Title: Joint Injection (A Current Concept Review)
Author(s): Mehrnoush Hassas Yeganeh MD *, Touraj Shafaghi MD, Mohamad Qoreishy MD
Shahid Beheshti University of Medical Sciences, Tehran, Iran
* Corresponding Author
Vol 2, Num 2, April 2015
Classification of Joints
Joints may be classified as fibrous, cartilaginous, or synovial. Fibrous joints (synarthroses) are those in which little or no motion occurs, and the bones are separated by fibrous connective tissue. Cartilaginous joints (amphiarthroses) are those in which little or no motion occurs, but the bones are separated by cartilage. Diarthrodial joints are those in which considerable motion occurs, and a joint space lined with a synovial membrane is present between the bones. The synovial joint is the site of inflammation in most of the chronic arthritides of childhood. Diarthrodial joints may be further classified according to their shape.
Anatomy of Synovial Joints
The bones of the articular surfaces of diarthrodial (synovial) joints are usually covered by hyaline cartilage. The synovial membrane attaches at the cartilage–bone junction so that the entire joint “space” is surrounded by either hyaline cartilage or synovium.(Figure 1) The temporomandibular joint is unusual in that the surface of the condyle is covered by fibrocartilage (fibroblasts and type I collagen).
In the sacroiliac joint, the sacral side is covered by thicker hyaline cartilage, whereas the iliac side of the joint is covered by fibrocartilage. In some synovial joints, intraarticular fibrocartilaginous structures are present. A disk (or meniscus) separates the temporomandibular joint into two spaces; the knee joint contains two menisci that separate the articular surfaces of the tibia and femur; and the triangular fibrocartilage of the wrist joins the distal radioulnar surfaces. Other intraarticular structures include the anterior and posterior cruciate ligaments of the knee, the interosseous ligaments of the talocalcaneal joint, and the triangular ligament of the femoral head. These structures are actually extrasynovial, although they cross through the joint space.
The hyaline cartilage, which covers subchondral bone, facilitates relatively frictionless motion and absorbs the compressive forces generated by weight-bearing. The cartilage is firmly fixed to subchondral bone in adults by collagen fibrils, although there is little collagen at the osteochondral interface in the growing child. Its margins blend with the synovial membrane and the periosteum of the metaphysis of the bone. In children hyaline cartilage is white or slightly blue and is somewhat compressible.
It is composed of chondrocytes within an extracellular matrix (ECM) and becomes progressively less cellular throughout the period of growth; the cell volume in adult articular cartilage is less than 2%. The matrix consists of collagen fibers, which contribute to tensile strength and ground substance composed of water and proteoglycan, which contributes resistance to compression.
Articular hyaline cartilage is organized into four zones. Zones 1, 2, and 3 represent a continuum from the most superficial area of zone 1, in which the long axes of the chondrocytes and collagen fibers are parallel to the surface; through zone 2, in which the chondrocytes become rounder and the collagen fibers are oblique; to zone 3, in which the chondrocytes tend to be arranged in columns perpendicular to the surface.
The tidemark, a line that stains blue with hematoxylin and eosin, separates zone 3 from zone 4 and represents the level at which calcification of the matrix begins. Chondrocytes in each of the cartilage zones differ not only in appearance but also in metabolic activity, gene expression, and response to stimuli.
In the child end-capillaries proliferate in zone 4, eventually leading to replacement of this area by bone. This is probably the manner in which the chondrocytes are nourished, although, in the adult, constituent replacement (through the exchange of synovial fluid [SF] with cartilage matrix) may play the predominant role.
Chondrocytes are primarily mesodermal in origin and are the sole cellular constituents of normal cartilage. Their terminal differentiation determines the character of the cartilage (hyaline, fibrous, or elastic). This complex process has been recently reviewed. Chondrocytes in articular cartilage persist and do not ordinarily divide after skeletal maturity is attained. Those in the epiphyseal growth plate differentiate to facilitate endochondral ossification, after which they may undergo apoptosis or become osteoblasts.
