4.06 Osteoarthritis vs Rheumatoid Arthritis

Rheumatology review for the USMLE Step 1 exam

• Rheumatoid arthritis and osteoarthritis both cause joint inflammation, joint pain, and can limit joint range of motion
• Osteoarthritis is a degenerative joint disease that occurs when the articular cartilage that covers the ends of bones begins to degrade and erode
• The most common joints affected by osteoarthritis are the hips and knees, and the distal interphalangeals of the hands are also commonly affected
• Osteoarthritis tends to be more asymmetric and localized, presenting as a single degenerated joint
• Rheumatoid arthritis is an inflammatory autoimmune disease that affects the joints and other parts of the body
• RA typically develops in patients who are genetically predisposed and triggered by environmental factors, such as smoking
• The two autoantibodies present in RA are rheumatoid factors and anti-cyclic citrullinated peptide (anti-CCP) antibodies
• Rheumatoid factors activate the complement system and stimulate the inflammatory response in the body.
• Anti-CCP antibodies bind citrullinated peptides and stimulate inflammation in the synovium of joints
• Rhematoid arthritis has extra-articular manifestations, the most common of which are rheumatoid nodules

4.05 Scleroderma

Rheumatology review for the USMLE Step 1 exam

• Scleroderma is a chronic autoimmune connective tissue disease that causes thickening and hardening of the skin, as well as fibrosis (excess deposition of collagen and other ECM proteins) throughout the body.
• Autoreactive immune cells activate endothelial cells, which produce large amounts of endothelin 1, leading to overactivation of fibroblasts that overexpress collagen.
• It typically affects younger women (35-50 years old) with a F:M ratio of 5:1.
• There are two distinct forms of scleroderma: diffuse (systemic) and limited, each associated with unique antibodies and clinical presentations.
• Diffuse scleroderma involves the skin and internal organs and is rapidly progressive. Skin tightens especially in the fingers, and internal organs including the lungs, kidneys, GI system, and heart can be affected. It is associated with anti-Scl-70 antibody and anti-RNA III polymerase.
• Limited scleroderma tends to only affect the skin, characterized by the mnemonic CREST: Calcinosis cutis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia. It is associated with anti-Centromere antibody.
• Treatment involves NSAIDs and DMARDs for musculoskeletal pain, H2 blockers or PPIs for esophageal reflux, and Ace inhibitors for scleroderma renal crisis. There is no cure for the disease.

HIGH YIELD 2: Marfan's vs Homocystinuria vs Ehlers-Danlos

High yield review for the USMLE Step 1 exam.

• Marfan's syndrome, Ehlers-danlos, and homocystinuria are three distinct diseases that affect connective tissue.
• They share similarities like tall stature, long fingers, scoliosis, high arched palate, chest wall deformities, joint hypermobility, and lens dislocation.
• Marfan's syndrome is caused by FBN1 gene mutation on chromosome 15, and it results in defective fibrillin-1. It causes aortic root dilation, and upward lens dislocation.
• Homocystinuria is caused by a defect in homocysteine breakdown, and it results in elevated levels of homocysteine, which is toxic to the body. It causes thrombosis and downward lens dislocation.
• Ehlers-Danlos syndrome is caused by a deficiency in type III collagen, and it results in hyperextensible skin, easy bruising and bleeding. It can cause vascular rupture, and it usually occurs in the arterial system.
• Patients with Marfan's syndrome present with scoliosis, long fingers and toes, and caved-in chest wall.
• Patients with homocystinuria present with developmental delay, long fingers and toes, and upward lens dislocation.
• Patients with Ehlers-Danlos syndrome present with recurrent bruising, soft hyperextensible skin, and joint hyperextensibility

4.04 Systemic Lupus Erythematosus

Rheumatology review for the USMLE Step 1 Exam

• Marfan's syndrome, Ehlers-danlos, and homocystinuria are three distinct diseases that affect connective tissue.
• They share some clinical features like tall stature, long fingers, scoliosis, high arched pallet, chest wall deformities, joint hypermobility, and lens dislocation.
• Marfans is caused by a mutation in the FBN1 gene, resulting in defective fibrillin-1, and the main complication is aortic root dilation.
• Homocystinuria is a metabolic disorder caused by a defect in homocysteine breakdown, leading to elevated levels of homocysteine, and the main complication is thrombosis.
• Ehlers-Danlos is caused by a deficiency in type III collagen, and the main complication is vascular rupture.
• Marfans has an upward lens dislocation, homocystinuria has a downward lens dislocation, and Ehlers-Danlos has hyperextensible skin and joint hyperextensibility.
• Marfans usually presents in teens, homocystinuria in children, and Ehlers-Danlos in young adults.
• Patient presentations: Marfans - scoliosis, long fingers, and caved in chest wall in a tall teen; Homocystinuria - developmental delay, long fingers, and tall stature in a child; Ehlers-Danlos - recurrent bruising, hyper extensible skin, and joint hyperextensibility in a young adult.

4.03 Large Vessel Vasculitis

Rheumatology review for the USMLE Step 1 Exam

• Vasculitis is inflammation of blood vessels
• Vasculitis is split into three groups based on the size of blood vessels affected: large, medium, and small vessel vasculitis
• Large vessel vasculitis involves inflammation of the aorta and its main branches
• Two distinct large vessel vasculitidies: temporal (or giant cell) arteritis and takayasu arteritis
• Temporal (giant cell) arteritis primarily affects older women (>60) and the branches of the common carotid arteries
• Symptoms of temporal arteritis: jaw pain (jaw claudication), headaches, tenderness along temporal artery
• Complication of temporal arteritis: blindness
• Takayasu arteritis mostly affects young Asian women (

4.02 Medium Vessel Vasculitis

Rheumatology review for the USMLE Step 1 exam.

