Rheumatology – Dra.

Ruth Saguil - Sy
I will present a case of a female in her 30s
who presents with neurologic manifestation.
Lupus cannot be diagnosed with just 1
laboratory test.
You need a criteria wherein you will fulfill 4
out of 11 criteria, this is the old criteria
because now, ALOPECIA has been added to
the new criteria, as well as skin lesions.
Steroids are used for the management of mild
lupus because your difficult lupus involving the
brain, myocardium and kidneys will be
managed by other specialists.
So going back to the patient, her symptoms
started just a 4 weeks ago, where she
complained of having dry cracked lips.
A whitish lesion at the hard palate was
noted, which is impossible to be
candidiasis because of her age.
Always remember, 20-40 years old males and
Lupus is thought to be an interplay of several females are supposed to be at the peak of
factors such as patient’s genetic make-up, their immunity, so it is impossible to get
the environment, infectious disease and infections common in the
probably chemicals. immunocompromised. You will only get the
One chemical that is thought to be involved most common infections.
in lupus is the HAIR DYE WITH YELLOW So this patient was referred to ENT and
TINGE, yung mga blondie. was given Nystatin.
There are anecdotal reports that these Soon, she developed other symptoms such as
hair dyes can cause the lupus to flare up. fever, chest pain and dry cough, but her
Other factors involve silicon implants and cracked lips were always the chief
infection of EBV. complaint. She has no history of other past
Lupus is common among females in the illnesses, smoking or alcohol intake.
reproductive age. In this patient, the GYNE history must be
SLE involves the whole system because it is asked because there are some lupus that are
systemic. secondary to APAS (Anti-phospholipid
There are other types of lupus (e.g. discoid, antibody syndrome), this is the antibody
subacute cutaneous) that are localized and against the negatively charged
does not involve other organ systems. phospholipase and this manifests as
There is also lupus nephritis that affects only ARTERIAL AND VENOUS
the kidney. THROMBOSIS, RECURRENT
There is also a neuropsychiatric SLE ABORTIONS and THROMBOYTOPENIA.
that affects only the brain but these are APAS can present without lupus.
rare diseases.

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So this patient is presenting with influenza
like symptoms because even in the review
of systems there were no pertinent data.
If you are going to get the history of
patients with lupus, you should ask them
how they are when they wake up because
most of these patients have difficulty rising
from the bed, they have morning stiffness
like in RA. If you will see in the physical
exam the butterfly or malar rash, it is one of
the criteria for lupus.
The index case of lupus presented with malar
rash and wolf bitten appearance.
Lupus is common in dark people,
particularly Africans.
The butterfly rash of lupus spares
the nasolabial fold.
During the course of the stay in the hospital,
the patient developed more problems such as
skin lesions, but the dry cracked lips
persisted.
In this patient, you have to look if there is
oral ulcer because oral ulcer will not be
reported by the patient. It is the doctor’s role
to look for that ulcer.
You also have to ask if the patient
experiences hair loss because patients with
lupus experience massive hair loss upon
waking up.

Autoimmunity and Autoimmune Disease

Immunologic reaction of organism against

its non-tissue
Seen in normal individual
Antibody production maybe These mechanisms of autoimmunity may not
increased following an inciting event function well in patients with connective
(IgM) Self-limiting or persistent tissue disease.
In autoimmunity, the problem is the
increased number of inflammatory cytokines.

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Between the 2, anti-dsDNA is not only
sensitive but also specific and has
higher yield (70%) than anti-Sm, so it is
used to monitor disease activity.
If the lupus is active, anti-dsDNA is
positive. If the lupus is inactive, it is
negative. Anti-Sm has low yield so it is not
commonly used.
ANTI-DS-DNA DETECTS DISEASE ACTIVITY,
NEPHRITIS AND VASCULITIS.
ANA IS USED TO SCREEN ANYONE (female,
with body pains, with alopecia) WHOM YOU
SUSPECT TO HAVE LUPUS.
All the others (anti-Ro, anti-La, anti-histone)
are antibodies to detect the presence of
other connective tissues.
Anti-RNP is used for mixed
connective tissue disease.
Anti-Ro and anti-La are used for Sjogren’s
Syndrome.
Anti-histone is used for drug induced SLE.
Anti-histone is utilized in patients who
present with myalgia, arthralgia, stiffness
and rashes and TAKING DRUGS, but with
no major organ involvement such as
nephritis, cerebritis or hemolytic anemia.
When you talk of lupus, you are actually talking IN DRUG INDUCED LUPUS, THERE IS NO
of several autoantibodies. MAJOR ORGAN INVOLVEMENT. Anti-
Refer to the table above, yung naka-dark blue phospholipid antibody is positive in patients
na box ay screening test for lupus, which is with APAS syndrome. Anti-erythrocyte and
ANA. Yung dalawang naka-red na box ay anti-platelet are minor tests because not all
yung most sensitive tests for lupus. patients with lupus will have anemia,
though THE MOST COMMON BLOOD
MANIFESTATION OF LUPUS PATIENTS IS
In the Philippines, the antibodies requested
ALWAYS ANEMIA.
are ANA which is the best screening test, so
if you are considering lupus in a patient, ANEMIA IN LUPUS IS ANEMIA OF CHRONIC
request for ANA to screen the patient. ILLNESS, and not hemolytic anemia.
ANA has to be positive and in high titers
because any person can have positive
ANA but without the disease.
THE MOST SPECIFIC TEST FOR LUPUS IS DS-
DNA AND ANTI-SMITH or ANTI SM.

