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RheumatologyACP Puerto Rico Chapter Meeting March 8-10, 2019Elena Myasoedova, MD, PhDAssistant Professor of MedicineMayo Clinic Rochester, [email protected]

mailto:[email protected]


Disclosures

• None


Learning objectives1) Diagnosis and approach to management of:• Autoimmune inflammatory arthritis and crystalline arthritis

• Connective tissue disease• Vasculitis2) Rheumatologic emergencies –overview


Inflammatory Arthritis vs DJDInflammatory

• Sudden onset• Bilateral symmetric

symptoms• Constitutional symptoms• Elevated inflammatory

markers• Morning stiffness > 30

minutes • MCP/ MTP squeeze

tenderness

Degenerative

• 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)

Presenter

Presentation Notes

Inflammatory arthritis: features of systemic involvement including symmetric pattern, constitutional symptoms, elevated inflammatory markers Degenerative arthritis: more localized, often asymmetric, pain mechanical in nature, no symptoms of a systemic process.


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 factorHochberg et al. Arthritis Care & Research 2012, 64: 465–74

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwjZ_sTfu-HgAhWM3oMKHQwyCpAQjRx6BAgBEAU&url=https://www.pinterest.com/pin/528117493773742384/&psig=AOvVaw2iJyB3MIV1JGSQ4YcUZLAl&ust=1551547700737614

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwjZ_sTfu-HgAhWM3oMKHQwyCpAQjRx6BAgBEAU&url=https://www.pinterest.com/pin/528117493773742384/&psig=AOvVaw2iJyB3MIV1JGSQ4YcUZLAl&ust=1551547700737614

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwjyr7nUvOHgAhUM94MKHYAzA9IQjRx6BAgBEAU&url=https://www.doctorramey.com/osteoarthritis/&psig=AOvVaw1x0CISdftoNuWMCuUL-l1E&ust=1551547916811289

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwjyr7nUvOHgAhUM94MKHYAzA9IQjRx6BAgBEAU&url=https://www.doctorramey.com/osteoarthritis/&psig=AOvVaw1x0CISdftoNuWMCuUL-l1E&ust=1551547916811289


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, 3rd and 5th MCPs bilaterally, 2-4th PIPs bilaterally, right wrist, left knee and 2-5th MTPs.


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


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

Presenter

Presentation Notes

Parvovirus B19 infection should be suspected in patients with acute onset of small joint symmetric polyarthritis after febrile illness with rash, who have exposure to children. Circulating anti-parvovirus IgM antibodies are consistent with active disease; positive IgG antibodies indicate prior infection and are found in many healthy persons.


Rheumatoid arthritisRisk 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: 538-41Viatte S et al. Arthritis Rheumatol 2016van Beers-Tas MH et al. Best Pract Clin Rheumatol 2015

Presenter

Presentation Notes

Prevalence: 0.6-1% of US population Female predominance Peak incidence: ~50 years 2-fold increased mortality as compared to the general population Life expectancy is decreased by 10 years


Aletaha D et al. Arthritis Rheum 2010; 62: 2569–81


Rheumatoid MimicsEarly Synovitis Patients• Viral Arthritis

• Rubella• Parvovirus B19

• Reactive Arthritis Syndromes• Seronegative Arthritis Syndromes/PMR in the

Elderly• Lupus• Atypical crystalline arthritis – CPPD, gout


RA laboratory panelAnti-CCP RF

SensitivitySpecificity

70%95%

72%80%

Utility - 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

- Higher likelihood of detection and higher titers in established disease - High titers correlate with more severe disease

Impact of other factors

Smoking Smoking, age

Presenter

Presentation Notes

Tobacco increases production of anti CCP in the lung RF = IgM antibody against Fc portion of IgG


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 5th MTP


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


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


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 down-regulator of RA inflammation

Presenter

Presentation Notes

Blocking dehydrofolate reductase


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


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;68:1-25


RA treatment strategies

• Glucocorticoids: - bridge-therapy, - management of

flares,- low-moderate doses,

limited duration.

Singh JA. Arthritis Care Res (Hoboken). 2016;68:1-25


Case 2A 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 acidPhysical 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.


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


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


Management:• Immobilization of cervical

spine• MRI/ CT with myelography• High-dose IV steroids• Neurosurgery consult

C1-C2 subluxation; cervical myelopathy

Presenter

Presentation Notes

The magnified view (B) shows a 12 mm separation between the posterior border of the arch of C1 (arrowhead) and the anterior border of the odontoid process of C2 (arrow).

