Syphilitic Arthropathy: A Single‐Center Experience

Syphilis is a disease caused by the bacterium Treponema pallidum (TP) and is transmitted between individuals through sexual contact [1]. In Türkiye, syphilis cases are increasing alongside HIV infection, particularly in large cities where tourism is developed. Many clinicians have limited or no experience with this diagnosis, and many believe that syphilis has virtually disappeared. Recently, the rates of syphilis in Türkiye have been increasing with new diagnoses of syphilis increasing rapidly from 2017 to 2023 (1655–3646), along with an increased incidence of 4.3% between 2017 and 2023 years [2]. The symptoms of primary and secondary syphilis, including primary chancre and rash, are relatively innocuous and may be overlooked by clinicians with limited experience with this disease. If undiagnosed, the disease may remain latent until the more severe symptoms of tertiary syphilis appear. Therefore, early recognition of syphilis is crucial. Some syphilitic cases may present with musculoskeletal system findings and may resemble primary rheumatic diseases [3]. The exact prevalence of syphilitic arthropathy is unknown, and literature data are controversial. Herein, we describe the demographic, clinical, and laboratory features of syphilitic arthropathy followed up in a single center. A total of 18 syphilis patients who applied to rheumatology and infectious diseases outpatient clinics between 2016 and 2025 were evaluated retrospectively. Demographic, clinical, laboratory, radiological, and serological data obtained from these patients during follow-up and treatment were evaluated and analyzed. Serological tests used for the diagnosis of syphilis are quantitative and qualitative venereal disease research laboratory (VDRL)test, Treponema pallidum hemagglutination test (TPHA), fluorescent treponemal antibody-absorption (FTA ABS) IgG antibody test, and FTA ABS IgM antibody test. Eighteen patients with syphilis were included in the study. Of the 18 patients, 14 (77.7%) were male and 4 (22.3%) were female, with a mean age of 42.6 years (range, 25–68 years). Eleven patients were diagnosed with latent syphilis, and seven with secondary syphilis. No patients had congenital and/or tertiary syphilis. Syphilis was diagnosed using clinical and serological tests (VDRL, TPHA, FTA ABS IgG/IgM antibody tests). The most common clinical symptoms associated with syphilis are fever, skin rash, groin pain, fatigue, arthralgia, and myalgia. Cardiology, ophthalmology, and neurology examinations were performed on all patients to assess other organ and system involvement due to syphilis, and no pathology was detected. One of the 18 patients was also HIV positive and was being followed up in the infectious diseases department. Seven of the 18 patients presented with musculoskeletal symptoms mimicking autoimmune rheumatological diseases (Table 1). Of these seven patients, two presented with inflammatory back pain; two with arthritis in the wrist, MCP, and PIP joints; one with elbow arthritis and neuritis; one with bilateral knee arthritis; and one with arthritis in both knees and ankles. Unilateral sacroiliitis was detected in two patients with inflammatory low back pain; both patients were HLA-B27 negative. The patient, who had arthritis in both knees and ankles, had a poor general condition, persistent fever for 2 months, and maculopapular skin rashes. This patient was misdiagnosed as adult-onset Still's disease at another rheumatology center and was using immunosuppressive drugs (corticosteroids, hydroxychloroquine, and methotrexate). After being diagnosed with syphilis at our center, immunosuppressive therapy was stopped and antibiotic therapy was initiated. After antibiotic treatment, his symptoms completely resolved. Autoimmune serology panels were performed in all patients; antinuclear antibody (ANA) 1/320 granular positivity was detected in two of seven patients, and anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) positivity was detected in one patient. The ENA profile and complement C3/C4 were negative in patients with ANA positivity. Acute-phase reactants were evaluated; erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) elevation was found in four patients. All patients were treated with 2.4 mln of benzathine penicillin intramuscularly once a week. After antibiotic treatment, clinical symptoms (fever, skin rashes, etc.) and musculoskeletal complaints resolved, and syphilis serological tests became negative. VDRL 1:32 TPHA 1:640 FTA ABS IgG 1:320 FTA ABS IgM 1:5120 VDRL 1:32 TPHA 1:5120 FTA ABS IgG 1:320 FTA ABS IgM 1:320 VDRL 1:64 TPHA 1:2560 FTA ABS IgG 1:320 FTA ABS IgM 1:320 VDRL 1:32 TPHA 1:5120 FTA ABS IgG 1:320 FTA ABS IgM 1:5120 VDRL 1:64 TPHA 1:5120 FTA ABS IgG 1:160 FTA ABS IgM 1:5120 Anti-CCP positive RF positive VDRL 1:32 TPHA 1:2560 FTA ABS IgG 1:320 FTA ABS-IgM 1:5120 VDRL 1:32 TPHA 1:160 FTA ABS IgG 1:320 FTA ABS IgM 1:640 Musculoskeletal involvement of syphilis is a rare entity and has rarely been reported in the literature, but it should be kept in mind