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Disseminated Coccidioidomycosis of the Knee Joint Requiring Synovectomy and Arthrotomy


Disseminated Coccidioidomycosis of the Knee Joint Requiring Synovectomy and Arthrotomy

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Clinicians should consider disseminated coccidioidomycosis infection in patients presenting with a painful knee effusion, past respiratory illness, or travel to endemic regions and this uncommon fungal infection may become refractory to pharmacotherapy and require surgical intervention.

Case Report | Volume 11 | Issue 2 | JOCR February 2021 | Page  76-80 | Farhan Ahmad, Kavina Patel, Jorge Clint De Leon, Frank A Buttacavoli . DOI: 10.13107/jocr.2021.v11.i02.2034

Authors: Farhan Ahmad[1], Kavina Patel[1], Jorge Clint De Leon[1], Frank A Buttacavoli[1]

[1]Department of Orthopaedic, Joe R. and Teresa Lozano Long School of Medicine, University of Texas Health at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229.

Address of Correspondence:
Dr. Farhan Ahmad,
Joe R. and Teresa Lozano Long School of Medicine, University of Texas Health at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229.


Introduction: Coccidioidomycosis is a fungal infection endemic to the Southwestern United States, Mexico, and South America. While uncommon, inhalation of spores or direct cutaneous contact can lead to disseminated infection in the immunocompetent, with the involvement of the musculoskeletal and integumentary systems.
Case Report: A 49-year-old patient with a history of pulmonary coccidioidomycosis presented with the right knee pain and multiple symptomatic abscesses beneath the suprapatellar and infrapatellar fat pads. Arthrocentesis and culture confirmed the infection, and open synovectomy, arthrotomy, and drainage of the infection were performed without complication.
Conclusion: Disseminated coccidioidomycosis is an uncommon fungal infection that may involve joints and become refractory to pharmacotherapy. Management may require surgical intervention, along with infectious disease consultation and close follow-up. Patients from endemic regions should be evaluated with a comprehensive history of this disease.
Keywords: Coccidioidomycosis, knee, septic arthritis, arthrotomy, synovectomy, orthopedic surgery, fungal infection.

Coccidioidomycosis is a fungal infection caused by the Coccidioides immitis or Coccidioides posadasii species that are endemic to Southwestern United States, Mexico, and South America [1]. India is non-endemic and cases result from international travel, which is why a travel history is important to avoid missed diagnoses. The fungi are known to survive in arid and alkaline environments [2]. Most infections are established through inhalation of aerosolized arthrospores, but may less commonly inoculate patients through direct cutaneous contact. Initial pulmonary infections are typically asymptomatic or present with mild lower respiratory symptoms and resolve spontaneously [3, 4]. Symptomatic cases will present similar to community-acquired pneumonia, with flu-like symptoms and a possible rash–also known as “Valley Fever.” There are no pathognomonic chest imaging findings. Hematogenous extrapulmonary systemic dissemination may present in 1% of infections and may involve the integumentary and musculoskeletal systems, with comparatively more cases occurring in older individuals and males [5, 6]. About 10–30% of disseminated coccidioidomycosis cases will have musculoskeletal involvement [3]. Epidemiologic studies posit that about 1500 Americans per year are infected with disseminated coccidioidomycosis [7, 8]. Due to the low prevalence of this form of the disease, clinicians surgeons should maintain a high index of suspicion and obtain comprehensive histories for patients from endemic areas, especially those with a history of the infection [9]. In this article, we present a case of an immunocompetent patient from an endemic area diagnosed with disseminated coccidioidomycosis of the knee joint, which required operative management. The patient’s risk of exposure was determined by his endemic residence and occupation history. The rarity of this presentation of coccidioidomycosis is noteworthy and an opportunity for clinicians to review the diagnosis and treatment of disseminated coccidioidomycosis.

