Académique Documents
Professionnel Documents
Culture Documents
i n C r y s t a l Ar t h r i t i s
Gout, Calcium Pyrophosphate Deposition,
and Basic Calcium Phosphate Crystals
Thibaut Jacques, MD, MSca,b,*, Paul Michelin, MDc,
Sammy Badr, MD, MSca,b, Michelangelo Nasuto, MDd,
Guillaume Lefebvre, MDa,b, Neal Larkman, MD, MPHe,
Anne Cotten, MD, PhDa,b
KEYWORDS
Gout Calcium pyrophosphate CPPD Crystal deposition Crystal arthropathy
Basic calcium phosphate Hydroxyapatite
KEY POINTS
Crystal deposition diseases are a common finding and their radiographic features should be known
to help the referring physician in the differential.
Classic features of gout are tophi, large para-articular erosions contrasting with articular-space
sparing, and bone hyperostosis without bone rarefaction.
CPPD arthropathy involves joints usually spared by osteoarthritis, with severe joint narrowing,
marked subchondral osteosclerosis, with no or few osteophytes.
Basic calcium phosphate deposits are usually amorphous and frequently asymptomatic.
Their density and shape vary when resorbing or migrating into an adjacent structure during an acute
and painful flare.
This article reviews the radiographic aspects affects up to 1% of the general population. Its
of the 3 main crystal deposition diseases: mono- prevalence is increasing in both developed1,2
sodium urate (gout), calcium pyrophosphate and developing3,4 countries, mostly because of
(CPPD), and basic calcium phosphate (BCP). the evolution of lifestyle and particularly eating
habits.5
Men are affected 4 to 10 times more often than
GOUT
women,6 gout being the most frequent cause of in-
Introduction
flammatory arthritis in men older than 60 years.7 In
Gout is a crystal-induced deposition disease cases of early onset, secondary causes must be
caused by saturation and precipitation of monoso- considered, because their diagnosis can change
dium urate (MSU) crystals. This common condition further patient care.
a
Division of Radiology and Musculoskeletal Imaging, University Hospital of Lille, Rue du Professeur Emile
Laine, Lille Cedex 59037, France; b University of Lille, 42, rue Paul Duez, Lille 59000, France; c Department
of Radiology, CHRU de Rouen, 1 rue de Germont, Rouen Cedex 76031, France; d Department of Radiology,
University of Foggia, Viale Luigi Pinto 1, Foggia 71100, Italy; e Department of Radiology, Leeds Teaching Hos-
pital Trust, Chapeltown Road, Leeds, West Yorkshire LS7 4SA, UK
* Corresponding author. Division of Radiology and Musculoskeletal Imaging, University Hospital of Lille, Rue du
Professeur Emile Laine, Lille Cedex 59037, France.
E-mail address: thib.jacques@gmail.com
Several factors are required for MSU crystals Acute gouty arthritis is typically of sudden on-
to form. The main underlying factor is hyperuri- set, involving one or few joints (less frequently
cemia, which is a consequence of either exces- polyarticular), with a preference for inferior limbs
sive production of uric acid or a lack of its (in 85% of cases12), particularly for the first meta-
clearance. tarsophalangeal space. Clinical and biological
Excessive production can be either exoge- inflammatory patterns are frequently noted,13
nous, due to excessive intake of purines (eg, sometimes mimicking an infectious process,
meat, seafood, alcohol),6,8 or endogenous, espe- also leading to difficult differential diagnoses
cially in case of massive cell lysis (eg, with inflammatory diseases, such as rheumatoid
chemotherapy or myeloproliferative disorders). arthritis. The synovial fluid analysis would display
Insufficient uric acid clearance can result from an inflammatory fluid containing 2000 to 5000
chronic kidney disease, drug interactions, or ge- white blood cells per mm3 (sometimes more)
netic predispositions. Familial diseases that and typical MSU crystals, elongated and birefrin-
directly affect enzymes involved in purine meta- gent under polarized light, but no germs on Gram
bolism are less frequent, such as Lesch-Nyhan staining.
disease. These acute flares usually resolve spontane-
Several local factors can play a crucial role in ously in 5 to 10 days, followed by an asymptom-
MSU crystal formation, such as trauma or repeti- atic period lasting from months to years before
tive microtrauma, arthritis, infection, lack of tissue recurring.14 Chronic tophaceous gout is char-
perfusion, lower blood pH, or lower tissue acterized by the presence of tophi, which
temperature.9 are MSU deposits in either hypodermic soft tis-
Clinically, gout is characterized by recurrent sues, articular and para-articular spaces, ten-
episodes of arthritis involving one or multiple dons, or bursae. It tends to occur years after
joints. In the absence of care, the disease can the initial episode of gout and in the absence of
evolve into chronic tophaceous gout. Ultimately, adequate treatment (5 years for 30% of pa-
patients can suffer from visceral consequences, tients).12 Tophi are related to the duration and
such as gouty nephropathy. However, hyper- levels of hyperuricemia, and tend to diminish
uricemia remains asymptomatic in 90% of under treatment.
patients.
