1. Teaching Fellows in Lupus Project
Demystifying
Teaching Fellows in Lupus Project
Systemic Lupus Erythematosus:
Signs and Symptoms for Early Recognition

2. Introduction: Why are we here?
Lupus can take 4-6 years and 3 providers before diagnosis*
During that time, organ damage can develop leading to 5 fold increased risk of death
Patients go to primary care providers or emergency rooms at onset of illness, so detection of lupus by these providers is critical to early diagnosis
These providers may have received only 90 minutes of training on lupus in medical school*
It is not a disease for just Rheumatologists or Nephrologists.
Lupus is characterized by heterogeneous signs and symptoms, so most providers will encounter a lupus patient
Providers in primary and emergency care are the gateway to treatment for most patients
* Survey data of health professionals
Abu-Shakra M, Urowitz MB, Gladman DD, Gough J. Mortality studies in systemic lupus erythematosus. Results from a single center. II. Predictor variables for mortality. J Rheumatol. 1995;22(7):

3. How you can help: Teaching Fellows Project
Problem: Education about lupus is important for all providers, but there is a shortage of peer educators
Solution: Recruit fellows/junior faculty in Rheumatology to serve as lupus educators for practicing physicians
What you can do: Participate in the voluntary pre and post assessment and follow up so we can evaluate the project
Benefits to you: Increased self efficacy in lupus detection, access to CMEs from the ACR
Our goal: To bring this project to Rheumatology Fellowship Programs nationally to expand quality education on lupus to improve detection, increase appropriate referral, and decrease diagnosis time
Benefits: Participation in pre/post assessments has been shown to improve knowledge retention
Goal: Currently piloting in NYC, Chicago, San Francisco, Atlanta. We need to evaluate the model and show the benefit so other fellowship programs want to adopt the project.

4. Pre/Post Assessment and Follow Up
Voluntary, Used solely to rate the quality of this seminar
De-identified: Linked by numeric identifier
Pre- assessment (before seminar)
10 multiple choice or true/false questions and 1 efficacy question
About 3 minutes to complete
Post- assessment (after seminar)
Repeat pre assessment
Additional qualitative and demographics questions
About 5 minutes to complete
Follow up assessment (4-6 weeks after seminar)
Option for comment
Requires an address
Access to CME modules available from ACR for completion
Answers available after session
**Walk attendees through the packet they will receive**
Pre/post assessment and follow up is VOLUNTARY and will be used solely to evaluate the quality of this seminar. If you do not wish to participate, you can still listen in on the seminar.
The pre/post assessment and follow up is linked by a numeric identifier. In order to participate in the 4-6 week follow up, we will ask that you fill out the card with the best address to reach you to send the online version of the assessment. The same numeric identifier will be on the card so we can match your to your pre/post assessments from today’s seminar.

5. We appreciate your time in taking our pre seminar assessment
Thank you
We appreciate your time in taking our pre seminar assessment

6. Presentation Goals
To improve recognition of lupus and increase appropriate referral for diagnosis by:
Increasing lupus knowledge in:
Epidemiology
Health Disparities
Genetics, Pathogenesis, ANA and other Autoantibodies
Disease characteristics: activity, severity, mortality
Reviewing the classification criteria
Discussing real case presentations of patients with lupus

7. Patient Voices

8. 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
70% = Systemic lupus erythematosus
10% = Cutaneous lupus erythematosus (includes Discoid)
10% = Drug- induced lupus erythematosus
10% = Other overlap syndrome or mixed connective tissue disease (MCTD)

9. Why is diagnosis so hard?
The Great Masquerader: can mimic viral syndromes, malignancies, allergic reactions, stress, etc.
May be associated with depression and/ or fibromyalgia.
Initial symptoms might be non-specific: fatigue, achiness, stiffness, low grade fevers, swollen lymph nodes, rashes.
Symptoms may develop slowly or suddenly.
There is no gold standard diagnostic test for lupus
Wide variety of symptoms and organ involvement may be present.
Hard to diagnose even for Rheumatologists.

10. Examples of Organs Involved, Signs, and Symptoms
Raynaud’s & vasculitis
Eyes
Skin
Pleurisy
Kidney disease
Central nervous system
Oral & nasal ulcers
Pericarditis
Blood disorders
Joints & arthritis
Muscle
Medical Illustration Copyright © Nucleus Medical Media. All rights reserved.

