Scleroderma, Sjogren's & Myositis Flashcards
Scleroderma (Systemic Sclerosis)
etiology
Scleroderma (SS)
Etiology
- a systemic autoimmune disease with unknown origin, effecting all organ systems
- females > males
Three Features of the Disease
- Excessive deposition of ocllagen and other connective tissue molecules in skin and internal organs
- Vascular lesions of capillaries and small arteries
- alterations in the cellular and humoral immunity
high mortality rates: because the tissue fiberosis taht occurs in vital organs compromises function
Pathology - Collagen
- the excessive collagen deposition is due to overproduction of the collagen protein by fibroblasts
- there is alteration in the collagen regulation gene expression pathway due to cytokines and growth factors being released from the inflmmatory cells
- TGF-beta and SMAD pwathways
Pathology - Vascualr
- endothelial cell dysfunction: inital event the disease
- vascuarl abnormalities become apparent BEFORE tissue fiberosis
- cellular infiltrates with T cells and macrphages
Pathology - Immunity
- ANA pathology: triggers over activation of the system
Scleroderma
organ systems most commonly invovled
Organ Systems Involved
- always skin: collagen buildup
- Raynauds! (vasucular)
- GI tract
- lungs
can be (less comon)
bones/joints, muscles, heart, kidneys
Scleroderm: Skin Symptoms
limited v diffuse
face findings
other key signs
virtually everyone with scleroderma has skin findings
if they dont have the skin = scleroderma sine scleroderma
Symptoms
- thickened skin appears distally first and progresses proximally
- Limited Scleroderma: hands, feet, face, forearms and legs
- diffuse Scleroderma: upperarms, thighs, chest, abdomen also invovled
Face
- face becomes expressionless: no wrinkles
- talengiectagias
Diffused Hyper/hypo-pigmentation
- areas near hiar follicles are depigmeneted
Painful Ulcerations: fingertips and areas where the skin is so tight
cutaneous calcifications at fingertips (calcium deposits)
Raynauds and Scleroderma
Other Vascualture Symptoms of Scleroderma
Scleroderma: raynauds is the vascualr finding
- often happens before the skin findings
Raynauds
- temporary occculsion: white then blue, then excessve vasodilation leading to rednes and pain
- develops in virtually all pt. with scleroderma
Vascualr Symptoms
- capillarie heohrrages at the cuticle line : “WIre Loop” as the vessels try to go around the collagen blockage and divert
- necrotici lesions in the fingers and toes emergency
Scleroderma: Skeletal Symptoms
Skeletal Involvement
- symmetrical polyarthrialgia (pain) but TRUE arthritis or synovitis are rare
- contractures of teh hands and wrists with lost hand function
- carpel tunnel
- coarse leathery crepitus (tendon friction rub) rare but specific for diffuse scleroderma (since chest)
Xray Findings
- shows resporbtion and dissolution of teh distal phalanx : such bad circulation the bone goes away
- muscle fiber atrophy & possible polymyositis
Scleroderma: GI changes
GI Symptoms
- esophageal abnormalities in 90%
- incomplete LES and decreased/gone peristalsis leads to EXTREME REFLUX, odyniphagia and dysphaiga
- barretts esopahgus (and icnreased transition to CA) and lower esophageal stricture can occur
- causes hoarsness, and aspiration to pneumonitis
watermelon stomach: when there are big vessles that are dilated trying to compensate: high risk of GI bleeding
disordered gut motility: malabosrbtion, diarrhea, bacterial overgrowth
colonic disease with psueodiverticular (wide-mout sacculation)
Scleroderma: Respiratory Changes and Symptoms
tests for detecing these changes
lung involvement is the leading cause of morbitiy/mortality
Results in Pulmonary Fiberosis & Pulmonary Hypertension
PUlmonary Fiberosis
- insidious in onset
- hear fine inspiratory crackels as the lungs start to harden at the bases
Pulmonary Hypertension & Cor Pulmonale
- in those with limited and diffuse
Tests for Pulmonary invovledment
PFTs are the best
- if DLCO is low = pulmonary HTN
