Crystal-Induced Rheumatic Disorders

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[edit] Crystal-Induced Rheumatic Disorders

David F. Giansiracusa

Leslie R. Harrold

[edit] GOUT

Gout is caused by elevated serum levels of monosodium urate, which result in deposition of urate crystals in joints and soft tissues and excessive urinary excretion of uric acid.Clinical manifestations of gout include (1) recurrent attacks of acute arthritis; (2) chronic, deforming, erosive arthritis related to deposition of large deposits of monosodium urate (tophi) in and around joints; (3) deposition of monosodium urate crystals in the kidneys, causing urate nephropathy; (4) uric acid kidney stones; and (5) uric acid crystallization in renal tubules, or acute hyperuricemic (uric acid) nephropathy.^[1]

[edit] Epidemiology and Etiology

Hyperuricemia is a requisite for the development of gout.Statistically, hyperuricemia can be defined as a serum urate level greater than 2 standard deviations (SD) above the mean.Since gout represents a group of diseases that result from excessive amounts of monosodium urate, however, hyperuricemia is better defined in physicochemical terms as the level above which urate concentration exceeds the saturation point.Since the solubility of urate in plasma at 37° C is approximately 7 mg/dl, which by most chemical and automatic analyzer techniques corresponds to a serum urate level of approximately 7.5 to 8 mg/dl, hyperuricemia can be defined as a serum urate level that exceeds this concentration.Hyperuricemia may result from overproduction of urate and diminished urinary excretion of uric acid.The term primary gout refers to the clinical disease that results from hyperuricemia caused by a genetically determined metabolic error of excessive de novo biosynthesis and impaired excretion of uric acid.

The overproduction of uric acid is determined when a patient follows a purine-restricted diet for 5 days and excretes more than 600 mg of uric acid in 24 hours.This group of patients constitutes less than 15% of individuals with gout.In a few patients who produce too much uric acid, a primary enzymatic abnormality such as hypoxanthine guanine phosphoribosyltransferase (HGPRTase) deficiency or increased phosphoribosylpyrophosphate (PRPP) synthetase activity is responsible for excessive biosynthesis of uric acid.In approximately 75% to 90% of individuals with primary gout, hyperuricemia is the result of diminished renal clearance of uric acid.These individuals require serum urate levels 2 to 3 mg/dl higher than normal to achieve comparable uric acid excretion rates.

Secondary gout results from an acquired disease state or a drug that causes an overproduction or impaired excretion of uric acid.Secondary causes of hyperuricemia includemyeloproliferative and lymphoproliferative diseases, multiple myeloma, hemolytic anemia, polycythemia vera, and psoriasis.Acquired renal disease, acidosis, and drugs are the most common causes of secondary hyperuricemia resulting from diminished renal excretion of uric acid.^[2] Implicated drugs include low-dose salicylates, nicotinic acid, ethambutol, cyclosporine, and any diuretic that causes volume contraction, especially thiazides, which also compete with urate for secretion by the renal tubule.

Lead-induced renal tubular injury also impairs uric acid excretion.Alcohol consumption elevates serum urate levels because of the generation of organic acids, which compete with tubular secretion of uric acid and enhance uric acid production secondary to accelerated conversion of adenosine triphosphate to adenosine monophosphate, which is metabolized in uric acid.

[edit] Pathophysiology

Urate crystals are typically present in the synovial fluid of patients with acute gouty arthritis.Laboratory studies of crystal growth indicate that the saturation concentration varies with temperature; at temperatures below 37° C, as in the extremity joints, the saturation point for uric acid is significantly less than 7 mg/dl.This biochemical phenomenon correlates well with the clinical observations that gouty arthritis characteristically affects the joints of the feet, ankles, knees, hands, and elbows and that tophi deposit in cool sites, such as the cartilaginous helix of the external ear, the olecranon bursae, and the peripheral joints.

