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Doctor: Khaldon Alawneh.

Lec: RA, SLE & FMF

Done by: Hadeel Al-Kofahi


& Sara Al-Zubi

Rheumatoid arthritis
Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that may affect
many tissues and organs, but principally attacks flexible (synovial) joints , and it's the
most common persistent inflammatory arthritis, occurring throughout the world and in
all ethnic groups.
Generally, all rheumatic diseases can be local diseases but generally, they have
systemic involvement and RA is one of the common rheumatic diseases; at least, 1% of
people worldwide are affected by RA.
So, RA is a systemic disease, primarily presents as Arthritis -affecting the joints- so the
main problem is arthritis & Other Organs can be involved.
Etiology is not clear, probably Multifactorial [both genetic and environmental factors appear to
be involved], but we know the mechanism of the disease [RA is characterized by infiltration of
the synovial membrane with lymphocytes, plasma cells, and macrophages. CD4+ T cells play a central
role by interacting with other cells in the synovium. Activated T cells stimulate B cells to produce
immunoglobulins including RF, and macrophages to produce pro-inflammatory cytokines. These act on
endothelium, synovial fibroblasts, bone cells and chondrocytes to promote swelling and congestion of
the synovial membrane and destruction of bone, cartilages and soft tissue.] and because of that, we

have more options for treatment. (TNF, iL-1, 6 are important so they create drugs that
block them)

Diagnosis:
-

Typical clinical presentation [joint pain, swelling and stiffness affecting the small
joints of hand, feet and wrist (without swelling, no Dx of RA)]

Rheumatoid factor presence or absence does not make or exclude diagnosis but
positive RF means more extra-articular manifestations and more severe
manifestations [because RF can form immune complexes within the joint and extra articular
tissues, leading to vasculitis.]. In old days, we said that 70% of affected are RF positive
and it was part of the criteria and now its more important in the criteria than
before.

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Doctor: Khaldon Alawneh.


Lec: RA, SLE & FMF

Done by: Hadeel Al-Kofahi


& Sara Al-Zubi

You have to exclude other diseases that may mimic RA or cause arthritis (other
than RA).

ACR 1987 classification criteria for RA, the old criteria:


1- Morning stiffness lasting at least for 1 hour.*
2- Swelling in 3 or more joints.*
3- Swelling in hand small joints.*

*These 4 must be present at least 6


weeks.

4- Symmetric joint swelling.*


5- Erosions or decalcification on X-ray of the hand [radiological changes].
6- Rheumatoid nodules.
7- Abnormal serum rheumatoid factor.
<< This is the old criteria in the new one, the only 2 differences are: rheumatoid
nodules are not present any more in the new criteria and they added anti-citrullinated
protein antibody (ACPA). >>

This is a normal joint, the joint is surrounded by a


synovium, and its the site of the inflammation; normally
it consists of 1-2 cells thickness.

With synovial inflammation, the thickness becomes hundreds of cells. In this case, the
synovium will act as a tumor, it will invade the bone and the cartilage and destruct
them and for that reason, the erosions in RA are lateral on the sides while the inside
damage will be later.

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Doctor: Khaldon Alawneh.


Lec: RA, SLE & FMF

Done by: Hadeel Al-Kofahi


& Sara Al-Zubi

Constitutional Signs and symptoms of systemic RA:


Fatigue, tiredness, weakness, weight loss, myalgia, excessive sweating, low grade
fever, morning stiffness, lymphadenopathy . Those are general vague symptoms due
to the generalized systemic inflammation.
Laboratory features in RA:
1)
2)
3)
4)
5)
6)
7)
8)

Anemia*.
Eosinophilia*.
Thrombocytosis*.
Increased levels of alkaline phosphatase, Aspartate amino-transferase, and gammaglutamyl-transferase.
Decreased albumin and pre-albumin.
Elevated erythrocyte sedimentation rate [ESR]*.
Elevated C-reactive protein [CRP]*
Increase ferritin* (ferritin is considered as acute phase reactant; any patient with
anemia & increased ferritin then think of chronic inflammatory disease).