- if FVC/DLCO are both decreased = pulmonary fiberosis
CT can see the alvolitis: ground glass appearnce
Pulm HTn (lmitied)
interstital dx. (diffuse)
Renal Involvment in Scleroderma
renal involvement is the most deadly
- less commong, but it happens QUICKLY
- severe HTN and volume overload = lead to the crisis
Scleroderma Renal Crisis
- HTN, cardiac failure, MI, stroke = renal crisis
can be countered with prompt adminstration of ACE inhibitor
diffuse scleroderma at highest risk
Cardiac Involvement of Scleroderma
Cardiac
- heart will be effected; but symptomaitc andcardiac dysfunction less common
Tachyarrythmias and pericardial effusions are seens
Right heart strain due to pulmnary HTN can happen
Organ Invovlement Scleroderma
- neuro
- GU
- thyroid
- bile
Nero: periphearl neuropathy CNS is typically spared
GU: erectile dysfunction
thyroid: hypothyroid
can give secondayr sjogrens syndrome
pirmary biliar cirrhosis can happen too
Scleroderma: Diagnosis & prognosis
Diagnosis is made clinically
lab data can help decide what type of scleroderma
- ESR = usually normal
- ANA is typically positive in 90% +:
- diffuse = speckled or nucelor formation
- anti-centromere = limited
ANA findings
anti-centromere is most important = limited
anti-SCL70 (topoisomerase I) + RNA polymerase = diffuse
anti-scl70 = increased risk of pulmonary interstital involvement
Prognosis
highest risk in first 2-5 years
diffuse = shorter life span
limited = a bit longer
renal, cardiac or pulm involvemen t= worse off
Sjogrens Syndrome
Etiology
Etiology
- a chronic autoimmune disorder or the exocrine: mositrue producing glands
- creates a “Sicca Syndrome” of dry mouth and dry eyes
- reduced lacrimal and salivary gland function due to autoantibodies attacking
- second most common autoimmune after RA
Primary Sjogrens
- the dry eyes and mouth in a previously healthy individaul
Secondary Sjogrens
- the association of sjogrens from antoher rhum. disease: usually RA but also SLE too
Sjogrens Syndrome
Symptoms
Occular Specifics
slow, benging course of disease progression
Dry eyes and Dry Mouth = initial presenation for most pt.
Classic Traid
- keratoconjunctivitis sicca (dry eyes)
- dry mouth (xerostomia)
- arthritis
Occular Involvement
- chronic inflmamed lacrimal = decrease tear production
- dilation of conj. vessels & pericornal injection = red eye
- irregualr cornea
- burnchin, sandy, scratchy sensation and photosensitivtiy
- failure to treat dry eyes = ulcers and corneal perforation/melting and infection
Asked via these questions
- FB sensation in teh eye ?
- dry eye for 3+ months?
- using artifical tears 3+ months
Sjogrens Syndrome: Symptoms
Oral Involvement
Dry mouth due to decrease saliva production by the glands
- difficult to swallow
- inability to speak continuously
- changes in taste
- buring sensation in mouth
- **parotid and salivary galnd enlargement can occur in 60% of pt. **due to the destruction
the dry mouth can lead to
- cavities
- sialolithiasis (stones)
- oral candidias
- infections
- weight loss
Ask…
sympomts for 3+ months
recurrent or persistnat swollen glands
need liquid to swallow dry food
Sjogrens Syndrome : Symptoms
Arthritis
symmetrical polyarthritis simialr to RA but milder and non-erosive
Sjogrens Syndrome : Pathology
the B and T cells overactivate and direclty impact the salivary and lacrimal glands
this overreaction of cytokines and lymphocytes and antibodies = leads to fiberosis and scarring
fatty tissue is replaced instead of glandular tissue in these areas
this disrupts innervation and decrease function = irreversible destruction of the glands
Sjogrens Syndrome Diagnosis
3 of the 4 of the following need to be met for a dx.
Objective documentation of dry eyes
- schirmers test 5mm or less
- Occular Staining score
Objective documentaion of dry mouth
- unstimulated whole saliva flow
Autoimmunity via blood : SS-A
confirmation of histological involvement through gland biopsy of the sailvary gland
+ symptomatic ocular or oral symptos reported by pt. (need both)
4+ points = dx.