Chondrocytes are responsible for the synthesis of the two major constituents of the matrix, collagen and proteoglycan, and enzymes that degrade matrix components (collagenase, neutral proteinases, and cathepsins). This dual function places the chondrocyte in the role of regulating cartilage synthesis and degradation. Immediately surrounding the chondrocyte is the pericellular region, which contains type VI collagen and the proteoglycans decorin and aggrecan. Chondrocytes in zone 1 produce superficial zone protein (lubricin), which is important in maintaining relatively frictionless joint motion. Synthesis of this protein is defective in the camptodactyly-arthropathy-coxa vara-pericarditis syndrome.
Extracellular Matrix (ECM)
The ECM of hyaline cartilage consists of collagen fibers, which contribute tensile strength, water, diverse structural and regulatory proteins, and proteoglycans (mainly aggrecan). The ECM is heterogeneous and can be subdivided into three compartments. A thin inner rim of aggrecan-rich matrix surrounds the chondrocytes and lacks cross-linked collagen. An outer rim contains fine collagen fibrils.
The remainder of the ECM consists primarily of aggrecan, which binds via the link protein to hyaluronan. The endoskeleton of hyaline cartilage consists of a network of collagen fibrils, 90% of which are type II collagen, with minor components of collagen types IX and X.
Proteoglycans are macromolecules consisting of a protein core to which 50 to 100 unbranched glycosaminoglycans (chondroitin sulfate [CS] and O-linked keratan sulfate [KS]) are attached. At least five different protein cores have been defined. The principal proteoglycan of hyaline cartilage is called aggrecan. Its attachment to hyaluronan is stabilized by link protein to form large proteoglycan aggregates with molecular weights of several million. With increasing age, the size of the proteoglycan aggregate increases, the protein and KS content increase, and the CS content decreases.
CS chains also become shorter with increasing age, and the position of the sulfated moiety changes, from a combination of 4-sulfated and 6-sulfated N-acetylgalactosamine at birth to mainly 6-sulfated N-acetylgalactosamine in the adult. Dermatan sulfate and chondroitin-4-sulfate are the principal mucopolysaccharides in skin, tendon, and aorta; heparan sulfate is present in basal lamina. The significance to inflammatory joint disease, if any, of these and other age-related changes, is unknown.
Collagens, the most abundant structural proteins of connective tissues, are glycoproteins with high proline and hydroxyproline content. Many are tough, fibrous proteins that provide structural strength to the tissues of the body. There are at least 29 different collagen α chain trimers grouped into three major classes: fibril forming, fibril-associated collagens with interrupted triple helices (FACIT), and non-fibril forming.
Types I, II, and III are among the most common proteins in humans. Type II collagen, the principal constituent that accounts for more than one half the dry weight of cartilage, is a trimer of three identical α-helical chains. Collagen types III, VI, IX through XII, and XIV are all present in minute quantities in the mature cartilage matrix. The content of types IX and XI collagen is greater in young animals (20%) than in mature animals (3%).
Collagen synthesis is minimal in the mature animal. The degree of stable crosslinking of collagen fibers increases with advancing age up to the fourth decade of life. This results in increased resistance to pepsin degradation and may contribute to the increased rigidity and decreased tensile strength of old cartilage. Collagen undergoes extensive changes in primary and tertiary structure after it is secreted from the fibroblast into the extracellular space as a triple-helical procollagen.
Specific peptidases cleave the amino and carboxyl extension peptides, yielding collagen molecules that form crosslinks and fibrils via lysyl and hydroxylysyl residues in some types. Glycosylation also occurs at this posttranslational stage. Collagen genes are named for the type of collagen (e.g., COLI) and the fibril (e.g., A1), and they encode the large triple-helical domain common to human collagens. Mutations in the collagen genes account for human diseases, such as Ehlers-Danlos syndrome and osteogenesis imperfect.
Other Connective Tissue Constituents
In addition to collagens, a number of specialized tissues derived from embryonic mesoderm contribute to connective tissue structures other than cartilage. Elastin occurs in association with collagen in many tissues, especially in the walls of blood vessels and in certain ligaments. Fibers of elastin lack the tensile strength of collagens but can stretch and then return to their original length. Elastin is produced by fibroblasts and by smooth muscle cells.
