15 October 2022: Articles
Case of Secondary Syphilis with Mucocutaneous, Articular, and Pulmonary Involvement in a 74-Year-Old Moroccan Man
Challenging differential diagnosisAhmed Mougui1ABCDEF*, Zineb Baba1EF, Imane El Bouchti1ABCDEF
Am J Case Rep 2022; 23:e937513
BACKGROUND: Syphilis is a sexually transmitted infection (STI) caused by Treponema pallidum. If untreated, primary syphilis can progress to secondary syphilis, which has a characteristic rash and diverse systemic features. This report is of a case of secondary syphilis with mucocutaneous, articular, and pulmonary involvement.
CASE REPORT: A 74-year-old Moroccan man presented with an 8-week history of bilateral knee pain and swelling. On examination, he had bilateral knee effusions. Articular puncture brought an inflammatory fluid with a significant presence of white blood cells. Inflammatory markers were elevated. X-rays of both knees showed bilateral osteoarthritis with intra-articular calcification in the left knee. Nonsteroidal anti-inflammatory drugs and colchicine were prescribed, but were ineffective. A closer clinical examination of the patient revealed pigmented papules on the palms, soles, oral mucosa, trunk, and genitals. Treponema pallidum hemagglutination assay and Venereal Disease Research Laboratory results were positive in the blood (titers 1: 32) and joint fluid. A computed tomography scan of the chest revealed a focal opacity in the lateral basal segment of the right lung. The diagnosis of secondary syphilis with mucocutaneous, articular, and pulmonary involvement was made. The evolution was favorable after a single intramuscular injection of benzathine-penicillin.
CONCLUSIONS: Arthritis, mucocutaneous involvement, and lung lesions can be manifestations of secondary syphilis. A detailed anamnesis, clinical examination, serology, and imaging techniques are the pillars of diagnosing this condition.
Keywords: Diagnosis, Arthritis, Lung, Skin, syphilis
Syphilis is an infection caused by contact, usually sexual, with mucosal lesions infected with Treponema pallidum . The incidence of syphilis has increased considerably worldwide in recent years, particularly in men who have sex with men [1,2]; therefore, awareness, screening, and prevention of syphilis should be strengthened in this population . Syphilis is a chronic infection that evolves in several stages with variable, polymorphic, and often silent clinical manifestations . If untreated, primary syphilis can progress to secondary syphilis, which has a characteristic rash and diverse systemic features [3,4]. Articular, mucocutaneous, and pulmonary involvement during secondary syphilis have been reported in several case reports [5–11]. Syphilis represents a diagnostic challenge for the practitioner because it mimics several conditions [12–15]. Current guidelines on syphilis management support the place of benzathine penicillin as a treatment for all forms of syphilis . This report is of a case of secondary syphilis with mucocutaneous, articular, and pulmonary involvement in a 74-year-old Moroccan man.
A 74-year-old Moroccan man with no significant medical history was admitted to our hospital for an etiological assessment of bilateral knee pain and swelling that started 8 weeks prior. There were no symptoms of an infection. The patient was afebrile and hemodynamically stable. The osteoarticular examination showed bilateral palpable knee effusion (Figure 1). The articular puncture (Figure 2) brought an inflammatory fluid with a significant presence of white blood cells. A Gram stain, bacterial culture, and search for microcrystals were negative. Blood culture results remained negative. Initial laboratory tests collected at hospital admission showed hypochromic and microcytic anemia, high C-reactive protein level, and high erythrocyte sedimentation rate. The results of the immunological workup, including anti-nuclear antibodies, anti-cyclic citrullinated peptide, rheumatoid factor, and anti-neutrophil cytoplasmic antibody, were negative. All additional laboratory values are shown in Table 1. X-rays of both knees showed bilateral osteoarthritis with intra-articular calcification in the left knee (Figure 3). The diagnosis of pseudo gout was made.
The patient was first put on nonsteroidal anti-inflammatory drugs (NSAIDs) for 7 days (13 days before the later diagnosis) and then colchicine for 5 days (3 days before the later diagnosis), without any improvement. A closer clinical examination of the patient revealed pigmented papules on the palms (Figure 4), soles (Figure 5), oral mucosa, trunk, and genitals. There were no other extra-articular signs. A review of the patient’s history revealed he had unprotected extramarital sexual intercourse 4 months before. He had not noted the presence of genital ulceration. Syphilis serology was performed. Treponema pallidum hemagglutination assay and Venereal Disease Research Laboratory (VDRL) results were positive in the blood as well as in the joint fluid and negative in the cerebrospinal fluid. The quantitative VDRL was at a titer of 1: 32. Serologies for hepatitis B, C, and human immunodeficiency virus (HIV) were negative. Results of screening for Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and Trichomonas vaginalis in the urethral swab were negative. A diagnosis of secondary syphilis was made. As part of the workup for secondary syphilis, a computed tomography (CT) scan of the chest was performed, revealing a focal opacity in the lateral basal segment of the right lung (Figure 6). Screening for tuberculosis in sputum samples in 3 tests by direct examination and culture was negative. Bronchoalveolar lavage did not show abnormal cells or microorganisms. The search for Treponema pallidum by polymerase chain reaction in bronchioalveolar lavage was not performed owing to the unavailability of this technique in the laboratories of our region. No biopsies were performed. Ophthalmological and cardiovascular investigations were unremarkable. The diagnosis of secondary syphilis with mucocutaneous, articular and pulmonary involvement was made. The patient received a single intra-muscular injection of benzathine penicillin 2.4 MIU. The evolution was favorable, with regression of arthritis, biological inflammatory syndrome, and skin lesions. A follow-up chest CT scan was not performed, at the patient’s request. At the 4-month follow-up, the patient was asymptomatic, with a negative VDRL test. Follow-up laboratory testing after treatment is shown in Table 2.
