Osteomyelitis of the Hip secondary to Aspergillus fumigatus-A Case Report and Comprehensive Review of the Literature

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Osteomyelitis of the Hip secondary to Aspergillus fumigatus -A Case Report and Comprehensive Review of the Literature
Antony SJ *1,2 and Hadi Y 1   1   Texas Tech University Health Science Center, El Paso, Texas 2 Center for Infectious Disease and Travel Medicine, El Paso, Texas The patient was evaluated for a persistent mild cough without fever, chills, chest pain or any muscular or musculoskeletal pain.During the process of this particular illness, he complained of pain to the right hip.Further work up three months later revealed increasing pain localized to the right hip, non-radiating, severe in nature, aggravated with walking and weight bearing.At that time, he denied any trauma to the area or any direct injury to any related area.
A Magnetic Resonance Imaging (MRI) of right hip was done and showed evidence of osteomyelitis of the right sacral iliac joint.He underwent a biopsy of the right iliac joint.The gram stain of biopsy did not show any bacteria/organism with normal White Blood Cell (WBC) and Red Blood Cell (RBC) count.However, the pathology revealed extensive fibrosis, focal necrosis and osteomyelitis.In addition, the culture grew Aspergillus fumigatus species.Further workup did not reveal the primary source of infection especially in the lung.Susceptibility studies were not done unfortunately.
A bronchoalveolar lavage was done because a small speculated lesion in the right lower lobe.This was unremarkable for malignant cells, fungal organisms or acid-fast bacilli.Complete blood count and comprehensive metabolic panel was unremarkable.Erythrocyte Sedimentation Rate (ESR) was 90 mm/hour and C-Reactive Protein (CRP) was 4.5.
The patient was started on oral Voriconazole 200 mg once a day for six months.He tolerated the therapy without much problem.The MRI done of the right hip six months later revealed stabilization of the osteomyelitis.

Discussion
Fungal osteomyelitis, mainly caused by Candida sp and Aspergillus sp, is a severe and debilitating disease [1].It is primarily a disease of the immunocompromised patients, even though it can affect immunocompetent patients.The majority of the cases have been reported in developed regions with outstanding healthcare systems, such as North America (47% of the reported cases) and Europe (33% of the reported cases).The most common mode of transmission of Aspergillus osteomyelitis is contiguous spread from pulmonary infection and/or from contiguous skin infection.This may be the reason why the vertebrae and the ribs were the most common sites affected [2].In adults, vertebrae is also the most common infection site but most of the time due to hematogenous spread or direct inoculation due to trauma with penetrating injury/surgical procedures [2][3][4][5][6][7].Most cases of Aspergillus osteomyelitis appeared to be affecting immunocompromised hosts with chronic granulomatous infections and immunodeficiency condition [2,[4][5][6][8][9][10].Among adults, prolonged and high dose immunosuppressive drug therapy is considered the most important predisposing condition [2,4].Journal of Immunology and Infectious Diseases In a paper published in 1999, a review of the literature on fungal osteomyelitis was done, which revealed less than 40 cases of Aspergillus osteomyelitis.Noticeably, the increased usage of chemotherapy, immunomodulator and steroids may indirectly cause the increased incidence of Invasive Aspergillosis, in particular Aspergillus osteomyelitis.Other important risk factors that should be considered are the use of central venous catheters and abdominal surgery.Therefore, in our case, it is possible that the history of bilateral inguinal hernia repair may have played a role as an entry route of Aspergillus fumigatus.
The incidence of Aspergillus affecting the bone among all cases of invasive Aspergillosis is thought to be around 3% [11,12].In a series by Horn et al, the incidence of invasive Aspergillosis was 2.6%, similar to those reported by Denning and Stephen in 1990 [12].In most cases it appears to present as diskitis or osteomyelitis of the spine.Involvement of the long bones and hip etc. has rarely been documented [3,4].
Aspergillus infection remains extremely rare in immunocompetent hosts [13].In 1987, Brown et al reported 2 cases of seemingly immunocompetent adults who used intravenous drugs [14].Vaishya et al reported a case of vertebral osteomyelitis in an immunocompetent adult; noting only 4 other cases have been previously reported [15].In 2005, Mouas et al discussed 20 cases of osteomyelitis, 6 of which were immunocompetent [13].
Our case is particularly unique not only because the patient is immunocompetent, but also this is one of a few case of Aspergillus osteomyelitis that affecting long bone, particularly hip joint.There were no history of penetrating trauma/surgical event to the hip joint nor any signs of affected portal of entry of Aspergillus infection; which are lung, skin, gastrointestinal tract or sinuses [8].
It requires three major criteria to document that the osteomyelitis is secondary to a fungus: 1. Accurate identification and isolation of the pathogen from the actual site of infection.2. Direct microscopic demonstration of the pathogenic invasive form of the fungus from the site where the cultures were obtained.3. Correlation of the results of the culture to the osteomyelitis process.Concomitant bacterial infections can occasionally occur in these fungal bone infections.
Aspergillus fumigatus was the most commonly isolated species followed by Aspergillus flavus, Aspergillus niger, Aspergillus terreus [4,5,7].Unlike Candida, which is the most common organism causing mycotic infections [16,17], Aspergillus is slow growing, difficult to isolate and most of the time is a contaminant since the spores are really small [9,18].Therefore, a culture and histopathological examination are still important to obtain the correct diagnosis [7,9,18].Another proposed method for diagnostic are Galactomannan (GM) and (1→3)-β-d-glucan (BG) antigen quantification by enzyme-linked immunosorbent assay and detection of fungal DNA by PCR methods or single nucleotide polymorphism (SNP) markers.This test is not easily available and has not been studied as an indicator for osteomyelitis caused by Aspergillus.
Recent studies of patients with invasive Aspergillosis have shown that treatment with Voriconazole is more effective than treatment with Amphotericin B [7,10,23,24].Length of therapy is generally between 6-12 weeks [1,7].Many of the literature supports the use of prolonged therapy for up to a year [13].Recurrences are not uncommon [25].