Basic calcium phosphate (BCP) crystal-

associated calcific periarthritis (tendinopathy)

Author:
Ann K. Rosenthal, MD, FACP
Section Editor:
Nicola Dalbeth, MBChB, MD, FRACP
Deputy Editor:
Paul L Romain, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: May 2019. | This topic last updated: Dec 13, 2017.

INTRODUCTION Basic calcium phosphate (BCP)-associated

musculoskeletal syndromes can be organized into calcific periarthritis and

arthritis associated with BCP crystals. The predominant mineral type in BCP-
associated musculoskeletal pathology is carbonated hydroxyapatite [1].

The term "basic calcium phosphate" refers to a trio of submicron-sized calcium

phosphate crystals. These include partially carbonate-substituted
hydroxyapatite, octacalcium phosphate, and tricalcium phosphate (whitlockite).
The terms "calcium phosphate" and "hydroxyapatite" are often used
synonymously with the more accurate term "basic calcium phosphate." BCP
crystals are similar in composition to the normal mineral found in bones and
teeth as well as to the pathologic mineral found in atherosclerotic plaques and
calcinosis cutis.

An overview of the pathogenesis of BCP-associated musculoskeletal

syndromes and the clinical manifestations, diagnosis, and treatment of BCP-
associated calcific periarthritis, also termed calcific tendinitis or tendinopathy,
will be discussed here. Calcific tendinopathy of the shoulder and BCP-
associated arthritis are presented in detail separately. (See "Calcific
tendinopathy of the shoulder" and "Basic calcium phosphate (BCP) crystal
arthritis, including Milwaukee shoulder syndrome".)

PATHOGENESIS OF BCP-ASSOCIATED

MUSCULOSKELETAL SYNDROMES The etiology of pathologic

basic calcium phosphate (BCP) crystal formation is not fully understood [2].
BCP mineral formation often occurs at sites of local tissue damage associated
with injury or inflammation. Once formed, BCP crystals can produce symptoms
and mediate tissue damage by several mechanisms, including the induction of a
vigorous inflammatory response, biomechanical disruption, and through direct
interactions with nearby cells, resulting in tissue damage in the absence of
inflammation [3-7]. Relatively little is known about the factors that specifically
initiate symptomatic arthritis or periarthritis associated with BCP crystals.

There are several contributors to BCP crystal formation, which together with
locally high levels of extracellular calcium and phosphate tip the balance of pro-
and antimineralization factors to allow BCP crystals to form. These include
chondro- or osteometaplasia, which may serve as an inciting factor in BCP
mineral formation at sites of local tissue damage [8]. Cytokines and growth
factors found at sites of tissue damage also contribute to BCP crystal formation
[9], and alterations in extracellular matrix proteins may permit pathologic mineral
formation as well [10].

Once formed, BCP crystals can produce symptoms and mediate tissue injury in
several ways. Under certain circumstances, BCP crystals induce a vigorous
inflammatory response [3]. The mechanism linking BCP crystals to inflammation
may involve innate immune pathways, which are shared by other particulates,
including monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals.
Candidate factors that modulate the inflammatory potential of crystals include
crystal size, the type and amount of protein coating the crystals, and the
presence of nearby tissue trauma.

Little is known about the factors that initiate symptomatic arthritis or periarthritis
associated with BCP crystals. One theory is that BCP tissue deposits are
asymptomatic until something triggers their dissolution, following which
osteoclast-mediated resorption introduces pain-producing factors into the
surrounding tissues. BCP crystal deposition also disrupts normal tissue
biomechanics [4], which may have important negative consequences in
musculoskeletal tissues. Lastly, BCP crystals can directly interact with resident
connective tissue cells, even in the absence of an inflammatory response, to
produce destructive cytokines, growth factors, and enzymes. As an example,
BCP crystals directly induce synovial fibroblasts to increase mitogenesis [5] and
secrete tissue-damaging factors such as collagenase and prostaglandin E2
(PGE2) [6]. BCP crystals have also been shown to promote osteoclastogenesis,
resulting in local bone destruction [7].