Fibronectin is a dimeric glycoprotein with a molecular weight of 450,000 that acts as an attachment protein in the ECM. It is produced by many different cell types, including macrophages, dedifferentiated chondrocytes, and fibroblasts, and has the ability to bind to collagens, proteoglycans, fibrinogen, actin, and to cell surfaces and bacteria. Fibronectin is present in plasma and as an insoluble matrix throughout loose connective tissues, especially between basement membranes and cells.
Laminin is a major constituent of the basement membrane together with type IV collagen. Reticulin may be an embryonic form of type III collagen. It is present as a fine branching network of fibers widespread in the spleen, liver, bone marrow, and lymph nodes.
The synovial membrane is a vascular connective tissue structure that lines the capsules of all diarthrodial joints and has important intraarticular regulatory functions. The synovium consists of specialized fibroblasts, one to three cells in depth, overlying a loose meshwork of type I collagen fibers containing blood vessels, lymphatics, fat pads, unmyelinated nerves, and isolated cells such as mast cells. There is no basement membrane separating the joint space from the subsynovial tissues.
The synovial membrane is discontinuous, and within the joint space there are so-called bare areas between the edge of the cartilage and the attachment of the synovial membrane to the periosteum of the metaphysis. These bare areas are especially vulnerable to damage (erosion) by inflamed synovium (pannus) in inflammatory joint diseases. Folds, or villi, of synovium provide for unrestricted motion of the joint and for augmented absorptive area.
The synoviocytes are of two predominant types, a subdivision that may reflect different functional states rather than different origins. Synovial A cells are capable of phagocytosis and pinocytosis, have numerous microfilopodia, a prominent Golgi apparatus, and synthesize hyaluronic acid. Synovial B cells are more fibroblast-like, have a prominent rough endoplasmic reticulum, and synthesize fibronectin, laminin, types I and III collagen, enzymes (collagenase, neutral proteinases), and catabolin.
Synovial Fluid (SF)
SF, present in very small quantities in normal synovial joints, has two functions: lubrication and nutrition. Normal fluid is clear and pale yellow; SF is a combination of a filtrate of plasma, which enters the joint space from the subsynovial capillaries, and hyaluronic acid, which is secreted by the synoviocytes. Hyaluronic acid provides the high viscosity of SF and, with water, its lubricating properties.
Concentrations of small molecules (electrolytes, glucose) are similar to those in plasma, but larger molecules (e.g., complement components) are present in low concentrations relative to plasma unless an inflammatory state alters vasopermeability. Notably absent from SF are elements of the coagulation pathway (fibrinogen, prothrombin, factors V and VII, tissue thromboplastin, and antithrombin). As a result, normal SF is resistant to clotting. There appears to be free exchange of small molecules between SF of the joint space and water bound to collagen and proteoglycan of cartilage.
Synovium lines bursae, tendon sheaths, and joints. Bursae facilitate frictionless movement between surfaces, such as subcutaneous tissue and bone, or between two tendons. Bursae located near synovial joints frequently communicate with the joint space. This is particularly evident at the shoulder, where the subscapular bursa or recess communicates with the glenohumeral joint; and around the knee, where the suprapatellar pouch, the posterior femoral recess, and occasionally other bursae communicate with the knee joint.
Tendon sheaths lined with synovial cells are prominent around tendons as they pass under the extensor retinaculum at the wrist and at the ankle. Although they are closely associated with joints, tendon sheaths do not communicate with the synovial space.
Joint aspiration and injection
Scientific efforts have been made for arthrocentesis and synovial fluid analysis since 1930s. these results have been published in two invaluable books: 1) Pemberton's first US rheumatology textbook in 1935. and 2) Ropes' book, a compilation of twenty years of clinical experience, which was published in 1953.
Of the substances were injected into joints during the early years of the 20th century; Formalin and glycerin, lipiodol, lactic acid, and petroleum jelly could be named.