Sjogrens Syndrome
once objective dry mouth has been determiend
what testis conducted
salivary gland biopsy
- lower lip incision to get the biopsy of gland
Results
- focal lymphocytic sialadenitis of 50 or more cells around a salivary duct
- determined as a focus score
- focus score > 1 per 4 mm is a diagnosis
Sjogrens Syndrome : Lab tests
postive Anti-SSa
can also have postive anti-SSb
- ANA and RF can be postive = not specific
- can have elevated ESR
- elevated B2 microglobulin
only ss-A is used in the diagnosis criteris for sjogrens
___________________________________________
alwasy rule out medications causing the symptoms simialr to sjogrens!!!
Objective Documentation of the eye and mouth for dryness for dx. of Sjogrnes how
Objective Documentaion of Eye
- Schirmer’s test (paper and measure tears): nomal > 10mm/5min)
- Rose Bengal or fluorescein corneal staining: see irregualr surfaces
- tear break film test: measures the staibiltiy betwen blink and if it leakssooner = +
Objective Documentation of Dry mouth
- sialmetry: lashely cup to measure amount of salivation
- flow at normal rate should be > 0.1 ml/min
- stimulated with citric acid
- salivary scintigraphy not used
- salivary sialography: to see the ducts (Xray or MRI)
what are inflammatory myopathies
a group of autoimmune disorders characterized by muscle inflammation and loss of function
Dermatomyositis
polymyositis
necorttizing autoimmune myositis
inclusion body myositis
Inflammatory Myositis
symptoms
symptoms
- proximal muscle weakness: difficulty getting out of a chair or blow drying hair
- neck extensor weakness: difficult to hold up head: eyes look up
- distal strength is preserve: except in inclusion body where this is an issue (exaple: can still button buttons)
- no occular muscle issued
- painless
- assocaited with cancer!!! dermato more than poly
non-muscle symptoms
- rash, swelling of hands
- arthralgias
- raynauds and interstiatnl lung disease also possible
Inflammatory Myositis (dermato and poly)
lab tests
- CPK!! will be high (CPK, CK and aldoase) since this is a muscle issue
- other liver enzymes will be normal (LDH, AST/ALT)
Dermatomyositis
specific symptoms & key pearls
labs
signs on imaging (Ct and EMG)
Dermatomyositis
- subacute presentaion of proximal muslce weakness
- CK HIGH
- EMG done: shws irritable EMG with shapr waves and decreases amplitude and duration
- Muscle biopsy to show necrosis of fibers and perivesicualr perimysal inflammation : infiltreation of inflammatory cells around the vesicles
- autoantibodies: anti-MDA-5 and anti-Mi2
- MRI can show active inflammation: muscle edema on T2 (good for monitoring)
Rash: Chracteristics of the disease:
- eyes: helotrope rash
- shawl sign on upper shuolders
- mechanics hands
- knuckles “gottron” sign
Calcinosis (more common in kids)
Polymyositis
what is is
symptoms
labs and findings
Polymyositsi = no skin invovlement
Symptoms
- subacute onset of proximal muscle weakness
Findings
- CK elevated
- EMG shows myopathic units
- muscle biopsy: lots of CD8 cells INVADING the fibers
- auto-antibodies: antisyntehase = think interstital lung disea and mechanics hands
- MRI: shows active inflammation
Nectortizing Autoimmune Myositis
Necortizing
- THIS IS PAINFUL!!! none of the others are
- this is associtaed with statin use
acute or subacute onset of proximal muscle weakness: severely in adults
CK = will be very high over 50x normal
EMG: scute myopathic uints
Muscle Biopsy scatter necortic fibers, no CD8+ cells (dead fibers at this one)
labs : anti-SRP and HMGCR
MRI: inflammation
Inclusion Body Myositis
INclusion Body
- think of this as the AD of msucles
- slow and progression degeration adn misoflding proteins invading healthy cells
slow onset of proximal and distal muscle weakness in qudas, forearms, face
CK wil be 10x ULN
EMG: myopathic units
Muscle Biopsy: CD8+ cells invading health fibers and VACUOLES forming : from misfolded
labs: anti-cNIA
MRI: selective muslce invovlement
inflammatory myositis autoantibodies and treatment
the treatment is guided by the prescene of which antibodies
myositis specific
- non-synthestase
- synthestase
- myositis assocaited autoantibodies
