Ann Rheum Dis: first published as 10.1136/ard.42.Suppl_1.49 on 1 January 1983. Downloaded from

Ann Rheum Dis (1983), 42, Supplement p 49

Calcified tendinitis: a review

G. FAURE,' G. DACULSI2 From the 'Clinique Rhumatologique et Laboratoire d'immunologie, Faculte A de Medecin, Universite de Nancy I, 54500 Vandoeuvre les Nancy, France and 2U225 INSERM, Faculte de Chirurgie Dentaire, Place Alexis Ricordeau, 44042 Nantes, France

Introduction Calcified tendinitis in clinical practice

Calcified tendinitis is a common CLINICAL FEATURES disorder. Many names have been used According to Welfling calcific to describe it: some of them, such as periarthritis is responsible for 7% of 'calcific periarthritis', emphasise the painful shoulder syndromes,' which extra-articular site of the deposit; have various presentations. others, such as 'periarticular apatite (1) Chronic symptoms-more or deposition', mention the nature of the less severe pain; tenderness leading to compound found in the calcification; various degrees of incapacitation. and more recent ones, such as These symptoms induce the demand 'calcifying tendinitis',-'3 emphasise the. for radiographs, which reveal the Fig. 1 Calcific periarthritis ofthe active process that might explain the presence of deposits. shoulder. Calcification is obvious; it deposition. Differentiated from (2) Acute inflammatory crisis with has already migrated from copyright. arthritis at the end of the nineteenth severe pain, tenderness, and local supraspinatus region to bursa area. century, this syndrome has only oedematous inflammation sometimes recently been related to the presence leading to restricted active an*d passive of apatite in tendon sheaths.4'5 It can motion. Fever and malaise may be affect almost any tendon at its observed. usually varies between a few insertion and is most common around (3) Totally asymptomatic deposits. millimetres and about 1-5 cm. Calcification has been described the shoulder joint. Rheumatologists According to Bosworth et al., near almost every joint"2 although the and radiologists have often described clinical symptoms occur in from 34% this shoulder abnormality, leading to to 45% of patients in whom precise intratendinous or paratendinous location of the stone is its progressive differentiation from calcifications are found.' Biochemical not always seen. The deposits may be other painful shoulder syndromes. 12 and haematological tests are not This review will discuss calcific useful, and will only show non-specific multiple,'4 which French authors http://ard.bmj.com/ periarthritis of the shoulder as a evidence of inflammation. identify as 'maladie des calcifications model. Clinical features of the tendineuses multiples'.' 1" Bilateral syndrome are variable and include calcification is seen in about half of pain and inflammation. The key RADIOLOGICAL FEATURES shoulder cases and deposits are often diagnostic feature is the radiograph. Simple anteroposterior and lateral seen in other locations-for example, Clinical evolution is simple and the x-ray films are usually sufficient to see near the hip joint-if other condition often resolves shoulder calcification, though special radiographs are taken. views in internal or external spontaneously. Some cases are rotation on October 2, 2021 by guest. Protected persistent and may require aggressive may be necessary.'2 Other techniques treatment, including surgery. have been described to obtain better Numerous questions are still pick up, including xerography and unanswered about this disorder, which scanning, but many small deposits are is rarely associated with metabolic probably missed. abnormalities of calcium and The calcification is usually in the phosphorus. These include: (a) the supraspinatus tendon, and various nature of the mechanism leading to appearances have been described. The calcium salt deposition; (b) the deposits may be very thin, outlining frequent asymptomatic tolerance of the tendon sheath, or hazy, and they such calcification, and, conversely, (c) vary in density and definition (Fig. 1). the initiating agent of inflammatory Only in cases of disturbance of the Fig. 2 Acute bursitis ofthe shoulder flares; and (d) the way in which the calcium to phosphorus ratio-for (same patient). Morphological aspects material disperses. example hyperparathyroidism ofprevious calcification is modified; it secondary to renal failure-is there is less dense and probably located Request for reprints to: G. Faure. massive calcification.'3 The size inside bursa. Ann Rheum Dis: first published as 10.1136/ard.42.Suppl_1.49 on 1 January 1983. Downloaded from

