Ch. 43 Systemic sclerosis Flashcards
What is the difference between limited cutaneous SS and diffuse cutaneous SS
Limited-up to elbows and knees, face (most often just hands and feet)
Diffuse-trunk, upper arms and legs
Name the 7 main conditions on ddx for sclerodermoid conditions
- Scleroderma
- Generalized morphea
- Scleredema
- Scleromyxedema
- Eosinophilic fasciitis
- Chronic GVHD
- Nephrogenic systemic fibrosis
Drugs:
-Bleomycin exposure
Paraneoplastic: -POEMS -carcinoid -amyloidosis -Paraneoplastic scleroderma-like syndrome Immunologic: -Fibroblastic rheumatism
Metabolic:
- PCT-porphyria
- Diabetic cheiroroarthropathy
Neoplastic:
-Carcinoma en cuirasse
Neurologic:
-reflex sympathetic dystrophy, spinal cord injury
Toxin mediated:
- Toxic oil syndrome
- eosinophilic myalgia (L tryptophan)
- silicosis
Drug induced: bleomycin, taxanes, vinyl chloride, chlorinated hydrocarbons
other: lipodermatosclerosis
Genetics: Stiff skin syndrome ad many others…
Incidence and prevalence systemic sclerosis
20 per 1 million
275 per 1 million
Average age onset scleroderma
35-50
Name 5 RF for worse prognosis systemic sclerosis
African american Male sex Older age ILD/internal organ involvment More diffuse disease (trunk involvement) Elevated ESR
What are 3 pathogenic mechanisms causing systemic sclerosis
- Vascular dysfunction with increased VEGF
- Immune activation with autoantibody production
- Extra-cellular matrix dysregulation: sclerosis characterized by deposition of collagen and other extracellular matrix proteins
What are the diagnostic criteria for systemic sclerosis
Skin thickening proximal to MCPS = automatic dx
Otherwise need 9 points
Skin thickening distal to MCPS or skin puffiness
Finger tip lesions-fingertip scar or ulcers
Nailfold capillary changes
Telengiectasias
Raynauds
PAH or ILD
Autoantibodies
What are the 8 diagnostic criteria for systemic sclerosis
Skin thickening proximal to MCPS = automatic dx
Otherwise need 9 points
Skin thickening distal to MCPS or skin puffiness
Finger tip lesions-fingertip scar or ulcers
Nailfold capillary changes
Telengiectasias
Raynauds
PAH or ILD
Autoantibodies
What 3 antibodies are most specific for scleroderma and what are their clinical correlates
Anti-centromere with CREST/limited and PAH
Anti SCL70 (Topoisomerase I) with diffuse SS and ILD
RNA polymerase III with rapidly progressive diffuse skin disease and renal involvement
What are 5 major differences (beyond skin) between limited and diffuse sclerosis
1) Lungs
- PAH more in limited, ILD more in diffuse
2) Raynauds
- longstanding hx raynauds in limited vs. acute onset in systemic
3) Skin progression
- slowly progressive skin disease in limited, quickly in diffuse (peak in 1-1.5 yrs
4) onset internal organ involvement
- 10-15 yrs limited, most in first 5 yrs in diffuse
5) more kidney/SRC in diffuse
Prognosis worse in diffuse
What are the 4 major internal organs affected in systemic sclerosis
Lungs: PAH, ILD
GI: GERD, esophageal dysmotility
Renal: renal crisis, htn
Cardiac: fibrosis/restrictive pericarditis, CHF from PAH
Leading cause death scleroderma
lung disease
What are 5 features that suggest secondary raynauds
Later onset > age 25 Digital ulcerations Fingertip scars Abnormal nail fold capillaroscopy Sclerodacltyl ANA+
Name 12 physical findings of scleroderma
- Puffy/edematous fingers–>skin thickening and sclerodactlyl
- Raynauds
- Nailfold changes –> alternating dilation with drop out
- Salt and pepper skin (leukoderma with hypopigemntation with preservation follicular pigment)
- Calcinosis cutis-often over joints, extremities
- Telengiectasias-face, lips, palms
- Fingertip pitted scars
- Microstomia and peri-oral wrinkles
- Beaked nose
- Tendon friction rubs
- Flexion contractures
- Dry skin, loss sweating,
- Ulcers-f fingertip and over joints
Name 6 pathology findings scleroderma
- compact or hyalinized collagen
- excessive deposition of collagen
- atrophic eccrine and pilosebaceous glands,
- loss of subcutaneous fat
- sparse lymphocytic infiltrate in the dermis and subcutis
- Trapped adnexal structures
Name 8 treatments for raynauds
- avoid cold, warming packs, stop smoking= 1st line
- calcium channel blockers=2nd line