because it can mimic many primary rheumatic diseases [4]. Syphilitic arthropathy is associated with hematogenous spread of TP. The bacteria spread hematologically to the metaphyseal region and enter the medullary spaces of the bones, triggering an inflammatory response by lymphocytes and plasma cells. Generally, if defense mechanisms are working, inflammation resolves with fibrosis. However, if defense mechanisms are inadequate, bacterial persistence destroys tissue and causes necrosis. In general, musculoskeletal findings have been reported in congenital, secondary, or tertiary acquired syphilis (Table 2). Classification of congenital syphilitic arthritis includes Clutton joints, chondroarthritis, suppurative arthritis, gummatous synovitis, hydrarthrosis, symmetric serous synovitis, ulcerating or Von Gie joints [5]. Tertiary syphilitic arthritis can be described in two main forms: osseous and synovial. The synovial form presents as perisynovitis, characterized by inflammation around the synovial membrane. The bony form, usually seen in young patients, presents with eroded and irregular joint surfaces, cavitation, and bony prominences within the bone. In latent and secondary syphilis, the main lesions are bone involvement and arthritis, but involvement of muscles, tendons and their sheaths, and rarely bursitis has also been reported. Syphilitic arthritis presents with significant swelling, tenderness, and limited range of motion in the affected joints. The pattern of joint involvement may include monoarthritis, asymmetric oligoarthritis, polyarthritis, and/or axial involvement. Tenosynovitis or dactylitis has also been reported in some patients [6]. The most commonly affected joints are bilateral knees, hips, shoulders, and proximal interphalangeal joints. Joint involvement may mimic various rheumatologic diseases, such as connective tissue diseases, Lyme disease, vasculitis, or sarcoidosis [7]. In addition to the presence of acute or subacute polyarthritis, attention should be paid to pauciarticular, less frequently migratory, and primary involvement of the knee. Low back pain secondary to spondylitis or sacroiliitis has also been reported [8]. Our series was similar to the syphilis joint pattern reported in the literature. Two patients had bilateral knee joint involvement; two had wrist, MCP, and PIP joint involvement mimicking connective tissue disease; one had asymmetric oligoarthritis; and two had unilateral sacroiliitis mimicking spondyloarthritis. Our patient, who presented with asymmetric oligoarthritis, also had persistent fever and maculopapular skin lesions, mimicking adult-onset Still's disease. The occurrence of autoantibodies in syphilitic arthropathy is not expected. RF positivity has been reported in some patients, but there is no literature information regarding ANA and/or anti-CCP positivity [9]. ANA positivity was detected in two of our patients, and anti-CCP and RF positivity was detected in one patient. Some of the antibodies detected in syphilis have been explained by cross-reactivity with substances used in some diagnostic methods. We do not know whether the autoantibodies detected in our cases are an overlap, a coincidence, or an association with an underlying primary rheumatic pathology. Further studies on this topic are needed. In recent years, syphilis infection has been reported with various biological drug treatments frequently used in rheumatology practice [10]. Therefore, in addition to recommended screenings (HBV, HCV, latent TB, etc.), latent syphilis screening may also be necessary before initiating biological drug treatment, especially in young patients with multiple sexual partners. More studies are needed on this topic. Arthralgia/Arthritis Myalgia Periostitis Migratory polyarthritis, symmetric or asymmetric; nonerosive Generalized muscle pain, sometimes mimicking polymyositis Deep bone pain, especially nocturnal; radiolucent lesions on X-ray Knees, ankles, shoulders, fingers Generalized Tibia, skull, sternum, clavicle Gummatous arthritis/osteitis Charcot joint (neuropathic arthropathy) Saber shin (congenital or acquired) Chronic granulomatous inflammation, destructive arthritis Painless joint swelling, instability, deformity due to tabes dorsalis Bowing of the tibia due to chronic periostitis Long bones, skull, vertebrae Knee, hip, ankle Tibia Clutton's joints Saber shins, frontal bossing Painless symmetrical joint effusions, typically in knees Bone deformities due to periostitis Knees (bilateral) Tibia, skull In conclusion, syphilitic arthritis is one of the more unusual presentations of syphilis and can mimic many rheumatologic diseases. Rheumatologists should be aware of syphilitic arthritis and keep it in their differential diagnosis. Family history and suspicious sexual history are the most important elements in identifying high-risk patients. Adequate and early diagnosis should be made and the condition treated promptly to prevent long-term morbidity. The author contributions for article is equal for both authors. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.