Suppl p 50 Annals of the Rheumatic Diseases

Sequential x-ray films may show or articular origin present with prove necessary, and some authors static calcification, a growing deposit, different symptoms. Analysis of fluid recommend adding colchicine as in change in the location, and even and radiological investigations are also gout and pseudogout. Aspiration of spontaneous disappearance without discriminative. Extra-articular fluid may also reduce symptoms. Local any acute clinical flare. During the ossification is radiologically different, injections of corticosteroids are used inflammatory crisis, the calcifications the deposits being trabeculated. and by some clinicians, but may themselves usually follow a very well described articular chondrocalcinosis also cause microcrystal-induced course. They become less defined, appears quite different on a inflammation, and the risk of infection more cloudy, and migrate into the radiograph. Tendinous calcification must be taken into account. Lavage bursa (Figs. 2 and 3); they may or may containing calcium pyrophosphate between attacks has been advocated, not disappear completely within a few dihydrate may be misleading2" but but does not always seem rewarding. days or weeks. The reappearance of is usually associated with Very painful resistant cases have calcification is not well substantiated chondrocalcinosis. received x-rav treatment. Calcium (Fig. 4). Some authors emphasise the inhibitors have also been tried but the relation of the deposit to the bone TREATMENT results are not convincing. surrounding the tendon insertion As both symptoms and deposits often Surgery may prove successful, and a point.17 Destructive changes have disappear spontaneously, both few well documented cases treated by been reported in advanced cases, and clinician and patient should generally surgical removal of the deposit have McCarty et al. have described a special abstain from interfering. Analgesics been described.:' syndrome associating a destructive and non-steroidal anti-inflammatory arthropathy of the shoulder, apatite drugs (NSAID) are useful, as well as LABORA1 ORY INVESTIGATIONS deposits. and high collagenase patience. The material aspirated from acutely activities in the synovial fluid. They During an acute inflammatory crisis painful shoulders has been studied call it the 'Milwaukee shoulder more powerful NSAID drugs such as thoroughly in a few cases, with syndrome'. 19 indomethacin or phenylbutazone may interesting results. Firstly. they

DIFFERENI IAL D)IAGNOSIS The diagnosis is usually easy. Other copyright. painful shoulder syndromes of osseous http://ard.bmj.com/

Fig. 3 Sanme patient one month later. Calcification has comnpletel/v disappeared, though vestigial one remains in the supraspinatus region. on October 2, 2021 by guest. Protected

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Fig. 4 Same patient one year later. Calcification has reappeared, patient Fig. 5 Scanning electron microscopy. Bar 5 in. One globule-like structure is presents with a moderately painful seen here in situ in section ofa tendon sheath calcification, appearing like a stone shoulder. engulfed in mortar. Ann Rheum Dis: first published as 10.1136/ard.42.Suppl_1.49 on 1 January 1983. Downloaded from

Calcified tendinitis: a review Suppl p 51 allowed the identification of the in mortar (Fig. 5). Study of individual carbonate apatite,26" but the great material.4 Recent studies by our group crystals needed even more heterogeneity of the material is a new have also isolated another compound, sophisticated means. Transmission feature that may open new fields of unidentified so far, which is different electron microscopy (TEM) allows the research. The differences observed from stoichiometric apatite, and could visualisation, on ultrathin sections, of between patients also deserves study. be the result rather than the cause of dense globular structures among The exact location of deposits is not the inflammation.2' numerous isolated or clumped crystals well elucidated, but Welfling describes The usual specimens obtained at (Fig. 6). Individual crystals may be some as intratendinous and some operation consist of a gritty mass of seen in high resolution transmission superficial.9 sandy material or a toothpaste-like electron microscopy. The crystals are Sandstrom described necrosis fluid. These have been recognised much larger than classic apatite crys- interpreted as being secondary to since Codman first described the tals, such as those observed in bone or 'local anaemia and vascular changes', calcifications, and in 1934 the deposits dental enamel; some ofthem appear as which favoured deposition of were described as 'a white amorphous homogeneous hexagons, the width and calcifying material.7 Uhthoff's group mass composed of many small round thickness of which can be measured. favour an active mechanism of or ovoid bodies'.6 Microscopically, at The parameters differ from one calcification, with an initial cartilage low magnification, calcifications patient to another. Some of them have degeneration of the tendon followed appear as shiny amorphous coins (in a clear cut edges, while others seem to by calcification of the transformed liquid phase).4 possess some sort of coating; defects tissue.'` They describe four stages in Physical studies first used x-ray can also be seen in several crystals the calcifying process: precalcific diffraction then infrared spectrometry. (Fig. 7). phase; calcific phase; resorptic phase; McCarty et al.4 and Thompson et al.5 Interplanar spacings may sometimes and repair phase. These four patterns identified an apatite compound by be measured, and are consistent with may occur concomitantly in an x-ray diffraction, and infrared these parameters in stoichiometric individual patient. This hypothesis spectrometry showed that it was a hydroxyapatite. These isolated would explain the heterogeneity and carbonated apatite.22 This has been crystals are, however, different from pleomorphic nature of the lesions, but other physical means the globular material. Wavelength the so-called 'resorptive phase' seems confirmed by copyright. such as thermogravimetry.22 Our dispersive spectrometry in a scanning arguable, particularly because of the results are similar but it should be mode gave calcium to phosphorus very small number of cells observed. noted that all these methods consider molar ratios in both globules and Using TEM, the same group studied the material as a whole and do not isolated crystals not statistically the ultrastructural localisation of allow definition of individual particles. different from control geological calcium in tendinitis. They found it in Scanning electron microscopy apatites, but similar microanalysis in a matrix vesicle-like structures seen allowed us to have a closer look at the transmission mode provided lower either singly among collagen or in external aspect of deposits24-25; we ratios, with differences between the aggregates.2"2' observed an extremely heterogeneous inside and outside of globular bodies. material, composed of globular bodies All these techniques identified the Discussion

