2 . Which of the following is a systemic autoimmune disease?
A)
Thyroiditis
B)
Type 1 diabetes
C)
Sjögren syndrome
D)
Inflammatory bowel disease
OVERVIEW OF AUTOIMMUNE DISEASES
In organ-specific diseases, such as thyroiditis, type 1
diabetes, inflammatory bowel disease, or multiple sclerosis, a normal immune response is
misdirected against a self-antigen or organ, and inflammation and production of
autoantibodies are usually confined to antigens specific to the target organ [31]. Multiple organs are targets in systemic
autoimmune diseases, such as systemic lupus, Sjögren syndrome, or systemic sclerosis. In
these types of autoimmune diseases, autoantibodies are directed to different autoantigens,
typically resulting in chronic activation of innate and adaptive immune cells and an array
of clinical manifestations [31]. Some
autoimmune diseases are characterized by an organ-specific immune process but are systemic
because they also involve autoantibodies to autoantigens outside of a specific organ. For
example, rheumatoid arthritis is primarily a joint-selective disease, but other
autoantibodies can cause extra-articular manifestations [31].
3 . Which of the following statements regarding the pathogenesis of autoimmune diseases is TRUE?
A)
Some level of autoimmunity is present in all individuals.
B)
Autoantibodies circulate only after the onset of symptoms.
C)
Immune complexes are associated with organ-specific autoimmune diseases.
D)
The detection of an autoantibody indicates the presence of an autoimmune disease.
OVERVIEW OF AUTOIMMUNE DISEASES
In organ-specific diseases, such as thyroiditis, type 1
diabetes, inflammatory bowel disease, or multiple sclerosis, a normal immune response is
misdirected against a self-antigen or organ, and inflammation and production of
autoantibodies are usually confined to antigens specific to the target organ [31]. Multiple organs are targets in systemic
autoimmune diseases, such as systemic lupus, Sjögren syndrome, or systemic sclerosis. In
these types of autoimmune diseases, autoantibodies are directed to different autoantigens,
typically resulting in chronic activation of innate and adaptive immune cells and an array
of clinical manifestations [31]. Some
autoimmune diseases are characterized by an organ-specific immune process but are systemic
because they also involve autoantibodies to autoantigens outside of a specific organ. For
example, rheumatoid arthritis is primarily a joint-selective disease, but other
autoantibodies can cause extra-articular manifestations [31].
Organ-specific autoimmune diseases differ according to
whether disease is mediated primarily though autoantibodies, autoreactive T cells, or a
combination of the two [31]. Systemic
autoimmune diseases may be categorized according to the prevailing character of the
autoimmune response as cell-mediated, autoantibody-mediated, or immune complex disease.
T-cell or B-cell activation causes tissue damage directly by binding to cell-surface
autoantigens, or indirectly by forming antibody-antigen complexes that become deposited in
tissues. The autoimmune inflammatory process often becomes self-perpetuating, as tissue
damage leads to the release of cytokines, activated T cells, and additional self-antigens,
thereby stimulating and augmenting the immune response.
4 . Studies with monozygotic twins have shown that the highest concordance rate is associated with
A)
celiac disease.
B)
systemic lupus.
C)
Graves disease.
D)
rheumatoid arthritis.
OVERVIEW OF AUTOIMMUNE DISEASES
Studies with monozygotic twins have been done to determine
the genetic basis for many autoimmune diseases. Reported concordance rates include 12% to
30% for rheumatoid arthritis, 25% to 57% for systemic lupus, 30% for multiple sclerosis,
30% to 50% for type 1 diabetes, 70% to 75% for celiac disease, and up to 80% for Graves
disease [22,30,37,38]. The concordance
rate does not reach 100% for any autoimmune disease, which means that factors other than
genetics must have a role in the pathogenesis [31].
5 . The strongest evidence for a role of sex hormones as a pathogenic factor is associated with
A)
fibromyalgia.
B)
systemic lupus.
C)
multiple sclerosis.
D)
Sjögren syndrome.
OVERVIEW OF AUTOIMMUNE DISEASES
Sex hormones and their metabolites and receptors are
involved in immunoregulation and the development of autoreactivity through their roles in
lymphocyte maturation, activation, and synthesis of antibodies and cytokines [51]. Studies have shown that sex hormones are
a factor in the pathogenesis of autoimmunity and that the expression of sex hormones is
altered in individuals with autoimmune diseases [51]. Evidence for sex hormones as a causative factor is strongest for
systemic lupus because of its incidence trend (i.e., high after puberty and low after
menopause) and observed fluctuations in disease activity according to menstrual cycle and
pregnancy [51,52]. More research is needed to better
understand the role of sex hormones in autoimmunity and in specific autoimmune
diseases.
