SYSTEMIC LUPUS ERYTHEMATOSUS,

RHEUMATOID ARTHRITIS
SALOME SIBASHVILI
 Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that predominantly affects women of
childbearing age and is the most common form of lupus.
 The exact cause is still unknown, but hormonal and immunological features and genetic predisposition are
considered likely etiological factors.
 Disease presentation is variable but is usually characterized by phases of remission and relapse.
 Symptoms can range from mild and localized to life-threatening systemic disease. SLE can affect any organ, but
typical findings include arthritis, a malar rash (facial butterfly rash), and constitutional symptoms such as fever
and fatigue.
 Many different autoantibodies are found in patients with SLE. The most frequent are antinuclear, particularly
anti-DNA, antibodies; others include antibodies against ribonucleoproteins, histones, and nucleolar antigens.
ETIOLOGY

 The exact etiology is unknown, but several predisposing factors have been identified.

Genetic predisposition
 HLA-DR2 and HLA-DR3 are commonly present in individuals with SLE.
 Genetic deficiency of classical pathway complement proteins (C1q, C2, C4) in approx. 10% of affected individuals

Hormonal factors: Hyperestrogenic states (e.g., due to oral contraceptive use, postmenopausal hormonal therapy,
endometriosis) are associated with an increased risk of SLE.
Environmental factors
 Cigarette smoking and silica exposure increase the risk of developing SLE.
 UV light and EBV infection may trigger disease flares, but there is insufficient evidence on whether they cause SLE.
 Drugs such as procainamide or hydralazine (see “Drug-induced lupus erythematosus”)
PATHOPHYSIOLOGY

 The exact pathomechanism of SLE is not fully understood, but the following two processes are the most widely
accepted hypotheses:
 Autoantibody development: deficiency of classical complement proteins (C1q, C4, C2) → failure of
macrophages to phagocytose immune complexes and apoptotic cell material (i.e., plasma and nuclear antigens) →
dysregulated, intolerant lymphocytes targeting normally hidden intracellular antigens → autoantibody production
(e.g., ANA, anti-dsDNA)
 Autoimmune reactions
 Type III hypersensitivity (most common in SLE) → antibody-antigen complex formation in microvasculature →
complement activation and inflammation → damage to skin, kidneys, joints, small vessels
 Type II hypersensitivity → IgG and IgM antibodies directed against antigens on cells (e.g., red blood cells) →
cytopenia
COMMON CLINICAL FEATURES
 SLE is a systemic disease characterized by phases of remission and relapse. Some individuals only experience mild
symptoms, while others experience severe symptoms and rapid disease progression. SLE can affect any organ.
 Constitutional: fatigue, fever, weight loss
 Joints (> 90% of cases)
 Arthritis and arthralgia
 Distal symmetrical polyarthritis: most commonly affects the joints of the fingers, carpal joints, and the knee
 Skin (85% of cases)
 Malar rash (butterfly rash): flat or raised fixed erythema over both malar eminences (nasolabial folds tend to be spared)
 Raynaud phenomenon
 Photosensitivity → maculopapular rash
 Discoid rash
 Oral ulcers (usually painless)
 Nonscarring alopecia (except with discoid rashes)
 Periungual telangiectasia
LESS COMMON CLINICAL FEATURES

 Hematological: petechiae, pallor, or recurrent infections due to cytopenias

 Musculoskeletal: myalgia
 Serositis: pleuritis and pericarditis → effusions
 Kidneys: nephritis with proteinuria (see “Lupus nephritis”)
 Heart - Pericarditis, myocarditis, endocarditis (Libman-Sacks endocarditis) , Aortic valve lesions, Coronary artery
disease
 Lungs – Pneumonitis , Interstitial lung disease , Pulmonary hypertension
 Vascular- Vasculitis , Thromboembolism (see “Antiphospholipid syndrome”)
 Neurological- Seizures, Psychosis , Personality changes , Lupus cerebritis , Aseptic meningitis, Polyneuropathy
 Eyes: keratoconjunctivitis sicca
DIAGNOSTICS

 Antinuclear antibodies (ANAs)

 Positive titers of ≥ 1:80 have ∼ 98% sensitivity for SLE (entry criterion for the 2019 EULAR/ACR classification criteria for
SLE).
 If negative, consider differential diagnoses and/or follow-up with the patient regularly.
 Antigen-specific ANAs: Request only if ANAs are positive.
 Anti-dsDNA antibodies
 Autoantibodies against double-stranded DNA
 Positive in 60–70% of patients
 Highly specific for SLE
 Levels correlate with disease activity (especially lupus nephritis activity).
 Anti-Sm antibodies
 Autoantibodies against Smith antigens (nonhistone nuclear proteins)
 Positive in < 30% of patients, but highly specific for SLE
 Anti-histone antibodies specific for drug induced lupus (hydralazine-antihypertensive medication)
DIAGNOSTICS

 Antiphospholipid antibodies: Screen all patients for antiphospholipid syndrome.