Arthritis, which may be traumatic or inflammatory. Inflammatory arthritis, such as rheumatoid, is probably the most.
Pain is felt over the elbow and, depending on the severity, may be referred into the forearm. If traumatic in origin the possibility of fracture will need to be excluded.
On examination, there will be a capsular pattern of more limitation of flexion than extension, with the flexion having an abnormal hard end-feel. The superior radioulnar joint may be involved, since it shares a common capsule with the elbow joint proper. The capsular pattern at the superior radioulnar joint is pain felt at the end of range of both rotations.
Treatment by injection
Despite the complicated anatomical structure of the elbow joint, a bolus injection via the radiohumeral articulation is the easiest intra-articular route.(Figure 2) The corticosteroid injection aims to reduce pain and inflammation, allowing recovery of the range of movement.
INFERIOR (DISTAL) RADIO-ULNAR JOINT
Arthritis, most commonly rheumatoid arthritis at this Joint, although traumatic arthritis may also cause symptoms.
The patient complains of pain felt in the lower forearm. On examination, a capsular pattern is present with pain reproduced at the end of both extremes of passive pronation and supination. Limitation of these movements is not usually found, except in advanced cases of arthritis.
Treatment by injection
A bolus injection of corticosteroid aims to reduce inflammation and pain.(Figure 3)
Arthritis, most commonly rheumatoid arthritis at this joint, although traumatic arthritis may also cause symptoms. If the lesion is due to trauma, fracture of one of the carpal bones, usually the scaphoid, should be excluded.
The patient presents with pain felt locally at the wrist. There may be a history of trauma, or if due to inflammatory arthritis the patient may have other joint involvement.
On examination the joint may be swollen, and heat and synovial thickening may be palpated at the wrist. Assessment by selective tension will reveal a capsular pattern of equal limitation of flexion and extension.
Treatment by injection
The aim of treatment by corticosteroid injection is to reduce inflammation and pain.(Figure 4)
KNEE JOINT(Figure 5)
Arthritis, which may be due to an acute episode of degenerative osteoarthrosis or inflammatory arthritis. Traumatic arthritis is usually a secondary response to a ligamentous lesion at the knee and should be treated as such.
The patient may complain of a gradual or sudden onset of pain and swelling at the knee. The pain may be anterior and/or posterior. Symptoms are generally aggravated by weight- bearing activities and the knee may be stiff after rest.
On examination, swelling and synovial thickening may be palpated. A capsular pattern of greater limitation of flexion than extension is present and flexion has a harder than normal end-feel.
ANKLE (TALOCRURAL) JOINT
Arthritis, which may be an acute episode of inflammatory arthritis, such as rheumatoid arthritis, or traumatic arthritis associated with fracture or ligamentous injury.
The patient complains of pain and swelling located locally around the ankle.
On examination, a capsular pattern of limited movement will be evident, with a greater limitation of plantarflexion than dorsiflexion. Plantarflexion will exhibit an abnormal hard end-feel.
Treatment by injection
An intra-articular injection may reduce the pain and swelling, allowing an increase in the range of mobility at the ankle joint.(Figure 6)
As all medical procedures some complications could be observed after intra-articular injections. These complications are infrequent and rarely serious among children.
Post-injection inflammatory reaction: An inflammatory reaction. It is thought to be because of the microcrystals of steroid, which irritate the synovium. This reaction is very uncommon.[42-44] The reaction is expected to resolve within two or three days, spontaneously. It is necessary to repeat aspiration for excluding possible risks of infection If there is marked heat and/or pain.
Subcutaneous atrophy and depigmentation: If there has been an escape of the long acting steroids to the soft tissue while injecting, subcutaneous atrophy and depigmentation could be expected. The incidence of this complication varies from 1 to 8 percent.[44,46,47]
Intra-articular calcifications: After intra-articular injections small particles may be seen on radiographs. [48-50]. Almost all patients are asymptomatic [44,48,49]. The pathogenesis of these calcifications is not yet clear.
Infection: The incidence of infection during joint aspiration/injection is always probable. To prevent this complication, cautions like; use of aseptic techniques and avoiding injection, if there is bacteremia or overlying tissue infection are mandatory to obtain.