6 . Cigarette smoking has been found to be a potential trigger for the development of
A)
vitiligo.
B)
multiple sclerosis.
C)
rheumatoid arthritis.
D)
autoimmune hepatitis.
OVERVIEW OF AUTOIMMUNE DISEASES
Cigarette smoking and exposure to tobacco smoke has also
been found to be a potential trigger for autoimmune diseases, most notably rheumatic
diseases (rheumatoid arthritis and systemic lupus) and, to a lesser degree, thyroiditis
[53,54]. The exact mechanisms behind the influence of cigarette smoking on the
pathogenesis of autoimmune diseases are uncertain [31,53].
7 . A diagnosis of an autoimmune disease or fibromyalgia typically takes
A)
2 to 4 months.
B)
5 to 10 months.
C)
1 to 2 years.
D)
2 to 5 years.
OVERVIEW OF AUTOIMMUNE DISEASES
Evidence of the difficulty in diagnosing autoimmune
diseases is demonstrated in the results of surveys that have shown that individuals
consult an average of 4 (and as many as 13) healthcare providers, typically over two to
five years, before a confident diagnosis is reached [10,49,310]. There are several reasons for the
difficulty. First, the initial symptoms are often subtle, nonspecific, and intermittent
until the disease enters the acute stage. Symptoms can also affect many body organs,
making it difficult for specialists in one area to recognize a disease within another
specialty area. In addition, because many individual autoimmune diseases are rare, a
primary care clinician may be unfamiliar with the clinical manifestations of each disease.
Lastly, for the most part these diseases lack a single distinguishing feature or specific
laboratory diagnostic test; clinicians must rely on varying combinations of information
gathered from the history, physical examination, and laboratory and imaging studies [6,60,61,62,64]. Diagnostic criteria have been developed to aid in the diagnosis of
some autoimmune diseases.
8 . Autoimmune diseases affecting what area(s) have generally been associated with higher rates of co-occurrence of other autoimmune diseases?
A)
Thyroid glands
B)
Connective tissue
C)
Endocrine system
D)
Gastrointestinal tract
OVERVIEW OF AUTOIMMUNE DISEASES
Other studies have indicated an increased risk of type 1
diabetes and ulcerative colitis among persons with multiple sclerosis, and an increased
risk of rheumatoid arthritis, multiple sclerosis, and a combined category of six other
diseases (Addison disease, hemolytic anemia, primary biliary cirrhosis, immune
thrombocytopenia purpura, Sjögren syndrome, and systemic sclerosis) among persons with
inflammatory bowel disease [66]. In
approximately 60% of individuals with Sjögren syndrome, the syndrome is secondary to
another autoimmune disease, most commonly rheumatoid arthritis, systemic lupus, or
systemic sclerosis [67]. Celiac disease
has been associated with the co-occurrence of several autoimmune diseases, most notably
Sjögren syndrome and type 1 diabetes [22,68]. Autoimmune diseases of
connective tissue have generally been associated with higher rates of co-occurrence of
other autoimmune diseases [69].
Higher-than-expected rates of fibromyalgia have also been found in individuals with
autoimmune diseases, most notably systemic lupus, rheumatoid arthritis, thyroiditis, and
Sjögren syndrome [17,25,70,71,72].
9 . Which of the following is NOT a predictor of limited health literacy?
A)
Male gender
B)
Socioeconomic status
C)
Low level of education
D)
Poor self-rated reading ability
OVERVIEW OF AUTOIMMUNE DISEASES
Knowledge of the patient's health literacy is also
important, as the patient's understanding of his or her disease and its management is
essential to ensuring adherence to the treatment plan and the patient's role in
self-management. Yet most individuals lack adequate health literacy. According to the
National Assessment of Health Literacy, 14% of individuals in the United States have "below
basic" health literacy, which means they lack the ability to understand health information
and make informed health decisions [73,98]. A systematic review of more than 300
studies showed that an estimated 26% of patients had inadequate literacy and an additional
20% had marginal literacy [99]. Health
literacy varies widely according to race/ethnicity, level of education, and gender, and
clinicians are often unaware of the literacy level of their patients [87,100]. Predictors of limited health literacy are poor self-rated reading
ability, low level of education, male gender, and nonwhite race [100,101]. Several instruments are available to test patients' literacy levels,
and they vary in the amount of time needed to administer and in their reliability in
identifying low literacy [73,87,100,102].
10 . Among individuals with Graves disease, mild ophthalmopathy is present in as many as
A)
25% of cases.
