Gout and pseudogout

CRYSTAL ARTHRITISDr. Angelo Smith M.DWHPL

Ben Franklin (1706 -1790)

"Be temperate in wine, in eating, girls, and sloth, or the Gout will seize you and plague you…"

-- Franklin

History: Galen (129-199 AD), an ex-

gladiatorial surgeon in the Pergamon arena in Asia Minor who moved to Rome, described gout as a discharge of the four humors of the body in unbalanced amounts into the joints (hence gout = gutta, a drop).

The first radiological description of gout was made by Huber in 1896, a few months after Röentgen described the x-ray.

MAJOR ARTHRITOGENIC CRYSTALS

Monosodium urateCalcium pyrophosphate dihydratte

HydroxyapatiteCorticosteroid estersCalcium oxalate

CRYSTAL ARTHRITIS

GOUT (monosodium urate)

PSEUDOGOUT (calcium pyrophosphate)

HYDROXYAPATITE

GOUT

Inflammatory arthritis mediated by the crystallization of uric acid within joints, tophi

Often associated with hyperuricemia Incidence: 62.3 /100,000 (2-fold increase) Associations: DM, HTN, metabolic

syndrome, obesity, CVD, renal stones, CPPD

Risk Factors: genetics, age, CRF, serum uric acid, diet, alcohol, medications

Uric Acid Balance

Gout: Pathophysiology

Uric acid: overproduction vs. underexcretion

Mechanisms of urate “production” cellular nucleoproteins/nucleotides (~ 66%) diet (~33%)

Mechanisms of urate excretion kidney (~66%) gut (~33%)

Renal Excretion of Uric Acid

Completely filtered by the glomerulus Completely (essentially) reabsorbed in the

proximal tubule Approximately 50% is secreted back into the

tubule in the descending loop Approximately 80% (of the 50% now in the

loop) is reabsorbed in the ascending loop Net excretion = 10% of filtered load

Diet

Diet

Asymptomatic Hyperuricemia

Hyperuricemia alone does NOT make a diagnosis of gout-only a subset of people with hyperuricemia will

develop gout

-probability of gout increases with higher uric acid levels

Asymptomatic hyperuricemia generally requires no treatment

Hyperuricemia – Preclinical Period

Hyperuricemia (>7.0 mg/dl) in 5% - 8% of male population.

Most (about ⅔) are forever asymptomatic.

80% of gouty patients have uric acid < 9 mg/dl.

Above 10 mg/dl, risk rises rapidly. Gout is the most common cause of

monarthritis in middle-aged and elderly men (8% yearly prevalence).

Conditions AssociatedWith Hyperuricemia

Lymphomas (esp. Hodgkin’s disease) Myeloproliferative disorders Diabetes Psoriasis Sarcoid Glycogen storage disease

GOUT

Urate precipitation leads to acute gouty arthritis Local factors – temperature, pH, trauma,

joint hydration Systemic factors – hydration state,

fevers, meds, alcohol, co-morbid conditions

Attack resolves spontaneously 10-15 days

A Typical Attack of Gout

Lasts several days to several weeks.May spread from joint to joint.Often accompanied by fever,

leukocytosis.Gets worse as the years go on.Pain appears last, disappears first.Petite attacks occur (lasting hours).

GOUT

ACUTE GOUT First attack 4th-6th decade for men Women almost always

postmenopausal Classically monoarticular LE– podagra

(50%), (vs pseudopodogra) >ankle >gonagra >upper extremity.

Proximal joint, central arthropathy uncommon

Causes of Podagra

MSUCPPDHydroxyapatiteSepticPsoriatic, Reiter’sRheumatoid

Diagnosis

Evidence-based medicine based on EULAR (ESCISIT) – 10 key points Acute attack 6-12 peak intensity with S/W/E/T Aspiration always recommended if possible Prompt polarized microscopic analysis

performed Definitive Dx – requires crystal confirmation Gout and Sepsis can coexist – fluid should be

sent Gram’s stain, culture Serum uric acid levels neither confirm nor

exclude gout Radiographs not necessary Risk factor assessment

Laboratory

Hyperuricemia biochemical hallmark of gout, but not by itself

diagnostic for gout Leukocytosis Increased ESR Synovial Fluid 

leukocyte counts = septic arthritis viscosity is < septic or inflammatory arthritis  

