Study guide
6.1 Rheumatoid Arthritis: Diagnosis & Systemic Manifestations
ABIM Internal Medicine Exam
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1 Chapter 0: The ABIM Exam, Blueprint & Study Strategy
0.1 Exam Format, Question Types & the 2026 Blueprint 0.2 Eligibility, Registration, Fees & Exam-Day Logistics 0.3 Scoring, the Passing Standard & Score Reports 0.4 Building a Blueprint-Weighted Study Plan
2 Chapter 1: Cardiovascular Disease (14% of Exam)
1.1 Ischemic Heart Disease & Acute Coronary Syndromes 1.2 Antithrombotic Therapy, Secondary Prevention & Mechanical Complications of MI 1.3 Atrial Fibrillation, Atrial Flutter & Stroke Prevention 1.4 Supraventricular Tachycardias, Ventricular Arrhythmias & Bradycardias 1.5 Heart Failure: Classification, Staging & Guideline-Directed Medical Therapy 1.6 Device Therapy, HFpEF & the Cardiomyopathies 1.7 Valvular Heart Disease & Endocarditis Prophylaxis 1.8 Pericardial Disease & Acute Aortic Syndromes 1.9 Hypertension: Classification, Diagnosis & Secondary Causes 1.10 Hypertensive Crises & Dyslipidemia 1.11 Adult Congenital Heart Disease & Coarctation of the Aorta 1.12 Syncope: Reflex, Orthostatic & Cardiac Causes 1.13 Cardiac Physical Examination, Murmurs & Antithrombotic Selection
3 Chapter 2: Endocrinology, Diabetes & Metabolism (9% of Exam)
2.1 Diabetes Mellitus: Diagnosis, Glycemic Targets & Pharmacotherapy 2.2 Insulin Therapy, Hyperglycemic Emergencies & Chronic Complications 2.3 Thyroid Function Testing & Hypothyroidism 2.4 Thyrotoxicosis, Thyroid Storm & Thyroid Nodules 2.5 Adrenal & Pituitary Disorders 2.6 Hypercalcemia, Hypocalcemia & Disorders of Mineral Metabolism 2.7 Osteoporosis & Paget Disease of Bone 2.8 Ovarian, Testicular & Reproductive Endocrine Disorders 2.9 Hypoglycemia, Endocrine Tumors, Polyglandular Syndromes & Severe Hypertriglyceridemia
4 Chapter 3: Gastroenterology & Hepatology (9% of Exam)
3.1 Esophageal Disease 3.2 Stomach & Duodenal Disease and Gastrointestinal Hemorrhage 3.3 Inflammatory Bowel Disease 3.4 Celiac Disease & Irritable Bowel Syndrome 3.5 Diverticular Disease & Colorectal Cancer Screening 3.6 Viral Hepatitis, Steatotic & Alcohol-Associated Liver Disease 3.7 Cirrhosis & the Complications of Portal Hypertension 3.8 Acute Pancreatitis 3.9 Chronic Pancreatitis & Biliary Tract Disease 3.10 Inherited, Autoimmune & Drug-Induced Liver Disease 3.11 Small Intestinal Disease, Ischemia & Gastrointestinal Complications of HIV
5 Chapter 4: Infectious Disease (9% of Exam)
4.1 Lower Respiratory Tract Infections & Sepsis Syndromes 4.2 Viral Respiratory Pathogens & Tuberculosis 4.3 Central Nervous System Infections 4.4 Skin, Soft Tissue, Bone & Joint Infections 4.5 Infective Endocarditis & Cardiovascular Infection 4.6 Clostridioides difficile & Catheter-Related Bloodstream Infection 4.7 HIV Diagnosis, Antiretroviral Therapy & Prevention 4.8 Opportunistic Infections & Sexually Transmitted Infections 4.9 Fever of Unknown Origin, Neutropenic Fever & Toxic Shock 4.10 Travel-Related Illness, Vector-Borne Disease & Outbreaks 4.11 Infection Prevention, Nosocomial Infection & Postexposure Prophylaxis 4.12 Rheumatic Fever, Poststreptococcal Disease, Enteric & Hepatic Infections
6 Chapter 5: Pulmonary Disease (9% of Exam)