looking like large rocky bulks engulfed material of calcific deposits as calcium http://ard.bmj.com/ New light should soon be shed on calcification in several aspects: (a) better identification of the calcifying processes; (b) more knowledge on epidemiology; (c) better definition of the nature of the compounds, hopefully leading to understanding of

the aetiopathological mechanisms of on October 2, 2021 by guest. Protected the disease. The identification of deposits has improved since the features of the condition have become recognised, and should be made even easier by further technical improvements allowing visualisation of tiny calcifications. This should help define the epidemiology and explain apparent differences in the incidence and age of onset between France and Britain. So far, only one epidemiological study has been performed in the United States.? The Fig. 6 Transmission electron microscopy. Bar =5 p.m. Dense globularstructures existence of a possible genetic link ofvarious size among scattered isolated crystals. should also be re-evaluated,3' in spite Ann Rheum Dis: first published as 10.1136/ard.42.Suppl_1.49 on 1 January 1983. Downloaded from

Suppi p 52 Annals ofthe Rheumatic Diseases

diseases such as hyperparathyroidism, hvpervitaminosis D, collagen vascular disease, and the milk alkali syndrome. Is The exact incidence of other types of deposits such as pyrophosphate, reported in tendons by Gerster,2" should also be examined. Several aetiopathological schemes have already been proposed.' 2 7 15 16 35 The classic hypothesis favours a local and initial necrosis of the tendon. leading to the deposition of calcified material. However, some calcifications obviously occur in the absence of anv necrotic phenomenon. A more recent idea, based on histological and ultrastructural observations, suggests the occurrence of an initial cartilage metaplasia of the tendon, followed by an active multifocal and cell-mediated calcifying process. The intracellular or extracellular site of the first deposit is not completely clear and requires an ultrastructural or physical study of collagen fibres.

Some other mvsterious features copyright. remain for example, why should calcifications be most common around the supraspinatus tendon? How can the long-lasting tolerance of some deposits be explained, while others lead to acute crisis? What is the initiating mechanism in these acute episodes? Does it involve a

...... modification of the physicochemical structure of the material or a change in

its microenvironment? How is it that http://ard.bmj.com/ some pathological, and eventually painful, deposits disappear spontaneously? Experimental models aid understanding of some of these problems. For instance, synthetic Fig. 7 High resolution transmission electron microscopy. Bar= 0 01 ,um. Single apatite crystals and/or natural apatites hexagonal crystal ofapatite presenting a coat on its surface. have phlogistic properties in on October 2, 2021 by guest. Protected inflammation models.:"- A thorough ot the negative results of the HLA The physicochemical findings in the study of the macrophage in such studies already published.'6 past few years have been rewarding. In models might help us to understand Associations have been reported a recent review, Legeros brings many how calcified material can disappear. between calcifications and several data favouring a calcium This could also be elucidated by diseases: diabetes, thyroid disorders, carbonate/apatite composition for metabolic studies if a dissolution and others.3' A metabolic link was also heterotopic calcifications in man." process takes place in these noted between calcifications, uraemia, Our results, however, made it obvious phenomena. and haemodialysis.32 33 Finally, that there is a high degree of More sophisticated models are Bosworth suspected the influence of heterogeneity in these compounds and obviously necessary, if not to explain repetitive motion performed in a that the answer is probably not that all the mysterious events of this professional context.' The relationship simple. Every possible analytical and syndrome, at least to define new between shoulder use and the microscopical means should be used to preventive or curative treatments, or appearance of calcification is not well study all types of calcification. It might both. Special care should, however, be documented and should be be rewarding to compare idiopathic taken in extrapolating such results to re-examined. deposits with those found in other human disease,39- 42 mainly because, to Ann Rheum Dis: first published as 10.1136/ard.42.Suppl_1.49 on 1 January 1983. Downloaded from