11. 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:

12. 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*
*Indicates opportunity for improvement.
Bernatsky S, Boivin JF, Joseph L, et al. Arthritis Rheum. 2006;54:

13. Epidemiology
Prevalence: 2–140/100,000 worldwide but as high as 207/100,000
Incidence: 1–10/100,000 worldwide
Health Disparities and At-Risk Populations:
Women in their reproductive years
Women are 9 times more likely to develop lupus than men
Non-Caucasians have the highest prevalence:
Affects up to 1/250 Black women in US
2-3 times higher risk than white women
Cost: Direct costs associated with treatment (e.g., $100 billion in healthcare cost associated with autoimmune diseases) and indirect cost related to lost productivity and wages
Prevalence: More prevalent than AIDS, cerebral palsy, multiple sclerosis, sickle-cell anemia and cystic fibrosis combined.
A health disparity is a particular type of health difference that is closely linked with social or economic disadvantage. 
Health disparities adversely affect groups of people who have systematically experienced greater social and/or economic obstacles to health and/or a clean environment based on their racial or ethnic group; religion; socioeconomic status; gender; age; mental health; cognitive, sensory, or physical disability; sexual orientation or gender identity; geographic location; or other characteristics historically linked to discrimination or exclusion.
Helmick CG, Felson DT, Lawrence RC, et al. Arthritis Rheum. 2008;58(1):15-25; Chakravarty EF, Bush TM, Manzi S, Clarke AE, Ward MM. Arthritis Rheum. 2007;56(6): ; Fessel WJ. Rheum Dis Clin North Am. 1988;14(1):15-23.

14. Other Health Disparities in Lupus
Specific racial/ethnic minorities are more likely to develop lupus at a younger age and to have more severe symptoms at onset
Specific racial/ethnic minorities with lupus have mortality rates at least 3 times as high as White individuals
Low income individuals less likely to receive recommended care
Poverty associated with poor outcomes
Healthcare disparities refer to differences in access to or availability of facilities and services.
Poverty is associated with a variety of poor outcomes in lupus
Higher mortality
Greater disease activity
More disease-related damage
Poorer physical function
Worse health-related quality-of-life
Higher rates of depression after disease onset
Duran S, Apte M, Alarcón GS. J Natl Med Assoc. 2007;99(10): ; Ward MM, Pyun E, Studenski S. Arthritis Rheum. 1995;38(2): ; Alarcón GS, McGwin G Jr, Bastian HM, et al. Arthritis Rheum. 2001;45(2):
McCarty DJ, Manzi S, Medsger TA Jr, Ramsey-Goldman R, LaPorte RE, Kwoh CK. Arthritis Rheum.
1995;38(9): ; Cooper GS, Parks CG, Treadwell EL, et al. Lupus. 2002;11(3):
CDC. MMWR Morb Mortal Wkly Rep. 2002;51:

15. Disease Activity and Severity
Predictors of flare (in some but not all cases)
New evidence of complement consumption
Rising anti-dsDNA titers
Increased ESR
New lymphopenia
Severity characterized by:
Abrupt onset of symptoms
Increased renal, neurologic, hematologic, and serosal involvement
Rapid accrual of damage (irreversible organ injury)
Associated with race, younger age, male gender, poverty

16. Abnormally functioning
Genetic
alterations
Autoantibodies
ICs
Proinflammatory
molecules
TISSUE INJURY
Environmental
Exposures & Behavior
SLE
Initiation
Amplification
Perpetuation
Abnormally functioning
B-cells
T-cells
pDC
Medical Illustration Copyright © 2012
Nucleus Medical Media. All rights reserved.
Antigen
Hormones (estrogen)
Infections
Toxins
Medications
Sun exposure
Vitamin D deficiency
Smoking
Stress
Phases of Disease Pathogenesis:
Initiation
Multiple proposed mechanisms that may vary from patient to patient
Occurs years prior to onset of clinical symptoms
Amplification and perpetuation of dysregulated immune mechanisms and response of target organs to inflammatory insults
Irreversible damage from disease and secondary effects of treatment
Genetic Susceptibility—Clinical Studies
Rate of SLE concordance in monozygotic twins is 24%–35%; in dizygotic twins is 2%–5%
10%–12% of SLE patients have 1st- or 2nd-degree relatives with SLE compared with <1% in healthy individuals
SLE patients may have family members with other autoimmune diseases

17. Pathogenesis of Lupus- Important Concepts
Autoimmunity is an altered immune homeostasis that leads to autoreactivity, immunodeficiency, and malignancy.
Immune dysregulation leading to autoreactivity and autoantibodies in SLE occurs in different phases and likely represents the untoward effects of environmental triggers on the genetically susceptible host.