Acute flares are either due to oversaturation of
Imaging Findings
MSU crystals in synovial fluid or to their relapse
from hyaline cartilage into the joint, triggering In the event of an acute arthritis (if the patient
inflammation pathways and resulting in the has not yet reached the chronic tophaceous
production of cytokines such as tumor necro- gout stage), plain radiographs are most of the
sis factor-a and interleukin (IL)-1b.10 Secon- time normal or display a nonspecific joint effu-
dary recruitment of neutrophils worsen local sion and/or periarticular soft tissue edema
inflammation.11 (Fig. 1).
Fig. 1. (A) Acute knee arthritis with nonspecific intra-articular effusion (arrow); joint aspiration showed MSU crys-
tals. (B) Severe chronic tophaceous gout with large subcutaneous tophi (arrowheads) and polyarticular involve-
ment of the hand.
Downloaded for Dept. Radiologi Kariadi (ksmradrsdk@gmail.com) at Dr Kariadi General Hospital Medical Center Department of Anaesthesiology from
ClinicalKey.com by Elsevier on March 15, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Conventional Radiology in Crystal Arthritis 969
The following are the main radiographic features erosions (Fig. 2C). Para-articular location, at
seen in chronic tophaceous gout: a distance from the joint, is also highly sug-
gestive of gout.
Polyarticular involvement, typically asym- Intraosseous tophi (Fig. 3B), less frequent,
metric and more frequently in the lower and not to be confused with bone erosions,
limbs. although they share similar features, such as
Subcutaneous tophi, of variable sizes, large size, sclerotic margins, and long-axis
shapes, and topography, most of the time parallelism. These pseudo-cystic lesions are
asymmetric. Although this can vary, their in- usually found around joints and can also
termediate to high density is highly suggestive mimic subchondral cysts (geodes) and even
of gout (Fig. 2A). However, tophi rarely calcify sometimes destroy the articular space and
in the absence of renal disease. Tophi can lead to ankylosis. They are typically seen in
erode the underlying bone or even the skin severe disorders and in association with the
in front of them, which can result in the pres- other typical radiographic features of gout.
ence of internal gas. Exuberant bone hyperostosis in front of a
Bone erosions, adjacent to a tophus, most of tophus (with or without associated bone ero-
the time well circumscribed with overhanging sions). It can range from large and irregular
sclerotic margins (Fig. 2B). These erosions are bony formations (Fig. 2D), osteophytes, or en-
typically large and parallel to the long axis of thesophytes, to regular periosteal apposition
the bone diaphysis (see Fig. 2B; Fig. 3A). (Fig. 4A).
Gout is strongly suspected whenever bone Long period of articular-space sparing, which
spicules are found at the edges of these contrasts with the usual large size of the
Fig. 2. (A) Subcutaneous tophus suggestive of gout because of its intermediate density. (B) Large erosion, well
circumscribed with overhanging sclerotic margins, in front of a tophus of low density (asterisk). (C) Large erosion
with proximal bone spicule (arrow). (D) Large bony formations (arrowhead) around an interphalangeal joint,
adjacent to a tophus (asterisk).
Downloaded for Dept. Radiologi Kariadi (ksmradrsdk@gmail.com) at Dr Kariadi General Hospital Medical Center Department of Anaesthesiology from
ClinicalKey.com by Elsevier on March 15, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
970 Jacques et al
Fig. 3. (A) Two large and symmetric para-articular erosions (arrows) near subcutaneous tophi (asterisks). (B)
Intraosseous tophus (arrowhead) mimicking a large subchondral cyst. Note the sparing of the joint-space
width.
Fig. 4. (A) Subtle periosteal appositions in gout (arrow). (B) Large erosions contrasting with a preserved articular
space. (C) Cortical irregularities in gout (arrowheads). (D) “Spiky-foot” aspect on lateral view.
Downloaded for Dept. Radiologi Kariadi (ksmradrsdk@gmail.com) at Dr Kariadi General Hospital Medical Center Department of Anaesthesiology from
ClinicalKey.com by Elsevier on March 15, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Conventional Radiology in Crystal Arthritis 971
erosions (as opposed to other rheumatisms) In the knee, the patella is frequently involved,
(Figs. 4B and 5B). mostly because of the existence of pre-
No rarefaction of the adjacent bone, which is a patellar tophi leading to anterior patellar ero-
reliable tool to help differentiating gout from sions or reactional anterior bony formations
other inflammatory rheumatisms, when mar- (Fig. 5A). Large erosions of the lower femoral
ginal bone erosions are seen. cortical bone also can be noted, especially
in the intercondylar notch.
