Rheumatology ACP Puerto Rico Chapter Meeting March 8-10, 2019
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1 Rheumatology ACP Puerto Rico Chapter Meeting March 8-10, 2019 Elena Myasoedova, MD, PhD Assistant Professor of Medicine Mayo Clinic Rochester, Minnesota 2017 MFMER slide-1
2 Disclosures None 2017 MFMER slide-2
3 Learning objectives 1) Diagnosis and approach to management of: Autoimmune inflammatory arthritis and crystalline arthritis Connective tissue disease Vasculitis 2) Rheumatologic emergencies overview 2017 MFMER slide-3
4 Inflammatory Arthritis vs DJD Inflammatory Degenerative Sudden onset Bilateral symmetric symptoms Constitutional symptoms Elevated inflammatory markers Morning stiffness > 30 minutes MCP/ MTP squeeze tenderness Gradual onset of scattered symptoms in joints of fingers, knees, spine No constitutional symptoms Normal inflammatory markers Use related pain with minimal stiffness Heberden nodes (DIP), Bouchard nodes (PIP) 2017 MFMER slide-4
5 Osteoarthritis Management: Tylenol, NSAIDs (topical NSAIDs for patients >75 yo) Intra-articular steroid injections Viscous supplementation Physical therapy Joint replacement Emerging treatments: Tanezumab, a humanized monoclonal antibody that blocks nerve growth factor Hochberg et al. Arthritis Care & Research 2012, 64: MFMER slide-5
6 Case 1 A 36 year old woman presents with a 2-month history of morning stiffness in her hands, wrists, knees, feet for 1.5 hours. Her only medication is ibuprofen which is helpful. Physical exam: normal vital signs. Tenderness and swelling of the 2nd, 3 rd and 5 th MCPs bilaterally, 2-4 th PIPs bilaterally, right wrist, left knee and 2-5 th MTPs MFMER slide-6
7 What is the most appropriate diagnostic test to perform next? A) Anti-cyclic citrullinated peptide antibodies B) HLA-B27 C) Parvovirus IgG antibodies D) Serum urate E) TSH 2017 MFMER slide-7
8 What is the most appropriate diagnostic test to perform next? A) Anti-cyclic citrullinated peptide antibodies B) HLA-B27 C) Parvovirus IgG antibodies D) Serum urate E) TSH 2017 MFMER slide-8
9 Rheumatoid arthritis Risk factors Genetic (60%): HLA-DRB1 and other HLA and non-hla susceptibility genes Environmental (40%): smoking, air pollution Other: periodontitis (Porphyromonas gingivalis), hormonal (?) Hill JA et al. J Immunol 2003; 171: Viatte S et al. Arthritis Rheumatol 2016 van Beers-Tas MH et al. Best Pract Clin Rheumatol MFMER slide-10
10 Aletaha D et al. Arthritis Rheum 2010; 62: MFMER slide-11
11 Rheumatoid Mimics Early Synovitis Patients Viral Arthritis Rubella Parvovirus B19 Reactive Arthritis Syndromes Seronegative Arthritis Syndromes/PMR in the Elderly Lupus Atypical crystalline arthritis CPPD, gout 2017 MFMER slide-12
12 RA laboratory panel Sensitivity Specificity Utility Impact of other factors Anti-CCP 70% 95% - Identifying early inflammatory arthritis patients at risk for erosive disease - Evaluating RF negative inflammatory arthritis patients - Evaluating a positive RF in a person who doesn t seem to have RA - In high titers uniquely specific for potentially erosive rheumatoid arthritis Smoking RF 72% 80% - Higher likelihood of detection and higher titers in established disease - High titers correlate with more severe disease Smoking, age 2017 MFMER slide-13
13 Case 1, continued Patient returns with the following results of additional work-up: CRP 36.0 mg/dl Positive CCP antibody >250 U Positive Rheumatoid factor 120 IU Hand x-rays reveal periarticular osteopenia Magnified view of the left 5 th MTP 2017 MFMER slide-15
