Intro, JIA, RA

Rheumatology

A branch of internal medicine devoted to managing/diagnosing disorders with inflammation of the joints, muscles, tendons, and internal organs

Warmth, swelling, systemic symptoms, lab abnormalities, erythema, prolonged stiffness

Inflammatory Rheumatologic clues

Mechanical pain, improves with rest, stiffness, absence of systemic signs

Non-Inflammatory Rheumatologic clues

Mono, Oligo (2-4), Poly (4+), symmetric, asymmetric, distal, proximal

Patterns of Rheumatologic joint pain

fever, rash, nodules, neuropathy, ocular inflammation

Extra-articular manifestations of rheumatic diseases

CBC (WBC, Hgb, platelets), BMP (creat), Hep panel, ESR/CRP, HLA-B27 (AS, PSA), RF (RA, Sjogren’s SLE, sarcoidosis), CCP (RA), ANA (Lupus, MCTD, Sjogren’s, Scleroderma, Dermatomyositis), Uric Acid (gout)

General lab workup for rheumatic diseases (after OLDCARTs, family hx, PE, etc)

Xrays, U/S, MRI, CT

General imaging workup for rheumatic diseases (after OLDCARTs, family hx, PE, etc)

gout, pseudogout, inflammatory, infections (DO NOT PASS THROUGH CELLULITIS OR PSORIASIS)

An arthrocentesis with cell count and crystals can be use to diagnose…

Sjogren’s (lip), dermatomyositis (muscle)

A biopsy can be helpful in diagnosing…

Sjogren’s, Dermatomyositis

An EMG can be helpful in diagnosing…

Lupus, psoriasis, vasculitis, dermatomyositis

A dermatology consult can be helpful in diagnosing…

lube, shock absorption, nutrient distribution, joint health

What is the purpose of Synovial Fluid?

T cells (release cytokines), Dendritic cells (APCs)

What are the immune response initiators

Macrophages (release TNF-alpha, Il-1), Mast cells (release histamine), PNMs

What are the Inflammatory mediators?

Fibroblast-like synoviocytes (proliferate abnormally and produce cartilage/bone degrading enzymes), Osteoclast (activity is increased in inflammatory arthritis)

What are the Tissue Destruction contributors?

Cytokines

Small proteins released by cells that act as signaling molecules, regulate immune responses, inflammation, and hematopoiesis.

Antigen

Substances (proteins, polysacchs, lipids, nucleic acids, etc) deemed foreign or dangerous by the immune system that trigger an immune response

Antibody (Immunoglobulin)

Proteins produced by plasma B cells in response to a specific antigen that work to neutralize or target it for destruction (ADCC)

TNF-alpha, IL-1, IL-6, IL-17 (early and chronic), Granulocyte macrophage colony stimulating factor (GM-CSF - stimulates immune cells)

Pro-inflammatory Cytokines

IL-10, Transforming growth factor beta (TGF-beta - regulates immune responses and promotes repair)

Anti-inflammatory Cytokines

Juvenile Idiopathic arthritis (JIA)

The most common type of chronic (6+ weeks), inflammatory arthritis in kids and teens (prior to 16 y/o) that is idiopathic in nature and more common in females.

Genetic predisposition or environmental triggers lead to the autoimmune destruction cartilage, increased synovial fluid, and thickening of the synovium (TNF-alpha, IL-1, IL-6)

Patho for JIA

Joint pain, stiffness, swollen/warm joints, fatigue, eye symptoms, rash, loss of appetite, high fever

General symptoms of JIA - depends on the subtype

Uveitis (can become chronic and lead to blindness), macrophage-activation syndrome (MAS), contractures, joint destruction and deformities, limb length discrepancy, growth retardation (early epiphyseal closure), Pericarditis, pleuritis

Complications of general JIA

Uveitis (get a slit lamp exam at diagnosis)

One of the most serious complications (20%) of JIA that involves the ciliary body and iris

young at diagnosis, ANA+, shorter disease duration in oligoJIA and RF neg polyJIA

Risk factors for Uveitis in JIA

Macrophage Activation syndrome

A potentially life threatening complication of JIA (mostly systemic) that is treated with high dose steroids, IL-1 blockade (anakinra), and a calcineurin inhibitor (cyclosporin, tacrolimus)

