rheum: 1/ gout ACR criteria for diagnosis, anti-inflammatories (NSAID, colchicine, steroid) indication, doses, monitoring, duration of therapy, ULT first line choices and monitoring 2/ osteoarthritis pain relief with NSAIDs, indication, doses, monitoring, duration of therapy, Xray findings (description) 3/ rheumatoid arthritis ACR classification criteria, DMARDS for long term management, indication, doses, monitoring, duration of therapy, evaluation for disease activity 4/ osteoporosis meds, indication, doses, monitoring, duration of therapy, DEXA (to check BMD) when? WHO classification criteria?

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Rheumatology Review: 4 Core Topics

1. GOUT

2015 ACR/EULAR Classification Criteria

The criteria apply only if the patient has at least one episode of swelling, pain, or tenderness in a peripheral joint or bursa.

Sufficient criterion (auto-classifies as gout): Documented MSU crystals in symptomatic joint/bursa fluid, or in a tophus - no further scoring needed.

If MSU crystals not documented, score the following domains; total score ≥8 = gout:

Domain	Category	Score
Joint/bursa pattern	Non-ankle/midfoot/MTP1	0
	Ankle or midfoot (without MTP1)	+1
	MTP1 (first metatarsophalangeal)	+2
Flare characteristics (erythema, unable to bear touch, great difficulty walking)	0 features	0
	1 feature	+1
	2 features	+2
	3 features	+3
Flare time course (≥2 of: max pain <24h, resolution ≤14 days, complete resolution between episodes)	No typical episodes	0
	1 typical episode	+1
	Recurrent typical episodes	+2
Clinical tophus	Absent	0
	Present	+4
Serum urate	<4 mg/dL	-4
	4 to <6 mg/dL	0
	6 to <8 mg/dL	+2
	8 to <10 mg/dL	+3
	≥10 mg/dL	+4
Synovial fluid	Not done	0
	MSU negative	-2
Imaging urate deposition (US double-contour sign or DECT)	Absent/not done	0
	Present	+4
Imaging erosion (plain X-ray hands/feet)	Absent/not done	0
	Present	+4

Note: These are classification criteria (for research enrollment), not strict diagnostic criteria. The gold standard for diagnosis remains MSU crystal identification under polarized light microscopy. - Firestein & Kelley's Textbook of Rheumatology

Anti-Inflammatory Treatment of Acute Gout Flares

The goal is to relieve pain and terminate the flare as quickly as possible. Early initiation is critical. Continue anti-inflammatory therapy until the flare has completely resolved (usually 6-10 days). - Goldman-Cecil Medicine

NSAIDs

Indication: First-line for acute flare in patients without renal insufficiency, peptic ulcer disease, or anticoagulation therapy.
First-line agents: Indomethacin or naproxen.
- Indomethacin 50 mg TID x 5-7 days (taper possible)
- Naproxen 500 mg twice daily
- Ibuprofen 400 mg four times daily
Monitoring: Renal function (especially with baseline CKD), GI symptoms, blood pressure, edema.
Duration: 5-10 days, until flare completely resolved.
Contraindications: Renal insufficiency, PUD, anticoagulation, heart failure.

Colchicine

Indication: First-line alternative when NSAIDs are contraindicated; also used for prophylaxis when initiating ULT.
Acute flare dosing: 1.2 mg (2 tablets of 0.6 mg) at first sign of flare, then 0.6 mg one hour later. Then 0.6 mg once or twice daily for 7-10 days depending on renal function.
Prophylaxis dosing: 0.6 mg once or twice daily (low dose).
Monitoring: GI side effects (diarrhea, nausea), renal function, avoid with strong CYP3A4/P-gp inhibitors (clarithromycin, cyclosporine - risk of fatal toxicity).
Duration (acute): Until flare resolves (~7-10 days). Prophylaxis when starting ULT: continue for 3-6 months (or until serum urate target achieved and maintained).
Note: The acute dosing regimen (load + 1 hour) should NOT be used in patients already on chronic prophylactic colchicine. - Goldman-Cecil Medicine

