A 53-year-old woman presents to her primary care physician with complaints of pain and swelling in her hands and fingers. She states that she has had these symptoms since she was in her 20s, but they have recently become more severe. She states that her wedding ring no longer fits, due to increased swelling of her fingers. She is a 30-pack-year smoker with a body mass index (BMI) of 31 kg/m2. The vital signs include: blood pressure 122/78 mm Hg, heart rate 72/min, and respiratory rate 15/min. On physical exam, a mild systolic murmur is heard over the apex, and her lungs are clear bilaterally. There is swelling of all the digits bilaterally, and a yellow-white plaque is noted beneath 3 of her nail beds. When asked about the plaques, she states that she was given itraconazole for them about 3 weeks ago; however, the plaques did not resolve. When asked further about joint pain, she notes that she has had shoulder and knee pain for the last several years, although she has not sought medical care for this. Which of the following is the best initial step in this patient’s therapeutic management?

Administer indomethacin and methotrexate

Administer indomethacin and sulfasalazine

A 55-year-old woman presents to the office complaining of leg ulcers for the past 6 months. She has a chronic history of severe rheumatoid arthritis controlled with methotrexate. She does not drink alcohol or smoke cigarettes. Her vitals are normal. Her lungs are clear to auscultation. The abdomen is soft and non-tender with a palpable spleen tip on inspiration. Skin examination shows scattered ulcers on the legs in various stages of healing. Additionally, metacarpophalangeal and proximal interphalangeal joints are tender. Varicose veins are not observed. Laboratory results are as follows: Hemoglobin 10.5 g/dL MCV 74 fl Platelets 226,000/mm3 White blood cells 2500/mm3 Neutrophils 20% Alanine aminotransferase 36 U/L Aspartate aminotransferase 39 U/L Creatinine 1.0 mg/dL HIV test is negative. Which of the following is the most likely cause of this patient's condition?

Venous stasis and valve insufficiency

A 28-year-old man presents with one week of redness and discharge in his eyes, pain and swelling in his left second and third toes, and rash on the soles of his feet. He is sexually active with multiple partners and uses condoms occasionally. He denies any recent travel or illness and does not take any medications. Review of systems is otherwise unremarkable. On physical exam, he has bilateral conjunctivitis, dactylitis of the left second and third toes, and crusty yellow-brown vesicles on his plantar feet. Complete blood count and chemistries are within normal limits. Erythrocyte sedimentation rate (ESR) is 40 mm/h. Toe radiographs demonstrate soft tissue swelling but no fractures. Which diagnostic test should be performed next?

Nucleic acid amplification testing for Chlamydia trachomatis

Anti-cyclic citrullinated peptide antibody assay

A 34-year-old man with a 2-year history of rheumatoid arthritis is being evaluated on a follow-up visit. He is currently on methotrexate and celecoxib for pain management and has shown a good response until now. However, on this visit, he mentions that the morning stiffness has been getting progressively worse. On physical examination, both his wrists are erythematous and swollen, nodules on his elbows are also noted. Rheumatoid factor is 30 (normal reference values: < 15 IU/mL), ESR is 50 mm/h, anti-citrullinated protein antibodies is 55 (normal reference values: < 20). What is the next best step in the management of this patient?

Methotrexate and Corticosteroids

A 64-year-old woman presents to the physician with fever and sore throat for 2 days. She was diagnosed with rheumatoid arthritis 15 years ago. She has had several flares necessitating admission to the hospital in recent years. She has developed deformity in her joints despite aggressive therapy. She is a candidate for surgical correction. Her temperature is 38.2°C (100.9°F), and the rest of her vital signs are stable. Physical examination of the hands reveals multiple swan-neck, boutonniere, and Z-line deformities. Ulnar deviation is evident in both hands. She has flat feet. There are 3 firm, nontender nodules palpated around the right elbow and one on the left Achilles tendon. The spleen is palpated 5 cm below the costal margin with a percussion span of 15 cm. Lymphadenopathy is absent on exam. The laboratory test results show: Hemoglobin 11 g/dL Mean corpuscular volume 90 μm3 Leukocyte count 3,500/mm3 Segmented neutrophils 20% Lymphocytes 70% Platelet count 240,000/mm3 Erythrocyte sedimentation rate 65 mm/hour Rheumatoid factor 85 IU/mL (Normal: up to 14 IU/mL) Which of the following is the most likely cause of this patient’s current condition?

T cell large granular lymphocytic leukemia

A 33-year-old woman presents to her primary care physician for gradually worsening pain in both wrists that began several months ago. The pain originally did not bother her, but it has recently begun to affect her daily functioning. She states that the early morning stiffness in her hands is severe and has made it difficult to tend to her rose garden. She occasionally takes ibuprofen for the pain, but she says this does not really help. Her medical history is significant for diabetes mellitus and major depressive disorder. She is currently taking insulin, sertraline, and a daily multivitamin. The vital signs include: blood pressure 126/84 mm Hg, heart rate 82/min, and temperature 37.0°C (98.6°F). On physical exam, her wrists and metacarpophalangeal joints are swollen, tender, erythematous, and warm to the touch. There are no nodules or vasculitic lesions. Which of the following antibodies would be most specific to this patient’s condition?

