Adie’s pupil, also known as Tonic pupil or Adie’s tonic pupil, is characterized by enlarged pupil, disappeared light reflex under ambient light, slow contraction under bright light in dim environment and tonic re-dilation when the light removes (8). Moreover, the convergence is slow, and the accommodation reflex is attenuated (8). In addition, Adie’s pupil is sensitive to diluted pilocarpine with an optimum concentration of 0.125% and constrict remarkably to its administration, but normal pupil or AR pupil will remain indifferent (9-11). It is generally believed that Adie’s pupil is a characteristic pupillary change of Holmes-Adie syndrome (HAS), which is absence of deep tendon reflexes and usually idiopathic and more common in young women (8). However, the occurrence of Adie’s pupil in neurosyphilis appears to be far from exceptional. Reviewing previous researches, we found that about 8-17% of the Adie’s pupils is caused by syphilis (12). It could onset either unilaterally or bilaterally and could extend from a single pupil to both pupils with time (13, 14).
We evaluated many possible conditions that may lead to the pupillary changes in our patient, and finally confirmed the diagnosis of Adie’s pupil caused by neurosyphilis. In this patient, the pupillary changes were consistent with the characteristics of the Adie’s pupil: bilateral pupil dilated, light reflex disappeared, and the convergence reflex was slow. Bilateral pupils were sensitive to diluted pilocarpine, consistent with the cases reported in previous literatures (8, 12, 15, 16). The evaluation revealed serum positive of CLIA, TPPA and RPR (1:32) test. The CSF examination revealed pleocytosis, elevated protein, and positive RPR (1:2), TPPA and CLIA. Neurosyphilis was diagnosed according to the guidelines proposed by the American Centers for Disease Control (CDC) in 2015 (17). Other causes of pupil abnormality were excluded, include HAS, diabetic ophthalmoplegia, localized ocular traumas and intracranial space-occupying lesions.
Growing evidence suggests that pupillary abnormalities are important clinical manifestations and signs of neurosyphilis. Nearly half of the patients with neurosyphilis could present with pupil changes (14). Despite the most typical pupillary change of neurosyphilis is AR pupil, which manifests as bilateral miosis, lack of light reflex but brisk constriction with accommodation reflex, it mainly exists in late neurosyphilis such as Tabes Dorsalis and dementia paralytica (14, 15, 18). On the contrary the Adie’s pupil onsets early in neurosyphilis, and may even be the first clinical sign or the only performance of neurosyphilis (12). Therefore, the Adie’s pupil changes could be more important than AR pupil in the identification of neurosyphilis, especially early neurosyphilis. Patients with Adie’s pupil usually present with mild symptoms, such as blurred vision, visual fatigue or can even be asymptomatic. Abnormalities can be found during PE or when patients themselves look in the mirror.
Parenterally Penicillin G administration is recommended for treating patients in all stages of syphilis, including neurosyphilis (17, 19). For patients who are allergic to penicillin, cephalosporin can be used as an alternative treatment (17, 20). For patients with unilateral Adie’s pupil, timely anti-syphilis treatment may promote partial or complete recovery of the pupil (13, 15, 21). However, when the disease progresses and extends to bilateral pupils, the pupils remain unchanged after effective treatment (12, 16). Therefore, for patients presented with Adie’s pupil, it should warrant an evaluation of neurosyphilis timely due to further treatment consideration.
In conclusion, Adie’s pupil is one of the most important pupillary changes in neurosyphilis, it can occur in early neurosyphilis and deserves more attention. For patients with Adie’s pupils, the possibility of neurosyphilis should be considered, and syphilis screening should be carried out in time. Our studies further underscore the need for syphilis screening for patients with abnormal pupil changes.