SSc/Mimickers/CTD-ILD Flashcards
SSc classification
Localized: Morphea vs Linear scleroderma
Generalized: Limited vs Diffuse vs SSc sine scleroderma
Morphea manifestation
Single/multiple plaques on trunk SPARING hands/fingers
**NO ORGAN involvement
**Does NOT progress to SSc
Linear scleroderma manifestations
Bands of skin thickening on legs/arms, face
Limited scleroderma manifestation and AB
Calcinosis
Raynaud’s
Esophageal reflux
Skin thickening of neck, face, DISTAL to elbow/knees
Swollen fingers
Telangiectasia
MINIMAL ILD
PAH
AB:, ACA, PM-Scl, Th/To
Limited Scleroderma antibodies
- Anticentromere
- TH/TO
- U1 RNP
- PM-Scl
Diffuse Scleroderma antibodies
- SCL70 (aka Anti-topoisomerase)
- U3RNP
- RNApol3
Associated diseases w/ this antibody: Anticentromere
Limited
PAH
Bad gut disease
PBC
Associated diseases w/ this antibody: TH/TO
Limited
PAH
ILD
Associated diseases w/ this antibody: U1-RNP
Limited
ILD
PAH
Associated diseases w/ this antibody: U3RNP
Diffuse
ILD
PAH
Myositis
SRC
Associated diseases w/ this antibody: PM-Scl
Limited
ILD
Myositis
Associated diseases w/ this antibody: SCL70
Diffuse
ILD
SRC
Associated diseases w/ this antibody: Anti-topoisomerase
Diffuse SSc
ILD
SRC
Associated diseases w/ this antibody: RNApol3
Diffuse SSC
SRC
Malignancy
Diffuse scleroderma manifestations
Skin thickening PROXIMAL to elbows/knees with truncal involvement
Friction rub
Raynaud’s, Puffy hands,
Arthritis, Carpal Tunnel
Severe ILD
PAH/PH
GI involvement
SSc mortality cause
Lung: ILD, PAH
Cardiac: HF, arrhythmia
Renal: SRC
Infection
Cancer
SSc sine scleroderma manifestations and AB
Internal manifestations of SSc
ANA (nuclear pattern), ACA, SCl70, RNApol
NO SKIN THICKENING
SSc Pathogenesis
Vascular damage (infxn, ROS, silica, etc) activates DCs via TLRs → Type 1 IFN →
- Th2 activation→ profibrotic IL4 and 13 production
- Activate M2 macrophages → TGFb → endothelial cell differentiation into mesenchymal cells
- B cell activation → IL6 and autoantibody production
Plt activation
SSc skin biopsy changes
Tissue fibrosis - excessive collagen fiber accumulation
Perivascular inflammation (T cells and monocytes)
Loss of hair follicles and sweat glands, and dermal capillaries (assoc’d w/ hypoxia → VEGF production)
Skin Tx Thickening SSc
MMF, MTX,
CYC, RTX
Toci
Abatacept
IVIG 2g/kg / month
HSCT
Skin Pruritus Tx SSc
Low dose pred (<15mg/d)
BZD
Topical: emolient, oatmeal bath
Gabapentin, pregabalin
Low dose naltrexone
Clues for early SSc in pt w/ Raynaud
Positive AB (nucleolar ANA, SCL70, ACA, P-SCl, RNP3)
Nail changes: capillary dropout, dilatation
Disease activity: Tendon friction rub, Ulcer, Infarct
Puffy hands, edema
Esophageal hypomotility (dilated esophagus)
** Patterns of nailfold capillaroscopy **
Early: few giant capillaries & capillary microhemorrhages. NO loss of capillaries. Preserved capillary distribution
Active: freq giant capillaries & capillary microhemorrhages. Mod loss of capillaries. Mild disorg of capillary architecture
Late: nearly absent giant capillaries & microhemorrhages. . Severe loss of capillaries. Capillary ramification 2/2 neoangiogenesis and disoganized capillaries
Raynaud Tx
Core/hand warming
STOP smoking
CCB, ARB, SSRI (fluoxetine)
Topical nitrates, PDE5i, Prostacyclin analogs, Endothelin ANT
Antiplatelet
Statins
Digital Ulcer NonPharm Tx
Avoid cold (Warming core, warming hands/feet),
Avoid trauma,
Smoking cessation,
Local wound care,
Avoid sympathomimetics
Digital Ulcer Vasodilator Tx
Which prevent new and which heal ulcer
Vasodilator:
HEAL ULCER and PREVENT new:
- CCBs = 1st line
- PDE5 inhibitors = 2nd line
- IV prostacyclin analogues = 3rd line
ONLY prevent new:
- Bosentan
Digital Ulcer Non-Vasodilator Tx
Statin,
Botox injections,
Analgesia, Digital sympathectomy,
Surgical debridement/amputation
Fat grafting,
Antibiotics if infection
Drugs to avoid in patients with ulcers
Vasoconstrictors: decongestants, Triptans
Stimulants: Amphetamines, Cocaine, ADHD medications
Weight loss,
Baseline testing SSc
HRCT
PFT (lung vol, spirometry, DLCO)
TTE
6MWT
EKG
Most common ILD in SSc
2/3 NSIP
1/3 UIP
Highest risk for progressive ILD
Older black/native man
Diffuse
SCL70 or Isolated Nucleolar ANA (ie NEG antiScl70)
Definition of ILD progression
Predicted FVC decline >10%
Predicted DLCO decline >15%
When to biopsy lung in SSc-ILD
Atypical lung injury on CT
Concern for alternative dx
** SSc ILD Tx**
Preferred: MMF, Toci, Ritux
Additional: CYC,AZA, Nintedanib
Others:
CNI (cyclosporine, tacro)
HSCT
Strong recommendation to avoid GC
When to consider HSCT
Early diffuse (<5y)
Mild/mod organ
Refractory/worsened on conventional immunosuppression
Tests before HSCT
PFT
HRCT
TTE
cMRI
RHC
Exclusion for HSCT
Smokers
Cardiopulmonary involvement
Severe internal organ
pHTN groups & which type in SSC
1: PAH
2: PH assoc’d w/ L heart dz
3: assoc’d w/ chronic hypoxia (eg ILD)
4: chronic thromboembolic-assoc’d PH
5: unclear/multifactorial (eg sarcoid)
1,2, 3 in SSC
** Right heart cath results in each type pHTN**
1:
Mean pulm artery pressure >20mmHg
Pulm capillary wedge pressure (PCWP) <15mmHg
Pulmonary vascular resistance >3woods (nonspecific for etiology)
2: Mean pulm artery pressure >25mmHg PCWP > 15mmHg
- Elevated pulm pressures due to chronic hypoxia
PAH manifestations
Dyspnea
Fatigue
Right heart dysfunction: TR, JVD, RV heave
Hepatomegaly and LE edema
** PAH risk factors in SSc**
Limited (esp longstanding)
AB: ACA, Isolated nucleolar pattern ANA
Sx: Longer duration Raynauds, Extensive telangiectasia
DLCO <60% w/o ILD or other cause
FVC/DLCO >1.6 (disproportionately low DLCO)
TTE findings of PH
Dilated RA & RV
RV dysfunction
Interventricular septal flattening
Pericardial effusion
Elevated RVSP (>40)
** PAH Tx**
CCB
Diuretics, fluid restriction, low salt
Warfarin for idiopathic, not SSc-assoc’d
**Prostacyclins (ie vasodilators) **(inhaled ilioprost, PO treprostinil, SC/IV epoprostenol, treprostinil)
**Endothelin R ANT (bosentan, ambrisentan, macitentan) **
Nitric oxide potentiators:
- PDEi (more cGMP for vasodilation) eg sildenafil or tadalafil;
- Guanylate cyclase stimulator eg riociguat
Cardiac manifestations SSc
Cardiomyopathy (infiltrative/fibrotic on cMRI) - risk factors = blacks, diffuse skin, RNAPol3
Pericardial effusion (asymptomatic)
Pericarditis
CAD
** SRC risk factors **
Sx: Early diffuse skin (1st 1-4years),
Friction rub
AB: RNAPol3
Tx: Steroids (pred >20 or prolonged low dose)
Cyclosporine
Proteinuria
HTN
CKD
Elevated ESR
Thrombocytopenia
SRC manifestations
Arterial HTN >150/90 (10% normotensive)
Grade 3 retinopathy (flame shaped hemorrahge and/or cotton wool exudates) or Grade 4 (papilledema)
Rapid renal failure (within a month)
Pericardial effusion
SRC labs
AKI
Proteinuria
Consumptive thrombocytopenia
Microangiopathic hemolysis (schistocytes)
Hemolysis labs: hapto, bili, LDH, DAT, smear,
Elevated renin
Normal/mildly decreased ADAMTS13
ANCA GN vs SRC
ANCA GN:
No hemolytic manifestations
HTN does not predominate
RBC casts present
ANCA present
Biopsy shows AAV
** SRC Tx and dose **
Short acting ACE (captopril, enalapril) → decrease sBP by 20 w/i 1st 24h
If still HTN: CCB, then AB
Captopril 6.25–12.5 mg every 8h, and increased to 50 mg TID
- NO prophylaxis w/ ACE (worse prognosis bc can hide HTN)
SRC poor prognostic markers
Male
Initial creatinine >3mg/dL