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Sex steroids such as estrogen, which is why
lupus is common in the reproductive age (
cut off is 16 years old)
Genetics
Environment (lupus patients can never be
exposed to the sun, so you tell them to put
sunblock lotion SPF 30 and above all over
the exposed skin. If they want to swim, they
can provided that they wear long sleeves or,
go night swimming)
Major histocompatibility complex alleles
(HLA, B8, DR2)

Pathogenesis of SLE

2 Mechanisms of Tissue Damage

AUTOANTIBODY BINDING
IMMUNE COMPLEX DEPOSITION

So pag tinanong ko sa inyo, the mechanism of

lupus is by: autoantibody binding and
immune complex deposition.

Systemic Lupus Erythematosus

Autoimmune disease in which organs and cells

undergo damage initially mediated by tissue
binding auto antibodies and immune complex

Characteristic Features

Presence of auto antibodies that react with Always remember that the complement level is
various component of the cell nucleus (ANA)
down when lupus is active and if the lupus is
inactive, the complement level is also normal.
Etiology of SLE Before, only UVA is prohibited but now, both
UVA and UVB are prohibited so patients should
Unknown (?) really be not exposed to the sun.

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One factor that can cause the lupus to become Demographics
☺ ☺
active is usually STRESS (yung walang pera
☺☺
walang pamasahe, este pambili ng gamot Women – affected 10x as common as men
☺ 15-40 years of age
na-stress siya dun kaya active lagi yung lupus)
☺ ☺ Racial disparity (Africans)
tumatawa si Kim may naalala siya
Prevalence: 25-50/100,000
Rash is due to immune complex deposition.
Lupus band test is done in the skin, when you Pathology
biopsy it under the electron microscope, you
will see between the epidermis and the
Organ Symptoms
dermis a bright neon green color line.
This is the immune complex deposition. If Skin Deposition of Ig at the
the immune complex deposits in the dermoepidermal junction
kidney, the patient will have proteinuria seen when you do Lupus
☺
>500 mg/day or CAStanuria (e.g. WBC, band test
☺ Injury to basal keratinocyte
fine or course CASts ) or leukopenia.
If this is left untreated, the organ will have Inflammation
chronic inflammation and there will be Kidney Glomerular involvement
fibrosis and this can lead to renal failure. Blood Vessels Vasculitis
Because of the inflammation, there is
hastened atherosclerosis so these patients Diagnostic Criteria for SLE
die of heart disease.
They also develop pulmonary fibrosis or
stroke.
The moment lupus is identified, we want to
suppress the inflammation that is why
patients with lupus are on steroids,
however, too much steroids is not good also
because steroids have many side effects
including recurrent infections, osteoporosis,
Cushing syndrome.
Lupus is common in dark skinned people,
hanggang pumuputi siya nababawasan ang
prevalence.

Male Female
Gout Lupus
Spondyloarthropathy Osteoarthritis
Rheumatoid
arthritis

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The criteria for diagnosing lupus is SOAP Sometimes the cardiac shadow is enlarged
BRAIN MD. due to the massive pericardial effusion.
The effusion in the lungs and heart can be
S – erositis managed well with only NSAIDs.
O – ral ulcer The most common neurologic
A – rthritis or arthralgia manifestation of lupus is cognitive
P – hotosensitivity dysfunction and headache not relieved by
B – lood problem paracetamol. Patients may also manifest
R – enal problem with stroke like, Guillain Barre like or
A – NA positivity schizophrenia like symptoms.
I – mmunologic Hematologic problems involve anemia,
N – eurologic probably hemolytic anemia but remember
M – alar rash that the anemia in lupus is anemia of
D – iscoid rash chronic disease.
It can also present with thrombocytopenia as
You have to fulfill 4 out of the 11 criteria opposed to rheumatoid arthritis that
to be diagnosed with lupus. presents with thrombocytosis.
In the new criteria, alopecia and skin Patients also have anti-dsDNA, anti-Sm and
rash were added. antiphospholipid and of course, the criteria
Remember that the malar rash is non- given prominence is ANA positivity.
scarring. If ANA is already positive, do not repeat the
Remember also that the discoid rash is the test.
one which is highly scarring. If ANA is negative, repeat the test after 3-6
If this discoid rash occurs in the scalp it will months.
produce a patchy area with permanent Anti-dsDNA becomes positive if the disease is
hair loss. active.
The arthritis may be arthralgia or myalgia but Between the 2, dsDNA is the one you can
there will be manifestations similar to repeat over and over again to detect
rheumatoid arthritis such as swan neck vasculitis, nephritis and skin inflammation.
deformity, Boutonniere and ulnar deviation.
The difference is in patients with lupus, if
they have these deformities, it can be
reverted back to normal unlike in
rheumatoid arthritis, and this is called
Jaccoud’s arthropathy.
Jaccoud’s arthropathy is a non-erosive
arthritis of 2 or more joints.
Serositis may manifest with pericarditis,
myocarditis and ascites.
If the patient has myo or pericarditis, she will
manifest with chest pain or cough.

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Sy

Remember that the anemia is not

hemolytic in nature.
Note that the systemic manifestations of Most patients have anemia of chronic illness
lupus are nonspecific. so you do not give iron supplements in
You would see that arthralgias and patients with lupus.
myalgias is 95% in most patients.
The patient has a lot of iron in the body but
The non-erosive arthritis which is the the bone marrow is too lazy to utilize the
Jaccoud’s arhtropathy is only 60%. iron stores.
The most common cutaneous manifestation If the anemia is very severe and the
is photosensitivity.
hemoglobin is only 4 or 5, then think of
hemolytic anemia already because this is not
very common.
As you can see the most common neurologic
manifestation is cognitive at 50%.
 Rheumatology – Dra. Ruth Saguil - Sy
Treatment

NO CURE
All the available drugs for lupus are just
indicated to control the inflammation because
the basic problem in lupus is inflammation
and this inflammation can cause damage.

