Fungal Musculoskeletal Infections. Comprehensive Approach to Proper Diagnosis (2024)

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Fungal Musculoskeletal Infections:

Comprehensive Approach to Proper Diagnosis


Marina C. Akuri, MD • Jenny T. Bencardino, MD • Júlia B. Peixoto, MD • Vitor N. Sato, MD • Lucas K. Miyahara, MD • Daisy T. Kase, MD
Adriana M. Dell’Aquila, MD, PhD • Adham do Amaral e Castro, MD, PhD • Artur R. C. Fernandes, MD, PhD • André Y. Aihara, MD, PhD
Author affiliations, funding, and conflicts of interest are listed at the end of this article.

Fungal musculoskeletal infections often have subacute or indolent manifestations, making it difficult to distinguish them
from other diseases and infections, given that they are relatively uncommon. Fungal infections occur by hematogenous
spread, direct inoculation, or contiguous extension and may be related to different risk factors, including immunosuppres-
sion and occupational activity. The infection can manifest in isolation in the musculoskeletal system or as part of a systemic
process. The fungi may be endemic to certain regions or may be found throughout the world, and this can help to narrow
the diagnosis of the etiologic agent. Infections such as candidiasis, cryptococcosis, aspergillosis, and mucormycosis are
often related to immunosuppression. On the other hand, histoplasmosis, paracoccidioidomycosis, coccidioidomycosis, and
blastomycosis can occur in healthy patients in geographic areas where these infections are endemic. Furthermore, infections
can be classified on the basis of the site of infection in the body. Some subcutaneous infections that can have osteoarticular
involvement include mycetoma, sporotrichosis, and phaeohyphomycosis. Different fungi affect specific bones and joints
with greater prevalence. Imaging has a critical role in the evaluation of these diseases. Imaging findings include nonspecific
features such as osteomyelitis and arthritis, with bone destruction, osseous erosion, mixed lytic and sclerotic lesions, and
joint space narrowing. Multifocal osteomyelitis and chronic arthritis with joint effusion and synovial thickening may also
occur. Although imaging findings are often nonspecific, some fungal infections may show findings that aid in narrowing the
differential diagnosis, especially when they are associated with the patient’s clinical condition and history, the site of osteo-
articular involvement, and the geographic location.
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RSNA, 2024 • radiographics.rsna.org

MUSCULOSKELETAL IMAGING
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July 2024 Akuri et al

They involve the skin and surrounding soft tissues, including


RadioGraphics 2024; 44(7):e230176
TestYour https://doi.org/10.1148/rg.230176
muscles and fascia (2). Systemic spread of subcutaneous in-
Knowledge fections is rare (8). Systemic infections occur by means of dis-
Content Codes: MK, MR
semination of the pathogen through the hematogenous route
Abbreviations: FDG = fluorine 18 fluorodeoxyglucose,
STIR = short-tau inversion-recovery
from a distant focus, occasionally with lymphatic involve-
ment (8). The first site involved is usually the respiratory tract
TEACHING POINTS after inhalation of the agent, followed by dissemination to
„ Musculoskeletal infections are often subacute or indolent at patient other organs including the musculoskeletal system (8). Based
presentation and can mimic other diseases such as neoplasia, bacterial on the acquisition route, fungal infections can be classified as
infections, and tuberculosis. Fungal osteoarticular infections can affect endogenous or exogenous infections. Endogenous infections
bones, joints, muscles, ligaments, and tendons and can occur in isolation
or as part of a systemic infection when other organs are involved.
occur by means of colonization of flora or reactivation of a
„ Diagnosis can be challenging, requiring a high degree of clinical suspi-
previous infection, while exogenous infections include air-
cion to consider fungal disease as a possibility. Imaging is fundamental way, cutaneous, or percutaneous entry points (7). Based on
to early diagnosis, follow-up, and assessment of fungal musculoskeletal fungal virulence, primary endemic pathogens can cause dis-
infections, showing bone and soft-tissue involvement, the extent of the ease in immunocompetent hosts, while opportunistic patho-
infection, and complications and allowing differentiation from conditions
gens cause infection in immunocompromised patients (7).
that mimic infection.
Moreover, fungal infections are endemic in some regions and
„ Regarding geographic distribution, some fungi can be found worldwide,
while others are usually found in endemic areas. Primary pathogens oc- sporadic in others (9).
cur in relatively well-defined geographic locations, while opportunistic Diagnosis can be challenging, requiring a high degree of
fungi are ubiquitous. clinical suspicion to consider fungal disease as a possibility
„ Fungal diskitis osteomyelitis can mimic tuberculosis, with spared inter- (2). Imaging is fundamental to early diagnosis, follow-up,
vertebral disks, multilevel involvement, and subligamentous spreading and assessment of fungal musculoskeletal infections, show-
of the abscess. Other imaging features include a focal paravertebral
soft-tissue abnormality and partial disk involvement, sometimes spar-
ing bone and soft-tissue involvement, the extent of the in-
ing the intranuclear disk cleft. fection, and complications and allowing differentiation from
„ Fungi are important to consider in the differential diagnosis of muscu- conditions that mimic infection (1,10–12). Prolonged drug
loskeletal infections. Their presence on images can be nonspecific and treatment is usually necessary, sometimes requiring surgi-
should always be considered when there is suspicion for musculoskele- cal intervention (1,2). This article reviews the main aspects of
tal infectious involvement, especially if there is extensive bone destruc-
tion and/or an inflammatory process of soft tissue, with a relatively in-
fungal infections in the musculoskeletal system.
dolent clinical picture.
Epidemiology
Fungal bone infection is rare (4). However, the incidence of
Introduction invasive fungal infections has increased worldwide, probably
Fungi are uncommon causes of musculoskeletal infections due to the increased number of patients at risk (4,5). Epidemi-
(1,2). Musculoskeletal infections are often subacute or indo- ologic characteristics differ among types of fungi (12).
lent at patient presentation and can mimic other diseases Osteoarticular fungal infections can affect both immuno-
such as neoplasia, bacterial infections, and tuberculosis suppressed and immunocompetent individuals (1,2,4). Im-
(2,3). Fungal osteoarticular infections can affect bones, munosuppression is a risk factor for some osteoarticular fun-
joints, muscles, ligaments, and tendons and can occur in gal infections, and its causes include HIV infection and AIDS,
isolation or as part of a systemic infection when other organs organ transplant, chemotherapy, chronic corticosteroid treat-
are involved (2). When such infections occur, they are often ment, diabetes, and autoimmune diseases (1,5,10). Some risk
destructive, and their severity is mainly associated with the factors can be related to specific types of fungal infection (4).
immune status of the host and the inherent pathogenicity of For example, candida osteomyelitis may be related to risk fac-
the organism (2). tors such as surgery (mainly abdominal), trauma, and use of
Spreading mechanisms of fungal infection are triggered illicit intravenous drugs (4). In general, immunosuppressed
by direct inoculation due to trauma or surgical manipula- patients have a higher predisposition for complications from
tion, contiguous extension, or hematogenous dissemination both endemic and ubiquitous fungal diseases (13).
(1) (4,5). Direct inoculation can occur through trauma or con- Regarding geographic distribution, some fungi can be found
tamination of a traumatic injury with soil, intravenous drug worldwide, while others are endemic to specific areas. Prima-
use, parenteral treatment, intra-articular injection, arthro- ry pathogens occur in relatively well-defined geographic loca-
centesis, implantation of a prosthesis, or exposure to contam- tions, while opportunistic fungi are ubiquitous (7).
inated surgical instrumentation (5,6). Thus, fungal musculoskeletal infections can be divided
Fungal conditions can be divided based on the site of in- into endemic systemic infections, which are infections caused
fection, the acquisition route, or the virulence of the fungus by endemic fungi and can occur in healthy hosts; opportunis-
(7). Based on the site of infection, mycoses are classified as su- tic systemic infections, which occur in patients immunosup-
perficial, cutaneous, subcutaneous, or systemic (7). Superfi- pressed by ubiquitous fungi; and subcutaneous infections, in
cial and cutaneous infections are not addressed in this article. which the main infection site is the subcutaneous tissue. The
Subcutaneous infections usually spread contiguously from geographic distribution and endemic areas of each fungus are
an initial skin inoculation site, commonly after trauma (2). represented in Figure 1.

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Figure 1. Geographic regions of endemic mycoses and areas with multiple cases reported.

