Disclosures. Introduction: Why are we here? Objectives. Erythematosus (SLE): Systemic Lupus. Demystifying. for Early Recognition

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1 Demystifying Systemic Lupus Erythematosus (SLE): Labs, Signs, and Symptoms for Early Recognition Heather Hansen, MD in collaboration with the American College of Rheumatology and St. Charles Health System Office of Continuing Medical Education April 7, 2017 Bend, Oregon Introduction: Why are we here? J Rheumatol Disclosures Heather Hansen, MD, rheumatologist at St. Charles Rheumatology Clinic No relevant financial relationships to disclose. This activity was reviewed by S. Sam Lim, MD, MPH, Associate Professor of Medicine, Emory University, Atlanta, GA. No relevant financial relationships to disclose. REMINDER To claim CME credit for this activity, you must go to Center/Educational Activities. Search for Central Oregon Virtual Lupus Education Series. You will need to complete the pre assessment, post assessment, and evaluation in order to claim and receive credit. If you have questions about claiming credit, please contact Anna Hutchins at the ACR, ahutchins@rheumatology.org. PHARMACISTS: This program has been reviewed by the Oregon Board of Pharmacy and is acceptable for up to 1 Therapeutic CE Credit Hour. For assistance, please contact Karen Kruger, M.Ed., CME Event Coordinator, Office: X2603, kmkruger@stcharleshealthcare.org Objectives

2 Objectives Why is diagnosis so hard? Systemic Lupus Erythematosus (SLE) An inflammatory, multisystem, autoimmune disease of unknown etiology with protean clinical and laboratory manifestations and a variable course and prognosis Lupus can be a mild disease, a severe and life threatening illness, or anything in between The diversity of clinical symptoms in SLE is great, and all organ systems are vulnerable Disease is characterized by periods of flare and remission (or low level activity) and can culminate in irreversible end organ damage Examples of Organs Involved, Signs, and Symptoms Eyes Central nervous system Skin Pleurisy Oral & nasal ulcers Kidney disease Pericarditis Muscle Blood disorders Raynaud s & vasculitis Joints & arthritis

3 Epidemiology Prevalence: Incidence: Health Disparities and At Risk Populations: Cost: Arthritis Rheum. Arthritis Rheum Rheum Dis Clin North Am. What Do Most Lupus Patients Have in Common? Antinuclear Antibodies (ANA) SLE Prevalence Central Oregon Arthritis & Rheumatology (Hoboken, N.J.) 66 Antinuclear Antibodies (ANA) 1948 LE cell test (phagocyte with ingested nucleus) Hargraves MM. Discovery of the LE cell and its morphology. Mayo Clin Proc. 1969;44: Today s techniques *

Incidence of Positive ANA Interpret the ANA in context

ANA+ does not = SLE When to suspect SLE 1.Serositis 2.

4/11= 95% Specificity; 85% Sensitivity Arthritis Rheum.

4 Incidence of Positive ANA Interpret the ANA in context of clinical complaints. ANA+ does not = SLE When to suspect SLE 1.Serositis 2.Oral ulcers 3.Arthritis 4.Photosensitivity 5.Blood cells 6.Renal involvement 7.Antinuclear antibodies (ANA) 8.Immunologic disorder 9.Neurologic disorder 10.Malar rash 11.Discoid rash ACR (Revised) Criteria for Classification 4/11= 95% Specificity; 85% Sensitivity Arthritis Rheum. Arthritis Rheum. 32 Million Persons in US (13.8% > 12 yo) with + ANA Signs and Symptoms Arthritis & Rheumatism, July 2012 Arthritis & Rheumatism, July 2012

ANA Testing Algorithm for ANA testing in suspected SLE: Very low pre test probability: do not test Reasonable pre test probability: screen with ANA.

