USMLE Rheumatology III

  1. Psoriatic arthritis
    • It occurs in 5%-30% of patients who have psoriasis. Psoriatic arthritis can present with many different patterns, but the classic presentation involves the distal interphalangeal (DIP) joints.
    • Morning stiffness is present, as it is in all inflammatory arthritides.
    • Deformity of involved joints, dactylitis ("sausage digit," a diffusely swollen finger), and nail involvement are common.
    • Classic signs:
    • 1. All of the fingers (particularly the left index finger) are swollen, consistent with dactylitis
    • 2. many of the nails show pitting and onycholysis (separation of nail bed)
    • 3. DIP joints are prominently involved.
    • 4. Well-demarcated red plaques with silvery scaling-the classic lesions of psoriasis-are seen on the dorsum of hand.
    • Current treatment options includes nonsteroidal antiinflammatory agents, methotrexate, and anti-tumor necrosis factor agents.
  2. pyoderma gangrenosum (PG)
    • It is a neutrophilic ulcerative skin disease.
    • PG starts as an inflammatory papule, pustule, vesicle, or nodule, and progresses to form an expanding ulcer with a purulent base and ragged violaceous borders.
    • PG can present as single or multiple lesions, usually on the trunk or lower extremities.
    • Nearly 30% of cases are triggered by local trauma (pathergy).
    • More than 50% of patients with PG have an associated underlying systemic disorder such as inflammatory bowel disease, arthropathies (eg, rheumatoid arthritis), or hematologic conditions (eg, acute myeloid leukemia).
    • PG is diagnosed clinically after excluding other diagnoses (eg, venous ulcers, panniculitis, cutaneous cancers), usually with skin biopsy.
    • Treatment requires local or systemic corticosteroids.
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  3. Ecthyma gangrenosum (EG)
    • It typically presents as hemorrhagic pustules with surrounding erythema that evolve into necrotic ulcers.
    • EG is a skin infection often due to Pseudomonas aeruginosa and occurs most commonly in the setting of profound neutropenia and Pseudomonas aeruginosa bacteremia.
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  4. Raynaud Phenomenon
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  5. Primary Raynaud phenomenon (RP),
    • It is an increased vascular response to cold temperature or emotional stress without an underlying cause.
    • Primary RP occurs usually in women age <30 with symptoms of symmetrical episodic attacks and without evidence of peripheral vascular disease, connective tissue disease, tissue injury, or abnormal nailfold capillary examination.
    • Abnormalities such as dilated or dropout vessels in the nailfold capillaries are predictive for future development or the presence of a connective tissue disease.
    • Episodes can also involve tingling, numbness, and pain with skin color changes of pallor (white attack) or cyanosis (blue attack).
  6. Management of Primary Raynaud Phenomenon
    • Laboratory studies (eg, antinuclear antibodies, erythrocyte sedimentation rate) are usually negative.
    • Primary RP does not require further evaluation.
    • Treatment mainly involves avoiding aggravating factors (ie, cold stimuli, emotional stress). Dihydropyridine calcium channel blockers (eg, nifedipine, amlodipine) are the drugs of choice for continuing symptoms
  7. Workup of Secondary Raynaud Phenomenon
    • Patients with secondary RP are generally older (age >40, often male) and have asymmetric attacks with clinical features of tissue ischemia ( eg,
    • numbness, ulcers) and systemic disease (autoimmune or vascular).
    • Based on history and physical examination, workup for patients with suspected secondary RP may include:
    • • Complete blood count and metabolic panel
    • • Urinalysis
    • • Antinuclear antibody (ANA) and rheumatoid factor
    • • Erythrocyte sedimentation rate and complement levels (C3 and C4)
    • If the ANA screen is positive, specific antibodies (eg, antitopoisomerase-1 for systemic sclerosis) may be obtained.
  8. Reactive arthritis
    • It is a type of seronegative spondyloarthropathy.
