SYSTEMIC SCLEROSIS (SCLERODERMA) AND RELATED DISORDERS  Survival is determined by visceral disease (lungs,

heart and/or kidney)

• Chronic multisystem disorder of unknown etiology
• Thickening of the skin cased by accumulation of connective • Criteria for Classification of Systemic Sclerosis
tissue and functional abnormalities of visceral organs (GI,  Major Criteria
lungs, heart, kidney)
 Sclerodermatous involvement of proximal
digits,affecting proximal portions of the
Classification of Systemic Sclerosis and Scleroderma-like
extremities, face, neck, or trunk (usually bilateral
disorders
Systemic Limited cutaneous disease and symmetrical) → present in 90% of patients
sclerosis Diffuse cutaneous disease
Sine sleroderma  Minor Criteria
Undifferentiated connective tissue disease  Sclerodactyly
Overlap syndromes  Digital pitting scar or tissue loss of the volar pads of
Localized Morphea the fingertips
scleroderma Linear scleroderma  Bibasilar pulmonary fibrosis
En coup de saber
Chemically Toxic-oil syndrome Diagnosis: major criterion OR ≥2 minor criteria
induced Vinyl chloride-induced disease (97 % sensitive and 98% specific)
sleroderma- Belomycin-induced fibrosis
like disorders Pentazocine-induced fibrosis • Can occur as Localized Scleroderma
Epxy- and aromatic hydrocarbons-induced Affects children and young women
fibrosis  Morphea: single or multiple plaques of skin induration
Eosinophilia-myalgia syndrome  Liner scleroderma: involves extremity or the face
Other Scleredema adultorum of Buschke
scleroderma- Scleromyxedema  En coup de saber: resembles would from a sword;
like disorders Chronic graft-vs.-host disease associated with hemiatrophy of the same side of the face
Eosinophilic fascitis
Digital sclerosis in diabetes • Overlap syndrome: systemic sclerosis that occurs in
Primary amyloidosis and amyloidosis
association with features of other connective diseases
associated with multiple myeloma

• Prominent features of systemic sclerosis • Undifferentiated connective tissue disease: designation for
 Vascular damage patients who do not have diagnostic criteria for any one
 Immune activation connective tissue disease
 Excessive synthesis and deposition of extracellular matrix
• Mixed connective tissue disease had features of
• Subsets of skin and internal organ involvement  SLE
 Diffuse cutaneous scleroderma  Systemic sclerosis
 Rapid development of skin thickening of proximal  Polymyositis
and distal extremities, face and trunk  RA
 Greater risk for kidney and visceral disease early  High titers of RNP
 Limited cutaneous scleroderma
 Symmetric skin thickening limited to distal • Eosinophilic fascitis: associated with contaminated L-
extremities and face tryptophan ingestion
 (+)Features of CREST syndrome (Calcinosis,
Raynaud’s phenomenon, Esophageal dysmotility, • Eosinophilia-myalgia syndrome: associated with
Sclerodactyly, Telangiectasia)
contaminated L-tryptophan ingestion
 Better prognosis (except if pulmonary arterial
hypertension or biliary cirrhosis develops)
EPIDEMIOLOGY
Subsets of Systemic Sclerosis
• Affects all races
Diffuse Limited
• Incidence increases with age (peaks at 30-50 years old)
Skin Distal and proximal Distal to elbows,
involvement face • Women > Men (3x more)

Raynaud’s
Onset within 1 year May precede skin • During mid to late childbearing years (≥8:1)
or at time of skin disease by years • African American twice as frequently with lower age of onset
phenomenon
changes and often have diffuse cutaneous involvement and pulmonary
Pulmonary Pulmonary arterial fibrosis (than Caucasians)
(interstitial hypertension • Hispanics, more severe than Caucasians
fibrosis) after 10-15 years
• Highest incidence in Choctaw naïve Americans in Oklahoma
Organ Renal (renovascular of disease in
involvement hypertensive <10% of patients • Increased incidence of other autoimmune disease (SLE and
crisis) Gastrointestinal RA)
Gastrointestinal Biliary cirrhosis
Cardiac • Rate of concordance
Nail fold Dilatation and Dilatation without  Twins = 4.7% (systemic sclerosis)