18. Memory thief “brain fog”
Lupus Intangibles
Depression
Fatigue
Memory thief “brain fog”
Achiness, Headache
Studies have shown that some physicians lack tolerance when dealing with these kinds of “vague” symptoms and may, especially in women, attribute them to psychological causes.
Among primary care providers, however, there is a lack of tolerance for somaticizing. Somaticizing patients are one of the most difficult groups of patients that primary care providers serve (Green et al., 2005; May et al., 2004), because it is not clear what problem they are bringing for the provider to address. These patients are frustrating for primary care providers, (Green, Kaltman, Chung and Frank, 2005; May, Allison, Chapple, Chew-Graham, et.al.,2004) who may show little empathy with them (May et.al., 2004.; Ring, Dorwick, Humphris, Davies, et.al., 2005), and indeed may be hostile to them (May et al, 2004.).
Green, B., Kaltman, S., Chung, J., & Frank, L. (2005 November). Primary Care Providers' Interactions with Trauma Patients. Paper presented at the 21st annual meeting of the International Society for Traumatic Stress Studies, Toronto, Canada.
May, C., Allison, G., Chapple, A., Chew-Graham, C., Dixon, C., Gask, L., Graham, R., Rogers, A., & Roland, M. (2004). Framing the doctor-patient relationship in chronic illness: a comparative study of general practitioners' accounts. Sociology of Health & Illness, 26(2),
Ring, A., Dowrick, C., Humphris, G., Davies, J., & Salmon, P. (2005). The somatising effect of clinical consultation: What patients and doctors say and do not say when patients present medically unexplained physical symptoms. Social Science & Medicine, 61(7),

19. Jaccoud’s arthropathy
Lupus on the Outside
Malar rash
Synovitis
Painless oral ulcer
Discoid rash
Alopecia
Vasculitis
Jaccoud’s arthropathy
Raynaud’s Phenomenon

20. Lupus on the Inside Serositis Pericardial effusion Cerebral infarct
Glomerulonephritis
Spherocytes
Brain atrophy C

21. What Do Most Lupus Patients Have in Common—Antinuclear Antibodies (ANA)
Autoantibodies against various components of the cell nucleus
Present in many autoimmune disorders as well as some healthy subjects
Sensitive (not specific for SLE)
Because of low specificity, ANA usefulness increases if the pretest probability for lupus is high; ie, the patient has symptoms and signs that can be attributed to SLE
Because of the high sensitivity of the ANA, a patient with negative ANA is unlikely to have lupus even when her/his clinical presentation is suggestive of lupus

22. Incidence of Positive ANA
Non- lupus subjects 3%−4%
SLE 95%−99%
Scleroderma 95%
Hashimoto’s thyroiditis 50%
Idiopathic pulmonary fibrosis 50%
Incidence increases with age, chronic infections, and other chronic conditions
Interpret the ANA in context of clinical complaints ANA+ does not = SLE

23. Clinical Associations
Autoantibodies in SLE
Antibodies
Lupus Specificity
Clinical Associations
ANA
Low
Nonspecific
Anti-dsDNA
High
Nephritis
Anti-Sm
Anti-RNP
Arthritis, myositis, lung disease
Anti-SSA
Dry eyes/mouth, subacute cutaneous lupus erythematosus (SCLE), neonatal lupus, photosensitivity
Anti-SSB
Same as above
Antiphospholipid
Intermediate
Clotting diathesis

24. When to suspect SLE:
ACR (Revised) Criteria for Classification 4/11= 95% Specificity; 85% Sensitivity
Serositis
Oral ulcers
Arthritis
Photosensitivity
Blood cells
Renal involvement
Antinuclear antibodies (ANA)
Immunologic disorder
Neurologic disorder
Malar rash
Discoid rash
Stress that there are no diagnostic criteria for SLE- only classification criteria for research which can be used to make a clinical diagnosis
Serositis: Pleuritis/Pericarditis > 1 day on exam or ECG
Oral ulcers: non vasculitis or infection, usually painless
Arthritis: > 2 joints swelling or tender with AM stiffness for > 30 minutes
Photosensitivity: Unusual reaction to sun exposure
Blood disorder: Immune-mediated hemolytic anemia, leukopenia (< 4 × 103 cells/µL on >1 occasion), lymphopenia (< cells/µL on >1 occasion), thrombocytopenia (< 100 × 103cells/µL in the absence of offending medications)  
Renal involvement: Proteinuria (>0.5 g/day or 3+ positive on dipstick testing) or cellular casts (including red blood cells [RBCs], hemoglobin, granular, tubular, or mixed)
Antinuclear antibodies (ANA): Higher titers generally more specific (>1:160) in absence of medications associated with drug-induced lupus.
Immunologic disorder: anti-DNA antibody, anti-Sm antibody, or antiphospholipid antibodies, low complements, biologic false-positive serologic test results for syphilis
Neurologic disorder: Seizures, psychosis, mononeuritis, myelitis, acute confusional state in absence of other causes
Malar rash: Fixed, flat or raised, erythema over cheeks and nose
Discoid rash: Raised-rimmed lesions with keratotic scaling and follicular plugging, often scarring
Tan EM, Cohen AS, Fries JF, et al. Arthritis Rheum. 1982;25: Hochberg MC. Arthritis Rheum. 1997;40:1725. [Letter].

