Scleroderma/morphea/lichen sclerosus Flashcards
What is the biggest cause of mortality in systemic sclerosis?
Lung involvement (used to be kidney)
Do you see eosinophils in the tissue bx in eosinophilic fasciitis?
Not necessarily, you have to go off the peripheral blood test.
What is a key component of nephrogenic systemic sclerosis diagnosis?
It retains the CD34 cells (there are increased numbers of CD34 cells) this is lost in the morphea and systemic sclerosis
Does morphea turn to systemic sclerosis?
No
Why is it important to see if morphea crosses joint lines?
If this occurs you have to treat much more aggressively as this can affect the joint function
Why do you have to treat the morphea?
The effects of the scarring is irreversible once it occurs. You can treat the disease but the scarring can continue.
What is the most common variant in adults of morphea?
Morphea en plaque
What happens to the adnexal structures in morphea?
You get loss of the adnexal structures, so look for that clinically.
What specialty must be consulted for morphea on the head/face?
Ophthalmology, you can get the involvement of the eye.
How should you dose the topical CS in lichen sclerosis et atrophicus?
You should treat aggressively, you don’t need to take the week break and such. You already have the atrophy.
What are the 3 major clinical varients of systemic sclerosis?
- Limited cutaneous systemic sclerosis
- Diffuse cutaneous systemic sclerosis
- Systemic sclerosis sine scleroderma
What is the first presenting sx in all 3 of the tyeps of systemic sclerosis?
Raynouds phenomenon, all have capillary nailbed changes.
Clinical of limited cutaneous systemic sclerosis?
Formally known as CREST -Early-onset of raynouds that predates the other sx’s. -Then the progression of distal skin findings, sclerosis of hands, face -Internal sx’s occurs 10-15 years later after onset of skin findings. Usually pulmonary artery hypertension
What antibody is a/w limited cutaneous systemic sclerosis?
Anti-centromere
What are the 2 “other” types of systemic sclerosis?
- Pre-systemic sclerosis (full extent of skin dz not reached)
- Overlap systemic sclerosis (polymyositis, SLE, CREST (calcinosis, Raynaud’s, esophageal dysmotility, sclerodactyly, telangiectasia)
Clinical of diffuse systemic sclerosis?
Sudden onset of Raynauds, rapid onset of progressive and widespread sclerosis (lasts 12-18 months), 90% have systemic sx’s within 5 years (ILD in lungs mc, kidney disease also common)
Clinical of systemic sclerosis sine scleroderma?
Basically limited cutaneous systemic sclerosis w/o the skin findings.
Physical exam findings in systemic sclerosis?
RP - mat telangiectasias - dilated capilary loops - cutaneous ulcers - calcinosis cutis - dyspigmentation (diffuse hyperpigmentation in sun-exposed areas or pressure related areas, leukoderma of SSc ‘salt and pepper sign’)
Tx for cutaneous sclerosis?
UVA1 tx -maybe tyrosine kinase inhibitors like imatinib (experimental)
Tx for Renaud’s phenomenon?
1st line: cold avoidance, hand/feet warming products, discontinue all tobacco products 2nd line: CCB: nifedipine (SR 30mg BID) or amlodipine (2.5-10 mg /day) 3rd line: Sildenafil, prazosin, arb’s, endothelin receptor antagonists (bosartan)
Tx for calcinosis cutis in systemic sclerosis?
- Low dose warfarin
- CCB
- Physical (surgery, laser, etc)
Does the degree of skin sclerosis correlate with systemic disease in systemic sclerosis?
No
Most common cause of death in systemic sclerosis?
Pulmonary dz (ILD >> PAH) is mcc of mortality
What are the 3 cutaneous clinical phases of systemic sclerosis?
(i) early edematous - puffy hands and pitting edema of digits
(ii) indurated - hardening of skin with taut and shiny appearance
(iii) atrophic - potential / gradual softening of skin
What can occur with the hands and the mouth that should be measured in systemic sclerosis?
- Ask the patient to make a fist, measure the distance from fingers to palm.
- have the patient open their mouth as wide as they can, measure aperture diameter.
These are done because as sclerosis worsens the patient can’t close their hands at times and they can get the masked facies and decreased aperture of the mouth.
What workup for systemic signs should be done w/ a dx systemic sclerosis?
Lung
ILD (dcSSc, ssSSc): PFTs (DLCO), high-resolution CT
PAH (lcSSc, ssSSc): TT-ECHO, serum BNP level
Kidney
Renal crisis and HTN (dcSSc): close monitoring of BP, BUN/Cr, U/A
Cardiac
Restrictive cardiomyopathy (dcSSc, ssSSc): ECHO
GI
Esophageal dysmotility (dcSSc): barium swallow, manometry, endoscopy
Clinical presentation of Raynauds phenomenon?