Gout can affect any joint, but some are more Hands and wrists are involved in advanced
common: gout (see Fig. 5B), especially when hyperuri-
In the foot, the first metatarsophalangeal cemia is related to a diuretic treatment,16 usu-
space is the initial site in up to 50% of pa- ally asymmetrically. Interphalangeal joints
tients, followed in order of frequency by the (see Fig. 2D) are more often affected than
interphalangeal spaces, then the tarsometa- metacarpophalangeal or carpometacarpal
tarsal joints.15 It is first seen on the medial joints (Fig. 5B). Carpal ankylosis can happen
and dorsal sides of the first metatarsal head, in very advanced stages.
and erosions can be seen only as cortical ir- In the elbow, the most common site is the
regularities (Fig. 4C). Gout can also frequently olecranon, with either an olecranon bursitis,
affect sesamoid bones, sometimes mimicking erosions, or bony formations of the olecranon
a tumoral process. Bone overgrowth (osteo- (see Fig. 5C, D).
phytes, enthesophytes) is frequently seen on Other joints (eg, shoulder, hip, spine, sacro-
the dorsal side of the foot, giving a “spiky- iliac, temporomandibular) can also be affected,
foot” aspect on lateral views (Fig. 4D). but rarely with an isolated pattern.17,18
Fig. 5. (A) Anterior cortical irregularities of the patella in gout (arrowheads). (B) Large carpal and metacarpal ero-
sions (asterisks) contrasting with the absence of joint narrowing and no subchondral bone rarefaction. (C) Large
olecranon tophus (asterisk). (D) Olecranon erosion in gout (arrow).
Downloaded for Dept. Radiologi Kariadi (ksmradrsdk@gmail.com) at Dr Kariadi General Hospital Medical Center Department of Anaesthesiology from
ClinicalKey.com by Elsevier on March 15, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
972 Jacques et al
Diagnostic criteria
Differential diagnosis
CALCIUM PYROPHOSPHATE DEPOSITION is due in the clear majority of cases to CPP crystals,
DISEASE sometimes associated with calcium phosphate
Introduction crystals or calcium oxalate crystals.21 The diag-
nosis is theoretically proven only by the micro-
CPPD is caused by the deposition of calcium pyro- scopic evidence of CPP crystals in either synovial
phosphate crystals in joints. This condition is fluid or a fragment from synovium or cartilage.
frequent, affecting up to 1% to 2% of the general These crystals have a small size (5–10 mm), and a
population between the ages of 60 and 70, 6% rodlike shape. Recommendations for the positive
to 8% between 70 and 80, and 20% to 30% after diagnosis of CPPD21 have been proposed, based
the age of 80.19,20 on the following:
Calcium pyrophosphate (CPP) crystals can
lead to several clinical manifestations, such as Clinical features: symptoms usually develop
acute arthritis, chronic arthritis, or destructive quickly (from 6 to 24 hours) with an important
arthropathy.21 inflammatory pattern (fever, local swelling).
Chondrocalcinosis is defined by radiological or Topography is highly suggestive when in-
histologic articular cartilage calcification, either hy- volving knee, shoulders, or wrists, especially
aline cartilage or fibrocartilage. Chondrocalcinosis in patients older than 65.
Downloaded for Dept. Radiologi Kariadi (ksmradrsdk@gmail.com) at Dr Kariadi General Hospital Medical Center Department of Anaesthesiology from
ClinicalKey.com by Elsevier on March 15, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Conventional Radiology in Crystal Arthritis 973
Biological features: fluctuant inflammatory Other metabolic causes are less frequent: hy-
syndrome. pomagnesemia (eg, in Gitelman syndrome),
Radiographic and/or ultrasonographical fea- hypophosphatasia, or familial hypocalciuric
tures. The absence of chondrocalcinosis in hypocalcemia.19,27,28
conventional radiography does not exclude
the diagnosis of CPPD, especially during an Imaging Findings
acute event.
The absence of clinical findings consistent On conventional radiography, CPPD is character-
with another disease, especially rheumatoid ized by 2 main abnormalities: calcifications (artic-
arthritis or septic arthritis. ular or soft tissues) and arthropathy.
Calcifications tend to be symmetric and can
Acute CPPD flares (“pseudo-gout”) are due involve the following20:
to the relapse of CPP crystals (from cartilage,
fibrocartilage, or synovium) into the synovial fluid. Hyaline cartilages, delineating a thin linear
Crystals are then phagocyted by leukocytes, opacity parallel to subchondral bone but
which triggers an inflammatory response, induc- separated from it by 1 to 2 mm (Fig. 6A).
ing cytokines and interleukin secretion, especially This opacity can be continuous or not, less
IL-1b.22 Acute flares resolve spontaneously in frequently granular (Fig. 6B).
3 to 4 days, quicker under appropriated Fibrocartilages, displaying thicker calcifi-
treatment.23 cations, frequently stratified or granular29
The exact mechanism leading to chronic CPP (Fig. 6C).
arthritis and its relation with osteoarthritis remains Synovial membranes (Fig. 6D) and bursae, dis-
unclear. playing cloudy and blurry calcifications, partic-
Clinical features of CPPD are highly variable, be- ularly involving knees, wrists, and hands.
ing most of the time monoarticular or oligoarticu- Articular capsules, with thin, linear, and regu-
lar, polyarticular involvement happening in only lar calcifications.