14 Which of the following is the most appropriate treatment at this time? A) Continue ibuprofen B) Initiate mycophenolate mofetil C) Initiate methotrexate D) Initiate monotherapy with prednisone 2017 MFMER slide-16
15 Which of the following is the most appropriate treatment at this time? A) Continue ibuprofen B) Initiate mycophenolate mofetil C) Initiate methotrexate D) Initiate monotherapy with prednisone 2017 MFMER slide-17
16 RA management: Methotrexate Methotrexate is the anchor DMARD Prevents radiologic progression (disease-modifying!) Weekly PO or SQ dosing Potential up-titration to max 25 mg/week Folic acid supplementation 1 mg/day Safety monitoring: CBC, Creatinine, AST, ALT Adenosine pathway is the likely primary downregulator of RA inflammation 2017 MFMER slide-18
17 Methotrexate Toxicity One of the mechanisms: folate depletion Minor: Nausea, stomatitis, hair loss, headache, fatigue Serious but rare: Megaloblastic anemia and pancytopenia Increased risk with folate deficiency or azotemia Liver fibrosis Increased risk in NAFL/NASH patients Hypersensitivity pneumonitis Teratogenic effect 2017 MFMER slide-19
18 RA treatments Treatment goal: Remission or low disease activity Synthetic DMARDs: Methotrexate, Sulfasalazine*, Hydroxychloroquine*, Leflunomide Biologic DMARDs: - TNF inhibitors (Infliximab, Adalimumab, Etanercept, Golimumab, Certolizumab*) - IL6-receptor antagonists (Tocilizumab, Sarilumab) - T-cell co-stimulator blocker (Abatacept) - JAK kinase inhibitor (Tofacitinib) - Rituximab - antibody against CD20 on B-lymphocytes * safe in pregnancy and breastfeeding Singh JA. Arthritis Care Res (Hoboken). 2016;68: MFMER slide-20
19 RA treatment strategies Glucocorticoids: - bridge-therapy, - management of flares, - low-moderate doses, limited duration. Singh JA. Arthritis Care Res (Hoboken). 2016;68: MFMER slide-21
20 Case 2 A 53-year-old woman with a 15-year history of RA is evaluated for intermittent sensory loss in her hands and occasional shock-like sensation from the neck down the back with neck flexion. No muscle weakness. Medications: Methotrexate, Etanercept, Folic acid Physical exam: normal vitals signs. No active synovitis. Ulnar deviation of her MCP joints bilaterally. Neck flexion triggers her symptoms. Reflexes, strength and sensation of the upper and lower extremities are normal MFMER slide-22
21 Which of the following is the most appropriate diagnostic test to perform next? A) EMG of the upper extremities B) Flexion/ extension X-rays of the cervical spine C) Serum vitamin B12 level D) TSH 2017 MFMER slide-23
22 Which of the following is the most appropriate diagnostic test to perform next? A) EMG of the upper extremities B) Flexion/ extension X-rays of the cervical spine C) Serum vitamin B12 level D) TSH 2017 MFMER slide-24
23 C1-C2 subluxation; cervical myelopathy Management: Immobilization of cervical spine MRI/ CT with myelography High-dose IV steroids Neurosurgery consult 2017 MFMER slide-25
24 Extra-articular manifestations of RA Rheumatoid nodules Interstitial lung disease (rule out methotrexate toxicity) Pleural effusion (Exudate, low glucose, high LDH) Pericarditis Secondary Sjogren s Rheumatoid vasculitis Felty s syndrome (always sero+) Cervical myelopathy Amyloidosis Rheumatology, 7 th Edition by M. Hochberg P MFMER slide-26
25 Case 3 A 32 year old man is evaluated for 10-year history of low back pain. The pain is worse at rest, improves with movement, and can awaken him during the night. He takes Naproxen BID with some relief. Family Hx: three paternal uncles with back problems Physical exam: normal vital signs. No swollen joints. Tenderness over SI joints bilaterally, reduction in ROM in lumbar spine Labs: CBC and inflammatory markers - normal Plain A/P X-ray of the pelvis: fusion of SI joints 2017 MFMER slide-27