Anti-cyclic citrullinated peptide

Rheumatoid arthritis for USMLE Step 2 CK: High-Yield Internal Medicine Lessons

Pathophysiology & Presentation - The Synovial Showdown

Pathogenesis: Genetic susceptibility (HLA-DR4) + environmental trigger → T-cell activation.
- B-cells produce Rheumatoid Factor (RF) & highly specific Anti-Citrullinated Protein Antibodies (ACPA).
- Synovial inflammation & proliferation → pannus formation (destructive granulation tissue).
- Pannus erodes articular cartilage and bone.
- Key cytokines: TNF-α, IL-1, IL-6.
Clinical Presentation: Insidious, symmetric, inflammatory polyarthritis.
- Morning stiffness > 1 hour, improves with activity.
- Affects small joints: MCPs, PIPs, wrists, MTPs.
- Systemic symptoms: low-grade fever, fatigue, weight loss.

⭐ Exam Favorite: RA characteristically spares the distal interphalangeal (DIP) joints, a key feature distinguishing it from osteoarthritis.

Rheumatoid Arthritis vs. Osteoarthritis Joint Comparison

Diagnosis & Serology - Cracking the RA Code

ACR/EULAR 2010 Criteria: Score ≥6/10 for definitive RA diagnosis.
- Joints (0-5): Based on number & size of joints.
- Serology (0-3): RF & anti-CCP levels.
- Acute Phase Reactants (0-1): ↑ESR or ↑CRP.
- Duration (0-1): Symptoms ≥6 weeks.
Key Antibodies:
- Anti-CCP (ACPA): Most specific marker (~95%); predicts erosive disease.
- Rheumatoid Factor (RF): Sensitive but not specific.
Other Labs:
- Synovial Fluid: Inflammatory (WBC 2,000-75,000/μL, >50% PMNs).
Imaging (X-ray):
- Early: Soft tissue swelling, periarticular osteopenia.
- Late: Joint space narrowing, marginal erosions.

⭐ High-Yield: Anti-CCP antibodies may be positive years before clinical symptoms manifest, identifying individuals at high risk for developing RA.

X-ray of hand with rheumatoid arthritis and ulnar deviation

Extra-Articular Manifestations - Systemic Synovial Strike

General: Fever, weight loss, fatigue, myalgias.
Dermatologic:
- Rheumatoid nodules: Firm, subcutaneous on extensor surfaces (e.g., olecranon, occiput).
- Rheumatoid vasculitis: Palpable purpura, skin ulcers.
Pulmonary:
- Pleuritis, pleural effusion (exudative, low glucose).
- Interstitial Lung Disease (ILD).
- Caplan Syndrome: Pneumoconiosis + rheumatoid nodules in lungs.
Cardiovascular:
- Pericarditis is most common.
- Accelerated atherosclerosis, ↑ risk of MI.
Ocular: Keratoconjunctivitis sicca, scleritis.
Hematologic: Anemia of chronic disease, thrombocytosis.

⭐ Felty Syndrome: A severe complication characterized by the triad of long-standing RA, splenomegaly, and neutropenia (<2,000/mm³), leading to recurrent infections.

Extra-articular manifestations of Rheumatoid Arthritis

RA Management - Taming the Flame

Goal: Control synovitis, prevent joint damage, preserve function. Bridge with NSAIDs/corticosteroids for flares.

DMARDs:
- csDMARDs: Methotrexate, Sulfasalazine, Hydroxychloroquine (retinal toxicity), Leflunomide.
- bDMARDs (TNF-α inhibitors): Etanercept, Infliximab. ↑ risk of infection.
- tsDMARDs (JAK inhibitors): Tofacitinib. ↑ risk of thrombosis, shingles.

Normal vs. Rheumatoid Arthritis Joint Comparison

⭐ Before initiating biologic DMARDs (e.g., TNF-α inhibitors), screening for latent Tuberculosis (PPD/IGRA) and viral hepatitis (B & C) is mandatory.

High‑Yield Points - ⚡ Biggest Takeaways

Symmetrical, inflammatory polyarthritis primarily affecting small joints (MCP, PIP) while sparing the DIP joints.

Hallmark is morning stiffness lasting > 60 minutes that improves with activity.

Key serological markers include Rheumatoid Factor (RF) and the more specific anti-citrullinated peptide (anti-CCP) antibodies.

Characteristic deformities include ulnar deviation, swan-neck, and boutonnière deformities.

Methotrexate is the cornerstone first-line DMARD for management.

Associated with C1-C2 subluxation (atlantoaxial instability) and systemic features like rheumatoid nodules.

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