    • Classic reactive arthritis consists of a triad of nongonococcal urethritis, asymmetric oligoarthritis and conjunctivitis.
    • Arthritis often involves the knee and sacroiliac spine.
    • In addition to the classic triad, mucocutaneous (mouth ulcers) lesions and enthesitis (Achilles tendon pain) are common findings in reactive arthritis.
    • Synovial fluid analysis is usually sterile.
    • Nonsteroidal anti-inflammatory agents (NSAIDs) are the first line therapy during the acute phase of this condition
  9. Rheumatoid Arthritis
    • RA is a chronic, systemic inflammatory disorder with progressive erosion of the bone and cartilage and significant joint destruction and deformity.
    • Patients typically present with joint findings (eg, pain, stiffness, swelling), morning stiffness, involvement of proximal interphalangeal and metacarpophalangeal joints, and radiographic evidence of erosions and/or periarticular osteopenia.
    • Treatment goals in RA are to induce and maintain early remission, control synovitis, and prevent progression of joint damage.
  10. Management of Rheumatoid Arthritis
    • All patients diagnosed with RA should be started on DMARDs as soon as possible as joint damage begins early in its course.
    • Nonsteroidal anti-inflammatory drugs and COX-2 inhibitors (eg, celecoxib) are adjunctive therapies for symptomatic relief but do not reduce disease progression.
    • Glucocorticoids can also relieve symptoms and short term radiographic progression but are also not effective in preventing eventual joint destruction and they can result in generalized bone loss (ie, osteoporosis).
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  11. DMARDS
    • DMARDs include nonbiologic agents (eg. methotrexate, hydroxychloroquine, sulfasalazine, leflunomide, azathioprine) and biologic agents (eg, etanercept, infliximab, adalimumab, tocilizumab, rituximab).
    • Methotrexate is the preferred initial DMARD in patients with moderately to severely active RA. Patients should be tested for hepatitis B and C and tuberculosis before starting therapy.
    • Methotrexate should not be used in patients who are pregnant or are planning to become pregnant in the near future and those with severe renal insufficiency, liver disease, or excessive alcohol intake.
    • Patients who do not respond after 6 months may require biologic DMARDs such as tumor necrosis factor-alpha inhibitors (eg. etanercept, infliximab) as step-up therapy
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  12. Methotrexate
    • It is a DMARD which works by inhibiting dihydrofolate reductase.
    • Hematologic toxicity with macrocytic red blood cells may occur with its usage, and one of the more serious abnormalities is development of pancytopenia.
    • There is recommendation for routine peripheral blood counts every three months.
    • Other side effects of methotrexate include: nausea, stomatitis, rash, hepatotoxicity, Bone marrow suppression, interstitial lung disease, alopecia and fever.
    • Methotrexate acts by interfering with the cellular utilization of folic acid, and folate depletion is considered to be the cause of most of these complaints.
    • Prevention of ADRs can be done by supplemental folic acid, without changing the efficacy of MTX.
  13. S/Es of Drugs
    • 1. Hydroxychloroquine: Gl distress, visual disturbances, and hemolysis in G6PD deficiency.
    • 2. Prednisone: Iatrogenic Cushing's syndrome, osteoporosis, adrenocortical atrophy and poor wound healing.
    • 3. Cyclosporine: It predisposes to viral infections and lymphoma, and can be nephrotoxic.
    • 4. Azathioprine: It is associated with pancreatitis, liver toxicity and dose dependent bone marrow suppression.
  14. Clinical Features of Rheumatoid Arthritis
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  15. Mechanism of Osteoporosis in RA
    • Increased levels of proinflammatory cytokines, corticosteroid therapy, and lack of physical activity may contribute to local (around inflamed joints) or generalized loss of bone mass in RA patients.
    • There is an increased risk of osteopenia, osteoporosis, and bone fractures, especially if other risk factors (eg, low body weight, female sex, family history of osteoporosis, cigarette smoking, postmenopausal state, excessive alcohol use, other comorbidities) are present.