Calcified tendinitis: a review Suppl p 53

our knowledge, no similar disease is Rev Rhum Mal Osteoartic 1965; 32: systems. Progress in Crystal Growth and described in veterinary publications, 325-34. Characterization 1981; 4: 1-45. 28 Sarkar K, Uhthoff H K. Ultrastructural implying that metabolic pathways may 16 Amor B, Kahan A, Cherot A, Delbarre F, Rabaud M, Aubouy G. Le localization of calcium in calcifying be very different in man and in rhumatisme a hydroxyapatite (la tendinitis. Arch Pathol Lab Med 1978; animals. maladies des calcifications tendineuses 102: 266-9. multiples). II. Etude microscopique. 29 Dereszewski G, Howell D S. The role of References Antigene HLA arthrite experimentale. matrix vesicles in calcification. Trends in Pathogenie. Rev Rhum Mal Osteoartic Biochemical Sciences 1978; 3: 151-2. 1 Uhthoff H K. Calcifying tendinitis an 1977; 44: 309-16. 30 Cannon R B, Schmid F R. Calcific active cell mediated calcification. 17 Meneghello A, Bertoli M, Romagnoli G periarthritis involving multiple sites in Virchows Arch [PatholAnat] 1975; 366: F. Unusual complication of soft tissue identical twins. Arthritis Rheum 1973; 51-8. calcifications in chronic renal disease 16: 393-6. 2 Uhthoff H K, Sarkar K, Maynard J A. the articular erosions. Skeletal 31 Wright V, Haq A M. Periarthritis of the Calcifying tendinitis. A new concept of Radiology 1980; 5: 251-2. shoulder. I. Aetiological considerations its pathogenesis. Clin Orthop 1976; 118: 18 McCarty D J, Halverson P B, Carrera with particular reference to personality 164-8. G F, Brewer B J, Kozin F. 'Milwaukee factors. Ann Rheum Dis 1976; 35: 3 McKendry R J R, Uhthoff H K, Sarkar shoulder': association of 213-9. K, Hyslop P S G. Calcifying tendinitis of microspheroids containing hydroxy 32 Caner J E Z, Decker J L. Recurrent the shoulder: prognostic value ofclinical apatite crystals, active collagenase and acute (gouty) arthritis in patients with histologic and radiologic features in 57 neutral protease with rotator cuff chronic renal failure treated with surgically treated cases. J Rheumatol defects. I Clinical aspects. Arthritis periodic hemodialysis. Am J Med 1964; 1982; 9: 75-80. Rheum 1981; 24: 464. 36: 571-82. D Gatter R A. Recurrent 33 Moskowitz R W, Vertes V, Schwartz A, 4 McCarty J, 19 Halverson P B, Cheung H S, McCarty D Marshall G, Friedman B. Crystal- acute inflammation associated with J, Garancis J C, Mandel N. 'Milwaukee induced inflammation associated with focal apatite crystal deposition.Arthritis shoulder': association of 9: 804-19. chronic renal failure treated with Rheum 1966; microspheroids containing hydroxy periodic hemodialysis.Am J Med 1969; 5 Thompson G R, Ming Ting Y, Riggs G apatite crystals, active collagenase and 47: 450-60. A, Fenn M E, Denning R M. Calcific neutral protease with rotor cuff defects. 34 Legeros R Z, Legeros J P. Phosphate and soft tissue calcification tendinitis II. Synovial fluid studies. Arthritis minerals in human tissues. In: Nriago J, resembling gout. JAMA 1968; 203: Rheum 1981; 24: 474-83. Moore P, eds. Phosphate mineral. (in copyright. 464-72. 20 Gerster J C, Baud C A, Lagier R, press). 6 Codman E A. The shoulder. Boston: Boussina I, Fallet G H. Tendon 35 Urist R, Moss M J, Adam J M. Thomas Todd, 1934. calcifications in chondrocalcinosis. A Calcification oftendon. A triphasic local 7 Sandstrom C. Peridentinis calcarea. A clinical, radiologic, histologic and mechanism. Archives of Pathology common disease of middle life. Its crystallographic study. Arthritis Rheum 1964; 77: 594-608. diagnosis pathology and treatment. AJR 1977; 20: 717-22. 