RISK FACTORS Trauma, metabolic, and genetic factors may each

be associated with increased risk of basic calcium phosphate (BCP)-associated

calcific periarthritis. (See 'Exogenous or acquired risk factors' below
and 'Genetic risk factors' below.)

Exogenous or acquired risk factors — Most patients with calcific periarthritis

are in good general health, although a history of recent trauma or overuse as an
antecedent to symptomatic periarthritis is reported by some patients, while
absent in many others.

The metabolic abnormalities associated with end-stage renal disease (ESRD)

have been implicated in causing symptomatic periarthritis, but this association is
not well documented by population-based studies. This issue is complicated by
metabolic abnormalities, such as secondary hyperparathyroidism, that produce
systemic elevations of calcium and phosphate and cause widespread BCP
mineral deposition known as calciphylaxis. (See "Calciphylaxis (calcific uremic
arteriolopathy)".)

Diabetes [11], altered estrogen states, and thyroid disease [12] have also been
suspected as risk factors for calcific periarthritis, but sufficient evidence is
lacking to establish clear associations with these conditions. Most patients have
no known risk factors.

Genetic risk factors — A number of genetic disorders, including some

affecting phosphate metabolism, have been associated with calcific periarthritis.
As examples, some adult patients with familial recurrent calcific periarthritis
have subtle forms of hypophosphatasia, a congenital deficiency of alkaline
phosphatase [13] (see "Skeletal dysplasias: Specific disorders", section on
'Hypophosphatasia'). In addition, several kindreds with an Augustine-null blood
type related to mutations in the equilibrative nucleoside transporter 1 (ENT1)
have affected family members with symptomatic calcific periarthritis [14].

Dramatic familial presentations with large periarticular calcified masses are

usually associated with congenital causes of hyperphosphatemia. These
patients typically present in childhood and have mutations of GLANT3 or the
genes encoding fibroblast growth factor 23 (FGF23) or alpha-Klotho. Calcific
periarthritis may be the first manifestation of these syndromes in patients with
milder phenotypes. (See "Overview of the causes and treatment of
hyperphosphatemia".)

Other forms of familial calcific periarthritis have been described in association

with mutations that produce spondyloepiphyseal dysplasia [15]. These cases
are distinguished from other syndromes by the presence of short stature.
(See "Skeletal dysplasias: Specific disorders", section on 'Spondyloepiphyseal
dysplasia congenital' and "Skeletal dysplasias: Specific disorders", section on
'Spondyloepiphyseal dysplasia tarda'.)

CLINICAL MANIFESTATIONS Calcific periarthritis typically

causes the acute onset of severe pain involving a single joint, tendon, or bursal
area; it can occur around both large and small joints as well as in the spine [16].
Patients sometimes report fever and chills. Most patients with calcific
periarthritis are healthy and middle-aged. Case collections demonstrate two- to
threefold more women than men are affected [17,18]. A broad age range is
typically noted, and calcific periarthritis can also occur in children. The
prevalence of radiographic calcific tendinitis in the shoulder is 2.7 percent [18].
The prevalence around other joints is not known.

The affected joints are focally tender with a variable degree of warmth and
swelling. Erythema may be present. Joint effusions are typically absent, and the
area of tenderness may not correlate with the typical location of the joint line.

Attacks are self-limited, lasting a few weeks to several months. There are case
reports of more chronic symptoms, but it remains unclear whether persistent
radiographically evident calcifications contribute to such persistent symptoms
[19].