Fever with confirmed/suspected systemic JIA with a serum ferritin level above 684 ng/ml PLUS 2 of these (platelets less than 181, AST above 48, Triglycerides above 156, fibrinogen under 360)

Macrophage Activation syndrome diagnostic criteria

joint space narrowing and erosions → lower limb discrepancies, contractures, limited ROM, bony deformities

Chronic joint inflammation (like in polyarticular arthritis) can lead to

Pannus

An unusual, additional layer of tissue that forms in the joints, leading to discomfort, inflammation, and harm to bones, cartilage, and surrounding tissues

Oligoarthritis, Polyarthritis (RF+ and neg), Systemic JIA, Psoriatic, Enthesis-related, Undifferentiated

Types of JIA

Oligoarthritis (2-4 joints)

The most common form of JIA (30-80%) that tends to affect the females 1-3 y/o

Asymmetrically affects large joints (knees, elbows, wrist, ankles), ANA+ (but don’t rely on this), Risk of Asymmetric uveitis

Tell me about oligoarthritis JIA

Polyarthritis JIA

Another form of JIA (20% of cases) that affects 5+ joints (large and small) during the 1st 6 months of disease and involves a more widespread autoimmune response

Associated weight loss, fatigue, and low grade fever; Can be RF + or neg

Tell me about Polyarthritis JIA

Peaks at 1-3 y/o and later in adolescence, Female dominant, symmetrical, larger joints including cervical spine and TMJ, ANA+

Tell me about RF neg (seronegative) Polyarthritis JIA

Onsets during early adolescence, female dominant, Symmetric and erosive, Large and small joints, Rheumatoid nodules over elbows and achilles

Tell me about RF+ (seropositive) Polyarthritis JIA

Systemic JIA

JIA characterized by inflammation in the joints, skin, and internal organs that affects with equal sex distribution and a peak onset of 2 y/o

Pain in 1+ joints with a intermittent fever of a least 2 weeks in duration PLUS one of these (transient, non-fixed erythematous rash, generalized lymphadenopathy, hepatosplenomegaly, or serositis)

Diagnostic criteria for Systemic JIA

RF neg, Elevated ESR/CRP, Elevated Ferritin, anemia, leukocytosis, thrombocytosis

What do the labs look like for Systemic JIA

Psoriatic JIA

A subtype of JIA that involves both arthritis and psoriasis caused by genetic factors and immune dysregulation (T cells) that peaks during preschool years (mostly females) OR middle-late childhood

Arthritis and Psoriasis OR arthritis plus 2 of these (dactylitis, nail pitting, onycholysis, or psoriasis in a 1st degree relative), chronic uveitis

Psoriatic JIA Diagnostic Criteria

ANA +, elevated ESR/CRP

What do the labs look like for Psoriatic JIA

Enthesis-Related JIA

What subtype of JIA is strongly associated with HLA-B27 characterized by inflammation at tendon and ligament attachment sites - more common in older males and teens

Arthritis AND enthesitis (pain where the tendon/ligament attaches); OR either one + 2 of theses (SI joint tenderness or inflammation on imaging, Positive HLA-B27, hx of anterior uveitis, 1st degree relative with HLA-B27 associated disease, Onset of arthritis in a male over 6 y/o)

Enthesis-Related JIA Diagnostic criteria

Asymmetric peripheral arthritis, anterior uveitis, IBD, hip involvement is a red flag

Manifestations of Enthesis-Related JIA

undifferentiated

The catch all category for JIA - like if they meet for 2 subtypes or none of them

X-ray (joint space narrowing in RF+ late in disease, erosive changes), U/S (synovial hypertrophy, early bone erosions), MRI (monitor progression in TMJ, SI, cervical)

Imaging work up for JIA (general)

Synovial biopsy (infiltration of Bs and Ts - definitive), Slit lamp (screen for anterior uveitis q3 months in high risk, q 1yr everybody else)

Other testing for JIA (general)

NSAIDs (Naproxen, ibuprofen, maloxicam, celecoxib)

1st line therapy for JIA (no longer a monotherapy longer than 1-2 months)

DMARDs (methotrexate (most common), leflunomide, Sulfasalazine in ERA), Biologic DMARD if no response to 3 months methotrexate (polyJIA that’s moderate/severe)

Second line therapy for JIA

Severe systemic involvement (severe serositis in Still’s), bridge DMARDs, acute anterior uveitis

When do you use short-course systemic glucocorticoids in JIA treatment?