Imaging Techniques patients with these infections. FDG PET/CT pinpoints the site
Imaging findings may be nonspecific, and the differential of infection and its extension and allows monitoring of the
diagnosis with other etiologic infections and inflammatory disease activity and response to therapy (10)(Fig 2).
arthropathies may be difficult, thus requiring clinical data, Imaging is also used to guide biopsy sampling, which is re-
epidemiologic information, biopsy, and culture for confir- quired to confirm the diagnosis of fungal infection. Biopsies
mation (2,3,14). Imaging modalities include radiography, US, may be performed percutaneously (closed biopsy under im-
CT, MRI, and PET/CT. aging guidance) or surgically (open biopsy) (17). Biopsies can
Findings of osteomyelitis on radiographs and CT images be guided by CT, CT fluoroscopy, or in some cases, US. MRI is
include bone destruction, osseous erosion, mixed lytic and not commonly used for guiding biopsies; however, informa-
sclerotic lesions, and joint space narrowing (3,5). Osteomyeli- tion obtained from MRI studies, such as bone and soft-tissue
tis may progress to marked bone destruction, causing defor- involvement, can be used in planning the procedure, espe-
mity (3). Although some agents may appear as a single lytic cially when the findings are correlated with those of CT (17).
lesion resembling a bone tumor, in cases of hematogenous At least three tissue samples must be obtained, and the bulk
spread, involvement of multifocal noncontiguous bones and of the specimens should be placed in various culture tubes (17).
joints may be seen (2). US findings in fungal infections, with For histologic specimens, 10% formalin is added; for cytolog-
the exception of mycetoma, are nonspecific and include ic and microbiologic specimens, saline is added or an empty
chronic joint involvement, with joint effusion and synovial sterile container is used (17). Paraspinal fluid collections and
thickening (5), tenosynovitis, bursitis and edema, and swell- intradiskal fluid may not contain organisms, but if there are
ing of the soft tissues, which can become hardened due to any fluid collections, they must be aspirated and the aspirate
chronicity (15,16). should be sent for culture in sterile containers (17).
MRI is the most sensitive modality in diagnosis of muscu- Although the imaging findings of fungal infections, in gen-
loskeletal fungal infection and for detecting soft-tissue col- eral, are relatively nonspecific for indolent infections, some
lections (3). Imaging findings are generally nonspecific and infections may show findings that aid in narrowing the differ-
include bone marrow involvement with hypointensity on ential diagnosis. Tables 1 and 2 show the most affected joint
T1-weighted MR images and hyperintense foci on T2-weight- and bone sites for each fungal infection.
ed MR images, with enhancement on contrast-enhanced MR
images (3). Other findings include multifocal osteomyelitis Systemic Endemic Fungal Infection
and chronic arthritis, with synovial thickening resembling os- Systemic endemic fungal infections are found in distinct geo-
teoarticular tuberculosis (5). Some studies (1,10) have demon- graphic regions (9) and are frequently encountered through-
strated the potential role of fluorine 18 (18F) fluorodeoxyglu- out Latin America (defined as countries in Central and South
cose (FDG) PET/CT in fungal infections. FDG is a nonspecific America), where they have an important effect on public
marker that accumulates at sites of infection, including fungal health (18). Unlike most other fungal pathogens, which pri-
disease, and has potential in initial diagnosis and follow-up of marily infect people with a compromised immune system,

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Figure 2. Fungal olecranon bursitis in an


80-year-old man who presented with elbow
pain. Drainage was performed, and cultures
showed Fonsecaea species (chromoblastomyco-
sis). (A) FDG PET/CT image shows an FDG-avid
region overlying the olecranon (arrow). (B) FDG
PET/CT image after drainage and treatment with
voriconazole for 2 months shows reduced FDG
uptake as a sign of response to therapy (arrow)
(C) Color Doppler US image shows a complex
fluid collection in the olecranon bursa, with
intense peripheral hypervascularity (arrow).
(D) Coronal contrast-enhanced T1-weighted MR
image shows an encapsulated fluid collection
with thick peripheral enhancement in keeping
with olecranon bursitis (arrow).

the endemic fungi can act as primary pathogens and cause tent patients. However, more severe or symptomatic infection
infections in immunocompetent people (19). Diagnosis and may occur, especially in more heavily exposed or immunocom-
management of these infections are challenging, particular- promised individuals (13,20). H capsulatum has an affinity for
ly because of the variability of clinical presentation, the fas- the reticuloendothelial system (3). It may spread to the skin,
tidious and slow-growing nature of the pathogens, and the oral mucosa, brain, liver, spleen, lymph nodes, adrenal glands,
paucity of diagnostic tests (20). The main endemic fungal in- bones, intestines, mediastinum, and pericardium (3,5,9).
fections with musculoskeletal involvement in South, Central, Musculoskeletal involvement of histoplasmosis usually oc-
and North America are histoplasmosis, paracoccidioidomyco- curs in patients with disseminated disease, frequently being
sis, coccidioidomycosis, and blastomycosis. Table 3 summa- multifocal, resembling sarcoidosis and tuberculosis (2,9). Some
rizes epidemiologic data for these infections. patients may also have cutaneous lesions, hepatomegaly, or
lymphadenopathy (1). Lung disease is rarely described during
Histoplasmosis the course of osteoarticular infection (1). Histoplasmosis mainly
Histoplasmosis is caused by Histoplasma capsulatum, which causes osteomyelitis of the spine and long bones and septic ar-
is distributed worldwide, but particularly in the Americas, thritis of the knees and wrists (2). A focal osteolytic lesion in the
although it can be found in parts of southern and eastern Eu- diaphysis of a long bone with or without an associated periosteal
rope, Africa, Asia, and Australia (9,18,20). In the United States, reaction can be detected in patients with chronic osteomyelitis
it is the most frequent endemic mycosis, with the distribution (1,5). Histoplasmosis can also result in wrist and hand tenosy-
traditionally in the Mississippi and Ohio river valleys (2,13). novitis and carpal tunnel syndrome (Fig 3) (21). A case report
Histoplasma duboisii is endemic in Africa (5). (5) of myositis in an immunocompromised patient describes
Histoplasma is found in soil containing large amounts of multiple painful nodules in the skeletal muscles. Systemic
bird droppings and bat guano (13,18). After inhalation of spores, treatment is recommended for disseminated disease for at
most patients are asymptomatic or manifest with an acute re- least 12 months; itraconazole is the antifungal agent of choice,
spiratory illness that is usually self-limited in immunocompe- with amphotericin used for the first 2–6 weeks (2).

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Table 1: Main Sites of Infection for Each Fungus

Fungal Infection Vertebra Knee Foot and Ankle Lower Limbs Long Bones Pelvis and Hip
Histoplasmosis X X X
Paracoccodioidomycosis X
Coccidioidomycosis X X X X X
Blastomycosis X X X
Cryptococcosis X X X* X
Candidiasis X X X X X X
Aspergillosis X X
Sporotrichosis X X X X
Mycetoma X X X
Sources.—References 1, 2, 5, 6, 9, 24, 25, 35, 43.
* Lower limbs in cryptococcosis involve the tibia.

Table 2: Main Sites of Infection for Each Fungus

Clavicle, Scapula,
Fungal Infection Hand and Wrist Ribs Sternum and Shoulder Skull Elbow
Histoplasmosis X
Paracoccodioidomycosis X X X
Coccidioidomycosis X X
Blastomycosis
Cryptococcosis X X X
Candidiasis X X X
Aspergillosis X X
Sporotrichosis X X
Mycetoma X
Sources.—References 1, 2, 5, 6, 9, 24, 25, 35, 43.

Paracoccidiodomycosis skeletal involvement of the disease includes bone lesions, with


Paracoccidioidomycosis is a systemic granulomatous disease a prevalence of 2%–30% of cases (24, 25–27), and, more rarely,
caused by thermodimorphic fungi that currently encompass- the joints and muscles are involved (24,28,29).
es two species: Paracoccidoides brasiliensis and Paracoccidoides The disease can affect any bone in the axial or appendicular
lutzii. This disease is found in South America, especially in skeleton, but most frequently it affects long bones, clavicula,
Brazil, Venezuela, Colombia, Ecuador, and Argentina, where ribs, scapulae, and sternum. On the long bones, lesions usual-
it is considered endemic (22–24). It typically infects individu- ly originate in the medullary cavity of the diaphysis and extend
als in rural or suburban environments (24). to the metaphysis and epiphysis, which are the most affected
Paracoccidioidomycosis can be classified as acute, subacute, sites due to their greater vascularization. The bone lesions
or chronic (22). The acute, subacute, or juvenile form (5%–25% have been described as well-defined osteolytic lesions without
of cases) predominantly affects children, adolescents, and marginal sclerosis and little or no periosteal reaction (Fig 4)
young adults (22) and it is characterized by a fast progression, (24). On CT images, the presence of fine reactive osteosclerosis
with lymphadenopathy, gastrointestinal manifestations, hep- in the margins can be identified (30). At MRI, the main finding
atosplenomegaly, osteoarticular involvement, and cutaneous is osteomyelitis (31). Joint involvement most often occurs by
lesions (22–23). The chronic or adult form (74%–96% of cases), means of extension of epiphyseal bone lesions (30).
typically manifests in adults aged 30–60 years, predominant- The treatment of choice is antifungal medication, mainly
ly affecting the lungs (22,24). However, some cases of chronic itraconazole, cotrimoxazole, and amphotericin B (22). After
unifocal bone involvement have been reported (25). Musculo- adequate treatment is initiated, bone lesions show slow and

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Table 3: Epidemiologic Data for Main Fungal Endemic Systemic Infections

Infection Agent Condition to Grow Endemic Areas Transmission


Histoplasmosis Histoplasma Range from tropical Worldwide, including parts of Inhalation of spores in soil or
capsulatum to temperate Central and South America, dust contaminated with bird
climates Africa, Asia, and Australia or bat excreta (eg, during cave
Ohio and Mississippi River exploration)
valleys
Paracoccidioidomy- Paracoccidioides Tropical and sub- South and Central America, Inhalation of spores; spores
cosis brasiliensis tropical regions especially Brazil convert to invasive yeasts in
the lungs and are assumed to
spread to other sites via the
blood and lymphatic systems
Coccidioidomycosis Coccidioides im- Warm and dry Southwestern desert of the Inhalation of spores; the dissemi-
mitis or Coccidi- climates of semi- United States, Mexico, and nated form appears by hema-
oides posadasii deserts Central and South America togenous spread

Blastomycosis Blastomyces Temperate climates Ohio and Mississippi River Inhalation of spores; fungi grow as
dermatitidis valleys, Northern Midwest, mold at ambient temperature
Upstate New York, southern in soil enriched with animal
Canada, Africa, India, and excreta and in moist, decaying,
Israel acidic organic material, often
near rivers
Sources.—References 5, 9, 13–16, 21, 23, 32–34.