26 Which of the following is the most appropriate diagnostic test to perform next? A) Anti-neutrophil cytoplasmic antibodies B) Anti-CCP antibodies C) Antinuclear antibodies D) HLA-B27 antigen E) No additional testing 2017 MFMER slide-28
27 Which of the following is the most appropriate diagnostic test to perform next? A) Anti-neutrophil cytoplasmic antibodies B) Anti-CCP antibodies C) Antinuclear antibodies D) HLA-B27 antigen E) No additional testing 2017 MFMER slide-29
28 Inflammatory back pain Hallmark of ankylosing spondylitis Age of onset < 40 years Insidious onset Improvement with exercise or activity No improvement with rest Pain at night with improvement upon getting up If four of the five criteria are present Sensitivity 80% Specificity 74% Sieper J. et al. Ann Rheum Dis. 2009;68: MFMER slide-30
29 Traditional Classification of the Spondyloarthropathies Ankylosing spondylitis Psoriatic arthritis Reactive arthritis Arthritis associated with IBD 2017 MFMER slide-31
30 Broadening the perspective of spondyloarthropathy classification Undifferentiated Spondyloarthropathy This is the most common variant that you will encounter in practice Characteristics at disease onset Inflammatory back pain 69% Peripheral arthritis 29% Enthesitis 29% Uveitis 2.5% Dactylitis( sausage digits ) 3.3% Positive FHx 32.1% Rudwaleit M et al. A&R (suppl):S MFMER slide-32
31 AS/SpA: Diagnostic algorithm (ASAS) SpA: spondyloarthritis; AS: ankylosing spondylitis; X-rays: plain radiographs of the pelvis; IBP: inflammatory back pain; IBD: inflammatory bowel disease; * >3 months, onset < 45. van den Berg R et al. Ann Rheum Dis, 2013: 72: MFMER slide-33
32 Association with HLA-B27 - A strong genetic association, controversial mechanisms - Helpful, but the clinical picture is most useful Disorder + HLA-B27 (%) Ankylosing spondylitis Reactive arthritis Enteropathic arthritis Psoriatic spondylitis Undifferentiated SpA Acute anterior uveitis MFMER slide-34
33 MRI Early SI inflammation 2017 MFMER slide-35
34 Management of spondyloarthropaties Treatment goals: relief of symptoms, maintenance of function, prevention of progression of spinal disease Physical activity, smoking cessation Except for IBD patients, NSAID trial first For axial disease (spondylitis, sacroiliitis): If a patient fails two NSAIDs TNF inhibitor or anti- IL-17 monoclonal antibody (Secukinumab) For peripheral synovitis: Sulfasalazine if not sulfa allergic Methotrexate Ward M. et al. Arthritis Rheumatol. 2016;68: MFMER slide-36
35 Gout 2017 MFMER slide-37
36 Gout facts Most common type of inflammatory arthritis world-wide Genetic component Diet and lifestyle Comorbidities and medications Hyperuricemia (> 6.8 mg/dl) Clinical manifestations of gout: Recurrent flares of inflammatory arthritis (gout flare) A chronic arthropathy Tophaceous deposits Uric acid nephrolithiasis Chronic nephropathy 2017 MFMER slide-38
37 Diagnosis Physical exam Synovial fluid: negatively birefringent needle-shaped crystals using compensated polarizing light microscopy Mnemonic: yellow-parallelallopurinol X-ray: punched out lytic lesions Dual energy CT Khanna D. et al. Arth Care & Res 2012, 64: MFMER slide-39
38 Case 4 A 54-old man with acute gout flare after recent exacerbation of CHF and optimizing his diuretics dosing. Comorbidities: CHF, CKD, stage 3. No improvement with intra-articular steroids and 60 mg/day of IV methylprednisone for 3 days. What would you use to treat this acute gout flare? A) Colchicine B) Ibuprofen C) Anakinra D) Allopurinol 2017 MFMER slide-40