B)
50% of cases.
C)
75% of cases.
D)
90% of cases.
THYROIDITIS
In Graves disease, circulating thyroid antibodies target the
TSH receptor, which stimulates the thyroid gland, causing enlargement of the thyroid gland and
increased production of thyroid hormone. As with Hashimoto disease, thyroid dysfunction with
Graves disease may be subclinical or overt. Mild ophthalmopathy is present in as many as half
of individuals with Graves disease, and severe ophthalmopathy occurs in 3% to 5% [50,105]. This ophthalmopathy is the result of edema and lymphocytic infiltration
of orbital fat, connective tissue, and eye muscles, and exophthalmos is the characteristic
sign of Graves disease [106]. If not treated,
overt hyperthyroidism can result in atrial fibrillation, congestive heart failure,
osteoporosis, and neuropsychiatric problems.
12 . The finding with the most clinical significance for the diagnosis of hypothyroidism is
A)
hair loss.
B)
weight loss.
C)
hypothyroid speech.
D)
enlarged thyroid gland.
THYROIDITIS
Hypothyroid speech—a low-pitched, hyponasal voice (as if
speaking with a cold), spoken at a slow pace—is found in about one-third of individuals with
hypothyroidism [106]. This speech is the
finding with the most clinical significance for diagnosis of hypothyroidism [106].
13 . Which of the following is among the most significant in ruling out hyperthyroidism?
A)
Coarse skin
B)
Cold intolerance
C)
Increased appetite
D)
Lack of fine finger tremor
THYROIDITIS
No single clinical finding, when absent, is significant for
ruling out hypothyroidism [106]. The lack of
thyroid enlargement, a pulse of less than 90 beats per minute, and the absence of finger
tremor are findings with the most significance in ruling out hyperthyroidism [106].
14 . Which of the following indicates subclinical hypothyroidism?
A)
Low TSH level with increased T3 and T4 levels
B)
Low TSH level and high thyroglobulin antibody titer
C)
Repeatedly high TSH level with normal free T4 and T3 levels
D)
Elevated TSH level with low levels of T3 and free T4
THYROIDITIS
Thyroid function tests can confirm a diagnosis of
Hashimoto thyroiditis or Graves disease. The single best screening test for either disease
is the sensitive TSH assay (also known as thyrotropin level), and the free thyroxine (T4)
level and the total triiodothyronine (T3) level also help confirm the diagnosis [113,115,316]. An elevated TSH
level with low levels of T3 and free T4 indicates hypothyroidism [108,113]. Subclinical hypothyroidism is indicated by a repeatedly high TSH
level with normal free T4 and T3 levels [108,113]. In contrast, a
low TSH level with increased T3 and T4 levels indicates hyperthyroidism [50]. The patient's history is important to
remember when interpreting the results of laboratory testing, as a low TSH level can also
be caused by glucocorticoids, dopaminergic drugs, severe illness, pregnancy, diurnal
variation, or pituitary dysfunction; elevated TSH levels may be caused by adrenal
insufficiency [113]. Thyroid
autoantibodies (i.e., thyroid peroxidase and thyroglobulin antibodies) may be helpful in
the diagnosis [113,316].
15 . Which of the following statements about radioactive iodine treatment for hyperthyroidism is TRUE?
A)
The cure rate is more than 80%.
B)
The risk for some types of cancer is decreased.
C)
A calculated dose is more effective than a fixed dose.
D)
Hypothyroidism generally occurs 8 to 10 months after treatment.
THYROIDITIS
The isotope is given orally (as a capsule or in water),
and there is no consensus on the optimal dose [127]. The dose is usually determined with a dose-calculation algorithm, and
the typical dose range is 5–15 mCi of 131I [115,127]. Randomized trials have shown no significant differences in outcome
between the use of calculated doses and fixed doses, and fixed doses are now used in many
institutions [128,129].
Treatment with antithyroid drugs may be indicated for some
individuals, particularly older individuals or those with cardiac disease, before
administration of 131I. Antithyroid drugs should be stopped one
week before treatment with radioactive iodine is begun and should not resume until
approximately six weeks after treatment.
The American Thyroid Association and the AACE recommend
that individuals be followed up within the first one to two months after treatment to
monitor the transition to a euthyroid and/or hypothyroid state [115]. Hypothyroidism can occur at any time
after treatment, but most commonly occurs within two to six months [50]. Treatment with partial replacement doses
of levothyroxine can usually begin two months after treatment. The timing of
thyroid-replacement treatment depends on the findings of laboratory testing and clinical
evaluation [115].
