Recipient(s) will receive an email with a link to 'Pseudogout (Calcium Pyrophosphate Dihydrate)' and will have access to the topic for 7 days.
Subject: Pseudogout (Calcium Pyrophosphate Dihydrate)
(Optional message may have a maximum of 1000 characters.)
Autoinflammatory disease triggered by calcium pyrophosphate dihydrate (CPPD) crystal deposition in the joints
One of many diseases associated with pathologic deposition of crystal, mineralization, and ossification
Suspect pseudogout in arthritis cases with a pattern of joint involvement not usually affected by degenerative joint disease (e.g., metacarpophalangeal joints, wrists)
Clinical presentation is broad:
Chronic CPPD crystal deposition may cause a progressive degenerative arthritis in numerous joints:
Symptom onset is usually insidious.
Definitive diagnosis requires the identification of CPPD crystals in synovial fluid.
System(s) affected: endocrine/metabolic; musculoskeletal
Synonyms: pseudogout; CPPD; pyrophosphate arthropathy; chondrocalcinosis—when calcification visibly seen within tissues on imaging
Predominant age: 80% of patients >60 years
Predominant sex: male > female 1.4:1
Prevalence varies on method of identification (chondrocalcinosis on radiograph vs. CPPD crystals in synovial fluid)
Chondrocalcinosis is present in 1:10 adults age 60 to 75 years and 1:3 by >80 years; however, only a small percentage develop arthropathy.
20-43% prevalence of CPPD cyrstals in synovial fluid of osteoarthritic joints at time of joint replacement
Arthropathy results from an acute autoinflammatory reaction to CPPD crystals in the synovial cavity.
CPPD crystal deposition occurs in three general stages:
CPPD often may occur as a complication in patients hospitalized for other medical and surgical illnesses.
Familial hypocalciuric hypercalcaemia
X-linked hypophosphatemic rickets
Presentation often mimicks gout (“pseudogout”).
Acute CPPD: pain and swelling of ≥1 or more joints; knee involved in 50% of cases; ankle, wrist, toe, and shoulder are also common.
Can present in proximal joints (mimicking polymyalgia rheumatica), often accompanied by tibiofemoral and ankle arthritis and tendinous calcifications
Multiple symmetric joint involvement (mimicking RA) in ≪5% of cases
May develop after intra-articular injection of hyaluronic acid (Hyalgan, Synvisc)
Chronic CPPD: progressive degenerative arthritis with superimposed acute inflammatory attacks
Inflammation (erythema, warmth, tender to touch), joint effusion, decreased range of motion of joint
50% associated with fever
Any synovial joint may be involved.
Illnesses that may cause acute inflammatory arthritis in a single or multiple joint(s):
Other illnesses that may present with an acute inflammatory arthritis:
Cell count 2,000 to 100,000 WBCs/mL
Differential predominantly neutrophils (80-90%)
>50,000 WBC count increases likelihood of septic arthritis, 11% prevalence; number needed to treat (NNT) = 9; >100,000 WBCs/mL, 22% prevalence
Wet prep with polarized microscopy may demonstrate small numbers of crystals. False-negative rate is high.
Rhomboid-shaped weakly positively birefringent crystals in the fluid and within neutrophils is pathognomonic. In contrast, gout crystals are needle-shaped and negatively birefringent.
Obtain the following metabolic studies in patients ≪50 years of age and consider in the elderly to exclude underlying disease:
Aspiration of joint fluid with synovial fluid analysis and demonstration of CPPD crystals is required for diagnosis; aspiration may relieve symptoms and speed resolution of the inflammatory process.
Rest and elevate affected joint(s).
Apply ice/cool compresses to affected joints.
Nonweight bearing on affected joint while painful; use crutches or a walker.
A combination of pharmacologic and nonpharmacologic measures is recommended.
Acute attacks should be treated with cool packs, rest, and joint aspiration with or without steroid injection.
