Secondary syphilis in cali, Colombia: new concepts in disease pathogenesis

Abstract

Venereal syphilis is a multi-stage, sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum (Tp). Herein we describe a cohort of 57 patients (age 18-68 years) with secondary syphilis (SS) identified through a network of public sector primary health care providers in Cali, Colombia. To be eligible for participation, study subjects were required to have cutaneous lesions consistent with SS, a reactive Rapid Plasma Reagin test (RPR-titer > or = 1 : 4), and a confirmatory treponemal test (Fluorescent Treponemal Antibody Absorption test- FTA-ABS). Most subjects enrolled were women (64.9%), predominantly Afro-Colombian (38.6%) or mestizo (56.1%), and all were of low socio-economic status. Three (5.3%) subjects were newly diagnosed with HIV infection at study entry. The duration of signs and symptoms in most patients (53.6%) was less than 30 days; however, some patients reported being symptomatic for several months (range 5-240 days). The typical palmar and plantar exanthem of SS was the most common dermal manifestation (63%), followed by diffuse hypo- or hyperpigmented macules and papules on the trunk, abdomen and extremities. Three patients had patchy alopecia. Whole blood (WB) samples and punch biopsy material from a subset of SS patients were assayed for the presence of Tp DNA polymerase I gene (polA) target by real-time qualitative and quantitative PCR methods. Twelve (46%) of the 26 WB samples studied had quantifiable Tp DNA (ranging between 194.9 and 1954.2 Tp polA copies/ml blood) and seven (64%) were positive when WB DNA was extracted within 24 hours of collection. Tp DNA was also present in 8/12 (66%) skin biopsies available for testing. Strain typing analysis was attempted in all skin and WB samples with detectable Tp DNA. Using arp repeat size analysis and tpr RFLP patterns four different strain types were identified (14d, 16d, 13d and 22a). None of the WB samples had sufficient DNA for typing. The clinical and microbiologic observations presented herein, together with recent Cali syphilis seroprevalence data, provide additional evidence that venereal syphilis is highly endemic in this region of Colombia, thus underscoring the need for health care providers in the region to be acutely aware of the clinical manifestations of SS. This study also provides, for the first time, quantitative evidence that a significant proportion of untreated SS patients have substantial numbers of circulating spirochetes. How Tp is able to persist in the blood and skin of SS patients, despite the known presence of circulating treponemal opsonizing antibodies and the robust pro-inflammatory cellular immune responses characteristic of this stage of the disease, is not fully understood and requires further study.

Figure 1. Study site and syphilis network.

The city of Cali is located in south-western Colombia (see inset). Cali is divided into 22 (numbered in the figure) distinct geographic districts called “comunas”. These are clustered within 5 administrative regions called Empresas Socials del Estado “ESEs”: Ladera (yellow), North (blue), Center (pink), South-East (purple) and East (green). Public health hospitals are strategically distributed within the “ESEs”. The syphilis patient recruitment network was comprised of 13 hospitals and health centers located throughout the city.

Figure 2. Palmar and plantar rash of secondary syphilis.

Typical palmar and plantar rash of secondary syphilis is shown in the representative figures. Similar lesions were evident in 59.6% of all secondary syphilis subjects enrolled. These lesions consist of smooth or scaly plaques and papules, which can become hyperpigmented in dark-skinned individuals as shown in the figure.

Figure 3. Mucosal and cutaneous lesions of secondary syphilis.

Secondary syphilis has been known as the “Great Imitator” due to the diversity of dermatologic lesions and which can be confounded with other cutaneous diseases. (A and B) Diffuse erythematous papular exanthem is shown over abdomen in A and lower extremity in B. (C and D) Multiple moist, hypopigmented, flattened plaques consistent with condyloma lata are shown on external genital areas (male and female respectively in C and D). (E) Inflammatory responses can affect hair follicles leading to “moth-eaten alopecia” as depicted in the figure. (F) Oral mucosal patches, as shown in the figure can be present during secondary syphilis. (G) Pigmentary plaques are shown over the buttocks of a dark-skinned secondary syphilis patient. (H) Psoriasiform syphilitic lesions, as shown in the representative micrograph, could easily be misdiagnosed as psoriasis.

Figure 4. Secondary syphilis histopathology.

The figure shows histopathologic anomalies seen in punch biopsies obtained from four secondary syphilis patients skin lesions. Corresponding clinical appearance of the lesions are also shown. (A) Markedly inflamed hair follicle (“folliculitis”) with extension of inflammatory cell infiltrate into parafollicular blood vessel and connective tissue. Corresponding “moth-eaten” alopecia is shown in the adjacent micrograph. (B) Dark-skinned patient (pigmented basal keratinocytes); further darkening of a patch of skin in the form of a macule, as shown herein, is caused by deposition of dermal melanophages (“pigment incontinence”) (C) Skin biopsy obtained near the sole reveals a thick stratum corneum layer, epidermal reactive psoriasiform hyperplasia associated with chronic inflammation of the dermal papilla, and a superficial perivascular lymphoplasmocytic infiltrate. (D) Edge of an ulcer located in the lower extremity reveals fibrinoid exudate on the ulcer bed, surrounded by granulation tissue and reactive hyperplasia of the epidermis.