Figure 3. Histoplasmosis in a 29-year-old man who presented with progressive pain and swelling of the wrist
and hand of 6 months’ duration and no history of lung disease. Cultures showed H capsulatum. (A) Radio-
graph of the hand shows focal soft-tissue swelling in the thenar region (arrow). (B) Static US image shows fluid
distention of the flexor tendon sheaths, outlining multiple internal hyperechoic rice bodies (*). (C) Coronal
short-tau inversion-recovery (STIR) MR image shows tenosynovitis with loculated fluid along the flexor tendon
sheaths (arrow) associated with hypointense layered rice bodies (*).

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Figure 4. Paracoccidioidomycosis in a 54-year-old man who was a frequent traveler, with a history
of recent weight loss and chronic neck pain. He presented with diffuse cutaneous nodules, dyspha-
gia, odynophagia, cough, fever, night sweats, and paresthesias and weakness in the upper limbs for 1
month. (A) Axial contrast-enhanced CT image shows diffuse lung involvement with innumerable bilat-
eral small parenchymal nodules in random distribution. (B, C) Axial contrast-enhanced CT images (mediastinal [B] and bone [C] windows) show
destructive lytic lesions (left arrow in B) involving the left scapula, with associated loculated complex joint articular and periarticular effusions
(* in B and C) and vertebral bodies at different thoracic levels (right arrow in B). (D) Axial contrast-enhanced CT image (mediastinal window)
also shows a destructive lytic rib lesion with an adjacent extraosseous complex fluid collection (arrow). (E) Follow-up sagittal CT reconstruction
image acquired after 2 years of treatment shows interval healing of the lytic lesions replaced by sclerotic reactions (arrowheads).

gradual change, marked by fibrosis and neo-osteogenesis, with ton, particularly the spine, ribs, pelvis, and skull, is the most
a coarse and dense trabecular appearance (Fig 4E) (25,26,30). common site of infection (9,14), but all bones can be affect-
ed (14). Radiologic patterns vary, including well-demarcated
Coccidioidomycosis punched-out osteolytic lesions and lytic permeative patterns
Coccidioidomycosis, or valley fever, is the infection caused by with periosteal reaction and soft-tissue swelling (14). The
the dimorphic fungus Coccidioides immitis, which has a world- spine is the most common site of involvement, with the in-
wide distribution and is endemic in the arid areas of the South- fection typically starting in the vertebral body and extend-
western United States, Mexico, and South America (32). Typ- ing to the periosteum and surrounding soft tissues, leading
ically, transmission occurs through inhalation of aerosolized to formation of a phlegmon or an abscess (14,33). The disease
spores or arthroconidia from the soil (32,33), with an estimated can spread to several contiguous vertebral levels or appear as
incidence of 248 cases per 100 000 people according to the Ar- skip lesions affecting nonconsecutive levels (14). Interverte-
izona Department of Health Services (33). The primary focus bral disk spaces are usually spared (33). Vertebral body col-
of infection is the lungs. Nonspecific flulike symptoms develop lapse, when present, may be asymmetric, and involvement
in only approximately 40% of patients, and the remainder of of posterior elements is rare (33). In long tubular bones, coc-
patients are asymptomatic (14,32). The incidence of systemic cidioidomycosis occurs mainly in the metaphysis, and the phy-
spread is still not clear, but it is estimated at 1%–5%, with at least seal plates cannot prevent the infection from spreading. Bone
three risk factors associated with disseminated disease: ethnic- protuberances such as the iliac and ischial spines, trochanters,
ity (especially African or Pacific Island ancestry), sex (more in and tubercules are frequently affected (14).
male than female patients), and suppression of cell-mediated Another form of disease is a self-limited migratory sterile
immunity (14,32). The disseminated form can involve any or- polyarthritis (“desert rheumatism”) that occurs as a hyper-
gan including the skin, lymph nodes, lungs, bones, kidneys, sensitivity syndrome in some cases of acute nondisseminat-
and the central nervous system (14). ed disease (9,14). Coccidioidal arthritis develops by means
A musculoskeletal coccidioides infection can affect the of direct extension of an adjacent bone infection. The knees,
skeleton, joints, and soft tissues, typically in a multifocal ankles (9,14), and wrists are the most commonly affected pe-
pattern involving multiple bones or joints (33). It can be as- ripheral joints (2). Soft-tissue abscesses, tenosynovitis, and
sociated with lung and cutaneous lesions (1). The axial skele- septic bursitis are also possible manifestations (14). Treatment

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guidelines suggest initial therapy with amphotericin B, fol- include immunocompromised status (eg, neutropenia, use
lowed by long-term fluconazole or itraconazole. Surgical inter- of glucocorticoid therapy), antibiotic therapy, use of injected
vention depends on the presence of a neurologic deficit, per- drugs (38), surgical procedures, orthopedic devices or pros-
sistent instability, or intractable pain (2). theses, trauma, or open wounds, as well as conditions that are
associated with candidemia, such as the use of central venous
Blastomycosis catheters and total parenteral nutritional support (41,42). Re-
Blastomycosis is a disease caused by fungi in the genus Blasto- garding candidal arthritis, the main risk factor is disseminat-
myces dermatidis, a dimorphic fungus, which is endemic in the ed candidiasis and its associated conditions and treatments
upper Midwest United States and Canada (5,13,34). The preva- including hematologic malignancies, diabetes mellitus, solid
lence of blastomycosis is 1:100 000 individuals in endemic re- organ transplant, open wounds, and hemodialysis (40). The
gions, reaching up to 40 times more prevalence in the hyper­ most common mechanism of osteoarticular Candida infection
endemic regions, such as north and central Wisconsin (13). is hematogenous dissemination, followed by direct traumatic
After the lungs and skin, osteoarticular involvement is the inoculation (43). The most common site is the vertebrae (Fig 5),
third most frequent site for blastomycosis (1). More than 90% followed by the femora, ribs, sternum, humeri (43), foot, ankle,
of clinical cases are pulmonary infections, although many and tibia (6).
cases are asymptomatic. Hematologic dissemination occurs Arthritis manifests in 70% of patients as a monoarticular
in up to 25% of symptomatic patients, with primary sites of infection, and the knee is the most frequently infected site, fol-
dissemination including the skin (in up to 80% of individu- lowed by the hip and shoulder joints (1). Spinal involvement is
als), musculoskeletal system (particularly the bones in up to more common in the lumbar or thoracic spine (40). Candida
25%–60% of cases), central nervous system, and genitouri- infection may be suspected when low-signal-intensity spinal
nary system (13,19,35). inflammatory masses on T2-weighted MR images and small
Blastomycosis may affect almost any bone in the skeleton, paraspinal abscesses are present in immunocompromised pa-
particularly the spine and lower limbs (5,35). Thoracic and tients (44). Percutaneous closed guided biopsy or open biopsy
lumbar vertebrae (and the thoracolumbar junction) are the should be performed to establish a definitive diagnosis of os-
most commonly involved bones, often with large paraverte- teomyelitis. Regarding candidal arthritis, a definitive diagnosis
bral abscesses, similar to tuberculosis (5,36). Imaging reveals requires needle aspiration, open biopsy, or arthroscopic surgery
destruction and collapse of multiple vertebral bodies, with for the acquisition of synovial fluid or tissue (1). The use of anti-
noncontiguous vertebral involvement and spread through fungal agents for 6–12 months is the main treatment option (45).
the anterior longitudinal ligament (36). The vertebral disk
can be involved or can be relatively spared (5,36). In the long Cryptococcosis
bones, although there is no typical radiographic appearance Cryptococcosis (ie, torulosis, European blastomycosis, or
of blastomycosis osteomyelitis, lesions can be classified as Busse-Buschke disease) is a systemic mycosis caused by fun-
focal or diffuse. The focal pattern may have a sclerotic mar- gi of the Cryptococcus neoformans complex, currently with two
gin and expand slowly, generally with a periosteal reaction species: C neoformans and Cryptococcus gattii. The former is
in the long bones. The diffuse pattern has a more aggressive usually associated with opportunistic cryptococcosis, while
appearance, with rapid bone destruction (ie, a moth-eaten the latter is associated with the primary form of an immu-
pattern) and vigorous periosteal reaction (5,35,37). Treatment nocompetent host, being endemic in tropical areas (46). The
generally consists of amphotericin induction followed by most common sites of infection for cryptococcosis are the cen-
oral itraconazole (2). In more severe cases, with spinal canal tral nervous system and the lungs (1). Skeletal involvement
compromise, surgical intervention may be indicated (36). has been reported in 5%–10% cases of cryptococcosis and is
usually secondary to disseminated disease (9). In some stud-
Systemic Opportunistic Disease ies (5,9,46), investigators describe the lesions as restricted to
Usually opportunistic fungi prefer habitats that are inde- a single bone, and the most frequently involved sites are the
pendent from the host organism but can cause infections by pelvis, vertebrae, skull ribs, clavicles, knees, and tibia, with
breaching the host’s immune defenses (38). The incidence vertebral involvement occurring particularly in the dissemi-
of invasive mycoses has been increasing significantly due to nated forms of the disease. Vertebral lesions appear similar to
opportunistic fungal pathogens (39). Aspergillus and Candida those of pyogenic osteomyelitis, with more frequent paraver-
species are the main organisms most frequently isolated from tebral abscesses and extradural cryptococcal granulomas (9).
immunocompromised patients. The other relevant etiologic Radiography and CT show one or more osteolytic lesions, usu-
agents are Zygomycete, Cryptococcus species, Fusarium species, ally with no periosteal reaction, with minimal or no sclerosis
and dematiaceous fungi (39). The opportunistic systemic fun- (9,46). In rare cases, musculoskeletal cryptococcosis infection
gal infections addressed in this article are candidiasis, crypto- produces osteomyelitis or septic arthritis (2,46). In the case
coccosis, aspergillosis, and mucormycosis. of osteoarticular infection, infection in other sites should be
ruled out, including that in the central nervous system (1). To
Osteoarticular Candida Infection our knowledge, there is no standard of care in the literature for
Osteoarticular candidiasis is caused most commonly by Candi- the treatment of osteoarticular lesions caused by Cryptococcus.
da albicans, Candida glabrata, Candida parapsilosis, and Candida The reported cases were most often treated with a combina-
tropicalis (38,40). Risk factors for osteoarticular candidiasis tion of antifungal drugs and surgical treatment (46).

