494

Autoimmune
Conditions
July 2020

Rheumatoid Arthritis
pp 11-17

Systemic Lupus Erythematosus

pp 18-24

Polymyalgia Rheumatica and

Dermatomyositis
pp 25-29

Ankylosing Spondylitis
pp 30-35
FP Essentials ™

Faculty Stephanie Hanaway

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ISSN# 2159-3000

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For reference citations, use the following format: Lam NCV, Langan RC, Ghetu MV, Metzgar MM.
Autoimmune Conditions. FP Essent. 2020;494:1-44.
 FP Essentials 494 ™

Autoimmune
Conditions
AUTHORS
Nguyet-Cam Vu Lam, MD, FAAFP
Robert C. Langan, MD, FAAFP
Maria V. Ghetu, MD, FAAFP
Martha McGarey Metzgar, DO, FAAFP

Nguyet-Cam Vu Lam, MD, FAAFP, is the program director of
St Luke’s Family Medicine Residency Program in Bethlehem,
Pennsylvania. She is an adjunct associate professor in the
department of family and community medicine at Temple
University School of Medicine.
Robert C. Langan, MD, FAAFP, is the program director of
St Luke’s Family Medicine Residency Program-Sacred Heart
in Allentown, Pennsylvania. He is an adjunct professor in the
department of family and community medicine at Temple
University School of Medicine in Philadelphia.
Maria V. Ghetu, MD, FAAFP, is a clinical faculty member
and staff geriatrician at St Luke’s Family Medicine Residency
Program in Bethlehem, Pennsylvania. She is an adjunct asso-
ciate professor in the department of family and community
medicine at Temple University School of Medicine. Dr Ghetu
completed a fellowship in geriatric medicine and holds a cer-
tificate of added qualifications in geriatric medicine.
Martha McGarey Metzgar, DO, FAAFP, is an associate pro-
gram director and director of osteopathic medical education
at St Luke’s Family Medicine Residency Program in Bethle-
hem, Pennsylvania. Her clinical interests include osteopathic
medicine, women’s health, and pediatrics.

Disclosure: It is the policy of the AAFP that all individuals in a position to control content disclose any relationships with
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Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or
medium.
Foreword
Autoimmune diseases affect approximately 8% of
the population.1 Through years of study, we know,
as this edition of FP Essentials™ says, that the body
experiences “a loss of self-tolerance.” Yet the etiol-
ogy underlying this breakdown in communication
between the immune system and the rest of the body
is somewhat mysterious, to the physician and patient
alike. How does the immune system decide that
the synovium, the muscle, or the DNA itself is the
enemy? Why does it not relearn what is friendly? Once
an autoimmune process begins, the body and the
immune system never fully align again.
In the abstract, the concept is so unusual that for
many years it was rejected by medical science. In the
early 1900s, a theory called horror autotoxicus postu-
lated not that autoantibodies could not exist, but that
the body would be unwilling to be a danger to itself.
The idea was so compelling that it delayed dissemina-
tion of research that found autoantibodies.2
In practice, we are learning more about what goes
wrong at the cellular level, but answers remain vague.
In a susceptible patient, a trigger—possibly infec-
tion, stress, hormones, or something else—induces an
inflammatory response, autoantibody production, and
often widespread harm, refuting the horror autotoxicus
theory. Yet not all susceptible patients develop auto-
immune disease, and the degree of inflammation and
clinical symptoms varies widely.
Learning Objectives
1. Describe the symptoms of rheumatoid arthritis (RA).
2. Evaluate patients with bilateral arthritis for RA.
3. Diagnose systemic lupus erythematosus (SLE).
4. Explain the effects of SLE on pregnancy.
5. Identify polymyalgia rheumatica in patients with typical symptoms.
6. Discuss management of the skin and muscle symptoms of dermatomyositis.
7. Describe inflammatory back pain.
8. Diagnose ankylosing spondylitis in patients with typical symptoms.
2
If an autoimmune disease does develop, conse-
quences of this process are profound. Some diseases
are associated with decreased life expectancy, and
nearly all confer substantial morbidity. Family physi-
cians must be skilled at identifying the risk factors and
the sometimes subtle symptoms, which can occur in
patients without risk factors. Many of these conditions
can be managed, and morbidity and mortality can be
reduced with effective therapy.
This edition covers the autoimmune conditions
commonly encountered in family medicine. Section
One discusses the diagnosis and management of
rheumatoid arthritis, the most common inflamma-
tory arthritis. Section Two covers the symptoms and
evaluation of systemic lupus erythematosus. Section
Three will help you distinguish between two autoim-
mune diseases that affect the muscles, polymyalgia
rheumatica and dermatomyositis. Finally, Section Four
describes the symptoms, evaluation, and management
of ankylosing spondylitis.
I hope you learn as much from this edition as I have.
Kate Rowland, MD, FAAFP, Associate Medical Editor
Assistant Professor, Department of Family Medicine
Rush University, Chicago, Illinois
1. Fairweather D, Rose NR. Women and autoimmune diseases.
Emerg Infect Dis. 2004;10(11):2005-2011.
2. Silverstein AM. Autoimmunity versus horror autotoxicus: the
struggle for recognition. Nat Immunol. 2001;2(4):279-281.
 Contents
Page Page
Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2
Learning Objectives . . . . . . . . . . . . . . . . . . . . . . . .2 SECTION THREE
Tables and Figures . . . . . . . . . . . . . . . . . . . . . . . . .4 Polymyalgia Rheumatica and
Editorial Mission and Policies . . . . . . . . . . . . . . . . 5 Dermatomyositis . . . . . . . . . . . . . . . . . . . . . . . .25
Pretest Questions . . . . . . . . . . . . . . . . . . . . . . . . . .7 Polymyalgia Rheumatica . . . . . . . . . . . . . . . . . 25
Pretest Answers. . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Prevalence, Incidence, and Risk Factors
Key Practice Recommendations. . . . . . . . . . . . . . 9 Pathophysiology and Etiology
Presentation
SECTION ONE Classification Criteria
Rheumatoid Arthritis . . . . . . . . . . . . . . . . . . . . . . . 11 Evaluation
Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . 11 Management
Risk Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Comorbidities
Dermatomyositis . . . . . . . . . . . . . . . . . . . . . . . 27
Clinical Presentation . . . . . . . . . . . . . . . . . . . . 12
Description and Pathophysiology
Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Presentation
Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Diagnostic Evaluation
Management . . . . . . . . . . . . . . . . . . . . . . . . . . 13 Management
Pharmacotherapy Comorbidities
Lifestyle Modification
Integrative Medicine
Primary Care . . . . . . . . . . . . . . . . . . . . . . . . . . 16 SECTION FOUR
Ankylosing Spondylitis . . . . . . . . . . . . . . . . . . . . 30
Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . 30
SECTION TWO Prevalence, Incidence, and Risk Factors . . . . 30
Systemic Lupus Erythematosus . . . . . . . . . . . . . . 18 Clinical Presentation . . . . . . . . . . . . . . . . . . . . 30
Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . 18 Diagnostic Criteria . . . . . . . . . . . . . . . . . . . . . . 31
Prevalence, Incidence, and Risk Factors . . . . 18 Physical Examination
Clinical Presentation . . . . . . . . . . . . . . . . . . . . 18 Diagnostic Criteria
Common Nonmusculoskeletal Symptoms Management Options and Prognosis . . . . . . . 32
When to Suspect SLE Associated Conditions . . . . . . . . . . . . . . . . . . 34
Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 Complications . . . . . . . . . . . . . . . . . . . . . . . . . 35
Classification Criteria
Evaluation
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
Management . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . 40
Family Physician Role
Posttest Questions . . . . . . . . . . . . . . . . . . . . . . . . 41
Pharmacotherapy
Posttest Answers . . . . . . . . . . . . . . . . . . . . . . . . . 43
Preconception and Pregnancy Care
Lifestyle Modification and Integrative Medicine
* websites accessed June 2020
Prognosis and Complications . . . . . . . . . . . . . 23
Progression
Complications and Comorbidities
Complications From Undiagnosed, Unmanaged,
and Poorly Controlled SLE
Complications From Immunosuppressive
Therapy

3
Tables and Figures
Page
Tables
1. Extra-Articular Manifestations of RA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
2. ACR and EULAR Classification of RA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
3. EULAR Defined Characteristics Describing Arthralgia at Risk for RA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
4. Disease-Modifying Antirheumatic Drugs for RA Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
5. Comparison of Recommended RA Management Regimens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
6. Classification Criteria for SLE. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
7. EULAR SLE Management Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
8. EULAR/ACR Classification Criteria for PMR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
9. ACR Criteria for Giant Cell Arteritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
10. Bohan and Peter Criteria for Diagnosis of Dermatomyositis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
11. Current and Classic Classifications of Spondyloarthritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
12. Drugs for Ankylosing Spondylitis Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

Figures
1. Algorithm to Diagnose AS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

4
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1. Which one of the following is the most common
autoimmune inflammatory arthritis?
❏ A. Ankylosing spondylitis.
❏ B. Lupus arthritis.
❏ C. Psoriatic arthritis.
❏ D. Rheumatoid arthritis.
2. Which one of the following environmental factors is
most strongly associated with rheumatoid arthritis
development?
❏ A. Air pollution.
❏ B. Occupational silica exposure.
❏ C. Tobacco exposure.
3. Which one of the following is true of serum
testing in patients with suspected systemic lupus
erythematosus (SLE)?
❏ A. A positive antinuclear antibody (ANA) titer
does not require further testing.
❏ B. An elevated complement level is highly
predictive of SLE.
❏ C. Antiphospholipid testing is indicated only if
there is a history of venous thrombotic events.
❏ D. Approximately 95% of patients with SLE will
have a positive ANA titer.
4. Which one of the following drugs is recommended
for all patients with systemic lupus erythematosus?
❏ A. Azathioprine.
❏ B. Hydroxychloroquine.
❏ C. Methotrexate.
❏ D. Mycophenolate.
Pretest Questions
5. Which one of the following is true of polymyalgia
rheumatica?
❏ A. C-reactive protein levels will be normal.
❏ B. It is characterized by pain and stiffness of the
neck and shoulders.
❏ C. It typically is not associated with other
autoimmune conditions.
❏ D. Less than 50% of cases are in women.
6. Which one of the following is considered
pathognomonic for dermatomyositis?
❏ A. Gottron papules.
❏ B. Heliotrope rash.
❏ C. Shawl sign.
❏ D. V sign.
7. Which one of the following is a first-line treatment
for active ankylosing spondylitis?
❏ A. Nonsteroidal anti-inflammatory drugs.
❏ B. Slow-acting antirheumatic drugs.
❏ C. Tumor necrosis factor-alpha inhibitors.
8. Patients with ankylosing spondylitis most
commonly experience which one of the following
comorbidities?
❏ A. Anterior uveitis.
❏ B. Crohn disease.
❏ C. Psoriasis.
❏ D. Ulcerative colitis.
7
Pretest Answers
Question 1: The correct answer is D.
Rheumatoid arthritis is the most common autoimmune
inflammatory arthritis. See page 11.
Question 2: The correct answer is C.
Tobacco exposure is the environmental factor most
strongly associated with rheumatoid arthritis develop-
ment. See page 11.
Question 3: The correct answer is D.
Antinuclear antibody is present in approximately 95%
of patients with systemic lupus erythematosus. See
page 19.
Question 4: The correct answer is B.
Hydroxychloroquine, at a dose not exceeding
5 mg/kg of body weight, is recommended for all
patients with systemic lupus erythematosus. It should
be continued indefinitely unless contraindicated or
complications, such as retinal toxicity, develop. See
page 19.
Question 6: The correct answer is A.
Gottron papules, which are pathognomonic for der-
matomyositis, are thickened red or purple plaques or
papules over the dorsal hands, particularly the knuck-
les. See page 27.
Question 7: The correct answer is A.
For patients with active ankylosing spondylitis, nonste-
roidal anti-inflammatory drugs are the first-line drugs.
See page 32.
Question 8: The correct answer is A.
Between 30% and 40% of patients with ankylos-
ing spondylitis (AS) will experience anterior uveitis.
Approximately 10% to 25% of patients with AS have
psoriasis, and 5% to 10% have inflammatory bowel
disease. See pages 34-35.

Question 5: The correct answer is B.

Polymyalgia rheumatica (PMR) is a chronic systemic
inflammatory disease characterized by stiffness of
the proximal large joints. Classic symptoms of PMR
include pain in the neck, pelvic girdle, and shoulders.
See page 25.

8
 Key Practice Recommendations
1. For patients diagnosed with rheumatoid arthritis (RA), initiate disease-modifying antirheumatic drug (DMARD)
treatment promptly after diagnosis.

2. For patients with early RA for whom a DMARD is indicated, prescribe methotrexate initially.

3. For all patients with systemic lupus erythematosus (SLE), unless contraindicated, prescribe hydroxychloroquine
at a dose not exceeding 5 mg/kg of body weight.

4. In patients with SLE with inadequate benefit from hydroxychloroquine and a glucocorticoid, consider prescribing
belimumab as an additional drug.

