MRI Web Clinic — March 2009

Hydroxyapatite Deposition Disease
Stephen F. Quinn, M.D.

Clinical History: A 48 year-old female presents with pain in the left shoulder with reduced range of motion. (1a) A coronal oblique T2-weighted fat-suppressed image and (1b) an axial T2-weighted image are provided. What are the findings? What is the diagnosis?

1a
1b
Figure 1:

(1a) A coronal oblique T2-weighted fat-suppressed image and (1b) an axial T2-weighted image

Findings

 

2
Figure 2:

The coronal oblique T2-weighted fat-suppressed image shows a rounded focus of decreased signal intensity along the bursal surface of the supraspinatus tendon insertion site (arrow). Water signal is present in the subdeltoid bursa indicative of inflammation. Additionally, tendinopathy of the supraspinatus tendon is present.

3
Figure 3:

The axial plane T2-weighted fat-suppressed image reveals a rounded focus of decreased signal intensity along the bursal surface of the anterior insertion site of the supraspinatus tendon (arrow).

Diagnosis

Hydroxyapatite deposition disease (HADD), with calcium hydroxyapatite crystal deposition along the bursal surface of the supraspinatus tendon.

Introduction

Hydroxyapatite deposition disease (HADD) refers to a spectrum of abnormalities that includes calcific tendinitis, other periarticular hydroxyapatite deposition, and hydroxyapatite induced arthritis.1,2 Other names for HADD include calcific tendinosis, peritendinitis calcarea, calcific peritendinitis and bursitis, and hydroxyapatite rheumatism.3 Calcium hydroxyapatite (CHA) is the most common type of calcium in human bone and is also the most common pathologic calcification found in the body.4 CHA, as well as other basic calcium phosphate crystals, are considered the causal agents in some entities. In other situations, the basic calcium phosphates are considered secondary to underlying diseases. For example, the calcifications associated with severe renal disease, collagen vascular disease (dermatomyositis and scleroderma), chronic neurologic conditions, Vitamin D overload, tumoral calcinosis and dystrophic calcification are composed largely of CHA.4

Pathogenesis

CHA deposits occur in tendons, peritendinous tissues, bursae, and ligaments. The pathogenesis of periarticular CHA deposits is uncertain and several explanations have been offered. Possible etiologies for CHA deposition include local trauma, ischemia, and necrosis of tendons. CHA deposits in the supraspinatus tendon are typically located in the poorly vascularized critical zone, which is a few millimeters medial to the osseous insertion. CHA deposits in other tendons occur preferentially in hypovascular segments, supporting the hypothesis that local necrosis leads to crystal deposition.3 CHA deposition is a cell-mediated process where tissue changes result in transformation of tendinous tissues into chondrocytes. The CHA crystals are deposited in an extracellular matrix derived from the chondrocytes.5 Metabolic and genetic factors can predispose patients to CHA deposition.4

Laboratory Findings

Laboratory tests are usually negative in patients with HADD. CHA crystals are 75-250 nm, and are not visible with light microscopy, except when the crystals form aggregates. The CHA crystals are non-birefringent in polarized light. Transmission electron microscopy or electron diffraction studies are needed to identify CHA crystals. Alizarin red S stain reportedly is a sensitive but non-specific tool for screening for CHA crystals.6

Clinical Presentation

HADD typically presents in a monoarticular fashion. Most patients are between the ages of 40 and 70 years7 and HADD is rare in children.8 Approximately 50% of patients present with pain, erythema, swelling, and limitation of motion of the affected joint.9 The signs and symptoms of HADD are likely from rupture of a calcific deposit into an adjacent soft tissue space or bursa (4a), resulting in an acute inflammatory reaction. Phagocytosis of CHA crystals leads to the release of lysosomal enzymes and other inflammatory mediators.10,11 This presentation is called acute calcific periarthritis and most commonly involves the shoulder.12,13 HADD can be associated with a fever and can be confused with an infection. Unlike patients with infection, patients with HADD have normal erythrocyte sedimentation rates and leukocyte counts.9

 

4
Figure 4:

A coronal oblique T2-weighted fat suppressed image shows a deposit of CHA crystals (arrow). Prominent subdeltoid bursitis is also present (arrowheads).