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Figure 5. Candidiasis in a 38-year-old woman who underwent lumbar microdiskectomy and right laminectomy of the L5 vertebra. She
presented 5 days after surgery with low back pain associated with erythema, warmth, and hypersensitivity at the surgical site. Surgical
drainage was performed, and cultures were positive for C albicans. (A) Sagittal T1-weighted MR image shows marked hypointensity involv-
ing the intervertebral L5-S1 disk and adjacent vertebral endplates (arrow). (B) Sagittal STIR MR image shows increased signal intensity in
the L5-S1 disk and respective endplates (arrow), with an associated paraspinal fluid collection (*). (C) Axial contrast-enhanced T1-weight-
ed MR image shows enhancement of the L5-S1 intravertebral disk and an encapsulated fluid collection at the surgical site (arrow).

Osteoarticular Aspergillus Infection er major risk factors include chemotherapy, stem cell trans-
Aspergillus is the second most common fungal group that plant, hematologic malignancies, solid organ transplant (52),
causes osteoarticular infections in immunocompromised and HIV and AIDS (53).
patients (1,47). Most affected patients have chronic granulo- Osteoarticular mucormycosis is an extremely aggressive dis-
matous disease, followed by hematologic malignancies, im- ease usually manifesting with soft-tissue compromise and bone
munosuppression therapy, neutropenia, and diabetes (48). destruction that occasionally is subject to amputation of an ex-
Orthopedic surgery, solid organ transplant, and hematologic tremity. Osteomyelitis caused by Mucorales infection may affect
neoplasia are often observed in patients with aspergillus ar- virtually any bone. Imaging findings are nonspecific (54,55),
thritis (49). The most frequently infected bones in aspergillus and in a reported case of diskitis osteomyelitis (56), multiple
osteomyelitis are the vertebrae and the osseous structures of small erosions of the vertebral bodies were described. Bone de-
the thoracic cavity including the ribs and sternum. The tibia is struction may be present, especially in the extremities (57).
the most infected long bone, and the knee is the most infected
joint (1). Aspergillus diskitis osteomyelitis should be consid- Subcutaneous Infection
ered in the differential diagnosis for immunocompromised Subcutaneous fungal infections are a heterogeneous group of
patients when multiple vertebral segments are involved, with mycoses that typically occur in tropical and subtropical coun-
skip lesions or subligamentous spread (44). Other features tries after penetrating trauma to the skin (58). Sporotrichosis,
that may suggest aspergillus diskitis osteomyelitis are irreg- mycetoma, and chromoblastomycosis are the most frequent
ularities or a serrated appearance of the vertebral endplates subcutaneous mycoses (59). Chromoblastomycosis, phaeohy-
and subchondral hypointensity on T2-weighted MR images, phomycosis, and mycetoma are part of the melanized or dema-
which is probably related to the presence of a paramagnetic tiaceous fungi (60). Melanin is a virulence factor for these fungi
and ferromagnetic element within the fungi (50). Figure 6 (58). This group of fungi is associated with a variety of diseases,
shows a case of sacroiliac involvement. Definitive diagnosis and many are soil organisms (58,61). Subcutaneous infections
of osteoarticular aspergillus infection is usually established may extend to deep planes and cause musculoskeletal infection
with arthrocentesis, open surgery, or bone biopsy (47). Treat- (60).
ment involves prolonged antifungal therapy that may be com-
bined with débridement or drainage (1). Sporotrichosis
Sporotrichosis, also known as farmer’s disease or “rose gar-
Osteoarticular Mucormycosis dener’s disease,” is most commonly caused by the fungus Spo-
Osteoarticular mucormycosis remains a rare entity. The main rothrix schenckii, a common dimorphic fungus found in soil,
risk factor for its development is diabetic ketoacidosis (51). Oth- roses, and decaying wood (1,62). Infection occurs after skin

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The osteoarticular form is the main extracutaneous form,


manifesting with arthritis or osteomyelitis (1,62). Arthritis is
most common, occurring in one or more joints (1). The knee
is the primary joint involved, followed by the hand, wrist,
metacarpophalangeal joint, elbow, foot, and ankle (1,9,55,63).
The affected joint may exhibit swelling, without other spe-
cific signs (1), or may manifest with multiple sinus tracts (5).
Isolated osteomyelitis occurs more commonly in long bones,
mainly in the lower limbs, flat bones, and hands, where it can
be associated with tenosynovitis (1). In addition, olecranon
and popliteal bursitis have also been described (9,64).
Imaging findings may be nonspecific and may include
“moth-eaten” or patchy radiolucencies without periosteal
reaction, juxta-articular bone destruction or erosion, joint
space narrowing, and osteopenia (Fig 7) (1,63). The lesions
are also described as sclerotic and proliferative (5). Although
the imaging findings of sporotrichosis are similar to those of
other fungal infections and tuberculosis, the involvement of
small joints of the hands and feet is characteristic of this fun-
gal disease (9).