MSU needle - like intracellular & extracellular crystals

Negatively birefringent crystals under polarized light microscopy

ACUTE GOUT

THERAPY (for all crystal diseases): Corticosteroids: intrarticular > systemic NSAIDs – fast acting full dose if no

contraindications Colchicine (PO,IV route dangerous)

▪ narrow therapeutic window▪ Bone marrow suppression, myopathy, neuropathy

▪ purgative effects – “Pt often run before they walk”

ACTH NEVER ALLOPURINOL

Intercritical Period

70% prevelance of MSU crystals remain in the joint

Lasts months to years for 75-80%, 20% never have another attack

Uric Acid Lowering Therapy

Lifestyle, dietary modification Diet high in vegetables, dairy, water

beneficial Initiate uric acid lowering therapy

after 1(?) or 2 episodes of acute gouty arthritis

Always prophylaxis for first 6 months with low dose steroids, NSAIDs, or colchicine

CHRONIC GOUT

USUALLY PRESENT AFTER 10 YEARS OF ACUTE INTERMITTANT GOUT

TOPHI DEPOSITION CHRONIC SWOLLEN JOINTS JOINT DESTRUCTION ABSOLUTELY REQUIRES

ALLOPURINOL

CHRONIC GOUT

Radiographic Hallmarks of Gout

Overhanging edges Punched out lesions with sclerotic

borders. Preservation of joint space (till late) Degenerative changes

The “Double Contour Sign” of Gout. Filippucci E, Grassi W Department of Rheumatology, University of Ancona, Italy

Gout vs. Pseudogout

Gout hallux, ankle, knee, hand younger, male

Pseudogout knee, wrist, ankle older, female

Almost any joint can be affected by either disease!

Clinical Associations with Psuedogout

Aging Previous joint surgery Previous joint trauma Familial types Gout Amyloidosis

Hyperpara Hemochromatosis Hypomagnesemia Familial

hypocalciuric hypercalcemia

Hypophosphatasia Wilson’s disease Ochronosis

PSEUDOGOUT

CHONDROCALCINOSIS Acute arthritis caused by Calcium pyrophosphate

dihydrate (CPPD) crystal-induced inflammation May perfectly mimic gout during acute flare Attacks occurring before age 50 are uncommon

Clinical:  Most often affects the knee and the wrists

Radiology:  Calcification densities in hyaline or fibrocartilage,

which are found in knee menisci, acetabular labrum, & TFCC

Laboratory

Fluid analysis: CPPD crystals are visualized under compensated

polarized light microscopy  crystals may be more difficult to detect than MSU

crystals because of their smaller size, more intralysosomal location, & less brilliant colors

CPPD crystals show weak positive birefringency and have squared or rhomboidal shaped ends

alizarin red stain, can confirm that these clumps are masses of calcium crystals

Treatment: aspiration of the involved joint and steroid

injection, once diagnosis of infection has been excluded, will usually control symptoms

The Basic (Non-Acidic) Calcium Phosphates

HydroxyapatiteCalcium carbonateOctacalcium phosphateTricalcium phosphate (whitlockite)

Hydroxyapatite is non-birefringent.

Syndromes Associated with Hydroxyapatite

Acute monoarthritis (pseudopseudogout)

Acute calcific tendinitis, bursitis Scleroderma, dermatomyositis Heterotopic calcification Milwaukee shoulder Crowned Dens Syndrome

Acute Apatite Monoarthritis(Pseudopseudogout)

Is usually a peri-arthritis. Intense inflammation (looks septic) Synovial fluid often non-

inflammatory. Often causes podagra (especially

in younger women). Look for the telltale calcifications

on radiographs.

Milwaukee Shoulder

Severe, destructive shoulder arthropathy.

Seen in elderly females with DJD of shoulder.

High-riding humeral head on radiographs (large rotator cuff tear).

Non-inflammatory fluid with BCP crystals.

Crowned dens syndrome

Is an association of acute cervical pain and calcifications in the peri-odontoid space.

This disease affects only adult females. Patients present with inflammatory signs,

can be treated with non-steroid anti-inflammatory drugs and recover without sequela.

CPPD deposition can also lead to this syndrome.

Radiologically - crowned dens.