Now, the dr. had moved on to show us different pictures to patients with RA:

This looks normal once you


look at it, but if you look
more carefully, you see early
changes in the MCPs & PIPs
with symmetrical synovitis,
no deformity
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Early RA with soft tissue


swelling, involving PIPs
Joints.
Note that DIPs are spared
and this is typical for RA.

Doctor: Khaldon Alawneh.


Lec: RA, SLE & FMF

Done by: Hadeel Al-Kofahi


& Sara Al-Zubi

This is severe disease,


synovitis & Subluxation of
MCPs, RA nodules.
Again; DIPs are relatively
spared.

This is ulnar deviation,


damage of MCPs & PIPs &
rheumatoid
nodules
&
muscle atrophy.
The DIPs
spared.

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still

relatively

This is swan neck deformity


(arrow)
&
boutonniere
deformity (arrowhead).
Maybe, youll never see
these deformities because of
better
treatment
than
before.

Ruptured tendon in RA patients

Doctor: Khaldon Alawneh.


Lec: RA, SLE & FMF

Done by: Hadeel Al-Kofahi


& Sara Al-Zubi

This is metatarso-phalygeal
[MTP] joint, it can be also
affected.

There is distal involvement and it could


be part of osteoarthritis.
Deformity, subluxation,
erosions (MCP).
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osteoporosis,

RA patient with carpal tunnel


syndrome [CTS]

This is a typical X-Ray where the carpal


bones affected and damaged and soft
tissue swelling around the MCPs (are
damaged) and PIPs, osteoporosis.

Doctor: Khaldon Alawneh.


Lec: RA, SLE & FMF

Done by: Hadeel Al-Kofahi


& Sara Al-Zubi

The dr. said that hell not comment that much on the X-Ray but if you see X-Ray in
the exam that shows ulnar deviation and damage on the MCP joint, it will be
rheumatic Arthritis, there will be no another question about it.

Here ulna styloid erosion, as I said it starts as


erosion from sides, later on, it will be inside.

Metatarsal joint, there could be damage or


erosion (in 5th MTP) and fibular deviation rather
than ulnar deviation in the upper extremities.

MTP joints with erosions, subluxation,


osteopenia [a condition where bone mineral density is
lower than normal. It is considered by many doctors to be
a precursor to osteoporosis]

Bone uptake in RA; carpal bones, MCPs and


PIPs
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Doctor: Khaldon Alawneh.


Lec: RA, SLE & FMF

Differential Diagnosis:
-

Viral syndromes.

Post Streptococcal/other infections.

Psoriatic arthritis, reactive arthritis, and


other systemic rheumatological diseases.

Crystal arthropathy like Gout.

Septic arthritis also may coexist.

Here is Subcutaneous nodules. the typical site for it


is the elbows, extensors, hands.
* Rheumatoid nodules occur almost exclusively in
seropositive patients, usually at sites of pressure or
friction such as the extensor surfaces of the forearm
[elbows], sacrum, Achilles tendon and toes. They
may be complicated by ulceration and secondary
infection. Similar nodules may occur in the pleura,
lung, pericardium, and sclera.

This slide is just to show


you that this is a systemic
disease that can affect
even the heart, the lungs,
kidneys (although it is not
common), joint, skin and
everywhere.

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Done by: Hadeel Al-Kofahi


& Sara Al-Zubi

Doctor: Khaldon Alawneh.


Lec: RA, SLE & FMF

Here we see lung nodules which is


part of the disease.

Done by: Hadeel Al-Kofahi


& Sara Al-Zubi

ILD [interstitial lung disease],


Cavitation, TB, abscess, fungi, tumor,
Nodule

Major ocular manifestations:


-

Keratoconjunctivitis sicca.

Scleritis:painful and serious

Episcleritis; an inflammatory condition affecting the episcleral tissue that lies


between the conjunctiva and the sclera, it's painful and may cause perforation.

Uveitis

Episcleritis is common in RA, Superficial but


cause irritation.

