Download Connective Tissue Diseases

Connective Tissue Diseases
Betsy Evans PA-C
Rheumatology Associates
Portland, ME
Systemic Lupus Erythematosis
(SLE)
• Multi- system variable autoimmune disease of
unknown etiology
• Rare: 40-150 cases/100,000
• Hormones play a role!
– Adult female:male 7-15:1
• Children female:male 3:1
– Age of onset: 65% between 16-55 yrs
– Later onset (>50) usually has milder disease
Pathophysiology
• Precise mechanism is still not known but
abnormal cell apoptosis resulting in cellular
breakdown and cellular antigens appear to
play key role in the formation of polyclonal Bcell activation and autoantibody production.
These lead to immune complex formation and
deposition, resulting in complementdependent inflammation of involved organs
Race Plays a Role
• SLE occurs 3x more common in AfroAmericans than whites
• Disease is more prevalent and tends to be
more severe in Asians, Afro-Americans, AfroCaribeans & Hispanics
• More common in urban areas
Clinical Features
• Must meet 4/11 Criteria defined by the American
College of Rheumatology:
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Malar rash
Discoid rash
Photosensitivity
Oral or nasal ulcerations
Arthritis of 2 or more joints
Serositis (pleuritis or pericarditis)
Renal disorder
Neurologic disorder
Hematologic disorder
Immunologic disorder
Antinuclear antibody
Other Nonspecific Sxs of SLE
• Raynaud’s Phenomenon: fingers turn stark
white, followed by blue and then painful red
when they re-prefuse upon cold/stress
exposure
• Unexplained Fever
• Alopecia
• Fatigue
• Myalgias/arthalgias
Malar Rash
Discoid Rash
Oral Ulcerations
Arthritis
Renal Involvement
• Nephritis (5 different classes)
• Nephrotic Syndrome
• Tubulointerstitial disease
• Clinically look for persistant proteinuria and
cellular casts
• Definitive diagnosis by biopsy
IgG Deposition, Glomerulus
Membranous Lupus Nephritis
showing immune complex
deposition
Neurologic Involvement
• Seizures
• Psychosis
Hematologic Involvement
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Hemolytic Anemia
Leukopenia
Lymphopenia
Thrombocytopenia
Immunologic Disorder
• Antiphospholipid Syndrome
– A syndrome characterized by vascular thrombosis
(can be arterial or venual), pregnancy mortality, +
anticardiolipin Abs
• +Lupus anticoagulant
• Antibodies to double-stranded DNA
• False positive serologic test for syphilis
ANA Patterns
• Various patterns react to different parts of a
cell
• ‘Diffuse’ or ‘homogenous’ pattern is the least
specific but can be associated with SLE if titers
are high (usually >1:512)
• dsDNA is the most specific; speckled and
nucleolar are also important
• Histone pattern -> think DRUG INDUCED!
• Centromere pattern -> think CREST Syndrome
Drug Induced Lupus
• Can act and look like SLE but entirely
reversible once the offending drug is d’ced.
• Known Offenders: Hydralazine, Procainimide,
Minocycline, Chlorpromazine, Isoniazid,
Penicillamine, Methyldopa, & Interferon-alpha
Discoid Lupus
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Subset of lupus limited to the skin
Diagnosis confirmed by skin biopsy
ANA often negative
Prognosis usually good; <10% develop SLE
SLE Clinical Course
• Highly variable. 5 year survival rate >90%
• Poor prognostic indicators:
– Renal disease
– CNS disease
– Early or late age
– Males
– Non whites
– Overall disease activity
Clinical Course cont’d
• Late in disease (>5 years) complications/death
more likely due to thromboembolic disease
– ? Due to steroid requirements vs chronic
inflammatory states
SLE Diagnostic Studies
• Good History and ROS!
• Tissue biopsy if suspect renal involvement
• Labs: CBC (look for cytopenias, anemia)
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BUN/Cr (renal disease)
UA (proteinuria/cellular casts)
ANA (increased- watch the pattern)
C3/C4 (decreased)
CRP (normal or increased)
ESR (increased)
Ds DNA (present)
SLE Interventions/Therapeutics
• Depends on the severity of disease
• Hydroxychloroquine helpful for fatigue and
skin rashes
• Renal disease often requires high dose
corticosteroids and/or powerful
immunosuppressants like Cyclophosphamide
• Other immunosuppressants often used and
considered ‘steroid-sparing’: Azathioprine,
Mycophenalate, Methotrexate
SLE Interventions
• Other considerations:
– Treat side effects of medications eg
atherosclerosis and osteoporosis
– Pregnancy can be very risky for a female with SLE.
Effective birth control and family planning are
important. All efforts to have her disease under
excellent control prior to conception and then
close monitoring during pregnancy for any flares
are imperative
SLE Final Thoughts
Don’t rely on the ANA to make or break the
diagnosis; instead listen to your patient and
look for other criteria. If they aren’t present, it
probably isn’t SLE.
If in doubt, refer to a Rheumatologist for eval
Don’t be fooled by a low titer + ANA- remember
it is NONSPECIFIC!
SCLERODERMA
Systemic Sclerosis (SS)
CREST Syndrome
Scleroderma
• From the Greek “scleros”, describing
thickened, hardened skin
• 2 forms: Systemic Sclerosis (SS) and Crest
Syndrome (limited)
• Very rare: 240 cases/million
• Cause unknown
• Females>>males, peak onset 30-50 y.o.
