Rheumatology Board Review

1. Rheumatology Board Review Michelle M Santiago, MD May 4, 2010

2. Board Favorites Joint pain Juvenile Dermatomyositis Systemic/Neonatal Lupus Erythematosus Miscellaneous

3. Joint Pain 1) Duration of complaints. 2) Preceding events. 3) Associated Symptoms. 4) Characteristic of complaints. 5) Joint distribution.

4. Arthritis vs Arthralgias Arthralgia – complaint of joint pain arthralgia does not equal arthritis Arthritis – collection of exam findings that result in the Swelling, pain on palpation/motion, erythema, increased warmth or decreased range of motion at a joint, evidence of synovial thickening/hypertrophy

5. Inflammatory vs. non-inflammatory complaints Inflammatory- stiffness, stiffness after immobility, improvement with warmth and activity, worsened by rest, persistent complaints. Pain tends to be a minimal feature. DOES NOT WAKE UP PATIENT AT NIGHT Non-inflammatory- PAIN, transient complaints, relieved by rest, worsened by activity, no stiffness.

6. Navigating joint pain (arthritis) Complaint <6 weeks or > 6 weeks or in between

7. Short Duration- <6 weeks Its not JIA (JRA).

8. Differential Diagnosis Injury- Acute sudden onset, painful, history of injury, improvement with rest, specific movements/actions worsen pain. If chronic injury (athlete)- can have smoldering chronic pain, improved with rest and avoidance of activity, injury makes sense with reported activity. Lack of associated symptoms (no rash, no fever, usually no lab abnormalities)

11. Infection- (much more common than JIA) Septic joint- pathogen inside joint acute (hrs-days) onset severe intense pain, limits in ROM due to pain, worse with activity redness, warmth and swelling. Associated with fever, lab changes (high WBC, inflammatory markers, BCx). Can be preceded by trauma or skin breakdown. Usually monoarticular (knee>hip) Joint Neutrophils 50,000-300,000 Trick- JIA patient s/p injectionTrick- JIA patient s/p injection

12. Infection Gonococcal arthritis- Acute onset (days) Usually Teens Monoarthritis to multiple joints, assymetric (hands, knees, wrists, ankles, elbows) Painful- Tenosynovitis. Associated with fever, rash.

13. Infection Other infections associated with joint complaints (not an antibody mediated process) Brucella- fevers, GI sx, lymphadenopathy, dermatitis, HSM and arthritis or arthralgias. Hip and knees most common. (sometimes sacroiliac joint not assoc. with HLA B-27) Mycoplasma- common myalgias and arthralgias. (Any number of joints or migratory) Bartonella, Rubella, Parvo, Hepatitis B, HIV… IMPORTANT will have signs of active infection with associated joint pain or swelling. Endocarditis. Onset of joint complaint from onset of infx symptoms to usually 2 and up to 4 weeks. IMPORTANT will have signs of active infection with associated joint pain or swelling. Endocarditis. Onset of joint complaint from onset of infx symptoms to usually 2 and up to 4 weeks.

14. Post-infectious Needs to occur at least 2-4 weeks after an infection. (Antibody Mediated Process) Acute Rheumatic Fever 2-3 weeks after GAS infx (Asx latency period) Assoc. Sx. Carditis, chorea, subcutaneousnodules, rash, fever (Jones criteria) Large joints more commonly. Painful, swollen, warm +/- red joints. Migratory or additive. Very responsive to aspirin. So painful can lead to pseudoparalysis. So painful can lead to pseudoparalysis.

15. Post-infectious Post-strep reactive arthritis. Arthritis post strep and does not fulfill Jones criteria. Unlike ARF- Non-migratory, protracted course, poorly responsive to ASA and NSAIDs Assoc. sx.- can have low grade fever and rash (usually before arthritis) 10% arthralgias only. Arthritis- acute onset, asymmetric, one or more joints. Can last 5 days to 8 months.

