Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2745_Библиотеки_им_академика_М_И_Перельмана
.pdf
Test RA SLE MS
Anti-cyclic
citrullinated
peptide (CCP)
antibodies
Positive in
nearly all RA
patients
(>95%)
Specificity for
RA increases
when both RF
and anti-CCP
are positive
Negative in
most patients
with SLE
Negative
Plain
radiographs
Normal early
in disease
Swollen joints
with erosions
later on
Swollen joints
without erosions
Deformities
(also present on
physical
examination)
Unremarkable
Erythrocyte
sedimentation
rate and serum
C-reactive
protein
Both elevated
in RA
Both elevated
in SLE
Unremarkable
Cerebrospinal
fluid (CSF)
analysis
Unremarkable Oligoclonal
bands found in
patients with
neuropsychiatric
manifestations
of SLE,
distinguishable
from those
found in MS
CSF analysis
with antibody
analysis
Presence of
oligoclonal
bands found in
95% of patients
with MS
Magnetic
resonance
imaging
No established
role in RA
evaluation
Could be
helpful in
detecting
inflammatory
changes or the
presence of
synovitis
Small punctate
hyperintensity
focal lesions on
T2-weighted
images in
subcortical and
periventricular
white matter,
usual in frontal
parietal regions
Multifocal areas
of demyelination
with loss of
oligodendrocytes
and astroglial
scarring
https://t.me/medicina_free
Test RA SLE MS
Electroencepha-
lography
No established
role in RA
evaluation
In NPSLE,
abnormal (but
not specific) in
60%-91% of
patients
No established
role in RA
evaluation
Comorbidities
As demonstrated in Figure 12.1,
26-30
there is a great deal of
overlap in the symptoms of these autoimmune diseases. As
discussed in the chapter regarding pain in MS, determining the
source of pain is necessary to determine which treatment will be
the most effective.
FIGURE 12.1 Types of pain in multiple sclerosis, systemic lupus
erythematosus, and rheumatoid arthritis.
Treatment
The primary consideration for managing the comorbidity of RA,
SLE, and MS comes from balancing the effects of disease-
https://t.me/medicina_free
modifying immunotherapies on each disease. Treating either of
these diseases in MS requires extensive communication between
the neurologist and rheumatologist regarding treatment to avoid
excessive immunosuppression via disease-modifying therapies.
This section will discuss both the beneficial and deleterious
effects of disease-modifying antirheumatic drugs (DMARDs) and
antirheumatic biologics in patients with MS (see Table 12.2 for a
complete list of RA AND SLE drugs and their effect in patients
with MS).
Table 12.2
Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE)
Drugs and Their Effect on Multiple Sclerosis (MS) Progression
31-46
Drug Class Drug Names Effect on MS Progression
Diseasemodifying
antirheumatic
drugs
Methotrexate
(Trexall, Rasuvo,
Otrexup, Xatmep)
Common treatment for RA
Not proven effective in the
treatment of MS
Hydroxychloroquine
(Plaquenil)
Common treatment for SLE
Not proven effective in the
treatment of MS
Leflunomide
(Arava)
Common treatment for RA
Cannot take teriflunomide because
share same active metabolite
Sulfasalazine
(Azulfidine)
Common treatment for RA,
ulcerative colitis
Biologic—
TNFi
Adalimumab
(Humira)
Certolizumab pegol
(Cimzia)
Etanercept (Enbrel)
Golimumab
(Simponi)
Infliximab
(Remicade)
Not recommended in patients with
MS (see section on TNFis)
Potential exacerbation of CNS
myelin lesions or creation of new
lesions because of the inhibitory
effect on protective/regenerative
function of TNF/TNFR2 in CNS
Biologic—
Non-TNFi
Ustekinumab
(Stelara)
Treatment for severe cases of
psoriatic arthritis
No significant effect
Tocizumab
(Actemra)
No significant effect
https://t.me/medicina_free
Drug Class Drug Names Effect on MS Progression
Rituximab (Rituxan)
Potential positive effect in RRMS,
but not progressive forms via
depletion of B cells
37-39
Glucocorticoid Prednisone (or
equivalent)
Consult with neurologist before
prescribing to avoid adverse events
from excess dosage
Main concern is with long-term use
—can exacerbate disease
progression of SLE
Used to decrease inflammatory
response in both RA and MS
CNS, central nervous system; RRMS, relapsing-remitting MS;
TNF, tumor necrosis factor; TNFi, TNF inhibitor; TNFR, TNF
receptor.
