Understanding Secondary Syphilis: When a Common Infection Masquerades as Arthritis and Skin Disease

Table of Contents

• Background: Why This Case Matters
• Case Presentation: The Patient's Story
• Detailed Symptoms and Examination Findings
• Differential Diagnosis: What Else Could It Be?
• Diagnostic Testing and Results
• Final Diagnosis: Secondary Syphilis
• Treatment and Management
• Clinical Implications for Patients
• Limitations and Considerations
• Patient Recommendations
• Source Information

Background: Why This Case Matters

This case is important because it demonstrates how syphilis, a sexually transmitted infection that has increased by 74% in the United States between 2017-2021, can present with symptoms that mimic autoimmune diseases like rheumatoid arthritis or lupus. Many patients and doctors might not initially consider syphilis when evaluating joint pain and rashes, leading to delayed diagnosis and treatment. The case also shows how infections can sometimes trigger inflammatory responses that persist long after the initial infection has resolved.

Secondary syphilis is particularly challenging to diagnose because it can affect multiple body systems with varied symptoms. Understanding these presentations helps patients recognize when they might need specific testing and helps healthcare providers consider infectious causes alongside autoimmune conditions.

Case Presentation: The Patient's Story

A 46-year-old man presented to Massachusetts General Hospital with arthritis and a rash that had developed over several months. His symptoms began approximately four months after a mild case of COVID-19 that he contracted during vacation in Central America and the Caribbean. The COVID-19 symptoms resolved after five days, but one week later, he developed pain and swelling in his wrists.

The patient experienced morning stiffness in both wrists that made it difficult to form a fist, though the stiffness improved with activity and hot showers. He also noticed instability in his ankles toward the end of the day. Alongside the joint symptoms, he developed a widespread rash on his chest, back, and legs that was mildly itchy at night but not painful.

Additional symptoms included patchy hair loss (alopecia), an estimated 8 kg (17.6 pounds) of weight loss, nasal crusting with occasional bleeding, and an ulcer at the corner of his mouth. He had episodes of lightheadedness when standing up, which prompted his emergency department visit where he was found to have an elevated heart rate (109 beats per minute) and required intravenous fluids.

Detailed Symptoms and Examination Findings

On examination, doctors found multiple concerning signs:

• Vital signs: Elevated blood pressure (156/90 mm Hg) and rapid heart rate (105 beats per minute)
• Skin findings: Hyperpigmented macular rash with scaling on trunk, back, and legs extending to the top of the feet
• Joint involvement: Swelling, warmth, and tenderness in wrists, ankles, and several knuckle joints
• Other findings: Patchy hair loss throughout scalp, crusting in nostrils, and an ulcer at the left corner of the mouth

Laboratory tests revealed several abnormalities:

• Highly elevated erythrocyte sedimentation rate (104 mm/hour, normal range 0-14), indicating significant inflammation
• Elevated d-dimer level (990 ng/mL, normal <500), suggesting possible inflammation or clotting activation
• Mildly elevated alkaline phosphatase (157 U/L, normal 45-115), a liver enzyme
• Normal complete blood count, kidney function, and other liver enzymes

Imaging studies including chest CT showed no evidence of pulmonary embolism, lung nodules, or enlarged lymph nodes. The electrocardiogram showed only sinus tachycardia (rapid heart rate).

Differential Diagnosis: What Else Could It Be?

The medical team considered multiple possible diagnoses before arriving at the correct one. They systematically evaluated different categories of diseases:

Autoimmune Diseases: The doctors considered several autoimmune conditions but found inconsistencies:

• Psoriatic arthritis was unlikely because the rash didn't resemble typical psoriasis plaques
• Systemic lupus erythematosus (SLE) was considered but the rash pattern and mouth ulcer location weren't typical
• Dermatomyositis was unlikely because the rash didn't show characteristic patterns like the shawl sign or Gottron's papules
• VEXAS syndrome was considered but ruled out due to absence of macrocytic anemia

Other Inflammatory Conditions:

• Sarcoidosis can cause similar joint and skin symptoms, but the patient lacked typical lung involvement or specific skin lesions
• Various vasculitis conditions were considered but the rash wasn't consistent with these diagnoses

Infectious Diseases: Several infections were evaluated:

• Tuberculosis reactive arthritis (Poncet's disease) was considered but the patient had no respiratory symptoms or typical tuberculid rash
• Arthritogenic alphaviruses (like Chikungunya) were possible given travel history, but the persistent rash wasn't typical
• Parvovirus B19 can cause similar arthritis and rash, but symptoms usually resolve within 6 weeks, not persist for 14+ weeks
• Syphilis emerged as the most likely diagnosis because it could explain all symptoms: the specific rash pattern, patchy alopecia, mouth and nasal lesions, and inflammatory arthritis

Diagnostic Testing and Results

The diagnostic process involved specific blood tests for syphilis. Doctors used a two-test approach to confirm the diagnosis:

First, they performed a treponemal antibody test, which detects antibodies specific to the syphilis bacteria (Treponema pallidum). This test was reactive (positive).

