A 76-Year-Old Man With Acute Onset Knee Pain

Correct answer: C. After septic arthritis has been reasonably excluded, prednisone 30 mg orally for 2 days is an effective and convenient initial therapy for this patient.

Discussion. The presented case involves the differential diagnosis and therapeutics for an older patient presenting with acute onset of monoarticular arthritis in a large joint. The diagnosis is pseudogout or calcium pyrophosphate deposition disease (CPPD), a more common diagnosis than one likely expects. Symptomatic CPPD has been reported in up to 13.7% of patients older than 60 years of age, and if one accepts radiological findings, as high as 50% in populations older than 80 years of age. Advanced age is the main risk factor; smoking and alcohol history are not considered prominent risk factors. However, metabolic disorders involving calcium or iron metabolism are associated with increased risk. These disorder-related cases may offer clinical clues, particularly when CPPD develops before age 80 years, and especially before age 60 years, at which point, screening for associated metabolic disorders is warranted.² Additional associations include events related to arthritis onset such as postoperative states, hospital admissions, and new use of diuretics. The classical presentation is the acute onset of a painful monoarthritis in an adult older than 60 years, likely closer to 70 or 80 years of age. There is a distinct predilection for larger joints in CPPD, unlike uric acid gout, which more often favors smaller joints such as the great toe. The order of preference in CPPD is knee, then wrist, then first metacarpophalangeal joint, with typical findings including pain, redness, heat, swelling, and joint effusions.^1,2

At this point of the patient’s timeline, the major differentials included septic joint and uric acid gout. When practical and available, joint aspiration for gram stain, culture and sensitivity, and microscopic examination for crystal forms can firm up the diagnosis and clear the way for essential immediate therapy. Plain x-rays are also very helpful because the imaging is easy, prompt, and widely available. Bedside ultrasound can also demonstrate the typical linear calcification lines in the articular cartilage of the involved joints as well as elsewhere in the body.^1,2

It wouldn't be rheumatology if there wasn't a somewhat complex scheme of counting things, assigning point values, which when added up yield a discriminant number above which the diagnosis is confirmed. (Elderly sportsman that I am it reminds me of baseball scorelines-runs, hit, errors, left on base and final score!). The most used and current is the American College of Rheumatology and European Alliance of Associations for Rheumatology for CPPD.³ Age, time course of arthritis, site of episodes, synovial fluid analysis, and imaging are evaluated and assigned a point score value. A score above 56 meets the ACR/EULAR classification threshold for CPPD and supports the diagnosis. In this case, the patient scored 59 points.

Generally, the formation of calcium pyrophosphate crystals is poorly understood. Once calcium pyrophosphate crystals are released into the joint space, they trigger an acute inflammatory response involving cytokine release and recruitment of neutrophils into the joint, producing the clinical findings of acute arthritis. There is little difference between the inflammatory cascade induced by calcium pyrophosphate crystals and, for example, that of uric acid crystals in gout or the bacteria of septic arthritis.

After the typical patient with pseudogout has been promptly evaluated, and once the diagnosis is firm based on clinical data and joint aspiration (note that it is always important to exclude the septic joint), the next step is determining the treatment option for acute flare. In the rheumatology literature, the use of colchicine is a well-known mode of therapy. One study compared colchicine 1.5 mg BID regimen with a prednisone 30 mg/d for 2-3 days.⁴ The authors included patients with diabetes. Although the efficacy was equivalent, the “toxicity" side effects were not. Colchicine caused diarrhea in 22% of cases, a burden for older patients with knee involvement impairing ambulation. Of note, only 6% of patients with diabetes in the prednisone group experienced hyperglycemia.4 In my view, this is no contest. My decades-long avoidance of colchicine will continue. If available and practical, intra-articular steroid injection helps but will generally require a second arthrocentesis. Symptoms often improve substantially over 1 to 2 weeks, although recurrence can occur.

The literature on the use of biologics for CPPD is evolving. The anti-inflammatory agent anakinra does have efficacy, but the costs for daily 100 mg anakinra injections can range from the high hundreds to thousands of dollars.⁵ Tocilizumab has also been studied,^2,6 but its cost is substantial as well, with expenses exceeding thousands of dollars a month, or more than $30,000 per year for such therapy, according to the NIH.

Rarely, genetic disorders of phosphate metabolism can be associated with lifelong CPPD, and uncommon chronic variants may occur even in patients without an identifiable metabolic disorder. These are usually atypical in their younger age onset and widespread radiologic and clinical features.² In my view, secondary anti-inflammatory therapies should be strictly reserved for only these unique cases. Otherwise, a course of prednisone at a manageable expense is the mainstay of therapy in CPPD.

