Sjorgren/Scleroderma Flashcards
Sjögren Syndrome (SS)
general
whatis primary called
Autoimmune, inflammatory condition where glandular tissues, such as the salivary and lacrimal glands, are infiltrated by lymphocytes, resulting in decreased tear and saliva production
Affects ~4 million people in the United States
Predominantly seen in middle-aged women (age 40-55 years of age)
Classification
Primary - known as sicca syndrome
Secondary
Sjorgens
Primary SS
Etiology is unknown
Possible genetic predisposition
HLA genes
Possible viral connection
Epstein-Barr virus (EBV)
Chronic hepatitis C
Human T cell leukemia virus 1
Human herpesvirus 6
Human immunodeficiency virus (HIV
Sjogrens
Secondary SS
Presents in association with another autoimmune disease
Rheumatoid arthritis
Systemic lupus erythematosus
Polymyositis
Scleroderma
Hashimoto thyroiditis
Sjogren
Patho
The exact mechanism of SS is unknown
Process may be set off by an environmental trigger in a patient with a genetic predisposition
Salivary, lacrimal, and other exocrine glands become infiltrated with CD4+T cells and to a less extent with B cells
T cells produce inflammatory cytokines (IL-2, interferon-gamma)
Interferons stimulate B cell activating factor (BAFF) production → promotes irregular B cell maturation → B cells release autoantibodies (Anti-SSA and Anti-SSB)
Cytokines and autoantibodies cause damage and atrophy of the glandular and ductal epithelium → ↓ exocrine production (↓ tear and saliva production)
Other exocrine glands throughout the body can be involved, as well
Sjogrens
Eye Sx
Often affects the eyes and mouth initially
Eyes:
Dry eyes (xerophthalmia)
Sandy, gritty sensation
Burning
Redness
Blurry vision
Visual impairment
Advanced disease the cornea can be severely damaged
Epithelial strands hang from the corneal surface (keratitis filiformis)
Corneal ulceration
Sjogrens
Mouth Sx
Dry mouth (xerostomia)
Difficulty tasting, chewing, and swallowing
Difficulty speaking for long periods of time
Tooth decay
Parotid gland enlargement
Sjogrens
Cutaneous and other Sx
Cutaneous:
Dry skin (xerosis)
Raynaud’s phenomenon
Cutaneous vasculitis
Palpable purpura
Urticarial lesions
Ulcerations
Erythema nodosum -shins
Nasal dryness → bleeding, ulceration and perforation of the nasal septum
Dry cough
Vaginal dryness:
Vulvar infections
Dyspareunia- pain during sex
Can also have respiratory, cardiac, endocrine, neurological, and renal manifestations
Sjogrens
Arthralgia/Arthritis:
Similar distribution to rheumatoid arthritis
Nonerosive and nondeforming
Sjogrens
Labs
Labs
Anti-SSA/Ro and anti-SSB/La antibodies (60%–70% of patients)
Antinuclear antibodies
Rheumatoid factor (40%–60% of patients)
Complete blood count:
Anemia
Leukopenia
Thrombocytopenia
↑ Erythrocyte sedimentation rate (ESR)
Sjogrens
Ophthalmologic evaluation
Schirmer’s test
Measures tear production
Filter paper is placed in the lower eyelid
Wetness is measured after 5 minutes
< 5 mm wetness is considered a positive test
Fluorescein slit-lamp examination
Evaluates the cornea and conjunctiva for damage
Sjogrens
Dx for salivary function
Evaluate salivary production
Sialometry
Measures the rate of saliva production
Unstimulated saliva is collected and measured over 15 minutes
Scintigraphy:
Measures salivary gland function through radionuclide uptake
Very low uptake is highly specific for SS
Biopsy
Performed on a lower lip salivary gland
↑↑ CD4+ T-cells
Thickening of the inner duct wall
Sjogrens
Diagnostic Criteria
Developed by the American-European Consensus Group 2016
Requires 4 of 6 criteria, including a positive biopsy or autoantibodies
Ocular symptoms(at least 1):
Dry eyes for ≥ 3 months
Foreign body sensation in the eyes
Use of artificial tears ≥ 3 times per day
Oral symptoms(at least 1):
Dry mouth for ≥ 3 months
Recurrent or persistently swollen salivary glands
Need for liquids to swallow dry foods
Ocular signs(at least 1):
Positive Schirmer’s test
Positive dye staining on the surface of the eye
Oral signs(at least 1):
Positive sialography
Positive scintigraphy
Positive biopsy
Positive anti-Ro and/or anti-La
Sjogrens
Primary SS Tx
disease limited to ocular and oral symptoms
Multidisciplinary approach (rheumatologist, dentist, and ophthalmologist)
Primary SS- disease limited to ocular and oral symptoms
Oral hygiene
Regular dental visits
Smoking cessation
Artificial tears
Avoidance of drugs that decrease salivary secretions (antihistamines, anticholinergics)
Salivary stimulants (muscarinic agonists)
pilocarpine (Salagen)
cevimeline (Evoxac)
Sjogrens
Systemic Tx
Systemic manifestations
Glucocorticoids
Hydroxychloroquine (Plaquenil)
Disease-modifying antirheumatic drugs (DMARDs)
Methotrexate
Leflunomide
Azathioprine
Sulfasalazine
Rituximab for severe disease that does not respond to the above therapies
Secondary SScan be improved by managing the primary autoimmune disease
Sjogrens
Complications of disease
Complications
Non-Hodgkin’s lymphoma
Occurs in 5%–10% of patients
40x the normal rate
Usually presents around 7 years after onset
Secondary oral Candida infection
Blindness due to corneal scarring