11% of cases. CPPD is frequently asymptomatic, Tendons, with linear and stratified calcifica-
discovered by incidental calcifications seen on tions, oriented toward the long axis of the
conventional radiography.23 tendon (as opposed to BCP deposition) (see
Sex ratio of chondrocalcinosis is 1:1, with Fig. 10A), and ligaments, especially in the
degenerative arthropathy (osteoarthritis) being an wrist.
important underlying factor for the development Other tissues with a pseudotumoral form that
of sporadic CPPD. For example, patients suffering can mimic gout or soft tissue sarcoma.30
from knee osteoarthritis have 3 times more risk to The main specificities of CPPD arthropathy,
develop chondrocalcinosis.23 when compared with osteoarthritis are as follows:
Familial forms are rare and revealed by early pol-
yarticular calcifications (20–40 years old), The involvement of joints usually spared by
frequently followed by severe arthropathy.24 osteoarthritis: radiocarpal (Fig. 7A), metacar-
Secondary CPPD is the consequence of meta- pophalangeal, talo-calcaneo-navicular, or
bolic diseases, which are to be searched for, espe- elbow for example.
cially in young patients or when facing a diffuse Severe joint narrowing, sometimes with
and polyarticular disease. crenated aspect of articular surfaces (Figs.
The following are the most frequent metabolic 7B and 8), rapidly worsening with subchondral
causes: bone fragmentation and intra-articular foreign
bodies (see Fig. 8).
Hyperparathyroidism (primary or secondary). Marked subchondral and well-defined osteo-
Eight percent to 57% of these patients will sclerosis (Fig. 7C).
eventually suffer from CPPD.25 Radiological Sometimes absent or few osteophytes, con-
calcifications do not resolve after trasting with the severity of joint narrowing
parathyroidectomy. (see Fig. 7A, B).
Hemochromatosis. The exact mechanism is Numerous subchondral cysts (geodes),
yet unclear, but excessive iron concentration frequently displaying a microcystic pattern in
is thought to increase intra-articular CPP con- subchondral bone (with sometimes larger
centration. Thirty-eight percent of patients cysts) (Fig. 7D).
who are homozygotes for C282Y mutation
will eventually have CPPD, whereas 21% of The most frequently affected joint is the knee,
heterozygotes will.26 where any kind of calcification can be seen.31,32
Downloaded for Dept. Radiologi Kariadi (ksmradrsdk@gmail.com) at Dr Kariadi General Hospital Medical Center Department of Anaesthesiology from
ClinicalKey.com by Elsevier on March 15, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
974 Jacques et al
Fig. 6. (A) Linear calcification of hyaline cartilage, parallel to subchondral bone. (B) Granular calcification of hy-
aline cartilage. (C) Stratified calcifications of meniscus. (D) Cloudy synovial calcifications (arrow).
CPPD can affect either 1 or both femorotibial second and third spaces), with cartilage calcifi-
compartments at the same time, which is not cations, synovial calcifications, and/or joint-
frequent in osteoarthritis and helps in the differen- space narrowing (Fig. 9C, D). Interphalangeal
tial. The femoropatellar joint also can be affected, spaces are rarely affected, as opposed to osteo-
and suggests CPPD when isolated and severe, arthritis, in which metacarpophalangeal spaces
sometimes with a crenated aspect (see Figs. 7B are spared.
and 8). In the hip and shoulder, CPPD can affect hyaline
In the wrist, an isolated scaphotrapezial joint cartilage, periarticular tendons, articular capsule,
involvement is typical, with features highly sug- or articular labrum (Fig. 10A). Ultimately, shoulder
gestive of CPPD: severe joint narrowing, dense or hip osteoarthritis can be seen. Several features,
and well-limited subchondral sclerosis, with no such as bone fragmentation or microcystic sub-
or few osteophytes33 (see Fig. 7C; Fig. 9A). chondral geodes, can help differentiating from
CPPD also can affect ligaments, especially degenerative arthropathy, but these are not al-
the lunotriquetral ligament, scapholunate liga- ways present.
ment, and the triangular fibrocartilage complex In the elbow, except for classic CPPD features,
(TFCC) (Fig. 9B). Scapholunate ligament involve- specific calcifications of the triceps tendon are
ment and rupture can then lead to a scapholu- important to recognize.
nate advanced collapse (SLAC-Wrist)34 (see In the ankle and foot, the most commonly
Fig. 9B). Other patterns can be seen less affected joints are the talo-calcaneonavicular and
frequently, such as a distal radioulnar joint tarsometatarsal joints, where it may sometimes
involvement. In the hand, metacarpophalangeal mimic neuropathic arthritis due to the extent of
spaces are frequently affected (particularly the lesions.35
Downloaded for Dept. Radiologi Kariadi (ksmradrsdk@gmail.com) at Dr Kariadi General Hospital Medical Center Department of Anaesthesiology from
ClinicalKey.com by Elsevier on March 15, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Conventional Radiology in Crystal Arthritis 975
Fig. 7. (A) Radiocarpal CPPD arthropathy; severe joint narrowing contrasting with the relative absence of osteo-
phytes. (B) Severe femoro-patellar joint narrowing without osteophytes. (C) Marked osteosclerosis, well defined,
in the subchondral bone of a scaphotrapezial joint. (D) Microcystic pattern of subchondral bone in CPPD
(arrowheads).