5.1 COPD: Diagnosis, GOLD Classification & Initial Pharmacotherapy 5.2 Interventions That Reduce COPD Mortality & Exacerbation Management 5.3 Asthma: Diagnosis, Stepwise Therapy & Status Asthmaticus 5.4 Interstitial Lung Disease & Idiopathic Pulmonary Fibrosis 5.5 Sarcoidosis, Hypersensitivity Pneumonitis & Occupational Lung Disease 5.6 Pulmonary Embolism: Diagnosis, Risk Stratification & Anticoagulation 5.7 Pulmonary Hypertension & Sleep-Disordered Breathing 5.8 Acute Respiratory Distress Syndrome & Mechanical Ventilation 5.9 Pleural Disease, Empyema & Pneumothorax 5.10 Bronchiectasis, Cystic Fibrosis & Restrictive Lung Disease 5.11 Evaluation of Cough, Dyspnea, Hemoptysis & the Solitary Pulmonary Nodule
7 Chapter 6: Rheumatology & Orthopedics (9% of Exam)
6.1 Rheumatoid Arthritis: Diagnosis & Systemic Manifestations 6.2 Antirheumatic Pharmacotherapy & the Spondyloarthropathies 6.3 Gout: Pathophysiology & Acute Management 6.4 Urate-Lowering Therapy & Calcium Pyrophosphate Deposition Disease 6.5 Osteoarthritis 6.6 Systemic Lupus Erythematosus 6.7 Systemic Sclerosis, Sjogren Syndrome & Inflammatory Myopathies 6.8 The Vasculitides 6.9 Regional Musculoskeletal Syndromes, Back Pain & Sports Injuries 6.10 Other Primary Rheumatic Disorders & Mixed Connective Tissue Disease 6.11 Osteonecrosis & Metabolic Bone Disease
8 Chapter 7: Hematology (6% of Exam)
7.1 Approach to Anemia & the Microcytic Anemias 7.2 Macrocytic, Normocytic & Hemolytic Anemias 7.3 Hemoglobinopathies, Thalassemias & Paroxysmal Nocturnal Hemoglobinuria 7.4 Platelet Disorders, Thrombocytopenia & the Bleeding Patient 7.5 Coagulation Factor Disorders, Thrombophilia & Anticoagulant Reversal 7.6 Acute Leukemias, Chronic Leukemias & Myeloproliferative Neoplasms 7.7 Lymphomas & Plasma Cell Disorders 7.8 Myelodysplastic Syndrome, Myeloproliferative Neoplasms & Porphyria 7.9 Transfusion Medicine & Late Complications of Transplantation
9 Chapter 8: Medical Oncology (6% of Exam)
8.1 Breast, Lung, Colorectal & Prostate Cancer 8.2 Oncologic Emergencies 8.3 Genitourinary & Gynecologic Malignancies 8.4 Head and Neck, Bone & Soft Tissue Cancer and Cancer of Unknown Primary 8.5 Complications of Cancer & Its Treatment 8.6 Cancer Prevention, Survivorship & Psychosocial Care
10 Chapter 9: Nephrology & Urology (6% of Exam)
9.1 Acute Kidney Injury: Staging, Etiology & Urine Microscopy 9.2 Glomerular Disorders & Nephrotic Syndrome 9.3 Nephritic Syndromes, RPGN & Indications for Renal Replacement Therapy 9.4 Chronic Kidney Disease: Staging & Progression Retardation 9.5 Complications of Chronic Kidney Disease: Anemia, CKD-MBD & Acidosis 9.6 Hyponatremia, Hypernatremia & Water Balance 9.7 Potassium Disorders & Systematic Acid-Base Analysis 9.8 Renal Tubular Acidosis & Nephrolithiasis 9.9 Prostate Disorders, Urinary Incontinence & Other Urologic Conditions 9.10 Cystic Kidney Disease, Obstructive Uropathy, Tubulointerstitial Disease & Hematuria
11 Chapter 10: Neurology (4% of Exam)
10.1 Acute Ischemic Stroke: Syndromes & Reperfusion 10.2 Transient Ischemic Attack, Secondary Prevention & Hemorrhagic Stroke 10.3 Headache & Facial Pain 10.4 Seizures, Epilepsy & Movement Disorders 10.5 Multiple Sclerosis & Neuromuscular Junction Disorders 10.6 Motor Neuron Disease & Acute Peripheral Neuropathy 10.7 Cranial Neuropathies & Neuro-Ophthalmology 10.8 Peripheral Neuropathies, CNS Tumors & Other Neurologic Disorders
12 Chapter 11: Psychiatry & Behavioral Health (4% of Exam)
11.1 Major Depressive Disorder & Medical Mimics 11.2 Antidepressant Pharmacotherapy & Treatment-Resistant Depression 11.3 Bipolar Disorder, Mood Stabilizers & Lithium Toxicity 11.4 Anxiety, Stress-Related & Obsessive-Compulsive Disorders 11.5 Alcohol Use Disorder & Withdrawal 11.6 Pharmacotherapy for Alcohol & Opioid Use Disorder 11.7 Toxidromes, Psychiatric Emergencies & Suicide Risk Assessment 11.8 Psychotic, Somatic Symptom, Factitious & Personality Disorders 11.9 Eating Disorders, Sleep Disorders & Sexual Health