- endothelia receptor antagonists- bosentan
- PDE-5 inhibitors-sildenafil
- ARBs-losartan
- alpha adrenergic blockers-prazosin
- SSRI-fluoxetine-4th line
- botox
Name 5 treatments for cutaneous ulcers from raynauds
Avoid aggressive debridement, moist adherent dressings
All therapies listed for raynauds
ASA or clopidogrel
Endothelial receptor antagonists- bosentan
IV prostanoid (e.g. epoprostenol)
High dose statins
Name 8 treatments for calcinosis cutis
- excision
- shock wave litho
- sodium thiosulfate-IV or injection or topical
- warfarin
- bisphosphonates
- CCBs-diltiazem
- aluminum hydroxide
- probenecid
Name 4 treatments cutaneous sclerosis
Often not treated unless internal involvement:
- Topical steroids
- Phototherapy
- Methotrexate-if no ILD
- MMF -esp if ILD
Treatment scleroderma renal crisis
ACEi
Name 2 major treatment internal organ involvement scleroderma
MMF or cyclo
What are the clinical features of eosinophilic fascitis
- Hx strenuous physical activity in 30%
- Pain and edema that progresses to fibrosis and psuedo-cellulite appearance, rippling
- Distribution symmetric extremities and usually spares the hands, feet and face
- Groove sign
What is the groove sign
“groove sign” refers to linear depressions where veins appear to be sunken within the indurated skin.
Name 3 laboratory findings in eosinophilic fascitis
- Elevated ESR
- Peripheral eosinophilia
- hypergammaglobulinemia
What are 4 conditions that have been associated with eosinophilic fasciitis
Pancytopenia
Anemia
Thrombocytopenia
Myeloproliferative d/o –> some advocate for marrow bx
What does pathology show for EF?
Thickening deep fascia
Lymphocytes and plasma cell infiltrates
Sometimes dermal fibrosis
NAme 2 tests you’d order for workup EF?
Fascial biopsy
MRI
What is first line treatment EF
prednisone 1-2 mg/kg daily tapered over 6-24 months
Name 6 treatments other than prednisone for EF
- hydroxychloroquine
- cyclosporine
- dapsone
- methotrexate
- PUVA
- infliximab
* may be used alone or in combination with prednisone.
UVA1, alone or in combination with an oral retinoid, can also be considered
What 2 risk factors lead to nephrogenic systemic fibrosis
- kidney injury (AKI or ESRD)
- gadolinium
How does NSF present on the skin
Thick indurated patterned plaques on extremities or trunk,
can have advancing “ameboic” border
Erythematous or hyperpigemented
What internal organ involvement can there be in NSF
yellow scleral plaques
systemic fibrosis affecting–> the heart, lungs and skeletal muscle.
Treatment NSF
anecdotal reports:
-imatinib, rapamycin, UVA1 phototherapy, extracorporeal photochemotherapy, photodynamic therapy, plasmapheresis,
high-dose IVIg, discontinuation of erythropoietin.
-case reports with;
improvement renal function with transplant
What is stiff skin syndrome ?
Genetic condition with heterozygosity for a mutation in the gene that encodes fibrillin-1 ( FBN1 ).
The presence of giant “amianthoid-like” collagen fibrils in affected fascia had been postulated to reflect a disturbance in the organization of collagen and glycosaminoglycans within the extracellular matrix.
Describe the clinical features of stiff skin syndrome
Rock hard thickening skin and subcutaneous tissues over buttocks and thighs with sparing inguinal folds, sometimes hypertrichsosi
Spares hands and feet
Postures hip and knee flexion and excess lumbar lordosis
internal organ manifestations stiff skin?
None usually
Name 5 drugs/ that can cause sclerodermoid changes
- Bad L-tryptophan –> eosinophilic myalgia syndrome
- Chemo: esp. taxanes and bleomycin, can cause pull fibrosis
- Bad rapeseed oil–> toxic oil syndrome
- vinyl chloride
- organic solvents
- epoxy resins
How does chemical induced sclerosis present
- insidious acrosclerosis and Raynaud phenomenon (especially with vinyl chloride exposure), but morpheaform plaques and fibrotic nodules can also develop.
- Acral osteolysis, hepatic toxicity, and pulmonary involvemen fatigue, weight loss, arthralgias, and myalgias.
- Autoantibodies are absent, and cessation or reversal of the disease process follows removal of the exposure.
What chemical exposure has been associated with AI-CTD and scleroderma specifically
Silica and silicosis
