B6.023 Dermatomysositis and Scleroderma Flashcards
what is interface dermatitis?
inflammation at the dermal-epidermal junction
histo characteristics of interface dermatitis
vacuolar change
lymphocytic inflammation that obscures the D/E junction
differential diagnosis associated with interface dermatitis
SLE DM cutaneous lupus erythema multiforme drug eruption GVHD
def of dermatomyositis
idiopathic inflammatory myopathy characterized by muscle weakness and rash
complex, chronic, systemic autoimmune disease that can also cause constitutional symptoms, inflammatory arthropathy, calcinosis, and ILD
clinical and serological patterns can vary
skin findings associated with DM
gottrons papules periungal erythema nailfold capillary changes heliotrope rash V sign Shawl sign muscle wasting calcincosis
gottron’s papules
interface dermatitis over IP joints
nailfold capillary changes
palisading array of vessels
cause erythematous appearance
V-sign and Shawl sign
rash in pattern of photo-distribution
calcinosis
nodular or linear densities appearing under the skin
show up on xray
epidemiology of DM
2/100,000
2x more common in females
peak incidence age 40-50
juvenile DM
prominent vasculopathy including GI vasculitis leading to GI bleed or perforation
DM features
proximal muscle and skin
polymyositis features
absent skin involvement
Jo-1-Ab
inclusion body myositis features
older adults
distal extremities involved
poor response to treatment
what is antisynthetase syndrome
present in up to 30% of PM and DM patients
constellation of involved organs
antibodies directed against tRNA synthetases (50% are anti-Jo-1)
pentad of symptoms of antisynthetase syndrome
myositis ILD** Raynaud's inflammatory arthropathy mechanic's hand
histo of DM
early complement deposition
vascular changes
later B cell and CD4+ helper T cell infiltrate in a perivascular pattern
perifascicular atrophy
histo of PM
endomysial CD8+ cytotoxic T cells with fewer macrophages around non necrotic fibers
histo of IBM
same as PM +
vacuoles with a rim of eosinophilic granules of varying sizes distributed throughout myocytes
pre treatment assessment of DM
overlapping immune conditions (ILD, SSc, SLE) comorbid conditions (DM2, liver disease, cancer)
mainstay of DM treatment
prednisone
high dose, tapered over months
+ second immunosuppressive agent
immunosuppressive agents added to prednisone for DM treatment
methotrexate and azathioprine (first line)
IVIg (second line, more transient, used for dysphagia)
rituximab and mycophenolate (for ILD or resistant disease)
hydroxychloroquine (skin and joints)
what % of PM and DM are associated with malignancy
10%
1/3 before, 1/3 concurrently, 1/3 after
common cancers associated with PM and DM
adenocarcinomas of the cervix, lung, ovaries, pancreas, bladder, and stomach
antibodies with a positive association with malignancy
antibodies to TIF-1gamma (anti-p155, anti-p155/140)
antibodies to NPX-2 (anti-MJ or anti-p140)
antibodies with a negative association with malignancy
anti-synthetase antibodies
anti-Mi-2
anti-SRP
myositis associated antibodies (anti-RNP, anti-PM-Scl, anti-Ku)
overlap CTD
multiple identifiable CTDs
mixed CTD
patients DO have features of multiple CTDs (systemic sclerosis, myositis, RA, and SLE)
anti-RNP must be positive
various clinical features often present at different times, often separated by years
undifferentiated CTD
patients have features of CTD (arthralgia, myalgia, fatigue, Raynaud’s, ANA positive) but DO NOT have specific features of any one CTD
many will not progress, but some will
what is Raynaud’s
an exaggerated response of the digital arterial circulation triggered by cold temperature and emotional stress
exaggeration of a normal response
epidemiology of Raynauds
present in 3-15% of the normal population
more common in women (3-4:1)
often beings before age 20
discuss the pathophysiology of Raynauds
vasoconstriction at the level of the digital arteries, precapillary arterioles, and/or cutaneous AV shunts
thermoregulation of the skin
sympathetic nervous system regulates this process through AV shunts in the skin
nutritional flow to the skin is provided by a separate network of capillaries
primary Raynauds
