15. Scleroderma Flashcards
What is the name of this lesion?
Morphea (type of Localized Scleroderma, usually seen in kids)
What are the two main types of scleroderma?
Within each type, what are the subtypes?
Scleroderma –> Localized and Systemic
Localized (KIDS) –> Morphea and Linear
Systemic –> Limited, Diffuse, Sine
Systemic Scleroderma is divided into 2 types. What is the distribution on the skin of each type?
Limited Scleroderma: Appears on legs from knees down; on arms from elbows down, and on face
Diffuse Scleroderma: entire body
General skin findings with scleroderma?
Early on?
Later changes?
Swelling of fingers and hands, with erythema and pruritis
Early on: Edema. Fingers, hands, FACE involved.
Later: Edema fades, skin is shiny, tight, thick. Pigment changes. Sclerodactyly. Digital ulcers, pitting.
What disease, what stage?
Scleroderma, early phase
Edema, swelling
What disease, what phase?
How would we describe?
Scleroderma, late phase.
Tapering digits, digital ulcers, nail changes, pigment change (hypo and hyper pigmentation), joint contractures.
What disease? What features and sequelae?
Scleroderma
Left: tightened skin around the mouth. Skin is hard, not pliable. Reduced oral opening.
Right: areas of hypopigmentation, shiny skin on chest.
Scleroderma Sine Sclerosis: how does it look clinically?
Prognosis?
Pt has all components of sclerosis except skin findings.
–> Raynaud’s, GI abnormalities, autoantibodies, telangiectasias.
Prognosis is similar to pts with Limited disease (the type that is more common in kids, covered in derm)
Systemic sclerosis - Limited type used to be called what?
Why not called that anymore?
CREST (Calcinosis, Raynaud’s, Erythroderma, Sclerodactyly, Telangectasia)
Not called that anymore because we don’t need all 5 sx for a diagnosis.
What is this? In what disease/type does it occur?
What are possible complications?
Calcinosis.
Get this with Systemic Sclerosis - Limited type (NOT diffuse type)
Complications: necrosis, infection possible.
No treatment.
Histo below.
What is this? What disease/subtype is it associated with?
Calcinosis.
Systemic Sclerosis - Limited type.
May have resorbtion of the bone (acro-osteolysis)
In what % of scleroderma patients will we see Raynaud’s? At what point in the disease process does it present?
What general category of vascular problem is it?
Present in 95% of patients.
Can precede other manifestations of scleroderma by months or years.
Vasculopathy, not vasculitis!
What is this a picture of? What disease?
Why is it important?
Vasculopathy associated with scleroderma.
Impt to note that the Raynaud’s assocaited with scleroderma is a vasculopathy, not a vasculitis.
You are seeing a 45 year old female for new-onset Raynaud’s. What is the most important physical exam finding in helping you make a diagnosis?
- Erythematous facial rash
- Tender MCP joints
- A holosystolic murmur
- Dilated nailfold capillaries
- Oral aphthous ulcers
- Dilated nailfold capillaries.
Because this will help you determine whether the RN is primary (normal capillaries) or secondary (dilation, dropout capillaries).
If secondary, predictive of eventual connective tissue disease.
This is a pic of what? What disease is it associated with?
Barium swallow: indicates esophageal dysmotility.
Would be the E of CREST
Systemic Scleroderma, Limited type
Picture of what? What disease/type?
Sclerodactyly: Systemic Sclerosis, Limited type.
Xray of sclerodactyly (below) indicates resorption of the terminal phalanges (acro-osteolysis).
What is this? Disease, subtype?
Telangiectasia
Systemic Sclerosis: Limited Type.
Can show up on fingers, hands, face.
In GI tract, can cause significant blood loss
What is this? Disease, subtype?
Systemic Sclerosis - Diffuse type
obvious involvement of trunk
What are the major differences between Diffuse and Limited Systemic Scleroderma (SSc)?
(symptoms, other organs involved, related antibodies)
which type is more deadly?
Diffuse: Early organ involvement, Renal Crisis, Pulmonary Fibrosis, Topo I (Scl-70) antibody +
Limited: CREST sx, Pulmonary HTN, Centromere antibody +
Diffuse type is more deadly due to early organ involvement
The pathophysiology of scleroderma does NOT include:
- Vasculopathy
- Activation of cellular immunity
- Activation of humoral immunity
- Fibrosis
- Vasculitis
No vasculitis! No inflammation of blood vessels.
