Rheumatology 1: Rheumatoid Arthritis and SLE

polyarthritis, >, IV, DRB, 1, 4, smoking

Rheumatoid Arthritis: Background

-Chronic, systemic disease characterized by inflammatory ____________, involving small and large joints, some other organ systems, and some constitutional features

-Epidemiology

• Females _ males

• Onset between 30-50 y/o

-Pathogenesis

• Type __ reaction (T cell mediated)

-Genetics

• Most associated with HLA ___ _ and _

-Environmental Trigger

• Mostly unknown

• __________ highly linked trigger to RA

Pannus

A thickened, inflamed layer of synovial tissue that grows over and destroys articular cartilage and bone within a joint

synovitis, ankylosis, bony

Stages of Rheumatoid Arthritis

1. ____________ → synovial membrane inflamed and thickened, bones and cartilage gradually erode

2. Pannus formation → excessive cartilage loss, exposed and pitted bones

3. Fibrous ___________ → joint invaded by fibrous connective tissue

4. ____ ankylosis → bones fused

symmetrical, gradual, MCP, PIP, DIP, pain, >, boggy

Rheumatoid Arthritis: Signs and Symptoms

-____________, polyarticular disease with ______ onset. Classically affects the ___, ___, MTP joints, and wrists (usually spares the ___ joints)

-Joint ____

-Joint stiffness → morning stiffness _ 30-60 minutes, improves with activity

-"_______” joint swelling (synovitis) → much more inflamed than in osteoarthritis

MCP, PIP, ulnar, swan neck, lateral, subluxation, extension, ulnar, ankles, 1, 2

Rheumatoid Arthritis: Joints Affected

-Fingers

• ___ and ___ joints most common

• MCP subluxation, ______ deviation, ____ ____ and Boutonniere deformities, and decreased grip

-Feet

• MTP joints most common

• _____ drift of toes, plantar ___________ of metatarsal heads

-Wrists

• Loss of __________, volar subluxation, and _____ drift

-Elbows

-_______

-Knees

-C_ and C_ can also be affected, leading to life threatening subluxation

Swan Neck

What deformity is this?

-Associated with RA, characterized by the hyperextension of the PIP joint and flexion of the DIP joint

Boutonniere deformity

What deformity is this?

-Associated with RA, characterized by a flexed PIP joint and extended DIP joint, creating a “button hole” appearance

myalgia, fever, nodules, scleritis, splenomegaly

Rheumatoid Arthritis: Systemic Symptoms

-_________, fatigue, low grade _____, and weight loss

-Rheumatoid subcutaneous _______, lung disease, episcleritis/________, vasculitis, and Felty Syndrome

-Felty Syndrome = RA, ___________, and neutropenia

Anti-CCP

What lab test is the most sensitive/specific for RA?

elevated, RF, anemia, inflammatory

Rheumatoid Arthritis: Diagnosis

-ESR and CRP → __________

• Assess disease activity/severity, monitor therapeutic response

-__ and anti-CCP

• More sensitive/specific for RA

• About 20% are seronegative

-ANA → often positive

-CBC w/ diff

• _______ and thrombocytopenia (chronic inflammation)

-Synovial fluid analysis

• ____________ → 10,000 WBC, mostly PMNs

6/10

In order to be diagnosed with rheumatoid arthritis, a patient must meet _/__ of the diagnostic criteria

osteopenia, narrowing, erosions, subluxation

Rheumatoid Arthritis: Imaging (X-Ray)

-Could show periarticular ___________ (bone loss), joint space ___________, bone ________, and joint deformities (like ___________)

smoking, DMARD, non-biologic, methotrexate, biologic, JAK

Rheumatoid Arthritis: Treatment

-Treatment

• _______ cessation

• Control synovitis and prevent joint injury/damage

• Refer to rheumatology

• Start on ______ ASAP

-Medications

• NSAID or glucocorticoids → ASA, COX-1 and 2, prednisone. Use these as a bridge therapy until DMARD starts working

• ___-_______ DMARD is the gold standard → ___________ is the most common. Could also use leflunomide, hydroxychloroquine, and sulfasalazine

• _______ DMARD → TNF blocker (etanercept/infliximab) or IL-6 receptor antagonists (tocilizumab)

• Target synthetic DMARD → ___ inhibitor (tofacitinib)

hepatic, Hep B, C, PPD, immunizations, contraceptives

Rheumatoid Arthritis: Health Maintenance

-Get baseline CBC, _______ function, and BMP

-Screen for ___ _ and _

-___ before starting biologic

-Continue with routine ______________

-Varicella zoster vaccine before starting biologic or tofacitinib in those > 50

-_____________ in child bearing ages

autoantibodies, dermatologic, failure, black, >, hormonal, UV light

Systemic Lupus Erythematous: Background

-Chronic, multisystem, inflammatory disease with various _____________

-Ranges from mild _________ and joint symptoms to life threatening internal organ ________ and cytopenias

-Periods of active disease and remission

-Epidemiology

• Highest among Asian, _____, and Hispanic patients

• F _ M (8:1)

• Peak age at diagnosis is 20-40

-Etiology

• Mostly unknown

• Genetic

• _________ (contraceptives, pregnancy)

• Immune (Type III reaction or abnormalities in complement)

• Environmental (infection, __ _____, smoking)

autoantibodies, DNA, histones, immune complex, glomerular, renal, GI

SLE: Pathogenesis

-Variety of _____________ against → nucleic acids, erythrocytes, coagulation proteins, phospholipids, lymphocytes, platelets, etc.