39 Management of acute gout Treatment Adult Regimen NSAIDs Colchicine Corticosteroids Naproxen 3 to 5 days Indomethacin 3 to 5 days 1.2 mg PO at the first sign of a flare 0.6 mg 1 hour later (MAX 1.8 mg over 1 hour) Then 0.6 mg PO 1-2 times a day (MAX 1.2 mg/day) A) Oral prednisone 30 mg/day for 3 to 5 days B) IV methylprednisolone 25 mg/day for 3-5 days C) Intra-articular injection: methylprednisolone 20 to 80 mg in a single injection Anakinra IL-1 inhibitor - off label use: SubQ: 100 mg once daily x 3 days Khanna D. et al. Semin Arthritis Rheum. 2014; 44: MFMER slide-41
40 Management of chronic gout Medication Action Adult Regimen Relative Contraindications Allopurinol* Febuxostat Probenecid (in underexcretors of uric acid) Reduced uric acid production Reduced uric acid production Increased uric acid excretion Starting dose 100 mg/day with up-titration to achieve a goal uric acid of < 6 mg/dl (< 5 mg/dl if tophaceous gout). 40 mg PO daily, can be increased to 80 mg PO daily goal uric acid:< 6 mg/dl (< 5 mg/dl if tophaceous gout). 250 mg PO BID for 1 week; if tolerated, increase to 500 mg PO BID. interactions with azathioprine, mercaptopurine, didanosine Renal insufficiency CV thromboembolic events Hepatic dysfunction interactions with azathioprine, mercaptopurine, didanosine Renal impairment: creatinine clearance <50 ml/min * Screen for HLA-B*5801 in Thai, Han Chinese or Korean patients: high risk for allopurinol hypersensitivity (DRESS syndrome) Pegloticase porcine-derived uricase in patients with high tophaceous burden. IV administration Khanna D. et al. Arthritis Care Res (Hoboken). 2012;64: MFMER slide-42
41 Calcium pyrophosphate deposition disease (CPPD) and pseudogout Mono-/ oligo- or polyarthritis Chondrocalcinosis on X-rays Assess for: hyperparathyroidism, hypothyroidism, hypophosphatasia, hypomagnesemia, hemochromatosis Rhombus-shaped calcium pyrophosphate crystal: positively birefrigent on polarized light microscopy Intra-articular steroid injections, NSAIDs, +/- colchicine 2017 MFMER slide-43
42 Acute monoarthritis Aspirate Synovial fluid WBC counts: <200/ µl normal / µl non-inflammatory conditions >2000 / µl inflammatory states >50,000 / µl (>75% neutrophils) septic arthritis, until proven otherwise, regardless of presence of crystals + Gram stain, + culture Management: Joint debridement, antibiotics 2017 MFMER slide-44
43 Case 5 A 21-year-old woman is evaluated for an 8-week history of fatigue, low-grade fever, facial rash, oral sores. Medications: multivitamin. Physical exam: normal vital signs. Tenderness of multiple MCPs and PIPs bilaterally. T 37.3 C (99.1F). No other findings. CBC: normocytic anemia 2017 MFMER slide-48
44 Which of the following is the most likely diagnosis for the rash? A) Acute cutaneous lupus erythematosus B) Erysipelas C) Rosacea D) Seborrheic dermatitis E) Subacute cutaneous lupus erythematosis 2017 MFMER slide-49
45 Which of the following is the most likely diagnosis for the rash? A) Acute cutaneous lupus erythematosus B) Erysipelas C) Rosacea D) Seborrheic dermatitis E) Subacute cutaneous lupus erythematosis 2017 MFMER slide-50
46 Systemic Lupus Erythematosus Rare disease with genetic predisposition Strong female predominance Flare immune complexmediated glomerulonephritis 2017 MFMER slide-51
47 SLE management Mild lupus: hydroxychloroquine, NSAIDs, low dose prednisone Moderate lupus: Azathioprine, mycophenolate mofetyl (CellCept), methotrexate, corticosteroids Belimumab: blocks binding of B lymphocyte stimulator protein (BLyS) to receptors on B lymphocytes. IV or SQ Severe lupus: Cyclophosphamide, CellCept, pulse-steroids Hahn B. et al. Arthritis Care & Res 2012; 64: MFMER slide-53
