Calcium Pyrophosphate Deposition Disease (CPPD / Pseudogout)

Meet the patient

A 76-year-old woman, day four after a hemicolectomy, is febrile and holding her right knee rigid. The knee is hot, swollen, exquisitely tender, and will not bend. The surgical team has cultured the urine, the wound and the line — all negative — and is about to start IV antibiotics for "septic arthritis".^[1]

Two questions decide her next hour, and they decide every pseudogout stem: is this joint septic? and which crystal is it? Hold those two and the rest of the page slots into place.^[1]

Rhomboid, knee or wrist, treat like gout — three facts that earn the marks

Rhomboid and weakly positive; knee or wrist in the old; treat like gout but there is no allopurinol. That is the whole topic in one breath. Everything below deepens it; nothing replaces it.^[1]

The crystal is calcium pyrophosphate dihydrate — rhomboid or rod-shaped, and weakly positively birefringent (blue when its long axis lies parallel to the compensator's slow axis). That single property is the exact opposite of gout's needle-shaped, strongly negative urate crystal, and it is the most reproduced fact in the crystal-arthropathy viva.^[1]

The joint is the knee (commonest by far) or the wrist — the radiocarpal joint and the triangular fibrocartilage complex. Gout takes the first MTP; pseudogout takes the knee and wrist. Remember the joint and you have half the diagnosis before the fluid comes back.^[1][3]

The patient is older than 65, usually with established osteoarthritis. Prevalence climbs steeply with age — 7 to 10 per cent over 60, and 30 to 60 per cent over 85 — so chondrocalcinosis in an octogenarian is near-physiological; the same finding under 55 is a metabolic alarm bell.^[7]

Etymology for viva gold: chondrocalcinosis stitches Greek chondros (cartilage) to Latin calx (calcium) plus -osis (a process) — "calcium happening in cartilage". Pseudogout was coined by Zitnan and Sitaj in 1960 precisely because the acute attack masquerades as gout; the modern name acute CPP crystal arthritis strips the disguise, but the old word clings because it teaches.^[5]

The EULAR terminology — five words that mean five different things

The 2011 EULAR task force (Zhang, Part I) fixed the vocabulary so a clinician, a radiologist and an examiner all mean the same thing by each term. Examiners test these distinctions directly.^[5]

• CPP crystal deposition — the biochemical fact. Crystals are sitting in tissue; whether they cause trouble is a separate question.
• Chondrocalcinosis — strictly a radiographic or pathological term: CPP calcification of cartilage or fibrocartilage. It may be entirely silent (the "lanthanide" form).
• Acute CPP crystal arthritis — the modern name for pseudogout: an acute mono- or oligo-articular inflammatory attack from crystals shedding into a joint.
• Chronic CPP crystal inflammatory arthritis — a chronic, often polyarticular, inflammatory arthritis that mimics rheumatoid arthritis.
• Osteoarthritis with CPPD (pseudo-OA) — degenerative change in joints unusual for primary OA (MCPs, wrists, shoulders), with CPP deposition alongside. ^[1]

The trap within the terminology: chondrocalcinosis is a finding, not a diagnosis. An elderly knee X-ray dotted with calcification tells you crystals exist; it does not tell you the current hot swollen joint is pseudogout. The synovial fluid decides that.^[5]

Where CPPD sits in the crystal family

CPPD is one of four crystal arthropathies, each defined by its chemistry and morphology. Knowing the family sharpens both the differential and the polarised-light reading.^[3]

^[3]

The practical point for the microscope: only CPP and urate are visible to routine polarised light. Basic calcium phosphate (apatite) is sub-micron — infer it from a negative crystal search in an inflammatory fluid, or confirm with alizarin red, and meet it as the Milwaukee shoulder in older women. Oxalate belongs to primary hyperoxaluria or dialysis.^[3]

Aetiology — sporadic, familial, metabolic

CPPD sorts by why the crystals formed into three groups, because the cause sets the work-up.^[5]

^[5]

Aetiology is separate from clinical pattern. A patient can drift between patterns over a lifetime — silent chondrocalcinosis in their sixties, an acute pseudogout knee after surgery at seventy, a chronic inflammatory wrist at seventy-five. The current pattern drives the investigation; the aetiology drives the screen.^[1]

