gms | German Medical Science

Syphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum [1]. Syphilis is a re-emerging and rising infection in the developed world. In up to one-quarter of patients with syphilis, ocular involvement manifests at any time during the disease course. Ocular syphilis may precede the diagnosis of systemic disease in up to one-half of cases [2]. Ocular syphilis, known as “the great masquerader”, may affect almost every structure of the eye and has a broad spectrum of presentation, including, among others, interstitial keratitis, optic neuropathy and posterior uveitis, the latter commonly represented by chorioretiniti [3], [4].

In 1988, de Souza et al. [5] reported three young patients with “unilateral central chorioretinitis” as manifestation of ocular syphilis. Two years later, Gass et al. [6] reported six additional similar cases. They concluded that this condition was a separate clinical entity, and coined the term “acute syphilitic posterior placoid chorioretinitis” (ASPPC).

ASPPC is defined by the presence of one or more placoid, yellowish, outer retinal lesions, typically involving the posterior pole and the mid-periphery of the retina near the temporal vascular arcade [6]. ASPPC may have a unilateral or bilateral involvement with a presenting visual acuity ranging from 20/20 to no light perception [7]. The advent of multimodal imaging (MMI) of the retina, especially of spectral domain optical coherence tomography (SD-OCT), has made it possible to report pathognomonic features of ASPPC, which include punctate hyperreflectivity in the choroid, disruption and loss of the ellipsoid zone, nodular irregularity of the retinal pigment epithelium, and transient localized subretinal fluid [8], [9].

Since patients with ASPPC usually receive prompt antimicrobial treatment after serologic results, little is known about the natural course of the disease. To the best of our knowledge, only 5 cases of ASPPC with spontaneous improvement have been reported [10], [11], [12], [13]. We report the natural course and the multimodal retinal imaging features of an additional case, and discuss the pathogenetic implications and the importance of early recognition of this rare clinical entity.

A 45-year-old man with no relevant past medical history presented to the eye casualty service complaining of sudden onset central ‘white ring’ and decreased vision in the right eye (RE) over the past seven days. Best-corrected visual acuity (BCVA) was 6/12 in the right eye and 6/6 in the left eye (LE). Intraocular pressure was 14 mmHg in both eyes. Examination of the RE showed no cells in the right anterior chamber and 1+ vitreous cells; fundus examination revealed a yellow placoid lesion involving the macular area with no signs of vasculitis or retinal necrosis. Examination of the LE was unremarkable.

MMI of the retina including colour fundus photograph, fundus autofluorescence, SD-OCT, fluorescein angiography and indocyanine green angiography are presented in Figure 1 [Fig. 1], Figure 2 [Fig. 2], and Figure 3 [Fig. 3].

The medical history was carefully reviewed; the patient admitted to be addicted to poppers and cocaine, and reported promiscuous homosexual activity over the last months. He denied intravenous drug use and any systemic symptoms such as headache, skin rash, nausea, weight loss, cough, or night sweats. A complete laboratory work-up was ordered, including TB QuantiFERON-TB testing, syphilis serology and human immunodeficiency virus (HIV) antibodies. Seven days after presentation, the patient reported spontaneous improvement in the vision of the RE, and BCVA improved to 6/9 in the RE and was stable in the LE. Full blood count, liver function test, kidney function, angiotensin-converting enzyme level were within normal range, HIV antibodies were negative. However, results for QuantiFERON-TB testing and syphilis had not been available yet. MMI revealed spontaneous improvement of the placoid lesion (Figure 2 [Fig. 2], Figure 3 [Fig. 3]).

Two weeks after presentation, BCVA further improved to 6/6 in the RE and MMI showed signs of early resolution of the placoid lesion. Laboratory results returned negative for QuantiFERON-TB testing, and positive for venereal disease research laboratory test and fluorescent treponemal antibody testing. Therefore, a definite diagnosis of ASPPC was made, and the patient was promptly referred to the Infectious Disease Department for systemic treatment with penicillin.