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwjztcTkjOLgAhWEnoMKHWJsATwQjRx6BAgBEAU&url=https://www.orthobullets.com/spine/2049/atlantoaxial-instability&psig=AOvVaw3wNoWJss7MvPnYRF3_jngq&ust=1551569453970965

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwjztcTkjOLgAhWEnoMKHWJsATwQjRx6BAgBEAU&url=https://www.orthobullets.com/spine/2049/atlantoaxial-instability&psig=AOvVaw3wNoWJss7MvPnYRF3_jngq&ust=1551569453970965


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, 7th Edition by M. Hochberg. 2019. P. 768-76


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


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


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


Inflammatory back painHallmark 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;68:784


Traditional Classification of the Spondyloarthropathies

• Ankylosing spondylitis

• Psoriatic arthritis

• Reactive arthritis

• Arthritis associated with IBD

Presenter

Presentation Notes

DISH – non-inflammatory condition with ossification of spinal ligaments: confluent ossification of at least 4 contiguous vertebral levels, usually on the right side of the spine


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 2004. 50(suppl):S617

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiuyI_VncHgAhXJ4IMKHQSzALAQjRx6BAgBEAU&url=http://enthesis.info/spondyloarthritis/dactylitis_and_enthesitis.html&psig=AOvVaw3TA7dTyvFfl7ntkjSVLaQv&ust=1550440109909411

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiuyI_VncHgAhXJ4IMKHQSzALAQjRx6BAgBEAU&url=http://enthesis.info/spondyloarthritis/dactylitis_and_enthesitis.html&psig=AOvVaw3TA7dTyvFfl7ntkjSVLaQv&ust=1550440109909411


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: 1646-53


Association with HLA-B27

50Acute anterior uveitis70Undifferentiated SpA50Psoriatic spondylitis

35-75Enteropathic arthritis 90Reactive arthritis 90Ankylosing spondylitis

“+”HLA-B27 (%)Disorder

- A strong genetic association, controversial mechanisms- Helpful, but the clinical picture is most useful

Presenter

Presentation Notes

Immunogenetics: HLA-B27 HLA-B27 is the gene associated with ankylosing spondylitis and spondyloarthritis (> 90% positivity in AS cases) 23 subtypes of HLA-B27 identified (B*2701 to B*2703) 20% risk of AS in HLA-B27+ relatives 1–3% of HLA-B27 positive Caucasians develop AS Different clinical disorders within the SpAs differ in how tightly associated they are with HLA-B27. Khan MA. Update on spondyloarthropathies. Ann Intern Med. 2002;136:896-907. HLA-B27 and Disease Expression HLA-B27+ individuals more likely to have earlier onset, sacroiliitis, spondylitis, acute anterior uveitis, and more severe clinical course HLA-B27- patients more likely to develop peripheral arthritis, skin and nail disease, or inflammatory bowel disease Thus, HLA-B27+ increases risk of spondylitis and uveitis The human leukocyte class I MHC antigen, HLA-B27, was reported in 1973 to be highly prevalent in AS. HLA-B27 is a normal gene that is found in nearly 8% of normal North American Caucasians. Although it is present in over 90% of patients with AS, the actual risk of developing AS by any HLA-B27+ person is only 1%-2%. As only 20% of HLA-B27+ first degree relatives of HLA-B27+ spondylitis patients will develop AS, there must be factors other than HLA-B27 that determine disease susceptibility. The prevalence of HLA-B27 varies greatly between different ethnic groups. A higher prevalence is seen in the Haida and Pima indians and the lowest prevalence seen among Africans and some Asians. In addition, HLA-B27 may also influence disease expression for most of the spondyloarthropathies. HLA-B27+ individuals are more likely to manifest an earlier disease onset, sacroiliitis, spondylitis, a severe clinical course, or acute anterior uveitis. By contrast, HLA-B27- patients are more likely to develop peripheral arthropathy, skin and nail disease, or inflammatory bowel disease. Diagnostic Testing for HLA-B27 is not necessary to diagnose most patients with SpA (eg, AS, reactive arthritis). It may be useful in diagnosing patients with an incomplete or undifferentiated SpA. Cush JJ, Lipsky PE. The spondyloarthropathies. In: Bennett JC, et al, eds. Cecil Textbook of Internal Medicine. WB Saunders, 1996: 1466-1472.


MRI

Early SIinflammation


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;68:282-98.


