Clinical Review

Calcium-Containing Crystal-Associated Arthropathies in the Elderly

Challenges still remain in the diagnosis, crystal identification, and treatment of pseudogout due to coexisting comorbid conditions and polypharmacy commonly found in veterans.

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Calcium pyrophosphate (CPP) crystals may deposit in both articular tissues (predominantly hyaline cartilage and fibrocartilage) and periarticular soft tissues.1,2 Calcium pyrophosphate deposition disease (CPPD) may be asymptomatic or be associated with a spectrum of clinical syndromes, including both acute and chronic inflammatory arthritis.2

The European League Against Rheumatism (EULAR) recently suggested changes in CPPD terminology.2 According to the new EULAR classification, pseudogout, or CPPD, has been reclassified based on new key terms that include several of the previously described disease phenotypes: asymptomatic CPPD; acute CPP crystal arthritis (previously known as pseudogout); osteoarthritis (OA) with CPPD (previously, pseudo-OA); and the chronic CCP crystal inflammatory arthritis (previously, pseudorheumatoid arthritis). In similar fashion, chondrocalcinosis (CC) refers to calcification of the fibrocartilage and/or hyaline cartilage identified by imaging or histologic analysis. Although CC is most commonly seen in CPPD, it is not exclusive to this disease, as it can be seen in other crystal diseases (oxalosis, basic calcium phosphate [BCP]) and can appear as casual finding or coexist with OA.2

Clinical Manifestations

In clinical practice, CPPD may present with several phenotypic forms. In asymptomatic CPPD, CC is a common radiographic finding without clinical symptoms. Acute CPP arthritis always should be suspected in any patient aged > 65 years presenting with acute monoarticular or oligoarticular, migratory or additive, symmetrical, or polyarticular arthritis.3 Acute CCP arthritis is characterized by self-limited acute or subacute attacks of arthritis involving 1 or several extremity joints (knees, wrists, ankles; rarely affects large toe). Typically, the acute attacks last 7 to 10 days. Several unusual sites (eg, the hip joints, trochanteric bursa, and deep spinal joints) also may be affected. However, differences in pattern of joint involvement are insufficient to permit definitive diagnosis without demonstration of the specific crystal type in the inflammatory joint fluid.

Pseudogout attacks closely resemble gouty arthritis; CPPD presents as intermittent flares and often is asymptomatic between flares. Trauma, surgery, or severe medical illness frequently provokes attacks of monosodium urate (MSU) as well as acute CPP arthritis. Systemic findings, such as fever; leukocytosis with a left shift in the differential count; inflammatory markers, such as elevated sedimentation rate (ESR); or C-reactive protein, also can occur, resembling pyogenic arthritis, osteomyelitis, and/or systemic sepsis in the elderly patient.

Diagnosis must be confirmed with aspiration, Gram stain and cultures of the synovial fluid, and evaluation for the presence of CPP crystals under polarized light microscopy.2 The diagnosis can be difficult to confirm secondary to the weakly birefringent nature of CPP crystals.4 Coexistence of MSU and CPP crystals in a single inflammatory effusion is neither uncommon nor unexplained given increased frequencies of both hyperuricemia/gout and CC among elderly patients.5

Chronic CPP crystal inflammatory arthritis may present as a chronic, symmetrical, bilateral, and deforming polyarthritis. It frequently affects the wrists and metacarpophalangeal joints and tendon sheaths. Chronic CPP may resemble rheumatoid arthritis (RA) and produce wrist tenosynovitis, which may manifest as carpal tunnel syndrome and/or cubital tunnel syndrome. Calcium pyrophosphate deposition disease should be on the differential diagnosis in the elderly patient presenting with a clinical picture that resembles “seronegative” RA, with morning stiffness, synovial thickening, localized edema, and restricted motion due to active inflammation or flexion contracture of the hands/wrist. It may present with prominent systemic features, such as leukocytosis, fevers, mental confusion, and inflammatory oligoarthritis or polyarthritis. The diagnosis of CPPD still may be possible even though the rheumatoid factor (RF) is positive, given the increasing likelihood of elevated RF in the older population. In this setting, aspiration of joint fluid and radiography will assist in clarification of the diagnosis. Furthermore, CPPD typically does not cause the type of erosive disease that is often seen in RA.

Calcium pyrophosphate deposition disease also can mimic polymyalgia rheumatica (PMR). A direct comparison of a cohort of patients with pseudo-PMR (PMR/CPPD) with actual PMR patients found that increased age at diagnosis, presence of knee osteoarthritis, tendinous calcifications, and ankle arthritis carried the highest predictive value in patients with CPPD presenting with PMR-like symptoms.6 However, the PMR/CPPD variant can be difficult to distinguish, because both conditions can have elevated systemic inflammatory markers, and both are steroid responsive.

Calcium pyrophosphate deposition disease involving a single joint can rarely lead to extensive destruction—as with neuropathic joints in the absence of any neurologic deficits—and is extremely debilitating. This presentation is not well understood and does not have good treatment alternatives. Calcium pyrophosphate crystals often are associated with manifestations of OA.1,2 Indeed, up to 20% of OA joints have been found to be positive for CPP crystals in various studies. Given the extensive evidence supporting treatment of OA, usually they are treated in a similar fashion with good results. Occasionally, these will have unusual manifestations for typical OA, such as involvement of wrists and metacarpophalangeal joints; however, the presentation is often indolent like OA.


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