Mycetoma
Mycetomas are chronic suppurative infections characterized
by swelling, nodular lesions on the skin with multiple sinus
tracts, and fistulization of granules (grains). The disease occurs
in the skin and subcutaneous tissue and can extend to deep tis-
sues such as muscles, bones, fascia, joints, and tendons (65).
Mycetomas can be caused by bacteria (actinomycetomas) or
fungi (eumycetomas). The most common bacteria are Nocardia
brasiliensis and Actinamadura maturee, and the main fungi in-
clude Madurella mycetomatis, Madurella grisea, and white fungi
(65). Mycetomas are more frequent in the “mycetoma belt,” an
endemic area encompassing tropical and subtropical countries
located between 15° south and 30° north latitude. This area
mainly includes regions in Africa (eg, Sudan, Somalia, Senegal,
Nigeria, Chad, and Niger), India, and America (eg, Mexico, Ven-
ezuela, and Brazil) (65), typically in rural areas (66). The lower
Figure 6. Aspergillosis in a 63-year-old woman who
limbs are predominantly affected by the disease, with the feet
presented with left hip pain and subacute low back
pain. (A) Sagittal T1-weighted MR image of the pelvis being involved in 50% of cases. Other commonly affected sites
shows hypointensity of the subchondral marrow include the ankles, knees, and hands (65,66). Actinomycetoma
involving the left sacroiliac joint (arrow). (B) Coronal affects joints earlier than does eumycetoma (11).
STIR MR image shows bone marrow edema in the The radiographic findings include soft-tissue enlargement,
left sacroiliac joint (arrow) with a periarticular fluid superficial nodules, bone alterations such as sclerotic or lytic
collection (arrowhead). (C) Axial contrast-enhanced destruction, periosteal reaction, extrinsic cortical scalloping,
T1-weighted MR image shows synovial enhancement, and disorganization of the foot bones (5,67,68). Radiographic
sacroiliitis (arrow), and a fluid collection in the gluteus findings with a pattern of spreading were classified by Abd El
maximus muscle (arrowhead).
Bagi et al (67) in 2003. Because the spreading occurs contig-
uously, early bone involvement occurs mainly in the cortical
trauma in rural areas in patients with occupational activities bone (69). CT early findings include periosteal elevation, cor-
such as agriculture, floriculture, and wood exploitation, par- tical erosions, cortical hyperostosis, and endosteal prolifera-
ticularly in tropical and subtropical zones, mainly in Japan, tion (Fig 8) (69). Later bone imaging findings include a coarse
India, Mexico, Brazil, Uruguay, Peru, and the United States. trabecular pattern, sequestrum, and frank bone destruction
Zoonotic transmission, particularly by cats, has also been de- (69). Soft-tissue changes include an infiltrating mass with
scribed (62). Sporotrichosis can be present in different clini- moderate and diffuse enhancement after injection of con-
cal forms. The most common form (75% of cases) is the lym- trast material (69). Muscles may be thickened or partially de-
phocutaneous form, in which there is involvement of the skin stroyed (69).
and lymphatic system. Rarely does sporotrichosis manifest as At MRI, a specific finding referred to as “dot in circle” is iden-
an extracutaneous form (62). tifiable. It is characterized by multiple small spherical lesions

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Figure 7. Sporotrichosis in a 68-year-old


woman who presented with pain, swelling,
and a purulent wound at the fourth right
finger for 6 months. The patient also had
an ulcer in the left lower limb for 1 year and
other disseminated lesions for 11 months.
(A) Photograph shows skin lesions on the
fourth finger. (B) Radiograph of the fourth
finger shows marked bone destruction of the
proximal phalanx (arrowhead), associated
with swelling and edema of the adjacent soft
tissues. (C, D) Coronal T1-weighted (C) and
STIR (D) MR images show erosive changes,
marrow replacement of the fourth proximal
phalanx, and an associated extraosseous
soft-tissue component (arrow). (E) Axial con-
trast-enhanced T1-weighted MR image shows
a peripherally enhancing fluid collection, with
adjacent synovitis and inflammatory signs
(arrowhead).

Figure 8. Mycetoma in a 47-year-old man


with ankle pain and swelling for 3 years that
was associated with purulent discharge. (A) Ax-
ial unenhanced CT image (bone window) shows
an expansile lesion on the lateral aspect of the
calcaneus (arrowhead), with cortical disruption,
bone erosion (arrow), and extraosseous exten-
sion (arrowhead). (B, C) Axial fat-suppressed
T2-weighted (B) and T1-weighted (C) MR imag-
es show an expansile lesion (arrowhead) with
well-defined margins on the lateral aspect of
the calcaneus, with cortical breakthrough and
extension to adjacent soft tissues.

that appear hyperintense on T2-weighted MR images, with a which correspond to the grains (70). In eumycetoma, these le-
surrounding area of low signal intensity (hypointense rim) as- sions manifest as multiple acute hyperreflective echoes and
sociated with a central hypointense dot, visible on T2-weight- single or multiple nonechogenic cavities with thick walls, while
ed, STIR, and contrast-enhanced T1-weighted fat-suppressed actinomycetoma shows similar findings but with smaller, ag-
MR images. The high-signal-intensity foci represent granu- gregated hyperreflective echoes mainly located at the bottom
lomas interspersed with a low-signal-intensity matrix repre- of the cavities (66,72).
senting fibrosis, and the hypointense central foci seen in many A deep tissue biopsy with histopathologic and immunohis-
lesions represent grains or fungal balls (Figs 9, 10) (70,71). US tochemical analysis is performed to confirm the diagnosis (66).
reveals hypoechogenic lesions with small hyperechogenic foci, Treatment depends on the type of infection: Actinomycetoma

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Figure 9. Mycetoma in two patients. (A) Long-axis fat-suppressed T2-weighted MR image in a 59-year-old man with probable
osteomyelitis shows multiple confluent hyperintense soft-tissue cystlike areas with central low-signal-intensity foci (ie, dot-in-
circle) lesions (arrowhead), located in the subcutaneous soft tissues of the fifth toe. (B) Short-axis fat-suppressed T2-weighted
MR image in the same patient shows a lack of osseous involvement (arrowhead). (C) Sagittal T2-weighted MR image in a 55-year-
old patient with a 3-year history of a palpable mass on the dorsum of the foot shows lesions (arrow) in soft tissues without reach-
ing the bone surface. (D) Long-axis contrast-enhanced T1-weighted MR image shows multiple nodules (arrow) along the dorsum
of the foot, with mild peripheral enhancement and the dot-in-circle sign.

Figure 10. Mycetoma in a 40-year-old male farmer who presented with a tumor along the plantar surface of the
foot that was associated with swelling and discharge (A) Contrast-enhanced fat-suppressed T1-weighted MR image
shows a rounded mass (arrow) in the plantar subcutaneous tissue, with multiple cystlike lesions and the dot-in-cir-
cle sign (arrowhead) involving the plantar fascia and midfoot bones. (B) Short-axis contrast-enhanced T1-weighted
MR image shows osteomyelitis in the fifth metatarsal head (arrow) with marrow replacement, cortical destruction,
and enhancement.

is typically treated with antibiotics or chemotherapy, while eu- gone a transplant, those with HIV and/or AIDS, patients with
mycetoma is managed with antifungal drugs such as itracon- neuropenia, and individuals with autoimmune disease are
azole and voriconazole, but recurrence rates are high (73). more vulnerable to osteoarticular involvement (1,59). Imag-
Surgical intervention may be indicated, with amputation in ing findings of phaeohyphomycosis are not specific (Figs 11,
advanced cases (66). 12). Treatment includes prolonged antifungal therapy such as
amphotericin B and voriconazole and surgical interventions
Phaeohyphomycosis such as débridement (1,60).
Phaeohyphomycosis is an uncommon fungal infection
caused by a heterogeneous group of melanized fungi (1,60). Differential Diagnosis
The incidence is higher in warmer climates and lower lati- Imaging findings of fungal infections are nonspecific, and
tudes (1). The fungus is found in soil, plants, vegetable de- the differential diagnosis should include pyogenic infections,
bris, and wood (48). The infection may spread to the bones tuberculosis, neuroarthropathy, and other inflammatory ar-
or joints (60). Immunosuppressed patients who have under- thropathies. In the context of diskitis osteomyelitis, some
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July 2024 Akuri et al

Figure 11. Phaeohyphomycosis in a 54-year-old man who presented with os-


teomyelitis and arthritis of the right knee 3 years after an open traumatic injury.
(A) Radiograph shows joint space narrowing, marginal erosions in the lateral
femoral condyle and lateral tibial plateau, and juxta-articular decreased bone
density (arrow). (B, C) Coronal nonenhanced T1-weighted (B) and contrast-en-
hanced fat-suppressed T1-weighted (C) MR images show marrow replacement
and a focal intramedullary fluid collection (arrow in B), with an enhancing pe-
ripheral capsule (arrowhead in C) suggestive of an abscess. Culture of the fluid
was positive for Phialophora and Fusarium species.

Figure 12. Melanized fungi in a 58-year-old male construction worker


with a 2-year history of progressive edema and skin hyperpigmentation of
the third finger, with local hyperemia, pain, and pus drainage. (A) Coronal
STIR MR image shows a markedly hyperintense soft-tissue lesion along the
volar face of the third finger (arrow). (B) Sagittal T1-weighted MR image
shows involvement of the third proximal phalangeal base, with erosion of
the palmar cortex (arrowhead). (C) Axial contrast-enhanced fat-suppressed
T1-weighted MR image shows the lesion centered in the flexor mechanism,
involving the proximal aspect of the A2 pulley, with edema and thicken-
ing of the flexor tendon (arrowhead). Biopsy results showed spores and
hyphae of melanized fungi.

with early intervertebral disk involvement and compromise


of adjacent vertebral bodies. There is homogeneous enhance-
ment of the affected vertebral bodies and a poorly defined
paravertebral mass (74). Tuberculous diskitis osteomyelitis
more frequently affects the thoracic spine and less commonly
affects the lumbar spine. Large paravertebral abscesses with
thin and smooth walls may be present, with subligamentous
spread involving three or more vertebral levels, affecting mul-
tiple vertebrae or the entire vertebral body. Intervertebral
disks are relatively spared. There are focal areas of signal in-
tensity alteration on T1 and T2-weighted MR images and het-
erogeneous enhancement of vertebral bodies. Calcifications
can be visualized within the paravertebral abscesses on CT
images (74). Tuberculosis rarely affects the posterior elements
(ie, the pedicles) (Fig 13) (75). A feature that can also help in the
imaging characteristics can aid in the etiologic differential differential diagnosis with other spine infections is the ante-
diagnosis. Pyogenic diskitis osteomyelitis most commonly in- rior meningovertebral ligament, a midvertebral ligament that
volves the lumbar spine, followed by the thoracic and cervical can be preserved in patients with an anterior epidural abscess
spine, affecting a single vertebral segment, which includes that originates from slow-growing infections and metastasis
one intervertebral disk and two adjacent vertebral bodies, but is typically involved in pyogenic infections (76).