Corticosteroids

Indication: When NSAIDs and colchicine are contraindicated or not tolerated (e.g., significant renal impairment, multiple drug interactions).
Dosing:
- Oral: Prednisolone/prednisone 30-40 mg/day, tapering over 7-10 days.
- Intra-articular: Methylprednisolone or triamcinolone (especially useful for monoarticular flare).
- IM: Methylprednisolone or triamcinolone for polyarticular flare.
Monitoring: Blood glucose (especially in diabetics), blood pressure, fluid retention.
Duration: 7-10 days with taper; of similar efficacy to NSAIDs and slightly safer profile in some patients.

Urate-Lowering Therapy (ULT)

Indications to initiate ULT:

≥2 gout flares per year
Single flare + CKD stage ≥2, serum urate ≥9 mg/dL, tophi, or radiographic damage
"Treat-to-target": reduce serum urate to <6.0 mg/dL (most patients); <5.0 mg/dL for severe/tophaceous disease.

Important: ULT should NOT be started during an acute flare (unless patient is already on it). Anti-inflammatory prophylaxis (low-dose colchicine) must be co-prescribed when starting ULT to prevent flares. Patients already on ULT during a flare should continue it without interruption.

First-line: Allopurinol (xanthine oxidase inhibitor)

Starting dose: 100 mg/day (50 mg/day in CKD); titrate by 100 mg every 2-4 weeks.
Target dose: Titrate to achieve serum urate target; may require 300-900 mg/day.
Monitoring:
- Renal function and serum urate (every 2-4 weeks during titration, then every 6 months once stable)
- CBC, LFTs at baseline
- Screen for HLA-B*5801 before starting in high-risk populations (Han Chinese, Thai, Korean) - severe cutaneous reactions (DRESS, SJS/TEN)
- Watch for allopurinol hypersensitivity syndrome
Duration: Indefinite (lifelong) - gout is a chronic crystal deposition disease.

Second-line: Febuxostat (xanthine oxidase inhibitor)

Indication: If allopurinol not tolerated or target not achieved.
Dose: 40 mg/day initially; increase to 80 mg/day if serum urate >6 mg/dL after 2 weeks.
Monitoring: LFTs, serum urate; caution - increased CV risk demonstrated in CARES trial (higher all-cause and CV mortality vs. allopurinol in patients with established CV disease); use with caution in those with recent MI/stroke. - Goldman-Cecil Medicine
Duration: Indefinite.

Other options:

Uricosuric agents (probenecid, benzbromarone): second-line; require adequate renal function, high fluid intake, avoid in nephrolithiasis.
Pegloticase (IV recombinant uricase): for severe refractory tophaceous gout unresponsive to oral therapy; given IV every 2 weeks; requires monitoring of serum urate before each infusion (stop if urate rises - risk of infusion reactions/anaphylaxis).

2. OSTEOARTHRITIS (OA)

X-Ray Findings (Description)

Classic plain radiograph findings of OA (the "LOSS" mnemonic is helpful):

L - Loss of joint space (narrowing, typically asymmetric/focal) - the most characteristic finding
O - Osteophyte formation (bony spurs at joint margins - the hallmark of OA)
S - Subchondral sclerosis (increased bone density beneath the cartilage)
S - Subchondral cysts (geodes - radiolucent areas beneath the joint surface)

Additional findings:

Joint deformity and malalignment in advanced disease
No periarticular osteopenia (distinguishes from RA/inflammatory arthritis)
No erosions (erosions are NOT typical of primary OA; exception = erosive/inflammatory OA affecting DIP joints)
Preservation of bone density (unlike inflammatory arthritis)

Site-specific notes:

Knee: Medial compartment narrowing most common; varus deformity; lateral can also be affected.
Hip: Superior (weight-bearing) or medial joint space narrowing; osteophytes at femoral head margin.
Hands: DIP and PIP joints involved; Heberden nodes (DIP) and Bouchard nodes (PIP) clinically.
Spine: Disk space narrowing, endplate sclerosis, osteophyte formation (spondylosis). - Firestein & Kelley's Textbook of Rheumatology; Grainger & Allison's Diagnostic Radiology

NSAIDs for OA Pain Relief

Indication: Persistent pain inadequately controlled by non-pharmacologic measures (exercise, weight loss, physiotherapy) and acetaminophen.