Scleroderma Pathophysiology
• Poorly understood. Unknown trigger in a
genetically susceptible person leads to
immune system activation and vascular
reactivity followed by the deposition of
collagen and other matrix proteins in affected
tissues.
Clinical Presentation of SS
• Skin: Raynaud’s phenomenon with diffuse thickening
including chest, abdomen, face, upper arms, shoulders as
well as hands and feet
• Pulmonary: interstitial lung disease and fibrosis, less often
pulm HTN
• GI: dysmotility, “watermelon stomach”
• Renal: Scleroderma Renal Crisis: acute renal failure with
abrupt onset of HTN. UA reveals only mild proteinuria.
• Cardiac
• Musculoskeletal: arthralgias, puffy hands early on, carpal
tunnel
• + ANA: often speckled pattern
Raynauds
Puffy hand stage
SS Clinical Intervention
• No single disease modifier. Instead treatment
is aimed at the organs involved:
– ACE inhibitors for renal protection
– Calcium channel blockers for Raynaud’s
– Promotility agents for GI
– Cyclophosphamide debatable for lung disease,
Viagra/Levitra and Bosantan for pHTN
– AVOID high dose steroids; can lead to renal crisis
SS Clinical Course
• Variable. Early stages: Raynaud’s, puffy hands,
fatigue malaise, arthalgias/myalgias. Patients
can also present with dyspnea +/- GI
symptoms
• Poor prognosis with pulmonary involvement
and rapid progression. Use of ACE inhibitors
has improved renal outcomes.
CREST Syndrome
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AKA Limited Scleroderma
Calcinosis
Raynaud’s
Esophageal Dysmotility
Sclerodactyly of the fingers to the MCPs
Telangiectasia
Calcinosis
CREST Clinical Course
• Tends to be more benign than Systemic
Sclerosis
• Complication: pulmonary HTN- get annual
PFTs/DLCO
• Treat symptomatically
POLYMYOSITIS/DERMATOMYOSITS
• Autoimmune inflammatory myopathy
resulting in painless muscle weakness +/- rash
• DM is often associated with an underlying
malignancy in adults but not in children
• Rare: 2-10/100,000, more common in females
• Peak ages 40-60 yo
Clinical Manifestations
• Painless muscle weakness of the proximal
muscle groups with gradual onset. Patients
will complain that they have difficulty getting
out of a chair, climbing stairs, styling their hair
due to lack of power
• Early on no signs of fasiculations or muscle
atrophy
Skin Manifestations of DM
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Heliotrope rash of eyelids
Gottren’s papules on hands
Shawl sign
Mechanic hands
Periungal erythema
Calcinosis cutis
Heliotrope Rash
Gottron’s Papules
Shawl Sign
Mechanic’s hands
Periungual Involvement
Other Manifestations
• Pulmonary: Interstitial Lung Disease, BOOP,
diffuse alveolar damage
• Esophagus: dysphagia and gagging
• Misc: fever, polyarthritis, Raynaud’s
• + ANA plus other autoantibodies
• Elevated CPK. Aldolase, AST and ALT may also
be elevated
Diagnostic Tools
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EMG
MRI
Muscle Biopsy
Additional imaging if suspect malignancy
Treatment
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High dose corticosteroids
Methotrexate or Azathioprine
IV Ig for refractory/severe cases
If malignancy present, focus treatment on it
DM with resolve
Sjogren’s Syndrome
• Autoimmune disease affecting the exocrine
glands causing dry eyes and dry mouth (sicca)
• Cause unknown.
• Classified as primary or secondary (often seen
with rheumatoid arthritis or SLE)
• Rare: incidence ~5/100,000
• Female to male ratio 20:1; peak age 30-40
SjS Pathophysiology
• Trigger unknown. Infiltration of lymphocytes
to the glands and are activated. Cytokines are
released and promote parotid swelling,
destruction and localized inflammation. B cells
produce autoantibodies (SSA and SSB) and
over time can transform from a benign
polyclonal expansion to malignant expansion
of lymphocytes resulting in lymphoma
SjS Clinical Presentation
• Sicca Symptoms: Dry eyes and dry mouth. Ask
if the patient can cry or chew a saltine without
any water.
• Parotid Swelling
• Rash less common. Purpura of the lower
extremities
• Complications: Lymphoma & Primary Biliary
Cirrhosis. Locally, accelerated dental caries,
corneal atrophy and ulceration, oral candiasis
Parotid Swelling
SjS Diagnostic Studies
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+ Rheumatoid Factor and ANA > 90%
+ anti SSA 70-90%, anti SSB in 50%
Elevated ESR in the face of a normal CRP
+ Shirmer’s test: strip of paper left in the
corner of patient’s eye against the cornea.
Wetness at 5 minutes should be >10mm
• Biopsy of salivary gland not often performed
as treatment is usually symptom based
Shirmer’s Test
SjS Treatment
• Dry mouth: good hydration. Frequent dental
visits (q3m), avoid medications that make
symptoms worse. Salagen or Evoxac can be
beneficial but not usually earth-shattering
• Dry eyes: Artificial tears, lacrimal duct plugs,
Restasis eye drops