More common syndromes include the following:

●Large joint involvement – Shoulder involvement is the most commonly

recognized and best-studied form of calcific periarthritis [20]. Typically,
patients report a gradual onset of shoulder pain without trauma. Pain is
localized on the top or lateral aspect of the shoulder or both, often with
radiation towards the insertion of the deltoid. Most patients report increased
pain at night and an inability to lie on the affected shoulder, while during the
day, use of the arm above shoulder height causes pain. This condition is
described in detail separately (see "Calcific tendinopathy of the shoulder").
Elbow involvement is uncommon and typically involves the distal biceps
tendon [21].
Calcific periarthritis around the hip has been well described, but its
prevalence is not known. It most frequently involves the rectus femoris, the
gluteus maximus, or the gluteus minimus tendon, usually near the femoral
insertions [22]. Symptoms from rectus femoris involvement include pain
and tenderness near the anterior-inferior iliac spine and are exacerbated by
hip flexion. Snapping hip syndrome has been associated with calcific
deposits in the rectus femoris. Involvement of the gluteus maximus
produces pain in the proximal thigh, while gluteus minimus involvement
causes pain in the low back, buttock, or posterolateral thigh. Iliopsoas
involvement is less common and can produce pain in the hip or knee. Knee
involvement is uncommon and, when it does occur, can affect any of the
ligaments, bursae, and tendons around the knee [23].
●Small joint involvement – Calcific periarthritis may develop around the
small joints of the hands and feet. Hand involvement often occurs at the
flexor carpi ulnaris but may affect any of the hand tendons. Involvement of
the wrist or base of the thumb may cause acute onset of symptomatic
carpal tunnel syndrome [24], and trigger finger has been reported [25].
Foot involvement is most frequently reported at the first metatarsal
phalangeal joint, where it typically presents with symptoms at the plantar
aspect of that joint. This syndrome has been referred to as "hydroxyapatite
pseudopodagra" and may be particularly common in young women [26].
Calcific periarthritis of the foot less commonly involves the peroneus longus
tendon or the navicular insertion of the tibialis posterior tendon.
●Other sites of involvement – Retropharyngeal calcific tendinitis involves
the longus colli high in the cervical spine and can present with acute onset
of neck pain and stiffness associated with dysphagia and odynophagia [27].

LABORATORY TESTING Acute phase responses (as indicated by

the erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP] levels) are
elevated in some symptomatic patients. Other laboratory studies, including
complete blood count (CBC), basic chemistries, and levels of calcium,
phosphorus, and alkaline phosphatase are typically normal.
 IMAGING

●Plain film radiography – Radiographs show amorphous-appearing

extraarticular calcifications. These are often in or near tendons or bursae.
Calcifications may be present in tendons, bursae, ligaments, or soft tissues,
and bone erosions may occur adjacent to the calcific density [28].
Periarticular calcific densities are often described as amorphous or "cloud-
like" when they are acute, while chronic calcifications may be denser and
more homogeneous. Grading systems have been developed that are
based upon the radiographic density of the calcification [29]. However, the
size and grade of calcification correlates poorly with clinical manifestations
or outcomes [19,22].
●Ultrasonography – Ultrasonography is helpful in expert hands and has
been well studied in calcific tendinitis of the shoulder [30]. In the resting
phase, calcifications usually appear as hyperechoic lesions with acoustic
shadowing (image 1). In the resorptive phase the deposit may appear more
fluffy, fragmented, or punctuated (image 2). (See "Calcific tendinopathy of
the shoulder", section on 'Ultrasound'.)
●Magnetic resonance imaging – Magnetic resonance imaging (MRI)
cannot readily distinguish calcified material from other types of tissue
damage. T2 and short tau inversion recovery (STIR) images on MRI often
demonstrate edema in the area around the calcific deposit.
●Computed tomography – Computed tomographic (CT) scanning, by
contrast with MRI, readily identifies calcifications, and CT scans can be
used to confirm the anatomic location of the calcific deposit.
●Other – Bone scanning with technetium-99m and positron emission
tomography (PET) scanning show concentrated tracer at sites of
inflammation around basic calcium phosphate (BCP) deposits that may
mimic the appearance of malignant lesions [31].