very low risk to progress to systemic sclerosis (scleroderma) or another CTD (<1%)
therapy for primary Raynauds
focused on conservative measures and dihydropyridine Ca channel blockers when necessary
-amlodipine, nifedipine
characteristics of primary Raynauds
- younger age <40
- symmetric
- absence of necrosis, ulceration, gangrene
- normal nailfold capillaries
- negative ANA
- normal ESR
- absence of finding to suggest a secondary cause
characteristics of secondary Raynauds
- older age (>40)
- asymmetric attacks
- severe attacks with ischemia and necrosis
- abnormal nailfold capillaries
- positive ANA or other lab studies
- other systemic disease or causal factors
asymmetric Raynaud events or single digit only
digital ischemia with vasospasms mimicking RP
metabolic disease that could cause Raynauds
hypothyroid
progression of nailfold capillary changes in scleroderma
palisading levels of vessels (normal)
micro hemorrhages
loss of capillary dilated loops
disorganization
what is scleroderma
heterogenous group of conditions which are linked by having thickened and sclerotic skin lesions
great diversity in manifestations w regard to the extent of skin disease and internal organ involvement
2 types of scleroderma classifications
localized -skin and soft tissue involvement, no internal organ disease
systemic - have systemic manifestations
classes of localized scleroderma
morphea
linear scleroderma
scleroderma en coup de sabre
what is a morphea plaque
large plaque presenting with scaling, induration, and redness on the border
can appear alone or all over body
epidemiology of localized scleroderma
kids > adults
results of localized scleroderma
long term morbidity from skin, muscle, and bone atrophy causing growth defects and deformities
what is a coup de sabre manifestation
sclerotic line of scar tissue down forehead
can get cranial nerve palsies
classes of systemic scleroderma
limited cutaneous (lcSSc) diffuse cutaneous (dcSSc) sine scleroderma (no skin involvement) overlap
distribution of limited cutaneous systemic scleroderma
distal involvement only
distribution of diffuse cutaneous systemic scleroderma
involvement anywhere on body
manifestations of systemic sclerosis
puffy hands with shiny, taught skin that are not tender on palpation thickened skin reduced oral aperture sclerodactyly (shortening of appendages) vitiligo
3 primary pathophysiological components of scleroderma
- autoantibodies
- obliterative vasculopathy
- fibrosis
main cytokine driving process of scleroderma
TGF-B
most common manifestations of scleroderma
96% get raynauds
94% are ANA positive
compare the disease timelines of diffuse cutaneous and limited cutaneous scleroderma
diffuse has a rapidly progressing skin thickness that leads to other manifestations over time, and eventually improves after reaching a peak
limited progresses much more slowly
examples of manifestations of scleroderma outside of skin involvement
diffuse: joint contractures skeletal myopathy ILD myocardial involvement renal crisis limited: digital ischemia esophageal disease pulm hypertension malabsorption
what is anti-centromere-Ab (ACA)
strongly associated with limited cutaneous systemic sclerosis (seen in 50% of cases)
what is CREST syndrome
name CREST has been replaced by lcSSc to emphasize the occurrence of systemic manifestations like pulmonary hypertension C-calcinosis R-raynauds E-esophageal dysmotility S- sclerodactyly T- telangectasia
associations with ACA
female predominance
increased risk for progressive Raynauds and digital ischemia
increased risk of isolated PAH
associations with Anti-topoisomerase-1 Ab (Scl-70-Ab)
more likely to have dcSSc
less likely to have isolated pulmonary hypertension
patients with early diffuse SSc and anti-Scl70-Ab have high risk of severe ILD (23%) and lower risk of renal crisis (10%)
associations with anti-RNA polymerase III-Ab (RNA-pol3)
present in 3.4-23% of patients with SSc
rapidly progressive skin thickening which can PREDATE onset of Raynaud’s
sclerodermal renal disease develops in 24-33% of patients (5x all other SSc patients)
only 7% develop significant ILD
strongly associated with cancer
how to monitor for sclerodermal renal disease
vigilant ambulatory BP monitoring