Late detection bc normal BP at onset
Cardiac involvement (myocarditis, arrythymia
GI manifestation SSc
Upper GI:
- Dysphagia
- GERD
- Strictures
- Barrett’s
- GAVE
Lower GI:
- SIBO (constipation alternating diarrhea),
- Malabsorption
- Pseudoobstruction,
- Fecal incontinence (rectal spincter tone loss),
- Rectal prolapse
SSc GI pathophysiology
Neural dysfcn from arteriolar changes of vasa nervorum → dysmotility
Smooth muscle fibrosis and atrophy
How to assess upper GI manifestations
Manometry
Barium esophagram
Barium swallow (NOT if poor motility bc risk o impaction)
CT scan showing dilated esophagus
Endoscopy (relux esophagitis, candidiasis, Barrett’s, strictures)
Esophageal dysmotility Tx SSc
Elevate head of bed
No food 2-3h pre bedtime
Antacids, H2 blockers, PPI
Motility agents:
- Metoclopramide, erythromycin → tachyphylaxis and GI smooth muscle fibrosis
- Domperidone and erythromycin → prolong QTc
Refractory: injectable octreotide or botox
GAVE: What is it and how to tx
Gastric antral vascular ectasia (GAVE)
Telagiectasis of gastric mucosa → bleed/anemia
Tx: Laser or Argon plasma coagulation
Small intestine manifestations SSc
Dysmotility →
SIBO →
Diarrhea →
Electrolyte abN and Malabsorption (low albumin, vit B6, B12, vit D folic acid) D-xylose absorption, beta carotene; high fecal fat)
Large intestine manifestations SSc
Fecal incontinence
Wide mouth diverticulae (wall thinning/atrophy)
Rectal prolapse
Dysmotility Tx SSc
Domperidone,
Metoclopramide,
Erythromycin,
Injectable ocreotide,
Fiber
Diarrhea Tx SSc
Empiric tx for SIBO (rixamin 550mg TID, cipro 500 BID, amox clav 875 BID, or flagyll 500 TID x 10d)
AVOID drugs that slow motility (loperamide, paregoric) and FODMAP (fermentable oligosacch, disachh, monosacch, polyols)
Supplements if malabsorption
Rectal involvement Tx SSc
Fecal incontinence → bioeedback, sacral nerve stim +/- surgery
Rectal prolapse: manage constipation +/- sugery
What/Where calcinosis
Calcium phosphate
Hands (PIP, finger tips), periarticular, bony prominence (extensor elbow/knee)
What diseases hv calcinosis
- Idiopathic
- Rheum: SSc, DM, SLE, Sarcoid, EDS
- HyperCa: Paraneoplastic, HyperPTH, Milk Alkali, CKD, Calciphylaxis, Pagets
- Infxn
- Tumors
- Pseudoxanthoma elasticum
- Panniculitis
- Trauma
Calcinosis Tx
Weak evidence: steroids, Colchicine, Probenecid, Diltiazem
Topical/IV sodium thiosulfate BINDS Ca
**check BMD bc can bind any salt
IV bisphosphonate block OC and lower systemic Ca (if JDM)
Surgery (recurrence common)
Telangiectasia - what and where
Dilated venules, capillaries, arterioles
Hands, face, lips oral mucosa
Tx Telangiectasia
Laser therapy
MSK involvement SSc
Acrosclerosis w/ osteolysis
Resorption (ribs, mandible, acromion, radius, ulnar)
Tendon friction rub (wrists, ankles, knees)
Friction rub pathophys
Inflammation, edema, and fibrosis of tendon/tenosynovial sheath
- Increased fibrin deposition
- Increased thickness of tendon retinacula
Muscle abnormalities in SSc, histology, and tx
Noninflammatory benign myopathy from inactivity/steroid use
- H\istology normal (type 2 muscle fiber atrophy), normal CK
Mild elevated CK w/ intermittent sx
Biopsy: interstitial fibrosis and fiber atrophy. Minimal inflammatory cell infiltration
NO steroids
Inflammatory myopathy (ie overlap/MCTD) - elevated CK. Tx w/ immunosuppression
** Features that separate mimickers from SSc **
NO Raynaud’s
NO nailfold capillary abnorm (dilatation/ dropout)
NO ANA+
NO cutaneous sclerosis progression in centripetal fashion (finger/toe spreading proximally)
NO organ involvement (telangeictasia, ILD)
May see eosinophilia (eg in EF)