Acute gouty arthritis occurs when monosodium urate crystals appear in the synovial fluid as a result of shedding from articular cartilage or synovium or precipitation of new crystals.Mechanical stresses, such as twisting an ankle or stubbing the great toe, may dislodge urate crystals.Crystal shedding may also result from rapid changes in urate concentration, as in the institution of uric acid-lowering therapy (e.g., allopurinol, uricosuric agents) or the ingestion of alcohol or salicylates.^[1] Once in the joint fluid, a series of processes occurs, including coating of the crystals with immunoglobulins.Polymorphonuclear neutrophil leukocytes (PMNs) ingest the crystals, releasing lysosomal enzymes and other inflammatory mediators, including toxic superoxide radicals, prostaglandins, leukotrienes, kinins, and components of the complement pathways, causing inflammation and, with repeated attacks, joint damage.

[edit] Patient Evaluation

After prolonged asymptomatic hyperuricemia, often 20 to 30 years, approximately 5% to 10% of individuals develop acute gouty arthritis, characterized by the abrupt onset of exquisite pain, tenderness, swelling, and erythema that most often affects a single joint.Approximately 50% of individuals experience their first attack in the metatarsophalangeal (MTP) joint of the great toe.Other peripheral joints, including the joints of the midfoot, ankles, knees, fingers, wrists, and elbows, may be involved in a monoarticular presentation.^[1] Approximately 10% to 15% of patients present initially with polyarticular gout.^[3] Gouty arthritis most frequently affects men in the fourth through sixth decades of life and, less often, postmenopausal women.Attacks often occur at night and may be associated with inflammation of the surrounding tendons, bursae, and skin, raising the differential diagnosis of joint infection and cellulitis.Even if untreated the acute attack is self-limited, generally lasting 3 to 7 days, after which the patient is completely asymptomatic.The attacks may become more frequent and more prolonged, and the individual may eventually develop chronic, persistent gout, with increasing accumulation of urate deposits, clinically evident as palpable tophi on examination, or erosions and soft tissue swelling on radiographs.

[edit] Laboratory Studies and Diagnostic Procedures

Characteristic bone radiographic features of chronic tophaceous gout include cortical indentations or erosions with sharply defined sclerotic margins resulting from tophi in adjacent soft tissues, cortical erosions with an overhanging or hooklike margin as a result of tophaceous deposits in the periosteum or cortical bones, and round or oval cysts generally with sclerotic margins in medullary bone close to joints.Relative preservation of joint space, absence of profound periarticular demineralization, and eccentric location of soft tissue swelling help differentiate tophaceous gouty arthritis from rheumatoid arthritis.

A definitive diagnosis of gouty arthritis is established by the demonstration of needle-shaped monosodium urate crystals within synovial fluid PMNs aspirated from clinically affected joints^[1][3](Fig.136-1).Because of birefringent characteristics, urate crystals (and in pseudogout, calcium pyrophosphate crystals) are more readily visualized by polarizing microscopy than by plain light microscopy.The monosodium urate crystal appears as a bright, needle-shapedobject on a dark background.With a red compensator, the negatively birefringent urate crystals are yellow when they lie parallel to the axis of the light coming through the microscope, whereas the positively birefringent, rhomboid, or square calcium pyrophosphate crystals are blue when parallel to the microscope's plane of light.The more acute the attack of gout, the more likely monosodium urate crystals are visualized within synovial PMNs.

Figure 136-1 Monosodium urate crystals phagocytosed by polymorphonuclear leukocyte in synovial fluid. Top, Compensated polarized light clearly demonstrates two longer crystals and one shorter one. Bottom, Same field under ordinary light.Comparison of two views demonstrates superiority of compensated polarized light over ordinary light microscopy when evaluating joint fluid for crystals. (From American College of Rheumatology:Clinical slide collection on the rheumatic diseases, 1991, The College.)

The differential diagnosis of gout is that of an acute monoarticular or oligoarticular (four or fewer joints) arthritis (Box 136-1).

[edit] Renal Complications

Excesses of serum urate and urinary uric acid may affect the kidneys and cause a variety of medical problems, including urate nephropathy, acute hyperuricemic (uric acid) nephropathy, and uric acid urolithiasis.