    • Strategies to prevent bone loss (adequate physical activity, optimization of vitamin D and calcium intake, minimization of glucocorticoid dose) should be implemented.
    • Most experts suggest a low threshold for starting bisphosphonate therapy in RA patients
  16. Osteitis fibrosa cystica (Von Recklinghausen disease of bone)
    • It presents with bony pain, is characterized by excessive osteoclastic resorption of bone, leading to replacement with fibrous tissue (brown tumors).
    • It is very rare and is seen primarily in patients with parathyroid carcinoma.
    • It can also occur in primary and secondary/tertiary (advanced renal disease) hyperparathyroidism.
  17. Felty syndrome
    • It is a clinical disorder seen in patients with severe, longstanding (more than 10 years) RA that is characterized by neutropenia and splenomegaly.
    • Splenomegaly without neutropenia can also occur in patients with RA, but the diagnosis of Felty syndrome should not be made in the absence of neutropenia.
    • Oral ulcers are not present in this syndrome.
    • Associated with HLA DR4 and treatment is as that of RA.
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  18. RA and Spine Involvement
    • RA most commonly affects the cervical spine joints in the axial skeleton and can lead to cervical spine subluxation, which can also cause spinal cord compression.
    • Patients with cervical spine involvement often complain of neck pain, stiffness, and radicular pain in the upper extremity.
    • Subluxation with spinal cord compression can present with hyperreflexia or upgoing toes on Babinski testing.
  19. Rotator cuff tears
    • It mainly occur in patients age >40, usually after a fall on an outstretched arm.
    • Patients present with pain at the lateral shoulder that is worsened with raising the arm overhead or with external rotation and abduction.
    • Examination shows the drop arm sign (unable to smoothly control shoulder adduction) and weakness with external rotation (passive range of motion is normal).
    • Rotator cuff tendinopathy (tendinitis) may also present with pain on abduction, but tendinopathy without tear does not cause weakness.
  20. Management of Rotator Cuff Tears
    • Posttraumatic shoulder pain with limited active abduction-is suggestive of rotator cuff tears
    • X-ray of the shoulder in a rotator cuff tear may show underlying calcific tendinitis but has low sensitivity for confirming the diagnosis of a tear.
    • MRI can visualize the soft tissues around the humeral head and can accurately diagnose a rotator cuff tear.
    • Treatment of an acute tear usually involves surgery, with best results if performed within 6 weeks of the injury.
  21. Common causes of shoulder pain
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  22. Adhesive capsulitis (AC) (frozen shoulder syndrome)
    • It is characterized by markedly decreased range of motion (ROM).
    • The glenohumeral joint loses its normal distensibility due to chronic inflammation, fibrosis, and contracture of the joint capsule.
    • AC can be idiopathic or secondary to underlying conditions such as rotator cuff tendinopathy (most common), subacromial bursitis, paralytic stroke, diabetes mellitus, or humeral head fracture.
    • Patients with AC typically report a gradual onset of shoulder stiffness, with or without mild pain, that limits their ability to flex, abduct (eg, reach overhead), or rotate the humerus.
    • Diagnosis is confirmed on examination with >50% reduction in both passive and active ROM.
  23. Erythema nodosum (EN)
    • It is characterized by painful, subcutaneous nodules that are most common on the anterior lower legs.
    • Arthralgias and malaise can develop alongside the nodules.
    • EN is thought to represent a delayed hypersensitivity reaction to antigens associated with various conditions and is often relatively benign with self-resolution in several weeks.
    • However, EN can be an early sign of more serious disease, and identification of the cause may prevent morbidity.
    • Diseases associated with EN include streptococcal infection, sarcoidosis, tuberculosis (TB), coccidioidomycosis, inflammatory bowel disease (IBD), and Bechet disease.
  24. Sarcoidosis
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    • Patients with sarcoidosis who are asymptomatic are often followed without treatment due to a high rate of spontaneous remission.