The clinical course of HADD is variable. Although many patients have complete resolution of symptoms, other patients develop chronic pain syndromes. In the shoulder it is difficult to determine what contribution, if any, the CHA deposits themselves make to an individual patient. Some patients with HADD have a pattern of recurrent episodes of acute shoulder pain, followed by pain-free periods of months or years, and subsequently develop chronic pain. These patients seem to be predisposed to full thickness rotator cuff tendon tears.3

Mosely divided HADD into three phases and this classification is commonly referenced.14 According to Mosley, HADD begins with the silent phase where the CHA is completely contained within the tendon. Radiographs will show well defined CHA deposits which represent dry granular or “cheesy” material. In the silent phase, patients have minimal symptoms.

In the second or mechanical phase, enlargement of the deposit occurs followed by impingement-like symptoms which result from CHA deposit enlargement. The deposits liquefy and cause increased intratendinous pressure and bursitis. The CHA deposits become less defined radiographically. The CHA deposits rupture either into or around the adjacent bursa. This phase is characterized clinically by acute painful attacks. On radiographs the CHA deposits disperse into the adjacent bursa or peribursal soft tissues. The CHA deposits frequently disappear on the radiographs but this disappearance may or may not correlate with regression of clinical symptoms.

The third and last phase is called adhesive periarthritis. This is a late stage that presents with general debility, pain, and limited range of motion. In the adhesive periarthritis phase, patients have adhesive bursitis, CHA deposits within the rotator cuff and intraosseous and dumbbell-like CHA deposits.14

Anatomic Sites of Involvement

The shoulder is the most common site of HADD. In one study that examined the prevalence of calcific tendinitis in the general population, 2.7% of study participants had calcified deposits (presumed CHA deposits) in the rotator cuff complex.15 Of these patients, only 34% to 45% had problems that could be associated with the CHA deposits. In this study, women were more often symptomatic than men and disease occurred most commonly between the ages of 31 and 40. The shoulder is said to account for 60% of cases of acute calcific periarthritis.16 HADD can involve any of the components of the rotator cuff complex (5a) and the supraspinatus tendon is most commonly involved. HADD can also involve adjacent tendon structures including the long and short heads of the biceps tendon, the coracobrachialis tendon, the triceps tendon and pectoralis tendon. Subacromial and subdeltoid bursal calcifications appear as a teardrop-shaped radiodense areas below the acromion and deltoid muscle.7

 

5
Figure 5:

A small deposit of CHA crystals at the lateral insertion site of the subscapularis tendon (arrow) is seen on this axial proton density weighted fat-suppressed image.

After the shoulder, the hip is the next most common location for HADD. CHA deposits at the hip are most common in the gluteus medius tendon either at the greater trochanter or the acetabulum.17 HADD not uncommonly involves the posterolateral femoral attachment of the gluteus maximus as well.18 Other areas of HADD involvement include the iliopsoas tendon insertion at the lesser trochanter, and the ischial origins of the common hamstring tendons.7

At the elbow, HADD can affect the flexor and extensor tendon complexes at the epicondylar origins. HADD can also occur in the medial and lateral collateral ligamentous complexes. As would be expected, HADD may involve the regional tendon groups of the elbow, including the triceps, brachialis, and biceps tendons.19 The bursa around the elbow can also be involved with HADD.20

HADD can involve the tendons and ligaments of the wrist and hand. The wrist is more commonly affected than the hand.21 The pisiform insertion site of the flexor carpi ulnaris tendon is reportedly the most common site of involvement in the wrist.22 In the hand, HADD involvement of the metacarpophalangeal and interphalangeal regions is not uncommon.

In the knee, HADD tends to occur near tendon attachments rather than other periarticular structures. The CHA deposits are usually next to the femoral condyles (6a), fibular head, and prepatellar region.23 HADD can also involve other sites around the knee including the popliteus tendon and lateral collateral ligament.24,25

 

6
Figure 6:

A coronal T-2 weighted image of the knee demonstrates a deposit of CHA crystals adjacent to the medial femoral condyle (arrow). Prominent soft tissue inflammation is present.

