9. Connective Tissue Disease

Systemic sclerosis

Non-inflammatory obliterative vasculopathy & pathologic accumulation of collagen in skin & organs (FIBROSIS)

**Must distinguish local / limited & systemic

Hallmark S/S of systemic sclerosis

Skin thickening w/ waxy appearance

Cause/pathophysiology of systemic sclerosis

Fibroblasts & high deposition of collagen

Local scleroderma AKA

Morphea

Risk factors for systemic sclerosis

AA women age 20-30

Diffuse vs. Limited systemic sclerosis

Diffuse: Skin thickening only affecting extremities BELOW elbows OR knees

Limited: Skin thickening PROXIMAL to elbows OR knees

S/S of systemic sclerosis

- Skin thickening — Sclerodactyly (appears like edema, but HARD)

- Raynauds

- Stiff joint arthralgias

- Loss of strength

- Esophageal dysmotility (CT)

When should scleroderma-like skin disease be considered?

2/3 of following:

- Positive ANA

- Sclerodactyly

- Raynaud's

What organ involvement is associated with major cause of death with systemic sclerosis? Early mortality

- Major cause of death → Lungs

- Early mortality → Kidneys

Presentation of systemic sclerosis & heart involvement

RHF / Pulm A. HTN

Diagnostic workup of systemic sclerosis

- ANA

- Anti-centromere antibody — Highly specific for limited form

- Anti-Scl-70 — Highly specific for diffuse form

Management of systemic sclerosis

- Manage pruritis, gentle skin care, sun protection, prevent infection

- CCB — Raynauds

**NO anti-fibrotic medications

Management of digital ulcers with systemic sclerosis

Sildenafil

Management of renal disease with systemic sclerosis

Renal scleroderma crisis — ACEI

**Important to monitor for renal crisis

What is a form of limited scleroderma?

CREST syndrome

CREST syndrome

Calcinosis

Raynaud's

Esophageal dysmotility

Sclerodactyly

Telangiectasia — Highly associated with CREST

PE findings of CREST with capillaroscopy

Periungual infarcts

Management of limited sclerosis

- CCB (nifedine) — Raynauds

- PPI / H2 blocker — Esophageal dysmotility

- ACEI — Renal involvement

Sjögren's syndrome

AI inflammatory disorder affecting exocrine organs characterized by lymphocytic infiltration of lacrimal, salivary,, parotid glands

**SLOW progression

Risk factors for Sjögren's syndrome

- Women age 30-50

- Frequent in children

- Genetic & environmental

Pathophysiologic of Sjögren's syndrome

Lymphocytic infiltrate → Decreased secretion & neural stimulation

S/S & PE of secondary Sjögren's syndrome

- Rose bengal staining flecks of reddish staining in lower portion of cornea & conjunctiva

- Xerostoma & keratoconjunctivitis sicca (dry eyes / mount)

- Parotid gland

- Schirmer test — Assess level of dry eye

PE findings with keratoconjunctivitis sicca with Sjögren's syndrome

- Thick-rope strangs at inner canthus

- Dilated vessels at bulbar conjunctiva

- Fullness of conjunctiva & cornea

Complications of keratoconjunctivitis sicca with Sjögren's syndrome

Corneal ulcerations & eyelid infections

Autoantibodies associated with Sjögren's syndrome

SS-B & SS-A — B is more closer associated

SS-B & SS-A can also be seen in...

Pregnancy women & neonatal lupus

Diagnostic workup of Sjögren's syndrome

- ANA

- Anti-SSA OR anti-Ro

- Anti-SSB OR anti-LA

Secondary Sjögren's syndrome

Associated with other AI conditions — SLE, RA, Scleroderma, Idiopathic inflammatory myositis

Risk factors for secondary Sjögren's syndrome

- Female age >40

- Congenital heart block (antibodies cross placenta barrier)

What conditions does Sjögren's syndrome increase risk for?

Lymphoma

Management of dry eyes with Sjögren's syndrome

- Environment / humidity, increase fluids, reduce caffeine, lubricant unguents (1st line)

- Mod to severe dry eyes — Topical corticosteroids, cyclosporine drops (2nd line)

Management of dry mouth with Sjögren's syndrome

- Biotene, sugar-few gum & lozenges, xylitol sweetened products (1st line)

- Muscarinic cholinergic agonists to increase salivary gland secretion (2nd line)

ADRs of muscarinic cholinergic agonists for management of dry mouth with Sjögren's syndrome

Affects cardiac conduction / HR

Idiopathic inflammatory myositis

Heterogenous AI syndromes with muscle weakness with inflammation of muscle tissue & multi system involvement

Types & associated causes of idiopathic inflammatory myositis (4)

- Dermatomyositis — DM

- Antisynthetase syndrome

- Inclusion body myositis — IBM

- Necrotizing inflammatory myositis (statins)

Demographic associated with idiopathic inflammatory myositis

- AA, asian female

- Childhood 5-15 years

- Adult 30-50 years

- Proximity to equator

S/S & Presentation of idiopathic inflammatory myositis

- Gradual symmetric proximal muscle weakness

- Later stage muscle weakness → Head drop (weak neck flexors)

- Fatigue / malaise

- Severe → Pharynx involvement & swallowing difficulties

Diagnostic criteria of idiopathic inflammatory myositis

- Symmetric proximal muscle weakness

- Elevated muscle enzymes — CK, aldolase, AST, ALT, LDH

- EMG abnormalities

- Muscle biopsy — Myofibril degen/regen infiltrates, perifascucular atrophy

- Skin / derm — Gottron's papules, heliotrope rash, shawl sign, periungual involvement

Autoantibodies associated with idiopathic inflammatory myositis

- "Myositis specific" — Anti Jo-1 (MC autoantibody)

- Nonspecific — ANAs, anti-thyroid autoantibodies (TPO, anti-thyroglobulin)

S/S of dermatomyositis

- Gottron's papules — Red flat papules over knuckles

- Heliotrope rash — Purple rash over upper eyelids

- Shawl sign — Macular rash over posterior shoulders & neck

- Mechanics hands — Dirty appearance of hands

Examples of mixed connective tissue disease

Lupus, scleroderma, polymyositis

**BV common target

Demographic associated with mixed connective tissue disease

Women age

S/S of mixed connective tissue disease

- Red / brown patches over knuckles

- Sclerodactyly

- Muscle & point pain — Polymyositis

- ILD

Diagnostic workup of mixed connective tissue disease

- ANA → High titer

- Anti-U1 RNP small nuclear ribonucleoprotein antibodies (high specificity)

Complications of mixed connective tissue disease

- Pulm HTN

- ILD

- Heart disease → HF

- Kidney damage

- Hearing loss

Undifferentiated connective tissue disease

Characteristics of CT diseases BUT do not meet criteria