Fig. 8. Crenated aspect (arrows) with intra-articular Many more joints can be affected, such as
fragments (arrowhead) of the medial femorotibial sternoclavicular, acromioclavicular, sacroiliac and
compartment in CPPD. temporomandibular joints, or pubic symphysis.38,39
Downloaded for Dept. Radiologi Kariadi (ksmradrsdk@gmail.com) at Dr Kariadi General Hospital Medical Center Department of Anaesthesiology from
ClinicalKey.com by Elsevier on March 15, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
976 Jacques et al
Fig. 9. (A) Scaphotrapezial arthropathy with severe joint narrowing and well-limited marked subchondral osteo-
sclerosis, highly suggestive of CPPD. (B) SLAC-wrist with scapholunate diastasis and calcifications of both scapho-
lunate ligament and TFCC. (C, D) Joint narrowing of the second and third metacarpophalangeal spaces,
suggestive of CPPD (arrows 5 capsulo-synovial calcifications).
Fig. 10. (A) Calcification of the acetabular labrum (arrowhead) and linear calcifications of the hamstring tendons
(arrow) in CPPD. (B) CPPD discal involvement with subtle linear calcifications located on the peripheral part of the
discs.
Downloaded for Dept. Radiologi Kariadi (ksmradrsdk@gmail.com) at Dr Kariadi General Hospital Medical Center Department of Anaesthesiology from
ClinicalKey.com by Elsevier on March 15, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Conventional Radiology in Crystal Arthritis 977
Diagnostic criteria
Differential diagnosis
BASIC CALCIUM PHOSPHATE DEPOSITION showed that only approximately 30% of calcifica-
DISEASE tions would eventually become symptomatic.46
Introduction They can resorb locally or extrude in adjacent
bursa, joint, or bone. This extrusion can be chronic
BCP crystal deposition disease is characterized
(no symptoms or chronic pain) or acute, and
by the presence of BCP crystals, mostly hydroxy-
associated with excruciating pain (acute
apatite but also tricalcium phosphate and octa-
tendinobursitis).47
calcium phosphate, in either the periarticular soft
When intra-articular, BCP crystals are rarely
tissues (tendons and bursae) or in the intra-
proven microscopically because they are too small
articular space, where it can lead to acute arthritis
to be reliably detected even under polarized light.
or destructive arthropathy (eg, Milwaukee
They can result from either periarticular calcifica-
shoulder).40,41
tion resorption into the joint, or from primary
The most frequent topography for this crystal
intra-articular deposit.48 Consequences are either
deposition disease is the shoulder, accounting
acute arthritis, mimicking septic arthritis because
for 60% of cases, followed in order of frequency
of the frequent fever and swelling, or destructive
by hip, knee, elbow, wrist, and hand, but any joint
arthropathy, especially in the shoulder (Milwaukee
can theoretically be affected.
shoulder), knee, and hip. BCP-related destructive
Although its etiology is still unclear,42 and only
arthropathy is more frequent in women between
a few familial forms have been reported,43 no sys-
the ages of 50 and 90, bilateral in 65% of cases,
temic factors are found in most cases. Inter-
with coexistent trauma or excessive use found in
estingly, periarticular depositions, especially in
25% of cases.40
tendons, tend to not be related to physical activity
or professional activity, and happen mostly on pre-
Imaging Findings
viously intact tendons.44,45
Most calcifications are asymptomatic and inci- BCP crystal deposition disease diagnosis is based
dental findings; reports on shoulder calcifications primarily on conventional radiography.
Downloaded for Dept. Radiologi Kariadi (ksmradrsdk@gmail.com) at Dr Kariadi General Hospital Medical Center Department of Anaesthesiology from
ClinicalKey.com by Elsevier on March 15, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
978 Jacques et al
Fig. 11. (A) Internal rotation of shoulder displaying an amorphous, dense, and well-limited quiescent calcification
of the infraspinatus tendon. (B) Cloudy, ill-defined calcification of the medial collateral ligament, of lesser den-
sity, in a patient with acute knee pain, typical of acute resorption (arrow).
Periarticular calcifications are typically amor- Intra-articular BCP crystal deposition disease
phous, dense, round or oval-shaped, with well- can lead to destructive arthropathy, such
limited borders while quiescent (Fig. 11A). They as “Milwaukee shoulder,” which combines gleno-
locate on insertion sites of tendons, especially humeral space narrowing, humeral head ascent,
zones of relative hypoxia (eg, in the supraspinatus moderate subchondral bone sclerosis, and
tendon) but also in tendon sheets and bursae. subtle or absent osteophytosis. Ultimately, sub-
When calcifications resorb, they tend to become chondral bone fragmentation and even neoarti-
cloudy, less dense with an ill-defined shape culations are seen40 (Fig. 13). Destructive
(Fig. 11B), and can migrate into adjacent structures: arthropathy with bone fragmentation also can
bursae, joints, or bones (leading to cortical erosions) be seen; for example, in the knee and spine
(Fig. 12). It is important to notice that in the event of (erosive spondylodiscitis).