H/o sensitivity to cold and episodic pallor, cyanosis or both after cold exposure.
- Clinical: presents with episode vasospasm of digital arteries: white –> blue –> red discoloration.
What is the difference between primary (idiopathic) Raynaud’s vs secondary Raynaud’s?
Primary: affects 3-5% of the population and is m/c in adolescent girls and young women
- not a/w with underlying medical illness
- exacerbated by cold temp and / or strong emotional stimuli
-normal nailfold capilaries and hand exam
Secondary:
-uncommon and a/w underlying medical problem - SSc is one of the leading causes of secondary RP
-exacerbated by cold temp only
(+) for nucleolar ANA pattern, anti-topoisomerase I, anti-centromere Abs
Significance of Anti-Centromere antibody?
Increased risk of isolated pulmonary hypertension and limited cutaneous systemic sclerosis
Which antibody gives an increased risk of pulmonary hypertension in limited cutaneous systemic sclerosis?
Anti-centromere
What is the significance of the Anti-Th/To antibody?
Frequent in patients with systemic sclerosis sine scleroderma
Which antibodies are common in patients with systemic sclerosis sine scleroderma
Anti-Th/To
What is the significance of the Anti-U11/U12 RNP antibody?
Greatest risk for developing ILD in limited cutaneous systemic sclerosis, which is often severe and rapidly progressive
Which antibody is associated with the greatest risk of developing ILD that is rapid and progressive in limited cutaneous systemic sclerosis?
Anti-U11/U12 RNP
Significance of the Anti-topoisomerase-I or Scl-70 antibody
Increased risk of ILD and poor prognosis in diffuse skin sclerosis
Which antibody is found in diffuse systemic sclerosis and increases risk of ILD?
Anti-topoisomerase-I
What is the significance of the Anti-RNA polymerase III antibody?
Most severe diffuse skin sclerosis. Increased risk of renal crisis, usually better prognosis
Which antibody portends to the most severe skin sclerosis but better overall prognosis? (Also has increased risk of renal crisis)
Anti-RNA Polymerase III
What is the significance of the Anti-U3 RNP antibody?
This antibody is for diffuse skin sclerosis and is more frequent in African-Americans. A/w myopathy and cardiomyopathy and increased risk of pulmonary artery hypertension
Which antibody is more common in African Americans, is a/w diffuse skin sclerosis and myopathy, cardiomyopathy and increased risk of pulmonary artery hypertension?
Anti-U3 RNP antibody
What is the significance of the Anti-PM/Scl
Overlap syndrome antibody, polymyositis-systemic sclerosis overlap.
- acute onset inflammatory myositis, less serious internal organ involvement, usually better prognosis because responsive to oral CS
Which antibody is associated with systemic sclerosis and mixed connective tissue disease overlap and what is the prognosis?
Anti-U1RNP, increased risk of ILD, pulmonary artery hypertension and myositis. However, better prognosis because responsive to oral CS.
Which antibody is a/w myositis and systemic sclerosis overlap?
Anti-Ku
3 most common antibodies in systemic sclerosis?
- Anti-centromere (limited cutaneous systemic sclerosis)
- Anti-topoisomerase-I (diffuse skin sclerosis)
- Anti-RNA polymerase III (Diffuse skin sclerosis/renal crisis)
What is the pathogenesis of scleroderma?
Vascular, immune dysregulation → excessive collagen / ECM deposition in skin and visceral organs (major growth factor is TGF-β)
Two earliest and m/c presenting sx’s of systemic sclerosis?
Raynaud’s and hand edema
What is the most common visceral dz in systemic sclerosis?
GI system dz. Not a/w increased mortality but a/w increased morbidity (m/c is lower esophageal dysmotility–>dysphagia)
Clinical of eosinophilic fasciitis?
P/w rapid onset of edema and pain of extremities → symmetric, woody induration + peripheral eosinophilia - of note, spares hands, feet, face (less fatty area / fascial plane)
Tx for eosinophilic fasciitis?
Oral CS with slow taper over 6-24 mos
Dx of eosinophilic fasciitis?
Can mimic GVHD, dx by MRI or bx of fascia
Clinical of nephrogenic systemic fibrosis?
On the extremities, p/w ill-defined, thick, indurated erythematous to hyperpigmented plaques
What is nephrogenic systemic fibrosis a/w?