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Figure 13. Tuberculosis in a 34-year-old man with low back pain for 9 months associated with a nocturnal fever that worsened in the past 3
months. (A) Axial contrast-enhanced T1-weighted MR image shows osteomyelitis of the L3 vertebral body (arrow) with formation of intra- and
paravertebral abscesses (arrowhead) extending to the left psoas muscle. (B) Sagittal STIR MR image shows spondylodiskitis at the level of
L3-L4 (arrow), with reactive bone marrow edema (arrowhead) extending to the L2 vertebral body. (C) Sagittal contrast-enhanced T1-weight-
ed MR image shows infectious arthritis (arrowhead) of the left costovertebral joint of T9. (D) Axial contrast-enhanced CT image (soft-tissue
window) shows a fluid collection that extends to the left psoas muscle with calcific foci (arrowhead). (E, F) Axial contrast-enhanced chest (E)
and abdominal (F) CT images show pulmonary micronodules with miliary distribution and a renal abscess (arrowhead in F), respectively,
also caused by a tuberculosis infection.

Clinical predictors of fungal diskitis osteomyelitis include having a predilection for the lumbar and thoracolumbar
back pain for 10 weeks or longer, current antibiotic use for 1 junction and possibly forming paravertebral abscesses)
week or more, and intravenous drug use (77). Fungal diskitis is involvement of posterior elements and extension to the
osteomyelitis can mimic tuberculosis, with spared interverte- posterior aspect of the ribs, which are highly suggestive of
bral disks, multilevel involvement, and subligamentous spread blastomycosis and rare in tuberculosis (36). In cases of As-
of the abscess (3,74). Other imaging features include a focal pergillus diskitis osteomyelitis, disks may be hypointense on
paravertebral soft-tissue abnormality and partial disk involve- T2-weighted MR images (50). Table 4 (77,78) summarizes the
ment, sometimes sparing the intranuclear disk cleft (77). main clinical and imaging findings that aid in the differen-
Although there are no pathognomonic imaging findings tial diagnosis of fungal infections, tuberculosis, and pyogenic
to differentiate between fungal diskitis osteomyelitis and diskitis osteomyelitis.
tuberculosis, the location of lesions and the development of Other disorders that can mimic spinal infections include
soft-tissue abscesses can be very useful. Blastomycosis and spinal neuroarthropathy and SAPHO syndrome (74). Spinal
tuberculosis have a predilection for the thoracolumbar junc- neuroarthropathy, or Charcot spine, is a rare condition that
tion, coccidioidomycosis for the thoracic spine, and crypto- results from the loss of deep sensation and proprioception
coccosis for the lumbar spine. As for paravertebral abscess- due to a preexisting neurologic condition, leading to progres-
es, blastomycosis and tuberculosis can form large abscesses sive osseous and ligamentous injury in response to repeated
that may extend into the inguinal region and proximal thigh, trauma. It most commonly occurs at the thoracolumbar, lum-
whereas blastomycosis has a greater predilection for forma- bosacral junction, and lumbar spine. It may involve one or
tion of fistulas. Candida diskitis osteomyelitis may manifest more vertebral segments. Imaging findings include vertebral
with low-signal-intensity spinal inflammatory masses on endplate and facet erosions, soft-tissue masses or fluid collec-
T2-weighted MR images and small paraspinal abscesses tions containing bone debris, osseous fragments, an altered
(44). Cryptococcosis often involves pedicles and laminae, articular contour with incongruity of the intervertebral joint,
but formation of fistulas is not common. An element that listhesis, intervertebral gas, and involvement of both anterior
helps to differentiate blastomycosis from tuberculosis (both and posterior elements (74,79).

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Table 4: Main Clinical and Imaging Findings of Fungal, Tuberculosis, and Acute Pyogenic Diskitis Osteomyelitis

Finding Fungal Tuberculosis Pyogenic


Imaging
Soft tissue Focal paravertebral soft-tissue Large and well-defined paraspinal Diffuse paravertebral soft-tissue
abnormality. abscess abnormality
Disk involvement Partial disk and endplate involve- Early stages may spare the disk space, Diffuse disk involvement
ment with only body involvement
Spinal involvement Thoracic and lumbar Thoracic spine Lumbar > thoracic > cervical
Skip lesions spine
Clinical
Inflammatory markers Usually normal Usually normal Increased
Symptoms Long-standing back pain (> 10 Systemic symptoms from other Acute back pain (<10 weeks)
weeks) systems
Other Current antibiotic use for >1 week ... Invasive instrumentation
Sources.—References 77, 79.

Figure 14. Rice bodies in a 47-year-old male farmer who presented with swelling in the dorsal region of the right wrist for 3 years. On physical
examination, there was a palpable abnormality with a soft consistency and not adhered to deep planes. (A) Radiograph shows an attenuating
soft-tissue prominence in the dorsal wrist (arrowhead). (B, C) Sagittal (B) and axial (C) fluid-sensitive MR images show a large complex fluid col-
lection in the dorsal wrist outlining rice bodies and communicating with the sixth extensor compartment (arrows). (D) Macroscopic photograph
of the surgical resection specimen shows that the culture was consistent with filamentous fungi.

SAPHO is an acronym that means synovitis, acne, pustu- of synovial elements and exhibit progressive enlargement due
losis, hyperostosis, and osteitis (74). It affects the spine in ap- to fibrin aggregation. The differential diagnosis of inflammato-
proximately one-third of patients. The findings on MR images ry conditions associated with formation of rice bodies includes
are a focal or diffuse bone marrow signal intensity abnormal- rheumatoid arthritis, tuberculosis, nontuberculous mycobacte-
ity, endplate irregularities, paravertebral soft-tissue hyperin- rial arthritis, seronegative inflamammatory arthritis (81), and
tensity at T2-weighted MRI, disk space narrowing, and fluid- fungal infections (80). Rice bodies can be detected on US and
like signal intensity in the intervertebral disks, with contrast MR images. However, if these rice bodies are small, they can
enhancement (74). be misclassified as soft-tissue masses, debris, or viscous flu-
id in the bursae (81). Rice bodies are slightly hyperintense on
Rice Bodies T2-weighted MR images and isointense to muscle on T1-weight-
Rice bodies occur in patients with chronic inflammation or ed MR images (Fig 14) (81).
infections affecting joints or bursae (80). The pathogenesis is
uncertain, and it occurs in response to synovial inflammation. Conclusion
Some authors (80) believe that they may arise from microin- Fungi are important to consider in the differential diagnosis
farcted synovium released into the joint, encased by fibrin depo- of musculoskeletal infections. Their presence on images can
sition, while others believe that they are formed independently be nonspecific and should always be considered when there

