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pseudogout [calcium pyrophosphate dihydrate crystal deposition] or CPPD disease

Calcium pyrophosphate dihydrate (CPPD) crystal deposition in joint space. Etiology: 1) idiopathic 2) hereditary 3) associated disorders: - hyperparathyroidism - hypothyroidism - diabetes mellitus [3] - acromegaly [3] - hemochromatosis - Wilson's disease - hemosiderosis - gout - hypercalcemia [3], familial hypocalciuric hypercalcemia [2] - hypomagnesemia - hypophosphatasia - ochronosis - amyloidosis - Bartter's syndrome - osteoarthritis - Paget's disease - neuropathic joints [3] 4) older age is risk factor [3] 5) may be precipitated by - trauma - surgery - joint hypermobility - severe illness - dehydration Epidemiology: 1) generally affects middle-age & older individuals 2) more common in women [1]; affects both sexes equally [2] 3) half as common as gout Clinical manifestations: 1) CPPD deposition may occur without symptoms 2) CPPD has a varied presentation with symptoms [2] a) asymptomatic chondrocalcinosis (cartilage calcification) b) acute calcium pyrophosphate crystalline arthritis (pseudogout) c) chronic calcium pyrophosphate crystalline inflammatory arthritis - resembles rheumatoid arthritis [2] d) osteoarthritis with calcium pyrophosphate deposition disease (CPPD) - involvement of joints unusual for osteoarthritis - shoulders, wrists, metacarpophalangeal joints 3) acute inflammatory arthritis (generally monoarticular) - generally indistinguishable clinically from gout attack - may be become chronic (chondrocalcinosis) [2] 4) presentation is acute 16%, subacute 16%, chronic 29% or mixed 39% 5) acute episodes may follow trauma, surgery or medical illness - several joints may be painful 6) joint involvement a) rarely involves the 1st metatarsophalangeal (MTP) joint b) most commonly affects the knees c) other joints include: 1] wrists, elbows, ankles, intervertebral disks 2] metacarpophalangeal joints [2] 3] shoulders [2] d) monoarticular (80%), asymmetric 7) fever is common 8) swelling, deformity, morning stiffness (chronic) 9) degenerative cartilage disease (chondrocalcinosis) [2] 10) episodes of acute CPPD may last 3-8 days [2] 11) when associated with osteoarthritis (OA) may masquarade as atypical OA involving joints not usually affected in OA (shoulders, metacarpophalangeal joints) [2] * image of woman with hypoglossal nerve palsy due to CPPD [12] Laboratory: 1) synovial fluid a) CPPD crystals are rhomboid-shaped & weakly positively birefringent b) 5000-75,000 neutrophils/mm3 2) screen for associated disorders in patients < 50 years a) iron studies (hemochromatosis) b) serum TSH (hypothyroidism) c) serum calcium, serum albumin, serum PTH (hyperparathyroidism) d) serum uric acid (gout) e) serum magnesium (hypomagnesemia) Radiology: - chondrocalcinosis most common in knee, shoulder, wrist, pubic symphysis (not specific or diagnostic) [2] - radiograph of wrist - calcification of the triangular fibrocartilage of the wrist joint (space between the carpal bones & distal ulna) or of the metacarpal bone - radiograph of hand: calcification of metacarpophalangeal joints - radiograph of knee - menisci of the knee (appears as a line in the cartilage) - absence of chondrocalcinosis on X-ray does not rule out CPPD * CT & MRI images of hypoglossal nerve palsy due to CPPD [12] Differential diagnosis: 1) gout - more common in lower extremities - more common in men 2) osteoarthritis - condrocalcinosis & involvement of metacarpophalangeal joints suggest pseudogout 3) rheumatoid arthritis 4) neuropathic joint disease Management: 1) acute attack a) NSAIDS are 1st line [2] - indomethacin 25-50 mg PO TID b) colchicine is less effective than for gout [3] - Colcrys 1.2 mg followed in 1 hour by 0.6 mg c) intra-articular saline irrigation to remove crystals & mediators of inflammation d) intra-articular glucocorticoids after infection has been ruled out e) low-dose oral prednisone if multiple joints involved [2] f) low-dose colchicine or prednisone for 2 days with short-term efficacy [13] 2) propylaxis/maintenance (> 3 attack/year) [3] - colchicine, start with 0.6 mg PO QD - daily NSAID with GI prophylaxis (proton pump inhibitor) [2] - low-dose glucocorticoid [2] - hydroxychloroquine - methotrexate 3) treat osteoarthritis with CPPD as osteoarthritis 4) treatment of associated metabolic disorders does not seem to affect the course of CPPD disease 5) when CPPD is diagnosed in patients < 50 years of age, screen for hemochromatosis, hyperparathyroidism, hypothyroidism, gout 6) physical therapy as needed