** Mimickers of SSc **
Localized scleroderma (morphea, linear scleroderma)
Immune mediated:
- Eosinophilic fasciitis
- chronic GVHD
Deposition
- NSF (nephrogenic systemic fibrosis)
- Scleredema
- Scleromyxedema
- Amyloid
Metabolic (DM cheiroarthropathy, hypothyroid, phenylketonuria)
Paraneoplastic
Meds (Docetaxel, radiation, carbidopa, bleomycin, tryptophan, rapeseed oil)
Silica, pesticide, organic solvent, epoxy
POEM (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes)
Morphea subtypes & characteristics
Circumscribed: most common in adults
Linear: MC children, unilateral limb or coup de sabre (scalp/face → neurologic sx or uveitis). Can → tissue atrophy
Generalized: 4+ (>3cm) involving 2+ body sites.
-Ulcers/necrosis, muscle atrophy, contracture.
-RISK cutaneous SCC.
Deep: rarest. Includes layers of fat, fascia, muscle. Symmetric, over extremities
Morphea Tx
Acute:
- Topical (steroid, CNI, calcipotriene),
- Intralesional steroid
- Phototherapy
- PO prednisone,
- MTX, MMF, HCQ, IFX, cyclosporine
Chronic:
- PT/OT: for contracture/functional impairment
- Surgery: filler injection, autologous fat transfer
Scleredema manifestions
Nonpitting woody skin edema
Neck, UPPER BACK, shoulder trunks, face, extremities
SPARES FEET/HANDS
Dysphagia, myalgia, contractures, diploplia
Scleredema biopsy
Normal epidermis
Thickened dermis with mucin between collagen bands
Scleredema Subtypes
1: AFTER infection or febrile illness, can cause carditis, myositis, CHF
2: Assoc’d w/ paraproteinemia (IgG, IgA), MM, amyloid, can precede Ca
3: Associated with diabetes
Scleromyxedema manifestations
Wide spread small (2-3mm), nonpruritic, waxy papules
- Face, neck, upper trunk, distal forearms, dorsal hands - NO PALMS
Extracutaneous:
-Myopathy, Dysphagia,
-Arthritis,
-Dermato-neuro syndrome (fever, sz, coma s/p flu prodrome),
-Cardiac, pulm, renal
- Monoclonal gammopathy
Scleromyxedema biopsy
- Mucin deposition in dermis (normal epidermis)
- Fibrosis: Fibroblast proliferation
- Perivascular mononuclear cell infiltrate
Scleromyxedema Tx
IVIG
Corticosteroid,
Thalidomide
MM tx (melphalan, CYC)
EF stages
1: pitting edema of symmetric arms/legs (calves & forearms), ** SPARES HANDS/FEET **, NO finger/toes,
2: woody, peau d’orange, groove sign (indentated from dermis tethering to fascia & muscle along veins).
Induration of extremities, trunk, face.
NORMAL CK with low grade myositis
- Fascial involvement → early carpal tunnel
Flexion contracture, muscle atrophy.
**NO sclerodactyly or nailfold change
EF labs/imaging
Eosinophilia (20% normal; only in early stage; resolves w/ steroids)
ESR, CRP
Immune mediated aplastic anemia,
Thombocytopenia,
MDS, MM, lymphoma
Hypergammaglobulinemia
Aldolase elevated (normal CK)
MRI: fascial thickening and enhancement Gad
EF biopsy instruction and result
** Full thickness deep wedge biopsy (for skin, subcutis, fascia, muscle) **
Inflamm infiltrate (lymph, plasma cells, histiocyte)
Eosinophilic infiltration in early disease
EF complication if untreated
Joint contracture
Peau d’orange (bound down indurated skin)
Some self limited
Poor prognostic features EF
Young age
Trunk involvement
Peau d’orange
** EF Tx **
High dose pred (40-60mg) EARLY
Refractory: MTX > MMF
Case report: Toci, TNFi, Tofa, Ritux, IVIG
PT for flexion contracture
Nephrogenic systemic fibrosis manifesetations
HISTORY OF GADOLINIUM EXPOSURE in CKD
ABSENCE OF MONOCLONAL GAMMOPATHY
NOT REVERSIBLE
Woody induration
Plaques
Cobble stone, Peau d’orange
Pruritus
Hyperpigmentation
Fibrosis of visceral organ : renal failure, cardiopulm, GI, diaphragm atrophy
NO Raynauds
NO FACIAL INVOLVEMENT
NSF (nephrogenic systemic fibrosis) labs
No diagnostic labs.