Control of Inflammation

NSAIDs – can be used for myalgia, arthralgia,

pleuritic and pericarditis
Glucocortcoid – given at 1 mg/kg/day and is
used for major organ involvement (hemolytic
anemia, nephritis, cerebritis)
Prednisone is everywhere so you use
Prednisone for lupus but in the absence of
Prednisone you can use other steroids
provided you know the duration of action
(Dexamethasone has an action of 30 hours)
and you know its equivalent to Prednisone.
Always make sure that the Prednisone
dose is 5 mg or less.
In the cardiopulmonary, you can see that it is Disease modifying antirheumatic drugs
always pericardium and pleura which are (DMARDs) – all patients should be on
affected. Hydroxychloroquine at 7mg/kg/day.
Methotrexate can also be used especially
The patient can have pleural effusion,
pericardial effusion and ascites. for the arthritis.
The cause of death of SLE patients is Cyclophosphamide and Azathioprine –
hastened atherosclerosis. reserved for nephritis
Even in the absence of kidney biopsy you can Biologics (Rituximab) – this is anti B cell so
make a diagnosis of SLE nephritis by looking you give it twice a year and you kill all B
at the urinalysis. cells because it is the B cells that produce
autoantibodies
If the protein is very high, request for 24
hour urine test or spot urine test. Patient can undergo plasmapheresis.
You request for kidney biopsy because you
want to know if the nephritis is manageable. Prevention of Flare of SLE
In the GIT, the more commonly seen is ☺
abnormal SGPT and SGOT. Avoid stress.
Avoid sun exposure.

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The goal for lupus is just to reach the stage If your ANA is positive, look at the other
of remission. criteria (SOAPBRAINMD).
You diagnose lupus as either SLE in remission If the case is life threatening, give high
or SLE active. dose steroids.
If not, just give low dose steroids.
If the patient is ANA negative, 95-99% she is
negative because ANA negative lupus is not
present anymore.
The substrate to test for ANA negative lupus
is the mice liver.
Now the substrate to test for ANA is squamous
cell of humans.

Drug Induced Lupus

Positive anti-histone
Fever, malaise, arthritis
Drug induced lupus does not have major
organ involvement.
The management is to withdraw the use of the
drugs that can cause it.
Remember the autoantibody is antihistone.

Drugs (PHP)

Procainamide
Hydralazine
Phenytoin
Initially, patient will come to you manifesting
with arthralgia or myalgia. If you are the
attending physician, you look at the patient, To determine if the disease is active, look at the
patient’s hair. Even if there is no massive hair
female, reproductive age group, so the patient
loss their hair turns very dry and stubby and it
has no reason to develop such symptoms.
loses the normal hair luster.
Screening is very important so you request
ANA, and what laboratory test will you request
after ANA? dsDNA. Why? Because you want to
know if the disease is active or not.
You request for ANA, dsDNA, BUN
creatinine, SGPT and SGOT.

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Epidemiology

IM – rare: estimated 1 in 100,000 incidence PM

and DM – bimodal distribution: 1 in childhood
(ages 5-15) and other in midlife (ages 30-50)

IBM peak – after age of 50

PM and DM – Female-male ratio is 3:1
IBM – Female-male ration is 1:3 IM –
African American
General Principles
Etiology

Inflammatory myopathies (IM) are

Etiology is unknown.
heteregeneous group of disorders
characterized by muscle weakness and
inflammation of skeletal muscles (myositis). Autoimmunity
The first manifestations will always be bilateral
and symmetrical (e.g. inability to climb the 50% myositis-specific has association with
anti-Jo autoantibodies.
stairs or inability to raise their arms) and these
25% myositis-associated antibodies
are the most common complaints.

Environment influence
Classification

Pathophysiology
3 major distinct of IM Other IM
Polymyositis (PM) Juvenile
IM – idiopathic but immune mediated
Dermatomyositis dermatomyositis
Unique pathologic features
(DM) Malignancy
Inclusion body associated myositis
myositis (IBM) Eosinophilic
Granulomatous
Take note that Etc.
inclusion body
myositis does not
respond to steroids
unlike the other
two.
Also take note
that these 3 have
an association
with malignancy.

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Polymyositis

History

Progressive painless muscle weakness –

inability to climb the stairs, to raise the
hand and comb the hair
Fatigue and anorexia (after 3 to 6 months)
Dyspnea Due to skeletal muscle
Dysphagia involvement

Examination

The only antibody that you have to Difficulty of getting up

correlate is your anti-Jo antibody which is Sensation to gross touch
your antisynthetase because this is the most Weakness of diaphragmatic and intercostal
common. muscle (dyspnea)
This is associated with polymyositis Fine crackles
and dermatomyositis. Cardiac arrhythmias
The feature of anti-Jo antibody since it is In the lungs, the more common is
associated with polymyositis and diaphragmatic problem, and the patient cannot
dermatomyositis, it can present with your breath.
interstitial lung disease, fever, arthritis and
skin manifestations.
Diagnosis
Remember that these diseases respond well
to steroids.
Muscle biopsy – degeneration and
Diagnosis regeneration of muscle fibers and CD8 + T
lymphocytes
History and Physical Examination Diagnostic criteria
Selected tests – aside from anti-Jo, you should Request for autoantibodies, CRP, ESR, CPK since
also request for CRP and ESR and CBC because it is very elevated in muscle inflammation.
CRP is high in inflammatory diseases.
Clinical manifestation

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Diagnostic Criteria for Polymyositis patient is treated then the CPKMM goes
down.
Routine EMG is not usually done.
Skin finding is essential if the patient has
dermatomyositis.