Interactions

disease interactions

Related

chondrocalcinosis crystals in synovial fluid gout

General

chronic inflammation crystalline arthritis (crytalline arthropathy)

References

  1. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 861-62, 407
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2022. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  3. Geriatrics at your Fingertips, 13th edition, 2011 Reuben DB et al (eds) American Geriatric Society
  4. Schlesinger N, Hassett AL, Neustadter L, Schumacher HR Jr. Does acute synovitis (pseudogout) occur in patients with chronic pyrophosphate arthropathy (pseudo-osteoarthritis)? Clin Exp Rheumatol. 2009 Nov-Dec;27(6):940-4. PMID: 20149309
  5. Rosenthal AK. Update in calcium deposition diseases. Curr Opin Rheumatol. 2007 Mar;19(2):158-62. PMID: 17278931
  6. Announ N, Guerne PA. Treating difficult crystal pyrophosphate dihydrate deposition disease. Curr Rheumatol Rep. 2008 Jul;10(3):228-34. PMID: 18638432
  7. Richette P, Bardin T, Doherty M. An update on the epidemiology of calcium pyrophosphate dihydrate crystal deposition disease. Rheumatology (Oxford). 2009 Jul;48(7):711-5. PMID: 19398486
  8. Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
  9. Zhang W, Doherty M, Bardin T et al European League Against Rheumatism recommendations for calcium pyrophosphate deposition. Part I: terminology and diagnosis. Ann Rheum Dis. 2011 Apr;70(4):563-70 PMID: 2121681
  10. Zhang W, Doherty M, Bardin T et al European League Against Rheumatism recommendations for calcium pyrophosphate deposition. Part I: terminology and diagnosis. Ann Rheum Dis. 2011 Apr;70(4):563-70 PMID: 21216817 - Zhang W, Doherty M, Pascual E et al EULAR recommendations for calcium pyrophosphate deposition. Part II: management. Ann Rheum Dis. 2011 Apr;70(4):571-5. PMID: 21257614
  11. Rosenthal AK, Ryan LM. Calcium Pyrophosphate Deposition Disease. N Engl J Med. 2016 Jun 30;374(26):2575-84. Review. PMID: 27355536 Free PMC Article
  12. Molina-Gil J, Pena-Suarez J, Garcia-Cabo C Craniocervical Junction Calcium Pyrophosphate Deposition Causing Hypoglossal Nerve Palsy. JAMA Neurol. 2023;80(2):205-206 PMID: 36508204 https://jamanetwork.com/journals/jamaneurology/fullarticle/2799182
  13. Pascart T et al. Evaluating the safety and short-term equivalence of colchicine versus prednisone in older patients with acute calcium pyrophosphate crystal arthritis (COLCHICORT): An open-label, multicentre, randomised trial. Lancet Rheumatol 2023 Sep; 5:E523. PMID: 38251496 https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(23)00165-0/fulltext - Dalbeth N, Tedeschi SK. Calcium pyrophosphate deposition disease moves into the spotlight. Lancet Rheumatol 2023 Sep; 5:E497. PMID: 38251492 https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(23)00188-1/fulltext