Urate nephropathy manifests in the development of proteinuria, loss of maximal tubular concentrating ability, hypertension, and azotemia related to the deposition of monosodium urate crystals within the medullary and pyramidal interstitium of the kidney as a result of longstanding hyperuricemia.This condition rarely occurs in the absence of gouty arthritis and generally correlates with the severity of the joint disease.Urate nephropathy is diagnosed clinically.Pathologically the condition is characterized by urate crystal deposition in the medullary interstitium and pyramids with surrounding giant cell reaction.In most gouty patients, hypertension, heart disease, peripheral atherosclerosis, aging, diabetes mellitus, nonsteroidal antiinflammatory drug (NSAID) use, analgesic abuse, lead exposure, other intrinsic renal disease (e.g., glomerulonephritis, pyelonephritis, interstitial nephritis), and urinary obstruction are generally more important contributors to renal function impairment than urate nephropathy.

Acute hyperuricemic nephropathy(acute uric acid nephropathy) is characterized by oliguria and renal failure related to the precipitation of massive amounts of uric acid within renal tubules and collecting ducts, causing tubular obstruction.This condition most often develops during cytotoxic therapy for myeloproliferative disorders as a result of massive cell death and an increased release of uric acid.Therapy to prevent uric acid nephropathy includes vigorous hydration and the use of the xanthine oxidase inhibitor, allopurinol, generally 600 mg/day begun 2 to 3 days before the institution of cytotoxic radiation or chemotherapy.

Approximately 10% to 25% of individuals with gouty arthritis develop urolithiasis, usually with stones composed of a mixture of uric acid and calcium oxalate.The incidence of nephrolithiasis increases with the degree of hyperuricemia but more closely correlates with the amount of uric acid excreted in the urine (i.e., the degree of uricaciduria).Approximately 50% of individuals who excrete more than 1100 mg of uric acid in 24 hours develop stones.Other factors that predispose to uric acid urolithiasis include high urine concentration, low pH, and urinary solubility.^[4] Therapeutic measures to prevent uric acid calculi include adequate hydration, alkalinization to maintain a urine pH more than 6, moderation of dietary intake of alcohol and protein, prompt treatment of any urinary tract infection, and reduction of uric acid production with allopurinol and thus reduction in the amount of uric acid excreted.

[edit] Treatment

[edit] Hyperuricemia.

Asymptomatic hyperuricemia is an elevated serum urate level without gouty arthritis, tophi, urate nephropathy, or uric acid renal calculi (Box 136-2).Treatment with pharmacologic agents is rarely indicated.Arguments against treating asymptomatic hyperuricemia include the following: (1) although up to 5% of the U.S.population may have hyperuricemia, most (80% to 90%) never develop recognizable consequences; (2) gouty arthritis is a treatable condition; (3) urate nephropathy and tophaceous gout rarely develop in the absence of a history of acute gouty arthritis; (4) renal function is not adversely affected by hyperuricemia, and its normalization has little effect on renal function; and (5) treatment with an agent that lowers uric acid requires lifelong therapy, which is expensive and may be associated with potentially serious side effects.The risk of uric acid stone formation is more closely related to uric acidexcretion rates than to the degree of serum urate elevation.Detailed studies on cardiovascular disease indicate that hyperuricemia does not appear to be an independent risk factor for coronary artery disease (CAD) but rather is associated with other risk factors, such as obesity, hypertension, and hyperlipidemia.Conversely, no evidence supports the contention that lowering serum urate to normal levels independently reduces the risk of CAD.

Appropriate management of asymptomatic hyperuricemia consists of weight reduction for the obese patient; moderate consumption of alcohol, protein, and foods high in purine content; cessation of smoking; and treatment of hypertension and hypercholesterolemia.A diet low in purine content allows patients to reduce their serum urate levels by 1 mg/dl and the 24-hour urinary uric acid excretion by 200 to 400 mg/day.Foods rich in purines include all meats, including organ meats, seafood, meat extracts, and gravies; yeast and yeast extracts; beer and other alcoholic drinks; and beans, peas, lentils, oatmeal, spinach, asparagus, cauliflower, and mushrooms.^[5] Diuretics and other drugs that contribute to hyperuricemia should be avoided if possible.Any primary condition that contributes to hyperuricemia (e.g., renal disease, high cell turnover) should be treated.

[edit] Gouty Arthritis.