Gout

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiolcqzpsHgAhWPn4MKHbK2D1sQjRx6BAgBEAU&url=http://www.eatonhand.com/img/img00137.htm&psig=AOvVaw3JiLY7jZzkHFl6_0wyObH9&ust=1550442452762487

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiolcqzpsHgAhWPn4MKHbK2D1sQjRx6BAgBEAU&url=http://www.eatonhand.com/img/img00137.htm&psig=AOvVaw3JiLY7jZzkHFl6_0wyObH9&ust=1550442452762487


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

Presenter

Presentation Notes

Hyperuricemia is a necessary but not sufficient precondition for the development of urate crystal deposition disease and should be distinguished from gout, the clinical syndrome. Most hyperuricemic individuals never experience a clinical event resulting from urate crystal deposition


Diagnosis

• Physical exam• Synovial fluid: negatively

birefringent needle-shaped crystals using compensated polarizing light microscopy

Mnemonic: “yellow-parallel-allopurinol” • X-ray: “punched out” lytic

lesions• Dual energy CT

Khanna D. et al. Arth Care & Res 2012, 64: 1431–46

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwj637TnpcHgAhUj9YMKHWd7ADEQjRx6BAgBEAU&url=https://www.diffen.com/difference/Gout_vs_Pseudogout&psig=AOvVaw1hm7XrwBCKdkgaol6dXGuh&ust=1550442294743516

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwj637TnpcHgAhUj9YMKHWd7ADEQjRx6BAgBEAU&url=https://www.diffen.com/difference/Gout_vs_Pseudogout&psig=AOvVaw1hm7XrwBCKdkgaol6dXGuh&ust=1550442294743516

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwih6s2yksvgAhWO3lQKHU3lA6gQjRx6BAgBEAU&url=http://radsource.us/gout/&psig=AOvVaw16NndQh284oJ7VDcKCSnnq&ust=1550780604659672

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwih6s2yksvgAhWO3lQKHU3lA6gQjRx6BAgBEAU&url=http://radsource.us/gout/&psig=AOvVaw16NndQh284oJ7VDcKCSnnq&ust=1550780604659672


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


Management of acute goutTreatment Adult Regimen

NSAIDs Naproxen 3 to 5 daysIndomethacin 3 to 5 days

Colchicine1.2 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)

Cortico-steroids

A) Oral prednisone 30 mg/day for 3 to 5 daysB) IV methylprednisolone 25 mg/day for 3-5 daysC) 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; 44:31–8


Management of chronic goutMedication Action Adult Regimen Relative Contraindications

Allopurinol* Reduced uric acid production

Starting dose 100 mg/day with up-titration to achieve a goal uric acid of < 6 mg/dL (< 5 mg/dL if tophaceous gout).

• interactions with azathioprine, mercaptopurine, didanosine•Renal insufficiency

Febuxostat Reduced uric acid production

40 mg PO daily, can be increased to 80 mg PO daily goal uric acid:< 6 mg/dL (< 5 mg/dL if tophaceous gout).

•CV thromboembolic events•Hepatic dysfunction• interactions with azathioprine, mercaptopurine, didanosine

Probenecid (in underexcretorsof uric acid)

Increased uric acid excretion

250 mg PO BID for 1 week; if tolerated, increase to 500 mg PO BID.

•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;64:1447-61


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

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwjM_uO4oOTgAhVJ0oMKHdBKArUQjRx6BAgBEAU&url=https://www.flickr.com/photos/jeckel/2741821280&psig=AOvVaw2ypDMX3NLM0m5GbztXa6Ai&ust=1551643383222953

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwjM_uO4oOTgAhVJ0oMKHdBKArUQjRx6BAgBEAU&url=https://www.flickr.com/photos/jeckel/2741821280&psig=AOvVaw2ypDMX3NLM0m5GbztXa6Ai&ust=1551643383222953


Acute monoarthritis• Aspirate• Synovial fluid WBC counts:<200/ µL – normal200-2000 / 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


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

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwjD77PwvOTgAhUp5YMKHWCiCX8QjRx6BAgBEAU&url=https://www.wjgnet.com/2218-6190/full/v4/i2/80.htm&psig=AOvVaw06lbvEsNnnkPJjyZVDIPfk&ust=1551651064897948

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwjD77PwvOTgAhUp5YMKHWCiCX8QjRx6BAgBEAU&url=https://www.wjgnet.com/2218-6190/full/v4/i2/80.htm&psig=AOvVaw06lbvEsNnnkPJjyZVDIPfk&ust=1551651064897948


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


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


Systemic Lupus Erythematosus• Rare disease with genetic predisposition• Strong female predominance