The cure rate for treatment with radioactive iodine is
more than 80% [130]. Retrospective studies
have shown that factors associated with a lack of response to
131I are a young age, a large thyroid, severe thyrotoxicosis,
previous exposure to antithyroid drugs, and a higher 131I
uptake value [131,132]. When necessary, a second dose should be
given at least 6 to 12 months after the initial treatment, and antithyroid drugs should be
stopped before and after a second treatment [127].
Treatment with 131I is safe,
with the primary side effects being acute radiation thyroiditis and hypothyroidism; there
is no adverse effect on fertility or on offspring conceived after treatment [50,115]. Radioactive iodine administration is the recommended modality for
women who wish to become pregnant four to six months after treatment. The findings of some
studies have suggested an increased risk for some types of cancer after treatment with
131I, but the results of other studies have demonstrated
conflicting data, with no increases in the incidence of cancer [133,134].
16 . Which of the following has been associated with a lack of response to treatment with radioactive iodine?
A)
Older age
B)
Small thyroid
C)
Lower radioactive iodine uptake
D)
Previous exposure to antithyroid drugs
THYROIDITIS
The cure rate for treatment with radioactive iodine is
more than 80% [130]. Retrospective studies
have shown that factors associated with a lack of response to
131I are a young age, a large thyroid, severe thyrotoxicosis,
previous exposure to antithyroid drugs, and a higher 131I
uptake value [131,132]. When necessary, a second dose should be
given at least 6 to 12 months after the initial treatment, and antithyroid drugs should be
stopped before and after a second treatment [127].
17 . Which of the following is a specific indication for thyroidectomy?
A)
Large goiter
B)
Severe ophthalmopathy
C)
Allergy or intolerance to antithyroid drugs
D)
All of the above
THYROIDITIS
Surgery was once frequently used to treat hyperthyroidism,
but it is now the least-used treatment option. The AACE and the American Thyroid
Association recommend that the specific indications for thyroidectomy are a large goiter,
especially with compressive symptoms (which may be resistant to radioactive iodine
treatment); severe ophthalmopathy (because of the risks associated with radioactive
iodine); or an allergy or intolerance to antithyroid drugs [115]. The primary advantage of thyroidectomy
is that it provides definitive treatment of hyperthyroidism with none of the hazards
associated with radioactive iodine, the other option with a good cure rate [127,138]. In addition, surgery offers a rapid normalization of thyroid function
[127]. Thyroidectomy usually results in
hypothyroidism, occurring in 12% to 80% of individuals during the first year and at a
subsequent annual rate of 1% to 3% [127].
is most often precipitated by a concurrent illness or injury.
D)
may occur following initiation of treatment with antithyroid drugs.
THYROIDITIS
A complication of Graves disease is thyroid storm, a
syndrome characterized by exaggerated signs and symptoms of hyperthyroidism accompanied by
fever and altered mental status. Thyroid storm is most often precipitated by a concurrent
illness or injury and may also occur following discontinuation of treatment with
antithyroid drugs or with radioactive iodine [115,142]. The diagnosis of
thyroid storm relies on clinical evaluation, as laboratory testing cannot distinguish
thyroid storm from uncomplicated hyperthyroidism [115]. Thyroid storm is a complex, life-threatening syndrome, and an
endocrinologist should be involved in the care. Individuals with thyroid storm should be
treated in the intensive care unit, with treatment consisting of an antithyroid drug, a
drug that inhibits release of thyroid hormone from the thyroid gland, and agents that
decrease the peripheral effects of thyroid hormone [115,142].
19 . The most common extra-articular manifestation of rheumatoid arthritis is
A)
pleuritis.
B)
neuropathy.
C)
dry eye syndrome.
D)
rheumatoid nodules.
RHEUMATOID ARTHRITIS
Pain and stiffness in multiple joints are the primary
characteristics of rheumatoid arthritis; approximately one-third of individuals with the
disease initially have pain in only one joint [156]. Other common symptoms of rheumatoid arthritis include fatigue,
weakness, generalized muscular aches, and anorexia [151]. Approximately 46% of individuals with rheumatoid arthritis have
extra-articular manifestations, the most common of which is rheumatoid nodules, followed by
pulmonary fibrosis, dry eye syndrome, and anemia of chronic disease [143,144,151]. Rheumatoid nodules
are soft, poorly delineated subcutaneous nodules, and they also occasionally affect internal
organs such as the pleura, sclera, vocal cords, and vertebral bodies [143,151]. Other frequently occurring extra-articular manifestations include
pericarditis, pleuritis, vasculitis, cervical myelopathy, and neuropathy [143]. No reliable predictors of extra-articular
manifestations have been identified, but they have been reported to be associated with male
gender, smoking, more severe joint disease, worse function, high levels of inflammatory
markers, and a positive rheumatoid factor and antinuclear antibody (ANA) titer [144].