an acute resorption, calcification may not be seen in In the shoulder, rotator cuff calcifications are
conventional radiography, thus leading to misdiag- well known, frequent, and sometimes multiple.
nosis49 (see Fig. 12). When calcification is seen in They can be bilateral in up to 46% of cases and
such a situation around cortical erosion, it affect by order of frequency the supraspinatus
frequently displays a “comet-tail” shape, better (80%) (Fig. 14A), infraspinatus (15%) (see
seen on computed tomography (CT). Fig. 11A), and subscapularis (5%) tendons.46 On
Fig. 12. Intraosseous resorption of BCP calcification of the infraspinatus tendon in a patient with acute shoulder
pain. On conventional radiography (A), the calcification is not seen but there is a focal zone of bone lucency (ar-
rows). (B) On CT (performed the same day), the calcification is better seen (asterisk) with a focal zone of cortical
bone interruption in front of it, and an intraosseous resorption (arrowhead).
Downloaded for Dept. Radiologi Kariadi (ksmradrsdk@gmail.com) at Dr Kariadi General Hospital Medical Center Department of Anaesthesiology from
ClinicalKey.com by Elsevier on March 15, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Conventional Radiology in Crystal Arthritis 979
Fig. 14. Examples of BCP calcifications in the upper limb. (A) Supraspinatus tendon. (B) Labral insertion of the
long head of biceps brachii (arrowhead), labral insertion of triceps brachii (arrow), and subacromial-subdeltoid
bursa (asterisk). (C) Flexor carpi ulnaris above the pisiform bone. (D) Periarticular deposit in front of the radiocar-
pal space.
Downloaded for Dept. Radiologi Kariadi (ksmradrsdk@gmail.com) at Dr Kariadi General Hospital Medical Center Department of Anaesthesiology from
ClinicalKey.com by Elsevier on March 15, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
980 Jacques et al
junction of lumbrical and interosseous muscles In the spine, BCP crystal deposition disease
also can be calcified. appears as dense and amorphous calcifications,
The most frequent calcification site around the in a central position inside the intervertebral discs,
hip is the insertion of the gluteal muscles onto the affecting one or several discs, especially in the
greater trochanter (Fig. 15A) and adjacent bursae. lower thoracic spine56 (Fig. 16A), but the cervical
Cortical erosions can be associated.50,53,54 Nearly spine also can be involved, particularly in chil-
any tendon can be affected in the pelvic region, dren. They can usually be easily distinguished
thus leading to frequent misdiagnoses. from CPPD, which displays linear calcifications
Around the knee, calcifications can involve in the peripheral part of the disc. Their size and
collateral ligaments (less frequently cruciate liga- shape can vary over time and resorb during an
ments), bursae, or tendons, especially biceps fem- acute episode of pain, mimicking spondylodisci-
oris above the fibular head, mimicking sciatica tis, and/or migrate in the adjacent environment
when resorbing (Fig. 15B) or quadriceps tendon (epidural space, vertebral plates). Another classic
and/or patellar ligament.50,55 location for BCP crystal deposition disease is the
The most frequent site for BCP calcifications longus colli muscle, especially its superior and
around the ankle and foot are tendons of flexor hal- oblique fibers that are projecting on lateral view
lucis longus, flexor hallucis brevis, and fibular ten- under the anterior body of C1 (Fig. 16B) (less
dons50 (Fig. 15C, D). Soft tissues around frequently its vertical fibers, seen from C4 to
metatarsophalangeal spaces also can be involved. C6).57 Its acute resorption is responsible for acute
When affecting the hallux, the diagnosis may often cervicalgia and/or dysphagia, mimicking meningi-
be misinterpreted as gout, thus probably underes- tis, spondylodiscitis or cervical tumor. In addition
timating the real incidence of BCP in this region. to the visible calcification, a frequent prevertebral
Fig. 15. Examples of BCP calcifications in the lower limb (arrowheads). (A) Gluteal tendons near the greater
trochanter. (B) Resorbing calcification in the tendon of biceps femoris above the fibular head, in a patient
with acute sciatica. (C) Tibialis posterior tendon. (D) Flexor hallucis brevis tendon.
Downloaded for Dept. Radiologi Kariadi (ksmradrsdk@gmail.com) at Dr Kariadi General Hospital Medical Center Department of Anaesthesiology from
ClinicalKey.com by Elsevier on March 15, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Conventional Radiology in Crystal Arthritis 981
Fig. 16. (A) Amorphous calcification in a central position inside a thoracic intervertebral disc, highly suggestive of
BCP. (B) Typical appearance of longus colli calcification (arrowhead), projecting under the anterior body of C1, in
a patient with acute cervicalgia.
soft tissue enlargement in the upper cervical re- CT. This syndrome also can be seen in CPPD
gion can be seen on conventional radiography with overlapping radiological findings, none being
during acute resorption. An anterior accessory specific on conventional radiography.58,59 Both
bone of C1 can be mistaken for a longus colli can lead to acute resorption and acute cervical
calcification. symptoms.
