Basic calcium phosphate crystal deposition disease

Calcific Periarthritis

Calcific scapulohumeral periarthritis was first described in 1870, and radiographic demonstration of periarticular shoulder calcifications was reported by 1907. These calcifications were initially regarded as having arisen in the subdeltoid bursa but were subsequently demonstrated to occur chiefly in the supraspinatus tendon or the shoulder joint capsule. Thirty years later, renewed interest in periarthritis of the shoulder led to further descriptions of the phenomenon, as well as recognition of periarticular calcifications at other sites. After another 30 years, it was recognized that the calcific material consisted of hydroxyapatite, and the pathophysiologic theory of primary tendon necrosis leading to secondary calcification followed. Subsequently, aggregates of basic calcium phosphate (BCP) crystals with their various crystalline structures and chemical compositions were further defined via ultrastructural and physical microanalysis techniques, including analytic electron microscopy, x-ray diffraction, and Fourier transform infrared (FTIR) spectroscopy. Included in the term BCP are crystals of partially carbonate-substituted hydroxyapatite, octacalcium phosphate, and rarely, tricalcium phosphate.

Intraarticular Basic Calcium Phosphate Crystal Deposition

The earliest description of the pathoanatomic features of the consequences of intraarticular BCP crystal deposition appears to have been by Robert Adams in 1857, who called it “chronic rheumatic arthritis of the shoulder.” In his 1934 monograph, Codman reported the case of a 51-year-old woman who had what he called “subacromial space hygroma.” He described recurrent swelling of the shoulder, absent rotator cuff, cartilaginous bodies attached to synovial tissue, and severe destructive glenohumeral arthritis. These clinical descriptions were made without the benefit of modern diagnostic tests. The condition has subsequently been known by many different names. In the French-language literature, the terms les caries séniles hémorragique de l’épaule and l’arthropathie destructrice rapide de l’épaule have been used, and in the English-language literature, terms such as cuff tear arthropathy appear. All early descriptions stress the involvement of older females and localization to the shoulder joint.

The association of intraarticular deposits of BCP crystals with joint disease is much more recent. The presence of solid deposits of BCP crystals in the menisci of postmortem knees was noted in 1966, but it was not until 1976 that the first description of BCP crystals in degenerative joint diseases was recorded. Clumps of BCP crystals were discovered in the synovial fluid of patients with osteoarthritis (OA) via analytic electron microscopy, a finding that was confirmed by others. In 1981, McCarty’s group described a similar large-joint destructive arthropathy, seen most commonly in the shoulder joints of older women, and called it Milwaukee shoulder . They noted the presence of large quantities of BCP crystals associated with collagenase in synovial fluid and hypothesized that the BCP crystals caused the associated joint destruction. Subsequently, others noted that many large joints could be involved, and terms such as apatite-associated destructive arthritis and idiopathic destructive arthritis of the shoulder were added to the list of names. BCP crystals were also described in the joint fluid of a few patients with acute synovitis and other forms of arthropathy.

Calcific Periarthritis

Few systematic studies of the incidence or prevalence of juxtaarticular deposits of BCP crystals have been done. These deposits are often asymptomatic and most commonly noted by chance on a radiograph obtained for other reasons ( Fig. 197.1 ). In a unique, large study of office workers published in 1941, a 2.7% prevalence of shoulder deposits was noted in a North American, predominantly White population, 34% to 45% of which were associated with clinical problems. Women were affected more often than men, and the prevalence was highest in those between 31 and 40 years of age (19.5%). No comparable epidemiologic data have been reported subsequently, although a number of smaller pathologic or radiographic studies have documented the relatively high frequency of periarticular calcification. Calcific periarthritis has been reported in children as young as 3 years but appears to be uncommon in older adults. This suggests that many of the deposits seen in young adults must disappear spontaneously.

Articular Calcification

Whereas the prevalence of BCP crystals in normal joints in different age groups is not known, the association between BCP crystals and OA is well described. In a case series of 120 patients with knee OA undergoing joint replacement surgery, cartilage mineralization in the form of BCP crystal deposition was detected in all cases. BCP crystals have also been detected in the synovial fluid of patients with mild, moderate, and severe knee OA undergoing arthroscopy, and their presence appears to correlate strongly with the degree of radiographic severity. Milwaukee shoulder syndrome and the related BCP crystal–associated destructive arthropathies are uncommon, tend to occur in older adult individuals, and are of unknown prevalence.

Calcific Periarthritis

Periarticular calcific deposits are often asymptomatic. However, they are also associated with a number of clinical syndromes ( Table 197.1 ). The most striking clinical finding is acute calcific periarthritis, which most commonly involves the shoulder but can occur in almost any joint. The episode may be preceded by mild trauma or overuse, but most cases have a spontaneous onset.

Patients report sudden onset of severe pain, and within hours the affected part is usually swollen with redness and warmth of the overlying skin. There is extreme local tenderness and associated loss of function. The pain is most marked around the subacromial region and radiates down the outside of the arm. Glenohumeral movement is usually severely restricted. Severe pain may last for several days, but the symptoms then generally resolve slowly over a period of 2 to 3 weeks. A “frozen shoulder” may result.

Calcific periarthritis is thought to be caused by rupture of a calcific deposit into an adjacent soft tissue space or bursa along with initiation of an acute inflammatory reaction. The crystals may induce intense inflammation in the subacromial bursa ( Fig. 197.2 ). Radiographically, calcium deposits appear dense with well-defined borders before an attack. With the onset of an attack, however, these calcific deposits appear fluffy with poorly defined margins. Ultimately, there is a reduction in the size of the deposit seen radiographically, and it may disappear completely.

Calcific deposits in periarticular tissues are also associated with chronic pain syndromes without a history of a previous acute episode. However, in the shoulder, because both chronic shoulder pain and calcification are common and because previous damage to tendons may predispose to calcification, it is difficult to define what contribution, if any, the deposits themselves make to the clinical findings. Moderate to severe pain is described, with varying degrees of tenderness and restriction of motion. Pain usually radiates to the insertion of the deltoid and sometimes beyond to the forearm. Lying on the affected shoulder is painful and may interfere with sleep. In some patients, recurrent acute attacks around the shoulder, separated by pain-free periods lasting months or years, are followed by the development of chronic pain. Damage to the tendons and muscles of the rotator cuff may result and lead to total disruption of the cuff apparatus.

The shoulder is the most commonly affected site followed by the hip, knee, elbow, wrist, and ankle joints. The joints of the feet and toes are less commonly involved (<1% of all reported cases), as are those of the hands and fingers. Hydroxyapatite pseudopodagra is a term used to describe acute calcific arthritis involving the first metatarsal phalangeal joint, usually in young women. Acute neck pain attributed to calcifications surrounding the odontoid process has been described and called the crowned dens syndrome . Calcifications appear to be composed of apatite, calcium pyrophosphate (CPP), or a combination of both.

In some patients with multifocal deposits, symptoms develop at several sites, thus suggesting a more generalized condition rather than a chance localized process with resultant calcification. This manifestation can cause diagnostic confusion and may even mimic a seronegative polyarthritis. Several reports have described familial occurrences of calcific periarthritis.