Imaging and management of calcium pyrophosphate deposition disease

Abstract

The radiological manifestations of calcium pyrophosphate deposition (CPPD) revolve around two main axes: the asymptomatic form and CPPD disease. The latter is a consequence of an immune response to calcium phosphate crystals. Chondrocalcinosis is broadly considered the radiographic manifestation of CPPD regardless of whether it is asymptomatic or associated with inflammatory arthritis. CPPD is associated with osteoarthritis although the direction of such association is still unclear. Apart from the detection of CPP crystals in synovial fluid, imaging (mainly conventional radiography and increasingly ultrasound) plays a central role in the diagnosis of CPPD disease. Recently, CT has been added as a diagnostic tool, especially in deep anatomic locations such as crowned dens. To date, no treatment is effective in dissolving CPP crystals. For now, the focus of current treatment strategies remains inflammation control. Our aim is to review the epidemiology, pathogenesis, and clinical and imaging manifestations of asymptomatic and symptomatic CPPD. We will also discuss recent consensus definitions and classifications of CPPD disease.

Keywords: CPPD; Calcium crystal; Calcium pyrophosphate; Osteoarthritis.

Figure 1:

Acute CPP arthritis in a 77-year-old female admitted to the hospital with bilateral hand pain worse on the right. The clinical presentation was concerning for cellulitis and/or septic arthritis. Aspiration revealed CPP crystals. Anteroposterior (A) and lateral (B) radiographs of the right-hand show marked soft tissue thickening along the dorsal aspect of the hand (white solid arrows) and chondrocalcinosis in multiple areas including the triangular fibrocartilage and in the third MCP joint (black dashed arrows). The constellation of clinical and radiographic findings was consistent with acute CPP arthritis. Patient dramatically improved after starting colchicine and prednisone.

Figure 2:

66-year-old female with chronic CPPD arthritis. (A) Photograph of bilateral hands shows deforming arthropathy of the left second and third metacarpophalangeal (MCP) joints (solid arrows). Anteroposterior radiographs of the left (B) and right (C) hands show multiple radiographic findings consistent with CPPD arthropathy including diffuse mineralization of both radiocarpal joint more prominent at the triangular fibrocartilage on both sides (arrowheads), as well as widening of the right scapholunate interval consistent with ligament rupture (double-ended arrow). Right 2^nd and 3^rd MCP deformities as seen clinically (solid arrows). Additional evaluation with ultrasound at the rheumatology clinic was performed (D-F). (D, E) Longitudinal ultrasound images of the third MCP joint show osteophyte formation of the third metacarpal head (solid arrow) and intra-articular mineralization (arrowhead). The double contour appearance consistent with CPPD deposits is best displayed in image part (E) (arrowhead). (F) Longitudinal ultrasound images of the volar surface of the wrist shows hyperechoic material in the region of the carpal tunnel (solid arrow). This patient also had carpal tunnel symptoms.

Figure 2:

66-year-old female with chronic CPPD arthritis. (A) Photograph of bilateral hands shows deforming arthropathy of the left second and third metacarpophalangeal (MCP) joints (solid arrows). Anteroposterior radiographs of the left (B) and right (C) hands show multiple radiographic findings consistent with CPPD arthropathy including diffuse mineralization of both radiocarpal joint more prominent at the triangular fibrocartilage on both sides (arrowheads), as well as widening of the right scapholunate interval consistent with ligament rupture (double-ended arrow). Right 2^nd and 3^rd MCP deformities as seen clinically (solid arrows). Additional evaluation with ultrasound at the rheumatology clinic was performed (D-F). (D, E) Longitudinal ultrasound images of the third MCP joint show osteophyte formation of the third metacarpal head (solid arrow) and intra-articular mineralization (arrowhead). The double contour appearance consistent with CPPD deposits is best displayed in image part (E) (arrowhead). (F) Longitudinal ultrasound images of the volar surface of the wrist shows hyperechoic material in the region of the carpal tunnel (solid arrow). This patient also had carpal tunnel symptoms.

Figure 3:

CPPD and osteoarthritis in a 69-year-old woman with a long-standing history of bilateral knee pain from osteoarthritis (including prior intra-articular cortico-steroid injections and visco-supplementation). Anteroposterior (A, C) and lateral (B, D) radiographs of the left knee in 2006 (A and B) and 2024 (C and D) demonstrate progression of CPPD with increased burden of chondrocalcinosis in the medial and lateral menisci (dashed arrows) as well as the posterior capsule calcific deposits (solid arrows) between 2006 and 2024, as well as progression of osteoarthritis, more prominent at the patellofemoral joint which shows large superior patellar osteophyte in the follow-up visit (arrowhead). The association between CPPD and OA is often noted on imaging studies, though the direction is this association remains unknown.

Figure 4:

Frontal (A) and sunrise (B) views of the right knee in a 61-year-old female with long standing history of knee pain showing chondrocalcinosis projecting of the medial and lateral compartment (dashed arrows), as well as severe patellofemoral arthritis with bone-on-bone contact of the lateral patella and lateral trochlea. These findings are consistent with CPPD arthropathy. Lateral view of the left knee in another 68-year-old female patient shows anterior scalloping of the distal anterior femoral cortex, at the level pf the patella with severe patellofemoral joint space narrowing. Although chondrocalcinosis is not detected in this case, this finding may suggest CPPD arthropathy.

Figure 5:

Cervical spine compression in a 78-year-old male who presented with signs of cervical myelopathy and C2 neuralgia in the setting of CPPD with retro-odontoid ligament and multilevel ligamentum flavum thickening. (A) Sagittal T2-weighted MRI shows severe cord compression at the cranio-cervical junction secondary to T2 hypointense thickening of the retro odontoid ligaments (arrow). (B) Axial and (C) sagittal CT reformatted images show diffuse mineralization involving the peri-odontoid ligaments (black solid arrows), as well as the ligamentum flavum (white solid arrows) and intervertebral disc spaces (black arrowhead).

Figure 6:

Calcified chondroid mesenchymal neoplasm (CCMN), previously known as “tophaceous pseudogout” in a 72-year-old female who presented with pain around the right ear and jaw, and changes to her bite for 2 years. Coronal (A) and sagittal (B) unenhanced CT reformatted images centered around the right temporomandibular joint (TMJ) show intra-articular bilobed mineralized mass (arrows), without substantial degenerative changes or joint destruction. Upon surgical resection and molecular analysis, the mass was found to have a FN1-FGFR2 gene fusion, which is characteristic of calcified chondroid mesenchymal neoplasm.

Figure 7:

Sagittal computed tomography reformats of a the right knee in a 78-year-old patient with chronic knee pain prior to total arthroplasty. There are punctate mineralizations of the hyaline cartilage of the posterior third of the medial femoral condyle involving less than 75% of the cartilage region (arrowhead), corresponding to grade 2 according to the Boston University Calcium Knee Score (BUCKS). Linear mineralization of the anterior horn of the meniscus are also shown (arrow).