How common, and whose cartilage it takes

CPPD is a disease of ageing cartilage, and it is overwhelmingly non-modifiable. Prevalence of radiographic chondrocalcinosis rises steeply and roughly linearly with age.^[7]

^[7]

The risk factors, in order of weight:^[1]

• Age — by far the strongest; prevalence roughly doubles each decade after 50 as senescent chondrocytes pump out more PPi.
• Pre-existing osteoarthritis — CPPD and OA coexist so often that some consider them one degenerative continuum; the OA knee is the classic seedbed.
• Joint trauma and overload — meniscectomy, repetitive occupational loading, prior injury.
• Female sex — a slight predominance in the very elderly (women live longer and carry more OA).
• Metabolic disease — uncommon overall, but common in the young CPPD patient, which is exactly why anyone under 55 gets screened. ^[1][3]

Consultant confession: CPPD is the second commonest crystal arthritis overall (after gout) and the commonest in the elderly, yet it is the one most often mislabelled — as gout, as infection, as "just OA". It also tracks cardiovascular comorbidity, partly through shared demographics and partly through shared metabolic drivers. Treat the joint, but read the chart.^[3][7]

Why the crystals form — PPi, TNAP and the magnesium trap

CPPD is a PPi-overload disease of cartilage. Inorganic pyrophosphate (PPi) is the small anion that normally inhibits hydroxyapatite mineralisation, keeping cartilage uncalcified. When PPi accumulates, it teams up with calcium to precipitate as CPP crystals.^[3]

Three handles govern cartilage PPi:^[3]

• ENPP1 (PC-1) — the ecto-enzyme at the chondrocyte surface that cleaves ATP to AMP plus PPi. It makes extracellular PPi.
• ANKH — the multipass transporter (encoded by the ANKH gene) that pumps PPi out of the chondrocyte into the matrix. It exports PPi.
• TNAP — tissue-nonspecific alkaline phosphatase, which hydrolyses PPi back to inorganic phosphate, permitting the controlled mineralisation seen in bone and growth plate. ^[3]

The local PPi-to-Pi ratio is the switch: high PPi keeps cartilage clear, very high PPi grows CPP crystals, low PPi with high Pi grows apatite. In CPPD, excess PPi accumulates in the matrix and CPP crystals precipitate preferentially in avascular fibrocartilage and the mid-zone of hyaline cartilage — exactly where the transporters are busiest.^[3]

What raises cartilage PPi and drives crystallisation:^[1]

• Ageing chondrocytes — adopt a "hypertrophic", mineralising, growth-plate-like phenotype and over-produce PPi.
• TGF-β — released in OA cartilage, it stimulates PPi production; this is the OA–CPPD link.
• Hypomagnesaemia — magnesium is the essential cofactor for TNAP; low Mg disables PPi hydrolysis, PPi climbs, crystals form.
• Hypercalcaemia and hyperparathyroidism — surplus calcium feeds crystal nucleation.
• Iron overload (haemochromatosis) — deposited in cartilage, deranges chondrocyte metabolism, and produces a distinctive MCP arthropathy.
• Hypothyroidism, hypophosphataemia, Wilson disease (copper) and ochronosis (homogentisic acid) — rarer biochemistry disturbers. ^[1]

Why the acute attack looks identical to goutShowHide

When a CPP crystal is physically dislodged — by trauma, surgery, illness, or a shift in joint-fluid chemistry — macrophages and neutrophils phagocytose it. Phagolysosomal rupture exposes crystal surfaces and cathepsin B, which activate the NLRP3 inflammasome, driving caspase-1 cleavage of pro-IL-1β to active IL-1β. IL-1β then fires IL-6, IL-8 and TNF-α and recruits neutrophils. That is exactly the gout pathway — which is why the two attacks are clinically indistinguishable, and why IL-1β blockade works for both.