ASPPC is a rare clinical manifestation of ocular syphilis. Although the pathophysiology of ASPPC is not completely understood, timing and characteristics of SD-OCT findings may be the reflection of the sequence of disease events [9]. It has been suggested that circulating T. pallidum organisms may enter the choroidal circulation, giving the choroidal hyperreflective pinpoint lesions seen on SD-OCT; subsequent access to the outer retina may give a variable amount of subretinal fluid and impaired photoreceptor function expressed by disruption of EZ seen on SD-OCT [9].

However, the role played by the cellular immune system in the pathogenesis of this condition remains controversial. While it was initially suggested that ASPPC is secondary to immunocompromised status such as in HIV-positive patients [5], [6], [14], it was later described in both immunocompetent and immunocompromised individuals [7], [9], [15].

Of note, no differences have been found in terms of clinical characteristics and long-term visual outcome in HIV-positive versus HIV-negative patients with ASPPC [7].

To the best of our knowledge, spontaneous resolution of ASPPC before initiation of systemic antimicrobial treatment has been reported in 5 cases [10], [11], [12], [13]. The first cases were described in 2015 by Ji et al. [10], who reported two HIV-negative patients with ASPPC which spontaneously improved 10 days (for the first case) and 3 weeks (for the second case) after presentation. In the same year, Aranda et al. [11] reported an HIV-positive patient on anti-retroviral therapy for 4 years and CD4+ T-cell count of 204 cells/µL presenting with ASPPPC; spontaneous resolution of ASPPC was observed 10 days after presentation [11]. One year later, Franco et al. [12] reported an additional case of ASPPC in an HIV-negative patient with complete spontaneous recovery and no signs of reactivation until the patient was started on antimicrobial treatment, 45 days after presentation.

The spontaneous improvement observed in our case is in line with these previous reports [10], [11], [12] and may suggest that ASPPC is the result of the host’s cellular immune response which may be able to locally control the spirochete infection. Some authors have speculated that the immune privilege of the eye may contribute to the spontaneous resolution of ASPPC.

Alternatively, spontaneous resolution of initial ASPPC can be explained as the disease entering prolonged latency. Indeed it is known that syphilis is characterized by episodes of active disease that are interrupted by periods of latency because of the host’s cellular immune response [1], [12]. Therefore the placoid lesions may disappear in the same way the mucocutaneous syphilitic lesions disappear without treatment during the latent stage of the disease. The latter hypothesis has been supported by Baek et al. [13] who reported an HIV-negative patient presenting with ASPPC which spontaneously improved 7 days after presentation, but unlike the aforementioned cases [10], [11], [12] did not receive systemic antimicrobial treatment and returned 9 months later with progression to posterior uveitis [13].

Of note, in 2014 Armstrong et al. [16] had reported spontaneous evolution of unilateral ASPPC to panuveitis in a patient with HIV co-infection. In their case, panuveitis developed 6 weeks after the initial diagnosis of ASPPC, without spontaneous resolution of the lesion.

These latter cases may suggest that ASPPC could be an early manifestation of posterior uveitis, and in absence of an adequate host’s immune response, such as in patients with untreated HIV co-infection, progression without spontaneous improvement may be observed.

In addition, there is evidence that immunosuppression may be a major stimulator of ASPPC. Zamani et al. [17] reported a case of undiagnosed syphilitic chorioretinitis which evolved to multifocal placoid lesions following immunosuppression induced by corticosteroid therapy. Furthermore, Erol et al. [18] and Song et al. [19] published cases of ASPPC following local intravitreal triamcinolone injections. However, in contrast to these aforementioned cases [17], [18], [19], Ormaechea et al. [20] reported a patient with ASPPC who was initially misdiagnosed as having non-infectious uveitis and received corticosteroid as well as methotrexate for 7 months and demonstrated no worsening of the disease.

There is contrasting evidence about the role of the immune system in the pathogenesis of ASPPC which may be the manifestation of different pathogenetic pathways that ultimately lead to an inflammatory response driven by the presence of the spirochete. Since this condition may resolve spontaneously before antimicrobial treatment, the presence of a placoid macular lesion should raise a high suspicion of ASPPC, as the ophthalmologist may be the first to diagnose syphilis in the patient. Indeed, timely diagnosis and antimicrobial treatment are essential to preventing the progression of syphilis which may include irreversible visual damage [21].

The authors declare that they have no competing interests.

We obtained written informed consent from the patient for publishing the information and images.