Patient follow-up. Following the diagnosis, arthrocentesis was performed and showed leukocytosis of 35,000 cells/µl with a high percentage of PMNs and no blood. A gram stain was negative for organisms. Although initiating therapy on existing findings was considered, there was caution such that only analgesics would be used pending culture results. The patient was kept overnight and an examination for crystals would be performed the following morning. By morning rounds, the laboratory reported no growth in either joint fluid or blood cultures. At this point, the patient started on prednisone 30 mg/d orally. Another joint aspiration was performed for crystal analysis and intra-articular corticosteroid injection. Both specimens were positive for the presence of calcium pyrophosphate crystals, confirming the diagnosis of CPPD. The patient’s pain roughly halved at 24 hours, then halved again at 48 hours. He was discharged on nonsteroidal anti-inflammatory drugs and a physical therapy program to strengthen the knee and to improve ambulation. The patient reported feeling almost back to normal following 2 weeks of physical therapy.

What’s the take home? Pseudogout, also known as CPPD, is a form of crystal deposition disorder wherein the crystal involved is calcium pyrophosphate rather than the uric acid of classical gout. The onset of an acute, painful monoarticular arthritis (and many of the joint features) are similar to gout but significant differences include age demographic (patients older than 60 years of age and even older than 80 have been diagnosed with CPPD), joints involved (large joints such as knee and wrist in CPPD) compared to smaller joints (great toe) with gout, and the calcium pyrophosphate crystals on joint analysis.

The typical presentation is a large joint inflammatory arthritis in an older patient. A very strong radiological clue is linear calcification in the articular cartilage, which can be demonstrated in plain x-rays or bedside ultrasound, when available. A detailed scheme using clinical findings, demographics, joint fluid analysis, and radiology findings can generate a classification score that supports the diagnosis in the appropriate clinical context. A strong study found prednisone and colchicine to have equivalent efficacy, with fewer adverse effects reported with prednisone, even in patients with diabetes.⁴ Although there is potential for a variety of novel anti-inflammatory agents (eg, anakinra, tocilizumab) in therapy, the bar to using such agents for anything other than rare refractory and/or metabolic disorders must be very high due to their expense compared with the efficacious and safe prednisone.

AUTHOR
Ronald N. Rubin MD^1,2

AFFILIATIONS
¹Lewis Katz School of Medicine at Temple University, Philadelphia, PA
²Department of Medicine, Temple University Hospital, Philadelphia, PA

CITATION
Rubin RN. a 76-year-old man with acute onset knee pain. Consultant. 2026;67(7):doi:10.25270/con.2026.07.000001

DISCLOSURES
The author reports no relevant financial relationships.

CORRESPONDENCE:
Ronald N. Rubin, MD, Temple University Hospital, 3401 N. Broad Street, Philadelphia, PA 19140 (blooddocrnr@yahoo.com)

References

1. Rosenthal AK, Ryan LM. Calcium pyrophosphate deposition disease. N Engl J Med. 2016;374(26):2575-2584.
2. Pascart T, Filippou G, Lioté F, Sirotti S, Jauffret C, Abhishek A. Calcium pyrophosphate deposition disease. Lancet Rheumatol. 2024;6(11):e791-e804. doi:10.1016/S2665-9913(24)00122-X
3. Abhishek A, Tedeschi SK, Pascart T, et al. The 2023 ACR/EULAR classification criteria for calcium pyrophosphate deposition disease. Ann Rheum Dis. 2023;82(10):1248-1257.
4. Pascart T, Robinet P, Ottaviani S, 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;5(9):e523-e531. doi:10.1016/S2665-9913(23)00165-0
5. GoodRx. Kineret (anakinra): uses, side effects, dosage & reviews. Accessed July 6, 2026. https://www.goodrx.com/kineret/what-is
6. Cipolletta E, Di Matteo A, Scanu A, et al. Tocilizumab in symptomatic calcium pyrophosphate deposition disease: a pilot study. Ann Rheum Dis. 2020;79(8):1126-1128. doi:10.1136/annrheumdis-2020-217188

©2026 HMP Global. All Rights Reserved. Any views and opinions expressed are those of the author(s) and/or participants and do not necessarily reflect the views, policy, or position of Consultant360 or HMP Global, their employees, and affiliates.