A/w exposure to gadolinium-based contrast medium – m/c seen in pts with impaired renal fxn (CKD on HD)
Tx for nephrogenic systemic fibrosis?
Kidney transplant/ restore kidney fxn
Complications from nephrogenic systemic fibrosis?
As disease progress, → joint contracture, pain, loss of mobility - fibrosis of heart, lung, and skeletal m can occur
What is the clinical presentation stiff skin syndrome?
p/w rock-hard induration of skin and subQ tissues of b/l thighs and buttocks → joint contractures - spares inguinal folds
- The kids often will not be able to straighten their legs all the way so they are always postured with bent legs
Internal organ involvement in stiff skin syndrome?
No internal organ involvement
What does stiff skin syndrome occur and what is the cause?
Congenital or early childhood onset. Subset w/ fibrillin mutation
Clinical of morphea?
LOCALIZED cutaneous sclerosis with NO sclerodactyly, RP, nailfold capillary changes, and internal organ involvement
What are the 5 major clinical variants of morphea?
- Circumscribed (plaque): Most common in adults; several (<3) discrete indurated plaques, often on the trunk and pressure areas.
- Generalized: More than 3 indurated plaques larger than 3 cm, involving more than 2 body sites (spares hands and face); more likely to be ANA (+).
- Linear: Most common in children; can have ocular or CNS involvement, muscle atrophy, limb length discrepancies, and joint contractures.
- Pansclerotic morphea: Very rare; affects subcutaneous tissue, potentially extending to bone; presents as expanding plaques on the trunk that may coalesce and affect extremities, increasing the risk of SCC.
- Mixed: A combination of other morphea variants; often associated with lichen sclerosus (LS).
What form of morphea is most likely to have extracutaneous involvement?
The generalized variant and in children (arthralgia is m/c complaint)
What specialty must be consulted for morphea on the face?
Optho, even if asymptomatic
Clinical of morphea?
LOCALIZED cutaneous sclerosis with NO sclerodactyly, RP, nail fold capillary changes, and internal organ involvement
Treatment for circumscribed morphea?
First line: Topical class I CS or intralesional or topical tacrolimus
Second line: lesion limited phototherapy, topical imiquimod, topical vit D analog
What are the treatments for generalized morphea w/o joint contractures?
Phototherapy, 2nd line is weekly MTX or systemic CS
Treatment for linear morphea that crosses joint lines or is on the face?
1st line= MTX, systemic CS
2nd line= phototherapy or steroid-sparing agents
How does pansclerotic morphea respond to treatment and what are tx options?
It tends to respond poorly to tx, and first line tx is MTX or systemic CS
What types of UV therapy should be used for what types of morphea?
UVA = deeper lesions
NB-UVB= more superifical lesions
When you see morphea what antibodies should you check and what would you expect?
You should check anti-topoisomerase II antibodies - lacks topo I and ANA
What antibodies would you expect to find in generalized and linear morphea?
Most likely to be anti-ssDNA and anti-histone
What morphea is most likely to increase risk of SCC?
Pansclerotic morphea
Where is the pathology in lichen sclerosis?
Autoimmune inflammatory condition at the papillary / superficial dermis
What other autoimmune condition is associated with lichen sclerosis?
Autoimmune thyroid (most common) and morphea
What is seen on histology with lichen sclerosis?
(i) red (epidermal atrophy - compact corneum)
(ii) white (pallor from dermal edema)
(iii) blue (lymphocytic infiltrate below collagen)
What antibody is seen in lichen sclerosis?
anti-ECM-1 IgG
Most common location for Lichen Sclerosus?
Genitalia for both women and men
Clinical of lichen sclerosis for women?
Favor vulva and perianal region → can lead to narrowing of vaginal introitus - purpura and perineal fissures are common findings
- a/w pruritus, soreness, dysuria, dyspareunia, pain with bowel movements
keep sexual abuse on your ddx!
Clinical of lichen sclerosis for men?
Balanitis xerotica obliterans; m/c in uncircumcised men - rarely seen in the perianal region
Most common areas for extragenital lichen sclerosis?
- Clinical - favor neck, shoulders, trunk, proximal extremities, sites of trauma/pressure
- xerosis and pruritus, but < than genital LS
Treatment options for lichen sclerosis?
Topical steroids class I CS daily, topical calcineurin inhibitors, intralesional CS (1-3 times during clearance phase fo 6-12 weeks.
severe or refractory cases: oral retinoids or phototherapy
What treatment should be avoided in genital lichen sclerosis?
Phototherapy! Increased risk of genital SCC!