The goals of the treatment of gouty arthritis are termination of the acute attack, prevention of recurrent attacks, and prevention or resorption of tophi in joints and soft tissues.Pharmacologic agents used to treat gouty arthritis can be divided into antiinflammatory drugs, drugs used for prophylaxis against episodes of acute gouty arthritis, and drugs to lower urate (and uric acid) levels (Table 136-1).The earlier an acute attack of gouty arthritis is treated, the more rapidly the inflamed joints respond.Medications used to treat acute gouty arthritis include oral or intravenous(IV) colchicine, NSAIDs, and systemic or intraarticular corticosteroids.

Table 136-1 Medications Used to Treat Acute Gouty Arthritis

NSAIDs are generally given in high dosages for the first 2 to 3 days (‘pulse’ therapy) and then tapered to a lower dosage (e.g., indomethacin, 50 mg three to four times a day for 1 to 2 days with meals, followed by a taper to 25 mg three to four times a day with meals for 5 to 7 days).Other NSAIDs, including tolmetin, naproxen, ibuprofen, piroxicam, sulindac, ketoprofen, fenoprofen, and meclofenamate, may also be effective.Because of the potential adverse effects of phenylbutazone and the availability of other NSAIDs, primary care physicians should not treat patients with phenylbutazone.Intramuscular ketorolac (Toradol) has also been demonstrated to be effective.All NSAIDs may cause gastrointestinal (GI) and central nervous system (CNS) side effects as well as GI bleeding, inhibition of platelet function, fluid retention, aggravation of congestive heart failure (CHF), hypertension, and renal function impairment.

If the treatment of acute gouty arthritis is begun within several hours of the onset of the attack, oral colchicine may be effective (0.6 mg every hour for a maximum of 8 to 10 tablets or until GI side effects develop, followed by a maintenance therapy of 0.6 mg twice daily).The efficacy of oral colchicine is greatly reduced the longer that treatment is delayed after onset of the arthritis; therefore oral colchicine is not the ideal drug for the treatment of acute attacks.IV colchicine is useful for the patient who cannot take oral medications or who has a diarrheal illness (e.g., viral gastroenteritis, inflammatory bowel disease, drug-induced or dietary-induced diarrhea).IV colchicine may also be useful in the patient who should avoid NSAIDs because of other medical problems (e.g., peptic ulcer disease, anticoagulation, CHF).A total of 2 mg may be infused initially, followed by an infusion of 1.0 mg at 6-hour intervals, for a total dose of IV colchicine not to exceed 4 mg in 24 to 48 hours.^[5] No more colchicine should be administered for at least 7 days.Colchicine is extremely irritating to soft tissues and may cause tissue necrosis and cutaneous slough if extravasation occurs.Colchicine should be diluted in 20 ml of normal saline and infused over 10 to 20 minutes.Although IV colchicine usually does not cause the GI side effects associated with oral administration, it may result in myelosuppression.Excessive dosing of IV colchicine may also cause disseminated intravascular coagulation, shock, renal shutdown, hepatocellular necrosis, and CNS dysfunction.Colchicine excretion is reduced in patients with chronic liver disease and impaired renal function, including older individuals who appear to have normal serum creatinine levels.Myopathy and neuropathy are associated with long-term colchicine therapy in patients with renal insufficiency; therefore colchicine either should not be used or should be used carefully (including a reduction in the dosage) in patients with significant liver or renal disease.Colchicine should not be used in patients with combined renal and liver dysfunction, biliary obstruction, or severe renal disease (creatinine clearance less than 10 ml/min).

Corticosteroids may be required in patients with particularly severe or prolonged attacks or in patients who have contraindications to treatment with other agents.After joint sepsis has been excluded, corticosteroids may be administered directly into the inflamed joint or given systematically, such as 30 to 40 mg of prednisone or its equivalent on day 1, tapered over 6 to 10 days, or 40 to 80 units of adrenocorticotropic hormone (ACTH) intramuscularly or by slow IV infusion, repeated every 24 hours for 1 to 3 days as needed.^[6]

After an acute attack of gout has subsided, chronic maintenance therapy with colchicine (0.6 mg twice daily in patients with normal renal and hepatic function) or NSAIDs with meals may act as a prophylaxis against subsequent gouty attacks (see Table 136-1).