HISTOPATHOLOGY There are few histopathologic studies of calcific

periarthritis. In one study, a predominantly histiocytic infiltrate was

demonstrated on most pathologic samples from patients with calcific
periarthritis, but some tissue samples had neutrophilic infiltrates [17]. Most
calcifications appear as granular and psammoma-like, while larger amorphous
calcifications were less common [28]. Careful handling of specimens is
necessary in order to prevent dissolution of calcium phosphate by methods
commonly used for tissue staining and preservation.

DIAGNOSIS

Diagnosis and diagnostic evaluation

● All patients – The diagnosis of calcific periarthritis is based upon the
presence of a characteristic clinical presentation and typical findings on
plain radiographs; the most typical presentation is of an acute onset of pain
 and swelling around a single joint in a healthy young or middle-aged
woman (see 'Clinical manifestations' above). On physical examination,
there is no obvious joint effusion, and tenderness may not be located at the
joint line. The presence of periarticular calcifications on plain radiographs of
symptomatic areas are usually sufficient to confirm the diagnosis of calcific
periarthritis, and no further diagnostic testing is necessary in typical cases.
(See 'Imaging' above.)
●Selected patients – Further imaging such as computed tomography (CT)
scanning may be necessary to visualize calcific deposits in deep structures,
such as the iliopsoas or retropharyngeal areas, or to more accurately
localize calcification in areas where two-dimensional imaging with
conventional radiographs is inadequate. (See 'Imaging' above.)
In patients with an atypical presentation, increased concern for infection, or
in the absence of radiographic findings of calcification, biopsy of the
involved tissues with culture and histopathologic analysis may be helpful
[17]. (See 'Histopathology' above.)

Postdiagnostic evaluation — Multiple episodes or multiple sites of calcific

periarthritis should prompt a thorough family history as well as an evaluation for
metabolic disorders. In patients with any of these features, further testing should
include serum levels of calcium, phosphate, and alkaline phosphatase, and
these results may prompt genetic testing.