5. For patients with polymyalgia rheumatica, prescribe 12.5 to 25 mg/day of prednisone, or the equivalent, in a
single daily dose as the initial treatment.

6. For patients with active ankylosing spondylitis, prescribe a nonsteroidal anti-inflammatory drug (NSAID) to be
taken continuously as a first-line drug. (This is an off-label use of some NSAIDs.)

Evidence Ratings and Sources

1. Evidence rating: SORT A
Source: Ann Rheum Dis, reference 6
Website: https://ard.bmj.com/content/76/6/960
2. Evidence rating: SORT A
Sources: Arthritis Care Res (Hoboken), Ann Rheum Dis, references 5 and 6
Websites: https://onlinelibrary.wiley.com/doi/full/10.1002/acr.22783; https://ard.bmj.com/content/76/6/960
3. Evidence rating: SORT A
Source: Ann Rheum Dis, reference 47
Website: https://ard.bmj.com/content/78/6/736
4. Evidence rating: SORT A
Source: Ann Rheum Dis, reference 47
Website: https://ard.bmj.com/content/78/6/736
5. Evidence rating: SORT C
Source: Arthritis Rheumatol, reference 66
Website: https://ard.bmj.com/content/74/10/1799
6. Evidence rating: SORT C
Source: Arthritis Rheumatol, reference 103
Website: https://onlinelibrary.wiley.com/doi/full/10.1002/art.41042

9
Autoimmune Conditions

Strength of Recommendation Taxonomy (SORT)

Strength of
Recommendation Definition
A • Recommendation based on consistent and good-quality patient-oriented evidence.a
B • Recommendation based on inconsistent or limited-quality patient-oriented evidence.a
C • Recommendation based on consensus, usual practice, opinion, disease-oriented
evidence,a or case series for studies of diagnosis, treatment, prevention, or screening.

aPatient-oriented evidence measures outcomes that matter to patients: morbidity, mortality, symptom improvement, cost reduc-
tion, and quality of life. Disease-oriented evidence measures intermediate, physiologic, or surrogate end points that may or may
not reflect improvement in patient outcomes (eg, blood pressure, blood chemistry, physiologic function, pathologic findings).
(From Ebell MH, Siwek J, Weiss BD, et al. Strength of recommendation taxonomy [SORT]: a patient-centered approach to grading
evidence in the medical literature. Am Fam Physician. 2004;69:548-556.)

AAFP FP Essentials™ Approved

as CME Clinical Content
This Enduring Material activity, FP Essentials, has
been reviewed and is acceptable for credit by the Amer-
ican Academy of Family Physicians. Term of approval
begins 06/01/2020. Term of approval is for two years
from this date. Physicians should claim only the credit
commensurate with the extent of their participation in
the activity. Approved for 5 AAFP Prescribed credits.
The AAFP is accredited by the Accreditation Council
for Continuing Medical Education (ACCME) to provide
continuing medical education for physicians.
The American Academy of Family Physicians des-
ignates this Enduring Material activity for a maximum
of 12.00 AMA PRA Category 1 credit(s)™. Physicians
should only claim credit commensurate with the extent
of their participation in the activity.
CME activities approved for AAFP credit are rec-
ognized by the AOA as equivalent to AOA Category 2
credit.

10
 SECTION ONE
Rheumatoid Arthritis

Rheumatoid arthritis (RA) is the most common autoimmune inflammatory arthritis, and is seen more
commonly in women, smokers, and individuals with a family history of RA. It should be considered if
unexplained pain and swelling in the metacarpophalangeal and/or metatarsophalangeal joints and morning
stiffness of fingers lasting for longer than 30 minutes are present. RA may be present in the lungs, skin, and
eyes. It is associated with an increased risk of cardiovascular death independent of other risk factors. Disease
activity should be monitored using a validated scale, such as the Disease Activity Score 28 (DAS28), among
others. Earlier management to achieve remission or decrease disease activity is associated with less joint
damage, better quality of life, and improved survival rates. Methotrexate with consideration of low-dose glu-
cocorticoids is considered first-line therapy for RA. Other disease-modifying antirheumatic drugs, includ-
ing immunobiologics, may be used for patients who do not benefit from methotrexate. Before undergoing
treatment, patients should be screened for tuberculosis and hepatitis B and C infection. Drug dosages may
be tapered in patients with remission or decreased disease activity, but drugs should not be discontinued.

Case 1. Lisa is a 55-year-old woman, who comes to
your office with arthralgias that are becoming more
severe and affecting her daily life. She has worked on
the assembly line at an automotive plant for the past 28
years. Because of increasing pain in her hands and arms
coupled with decreased mobility and her inability to work
long shifts, she is concerned that she may not be able to
continue working for 2 more years until she is eligible
for full retirement benefits. Lisa says that her mother and
grandmother had arthritis; she assumes it runs in her
family and that now she has arthritis, too.
Rheumatoid arthritis (RA) is the most common
autoimmune inflammatory arthritis.1 It was estimated
to affect 1.28 to 1.36 million adults in the United
States in 2014.2 RA may manifest in individuals
between ages 35 and 60 years (mean age of 48 years).
Women are approximately 3 times more likely than
men to have RA.3 This condition is more common in
Native Americans from North America, with preva-
lence rates as high as 5% to 7%.4
The most recent guidelines on RA diagnosis and
management are the 2015 American College of
Rheumatology (ACR) and the 2016 European League
Against Rheumatism (EULAR) guidelines.5,6
Pathophysiology
The pathophysiology of RA is not completely
understood. Loss of self-tolerance, the ability of the
immune system to ignore the body’s own antigens,
may be the first step. Autoantibodies, such as rheuma-
toid factor (RF) and anticyclic citrullinated peptide
(anti-CCP) antibodies, have been found in asymptom-
atic patients who ultimately develop RA. Abnormal T
cells stimulate inflammatory pathways that are resis-
tant to normal inhibitory mechanisms.7
Rheumatoid arthritis affects the synovium covering
the articular surfaces of cartilage and bone, producing
a thickened synovium, thin articular cartilage, and
structural damage to underlying bone. The pres-
ence of autoantibodies within the synovium has been
shown to be associated with increased levels of inflam-
mation. Many extra-articular sites may be foci for this
inflammatory process.7
Risk Factors
A family history of RA in a first-degree rela-
tive increases the risk of RA.4 Multiple genetic sites
associated with an increased risk of developing RA
have been identified, particularly in RF-seropositive
patients, but the exact mechanism is unclear.
Tobacco exposure is the environmental factor most
strongly associated with RA development.4 Risk fac-
tors with weaker associations include occupational
silica exposure, air pollution, obesity, and high-sodium
diets. Observational studies suggest that RA may be
less common in individuals who consume fish, foods
rich in omega-3 fatty acids, and moderate amounts of
alcohol and in individuals who take statins.

11
Autoimmune Conditions

Clinical Presentation Diagnosis

Patients with RA present with bilateral polyarthritis Case 1, cont’d. Lisa reports hand pain and swelling
with pain and swelling of the joints of the hands and/ that are worse in the morning. She says sometimes it takes
or feet.7 The metacarpophalangeal, metatarsophalan- up to 90 minutes after awakening before she feels that she
geal, and proximal interphalangeal joints and wrists can use them. The metacarpophalangeal (MCP) joints
often are affected. The distal interphalangeal joints are swollen and tender on palpation and she has difficulty
typically are spared. The shoulders, elbows, knees, making a fist.
and ankles may be affected later. Stiffness for several Currently, there are no gold standard diagnostic
hours occurs after periods of inactivity, including sleep criteria for RA. A classification system created by the
and prolonged sitting. Malaise, fatigue, and low-grade ACR and EULAR may aid in the diagnosis.8 This
fever are common. system requires the presence of at least one clinically
Extra-articular manifestations (Table 1) are more swollen joint that is not better explained by another
common in men and patients with seropositive RA.1 condition and an additional 6 to 10 points from a
Smoking increases the risk of rheumatoid nodules, scoring system (Table 2). These criteria have an 82%
vasculitis, and interstitial lung disease. sensitivity and a 61% sensitivity for diagnosing RA.9
There is considerable vari-
ability in presentation. Patients
Table 1 may experience a transitional
Extra-Articular Manifestations of RA state before the development of
clinically significant RA, with
System Manifestation Comments subtle inflammatory synovial
changes and the presence of
Cardiovascular Atherosclerosis Accelerated atherosclerosis is the
most common cause of death in
autoantibodies.7
patients with RA Many strategies have been sug-
gested to assist in identification
Pericarditis May be present in one-third to one-
half of patients, rarely causes of high-risk patients. A EULAR
cardiac tamponade task force defined characteristics
Dermatologic Rheumatoid Subcutaneous, firm or rubbery of patients with arthralgia who
nodules nodules located at pressure points are at risk of developing RA
(eg, olecranon) (Table 3).10 The presence of three
Hematologic Felty syndrome Characterized by neutropenia, or more characteristics was found
splenomegaly, and to have a greater than 90% sensi-
thrombocytopenia tivity in detecting RA. This tool
Neurologic Cervical myelopathy Results from subluxation of C1 and C2 was developed in a subspecialty
Neuropathy May include carpal tunnel syndrome
setting, and further studies are
or foot drop needed to assess whether its use is
appropriate in primary care.
Ophthalmic Episcleritis/scleritis Acute painful erythematous eye, rare
finding
Evaluation
Keratoconjunctivitis Secondary Sjögren syndrome, dry
sicca mouth also may be present Not all patients with arthritis
require further testing for RA.
Pulmonary Interstitial lung May resemble idiopathic pulmonary
disease fibrosis or bronchiolitis obliterans
A reasonable approach is to test
with organizing pneumonia patients with pain and swelling
of the commonly affected joints
Pleural effusion Exudative effusion
(particularly the metacarpopha-
langeal joints), prolonged morn-
RA = rheumatoid arthritis.
ing stiffness (ie, 30 minutes or
Adapted with permission from Wasserman A. Rheumatoid arthritis: common questions
about diagnosis and management. Am Fam Physician. 2018;97(7):458. longer), or a first-degree relative
with RA.4,7

12
 Section One

Recommended testing includes assessment of inflam- maintain joint function and limit progression of joint
mation with a C-reactive protein level, erythrocyte damage.5,6,7 Overall, approximately 75% to 80% of
sedimentation rate, and autoantibody tests for RF (sen- patients can achieve remission or decreased disease
sitivity 69%, specificity 85%) and anti-CCP (sensitivity activity, with normal participation in work and a
67%, specificity 95%).1,11 X-rays of the affected joints normal life expectancy.7
are the preferred imaging modality but are not neces-
sary for diagnosis.12 Ultrasonography and magnetic Pharmacotherapy
resonance imaging study are more accurate than x-rays Disease-modifying antirheumatic drugs (DMARDs)
in detecting synovial inflammation, and can be used to are the cornerstone of RA management and should be
monitor disease progression or response to management. initiated promptly after diagnosis to optimize likeli-
hood of remission.6 DMARDs are classified as syn-
Management thetic (with no known target [conventional] or specific
Case 1, cont’d. You obtain x-rays of Lisa’s hands as molecular targets) or biologic (with specific extracellu-
well as a C-reactive protein (CRP) level and anticitrul- lar or cell membrane molecular targets) (Table 4).6,7
linated protein (anti-CCP)
test. The x-rays show mild joint
erosion in the bilateral MCP
Table 2
joints. The CRP level is markedly
elevated and the anti-CCP level ACR and EULAR Classification of RA
is reported as high positive. Based
upon your suspicion for rheuma- Category Criteria Points
toid arthritis, you refer Lisa to a
Joint involvement 1 large jointa 0
rheumatology subspecialist.
Rheumatoid arthritis is an 2-10 large joints 1
incurable disease, but early ini- 1-3 small jointsb 2
tiation of management is asso-
4-10 small joints 3
ciated with decreased disease
activity and less joint destruc- >10 joints (includes at least 1 small joint) 5
tion.7 Unmanaged or under- Serology (at least 1 test Negative RF and anti-CCP antibodies 0
managed RA causes irreversible result is needed for
classification) Low-positive RF or low-positive anti- 2
joint damage, decreased physi- CCP antibodies
cal function, impaired qual-
High-positive RF or high-positive anti- 3
ity of life, and extra-articular CCP antibodies
manifestations.7,13
Duration of symptoms <6 weeks 0
Meta-analyses have shown
that patients with RA have a 6 weeks 1
60% increased risk of myocar- Acute phase reactants Normal CRP and normal ESR 0
dial infarction (MI) and a 70% (at least 1 test result is
needed for classification) Abnormal CRP or abnormal ESR 1
increased risk of death due to
MI compared with the general
aLarge joints include ankles, elbows, hips, knees, and shoulders.
population.14 RA management
bSmall joints include metacarpophalangeal joints, proximal interphalangeal joints,
with tumor necrosis factor- second to fifth metatarsophalangeal joints, thumb interphalangeal joints, and wrists.
alpha inhibitors was shown to ACR = American College of Rheumatology; CCP = cyclic citrullinated peptide; CRP =
be associated with a 39% rela- C-reactive protein; ESR = erythrocyte sedimentation rate; EULAR = European League
tive risk reduction of MI. Against Rheumatism; RA = rheumatoid arthritis; RF = rheumatoid factor.
Patients should be treated Adapted from Aletaha D, Neogi T, Silman AJ, et al. 2010 rheumatoid arthritis classification
criteria: an American College of Rheumatology/European League Against Rheumatism
to remission (defined as no
collaborative initiative. Ann Rheum Dis. 2010;69(9):1580-1588. Erratum in Ann Rheum Dis.
evidence of disease activity) 2010;69(10):1892.
or to low disease activity to