Case Report
A 49-year-old male oil field worker from West Texas with a history of gastroesophageal reflux disease, hypertension, obstructive sleep apnea, and obesity presented with a painful right knee effusion for at least 1 year. He had a history of coccidioidomycosis pneumonia 15 months prior, which presented as left lower lobe nodular infiltrates on radiographs, along with fever, chills, dyspnea, and malaise. The patient’s pulmonary coccidioidomycosis was treated with fluconazole for 12 months without much response, and he concurrently developed worsening the right knee pain. Infectious disease consultants subsequently placed the patient on itraconazole for 3 months for disseminated coccidioidomycosis infection, which abated his pulmonary symptoms but not his knee pain. At the time of presentation to orthopedics, the lungs were clear, with no infiltrates or pleural effusions present on imaging.
Physical examination demonstrated right knee effusion and palpable soft-tissue mass in the lateral supra-patellar and lateral infra-patellar regions (Fig. 1a, b). The patient tolerated an axial load and was able to ambulate with an antalgic gait. His knee range of motion with discomfort was from full extension to 110 degrees of flexion. He had no pain with an examination of his hip or his other joints at the initial presentation. Knee joint aspirate demonstrated a yellow hazy fluid, elevated white blood cell count (12,579/mm3) with 56% polynuclear cells, and 44% monocytes. Fungal culture was positive for C. immitis and C. posadasii. Serum serologies demonstrated positive Coccidioides IgG (9.0) and IgM (2.8) antibodies. Serum complement fixation was elevated at 1:1024. Cerebrospinal fluid demonstrated positive Coccidioides IgG (2.9), and negative IgM (0). Radiographs of the right knee showed a large joint effusion without underlying osseous abnormality (Fig. 2a-c). Magnetic resonance imaging (MRI) of the knee confirmed extensive synovial thickening and enhancement throughout the right knee joint compatible with synovitis (Fig. 3a-c). In addition, subcutaneous abscesses superficial to the quadriceps and patellar tendons were identified. The patient provided informed consent to undergo a right knee open synovectomy, biopsy, arthrotomy, and drainage. During surgery, superficial abscesses (measuring 4 cm × 4 cm and 2 cm × 2 cm) with extensive synovial thickening were found with no knee joint involvement. The patient tolerated surgery well and encountered no intraoperative complications. The wound was primarily closed with an incisional vacuum placed. Histopathologic examination of drained fluid from surgery revealed spherules with endospores suggestive of coccidioides (Fig. 4a, b).
Post-operatively, an infectious disease consultant placed the patient on liposomal amphotericin B (AmB), vancomycin, metronidazole, and cefepime. The incisional vacuum was removed on the post-operative day 2. At discharge, the wound was healing well, and there was no evidence of surgical site infections. The patient was given a hinged knee brace but was advised to spend time without it to work on increasing his range of motion. The patient was also put on 200 mg itraconazole twice a day at discharge. The patient continued following up with orthopedics at 3 months and 6 months. At the 6-month follow-up visit, the patient endorsed improved functional status and was ambulating without assistance. Physical examination showed a well-healed surgical scar with no signs of reinfection or drainage. Knee range of motion had returned to greater than 90 degrees flexion and full extension (Fig. 5a, b). Infectious disease specialists decided to continue the itraconazole regimen indefinitely, periodically following the patient for his chronic coccidioidomycosis infection.