DIFFERENTIAL DIAGNOSIS Calcific periarthritis is frequently

misdiagnosed. It is most often mistaken for acute gouty arthritis, acute calcium
pyrophosphate (CPP) crystal arthritis (pseudogout), or infectious arthritis. Each
of these is a true arthritis, and thus either physical examination or imaging
studies should demonstrate a synovial effusion. Other conditions may also be
mistaken for calcific periarthritis.
●Acute crystal arthritis (gout and calcium pyrophosphate deposition [CPPD]
disease) – Acute pain in the region of the joint may be present with both
calcific periarthritis and acute gout or acute CPP arthritis. However, the
demographics of gout and pseudogout are quite different from those of
calcific periarthritis. Gout typically develops in older men with other
comorbidities, including metabolic syndrome, and pseudogout is very rare
in people under the age of 60. (See "Clinical manifestations and diagnosis
of gout" and "Clinical manifestations and diagnosis of calcium
pyrophosphate crystal deposition (CPPD) disease".)
Calcified tophi can be confused with periarticular calcifications but typically
appear in patients with well-defined gout and have a rim of calcification
rather than the cloud-like appearance seen in calcific periarthritis.
●Infectious arthritis – Both infectious arthritis and calcific periarthritis can
cause pain and swelling in the region of the joint, as well as fever and
chills. Unlike periarthritis, infections that involve the joint are associated
with demonstrable joint effusions, and infections involving the soft tissues
or bursae rarely cause radiographic calcifications. (See "Septic arthritis in
adults".)
●Osteosarcoma and chondrosarcoma – Calcifications with nearby osseous
erosions on radiograph can be mistaken for osteo- or chondrosarcomas.
 The correct diagnosis is established by biopsy of these lesions.
(See "Osteosarcoma: Epidemiology, pathogenesis, clinical presentation,
diagnosis, and histology" and "Chondrosarcoma".)
●Trauma and fracture – Trauma, particularly around the small joints of the
hands and feet, should also be considered in the differential diagnosis.
Metatarsal fractures, for example, can present with pain, swelling, and
erythema in the forefoot or midfoot without a clear history of injury, similar
to the findings of calcific periarthritis. Avulsion fractures may also be
confused with calcific periarthritis. Expert review of radiographs or
advanced imaging will typically aid in distinguishing a fracture from calcific
periarthritis. (See "Evaluation and diagnosis of common causes of forefoot
pain in adults" and "Overview of finger, hand, and wrist fractures".)
●Sesamoiditis – Sesamoiditis, a tendinopathy, can also be confused with
calcific periarthritis of the first metatarsal phalangeal joint, and advanced
imaging may be required to distinguish between these two entities.
(See "Evaluation and diagnosis of common causes of forefoot pain in
adults".)
●Synovial chondromatosis – Rarely, the calcifications of calcific periarthritis
may resemble lesions of synovial chondromatosis. These appear as
multiple intraarticular chondral bodies with "ring and arc" chondroid
mineralization and extrinsic bony erosions. Symptoms are frequently
chronic in synovial chondromatosis, and this may be more common in men.
(See "Radiologic evaluation of knee tumors in adults", section on 'Synovial
(osteo)chondromatosis' and "Imaging evaluation of the painful hip in
adults", section on 'Pigmented villonodular synovitis and synovial
osteochondromatosis' and "Radiologic evaluation of the painful shoulder in
adults", section on 'Magnetic resonance imaging'.)
●Other conditions – Less commonly, calcific periarthritis can be confused
with calcinosis cutis, myositis ossificans, or phleboliths. CT scanning
should allow for accurate localization of the calcific density if these
alternative diagnoses are entertained. Heterotopic ossification is often
considered in the differential diagnosis but has a distinct radiographic
appearance with a corticated rim of bone-like tissue around the density.
Unusual ossicles can be confused with calcific periarthritis but should have
visible trabeculae characteristic of bone. Tissue calcification can also occur
after intralesional injections, including glucocorticoid injections [32]. These
are typically asymptomatic, and a history of injections at the site of
involvement would support this possibility. (See appropriate topic reviews.)

MANAGEMENT

Overall strategy — The goals of therapy are the elimination of pain, reduction
of inflammation, and dissolution of the calcific deposit. Most patients do well
with nonsteroidal antiinflammatory drug (NSAID) therapy alone or with the
injection of intralesional glucocorticoids. Most symptoms resolve within four to
eight weeks [22]. (See 'Initial therapy' below.)

In patients whose symptoms are refractory to NSAIDs and local glucocorticoid

injection, percutaneous needling (barbotage) is generally both safe and well
tolerated. We reserve extracorporeal shockwave therapy (ESWT) or
arthroscopic or open surgical procedures for patients who continue to have
symptoms despite treatment with NSAIDs, local glucocorticoid injection, and
percutaneous needling. (See 'Resistant to initial therapy' below.)

This approach is supported by case reports, case series, our personal

experience, and by inference from the available, but somewhat limited,
evidence regarding treatment of shoulder disease. There are few randomized
trials of therapies in calcific periarthritis, but some systematic reviews have
been performed in patients with shoulder involvement. These studies focus on
ultrasound-guided needle lavage [33] and ESWT [34] and have uncertain
applicability to calcific periarthritis in other sites. The management of calcific
periarthritis of the shoulder is described in detail separately. (See "Calcific
tendinopathy of the shoulder".)