Secondary syphilis is a contagious venereal infection responsible for variable and systemic manifestations that give it the characteristics of a “great imitator” . The present case highlights that secondary syphilis can affect several systems, such as dermatological, musculoskeletal, and lung systems. Since 2001, there has been a worrying increase in the incidence of syphilis, aided by the underestimation of risks, increase in alcohol and drug use, development of social networks and dating applications that increase risky sexual activity, and number of sexual partners . This resurgence of the disease underscores the clinician’s interest in knowing its clinical forms, including secondary syphilis .
Syphilitic arthritis is reported in congenital and tertiary syphilis , but joint involvement in secondary syphilis is rarely reported . The joint disorders in secondary syphilis are polyarthralgia, monoarthritis, or migratory polyarthritis , and the most affected joints are the knees, hips, shoulders, and proximal interphalangeal joints [5,6,20,21]. Joint involvement usually occurs 3 to 12 weeks after the onset of the secondary stage . The differential diagnosis of syphilitic arthritis is septic arthritis, rheumatoid arthritis, rheumatic fever, reactive arthritis, psoriatic arthritis, gout, and chondrocalcinosis [5,23]. Other musculoskeletal symptoms of secondary syphilis include bone involvement and tenosynovitis [7,24]. Our patient was admitted for bilateral knee pain and swelling. The presence of chondrocalcinosis led to the initiation of treatment, first with NSAIDs and then with colchicine, without improvement. The Treponema pallidum hemagglutination assay and VDRL results were positive in the blood as well as in the joint fluid. As in previously reported cases for secondary syphilis involving joint and bone, there was complete resolution of symptoms following treatment with benzathine penicillin [5–7].
Mucocutaneous involvement is characteristic of secondary syphilis [3,4]. It is symptomized by a copper-red maculo-papular rash of variable size involving the trunk, extremities, and, most frequently, the palms and soles [4,25,26]. As in the case of our patient and reported cases by Crouzy et al , the diagnosis of syphilis was made when 1 skin lesion was noticed in the palms and soles, thereby enhancing the importance of a systematic examination of the palms and soles . Other mucocutaneous disorders can occur during secondary syphilis, including ulcerated plaques, painless and serpiginous lesions in the oral cavity, moth-eaten alopecia, which can be revealing, and condyloma lata [4,26,27]. These manifestations concern 25% of patients after 1 to 2 months of primary syphilis . With the current epidemic of syphilis, practitioners will likely encounter these manifestations . Cutaneous lesions resolved 2 to 3 weeks following treatment with benzathine penicillin .
Pulmonary involvement during secondary syphilis is rare and can go unnoticed in the absence of chest imaging, as seen in our case . Most patients are asymptomatic or minimally symptomatic, with cough, dyspnea, and chest pain , and the clinical and radiological manifestations are not specific [11,28]. Severe acute pneumonia revealed the diagnosis in the case reported by Campos et al . Florencio et al  reported syphilitic pulmonary involvement mimicking lymphoma with polyadenopathy and pulmonary nodules. Kassem Youssef et al  reported a case of syphilitic pulmonary involvement revealed by dyspnea, with thoracic imaging showing interstitial lung pattern, moderate pleural effusion, and hilar lymphadenopathy. A case of several bilateral, round, excavated opacities and 1 subtracheal adenopathy was reported by David et al . These clinical and radiological manifestations pose a problem of differential diagnosis with several conditions, including cancer, lymphoma, tuberculosis, sarcoidosis, and connective tissue disease [8–11]. The diagnosis of pulmonary syphilis is based on Coleman’s criteria and includes a history or presence of clinical signs consistent with secondary syphilis, pulmonary abnormalities on imaging with or without pulmonary symptoms, positive serological tests for syphilis, exclusion of other pulmonary diseases, and good therapeutic response [28–30]. In our case, bronchoalveolar lavage was unremarkable, and the patient refused a follow-up chest CT scan. In previously reported cases for secondary syphilis involving the lung, a follow-up chest CT scan showed a progressive disappearance of pulmonary lesions after treatment with benzathine penicillin [7,11].
The management of syphilis is based on early diagnosis, prompt and effective treatment of the patient and partners, and patient education to avoid reinfection. The World Health Organization , European , and United States  guidelines for the management of secondary syphilis recommend a single intramuscular injection of benzathine penicillin 2.4 MIU as first-line therapy. Intramuscular procaine penicillin for 10 to 14 days is an alternative treatment. In case of contraindication, the first treatment option is doxycycline 100 mg twice daily for 10 to 14 days. Intramuscular or intravenous injection of 1 to 2 g of ceftriaxone daily for 10 to 14 days is a second option.
Secondary syphilis should be considered in all patients with articular, mucocutaneous, and lung manifestations. Pulmonary involvement is rare and can go unnoticed in the absence of chest imaging. A detailed anamnesis, clinical examination, serology, and imaging techniques are the pillars of the diagnosis.
FiguresFigure 1.. Bilateral knee effusions. Figure 2.. Citrine yellow fluid at the articular puncture. Figure 3.. X-rays of both knees showed bilateral osteoarthritis with intra-articular calcification in the left knee (white arrow). Figure 4.. Pigmented papules on the palms (white arrows). Figure 5.. Pigmented papules on the soles (white head arrows). Figure 6.. (A) Axial and (B) sagittal plane in chest computed tomography scan with pulmonary window showing focal opacity in the lateral basal segment of the right lung (arrows).
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