13
Autoimmune Conditions
Table 3
EULAR Defined Characteristics
Describing Arthralgia at Risk for RA
These parameters are to be used in patients with
arthralgia without clinical arthritis and without other
diagnosis or other explanation for the arthralgia
History
Joint symptoms of recent onset (duration <1 year)
Symptoms located in MCP joints
Duration of morning stiffness 60 min
Most severe symptoms present in the early morning
Presence of a first-degree relative with RA
Physical examination
Difficulty with making a fist
Positive squeeze test of MCP joints
EULAR = European League Against Rheumatism; MCP =
metacarpophalangeal; RA = rheumatoid arthritis.
Reprinted from van Steenbergen HW, Aletaha D, Beaart-van
de Voorde LJJ, et al. EULAR definition of arthralgia suspi-
cious for progression to rheumatoid arthritis. Ann Rheum Dis.
2017;76(3):494.
The ACR and EULAR guidelines recommend use of
the synthetic DMARD methotrexate as first-line treat-
ment in early RA with consideration of short-term (ie,
less than 3 months) glucocorticoids (Table 5).5,6 (This
is an off-label use of some glucocorticoids.) The gluco-
corticoid dosage should be tapered as soon as clinically
feasible.6 This has been shown to induce remission in
a significant number of patients by 16 weeks.15
Common adverse effects, including nausea, alopecia,
stomatitis, and hepatotoxicity, may be prevented with
coadministration of folic acid.7 Typically, less than 5%
of patients need to discontinue methotrexate because
of adverse effects. Patients who cannot tolerate or who
have contraindications to methotrexate should receive
leflunomide or sulfasalazine.6
Glucocorticoids also may be used in bridging
therapies or during flares.5,6 The lowest effective dose
should be used for the shortest duration of time.5 One
study enrolled patients with RA who received less than
5 mg/day of prednisone for up to 6 years. It found
that these patients experienced greater disease activity
but similar incidences of cardiovascular disease, infec-
tion, and fracture compared with patients with RA
who did not receive steroids.16
14
Management effectiveness can be assessed using
tools such as the Clinical Disease Activity Index
(CDAI), the Disease Activity Score 28 (DAS28), or
the Simplified Disease Activity Index (SDAI).5,6 The
goal of management is reduction of disease activity by
at least 50% at 3 months and achievement of remis-
sion or low disease activity at 6 months.6,7
If patients do not benefit from initial therapy,
the ACR and EULAR guidelines suggest different
approaches. The ACR guidelines recommend a com-
bination of two conventional synthetic DMARDs,
a biologic DMARD with or without methotrexate,
or a targeted synthetic DMARD with or without
methotrexate.5
The EULAR guidelines base second-line manage-
ment on risk factors, including autoantibodies, early
joint damage, high disease activity, and failure of at
least two conventional DMARDs.6 Patients with mul-
tiple risk factors should add a biologic DMARD or a
targeted synthetic DMARD to methotrexate, whereas
patients without risk factors may be transitioned to
another conventional synthetic DMARD or start
combination therapy with two conventional synthetic
DMARDs (Table 5).
Targeted synthetic DMARDs and biologic
DMARDs have shown similar effectiveness when
combined with methotrexate.17 After remission for
more than 6 months, tapering of the dosage of tar-
geted synthetic and biologic DMARDs may be consid-
ered, but discontinuation is not recommended.1,5,6,18
Adverse effects of targeted synthetic and biologic
DMARDs are similar, including immunosuppression,
reactivation of latent tuberculosis infection, drug-
induced lupus, local reactions, and skin changes.7
Before starting biologic DMARDs, patients should be
screened for latent tuberculosis infection. If test results
are positive, patients should be treated for at least 1
month before starting DMARD therapy.1
Screening for hepatitis B and C infections is rec-
ommended before patients start immunosuppressive
therapy.1 Antitumor necrosis factor DMARDs may
exacerbate severe heart failure. Biologic DMARDs
increase the risk of some skin cancers and are contrain-
dicated in patients with a history of skin cancer.1,19
Lifestyle Modification
Dietary changes have not been shown to prevent
development of RA.20 The Mediterranean and vegetar-
ian diets were shown to improve pain scores in small
 Section One

trials.20,21 Probiotics were found to improve a disease The 2018 EULAR guidelines for physical activity
activity score, but there is insufficient evidence to sup- in RA recommend that patients participate in physical
port use of a specific probiotic.22 activity and exercise as tolerated.23 There is insufficient

Table 4
Disease-Modifying Antirheumatic Drugs for RA Management

Molecular
Drug Target Dose Common Adverse Effects

Conventional Synthetic
Methotrexate Unknown 10-25 mg/week PO or Elevated transaminase levels, hair loss,
subcutaneously stomatitis, teratogenicity
Leflunomide Dihydroorotate 20 mg/day PO Elevated transaminase levels, diarrhea,
dehydrogenase teratogenicity
Hydroxychloroquine Unknown 400 mg/day PO Retinopathy
Sulfasalazine Unknown 2-4 g/day PO Cutaneous hypersensitivity reactions,
drug-induced systemic lupus
erythematosus, diarrhea
Targeted Synthetic
Baricitinib JAK 1, 2 2-4 mg/day PO Infections, reactivation of tuberculosis,
anemia, hyperlipidemia
Tofacitinib JAK 1, 2, 3 10 mg/day PO
TNF-Alpha Inhibitor Biologic
Adalimumab TNF 40 mg every 2 weeks Infections, reactivation of tuberculosis,
subcutaneously drug-induced lupus, nonmelanoma
skin cancer, injection/infusion site
Certolizumab TNF 200 mg every 2 weeks reactions
subcutaneously
Etanercept TNF 50 mg/week subcutaneously
Golimumab TNF 50 mg/month subcutaneously
Infliximab TNF 3-5 mg/kg every 6-8 weeks IV
Non-TNF-Alpha Inhibitor Biologic
Abatacept CD80/86 125 mg/week subcutaneously Infections, reactivation of tuberculosis,
leukocytopenia
Anakinra IL-1 receptor 100 mg/day subcutaneously Infections
Rituximab CD20 1,000 mg every 6 months IV Reactivation of hepatitis B infection,
leukocytopenia, progressive multifocal
leukoencephalopathy
Sarilumab IL-6 receptor 150-200 mg every 2 weeks Infections, reactivation of tuberculosis,
subcutaneously neutropenia, hyperlipidemia
Tocilizumab IL-6 receptor 162 mg/week subcutaneously

IL = interleukin; IV = intravenous; JAK = Janus kinase; PO = oral; RA = rheumatoid arthritis; TNF = tumor necrosis factor.
Information from Aletaha D, Smolen JS. Diagnosis and management of rheumatoid arthritis: a review. JAMA. 2018;320(13):1360-
1372; Wasserman A. Rheumatoid arthritis: common questions about diagnosis and management. Am Fam Physician.
2018;97(7):458; Clinical Pharmacology. Available at https://www.clinicalkey.com/pharmacology/.

15
Autoimmune Conditions

Table 5
Comparison of Recommended RA Management Regimens

Treatment Goal/Step ACR (2015) EULAR (2017)

Treatment goal Treat to target Treat to target

Initial treatment
Adjunct to initial
treatment
Second-line treatment if
initial treatment failure
Remission treatment
Flare treatment
Treatment target should be low Reduce disease activity by at least 50% within 3 months
disease activity or remission Reach remission or low disease activity within 6 months
Methotrexate
Consider adding low-dose Consider adding short- term glucocorticoida (up to
glucocorticoida ( 10 mg/day 30 mg/day, with dosage tapered and discontinuation
for >3 months) within 3 months)
Any of the following: No risk factors presentb
Combination of conventional Any of the following:
synthetic DMARDsc Add conventional synthetic DMARD
TNF-alpha inhibitor DMARDd ± Change to a different conventional synthetic DMARD
methotrexate Risk factors presentb
Non-TNF-alpha inhibitor Any of the following:
DMARDe ± methotrexate
Biologic DMARD + methotrexate
Targeted synthetic DMARD + methotrexate
Do not discontinue all DMARDs
Consider dose reduction or interval increase of DMARD
Add short-term steroids for the lowest dosage and shortest duration possible

aThis is an off-label use of some glucocorticoids.

bRisk factors include high titers of autoantibodies, early joint damage, moderate to high disease activity, and no improvement with
two or more conventional synthetic DMARDs.
cConventional synthetic DMARDs: hydroxychloroquine, leflunomide, methotrexate, sulfasalazine.

dTNF-alpha inhibitor DMARDs: adalimumab, certolizumab, etanercept, golimumab, infliximab.

eNon-TNF-alpha inhibitor DMARDs: abatacept, baricitinib, rituximab, sarilumab, tocilizumab, tofacitinib.

ACR = American College of Rheumatology; DMARD = disease-modifying antirheumatic drug; EULAR = European League Against
Rheumatism; RA = rheumatoid arthritis; TNF = tumor necrosis factor.
Information from Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology guideline for the treatment of
rheumatoid arthritis. Arthritis Care Res (Hoboken). 2016;68(1):1-25; Smolen JS, Landewé R, Bijlsma J, et al. EULAR recommenda-
tions for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update.
Ann Rheum Dis. 2017;76(6):960-977; Aletaha D, Smolen JS. Diagnosis and management of rheumatoid arthritis: a review. JAMA.
2018;320(13):1360-1372.

evidence as to whether exercise improves short-term
hand pain or function, although there is no evidence
of harm.24 General exercise recommendations are
reasonable for all patients.
Integrative Medicine
A 2011 Cochrane review found that evening prim-
rose (Oenothera biennis) oil, borage (Borago officinalis)
seed oil, and blackcurrant (Ribes nigrum) seed oil prob-
ably improve pain, may improve function, and prob-
ably do not increase the risk of adverse events.25 The
Chinese herb Tripterygium wilfordii Hook F was shown
to be noninferior in improving DAS28 scores com-
pared with methotrexate monotherapy in a small trial.26
Biqi capsule has been found to improve RA symptoms,
but the trials evaluating its effectiveness were limited by
lack of blinding and methodologic flaws.27
Primary Care
Family physicians should continue to recom-
mend preventive services for patients with RA. These
patients have been shown to be slightly less likely to

16

receive aggressive treatment of dyslipidemia and to
undergo cervical, breast, or colorectal cancer screen-
ing, though no significant differences were observed
between patients with RA and those without RA.
However, patients with RA are more likely to undergo
bone mineral density testing and to receive influenza
and pneumococcal vaccinations.28 No differences in
management of hypertension, diabetes, and ischemic
heart disease care were shown between patients with
RA and those without RA.
Section One
Case 1, cont’d. After the appropriate screening tests,
Lisa is started on methotrexate and a low-dose gluco-
corticoid by a rheumatology subspecialist. Despite some
initial improvement in pain and swelling, she feels that
she has not made significant progress after 3 months of
therapy. Following the American College of Rheumatol-
ogy recommendations, the rheumatology subspecialist adds
a biologic disease-modifying antirheumatic drug to the
methotrexate. In addition, Lisa agrees to remain active
and has adopted a Mediterranean diet.
17
 SECTION TWO
Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that can affect the musculoskeletal,
integumentary, renal, neuropsychiatric, hematologic, cardiac, pulmonary, gastrointestinal, and reticuloen-
dothelial systems. Most patients with suspected SLE are comanaged with a rheumatology subspecialist to
confirm the diagnosis and assist in ongoing treatment. Management should focus on improving long-term
outcomes, achieving remission, preventing tissue damage, and improving quality of life. Disease activity
should be assessed at baseline and at follow-up visits using a validated instrument. Hydroxychloroquine is
recommended for all patients with SLE and should be continued indefinitely unless contraindicated. Low-
dose glucocorticoids can be used to manage most symptoms. When needed, immunosuppressive drugs and
biologics can be used, depending on the affected body system.