Initial therapy — For initial therapy of calcific periarthritis we suggest either

NSAID therapy or an intralesional glucocorticoid injection.
●We prefer an NSAID (eg, naproxen 500 mg twice daily or ibuprofen 400 to
600 mg four times daily or 800 mg two to three times daily, with a maximum
dose in young healthy individuals of 3200 mg daily) in patients with normal
renal function and without contraindications to NSAID use such as
cardiovascular disease or other risk factors for gastrointestinal disease.
(See 'NSAIDs' below.)
●We prefer an intralesional glucocorticoid injection in patients in whom a
local injection is feasible based upon the accessibility of the involved site;
availability of imaging guidance, where needed (eg, for deep sites); and the
expertise of the treating clinician. An injection is also appropriate in patients
unable to use NSAIDs (eg, due to contraindications) or who have
experienced an inadequate response to NSAIDs after 48 to 72 hours of
treatment. (See 'Intralesional glucocorticoids' below.)

NSAIDs — NSAIDs target both pain and inflammation and are the first-line
therapy for many patients with calcific periarthritis. In patients with normal renal
function and no contraindications to NSAID use, we would begin
with naproxen (500 mg twice daily). Alternatively, ibuprofen (eg, 400 to 600 mg
four times daily or 800 mg two to three times daily, with a maximum dose in
young healthy individuals of 3200 mg per day) could be used. Protection
against gastrointestinal toxicity with a proton pump inhibitor (PPI;
eg, omeprazole 20 mg orally twice daily) should be utilized in patients at high
risk of gastrointestinal toxicity from NSAIDs who require NSAID therapy.
(See "NSAIDs (including aspirin): Primary prevention of gastroduodenal
toxicity" and "NSAIDs (including aspirin): Secondary prevention of
gastroduodenal toxicity".)

An alternative to a relatively nonselective NSAID in patients poorly tolerant of

such agents is the use of an NSAID that is more cyclooxygenase-2 (COX2)
selective (eg, celecoxib 200 mg twice daily or meloxicam 7.5 mg daily).

Treatment should be given for the duration of symptoms. Significant reduction in

pain levels and improvement of function after 48 to 72 hours of therapy should
be used as an indication of adequate response. This approach is supported by
case reports and personal experience.

Intralesional glucocorticoids — Intralesional glucocorticoids are generally

believed to accelerate resolution of symptoms and may act more quickly with
fewer side effects than systemic medications. Ultrasound or fluoroscopic
guidance is warranted in situations where the calcification is not close to the
skin surface, such as the hip. Calcific periarthritis around a finger or toe can
often be injected without radiographic guidance.

We use 10 to 40 mg of methylprednisolone acetate administered once. The

dose should be based on the size of the area involved. Areas around small
joints typically have smaller calcifications and lower doses can be used. The
use of shorter-acting glucocorticoids, such as methylprednisolone acetate,
minimizes the risk of soft tissue atrophy that may occur with longer-acting
glucocorticoids. We typically wait 48 to 72 hours to see an effect on pain and
function. This approach is supported by case reports and personal experience.

Resistant to initial therapy — In patients who do not respond NSAIDs or local

glucocorticoid injection, there are several treatment options. Two of these are
minimally invasive nonsurgical options, needle aspiration (barbotage) and
ESWT, the other is arthroscopic surgery to remove calcific deposits.

We suggest needle aspiration as the next procedure in patients unresponsive to

NSAIDs and injection, and reserve referral for arthroscopic or open surgery to
patients refractory to NSAIDs, injection, and needling. All three approaches
have been reported as beneficial for calcific tendinopathy of the shoulder; most
data are from case series, with only limited and heterogenous randomized trial
data. (See "Calcific tendinopathy of the shoulder", section on 'Therapies for
refractory cases'.)

