Connective Tissue Diseases

Dx
Monitor
Background
Peds
Lab Tests
Algorithm

Diagnosis

Indications for Testing

Appropriate clinical presentation, including arthralgias or arthritis

Laboratory Testing

Nonspecific testing – CBC, erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)
Initial screen is ANA EIA; if musculoskeletal complaints are present, consider rheumatoid testing (rheumatoid factor, synovial fluid)
- If screen is positive, then proceed with ANA IFA
- Titer level has no bearing on diagnosis or disease severity once it is above established normal level
Further testing based on ANA IFA
- Anti-U1-RNP
  - High titers are associated with SSc/SLE/polymyositis overlap syndromes
- Urinalysis – rule out glomerulonephritis
- ANCA – rule out vasculitis
- For further testing strategies, consult the following
  - Systemic lupus erythematosus
  - Sjögren syndrome
  - Rheumatoid arthritis (RA)
  - Mixed connective tissue disease
  - Scleroderma (systemic sclerosis)
  - Inflammatory myopathies
  - Connective Tissue Disease Testing algorithm

Autoimmune connective tissue diseases and major autoantibodies

Autoimmune Connective Tissue Diseases and Major Autoantibodies
Systemic lupus erythematosus	dsDNA, smith, cardiolipin, lupus anticoagulant, histone (drug-induced lupus)
Rheumatoid arthritis	RF IgM, cyclic citrullinated peptide (CCP)/citrullinated protein antibodies
Scleroderma/systemic sclerosis	Scl-70, centromere, RNA polymerase I/III
Sjögren syndrome	Ro (SSA), La (SSB)
Mixed connective tissue disease	RNP
Polymyositis/Dermatomyositis	Jo-1, Mi

Differential Diagnosis

Arthritis
- RA
- Osteoarthritis
- Crystalline arthritis
- Reactive arthritis (Campylobacter spp, Salmonella, Shigella, group A streptococcus)
- Ankylosing spondylitis
- Psoriatic arthritis
- Sarcoidosis
Myositis
- Demyelinating disease (multiple sclerosis, etc)
- Peripheral neuropathy
- Paraneoplastic syndromes
- Guillain-Barré syndrome
- Cushing syndrome
Systemic presentation
- Drug-related autoimmune presentation
- Antiphospholipid syndrome
- Vasculitis
- Malignancy
  - B-cell lymphoma
  - T/NK-cell lymphoma
  - Thymoma
- Endocarditis
Renal
- Acute glomerulonephritis
- Vasculitis
Central nervous system
- Vasculitis
- Stroke
- Migraine
- Infectious meningitis/encephalitis
- Brain tumor
- Malignancy
  - Lymphoma
  - Leukemia (most commonly ALL)
Hematologic
- Autoimmune hemolytic diseases
- Malignancy
  - Infiltrative metastatic
  - Leukemia (ALL and AML)
  - Myeloproliferative neoplasms
  - Myelodysplastic syndromes

Monitoring

Once diagnosis is made, use monitoring tests based on organ involvement
- Urinalysis is reasonable screen for renal disease
- If cytopenias present, follow with sequential CBCs
- Certain treatment drugs require liver function testing

Clinical Background

Several autoimmune connective tissue diseases may present with similar features. These diseases include systemic lupus erythematosus, Sjögren syndrome, mixed connective tissue disease, scleroderma (systemic sclerosis), progressive systemic sclerosis, inflammatory myopathies (polymyositis/dermatomyositis [PM/DM]) and undifferentiated connective tissue disease.

Epidemiology

Incidence – ranges from 15-50/100,000 depending on disease
Age – onset is 15-40 years; peak onset in 20s
Sex – M<F, 1:6-10

Pathophysiology

Circulating antigen-antibody complexes affect a variety of organs
Multisystem disease presentation; major blood vessels are the predominant target

Clinical Presentation

Constitutional – fever, anorexia, weight loss
Musculoskeletal – arthralgias, arthritis, synovitis, myopathy
Dermatologic – skin rashes, Raynaud phenomenon, photosensitivity
Cardiopulmonary – pleuritis, pericarditis, fibrosis, chest pain
Renal – proteinuria, glomerulonephritis
Otorhinolaryngologic – sicca syndrome, oral ulcers
Gastrointestinal – gastroesophageal reflux disease
Neurologic – seizures, encephalopathy
Hematologic – cytopenias (involving neutrophils, erythrocytes and platelets)

Treatment

Anti-inflammatory therapies – glucocorticosteroids and other drugs such as methotrexate and mycophenolate

Pediatrics