16. Post-infectious Reactive arthritis (Reiters syndrome) 4 (1-4) weeks after infx. Non-specific arthritis after an extra-articular infection with arthritogenic bacteria (Chlamydia, Yersinia, Salmonella, Shigella or Campylobacter) Usually in HLA B-27 positive patients Arthritis- predominantly lower limbs, asymmetric, oligoarthritis, tenosynovitis, enthesitis

17. Reactive Arthritis Arthritis can last weeks to months. Can have recurrent episodes. Associated manifestations: Urethritis or cervicitis Balanitis, e-nodosum, keratoderma blenorrhagicum Conjunctivitis, anterior iridocyclitis Some can evolve into spondyloarthropathySome can evolve into spondyloarthropathy

18. Other causes of acute arthritis/joint pain/swelling Vasculitides- HSP, Kawasaki disease, SLE Malignancy- Leukemia Vaccine reactions Serum Sickness

19. Treatment for almost all Supportive NSAIDs Very rarely steroids (usually only for reactive arthritis)

20. The in-between

21. Spondyloarthropathies Refers to a group of arthritis that Inflammation of the joints of the axial skeleton and of the entheses Entheses are sites of attachment of ligament, tendon, fascia, or capsule to bone Relatives have a high frequency of HLA B27 Extra-articular features shared by several disease in this group including: iritis, cutaneous manifestation Rheumatoid factors are absent and other autoantibodies are infrequent

22. Spondyloarthropathies Arthritis and enthesitis with at least 2 of the following: -Sacroiliac joint tenderness and /or inflammatory spinal pain -Presence of HLA-B27 -(+) Family history medically confirmed HLA-B27-associated disease -Anterior uveitis -Onset of arthritis in a boy after 8 years of age

23. Spondyloarthropathies Juvenile Ankylosing Spondylitis Psoriatic Arthritis Arthropathy of IBD Reactive Arthritis/Reiters

24. Juvenile Ankylosing Spondylitis Usual onset: late childhood or adolescence Male/female ratio: 7:1 Etiology: Strong correlation with HLA-B27 suggests a genetically determined mechanism or serve as a gene marker.

25. Juvenile AS May be insidious or abrupt Enthesitis is an early manifestation - Peripheral arthritis : lower extremities, asymmetric joint involvement more common than polyarticular disease - Axial involvement may be presenting manifestation in 24% of children with JAS - Iritis: acutely red, painful, photophobic eye (usually unilateral) and rarely precedes onset of musculoskeletal complaints

27. Psoriatic Arthritis Arthritis and psoriasis OR Arthritis and at least 2 of the following: Dactylitis Nail pitting or onycholysis Family history in a 1st-degree relative

29. Notice ANA and Rheumatoid Factor not used at all.

30. Greater than 6 weeks…

31. > 6 weeks Juvenile Idiopathic Arthritis (JRA) 1. Age of onset <16 years 2. Arthritis in one or more joints Arthritis defined as swelling or effusion, or presence of 2 or more of the following signs: limitation of range of motion, tenderness or pain on motion, and increased heat)

32. JIA 3. Duration of disease 6 week or longer 4. Onset type as defined by disease type in first 6 months: a. Oligoarthritis /pauciarticular b. Polyarticular c. Systemic 5. Exclusion of other forms of arthritis

34. Pauciarticular JIAPauciarticular JIA

36. Quotidian pattern of fever Rash is intermittent and accompanies the fever. Cardiac disease- pericarditis, myocarditis, endocarditis. Pleuropulmonary- LAN, HSM Feared complication MAS.Quotidian pattern of fever Rash is intermittent and accompanies the fever. Cardiac disease- pericarditis, myocarditis, endocarditis. Pleuropulmonary- LAN, HSM Feared complication MAS.

37. Laboratories ANA- only needed to assess risk of developing Uveitis and need for frequent ophthalmological evaluation. DOES NOT HELP IN DIAGNOSIS. RF- only needed after diagnosis is made to determine prognosis. Can have elevated inflammatory markers but not necessarily.

38. Management 1) NSAIDs 2) NSAID + Steroid Injection (if mono or pauci articular) 3) NSAID + oral steroid 4) NSAID + oral steroid + immunomodulating agent (usually MTX) For systemics and severe polyarthrits- more aggressive therapy.