Case 2. Tara is a 23-year-old woman, who comes to your
office reporting several months of increasing fatigue, arthral-
gias, myalgias, and development of a new facial rash that she
describes as a mask. She has spent a significant amount of
time outdoors this summer and says she thinks she is becom-
ing allergic to the sun because of photosensitivity and the
development of an erythematous rash in sun-exposed areas.
Pathophysiology
Systemic lupus erythematosus (SLE) is an autoim-
mune disease that involves targeted autoantibody
production and immune complex formation.29,30
Autoantibodies and immune complex deposition con-
tribute to tissue damage.31
Several autoantibodies are implicated in SLE. Anti-
double-stranded DNA (anti-dsDNA) antibodies are
diagnostic markers for SLE.31 Anti-dsDNA antibody
levels are elevated in patients with SLE and muscu-
loskeletal and antiphospholipid manifestations. The
binding of maternal anti-Ro/anti-SS-A and anti-La/
anti-SS-B antibodies to fetal cardiac tissue can cause
congenital heart block.32
Prevalence, Incidence, and Risk Factors
The highest estimated incidence of SLE was found
to be in North America at 23.2 per 100,000 person-
years, with a lower incidence in Africa at 0.3 per
100,000 person-years.33 In the United States, SLE has
been estimated to affect approximately 161,000 to
322,000 individuals between ages 15 to 64 years.34
Black individuals have the highest incidence, fol-
lowed by Hispanic, Asian, and white individuals.33
SLE affects women more than men, with a 9:1 female
to male ratio, and a higher incidence is seen in women
in their reproductive years.31
A family history of SLE is a known risk factor.35
Environmental associations with SLE include exposure
to silica dust, smoking, and infection with Epstein-
Barr virus.36,37 There is a higher risk of SLE in women
49 years and younger who have undergone appendec-
tomy, although the causal link is unclear.38
Clinical Presentation
Common Nonmusculoskeletal Symptoms
Manifestations of SLE depend on the affected organ
systems. Fatigue and arthralgia are present in many
patients, and kidney disease is present in 50% of
patients.39,40 Other common nonmusculoskeletal symp-
toms are malar rash (31%), photosensitivity (23%),
pleuritic chest pain or pericarditis (16%), Raynaud
phenomenon (16%), and oral ulcers (12.5%).41
When to Suspect SLE
The American College of Rheumatology (ACR)
recommends that patients with presenting symp-
toms involving two or more of the following organ
systems be evaluated for SLE: constitutional, mus-
culoskeletal, integumentary, renal, neuropsychiatric,
hematologic, cardiac, pulmonary, gastrointestinal, or
reticuloendothelial.40
Case 2, cont’d. Given Tara’s concerns of fatigue,
arthralgia, myalgia, and rash, you ask about her family
history. She states that her mother has joint problems.
Tara says that sometimes her knuckles are red, swollen,

18

and painful. She says the facial rash appears in the shape
of a butterfly.
Diagnosis
Classification Criteria
In 1997, the ACR published revised clinical diag-
nostic criteria for SLE.42 In 2012, the Systemic Lupus
International Collaborating Clinics (SLICC) pub-
lished new SLE classification criteria (SLICC-12).43
Both of these sets of criteria include cutaneous mani-
festations, joint conditions, serositis, renal conditions,
hematologic conditions, and immunologic abnormali-
ties.44 The presence of four or more criteria is required
for SLE classification (Table 6).
Compared with the 1997 ACR criteria, the SLICC-
12 criteria have been shown to have a higher sensi-
tivity (94.6% versus 89.6%) and similar specificity
(95.5% versus 98.1%) rates in adults. However, for
juvenile SLE, the ACR criteria have been found to
have a higher specificity (94.1% versus 82.1%).45
In 2019, the European League Against Rheumatism
(EULAR) and the ACR jointly published validated
classification criteria for SLE.46 The sensitivity of these
criteria is similar to that of the SLICC-12 (96.1%);
the specificity is similar to that of the 1997 ACR
criteria (93.4%).
Evaluation
Antinuclear antibody (ANA) is present in approxi-
mately 95% of patients with SLE.30 The 2019
EULAR/ACR classification criteria include ANA titer
of 1:80 or greater on HEp-2 cells or an equivalent
positive test at least once as an entry criterion.40,46
Patients with suspected SLE with a positive ANA
titer should undergo evaluation to include a urine
protein level, anti-Smith antibody test, anti-dsDNA
antibody test, complete blood count, C3 and C4,
anticardiolipin antibody test, anti-beta2-glycoprotein I
antibody test, and lupus coagulant test.46 The pres-
ence of anti-dsDNA antibodies, low complement, or
anti-Smith antibodies is highly predictive of SLE in
patients with clinical symptoms.30
Patients with SLE should undergo antiphospholipid
testing at baseline, particularly patients with histories
of adverse pregnancy outcomes or arterial or venous
thrombotic events.30
Case 2, cont’d. The antinuclear antibody test result is
positive at 1:80 titer, the anti-double-stranded DNA test
result is positive at 16 IU/mL, and the white blood cell
Section Two
count is 3,900/mm3L. Results for the thyroid-stimulating
hormone level, erythrocyte sedimentation rate, and other
serologic studies are normal. Based on the American Col-
lege of Rheumatology/European League Against Rheu-
matism classification criteria, you diagnose Tara with
systemic lupus erythematosus. Tara is worried about her
future plan to have children.
Management
Family Physician Role
Management of SLE begins with a clinical assess-
ment that includes the medical history, physical
examination, assessment of health status and quality of
life, and measurement of disease activity.30 These fac-
tors can be assessed via use of standardized tools such
as the Systemic Lupus Erythematosus Disease Activity
Index (SLEDAI) or the SLICC/ACR Damage Index
(SDI). Disease activity is classified as mild, moderate,
or severe for management planning.
Goals of management are improving long-term out-
comes, achieving remission, preventing tissue damage,
and improving quality of life.47 Disease activity should
be assessed at baseline and at follow-up visits.
Referral to a rheumatology subspecialist is recom-
mended to confirm the diagnosis and for ongoing
care, while the family physician continues to provide
overall care, including management of comorbidities.48
Cardiovascular risk factors, such as obesity, smoking,
hypertension, diabetes, and dyslipidemia, should be
assessed on diagnosis and periodically.
Pharmacotherapy
Hydroxychloroquine, at a dose not exceeding
5 mg/kg of body weight, is recommended for all
patients with SLE.47 It should be continued indefi-
nitely unless contraindicated or complications such as
retinal toxicity develop.
Although the prevalence of retinal toxicity typically
is low (ie, occurring in less than 2% of patients taking
an intermediate dosage within the first 10 years of
therapy), rates can increase beyond 10 years of use.49
An ophthalmologic examination is recommended
at baseline, after 5 years, and annually thereafter.47
Recommended management of skin manifestations
includes topical drugs, such as glucocorticoids and/or
calcineurin inhibitors. (SLE is an off-label use of some
glucocorticoids and calcineurin inhibitors.)
For long-term management, a glucocorticoid should
be prescribed at a dosage of less than 7.5 mg/day, and
19
Autoimmune Conditions

Table 6
Classification Criteria for SLE

Criteria ACR 1997 SLICC-12 Proposed EULAR/ACR

Sensitivity (%) 82.8 96.7 96.1

Specificity (%) 93.4 83.7
Criteria At least 4 of 11 criteria At least 4 criteria with at least
1 clinical and 1 immunologic
criteria or biopsy-confirmed
lupus nephritis and elevated
ANA or anti-dsDNA antibodies
Constitutional
Mucocutaneous Malar rash Acute cutaneous lupus
Discoid rash Chronic cutaneous lupus
Photosensitivity Oral ulcers
Oral ulcers Alopecia
Musculoskeletal Arthritis Synovitis involving two or more
joints
Serosal Pleuritis or pericarditis Pleurisy for >1 day, or pleural
effusion or rub, or pericardial
pain for >1 day, or pericardial
effusion or rub, or pericarditis
on ECG
Renal Persistent proteinuria >0.5 Urine protein to creatinine ratio
g/day or >3+, or cellular (or 24-hour urine protein) of 0.5
casts g/24 hours or red blood cell
casts
Neuropsychiatric Seizures or psychosis in Seizures, psychosis,
the absence of offending mononeuritis complex, myelitis,
drugs or known metabolic peripheral or cranial neuropathy,
abnormalities or acute confusional state
93.4
ANA titer 1:80 as entry
criterion
Clinical criteria are assigned
points (in parentheses
below), which are added to
obtain a score
Diagnosis is confirmed with
score of 10 points or more
Fever (2)
Alopecia (2)
Oral ulcers (2)
Subacute cutaneous or
discoid lupus (4)
Acute cutaneous lupus (6)
Either synovitis or tenderness
and at least 30 min of
morning stiffness in two or
more joints (6)
Acute pericarditis (6)
Pleural or pericardial effusion
(5)
Proteinuria >0.5 g/24 hours
(4)
Class II or V lupus nephritis (8)
Class III or IV lupus nephritis
(10)
Delirium (2)
Psychosis (3)
Seizure (5)

continued

the dose should be tapered and withdrawn when possi-
ble. For patients who do not improve with hydroxychlo-
roquine alone or in combination with a glucocorticoid,
initiation of immunosuppressive drugs (eg, methotrex-
ate, azathioprine, mycophenolate) can expedite tapering
of the glucocorticoid dosage. (This is an off-label use of
methotrexate, azathioprine, and mycophenolate.)
Immunosuppressive drugs can reduce disease activ-
ity in patients with moderate lupus, prevent or reduce
flares, and lower the risk of accrued damage due to
disease and corticosteroid use.30 The biologic belim-
umab (Benlysta) is a monoclonal antibody that targets
B cells, reducing their autoimmune potential.50 Use
of this drug can be considered in patients who do not

20
 Section Two

Table 6 (continued)
Classification Criteria for SLE

Criteria ACR 1997 SLICC-12 Proposed EULAR/ACR

Hematologic Hemolytic anemia, or Hemolytic anemia Autoimmune hemolysis (4)

leukopenia <4,000
cells/mm3 on 2 or more
occasions, or lymphopenia
<1,500 cells/mm3 on
2 or more occasions,
or thrombocytopenia
<100,000 cells/mm3 in
absence of offending drugs
Immunologic Abnormal ANA titer at any
time
Abnormal anti-dsDNA
antibody titer, or anti-Smith
antibody, or positive finding
of aPLs
Leukopenia <4,000 cells/mm3 or
lymphopenia <1,000 cells/mm3
Thrombocytopenia <100,000
cells/mm3
ANA level > laboratory reference
range
Anti-dsDNA > laboratory
reference range
Anti-Smith antibody
aPL antibody
Low complement (C3, C4, total
complement)
Direct Coombs test
Thrombocytopenia (4)
Leukopenia (3)
Anti-Smith or anti-dsDNA
antibody (6)
Low C3 and low C4 (4)
Low C3 or low C4 (3)
Anticardiolipin antibodies
or anti-beta2-glycoprotein
I antibodies or lupus
anticoagulant (2)

ACR = American College of Rheumatology; ANA = antinuclear antibody; aPL = antiphospholipid; dsDNA = double-stranded DNA;
ECG = electrocardiogram; EULAR = European League Against Rheumatism; SLE = systemic lupus erythematosus; SLICC = Systemic
Lupus International Collaborating Clinics.
Information from various sources.

improve with hydroxychloroquine and a glucocor-
ticoid.47 Belimumab or rituximab (Rituxan) can be
considered for patients with persistently active or flar-
ing extrarenal disease and organ-threatening refractory
disease. (This is an off-label use of rituximab.)
Table 7 summarizes pharmacotherapy options for
SLE.
Preconception and Pregnancy Care
Women with SLE have a greater risk of adverse
pregnancy outcomes than women in the general popu-
lation.32 Adverse pregnancy outcomes include fetal
mortality, neonatal mortality, preterm delivery, and
termination of pregnancy.51 SLE in women who are
pregnant or planning pregnancy should be comanaged
by SLE and obstetric subspecialists.48
These patients should be assessed with a medical
history, physical examination, and laboratory tests
before pregnancy, in each trimester, and when a flare
is suspected.48 Routine tests should include com-
plete blood count, kidney and liver function tests,
urinalysis, anti-dsDNA antibody, and complement in
each trimester.32
For pregnant women with previous or active lupus
nephritis (LN), the serum creatinine level and urine
protein to creatinine ratio should be measured every
4 to 6 weeks, or more frequently as indicated.48 Blood
pressure should be measured and urinalysis obtained
every 4 to 6 weeks until 28 weeks’ gestation, every 1
to 2 weeks until 36 weeks’ gestation, and then weekly
until delivery. Congenial heart block occurs in 1% to
2% of anti-Ro/anti-La antibodies-positive pregnancies.
Anti-Ro and anti-La antibodies should be measured
before pregnancy or during the first trimester.
For pregnant women with SLE, uterine and umbili-
cal Doppler studies should be performed during the
second or third trimester or during an SLE flare.48
Abnormal Doppler flow analysis may suggest fetal
hypoxemia.51
Hydroxychloroquine is indicated and should be
continued during pregnancy to prevent flares and
reduce the risk of neonatal lupus.32 Low-dose aspirin