In the ankle and foot, HADD can involve multiple structures.26 Sites of involvement include the flexor hallucis longus and brevis and the peroneus muscles. Fam described a presentation of HADD that involves the metatarsophalangeal joints. This has been coined ?hydroxyapatite pseudopodagra?, and occurs predominantly in young women.12

No discussion of HADD would be complete without mentioning involvement of the longus coli muscle and tendon. In this location patients present with severe pain in the neck and throat that increases with swallowing and movement. Typically the CHA deposition is anterior to C2 and is associated with soft tissue swelling.27

HADD presenting with intra-articular deposition

Uncommonly, HADD can present with intra-articular deposition of crystals, producing an acute and sometimes destructive arthritis. This arthropathy has been given various names including chronic apatite arthropathy, apatite-associated destructive arthropathy, idiopathic destructive arthropathy and Milwaukee Shoulder Syndrome (MSS).7 It is not known whether MSS is caused by HADD, but some authorities believe that there is an association.28 MSS is usually seen in female patients in their seventies.7 It has a predilection for large joints, and although shoulder involvement is most common, other joints including the elbows, hips, and knees can be involved.28 Patients typically present with joint swelling, reduced range of movement, instability and loss of function. Characteristically, patients with MSS have mild pain and little or no evidence of inflammation.7 MSS is associated with rotator cuff tears.29 Joint effusions are common and may be large, extending into the subdeltoid and subacromial regions. The synovial fluid is typically blood tinged and has a low, predominantly mononuclear, cell count. The effusions can rupture leading to a massive extravasation of blood and synovial fluid into the surrounding tissues.30 The natural history has not been carefully studied, but in some patients MSS stabilizes after 1-2 years. In most patients no cause for the MSS has been found but a familial pattern of MSS has been described in a small group of patients.31 With imaging there is accelerated osteoarthritis, osseous destruction, and intra-articular osteochondral bodies. A milky white effusion may be seen on radiographs.7

Imaging

In the early phases of HADD, calcifications typically present as a thin, poorly defined deposits in tendons, ligaments, bursae, or synovium.7 Rarely, the CHA crystals can deposit within the joint.1 The calcifications subsequently become denser and more homogeneous, with sharper edges. The course of the calcifications is variable. The calcifications may be stable for years or may enlarge, change shape, or disappear.7 Sharply demarcated CHA deposits may be associated with fewer symptoms than ill defined deposits. HADD calcifications are homogenous and amorphous, lacking boney trabeculae seen with heterotopic ossifications or accessory ossifications.4 CHA deposits vary from a few millimeters to several centimeters in size.32 Most HADD calcifications are ovoid but they can be linear or triangular. Tendinous HADD is usually close to the tendon insertion site but infrequently the deposits are well away from the insertion.4 HADD can cause osseous erosions and in some cases the CHA deposits are within the erosions (7a).33

 

7
Figure 7:

An oblique coronal plane T-2 weighted fat-suppressed image reveals CHA crystal deposition within an osseous cyst (arrow) as well as in the adjacent supraspinatus tendon (arrowhead). Prominent marrow and subdeltoid inflammation is present.

HADD calcifications of the supraspinatus tendon are within 1 cm from the greater tuberosity insertion4 and are best seen with an anteroposterior external rotation view of the shoulder. HADD calcifications of the infraspinatus and teres minor tendons are best seen on internal rotation anteroposterior views. HADD calcifications of the pectoralis major tendon occur along the anterior aspect of the humeral shaft (8a).7

 

8
Figure 8:

An axial T-2 weighted fat suppressed image shows a focus of CHA deposition next to the humeral attachment site of the pectoralis major tendon (arrow). Inflammation is present around the deposit.

HADD deposits typically present on MR imaging as rounded areas of low signal intensity on all imaging sequences. The deposits are particularly conspicuous on gradient echo imaging. In the acute symptomatic phase of HADD (acute calcific periarthritis), the process has an aggressive appearance with marrow and soft tissue edema that may mimic infection, trauma, or neoplasm.34

Treatment

Treatment of HADD is symptomatic and most symptoms resolve within 2-3 weeks. Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered the treatment of choice for HADD. Local corticosteroid injections and oral or parenteral steroids have been used for patients who do not respond to or cannot tolerate NSAIDs. Recalcitrant CHA deposits can be removed surgically or with image-guided aspiration.35