20 . Which of the following joints is most commonly involved in rheumatoid arthritis?
A)
Knee
B)
Wrist
C)
Sacroiliac joints
D)
Distal interphalangeal joints
RHEUMATOID ARTHRITIS
The most commonly involved joints are the wrist joints and
the proximal interphalangeal and metacarpophalangeal joints; the distal interphalangeal
joints and sacroiliac joints are typically not affected [156]. Affected joints may become warm and tender after long periods of
inactivity, and joint symptoms are usually bilateral. Small joints of the hands and feet are
not usually painful at rest. Morning joint stiffness associated with rheumatoid arthritis
usually lasts more than one hour, in contrast to osteoarthritis, in which morning stiffness
usually resolves within 30 minutes after waking [157]. For most individuals, symptoms develop over a long period of time
(weeks to months); symptoms develop over days to weeks in approximately 15% of patients
[156].
In combination with methotrexate: Disease duration of less than 3
months, high disease activity, features of poor prognosis, and no previous
treatment with disease-modifying drugs
Alone: Inadequate response to methotrexate monotherapy AND disease
duration >3 months, moderate disease activity, and poor prognosis features
OR disease duration >3 months, high disease activity, with or without poor
prognosis features
Adalimumab: 40 mg SC every 2 weeks
Infusion reactions, increased risk of infection (especially
fungal)
Inadequate response to methotrexate-based combination or sequential
administration of other nonbiologic agents, moderate-to-high disease activity, and
features of poor prognosis
500–1,000 mg (depending on body weight) IV at weeks 0, 2, and 4, then every 4
weeks
In combination with methotrexate: Inadequate response to methotrexate-based
combination or sequential administration of other nonbiologic agents, high disease
activity, and features of poor prognosis
Moderately to severely active disease with an adequate response or
intolerance to one or more DMARDs
Do not use in combination with biologic DMARDs
200 mg SC every 2 weeks
Increased serum alanine aminotransferase, increased serum aspartate
aminotransferase, neutropenia, antibody development, erythema at injection
site
aDisease duration defined as short (less than
6 months), intermediate (6 to 24 months), or long (more than 24 months).
Degree of disease activity is defined according to scores on one of several
validated disease activity instruments; presence of poor prognosis features is
defined as functional limitation, extra-articular disease, positive rheumatoid
factor and/or positive anti-citrullinated protein antibody test, and/or
osseous erosions on radiograph.
bJAK inhibitors (tofacitinib, baricitinib,
and upadacitinib) should not be used in combination with other JAK inhibitors,
biologic DMARDs, or with potent immunosuppressants such as azathioprine and
cyclosporine.
22 . Which of the following disease-modifying antirheumatic drugs is generally considered to be the standard first-line treatment for rheumatoid arthritis?
A)
Infliximab
B)
Leflunomide
C)
Methotrexate
D)
Hydroxychloroquine
RHEUMATOID ARTHRITIS
Among the recommended nonbiologic agents are methotrexate,
generally considered to be the standard first-line treatment; the antimalarial drug
hydroxychloroquine; the JAK inhibitors tofacitinib, baricitinib, and upadacitinib; and
sulfasalazine and leflunomide, drugs developed specifically for rheumatoid arthritis [9]. The biologic agents include five
anti-TNF-α agents (adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab)
and three non-TNF-α agents, including abatacept, a selective costimulation modulator;
rituximab, an anti-CD20 monoclonal antibody that depletes B lymphocytes; and tocilizumab
and sarilumab, IL-6 receptor antagonists [9].
23 . Which nonpharmacologic therapy has high- quality evidence for improving function in individuals with rheumatoid arthritis?
A)
Splints
B)
Joint protection
C)
Assistive devices
D)
Transcutaneous electrical nerve stimulation
RHEUMATOID ARTHRITIS
Physical therapy and/or occupational therapy can help
individuals improve their ability to carry out activities of daily living at home, at
work, and socially [162]. In addition,
physical therapists can provide instruction in a program of range-of-motion and
strengthening exercises, in joint protection, and in ways to conserve energy. Evidence of
benefit from nonpharmacologic approaches is lacking, however. An overview of systematic
reviews found that there was unclear benefit (low quality of evidence) for most
nonpharmacologic therapies, including balneotherapy, electrical stimulation,
transcutaneous electrical nerve stimulation, assistive devices, and splints [183]. The exceptions were comprehensive
occupational therapy and joint protection, which were shown to improve function (with no
difference in pain) according to high-quality evidence, and low-level laser therapy, which
was shown to reduce pain and improve function according to evidence of moderate quality
[183].