36 Denko C W, Petricevic M. 1938; 40: 1-21. 21 Faure G, Daculsi G, Netter P, Gaucher Hydroxyapatite crystals-induced 8 Bosworth B M. Calcium deposits in the A, Kerebel B. Apatites in heterotopic inflammation and prostaglandin El. J shoulder and subacromial bursitis. A calcifications. Scanning Electron Rheumatol 1979; 6: 117-23. survey of 12,222 shoulders. JAMA Microscopy (in press). 37 Glatt M, Dieppe P, Willoughby D. 1941; 116: 2477-82. 22 Legeros R Z, Contiguglia S R, Alfrey A Crystals-induced inflammation, enzyme 9 Welfling J. Les calcifications de release and the effects ofdrugs in the rat http://ard.bmj.com/ l'6paule. I Diagnostic clinique. Rev C. Pathological calcifications associated with uremia: 2 types of calcium pleural space. J Rheumatol 1979; 6: Rhum Mal Osteoartic 1964; 31: 265-71. 251-8. F Dixon A phosphate deposits. Calcif Tissue Res 10 Swannell AJ, Underwood A, 1973; 13: 173-7. 38 Cheung H S, Halverson P B, McCarty D S J. Periarticular calcific deposits J. Release of collagenase neutral mimicking acute arthritis. Ann Rheum 23 Saez-Clavere L, Legros R, Arlet J, Bonel G. Etude cristallochimique de protease, and prostaglandins from Dis 1970; 29: 380-5. cultured mammalian synovial cells by 11 Fam A G, Pritzker K P H, Stein J L, deux calcifications sous deltoidiennes. Rev Rhum Mal Osteoartic 1980; 47: hydroxyapatite and calcium Houpt J B, Little A H. Apatite pyrophosphate dihydrate crystals. associated a clinical 383-92. arthropathy: study Arthritis Rheum 1981; 24: 1338-44. on October 2, 2021 by guest. Protected of 14 cases and of 2 patients with calcific 24 Faure G, Netter P, Coxam B, Raul P, Pourel J, Gaucher A. Place de l'apatite 39 Luben R A, Sherman J K, Wadkins C L. bursitis. J Rheumatol 1979; 6: 461-71. Studies of the mechanism of biological 12 Resnick D. Calcium hydroxyapatite en pathologie microcristalline. Annales Medicales de Nancy 1979; 18: 1281-4. calcifications. IV. Ultrastructural crystal deposition disease. In: Resnick analysis of calcifying tendon matrix. D, Niwayama G, eds. Diagnosis ofbone 25 Faure G, Netter P, Malaman B, Calif Tissue Res 1973; 11: 39-55. and joint disorders. Philadelphia: W B Steinmetz J, Duheille J, Gaucher A. 40 Bridges J B, McClure J. Experimental Saunders, 1981: 1575-97. Scanning electron microscopic study of calcifications in a number of species. 13 Smith F W, Junor B J R. Peri-articular microcrystals implicated in human Calif Tissue Res 1972; 10: 136-49. calcification with fluid levels in rheumatic diseases. Scanning Electron 41 McClure J, Gardner D L. The secondary hyperparathyroidism. Br J Microscopy 1980; II: 163-76. production ofcalcification in connective Radiol 1978; 51: 741-2. 26 Montel G, Bonel G, Trombe J C, tissue skeletal muscle using various 14 Pinals R S, Short C L. Calcific Heughewaert J C, Rey C. Progres dans chemical compounds. Calif Tissue Res periarthritis involving multiple sites. le domaine de la chirnie des composes 1976; 22: 129-35. Arthritis Rheum 1966; 9: 566-74. phrophores solides a structure d'apatite. 42 Doyle D V, Dunn C J, Willoughby D A. 15 Welfling J, Kahn M F, Desroy M, Application a la biologie et au Potassium permanganate induced Paolaggi J B, de Seze S. Les traitement des minerais. Pure and calcergy. A model to study the effects of calcifications de l'6paule. II. La maladie Applied Chemistry 1980; 52: 973-87. drugs on hydroxyapatite crystal des calcifications tendineuses multiples. 27 Legeros R Z. Apatites in biological deposition. J Pathol 1979; 128: 63-70.