What is vasculopathy?
In scleroderma, what does it cause?
Widespread obliterative vasculopathy and failure to replace damaged blood vessels (caps, arterioles and even large blood vessels)
Concentric proliferation and thickening of the intima
Little involvement of the media
Fibrosis of the adventitia
No inflammation
-->Leads to Raynaud’s phenomenon, pulmonary artery hypertension and sclerderma renal crisis
Pulmonary Artery Hypertension: which type of systemic scleroderma patients get this (Diffuse or Limited)?
What is the pathophys?
Systemic Scleroderma, Limited type.
Caused by smooth muscle hypertrophy: intimal proliferation as part of vasculopathy.
Renal crisis: characteristic of Diffuse or Limited scleroderma?
How does it typically present in these patients?
Diffuse type more at risk.
Rapid progression, creatinine rises quickly.
What do these biopsies show?
Both kidney biopsies (glomerulus and arteriole)
Left: normal patient
Right: scleroderma patient. note arteriolar wall thickening, and scarring of glomerulus. –> renal failure (Diffuse SSc)
What is the pathogenesis of scleroderma?
What antibodies are most associated with Diffuse type? Limited type?
Think generally about autoimmune processes.
Inciting event = damaged endothelial cells, which recruit the innate immune system. T cells are activated and accumulate in skin, lungs, etc –> produce profibrotic cytokines.
B cells then activated, produce autoantibodies.
-Anti-Topo I (Acl-70) antibody positive in 20-30% of pts with Diffuse Dz.
**-Anti-centromere antibody **positive in 50-90% of pts with Limited Dz
Scleroderma: how does the fibrosis occur? what does it lead to?
Fibroblasts in the skin are stimulated by pro-fibrotic cytokines (from T cells).
Leads to increased deposits of Collagen Types I and III, –> thickened skin.
Results in typical skin changes, pulm fibrosis, GI dysmotilty.
Interstitial Lung Disease: more likely in diffuse or limited scleroderma?
At what point in the dz progression does it typically appear?
Name 2 tests to detect ILD?
More likely in Diffuse.
Tests: Pulm Function Tests (will show restrictive pattern) or High-Res CT (will have ground glass opacities, honeycombing).
Occurs within first 3 yrs of disease.
Photo: High Res CT
GI problems with scleroderma: how common? What parts of the GI tract are affected?
90% of scleroderma pts
All parts of GI tract: upper, small int, colon.
What is this? characteristic of what disease?
Gastric antral vascular ectasia (GAVE)– classic GI finding in scleroderma patients.
Thinning of the gastric mucosa such that the underlying blood vessels resemble stripes on a watermelon - “Watermelon stomach”
Scleroderma: musculoskeletal findings?
- Arthralgias, stiffness
- Synovitis (may overlap with RA)
- Tendon friction rubs (fibrinous deposits on tendon sheaths, fascia)
- Joint contractures. Debilitating.
Scleroderma epidemiology:
Prevalence?
Age of onset? M v F?
Any ethnic groups to note?
Rare
F >> M (4:1)
peak incidence = Females 30-50. Think menopause-ish.
Two populations of note:
–Young Af-Am Females have earlier onset, more severe phenotype
–Oklahoma Choctaw Native Ams: 10x average prevalance
Scleroderma: what is the strongest risk factor?
Genetic associations?
Strongest risk factor = positive family history (Rel Risk = 13 with 1st degree relative)
Genetics are complex: HLA associations exist but they are more related to specific antibodies than to the dz itself.
Scleroderma treatment: general overview?
No one treatment exists: have to treat the various features with different things. Treatment will be very specific to an individual patient and her disease.
Scleroderma patients with ILD: what do we use to treat the ILD?
Not curative, but for for scleroderma pts with interstitial lung disease, cyclophosphamide slowed the eventual decline.
The most common scleroderma-related cause of death in patients with scleroderma is:
- Interstitial Lung Disease
- Pulmonary Hypertension
- Renal Crisis
- GI involvement
- Myocardial Fibrosis
1.Interstitial Lung Disease
Scleroderma: prognosis?