21
Autoimmune Conditions

Table 7
EULAR SLE Management Recommendations

Treatment Recommendations/Comments

Adjunct treatment for all Recommend use of sun protection; vaccinations; exercise; smoking cessation; maintenance
patients with SLE of ideal body weight; control of blood pressure, lipid, and glucose levels; antiplatelets or
anticoagulants for patients with antiphospholipid antibodies
Antimalarials
Hydroxychloroquine Recommended indefinitely for mild, moderate, and severe SLE at a dose not exceeding
5 mg/kg/day; monitor for retinal toxicity: refer for eye examination at baseline, after 5 years,
and then annually
Glucocorticoids a Monitor for serious infection, hypertension, hyperglycemia, hyperlipidemia, osteoporosis
Prednisone or Can be used for mild, moderate, severe SLE
Methylprednisolone Mild to moderate SLE: 0.5 mg/kg/day PO or IM with gradual tapering
Severe SLE: pulsed methylprednisolone IV (250-1,000 mg/day for 1-3 days) for immediate
effect then taper to 0.5-0.7 mg/kg/day PO
Minimize daily prednisone dose to 7.5 mg/day for maintenance therapy and promptly
withdraw when possible
Immunosuppressive Monitor for myelosuppression, serious infection, and malignancy
Methotrexate a For patients not benefitting from hydroxychloroquine ± glucocorticoids in mild, moderate SLE
at a dose of 10-25 mg/week in 1-2 doses
Azathioprinea For patients not benefitting from hydroxychloroquine ± glucocorticoids in mild, moderate SLE
at a dose of 2-3 mg/kg/day in 2-3 doses; consider tapering to <2 mg/day in remission
Mycophenolatea For mild, moderate SLE at 1-2 g/day in 2 doses
For severe or organ-threatening disease 3 g/day in 2 doses
Cyclophosphamidea For severe SLE at 0.75-1 mg/m2 body surface area per month for 6 months
Biologics Monitor for serious infection
Belimumab For moderate SLE with inadequate control with hydroxychloroquine ± glucocorticoids; 10 mg/
kg IV on weeks 0, 2, 4, then every 4 weeks or 200 mg/week subcutaneously
Rituximaba For severe organ-threatening SLE refractory to immunosuppressives
Calcineurin inhibitors Monitor serum creatinine and blood levels of calcineurin inhibitors to prevent drug toxicity
Cyclosporine A a Second-line drug for moderate SLE in lupus nephritis and refractory nephrotic syndrome at
dose of 1-3 mg/kg/day or 100-400 mg/day in 2 doses
Tacrolimusa Second-line drug for moderate SLE in lupus nephritis and refractory nephrotic syndrome at a
dose of 0.05-0.1 mg/kg/day or 2-4 mg/day in 2 doses
Treatment target
Treat to remission or Remission: SLEDAI = 0, hydroxychloroquine, no glucocorticoids
low disease activity Low disease activity: SLEDAI 3 on antimalarials or SLEDAI 4, PGA 1, with prednisone 7.5
mg/day, immunosuppressant in stable dose and well tolerated

a This is an off-label use of this drug or some drugs in this class.

EULAR = European League Against Rheumatism; IM = intramuscular; IV = intravenous; PGA = physician global assessment;
PO = oral; SLE = systemic lupus erythematosus; SLEDAI = Systemic Lupus Erythematosus Disease Activity Index.
Information from Fanouriakis A, Kostopoulou M, Alunno A, et al. 2019 update of the EULAR recommendations for the management
of systemic lupus erythematosus. Ann Rheum Dis. 2019;78(6):736-745; Clinical Pharmacology. Available at https://www.clinicalkey.
com/pharmacology/.

22

is recommended for pregnant patients with SLE who
are at risk of pulmonary embolism, and particularly
for patients with LN and antiphospholipid antibodies.
Low-dose prednisone (ie, 5-10 mg/day) can be used
during pregnancy if indicated.
Nonsteroidal anti-inflammatory drugs can be used
for less than 1 week for active disease during the first
and second trimesters.32 Their use should be avoided
around the time of conception because of implanta-
tion interference and in the third trimester because of
risk of premature closure of the ductus arteriosus and
oligohydramnios. Azathioprine and tacrolimus can be
used safely in pregnant kidney transplant recipients.
Lifestyle Modification and Integrative Medicine
Patients with SLE who smoke should be coun-
seled to quit because of the risk of skin damage and
increased disease activity.52 Patients with stable SLE
should be advised to consume a diet rich in polyun-
saturated fatty acids and to exercise.
These patients should be counseled on recom-
mendations for prevention and wellness, including
use of broad-spectrum sunscreen and other types of
sun protection; receiving appropriate vaccinations;
maintaining ideal body weight; and optimizing blood
pressure, lipid, and glucose levels.47,48 Patients with
SLE are at risk of vitamin D deficiency because of
photosensitivity and frequent use of sun protection
measures.53 Therefore, assessment of the vitamin D
level and recommendation of adequate supplementa-
tion are suggested.
There is limited evidence for the use of integrative
medicine in patients with SLE. A retrospective cohort
study showed that the combination of conventional
management (eg, nonsteroidal anti-inflammatory
drugs, glucocorticoids, antimalarial drugs, immunosup-
pressive drugs) with traditional Chinese medicine was
associated with reduced risk of death.54 Another ret-
rospective cohort study found that integrative therapy
that combined conventional management and herbal
medicine was associated with a reduced risk of LN.55
Prognosis and Complications
Progression
Systemic lupus erythematosus is associated with
frequent recurrences and remissions, which result in
considerable morbidity and mortality due to disease
flares and accumulated tissue damage.30 The rate of
SLE-associated death has decreased due to advances
Section Two
in management that have led to improved outcomes,
earlier diagnosis, and more effective management of
specific organ complications, particularly LN.56
Complications and Comorbidities
Patients with SLE have a 5 times greater risk of
mortality compared with patients in the general popu-
lation, primarily because of comorbidities.56 Deaths
occur from infection, cardiovascular disease, kidney
disease, osteoporosis, and malignancy (particularly
lymphoma, lung cancer, and hepatobiliary cancer).
End-stage renal disease is common in patients with
SLE.57 These patients have an increased risk of respira-
tory failure regardless of age, sex, and preexisting comor-
bidities.58 Long-term damage from SLE frequently
involves these systems: musculoskeletal (11.7%), neuro-
psychiatric (6.8%), renal (5.4%), cardiovascular (4%),
pulmonary (2.9%), skin (1.7%), peripheral vascular
(1.4%), and gastrointestinal (0.4%).59
Complications From Undiagnosed,
Unmanaged, and Poorly Controlled SLE
Organ damage from SLE accumulates over time
because of disease activity, comorbidities, and adverse
effects of drug treatment.59
Patients with undiagnosed, unmanaged, and poorly
controlled SLE can present with many complica-
tions. The majority of SLE patients starts to accrue
damage in the early disease stage.59 In severe SLE,
including LN and neuropsychiatric symptoms, it
is important to exclude other etiologies, including
infections, because pharmacotherapy may involve
immunosuppressants.30
Pharmacotherapy is dependent on the presentation,
but typically involves immunosuppressants, including
prednisone.30 Belimumab or rituximab can be con-
sidered if patients do not benefit from other immu-
nosuppressive drugs. Intravenous immunoglobulin
or plasmapheresis may be needed for patients with
Systemic lupus erythematosus is asso-
ciated with frequent recurrences and
remissions, which result in consider-
able morbidity and mortality due to
disease flares and accumulated tissue
damage.
23
Autoimmune Conditions
refractory cytopenia, thrombocytopenic purpura, or
rapidly deteriorating mental status.
Complications From Immunosuppressive
Therapy
The symptom reduction and quality of life
improvement achieved with immunosuppressive
therapy must be balanced against the increased risks
of infection and cytopenias.30 Monitoring for infec-
tion, cancer screening, and vaccination are recom-
mended.30,40 Close monitoring of immunosuppressives
should be done based on drug monitoring guide-
lines.30 For azathioprine, a complete blood count and
liver function tests should be obtained at baseline,
every 1 to 2 weeks at initiation of immunosuppressive
therapy, then 1 to 3 months thereafter.40
Patients with chronic kidney disease undergo-
ing long-term immunosuppressive therapy should
24
receive the pneumococcal 13-valent conjugate vaccine
(PVC13 [Prevnar 13]) followed by the pneumococcal
23-valent polysaccharide vaccine (PPSV23 [Pneu-
movax 23]). Live vaccines should not be administered
to patients receiving biologic immunosuppressive
therapy or more than 20 mg/day of prednisone, and
should be delayed for at least 1 month after comple-
tion of therapy.40,47,60
Case 2, cont’d. You refer Tara to a rheumatology
subspecialist who confirms the diagnosis of systemic
lupus erythematosus. Tara starts hydroxychloroquine
5 mg/kg/day and low-dose prednisone. She is referred to
an ophthalmology subspecialist for a baseline eye exami-
nation. You advise Tara to wear sunscreen, and the rash
improves in 1 month. Tara tells you she is considering
pregnancy in the next 1 to 2 years. You tell her that any
future pregnancies will be comanaged with an obstetrics
subspecialist.
 SECTION THREE
Polymyalgia Rheumatica and Dermatomyositis

Polymyalgia rheumatica (PMR) is a chronic systemic inflammatory disease that is common in individu-
als older than 70 years. Classic symptoms of PMR include pain in the neck, pelvic girdle, and shoul-
ders. Morning stiffness that lasts at least 30 minutes is typical. Glucocorticoids are the mainstay of PMR
management, and prednisone 12.5 to 25 mg/day or equivalent is recommended. Giant cell arteritis is a
comorbidity of PMR. Dermatomyositis is a rare, idiopathic inflammatory myopathy characterized by
erythematous skin lesions and inflammation of skeletal muscles. Dermatomyositis manifests as proximal
muscle weakness and fatigue that occurs when patients rise from a seated position, walk, climb stairs, or
lift objects. It is a systemic condition and also may affect joints, the esophagus, and lungs. Prednisone is
started at a dose of 60 mg/day and then tapered slowly, based on response, to prevent recurrence. Derma-
tomyositis may be associated with malignancy.

Case 3. Shirley is a 68-year-old woman, who comes to
your office reporting stiffness and pain in the shoulders
and hips, and decreased movement in these joints for
approximately 2 weeks. She also has had general weak-
ness, decreased appetite, and weight loss over the past
few months.
Polymyalgia Rheumatica
Prevalence, Incidence, and Risk Factors
Polymyalgia rheumatica (PMR) is a chronic sys-
temic inflammatory disease characterized by stiffness
of the proximal large joints.61,62 It is common in indi-
viduals older than 70 years, and age 50 years or older
is a diagnostic criterion. Approximately 65% to 75%
of cases occur in women.63
Pathophysiology and Etiology
Polymyalgia rheumatica is an autoimmune condi-
tion resulting in synovitis and bursitis. T cells, mac-
rophages, and proinflammatory cytokines have been
implicated, though the exact underlying mechanism of
disease is unclear.61
Presentation
Classic symptoms of PMR include pain in the neck,
pelvic girdle, and shoulders.61 Morning stiffness that
lasts at least 30 minutes is typical. Stiffness may recur
after prolonged sitting or other periods of immobility.
Approximately 40% to 50% of patients have systemic
symptoms, including fever, fatigue, anorexia, and mal-
aise.62 These and other symptoms, such as carpal tunnel
syndrome and peripheral edema, may delay diagnosis.
PMR is associated with other autoimmune conditions,
such as rheumatoid arthritis and spondyloarthritis,
which can further complicate the presentation.64
Case 3, cont’d. On physical examination, Shirley has
mild tenderness on palpation of the shoulder joints and
muscles but normal muscle bulk and strength. She can
hardly lift her hands to a horizontal level, cannot move
them behind her head, and has difficulty rising from
a seated position. Laboratory test results show elevated
inflammatory parameters, erythrocyte sedimentation rate
(52 mm/h), and C-reactive protein level (2.4 mg/dL).
Test results are negative for rheumatoid factor, anticitrul-
linated protein, and antinuclear antibody, and normal
for the creatine kinase level. X-rays of the joints reveal
osteoarthritis with no erosions detected.
Classification Criteria
The European League Against Rheumatism
(EULAR) and the American College of Rheumatology
(ACR) have developed a set of classification criteria
to help distinguish PMR from other autoimmune
conditions (Table 8).64 Three of the nine criteria are
required: age 50 years or older, bilateral shoulder pain,
and abnormal C-reactive protein (CRP) level and/or
erythrocyte sedimentation rate (ESR).
Evaluation
An ESR or CRP level should be obtained for patients
50 years or older with bilateral shoulder aching. A
prospective cohort of 177 patients with PMR showed

