Calcium Pyrophosphate Deposition Disease

Calcium pyrophosphate deposition disease (CPPD) is a crystal arthritis caused by deposition of calcium pyrophosphate dihydrate crystals in articular cartilage and periarticular tissue. It produces acute attacks (formerly pseudogout), chronic arthropathy that resembles osteoarthritis, and asymptomatic chondrocalcinosis on imaging.

• Prevalence increases with age: chondrocalcinosis in about 3 percent of adults aged 60, and 25 to 50 percent of those over 85; both sexes equally affected.
• Typical joints: knee (the commonest), wrist, shoulder, hip, ankle, elbow, and symphysis pubis; also the spine (crowned dens syndrome, acute neck pain and fever from deposits around the odontoid peg).
• Forms: asymptomatic chondrocalcinosis, acute CPP crystal arthritis, chronic CPP inflammatory arthritis, osteoarthritis with CPPD, and (rarely) tophaceous or destructive disease.
• Triggers for acute attacks: surgery, trauma, acute illness (myocardial infarction, stroke, sepsis), blood transfusion, dehydration, intra articular hyaluronate injection, bisphosphonates, G-CSF, and parathyroidectomy.
• Associated metabolic disease (screen in patients under 60 or with polyarticular disease): primary hyperparathyroidism, haemochromatosis, hypomagnesaemia, hypophosphatasia, hypothyroidism, Gitelman syndrome, familial CPPD, and gout (can coexist).

• Acute CPP crystal arthritis: rapid onset (within 6 to 24 hours) of a hot, red, swollen, very painful joint (usually the knee or wrist), with limited motion, fever, raised inflammatory markers, and resolution in 1 to 3 weeks; may mimic septic arthritis or gout.
• Chronic CPP inflammatory arthritis: persistent polyarticular synovitis resembling rheumatoid arthritis, morning stiffness, flares.
• Osteoarthritis with CPPD: slowly progressive pain and stiffness, involving unusual joints for osteoarthritis (wrist, metacarpophalangeal joints 2 and 3, shoulder, elbow, ankle), with episodic flares.
• Crowned dens syndrome: acute neck pain and stiffness, fever, and raised CRP.
• Rarer: spinal stenosis and tendinopathy from deposits, tophaceous deposits, destructive arthropathy.
• Examination: warm effusion, crepitus, bony enlargement, restricted motion; check for fever and signs of sepsis.
• Red flags: a single hot joint with fever or immunosuppression (septic arthritis until proven otherwise), prosthetic joint, skin breach, and polyarticular flare with systemic illness.

• Joint aspiration is the key test: synovial fluid cell count (raised white cells 2000 to 50 000, mainly neutrophils), Gram stain and culture (always, to exclude infection, because crystals and infection can coexist), and polarised light microscopy showing rhomboid or rod shaped, weakly positively birefringent crystals; gout (urate) crystals are needle shaped and strongly negatively birefringent.
• Imaging: plain X-ray shows chondrocalcinosis (linear calcification of fibrocartilage and hyaline cartilage: menisci, triangular fibrocartilage of the wrist, symphysis pubis, annulus fibrosus), together with osteoarthritic changes in atypical sites (patellofemoral compartment, radiocarpal joint, hook shaped osteophytes on the second and third metacarpal heads); ultrasound shows a hyperechoic band within hyaline cartilage and punctate deposits in fibrocartilage; dual energy CT identifies crystal type.
• Blood tests: FBC, ESR, CRP, urea and creatinine, calcium, phosphate, magnesium, alkaline phosphatase, parathyroid hormone, ferritin and transferrin saturation, thyroid function, and uric acid.
• Blood cultures if febrile; consider haemochromatosis genotype when iron indices are raised.
• Differentials: septic arthritis, gout, osteoarthritis, rheumatoid arthritis, spondyloarthritis, reactive arthritis, haemarthrosis, polymyalgia rheumatica (shoulder), and meningitis or odontoid fracture (neck pain).

Acute CPP crystal arthritis

• Exclude infection first: aspirate and culture before treating; start antibiotics if infection is suspected.
• Rest the joint and apply ice packs.
• Intra articular corticosteroid after aspiration (methylprednisolone acetate 40 to 80 mg for the knee, 20 to 40 mg for the wrist, triamcinolone acetonide 10 to 40 mg depending on the joint size) is highly effective for monoarticular attacks once infection is excluded.
• NSAIDs: naproxen 500 mg orally twice daily, or ibuprofen 400 to 600 mg three times daily, or etoricoxib 90 mg daily for 5 to 7 days with omeprazole 20 mg daily; avoid in renal impairment, heart failure, peptic ulcer, anticoagulation, and in older adults when possible.
• Colchicine 0.5 mg orally once to three times daily (for example 1 mg then 0.5 mg after 1 hour, then 0.5 mg twice daily) for 1 to 2 weeks; reduce the dose in renal impairment and with interacting drugs (clarithromycin, ciclosporin, statins); diarrhoea is common. Prophylactic colchicine 0.5 mg once or twice daily for 3 to 6 months for recurrent attacks.
• Oral prednisolone 30 to 40 mg daily for 3 to 5 days then taper over 7 to 10 days (or 0.5 mg/kg for 5 days) for polyarticular attacks or when NSAIDs and colchicine are contraindicated; watch blood glucose, blood pressure, and fluid.
• Intramuscular triamcinolone 40 to 80 mg or corticotropin for polyarticular disease.
• Interleukin-1 inhibition (anakinra 100 mg subcutaneously daily for 3 days) for refractory severe attacks (specialist).

Chronic CPP inflammatory arthritis and osteoarthritis with CPPD

• Colchicine 0.5 mg once or twice daily for prophylaxis and chronic inflammatory disease; low dose prednisolone 5 to 7.5 mg daily; hydroxychloroquine 200 mg twice daily; methotrexate 7.5 to 20 mg weekly with folic acid 5 mg weekly for refractory disease (specialist).
• Analgesia: paracetamol 1 g four times daily; topical NSAID (diclofenac 1 percent gel to the joint four times daily); weight loss; exercise and physiotherapy; walking aids; intra articular steroid for flares; joint replacement for end stage disease.

Treat associated conditions

• Hypomagnesaemia (magnesium replacement), hyperparathyroidism (parathyroidectomy), hypothyroidism (levothyroxine), haemochromatosis (venesection), hypophosphatasia; no treatment dissolves crystals.

Patient advice

• Maintain hydration and avoid dehydration, review diuretic use (magnesium loss), treat acute illness early, and avoid precipitating events where possible; weight management and joint protection.

Follow up

• Review at 1 to 2 weeks after an attack; check renal function, calcium, magnesium, and metabolic screen in patients under 60 or with polyarticular disease; refer to rheumatology for diagnostic uncertainty, recurrent attacks, chronic inflammatory disease, or when joint replacement is considered.

Special groups

• Older adults and renal impairment: favour joint aspiration with intra articular corticosteroid or a short oral prednisolone course; use colchicine at reduced doses (0.5 mg once daily) with monitoring and avoid NSAIDs.