Sickle cell, infection, malignancy, trauma, other autoimunes

DDX for JIA

Rheumatoid Arthritis (RA)

A chronic inflammatory autoimmune disease that tends to erode the small joints symmetrically that can lead to deformity and loss of physical function - early treatment and diagnosis is the standard

Females (3x), Onset tends to be 30-40s (female), 50s (male)

Epi Stats for RA

Age, sex, smoking, hx of live births, early life exposures (infectious, viral, etc), obesity, genetics, breastfeeding decrease risks

Risk factors of RA

Synovium becomes thickened with a pannus (erodes cartilage and bone) as well infiltrated by immune cells that release TNF-alpha, IL-1/6/17, or MMPs (matrix metalloproteinases)

Patho for RA

Initiation (unknown trigger), Propagation (cycle of immune activation and inflammation), Chronic inflammation (leads to joint damage, pain, and loss of function)

Stages of RA disease progression

morning stiffness for 2 hours, low-grade fever, weight loss, fatigue, myalgias, depression, decreased energy, symmetric polyarthritis joint swelling (most common), subcutaneous nodules, difficulty with ADLS

Clinical features of RA (usually an insidious onset)

PIP, MCP, wrist, MTPs

Most common joints affected by RA

Boutonniere (Pip flexed, DIP hyperextended), Swan Neck (MCP flexed, pip extended, DIP flexed)

Late stages joint changes in RA

C1-C2 (subluxation and instability - may compress central spinal cord)

Spinal involvement of RA

Nodules in the heart can lead to BBB, AV blocks, pericarditis, pericardial effusions

Cardiac involvement of RA

Pleural effusions, pleurisy, interstitial lung disease, pulmonary fibrosis (restrictive, honeycomb pattern), pulmonary infiltrates, rheumatic lung nodules

Pulmonary involvement of RA

Normocytic normochromic anemia, thrombocytosis, thrombocytopenia, Felty’s (splenomegaly with neutropenia), nonspecific transaminitis, peripheral nerve entrapment, cervical myelopathy, muscle atrophy, low grade membranous glomerular nephropathy, vasculitis

Other extra-articular involvements of RA

Scleritis, uveitis, ulcerative keratitis, keratoconjunctivitis sicca

Ocular involvement of RA

Subcutaneous rheumatoid nodules (usually extensor surfaces or visceral)

What is pathognomonic for RA (usually RF+)

Persistent symmetric polyarthritis of hands and feet

Hallmark of RA

ACR criteria, PE, Hx, labs, imaging, and synovial fluid analysis

Diagnosis of RA is based on

CMP, CBC with Diff, ESR/CRP, RF (nonspecific), CCP (95% specific), Fluid analysis (non-specific)

Lab workup for RA

X-rays (erosions, joint space narrowing (get neck too), ulnar deviation), U/S (erosions, synovial hypertrophy, tenosynovitis)

Imaging workup for RA

Reduce pain/inflammation, prevent/halt joint destruction, preservation of function, prevention of deformity

primary objectives of treating RA

PT/OT, reconstructive surgery, NSAIDs (Naprosyn 500 mg, Celecoxib for GI concerns), Analgesics (Tylenol - watch LFTs), corticosteroids (short-dose prednisone), DMARDs

Treatment plan for RA

Use to bridge DMARDs, adjunct for active or flare ups, taper!!

Rules for steroids in RA

DOC w/ improvement in 4-6 weeks, weekly injections or pill, Watch kidneys and liver, take with folic acid, TERATOGENIC

Tell me about Methotrexate in RA

Alt to methotrexate, daily, watch the liver, TERATOGENIC

Tell me about Leflunomide in RA

Get an eye exam (retinopathy), okay for pregs, based on weight 200-400 mg/day

Tell me about Hydroxychloroquine in RA

Check G6PD, NOT FOR LUPUS, SULFA OR ASA allergy

Tell me about Sulfasalazine in RA

Screen for TB (quantiferon gold), CXR, hep panel, NO live vaccines

Before starting biologics, what do we need to do?

TNF-inhibitor, T-cell inhibitors, IL-6 inhibitors, IL-1 inhibitors, JAK inhibitors

Examples of biologic classes