Flare

immune complex-mediated glomerulonephritis

Presenter

Presentation Notes

Systemic Lupus Erythematosus: IGG Deposition, Glomerulus, Description: the basement membrane of the glomerulus is partly outlined by irregular "lumpy and bumpy" deposits of antigen-antibody complexes. These fluoresce apple green because they bind fluorescein-conjugated rabbit anti-serum against human IgG. (cryostat section, stained with fluorescent human anti-IGG, high power) immune complex-mediated glomerulonephritis Lupus antibodies are nephritogenic Glomerular deposits that stain dominantly for IgG and contain co-deposits of immunoglobulin A (IgA), immunoglobulin M (IgM), C3, and C1q, the so-called "full house" immunofluorescence pattern

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwi_ivXeocvgAhUH3Z8KHZt6B7EQjRx6BAgBEAU&url=https://twitter.com/medicalce/status/783108595198136322&psig=AOvVaw1CDF7EZ1uuulfurU_NICIe&ust=1550784710099119

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwi_ivXeocvgAhUH3Z8KHZt6B7EQjRx6BAgBEAU&url=https://twitter.com/medicalce/status/783108595198136322&psig=AOvVaw1CDF7EZ1uuulfurU_NICIe&ust=1550784710099119


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: 797–808


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

Presenter

Presentation Notes

Annular lesions with central clearing – similar to subacute cutaneous lupus


Systemic sclerosis, classification

Limited cutaneous scl• Raynaud phenomenon for

years• Skin thickening: hands, face,

feet, and forearms (acraldistribution)

• 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;1:15002


Cutaneous manifestations of limited scleroderma

- Abnormal nail-fold capillaroscopy- Raynaud’s phenomenon- Telangiectasia- Digital pitting and ulcerations- Calcinosis

A B

E

C

D


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:

Presenter

Presentation Notes

Microangiopathic hemolytic anemia – you see helmet cells, a broken RBC


What is the next most appropriate action?• A) Hematology consult• B) Prednisone 30 mg daily• C) ACE inhibitor• D) Neurology consult


What is the next most appropriate action?• A) Hematology consult• B) Prednisone 30 mg daily• C) ACE inhibitor• D) Neurology consult


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

• DialysisPenn H, et al. CP SOQJM. 2007;100:485


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 2nd and 4th 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


Which of the following is the most likely diagnosis?

• A) Anti-synthetase syndrome• B) Sjogren syndrome• C) SLE• D) Systemic sclerosis


Which of the following is the most likely diagnosis?

• A) Anti-synthetase syndrome• B) Sjogren syndrome• C) SLE• D) Systemic sclerosis


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; 13:175

https://en.wikipedia.org/wiki/Aminoacyl_tRNA_synthetase


DermatomyositisShawl sign Heliotrope rash

T2 weighted image of thighs.Inflammation can be seen

Perivascular infiltrate around fascicle

Gottron’s papules

Heliotrope flower

Treatment: glucocorticoids, Azathioprine, Methotrexate, Hydroxychloroquine, IVIG;Rituximab, Cyclophosphamide, CellCept Amato AA, Barohn RJ SOJ Neurol

Neurosurg Psychiatry. 2009;80:1060

Presenter

Presentation Notes

In polymyositis inflammatory infiltrate – within fascicle


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


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


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


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


Vasculitis by vessel size

2012 Revised Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 2013. 65: 1-11


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

• Treatment: Glucocorticoids

• Vision changes –emergency: IV methylprednisone1000 mg x 3 days

• No vision changes –Prednisone 1 mg/kg/day PO with slow taper (60 mg/day)

• Methotrexate• Tocilizumab

Hayreh SS, Zimmerman B Ophthalmology. 2003;110:1204


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


Small Vessel VasculitisA 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 1st !• Multisystem disorders: Cryoglobulinemia, SLE, RA, HIV, IBD,

Paraneoplastic syndromes

Jennette JC et al. Arthritis Rheum. 2013;65:1

Presenter

Presentation Notes

Drugs associated with vasculitis: minocycline, anti-thyroid drugs (benzylthiouracil, methimazole, prophythiouracil), clonzapine, allopurinol, hydralazine, levamisole, phenytoin, sulfasalazine