13 Chapter 12: Dermatology (3% of Exam)
12.1 Dermatitis, Papulosquamous & Inflammatory Dermatoses 12.2 Acne, Rosacea & Cutaneous Infections 12.3 Herpes Zoster & Autoimmune Blistering Diseases 12.4 Nodules, Tumors & Cutaneous Oncology 12.5 Dermatologic Emergencies & Severe Cutaneous Adverse Reactions 12.6 Pigment Disorders, Alopecia, Nail Disease & Photosensitivity 12.7 Vascular Dermatoses, Environmental Injury & Cutaneous Signs of Systemic Disease
14 Chapter 13: Obstetrics & Gynecology / Women's Health (3% of Exam)
13.1 Contraception, Preconception Care & Teratogenicity 13.2 Hypertensive Disorders of Pregnancy & Gestational Diabetes 13.3 Thyroid Disease & Venous Thromboembolism in Pregnancy 13.4 Menopause & Menopausal Hormone Therapy 13.5 Abnormal Uterine Bleeding, Endometrial Disease & Gynecologic Cancer Screening 13.6 Breast Disorders & Diseases of the Vulva and Vagina 13.7 Menstrual Disorders, Fibroids, Endometriosis & Early Pregnancy Complications
15 Chapter 14: Geriatric Syndromes (3% of Exam)
14.1 Comprehensive Geriatric Assessment & Frailty 14.2 Falls, Gait Assessment & Polypharmacy 14.3 Urinary Incontinence & Pressure Injuries in Older Adults 14.4 Mild Cognitive Impairment, Dementia & Its Subtypes 14.5 Delirium & the Pharmacotherapy of Cognitive Disorders 14.6 Palliative Care, Hospice & Advance Care Planning 14.7 Chronic Wounds, Nutrition, Swallowing, Constipation & Hip Fracture 14.8 Sensory Impairment, Dizziness, Elder Mistreatment & Care Settings
16 Chapter 15: Allergy & Immunology (2% of Exam)
15.1 Anaphylaxis: Recognition & Emergency Management 15.2 Urticaria & Angioedema 15.3 Drug Allergy, Desensitization & Adult Immunodeficiency 15.4 Food Allergy, Insect Venom Hypersensitivity, Serum Sickness & Contrast Reactions 15.5 Rhinitis, Conjunctivitis, Eosinophilic & Mast Cell Disorders
17 Chapter 16: Preventive Medicine, Immunization & Clinical Epidemiology
16.1 The USPSTF Framework & Evidence-Based Cancer Screening 16.2 Cardiovascular & Metabolic Screening and Primary Prevention 16.3 Adult Immunization & Vaccines in Special Populations 16.4 Clinical Epidemiology, Biostatistics & Study Design
18 Chapter 17: Miscellaneous - Ethics, Patient Safety & Quality Improvement (2% of Exam)
17.1 Principles of Bioethics & Decisional Capacity 17.2 Informed Consent, Treatment Refusal & Special Scenarios 17.3 Surrogate Decision-Making, Advance Directives & Confidentiality 17.4 Patient Safety Science, Medical Error & Diagnostic Reasoning 17.5 Quality Improvement Methods, Health Disparities & Health Equity
19 Chapter 18: Perioperative Medicine & Medical Consultation
18.1 Preoperative Cardiovascular Risk Assessment 18.2 Preoperative Pulmonary Risk & Perioperative Medication Management 18.3 Perioperative Anticoagulation, Bridging & Postoperative Complications
20 Chapter 19: Ophthalmology (1% of Exam)
19.1 The Acute Red Eye & Ophthalmic Emergencies 19.2 Painless Vision Loss & Chronic Ophthalmic Disease 19.3 Uveitis, Scleritis & Orbital Disease
21 Chapter 20: Otolaryngology & Dental Medicine (1% of Exam)
20.1 Dizziness, Vertigo & Epistaxis 20.2 Ear Disorders, Hearing Loss & Upper Respiratory Infections 20.3 Oral Cavity, Salivary Gland, Laryngeal & Taste and Smell Disorders
6.1 Rheumatoid Arthritis: Diagnosis & Systemic Manifestations
Key Takeaways Explain This Topic AI
The rheumatoid arthritis blueprint subsection enumerates skeletal disease, systemic manifestations, adverse effects of antirheumatic drugs and other topics.