25
Autoimmune Conditions

an ESR greater than 40 mm/h in all but

6% of patients at the time of diagnosis.65 Table 8
Approximately 1% of patients had a CRP EULAR/ACR Classification Criteria for PMR
level of 7.8 mg/dL or less at diagnosis.
If the ESR or CRP rate is elevated, the Required/
initial evaluation assesses for other auto- Criteria Points
immune conditions and for the safety of
initial therapy, which is systemic cortico- Patients 50 years Required
steroids.66 The 2015 EULAR/ACR man- Bilateral shoulder pain Required
agement guidelines recommend obtaining Abnormal ESR and/or CRP Required
rheumatoid factor and anticitrullinated
protein levels, as well as a complete blood Morning stiffness >45 minutes 2
count; blood glucose, creatinine, calcium, New hip pain or limited range of motion 1
and alkaline phosphatase levels; liver Ultrasonography findings in one shoulder and at 1
function tests; and dipstick urinalysis. least one hip (eg, synovitis, tenosynovitis, bursitis)
Depending on patient symptoms and
Ultrasonography findings in both shoulders (eg, 1
risk factors, creatine kinase, thyroid-stim- synovitis, tenosynovitis, bursitis)
ulating hormone, and vitamin D levels;
Absence of peripheral joint pain 1
protein electrophoresis; and antinuclear
antibody and antineutrophil cytoplasmic Absence of positive rheumatoid arthritis or anti-CCP 2
autoantibody tests may be considered.66 antibody serology
Musculoskeletal ultrasonography can
Scale can be used with or without ultrasound criteria.
help identify characteristic features of the
With ultrasonography, 5 criteria are 66% sensitive and 81% specific for PMR.
condition. Biceps tenosynovitis, subacro-
Without ultrasonography, 4 criteria are 68% sensitive and 78% specific for
mial or subdeltoid bursitis, trochanteric PMR.
bursitis, glenohumeral effusion, and ACR = American College of Rheumatology; CCP = cyclic citrullinated peptide;
hip joint effusion can be identified in CRP = C-reactive protein; ESR = erythrocyte sedimentation rate; EULAR =
patients with PMR.64 European League Against Rheumatism; PMR = polymyalgia rheumatica.
Adapted from Dasgupta B, Cimmino MA, Kremers HM, et al. 2012 provisional
Management classification criteria for polymyalgia rheumatica: a European League Against
Rheumatism/American College of Rheumatology collaborative initiative.
Management of PMR consists of symp- Arthritis Rheum. 2012;64(4):943-954.
tom control, monitoring of therapy, and
surveillance for associated conditions.
Symptom control. The EULAR/ACR manage- taking glucocorticoids, methotrexate at a dose of 7.5
ment guidelines recommend oral glucocorticoids as to 10 mg/week has been shown to be beneficial.66
the first-line therapy for PMR.66 (This is an off-label (This is an off-label use of methotrexate.)
use of some glucocorticoids.) The goal of manage- There is no evidence of benefit of tumor necrosis
ment is rapid response to steroid therapy, which is factor-alpha inhibitors in PMR.66 There is limited
defined as at least 75% global improvement in clinical evidence to support use of tocilizumab (Actemra), an
and laboratory test parameters within 1 week of start- interleukin 6 inhibitor, in giant cell arteritis (GCA),
ing oral glucocorticoid therapy.64 To optimize the but good-quality trials are lacking to support its use in
response and minimize the risk of relapse, the target PMR management.67 (This is an off-label use of tumor
dosage range is 12.5 to 25 mg/day of prednisone, or necrosis factor-alpha inhibitors and tocilizumab.)
the equivalent, in a single daily dose.66 Oral glucocorticoid dose tapering. Regardless of
One study showed that approximately 55% of the chosen initial dose, the oral steroid dosage should
patients had a complete response to oral glucocorti- be tapered to a target dosage of 10 mg/day within 4
coid therapy.64 For patients who do not benefit from to 8 weeks in patients who benefit from therapy.66
oral glucocorticoids, who have a high risk of recur- The dose can then be tapered by 1 mg every 4 weeks
rence, or who experience frequent recurrences while as long as the patient remains symptom free. At any

26

sign of recurrence, the dose should be increased to the
previous symptom-free dose for 4 to 8 weeks and then
tapering attempted again.
Monitoring for adverse effects of steroids. The
EULAR/ACR guidelines recommend follow-up visits
every 4 to 8 weeks for the first year of therapy, then
every 8 to 12 weeks.66
The EULAR guidelines on glucocorticoid therapy rec-
ommend that comorbidities, such as heart failure, lung
disease, diabetes, glaucoma, and dyslipidemia be consid-
ered before patients begin taking medium- or high-dose
steroids.68 These risk factors are associated with an
increased risk of adverse effects of steroid therapy.
Patients taking daily doses greater than 7.5 mg of
prednisone or the equivalent for at least 3 months
should take calcium and vitamin D supplements. All
patients should receive an individualized assessment
of osteoporosis risk, which may include dual-energy
x-ray absorptiometry screening or empiric bisphospho-
nate therapy.68 Women are more likely to experience
adverse effects of steroid therapy.66
Case 3 cont’d. Shirley meets the criteria required for a
diagnosis of polymyalgia rheumatica. Following the rec-
ommendations from the European League Against Rheu-
matism/American College of Rheumatology (EULAR/
ACR), you initiate treatment with the minimum effective
dose of oral prednisone (12.5 mg/day).
At 2-week follow-up, Shirley’s symptoms have
improved, with near complete resolution of symptoms
after 5 weeks. The prednisone dosage is tapered to
10 mg/day when remission is achieved at 8 weeks. You
continue to taper the dosage by 1 mg every 4 weeks, with-
out a recurrence noted over 12 months. You did not con-
sider oral methotrexate at dosages of 7.5 to 10 mg/week as
adjunctive treatment because Shirley does not have a high
risk of recurrence and is not experiencing adverse effects of
glucocorticoid therapy.
Comorbidities
Giant cell arteritis is a systemic inflammatory
vasculitis of the large and medium arteries.63 PMR
is a risk factor for GCA; up to 50% of patients with
GCA have or have had PMR. Common symptoms of
GCA include new-onset headache or new headache
type, which typically is subacute in duration.63 The
ESR tends to be markedly elevated. One study found a
mean ESR of 93 mm/h in patients with GCA.69
The ACR diagnostic criteria for GCA are shown in
Table 9. Pharmacotherapy for uncomplicated GCA
Section Three
consists of oral prednisone 40 to 60 mg/day.70 (This is
an off-label use of prednisone.)
Dermatomyositis
Description and Pathophysiology
Dermatomyositis is a systemic inflammatory condi-
tion characterized by skin symptoms and proximal
muscle weakness. It is seen most often in patients
older than 40 years and is approximately twice as com-
mon in women as in men. A variety of autoantibodies
are implicated, but how they contribute to the muscle
and skin symptoms of the disease is not completely
understood.71,72A juvenile dermatomyositis subtype
exists that is not discussed in this edition.
Presentation
Skin changes often are an initial manifestation of
dermatomyositis, although vague systemic manifes-
tations, such as arthralgia, weight loss, dysphagia,
dyspnea, and dysphonia, also are common.71,73,74
Gottron papules, which are pathognomonic for
dermatomyositis, are thickened red or purple plaques
or papules over the dorsal hands, particularly the
knuckles.71,73 Skin manifestations characteristic of
dermatomyositis include purple-pink periorbital rash
(heliotrope); erythematous macular rash over the neck,
chest (V sign), or upper back and shoulders (shawl
sign); periungual thickening and telangiectasias. Up to
6% of patients may not have skin signs.75
Table 9
ACR Criteria for Giant Cell Arteritis
Age 50 years at onset
New headache or new type of headache
Decreased pulsation or tenderness of temporal artery
ESR 50 mm/h
Abnormal temporal artery biopsy result
3 positive criteria have a sensitivity of 93.5% and a specific-
ity of 91.2% in identifying giant cell arteritis.
ACR = American College of Rheumatology; ESR = erythro-
cyte sedimentation rate.
Adapted from Hunder GG, Bloch DA, Michel BA, Stevens
MB, Arend WP, Calabrese LH, et al. The American College
of Rheumatology 1990 criteria for the classification of giant
cell arteritis. Arthritis Rheum. 1990;33(8):1125.
27
Autoimmune Conditions
Muscle involvement manifests as proximal muscle
weakness and fatigue, which patients may notice
when rising from a seated position, climbing stairs,
or lifting objects.73 As the disease progresses, patients
may notice weakness of the neck extensors, leading
to head drop. The pharyngeal muscles also may be
affected, causing dysphonia or dysphagia. Up to 20%
of patients may have skin signs but never develop
muscle weakness, a variant known as amyopathic
dermatomyositis.75
Diagnostic Evaluation
The 1975 Bohan and Peter criteria commonly are
used for diagnosis of dermatomyositis.76 They have
98% sensitivity and 55% specificity for definite and
probable dermatomyositis, respectively (Table 10).
The 2017 EULAR/ACR criteria can distinguish
among different types of myositis, including dermato-
myositis, in patients who meet criteria for idiopathic
inflammatory myopathy.
Approximately 80% of patients with dermatomyo-
sitis will have abnormal levels of muscle enzymes,77,78
including creatine kinase, aldolase, aspartate and
alanine aminotransferase, and lactate dehydrogenase.75
The degree of elevation of the muscle enzymes typi-
cally correlates with severity of clinical disease.
Patients with characteristic skin findings and muscle
weakness should undergo electromyogram and muscle
Table 10
Bohan and Peter Criteria for Diagnosis
of Dermatomyositis
Progressive symmetric muscle weakness
Elevated muscle enzyme levels
Abnormal EMG results
Abnormal muscle biopsy
Typical skin rash
Definite diagnosis: 3 muscle criteria + skin rash.
Probable diagnosis: 2 muscle criteria + skin rash.
Possible diagnosis: 1 muscle criterion + skin rash.
EMG = electromyogram.
Information from Bohan A, Peter JB. Polymyositis and
dermatomyositis (second of two parts). N Engl J Med.
1975;292(8):403-407; Dalakas MC, Hohlfeld R. Polymyositis
and dermatomyositis. Lancet. 2003;362(9388):971-982.
28
biopsy regardless of whether the serum study results
are normal.79,80 Magnetic resonance imaging study can
identify inflamed muscle to target for biopsy,77 which
may be useful if results of an initial biopsy were unre-
markable or the initial evaluation is inconclusive.
Autoantibody measurements may be useful for
assessing prognosis and disease typing but are not used
routinely for diagnosis.74 One subgroup of antibod-
ies targets RNA synthetase enzymes and may present
clinically as synthetase syndrome, a constellation of
symptoms, including dermatomyositis, Raynaud phe-
nomenon, and interstitial lung disease (ILD). Other
antibodies are associated with amyopathic dermato-
myositis and rapidly progressive ILD.
Management
Management of dermatomyositis consists of disease
control, monitoring for adverse effects of therapy, and
surveillance for associated comorbidities.
Disease control. Clinical control of disease is
measured by improvement in muscle strength and
ability to perform activities of daily living.77 Minimal,
moderate, and major improvement are defined as a
20%, 30%, and 50% improvement in symptoms from
baseline, respectively.81
Corticosteroids, typically prednisone, are the first-
line pharmacotherapy, despite a lack of randomized
trials.77 The recommended initial dosage is up to 80
mg/day. If symptoms improve, the dose can be tapered
after 3 to 4 weeks by 20% to 25% per month to a
maintenance dose of 5 to 10 mg.82 The dose should
be increased again if evidence of weakness or impaired
activities of daily living recur.77,78 (This is an off-label
use of some corticosteroids.)
One prospective case series found that the aver-
age duration of steroid therapy was 42.3 months.83
Another study showed that approximately 65% of
patients experienced at least one relapse during predni-
sone dose tapering. When other immunosuppressants
are started concurrently, the duration and dose of
steroid therapy has been shown to be shorter.82
Patients who do not experience significant improve-
ments within the first 3 months of therapy are
unlikely to benefit from steroids.82 These patients
should be considered for a trial of intravenous immu-
noglobulin. Methotrexate, azathioprine, rituximab,
and mycophenolate are all second-line therapies that
can be used alone or in conjunction with prednisone
or intravenous immunoglobulin. (This is an off-label

use of intravenous immunoglobulin, methotrexate,
azathioprine, rituximab, and mycophenolate.)
Cutaneous symptoms may improve with any of
these or with hydroxychloroquine.83,84,85 (This is an
off-label use of hydroxychloroquine.) Patients with
dermatomyositis may experience photosensitivity
and should use sun protection.84 Topical steroids or
calcineurin inhibitors also are options for management
of skin symptoms.83,84 (This is an off-label use of some
calcineurin inhibitors.)
Monitoring for adverse effects of steroids. As
previously discussed, patients should be assessed for
comorbidities that could increase the risk of adverse
effects of systemic steroids before starting medium- or
high-dose steroids.68
Comorbidities
Approximately 50% of patients with dermato-
myositis have ILD.85 Refractory, progressive ILD is
associated with amyopathic dermatomyositis. Patients
Section Three
should be assessed for respiratory conditions, and
symptoms of cough, dyspnea, or exertional intolerance
should prompt an evaluation for ILD.71
Dermatomyositis also is associated with malig-
nancy. One study showed that approximately 20% of
patients were diagnosed with cancer 3 years before or
after dermatomyositis diagnosis, and malignancy was
more common in men and patients with a history of
diabetes.86
Recent recommendations suggest use of autoan-
tibodies to guide cancer screening. Patients with
autoantibodies associated with a high risk of malig-
nancy should undergo aggressive, whole body imaging
in addition to age-appropriate and symptom-targeted
screening.87 Patients without these autoantibodies
should receive age-appropriate and symptom-targeted
screening and regular follow-up.
29
 SECTION FOUR
Ankylosing Spondylitis

Ankylosing spondylitis (AS) is a rare yet significant cause of back pain in young adults that often is over-
looked. AS should be suspected if symptoms of inflammatory back pain are present or if the patient has a
personal or family history of related conditions. X-rays are the initial imaging modality of choice. If suspi-
cion of AS remains high but no sacroiliitis is present on x-ray, an HLA-B27 test should be obtained. The
Assessment of SpondyloArthritis International Society (ASAS) criteria are helpful in the diagnosis of AS.
Continuous use of nonsteroidal anti-inflammatory drugs is the first-line therapy, followed by tumor necro-
sis factor-alpha inhibitors, followed by slow-acting antirheumatic drugs (eg, methotrexate). Patients also
should undergo physical therapy and, if applicable, should quit smoking and maintain a healthy weight.
Patients with AS are at increased risk of complications, such as spinal fracture. Other conditions associated
with AS include anterior uveitis, inflammatory bowel disease, and osteoporosis.