Numerous other structures can be calcified in Careful analysis of the structure of BCP deposits
the spine, especially bursae, apophyseal joints, shows only calcified matter, without cortical or
or ligaments. One special feature is the trabecular bone organization, therefore distin-
“crowned-dens syndrome,” due to calcification guishing it from intervertebral ossifications (degen-
above and around the odontoid, better seen on erative or spondyloarthropathy-related).
Diagnostic criteria
Differential diagnosis
Downloaded for Dept. Radiologi Kariadi (ksmradrsdk@gmail.com) at Dr Kariadi General Hospital Medical Center Department of Anaesthesiology from
ClinicalKey.com by Elsevier on March 15, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
982 Jacques et al
Downloaded for Dept. Radiologi Kariadi (ksmradrsdk@gmail.com) at Dr Kariadi General Hospital Medical Center Department of Anaesthesiology from
ClinicalKey.com by Elsevier on March 15, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Conventional Radiology in Crystal Arthritis 983
17. King JC, Nicholas C. Gouty arthropathy of the lum- 31. Yang BY, Sartoris DJ, Resnick D, et al. Calcium py-
bar spine: a case report and review of the literature. rophosphate dihydrate crystal deposition disease:
Spine 1997;22(19):2309–12. frequency of tendon calcification about the knee.
18. Bhattacharyya I, Chehal H, Gremillion H, et al. Gout J Rheumatol 1996;23(5):883–8.
of the temporomandibular joint: a review of the liter- 32. Misra D, Guermazi A, Sieren JP, et al. CT imaging for
ature. J Am Dent Assoc 2010;141(8):979–85. evaluation of calcium crystal deposition in the knee:
19. Richette P, Bardin T, Doherty M. An update on the initial experience from the multicenter osteoarthritis
epidemiology of calcium pyrophosphate dihydrate (MOST) study. Osteoarthritis Cartilage 2015;23(2):
crystal deposition disease. Rheumatol Oxf Engl 244–8.
2009;48(7):711–5. 33. Donich AS, Lektrakul N, Liu CC, et al. Calcium pyro-
20. Neame RL, Carr AJ, Muir K, et al. UK community phosphate dihydrate crystal deposition disease of
prevalence of knee chondrocalcinosis: evidence the wrist: trapezioscaphoid joint abnormality.
that correlation with osteoarthritis is through a J Rheumatol 2000;27(11):2628–34.
shared association with osteophyte. Ann Rheum 34. Kahloune M, Libouton X, Omoumi P, et al. Osteoar-
Dis 2003;62(6):513–8. thritis and scapholunate instability in chondrocalci-
21. Zhang W, Doherty M, Bardin T, et al. European nosis. Diagn Interv Imaging 2015;96(1):115–9.
league against rheumatism recommendations for 35. Lomax A, Ferrero A, Cullen N, et al. Destructive
calcium pyrophosphate deposition. Part I: terminol- pseudo-neuroarthropathy associated with calcium
ogy and diagnosis. Ann Rheum Dis 2011;70(4): pyrophosphate deposition. Foot Ankle Int 2015;
563–70. 36(4):383–90.
22. Moltó A, Ea HK, Richette P, et al. Efficacy of anakinra 36. Lefebvre G, Pansini V, Dodre E, et al. Maladie des
for refractory acute calcium pyrophosphate crystal dépôts de cristaux de phosphate de calcium basi-
arthritis. Jt Bone Spine Rev Rhum 2012;79(6):621–3. que (rhumatisme apatitique). EMC Radiol Imag
23. Zhang W, Doherty M, Pascual E, et al. EULAR rec- Médicale Musculosquelettique Neurol Maxillofac
ommendations for calcium pyrophosphate deposi- 2015;10(4):1–10.
tion. Part II: management. Ann Rheum Dis 2011; 37. Chang EY, Lim WY, Wolfson T, et al. Frequency of at-
70(4):571–5. lantoaxial calcium pyrophosphate dihydrate deposi-
24. Gruber BL, Couto AR, Armas JB, et al. Novel ANKH tion at CT. Radiology 2013;269(2):519–24.
amino terminus mutation (Pro5Ser) associated with 38. Hanai S, Sato T, Nagatani K, et al. Pseudogout of
early-onset calcium pyrophosphate disease with the sternoclavicular joints. Intern Med 2014;53(5):
associated phosphaturia. J Clin Rheumatol 2012; 521–2.
18(4):192–5. 39. Kenzaka T, Wakabayashi T, Morita Y. Acute crystal
25. Huaux JP, Geubel A, Koch MC, et al. The arthritis of deposition arthritis of the pubic symphysis. BMJ
hemochromatosis. A review of 25 cases with special Case Rep 2013;2013 [pii: bcr2013009239].
reference to chondrocalcinosis, and a comparison 40. McCarty DJ, Swanson AB, Ehrhart RH. Hemorrhagic
with patients with primary hyperparathyroidism and rupture of the shoulder. J Rheumatol 1994;21(6):
controls. Clin Rheumatol 1986;5(3):317–24. 1134–7.
26. Pawlotsky Y, Le Dantec P, Moirand R, et al. Elevated 41. Gerster JC. Intraarticular apatite crystal deposition
parathyroid hormone 44-68 and osteoarticular as a predictor of erosive osteoarthritis of the fingers.
changes in patients with genetic hemochromatosis. J Rheumatol 1994;21(11):2164–5.