    • However, patients with symptomatic disease (eg, cough, dyspnea, fatigue, hypercalcemia) are treated with systemic glucocorticoids.
    • It is important to rule out infectious granulomatous diseases with similar presentations, such as tuberculosis (TB) and histoplasmosis, prior to initiation of glucocorticoids.
  25. Lumbosacral radiculopathy (sciatica)
    • It due to nerve root compression by a herniated disc.
    • Older patients or those with prior traumatic injury
    • can also have nerve root compression due to lumbar spondylosis.
    • Less common causes include infectious or inflammatory disorders, mass lesions, vascular disorders, and developmental anomalies.
    • Patients with uncomplicated lumbar strain can have radiation of pain to the buttocks or posterior thigh, but radiation to the calf and foot is more consistent with sciatica.
    • Traction on the nerve root during the straight leg raise test causes worsening or reproduction of pain.
  26. Management of Sciatica
    • Most patients with acute sciatica will experience spontaneous resolution; therefore, initial management is primarily focused on acute relief of symptoms.
    • Nonsteroidal anti-inflammatory drugs and acetaminophen are the preferred first-line drugs.
    • Short-term use of opioids or muscle relaxants can be considered in patients with persistent pain but is associated with significant sedation.
    • Activity modification is often advisable, but patients should be encouraged to maintain moderate physical activity.
  27. Septic Arthritis
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  28. Sjogren Syndrome
    • Sjogren syndrome (SS) is an autoimmune disorder characterized by inflammation of exocrine glands
    • Extraglandular features include arthritis, Raynaud phenomenon, cutaneous vasculitis, interstitial lung disease, and increased risk for non-Hodgkin lymphoma.
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  29. Diagnosis of Sjogren Syndrome
    • Diagnosis of SS is made in patients with ocular or oral dryness when there is:
    • • Evidence of dry mouth and eyes. In the Schirmer test, a sterile strip of filter paper is placed under the lower eyelid, and the area moistened by the absorbed fluid is measured after 5 minutes.
    • • Either histologic evidence of lymphocytic infiltration of the salivary glands or presence of serum autoantibodies directed against SSA (Ro) and/or SSB (La).
  30. Neurogenic and Vascular Claudication
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  31. Spinal stenosis
    • It is due to narrowing of the spinal canal with resulting compression of lumbar nerve roots.
    • Common contributing factors include degenerative arthritis (spondylosis), degenerative disk disease, and thickening of the ligamentum flavum.
    • The pain is often associated with activity, as lumbar extension during walking worsens the narrowing of the canal. This is termed neurogenic claudication and can resemble the lower extremity vascular claudication seen in obstructive atherosclerotic arterial disease.
    • Both spinal stenosis/neurogenic claudication and vascular claudication are generally seen in older patients with multiple atherosclerotic risk factors.
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  32. Neurogenic Claudication
    • Pain of neurogenic claudication is postural rather than exertional.
    • It can persist at rest if the spine remains extended but is lessened by spine flexion (eg, walking uphill, leaning on an assistive device), often referred to as the "shopping cart sign."
    • Extension of the lumbar spine (eg, standing, walking upright) further narrows the spinal canal and worsens the symptoms, whereas lumbar flexion (eg, walking uphill, leaning on a cane) relieves the pain
    • The diagnosis of SS can be confirmed on MRI of the spine.
    • Most patients are treated conservatively with physical therapy and exercise, although some require surgical intervention
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  33. Pathogenesis of Spinal Stenosis
    • SS is caused by narrowing of the spinal canal, leading to compression of one or more spinal roots.
    • It is primarily seen in degenerative arthritis with osteophyte formation affecting the facet joints (spondylosis).
    • However, other factors may contribute, including hypertrophy of the ligamentum flavum, bulging of the intervertebral discs, and spondylolisthesis (displacement of one vertebral body relative to another).
