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.

Additionally, history might reveal morning stiffness and fatigue, and in some cases, conditions, such as hypomagnesemia, hyperparathyroidism, and hemochromatosis.

Physical exam usually reveals enlarged, tender joints, with a limited range of motion. In some individuals, you might notice joint effusion or even contractures.

Finally, lab results typically reveal normal CBC with or without elevated ESR, CRP, and serum urate levels. With these findings, you should suspect chronic arthritis, Your next step is to then order X-rays of the affected joints.

Findings suggestive of chronic CPPD disease include chondrocalcinosis, meaning cartilage calcification, which can occur in the intra articular or peri articular tissues of the affected joint.

Findings depend on the joint affected, and classic examples are calcification of the fibrocartilaginous menisci in the knee, or hooked osteophytes and capsule calcifications of the metacarpophalangeal joints of affected hands.

With these findings, suspect chronic CPPD disease! Next, perform synovial fluid aspiration of an affected joint and send the fluid for microscopic analysis.

If microscopic analysis reveals positively birefringent, rhomboid-shaped crystals, diagnose chronic CPPD disease! Now, let’s take a look at management!

First-line medications include colchicine and NSAIDs, used alone or in combination to help control inflammation. Second-line options are similar to those used in acute CPPD, including systemic glucocorticoids, DMARDs, and interleukin-1 inhibitors.

Finally, don’t forget to screen for associated conditions by regularly checking serum magnesium, calcium, phosphate, parathyroid hormone, and transferrin saturation.Now here’s a clinical pearl to recall!

In gout, you can treat your patients with urate-lowering therapies, like allopurinol, which can specifically target the molecule implicated in crystal formation.

Unfortunately, no such targeted therapy exists for the treatment of CPPD disease.Finally, let's return to the x-ray findings.

If your x-ray findings are inconsistent with CPPD, then consider an alternative diagnosis, like osteoarthritis or rheumatoid arthritis.

One last clinical pearl! Up to 20 percent of patients with osteoarthritis also have CPPD disease, but many don’t have acute or chronic inflammatory symptoms.

These patients tend to have more severe and progressive joint degeneration, but the management remains the same as for osteoarthritis without CPPD.

In other words, these patients usually require physical therapy, NSAIDs, intra-articular glucocorticoids, and assistive devices.

Alright, as a quick recap… Calcium pyrophosphate deposition disease, or CPPD disease for short, 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.

The diagnosis primarily relies on synovial fluid analysis and findings of positively birefringent rhomboid-shaped crystals.

The management primarily relies on anti-inflammatory medications, but in some individuals, you can consider second-line treatment options, like systemic glucocorticoids, DMARDs, and interleukin-1 inhibitors.

In both acute and chronic CPPD disease, don’t forget to screen your patients for associated conditions,