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Meet the five faces of CPPD

CPPD is a spectrum, and a patient can occupy a different point on it each decade. The 2011 EULAR task force (Part I) named five overlapping presentations, and recognising the current one drives both investigation and counselling.^[1][5]

Acute CPP crystal arthritis — pseudogout

The classic and most examinable face. An older adult (over 65, often with OA) develops severe pain, swelling, warmth and stiffness of one large joint over hours to a day or two. The joint is hot, erythematous, exquisitely tender, with a large effusion and a markedly restricted range — clinically indistinguishable from gout or septic arthritis. Fever and a systemic inflammatory response are common, which is why aspiration is not optional.^[1]

The classic joints are the knee and the wrist (radiocarpal, TFCC). Shoulder, elbow, ankle and hip can join in; oligo- or poly-articular attacks happen but are less common. The high-yield trigger is precipitation by intercurrent illness or surgery — a hot swollen knee on day three to seven after a general anaesthetic, a chest infection, a stroke or an MI is the textbook pseudogout stem. Direct trauma and procedures (arthroscopy, injection) also shed crystals.^[1][3]

Chronic CPP crystal inflammatory arthritis — the RA mimic

A subacute or chronic, often polyarticular, inflammatory arthritis that mimics rheumatoid arthritis, especially when it takes the wrists, MCPs and shoulders symmetrically. It differs in the older patient, the coexisting OA and chondrocalcinosis, and the CPP crystals in the fluid. Synovial fluid plus RF and anti-CCP resolves the confusion.^[1]

OA with CPPD — pseudo-OA

A chronic degenerative pattern in joints unusual for primary OA — the 2nd and 3rd MCPs, wrists, elbows, shoulders, ankles — alongside typical OA in knees and spine. Coarse crepitus, bony swelling, varus and stiffness predominate; inflammation is relatively spared. MCP involvement with hook-like osteophytes plus chondrocalcinosis should trigger iron studies — that is the classical haemochromatosis arthropathy.^[8]

Asymptomatic (lanthanide) chondrocalcinosis

The commonest form in the very elderly: incidental chondrocalcinosis on an X-ray taken for another reason, with no attributable symptoms. Reassure — unless the patient is young enough to merit a metabolic screen.^[1]

Rare destructive (Charcot-like) arthropathy

A rare but examinable pattern — a rapidly progressive, destructive, Charcot-like arthropathy of a large joint (knee or shoulder) with fragmentation, subchondral collapse and disorganisation, in a neurologically intact patient. Recurrent haemorrhagic effusions and marked bone destruction; management is difficult and often ends in arthroplasty.^[3]

Atypical presentations — the ones examiners set deliberately

Examiners love the atypical stem because it tests recognition outside the textbook. In the very frail, fever, confusion and systemic upset may dominate over joint pain — delirium with a swollen knee in a nursing-home resident is a recognised presentation, so examine the joints in every delirious older patient. Oligo- or poly-articular attacks mimic RA or reactive arthritis. Axial CPP deposition in the annulus or facet joints causes inflammatory back pain in the elderly. Tendon and bursal deposition (calcific deposits in Achilles or supraspinatus) rounds out the oddities.^[1][3]

The acute-monoarthritis three — pseudogout, gout, sepsis

Clinical features alone cannot separate these three. The synovial fluid can. Aspiration with polarised-light microscopy, Gram stain, cell count and culture is the decisive step in every acute monoarthritis.^[1][5]

^[1]

The discriminator line: rhomboid and weakly positive points to CPPD; needle and strongly negative points to gout; a positive culture or a Gram stain full of organisms points to sepsis. One crystal shape under the microscope settles the crystal question in seconds.^[1]

The two must-not-miss mimics are gout (the crystal differential — settled on polarised light) and septic arthritis (the dangerous differential — settled on Gram stain, culture and suspicion). And the teaching point that costs patients: sepsis and CPPD can coexist in the same joint. Finding crystals does not exclude infection; culture is always sent, and a positive culture overrides a crystal diagnosis. Round out the list with traumatic haemarthrosis (blood, trauma), an OA flare (less inflammatory, no crystals), psoriatic arthritis and, in the chronic pattern, polymyalgia rheumatica.^[1][3]

The bedside round — three questions

The bedside assessment runs on three questions, in this order: is this joint septic, which crystal is it, and is there a metabolic cause?^[1]

Examine the affected joint for warmth, erythema, swelling, effusion, tenderness and range. A hot, swollen knee or wrist in an older adult with a large effusion and severe pain on passive motion is the pseudogout stem. Ballotte the patella for a knee effusion; look for the bulge sign at the wrist. Document the tempo (hours means crystal or sepsis; weeks means chronic arthritis), any fever or rigors (do not be reassured — pseudogout causes fever too), and the number and distribution of joints.^[1]

Then look beyond the hot joint for the diagnosis:^[1]