  34. Stress fracture
    • Risk factors:
    • • Repetitive activities (eg, running, gymnastics)
    • • Abrupt increase in physical activity
    • • Inadequate calcium & vitamin D intake
    • • Decreased caloric intake
    • • Female athlete triad: low caloric intake, hypomenorrhea/amenorrhea, low bone density
    • Clinical presentation:
    • • It usually causes sharp and localized pain over a bony surface (most commonly the 2nd, 3rd, or 4th metatarsals) that worsens with palpation of the area. Local swelling may also be seen.
    • • Point tenderness at fracture site
    • • X-ray can be negative in the first 6 weeks
    • Management:
    • • Reduced weight-bearing for 4-6 weeks
    • • Referral to orthopedic surgeon for fracture at high risk for malunion (eg, anterior tibial cortex, fifth metatarsal)
  35. Plantar fasciitis
    • It causes burning pain in the plantar (not dorsal) area of the foot that worsens with the first steps in the morning.
    • The pain decreases as activity increases during the day but usually worsens at the end of the day with prolonged weight bearing.
    • It is common in runners with repeated microtrauma who develop local point tenderness on the plantar aspect of the foot.
  36. Tarsal tunnel syndrome
    • It is due to compression of the tibial nerve as it passes through the ankle.
    • It is usually caused by a fracture of the ankle bones.
    • Patients develop burning, numbness, and aching of the distal plantar (not dorsal) surface of the foot/toes that sometimes radiate up to the calf.
  37. Antiphospolipid Syndrome
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    • A minority of healthy individuals may develop transient antiphospholipid antibodies, so all positive serology for APS should be repeated at 12 weeks to confirm diagnosis.
    • Patients with APS often require anticoagulation for life (heparin product or warfarin) as the risk of recurrent thrombus is high.
    • For those with concomitant SLE, hydroxychloroquine is also added.
  38. Systemic lupus erythematosus
    • Clinical presentation
    • • Gradual symptom onset, fatigue, weight loss
    • • Malar or discoid rash
    • • Joint, renal, serosal &/or neurologic involvement
    • Laboratory abnormalities
    • • Anemia, leukopenia, thrombocytopenia
    • • Positive ANA(Very sensitive), anti-dsDNA, anti-Sm
    • • Low complement levels, increased immune complexes, CRP level
    • • Creatinine and Urine Analysis for nephropathy
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  39. Arthritis In SLE
    • Arthritis and arthralgias affect 95% of patients with SLE and tend to be migratory, symmetric, polyarticular, and accompanied by brief morning stiffness (much shorter in duration than rheumatoid arthritis).
    • The knees, carpal joints, and joints of the fingers are most commonly affected.
    • Joint pain often exceeds the objective findings on examination, and X-rays usually show no evidence of joint destruction or erosion (unlike other inflammatory arthritides such as RA).
  40. Systemic Sclerosis (Scleroderma)
    • It is characterized by connective tissue thickening due to fibroblast dysfunction and increased collagen and ground substance production
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  41. Clinical Features of Systemic Sclerosis
    • Cutaneous features include thickening of the skin that begins in acral sites (hands and feet) with edema that transitions to dermal sclerosis (sclerodactyly) and obliteration of skin appendages (eg, hair follicles, sweat glands).
    • Vascular dysfunction (eg, Raynaud phenomenon) is present in most patients.
    • Extradermal manifestations are common, especially in patients with more extensive skin involvement.
    • Frequent complications include esophageal dysmotility, interstitial lung disease (eg, fatigue, breathlessness, fine crackles), and hypertension (due to renal involvement).
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  42. Diagnosis Of Scleroderma
    • The diagnosis of SSc is based primarily on clinical manifestations and serologic markers.
    • Antinuclear antibodies are present in almost all patients but are nonspecific.
    • Anti-topoisomerase I (anti-Scl-70) and anti-RNA polymerase III are less sensitive but more specific and are associated with extensive disease.