This case presents disseminated coccidioidomycosis infection of the knee joint with periarticular synovial involvement and abscess formation. Skeletal coccidioidomycosis typically presents as a chronic synovitis, arthritis, or osteomyelitis of axial structures such as the spine, but the knee is an appendicular joint also known to become infected. Periarticular manifestations include tenosynovitis, tendinitis, and effusion, along with concomitant soft-tissue infections. Joint space destruction can also happen in the later stages of the disease if left untreated [10]. Accurate diagnosis of this disease, especially in the immunocompetent, requires a high index of suspicion, especially in those from or recently visiting from endemic areas or with a history of the disease. A thorough history and physical examination should elucidate travel to or residence in endemic areas, as well as any past respiratory illness that can predate skeletal manifestations of coccidioidomycosis. Epidemiologic studies indicate that the disseminated form of this disease follows within a year of acute respiratory infection. Pregnant women and patients of Hispanic, African, or Filipino descent are at increased risk. Other risk factors include advanced age, diabetes, and pre-existing cardiopulmonary conditions. It should be noted that although immunocompromised patients are at the highest risk of serious disseminated infections, immunocompetent patients are still susceptible [11]. Fungal etiologies should remain on the clinician’s differential for patients presenting with signs of joint inflammation, such as swelling, redness, and pain – especially in endemic regions. Arthrocentesis should be performed on joints to assist with diagnosis, and a survey of other joints should be performed to assess for simultaneous and multifocal areas of infection. In addition, any laboratory receiving specimens with potential coccidioidomycosis should be alerted because the organism is a biosafety level 3 pathogen. The gold standard for diagnosis of skeletal coccidioidomycosis is culture and/or serological testing. Radiographs and/or MRI can be useful for assessing the extent of involvement and formulating surgical plans. However, imaging can introduce pitfalls as well. On MRI, coccidioidomycosis of the bone can present as hyperintense lesions that may be misconstrued as metastatic bone disease. The differential diagnoses for coccidioidomycosis lesions based on imaging include other fungal and granulomatous diseases or osteosarcomas and other malignancies [12]. Operative management of disseminated coccidioidomycosis typically requires incision and debridement and resection of disease sequestra. Necrotic tissue should be removed with healthy margins and the reduction of pathogenic burden is the mainstay of treatment [13]. In contrast to disseminated tuberculosis, debridement of coccidioidomycosis is indicated. Following operative removal of the fungal pathogen burden, the initiation of culture-specific antifungal pharmacotherapy, such as AmB, ketoconazole, fluconazole, or itraconazole, is needed [14]. Consult from an infectious disease physician is recommended for assistance with the management of antibiotic choice and duration of treatment. Our patient was initially treated with fluconazole followed by itraconazole due to the presence of significant pulmonary nodular infiltrates in the left lower lobe. Once the patient presented with disseminated infection, itraconazole was continued, and AmB was administered post-operatively per Infectious Disease Society of America and the Centers for Disease Control and Prevention guidelines [14]. Lifelong suppressive treatment is often required for patients, and it should be noted that lipid formulations of drugs may be more costly, less accessible, and lead to insurance denials if an alternative drug is available [15]. In general, itraconazole is preferred for patients with bone and joint manifestations of disseminated coccidioidomycosis infection. Antibody titers can be employed as needed to follow treatment progress. Research on future therapies appears promising and includes the development of a live attenuated immunization against C. immitis, which has been successful in murine in vitro experiments [16, 17].

Disseminated coccidioidomycosis may involve joints. Diagnosis requires a high index of suspicion and thorough evaluation of travel history to endemic areas, as well as other distinguishing factors in the patient history. Imaging may be useful to assess the degree of joint involvement. Additional biosafety precautions are recommended when handling a fluid sample with potential coccidioidomycosis. Recalcitrant cases of this infection may require operative approaches, such as synovectomy and arthrotomy, as well as infectious disease consultation and close follow-up.

Clinical Message
Clinicians should consider disseminated coccidioidomycosis infection in patients presenting with a painful knee effusion, past respiratory illness, and/or travel to endemic regions. This uncommon fungal infection may become refractory to pharmacotherapy and require surgical intervention.

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Dr. Farhan Ahmad Dr. Kavina Patel Dr. Jorge Clint De Leon Dr. Frank A Buttacavoli

How to Cite This Article: ?Ahmad F, Patel K, De Leon JC, Buttacavoli FA. Disseminated Coccidioidomycosis of the Knee Joint Requiring Synovectomy and Arthrotomy. Journal of Orthopaedic Case Reports 2021 February;11(2): 76-80.

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