48 Neonatal lupus In children from mothers with positive SS-A/SS-B Risk of complete heart block Follow with OB/GYN: OB ultrasound Hydroxychloroquine Steroids 2017 MFMER slide-54
49 Systemic sclerosis, classification Limited cutaneous scl Raynaud phenomenon for years Skin thickening: hands, face, feet, and forearms (acral distribution) Nail-fold capillary changes 10-15% late incidence of pulmonary hypertension Renal disease rare Anti-centromere antibody Diffuse cutaneous scl Raynaud phenomenon followed, within 1 year, by skin thickening Truncal and acral skin involvement; tendon friction rubs Nail-fold capillary changes Early and significant incidence of renal, interstitial lung, diffuse gastrointestinal, and myocardial disease Anti-Scl-70 and anti-rna polymerase-i, II, or III antibodies Allanore Y. Nat Rev Dis Primers. 2015;1: MFMER slide-58
50 A Cutaneous manifestations of limited scleroderma B C E D - Abnormal nail-fold capillaroscopy - Raynaud s phenomenon - Telangiectasia - Digital pitting and ulcerations - Calcinosis 2017 MFMER slide-59
51 Case 6 A 42 year old woman developed Raynaud s phenomenon last summer. Gradually, her fingers got tight and her grip weakened. This morning she awoke with a severe generalized headache. Her husband brought her to the ER: BP 232/118 mmhg Her peripheral smear: 2017 MFMER slide-60
52 What is the next most appropriate action? A) Hematology consult B) Prednisone 30 mg daily C) ACE inhibitor D) Neurology consult 2017 MFMER slide-61
53 What is the next most appropriate action? A) Hematology consult B) Prednisone 30 mg daily C) ACE inhibitor D) Neurology consult 2017 MFMER slide-62
54 Scleroderma renal crisis 5-20% of patients with systemic sclerosis AKI, severe hypertension, mild proteinuria, MAHA, thrombocytopenia Histology (kidney): intimal proliferation and thickening, with concentric "onion-skin" hypertrophy Emergent inpatient care Normalize BP within 72 hours with captopril Increase captopril dose Q 6 to 8 hours Add other agents if necessary Dialysis Penn H, et al. CP SOQJM. 2007;100: MFMER slide-63
55 Case 7 A 47-year-old woman presents with low-grade fever for 3 weeks; skin peeling on the sides of the second digits and palms, pain and swelling of 2 nd and 4 th PIP joints. Physical exam: t=37.6c (99.7F), pulse 95/min, respirations 20/min. Blood pressure and O2 sat normal. Erythema of her forehead and chin. Crackles at the lung bases bilaterally. No weakness. Labs: CK 115 U/L (normal); ANA 1:1280; anti-ds-dna negative, Anti-Jo1-antibodies positive, anti-smith antibodies negative 2017 MFMER slide-64
56 Which of the following is the most likely diagnosis? A) Anti-synthetase syndrome B) Sjogren syndrome C) SLE D) Systemic sclerosis 2017 MFMER slide-65
57 Which of the following is the most likely diagnosis? A) Anti-synthetase syndrome B) Sjogren syndrome C) SLE D) Systemic sclerosis 2017 MFMER slide-66
58 Anti-synthetase syndrome Acute onset Interstitial lung disease, risk of pulmonary hypertension Fever, inflammatory arthritis, Raynaud s phenomenon, inflammatory myopathy, mechanic s hands. Anti-synthetase antibodies - target trna synthetase enzymes Fair response to therapy (steroids) Katzap E. et al. Curr Rheumatol Rep 2011; 13: MFMER slide-67
59 Dermatomyositis Shawl sign Heliotrope rash Heliotrope flower T2 weighted image of thighs. Inflammation can be seen Gottron s papules Perivascular infiltrate around fascicle Treatment: glucocorticoids, Azathioprine, Methotrexate, Hydroxychloroquine, IVIG; Rituximab, Cyclophosphamide, CellCept Amato AA, Barohn RJ SOJ Neurol Neurosurg Psychiatry. 2009;80: MFMER slide-68