Differential Diagnosis

The CHA depositions of HADD have a characteristic appearance. Rounded deposits in the anatomic sites favored by HADD without an underlying disorder helps narrow the differential diagnosis. The calcifications of calcium pyrophosphate deposition disease (CPPD) are more linear and diffuse than the calcifications of HADD. Gouty tophi are more faintly calcified and are associated with elevated urate levels, though the MRI appearance of a tophus can be indistinguishable from a deposit of CHA crystals (9a). Heterotopic bone and myositis ossificans have a trabecular pattern, marrow signal, and a cortical rim, findings that are not seen with HADD. As would be expected, smaller CHA deposits of tumoral calcinosis, either primary, idiopathic, or secondary to renal disease (10a,10b), are indistinguishable from HADD. In clinical practice, most patients with tumoral calcinosis have a known diagnosis prior to imaging. Collagen vascular disease such as scleroderma or dermatomyositis can also produce calcifications but the calcifications are widespread, often involve the subcutaneous tissues, and are associated with a known underlying disease. Periarticular calcifications may be seen in association with sarcoidosis, hypervitaminosis D, hypoparathyroidism, and milk-alkali syndrome, but these calcifications typically do not resemble CHA deposits and affected patients typically have known underlying diseases.7 In the acute phase of HADD (acute calcific periarthritis), the soft tissue and marrow edema seen on MR imaging can mimic infection, trauma and tumor. Detection of CHA deposits differentiates HADD from the other diagnoses in such cases.

 

9
Figure 9:

Gout: An axial T2-weighted fat suppressed image of the foot shows a rounded soft tissue deposit adjacent to the peroneus brevis tendon (arrow). This is a surgically proven gouty tophus. A skin marker is also present (curved arrow).

 

10a
10b
Figure 10:

Tumoral calcinosis secondary to renal failure: The axial T1- weighted image of the shoulder (10a) reveals fluid-fluid levels containing CHA (arrows). The coronal T2- weighted fat suppressed image of the shoulder (10b) demonstrates areas of CHA crystal deposition as well as collections of fluid and solid synovial and fibrous prominence (arrowheads).

 

Conclusion

HADD is a common disorder hallmarked by peri-articular deposition of CHA crystals and an accompanying inflammatory process. Although any joint can be involved, the shoulder is the most commonly affected site. With MR imaging, CHA deposits present as small, oval foci of decreased signal intensity. In the acute symptomatic phase of HADD, called acute calcific periarthritis, soft tissue and osseous edema can be present and needs to be distinguished from infection, tumor and trauma.

References

1 Bonavita JA, Dalinka MK, Schumacher HR, Jr. Hydroxyapatite deposition disease. Radiology 1980; 134:621-625.

2 Resnick D. Calcium hydroxyapatite crystal deposition disease. In: Resnick D, Niawayama G, eds. Diagnosis of bone and joint disorders. 2nd ed. Philadelphia: Saunders, 1988; 1733-1764.

3 Molloy ES, McCarthy GM. Calcium crystal deposition diseases: update on pathogenesis and manifestations. Rheum Dis Clin North Am 2006; 32:383-400, vii.

4 Hayes CW, Conway WF. Calcium hydroxyapatite deposition disease. Radiographics 1990; 10:1031-1048.

5 Sarkar K, Uhthoff HK. Ultrastructural localization of calcium in calcifying tendinitis. Arch Pathol Lab Med 1978; 102:266-269.

6 Paul H, Reginato AJ, Schumacher HR. Alizarin red S staining as a screening test to detect calcium compounds in synovial fluid. Arthritis Rheum 1983; 26:191-200.

7 Steinbach LS. Calcium pyrophosphate dihydrate and calcium hydroxyapatite crystal deposition diseases: imaging perspectives. Radiol Clin North Am 2004; 42:185-205, vii.

8 Carroll RE, Seitz WH, Jr., Putnam MD. Acute calcium deposit in the hand of an 11-year-old girl. J Pediatr Orthop 1985; 5:468-470.

9 Selby CL. Acute calcific tendinitis of the hand: an infrequently recognized and frequently misdiagnosed form of periarthritis. Arthritis Rheum 1984; 27:337-340.

10 Terkeltaub RA, Ginsberg MH. The inflammatory reaction to crystals. Rheum Dis Clin North Am 1988; 14:353-364.

11 Elferink JG, Deierkauf M. A biochemical study of hydroxyapatite crystal induced enzyme release from neutrophils. Ann Rheum Dis 1987; 46:590-597.

