Following the identification of painless ulcers on the genitalia and mouth, the clinical diagnosis of syphilis was straightforward, although the patient had no complaints apart from visual impairment initially denying any risk factors. Interestingly, while multiple primary lesions were still present the patient also had generalized lymphadenopathy, neurosyphilis and ocular syphilis, which are characteristic of secondary syphilis. An overlap of primary and secondary syphilis occurs in 75% of HIV co-infected patients . The rate of ocular and neurological involvement is higher in patients with HIV infection [9, 10] and a CD4 count of <350/μl is associated with an increased risk of neurosyphilis .
We retained the diagnosis of early syphilis with ocular and CNS involvement upon clinical symptoms and microbiological findings in serum and CSF. Remarkably, CNS involvement possibly led to SIADH. This has not previously been described in neurosyphilis, as far as PubMed searches are concerned, for "neurosyphilis AND hyponatremia" or "neurosyphilis AND SIADH". Although hypothalamic and pituitary function were greatly altered, no structural changes could be found on the MRI.
Differential diagnosis of hyponatremia was considered in detail, especially cerebral salt-wasting syndrome, syphilis nephritis, hypothyroidism and adrenal insufficiency. The characteristics of cerebral salt-wasting syndrome are dehydration and polyuria  and were therefore excluded by clinical diagnosis. Syphilis nephritis is a membranous glomerulonephritis characterized by proteinuria and potentially microscopic haematuria with impaired renal function [13, 14]; none of which were found in the patient (Table 1). Primary adrenal insufficiency can cause hyponatremia by lack of mineralocorticoid secretion, leading to urinary sodium wasting, hyperkalemia and dehydration. Secondary adrenal insufficiency also causes an inappropriate antidiuresis by ADH secretion . Potential involvement of adrenal dysfunction in the pathology of the presented patient cannot be excluded, because an Adrenocorticotropic Hormone (ACTH) stimulation test was not performed.
Hypothyroidism can also be a cause of hyponatremia, although some authors doubt a causal relationship . Two possible mechanisms have been described. Hypothyroidism is thought to induce SIADH [17, 18], or lead to impaired renal function because of decreased cardiac output ; however, renal function in our patient was normal.
The absence of dehydration, normal potassium levels, and the elevated urine osmolality and urine sodium were highly suggestive of SIADH. Whether SIADH in this patient occurred secondary to hypothyroidism or "directly" by neurosyphilis cannot be conclusively determined. Previous descriptions of hyponatremia as a consequence of hypothyroidism report a milder decrease of sodium (> 120 mMol/l) and a urine osmolality of <500 mosm/kg . Furthermore, the anatomical proximity of the affected structures in the hypothalamic-pituitary region suggests that neurosyphilis might have played a direct role.
The combination of decreased TSH and decreased thyroid hormones T3/T4 points to a centrally-induced hypothyroidism . Other infectious causes of central hypothyroidism have been described, such as toxoplasmosis  and CMV-encephalitis , especially in HIV-positive patients , but not in neurosyphilis. According to serology and CSF analyses none of these infections were present in the patient. In one case HIV itself was thought to be the cause of central hypothyroidism , as improvement occurred under AZT treatment alone. In our case, it is unlikely that the virus itself was causative since remission occurred rapidly under treatment for syphilis alone, even though HIV could be detected in the CSF. ART was initiated after completion of ceftriaxone treatment. No signs of HIV encephalopathy were seen on the MRI.
In recent years non-thyroidal illness syndrome (NTIS) has been recognized as a cause of central hypothyroidism. NTIS has been described in malnourished and critically ill patients due to decreased leptin levels, leading to a diminution in hypothalamic Thyreotropin Releasing Hormone (TRH) . As the patient exhibited weight loss, this differential diagnosis had to be considered. The rapidity of the therapeutic response might suggest involvement of Treponema pallidum in the pathogenesis, but the complexity of the presented case makes it difficult to appoint one single cause.
The incidence of syphilis is rising again worldwide , in Germany it is currently 3.87 cases per 100000 persons . Disease rates in some countries of Eastern Europe are 10 times higher . Therefore, syphilis should always be included as a differential diagnosis not only in the infectious disease department, but also in other specialties, especially neurology, psychiatry, dermatology and ophthalmology.
Primary diagnosis of syphilis by ophthalmologists has been repeatedly reported in recent years [27–29]. In some cases antibiotic treatment alone was used. As papillitis was also present in our case, we chose to add prednisolone to the treatment. A considerable improvement of visual acuity and resolution of papillitis occured within 3 weeks (Figure 1).
Another notable feature of this case was the diagnosis of syphilis, HIV, and chronic hepatitis B and C co-infection at the same time. The exact time-course of the infections cannot be elucidated. Increasing incidence of co-infection of syphilis and HIV has been found in epidemiological studies [25, 30]. The reasons for this concomitance are shared risk factors especially, as in this case, MSM, but also due to increased transmission of HIV, HBV and HCV in the presence of syphilitic lesions [25, 31].