Doses (from Goldman-Cecil drug table):

NSAID	Dose
Celecoxib (COX-2 inhibitor)	100 mg PO twice daily or 200 mg PO once daily
Ibuprofen	400 mg PO four times daily
Naproxen	500 mg PO twice daily
Diclofenac	50 mg PO 2-4 times daily
Etodolac	300 mg PO 2-3x daily or 400-500 mg PO twice daily
Ketoprofen	75 mg PO three times daily

Topical NSAIDs (diclofenac gel): preferred in elderly and those with GI/renal/CV risk, especially for knee and hand OA.
Celecoxib preferred when GI risk is elevated; still carries CV and renal risk.

Monitoring:

Renal function (BUN/Cr) at baseline and periodically - especially in elderly, CKD, heart failure, diuretic/ACEI/ARB use.
Blood pressure.
GI symptoms; consider PPI co-prescription with non-selective NSAIDs in patients with GI risk factors.
LFTs if prolonged use.
Edema and fluid retention.

Duration: Use the lowest effective dose for the shortest duration necessary. For OA, chronic use is often required given the degenerative nature of the disease, but reassess regularly. Avoid chronic use in elderly (BEERS criteria) - use topical agents or intermittent dosing when possible.

Contraindications/cautions: CKD, peptic ulcer disease, heart failure, CV disease (especially with non-selective), ACEI/ARB combination (triple whammy).

3. RHEUMATOID ARTHRITIS (RA)

2010 ACR/EULAR Classification Criteria

Entry requirement: At least one joint with definite clinical synovitis not explained by another diagnosis.

Score ≥6 = definite RA:

Domain	Category	Score
A. Joint involvement	1 large joint	0
	2-10 large joints	1
	1-3 small joints (MCP, PIP, MTP, wrist, thumb IP)	2
	4-10 small joints	3
	>10 joints (at least 1 small joint)	5
B. Serology (at least 1 test needed)	Negative RF AND negative anti-CCP	0
	Low-positive RF or low-positive anti-CCP (<3x ULN)	2
	High-positive RF or high-positive anti-CCP (>3x ULN)	3
C. Acute phase reactants (at least 1 test needed)	Normal CRP AND normal ESR	0
	Abnormal CRP or abnormal ESR	1
D. Duration of symptoms	<6 weeks	0
	≥6 weeks	1

Notes:

~75% of RA patients are seropositive (RF and/or anti-CCP).
Anti-CCP (anti-citrullinated protein antibody, ACPA) has ~90% specificity and is linked to more aggressive disease.
Radiographic erosions and subcutaneous nodules not included (occur rarely in early disease).
Source: Aletaha D, et al. Arthritis Rheum 62:2569, 2010. - Harrison's Principles of Internal Medicine 22E; Miller's Review of Orthopaedics

Disease Activity Evaluation

Common validated indices used in clinical practice:

DAS28 (Disease Activity Score in 28 joints): uses tender joint count, swollen joint count, ESR or CRP, and patient global assessment. Remission: <2.6; low: 2.6-3.2; moderate: 3.2-5.1; high: >5.1.
CDAI (Clinical Disease Activity Index): sum of 28-joint tender count + 28-joint swollen count + physician global + patient global (no lab needed).
SDAI (Simplified Disease Activity Index): CDAI + CRP.
ACR response criteria (20/50/70%): used in clinical trials.
Imaging: Serial X-rays to detect joint erosion progression; MRI and ultrasound for earlier detection of synovitis and erosions.
Lab monitoring: ESR, CRP, RF, anti-CCP, CBC, LFTs, renal function (with DMARDs).