The most significant consideration in the pharmacologic
management of RA in patients with MS concerns the use of antiTNF therapies. The American College of Rheumatology (ACR)
suggests using an anti-TNF therapy either alone or in
combination with methotrexate once a primary DMARD (usually
methotrexate) alone fails in the treatment of RA. 47 Anti-TNF
therapies should not be used in the patient population with MS.
Early trials using anti-TNF biologics in the patient population
with MS were quickly halted owing to the finding that they
worsened myelin lesions and advanced disease progression.
48,49
It
is now known that anti-TNF therapies may lead to
neuroinflammation and demyelination. Anti-TNF therapies
increase immune cell migration to the CNS and impair
neuroprotective and regenerative functioning via inhibition of
TNFR2.
31-34
TNF is a cytokine that serves a number of important functions in
homeostasis and disease pathology. The importance of TNF
stems from its role as an inflammatory mediator and as a trigger
of many cellular mechanisms, including induction of tissue
repair, organogenesis, and inhibition of tumorigenesis. At normal
physiologic levels, TNF signaling contributes to homeostasis and
defense against pathogens through these mechanisms. When TNF
concentrations exceed normal levels, as seen in many rheumatic
diseases and cancers, it can contribute to chronic inflammation
https://t.me/medicina_free
and tissue destruction. This section will focus on TNF as a target
for the treatment of rheumatic diseases and on the deleterious
effect of global TNF inhibitors (TNFi) in patients with both a
rheumatic disease and MS.
31
There are five Food and Drug Administration–approved TNFi
biologics that are used in the treatment of RA, inflammatory
bowel disease, psoriasis, psoriatic arthritis, and ankylosing
spondylitis. Four of these are monoclonal antibodies infliximab
(Remicade), adalimumab (Humira), certolizumab pegol (Cimzia),
and golimumab (Simponi), and one is a soluble TNF receptor
etanercept (Enbrel). 31 Several of these biologics have
significantly improved outcomes for rheumatic diseases. A TNFi
in combination with methotrexate is the standard of care in the
majority of patients with RA (70%-80%) after methotrexate alone
fails. 32 Trials for treatment of MS with TNFis were initiated early
on in the evolution of anti-TNF therapies. However, these trials
were halted because of the surprising effect that, in patients with
MS, TNFis caused immune activation and an overall increase in
disease activity.
35,48
Even in TNFi trials involving otherwise
healthy patients afflicted with rheumatic diseases, demyelinating
events were reported.
49
The contradictory effect of TNFis in MS is likely due to the
multiple ways in which TNF receptors carry out an immune
response. 33 TNF is initially expressed as a transmembrane
cytokine but can be cleaved by TNF converting enzyme (TACE)
into a soluble form. 36 The bioactivity of each form of TNF
depends on which of two unique cellular receptors it interacts
with, TNFR1 (also p55) or TNFR2 (also p75). 37 Outcomes of the
two subsequent signaling cascades are considerably different.
TNFR1 receptors present on all cells and appear to induce a
proinflammatory response. This function can be seen in TNFR1
“knockout” mice, which have a markedly decreased
inflammatory response and are subsequently protected from
many diseases. TNFR2 is less widely expressed than TNFR1, and
its binding with TNF appears to trigger a cascade that results in
cellular repair, homeostasis, and survival. 31 The regulation of
outcomes stemming from these complexes, and their subsequent
effect on physiological and pathological processes, is not well
understood and is currently a subject of intensive research. It is
believed that outcomes of TNF/TNFR binding are distinct based
not only on receptor (TNFR1 vs. TNFR2) and TNF ligand type
https://t.me/medicina_free
(soluble vs. transmembrane) but also on local environment and
tissue type.
31-34
Another consideration in the treatment of RA and SLE in patients
with MS regards the use of glucocorticoids. The current
recommendation from both the ACR and the European League
Against Rheumatism is for glucocorticoids to be administered
while starting a DMARD or biologic for the management of
flare-ups.
21,38
Oral or intravenous glucocorticoids have long been
a short-term treatment option for acute manifestations of MS
owing to their immunosuppressive and anti-inflammatory
properties.
39,40
However, high dosages or long-term usage of
glucocorticoids can result in significant side effects. 41 Secondary
nociceptive pain due to chronic glucocorticoid usage has been
noted as a significant source of pain in the population with MS.