Inclusion Body Myositis

Most common myositis found in the elderly

The only disease that does not respond to
steroids
Remember that electromyogram is done
for this disease.

History
Dermatomyositis
onset of weakness over 1-10 years prior to
In dermatomyositis, you have to have at least 3 diagnosis
of the criteria above with rash. can cause neuropathic symptoms

Clinical Manifestations Examination

Gottron’s papules – eczematous like lesions decreased grip symmetric

on the knuckles foot drop proximal muscle
Heliotrope rash – lilac or violaceous coloring weakness
of the upper eyelid
Shawl sign or V neck sign Diagnosis
Mechanic’s hands or machinery hands – dry,
cracked hands especially on the distal areas Muscle biopsy – presence of lined or rimmed
Amyopathic dermatomyositis vacuoles and triangular cells

Diagnosis Inflammatory Muscle Biopsy

Myopathy Findings
Muscle Biopsy – CD4+ and CD8+ T lymphocytes Polymyositis degeneration and
with macrophages and B cells regeneration of
muscle fibers and
CD8+T
CPKMM will be your marker for
lymphocytes
improvement because the moment the
Dermatomyositis CD4+ and CD8+ T
lymphocytes with

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macrophages and Fibromyalgia Syndrome
B cells
Inclusion Body myositis Presence of lined
or rimmed
vacuoles and
triangular cells

Diagnostic Testing

Laboratories

Evaluation of enzymes: CK, AST, ALT, LDH

Inflammatory marker: ESR, C-reactive protein
(CRP)
Myositis-specific antibodies

Diagnostic Procedures

Electromyography differentiation
Chronic pain of unknown etiology
between
Present with musculoskeletal pain
neuropathic and
myopathic The patient has aches and pain everywhere,
condition sleep problems and hyperalgesia. The pain
is diffuse.
Muscle biopsy a negative biopsy does
not rule out Laboratory is done to rule out other
IM causes because SLE can also present with
Pulmonary function these symptoms.
test The tender points are essential, and you have
to put 4 kg pressure on these tender points.
Treatment No autoantibody for fibromyalgia

Corticosteroids – most PM/DM Characterized by:

patients respond to steroids.
IBM patient do not respond to steroids Unexplained diffuse pain
Steroid sparing agents (Methotrexate Tender points
or Azathioprine, Cyclosporine) Fatigue
Sleep disturbance
For patients with lung or breast cancers, they
have proximal muscle weakness and the rash
but you have to manage the primary problem.

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Epidemiology Symptoms must be present for 3 months or
more.
In 1980’s – prevalence estimated to 2-5% 11 out of the 18 tender point sites should be
Female to male ratio – 8:1 tender after applying 4 kg pressure to make
Mean age – 30-60 years a diagnosis of fibromyalgia.
Maybe present in children and elderly
Posttraumatic stress disorders (PTSD) – Treatment
more frequent in FMS patients
Antidepressants
Pathophysiology Antiepileptic
Analgesics
Poorly understood Pregabalin
Disorders heightened pain response
characterized by hyperalgesia and allodynia Sjögren’s Syndrome
may result of neuroendocrine axis alteration
(disturbances in mood, sleep and pain Chronic inflammatory disorder
perception) Characterized by lymphocytic infiltration and
Low serum serotonin, elevated cerebrospinal autoimmune destruction of exocrine glands
fluid (CSF) – not consistent with patients Salivary and lacrimal glands are commonly
with fibromyalgia. affected
Leading to dry mouth and eyes
Clinical Presentation The patient will tell you that there is sand in his
eyes and it is like he is eating donut covered
FMS cardinal feature is diffuse soft tissue with sand.
pain Complain of morning stiffness, fatigue, Associated with anti-Ro, anti-La and anti-SSa
sleep disturbances, headache Can be part of SLE, rheumatoid arthritis and
PE is normal except for presence of tenderness systemic

Diagnosis Epidemiology

The diagnosis of FMS is made More prevalent autoimmune condition

clinically Lab tests and radiologic Affecting approximately 0.5 to 3 million
studies often unrevealing but helpful person in USA
Sleep history Incidence per year – 1/1000 and 1/100 (new
Screening for co-existing depression There is cases)
no test that will tell you that the patient has Most often occur in women (female to
fibromyalgia, you really have to put pressure male ratio, 9:1)
on the tender point sites to diagnose it.

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Pathophysiology Laboratories

Consists of infiltration of lymphocytes CBC, ESR, CRP, RF, ANA and serum protein
into glandular tissue electrophoresis
Commonly associated with SSA/RO and SSB/La ANA is positive in about 80% and RF is
(antibodies against nuclear antigens) positive in up to 30% of SS patients
If the ANA is positive, obtain autoantibodies
Hypotheses SSA/Ro and SSB/La
Mild anemia and increased ESR or CRP in
Combination of genetic, hormonal and most patients
environmental factor play a role in the initiation
and progression Diagnostic Procedures
Associated with HLA-DR and HLA-DQ alleles
Viral infections might predispose patients to Schirmer’s test for tear secretion
SS by altering immune response. Rose bengal or fluorescein staining with slit-
lamp examination to detect corneal eithelium
Clinical Presentation damage – the dye deposits on the peripheray of
the cornea
Mucosal dehydration (dry eyes and Sialometry, sialography or scintigraphy
mouth) Symptoms of dry eyes include to measure salivary gland function
foreign body sensation, light sensitivity
worsen in the evening Treatment
Dry mouth manifest as increased thirst
and difficulty of swallowing of dry food Dry eyes artificial tear on regular
basis
Extraglandular Involvement Dry mouth drink water frequently
Sugar free gum to
Fatigue and arthralgias stimulate salivary gland
Skin lesions Avoid alcohol, smoking
Respiratory involvement and dry foods
Cardiac involvement Artificial saliva, etc.
Neurologic complications Dry skin Moisturizing lotion
Renal involvement Vaginal dryness Lubricants
Arthralgia NSAIDs
Physical Examination
Scleroderma
Salivary gland enlargement
Glands usually diffuse, firm and non-tender Scleroderma is a connective tissue disease
A hard, nodular gland may suggest a neoplasm Characterized by skin thickening and tightening