capillaries dropout significant dropout  ANA concordance = 90% in mono, 40$ in dizygotic
Antinuclear Anti-topoisomerase Anticentromere
antibodies 1 • ANA in spouses of systemic sclerosis patient suggests that
environmental factors are involved in the development of
 Systemic sclerosis sine scleroderma antinuclear antibodies
 No skin involvement
 Involves visceral organs
• Infectious agents may play a role in the pathogenesis of
systemic sclerosis
 Latent CMV infection 9by direct vascular injury or
immune-mediated mechanisms involving molecular
mimicry)
 Parvovirus B19 (in bone marrow) with presence of anti-
parvovirus B19 antibody
• Environmental factors associated with development
systemic sclerosis and scleroderma-like illness
 Coal and gold miners (silica exposure)
 Exposure to polyvinyl chloride → raynaud’s phenomenon,
acroosteolysis, scleroderma-like skin lesions, pulmonary
fibrosis and nail fold capillary abnormalities, hepatic
fibrosis nad angiosarcoma
 Exposure to epoxy resins and aromatic hydrocarbons
(benzene, toluene, trichloroethylene)
 Ingestion of aniline-adulterated cooking oil (rapeseed oil)
→ interstitial pneumonitis, eosinophilia, arthralgias,
arthritis and myositis then joint contractures, skin
thickening, Raynaud’s phenomenon, pulmonary
hypertension, sicca syndrome and resorption of distal
fingertips
 Pentazocine use → extensive sclerosis of the dermis and
subcutaneous tissue
 Bleomycin → fibrotic skin nodules, linear
hyperpigmentation, alopecia, raynaud’s phenomenon,
gangrene of fingers and pulmonary fibrosis
 Silicone breast implants → localized fibrosis around
implant
Events in the Pathogenesis of Systemic Sclerosis
1. Early event: Vascular injury of the small arteries, arterioles
and capillaries in the skin, GIT, kidneys, heart and lungs) →
Fibrosis
2. Initial symptom: RAYNAUD’S PHENOMENON (Expression of
abnormal regulation of blood flow resulting from vascular
of injury)
3. Injury to endothelial cells and basal lamina
4. Proliferation of the intima and smooth-muscle cells with
deposition of matrix and perivascular fibrosis → Narrowing of
the lumen and eventual obliteration of the vessels
5. ↓Microvascular bed in the skin and other sites → Chronic
ischemia → Drop-out of capillaries with dilatation and
tortuosity of remaining ones (seen in the nail folds by wide-
field microscopy)
6. In the skin: Proliferation and dilatation of remaining
capillaries → Telangiectasia
7. Endothelial damage → Reflected as ↑Factor VIII/vWF in serum
Mechanisms of Endothelial Injury or Activation
• Cytotoxic factor for endothelium degrades the basal lamina,
releasing fragments of type IV collagen and laminin
 Factor = Granzyme 1: a Type IV collagenase secreted by
activated T cells
 Type IV collagen and laminin stimulate immune response
to basal lamina
 Antibody-mediated
 Cell-mediated

PATHOGENESIS • Anti-endothelial cell antibodies (AECA)

• Overproduction and accumulation of collagen and other  Mediate antibody-dependent cell cytotoxicity against
extracellular matrix proteins (fibronectin, tenascin, fibrillin-1 human cells
and glycosaminoglycans) in skin and other organs  NOT SPECIFIC for systemic slcerosis and are found in
• Mechanisms: other connective tissue diseases
 Immunologic  Higher in patients with Diffuse Cutaneous Systemic
 Vascular endothelial cell activation and /or injury sclerosis
 Activation of fibroblasts → excessive collagen
 Associated with the following:
 Digital infarcts
 Pulmonary hypertension
Host
Genetic susceptibility  Impaired alveolocapillary diffusion
Infection
Environmental factors  Initiate apoptosis of endothelial cells
Microchimerism  Induce expression of the following adhesion molecules
leading to production of chemoattractants (IL-1, IL-8 and
monocyte chemotactic factors or MCP) thus with
elevated levels of the following in the serum
 Vascular adhesion molecule-1 (VCAM-1)
Vvascular Immune  Intercellular adhesion molecule-1 (ICAM-1)
Endothelial cell injury T cell activation  E-selectin
