E. P. Chow, D. P. Wilson, and L. Zhang, “HIV and syphilis co-infection increasing among men who have sex with men in China: a systematic review and meta-analysis,” PLoS One, vol. 6, no. 8, Article ID e22768, 2011.
[41]
E. Muldoon and F. Mulcahy, “Syphilis resurgence in Dublin, Ireland,” International Journal of STD & AIDS, vol. 22, no. 9, pp. 493–497, 2011.
[42]
P. Pathela, S. L. Braunstein, J. A. Schillinger, C. Shepard, M. Sweeney, and S. Blank, “Men who have sex with men have a 140-fold higher risk for newly diagnosed HIV and syphilis compared with heterosexual men in New York City,” JAIDS Journal of Acquired Immune Deficiency Syndromes, vol. 58, no. 4, pp. 408–416, 2011.
[43]
W. Jarzebowski, E. Caumes, N. Dupin, et al., “Effect of early syphilis infection on plasma viral load and CD4 cell count in human immunodeficiency virus-infected men: results from the FHDH-ANRS CO4 cohort,” Archives of Internal Medicine, vol. 172, no. 16, pp. 1237–1243, 2012.
[44]
A. C. Weintrob, W. Gu, J. Qin et al., “Syphilis co-infection does not affect HIV disease progression,” International Journal of STD and AIDS, vol. 21, no. 1, pp. 57–59, 2010.
[45]
R. Palacios, F. Jiménez-O？ate, M. Aguilar et al., “Impact of syphilis infection on HIV viral load and CD4 cell counts in HIV-infected patients,” Journal of Acquired Immune Deficiency Syndromes, vol. 44, no. 3, pp. 356–359, 2007.
[46]
K. Kofoed, J. Gerstoft, L. R. Mathiesen, and T. Benfield, “Syphilis and human immunodeficiency virus (HIV)-1 coinfection: influence on CD4 T-cell count, HIV-1 viral load, and treatment response,” Sexually Transmitted Diseases, vol. 33, no. 3, pp. 143–148, 2006.
[47]
K. Buchacz, P. Patel, M. Taylor et al., “Syphilis increases HIV viral load and decreases CD4 cell counts in HIV-infected patients with new syphilis infections,” AIDS, vol. 18, no. 15, pp. 2075–2079, 2004.
[48]
V. Ramirez-Amador, J. G. Sierra Madero, L. E. Pedraza et al., “Oral secondary syphilis in a patient with human immunodeficiency virus infection,” Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics, vol. 81, no. 6, pp. 652–654, 1996.
[49]
G. Ficarra, A. M. Zaragoza, L. Stendardi, F. Parri, and C. J. Cockerell, “Early oral presentation of lues maligna in a patient with HIV infection: a case report,” Oral Surgery Oral Medicine and Oral Pathology, vol. 75, no. 6, pp. 728–732, 1993.
[50]
A. J. Bruce and R. S. Rogers, “Oral manifestations of sexually transmitted diseases,” Clinics in Dermatology, vol. 22, no. 6, pp. 520–527, 2004.
[51]
G. P. Domantay-Apostol, E. B. Handog, and M. T. G. Gabriel, “Syphilis: the international challenge of the great imitator,” Dermatologic Clinics, vol. 26, no. 2, pp. 191–202, 2008.
[52]
M. Buffet, P. A. Grange, P. Gerhardt et al., “Diagnosing Treponema pallidum in secondary syphilis by PCR and immunohistochemistry,” Journal of Investigative Dermatology, vol. 127, no. 10, pp. 2345–2350, 2007.
[53]
A. W. Barrett, M. V. Dorrego, T. A. Hodgson et al., “The histopathology of syphilis of the oral mucosa,” Journal of Oral Pathology and Medicine, vol. 33, no. 5, pp. 286–291, 2004.
[54]
D. Daskalakis, “Syphilis: continuing public health and diagnostic challenges,” Current HIV/AIDS Reports, vol. 5, no. 2, pp. 72–77, 2008.