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July 2024 Akuri et al

is suspicion for musculoskeletal infectious involvement, espe- 15. Wilson DJ. Soft tissue and joint infection. Eur Radiol 2004;14(Suppl
3):E64–E71.
cially if there is extensive bone destruction and/or an inflam- 16. Cardinal E, Bureau NJ, Aubin B, Chhem RK. Role of ultrasound in muscu-
matory process of soft tissue, with a relatively indolent clinical loskeletal infections. Radiol Clin North Am 2001;39(2):191–201.
picture. 17. Srinivasan S, Peh WCG. Imaging-guided biopsy in musculoskeletal infec-
tions. Semin Musculoskelet Radiol 2011;15(5):561–568.
For the diagnosis of fungal infections, it is important to 18. Colombo AL, Tobón A, Restrepo A, Queiroz-Telles F, Nucci M. Epidemiol-
associate the site of infection and the clinical and occupa- ogy of endemic systemic fungal infections in Latin America. Med Mycol
tional history, immunosuppression status, geographic loca- 2011;49(8):785–798.
19. Lockhart SR, Toda M, Benedict K, Caceres DH, Litvintseva AP. En-
tion, history of travel to endemic areas, and place of origin demic and Other Dimorphic Mycoses in The Americas. J Fungi (Basel)
for the immigrant population. 2021;7(2):151.
20. Salzer HJF, Burchard G, Cornely OA, et al. Diagnosis and Management
Author affiliations.—From the Department of Diagnostic Imaging, Escola Pau- of Systemic Endemic Mycoses Causing Pulmonary Disease. Respiration
lista de Medicina, Universidade Federal de São Paulo, Napoleão de Barros 2018;96(3):283–301.
Street, 800 Vila Clementino, São Paulo, SP, Brazil 04024-002 (M.C.A., J.B.P., 21. Zorzenoni FO, Link TM, de Biase Cabral de Sousa B, de Menezes Y, Guim-
V.N.S., L.K.M., D.T.K., A.d.A.e.C., A.R.C.F., A.Y.A.); Department of Radiology, arães JB. Histoplasmosis tenosynovitis of the forearm and wrist: imaging,
Hospital das Clínicas da Faculdade de Medicina de Marília, Marília, São Pau- surgical and pathologic findings. Skeletal Radiol 2021;50(8):1723–1728.
lo, Brazil (M.C.A.); Department of Radiology, Montefiore Medical Center, The 22. Shikanai-Yasuda MA, Mendes RP, Colombo AL, et al. Brazilian guidelines
University Hospital for Albert Einstein College of Medicine, Bronx, NY (J.T.B.); for the clinical management of paracoccidioidomycosis. Rev Soc Bras
Department of Diagnostic Imaging, Laboratório Delboni, DASA, São Paulo, Med Trop 2017;50(5):715–740.
Brazil (J.B.P., V.N.S., L.K.M., D.T.K., A.Y.A.); Department of Radiology, Hospi- 23. Brummer E, Castaneda E, Restrepo A. Paracoccidioidomycosis: an up-
tal do Coração, HCor and Teleimagem, São Paulo, Brazil (V.N.S.); Department date. Clin Microbiol Rev 1993;6(2):89–117.
of Infectious Diseases, Universidade Federal de São Paulo, São Paulo, Brazil 24. Monsignore LM, Martinez R, Simão MN, Teixeira SR, Elias J Jr, Noguei-
(A.M.D.); Hospital Israelita Albert Einstein, São Paulo, Brazil (A.d.A.e.C.); and ra-Barbosa MH. Radiologic findings of osteoarticular infection in
Department of Radiology, Grupo de Radiologia e Diagnóstico por Imagem– paracoccidioidomycosis. Skeletal Radiol 2012;41(2):203–208.
Rede D’Or, São Paulo, Brazil (A.R.C.F.). Presented as an education exhibit at 25. Correa-de-Castro B, Pompilio MA, Odashiro DN, Odashiro M, Arão-Fil-
the 2022 RSNA Annual Meeting. Received June 22, 2023; revision requested ho A, Paniago AMM. Unifocal bone paracoccidioidomycosis, Brazil. Am J
August 17 and received October 2; accepted October 17. Address correspon- Trop Med Hyg 2012;86(3):470–473.
dence to M.C.A. (email: marina.akuri@gmail.com). 26. Trad HS, Trad CS, Elias J Junior, Muglia VF. Revisão radiológica de 173 casos
consecutivos de paracoccidioidomicose. Radiol Bras 2006;39(3):175–179.
Current address: A.M.D. Hospital do Servidor Público Estadual, São Paulo, Brazil. 27. Amstalden EM, Xavier R, Kattapuram SV, Bertolo MB, Swartz MN, Rosen-
berg AE. Paracoccidioidomycosis of bones and joints. A clinical, radiolog-
ic, and pathologic study of 9 cases. Medicine (Baltimore) 1996;75(4):213–
Acknowledgments.—The authors would like to thank Akemi Osawa, MD, for 225.
for providing Figure 2, and Luiz Ferreira Alves, MSc, for the commissioned 28. Silvestre MT, Ferreira MS, Borges AS, Rocha A, de Souza GM, Nishioka SA.
illustrations. Monoarthritis of the knee as an isolated manifestation of paracoccidioi-
domycosis [in Portuguese]. Rev Soc Bras Med Trop 1997;30(5):393–395.
Disclosures of conflicts of interest.—All authors, the editor, and the reviewers 29. Neves MT, Livani B, Belangero WD, Tresoldi AT, Pereira RM. Psoas ab-
have disclosed no relevant relationships. scesses caused by Paracoccidioides brasiliensis in an adolescent. Myco-
pathologia 2009;167(2):89–93.
30. Lima Júnior FVA, Savarese LG, Monsignore LM, Martinez R, Noguei-
Reference List ra-Barbosa MH. Computed tomography findings of paracoccidiodomyco-
1. Gamaletsou MN, Rammaert B, Brause B, et al; International Consortium sis in musculoskeletal system. Radiol Bras 2015;48(1):1–6.
for Osteoarticular Mycoses. Osteoarticular Mycoses. Clin Microbiol Rev 31. Savarese LG, Monsignore LM, de Andrade Hernandes M, Martinez R,
2022;35(4):e0008619. Nogueira-Barbosa MH. Magnetic resonance imaging findings of paracoc-
2. Henry MW, Miller AO, Walsh TJ, Brause BD. Fungal Musculoskeletal In- cidioidomycosis in the musculoskeletal system. Trop Med Int Health
fections. Infect Dis Clin North Am 2017;31(2):353–368. 2015;20(10):1346–1354.
3. Orlowski HLP, McWilliams S, Mellnick VM, et al. Imaging Spectrum of Inva- 32. Taxy JB, Kodros S. Musculoskeletal coccidioidomycosis: unusual sites of
sive Fungal and Fungal-like Infections. RadioGraphics 2017;37(4):1119–1134. disease in a nonendemic area. Am J Clin Pathol 2005;124(5):693–696.
4. Gamaletsou MN, Walsh TJ, Sipsas NV. Epidemiology of Fungal Osteomy- 33. Belthur MV, Blair JE, Shrader MW, Malone JB. Musculoskeletal coccidioi-
elitis. Curr Fungal Infect Rep 2014;8(4):262–270. domycosis. Curr Orthop Pract 2018;29(4):400–406.
5. Corr PD. Musculoskeletal fungal infections. Semin Musculoskelet Radiol 34. Thompson GR 3rd, Le T, Chindamporn A, et al. Global guideline for the
2011;15(5):506–510. diagnosis and management of the endemic mycoses: an initiative of the
6. Bariteau JT, Waryasz GR, McDonnell M, Fischer SA, Hayda RA, Born European Confederation of Medical Mycology in cooperation with the In-
CT. Fungal osteomyelitis and septic arthritis. J Am Acad Orthop Surg ternational Society for Human and Animal Mycology. Lancet Infect Dis
2014;22(6):390–401. 2021;21(12):e364–e374 [Published correction appears in Lancet Infect Dis
7. Walsh TJ, Dixon DM. Spectrum of Mycoses. In: Baron S, ed. Medical Micro- 2021;21(11):e341.].
biology. 4th ed. Galveston, TX: University of Texas Medical Branch at Gal- 35. Oppenheimer M, Embil JM, Black B, et al. Blastomycosis of bones and
veston, 1996. http://www.ncbi.nlm.nih.gov/books/NBK7902/. Accessed joints. South Med J 2007;100(6):570–578.
May 11, 2023. 36. Emamian S, Fox MG, Boatman D, Allard FD, Nacey NC. Spinal blastomy-
8. Pierini AM, Bujan MM, Lanoël A. Deep Mycoses and Opportunistic Infec- cosis: unusual musculoskeletal presentation with literature review. Skel-
tions. In: Irvine AD, Hoeger PH, Yan AC, eds. Harper’s Textbook of Pediat- etal Radiol 2019;48(12):2021–2027.
ric Dermatology. Oxford, UK: Wiley-Blackwell, 2011; 63.1–63.28. 37. Kalbhen C. Radiologic case study. Blastomycotic osteomyelitis. Orthope-
9. Arkun R. Parasitic and fungal disease of bones and joints. Semin Muscu- dics 1991;14(6):722–728.
loskelet Radiol 2004;8(3):231–242. 38. Miller DJ, Mejicano GC. Vertebral osteomyelitis due to Candida species:
10. Sharma P, Mukherjee A, Karunanithi S, Bal C, Kumar R. Potential role of case report and literature review. Clin Infect Dis 2001;33(4):523–530.
18
F-FDG PET/CT in patients with fungal infections. AJR Am J Roentgenol 39. Pfaller MA, Diekema DJ. Rare and emerging opportunistic fungal patho-
2014;203(1):180–189. gens: concern for resistance beyond Candida albicans and Aspergillus
11. Bahar ME, Bakheet OELH, Fahal AH. Mycetoma imaging: the best prac- fumigatus. J Clin Microbiol 2004;42(10):4419–4431.
tice. Trans R Soc Trop Med Hyg 2021;115(4):387–396. 40. Gamaletsou MN, Rammaert B, Bueno MA, et al. Candida Arthri-
12. Johnson MD, Perfect JR. Fungal Infections of the Bones and Joints. Curr tis: Analysis of 112 Pediatric and Adult Cases. Open Forum Infect Dis
Infect Dis Rep 2001;3(5):450–460. 2015;3(1):ofv207.
13. Kunin JR, Flors L, Hamid A, Fuss C, Sauer D, Walker CM. Thoracic En- 41. Crawford SJ, Swan CD, Boutlis CS, Reid AB. Candida costochondritis asso-
demic Fungi in the United States: Importance of Patient Location. Radio- ciated with recent intravenous drug use. IDCases 2016;4:59–61.
Graphics 2021;41(2):380–398. 42. Dupont B, Drouhet E. Cutaneous, ocular, and osteoarticular candidiasis
14. Taljanovic MS, Adam RD. Musculoskeletal coccidioidomycosis. Semin in heroin addicts: new clinical and therapeutic aspects in 38 patients. J
Musculoskelet Radiol 2011;15(5):511–526. Infect Dis 1985;152(3):577–591.