42,43
In SLE, high doses of glucocorticoids can have substantial
adverse effects, including infections, osteoporosis, and
cardiovascular disorders. 44 Therefore, rheumatologists and
neurologists should communicate regarding glucocorticoid usage
to ensure that excessive dosage or prolongation of glucocorticoid
treatment does not occur.
There are also drugs that have potentially positive off-label
effects in the treatment of MS. These drugs capitalize on points of
commonality between the complex autoimmune mechanisms
found in RA and MS and exert a mutually beneficial effect by
inhibiting some part of the shared pathophysiological immune
mechanism. For example, rituximab (Rituxan) is often used to
treat both RA and MS, and SLE. Rituxan is a genetically
engineered chimeric monoclonal antibody that depletes CD20+ B
cells through both cytotoxic effects and promotion of apoptosis
and has proven effective in treating both MS and SLE.
45,50
Because B cells have been implicated in the pathophysiology of
MS through their role in targeted and compartmentalized humoral
responses, depletion of B cells by Rituxan has shown preliminary
positive results in treating MS, although more clinical trials are
needed in this regard.
51-53
A summary of different treatments for
RA and SLE and their effect in patients with MS can be seen in
Table 12.2.
Psoriasis
https://t.me/medicina_free
Psoriasis is an immune-mediated skin disorder characterized by
scaly or silver-appearing erythematous plaques. The risk of
incident psoriasis is 54% higher among people with MS than in
the general population. 54 Psoriasis and MS seem to share some
risk factors; the prevalence of both diseases appears to increase
with increasing distance from the equator; obesity and smoking
appear to contribute to the pathogenesis.
13,55
Additionally,
fumarates have been shown to be effective disease-modifying
therapies in both diseases. Treatments for psoriasis include
topical corticosteroids and vitamin D analogs, ultraviolet light,
and systemic therapies, many of which overlap with MS
treatments. Methotrexate, administered in conjunction with a
folic acid supplement, is a common treatment for psoriasis.
56
Psoriatic arthritis develops in 30% of patients with psoriasis and
is characterized by a wide range of clinical features, which often
results in a delayed diagnosis and treatment. 13 Unlike MS, SLE,
and RA, it is equally common in both men and women and
primarily manifests as peripheral arthritis, axial disease,
enthesitis, dactylitis, and skin and nail disease. 56 Psoriatic
arthritis can mimic RA, ankylosing spondylitis, and gout, but
these can be ruled out by clinical and laboratory evaluation and
imaging in patients who have had the disease for a longer
interval.
The treatments for psoriatic arthritis depend on what systems are
affected by the disease, and treatment should be coordinated
between the rheumatology, general practitioner, and any
specialists involved. Patients with mild arthritis (involving fewer
than four joints) can take nonsteroidal anti-inflammatories, such
as (naproxen sodium) Aleve or (celecoxib) Celebrex, which can
control inflammatory symptoms and lessen pain and stiffness.
57
For patients who have not found relief of their peripheral arthritis
without erosions or substantial functional limitations,
methotrexate (leflunomide or sulfasalazine can be substituted if
the patient is unable to tolerate methotrexate) is suggested.
Because the incidence of psoriasis in MS is 54% higher than in
the general population, patients with MS have an increased risk
of developing psoriatic arthritis. 15 The treatment for more severe
forms of psoriatic arthritis, wherein erosive changes have
significantly limited function, is most often a TNF inhibitor.
31
Because TNFis can increase disease activity in patients with MS,
https://t.me/medicina_free
it is recommended that biologic disease-modifying antirheumatic
drugs (DMARDs) such as Stelara (ustekinumab) or Consentyx
(secukinumab) be used instead.
57,58
Glucocorticoids should be
avoided in patients with psoriatic arthritis because they have been
shown to increase the chances of developing erythroderma or
pustular psoriasis, as well as interfering with the effects of other
medications.
57
Sjögren Syndrome, Scleroderma, and
Barriers to Drug Absorption
Sjögren syndrome and scleroderma are two autoimmune
rheumatologic issues that affect fibrous tissue. Sjögren syndrome
is a chronic condition characterized by lymphocytic infiltration
and subsequent degeneration of exocrine glands, primarily the
salivary and ocular glands, that result in severe dryness in the
mouth, eyes, and other mucosal membranes of the body.
59
Scleroderma (or systemic sclerosis) is a complex disease similar
to Sjögren syndrome that involves extensive fibrosis, vascular
alterations, and autoantibodies proliferation. This disorder is four
times more common among women than among men, primarily
affecting people from 20 to 50 years old. There are two accepted
classifications of scleroderma: limited cutaneous scleroderma and
diffuse cutaneous scleroderma. 60 Patients with limited cutaneous
scleroderma display fibrosis only on the hands, face, and arms.