Anti cardiolipin Ab and Lupus anticoagulant Also check C3 and C4 Additional Testing if + ANA: CBC/CMP/U/A Autoantibodies in SLE Antibodies Lupus Specificity Clinical Associations ANA Low Nonspecific

5 ANA Testing Algorithm for ANA testing in suspected SLE: Very low pre test probability: do not test Reasonable pre test probability: screen with ANA. If negative ANA, highly unlikely to be SLE If positive ANA then check lupus specific autoantibodies: Anti dsdna and Anti Sm (included in criteria) Anti SSA(Ro), SSB(La), and RNP (not in criteria) Anti cardiolipin Ab and Lupus anticoagulant Also check C3 and C4 Additional Testing if + ANA: CBC/CMP/U/A Autoantibodies in SLE Antibodies Lupus Specificity Clinical Associations ANA Low Nonspecific Anti-dsDNA High Nephritis Anti-Sm High Nonspecific Anti-RNP Low Arthritis, myositis, lung disease Anti-SSA Low Dry eyes/mouth, subacute cutaneous lupus erythematosus (SCLE), neonatal lupus, photosensitivity Anti-SSB Low Same as above Antiphospholipid Intermediate Clotting diathesis ACR Choosing Wisely: Don t Test ANA Subsets Unless ANA Positive Sensitivity & Specificity of Some SLE Criteria ANA has high sensitivity, but relatively low specificity. Used to rule out SLE. Other tests have higher specificity. Used to rule in SLE, if reasonable probability.

ANA Patterns ANA Patterns Peripheral or rim Diffuse Many

proteins/peptides, etc) Different patterns observed Different

Oregon ANA Testing Options Centromere St.

52.37 Interpath: ANA with titer: $44.33, Autoimmune panel: $513.

6 ANA Patterns ANA Patterns Peripheral or rim Diffuse Many different substances/antigens in a cell nucleus (eg DNA, RNA, proteins/peptides, etc) Different patterns observed Different clinical associations Speckled Nucleolar ANA Patterns Central Oregon ANA Testing Options Centromere St. Charles: ANA with titer if positive: $63.13 ANA reflex panel : $ BMC/Peace Health: ANA with titer and ANA reflex panel both $ Interpath: ANA with titer: $44.33, Autoimmune panel: $ (ana with titer, dsdna, rnp, crp, c3,c4, histone, ssa/ssb, smith AB, RF, Jo 1, centromere) (smith, rnp, cetnromer, ssa/sssb, c3/c4, ribosomal p, Jo)

7 Why is early referral important? Mortality is higher in lupus patients compared to the general population 5 year survival rate in 1953 was 50%, increased to 90% with better detection and treatment Currently 80 to 90% of lupus patients survive 10 years after diagnosis, but that drops to 60% with advanced stages of organ threatening disease Leading causes of mortality are preventable Appropriate therapeutic management, compliance with treatment and improved treatment of long term consequences can prevent excess and premature deaths. This starts with clinical suspicion of the diagnosis and early recognition. American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus. Guidelines for referral and management of systemic lupus erythematosus in adults. Arth Rheum 1999;42: Definition of Health Disparities Health disparities are the differences in the incidence, prevalence, mortality, and burden of disease and other adverse health conditions that exist among specific population groups in the United States Healthcare disparities refer to differences in access to or availability of facilities and services National Institutes of Health Mortality Cardiovascular disease is the major cause of mortality in patients with longstanding lupus Factors contributing to increased mortality* Active lupus & infection (early stages of disease) High disease severity at diagnosis Younger age at diagnosis Ethnicity: Black, Hispanic, Asian, and Native American populations Male gender Low socioeconomic status Poor patient adherence* Inadequate patient support system* Limited patient education* Bernatsky S, Boivin JF, Joseph L, et al. Arthritis Rheum. 2006;54: Disparities in Lupus Prevalence Arthritis Rheum. Arthritis Rheum Rheum Dis Clin North Am.

Causes of Autoimmune Disease = Multifactorial Genes Risk Behavior Environm ent The Lupus Initiative

8 Other Health Disparities in Lupus J Natl Med Assoc. Arthritis Rheum Arthritis Rheum Arthritis Rheum. Lupus MMWR Morb Mortal Wkly Rep. Causes of Autoimmune Disease = Multifactorial Genes Risk Behavior Environm ent The Lupus Initiative Smoking Sun exposure Stress Toxins Antigen Hormones (estrogen) Infections Toxins Medications Sun exposure Vitamin D deficiency Reducing Health Disparities in Lupus Pathogenesis of Lupus