DMARDs - Indications, Doses, Monitoring, Duration

General principle: Start DMARD therapy early - the critical issue is initiating treatment early in the disease process, not which DMARD to start first. Conventional DMARDs require 2-6 months for maximal effect. - Goldman-Cecil Medicine

Conventional DMARDs

Methotrexate (MTX) - First-line anchor drug for most RA patients

Item	Detail
Indication	Initial DMARD for most RA patients; cornerstone of combination therapy
Dose	7.5-25 mg PO or SQ once weekly (titrate up from 7.5-10 mg/week)
Co-therapy	Folic acid 1-4 mg/day (or 5 mg/week) - reduces toxicity without reducing efficacy
Monitoring	CBC + AST/ALT every 8-12 weeks when dose stable (every 4-8 weeks when initiating/changing dose); renal function (MTX renally cleared - dose reduce in CKD); watch for pulmonary symptoms
Key toxicities	Oral ulcers, nausea, hepatotoxicity, bone marrow suppression, rare pneumonitis (stop immediately if occurs - can be fatal if MTX continued), rare lymphoma
Contraindications	Pregnancy (teratogenic), significant renal impairment (relative), significant hepatic disease
Duration	Indefinite/long-term; reassess response every 3-6 months

Hydroxychloroquine (HCQ)

Item	Detail
Indication	Mild/early RA; adjunctive in combination (triple therapy with MTX + SSZ); not shown to delay radiographic progression
Dose	200-400 mg/day (max 5 mg/kg/day to reduce retinal toxicity)
Monitoring	Annual ophthalmology exam after 5 years of therapy for retinopathy (hydroxychloroquine retinopathy is irreversible)
Duration	Long-term if effective

Sulfasalazine (SSZ)

Item	Detail
Indication	Early/mild RA; part of triple therapy (MTX + HCQ + SSZ)
Dose	Start 500 mg once or twice daily x 2 weeks, then 2 g/day in divided doses (may titrate to 3 g/day)
Monitoring	CBC for neutropenia - monthly for first 3 months, then every 6 months
Duration	Long-term

Leflunomide

Item	Detail
Indication	Alternative to MTX; similar efficacy; used as monotherapy or in combination
Dose	10-20 mg PO once daily (loading dose 100 mg/day x 3 days sometimes used but poorly tolerated)
Monitoring	CBC + AST/ALT every 4-8 weeks; note very long half-life (active metabolite persists for months - cholestyramine washout required before pregnancy/if toxicity)
Contraindications	Pregnancy (absolute - teratogenic); severe hepatic disease
Duration	Long-term

Biologic DMARDs

Used when conventional DMARDs (especially MTX) fail to achieve adequate disease control. Screen for latent TB (TST or IGRA) and hepatitis B before starting.

Drug	Class	Dose	Key Monitoring
Adalimumab	Anti-TNF	40 mg SQ every other week	Infections (TB reactivation), CHF worsening, demyelination, lupus-like
Etanercept	Anti-TNF	50 mg SQ once weekly	Same as adalimumab
Infliximab	Anti-TNF	3-5 mg/kg IV at 0, 2, 6 weeks, then every 4-8 weeks (with MTX)	Same; must use with MTX
Certolizumab	Anti-TNF	400 mg SQ at weeks 0, 2, 4; then 200 mg q2 weeks	Same
Golimumab	Anti-TNF	50 mg SQ once monthly	Same
Tocilizumab	Anti-IL-6R	4→8 mg/kg IV every 4 weeks	Infections, lipid elevation (check at 3 months), avoid if diverticulitis
Abatacept	Anti-CTLA4 (T-cell co-stimulation)	500-1000 mg IV at 0, 2, 4 weeks, then q4 weeks	Infections
Rituximab	Anti-CD20 (B-cell)	Two 1000-mg IV infusions 2 weeks apart, repeat q16-24 weeks	PML, infections, with MTX

Targeted Synthetic DMARDs (JAK inhibitors)