    • Anticentromere antibodies may also be seen, primarily in patients with limited disease.
  43. GI Complications In Scleroderma
    • Gl complications are common in SSc and primarily affect the esophagus.
    • SSc causes smooth muscle atrophy and fibrosis in the lower esophagus.
    • Common symptoms include dysphagia, choking, heartburn, and hoarseness.
    • Esophageal manometry in affected patients typically shows hypomotility and incompetence of the lower esophageal sphincter (LES)
  44. Takayasu Arteritis
    • It is a chronic large artery vasculitis that predominantly affects Asian women age <40.
    • It primarily involves the aorta and its branches and is characterized by mononuclear infiltrates and granulomatous inflammation of the vascular media, leading to arterial wall thickening with aneurysmal dilation or narrowing and occlusion.
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  45. Takayasu arteritis,
    • Initial symptoms are nonspecific (eg, fever, arthralgias, weight loss).
    • As the disease progresses, vascular involvement with arterio-occlusive manifestations (eg, claudication, distal ulcers) may develop, particularly in the upper extremities.
    • Examination findings include blood pressure discrepancies, pulse deficits, and bruits.
    • Patients commonly have anemia and elevated inflammatory markers (eg, erythrocyte sedimentation rate, C-reactive protein).
    • Chest x-ray can reveal aortic dilation and a widened mediastinum, and CT and MRI may reveal thickening of large artery walls and lumenal narrowing.
    • Initial treatment includes systemic glucocorticoids.
  46. Vertebral Compression Fracture
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  47. Acute Vertebral Compression fracture
    • An acute VCF can present with sudden onset of low back pain and decreased spinal mobility after bending, coughing, or lifting.
    • Pain typically increases with standing, walking, or lying on the back.
    • Examination can show tenderness at the affected level.
    • Each VCF can decrease a patient's height by more than 1 cm and lead to kyphosis, which is associated with decreased respiratory capacity and increased risk for atelectasis pneumonia.
    • Kyphosis can also cause a protuberant abdomen, early satiety, and weight loss.
  48. Whipple's disease
    • It is a multisystem disease that presents with a history of chronic malabsorptive diarrhea (steatorrhea, flatulence, abdominal distention), protein losing enteropathy, weight loss, migratory non-deforming arthritis, lymphadenopathy and a low-grade fever.
    • It may also cause damage to the eye, CNS and myocardium.
    • It is caused by infection with the gram-positive bacillus tropheryma whippelii.
    • The diagnosis is made with a small intestinal biopsy and PCR in patients with clinical symptoms consistent with the disease.
    • Small intestinal biopsy shows PAS-positive macrophages in the lamina propria containing non-acid-fast gram positive bacilli.
  49. Risk factors for the development of osteoporosis
    • 1.Modifiable risk factors: includes hormonal factors such as low estrogen levels, malnutrition, decreased calcium, decreased vitamin D, use of certain medications such as glucocorticoids or anticonvulsants, immobility, cigarette smoking, and excessive alcohol consumption.
    • 2. Non-modifiable risk factors: includes female gender, advanced age, small body size, late menarche/early menopause, Caucasian and Asian ethnicity, and a family history of osteoporosis.
    • Patients at risk for osteoporosis should be encouraged to make lifestyle modifications including weight bearing exercise, smoking cessation, and decreased alcohol consumption.
    • Alcohol consumption causes a dose-dependent increase in the risk of osteoporotic fractures, and patients have a significant increase in their fracture risk if they drink more than two drinks daily.
  50. Spondylolisthesis
    • It is a developmental disorder characterized by a forward slip of vertebrae (usually L5 over S1). It usually manifests in preadolescent children.
    • Such a displacement results in chronic back pain and in neurologic dysfunction (e.g.,urinary incontinence), if significant.
    • The area of vertebral displacement (a palpable "step off ") is detected on physical examination if the problem is severe.
Card Set
USMLE Rheumatology III
Arthritis, SLE