Arthritis Rheum 1999;42(4):799–806. 42. Doumas C, Vazirani RM, Clifford PD, et al. Acute
27. Volpe A, Guerriero A, Marchetta A, et al. Familial calcific periarthritis of the hand and wrist: a series
hypocalciuric hypercalcemia revealed by chondro- and review of the literature. Emerg Radiol 2007;
calcinosis. Jt Bone Spine Rev Rhum 2009;76(6): 14(4):199–203.
708–10. 43. Hajiroussou VJ, Webley M. Familial calcific periar-
28. Alix L, Guggenbuhl P. Familial hypocalciuric hyper- thritis. Ann Rheum Dis 1983;42(4):469–70.
calcemia associated with crystal deposition dis- 44. Serafini G, Sconfienza LM, Lacelli F, et al. Rotator
ease. Jt Bone Spine Rev Rhum 2015;82(1):60–2. cuff calcific tendonitis: short-term and 10-year out-
29. Steinbach LS. Calcium pyrophosphate dihydrate comes after two-needle US-guided percutaneous
and calcium hydroxyapatite crystal deposition dis- treatment–nonrandomized controlled trial. Radiology
eases: imaging perspectives. Radiol Clin North Am 2009;252(1):157–64.
2004;42(1):185–205, vii. 45. Uhthoff HK, Loehr JW. Calcific tendinopathy of the
30. Yamazaki H, Uchiyama S, Kato H. Median nerve and rotator cuff: pathogenesis, diagnosis, and manage-
ulnar nerve palsy caused by calcium pyrophosphate ment. J Am Acad Orthop Surg 1997;5(4):183–91.
dihydrate crystal deposition disease: case report. 46. Clavert P, Sirveaux F, Société française d’arthrosco-
J Hand Surg 2008;33(8):1325–8. pie. Shoulder calcifying tendinitis. Rev Chir Orthop
Downloaded for Dept. Radiologi Kariadi (ksmradrsdk@gmail.com) at Dr Kariadi General Hospital Medical Center Department of Anaesthesiology from
ClinicalKey.com by Elsevier on March 15, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
984 Jacques et al
Reparatrice Appar Mot 2008;94(8 Suppl):336–55 [in 54. Sakai T, Shimaoka Y, Sugimoto M, et al. Acute
French]. calcific tendinitis of the gluteus medius: a case
47. Pascual E, Bardin T, Richette P. Crystal arthropathies. report with serial magnetic resonance imaging find-
In: Bijlsma JWJ, editor. EULAR texbook on rheumatic ings. J Orthop Sci 2004;9(4):404–7.
diseases. UK: BMJ Group; 2012. p. 301–12. 55. Varghese B, Radcliffe GS, Groves C. Calcific
48. Gerster JC, Fournier D. Acute apatite arthritis of the tendonitis of the quadriceps. Br J Sports Med
shoulder in a young woman. Clin Rheumatol 1995; 2006;40(7):652–4 [discussion: 654].
14(1):95–9. 56. Chanchairujira K, Chung CB, Kim JY, et al. Interver-
49. Kraemer EJ, El-Khoury GY. Atypical calcific tendi- tebral disk calcification of the spine in an elderly
nitis with cortical erosions. Skeletal Radiol 2000; population: radiographic prevalence, location, and
29(12):690–6. distribution and correlation with spinal degeneration.
50. Holt PD, Keats TE. Calcific tendinitis: a review of the Radiology 2004;230(2):499–503.
usual and unusual. Skeletal Radiol 1993;22(1):1–9. 57. Park SY, Jin W, Lee SH, et al. Acute retropharyngeal
51. Kim KC, Rhee KJ, Shin HD, et al. A SLAP lesion calcific tendinitis: a case report with unusual location
associated with calcific tendinitis of the long head of calcification. Skeletal Radiol 2010;39(8):817–20.
of the biceps brachii at its origin. Knee Surg Sports 58. Malca SA, Roche PH, Pellet W, et al. Crowned
Traumatol Arthrosc 2007;15(12):1478–81. dens syndrome: a manifestation of hydroxy-apatite
52. Park JY, Gupta A, Park HK. Calcific tendinitis at the rheumatism. Acta Neurochir (Wien) 1995;135(3–4):
radial insertion of the biceps brachii: a case report. 126–30.
J Shoulder Elbow Surg 2008;17(6):e19–21. 59. Wu DW, Reginato AJ, Torriani M, et al. The crowned
53. Fritz P, Bardin T, Laredo JD, et al. Paradiaphyseal dens syndrome as a cause of neck pain: report of
calcific tendinitis with cortical bone erosion. Arthritis two new cases and review of the literature. Arthritis
Rheum 1994;37(5):718–23. Rheum 2005;53(1):133–7.
Downloaded for Dept. Radiologi Kariadi (ksmradrsdk@gmail.com) at Dr Kariadi General Hospital Medical Center Department of Anaesthesiology from
ClinicalKey.com by Elsevier on March 15, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.