Gout Ba or OA Lang?

Allan D. Corpuz, MD, FPCP, DPRA 01 July 2016

St. Louis University CCA

Objectives •  Summarize the approach to the diagnosis of patients

with musculoskeletal disease in 4 easy steps •  Use the 2015 Gout Classification Criteria with

confidence •  Understand the value of uric acid for both gout and

OA •  Ask the appropriate questions to be able to screen

patients with gout •  Be confident about urate lowering therapy and

concomitant prophylaxis of gout

Disclosures •  Sub-investigator for Clinical Trials: BASE and

AURINIA •  Speaker for Pfizer, LRI-Therapharma, Otsuka

CASE •  A 54 y.o male family driver consults for pain in the

left knee on going up and down the stairs, for 2 years now. About 2 months ago, after driving long distance, the pain got worse and he now limps when walking. There is no fever or malaise.

•  Joint PE: left knee is swollen, warm, + bulge sign. There is 2+ tenderness and limited flexion and extension. The right knee appears normal, but is positive for fine crepitations.

CASE •  A 48 y.o businessman came home from a party the

night prior to consult and woke up with an inflamed right big toe. He was feverish and could not walk. He admitted to drinking beer and had “pulutan” of kilawin. He had a similar episode 4 years prior, lasting 2 days.

•  Joint PE: Swollen, erythematous, warm and exquisitely tender right 1st MTP joint.

CASE •  A 45 y.o. housewife consulted for swelling and

pain of both wrists and small hand joints of 4 months duration. Pain is worse in the morning, associated with stiffness lasting for 1 hour. She takes Alaxan tablets as needed, with temporary pain relief.

•  Joint PE: Swelling , warmth and tenderness of both wrists, and 1st and second PIPs of both hands. Other joints and systemic PE are normal

CASE •  A 35 y.o. female PA of a famous celebrity consulted

for swelling and pain of the R wrist and 4 weeks duration. Pain is worse at the end of the day, especially after a long day of writing, texting and carrying her boss’ stuff. She takes Arcoxia tablets as needed, with temporary pain relief.

•  Joint PE: Tenderness of R wrist, with pain on thumb flexion, digit flexion and sharp ulnar deviation of the wrist. No Pain on PROM. Other joint PE are normal

THE FUNDAMENTALS: KNOWING WHAT TO ASK

Back to the Basics

• A • C • I • N

A: Is it Articular or Non-Articular? •  Active ROM •  Passive ROM

•  PAIN – Articular: +AROM,

+ PROM – Non-articular:

+AROM, -PROM

•  Both OA and Gout have articular manifestations

•  Gout may be non-articular in the case of gouty bursitis

C: Is is Chronic or Acute? •  Chronic: >= 6

weeks •  Acute <6 weeks

•  OA: usually chronic (pain on most days of the week)

•  Gout: Acute, episodic; may be chronic if with tophi

I: Is it Inflammatory or Non-Inflammatory

•  Inflammatory: calor, rubor, dolor, tumor, loss of function (LOM)

•  OA: non-inflammatory, except when in flare (rare)

•  Gout: inflammatory

N: How Many (Number) Joints are Involved?

•  1: monoarticular •  2-3: oligoarticular •  >3: polyarticular

•  OA: usually polyarticular – hand, knee, hip, lumbar spine

•  Gout: usually starts as mono- or oligoarticular, eventually becomes polyarticular

CLASSIFICATION CRITERIA

Gout Criteria (1977)

Gout Criteria (2014) •  Male sex = 2pts •  Previous patient-reported arthritis attack = 2 pts •  Onset within 1 day = 0.5 pt •  Joint redness = 1 pt •  MTP1 involvement = 2.5pts •  HTN or ≥ 1 CV diseases = 1.5 pts •  Serum Uric acid >5.88mg/dL = 3.5 pts

Kienhorst, LB et al. The Validation of a diagnostic rule for gout without joint fluid analysis: a prospective study. Rheumatology (Oxford) 2014; 16

Gout Criteria (2014) SCORE INTERPRETATION APPLICATION

<=4 Non gout in 95% Consider a different Dx such as CPPD, Reactive Arthritis, Septic Arthritis, Rheumatoid Arthritis,

OA, or Psoriatic Arthritis >4-8 Uncertain Perform joint fluid aspiration and analysis w/

polarization microscopy for the presence of crystals; if not possible or available, then

extensive follow-up of the patient >=8 Gout in 87% Manage the patient as having gout, including

care for CV risks

Kienhorst, LB et al. The Validation of a diagnostic rule for gout without joint fluid analysis: a prospective study. Rheumatology (Oxford) 2014; 16