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2 Main Forms Raynaud’s phenomenon (RP),
esophageal dysmotility, sclerodactyly,
Localized telangiectasias Diffuse cutaneous disease
Systemic (dcSSc) Scleroderma sine scleroderma
Skin involvement in lcSSc is limited to the face,
Localized Scleroderma Only involve the upper extremities distal to the elbow and
skin lower extremities distal to the knee
Morphea (patches dcSSc involves skin proximal to the elbow
of thickened skin) and knees
Linear scleroderma
Rare case with visceral organ involvement
Scleroderma en
with no skin changes is known as scleroderma
coup de sabre
sine scleroderma
Managed by
dermatologies
May have low titer Epidemiology
antinuclear
antibody (ANA) test Estimated annual incidence of SSc in the
Systemic Scleroderma Complex United State is 1.9/100,000
(SSc) multiorgan disease Prevalence rate is estimated as 28/100,000 SSc
Result of is about 3-5 times more common in women
autoimmunity, than men.
inflammation, Most common age of onset is between 30 and
vasculopathy and 50 years
progressive fibrosis
of the skin and Etiology
visceral organs
Unknown
Skin Involvement Only Linear No animal models stimulated
Morphea
Coup de sabre
Pathophysiology
Managed by
dermatologists
Four distinct interrelated pathogenic processes
Systemic Involvement Internal organs are
also involved.
Managed by Autoimmunity
Inflammation
rheumatologists
Vasculopathy
Fibrosis of the skin and visceral organ (e.g.
Systemic Scleroderma Classification
GERD if esophagus is affected and inability to
breathe if the lungs are fibrosed. The usual
Limited cutaneous diseases (lcSSc, formerly cause of death for scleroderma patients is
known as CREST syndrome: calcinosis,

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pulmonary (restrictive lung disease) Other Complaints
because they cannot breathe.)
GIT Gastroesophageal reflux is
Autoimmunity with vascular reactivity precedes the most common.
development of SSc Pulmonary dyspnea on exertion of
Autoantibodies against components of the non-productive cough
extracellular matrix found in 50% of SSc can chest pain due to
activate fibroblasts, induce collagen esophagitis
production and prevent collagen degration, pleurisy
resulting in tissue fibrosis pericarditis
Musculoskeletal arthralgias with stiffness
Endothelial injury occurs in early SSc course
of the joints
Produce adhesion molecules and inflammatory
cytokines causing endothelial damage causing
Physical Examination
tissue hypoxemia
Hypoxemia stimulates production of
angiogenesis factors which results to Sclerodactyly – skin changes affecting the
vasoconstriction without angiogenesis in fingers (appear tapered from ischemic loss
of the digital pulp
SSc patients
Finger ulcerations resulting from chronic
hypoxia
Clinical Presentation
Tight “purse-lip”, decrease oral aperture
Hyper and hypopigmentation
History
Telangiectasia may be appreciated
Subcutaneous calcinosis
Raynaud’s Phenomenon is universally present
and usually the earliest and first manifestation Bird’s beak appearance of the
of SSc so they cannot be exposed to cold. nose No wrinkles
Digital ulcers (dry gangrene)
Their skin becomes tethered to the underlying
Salt and pepper skin
tissue.
Scleroderma has vasculopathy and the blood
vessels become fibrotic. Others:
Skin changes does not occur overnight.
Crackles may be heard in patient with
It starts as edematous, then becomes fibrotic pulmonary fibrosis
then later on atrophic.
Sign of heart failure
Coarse friction rub can be heard
Skin changes occurs in three (3) phases: Hypertension with microangiopathic anemia

Edematous
Fibrotic
Atrophic

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Laboratories Digital ulcers Analgesic and local
wound care can be
95% of patient with scleroderma with have helpful
a positive ANA Sildenafil
Anti-Scl-70 (anti-topoisomerase-I) for diffuse Tadalafil
scleroderma Scleroderma renal ACE inhibitors
Less commonly assayed antibodies: anti-RNA crisis
polymerase I, II and III and U3- Systemic Cyclophosphamide
ribonucleoprotein (RNP) is associated with risk Scleroderma ILD
for pulmonary hypertension GIT Reflux symptoms can
be controlled by PPIs.
Treatment
Non Pharmacologic Therapies
SSc has the highest mortality among the
connective tissue disorders Avoiding excess bathing
There is no treatment for underlying disease Using proper moisturizing creams can aid in
process skin care
Aggressive and physical therapy may be helpful
Treatment is targeted at specific organ
complications and/or patients symptoms
Antiphospholipid Syndrome
Medications
APS is a hypercoagulable disorder manifested
Skin Involvement by recurrent arterial and venous thromboses
and adverse outcomes in pregnancy that is
No effective therapy has been discovered. associated with antiphospholipid (aPL)
antibodies
Raynaud’s Phenomenon
Classification
Non- Smoking cessation
pharmacologic Avoiding cold exposure APS may be primary (with no concomitant
Hands go through disorder) or secondary when associated with
triphasic color change another systemic diseases (e.g.; systemic lupus
(white, blue red) erythematous [SLE])
whenever exposed to Catastrophic APS is a variant of APS
cold and emotional characterized by acute thrombotic micro-
☺
stress angiopathy that results in multi-organs
Pharmacologic Diltiazem failure and a high mortality rate
Dihydropiridine
Calcium channel
blocker

