Rheumatology: Connective Tissue Disorders

Connective Tissue

any type of biologic tissue that supports+binds together+protects organs

• fat

• bone

• cartilage

main components

• elastin

• collagen

Inherited vs Autoimmune Connective Tissue Disorders

inherited

• marfan syndrome

• ehlers-danlos syndrome

• osteogenesis imperfecta

autoimmune

• rheumatoid arthritis

• systemic lupus erythematosus (SLE)

• scleroderma

• sjogren’s syndrome

• polymyositis

• dermatomyositis

• psoriatic arthritis

Autoimmune Disease (General)

PP/E: antibodies→attach “self” tissues

CM: synovitis
pleuritis
endo+myo+pericarditis
peritonitis
vasculitis
myositis
skin rash
nephritis

DX:
CBC
hemolytic anemia
thrombocytopneia
leukopenia

ANA→positive
cryoglobulins
antiphpspholipid antibodies
CK→elevated
complement→low
false-positive for syphillis test (RPR)

TX: disease-modifying anti-rheumatic drugs (DMARDS)
-synthetic
-biologic

Systemic Lupus Erythematosus (SLE)

PP: autoantibodies→nuclear antigens→trapped in capillaries of organ structures→antibody-mediated destruction of platelets

E: hormonal influence
HLA-DR2
HLA-DR3

CM:
constitutional

• fever

• anorexia

• weight loss

• malaise

arthralgias

• malar “butterfly” rash

• discoid rash

• raynaud’s phenomenon

• photosensitivity

neurologic/psychiatric

• psychosis

• seizures

renal

• glomerulonephritis
  -mesangial
  -focal proliferative
  -diffuse proliferative
  -membranous

• interstitial nephritis

DX: dx criteria
ANA
anti-dsDNA
anti-smith
anti-phospholipid antibodies
serum complement level
-exacerbation→low
-remission→normal

TX:
NP: skin→avoid sun exposure

MX: 1st line→hydroxychloroquine (plaquenil)
corticosteroids

corticosteroid-resistant

• cyclophosphamide

• mycophenolate

• azathioprine

• belimumab

skin→topical corticosteroid
arthralgia→NSAIDS

Types of Lupus

systemic lupus erythematosus (SLE)

• m/c

• most serious

• affects many parts of body
  -skin
  -kidneys
  -heart
  -lungs
  -etc.

discoid lupus

• dx→limited to skin

mx-induced lupus

• sxs similar to SLE

• resolve within x 6 months of discontinuing mx

neonatal lupus

• baby born to mom with lupus sxs

• self-tx in a few months

SLE CM List (Full)

constitutional

• fever

• anorexia

• weight loss

• malaise

arthralgias

• malar “butterfly” rash

• discoid rash

• raynaud’s phenomenon

• photosensitivity

• panniculitis

• fingertip lesions

• periungual erythema

• nail fold infarcts

• splinter hemorrhages

• alopecia

opthalmologic

• conjunctivitis

• photophobia

• transient/permanent monocular blindness

• blurry vision

• cotton-wool spots on retina

pulmonary

• pleurisy

• pleural effusion

• bronchopneumonia

• pneumonitis

• restrictive lung dx

• alveolar hemorrhage

cardiac

• pericarditis

• libman-sacks endocarditis
  -mitral regurgitation

• heart failure

vascular

• mesenteric vasculitis

neurologic/psychiatric

• psychosis

• seizures

• cognitive impirment

• peripheral+cranial neuropathies

• transverse myelitis

• stroke

• depression

renal

• glomerulonephritis
  -mesangial
  -focal proliferative
  -diffuse proliferative
  -membranous

• interstitial nephritis

SLE Dx Criteria

need 4/11 of following criteria:

SLE Corticosteroids Tx Indications

glomerulonephritis

HLA

pericarditis

myocarditis

alveolar hemorrhage

CNS involvement

TTP

not indicated

• minor arthritis

• skin rash

• leukopenia

• anemia of chronic disease (AOCD)

SLE Prognosis

10-yr survival→85+%

relapsing+remitting course

bimodal mortality pattern

• early years post-dx→death due to opportunistic infxns
  -annual flu shot
  -PNA vaccine Q5 years

• later years post-dx→atherosclerosis/chronic inflammation
  -MI incidence→5x greater than general population
  -no smoking
  -control modifiable cardiac RFs

higher malignancy risk

• lymphoma

• lung cancer

• cervical cancer

kidney dx→dialysis

avascular necrosis of bone

Raynaud’s Phenomenon

PP: cold/emotional stress→exaggerated response of digital arterioles
-initial phase→excessive vasocontriction
-recovery phase→excessive vasodilation