ACR/EULAR 2015 •  ENTRY Criterion •  SUFFICIENT Criterion •  CLINICAL Criteria •  LAB Criteria •  IMAGING Criteria

STEP 1: Entry Criterion •  At least one episode of swelling, pain or

peripheral tenderness in a peripheral joint or bursa

STEP 2: Sufficient Criterion •  Presence of MSU Crystals in a symptomatic joint or

bursa (ie Synovial Fluid) or tophus

STEP 3: Criteria •  CLINICAL •  LABORATORY •  IMAGING

CLINICAL CRITERIA

Pattern

•  Ankle or midfoot (w/o MTP1) = 1 pt •  MTP1 = 2 pts

Characteristics

• Erythema = 1 pt • Can’t bear touch or pressure = 1 pt • Great inability in walking or inability to use joint = 1 pt

Time Course

•  Time to maximal pain <24h • Resolution <= 14days • Complete resolution to baseline level between symptomatic episodes • 1 typical episode = 1 pt / Recurrent typical episodes = 2 pt

Tophus

•  Draining or chalk-like subcutaneous nodule under transparent skin, often with overlying vascularity, located in typical locations: joints, ears, olecranon bursae, finger pads, tendons (e.g., Achilles) = 4 pts

LABORATORY CRITERIA •  SERUM URATE – <4 mg/dL (<0.24 mmol/L) = -4pts – 6-8 (0.36-0.48) = 2pts – 8-10 (0.48-0.60) =3pts – >10 (>0.60) =4pts *Ideally not on ULT, >4wks from start of episode (if practicable, retest under those conditions)

•  SF Analysis (of Symptomatic joint or bursa) – By trained observer

IMAGING CRITERIA •  Urate deposition =

4pts – Ultrasound:

double contour sign

– DECT: deposition of urate

•  Gout related damage = 4 pts – At least 1 erosion

on hands and/or feet Xray

MAX SCORE = 23 THRESHOLD SCORE = 8

Comparison of Classification 2015 vs 2014 vs 1977

Criteria Sensitivity/Specificity

Advantage/Disadvantage

1977 100% SEN 51% SPEC

Gold standard / Criteria + in a other rheumatic conditions

2014 95% SEN 87% SPEC

Appropriate for clinical settings / Still need SF aspiration and microscopy if uncertain

2015 92% SEN 89% SPEC

Incorporates imaging modalities; appropriate for clinical setting if SFA

cannot be done; can be a “clinical-only” version in settings where lab and imaging

criteria are impossible to fulfill

CLINICAL PRESENTATION: GOUT

Initial Presentation •  Podagra = 50% •  Mono to Oligoarticular =90% •  Rarely involves the shoulder •  Polyarticular in 10%

Puig JG, Michan AD, Jimenez ML, et al. Female gout. Clinical spectrum and uric acid metabolism. Arch Intern Med. 1991 Apr. 151(4):726-32.

Meyers OL, Monteagudo FS. Gout in females: an analysis of 92 patients. Clin Exp Rheumatol. 1985 Apr-Jun. 3(2):105-9 Macfarlane DG, Dieppe PA. Diuretic-induced gout in elderly women. Br J Rheumatol. 1985 May. 24(2):155-7

Differential Diagnosis of Gout

ROLE OF URIC ACID

= ≠ GOUT

HYPERURICEMIA GOUT

HYPERURICEMIA

HOW MANY WILL PROGRESS?

HOW MANY WILL PROGRESS?

HOW MANY WILL PROGRESS?

Uric acid levels correlate with OA severity •  Uric acid (UA) is known to activate the NLRP3 •  NLRP3 (also known as NALP3) inflammasome à IL-18 and IL-1β. •  Synovial fluid uric acid was strongly correlated with synovial fluid IL-18

and IL-1β. •  Synovial fluid uric acid and IL-18 were strongly and positively associated

with OA severity as measured by both radiograph and bone scintigraphy •  Synovial fluid IL-1β was associated with OA severity but only by

radiograph. •  Synovial fluid IL-18 was associated with a 3x change in OA severity, on

the basis of the radiograph. •  Synovial fluid uric acid is a marker of knee OA severity. •  There is potential involvement of the innate immune system in OA

pathology and OA progression.

OA Pathogenesis by Phenotype

IN A NUTSHELL, WHAT SHOULD I ASK?