The issue of chronic uric acid–lowering therapy after one attack of gouty arthritis remains controversial.Indications for this therapy are (1) repeated attacks of disabling gouty arthritis, (2) tophaceous deposits on physical examination or radiographic studies, (3) clinical or radiographic signs of chronic gouty joint disease, (4) evidence of renal damage (glomerular filtration rate [GFR] less than 60 ml/min), (5) recurrent urolithiasis caused by pure uric acid stones or mixed stones in the setting of hyperuricosuria, (6) gross overproduction of uric acid (urinary uric acid excretion greater than 1000 mg/day), and (7) prevention of hyperuricemia and uricosuria in patients with lymphoproliferative and myeloproliferative disease before cytotoxic therapy.Allopurinol should be used for indications 4 through 7 and for indications 1 through 3 if urinary uric acid excretion on a low-purine diet exceeds 600 mg in 24 hours.Allopurinol should be instituted only after the resolution of an acute attack of gout and with the concurrent administration of NSAIDs or maintenance colchicine (0.6 mg once to twice daily) to prevent an attack of acute gout.Colchicine or NSAIDs should be continued for approximately 6 months after allopurinol has resolved all palpable tophi or, for the patient without tophi, for about 6 months after serum urate levels are suppressed below 6 mg/dl.^[5] Allopurinol is generally initiated at 100 mg/day and increased every 2 to 4 weeks by 100 mg to the dosage necessary to suppress the serum urate level below 6 to 7 mg/dl.The dosage of allopurinol must be kept low in the patient with renal failure, with as little as 100 mg every other day or every third day.Since allopurinol reduces the metabolism of warfarin, 6-mercaptopurine, and azathioprine, the dosage of these medications must be appropriately reduced.With azathioprine the dosage is generally reduced to approximately 25% of the usual dosage when given in the setting of allopurinol therapy.Potential toxicities of allopurinol include nausea, diarrhea, drug fever, leukopenia, hepatotoxicity, interstitial nephritis, vasculitis, and a rash that may evolve into toxic epidermal necrolysis.Serious side effects most often occur when allopurinol is prescribed to patients with renal insufficiency, particularly with concomitant thiazide therapy.

Uricosuric agents may be prescribed in hyperuricemic patients with gout who excrete less than 700 mg of uric acid per day.Patients must have normal renal function for the agents to be effective (GFR should be greater than 60 ml/min) and should maintain good urine volumes to minimize the risk of urolithiasis.The uricosuric agents used most often are probenecid (250 to 500 mg twice a day, increased to 1.5 gm twice a day as needed) and sulfinpyrazone (100 mg twice a day, increased to 400 mg).Similar to allopurinol therapy, prophylaxis against acute gouty arthritis should be administered when a uricosuric agent is prescribed, and the prophylactic medication should be continued for at least 6 months after the serum urate level is controlled below 6 mg/dl or for 6 months after resolution of all clinically apparent tophi.Side effects of probenecid include headache,nausea, anorexia, skin rash, and rarely, nephrotic syndrome, hepatic necrosis, and aplastic anemia.Sulfinpyrazone may cause bone marrow suppression.

If a patient experiences an attack of gouty arthritis while taking allopurinol or a uricosuric agent, the dosage of the agent needed to lower the uric acid level should not be changed until after resolution of the attack.

[edit] CALCIUM PYROPHOSPHATE DEPOSITION DISEASE

Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, also referred to as pyrophosphate arthropathy, is a calcium crystal–induced form of joint disease that is characterized by diverse clinical manifestations associated with the deposition of CPPD crystals in and around joints.^[7] The crystals most often deposit in fibrocartilage (e.g., menisci of knee, intervertebral disks, symphysis pubis) and in hyaline articular cartilage (knees, wrists, other joints).These deposits may also occur in tendons, ligaments, synovial membranes, and joint capsules.^[8] The deposition of CPPD increases with aging and in osteoarthritic joints.^[7] Thus pyrophosphate arthropathy is fairly common in older individuals, particularly in the acute form, called pseudogout. Asymptomatic articular cartilage calcifications may occur in as many as 15% of individuals 65 to 75 years of age and more than 40% of those 85 years of age and older.