• Coexisting OA — Heberden's and Bouchard's nodes, MCP squaring, knee deformity, crepitus.
• Metabolic stigmata — bronze or slate-grey skin (haemochromatosis); goitre, bradycardia, delayed reflexes (hypothyroidism); Kayser–Fleischer ring with hepatic and neurological signs (Wilson disease); ochronotic darkening of pinna or sclera (alkaptonuria); proximal weakness, hypertension, renal stones (hyperparathyroidism); tetany or Chvostek sign (hypomagnesaemia or hypocalcaemia).
• Precipitants — recent surgery, infection, trauma, hospitalisation, stroke or MI in the preceding days (the classic trigger).
• Joint-specific pattern — 2nd and 3rd MCP hook osteophytes point to haemochromatosis arthropathy: treatable, and easily missed. ^[8]

Assess the whole patient, because comorbidity picks the drug: renal function decides NSAID versus steroid; cardiovascular risk decides NSAID caution; diabetes decides steroid caution; anticoagulation decides injection timing. And keep asking, bedside, whether this joint could still be septic.^[1]

Investigations — aspirate, X-ray, ultrasound, the 4H screen

Synovial fluid — the definitive test

Aspiration with compensated polarised-light microscopy is the diagnostic investigation. Send every acute sample for crystal identification, cell count, Gram stain and culture.^[5]

^[1]

The fluid is inflammatory: white cell count commonly 2,000 to 100,000 per microlitre (often 15,000 to 30,000), neutrophil-predominant, typically clear to slightly turbid and yellow — unlike the bloody fluid of haemarthrosis or the opaque pus of sepsis. Mucin clot is poor, viscosity low. Crystals do not exclude sepsis: Gram stain and culture always go, a positive culture overrides the crystal diagnosis, and a count above 50,000 per microlitre with a neutrophil majority should heighten suspicion of infection even when crystals are present.^[1][5]

Plain radiographs — read for chondrocalcinosis

Chondrocalcinosis is the radiographic hallmark — CPP calcification of articular cartilage and fibrocartilage. Look for fine, linear or punctate calcification in the characteristic sites.^[1][5]

^[1]

The knee film is the single most useful — order AP and lateral of the symptomatic joint, plus wrist and pelvis (for the symphysis) when screening. Chondrocalcinosis plus compatible crystals confirms CPPD, but chondrocalcinosis alone — especially in the very elderly — does not prove the current arthritis is CPPD. The fluid does.^[5]

Advanced imaging — ultrasound first

The 2023 EULAR imaging recommendations put ultrasound first-line for crystal detection. CPP deposits in fibrocartilage throw a characteristic hyperechoic, dotted or chunky signal, distinct from the urate double-contour sign on hyaline cartilage. Ultrasound is more sensitive than plain film for early deposition, is radiation-free and works at the bedside. CT is highly sensitive for cartilage and tendon calcification in deep joints (hip, spine). MRI shows structural damage, synovitis and bone-marrow lesions but is less specific for crystals. Dual-energy CT can separate urate from calcium in research but is not routine.^[2]

The metabolic screen — the 4H plus others

Screen every patient under 55, and any atypical, severe, polyarticular or recurrent disease. The screen is cheap, treatable, and the single most useful thing an examiner wants you to remember.^[1][3]

^[1]

A pragmatic panel covers calcium, magnesium, phosphate, alkaline phosphatase, TSH, iron studies and ferritin, glucose and LFTs; add copper and caeruloplasmin if Wilson disease is plausible (younger patient with hepatic and neurological features). Hypomagnesaemia and haemochromatosis are the two most examinable because both are treatable — magnesium replacement can cut flares, and venesection (or iron chelation) slows extra-articular organ damage in haemochromatosis, even though neither dissolves existing crystals.^[8]

Other blood tests

CRP and ESR are raised in active disease — classically high in chronic CPP crystal inflammatory arthritis. U&E and eGFR govern drug choice (NSAID caution). RF and anti-CCP help when the chronic pattern mimics RA. Blood cultures if sepsis is suspected.^[1][4]

Acute management — aspirate first, then treat like gout

CPPD is not itself an emergency — the differential is. The only "resuscitation" is the rule that any acute hot swollen joint is septic arthritis until proven otherwise, and the first action is aspiration.^[1]