Vasoconstriction Macrophage activation  P-selectin
Vascular occlusion Autoantibodies
Tissue hypoxia Cytokines
 Adhesion molecules + Chemoattractants = Binding of T
and B cells, natural killer cells, and monocytes to the
endothelium and their migration into the perivascular
tissue

Fibrobalst activation Pathophysiology

and growth
Injury to the epithelium
↓
↓Prostacyclin
↓
FIBROSIS
Vasodilation and
 Inhibitor of Platelet Aggregation
Platelet binds Release of PDGF
to endothelium (chemotactic and mitogenic for
↓ smooth muscle cells and
Platelet fibroblasts)
Activation
↓ β
Thromboxane Release of TGF-β
Release
(Stimulates fibroblast
↓ collagen synthesis)
Vasoconstriction
Intimal fibrosis
Adventitial fibrosis
Perivascular fibrosis
↓ known to be associated with activated T cells
Vasoconstriction
• From the endothelium: Release of Endothelin-1 (cold
exposure) → Vasoconstriction
 Vasoconstrictor
 Stimulates fibroblast and smooth-muscle cells
 Opposed by EDRF which is also released by endothelial
cells (normal increase in EDRF is not seen in patients
with systemic sclerosis due to impaired synthesis)
• ↑α2-adrenergic-mediated vasoconstriction in dermal arterioles
of patients with systemic sclerosis + ↓Vasodilatory
neuropeptides (from nerve damage) → Vasoconstriction
• Vasoconstriciton → Reperfusion Injury → Release of oxygen
free radicals → Further endothelial damage
Role of Cell-Mediated Immunity in the Development of Fibrosis
in Patients with Systemic Sclerosis
• T cells, macrophages, endothelial cells and toher cells along
with cytokines and growth factors interact in a complex
manner to stimulate fibrosis
• Laminin and type IV collagen induce in vitro transformation of
lymphocytes from systemic sclerosis patients
• 2
Mononuclear cell infiltrate (T ) surrounds small blo0d vessels
H at dermal-epidermal basement membrane zone since
in the dermis
• T cell hyperactivity ↑CD4+ → ↑CD4+:CD8+ ratio
• Activated T cells → IL-2 production → Fibrosis
• Activated T cells → IL-4 production → stimulates fibroblast
chemotaxis and proliferation and collagen production
• Implicated in the development of pulmonary fibrosis
 IL-2
 IL-4
 IL-5
• Activated T cells → IFNγ → stimulates macrophages BUT
inhibits collagen synthesis by fibroblasts (IFNγ usually
decreased in patients with systemic sclerosis)
• ↑Macrophages → Secretion of IL-1, IL-6, TNF-α, TGF-β, PDGF
and fibronectin
 IL-1: Stimulate fibroblast proliferation and collagen
synthesis
 IL-6: Stimulate local release of tissue inhibitor of
metalloproteinases (TIMP) by fibroblasts → limit
breakdown of collagen
 Fibronectin: interacts with collagen where it binds
fibroblasts and mononuclear cells through receptors
called integrins; chemoattractant and mitogen for
fibroblasts
 TGF-β
 Upregulate expression of PDGF receptors
 Stimulates fibroblast proliferation
 Induces synthesis of CTGF which further stimulates
fibroblast proliferation and synthesis of
extracellular matrix
 With increased number of receptors found in
systemic sclerosis, they are more responsive to TGF-
 PDGF (no description from the book)
• Other evidences that cell-mediated immunity is involved
 Appearance of scleroderma-like lesions in:
 Patients with graft-versus-host disease (GVHD) after
bone marrow transplantation
 In a murine model of chronic GVHD, conditions
 Progressive skin induration
 Joint contractures
 Gastrointestinal involvement
 Pulmonary involvement
 Sjogren’s syndrome
 Raynaud phenomenon and kidney involvement are
infrequent
• Mast cells
 Interaction with T cells → Mast cell degranulation →
Release of tryptase → fibroblast collagen synthesis
 Rlease of histamine → edema 9early in disease)
• ↑Fibroblasts
 Aberrant regulation of growth
 Appear to be in a state of permanent activation due to
stimulation by TGF-β and CT growth factor (CTGF)
 Increased production of high-collagen producing
phenotype and decreased production of low-collagen
producing phenotype
 Collagen deposition is perivascular in myocardium,
muscle, kidney