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Epidemiology Pregnancy Morbidity

Most commonly occurs in young females >1 unexplained deaths of a morphologically

Both sexes and all ages may be affected normal fetus at or beyond the 10th week of
While aPL occurs in 1% to 6% of general gestation with normal fetal morphology
population, the prevalence of primary APS is documented by ultrasound or direct
less than 0.5% examination of fetus
In patient with SLE, 10% to 44% will develop >1 premature birth of morphologically normal
aPL neonate at or before the 34th week of
Catastrophic APS occurs > 1% of patients with gestation because of severe preeclampsia or
APS eclampsia or severe placental insufficiency >3
unexplained consecutive spontaneous
Pathophysiology abortions before the 10th week of gestation
with maternal anatomic or hormonal
APS is poorly understood although aPL abnormalities and paternal and maternal
is implicated in the disorders chromosomal causes excluded

aPL affects coagulation and thrombosis in Laboratory Criteria

different ways:
Lupus anticoagulant present in plasma,
The binding of aPL also on >2 occasions at
activates complements least 12 weeks
Can initiate an inflammatory cascade apart, detected
resulting to thrombosis. according to the
guidelines of the
Diagnosis International
Society on
APS should be suspected in patients Thrombosis and
presenting with venous or arterial Haemostasis
thromboembolism or pregnancy losses Anticardiolipin present in medium
antibody of IgG and/or or high titer, on >2
You have to know if the patient has history of
IgM isotype in blood occasions, at least
stroke because of the arterial and venous
12 weeks apart,
thrombosis in APAS.
measured by a
standardized
TRIAD OF APAS enzyme-linked
immunosorbent
ARTERIAL AND VENOUS THROMBOSIS assay
PREGNANCY LOSS
Anti-ß2 glycoprotein-I present in titer
THROMBOCYTOPENIA antibody of IgG and/or >99th percentile,
IgM isotype in blood on >2 occasions, at

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 Rheumatology – Dra. Ruth Saguil - Sy
least 12 weeks Myalgias and myositis range from mild to
apart, measured by severe and histologically indistinguishable from
standardized PM or SLE
enzyme-linked Raynaud’s Phenomenon is seen in MTCD with
immunosorbent findings on nailfold capillaroscopy similar to
assay those seen in scleroderma
Pulmonary hypertension is the leading cause of
Primary Prophylaxis death
Blood vessels have intimal hyperplasia
Aspirin 325mg PO daily Other manifestations: ILD, pleural effusion,
Hydroxychloroquine 400 mg PO daily etc. Gastroesophageal reflux disease (GERD)
and esophageal dysmotility occurs similar to
Mixed Connective Tissue Disease scleroderma

MCTD is a unique connective tissue disease

with overlapping features of systemic sclerosis
(SSc), systemic lupus erythematous (SLE), and
polymyositis (PM), along with the presence of
antibodies to UI ribonucleoprotein (RNP)
Combination of the other 2 or 3 connective
tissue diseases
They respond also to steroids.
Inflammatory infiltration of vessel walls
Epidemiology and Risk Factors with damage to mural structures
Effort must be made to determine the cause
Prevalence – 10/100,000 with female to male Scleroderma is vasculopathy and vasculitis is
ratio of 10:1. inflammation.
Not showed relative preponderance in
African-Americans that is seen in SLE Primary Vasculitis
Occupational exposure to vinyl chloride
has been describes as risk factor Autoimmune causes
Associated with HLA-DR3, DR1 and
less prominently DR2 Classified scheme in 1993 Chapel Hill Concensus
Conference
Clinical Features
Large
Have clinical features of SLE, SSc and PM Medium
Polyarthritis affect most patient of MCTD Small

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Classification of Vasculitis Patient has visual loss, jaw claudication and
severe temporal headache.
Large Vessels Takayasu’s Arteritis
Giant Cell Arteritis Medium Vessel Vasculitides
or Temporal
Arteritis Polyarteritis Nodosa
Medium Vessels Polyarteritis
nodosa (PAN) Necrotizing systemic vasculitis affecting both
Kawasaki disease medium and small muscular arteries
Primary angiitis of Without glomerulonephritis Associated with
the central nervous hepatitis B
system
Involved skin nodules, mononeuritis
Small Vessels Wegener’s
multiplex, orchitis and mesenteric artery
Granulomatosis
Churg Strauss With hypertension, testicular tenderness
syndrome and association with hepatitis B and C
Microscopic
Polyangiitis Kawasaki Disease
Henoch Schonlein
Purpura Can affect large and small vessels
Mostly in children
Large Vessel Vasculitides Predilection for coronary artery
Associated with mucocutaneous lymph node
Takayasu’s Arteritis syndrome
The child can have heart attack.
Granulomatous inflammation affects the
aorta and its main branches Primary Angiitis of the CNS
May involve all or just portion of vessels
Typically in women from Japan with pulseless Rare granulomatous isolated in
disease the leptomeninges

Giant Cell Arteritis or Temporal Arteritis Small Vessel Vasculitides

Granulomatous arteritis in cranial Subdivided into the presence or absence of

branches arising from aortic arch immunoglobulin within the vessels
Also affects medium-sized vessel
Involved the temporal artery Presents of immune complexes in vessels
Associated with polymyalgia rheumatica
Seen in patient >50 years old, erythrocyte Henoch-Schonlein purpura
sedimentation rate (ESR) >50 Cryoglobulinemic vasculitis