The majority of these patients suffer from pulmonary
hypertension and also a high prevalence of anticentromere
antibodies, which can be used to distinguish it from diffuse
cutaneous scleroderma.
Patients with either Sjögren syndrome or scleroderma who are
also diagnosed with MS face skin issues that may affect drug
absorption. For example, Acthar Gel is a subcutaneous
adrenocorticotropic hormone injection that helps treat patients
with MS by stimulating anti-inflammatory corticosteroids within
their bodies. 16 Patients with severe skin disorders, like those with
scleroderma, are unable to take Acthar Gel because they are
unable to absorb the drug. Thus, these patients with MS may be
unable to receive effective and appropriate treatments to treat
their MS.
16
https://t.me/medicina_free
Lyme Disease
Lyme disease is a bacterial infection caused by six species of
ticks in the Borreliaceae family. It is the most common tick-borne
disease in the United States, Canada, and Europe. 16 There is a
broad spectrum of disease manifestations, largely because of
differences in the infecting species. Lyme disease, or Lyme
borreliosis, can mimic the symptoms of MS, particularly
headache, fatigue, and muscle aches. About 10% to 15% of
patients infected with Lyme disease can develop central nervous
system involvement during the early disseminated stage of the
disease, and the condition appears similar to MS during CSF
analysis and MRI.
61,62
Symptoms
The clinical manifestations of Lyme disease can be classified into
three phases: early localized disease, early disseminated disease,
and late Lyme disease. It should be noted that clinical features
from these stages can overlap. Refer to Table 12.3 for a
comparison of clinical signs and symptoms of Lyme disease and
MS.
Early localized disease: Characterized by the presence of
erythema migrans (EM) skin lesion, and usually occurs
within 1 month of tick bite
Early disseminated disease: Presence of multiple EM lesions
(within days to weeks after infection), possibly with the
presence of neurologic and/or cardio findings (weeks to
months after infection), such as lymphocytic meningitis,
facial palsy, radiculoneuropathy, or carditis with heart block
Late Lyme disease: Associated with intermittent or
persistent arthritis involving one or a few large joints
(particularly the knee) and/or neurologic problems, such as
subtle encephalopathy or polyneuropathy (months to years
after initial infection)
16,61,63
Table 12.3
Signs and Symptoms of Lyme Disease and Multiple Sclerosis (MS)
22,62
Signs and Symptoms: Lyme Versus MS
Lyme Disease MS
https://t.me/medicina_free
Signs and Symptoms: Lyme Versus MS
Lyme Disease MS
Erythema migrans rash (within 3-30 d of tick bite),
typically expands over course of days, with central
clearing and bulls-eye appearance
No characteristic rashes or
lesions
Fatigue Fatigue (not caused by lack
of sleep or exertional
exhaustion due to disability)
Joint pain General pain (not in joints)
Headache N/A
N/A Sensory loss
N/A Motor issues; muscle
cramping, spasticity
Eye redness, tearing Optic neuritis
Diagnosis
A diagnosis of early Lyme disease can be determined on clinical
findings alone when patients present with EM lesions and live in
or have traveled to an endemic area. Patients who present with
EM lesions should not be tested for Lyme titers, as they will
likely be seronegative, because lesions appear before adaptive
immune response. 61 By the time a patient displays symptoms of
early disseminated disease, serologic tests are usually positive for
both IgM and IgG antibodies.
63
Clinical presentation should be considered before serologic
testing. Indications for Lyme titers are a recent history of living or
traveling in an endemic area, exposure to ticks, and symptoms
consistent with early disseminated disease or late Lyme disease,
such as meningitis, radiculopathy, arthritis, and carditis. Serologic
tests should not be conducted if the patient has no EM lesions or
does not live in endemic areas or for patients with nonspecific
symptoms only (i.e., fatigue, muscle pain).
61
A two-tier conditional strategy can assist in the diagnosis of
Lyme disease. This includes a sensitive enzyme immunoassay,
such as enzyme-linked immunosorbent assay (ELISA), followed
by a more specific Western blot test.
61
Negative ELISA: no further testing needed, patient negative
for Lyme disease
Positive ELISA: should be followed by Western blot
Negative Western blot: supersedes results of positive
ELISA, patient negative for Lyme disease
https://t.me/medicina_free
Соседние файлы в папке Библиотека им академика М.И. Перельмана