Calcium pyrophosphate deposition disease (pseudogout): Clinical sciences

Calcium pyrophosphate deposition or CPPD disease, also known as pseudogout, is a type of arthritis associated with the precipitation of calcium pyrophosphate crystals in the synovial and periarticular tissues. CPPD disease can be asymptomatic, so in some individuals, it can be diagnosed incidentally with X-ray imaging. However, some patients can develop an acute or chronic type of CPPD disease.

Now, if your patient presents with a chief concern suggesting CPPD disease, you should first perform a focused history and physical examination. Next, order labs, including CBC, inflammatory markers, such as erythrocyte sedimentation rate and C-reactive protein, and serum urate.

Now, first, let’s focus on acute CPPD disease! Your patient will usually be over 60 and report a rapid onset of monoarticular or oligoarticular joint pain, redness, and swelling. These changes most commonly involve the knee, wrist, and metacarpophalangeal joints.

Additionally, history might reveal systemic symptoms, like fever and fatigue, and in some cases, conditions, such as hypomagnesemia, hyperparathyroidism, and hemochromatosis.

Now, here’s a clinical pearl to keep in mind! Hypomagnesemia, hyperparathyroidism, and hemochromatosis are conditions commonly associated with CPPD disease. Other important risk factors that you should keep in mind include trauma or surgery to the joint, as well as bisphosphonate use.

Additionally, the physical exam typically reveals signs of joint inflammation, such as joint redness, warmth, swelling, and tenderness to palpation. You might also notice a limited range of motion. Finally, lab results may reveal normal CBC or leukocytosis, elevated inflammatory markers, and in some cases, normal serum urate.

With these findings, you should suspect acute inflammatory arthritis. Your next step is to perform synovial fluid aspiration of the affected joint and send the fluid for microscopic analysis, gram stain, and culture.

Now, here’s a high-yield fact! When viewed under a microscope, calcium pyrophosphate crystals appear rhomboid-shaped and when exposed to polarized light, they become positively birefringent. Don’t get confused with monosodium urate crystals seen in gout, which are needle-shaped and when exposed to polarized light appear negatively birefringent . In fact, without microscopic analysis of the synovial fluid, it's hard to distinguish CPPD disease from gout!

Okay, if you do not see any positively birefringent rhomboid-shaped crystals on microscopic analysis of the synovial fluid, and your patient does not meet clinical criteria for CPPD disease, you should consider an alternative diagnosis, such as gout, septic arthritis, and Lyme arthropathy.

On the other hand, if you do not see any positively birefringent rhomboid-shaped crystals on microscopic analysis of the synovial fluid, with negative gram stain and culture, but your patient still meets clinical criteria for CPPD disease, diagnose acute CPPD disease! Remember, the absence of positively birefringent rhomboid shaped crystals does not exclude the diagnosis of CPPD disease!

Now, let’s go back to the microscopic analysis and if it reveals positively birefringent, rhomboid-shaped crystals with negative gram stain and culture, diagnose acute CPPD disease!

Now, here’s a clinical pearl to keep in mind! Crowded dens syndrome is a rare condition commonly seen in familial CPPD disease. These patients report fever and severe acute or recurrent axial neck pain, neck and shoulder girdle stiffness. Labs are significant for elevated inflammatory markers and you’ll see findings consistent with CPPD on CT in and around the atlanto-axial articulation!

Once you diagnose acute CPPD disease, proceed with management! First-line medical treatment includes intra-articular glucocorticoid injection, colchicine, and NSAIDs, which can be used as monotherapy or combined.

If first-line medications are contraindicated, poorly tolerated, or ineffective, consider second-line treatment options. These include systemic glucocorticoids at the lowest effective dose; DMARDs like hydroxychloroquine and methotrexate; and interleukin-1 inhibitors, like anakinra.

Finally, don’t forget screening labs, so order serum magnesium, calcium, phosphate, parathyroid hormone, and transferrin saturation since CPPD disease is associated with hypomagnesemia, hyperparathyroidism, and hemochromatosis.

Now that we are done with acute CPPD disease, let’s go back and discuss individuals presenting with chronic CPPD disease! In this case, your patient will usually be over 60 years of age and report symmetric, polyarticular joint pain, most commonly involving the knee, wrist, and elbow.