39. Questions

40. An 18-year-old post-partum girl presents to your clinic with complaints of discomfort in her knees and hands. She denies any swelling or erythema of these areas or recent trauma. She takes no regular medications, and she has been healthy until 6 days ago, when she developed these complaints. She did receive a rubella vaccination about 1 month ago because on her first visit to an obstetrician during her pregnancy she was found to have a negative serum titer to rubella. Her physical examination findings are normal.Of the following, the MOST likely diagnosis is a. adverse effect of the rubella vaccine b. anicteric hepatitis B infection c. poststreptococcal arthritis d. reactive arthritis due to Salmonella sp e. recent infection with parvovirus

41. A 16-year-old boy presents with a very swollen, painful right knee. He is a soccer player, but there is no history of recent injury. During the interview, you notice the boy has injected conjunctivae Of the following, further evaluation MOST likely will reveal A. alopecia areata B. Gottron papules C. Kayser-Fleischer rings D. malar rash E. urethritis

42. An 11-year-old girl presents 2 weeks after an office visit for a presumed viral illness characterized by fever, malaise, and flushing of the cheeks. Today, her mother notes that she no longer has a fever, but she complains of pain in her knees and elbows. On physical examination, the left knee is slightly swollen and warm but not erythematous. The girl reports pain on movement of both elbows, but there are no physical findings on examination of the elbows or other joints. The remainder of the physical examination findings are normal, except for an oral temperature of 100.6°F (38.1°C). Results of laboratory studies include a white blood cell count of 8.9x103/mcL (8.9x109/L) with 40% polymorphonuclear leukocytes, 45% lymphocytes, and 15% monocytes; hemoglobin of 11.0 g/dL (110.0 g/L); platelet count of 472.0x103/mcL (472.0x109/L); and erythrocyte sedimentation rate of 20 mm/hr. Of the following, the MOST likely pathogen to cause this child’s joint complaints is A. Borrelia burgdorferi B. Coxsackievirus C. group A beta-hemolytic streptococci D. influenza A virus E. parvovirus B19

45. Juvenile Dermatomyositis

46. Diagnostic Criteria (rash + 2 others) Symmetric weakness of proximal muscles Characteristic cutaneous changes (Heliotrope, gottrons) Elevation in one or more: CK, Aldolase, AST or LDH EMG with myopathy and denervation Muscle biopsy with evidence of necrosis and inflammation

47. JDMS Usually 5-14 years Insidious progression of malaise, easy fatigue, muscle weakness, fever, rash that may predate dx by 3-6 months. Positive Gowers Can have arthritis but should be minimal Tx: Steroids, immunomodulators, Plaquenil

48. A 10-year-old girl presents with progressive fatigue without pain. Physical examination reveals edema and a pink-to-violet discoloration of the upper eyelids and malar areas. Scaly, red papules are observed over the knuckles

49. Of the following, the MOST appropriate laboratory investigation to support the diagnosis isa. antinuclear antibody assayb. creatine phosphokinase concentration c. epicutaneous patch testingd. erythrocyte sedimentation rate e. skin biopsy

50. Systemic Lupus Erythematosus

51. Diagnostic Criteria Total 11 : 4 mucocutaneous (malar rash, discoid, photosensitivity, oral ulcers) 2 itis (arthritis, serositis) 3 major organs/systems (renal, neurologic, hematological) 2 labs (ANA, specific autoantibodies) 4 out of 11 criteria provide a sensitivity of 96% and a specificity of 96%.

52. A RASH POINts MD Arthritis (non erosive) Renal disease (proteinuria, cellular casts) ANA (positive antinuclear antibody) Serositis (pleurisy or pericarditis) H aematological disorders (haemolytic anaemia/leucopenia/lymphopenia or thrombocytopenia) Photosensitivity Oral ulcers (also nasal ulcers) Immunological disorder (anti-DNA, anti-Sm,antiphospholipid antibody based on a false positive serological test for syphilis/lupus anticoagulant, or IgM or IgG anti-cardiolipin antibody) Neurological disorders (seizures or psychosis) Malar rash Discoid rash

53. Malar rash The rashes are extremely varied. At onset 50-80%, up to 85% during the course. Isolated discoid rash is rare. ~10% can turn to systemic disease. Erythematous ‘butterfly’ rash : 30-60% of children at onset, 80% during the course. Not pathognomonic Symmetric, spares nasolabial folds, quite well demarcated, may be slightly raised. Some follicular plugging. May be precipitated by sun exposure. Often heralds a disease flare The rashes are extremely varied. At onset 50-80%, up to 85% during the course. Isolated discoid rash is rare. ~10% can turn to systemic disease. Erythematous ‘butterfly’ rash : 30-60% of children at onset, 80% during the course. Not pathognomonic Symmetric, spares nasolabial folds, quite well demarcated, may be slightly raised. Some follicular plugging. May be precipitated by sun exposure. Often heralds a disease flare