12 Fam AG, Rubenstein J. Hydroxyapatite pseudopodagra. A syndrome of young women. Arthritis Rheum 1989; 32:741-747.

13 McCarthy GM, Carrera GF, Ryan LM. Acute calcific periarthritis of the finger joints: a syndrome of women. J Rheumatol 1993; 20:1077-1080.

14 Moseley H. Shoulder lesions. In. 3rd ed. Baltimore: Williams and Wilkins, 1969; 99-108.

15 Bosworth BM. Calcium deposits in the shoulder and subacromial bursitis. A survey of 12,222 shoulders. JAMA 1941; 116:2477-2482.

16 Faure G, Daculsi G. Calcified tendinitis: a review. Ann Rheum Dis 1983; 42 Suppl 1:49-53.

17 Jones GB. Acute episodes with calcification around the hip joint. J Bone Joint Surg Br 1955; 37-B:448-452.

18 Berney JW. Calcifying peritendinitis of the gluteus maximus tendon. Radiology 1972; 102:517-518.

19 Sakamoto K, Kozuki K. Calcific tendinitis at the biceps brachii insertion of a child: a case report. J Shoulder Elbow Surg 2002; 11:88-91.

20 Vizkelety T, Aszodi K. Bilateral calcareous bursitis at the elbow. J Bone Joint Surg Br 1968; 50:644-652.

21 Moyer RA, Bush DC, Harrington TM. Acute calcific tendinitis of the hand and wrist: a report of 12 cases and a review of the literature. J Rheumatol 1989; 16:198-202.

22 Gandee RW, Harrison RB, Dee PM. Peritendinitis calcarea of flexor carpi ulnaris. AJR Am J Roentgenol 1979; 133:1139-1141.

23 Rehak DC, Fu FH. Calcification of tendon of the vastus lateralis. A case report. Am J Sports Med 1992; 20:227-229.

24 Anderson SE, Bosshard C, Steinbach LS, Ballmer FT. MR imaging of calcification of the lateral collateral ligament of the knee: a rare abnormality and a cause of lateral knee pain. AJR Am J Roentgenol 2003; 181:199-202.

25 Tibrewal SB. Acute calcific tendinitis of the popliteus tendon–an unusual site and clinical syndrome. Ann R Coll Surg Engl 2002; 84:338-341.

26 Weston WJ. Case reports; peroneal tendinitis calcarea. Br J Radiol 1959; 32:134-135.

27 Hartley J. Acute Cervical Pain Associated with Retropharyngeal Calcium Deposit. A Case Report. J Bone Joint Surg Am 1964; 46:1753-1754.

28 Dieppe PA, Doherty M, Macfarlane DG, Hutton CW, Bradfield JW, Watt I. Apatite associated destructive arthritis. Br J Rheumatol 1984; 23:84-91.

29 McCarty DJ, Halverson PB, Carrera GF, Brewer BJ, Kozin F. “Milwaukee shoulder”–association of microspheroids containing hydroxyapatite crystals, active collagenase, and neutral protease with rotator cuff defects. I. Clinical aspects. Arthritis Rheum 1981; 24:464-473.

30 McCarty DJ, Swanson AB, Ehrhart RH. Hemorrhagic rupture of the shoulder. J Rheumatol 1994; 21:1134-1137.

31 Pons-Estel BA, Gimenez C, Sacnun M, et al. Familial osteoarthritis and Milwaukee shoulder associated with calcium pyrophosphate and apatite crystal deposition. J Rheumatol 2000; 27:471-480.

32 Stoller DW, Wolf EM, Li EE, Nottage WM, Tirman PFJ. The shoulder. In: Stoller DW, ed. Magnetic Resonance Imaging in Orthopaedics and Sports Medicine. 3rd ed. Baltimore: Lippincott Williams and Wilkins, 2007; 1031-1461.

33 Hayes CW, Rosenthal DI, Plata MJ, Hudson TM. Calcific tendinitis in unusual sites associated with cortical bone erosion. AJR Am J Roentgenol 1987; 149:967-970.

34 Yang I, Hayes CW, Biermann JS. Calcific tendinitis of the gluteus medius tendon with bone marrow edema mimicking metastatic disease. Skeletal Radiol 2002; 31:359-361.

35 Farin PU, Rasanen H, Jaroma H, Harju A. Rotator cuff calcifications: treatment with ultrasound-guided percutaneous needle aspiration and lavage. Skeletal Radiol 1996; 25:551-554.

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