Chronic inflammatory CPPD arthropathy should be managed prophylactically with oral NSAIDs and/or colchicine 3[C].
Intra-articular steroid injection
Significant adverse effects of NSAIDs:
May elevate BP in patients on antihypertensive therapy
May blunt antihypertensive effects of ACE inhibitors
May prolong prothrombin time (PT) in patients taking oral anticoagulants
Avoid concomitant aspirin use.
May blunt diuretic effect of furosemide and hydrochlorothiazide
May increase plasma lithium level in patients taking lithium carbonate
Oral prednisone: 30 to 50 mg/day for 7 to 10 days
IM triamcinolone acetonide 40 mg; may repeat in 1 to 4 days
Consider referring patients with large space-occupying tophaceous lesions for surgical removal.
Alternative therapies for chronic CPPD
Recent randomized trial showed no significant effect of methotrexate in chronic-recurrent CPPD 5[B].
Isometric exercises to maintain muscle strength during the acute stage (e.g., quadriceps isometric contractions, leg lifts if knee affected)
Begin joint range-of-motion (ROM) exercises as inflammation and pain subside.
Resume weight bearing when pain subsides.
Synovial fluid WBC count >50,000/mL
Treat with appropriate antibiotics pending culture results.
Rest affected joint.
Symptoms usually resolve in 7 to 10 days.
Acute attack usually resolves in 10 days; prognosis for resolution of acute attack is excellent.
Patients may experience progressive joint damage and functional limitation.
Recurrent acute attacks
Bruges-Armas J, Bettencourt BF, Couto AR, et al. Effectiveness and safety of infliximab in two cases of severe chondrocalcinosis: nine years of follow-up. Case Rep Rheumatol. 2014;2014:536856.
Daoussis D, Antonopoulos I, Andonopoulos AP. ACTH as a treatment for acute crystal-induced arthritis: update on clinical evidence and mechanisms of action. Semin Arthritis Rheum. 2014;43(5):648–653.
Demertzis JL, Rubin DA. MR imaging assessment of inflammatory, crystalline-induced, and infectious arthritides. Magn Reson Imaging Clin N Am. 2011;19(2):339–363.
Macmullan P, McCarthy G. Treatment and management of pseudogout: insights for the clinician. Ther Adv Musculoskelet Dis. 2012;4(2):121–131.
Richette P, Bardin T, Doherty M. An update on the epidemiology of calcium pyrophosphate dihydrate crystal deposition disease. Rheumatology (Oxford). 2009;48(7):711–715.
Sattui SE, Singh JA, Gaffo AL. Comorbidities in patients with crystal diseases and hyperuricemia. Rheum Dis Clin North Am. 2014;40(2):251–278.
M11.20 Other chondrocalcinosis, unspecified site
M11.269 Other chondrocalcinosis, unspecified knee
M11.29 Other chondrocalcinosis, multiple sites
275.49 Other disorders of calcium metabolism
712.30 Chondrocalcinosis, unspecified, site unspecified
712.26 Chondrocalcinosis, due to pyrophosphate crystals, lower leg
712.29 Chondrocalcinosis, due to pyrophosphate crystals, multiple sites
201637001 Chondrocalcinosis due to pyrophosphate crystals
239834007 Pyrophosphate arthritis (disorder)
239838005 Chondrocalcinosis (disorder)
239833001 Chondrocalcinosis due to pyrophosphate crystals of the knee (disorder)
201646007 Chondrocalcinosis due to pyrophosphate crystals, of multiple sites (disorder)
Suspect CPPD if arthritis case doesn’t follow a pattern typical of degenerative joint disease (e.g., metacarpophalangeal joints, wrists).
Perform arthrocentesis to confirm diagnosis.
If septic arthritis is considered, treat presumptively with antibiotics until culture results are available.
NSAID therapy is the preferred treatment for acute flare.
Oral steroids are useful if NSAIDs are contraindicated.
Intra-articular steroids can be used if septic arthritis has been excluded.