 Type VII collagen found throughout dermis accounting for
the indurated, tightly bound ksin in the disease (normally
they act as anchoring fibrils)
Other Events involved in
Pathogenesis of Systemic Sclerosis
• Microchimersism
 Can occur in nulligravid women
 Can occur in men via
 Blood transfusion
 Engraftment of cells from a twin
 From maternal cells in utero
• Predilection for women in the childbearing years
 Fetal progenitor cells can persist in the serum of normal
women for many years after childbirth
 Since there is increased quantity and frequency of
immune fetal cells in patients with systemic sclerosis
• Chromosomal abnormalities in >90% of patients with systemic
sclerosis
 Chromatic breaks: found in patients and in their first-
degee relatives
 Acentric Fragments
 Ring chromosomes (~30% of mitotic cells)
PATHOLOGY
- skin  dermal appendages are atrophied & rete pegs are
lost
- GI  thin mucosa, ↑ collagen in the lamina propria,
submucosa & serosa
 o Degree of fibrosis is less than @ skin
- Lung  diffuse interstitial fibrosis, thickening of the
alveolary membrane, peribronchial & pleural fibrosis
o Bronchiolar epithelial proliferation
o Rupture or septa  small cysts & areas of
bullous emphysema
o Small pulmonary areteries & arterioles show
intimal thickening, fragmentation of elastica
(esp @ limited cutaneous SSc)
- Musculoskeletal  synovium similar to RA
o Thick layer of fibrin overlying & within the
synovium
o Later, the synovium may become fibrotic
o Possible overlap syndrome of SSc &
polymyositis
- Heart  degeneration of myocardial fibers & irregular
areas of interstitial fibrosis
o Contraction band necrosiss
- Kidneys  intimal hyperplasia of interlobular arteries
o Fibrinoid necrosis of afferent arterioles
(including glomerular tuft)
o Thickening of GBM
o Small cortical infarctions & glomerulosclerosis
o Often indistinguishable from observed in
malignant HTN
o Renal vascular lesions may be present in the
absence of HTN
o IgM, complement & fibrinogen
o Cold induced raynauds has been shown to
decrease renal blodd flow
- Others
o Fibrosis of thyroid gland may dvlp in the
absence or presence of autoimmune thyroiditis
o Thickening of periodontal membrane w/
replacement of lamina dura
 Gingivitis & loosening of teeth
o ↓ oral aperture & mucosal dryness makes
eating & oral hygiene difficult.
CLINICAL MANIFESTATIONS
- First symptoms: Raynaud’s phenomenon (95%) and puffy
fingers
- Raynaud’s  episodic VC of small arteries & arterioles of
figers, toes, & sometimes the tip of the nose & earlobes
o Brought about by cold, vibration or emotional
stress
o Pallor/cyanosis (cold & numbness)  rubor on
rewarming (pain & tingling)
o Not all patients appreciate 3 color phases
o DIGIT PALLOR  most reliable symptom for the
presence of Raynaud’s
o May precede skin changes
- Skin features
o early  fingers & hands swollen, lower
extremities spared
 EDEMATOUS PHASE
 Pitting/non + erythema
o Begin distally  proximally
o The skin gradually becomes firm, thick &
tightly bound to the underlying subcutaneous
tissue
 INDURATIVE PHASE
o Rapid changes  greater risk of visceral
disease
o Skin thickening is usually greater in the DISTAL
extremity
o After many years, the skin may soften & return
to normal thickness or become thin and
atrophic
o  flexure contracture
o  ulcers @ volar pads of fingertips & over bony
prominences (elbows, malleoli, extensor surfac
of the proximal interphalangeal joints)
o skin over the extremities, face & trunk may
become darkly pigmented even w/o sun
exposure
 hyperpigmentation of the skin may
occur over superficial blood vessels &
tendons
o hypopigmentation may also dvlp (similar to
vitiligo)  @ eyebrows, scalp & trunk
o sparing of pigment around hair follicles  SALT
& PEPPER appearance
o  vaginal dryness
o  calcific deposits  @ intracutaneous &
subcutaneous tissue
 periarticular, digital pads, olecranon
& prepatellar bursae
o face involvement  thin lips, loss of skin
wrinkles & facial expression & microstomia 
eating & dental hygiene difficult!!