Scleromalacia: degeneration and thinning

(softening) of the sclera, occurring in rheumatoid


arthritis, a potential serious complication is the
perforation.
Some patients got perforation and they lose vision
(in the old days) but nowadays because of the
immunosupression, this doesnt happen.
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Doctor: Khaldon Alawneh.


Lec: RA, SLE & FMF

Done by: Hadeel Al-Kofahi


& Sara Al-Zubi

Scleromalacia perforance: In this condition


rheumatoid nodules may develop in the sclera and
cause perforation

And some patients their cornea may melt and they


need corneal transplant [Marginal corneal disease,
and perforation].

Rheumatoid vasculitis usually occurs in older seropositive patients in the context of


systemic symptoms and multiple extra articular features. Vasculitis can vary from
relatively benign nail-fold infarcts to widespread cutaneous ulceration and skin
necrosis. Involvement of medium sized arteries can lead to mesenteric, renal or
coronary artery occlusion.

Vasculitis; blood vessels


inflammation (here affecting
small vessels)

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Vasculitis causes gangrene like


this

Doctor: Khaldon Alawneh.


Lec: RA, SLE & FMF

Done by: Hadeel Al-Kofahi


& Sara Al-Zubi

The spinal cord may affected because it has synovioum around the odontoid process
and this synovioum may cause damage to the transverse ligament or to the odontoid, if
it causes damage to the ligament, it will cut & cause compression on the spinal cord.

Signs of SC damage:
-

Severe neck pain radiating to Occiput

Tingling or numbness in fingers and feet

Motor weakness

Urinary bladder dysfunction

Jumping legs

<<< When the spinal cord is affected the patient may die! They take him to the
surgery and the anesthetic resident dont know that he has RA and he push the patient
backward with force so the patient has trans-sectional cord and he die on the table!
>>>

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Doctor: Khaldon Alawneh.


Lec: RA, SLE & FMF

Done by: Hadeel Al-Kofahi


& Sara Al-Zubi

This is the new criteria, and you dont have to remember it.

If you have more than 10 joints involvement then you have at least 1 small joint
because this is a poly-articular arthritis affecting small and large joints, so if you have
more than 10 joints and one of them is small joint then you say yes and go to the next
step; the serology, if the serology is positive then this is definitely RA (serology means
RF OR ACPC).
If serology is negative then you look to the duration; if it is 6 weeks and more then it is
RA. If it is shorter than 6 weeks then you go to APR (Acute Phase Reactant, CRP &
ESR), If the APR positive then it is RA, if it is negative still not diagnosed.
Most of the patient, the APR is positive and the serology: 75% is positive.

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Doctor: Khaldon Alawneh.


Lec: RA, SLE & FMF

Done by: Hadeel Al-Kofahi


& Sara Al-Zubi

The dr. didnt explain this table and its not for
memorization.

The dr. said that the treatment is very complicated but the main action of drugs is that
they block the inflammatory mediators (TNF, iL 6, 2). And the earlier we diagnose and
the earlier we treat, the higher percentage the person will go to remission.
NAIDs are not good, they dont decrease the progression of the disease & nobody goes
into remission.
Prednisolone by itself dont make a difference (it increase CVS mortality) but if
combined with disease modifying drugs [DMARDs], theres some evidence about
increase the probability of remission.

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Doctor: Khaldon Alawneh.


Lec: RA, SLE & FMF

Done by: Hadeel Al-Kofahi


& Sara Al-Zubi

Systemic lupus erythromatosus


SLE: is an Autoimmune multisystem disease characterized by widespread
inflammation and production of autoantibodies (or autoimmune connective tissue
disease) that can affect any part of the body. As occurs in other autoimmune diseases,
the immune system attacks the body's cells and tissue, resulting in inflammation and
tissue damage. It is a Type III hypersensitivity reaction in which antibody-immune
complexes precipitate and cause a further immune response. Even the RF will be
positive in SLE (30% or more in SLE patients have RF positive and can present with
RA and then you misdiagnose SLE as RA.).
SLE is a systemic disease rather than local as RA, the difference is that: RA is a
disease of joints with systemic manifestations while SLE is a true systemic disease and
can mimic any disease including RA.
So, this disease is associated with wide spectrum of presentation.

