Pseudogout (CPPD) – Causes, Symptoms, Diagnosis, Treatment and Ongoing care
Acute inflammatory arthritic disease usually involving large joints; primarily affecting the elderly and caused by calcium pyrophosphate dihydrate (CPPD) crystal deposition in joints; associated with chondrocalcinosis:
- CPPD crystal deposition may cause a progressive degenerative arthritis in numerous joints.
- CPPD crystal deposition may cause a more insidious, smoldering, symmetric polyarthritis similar to rheumatoid arthritis (RA).
- System(s) affected: Endocrine/Metabolic; Musculoskeletal
- Synonym(s): Calcium pyrophosphate deposition disease
- Predominant age: 80% of patients >60 years of age
- Predominant sex: Male = Female
- Chondrocalcinosis is present in 1 in 10 adults age 60–75 years and 1 in 3 by >80 years; only a small percentage develops pseudogout (1).
- Pseudogout often occurs as a complication in patients hospitalized for other medical and surgical illnesses.
Uncommonly seen in familial pattern with autosomal dominant inheritance (<1% of patients); most cases are sporadic.
Colchicine 0.6 mg b.i.d. may reduce frequency of episodes in recurrent monoarthritic CPPD.
- Acute inflammatory reaction to CPPD crystals shed into synovial cavity
- Physical and chemical changes in aging cartilage that favor crystal growth
Commonly Associated Conditions
- Wilson disease
- Acute pain and swelling of ≥1 or more joints; knee involved in 1/2 of all attacks; ankle, wrist, and shoulder also common
- Can present with a chronic progressive arthritis on which acute inflammatory attacks are superimposed
- Progressive degenerative arthritis in numerous joints, including wrists, metacarpophalangeal, hips, shoulders, elbows, and ankles
- Low-grade inflammatory arthritis with multiple symmetric joint involvement (mimics RA) <5% of cases
- Can present in proximal joints mimicking polymyalgia rheumatica, often accompanied by tibiofemoral and ankle arthritis and tendinous calcifications (2)[C]
- May develop after intraarticular injection of hyaluronic acid (Hyalgan, Synvisc) (3)[C]
- Inflammation, joint effusion, limitation of motion
- 50% associated with fever
- Any other synovial joint may be involved, including 1st metatarsophalangeal joint.
Diagnostic Tests & Interpretation
Initial lab tests
Synovial fluid analysis consistent with an inflammatory effusion:
- Cell count from 2,000–100,000 white blood cells [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 (4)[C]
- Wet prep with polarized microscopy may demonstrate small numbers of weakly positively birefringent crystals in the fluid and within neutrophils; false-negative rate is high. Metabolic studies to exclude an underlying cause always should be obtained in patients <50 years of age and should be considered in the elderly:
- Serum calcium
- Serum phosphorus
- Serum alkaline phosphatase
- Serum parathormone (i-PTH)
- Serum iron, total iron-binding capacity, and serum ferritin
- Serum magnesium
- Serum thyroid-stimulating hormone (TSH) level
Radiographs of joints:
- May demonstrate punctate and linear calcification in articular hyaline or fibrocartilage: Knees, hips, symphysis pubis, and wrists are affected most often; also may be found in asymptomatic individuals
- In the chronic destructive indolent form of the disease: Subchondral cyst formation, fragmentation with formation of intra-articular radiodense bodies in joints not typically affected by degenerative joint disease
Aspiration of joint fluid with synovial fluid analysis required for proper confirmation of pseudogout; aspiration may relieve symptoms and speed resolution of inflammatory process.
CPPD crystal deposition in articular cartilage, synovium, ligaments, and tendons
- Illnesses that may cause acute inflammatory arthritis in a single or multiple joint(s):
- Septic arthritis
- Other illnesses that may present with an acute inflammatory arthritis:
- Reiter syndrome
- Lyme disease
- Acute RA
- Nonsteroidal anti-inflammatory drugs (NSAIDs): Choose 1 of the following:
- Ibuprofen (Motrin): 600–800 mg p.o. t.i.d.–q.i.d. with food; maximum of 3.2 g/d
- Naproxen (Naprosyn): 500 mg p.o. b.i.d. with food
- Other NSAIDs at anti-inflammatory doses are effective, although indomethacin has higher complication rates (relative risk [RR] = 2.2) compared with ibuprofen (RR = 1.2) (5)[B].
- History of hypersensitivity to NSAIDs or aspirin
- Active peptic ulcer disease or history of recurrent upper GI lesions
- Avoid in renal insufficiency if serum creatinine >1.6 mg/dL.
- Serious GI bleeding can occur without warning; follow the patient carefully for internal bleeding. Administer proton pump inhibitor (PPI) or misoprostol 200 µg p.o. q.i.d. in patients with peptic ulcer disease history.