25. Signs and Symptoms

26. Case Presentation A
History: A 23-year-old Hispanic female with no past medical history presented to the emergency department (ED) with an 8-week history of joint pain and swelling in the hands, knees, and ankles; fever; myalgias; pleuritic chest pain; weight loss; and a facial rash that worsened with sun exposure. She had been seen initially at a local clinic and treated for “cellulitis” with oral Keflex. Two days prior, she was seen in another ED, found to have a temperature of 103 F, proteinuria, and anemia; she was told it was a “viral syndrome” and discharged home.

27. Case Presentation A (cont.)
Exam: T 37.9 C, BP 130/90, painless ulceration on the palate, malar rash, diffuse lymphadenopathy, and synovitis of the MCP/PIP joints
Labs: WBC 2.5x109/L, total protein 9 g/dL, albumin 3 g/dL, Hgb 11g/dL, Hct 32%, BUN 11 mg/dL, Cr .06 mg/dL UA: 100 mg/dL protein, RBC 20–40/hpf, WBC 0–1/hpf ANA+, anti-dsDNA+, Sm+
Discuss case with audience
What symptoms of lupus did this patient present with? What are the exam and lab features in this case that suggest lupus?

28. Case Presentation B - What features are concerning for lupus?
23 year old woman from Western Africa with recently diagnosed anemia (presumed but not confirmed to be iron-deficiency anemia) presents with swelling of feet and hands and a non-specific rash on her face and arms. She reported swelling in the joints, enlarged lymph nodes, generalized body aches and sweating.
Chart review reveals:
Positive ANA of 1:1280
4.2 WBC with normal differential
Hb/Hct is 9.6/30.4 MCV 77.3
Plt 307
Discussion of case
Notes from Amanda Sammut: This was a patient who actually was seen in a primary care clinic but was not seen by a rheumatologist. She had Class IV lupus nephritis but her symptoms were not taken as seriously as they should have been – a young woman with swelling, lymphadenopathy, etc. I ask the audience to think about what in the case makes them think of lupus. I try make sure that this is a patient they would urgently refer or call me about. Then I tell them about how she had active class IV LN and those are the symptoms she had.

29. Lupus Detection—In Summary
Early symptoms can be
Non-specific, easily confused with other illnesses or syndromes
Transient or prolonged, independent of one another
Consider lupus if your patient presents with
Vague complaints from the signs and symptoms list
Family history of autoimmune disease
Do an initial screening
CBC, BMP, LFT’s, ESR, CRP, ANA, UA
Make a referral for assessment and diagnosis by a Rheumatologist

30. Final Thoughts Patient engagement and trust building is critical
Patients from different cultural/socioeconomic backgrounds experience illness and treatment differently
Physicians from different cultural/socioeconomic backgrounds perceive patients and symptoms differently
What you can do to reduce health disparities
Discuss lupus prevalence and disparities with colleagues
Pursue continuing education about causes of disparities and cross-cultural communication
Learn about and refer patients to community resources
Pursue continuing education about causes of disparities and cross-cultural communication
A place to start:
E.g., of patient provider communication technique: for non- English speaking patients, low health literacy patients, and all patients, rather than asking “do you understand,” ask them to repeat the treatment plan back to you in their own words.
Learn about and refer patients to community resources
Examples: where to go if patients lack insurance, alternative ways to pay for medication, where to go if they are experiencing employment discrimination based on health status, how can immigrants find educational courses

31. Resources and Information
Ongoing care of lupus patients is a team effort
For presentations, videos, interactive case studies and CE/CME courses that can help, visit the Lupus Initiative at
We appreciate your participation in the post assessment and 4-6 week follow up assessment

32. Thank you! Questions about the Project? Contact Amy Caron
This project is part of the American College of Rheumatology’s Lupus Initiative ( and is administered by the Lupus Research Institute (lupusresearchinstitute.org/).
This project is supported by Grant Number 1 CPIMP from the U.S. Department of Health and Human Services office of Minority Health.
Questions about the Project?
Contact Amy Caron
Lupus Research Institute
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