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Connective tissue disease-associated Pathophysiology
vasculitis
Poorly understood
Absence of immune complexes vessels Increased antigen load
Associated with antineutrophil Decreased clearance efficiency by the reticulo-
cytoplasmic antibodies endothelial system
Decreased solubility
Wegener’s Granulomatosis Pathogenic immune complexes fix
complement Lead to intense inflammation
Lower respiratory tract chronic granulomatous
vasculitis inflammation Diagnosis
Necrotizing, pauci-immune glomerulonephritis
Associated with anti-proteinase 3 Assign the patient’s signs and symptoms to
a particular vessels size category
Churg-Strauss Syndrome Determine features within the category best fit
the patient
Known as allergic granulomatosis and
angitis Also affects medium-sized vessels Clinical Presentation
Affects lungs and skin arteries
Extravascular granulomatosis Most common clinical presentation:
Associated in approximately 50% of cases with
anti-myeloperoxidase Fatigue
Malaise
Microscopic Polyangiitis Fever
Arthralgias
Systemic vasculitis similar to Wegener’s
granulomatosis Several clinical feature strongly suggest the
presence of vasculitis:
Anti-MPO antibodies
Purpura
Secondary Vasculitis Mononeuritis multiplex
Pulmonary-renal involvement
Non-autoimmune cause of vasculitis
If you see a patient with elevated BUN
Etiology creatinine, with asthmatic lesions, think of
vasculitis.
Medications Remember that the most common clinical
Infections manifestations can be present in any of
Malignancie the connective tissue diseases.
s

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Differential Diagnosis Based on type and severity of clinical
manifestations
Embolic disorders Immunosuppresant is the mainstay for
Infections treatment
SLE and amyloidosis
Ergots, cocaine and amphetamines Medications
Malignancies
Thrombocytopenia and Glucocorticoids
myelodysplastic syndromes Cyclophosphamide
Methotrexate, azarthioprine and
Laboratory mycophenolate mofetil
Rituximab
CBC, creatinine, ESR and C-reactive protein
(CRP), hepatitis and HIV serologies, Complications
urinalysis and urine toxicology screen
Antinuclear antibodies (ANA) Complement Inadequately treated may lead to permanent
(cryoglobulinemia, hypocomplementemic end-organ damage and death
urticarial vasculitis and vaculitis associated Relapse after induction treatment is
with SLE ANCA directed to PR3 by ELISA unfortunately common, but re-treatment
usually leads to a good response

Imaging Takayasu’s Arteritis

Chest x-ray Epidemiology

Sinus CT
ECG Most common in Asians
Angiogram Characteristically affects women
Peak onset is in the third decade
Diagnostic Procedures
Pathophysiology
Biopsy of affected tissue
Cause is unknown
Treatment Focal panarteritis affecting large vessels
and major branches
Goal of Treatment Subsequent stenosis and aneurysm formation

Induce remission of disease

Maintain less toxic immnusuppressant to
prevent relapses

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Clinical Presentation Most common primary form of
vasculitis among adults
Divided to 3 monophasic stages
Phase 1 Prepulseless 2 Major Symptom Complexes
inflammatory
phase Vascular insufficiency Vision-loss from
leads to: ischemic optic
Symptoms: neuropathy
Headache
Fever Large vessels GCA
Malaise lead to arm
Arthralgias claudication
Weight loss Systemic inflammation Malaise
Phase 2 Vessel Fever
inflammation
Patient with reasonable suspicion of GCA
Symptoms:
should be immediately started won high-dose
oral or intravenous glucocorticoid therapy to
Vessel pain
suppress related blindness
tenderness
Phase 3 Burn out or fibrotic Once visual compromise has started, recovery
stage in the affected eye rarely occurs even with
Lead to ischemic aggressive treatment
symptoms
Polymyalgia Rheumatica
Common Findings:
Seen in individual >50 years old
Pulselessness Manifest by symmetric pain and stiffness in the
Unequal brachial blood pressures muscles for at least 4 weeks Closely related to
Subclavian/carotid bruits GCA
Carotidynia Respond very well to low-dose glucocorticoid
therapy
Hypertension
Epidemiology
Giant Cell Arteritis
Mean age at diagnosis is >70 years
Also known as temporal arteritis Women are affected 15% patient
Affects the second to fifth order develop GCA
aortic branches
Characterized by granulomatous inflammation
in vessels walls

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Polyarteritis Nodosa c-ANCA in WG has been identified as antibody
to proteinase-3 (anti-PR3)
Necrotizing inflammation of medium- or small
sized arteries Clinical Presentation
Without glomerulonephritis or vasculitis of
the arterioles, capillaries or venule Initial Phase Chronic
inflammation
Epidemiology usually in the upper
airways.
Affect men more frequently than women Sinusitis as initial
Ages 40 to 60 years old, peak 50 years old symptoms in >50%
Rare with incidence rate of 2.0 to 9.0 million patients
May also occur in
the oral cavity,
Etiology
retrobulbar space
or airway
Mostly idiopathic obstruction
Substantial minority cases are caused
by Hepatitis B virus (HBV) Symptoms:
Also linked to other viral infection,
especially HIV and Hepatitis C virus (HCV) Myalgia
Arthralgia
Wegener’s Granulomatosis Generalized Phase Fever and weight
loss are common
Systemic vasculitis associated with Pulmonary disease
antineutrophil cytoplasmic antibodies is cardinal feature
Renal disease
(ANCA) Often affects respiratory tract and
develop in
then the kidney
approximately 80%
Treatment involved immunosuppresants
of patients
Also known as ANCA-associated granulomatous Some exhibit
vasculitis migratory
Involved respiratory tract and vasculitis polyarthritis
affecting small- to medium-sized vessels Neurologic disease
Commonly with necrotizing glomerulonephritis Common
gastrointestinal
Pathophysiology manifestation

ANCA is positive in WG about 80-90% of

the time

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Churg-Strauss Syndrome Henoch Schonlein Purpura