[edit] Patient Evaluation

CPPD is best known for causing acute arthritis (pseudogout) because of its similarities to acute gouty arthritis.Pseudogout most often affects the knees of older women, in contrast to gout, which usually affects the joint at the base of the great toe (first MTP joint) and the joints of the instep and ankle in middle-aged men.Pseudogout may also involve the wrists and, less frequently, metacarpophalangeal (MCP) joints, ankles, shoulders, and elbows.^[1]

In addition to the acute arthritis or pseudogout presentation, deposition of CPPD crystals may cause a more subacute, polyarticular presentation similar to rheumatoid arthritis (pseudorheumatoid form), a pseudoosteoarthritis form, and a destructive form, as seen with severe neuropathies (pseudoneuropathic form).CPPD crystals may be detected radiographically in an asymptomatic individual as articular chondrocalcinosis.

The most common association with CPPD deposition is aging.Other conditions are associated with CPPD deposition in articular and periarticular structures, including disorders related to elevated calcium levels (e.g., hyperparathyroidism) and metabolic disorders characterized by diminished activity of pyrophosphatases (e.g., familial hypophosphatasia and hypomagnesemia).In addition, familial hypocalciuric hypercalcemia, hemochromatosis, hypothyroidism, and Bartter's syndrome are associated with CPPD disease.Osteoarthritic degeneration of cartilage also facilitates CPPD deposition.^[8]

[edit] Diagnosis

Although the diagnosis of pseudogout is suggested by an acute arthritis with radiographic evidence of articular chondrocalcinosis, definitive diagnosis requires joint aspiration with synovial fluid examination and visualization by compensated polarized microscopy of the rhomboid or square, positively birefringent CPPD crystals within synovial fluid leukocytes^[1](Fig.136-2).Joint fluid aspirated from inflamed joints should also be examined for urate crystals and cultured for infectious agents (see Chapter 123 ).

Figure 136-2 Calcium pyrophosphate crystals phagocytosed by polymorphonuclear leukocytes in synovial fluid, demonstrating rectangular or rhomboid shapes. (From American College of Rheumatology:Clinical slide collection on the rheumatic diseases, 1991, The College.)

[edit] Treatment

A fundamental component of the management of acute CPPD crystal–induced arthritis (pseudogout) is joint aspiration and synovial fluid examination to identify the crystal and exclude joint sepsis.Management of pseudogout and other forms of CPPD arthropathy includes the evaluation and treatment of underlying medical disorders and the administration of antiinflammatory medications.NSAIDs, oral and IV colchicine, and intraarticular and systemic steroids, including ACTH, may be used.^[7] Screening laboratory studies may include those for calcium, phosphorus, albumin, magnesium, thyroid function, alkaline phosphatase, iron and total iron-binding capacity, and ferritin levels.The most cost-effective approach to the metabolic evaluation is to examine for hyperparathyroidism and hemochromatosis, since CPPD arthropathy may be the first clinically apparent manifestation of these conditions.Other associated metabolic diseases generally manifest with other signs and symptoms, such as liver disease in the case of Wilson's disease.

Chronic forms of pyrophosphate arthropathy are generally treated similarly to osteoarthritis, with NSAIDs, nonnarcotic analgesics, joint splinting as appropriate, and range of motion (ROM) and strengthening exercises.Joint lavage and arthroscopic irrigation may occasionally be beneficial.In severe, destructive cases of CPPD arthropathy, particularly those involving the hips and knees, joint replacement for alleviation of pain and deformity may be necessary.