Drug	Dose	Key Monitoring
Tofacitinib	5 mg PO twice daily	LFTs, creatinine kinase, creatinine; VTE risk; higher herpes zoster risk; avoid if thrombosis history
Baricitinib	2 or 4 mg PO once daily	Same as above; VTE risk
Upadacitinib	15 mg PO once daily	Same; also used in AS, PsA

All patients on DMARDs should be monitored by a rheumatologist. - Goldman-Cecil Medicine

4. OSTEOPOROSIS

WHO Classification (T-score based, DEXA)

T-score	Classification
≥-1.0	Normal
-1.0 to -2.5	Osteopenia (low bone mass)
≤-2.5	Osteoporosis
≤-2.5 + fragility fracture	Severe (established) osteoporosis

T-score: compares BMD to young adult female reference population (peak bone mass).
Z-score: compares to age-matched population - used in pre-menopausal women and men <50 years (Z-score ≤-2.0 = "below expected range for age").

DEXA Scan - When to Perform BMD Testing

All women aged ≥65 years
Postmenopausal women <65 years with risk factors (prior fragility fracture, parental hip fracture, smoking, alcohol, low body weight, glucocorticoid use, rheumatoid arthritis, secondary causes of osteoporosis)
Men aged ≥70 years (or younger with risk factors)
Any patient starting long-term glucocorticoids (≥3 months at ≥5 mg/day prednisone equivalent)
Patients with conditions associated with bone loss: RA, IBD, malabsorption, hypogonadism, hyperparathyroidism
After fragility fracture (fracture from minimal trauma, e.g., fall from standing height)
Repeat DEXA: every 1-2 years when on treatment; every 2-3 years for monitoring.

Pharmacologic Treatment

Indications to treat:

Osteoporosis (T-score ≤-2.5)
Fragility fracture (regardless of T-score)
Osteopenia (T-score -1.0 to -2.5) with FRAX 10-year probability ≥20% for major osteoporotic fracture or ≥3% for hip fracture (US thresholds)
Long-term glucocorticoid therapy (≥5 mg prednisone x ≥3 months)

Non-pharmacologic foundation: Adequate calcium intake (1000-1200 mg/day from diet + supplement), vitamin D (800-2000 IU/day), weight-bearing exercise, fall prevention, smoking cessation, minimize alcohol.

Bisphosphonates (First-line)

Drug	Dose	Route	Frequency	Key Monitoring/Notes
Alendronate	70 mg	PO	Weekly	Take on empty stomach with full glass of water, remain upright 30 min; avoid in GI erosions/esophageal motility disorders; CrCl <35 mL/min contraindicated
Risedronate	35 mg	PO	Weekly (or 150 mg monthly)	Same precautions as alendronate
Ibandronate	150 mg	PO	Monthly	Less evidence for hip fracture; 3 mg IV every 3 months
Zoledronic acid	5 mg	IV infusion	Annually	Acute phase reaction (flu-like) after first infusion; check renal function before each dose; CrCl <35 mL/min: use caution/avoid

Monitoring (all bisphosphonates):

Dental exam before IV bisphosphonates (risk of osteonecrosis of the jaw - ONJ)
Creatinine/eGFR before each IV dose and periodically with oral agents
DEXA every 1-2 years while on treatment
Watch for atypical femoral fractures with long-term use (>3-5 years)

Duration: Standard recommendation - 5 years oral or 3 years IV bisphosphonate, then reassess for "drug holiday" in lower-risk patients (T-score above -2.5, no prior hip fracture). Higher-risk patients continue or switch therapy.