Evaluation of Small Vessel VasculitisHistology Confirmation

• Skin; Nerve; Kidney; Lung Laboratory Testing

• Creatinine and UA• ANCA panel• ANA panel• RF/ CCP• Monoclonal protein study• C3, C4• Hepatitis B and C

serology• Chest imagingIndirect immunofluorescence assay

Presenter

Presentation Notes

Two types of antineutrophil cytoplasmic autoantibody (ANCA) assays are in wide use: ●Indirect immunofluorescence assay, using alcohol-fixed buffy coat leukocytes ●Enzyme-linked immunosorbent assay (ELISA), using purified specific antigens Of these two techniques, the immunofluorescence assay is more sensitive, and the ELISA is more specific. The optimal approach to clinical testing for ANCA is therefore to perform both immunofluorescence, if available, and ELISA to detect antibodies against the vasculitis-specific target antigens [6,7]. However, ANCA testing is not standardized, and therefore, the sensitivity and specificity will vary among laboratories; there are also no standardized reference values for normal. Ultimately, standardized testing with a highly sensitive and specific ELISA may replace the strategy of immunofluorescence followed by ELISA. (See 'Pitfalls of interpreting immunofluorescence results' below.) In vasculitis, the two relevant target antigens are proteinase 3 (PR3) and myeloperoxidase (MPO). Both PR3 and MPO are located in the azurophilic granules of neutrophils and the peroxidase-positive lysosomes of monocytes. Antibodies with target specificities for PR3 and MPO are called "PR3-ANCA" and "MPO-ANCA," respectively. Immunofluorescence patterns in vasculitis — When the sera of patients with ANCA-associated vasculitis are incubated with ethanol-fixed human neutrophils, two major immunofluorescence patterns are observed (picture 1A-B): ●With the cytoplasmic ANCA (C-ANCA) pattern, the staining is diffuse throughout the cytoplasm. In most cases, antibodies directed against PR3 cause this pattern [8,9], but MPO-ANCA can occasionally be responsible. ●The perinuclear ANCA (P-ANCA) pattern results from a staining pattern around the nucleus, which represents an artifact of ethanol fixation. With ethanol fixation of the neutrophil substrate, positively charged granule constituents rearrange themselves around the negatively charged nuclear membrane, leading to perinuclear fluorescence [3]. Among patients with vasculitis, the antibody responsible for this pattern is usually directed against MPO (and, only occasionally, PR3).

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiss9ecj-LgAhVh0YMKHandClwQjRx6BAgBEAU&url=https://www.mdedge.com/ccjm/article/95794/controversies-anca-testing&psig=AOvVaw2gYqaNuCXyyiJ-lzUBGGrx&ust=1551570024272489

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiss9ecj-LgAhVh0YMKHandClwQjRx6BAgBEAU&url=https://www.mdedge.com/ccjm/article/95794/controversies-anca-testing&psig=AOvVaw2gYqaNuCXyyiJ-lzUBGGrx&ust=1551570024272489


GPA

Initial immunosuppressive treatment• Glucocorticoids; Methotrexate• Cyclophosphamide OR Rituximab

Seo P, Stone JH. Am J Med. 2004;117:39


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

Presenter

Presentation Notes

Rheumatological conditions can sometimes present as emergencies. These can occur due to the disease process or may be iatrogenic. Some of the important articular emergencies are septic arthritis, acute polyarthritis and atlanto-axial dislocation. Classical polyarteritis nodosa may present with massive gastro-intestinal bleeding, intestinal perforation or acute pancreatitis. Adult respiratory distress syndrome, bilateral pneumonitis and diffuse alveolar haemorrhage due to systemic lupus erythematosus or systemic necrotising vasculitis and ventilatory failure due to polymyositis are some of the respiratory emergencies. Scleroderma is well known to cause renal crisis which can be fatal if not diagnosed and managed promptly. Microscopic polyangiitis and Wegener's granulomatosis may cause rapidly progressive renal failure. Cerebrovascular accident, cortical vein thrombosis, seizures and acute psychosis are important neurological complications of rheumatic disease. Cardiac emergencies include tamponade, acute myocarditis and acute myocardial infarction. Vision can be threatened in Behcet's disease, temporal arteritis and seronegative spondylarthritis. Catastrophic antiphospholipid syndrome is a devastating emergency. The management of above emergencies includes critical care, immunosuppression when indicated and withdrawal of the offending drug. Anticoagulants have to be used in the management of antiphospholipid syndrome. A good understanding of these conditions is of paramount importance for proper management.


Helpful resources• https://www.acponline.org/featured-

products/mksap-18• https://www.rheumatology.org/Practice-

Quality/Clinical-Support/Clinical-Practice-Guidelines

• https://www.rheumatology.org/Learning-Center/Medication-Guides

• https://www.uptodate.com/contents/search

https://www.rheumatology.org/Practice-Quality/Clinical-Support/Clinical-Practice-Guidelines

https://www.rheumatology.org/Practice-Quality/Clinical-Support/Clinical-Practice-Guidelines

https://www.rheumatology.org/Learning-Center/Medication-Guides

https://www.uptodate.com/contents/search


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