Case 4. Maurice is a 29-year-old man who comes
to your office as a new patient. He reports low back
pain that has been present for many years. He cannot
remember exactly when it began, but it has become more
bothersome in the past 3 months. The medical history is
unremarkable, but the family history shows that his father
has ulcerative colitis.
Ankylosing spondylitis (AS) is a chronic inflamma-
tory arthritis that primarily affects the axial skeleton,
sacroiliac joints, and entheses.88 AS may lead to signifi-
cant pain and impairment.
Spondyloarthritis (SpA) encompasses axial and
peripheral arthritides. Axial SpA can be classified as
with radiographic sacroiliitis or without radiographic
sacroiliitis. Peripheral SpA includes reactive arthritis,
psoriatic arthritis, SpA related to inflammatory bowel
disease, and undifferentiated SpA (Table 11).89,90
Hypotheses include abnormal peptide presentation to
immune cells causing an autoimmune inflammation
in the joints.91
Prevalence, Incidence, and Risk Factors
Ankylosing spondylitis has a prevalence of approxi-
mately 0.9% to 1.4% among US adults.90 The overall
prevalence of SpA in the United States is approxi-
mately 0.9%.92
Risk factors for developing AS include male sex,
HLA-B27 seropositivity, and a family history of AS.93
AS is more common in men than in women by at
least a 2:1 ratio, and some studies suggest the ratio is
significantly higher.88,93,94 However, one study showed
the rate of diagnosis in women had increased from
10% to 46% over a 30-year period, suggesting previ-
ous underdiagnosis in women.94

Pathophysiology Clinical Presentation

The pathophysiology of AS is unclear. AS involves
inflammation of the sacroiliac joints and spine.
Chronic inflammation causes changes in bone and
joint architecture, which leads to osteogenesis and
joint fusion.88,90 Fusion of the vertebrae results in the
characteristic bamboo spine of AS.88,91
The family of SpA conditions is associated with
HLA-B27.88 Approximately 90% to 95% of patients
with AS test positive for HLA-B27.88,91 However,
in the general population, 5% of patients who test
positive for HLA-B27 will develop AS.91 It is not well
understood how HLA-B27 causes arthritic changes.
The symptoms of AS are typical of inflammatory
back pain: insidious-onset dull pain, radiation to the
buttocks, worsening in the morning and with inactiv-
ity, and improving with activity.88,93,95
Patients with AS typically report back pain or stiff-
ness.96 Because back pain is common and the symp-
toms are relieved by nonsteroidal anti-inflammatory
drugs (NSAIDs), diagnosis may be delayed. On occa-
sion, patients will present with an associated condi-
tion, such as recurrent uveitis.
Case 4, cont’d. Maurice describes a dull pain that
worsens overnight and is relieved on arising in the

30
 Section Four

morning and with exercise. He takes ibuprofen and and physical examination are combined to reach a
notices significant relief. Physical examination shows diagnosis.88,89
decreased flexion of the lumbar spine. A thorough physical examination may help diagnose
patients with AS. The Assessment of SpondyloArthri-
Diagnostic Criteria tis International Society (ASAS) recommends use of
Physical Examination four instruments for assessing spinal mobility: lateral
There is no gold standard diagnostic test for AS. lumbar flexion, chest expansion, the modified Schober
Imaging and serologic test results, the medical history, test, and the occiput-to-wall distance.97
Lateral lumbar flexion is assessed with physical
examination, preferably with goniometry.97,98 Because
Table 11 of muscle spasm, the reduction in spinal mobility
Current and Classic Classifications of does not directly correlate to severity of ankyloses seen
Spondyloarthritis.* on x-ray.93 Chest expansion measures the difference
between full inspiration and full expiration at the level
Current classifications of the fourth intercostal space. Normal results depend
Axial spondyloarthritis on patient age and sex.98
With radiographic sacroiliitis The modified Schober test measures lumbar spine
Without radiographic sacroiliitis flexion.98,99 The patient stands erect, with the heels
Sacroiliitis on MRI together, and the clinician marks the spine at the
HLA-B27 positivity plus clinical criteria lumbosacral junction and 10 cm above. The patient
Peripheral spondyloarthritis then bends forward maximally with knees fully
With psoriasis extended and the distance between the two marks is
With inflammatory bowel disease (Crohn’s disease or
measured. A distance between the measurements of
ulcerative colitis) less than 4 cm indicates decreased mobility.98
With preceding infection The occiput-to-wall test measures kyphosis.100 In
Without psoriasis or inflammatory bowel disease or this test, the patient stands with the heels and back
preceding infection touching the wall, and the clinician measures the dis-
Classic classifications tance from the occiput to the wall.
Ankylosing spondylitis
Diagnostic Criteria
Reactive arthritis (infection-associated arthritis)
The ASAS published guidelines for the diagnosis of
Psoriatic spondyloarthritis
AS in 2009.99 The ASAS criteria are shown in Figure
Predominantly peripheral
1. These criteria have a sensitivity of 82.9% and a
Predominantly axial
specificity of 84.4%.101
Enteropathic spondyloarthritis (associated with The ASAS criteria can inform as to when to obtain
inflammatory bowel disease)
x-rays and test for HLA-B27.99 First, the patient
Predominantly peripheral
must have onset of back pain before age 45 years and
Predominantly axial
back pain lasting for 3 months or longer. Second, the
Juvenile-onset spondyloarthritis (enthesitis-related
juvenile idiopathic arthritis)
patient must have features of axial SpA as listed in
Figure 1. At least one feature of SpA is considered an
Undifferentiated spondyloarthritis
indication for x-rays to assess for sacroiliitis.
* Current classifications are adapted from the Assessment of
Radiographic sacroiliitis is graded using the New
SpondyloArthritis International Society (ASAS) by Rudwaleit York criteria. Under this criteria, sacroiliac joints are
et al.5,6 MRI denotes magnetic resonance imaging. graded from 0 to 4 with Grade 0 being normal, Grade
MRI = magnetic resonance imaging. 1 having blurred joint margins, Grade 2 showing min-
From N Engl J Med, Taurog JD, Chhabra A, Colbert RA. Anky- imal abnormalities, Grade 3 having partial ankylosis,
losing spondylitis and axial spondyloarthritis. 374(26):2564. and Grade 4 demonstrating complete ankylosis.102 If
Copyright © 2016 Massachusetts Medical Society. Reprinted
with permission from Massachusetts Medical Society. x-rays are positive for sacroiliitis (ie, grade 2 or greater
bilaterally or grade 3 to 4 unilaterally), the diagnosis

31
Autoimmune Conditions

of AS is confirmed.99 If x-rays are negative and the used continuously rather than on demand. No specific
patient has two or more axial SpA features, then an NSAID is recommended.103,104 (This is an off-label use
HLA-B27 test is indicated. If these results are positive, of some NSAIDs.)
a diagnosis of AS is confirmed.
HLA-B27 testing is not indi-
cated in patients with less than
two features of SpA because a Back pain for 3 months with
an onset at <45 years?
positive result will not confirm
the diagnosis.
Magnetic resonance imag- Yes No
ing study may be considered
if suspicion of AS remains and Sacroiliitis Consider other
HLA-B27 test results and x-rays on imaging? causes of back pain
are negative.93
Yes No
Management Options
and Prognosis
1 SpA feature?a Positive HLA-B27?
Case 4, cont’d. You obtain
x-rays, the results of which do
not show sacroiliitis. You subse- Yes No Yes No
quently obtain an HLA-B27 test,
the results of which are positive. Diagnosis of Consider 3 SpA features?a Consider
Given the positive HLA-B27 AS confirmed other causes other causes
of sacroiliitis of back pain
test result, symptoms of inflam-
matory back pain, a family Yes No

history of ulcerative colitis, and

improvement with nonsteroi- Diagnosis of Consider
AS confirmed other causes
dal anti-inflammatory drugs of back pain
(NSAIDs), Maurice meets the
Assessment of SpondyloArthritis
aSpA Features (See Box 2 Box 2
International Society (ASAS) for further definition) bAt least 4 out of 5 of the following: onset at <40 years,

criteria for ankylosing spondylitis Inflammatory back painb insidious onset, improvement with exercise, no improve-
(AS). You prescribe continuous Arthritisc ment with rest, pain at night that improves when getting
Enthesitis (heel)d up
NSAID therapy, which relieves Anterior uveitise cArthritis: diagnosed by a physician and currently pres-

the symptoms. Dactylitis ent or in the past

The American College of
Rheumatology (ACR), Spon-
dylitis Association of America
Psoriasis dEnthesitis: heel; past or present spontaneous pain or
Crohn disease or ulcerative tenderness at examination of the site of the insertion of
colitis the Achilles tendon or plantar fascia at the calcaneus
Good response to NSAIDsf eUveitis: past or present anterior uveitis; confirmed by

Family history of SpAg an ophthalmology subspecialist

(SAA), and Spondyloarthri- fPain is resolved or much improved 24-48 hours after a
HLA-B27
tis Research and Treatment Elevated CRP full dose of a NSAID
Network (SPARTAN) updated gPresence in first-degree or second-degree relatives

with any of the following: AS, psoriasis, acute uveitis,

guidelines for AS manage-
ment in 2019.103 Table 12 lists
recommended drugs for AS
management based on those
guidelines.
For patients with active
AS, NSAIDs are the first-line
drugs.103 NSAIDs should be
reactive arthritis, IBD
Figure 1. Algorithm to Diagnose AS
AS = ankylosing spondylitis; CRP = C-reactive protein; IBD = inflammatory bowel disease;
NSAID = nonsteroidal anti-inflammatory drug; SpA = spondyloarthritis.
Information from Rudwaleit M, van der Heijde D, Landewé R, et al. The development of Assess-
ment of SpondyloArthritis International Society classification criteria for axial spondyloarthritis
(part II): validation and final selection. Ann Rheum Dis. 2009;68(6):777-783.

32
 Section Four

Although not discussed in the AS recommenda- for prophylaxis of bleeding associated with NSAID
tions, the American Gastroenterological Association use if they are at high risk and will continue to take
(AGA) published a 2017 statement recommending NSAIDs.105 Factors that increase the risk of bleeding
that patients take long-term proton pump inhibitors include: age older than 60 years, medical history of

Table 12
Drugs for Ankylosing Spondylitis Management

Class Drug Dose Adverse Reactions Monitoring

NSAIDa GI irritation, bleeding, and CBC and kidney tests

ulcers; platelet inhibition; indicated annually
kidney impairment;
kidney failure
SAARD Sulfasalazinea 1 g every 12 hours Drug-induced lupus, CBC with differential and
hypersensitivity reaction, LFTs at baseline, then every
diarrhea 2 weeks for 3 months, then
every 3 months
Methotrexatea 7.5-25 mg/week PO/ Teratogenicity, stomatitis, Monitor CBC and complete
IM pulmonary fibrosis, metabolic panel every 2-3
hepatic fibrosis, months
myelosuppression
Leflunomidea 20 mg/day PO Hepatotoxicity, LFTs, CBC at baseline, then
myelosuppression, every month for 6 months,
pancytopenia, diarrhea, then every 2 months
hair discoloration
Apremilasta 30 mg 2 times/day Severe diarrhea and Creatinine at baseline and
vomiting, depression/ monitor for depression/
suicidal ideation behavior changes
TNFA Adalimumab 40 mg every 2 weeks Infections, reactivation Hepatitis B surface antigen
inhibitors subcutaneously of tuberculosis, and TB testing at baseline,
pancytopenia or other monitor for active hepatitis
Certolizumab 200 mg every 2 weeks hematologic conditions, B virus infection and active
subcutaneously exacerbation of TB signs and symptoms
Etanercept 50 mg/week demyelinating conditions
subcutaneously or heart failure, systemic
lupus erythematosus-
Golimumab 50 mg/month related autoantibodies
subcutaneously and clinical features,
severe allergic reaction,
Infliximab 3-5 mg/kg IV every 6 severe liver disease
weeks
IL-17 Ixekizumab 80 mg every 4 weeks Infections, inflammatory TB test at baseline, then
antagonists subcutaneously bowel disease, monitoring for active
neutropenia, TB signs and symptom
Secukinumab 150 mg every 4 weeks thrombocytopenia, during therapy and after
subcutaneously candidiasis discontinuation

This is an off-label use of this drug or some drugs in this class.

a

CBC = complete blood count; GI = gastrointestinal; IL = interleukin; IM = intramuscular; IV = intravenous; LFTs = liver function tests;
NSAID = nonsteroidal anti-inflammatory drug; PO = oral; SAARD = slow-acting antirheumatic drug; TB = tuberculosis; TNFA = tumor
necrosis factor-alpha.
Information from various sources.