54. Discoid lesions and other rashes

55. Other findings in SLE True vasculitis skin rash – 10-20%, can result in digital infarct. Oral ulcer – commonly at hard palate, painless – disease flare !!! Alopecia – up to 50%, occurs during active disease or after flare. Raynaud’s phenomenon – 10-20% True photosentive rash : - ~ one third of pediatric SLE. - can occur in any sun expose area, other than the face - may be maculopapular or papulosquamous - may be associated with anti-Ro and anti-La - sun exposure may not only exacerbate skin flare, but may cause systemic flare !!! True vasculitis skin rash – 10-20%, can result in digital infarct. Oral ulcer – commonly at hard palate, painless – disease flare !!! Alopecia – up to 50%, occurs during active disease or after flare. Raynaud’s phenomenon – 10-20% True photosentive rash : - ~ one third of pediatric SLE. - can occur in any sun expose area, other than the face - may be maculopapular or papulosquamous - may be associated with anti-Ro and anti-La - sun exposure may not only exacerbate skin flare, but may cause systemic flare !!!

56. What you need to know Remember criteria (don’t be fooled by just a positive ANA) Decreased C3 and C4 in active disease. High immuniglobulins. Other clinical Manifestations: Fever Weight loss Fatigue Lymphadenopathy (r/o lymphoma) Alopecia Will be asked to make diagnosis. Or what study do you need to make the diagnosis.Will be asked to make diagnosis. Or what study do you need to make the diagnosis.

57. Neonatal Lupus

58. Neonatal Lupus Need Maternal Anti –Ro antibody to occur. Suspect in baby with congenital heart block- greatest risk if mom has positive Anti-Ro and Anti-La. 2 major types: Cutanoeus- Self limited, onset first weeks of life, rarely beyond 6 mo. Cardiac- Congenital AV block. Can have liver and hematological involvement

59. You are evaluating a newborn who has complete heart block and several 1.5-cm erythematous macules and annuli located on the forehead, behind the ears, and in the scalp. Of the following, the test MOST likely to confirm the infant's diagnosis is a. anti-Ro (SSA) antibodiesb. creatine kinasec. hepatic function profiled. platelet counte. urinalysis

60. Miscellaneous

61. A 3-year-old girl is brought to your office for re-evaluation of a fever that began 6 days ago. Her mother tells you that her daughter's temperature has been as high as 102.2°F (39°C). Her physical examination was unremarkable when you examined her 3 days ago, but today you note injected sclera; cracked, red lips; a strawberry appearance of her tongue; and a swollen, nontender, cervical node. You tell her mother that you believe this is Kawasaki disease. Of the following, the MOST appropriate statement to make to the mother is that a. an exercise stress test should be performed as a baseline study b. aspirin therapy will be used until the fever subsidescardiac involvement may include abnormalities of the coronary arteries or the myocardiumc. echocardiography should be performed to evaluate for the presence of coronary aneurysmsd. immediate treatment with intravenous immune globulin will eliminate the chance of coronary involvement

62. A 14-year-old girl presents for evaluation of areas of skin thickening, tightness, and discoloration that developed 2 months ago. Physical examination reveals shiny, hypopigmented patches with brown borders on the leg and ankle. The affected skin is immobile, firm, and has a "bound-down" feeling.Of the following, the MOST likely diagnosis is a. lichen sclerosus et atrophicus b. linear scleroderma c. pityriasis albad. progressive systemic sclerosise. vitiligo

63. A 6-year-old boy has had difficulty walking and lower leg pain for 2 days. Five days ago, he had fever and cough that had lasted for 3 days. On physical examination, the child has no fever, and vital signs are normal, as are cranial nerves, speech, and language. Muscle bulk, tone, and reflexes are normal and symmetric, but his lower legs are painful to palpation. Serum creatine kinase is 2,000 U/L, and urine is negative for myoglobin. Of the following, the MOST likely diagnosis is a. dermatomyositis b. Duchenne muscular dystrophyc. Guillain-Barré syndromed. metabolic myopathye. viral myositis 

64. Which child with arthritis is at MOST risk of developing uveitis? a. male, 7 joints involved, ANA+ b. female, 7 joints involved, ANA+ c. male, 2 joints involved, ANA+ d. female, 2 joints involved, ANA + e. male, 12 joints involved, ANA –