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The principle is simple: aspirate first, treat second. Empiric antibiotics before aspiration (except in a patient you cannot stabilise) contaminate culture and obscure the diagnosis; corticosteroid injected into a septic joint is catastrophic. Once the fluid shows CPP crystals and culture is set up — or the Gram stain is negative and sepsis is clinically unlikely — specific therapy begins.^[1][5]

The classic trap: injecting corticosteroid before excluding sepsis. A steroid into a septic joint destroys cartilage. Aspirate, read the Gram stain, send the culture, then inject.^[1]

The second trap: assuming crystals exclude infection. Pseudogout and sepsis coexist in the same joint. Send the culture every time.^[1]

The third trap: reaching for naproxen in an elderly patient before checking the eGFR. CKD, heart failure, anticoagulation and active GI disease all push you away from NSAIDs and toward steroid.^[4]

The drug ladder for acute pseudogout

Acute CPP arthritis is treated identically to gout, because both share the NLRP3 to IL-1β neutrophilic pathway. The 2011 EULAR Part II recommendations and the 2021 systematic review underpin the ladder.^[4][6]

^[1]

Choice is governed by comorbidity, not by proven comparative efficacy — none of the commonly used agents has been tested in a randomised trial for acute CPP arthritis:^[6]

• Single large joint, sepsis excluded → aspiration combined with intra-articular corticosteroid — often sufficient on its own.
• Elderly, renal impairment, heart failure, anticoagulated, or multiple joints → oral or parenteral corticosteroid, short course; prednisone may offer the best benefit-risk ratio in acute CPP crystal arthritis.
• Fit patient, no contraindication → oral NSAID with gastroprotection.
• Alternative → low-dose colchicine (0.5 to 1.0 mg daily); mild diarrhoea is the main risk. ^[4][3]

Chronic and refractory — no crystal-lowering drug exists

The goal shifts from aborting attacks to cutting flare frequency and controlling chronic synovitis, because no drug dissolves existing CPP crystals.^[4][6]

• Colchicine prophylaxis — low-dose colchicine (0.5 to 1.0 mg daily), EULAR's option against recurrent acute attacks and for chronic inflammatory symptoms.
• Low-dose NSAID with gastroprotection — the other EULAR option for chronic symptoms; weigh cardiovascular, renal and GI risk.
• Methotrexate or hydroxychloroquine — limited evidence only, but both are suggested for prophylaxis of recurrent flares and persistent CPP crystal inflammatory arthritis.
• IL-1 blockade — anakinra appears efficacious in refractory disease; IL-6 inhibition has a similar experimental role. Off-label, specialist use.
• Intra-articular steroid — for refractory chronic monoarticular disease.
• Joint replacement — for end-stage destructive arthropathy. ^[4][3][6]

The trap that catches the well-read candidate: there is no allopurinol or febuxostat for pure CPPD. Urate-lowering drugs do nothing to pyrophosphate crystals. Prescribing them is the single most common pharmacological error in CPPD questions.^[4]

Treat the metabolic cause — the only disease-modifying lever

Treating the metabolic cause is the only disease-modifying move available, and the one most often forgotten. It does not dissolve crystals already deposited, but it may slow progression and reduce flare frequency.^[3][8]

^[8]

Consultant confession: in haemochromatosis the arthritis can keep progressing even after iron depletion — venesection protects the liver and the heart, not necessarily the joint. Set that expectation with the patient, or they will think the treatment has failed.^[8]

Supportive and rehabilitative care

Physiotherapy, joint protection, weight management and assistive devices address the OA component and prevent deconditioning between flares. Patient education — the episodic, non-life-threatening nature of CPPD, the value of early flare treatment, the rationale for metabolic screening — improves adherence. And repeat the central rule: no role for urate-lowering drugs in pure CPPD.^[4]

Subtypes and scenarios — the stems examiners set

Which CPPD scenarios must I be able to handle?ShowHide

The five scenarios examiners probe: (1) acute monoarthritis post-surgery — the classic stem; aspirate, then intra-articular steroid; (2) CPPD in renal impairment — avoid NSAIDs, prefer steroid; (3) a positive metabolic screen — treat the cause (venesection, parathyroidectomy, magnesium, levothyroxine); (4) refractory chronic inflammatory CPPD — escalate to methotrexate then IL-1β blockade; (5) CPPD and gout together — the fluid shows both crystals; treat the dominant one, having aspirated to confirm.