o  wrinkles perpendicular to mouth
o capillary beds of nail folds of fingers may show
enlargement of capillaries w/ little or no
capillary loss
 usually indicative of Limited
cutaneous scleroderma
o in diffuse cutaneous scleroderma  there is
disorganization of the capillary beds w/ dilated
capillaries interspersed with areas where
capillaries have disappeared
 these capillary changes are Not
found in px who have only Raynauds
- Muskuloskeletal
o pain, swelling, stiffness of fingers & knees
o symmetric polyarthritis may be seen
o leathery crepitation (esp knee)
o extensive fibrotic thickening of the tendon
sheaths in the wrist  carpal tunnel syndrome
o wkness is usually present in px w/ severe skin
involvement & is usually due to disuse atrophy
o  Myositis ch by proximal muscle wkness &
muscle enzyme elevations that are identical to
polymyositis (overlap syndrome)
- gastrointestinal
o esophageal >50%
 epigastric fullness
 burning pain in the epigastric or
retrosternal
 regurgitation of gastric contents
o most noticeable when px is flat or bending
over
o due to ↓ tone of sphincter & to dilatation of
the distal esophagus
o peptic esophagitis  seldom results to
bleeding
o barret’s  but seldom becomes adenoCA
o dysphagia  solids, caused by loss of
esophageal motitlity due to neuromuscular
dysfxn
o ↓ amplitude or disappearance of peristaltic
waves in the lower 2/3 of esophagus
o Raynauds w/o CT dse is assoc w/ esophageal
dysmotility
o Pseudoobstruction – hypomotility of small
intestine producing symptoms of bloating &
abdominal pain
o Malabsorption syndrome
o Loss of feathery pattern in roentgenographic
features of the second & third portions of the
duodenum & jejunum
 o SSc sine scleroderma  GI features of SSc w/
little or no involvement of cutaneous or other
organs
o Watermelon stomach  dilated submucosal
capillaries @ endoscopy as broad stripes
- Pulmonary
o leading cause of death in SSc (replaced renal)
o exertional dyspnea  most common symptom
 often accompanied by dry,
nonproductive cough
o ↓ vital capacity & ↓ lung compliance
o ↓ diffusing capacity & ↓ PO2 w/ exercise
 these pulmonary fxn test abn may be
present even if CXR is Normal
o active inflam alveolitis  ground glass
appearance
o interstitial fibrosis & vascular lesions
o interstitial fibrosis  predominant lesion in
patients w/ diffuse or limited cutaneous SSc
 Px w/ diffuse cutaneous involvement
who have antipolymerase 1 Ab 
severe!
o Prognosis is poor w/ the dvlpt of pulmonary
hypertension
o Aspiration pneumonia  less common problem
- Cardiac
o Primary cardiac involvement 
 pericarditis w/w/o effusions
 heart failure
 varying degrees of heart block
 arrythmias
o diffuse cutaneous SSc  majority have cardiac
problems
o contraction band necrosis  results from
cardiac muscle damage caused by intermittent
vasospasm of coronary vessels
o px may experience angina pectoris even though
angiogram is normal
- Renal
o Previously the leading cause of death
o Significant dse occur more in diffuse cutaneous
scleroderma (widespread skin thickening)
o Renal crisis
 Malignant hypertension  renal
failure
o Hypertensive encephalopathy
o Severe headache, retinopathy, seizures, LV
failure
o Renin angiotensin system  mech for
hypertensive crisis
o Microangiopathic anemia (& large chronic
pericardial effusion) indicator of impending
renal failure (may occur in normotensive px)
- Others
o Dry eyes/mouth – frequent!
o Lymphocytic infiltration of minor salivary
glands  characteristic of Sjogren’s syndrome
secondary to SSc
o (+) SS-A (Ro) & SS-B (La)
o hypothyroidism
o trigeminal neuralgia & male impotence
secondary to decreased penile tumescence
 BUT have normal testosterone
LAB FINDINGS
- ↑ESR
- hypoproliferative anemia related to chronic inflammation
 most common cause
- vit B12 / folic acid deficiency anemia
- microangiopathic hemolytic anemia  renal involvement
-  polyclonal hypergammaglobulinemia  IgG
- antitopoisomerase 1 (Scl-70)  antibodies w/c have high
specificity for SSc
o assoc w/ diffuse cutaneous involvement
o interstitial pulmonary dse
o renal ,etc
- anticentromere Ab
o 40-80% of px w/ lmited cutaneous scleroderma
or CREST syndrome
- antinucleolar Ab
o specific for SSc
DIAGNOSIS
- although raynaud’s phenomenon may be the first
symptom of SSc, most patients w/ raynauds alone do not
dvlp a CT d/o
- other causes of raynauds
o thoracic outlet (scalenus anticus & cervical rib)
o shoulder-hand syndrome
o trauma (jackhammer operators)…
o etc…
- localized forms of scleroderma
o linear scleroderma &
o morphea
- sclerederma adultorum of buschke  occurs in children
(painless edematous ulceration)
o previous strep infxn
- scleremyxedema  papules
- acid mucopolysaccharide depostis
- monoclonal IgG
- prayer hand deformitiy  px w/ IDDM; digital sclerosis &
contractures
- primary amyloidosis w/ multiple myeloma
- Biopsy will clearly differentiate!!!!