Threee clinical clues/questions (you should ask)

•  EPISODIC •  EXQUISITE PAIN/TENDERNESS •  EXACERBATING FACTORS –  Diuretics, IV Heparin,

Cyclosporine –  Trauma, alcohol ingestion,

surgery, dietary excess, hemorrhage, foreign protein therapy, infections, radiographic contrast exposure

–  20% of hospitalized patients develop a gout attack (esp if with previous Hx)

EPISODIC: Sample Questions •  Ang pagsakit po ba ng kasukasuan nyo: tuloy-

tuloy o pasulpot-sulpot lang? •  Ang sakit po ba ay araw-araw o umaatake lamang? •  Pag sumakit po ba, bumabalik sa normal pag

nakainom kayo ng gamot o pagkalipas ng ilang araw kahit walang gamot?

•  May mga araw po ba na walang sakit at normal lang o walang limitasyon ang galaw ng kasukasuan nyo?

EXQUISITE PAIN: Sample Questions •  Pag sumakit or umatake ang sakit, nahihirapan ba

kayong igalaw yun masakit na kasukasuan? •  Hindi nyo na ba naigagalaw or hindi na ba kayo

nakakalakad sa mga araw na inaatake ng sakit? •  Malubha po ba ang sakit na nagkakaroon ng

pagkakataon na ayaw nyong pahipo o pahawakan yun masakit na bahagi? Masakit ba kahit mahipan o madampian lang?

EXACERBATING FACTORS: Sample Questions

•  May nakain o nainom ka ba bago mo naramdaman yun sakit?

•  Nangyari na ba ito dati? •  Umiinom po ba kayo ng gamot para sa high blood

(diuretics) , sa sakit sa puso (Aspirin), o sa gout (Allopurinol or Febuxostat)?

•  Naospital po ba kayo kamakailan? •  Malakas ba kayo uminom ng alak o soft drinks?

REVIEW OF THE CASES

CASE 1 •  A 54 y.o male family driver

consults for pain in the left knee on going up and down the stairs, for 2 years now. About 2 months ago, after driving long distance, the pain got worse and he now limps when walking. There is no fever or malaise.

•  Joint PE: left knee is swollen, warm, + bulge sign. There is 2+ tenderness and limited flexion and extension. The right knee appears normal, but is positive for fine crepitations.

•  A: Articular •  C: Chronic •  I: Inflammatory •  N: Monoarticular

CASE 2 •  A 48 y.o businessman came

home from a party the night prior to consult and woke up with an inflamed right big toe. He was feverish and could not walk. He admitted to drinking beer and had “pulutan” of kilawin. He had a similar episode 4 years prior, lasting 2 days.

•  Joint PE: Swollen, erythematous, warm and exquisitely tender right 1st MTP joint.

•  A: Articular •  C: Acute •  I: Inflammatory •  N: Monoarticular

CASE •  A 45 y.o. housewife consulted

for swelling and pain of both wrists and small hand joints of 4 months duration. Pain is worse in the morning, associated with stiffness lasting for 1 hour. She takes Alaxan tablets as needed, with temporary pain relief.

•  Joint PE: Swelling , warmth and tenderness of both wrists, and 1st and second PIPs of both hands. Other joints and systemic PE are normal

•  A: Articular •  C: Chronic •  I: Inflammatory •  N: Polyarticular

CASE •  A 35 y.o. female PA of a famous

celebrity consulted for swelling and pain of the R wrist and 4 weeks duration. Pain is worse at the end of the day, especially after a long day of writing, texting and carrying her boss’ stuff. She takes Arcoxia tablets as needed, with temporary pain relief.

•  Joint PE: Tenderness of R wrist, with pain on thumb flexion, digit flexion and sharp ulnar deviation of the wrist. No pain on PROM. Other joint PE are normal

•  A: Non-Articular •  C: Acute •  I: Non-inflammatory •  N: Mono

APPROACH TO URATE LOWERING THERAPY AND PROPHYLAXIS

INDICATIONS FOR ULT •  At least 2 flares per

year •  Presence of tophi •  Radiographic changes

of arthropathy •  Nephrolithiasis •  Comorbid conditions

that may complicate treatment of gout (CKD, CVD)

TREAT TO TARGET: SUA in GOUT

SUMMARY •  Always go back to the basics: A-C-I-N •  The 2014 and 2015 Classification Criteria have

excellent SEN/SPEC and are appropriate for settings where lab and imaging are difficult

•  Gout is almost always associated with hyperuricemia but hyperuricemia in itself rarely leads to gout

SUMMARY •  High uric acid is a predictor for more severe OA.

SUA is not indicated for all arthritis Pxs but may be helpful in explaining prognosis in Pxs with OA

•  Gout affects joints previously damaged by OA. Gout, when recurrent, and in the long term, may cause secondary OA

•  Asking the thrEEE questions can be helpful in diagnosing gout and differentiating it from OA

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