E:
primary

• idiopathic

• 2-6% aults

• young women
  15-30 y/o

secondary

• sx of underlying rehumatic dx→scleroderma

CM:
initial phase

• well-demarcated pallor/cyanosis
  -1-2 fingers→whole palm
  -spares thumbs

recovery phase

• intense redness

• throbbing pain

• swelling

• paresthesias

m/c→fingers
-toes
-nose
-ears

primary→symmetric
secondary→UL+nail fold capillary changes
-due to scleroderma

DX:
r/o secondary cause→antibodies

nail fold capillary pattern

• scleroderma→abnormal

• grade B immersion oil+opthalmoscope

TX:
NP:
stay warm
avoid hand injuries
dry skin→lotion
no smoking
no decongestants/diet pills/amphetamines→sympathomimetic vasoconstrction

tx fail→surgical sympathectomy
-cervical
-digital

MX: 1st line→nifedipine

P: typically benign

secondary cases→more severe

• ulcerations

• gangrene

Systemic Sclerosis/Scleroderma

PP: diffuse fibrosis of skin+internal organs

RF: pulmonary HTN

E: unknown

mechanisms

• autoimmunity

• endothelial cell damage

• increased production of ECM

two forms:

• limited
  -80%
  -CREST syndrome

• diffuse
  -20%

CM:
CREST syndrome
Calcinosis cutis→calcium depsits in skin
Raynaud’s phenomenon→spasm in blood vessels due to cold/stress
Esophageal dysmotility
Sclerodactyly
Telangiectasia

diffuse scleroderma

• thick+hide-like skin

• loss of skin folds

• tendon fraction→rubs over forearms+shins

• kidneys→scleroderma renal crisis

GI

• conspitation

• diarrhea

• malabsorption

• pseudo-obstruction

constitutional

• weight loss

• malaise

• arthralgias

intersitial lung dx

DX:
CBC
mild anemia
-renal crisis→HLA
ANA
anti-SCL-70→diffuse
anti-centromere→limited

anti-RNAP

• severe dx

• increased mortality

ESR→normal

urinalysis

• renal involvement→proteinuria

TX:
NP: 1st line→sx+supportive tx

MX:
skin→methotrexate

raynaud’s→nifedipine
-calcium channel blocker

myositis→prednisone
-caution

scleroderma renal crisis/HTN→ACEi

GI:
-diet modification
-PPI
-pro-kinetic agnets
-malabsorption→abx

ILD:
-tocilizumab
-cyclophsophamide
-mycophenolate

pulmonary HTN:
-sidenafil
-prostaglandins

P: no therapy alters dx progression

Scleroderma Prognosis

CREST→better than diffuse scleroderma

limited dx

• life-threatening→pulmonary HTN

• digital ischemia→finger loss

10-yr survival rate→~70%
-prognosis improving

m/c mortality→lung dx
-heart dx
-renal dx

no severe organ involvement within 3 yrs of dx→better

Dermatomyositis+Polymyositis (General)

immune mediated inflammatory myopathies

polymyositis

dermatomyositis

inclusion body myositis

CC→”muscle weakness”

Dermatomyositis+Polymyositis

PP/E:
dermatomyositis
vascular inflammation→indirect myocyte injury

polymyositis
CD8+ mediated→direct myocyte injury

CM: muscle weakness
difficulty getting out of chair
difficulty climbing stairs

polymyositis

• progressive muscle weakness x weeks-months

• proximal muscles

• upper+lower extremities

• neck→dysphagia

• legs→arms

• spares face+eyes

dermatomyositis
polymyositis sxs+dermatologic sxs:

• “shawl sign”

• heliotrope rash

• gottron papules
  -violaceous legions over DIP+PIP+MCP joints

• gottron sign
  -erythema on extensor surfaces of fingers+elbows+knees

DX: AST→elevated
ALT→elevated
CK
aldolase
ESR→normal
CRP→normal
ANA
m/c→anti-Jo-1
dermatomyositis→anti-Mi-2
rapid progression+severe→anti-SRP
malignancy→anti-155/140
muscle involvement+biopsy guide→MRI

confirmation→muscle biopsy

• lymphoid inflammatory infiltrates

• dermatomyositis→+abnormalities localized to perivascular region

TX:
NP: skin→limit sun exposure

MX: corticosteroids
methotrexate
azathioprine
skin→hydroxychloroquine
skin+prednisone resistant→IVIG

Sjogren’s Syndrome

PP: lymphocyte+plasma cell infiltration→immune-mediated dysfunction of lacrimal+salivary glands

E: HLA-DR3
primary vs association
-RA
-SLE
-other autoimmune dxs

CM:
keratoconjunctivitis sixxa

• dry eyes

• foreign body sensation

xerostomia

• dry mouth

• dysphagia

• difficulty speaking

• poor dentition

loss of taste+smell
small vessel vasculitis
pleuritis
ILD
peripheral neuropathy
pancreatitis
renal tubular acidosis
chronic interstitial nephritis
thyroid dx
significantly increased lymphoma RF

DX:
CBC

• anemia

• mild leukopenia

• eosinophilia

ANA
RF
anti-SSA (Ro)
anti-SSB (La)
anti-thyroid antibodies
schirmer’s test (tear production)
lip biopsy→lymphoid foci on salivary glands
unclear dx→parotid biopsy

TX:
NP: hydration
sugar-free gum/hard candy
good PO hygiene

MX: no atropine
no decongestants
artificial tears
ocular cyclosporine

xerostomia:
-pilocarpine
-cevimeline

severe systemic features→prednisone
-vasculitis
-painful neuropathy