9 SLE Initiation Amplification Perpetuation Autoantibodies ICs Genetic alterations Abnormally functioning B-cells T-cells pdc Proinflammatory molecules Environmental Exposures & Behavior Antigen Hormones (estrogen) Infections Toxins Medications Sun exposure Vitamin D deficiency Smoking Stress Toxins TISSUE INJURY Lupus on the Outside Synovitis Malar rash Painless oral ulcer Raynaud s Phenomenon Discoid rash Jaccoud s arthropathy Vasculitis Alopecia C Lupus Intangibles Achiness, Headache Fatigue Memory thief brain fog Depression Lupus on the Inside Serositis Pericardial effusion Cerebral infarct Brain atrophy Spherocytes Glomerulonephritis

10 Disease Activity and Severity Monitors of Lupus Activity Target Organ Monitoring is MORE Important Which lupus is it? Drug Induced Lupus Definite Probable Possible Schur PH, et al. Drug-induced lupus. UpToDate. Accessed 05 May 2014.

11 SCLE PICTURE Systemic lupus erythematosus: Malar Rash American College of Rheumatology Slide Collection of Rheumatic Diseases, 3rd Edition, Neonatal Lupus

12 Jaccoud Arthropathy Current Therapy for SLE (FDA approved dates in parenthesis) Corticosteroids (1955) Cyclophosphamide Methotrexate Mycophenolate mofetil Azathioprine Hydroxychloroquine (1955) Belimumab (2011) Aspirin (1948)

Current Therapy Limitations Immunosuppressive drugs confer an increased risk for Infection Cancer Mood Disturbances Hypertension Lipid Abnormalities Infertility Common side effects of corticosteroids

13 Current Therapy Limitations Immunosuppressive drugs confer an increased risk for Infection Cancer Mood Disturbances Hypertension Lipid Abnormalities Infertility Common side effects of corticosteroids Infections Cushingoid appearance Osteoporosis Osteonecrosis Diabetes Quiz 1 1. Which of the following is not considered part of the current criteria for classification of systemic lupus erythematosus: a. discoid rash. b. rosacea. c. serositis. d. oral ulcers. New Therapeutic Strategies Targeted Immunotherapy Immune targeted therapy B cell directed Cytokine inhibitors Costimulation blockade Peptide inhibitors Kinase inhibitors T regulatory cells Stem cell transplant * *2014 FDA approved for lupus J Allergy Clin Immunol. Quiz 2 2. Which of the following ANA results is most likely clinically signficant? a. 1:160, speckled in a 85 y.o male with no other symptoms b. 1:1280, homogenous in a 20 y.o female with joint pain and 2+ proteinuria. c. 1:80, speckled in a 32 y.o. female with arthralgia/myalgia, sleep difficulty and fatigue. d. 1:40, homogenous in a 35 y.o female with low back pain.

14 Case Presentation 1 History: Case Presentation 2 Exam: Case Presentation 1 (cont.) Exam: Labs: Case 2 (cont'd) Exam:

15 Case 2 (cont'd) Clinical Diagnosis of SLE Nephritis Labs: Increase in proteinuria is most common Microscopic abnormalities on urinalysis Arthritis Care Res (Hoboken). Lupus Detection In Summary Lessons for Practice Early symptoms can be Consider lupus if your patient presents with Do an initial screening systems are vulnerable. If autoimmune rheumatic disease is likely, the ANA can be helpful for diagnosis and classification. If autoimmune rheumatic disease is unlikely, do not order an ANA. A positive ANA may cause anxiety, unnecessary investigations, and potential confusion for both patients and providers. A positive

16 When to refer Uncertain diagnosis Confusing Lab Results Uncomfortable with treatment Patient not responding Side effects Thank you! This project is part of the American College of Rheumatology s ( The Lupus Initiative ( in partnership with St. Charles Health System. Today s presentation was led by Heather Hansen, MD, hlhansen@stcharleshealthcare.org If you have a diagnosed lupus patient in need of case management assistance, please contact Shonta Chambers with the Patient Advocate Foundation (PAF) at (757) or online at PAF is providing free case management assistance for up to ten lupus patients as part of this educational series. This project is supported by Grant Number CPIMP from the U.S. Department of Health and Human Services Office of Minority Health. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the HHS, OMH. Final Thoughts Patient engagement and trust building is critical What you can do to reduce health disparities

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