Also known as allergic granulomatosis Defined as a vasculitis with IgA-dominant

and angiitis immune deposits affecting small vessels,
An eosinophil-rich granulomatous including capillaries, venules and arterioles
inflammation involving the respiratory tract Arthralgia, non blanching purpura and normal
Necrotizing vasculitis affecting small- to platelets
medium vessel vasculitis associated
with asthma and peripheral eosinophilia Epidemiology

Epidemiology Annual incidence is 14 cases per 100,000

people
Rare disease with an annual Majority of patient are children less than 10
incidence approximately 2.4 cases year old.
per million Affects the sexes equally Mean age at presentation is
The asthma associated with CSS usually begins 6 More common in male
in the fourth or fifth decade but occur at any Most common in the fall and winter
age months Often after respiratory infection

Pathophysiology Etiology

Two diagnostic lesions are arterial and venous Most cases follow respiratory infection
vasculitis and extravascular necrotizing May also associated with the administration
granulomas of drugs and vaccines.
Usually with eosinophilic infiltration of tissue No single dominant etiologic agent has
Antineutrophil cytoplasmic antibody been identified
Antimyeloperoxidase (anti-MPO) variant Genetic susceptibility with particular HLA alleles

Complications Pathophysiology

When cyclophosphamide is administered Characterized by deposition of IgA-dominant

intravenously, mercaptoethane sulfonate immune complexes
(MESNA) should be given to reduce risk of drug- With resultant complement activation
induced cystitis (dosing of MESNA is the same Leukocytoclastic vasculitis
as that of cyclophosphamide) Skin and gastrointestinal manifestation are
result of immune-complex driven inflammation

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Clinical Presentation Associated and may present problem as skin
lesions, joint complaints, vascular disease
Colicky abdominal pain associated with and neurologic manifestation
nausea and vomiting Unique among vasculitis in its ability to affects
Lower extremity arthritis vessels of any size
Skin lesions
Bloody diarrhea and palpable purpura Epidemiology
Boys may present with orchitis
Rare: headache or seizures Most commonly seen in ancient Silk Route
Upper respiratory tract infection extending from eastern Asia to the
Mediterranean basin
Physical Examination Turkey has the highest prevalence.
Estimated at 80 to 370
Palpable purpura cases/100,000 population
Arthritis Most common in men than in women
Gastrointestinal Peak age is in the mid 20-30
Genitourinary
Neurologic Pathophysiology

American College of Rheumatology 1990 Vascular injury

Criteria for the Classification of Henoch- Vasculitis of small vessels with subsequent
Schonlein Purpura vascular occlusion
Larger vessels demonstrate vasculitis of the
Presence of at least two of the following vasa vasorum with aneurysmal formation

Palpable purpura, not related to Clinical Presentation

thrombocytopenia Age <20
years
Erythema nodosum is observed in
Bowel angina, defined as wither diffuse
approximately 50% of patients in the course of
abdominal pain worsened by meal or bowel
disease and is more common in females
ischemia, usually with bloody diarrhea
Histologic changes showing granulocytes in
the wall of arterioles or venules Physical Examination

Behcet’s Disease Oral Aphthosis

Systemic vasculitis characterized by recurrent Lesions are typically round or oval shaped,
aphthous oral and genital ulcers and uveitis painful, 2 to 10 mm in size with sharp
erythematous border, a necrotic white-

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centered based, and a yellow Medications
pseudomembrane
Occur in gingiva, tongue, buccal and labial Treatment is based on system involved and
membrane the severity of that involved
Heal within approximately 10 Mucocutaneous aphthosis (oral and genital):
days Tend to recur frequently Colchicine at 1 mg/day
Uveitis/retinal vasculitis: tropical steroids
Ocular Findings and mydriatric agent

Anterior uveitis
Retinal disease

Cutaneous Manifestations END

Erythema nodusum
Pseudofolliculitis and acneiform
nodules Genital ulcers LEGEND:
Pathergy test – prick the forearm with gauge 25
needle and in 48-72 hours the patient will
develop sterile pustules BLACK – POWERPOINT
DARK BLUE – DRA. SAGUIL-
Articular manifestations
Venous Thrombosis SY RED –IMPORTANT POINTS

Superficial thrombophlebitis and deep venous

thrombosis

Central nervous system

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SUMMARY OF AUTOANTIBODIES AND ASSOCIATED DISEASE BY DDMD

ANTIBODY ASSOCIATED DISEASE/S

(+) ANA SLE (98%) , DM/PM (50-80%) ,
➔
Best screening and confirmatory test for SLE Sjogren’s syndrome (80%)

(+) Anti-dsDNA (70 %) SLE

➔
sensitive and specific for SLE
➔
used to monitor the disease activity of SLE
(+) Anti-Sm (25%) SLE
➔
sensitive but not specific for SLE ; low yield

(+) Anti-histone Drug-induced SLE

(+) Anti-Ro, Anti-La Sjogren’s syndrome

(anti-SSA, anti-SSB antibody)
(+) RF (65-90%)

(-) ANA, purely a clinical diagnosis FMS or fibromyalgia syndrome

(+) anti Jo-1 antibody Dermatomyositis/Polymyositis

(+) HLA-DR (DM/PM)

(+) UI RNP (ribonucleoprotein) Mixed Connective Tissue Disease (MCTD)

(+) HLA-DR-3, DR-1, and less of DR-2

(+) Anti-Scl 70 ( anti-topoisomerase I ) Scleroderma

(+) lupus anticoagulant Anti-phospholipid Antibody Syndrome (APAS)

(+) anticardiolipin antibody
(+) anti-beta2 glycoprotein 1

LAST PUSH BY GOKU AND FRIENDS

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