• Most characteristic are ___, ________, and ribonucleoproteins

-_______ ________ formation and deposition into tissues

• Damage and inflammation of __________ basement membrane, _____ tubular basement membrane (lupus nephritis), brain, heart, spleen, lung, __ tract, skin, and peritoneum

fever, non-erosive, Malar, rash, photosensitivity, ulcers

SLE: Clinical Manifestations

-Constitutional → _____, fatigue, weight loss

-MSK → ___-_______ arthritis, arthralgias, myositis

-Dermatologic → _____ (butterfly) ____, discoid lesions, _____________, oral/nasal ______ (painless), alopecia, urticaria

proteinuria, anemia, pericarditis, pleuritis, psychosis

SLE: Clinical Manifestations, cont.

-Renal → cellular casts, glomerulonephritis, _________, membranous nephropathy, nephrotic syndrome

-Hematologic → hemolytic ______, leukopenia, lymphopenia, thrombocytopenia

-Cardiovascular → ___________, vasculitis

-Pulmonary → ________, interstitial lung disease, PE, pulmonary hemorrhage

-Neurologic → __________, seizures, cerebritis, neuropathy

nephritis, scarring, destruction, deposition, biopsy, seizures, hemoptysis, failure, damage

SLE: Critical Clinical Manifestations

-Lupus _________

• Spectrum of glomerulopathies, ranging from focal _________ to diffuse ___________ with inflammation and immune complex ___________

• Renal biopsy can be helpful with diagnosis, but use UA for screening

-Lupus Cerebritis

• Include psychosis, _________, coma and other more subtle cognitive and psych manifestations

-Pulmonary Hemorrhage

• Can cause significant ____________ and respiratory ________

-Vasculitis of Major Organs

• Organ ______ and failure

Antiphospholipid, thromboses, abortions

SLE: Antiphospholipid Antibodies

-Detected in about 40% of SLE patients

-Can lead to ______________ syndrome

• Recurrent arterial/venous _____________, thrombocytopenia, and spontaneous __________

flares, abortions, premature, complications

SLE and Pregnancy

-Severe disease ______ → be sure to educate your patients

-High rates of spontaneous ___________

-High rates of ________ births

-Pregnancy ______________ d/t organ damage from SLE and/or medications for SLE

Procainamide, Hydralazine, reversible

Drug-Induced Lupus

-Most common drugs implicated are __________ and ___________

-Milder form of SLE → rarely any CNS or renal involvement

-Can have + SLE labs

-___________ with discontinuing the drug

Anti-dsDNA, Anti-Sm

What lab tests are the most specific and pathognomonic for SLE?

ANA

What lab test is the screening lab of choice in SLE?

clinical, renal, hematuria, ANA, antiphospholipid, urine

SLE: Diagnosis

-________ diagnosis → ask and assess for clinical manifestations

-Routine Labs

• CBC w/ diff, showing leukopenia, anemia, and thrombocytopenia

• BUN/creatinine to look for _____ dysfunction

• UA/microscopic urine to monitor for __________, proteinuria, and cellular casts

-More Specific Labs

• ___ → sensitive but not specific, screening lab of choice

• Anti-dsDNA and anti-Sm antibodies → specific but not as sensitive

-Other Common Labs

• ____________ antibodies

• C3 and C4 complement levels

• ESR/CRP

• _____ protein to creatinine ratio

4, rash, pericarditis, anemia, proteinuria, anti-dsDNA, psychosis

SLE: Classification Criteria (must meet _ of the following)

-____ → malar, discoid, oral ulcers, photosensitivity (each count as 1)

-Arthritis

-Serositis → ____________, pleuritis, peritonitis

-Hematologic → hemolytic ______, leukopenia, leukocytosis, thrombocytopenia

-Renal disease → glomerulonephritis, __________

-Anti-nuclear antibody (ANA)

-Immunologic disorders → ____-_____, anti-Sm, false positive syphilis tests

-Neurologic → seizures or __________ without another cause

inflammation, suppressing, rheumatologist, sun, HTN

SLE: Treatment Goals and Non-Pharmacologic Interventions

-Treatment

• Aimed at reducing ____________, ___________ immune system, and monitoring for serious manifestations

• Refer to _____________

-Non-Pharmacologic

• ___ protection

• Smoking cessation

• Immunizations

• Good control of comorbid conditions like ___ and DM

hydroxychloroquine, steroid, prednisone, high, immunosuppressive

SLE: Pharmacological Treatment

-Mild Lupus → anti-malarial w/ or w/o NSAIDs and/or short term low dose steroids

• Anti-malarials = ______________ or chloroquine

• Low dose _______ = < 7.5 mg prednisone/day

-Moderate Lupus (significant sx but non-organ threatening)

• Hydroxychloroquine + short term __________ daily

• Often require steroid sparing immunosuppressive agents like azathioprine or methotrexate

-Sever Lupus (life or organ threatening)

• Initial intensive = ____ dose steroids alone or in combo with other ______________ agents

• High dose steroid = IV “pulses” or oral methylprednisolone

• Other immunosuppressive agents = mycophenolate, azathioprine, cyclophosphamide, Rituximab

• Followed by less intensive and less toxic maintenance therapy