24 . Which of the following preoperative factors is most important for postoperative outcome in rheumatoid arthritis?
A)
Age
B)
Gender
C)
Functional status
D)
Disease severity on radiographs
RHEUMATOID ARTHRITIS
The goals of surgical intervention for rheumatoid
arthritis are to restore function and quality of life, prevent further deterioration of
the joint, relieve pain, and correct deformity [185]. Surgery is reserved for patients who have structural joint damage
that causes high pain levels, loss of range of motion, or severely limited function
(severe disability and/or inability to work) despite pharmacologic and nonpharmacologic
therapy [334]. The challenge with surgical
treatment is that many joints are often involved; priority should be given to the joint
that causes the greatest disability and pain [185]. Among the options for surgical treatment are synovectomy, carpal
tunnel release, resection of the metatarsal heads, specialized hand surgery, arthrodesis,
and joint replacement [185]. The
preoperative functional status is an important factor in the postoperative outcome, making
early referral for surgery important [334].
25 . In regards to prognosis, the greatest risk for increased mortality among individuals with rheumatoid arthritis is associated with
A)
infection.
B)
diminished function.
C)
cardiovascular disease.
D)
extra-articular manifestations.
RHEUMATOID ARTHRITIS
Of all the autoimmune diseases, rheumatoid arthritis is a
leading cause of mortality, especially among women older than 65 years of age [27,28]. Studies have consistently shown higher rates of mortality for
individuals with rheumatoid arthritis than for the general population [192,193,194]. Furthermore, the
increasing survival rates documented for the population at large since the 1950s and 1960s
have not been found for individuals with rheumatoid arthritis [195]. The increased mortality has been linked
to several factors, including extra-articular manifestations, markers of disease severity,
and diminished function within the first year [193,194]. By far,
cardiovascular disease has been thought to confer the greatest risk for increased
mortality [193,194].
26 . Which of the following autoimmune diseases has been found most often in individuals with systemic lupus?
A)
Vitiligo
B)
Celiac disease
C)
Type 1 diabetes
D)
Rheumatoid arthritis
SYSTEMIC LUPUS ERYTHEMATOSUS
Other autoimmune diseases occur frequently in individuals
with systemic lupus. In one study, 41% of subjects with systemic lupus had at least one
other autoimmune disease and approximately 5% had two or more autoimmune diseases in
addition to systemic lupus [217]. Among the
most common autoimmune diseases in individuals with systemic lupus are thyroiditis,
rheumatoid arthritis, antiphospholipid antibody syndrome, and Sjögren syndrome; in addition,
fibromyalgia often co-occurs with systemic lupus.
27 . Which of the following is less likely to be a clinical manifestation of systemic lupus in an older individual compared to a younger individual?
A)
Fever
B)
Serositis
C)
Malar rash
D)
Dry eye syndrome
SYSTEMIC LUPUS ERYTHEMATOSUS
The clinical manifestations of systemic lupus often differ
among older individuals. Malar and discoid rash, photophobia, arthritis, and
glomerulonephritis are less common in the older population compared with the younger
population, whereas fever, serositis, dry eye syndrome, and lung disease are more common in
the older population [207].
28 . Which of the following essentially rules out a diagnosis of systemic lupus?
A)
Lack of a malar rash
B)
Positive anti-Ro antibody test
C)
Decreased serum complement levels
D)
Negative antinuclear antibody (ANA) titer
SYSTEMIC LUPUS ERYTHEMATOSUS
A positive ANA titer (>1.80 on Hep-2 cells or an
equivalent positive test) is required as diagnostic entry criterion. The ANA titer is
highly sensitive for systemic lupus, with a positive result in approximately 93% to 100%
of individuals with the disease [230,231]. However, the specificity is low, and a
positive titer will also be found in 60% to 80% of people with systemic sclerosis and 40%
to 70% of people with Sjögren syndrome, as well as in a substantial number of healthy
individuals [230]. After a patient has
tested positive, additive criteria may be considered. A negative ANA titer (less than
1:160 on standard substrate) essentially rules out a diagnosis of systemic lupus.
30 . Which of the following drugs may be used in pregnant women with systemic lupus?