Anti-cyclic citrullinated peptide antibody is far more specific than rheumatoid factor and predicts erosive disease.
Symmetric small-joint synovitis with morning stiffness exceeding an hour distinguishes rheumatoid arthritis from osteoarthritis.
Atlantoaxial subluxation from cervical spine involvement is a risk during intubation and must be evaluated before elective surgery.
Cardiovascular disease is the leading cause of death, so risk factor modification is part of rheumatoid arthritis management.
Last updated: August 2026
Inflammatory arthritides represent a diverse group of systemic autoimmune and autoinflammatory conditions characterized by chronic synovial inflammation, cartilage destruction, bony erosions, and systemic extra-articular complications. On the ABIM Internal Medicine certification exam, high-yield mastery requires distinguishing symmetric inflammatory polyarthritis (e.g., Rheumatoid Arthritis) from seronegative spondyloarthropathies (e.g., Ankylosing Spondylitis, Psoriatic Arthritis, Reactive Arthritis), executing pre-treatment infectious screening, navigating DMARD toxicities, and identifying life-threatening structural complications.
- 1. Rheumatoid Arthritis (RA)
- Pathophysiology & Synovial Immunopathology
Rheumatoid Arthritis is a chronic, systemic autoimmune disease characterized by persistent symmetric inflammatory synovitis. Genetic susceptibility is strongly linked to the HLA-DRB1 locus (encoding the "shared epitope"). Environmental triggers, especially cigarette smoking and periodontal disease ( Porphyromonas gingivalis ), induce post-translational conversion of arginine to citrulline via peptidylarginine deiminase (PAD) enzymes in mucosal tissues.
This loss of self-tolerance triggers the production of Anti-Citrullinated Protein Antibodies (anti-CCP / ACPA) and Rheumatoid Factor (RF) (an IgM autoantibody directed against the Fc portion of human IgG). Synovial infiltration by CD4+ T helper cells (Th1 and Th17), B cells, and activated macrophages drives massive secretion of pro-inflammatory cytokines—primarily Tumor Necrosis Factor-alpha (TNF-α) , Interleukin-6 (IL-6) , and Interleukin-1 (IL-1) . This cytokine cascade stimulates synovial hypervascularization and fibroblast-like synoviocyte proliferation, forming a locally invasive hyperplastic tissue mass known as pannus . The pannus secretes matrix metalloproteinases (MMPs) that degrade articular cartilage and induces RANKL (receptor activator of nuclear factor-κB ligand) expression, triggering aggressive osteoclast-mediated marginal bone erosions.
Clinical Articular Manifestations
Joint Distribution: Symmetric polyarthritis predominantly targeting the Metacarpophalangeal (MCP) , Proximal Interphalangeal (PIP) , Metatarsophalangeal (MTP) , and Wrist joints. Knees, ankles, elbows, and shoulders are also commonly involved.
Sparing Patterns: RA characteristically spares the Distal Interphalangeal (DIP) joints and the Thoracolumbar spine .
Symptom Pattern: Severe inflammatory morning stiffness lasting >1 hour , which improves with physical activity and worsens with prolonged rest (gel phenomenon).
Late Structural Deformities:
Ulnar deviation of the digits at the MCP joints.
Swan-neck deformity: Hyperextension of the PIP joint with flexion of the DIP joint.
Boutonnière deformity: Flexion of the PIP joint with hyperextension of the DIP joint.
Z-deformity of the thumb: Hyperextension of the interphalangeal joint with fixed flexion and subluxation at the MCP joint.
Baker cyst (Popliteal cyst): Synovial fluid distension of the gastrocnemio-semimembranosus bursa; rupture mimics acute deep vein thrombosis (pseudothrombophlebitis with crescent-shaped ecchymosis below the medial malleolus).