^[1]

The post-operative pseudogout flare is the classic SAQ stem, and the literature backs it. Symptomatic knee effusions after hip-fracture surgery usually contain CPP crystals, and attacks in the early period after total knee arthroplasty are well described — misread one as periprosthetic sepsis and the patient undergoes surgery they never needed. Aspirate any new hot joint here: crystals confirm the flare and a negative culture excludes the must-not-miss prosthetic joint infection. Treatment follows the acute ladder — aspiration with intra-articular corticosteroid where the joint allows it, or short-course oral steroid.^[9][10][4]

Haemochromatosis arthropathy is the most examinable metabolic subtype. It classically takes the 2nd and 3rd MCP joints, often with hook-like osteophytes on X-ray, alongside chondrocalcinosis, and may be the presenting feature of the disease. Always check iron studies and ferritin (transferrin saturation over 45 per cent, ferritin markedly raised) and HFE genotyping in any young patient with chondrocalcinosis or this arthropathy. Venesection treats the systemic overload but does not reverse the joint disease.^[8]

Complications and the preventable-harm list

CPPD harms through structural joint damage and through iatrogenic injury from its own treatment. Both are examinable.^[1][3]

• Joint damage and secondary OA — recurrent shedding accelerates cartilage loss, especially in knee and wrist; many patients end up at arthroplasty.
• Recurrent acute attacks — episodic, triggered by illness or surgery, with cumulative disability and chronic pain between flares.
• Destructive (Charcot-like) arthropathy — rare but severe; rapid destruction, fragmentation, disorganisation.
• Iatrogenic harm — NSAID-induced AKI, GI bleeding and cardiovascular events in the elderly; colchicine toxicity in CKD (myelosuppression, neuromyopathy, diarrhoea); steroid hyperglycaemia, hypertension, osteoporosis and infection.
• Missed septic arthritis — the most dangerous pitfall. Crystals do not exclude infection; never inject without excluding sepsis.
• Cardiovascular comorbidity — through OA, metabolic disease and age. ^[1]

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Prognosis and disposition

Acute attacks are self-limiting, resolving over days to two or three weeks even untreated, and most respond to NSAIDs, colchicine or corticosteroid within 24 to 72 hours. Chronic forms, though, cause progressive joint damage for which no disease-modifying therapy exists; morbidity is driven by joint destruction, recurrent attacks and coexisting OA.^[1][3]

Natural history in one line: once CPP crystals form they persist for life; chondrocalcinosis is, in most elderly patients, a permanent radiographic finding. Attacks cluster — two or three in a year, then none for years — and flare frequency does not reliably predict structural damage, which depends more on OA burden, joint loading and metabolic control. Over years, recurrent inflammation and crystal-driven matrix degradation accelerate cartilage loss, subchondral sclerosis, cysts and joint-space narrowing.^[3][7]

Disposition: most acute pseudogout is managed as an outpatient with intra-articular steroid or oral therapy and rheumatology or primary-care follow-up. Admit when sepsis cannot be excluded, the patient is systemically unwell, the joint is a recent prosthesis, or comorbidity blocks safe outpatient management (severe CKD, anticoagulation, frailty). The safety-net is absolute: any patient whose pain, swelling or systemic features worsen — or who develops new fever or rigors after discharge — returns urgently for re-aspiration. Sepsis can declare itself days into a presumed crystal arthritis.^[1][5]

Special populations

• Elderly patients — the highest-prevalence and most drug-vulnerable group. Prefer intra-articular or low-dose oral corticosteroid over NSAIDs (renal, GI and CV risk); halve colchicine in CKD. Screen falls risk during a flare; address the OA component with physiotherapy and joint protection.^[1]
• Younger patients (under 55) — always screen metabolic causes. Haemochromatosis is treatable and easily missed; consider familial chondrocalcinosis (ANKH) with early-onset generalised disease and a family history.^[8]
• Renal impairment — avoid NSAIDs; prefer intra-articular steroid for a single joint or a short oral prednisolone course. Halve colchicine when eGFR is under 30; avoid it entirely with strong CYP3A4 inhibitors.^[4]
• Post-surgical or critically ill — flares classically follow surgery, sepsis, stroke or MI. Consider colchicine prophylaxis in known CPPD patients facing major surgery, and aspirate any new hot joint here to exclude prosthetic or iatrogenic infection.^[1]
• Anticoagulated patients — joint aspiration is generally safe with INR under about 3.0; discuss timing with haematology for high-INR patients. Intra-articular injection carries a small bleeding risk.^[5]
• Pregnancy — rare. NSAIDs are avoided after 20 weeks (and especially after 28); colchicine is avoided (foetal chromosomal risk); intra-articular corticosteroid is the preferred acute option.^[4]

