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Fungal Musculoskeletal Infections. Comprehensive Approach to Proper Diagnosis (2024)
Fungal Musculoskeletal Infections. Comprehensive Approach to Proper Diagnosis (2024)
Fungal Musculoskeletal Infections. Comprehensive Approach to Proper Diagnosis (2024)
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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July 2024 Akuri et al
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,
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).
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.
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.
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 (*).
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
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).
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
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
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
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
Volume 44 Number 7 12 radiographics.rsna.org
July 2024 Akuri et al
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).
Table 4: Main Clinical and Imaging Findings of Fungal, Tuberculosis, and Acute Pyogenic Diskitis Osteomyelitis
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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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-
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Hospital das Clínicas da Faculdade de Medicina de Marília, Marília, São Pau- surgical and pathologic findings. Skeletal Radiol 2021;50(8):1723–1728.
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University Hospital for Albert Einstein College of Medicine, Bronx, NY (J.T.B.); for the clinical management of paracoccidioidomycosis. Rev Soc Bras
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tal do Coração, HCor and Teleimagem, São Paulo, Brazil (V.N.S.); Department date. Clin Microbiol Rev 1993;6(2):89–117.
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Department of Radiology, Grupo de Radiologia e Diagnóstico por Imagem– paracoccidioidomycosis. Skeletal Radiol 2012;41(2):203–208.
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