A)
Azathioprine
B)
Methotrexate
C)
Cyclophosphamide
D)
Mycophenolate mofetil
SYSTEMIC LUPUS ERYTHEMATOSUS
Pregnancy in women with systemic lupus is associated with
risks for both the mother and the fetus, and pregnant women should be managed as high-risk
obstetric patients [75]. Pregnancy may
cause disease flares, especially in the third trimester and postnatal period, but flares
are usually mild and can be controlled without excessive risk to either the mother or the
fetus [75,233]. Many treatment agents may be used
during pregnancy, including hydroxychloroquine, prednisone, and azathioprine; evidence
suggests that mycophenolate mofetil, cyclophosphamide, and methotrexate should be avoided
[233]. Systemic lupus increases the risk
for fetal loss, especially in women who have antiphospholipid antibodies [75,233]. A history of lupus nephritis, antiphospholipid antibodies, and
anti-Ro and/or anti-La antibodies are associated with increased risk for pre-eclampsia,
miscarriage, stillbirth, premature delivery, intrauterine growth restriction, and fetal
congenital heart block [233]. Heparin and
aspirin are usually given throughout pregnancy to reduce the risk of miscarriage and
thrombotic events.
31 . Which of the following laboratory value changes often signals a systemic lupus flare?
A)
Increase in ESR and CRP level
B)
Increase in the serum complement levels
C)
Decrease in the anti-double-stranded DNA titer
D)
Increase in anti-double-stranded DNA titer and decrease in serum complement levels
SYSTEMIC LUPUS ERYTHEMATOSUS
Laboratory testing every 6 to 12 months should include
urinalysis, CBC, ESR, CRP, albumin, and creatinine levels [253]. Anti-double-stranded DNA titer and
serum complement levels should also be obtained, as an increase in the
anti-double-stranded DNA titer and decreases in the serum complement levels often signal a
disease flare [75,253]. As defined by an international panel of
experts, a flare is "a measurable increase in disease activity in one or more organ
systems involving new or worse clinical signs and symptoms and/or laboratory measurements.
It must be considered clinically significant by the assessor and usually there would be at
least consideration of a change or an increase in treatment" [256]. Early treatment with a glucocorticoid
may reduce the total dose needed to suppress the flare [75].
33 . Approximately 60% of cases of Sjögren syndrome are secondary to
A)
thyroiditis.
B)
fibromyalgia.
C)
type 1 diabetes.
D)
another autoimmune rheumatic disorder.
SJÖGREN SYNDROME
Approximately 60% of cases of Sjögren syndrome are secondary
to another autoimmune rheumatic disorder, such as systemic lupus, rheumatoid arthritis, or
scleroderma [67]. In addition, autoimmune
thyroiditis (and/or thyroid dysfunction) was found in 45% of individuals with Sjögren
syndrome in one study, and fibromyalgia was found in 22% [67].
34 . Which of the following is the most common extraglandular manifestation of Sjögren syndrome?
A)
Joint pain
B)
Lymphadenopathy
C)
Cutaneous vasculitis
D)
Raynaud phenomenon
SJÖGREN SYNDROME
Individuals with Sjögren syndrome may also have
extraglandular involvement; among the most common manifestations are joint pain and/or
swelling (37% to 75%), gastrointestinal symptoms (54%), pulmonary disease (e.g., chronic
cough, recurrent bronchitis, fibrosis) (29%), and Raynaud phenomenon (16% to 28%) [272,273]. Occurring less frequently are cutaneous vasculitis, lymphadenopathy,
and renal involvement (e.g., proteinuria, interstitial nephritis, glomerulonephritis) [272,273]. Peripheral neuropathies are often associated with Sjögren syndrome, and
the reported prevalence of this complication has ranged widely, from 10% to more than 60%
[226,274]. Cognitive dysfunction has been reported in about half of individuals
[226].
35 . In its guidelines, the AAO recommends which approach to the management of moderate dry eye associated with Sjögren syndrome?
A)
Pilocarpine
B)
Cevimeline
C)
Topical cyclosporine
D)
Artificial tear solutions with preservatives
SJÖGREN SYNDROME
In 2016, the first ever guidelines for the treatment of
Sjögren syndrome were published by the Sjögren's Syndrome Foundation (SSF). However, it was
noted that there are many unmet clinical needs in regard to treatment, and there is no cure
or remittive agent for Sjögren syndrome. Treatment goals are symptom palliation, prevention
of complications, and proper selection of patients for immunosuppressive therapy [58]. Treatment of dry eye involves patient
education regarding the nature of the problem and aggravating factors. Artificial tears have
been found effective to replace moisture, and a topical anti-inflammatory agent should be
used for moderate-to-severe symptoms. Preservative-free artificial tears have been better
tolerated than tear solutions with preservatives because of the irritation that can be
caused by frequent use of the latter type [58,67]. Randomized controlled trials have
shown that topical ocular cyclosporine (0.05%) significantly improves objective measures of
dry eye, blurred vision, and use of artificial tears in patients with moderate or severe dry
eye [278]. In its guidelines for dry eye,
the AAO includes topical cyclosporine as a level IA recommendation for moderate dry eye
[279].