Evidence, guidelines and regional differences

CPPD evidence is thinner than gout evidence — there are no large randomised trials, and management is largely extrapolated from gout and small observational studies.^[6]

^{[6] [1] [1] [1]}

The mantra — and the ward-round test

The mantra for the whole topic: rhomboid and weakly positive; knee or wrist in the old; aspirate to exclude sepsis; treat like gout but no crystal-lowering drug. Say it as one breath and you have the viva.^[1]

Ward-round test — cover the answersShowHide

^[1]

Q1. A 76-year-old woman, day four after a hemicolectomy, has a hot swollen right knee. eGFR 45. Diagnosis, definitive investigation, preferred treatment? A1. Acute CPP crystal arthritis (pseudogout) precipitated by surgery. Aspiration with polarised-light microscopy — rhomboid, weakly positively birefringent crystals, Gram stain and culture to exclude sepsis. Intra-articular corticosteroid after sepsis excluded (avoids NSAID nephrotoxicity); a short oral corticosteroid course is the alternative. Q2. A 48-year-old man has chondrocalcinosis in both knees and 2nd and 3rd MCP hook osteophytes. Which two tests, and what will they not fix? A2. Iron studies (transferrin saturation, ferritin) and HFE genotyping — haemochromatosis arthropathy. Venesection protects the liver and the heart but does not reverse the existing joint disease or dissolve crystals. Q3. A crystal-positive knee aspirate grows Staphylococcus aureus in culture at 48 hours. What happened, and what now? A3. Pseudogout and sepsis coexisted — crystals never excluded infection. Drop the steroid plan, admit, IV antibiotics and urgent orthopaedic washout. Q4. A 70-year-old with eGFR 28 and a flaring knee asks for "the gout tablet, allopurinol". Two reasons not to. A4. Allopurinol lowers urate, not pyrophosphate — it does nothing for pure CPPD (the crystal-lowering trap). And his eGFR of 28 rules out full-dose NSAIDs; reach for intra-articular corticosteroid after aspirating.

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References10ShowHide

1. [1]Ferrone C, Andracco R, Cimmino MA. Calcium pyrophosphate deposition disease: clinical manifestations Reumatismo, 2012.PMID 22303531
2. [2]Mandl P, D'Agostino MA, Navarro-Compán V, et al. 2023 EULAR recommendations on imaging in diagnosis and management of crystal-induced arthropathies in clinical practice Ann Rheum Dis, 2024.PMID 38320811
3. [3]Pascart T, Filippou G, Lioté F, et al. Calcium pyrophosphate deposition disease Lancet Rheumatol, 2024.PMID 39089298
4. [4]Zhang W, Doherty M, Pascual E, et al. EULAR recommendations for calcium pyrophosphate deposition. Part II: management Ann Rheum Dis, 2011.PMID 21257614
5. [5]Zhang W, Doherty M, Pascual E, et al. European League Against Rheumatism recommendations for calcium pyrophosphate deposition. Part I: terminology and diagnosis Ann Rheum Dis, 2011.PMID 21216817
6. [6]Parperis K, Papachristodoulou E, Kakoullis L, et al. Management of calcium pyrophosphate crystal deposition disease: A systematic review Semin Arthritis Rheum, 2021.PMID 33360232
7. [7]Ciancio G, Bortoluzzi A, Govoni M Epidemiology of gout and chondrocalcinosis Reumatismo, 2012.PMID 22303527
8. [8]Oppl B, Zwerina J [Hemochromatosis] Z Rheumatol, 2015.PMID 26197713
9. [9]Harato K, Yoshida H. Pseudogout in the early postoperative period after total knee arthroplasty J Arthroplasty, 2013.PMID 22522109
10. [10]Harato K, Yoshida H. Pseudogout at the knee joint will frequently occur after hip fracture and lead to the knee pain in the early postoperative period J Orthop Surg Res, 2015.PMID 25585622