Next, they confirmed with a rapid plasma reagin (RPR) test, which measures antibody levels that correlate with disease activity. The RPR test was strongly positive with a titer of 1:256, indicating active infection.

The combination of these test results along with the clinical presentation confirmed the diagnosis of secondary syphilis. The high RPR titer particularly indicated active disease requiring treatment.

Final Diagnosis: Secondary Syphilis

The patient was diagnosed with secondary syphilis, a stage of syphilis infection that occurs weeks to months after initial exposure. Secondary syphilis can present with diverse symptoms including:

• Rash (often on trunk, arms, and legs, sometimes involving palms and soles)
• Patchy hair loss with "moth-eaten" appearance
• Mouth ulcers and nasal crusting
• Joint inflammation and pain
• General symptoms like fever, weight loss, and fatigue

In this case, the infection likely occurred through sexual contact with a new partner approximately five months before symptoms appeared. The patient's history of being sexually active with men placed him in a higher-risk category, as syphilis rates have been rising particularly among men who have sex with men.

The timing of symptoms after COVID-19 was likely coincidental rather than related, as COVID-19 is not known to cause chronic inflammatory arthritis.

Treatment and Management

Syphilis is treated with antibiotics, specifically penicillin. The standard treatment for secondary syphilis is:

• A single intramuscular injection of benzathine penicillin G (2.4 million units)
• For penicillin-allergic patients, alternative antibiotics may be used under careful supervision

After treatment, patients require follow-up RPR testing to ensure treatment success. The RPR titer should decrease by at least fourfold (for example, from 1:256 to 1:64 or lower) within 12 months after treatment.

Equally important is partner notification and treatment. Any sexual partners from the previous 90 days should be evaluated and treated presumptively to prevent reinfection and further transmission.

Clinical Implications for Patients

This case has several important implications for patients:

First, it demonstrates that syphilis can present with symptoms that mimic other diseases. Patients with unexplained rashes, joint pain, hair loss, or mouth sores should discuss the possibility of syphilis testing with their healthcare providers, especially if they have any risk factors for sexually transmitted infections.

Second, it highlights the importance of complete sexual health histories. Patients should feel comfortable discussing their sexual history with healthcare providers, as this information can be crucial for accurate diagnosis.

Third, it shows that syphilis is increasingly common, with cases rising 74% in the United States between 2017-2021. This increase affects all populations, though rates are highest among men who have sex with men.

Finally, the case illustrates that syphilis is completely curable with appropriate antibiotic treatment, especially when caught early. Delayed diagnosis can lead to more serious complications including neurological and cardiovascular damage in later stages.

Limitations and Considerations

While this case provides valuable insights, there are some limitations to consider:

The diagnosis was based on clinical presentation and blood tests without tissue confirmation or direct detection of the bacteria. While this is standard for syphilis diagnosis, it means there's a small possibility of false positive results, though the combination of tests makes this unlikely.

The case represents a single patient's experience, and syphilis can present differently in different people. Not all patients will have the same combination of symptoms, and some may have fewer or more severe manifestations.

The patient had a family history of psoriasis and recent COVID-19 infection, which might have influenced his immune response or symptom presentation. These factors could potentially make his case somewhat unique compared to other syphilis presentations.

Finally, while treatment response is typically excellent for secondary syphilis, some patients may experience lingering symptoms or require retreatment if the RPR titer doesn't decrease appropriately.

Patient Recommendations

Based on this case, patients should consider the following recommendations:

1. Get tested regularly if you have risk factors for sexually transmitted infections, including new or multiple partners, sex without condoms, or sex with partners who may have other partners
2. Discuss symptoms openly with healthcare providers, including skin changes, joint pain, hair loss, or mouth sores, even if they seem unrelated to sexual health
3. Complete prescribed treatments fully if diagnosed with syphilis or any other sexually transmitted infection
4. Ensure partners get tested and treated to prevent reinfection and further transmission
5. Follow up for repeat testing after treatment to ensure the infection has been successfully treated
6. Practice safe sex using condoms to reduce transmission risk, though note that condoms don't prevent all syphilis transmission since sores can occur in areas not covered by condoms

Patients should remember that syphilis is completely treatable, especially when caught early. There should be no stigma associated with getting tested or treated for sexually transmitted infections—these are common medical conditions that require appropriate medical care.

Source Information

Original Article Title: Case 19-2024: A 46-Year-Old Man with Arthritis and Rash

Authors: April M. Jorge, M.D., Kevin L. Ard, M.D., and Sarah E. Turbett, M.D.

Publication: The New England Journal of Medicine, June 20, 2024

DOI: 10.1056/NEJMcpc2402482

This patient-friendly article is based on peer-reviewed research from the Massachusetts General Hospital Case Records series. The original article represents actual clinical case discussion and diagnosis from experienced physicians at Harvard Medical School.