Denosumab (Rank-L inhibitor - Second-line or alternative)

Item	Detail
Dose	60 mg SQ every 6 months
Indication	Postmenopausal osteoporosis; preferred when bisphosphonates contraindicated (e.g., severe renal impairment); also used in glucocorticoid-induced osteoporosis and cancer-related bone disease (at higher doses)
Monitoring	Serum calcium (hypocalcemia - especially in renal impairment; supplement calcium/vitamin D); dental exam (ONJ risk); infection risk (cellulitis)
Duration	Reassess after 5-10 years; critical: do NOT abruptly discontinue - rebound increase in bone resorption with multiple vertebral fractures reported; must transition to bisphosphonate if stopping

Teriparatide (PTH analog - Anabolic)

Item	Detail
Dose	20 mcg SQ once daily
Indication	Severe osteoporosis (T-score ≤-2.5 with fragility fracture); patients who fail or are intolerant of antiresorptive therapy; glucocorticoid-induced osteoporosis (approved)
Monitoring	Serum calcium, uric acid; orthostatic hypotension (especially with first doses); contraindicated in prior radiation therapy to bone, Paget's disease, bone malignancy, unexplained alkaline phosphatase elevation
Duration	Maximum 2 years lifetime use (historical concern for osteosarcoma based on rat studies; not confirmed in humans but regulatory limit retained). Follow with antiresorptive agent afterward to maintain gains.

Abaloparatide

PTHrP analog; same mechanism as teriparatide; 80 mcg SQ daily; also limited to 2 years.

Romosozumab (Sclerostin inhibitor - Dual anabolic/antiresorptive)

210 mg SQ monthly for 12 months; then transition to antiresorptive.
Black box warning: increased MI/stroke risk; avoid in patients with recent cardiac event.

Raloxifene (SERM - Selective estrogen receptor modulator)

60 mg PO daily.
Reduces vertebral fracture risk (not hip fracture).
Also reduces risk of invasive breast cancer (ER+).
Contraindicated: history of VTE; increases VTE risk; may worsen hot flashes.

Hormone Replacement Therapy (HRT)

Effective for fracture prevention and menopausal symptom relief.
Generally not used as primary treatment for osteoporosis given breast cancer, VTE, cardiovascular risks.

Monitoring on Osteoporosis Therapy

DEXA every 1-2 years on treatment to assess response.
Bone turnover markers (CTX, P1NP) can be used to monitor adherence and treatment effect (CTX decreases with antiresorptives; P1NP increases with anabolics).
Maintain calcium and vitamin D supplementation throughout.
Reassess fracture risk and need for continued therapy after 3-5 years.

Sources:

Firestein & Kelley's Textbook of Rheumatology, 2-Volume Set
Goldman-Cecil Medicine International Edition, 2 Volume Set
Harrison's Principles of Internal Medicine 22E (2025)
Miller's Review of Orthopaedics 9th Edition
Grainger & Allison's Diagnostic RadiologyAll four topics are fully covered above. Here's a quick orientation map for the content:

Quick Topic Navigator:

#	Topic	Key Highlights
1. Gout	2015 ACR/EULAR criteria (score ≥8 or MSU crystals); NSAIDs (indomethacin/naproxen), colchicine (1.2 mg load + 0.6 mg x1h), steroids (pred 30 mg/day); ULT = allopurinol (1st), febuxostat (2nd); target urate <6 mg/dL; prophylaxis 3-6 months when starting ULT
2. OA	X-ray: joint space narrowing + osteophytes + subchondral sclerosis + cysts, NO erosions/osteopenia; NSAIDs: naproxen 500 mg BID, ibuprofen 400 mg QID, celecoxib 100-200 mg/day; topical preferred in elderly; monitor renal/GI/BP; shortest effective duration
3. RA	2010 ACR/EULAR criteria (score ≥6); domains: joints + serology + APR + duration; MTX anchor (7.5-25 mg/week + folic acid, CBC/LFTs q8-12 wk); add biologic/JAK inhibitor if MTX fails; screen TB before biologics; disease activity = DAS28, CDAI
4. Osteoporosis	WHO T-score: normal ≥-1.0, osteopenia -1.0 to -2.5, osteoporosis ≤-2.5; DEXA: women ≥65, men ≥70, or younger with risk factors; Tx 1st-line = bisphosphonates (alendronate 70 mg weekly, zoledronic acid 5 mg/year x 3-5 years); severe = teriparatide (20 mcg/day, max 2 years); denosumab 60 mg q6 months (do NOT stop abruptly)

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