Epidemiology:
SLE is the most common connective tissue disease, the risk increases according to:
1) AGE: the peak of the age onset is between 15-40 years old [20-30 in the book] because of
complications as pregnancy, but it can affect any age.
2) SEX: around 90% of affected individuals are females. During the childbearing
age, the ratio is 10:1.
3) RACE: high prevalence in African in US and UK 1:250-500,also in high
prevalence in Latino and Asian.While rare in Africa. Caucasian prevalence
1:2000.
The overall 5 years survival of SLE is 90%. And the mortality within 5 years of
diagnosis occurs due to organ failure or overwhelming sepsis, both of which are
modifiable by early effective intervention.
>> The dr. said that he dont know the prevalence in Jordan and how much the
problem is but this disease is a bad disease, theres no one year without losing few
patients with lupus so its associated with high mortality (young females) and
morbidity.
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Doctor: Khaldon Alawneh.


Lec: RA, SLE & FMF

Done by: Hadeel Al-Kofahi


& Sara Al-Zubi

Clinical features

1) General Features:

- Nonspecific symptoms: Severe fatigue, Fever, Weight loss, Anorexia,


Lymphadenopathy.
>> those are similar to the RA symptoms with 2 differences:
The fever is much higher in SLE while in RA; its low-grade fever.
The typical presentation of SLE is much more than RA, where in RA (joint pain &
swelling with morning stiffness), while in SLE (extreme fatigue, febrile, dyspnea,
typical rashes on the face,etc).

2) Raynaud syndrome

(secondary Raynaud's): is a vaso-spastic disorder


causing discoloration of the fingers, toes, and occasionally other areas where it
is caused by other instigating factor [ other than the ones causing primary
Raynaud's], most commonly connective tissue disorders such as systemic lupus
erythematous.

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Doctor: Khaldon Alawneh.


Lec: RA, SLE & FMF

Done by: Hadeel Al-Kofahi


& Sara Al-Zubi

3) Dermatological features:

Malar rash: in 30-60%, its an erythematous butterfly rash


occurs over nasal bridge and malar bones [cheeks] and sparing the
naso-labial fold.
- It's erythematous, raised and painful or itchy.
- When taking medication, it becomes faint.
- Its superficial rash.

Photosensitivity: rash over the sun exposed areas; [face, neck


and V shaped area of chest].
- Rash varies in severity depending on exposure, Less under the
orbit protected areas.
- After theyre exposed to sun for 10-15 minutes, they come with
sloughed skin - like rash

Discoid rash: with erythematous hyper-pigmented margins and


flat scarred hypo-pigmented centers.
- This can be seen in SLE and pure cutaneous lupus.
- Its a deep rash with scarring mainly on the face and neck.
- Characterized by hyperkeratosis and follicular plugging and
may cause scarring alopecia if presented on the scalp.

4) Gastrointestinal features:
Oral ulcers:
Oral or nasopharyngeal ulceration, usually painless, observed
by physician

Oral lesions in SLE: Erythema of hard and soft palate.


Also you see papules, vesicles
erythematous rash of the tongue.
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and

petechiae.

Also

Doctor: Khaldon Alawneh.


Lec: RA, SLE & FMF

Done by: Hadeel Al-Kofahi


& Sara Al-Zubi

Mesenteric vacuities: is a serious complication which can present with abdominal


pain, bowel infraction or perforation.

5) Arthritis and Arthralgia:


Arthritis: Non-erosive arthritis involving 2 or more peripheral joints, characterized
by tenderness, swelling, or effusion
Symmetrical, but can be asymmetrical, affect large and small joints, it can be
anything!!

SLE arthropathy: Non erosive arthritis, Hand


may show diffuse soft tissue swelling, ulnar
deviation, swan neck deformity, MCP subluxation.

In old days; 20 years ago, the rheumatology was only an observational specialty, there
was no medications except methotrexate. So they was saying that the difference
between RA & SLE arthritis that SLE is non-erosive (but not 100% !!) with deformities.
Arthralgia: migratory arthralgia with early morning stiffness.
tenosynovitis and small joint synovitis that can mimic RA.