Hemorrhage: Risk of hemorrhage is always accompanied by any invasive procedure. Yet Hemarthrosis following by intra-articular injection is extremely uncommon.
Systemic Effects of Intra-Articular Glucocorticoids
Some studies have shown, patients often note improvement in joints that were not injected suggesting some corticosteroid may enter to the systemic circulation.[55,56] Studies in both children and adults have represented transient suppression of endogenous cortisol level after injection.[53,54] However, no case has been reported of developing signs or symptoms of adrenal suppression.
Mehrnoush Hassas Yeganeh MD Paediatric Rheumatologist, Assistant professor, Shahid Beheshti Medical Univerity, Tehran, Iran email@example.com
Touraj Shafaghi MD Orthopaedic surgeon, Assistant professor, Shahid Beheshti Medical University, Tehran, Iran firstname.lastname@example.org
Mohammad Qoreishi MD Orthopaedic surgeon, Assistant professor, Shahid Beheshti Medical University, Tehran, Iran email@example.com
Acknowledgements: None declared.
Financial disclosure: None declared.
1. Ernest D. Gardner. Physiology of Joints. J Bone Joint Surg Am, 1963 Jul 01;45(5):1061-1066.
2. Carter DR, Wong M. The role of mechanical loading histories in the development of diarthrodial joints. J Orthop Res. 1988;6(6):804-16.
3. Whillis J. The development of synovial joints. J Anat. 1940 Jan;74(Pt 2):277-83.
4. Luyten FP. Cartilage-derived morphogenetic protein-1. Int J Biochem Cell Biol. 1997 Nov;29(11):1241-4.
5. Iwanaga T, Shikichi M, Kitamura H, Yanase H, Nozawa-Inoue K. Morphology and functional roles of synoviocytes in the joint. Arch Histol Cytol. 2000 Mar;63(1):17-31.
6. Bowen V, Cassidy JD: Macroscopic and microscopic anatomy of the sacroiliac joint from embryonic life until the eighth decade. Spine 1981, 6:620–628.
7. Kumar P, Oka M, Toguchida J, Kobayashi M, Uchida E, Nakamura T, Tanaka K. Role of uppermost superficial surface layer of articular cartilage in the lubrication mechanism of joints. J Anat. 2001 Sep;199(Pt 3):241-50.
8. Osborn JW. The disc of the human temporomandibular joint: design, function and failure. J Oral Rehabil. 1985 Jul;12(4):279-93
9. Johnston SA. Osteoarthritis. Joint anatomy, physiology, and pathobiology. Vet Clin North Am Small Anim Pract. 1997 Jul;27(4):699-723.
10. Roughley PJ, White RJ. Age-related changes in the structure of the proteoglycan subunits from human articular cartilage. J Biol Chem. 1980 Jan 10;255(1):217-24.
11. Zhu W, Mow VC, Koob TJ, Eyre DR. Viscoelastic shear properties of articular cartilage and the effects of glycosidase treatments. J Orthop Res. 1993 Nov;11(6):771-81.
12. Wojtys E, Wilson M, Buckwalter K, Braunstein E, Martel W. Magnetic resonance imaging of knee hyaline cartilage and intraarticular pathology. Am J Sports Med. 1987 Sep-Oct;15(5):455-63.
13. Iwamoto M, Shimazu A, Nakashima K, Suzuki F, Kato Y. Reduction of basic fibroblasts growth factor receptor is coupled with terminal differentiation of chondrocytes. J Biol Chem. 1991 Jan 5;266(1):461-7.
14. Aigner T, Soeder S, Haag J. IL-1beta and BMPs--interactive players of cartilage matrix degradation and regeneration. Eur Cell Mater. 2006 Oct 26;12:49-56; discussion 56.
15. Gentili C, Cancedda R. Cartilage and bone extracellular matrix. Curr Pharm Des. 2009;15(12):1334-48.
16. Lindahl U, Höök M. Glycosaminoglycans and their binding to biological macromolecules. Annu Rev Biochem. 1978;47:385-417.