Renal failure from progressive renal involvement
Pulmonary infections
Reduced quality of life
Systemic Sclerosis
general
Also known as scleroderma
Rare, chronic autoimmune disorder in which there is progressive deposition of collagen in the skin, blood vessels, and internal organs causing tightening and fibrosis
♀>♂
Women more likely to present
Younger, with limited disease
Peak age at presentation 35-50 years
Most severe among African-American patients
Systemic Sclerosis
Three classifications:
CREST syndrome
Generalized systeic sclerosis (w diffuse skin involvement)
Systemic sclerosis sine scleroderma
Systemic Sclerosis
Limited systemic sclerosis (CREST syndrome)
Calcinosis cutis, Raynaud’s phenomenon, Esophageal dysmotility, Sclerodactyly (tight skin over digits), Telangiectasias
Characterized by slow progression and is often complicated by pulmonary hypertension
Systemic Sclerosis
Generalized systemic sclerosis (with diffuse skin involvement)
Raynaud phenomenon and gastrointestinal (GI) complications
Evolves rapidly
Interstitial lung diseaseand scleroderma renal crisis are the major complications
Systemic Sclerosis
Systemic sclerosis sine scleroderma
Systemic sclerosis–related antibodies and visceral manifestations of the disease but no skin tightening
Systemic Sclerosis
etiology
Etiology is unknown
Genetics likely play a role
Suspected environmental triggers include
Infectious (cytomegalovirus (CMV), herpesvirus, parvovirus B-19)
Environmental
Silica exposure
Solvents (vinyl chloride, benzene)
Drugs (bleomycin)
Radiation exposure
systemic sclerosis
patho
3 interlinked complex processes are involved:
Abnormal activation of both humoral and cell-mediated immunity→ autoimmune disorder
Microvascular endothelial injury likely caused by anti-endothelial antibodies
Perivascular accumulation of T and B lymphocytes, macrophages, and fibroblast precursors
Secretion of cytokines and growth factors by inflammatory cells
Abnormal stimulation of fibroblast activation and proliferation within small arteries and arterioles
Progressive deposition of collagenand other extracellular matrix molecules within the skin and internal organs
systemic sclerosis
Skin S/Sx
Raynaud phenomenon (most common initial symptom) often leading to ulceration
Skin and nail manifestations:
Swelling of the skin
Symmetric
Gradual thickening of the skin
Confined to the fingers (sclerodactyly) causes the fingers to curl inward
Face becomes mask-like
Perioral skin → reduced mouth opening
Telangiectasia on the fingers, chest, lips, and tongue
Subcutaneous calcifications
Most common over the fingertips and bony eminences
Abnormal capillary and microvascular loops in the nails
Scleroderma
Scleroderma
Constitutional/GI S/Sx
Constitutional symptoms:
Fever
Fatigue
Weight loss
Gastrointestinal (90%):
Dysphagia due to esophagus dysfunction (most common visceral symptom)
Gastroesophageal reflux disease → Barrett esophagus in 1/3 of patients
Hypomotility of the small bowel causing bacterial overgrowth → malabsorption
Vascular ectasia - “watermelon stomach”
Blood vessels in the lining of the stomach become fragile and are prone to rupture and bleeding
Scleroderma
Renal/MSK S/Sx
Renal:
Hypertension
Chronic kidney disease
Scleroderma renal crisis:
Life-threatening acute renal failure
Malignant hypertension
Musculoskeletal:
Polyarthralgias/arthritis
Flexion contractures
Fingers, wrists, and elbows
Tendon friction rubs
Tendinitis
Scleroderma
Pulm & Cardio S/Sx
Pulmonary (80%):
Interstitial lung disease (ILD) → pulmonary fibrosis
Pulmonary arterial hypertension
Pulmonary embolism
Cardiac:
Restrictive cardiomyopathy
Constrictive pericarditis
Arrhythmias
scleroderma
9+ is positive
The total score is determined by adding the maximum weight (score) in each category
Patients with a total score ≥9 are classified as having definite scleroderma
The European Alliance of Associations for Rheumatology formerly the European League Against Rheumatism
Scleroderma
labs and antibodies
Antinuclear antibodies (ANA)
Nucleolar pattern
90% of patients
Rheumatoid factor
Positive in 1/3 of patients
Antibodies
Anti-centromere (ACA) = limited disease (CREST)
Anti-Scl 70 or anti-DNA topoisomerase I = diffuse disease
Increased mortality and greater incidence of interstitial lung disease
Anti-RNA polymerase III (ARA) = diffuse disease
Scleroderma
Suspected lung involvement Diagnostics
Pulmonary function testing (PFT)
Chest CT
Assessing interstitial lung abnormalities
Echocardiography
Screening for PAH
Right heart catheterization
Gold standard to confirmpulmonary arterial hypertension
Scleroderma
Tx
There is no curative treatment
Management goals
Minimize symptoms
Delay the progression of organ-specific complications
Immunosuppressants: methotrexate, azathioprine, cyclophosphamide
Glucocorticoids- Used for myositis. Should be avoided if there is renal disease
NSAIDs for pain- Should be avoided if there is renal disease
Raynaud phenomenon-Calcium channel blockers
GERD- H2 blockers or proton-pump inhibitors
Esophageal strictures- Periodic dilation
Period screenings every 1-2 years
Pulmonary hypertension with PFT
Echocardiography