65. A 3 year old boy is brought to the office with complaints of intermittent abdominal pain for 2 days. His mother notes that he also had a limp and a faint rash on his legs for 1 day. He has been afebrile and otherwise well except for an upper respiratory tract infection a few weeks ago. On physical examination, he is alert and complains of mild abdominal tenderness on palpation. His left ankle is swollen and tender, a few 4-5 mm non-blanching lesions are visible on his lower legs bilaterally. Of the following, the MOST likely diagnosis is a. Henoch-Schonlein purpura b. immune thrombocytopenia c. Juvenile rheumatoid arthritis d. parvoviral infection e. poststreptococcal infection

66. You are evaluating a 16-year-old boy who has a 3 month history of bilateral leg pain and lower back pain. He also reports occasional low-grade fever and a 5-10 lb (2.25 to 4.5 kg) weight loss over the last 3 months. He denies rashes or other symptoms. His PE reveals loss of mobility of the low spine when bending forward and tenderness at both knees. The remainder of the exam findings are normal. Of the following, the MOST likely diagnosis is a. ankylosing spondylitis b. Chron’s disease c. diskitis d. psoriatric arthritis e. spondylolisthesis AS – ankylosing spondylitis Occurs more commonly in adolescent boys Presenting features Oligoarthritis in the LOWER extremities (knees and ankles most commonly involved) Enthesitis inflammation at insertion sites of tendons and ligaments to bone Spine involvment may occur early on in the disease Sacroiliitis may occur and be unilateral Generalized constitutional symptoms such as fever and weight loss can occur. Other features such as uveitis, renal involvement and rarely aortic insufficiency have been described. Labs: +/- Mildly elevated WBC, ESR, CRP. Negative RF and ANA. HLA B27 may be positive. Hip X-rays may show evidence of sacoillitis but MRI is more effective at demonstrating this finding. Chron disease – arthritis is an extra-intestinal manifestation of Chron disease. When present? polyarthritic and can involve the spine Active GI disease will cause flare of joint manifestations However, spine involvement may flare independent of GI status Diskitis Infection of the intravertebral disc (ie T2-T4), is the most common in young children (toddlers) and peripheral joints are NOT involved. Best imaging modality to evaluate for this is a technetium bone scan Psoriatic arthritis Asymetric oligoarthritis) w/ the addition of nail pitting & rash expected. Spondylolisthesis Forward displacement of one vertebra over another; “step-off’ at the affected area may be palpable AS – ankylosing spondylitis Occurs more commonly in adolescent boys Presenting features Oligoarthritis in the LOWER extremities (knees and ankles most commonly involved) Enthesitis inflammation at insertion sites of tendons and ligaments to bone Spine involvment may occur early on in the disease Sacroiliitis may occur and be unilateral Generalized constitutional symptoms such as fever and weight loss can occur. Other features such as uveitis, renal involvement and rarely aortic insufficiency have been described. Labs: +/- Mildly elevated WBC, ESR, CRP. Negative RF and ANA. HLA B27 may be positive. Hip X-rays may show evidence of sacoillitis but MRI is more effective at demonstrating this finding. Chron disease – arthritis is an extra-intestinal manifestation of Chron disease. When present? polyarthritic and can involve the spine Active GI disease will cause flare of joint manifestations However, spine involvement may flare independent of GI status Diskitis Infection of the intravertebral disc (ie T2-T4), is the most common in young children (toddlers) and peripheral joints are NOT involved. Best imaging modality to evaluate for this is a technetium bone scan Psoriatic arthritis Asymetric oligoarthritis) w/ the addition of nail pitting & rash expected. Spondylolisthesis Forward displacement of one vertebra over another; “step-off’ at the affected area may be palpable

67. Take home points Don’t stress. When asked about joint pain focus on Duration of complaints, Preceding events, Associated Symptoms, Characteristic of complaints, Joint distribution (there is a limitted number of possibilities and all have distinguishing features) Infectious, post infectious and injuries will be much more common than rheumatologic causes.

68. Take home points Remember ANA- only used as aid in diagnosis of SLE (positive in many normal individuals and other diseases) and to assess risk of uveitis in JRA patients. Rheumatoid Factor- only used as prognostic in JRA patients. Can be falsely positive in endocarditis and other infections. Review diagnostic criteria for SLE, JDMS, ARF and KD

69. Thank you and good luck.