17. Buckwalter JA, Roughley PJ, Rosenberg LC. Age-related changes in cartilage proteoglycans: quantitative electron microscopic studies. Microsc Res Tech. 1994 Aug 1;28(5):398-408.
18. Gelse K, Pöschl E, Aigner T. Collagens--structure, function, and biosynthesis. Adv Drug Deliv Rev. 2003 Nov 28;55(12):1531-46.
19. Sharpe WD. Age changes in human bone: an overview. Bull N Y Acad Med. 1979 Sep;55(8):757-73.
20. Prockop DJ. Seminars in medicine of the Beth Israel Hospital, Boston. Mutations in collagen genes as a cause of connective-tissue diseases. N Engl J Med. 1992 Feb 20;326(8):540-6.
21. Reiser K, McCormick RJ, Rucker RB. Enzymatic and nonenzymatic cross-linking of collagen and elastin. FASEB J. 1992 Apr;6(7):2439-49.
22. Engvall E, Ruoslahti E. Binding of soluble form of fibroblast surface protein, fibronectin, to collagen. Int J Cancer. 1977 Jul 15;20(1):1-5.
23. Kleinman HK, Cannon FB, Laurie GW, Hassell JR, Aumailley M, Terranova VP, Martin GR, DuBois-Dalcq M. Biological activities of laminin. J Cell Biochem. 1985;27(4):317-25.
24. Fleischmajer R, Perlish JS, Burgeson RE, Shaikh-Bahai F, Timpl R. Type I and type III collagen interactions during fibrillogenesis. Ann N Y Acad Sci. 1990;580:161-75.
25. Medina C, Radomski MW. Role of matrix metalloproteinases in intestinal inflammation. J Pharmacol Exp Ther. 2006 Sep;318(3):933-8. Epub 2006 Apr 27.
26. Woessner JF Jr. Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J. 1991 May;5(8):2145-54. Review.
27. Owen CA, Campbell EJ. The cell biology of leukocyte-mediated proteolysis. J Leukoc Biol. 1999 Feb;65(2):137-50.
28. Gruber BL, Marchese MJ, Suzuki K, Schwartz LB, Okada Y, Nagase H, Ramamurthy NS. Synovial procollagenase activation by human mast cell tryptase dependence upon matrix metalloproteinase 3 activation. J Clin Invest. 1989 Nov;84(5):1657-62.
29. Liu J, Sukhova GK, Sun JS, Xu WH, Libby P, Shi GP. Lysosomal cysteine proteases in atherosclerosis. Arterioscler Thromb Vasc Biol. 2004 Aug;24(8):1359-66. Epub 2004 Jun 3.
30. Davies DV. Anatomy and physiology of diarthrodial joints. Ann Rheum Dis. 1945 Dec;5:29-35.
31. Mizel SB, Dayer JM, Krane SM, Mergenhagen SE. Stimulation of rheumatoid synovial cell collagenase and prostaglandin production by partially purified lymphocyte-activating factor (interleukin 1). Proc Natl Acad Sci U S A. 1981 Apr;78(4):2474-7.
32. Ogston AG, Stanier JE. The dimensions of the particle of hyaluronic acid complex in synovial fluid. Biochem J. 1951 Oct;49(5):585-90.
33. Balazes EA ,The physical properties of synovial fluid and the special role of hyaluronic acid. Disorders of the Knee, JB LippincoU Co., Philadelphia. 1974: 63-75.
34. Benjamin M, Qin S, Ralphs JR. Fibrocartilage associated with human tendons and their pulleys. J Anat. 1995 Dec;187 ( Pt 3):625-33.
35. Cardone DA, Tallia AF. Diagnostic and therapeutic injection of the elbow region. Am Fam Physician. 2002 Dec 1;66(11):2097-100.
36. Moseley HF. Shoulder Pain. Can Med Assoc J. 1942 Apr;46(4):361-5.
37. Padeh S, Passwell JH. Intraarticular corticosteroid injection in the management of children with chronic arthritis. Arthritis Rheum. 1998 Jul;41(7):1210-4.