[edit] CALCIUM PHOSPHATE–ASSOCIATED ARTHROPATHY

Hydroxyapatite and other calcium phosphate–containing crystals deposit in and around joints, causing acute and chronic arthropathy and periarticular inflammation.^[7][8]

[edit] Periarthritis

The most familiar clinical form of hydroxyapatite-induced disease is supraspinatus tendinitis with or without calcific subacromial bursitis, presenting as shoulder pain aggravatedby abduction and the radiographic evidence of amorphous calcium deposits in the region of the greater tuberosity of the humerus.The deposition of hydroxyapatite in periarticular structures (tendons, bursae, and joint capsules) may cause acute calcific periarthritis at multiple sites.The most frequently affected areas are the subacromial and trochanteric bursae, the supraspinatus tendon, the Achilles tendon, tendons of the wrists, capsules of the knees, and MCP joints.The clinical features of periarticular hydroxyapatite disease are variable, ranging from no symptoms to severe pain, tenderness, localized edema, and restricted motion.On plain radiographs, hydroxyapatite appears as amorphous, soft tissue, calcium-dense deposits or clumps, often in the anatomic sites of bursae, tendon sheaths, or joint capsules.The absence of trabeculae and the presence of the amorphous, homogenously dense deposits help to distinguish these hydroxyapatite deposits radiographically from avulsion fractures.Conditions that may predispose to calcific periarthritis include repetitive motion, diabetes mellitus, hyperthyroidism, and chronic renal failure, particularly in the setting of chronic hemodialysis.

Treatment of calcific periarthritis may include analgesics, NSAIDs, IV colchicine, aspiration and local injection of a depot steroid preparation (after excluding an infectious process), ACTH, and physical measures, including the application of heat, cold, diathermy, and ultrasound.During the initial acute stage, joint rest with splinting may help.Gentle ROM exercises should progress to a full, active ROM program to prevent the development of joint contractures and adhesive capsulitis.In recurrent and refractory cases, surgical removal of the calcium deposits may be necessary.^[9]

[edit] Hydroxyapatite Crystal–Induced Arthritis

The presence of hydroxyapatite crystals may cause acute flares of osteoarthritis in joints (e.g., knees, fingers) and contribute to erosive osteoarthritis.^[10] Hydroxyapatite crystals also cause a destructive arthritis, which was initially described in the shoulders, called Milwaukee shoulder syndrome. This form of hydroxyapatite arthropathy usually occurs in older women and results in destruction of the rotator cuff and degenerative arthritis of the glenohumeral joint.The synovial fluid is characterized by a paucity of white cells but high concentrations of prostaglandins and destructive enzymes in the setting of hydroxyapatite crystals.Since hydroxyapatite crystals are not birefringent, they cannot be detected easily by polarized microscopic examination but can be screened using calcium phosphate stains (alizarin red or von Kossa) or examining synovial fluid with x-ray diffraction and electron microscopy.The destructive process initially described as Milwaukee syndrome may also involve other joints, such as the knees and hips.Treatment of hydroxyapatite crystal–induced arthritis consists primarily of controlling inflammation with NSAIDs and colchicine and administering analgesics.Intraarticular ‘depo’ corticosteroid preparations may provide transient benefit (see Chapter 167 ).

[edit] OTHER INTRAARTICULAR CRYSTALS

In addition to monosodium urate, CPPD, and hydroxyapatite crystals, cholesterol and calcium oxalate crystals and iatrogenically injected steroid crystals may play a role in rheumatic diseases.Patients with renal failure, particularly those on hemodialysis, may develop acute arthritis or periarthritis from calcium oxalate crystals.These crystals may appear on radiographs as amorphous calcifications similar to those of hydroxyapatite.The calcium oxalate crystals may be visualized under polarized light microscopy as positively birefringent crystals, thereby creating confusion with CPPD.

Injection of the intraarticular ‘depo’ corticosteroid preparation may also result in an inflammatory arthritis termed postinjection flare. This occurs in approximately 5% of the patients who receive such injections and generally begins within 3 to 6 hours after the injection, lasting up to 3 days.Aspiration of synovial fluid from these patients may reveal positively or negatively birefringent crystals, thus causing confusion with CPPD or monosodium urate crystals, respectively.

In some cases the identification of crystals in synovial fluid is simply the result of synovial fluid having been placed in tubes containing calcium oxalate or lithium heparin as the anticoagulant.Since these materials are birefringent crystals, their presence may be incorrectly interpreted as diagnostic of a crystal-induced process that is the cause of joint inflammation.

Cholesterol crystals have a platelike appearance with a notch in one corner and tend to be seen in fluid aspirated from chronic joint and bursal effusions, most often in patients with longstanding rheumatoid arthritis.

[edit] REFERENCES