60 Inclusion body myositis Age >50 years Muscle weakness in proximal and distal muscles of UE and LE with involvement of either finger flexors, wrist flexors, or quadriceps. Dysphagia Muscle biopsy with intracellular amyloid deposits or filamentous inclusions, rimmed vacuoles focal destruction of muscle fibers Resistant to treatment 2017 MFMER slide-69
61 Case 8 A 79-year-old man presents with aching in bilateral shoulders and hips, stiffness for 2 hours in the morning, aching in his jaw when chewing. Reports left-sided headaches. Physical exam: vital signs are normal. Tenderness and slight swelling over the left temple. No vision changes. Painful and limited ROM in hips and shoulders. T 37.3C (99.1F). ESR = 85 mm/hr 2017 MFMER slide-70
62 Which of the following is the most appropriate initial management? A) CT of the head B) Low-dose aspirin C) Methotrexate D) Prednisone E) Temporal artery biopsy 2017 MFMER slide-71
63 Which of the following is the most appropriate initial management? A) CT of the head B) Low-dose aspirin C) Methotrexate D) Prednisone E) Temporal artery biopsy 2017 MFMER slide-72
64 Vasculitis by vessel size 2012 Revised Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum : MFMER slide-73
65 Giant cell arteritis Consider GCA in a patient >50 years of age if: New headaches Monocular vision loss Jaw claudication Fever, anemia PMR-like symptoms High ESR, CRP TA biopsy: panarteritis, CD4+ lymphocytes and macrophages Vascular contrast imaging Hayreh SS, Zimmerman B Ophthalmology. 2003;110:1204 Treatment: Glucocorticoids Vision changes emergency: IV methylprednisone 1000 mg x 3 days No vision changes Prednisone 1 mg/kg/day PO with slow taper (60 mg/day) Methotrexate Tocilizumab 2017 MFMER slide-74
66 Polyarteritis nodosa Associated with Hep B infection Fever, malaise, weight loss Mononeuritis multiplex Skin purpura, necrotic ulcers Renal artery vasculitis with renal infarction, aneurysms (do not obtain kidney biopsy!) Orchitis Mesenteric vasculitis (GI bleed/ perforation) No serological markers Angiography Hep B serology, HIV serology, r/out ANCA Nerve, muscle or deep skin biopsy 2017 MFMER slide-75
67 Small Vessel Vasculitis A Practical Classification Primary small vessel vasculitis Anti-neutrophil cytoplasmic antibody (ANCA) vasculitis: GPA = granulomatosis with polyangiitis (c-anca/ PR3) MPA = microscopic polyangiitis (p-anca/ MPO) EGPA = eosinophilic granulomatosis with polyangiitis IgA-Associated Vasculitis ( Henoch-Schönlein purpura ) Secondary small vessel vasculitis Cutaneous only think of drugs 1 st! Multisystem disorders: Cryoglobulinemia, SLE, RA, HIV, IBD, Paraneoplastic syndromes Jennette JC et al. Arthritis Rheum. 2013;65: MFMER slide-76
68 Evaluation of Small Vessel Vasculitis Histology Confirmation Skin; Nerve; Kidney; Lung Indirect immunofluorescence assay Laboratory Testing Creatinine and UA ANCA panel ANA panel RF/ CCP Monoclonal protein study C3, C4 Hepatitis B and C serology Chest imaging 2017 MFMER slide-77
69 GPA Initial immunosuppressive treatment Glucocorticoids; Methotrexate Cyclophosphamide OR Rituximab Seo P, Stone JH. Am J Med. 2004;117: MFMER slide-78
70 Take home points Arthritis: Inflammatory or degenerative? - Monoarthritis aspirate! - Extra-articular/ systemic features? CTD: assess for organ damage (kidney, lung, heart) Vasculitis: vessel size, work-up (serologies, biopsy, imaging) Recognize rheumatologic emergencies 2017 MFMER slide-79
71 Helpful resources Quality/Clinical-Support/Clinical-Practice- Guidelines Center/Medication-Guides MFMER slide-80
72 Questions & Discussion 2017 MFMER slide-81
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