COMMENTARY

Ureaplasma Septic Arthritis: An Unusual Case Unfolds

Stephen Paget, MD

Disclosures

July 12, 2019

The following patient story highlights the importance of thoughtful reevaluation and clinician willingness to pivot when a case does not unfold as expected.

Patient Profile

A 56-year-old woman with a history of diffuse large B-cell lymphoma in remission presented for evaluation of polyarthritis.

The patient first experienced left lower abdominal pain due to a ruptured diverticulum and tubo-ovarian abscess that necessitated partial colectomy and left salpingo-oophorectomy. Her surgery was complicated by anastomotic leak that necessitated subsequent repair.

The day after her second operation, she developed acute right wrist and ankle pain and swelling. Ankle aspiration revealed one positively birefringent intracellular crystal and negative cultures. The patient subsequently developed synovitis of her right knee and left wrist.

The patient was started on intravenous methylprednisolone (1 mg/kg daily). MRI of her wrist demonstrated marked common flexor tendon tenosynovitis with reactive median nerve inflammation. On steroids, she experienced no clinical improvement over 4 weeks.

Laboratory testing was notable for elevated erythrocyte sedimentation rate (96 mm/hr) and negative rheumatoid factor, cyclic citrullinated peptide antibody, antinuclear antibody, human leukocyte antigen B27 (HLA B27) test, and extractable nuclear antigen panel. Blood cultures, QuantiFERON, and urine gonorrhea and chlamydia nucleic acid amplification tests were also negative.

Testing for immunoglobulin levels was performed to evaluate for common variable immune deficiency, and low immunoglobulin G levels were noted. She received intravenous immunoglobulin and a concurrent trial of colchicine 0.6 mg daily. Three weeks later, the patient developed neutropenia and colchicine was held. A bone marrow biopsy demonstrated agranulocytosis without evidence of cancer. PET-CT found no recurrence of her lymphoma.

While neutropenic, she experienced significant improvement in her joint pain. However, as her neutropenia resolved, she developed worsening joint pain and swelling. Aspiration revealed 174,500 white blood cells (92% polymorphonuclear neutrophils); 45,000 red blood cells; no crystals; and negative cultures, Lyme polymerase chain reaction (PCR), and acid-fast bacilli (AFB) stain. A synovial biopsy of her knee showed predominantly neutrophilic infiltration with fibrinous exudate and negative cultures and infectious staining (AFB, periodic acid-Schiff, and Grocott methenamine silver stains).

The patient was readmitted owing to severe functional disability. She received high-dose intravenous methylprednisolone (200 mg daily) for 3 days and weekly secukinumab for a possible seronegative reactive arthritis for 1 month. On this regimen, she had no clinical improvement. Repeat radiographs of her wrist demonstrated interval joint space narrowing during the 5 previous months. She was given doxycycline with rifampin for possible reactive arthritis; however, her neutrophil count fell within days, and both antibiotics were held. Secukinumab was discontinued, and anakinra (100 mg daily subcutaneously) was started, which improved her symptoms adequately enough to enable discharge. However, on outpatient follow-up, her synovitis remained severe and repeat knee arthrocentesis contained 96,750 white blood cells (94% polymorphonuclear neutrophils).

Making the Diagnosis

The patient has polyarthritis involving her bilateral wrists, and right knee and ankle with markedly elevated synovial fluid white blood cell count and prominent neutrophilic infiltration on synovial biopsy. An infectious disease and cancer work-up has thus far been negative. Her disease has been resistant to multiple immunosuppressive agents and only significantly improved in the setting of drug-induced neutropenia. Targeting the innate immunity with interleukin-1 inhibition provided only modest improvement.

The possibility of an ongoing infectious process was again considered despite negative infectious work-up owing to the degree of synovial inflammation and resistance to immunosuppression. Therefore, synovial fluid from her knee was sent to the Mayo Clinic Laboratory for broad-range bacterial PCR amplification and sequencing. This testing revealed ureaplasma parvum DNA present in the patient's synovial fluid. The patient was treated with doxycycline and experienced significant improvement in joint pain and swelling while maintaining her peripheral neutrophil count.

Ureaplasma parvum is commensal to the lower genitourinary tract. Therefore, the patient's tubo-ovarian abscess that required salpingo-oophorectomy may have been an important mechanistic factor. Cases of ureaplasma septic polyarthritis have been reported in immunocompromised patients, including those with hypogammaglobulinemia and hematologic cancer.[1,2,3] Ureaplasma is difficult to grow using conventional methods. Therefore, ureaplasma septic arthritis is typically diagnosed using bacterial DNA detection methods.

This case teaches important lessons. First, it is essential to keep bacterial infection on the differential for acute arthritis involving multiple joints, even in the absence of documented bacteremia or positive conventional synovial fluid cultures. This is especially true when there is a neutrophilic predominance in synovial fluid, which suggests a potential infectious etiology. This case also demonstrates the utility of advanced techniques for identifying fastidious organisms by bacterial DNA detection.

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