What is the prognosis dependent on?
Extent of internal organ involvement influences survival.
Diffuse Ssc: mortality rate 7x higher than general pop’n
Limited Ssc: mortality rate 2x higher
Advances in treatment (ie, ACE inh to treat renal dz) have increased survival
Define Sjogren’s
Primary and secondary types, focus on primary
-Dry eyes and mouth secondary to autoimmune dysfunction of exocrine glands.
To diagnose Sjogren’s, what symptoms need to be present?
Need at least two of these:
- Positive serology: SSA, SSB, or pos RF and ANA
- Salivary gland biopsy with focal lymphocytic sialadenitis with a focus score >1
- Objective signs of dry eyes
Sjogren’s epidemiology:
Prevalance?
age? M v F?
very rare (prevalence not exactly known due to lack of consensus on diagnostic criteria in past)
90% female, onset age 45-55 (menopause again!)
Sjogren’s: pathogenesis?
what are the main cell types involved?
Initial insult to epithelium (viral, genetic, estrogen deficiency?)
–>Dysregulated epithelium causes dendritic cells, T and B cells to hone in to glands
T cells secrete inflammatory cytokines (IL1-beta, IFN gamma, TNF) –> further dysregulation
Dendritic cells secrete Type 1 interferons, upreg B cell activating factor (BAFF), promotes aberrant B cells to produce SSA, SSB.
Main types: CD4+T cells, IgA, BAFF, SSA (anti-Ro) and SSB (anti-La)
What is this?
Sjogren’s on histo.
Inflamed salivary gland with invading T and B cells.
Called focal lymphocytic sialadenitis, can be quantified using ‘focus score’
Sjogrens: what are the ocular findings?
What test is used to determine these?
Dry eyes, Grittiness, Blurred vision
also irritation, inability to wear contacts, photophobia, encrusted eyelids
Lissamine Green stain - the devitalized tissue stains green. (Also Rose Bengal stain, which is less preferable/more paingul)
Sjogren’s: what can happen to eye if left untreated?
- Filamentary keratitis (corneal epithelium sloughs off, attaches to surface of eye) – top pic
- Corneal scarring – bottom pic
- Infection with gram +
Sjogren’s: oral symptoms?
Extreme dry mouth - so dry they cannot talk. “Water bottle sign:” they carry water everywhere.
Loss of saliva -> loss of antibacterial properties, tooth decay.
Susceptible to oral candidiasis (which appears RED in a very dry mouth)
Sjogren’s: the eyes and mouth get very dry: anything else?
Nose –> congestion, crusting, epixtaxis
Trachea -> dry cough
Skin -> pruritis, excoriation
Vagina -> prutiris, dyspareunia
Interstitial cystitis
With Sjogren’s, there is an increaed lifetime risk for what other disease?
What subset of that disease, how does it present?
incr lifetime risk of Lymphoma (40x general pop’n; 19% lifetime risk)
Non-Hodgkins type, mostly MALT lymphomas. Younger patient at higher risk than older patients. They are often indolent but can transform into large cell NHL.
Risk factors for lymphoma in Sjogren’s patients?
How often should we screen these pts?
Swelling of salivary glands, lymphadenopathy, splenomegaly, vasculitis, purpura, monoclonal protein, lymphopenia, Low C3/C4, peripheral neuropathy.
Screen Sjogren’s pts annually for Lymphoma. Be aware of lymphadenopathy, splenomegaly, pulmonary infiltrates.
Sjogren’s: what is the mortality rate?
No excess mortality from Sjogren’s: it is annoying but not deadly.
(unless Lymphoma develops, which is another story)
Sjogrens treatment: what are the general principles?
- Moisture replacement/capture in eyes, mouth
- Stimulation of endogenous secretion
- Immunosuppression for systemic disease (Interstitial Lung Dz, Renal tubular acidosis, Neuropathies)
Sjogren’s: ways to treat eye dryness? mouth dryness?
Eyes: start with OTC eye drops, optho may later plug a tear duct to slow drainage.
Mouth: artificial saliva available, humidifier, good dental care, oral meds to stimulate muscarinic receptors and incr salivary flow rate! Called Secretagogues: Pilocarpine and Cevimeline)