COURSE & PROGNOSIS
- until the dse differentiates into recognizable subsets,
prognosis in early dse is difficult to predict
- lmited cutaneous scleroderma (w/anticentromere Ab) 
good prognosis unless…
o pulmo arterial hypertension
o malabsorption syndrome
o primary biliary cirrhosis
- diffuse cutaneous scleroderma  generally worse
prognosis esp if older age
- males  worse prog
- sclerodactyly & flexion contractures may persist
- death occurs most moften from pulmonary, cardiac &
renal involvement.
TREATMENT
 SSc cannot be cured
 Treatment of involved organ systems can relieve symptoms and
improve function
Need to be monitored:
a. blood pressure
b. blood counts
c. urinalysis
d. renal function
e. pulmonary function
High-dose D-penicillamine (700-1000 mg/d)
 in the past, used to treat early diffuse cutaneous SSc
 rationale for using: interfered with inter- and intramolecular
cross-linking of collagen; immunosuppressive
 recent study showed no benefit of high versus low doses of this
drug
STUDIES ON SEVERAL DRUGS FOR SSc
Recombinant human IFN-γ
 positive effects: modest improvement in skin sclerosis
 negative effects: worsening of Raynaud’s phenomenon,  very important in SSc
development of renal crisis and influenza-like symptoms  Reduce dryness of skin by:
a. avoid frequent use of detergent soaps
Immunosuppressive agents b. regularly applying hydrophilic ointments & bath oils
 rationale for using: based on the cellular and humoral  regular exercise to maintain flexibility of extremities &
immunologic abnormalities that have been demonstrated in SSc pliability of skin
 results were disappointing  massage skin several times a day
 occlusive dressing (hydrocolloid duo-DERM): promote healing
Cyclosporine and protect finger
 decrease skin induration without improvement in pulmonary or  warfarin: reduce calcinosis
cardiac manifestations
 SE: nephrotoxicity Pilocarpine hydrochloride tablets
 increase salivary secretions
5-fluorouracil
 showed skin improvement Reflux esophagitis
 SE: significant gastrointestinal toxicity  small frequent meals, antacids between meals, elevation of
head of bed
Cyclophosphamide  do not lie down for a few hours after a meal
 used in early sclerodermal interstitial lung disease  avoid coffee, tea, alcohol, peppermint & chocolate: reduce
 showed improvement or stabilization of pulmonary function and pressure of lower esophageal sphincter
improvement of skin induration  avoid fatty foods and late-evening snacks

Antiplatelet therapy Grastric acid (proton) pump inhibitors

 low doses of aspirin: block the formation of thromboxane A2, a  more effective in treating erosive esophagitis than are H2
powerful vasoconstrictor and platelet aggregator blockers
 dipyridamole (200-400 mg, divided daily doses): decreases
platelet adhesion to damaged vessel walls NSAIDS
 for articular symptoms
Glucocorticoids
 not effective in improving or preventing skin induration & the N-acetylcysteine
progression of SSc  antioxidant to reduce lung damage in patients with RDS and may
 should not be used for the indolent primary form of muscle help in SSc lung disease
disease of SSc
 associated with the development of renal crisis Vaccine
 but, beneficial in certain situations….  polyvalent pneumococcal vaccine (Pneumovax) and yearly
a. short courses of low-dose prednisone (<10 mg/d): influenza immunizations
decrease edema associated with edematous phase of
MIXED CONNECTIVE TISSUE DISEASE (MCTD)
early skin involvement; useful in relieving joint and
tendon pains  overlap syndrome characterized by combinations of clinical
b. higher doses of a glucocorticoid (prednisone 20-30 features of SLE, SSc, polymyositis and RA and the presence of very
mg/d): inflammatory myositis, pericarditis, early active high titers of circulating autoantibodies to nuclear RNP antigen