6) Pulmonary features::
Pleuritis: the most common [30%] in life time of SLE patient.
Pneumonitis, pulmonary embolism, pulmonary hypertension, pulmonary
fibrosis & nodules
Pulmonary hemorrhage: the most dreadful with 50 % mortality with treatment.
Usually, males with SLE die because of pulmonary hemorrhage.
< It can cause any disease in the lung >

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Doctor: Khaldon Alawneh.


Lec: RA, SLE & FMF

Done by: Hadeel Al-Kofahi


& Sara Al-Zubi

7) Cardiovascular features:
Pericarditis: the most common.
Aortic insufficiency: the most common valvular lesion (it damages the valves)
Endocarditis, aortitis, myocarditis, valvulitis and antibiotic prophylaxis
indicated for dental and surgical procedures
Accelerated atherosclerosis & damage to the coronaries (CAD) with 10 times higher
mortality from myocardial infarction from age and sex matched.
Serositis: it includes:
- Pleuritis: convincing history of pleuritic pain, pleural rub heard by a physician or
evidence of pleural effusion, with dyspnea. OR
- Pericarditis: documented by ECG, pericardial rub or evidence of pericardial
effusion.
< So, SLE can affect the pleura or inside the pleura >

8) Hematological features:
Hemolytic anemia with reticulocytosis & mild jaundice & LDH
>> usually, in hemorrhage, if the bone marrow still working, reticulocyte count will
increase but if the bone marrow isnt working (aplastic crisis bcz of lupus),
reticulocyte count will decrease. But in normal person, reticulocyte count will
increase bcz the bone marrow will push more reticulocytes to the blood.
Leukopenia: less than 4,000/mm total on 2 or more occasions OR
Lymphopenia: less than 1,500/mm on 2 or more occasions OR
Thrombocytopenia: less than 100,000/mm, in the absence of offending drugs.

9) Renal features:

Lupus

glomerulonephritis: presented as Persistent proteinuria (due to


inflammation) greater than 0.5 grams per day or grater than 3+ or Cellular casts (due
to glomerulonephritis as in children); may be red cell, hemoglobin, granular, tubular,
or mixed.

Impaired kidney function, as if creatinine level increases, then you should treat or
the patient will develop renal failure.
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Doctor: Khaldon Alawneh.


Lec: RA, SLE & FMF

Done by: Hadeel Al-Kofahi


& Sara Al-Zubi

** Lupus nephritis predict out come (prognosis); the kidneys are the target of lupus, if
the kidney function is normal then the outcome is acceptable -except if theres other
serious organ involvement** Major cause of mortality & morbidity.

10) Neurological features:


Seizures OR psychosis: in the absence of offending drugs or known metabolic
derangements; e.g., uremia, ketoacidosis, or electrolyte imbalance
< So, the global function of the brain will be impaired >

11) Immunological disorders:


95% of lupus patients are Anti-Nuclear Antibody (ANA) positive, but this antibody
isnt specific for SLE since many diseases can be ANA positive. (so ANA test is
sensitive but not specific).
More specific tests:
1- Anti-DsDNA antibody. or
2- Anti smith antibody.
And/Or
3- An abnormal serum level of IgG or IgM anticardiolipin antibodies. Or
4- A positive test result for lupus anticoagulant using a standard method.

ACR criteria; 1982 classification criteria:


The diagnosis of SLE is based on a combination of clinical features and laboratory
abnormalities. To fulfill the classical criteria of SLE, You must have 4 criteria of 11
[simultaneously or serially] from the flowing:
Malar rash, discoid rash, photosensitivity, oral ulcers, arthritis, serositis, renal
disorder, neurological disorder, hematologic disorder, immunologic disorder,
antinuclear antibody.

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Doctor: Khaldon Alawneh.


