Unexplained Fever: A Comprehensive Approach to Diagnosis and Management

Persistent unexplained fever

Since the beginning of this year, I have been experiencing frequent urination and urinary weakness.
On March 9, I visited a urologist and was diagnosed with hematuria, with red blood cells >100, white blood cells 15, and hydronephrosis.
I started taking antibiotics, and after placing a double J stent on March 26, I continued to have fever and had the stent removed early on April 15.
The fever persisted, reaching 38.4°C.
On May 3, I underwent laparoscopic surgery for an ovarian teratoma.
To this day, the fever has not subsided, and I continue to experience urinary weakness, dry mouth, and lower back pain.
I have consulted nephrology, infectious disease, rheumatology, and obstetrics and gynecology specialists, and despite blood tests, urinalysis, and antibiotic treatments, the cause of the fever remains undetermined.

In the past two weeks, I tested positive for mumps IgM (slightly above the standard value), but IgG was also positive (five times above the standard value).
Previously, multiple tests for tuberculosis (TB) through blood tests were negative, and a chest X-ray showed no abnormalities.
However, a recent urine test indicated the presence of tuberculosis bacteria, and rapid gene testing returned negative.
I have seen many doctors and have been referred multiple times, but the cause of the fever has not yet been identified.
1.
Based on the above situation, what further investigative directions would you recommend?
2.
Could the negative PPD skin test for tuberculosis, conducted two weeks ago, potentially explain the recent urine test showing tuberculosis bacteria? Given that I have had multiple negative blood and urine tests for tuberculosis over the past few months, how could there suddenly be a positive result? Is this related to the fever and urinary weakness? I hope to receive some advice and direction.
Thank you!

Tracy, 20~29 year old female. Ask Date: 2019/06/21

Dr. Liao Yaopan reply Family Medicine

Hello, may I ask if you are still experiencing a fever? Infection remains the most common cause of fever, and the treatment duration varies depending on the cause and location of the infection.
If the fever persists, it is important to differentiate whether there are other underlying causes.
If the fever has lasted for more than two months, it is strongly recommended to consult an infectious disease specialist for a comprehensive evaluation.
Please note that online consultations are not equivalent to in-person visits and cannot provide a diagnosis or treatment recommendations.
Changhua Hospital cares about your well-being.

Reply Date: 2019/06/21

More Info

Unexplained fever can be a challenging clinical scenario, especially when it persists despite extensive investigations. Your case presents a complex interplay of symptoms, including fever, hematuria (blood in urine), urinary weakness, and other systemic signs. Given the timeline and the various specialists you have consulted, it is crucial to approach this situation methodically.

1. Suggested Directions for Further Investigation
Given the persistence of your fever and the various tests that have already been conducted, here are some potential avenues for further investigation:
- Infectious Disease Workup: Since you have had a positive IgM for mumps and a history of urinary symptoms, it may be worthwhile to consider other viral infections or atypical bacterial infections that could be causing your symptoms. Testing for viruses such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), and even less common pathogens like Q fever or leptospirosis could be beneficial.

- Imaging Studies: If not already done, consider advanced imaging studies such as a CT scan of the abdomen and pelvis to evaluate for any abscesses, masses, or other abnormalities that may not be visible on standard X-rays. This could help identify any underlying conditions that might be contributing to your fever and urinary symptoms.

- Bone Marrow Biopsy: If hematological malignancies or bone marrow disorders are suspected, a bone marrow biopsy might be warranted to rule out conditions like leukemia or lymphoma, which can present with fever and systemic symptoms.

- Autoimmune Disorders: Given the involvement of multiple systems, a thorough evaluation for autoimmune conditions such as systemic lupus erythematosus (SLE) or vasculitis might be appropriate. Specific autoantibody panels could provide insights.

- Repeat Cultures and Sensitivity Testing: Since you have had a history of urinary tract infections, repeating urine cultures and sensitivity testing after antibiotic therapy may help identify any resistant organisms. Additionally, consider testing for mycobacterial infections, especially if there is any suspicion of tuberculosis (TB).

2. Interpretation of Recent Test Results
Regarding your question about the PPD skin test and the recent positive urine test for tuberculosis bacteria, it is essential to understand the nuances of these tests:
- PPD Skin Test: A negative PPD test does not completely rule out tuberculosis, especially in immunocompromised individuals or those with atypical presentations. The timing of the test in relation to your symptoms and any recent infections could influence the results.

- Urine Test for Tuberculosis: The presence of TB in urine can indicate renal involvement, but it is also possible to have false positives or transient bacteriuria. The fact that your previous tests for TB were negative suggests that this may not be the primary cause of your fever, but it does warrant further investigation, especially if you have risk factors for TB.

Conclusion
In summary, your case requires a multidisciplinary approach, and it is essential to continue working closely with your healthcare providers. Given the complexity of your symptoms and the lack of a definitive diagnosis, consider seeking a referral to a specialized center for unexplained fevers or a comprehensive infectious disease clinic. They may have access to additional diagnostic tools and expertise that could help unravel the underlying cause of your persistent fever and associated symptoms.
Maintaining open communication with your healthcare team about your symptoms and any changes you experience is crucial in managing your condition effectively.

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