NO paraprotein and scleroderma assoc’d AB
Normal SPEP
NSF (nephrogenic systemic fibrosis) biopsy
NO inflamm cells
Increased dermal fibroblasts, collagen, mucin deposition
CD34+ fibrocyte and CD68+ monocytes
*similar to scleromyxedema but NO monoclonal gammopathy and NO face involvement in NSF
NSF (nephrogenic systemic fibrosis) Tx
PREVENTION - no gad if stage 4/5 CKD
No treatment
Anecdotal: phototherapy, extracorporeal photophresis, PLEx, imatinib
cGVHD manifestations
Trunk + extremities (vs SSc starts at digits)
Antibodies: sometimes Scl70, PM Scl, ANCA
**unique = underwent allogenic bone marrow transplant
cGVHD prevention & Tx
Prevent:
- Pre-transplant antithymocyte globulin
- Post-transplant cyclosporine, IVIG, Ritux
Tx: Pred, Cyclosporine
Anecdotal: phototherapy, extracorporeal photopheresis, sirolimus, imatinib, thalidomide, Ritux
Myositis ILD Tx
1st line: MMF, Aza, Ritux, CNI
Additional: JAKi, CYC
+Short term GC
MCTD ILD Tx
1st line: MMF, Aza, Ritux
Additional: Toci, CYC
+Short term GC
RA ILD Tx
1st line: MMF, Aza, Ritux
Additional: CYC
+Short term GC
Sjogrens ILD Tx
1st line: MMF, Aza, Ritux
Additional: CYC
+Short term GC
Autoimmune conditions associated with EF
PBC
SLE
Sjogrens
Immune mediated plastic anemia
Thombocytopenia
MDS, Lymphoma, Leukemia
** 2 mimics of Scleroderma associated with cancer **
Scleredema type II,
Scleromyxedema,
Eosinophilic fasciitis
** 2 REVERSIBLE mimics of Scleroderma **
Morphea,
Scleredema type 1,
Eosinophilic fasciitis (in some patient’s it is self-limited with spontaneous improvement, occasionally complete remission can occur).
** EF trigger
Strenuous physical activity (eg marathon)
3 cytokines important in scleroderma pathogenesis
IL 4
IL 13,
TGF beta
IL6, 8, 17
IFNg
TNF
** 5 hand findings suggestive of scleroderm**
- Arthralgias and inflammatory arthritis
- Joint contractures
- Tenosynovitis and tendon friction rubs
- Skin sclerosis
- Calcinosis (more so with limited disease)
- Raynaud’s phenomenon and digital ulcerations
- Puffy hands
- Acro-osteolysis / Pulp loss
- Nailfold capillary abnormalities
Nailfold capillary findings in SSc
- Enlarged, giant, dilated capillaries
- Micro-hemorrhages
- Capillary dropout
- Neovascularization
- Disorganization of capillary architecture
What rheum diseases cause NSIP
Scleroderma
PM/DM
Sjogrens
MCTD
RA
AAV
What rheum diseases cause UIP
RA
MPA
Scleroderma
What rheum diseases cause COP
DM
RA
Sarcoid
SLE
What rheum diseases cause LIP
Sjogrens
RA
SLE
SRC biopsy pathology
- Absence of inflammatory infiltrates
- Fibrinoid necrosis
- Arteriole THROMBOSIS → Glomerular ischemia
- ONION SKIN LESIONS
- Fibrointimal sclerosis
** Causes of soft tissue calcification?**
- Hyperparathyroidism
- SSc
- DM/PM/JDM
- SLE, MCTD
- Pseudoxanthoma elasticum (mineralization of elastic fibers)
- Panniculitis
- Trauma – heterotropic ossification and injection granulomas
- Gout/CPPD
- CKD - metastatic calcification
- Tumoral calcinosis (FGF23 mutation)