Lec: RA, SLE & FMF

Done by: Hadeel Al-Kofahi


& Sara Al-Zubi

Anti-phospholipid antibody syndrome [APS]


It is an autoimmune, hyper-coagulable state caused by antibodies against cellmembrane phospholipids that provokes blood clots (thrombosis) in
both arteries and veins as well as pregnancy-related complications such
as miscarriage, stillbirth, preterm delivery, or severe preeclampsia.
Can be:
- Primary (50%) without underlying disease.
- Secondary (50%) to SLE, malignancy or infection.
For diagnosis, you need 1 clinical & 1 lab criteria;
- Clinically:
1) Recurrent venous and arterial thrombosis.
2) OR/AND Recurrent fetal loss.
- Labs:
1) Lupus anticoagulant test by mixing studies: those which interfere with
phospholipid dependent coagulation tests.
2) OR Anti-Cardiolipin antibodies test: antibodies which bind to negatively chared
phospholipids on an ELISA plate.
Thrombocytopenia & prolonoged PTT are clinical findings but not part of the
criteria.

Labs in SLE
>> ANA: 95% positive, sensitive but not specific. 5-10% positive general population,
also positive in other auto immune diseases (eg. thyroiditis)
>> Anti-DNA antibody: specific but not sensitive, increase with active disease. 3060% of patients are positive.
>> Anti-smith antibody: specific for SLE. 30% are positive.
>> Rheumatoid factor: can be positive in 30%.

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Doctor: Khaldon Alawneh.


Lec: RA, SLE & FMF

Done by: Hadeel Al-Kofahi


& Sara Al-Zubi

Depend on organ involved


Leukopenia and lymphopenia are common
Thrombocytopenia
Anemia of chronic disease
Hemolytic anemia with high reticulocyte count, coombs positive
Proteinurea, casts
Abnormal liver and kidney function
RA (as polyarticular arthritis) Vs. SLE (as arthritis in a connective tissue
disorder):
- CBC: white count & platelets are increased & Hb in decreased in RA while in SLE,
Hb, white count & platelets are down.
- Hemolytic anemia: not significant in RA but common in SLE. Anemia in RA is
mainly due to GI hemorrhage, due to medications as NSAID & steroids.
- C-reactive protein: negative in lupus (except in infections) & positive in RA.
Always remember that pregnancy & SLE are not friends!!

Familial Mediterranean fever


-

This is the most common of the familial periodic fever, predominantly affecting the
Middle East, south Europe.
Autosomal recessive (so you need 2 mutations) disease characterized by attacks of
serositis and fever, attacks are acute and sudden (last from 6-96 hrs; few hours to
days); it come and resolve alone or by NSAID.
First attack occur before age 20 in 90%.
Symptoms: Abdominal pain in 95%, mostly as acute abdomen and peritonitis but
some times mild, Mono-arthritis with effusion in 75%, mostly knees, ankles or
wrists, Chest pain/ pleuritis (unilateral)in 30%, Pericarditis (rare 1%) WITH fever or may be fever alone-.

The main complication of this disease is amyloidosis; any chronic inflammation can
end with amyloidosis as RA. So its a chronic recurrent inflammation that ends with
amyloidosis and the most sensitive organ to amyloidosis is the kidneys so they end up
with dialysis.

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Doctor: Khaldon Alawneh.


Lec: RA, SLE & FMF

Done by: Hadeel Al-Kofahi


& Sara Al-Zubi

Genetics: the responsible gene has been located in short arm of chromosome 16,
MEFV gene encodes protein (pyrin, marenostrin), Pyrin mostly in cytoplasm of
neutrophils or monocytes /regulates inflammation [regulates neutrophil mediated
inflammation by indirectly suppressing the production of IL-1].
>> mutations: 28 mutation (most common), M694V and V726A.
>> M694V associated with more severe disease and higher risk of amyloidosis

Treatment: Colchicine (1-2 mg QD); decrease 60%


of attacks and modifies 20-30% & prevents amyloidosis.
It arrests cell division in the microtubules so decrease
the inflammation.
NSAIDs may help abort attack.

THE END
Best of luck ALL da3watkom :D
Done by: Sara AL-Zu'bi
& Hadeel Al-Kofahi.
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