- Significant possible interactions:
- May elevate BP in treated hypertensives
- May blunt antihypertensive effects of angiotensin-converting enzyme (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: Begin at 40–60 mg/d and taper over 10 days.
- IM triamcinolone acetonide 60 mg; may repeat in 1–4 days (4)[B]
- Intraarticular instillation of prednisolone–sodium phosphate 4–20 mg or triamcinolone diacetate 2–40 mg with local anesthetic
- Oral colchicines (6)[C] 0.6 mg q.i.d. or 0.6 mg hourly until symptoms relieved or vomiting/diarrhea develops; maximum dose per attack 4–6 mg; avoid with significant renal insufficiency
- Methotrexate may have a role in severe disease resistant to traditional therapy (76)[C].
- Rest and elevate affected joint(s).
- Apply ice/cool compresses to affected joints.
- Non-weight-bearing on affected joint while painful; use crutches or walker.
Issues for Referral
Consider consultation with orthopedist or rheumatologist if septic joint is a serious consideration or patient is not responding.
- Isometric exercises to maintain muscle strength during the acute stage (e.g., quadriceps isometric contractions, and leg lifts if knee affected)
- Begin joint range-of-motion (ROM) exercises as inflammation and pain subside.
- Resume weight-bearing when pain subsides.
Perform arthrocentesis and joint fluid analysis.
Consider admission for septic arthritis if synovial fluid WBC count >50,000/mL; strongly consider if >100,000/mL; treat with appropriate antibiotics pending culture results.
Reevaluate patient for response to therapy 48–72 h after treatment instituted; reexamine 1 week later and then as needed.
No known relationship to diet
- Rest affected joint.
- Symptoms usually resolve in 7–10 days.
- Acute attack usually resolves in 10 days; prognosis for resolution of acute attack is excellent.
- Some patients experience progressive joint damage with functional limitation.
- Erosive destructive arthritis in a pattern of joints not usually affected by degenerative joint disease (e.g., metacarpophalangeal joints, wrists)
Elderly patients treated with NSAIDs require careful monitoring and are at higher risk for GI bleeding and acute renal insufficiency.
1. Richette P, Bardin T, Doherty M. An update on the epidemiology of calcium pyrophosphate dihydrate crystal deposition disease. Rheumatology (Oxford).2009.
2. Pego-Reigosa JM, Rodriguez-Rodriguez M, Hurtado-Hernandez Z, et al. Calcium pyrophosphate deposition disease mimicking polymyalgia rheumatica: a prospective followup study of predictive factors for this condition in patients presenting with polymyalgia symptoms. Arthritis Rheum. 2005;53:931–8.
3. Hamburger MI, Lakhanpal S, Mooar PA, et al. Intra-articular hyaluronans: a review of product-specific safety profiles. Semin Arthritis Rheum. 2003;32:296–309.
4. Shah K, Spear J, Nathanson LA, et al. Does the presence of crystal arthritis rule out septic arthritis? J Emerg Med. 2007;32:23–6.
5. Richy F, Bruyere O, Ethgen O, et al. Time dependent risk of gastrointestinal complications induced by non-steroidal anti-inflammatory drug use: a consensus statement using a meta-analytic approach. Ann Rheum Dis. 2004;63:759–66.
6. Lioté F, Ea HK et al. Recent developments in crystal-induced inflammation pathogenesis and management. Curr Rheumatol Rep. 2007;9:243–50.
7. Chollet-Janin A, Finckh A, Dudler J, et al. Methotrexate as an alternative therapy for chronic calcium pyrophosphate deposition disease: an exploratory analysis. Arthritis Rheum. 2007;56:688–92.
Announ N, Guerne PA et al. Treating difficult crystal pyrophosphate dihydrate deposition disease. Curr Rheumatol Rep. 2008;10:228–34.
Wise CM. Crystal-associated arthritis in the elderly. Clin Geriatr Med. 2005;21:491–511, v-vi.
- 275.49 Other disorders of calcium metabolism
- 712.10 Chondrocalcinosis, due to dicalcium phosphate crystals, involving unspecified site
- 712.20 Chondrocalcinosis, due to pyrophosphate crystals, involving unspecified site
- 712.30 Chondrocalcinosis, cause unspecified, involving unspecified site
- 60782007 pseudogout (disorder)
- 201637001 chondrocalcinosis due to pyrophosphate crystals (disorder)
- 201625003 chondrocalcinosis due to dicalcium phosphate crystals (disorder)
- Perform joint fluid aspiration and analysis to evaluate acute arthritis.
- If septic arthritis is considered, treat presumptively with antibiotics until culture results are available.
- NSAID therapy is preferred treatment.
- Oral steroids are useful if NSAIDs are contraindicated.
- Intra-articular steroids can be used if septic arthritis has been excluded.