36 . The autoimmune disease with the strongest association with celiac disease is
A)
Sjögren syndrome.
B)
rheumatoid arthritis.
C)
autoimmune hepatitis.
D)
primary biliary cirrhosis.
CELIAC DISEASE
Autoimmune diseases are 3 to 10 times more likely in
individuals with celiac disease than in the general population [341]. The strongest associations have been
found between celiac disease and Sjögren syndrome (4.5% to 14.7%), type 1 diabetes (1% to
12%), Addison disease (1.2% to 8%), primary biliary cirrhosis (1.3 to 7%), autoimmune
hepatitis (4% to 6%), and autoimmune thyroid disease (up to 5.8%) [22,68].
37 . Which antibody test is recommended for the diagnosis of celiac disease in the primary care setting for all patients older than 2 years of age?
A)
IgA
B)
IgA TTG antibodies
C)
IgA endoymysial antibodies (EMA)
D)
Both IgA TTG and EMA antibodies
CELIAC DISEASE
The diagnosis of celiac disease should be made on the basis
of several factors, including the findings of the history and physical examination,
serologic testing, and biopsy of the small intestine [37,344]. The preferred
single test for detection of celiac disease in patients older than 2 years of age is the
immunoglobulin A (IgA) anti-tissue transglutaminase (TTG) antibody [344]. Diagnostic testing should be done while
the patient's diet includes foods that contain gluten. Children younger than 2 years of age
should be screened using the IgA TTG test combined with immunoglobulin G (IgG) based testing
(e.g., IgG-deamidated gliadin peptides [DGPs]) [344]. IgG-based testing (IgG DGPs and IgG
TTG) should also be used in adult patients in whom low IgA or selective IgA deficiency is
identified. Serum IgA endomysial antibodies (EMA) have also been used but are not
recommended in the ACG guidelines [22; 37; 344].
38 . Strict adherence to a gluten-free diet leads to normal antibody levels in
A)
2 to 4 weeks.
B)
6 to 9 weeks.
C)
3 to 6 months.
D)
3 to 12 months.
CELIAC DISEASE
Healthcare professionals should ensure that patients and
their families have the resources, education, motivation, and support to comply with a
gluten-free diet. Serologic testing should be done to monitor compliance with a gluten-free
diet; strict adherence usually leads to antibody levels becoming normal within 3 to 12
months after starting the diet [37]. A lack
of response according to serologic testing may indicate continued exposure to gluten; if the
patient has been adhering to the gluten-free diet, the clinician should explore other
diagnoses. Among other diseases that appear similar to celiac disease are microscopic
colitis, pancreatic insufficiency, inflammatory bowel disease, ulcerative jejunoileitis,
collagenous sprue, and T-cell lymphoma [37].
39 . Which of the following may not resolve in adults who adhere to a gluten-free diet for celiac disease?
A)
Fatigue
B)
Anemia
C)
Low bone mineral density
D)
Gastrointestinal symptoms
CELIAC DISEASE
Follow-up should also include monitoring of nutritional
deficiencies to ensure adequate levels of iron, folate, and vitamin B12. Low bone mineral
density usually resolves in children who adhere to a gluten-free diet, but it may not
resolve in adults. Thus, bone density testing may be appropriate to determine whether
treatment for osteopenia or osteoporosis is needed [37]. Children should be monitored for normal growth and development [344].
40 . Which of the following malignancies is increased in persons with celiac disease?
A)
Gastric cancer
B)
Esophageal cancer
C)
Colorectal cancer
D)
Non-Hodgkin lymphoma
CELIAC DISEASE
Celiac disease is associated with a risk of non-Hodgkin
lymphoma that is three to six times higher than that for the general population, and the
risk for lymphoma is higher for individuals in whom celiac disease is diagnosed later in
adulthood [351,352]. Data have suggested that the risk of
lymphoma decreases over time on a strict gluten-free diet [22]. New gastrointestinal symptoms or other signs of lymphoma should prompt
further evaluation. Studies have indicated that the risk of other gastrointestinal
malignancies, such as esophageal, gastric, and colorectal cancer, are not increased among
individuals with celiac disease [306,351,353].