●Needle aspiration (barbotage) – We generally reserve needle aspiration

for patients who have not responded well to NSAIDs or intralesional
glucocorticoids. The most commonly used procedure is also known as
barbotage and involves repeated aspiration and injection of the calcific
deposit. This is typically performed under ultrasound guidance.
The skin is cleaned with betadine and the area is injected with
1% lidocaine after radiographic confirmation of the location of the deposit.
A 22-gauge needle attached to a 20 mL syringe filled with lidocaine mixed
with sterile saline is used to break up the calcium deposit. Using repeated
injection of the liquid, movement of the needle, and then aspiration, small
pieces of the deposit are often visible in the syringe. In many centers, it is
performed by musculoskeletal radiologists. The use of this technique for
calcific tendinopathy of the shoulder and a summary of the evidence is
described in detail separately. (See "Calcific tendinopathy of the shoulder",
section on 'Barbotage'.)
●Extracorporeal shockwave therapy – ESWT may be useful in patients
who have not responded to initial therapy and have failed needle aspiration
[34]. However, this procedure requires specially trained personnel and
facilities, and although it has been studied in patients with shoulder
involvement, its utility in calcific periarthritis in sites other than the shoulder
 remains unclear. (See "Calcific tendinopathy of the shoulder", section on
'Extracorporeal shock wave therapy'.)
●Surgical procedures – Arthroscopic or open surgical procedures to
remove calcific deposits are generally safe and effective for patients with
shoulder involvement, and referral for evaluation for one of these more
invasive approaches is indicated in patients with involvement of other areas
who are refractory to conservative treatments, including NSAIDS,
intralesional glucocorticoids, and needle aspiration. (See "Calcific
tendinopathy of the shoulder", section on 'Surgery'.)

Adjunctive therapy for pain — Analgesic agents such as acetaminophen (500

to 1000 mg up to three times daily) can be used in calcific periarthritis in
patients who are intolerant of or unable to use NSAIDs. Acetaminophen can be
used alone or in combination with a local therapy such as intralesional
glucocorticoids or needling. In patients with pain that is refractory to
acetaminophen, other pain medications, including tramadol or opioids, may be
necessary, but should be used in the lowest dose and for the shortest time
necessary. This approach is based upon our clinical experience, but there are
no trials to document the benefit of these medications in this condition.

Other therapies for patients refractory to usual therapies — There is very

limited information to support the use of other therapies. Strategies that have
been employed include:
●Systemic glucocorticoids – Systemic glucocorticoids are rarely used in
this disorder. They might be most appropriate in patients in whom multiple
areas are involved or if the calcific deposit is inaccessible to regional
intervention, and the patient is intolerant of or unable to use NSAIDs. Low
to moderate doses of prednisone (10 to 30 mg daily) could be used initially
until symptoms resolve. Very limited case reports support this approach
[35].
●Interleukin-1 beta inhibition – Interleukin (IL)-1 beta inhibitors can also
be used for calcific periarthritis [36]. These drugs would be suitable for
patients with multiple sites of involvement, refractory to NSAIDs, or
inappropriate for intralesional interventions. We would use anakinra (100
mg subcutaneously for three days) in patients appropriate for this type of
therapy, based upon case reports and a small pilot study [36].
●Other treatments – Other therapies have been tried in refractory disease.
Intralesional platelet-rich plasma injection has been described in a case
report but has not been tested in clinical trials [37]; these types of injections
would be used for patients who failed or were intolerant of NSAIDs and
more conservative intralesional therapies such as intralesional
glucocorticoids. There is very little evidence for efficacy of
bisphosphonates, such as clodronate, or for topical or intralesional
applications of thiosulfate.

PROGNOSIS The natural history of calcific periarthritis is not well

studied and may be site-dependent. For example, in small joints such as those
in the foot, symptoms were present for a mean duration of 10 days with a range
of 3 to 30 days [26], while in hip involvement, symptoms in treated patients
resolved within four to eight weeks [22]. Recurrence rates are also not well
documented.

More information is available with respect to shoulder involvement, which is

discussed in detail separately. (See "Calcific tendinopathy of the shoulder",
section on 'Prognosis and complications'.)