38. Ritchie DM, Boyle JA, McInnes JM, Jasani MK, Dalakos TG, Grieveson P, Buchanan WW. Clinical studies with an articular index for the assessment of joint tenderness in patients with rheumatoid arthritis. Q J Med. 1968 Jul;37(147):393-406.
39. Zuber TJ. Knee joint aspiration and injection. Am Fam Physician. 2002 Oct 15;66(8):1497-500, 1503-4, 1507.
40. Tallia AF, Cardone DA. Diagnostic and therapeutic injection of the ankle and foot. Am Fam Physician. 2003 Oct 1;68(7):1356-62.
41. McCarty DJ Jr, Hogan JM. InflammatoryReaction after Intrasynovial Injection of Microcrystalline Adrenocorticosteroid Esters. Arthritis Rheum 1964; 7:359.
42. Hertzberger-ten Cate R, de Vries-van der Vlugt BC, van Suijlekom-Smit LW, Cats A. Intra-articular steroids in pauciarticular juvenile chronic arthritis, type 1. Eur J Pediatr 1991; 150:170.
43. Padeh S, Passwell JH. Intraarticular corticosteroid injection in the management of children with chronic arthritis. Arthritis Rheum 1998; 41:1210.
44. Job-Deslandre C, Menkes CJ. Complications of intra-articular injections of triamcinolone hexacetonide in chronic arthritis in children. Clin Exp Rheumatol 1990; 8:413.
45. Cassidy JT, Bole GG. Cutaneous atrophy secondary to intra-articular corticosteroid administration. Ann Intern Med 1966; 65:1008.
46. Breit W, Frosch M, Meyer U, et al. A subgroup-specific evaluation of the efficacy of intraarticular triamcinolone hexacetonide in juvenile chronic arthritis. J Rheumatol 2000; 27:2696.
47. Ravelli A, Manzoni SM, Viola S, et al. Factors affecting the efficacy of intraarticular corticosteroid injection of knees in juvenile idiopathic arthritis. J Rheumatol 2001; 28:2100.
48. Gilsanz V, Bernstein BH. Joint calcification following intra-articular corticosteroid therapy. Radiology 1984; 151:647.
49. Sparling M, Malleson P, Wood B, Petty R. Radiographic followup of joints injected with triamcinolone hexacetonide for the management of childhood arthritis. Arthritis Rheum 1990; 33:821.
50. Goldman RD, Benseler SM, Schneider R. Intra-articular calcifications in a child with juvenile rheumatoid arthritis. Arch Dis Child 2005; 90:1038.
51. Huppertz HI, Tschammler A, Horwitz AE, Schwab KO. Intraarticular corticosteroids for chronic arthritis in children: efficacy and effects on cartilage and growth. J Pediatr 1995; 127:317.
52. Earley A, Cuttica RJ, McCullough C, Ansell BM. Triamcinolone into the knee joint in juvenile chronic arthritis. Clin Exp Rheumatol 1988; 6:153.
53. Huppertz HI, Pfüller H. Transient suppression of endogenous cortisol production after intraarticular steroid therapy for chronic arthritis in children. J Rheumatol 1997; 24:1833.
54. Koehler BE, Urowitz MB, Killinger DW. The systemic effects of intra-articular corticosteroid. J Rheumatol 1974; 1:117.
55. Freyberg RH, Patterson M, Adams CH, et al. Practical considerations of the use of cortisone and ACTH in rheumatoid arthritis. Ann Rheum Dis 1951; 10:1.
56. Hollander JL, Brown EM Jr, Jessar RA, Brown CY. Hydrocortisone and cortisone injected into arthritic joints; comparative effects of and use of hydrocortisone as a local antiarthritic agent. J Am Med Assoc 1951; 147:1629.
57. Pemberton R. Arthritis and rheumatoid conditions: Their nature and treatment, Lea and Febiger, Philadelphia 1935.
58. Ropes MW, Bauer W. Synovial Fluid Changes in Joint Disease, The Commonwealth Fund, Harvard University Press, Cambridge 1953.