alveolitis (anti-U1 RNP)
 peak onset of disease: 2nd and 3rd decades
MANAGEMENT OF RAYNAUD’S PHENOMENON  women > men
 directed at control of vasospasm
a. dress warmly and wear mittens and socks Sclerodermal changes
b. do not smoke usually limited to the distal extremities and sometimes the face
c. remove causes of external stress but spare the trunk
d. avoid drugs like amphetamine & ergotamine  some with mucocutaneous features of SLE
 beta-blocking drugs may worsen Raynaud’s phenomenon  (+) joint pain, stiffness & swelling involving peripheral joints
 calcium channel blockers and longer-acting amlodipine:  myalgias are frequent
effective in alleviating Raynaud’s phenomenon
• SE: light headedness and palpitations Pulmonary involvement (asymptomatic)
 Nitroglycerin paste: improve local blood flow when applied to  ~85%
the affected digit  Pulmonary arterial HPN: most common cause of death in MCTD
 Sildenafil (phosphodiesterase inhibitor): primarily for erectile
dysfunction, may also be helpful Renal involvement
 SSRIs: decrease platelet 5-hydroxytryptamine  ~25%
 IV iloprost (prostacyclin analogue): decrease in frequency and  Membranous glomerulonephritis: most common; usually mild but
severity of Raynaud’s phenomenon and healing of digital ulcers can cause nephritic syndrome
 IV alprostadil (prostaglandin): effective in treating severe
Raynaud’s phenomenon with digital ulcers GI involvement
 IV epoprostenol & oral Bosentan (endothelin-1 receptor  ~70%
antagonist): used in treatment of pulmonary HPN, also effective in  most common manifestations: esophageal dysmotility, lower
Raynaud’s phenomenon esophageal sphincter laxity, gastroesophageal reflux
 Pentocifylline (400 mg TID): improve perfusion by increasing
deformability of red cell plasma membranes Cardiac involvement
 ~30% pericarditis
Distal ulnar artery occlusion should be considered in Raynaud’s
phenomenon LABORATORY FINDINGS
 positive Allen test: suggestive  majority: anemia of chronic inflammation
 angiography: confirmatory for the diagnosis  (+) direct Coomb’s test
 hypergammablobulinemia
SKIN CARE  rheumatoid factor (50%)
TREATMENT
 same as would be indicated for the respective CT diseases
defining this syndrome
 more than half have a favorable course
 10-yr survival rate: 80%

EOSINOPHILIC FASCIITIS
 scleroderma-like syndrome of unknown cause characterized by
inflammation followed later by sclerosis of the dermis, subcutis
and deep fascia
 affects adults
 usually after strenuous physical activity
 (-) Raynaud’s phenomenon & internal organ involvement
 abrupt onset of symmetric tenderness and swelling of
extremities, rapidly followed by induration of the skin and
subcutaneous tissue
 skin: cobblestone or puckered appearance
 carpal tunnel syndrome: appears early
 flexion contractures: develop later
 marked eosinophilia: early stage
 increased polyclonal IgG levels and immune complexes
 spontaneous improvement and occasionally complete remission
may occur after 2 to 5 years of disease

EOSINOPHILIA-MYALGIA SYNDROME
 in 1989, scleroderma-like changes, myalgias, eosinophilia
dramatically increased
 most cases: associated with ingestion of L-tryptophan
manufactured by a single Japanese company
 onset: abrupt or insidious
 early phases: low-grade fever, fatigue, dyspnea, cough,
arthralgias/arthritis, evanescent erythematous rashes, muscle
cramping, severe myalgias
 peripheral neuropathy
 most closely resemble toxic oil syndrome
 peripheral eosinophil count: >1000/ul
 tx: glucocorticoids, antimalarial drugs, immunosuppressive
drugs, plasmapheresis
 Prednisone: beneficial during acute inflammatory phase &
resulted in resolution of pulmonary infiltrates, peripheral edema
and eosinophilia
- This back-up summary is c/o gertzie, mia, & lessa
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