SOCIETY GUIDELINE LINKS Links to society and government-

sponsored guidelines from selected countries and regions around the world are
provided separately. (See "Society guideline links: Gout and crystal disorders".)

SUMMARY AND RECOMMENDATIONS

●Basic calcium phosphate (BCP) mineral formation often occurs at sites of

local tissue damage associated with injury or inflammation. BCP crystals
can then produce symptoms and mediate tissue damage by several
mechanisms, including the induction of an inflammatory response,
biomechanical disruption, and direct tissue injury. Trauma, metabolic, and
genetic factors may each be associated with increased risk of BCP-
associated calcific periarthritis, although most patients are in good general
health, and only a portion report recent trauma or overuse.
(See 'Pathogenesis of BCP-associated musculoskeletal syndromes' above
and 'Risk factors' above.)
●Calcific periarthritis typically causes the acute onset of severe pain
involving a single joint, tendon, or bursal area; there is focal tenderness
and variable warmth and swelling, sometimes with erythema. It can occur
around both large and small joints as well as in the spine. Patients
sometimes report fever and chills. Most patients are healthy and middle-
aged, with women affected more often than men. The area of tenderness
may not correlate with the typical location of the joint line. Attacks are
usually self-limited, lasting a few weeks to several months. (See 'Clinical
manifestations'above.)
●Radiographs show amorphous-appearing extraarticular calcifications,
especially when acute, often in or near tendons or bursae. Calcifications
may be present in tendons, bursae, ligaments, or soft tissues; bone
erosions may occur adjacent to the calcific density. Chronic calcifications
may be denser and more homogeneous. Calcifications can also be well
visualized by ultrasound and by computed tomography (CT).
(See 'Imaging' above.)
●The diagnosis is based upon a characteristic clinical presentation and
typical findings on plain radiographs; with an acute onset of pain and
swelling around a single joint, most often in a healthy young or middle-aged
woman; no obvious joint effusion; and tenderness that may not be located
at the joint line. The presence of periarticular calcifications on plain
radiographs of symptomatic areas are usually sufficient to confirm the
diagnosis. CT scanning may be necessary to visualize calcific deposits in
deep structures. (See 'Diagnosis' above.)
 ●The differential diagnosis includes acute gouty arthritis, acute calcium
pyrophosphate (CPP) crystal arthritis (pseudogout), infectious arthritis, and,
less frequently, other conditions. (See 'Differential diagnosis' above.)
●For initial therapy of calcific periarthritis, we suggest either nonsteroidal
antiinflammatory drug (NSAID) therapy or an intralesional glucocorticoid
injection rather than minimally or more invasive procedures. (See 'Initial
therapy' above.)
•We prefer an NSAID (eg, naproxen 500 mg twice daily
or ibuprofen 400 to 600 mg four times daily or 800 mg two to three
times daily, with a maximum dose in healthy young individuals of 3200
mg daily) in patients with normal renal function and without
contraindications to NSAID use such as cardiovascular disease or
other risk factors for gastrointestinal disease. (See 'NSAIDs' above.)
•We prefer an intralesional glucocorticoid injection in patients in whom
a local injection is feasible based upon the accessibility of the involved
site; availability of imaging guidance, where needed (eg, for deep
sites); and the expertise of the treating clinician. An injection is also
appropriate in patients unable to use NSAIDs (eg, due to
contraindications) or who have experienced an inadequate response to
NSAIDs after 48 to 72 hours of treatment. (See 'Intralesional
glucocorticoids' above.)
●In patients who do not respond to NSAIDs or local glucocorticoid injection,
we suggest needle aspiration (ie, "needling" or barbotage); we reserve
referral for arthroscopic or open surgery to patients refractory to NSAIDs,
injection, and needling. Extracorporeal shockwave therapy (ESWT) may be
a useful alternative in patients who have not responded to initial therapy
and have failed needle aspiration, where this technique is available.
(See 'Resistant to initial therapy' above.)
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