Volume 44 Number 7 16 radiographics.rsna.org


July 2024 Akuri et al

43. Gamaletsou MN, Kontoyiannis DP, Sipsas NV, et al. Candida osteomyeli- 62. Barros MB de L, de Almeida Paes R, Schubach AO. Sporothrix schenckii
tis: analysis of 207 pediatric and adult cases (1970-2011). Clin Infect Dis and Sporotrichosis. Clin Microbiol Rev 2011;24(4):633–654.
2012;55(10):1338–1351. 63. Appenzeller S, Amaral TN, Amstalden EMI, et al. Sporothrix schenckii
44. Lee SW, Lee SH, Chung HW, Kim MJ, Seo MJ, Shin MJ. Candida spondyli- infection presented as monoarthritis: report of two cases and review of
tis: Comparison of MRI findings with bacterial and tuberculous causes. the literature. Clin Rheumatol 2006;25(6):926–928.
AJR Am J Roentgenol 2013;201(4):872–877. 64. Chang AC, Destouet JM, Murphy WA. Musculoskeletal sporotrichosis.
45. Pappas PG, Kauffman CA, Andes DR, et al. Clinical Practice Guideline for Skeletal Radiol 1984;12(1):23–28.
the Management of Candidiasis: 2016 Update by the Infectious Diseases 65. Bonifaz A, Vázquez-González D, Perusquía-Ortiz AM. Subcutaneous
Society of America. Clin Infect Dis 2016;62(4):e1–e50. mycoses: chromoblastomycosis, sporotrichosis and mycetoma. J Dtsch
46. Revista da Sociedade Brasileira de Medicina Tropical Volume 41(5): pá- Dermatol Ges 2010;8(8):619–628.
gina 524. Rev Soc Bras Med Trop 2008;41(6):695. 66. Fahal AH, Shaheen S, Jones DHA. The orthopaedic aspects of mycetoma.
47. Tsantes AG, Papadopoulos DV, Markou E, et al. Aspergillus spp. os- Bone Joint J 2014;96-B(3):420–425.
teoarticular infections: an updated systematic review on the diag- 67. Abd El Bagi ME. New radiographic classification of bone involvement in
nosis, treatment and outcomes of 186 confirmed cases. Med Mycol pedal mycetoma. AJR Am J Roentgenol 2003;180(3):665–668.
2022;60(8):myac052. 68. Davies AGM. The bone changes of Madura foot; observations on Uganda
48. Grossman ME, Fox LP, Kovarik C, Rosenbach M. Subcutaneous and Africans. Radiology 1958;70(6):841–847.
Deep Mycoses. In: Cutaneous Manifestations of Infection in the Immu- 69. Sharif HS, Clark DC, Aabed MY, et al. Mycetoma: comparison of MR im-
nocompromised Host. New York, NY: Springer New York, 2012; 1–63. aging with CT. Radiology 1991;178(3):865–870.
49. Gamaletsou MN, Rammaert B, Bueno MA, et al. Aspergillus arthritis: 70. Sarris I, Berendt AR, Athanasous N, Ostlere SJ; OSIRIS collaborative study
analysis of clinical manifestations, diagnosis, and treatment of 31 re- group. MRI of mycetoma of the foot: two cases demonstrating the dot-in-
ported cases. Med Mycol 2017; 55(3):246–254. circle sign. Skeletal Radiol 2003;32(3):179–183.
50. Kwon JW, Hong SH, Choi SH, Yoon YC, Lee SH. MRI findings of Aspergil- 71. Laohawiriyakamol T, Tanutit P, Kanjanapradit K, Hongsakul K, Ehara S.
lus spondylitis. AJR Am J Roentgenol 2011;197(5):W919–W923. The “dot-in-circle” sign in musculoskeletal mycetoma on magnetic reso-
51. Roden MM, Zaoutis TE, Buchanan WL, et al. Epidemiology and out- nance imaging and ultrasonography. Springerplus 2014;3(1):671.
come of zygomycosis: a review of 929 reported cases. Clin Infect Dis 72. Fahal AH, Sheik HE, Homeida MM, Arabi YE, Mahgoub ES. Ultrasono-
2005;41(5):634–653. graphic imaging of mycetoma. Br J Surg 1997;84(8):1120–1122.
52. Navanukroh O, Jitmuang A, Chayakulkeeree M, Ngamskulrungroj P. 73. White EA, Patel DB, Forrester DM, et al. Madura foot: two case reports,
Disseminated Cunninghamella bertholletiae infection with spinal epi- review of the literature, and new developments with clinical correlation.
dural abscess in a kidney transplant patient: case report and literature Skeletal Radiol 2014;43(4):547–553.
review. Transpl Infect Dis 2014;16(4):658–665. 74. Hong SH, Choi JY, Lee JW, Kim NR, Choi JA, Kang HS. MR imaging
53. Mostaza JM, Barbado FJ, Fernandez-Martin J, Peña-Yañez J, Vazquez-Ro- assessment of the spine: infection or an imitation? RadioGraphics
driguez JJ. Cutaneoarticular mucormycosis due to Cunninghamella 2009;29(2):599–612.
bertholletiae in a patient with AIDS. Clin Infect Dis 1989;11(2):316–318. 75. Burrill J, Williams CJ, Bain G, Conder G, Hine AL, Misra RR. Tuberculosis:
54. Arockiaraj J, Balaji G, Ashok A, Kokil G. Amphotericin B cement beads: A a radiologic review. RadioGraphics 2007;27(5):1255–1273.
good adjunctive treatment for musculoskeletal mucormycosis. Indian J 76. Strauss SB, Gordon SR, Burns J, Bello JA, Slasky SE. Differentiation be-
Orthop 2012;46(3):369–372. tween Tuberculous and Pyogenic Spondylodiscitis: The Role of the An-
55. Chowdhary G, Weinstein A, Klein R, Mascarenhas BR. Sporotrichal ar- terior Meningovertebral Ligament in Patients with Anterior Epidural Ab-
thritis. Ann Rheum Dis 1991;50(2):112–114. scess. AJNR Am J Neuroradiol 2020;41(2):364–368.
56. Buruma OJS, Craane H, Kunst MW. Vertebral osteomyelitis and epidur- 77. Simeone FJ, Husseini JS, Yeh KJ, Lozano-Calderon S, Nelson SB, Chang CY.
al abcess due to mucormycosis, a case report. Clin Neurol Neurosurg MRI and clinical features of acute fungal discitis/osteomyelitis. Eur Radi-
1979;81(1):39–44. ol 2020;30(4):2253–2260.
57. Muscolo DL, Carbo L, Aponte-Tinao LA, Ayerza MA, Makino A. Massive 78. Ledbetter LN, Salzman KL, Sanders RK, Shah LM. Spinal Neuroarthrop-
bone loss from fungal infection after anterior cruciate ligament ar- athy: Pathophysiology, Clinical and Imaging Features, and Differential
throscopic reconstruction. Clin Orthop Relat Res 2009;467(9):2420–2425. Diagnosis. RadioGraphics 2016;36(3):783–799.
58. Brandt ME, Warnock DW. Epidemiology, clinical manifestations, and 79. Boody BS, Tarazona DA, Vaccaro AR. Evaluation and Management of
therapy of infections caused by dematiaceous fungi. J Chemother Pyogenic and Tubercular Spine Infections. Curr Rev Musculoskelet Med
2003;15(Suppl 2):36–47. 2018;11(4):643–652.
59. Queiroz-Telles F, Esterre P, Perez-Blanco M, Vitale RG, Salgado CG, Bon- 80. Jeong YM, Cho HY, Lee SW, Hwang YM, Kim YK. Candida septic arthritis
ifaz A. Chromoblastomycosis: an overview of clinical manifestations, with rice body formation: a case report and review of literature. Korean J
diagnosis and treatment. Med Mycol 2009;47(1):3–15. Radiol 2013;14(3):465–469.
60. Revankar SG. Phaeohyphomycosis. Infect Dis Clin North Am 81. Chau CLF, Griffith JF, Chan PT, Lui TH, Yu KS, Ngai WK. Rice-body forma-
2006;20(3):609–620. tion in atypical mycobacterial tenosynovitis and bursitis: findings on so-
61. Revankar SG, Sutton DA. Melanized fungi in human disease. Clin Mi- nography and MR imaging. AJR Am J Roentgenol 2003;180(5):1455–1459.
crobiol Rev 2010;23(4):884–928.

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