2010 ACR / EULAR Classification Criteria for RA
A confirmed diagnosis requires a score of >= 6 out of 10 in patients with at least 1 joint exhibiting definite clinical synovitis not explained by another disease:
- Domain Criteria Categories Assigned Points
- A. Joint Involvement 1 medium-to-large joint (shoulders, elbows, hips, knees, ankles) 0
- 2–10 medium-to-large joints 1
- 1–3 small joints (MCP, PIP, 2nd–5th MTP, thumb IP, wrists) 2
- 4–10 small joints 3
- >10 joints (at least 1 small joint) 5
- B. Serology Negative RF and negative Anti-CCP 0
- Low-positive RF or low-positive Anti-CCP (<=3x upper limit of normal) 2
- High-positive RF or high-positive Anti-CCP (>3x upper limit of normal) 3
- C. Acute-Phase Reactants Normal CRP and normal ESR 0
- Abnormal CRP or abnormal ESR 1
- D. Duration of Symptoms <6 weeks 0
- >=6 weeks 1
- Diagnostic Serology & Radiographic Findings
Serologies:
Rheumatoid Factor (RF): Present in ~70–80% of established RA (sensitive ~70%), but lacks specificity (seen in Sjögren syndrome, hepatitis C, subacute bacterial endocarditis, SLE, and healthy elderly).
Anti-Citrullinated Protein Antibodies (anti-CCP / ACPA): Equal sensitivity (~70–80%) but superior specificity (95–98%) . High anti-CCP titers strongly correlate with aggressive, rapidly progressive erosive disease and poor prognosis.
Radiographic Progression:
Early: Soft tissue swelling and periarticular osteopenia (juxta-articular demineralization).
Intermediate/Late: Marginal bone erosions (at the bare areas of bone unprotected by hyaline cartilage) and symmetric uniform joint space narrowing.
Cervical Spine Atlantoaxial Subluxation (C1–C2 Instability):
Synovial inflammation of the transverse ligament of the atlas and the odontoid process leads to ligamentous laxity, pannus destruction of the dens, and posterior displacement of the odontoid into the cervical spinal cord.
Symptoms: Occipital neck pain, electric shock-like sensations down the spine with neck flexion (Lhermitte sign), spastic quadriparesis, hyperreflexia, and bowel/bladder incontinence.
Board Rule: Every patient with longstanding RA undergoing endotracheal intubation or elective surgical procedures requiring neck manipulation MUST undergo flexion and extension cervical spine radiographs to evaluate the anterior atlantodental interval (ADI >3 mm indicates instability; >5-9 mm warrants neurosurgical stabilization prior to elective surgery).
Extra-Articular Manifestations of RA
Extra-articular features occur in up to 40% of patients, predominantly those with high-titer RF/anti-CCP and long-standing severe disease:
System Extra-Articular Manifestation Clinical Features & Pathology
Cutaneous Rheumatoid Nodules Subcutaneous, firm, non-tender nodules located over mechanical pressure points (olecranon bursa, extensor forearm, Achilles tendon); central fibrinoid necrosis surrounded by palisading histiocytes.
Rheumatoid Vasculitis Necrotizing small-to-medium vessel vasculitis causing digital infarcts, palpable purpura, cutaneous ulcerations, and mononeuritis multiplex.
Pulmonary Interstitial Lung Disease (ILD) Most common pulmonary manifestation (~10%); Usual Interstitial Pneumonia (UIP) or Nonspecific Interstitial Pneumonia (NSIP) pattern. Presents with progressive exertional dyspnea, dry cough, and bibasilar end-inspiratory crackles.
Pleural Effusions Characteristically very low pleural fluid glucose (<30 mg/dL) , low pH (<7.20), markedly elevated LDH (>1000 U/L), and low complement levels.
Caplan Syndrome Combination of rheumatoid arthritis and progressive pulmonary rheumatoid nodules in individuals with occupational coal-worker pneumoconiosis.
Hematologic Felty Syndrome Classic triad: Seropositive RA , Splenomegaly , and Severe Neutropenia (Absolute Neutrophil Count [ANC] <1,500/µL, often <500/µL). Associated with high risk of recurrent life-threatening bacterial infections and lower extremity cutaneous ulcers.
Anemia of Chronic Disease Normocytic or microcytic anemia driven by IL-6 induced hepcidin upregulation.
Cardiovascular Accelerated Atherosclerosis Cardiovascular disease (ischemic heart disease/MI) is the #1 cause of mortality in RA . Chronic systemic inflammation accelerates coronary plaque formation independent of traditional Framingham risk factors.
Pericarditis Asymptomatic pericardial thickening or symptomatic acute pericarditis/pericardial effusion.
Ocular Episcleritis & Scleritis Scleritis presents with severe, deep, boring eye pain waking the patient at night, violaceous scleral injection, and potential scleral thinning ( scleromalacia perforans ).
Secondary Sjögren Keratoconjunctivitis sicca (dry eyes) and xerostomia (dry mouth) due to secondary exocrine gland inflammation.