33
Autoimmune Conditions
dyspepsia or peptic ulcers, cigarette smoking, alcohol
use, and known Helicobacter pylori infection.
If NSAIDs are not effective (ie, lack of benefit with
two different NSAIDs over 1 month or incomplete
response with at least 2 different NSAIDs over 2
months), a tumor necrosis factor (TNF)-alpha inhibi-
tor is recommended.103 If inflammatory bowel disease
or recurrent iritis is present, TNF inhibitor monoclo-
nal antibodies are preferred.
The risks of TNF-alpha inhibitors are significant.
Patients should be counseled on the risks and ben-
efits of TNF-alpha inhibitors;106 patients using them
often are comanaged with a rheumatology subspecial-
ist. Depending on clinical need and patient prefer-
ences, the risks may outweigh the benefits. However,
a Cochrane review showed no increase in rates of
serious adverse events with use of a TNF-alpha
inhibitor but did show an improvement in clinical
symptoms.106,107
The 2019 ACR management guidelines condition-
ally recommend use of slow-acting antirheumatic
drugs (SAARDs), including sulfasalazine, methotrex-
ate, or tofacitinib (Xeljanz), in patients with active AS
despite NSAID treatment.103,106 (This is an off-label
use of these SAARDs.) Sulfasalazine or methotrexate
should be considered only in patients with prominent
peripheral arthritis or when TNF-alpha inhibitors
are not available.103 If a patient has active AS despite
use of a TNF-alpha inhibitor, guidelines recommend
using secukinumab (Cosentyx) or Ixekizumab (Taltz)
instead of a different TNF-alpha inhibitor.
Use of systemic corticosteroids is not recom-
mended.103 Local corticosteroid injections into areas of
active sacroiliitis or enthesitis despite NSAID therapy
are acceptable.
Physical therapy is strongly recommended, specifi-
cally active (ie, supervised exercise) rather than passive
(eg, massage, heat) physical therapy.103 Both aquatic
and land-based exercise can be beneficial, but land-
based interventions are recommended conditionally
It is recommended patients maintain
a healthy weight. There is an associa-
tion between smoking and disease
activity, so use of tobacco should be
avoided.
34
because they are more accessible. Studies comparing
the most effective exercises are ongoing.108
After AS becomes stable, NSAIDs should be
changed from continuous to on-demand.103 If the AS
is stable with a TNF-alpha inhibitor and an NSAID,
or a TNF-alpha inhibitor and a SAARD, then the
TNF-alpha inhibitor should be continued alone.
Disease activity can be monitored with a validated
AS activity measure (eg, Bath Ankylosing Spondylitis
Disease Activity Index [BASDAI] or Bath Ankylos-
ing Spondylitis Functionality Index [BASFI]) as well
as periodic monitoring of C-reactive protein level or
erythrocyte sedimentation rate.103
All patients with AS should receive self-management
education and undergo evaluation for fall risk.103 Self-
management for patients with AS includes education
on medical management and strategies to cope with
the stress that may accompany the diagnosis.106,109 The
optimal strategies for teaching self-management are
under review.109
One study showed a relationship between low
vitamin D level and increased AS disease activity.110
No dietary approaches have proven beneficial in the
management of AS, although studies are ongoing.111 It
is recommended patients maintain a healthy weight.
There is an association between smoking and disease
activity, so use of tobacco should be avoided.89
Although AS is chronic and progressive, with man-
agement, most patients maintain function. However,
some studies have shown an overall decrease in life
expectancy with death related to spinal fracture, aor-
tic insufficiency, respiratory failure, or complications
of treatment.103,112
Associated Conditions
Case 4, cont’d. Maurice returns 1 year after the diagno-
sis of AS and reports a painful pink eye with light sensitiv-
ity. No discharge is present, but there is hyperemia around
the iris. You refer him to an ophthalmology subspecialist.
Several conditions are associated with AS. Between
30% and 40% of patients with AS will experience
anterior uveitis.90,94 Anterior uveitis is characterized by
unilateral eye pain, light sensitivity, decreased visual
acuity, and the characteristic ciliary flush.90 A patient
with known AS who is experiencing a painful red eye
should be referred promptly to an ophthalmology
subspecialist.
Approximately 10% to 25% of patients with AS
have psoriasis and 5% to 10% have inflammatory

bowel disease (IBD).94 Crohn disease is more common
than ulcerative colitis in these patients. No screening
test is needed for IBD but suspicion should remain
high if a patient experiences symptoms of IBD, such as
abdominal cramping, diarrhea, and hematochezia.103
The ACR conditionally recommends screening
patients with AS for osteopenia and osteoporosis with
dual-energy x-ray absorptiometry.103 Patients should
be screened for obstructive sleep apnea based on clini-
cal symptoms.113
Complications
Because the spinal column becomes rigid and fragile
in patients with AS, even small injuries can cause
fractures and concern for spinal cord injuries is high.93
Changes in back pain should prompt evaluation for
fracture, which may occur in up to 10% of patients.89,90
Section Four
Less than 10% of patients have cardiac conduction
defects.106 However, screening with routine electrocar-
diogram is not recommended.103
Screening with echocardiography for aortic regur-
gitation is controversial. The ACR guidelines recom-
mend against routine echocardiography, but a study of
187 patients with AS showed that aortic regurgitation
was present in 18% of patients.106,114 Because symp-
toms of aortic regurgitation may be subtle, an echocar-
diogram may be reasonable.114
Case 4 cont’d. The ophthalmology subspecialist diagno-
ses Maurice with anterior uveitis and provides appropri-
ate treatment. The AS is stable with continuous NSAID
use, so you change his prescription for an on-demand
NSAID. He continues to have good functional capacity
on follow-up.
35
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Suggested Reading
American College of Rheumatology Ad Hoc Committee on Sys-
temic Lupus Erythematosus Guidelines. Guidelines for referral
and management of systemic lupus erythematosus in adults.
Arthritis Rheum. 1999;42(9):1785-1796.
Fanouriakis A, Kostopoulou M, Alunno A, et al. 2019 update of
the EULAR recommendations for the management of systemic
lupus erythematosus. Ann Rheum Dis. 2019;78(6):736-745.
Gordon C, Amissah-Arthur MB, Gayed M, et al. The British Soci-
ety for Rheumatology guideline for the management of systemic
lupus erythematosus in adults. Rheumatology (Oxford). 2018;
57(1):e1-e45.
Harper GM, Lyons WL, Potter JF. Geriatrics Review Syllabus: A
Core Curriculum in Geriatric Medicine. 10th ed. American Geriat-
rics Society; 2019.
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Reuben D, Herr K, Pacala J, et al. Geriatrics at Your Fingertips.
21st ed. American Geriatrics Society; 2019.
Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College
of Rheumatology guideline for the treatment of rheumatoid arthri-
tis. Arthritis Care Res (Hoboken). 2016;68(1):1-26.
Smolen JS, Landewé R, Bijlsma J, et al. EULAR recommenda-
tions for the management of rheumatoid arthritis with synthetic
and biological disease-modifying antirheumatic drugs: 2016
update. Ann Rheum Dis. 2017;76(6):960-977.
Ward MM, Deodhar A, Akl EA, et al. American College of Rheu-
matology/Spondylitis Association of America/Spondyloarthritis
Research and Treatment Network 2015 recommendations for the
treatment of ankylosing spondylitis and nonradiographic axial
spondyloarthritis. Arthritis Rheumatol. 2016;68(2):282-298.

1. Which one of the following is the most common
autoimmune inflammatory arthritis?
❏ A. Ankylosing spondylitis.
❏ B. Lupus arthritis.
❏ C. Psoriatic arthritis.
❏ D. Rheumatoid arthritis.
2. Which one of the following environmental factors is
most strongly associated with rheumatoid arthritis
development?
❏ A. Air pollution.
❏ B. Occupational silica exposure.
❏ C. Tobacco exposure.
3. Which one of the following is part of the
recommended diagnostic evaluation of suspected
rheumatoid arthritis?
❏ A. Anticyclic citrullinated peptide.
❏ B. Joint ultrasonography.
❏ C. Magnetic resonance imaging study.
❏ D. Plain x-rays.
4. Which one of the following statements about the
management and prognosis of rheumatoid arthritis
is correct?
❏ A. Even with remission, life expectancy is
reduced.
❏ B. Management with tumor necrosis factor
inhibitors does not affect the risk of
cardiovascular disease.
❏ C. Remission is achieved in less than 50% of
patients.
❏ D. The management goal is disease remission.
5. Which one of the following drugs is recommended
as first-line treatment to induce remission in
rheumatoid arthritis?
❏ A. Leflunomide.
❏ B. Methotrexate.
❏ C. Prednisone.
❏ D. Sulfasalazine.
6. Which one of the following fetal consequences can
occur as a result of maternal anti- Ro/anti-SS-A
or anti-La/anti-SS-B autoantibodies in pregnant
patients with systemic lupus erythematosus?
❏ A. Congenital heart block.
❏ B. Interference with embryo implantation.
❏ C. Premature closure of the ductus arteriosus.
❏ D. Oligohydramnios.
Posttest Questions
7. Which one of the following is true of the
epidemiology of systemic lupus erythematosus?
❏ A. It is more common in white individuals than in
black individuals.
❏ B. It is more common in Africa than in North
America.
❏ C. Smoking is an environmental risk factor.
❏ D. There is a higher incidence among
postmenopausal women.
8. Which one of the following is true of serum
testing in patients with suspected systemic lupus
erythematosus (SLE)?
❏ A. A positive antinuclear antibody (ANA) titer
does not require further testing.
❏ B. An elevated complement level is highly
predictive of SLE.
❏ C. Antiphospholipid testing is indicated only if
there is a history of venous thrombotic events.
❏ D. Approximately 95% of patients with SLE will
have a positive ANA titer.
9. Which one of the following drugs is recommended
for all patients with systemic lupus erythematosus?
❏ A. Azathioprine.
❏ B. Hydroxychloroquine.
❏ C. Methotrexate.
❏ D. Mycophenolate.
10. Which one of the following is true of belimumab for
systemic lupus erythematosus?
❏ A. It can be considered in patients with organ-
threatening refractory disease.
❏ B. It can be used as first-line treatment for some
patients.
❏ C. It reduces the immune potential of T cells.
❏ D. It should not be used in patients who were
taking glucocorticoids.
11. Which one of the following is true of polymyalgia
rheumatica?
❏ A. C-reactive protein levels will be normal.
❏ B. It is characterized by pain and stiffness of the
neck and shoulders.
❏ C. It typically is not associated with other
autoimmune conditions.
❏ D. Less than 50% of cases are in women.
41
Autoimmune Conditions

12. Which one of the following studies should be
obtained first in patients who are being evaluated
for polymyalgia rheumatica?
❏ A. Anticyclic citrullinated peptide.
❏ B. Antineutrophil cytoplasmic autoantibody.
❏ C. Antinuclear antibody.
❏ D. Erythrocyte sedimentation rate.
13. Which one of the following drugs is recommended
for polymyalgia rheumatica for patients who do not
benefit from prednisone?
❏ A. Belimumab.
❏ B. Infliximab.
❏ C. Methotrexate.
❏ D. Tocilizumab.
14. Which one of the following is considered
pathognomonic for dermatomyositis?
❏ A. Gottron papules.
❏ B. Heliotrope rash.
❏ C. Shawl sign.
❏ D. V sign.
15. Which one of the following treatments should be
considered next for patients with dermatomyositis
who do not improve after initial treatment with
corticosteroids?
❏ A. Azathioprine.
❏ B. Intravenous immunoglobulin.
❏ C. Methotrexate.
❏ D. Rituximab.
17. Which one of the following factors is an indicator of
ankylosing spondylitis?
❏ A. Acute onset of back symptoms.
❏ B. Age older than 50 years.
❏ C. Female sex.
❏ D. Relief of back pain with activity.
18. Which one of the following is a first-line treatment
for active ankylosing spondylitis?
❏ A. Nonsteroidal anti-inflammatory drugs.
❏ B. Slow-acting antirheumatic drugs.
❏ C. Tumor necrosis factor-alpha inhibitors.
19. Which one of the following adjunct treatments is
most strongly recommended if first-line treatment
does not adequately control symptoms in active
ankylosing spondylitis?
❏ A. Local corticosteroid injections.
❏ B. Physical therapy.
❏ C. Systemic corticosteroids.
❏ D. Water-based exercise.
20. Patients with ankylosing spondylitis most
commonly experience which one of the following
comorbidities?
❏ A. Anterior uveitis.
❏ B. Crohn disease.
❏ C. Psoriasis.
❏ D. Ulcerative colitis.

16. Which one of the following reflects the percentage

of individuals with the HLA-B27 haplotype who have
ankylosing spondylitis?
❏ A. 5%.
❏ B. 25%.
❏ C. 50%.
❏ D. 75%.
❏ E. 90%.

42
The next edition of AAFP FP Essentials™ will be:

Mental Disorders