• Vasculitis: inflammation of blood vessels, classified by the size of the blood vessels affected
• Medium vessel vasculitis affects the main visceral arteries and veins, and their initial branches
• Three types of medium vessel vasculitis are discussed: polyarteritis nodosa, Kawasaki disease (mucocutaneous lymph node syndrome), and Buerger disease (thromboangiitis obliterans)
• Polyarteritis nodosa affects middle-aged to older men and is idiopathic, but can be secondary to other diseases, including hepatitis B
• Histology findings show transmural inflammation with fibrinoid necrosis in early lesions, and string-of-beads sign in angiogram
• Symptoms include constitutional symptoms, abdominal pain and melena, and hypertension caused by damage to the renal arteries
• Kawasaki disease most commonly affects young Asian children, and is triggered by upper airway infections
• Symptoms include conjunctival injection, desquamating rash, cervical lymphadenopathy, strawberry tongue, and prolonged fever
• Kawasaki disease has a predilection for the coronary vessels, which can lead to aneurysm rupture and thrombi development
• Treatment for Kawasaki disease includes IVIG and aspirin to prevent complications

4.01 Small Vessel Vasculitis

Rheumatology review for the USMLE Step 1 exam

• Vasculitis is inflammation of blood vessels and is classified into three categories based on vessel size: large, medium, and small vessel vasculitis.
• Small vessel vasculitis affects arterioles, capillaries, and venules, leading to symptoms associated with damage to these vessels, such as palpable purpura.
• Five types of small vessel vasculitis include IgA vasculitis (Henoch-Schonlein Purpura), Granulomatosis with polyangiitis (Wegener Granulomatosis), Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome), Microscopic polyangiitis, and Behçet syndrome.
• IgA vasculitis is the most common in children, and anti-neutrophil cytoplasmic antibody + vasculitis are the most common in adults.
• IgA vasculitis is caused by the deposition of IgA immune complexes after an upper respiratory or GI tract infection, leading to palpable purpura, renal, GI, and joint involvement. It resolves on its own in a few weeks, and steroids and NSAIDs are used to reduce severity of symptoms.

HIGH YIELD 1: Top Weird Drug Reactions

Review for the USMLE Step 1 exam

The podcast discusses high yield weird drug side effects that are unexpected.

1. Cyanopsia (blue vision) with sildenafil (PDE-5 inhibitor)
2. Hepatic necrosis with halothane (inhaled anesthetic)
3. Tendon/cartilage damage with fluoroquinolones (antibiotics)
4. Cinchonism with quinidine (class IA antiarrhythmic)
5. Hemorrhagic cystitis with cyclophosphamide and ifosfamide (chemotherapeutic agents)
6. Muscle pain and rhabdomylitis from statin use (cholesterol lowering med)
7. Tartive dyskinesia with antipsychotics 
8. Fanconi syndrome from expired tetracyclines (antibiotics)

3.30 Spirochetes

Microbiology review for the USMLE Step 1 Exam

• Spirochetes are spiral or corkscrew-shaped bacteria that stain gram negative.
• They have a unique endoflagella that distinguishes them from other species of bacteria.
• The endoflagella rotates within the periplasmic space and causes the bacteria to move, acting as its own propeller.
• Borrelia burgdorferi, Treponema pallidum, and Leptospira interrogans are the three important species of spirochetes to know.
• Borrelia burgdorferi causes Lyme disease, which is spread from wildlife to ticks and then to humans.
• The deer tick, also known as ixodes scapularis, is associated with Borrelia burgdorferi, but deer are not the reservoir for the bacteria.
• Lyme disease presents in three stages: erythema migrans (bulls-eye rash), flu-like symptoms, Bell's palsy, myocarditis, transient myalgias, arthritis, and neurological symptoms like encephalopathy and peripheral neuropathy.
• Treponema pallidum causes syphilis, which presents in stages: primary (chancre), secondary (rash), latent, and tertiary (gummas, neurological symptoms).
• Leptospira interrogans causes leptospirosis (Weil's disease), which is spread from infected animal urine to humans through broken skin, mucous membranes, or ingestion.
• Leptospirosis presents with flu-like symptoms, jaundice, renal failure, and meningitis.

3.29 Mycoplasma and Ureaplasma

Microbiology review for the USMLE Step 1 Exam

• Mycoplasma and Ureaplasma are bacteria without cell walls, making them invisible to gram stain.
• They cause respiratory and genital infections and have a cell membrane containing cholesterol.
• Main species causing infections in humans include Mycoplasma pneumoniae, Mycoplasma genitalium, Mycoplasma hominis, and Ureaplasma urealyticum.
• Mycoplasma pneumoniae causes atypical pneumonia and is spread through respiratory droplets. Symptoms include non-specific fever, headache, and sore throat, and diagnosis is done through PCR. Treatment is with macrolides, tetracyclines, and fluoroquinolones.
• Mycoplasma genitalium, Mycoplasma hominis, and Ureaplasma urealyticum cause genital infections and are acquired through sexual contact. They cause dysuria, urgency, urethral discharge, and pelvic pain. Diagnosis and treatment are similar to Mycoplasma pneumoniae with PCR and tetracyclines being the preferred treatment.