 Laboratory markers of disease activity and/or organ damage in SLE
 Complement levels: ↓ C3 and/or ↓ C4 in patients with active disease
 Inflammatory markers
 ESR: may be elevated in patients with active disease
 CRP: often normal (may be elevated in patients with serositis, arthritis, or infections)
 CBC: may show leukopenia, thrombocytopenia, and/or autoimmune hemolytic anemia or anemia of chronic
disease
 CMP: may show ↑ BUN and/or creatinine, and/or electrolyte abnormalities
 Urinalysis and urine microscopy: may show proteinuria, hematuria, and/or urinary casts
 Additional diagnostics
 Request additional tests based on suspected organ involvement (see also “Specific clinical manifestations” and “Clinical
features”).
 Imaging studies
 Imaging studies can help in the assessment of organ or joint involvement.
 X-ray joints: Perform in patients with articular symptoms.
 X-ray or CT chest: Perform in patients with symptoms of pulmonary involvement (e.g., interstitial lung disease,
pleuritis).
 Echocardiography: Consider in patients with suspected pericardial effusion or Libman-Sacks endocarditis.
 Histopathology
 Skin biopsy
 Consider in patients with atypical dermatologic presentation or no response to initial therapy.
 Lupus band test (LBT): a direct immunofluorescence staining technique used to detect immunoglobulin and complement
component deposits along the dermoepidermal junction in affected and unaffected skin in patients with SLE [14]
CRITERIA
TREATMENT

 Patients with SLE usually require life-long immunosuppressants.

 NSAIDs can provide symptomatic relief.
 Non-pharmacological measures include:
 Lifestyle modifications (e.g., smoking cessation, aerobic exercise)
 Avoidance of UV light
 All patients: Hydroxychloroquine is the cornerstone of therapy (regardless of disease activity). [13][16]
 Mild to moderate disease (no vital organs affected): Consider the addition of oral glucocorticoids with or without
other immunosuppressive agents to achieve remission.
RHEUMATOID ARTHRITIS

 Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory autoimmune disorder that primarily affects the
joints (e.g., causes pain, swelling, synovial destruction, deformities), but may also manifest with extraarticular
features (e.g., rheumatoid nodules, pulmonary fibrosis).
 The risk of RA increases with age, and the disease predominantly affects women.
ETIOLOGY

 Idiopathic inflammatory autoimmune disorder of unknown etiology

 Risk factors include:
 Genetic disposition: associated with HLA-DR4 and HLA-DR1
 Environmental factors (e.g., smoking)
 Hormonal factors (premenopausal women are at the highest risk, suggesting a predisposing role of female sex
hormones)
 Infection
 Obesity
 Family history of RA
PATHOPHYSIOLOGY
 Certain interstitial tissue proteins (e.g. intracellular filament protein vimentin, filaggrin, type II collagen) undergo
a posttranslational modification that involves the conversion of arginine to citrulline (citrullination).
 Citrullinated proteins are recognized as foreign by the antigen-presenting cells that present them to CD4+ T cells.
 Activation of CD4+ T cells leads to the following sequences of events:
 IL-4 production → B-cell proliferation and differentiation → production of anticitrullinated peptide antibodies →
type II hypersensitivity reaction and type III hypersensitivity reaction
 Migration of CD4+ T cells to synovial joints → secretion of cytokines (IFN-γ, IL-17) → recruitment of
macrophages → secretion of cytokines (TNF-α, IL-1, IL-6) → inflammation and proliferation
 Bouts of inflammation, angiogenesis, and proliferation → proliferative granulation tissue with mononuclear
inflammatory cells → pannus and synovial hypertrophy → invasion, progressive destruction, and deterioration of
cartilage and bone
 Antibodies against Fc portion of IgG (rheumatoid factor, RF) are produced to aid in removing autoantibodies and
immune complexes.
 RF excess triggers formation of new immune complexes and type III HSR
 Individuals with positive RF are more likely to develop extraarticular manifestations.
CLINICAL FEATURES (ARTICULAR MANIFESTATIONS )
 Polyarthralgia
 Symmetrical pain and swelling of affected joints (also at rest)
 Frequently affected joints  Metacarpophalangeal joints (MCP joints) , Proximal interphalangeal joints (PIP joints), Wrist
joints, Knee joints, Metatarsophalangeal joints (MTP joints)
 Rarely affected: distal interphalangeal joints (DIP joints), first carpometacarpal (CMC) joint, and the axial skeleton (except for
the cervical spine)
 Morning stiffness (often > 30 min) that usually improves with activity
 Joint deformities
 Rheumatoid hand is characteristic and typically manifests with one or more of the following deformities:  Deepening of the
interosseous spaces of the dorsum of hand , Swan neck deformity: PIP hyperextension and DIP flexion , Boutonniere
deformity: PIP flexion and DIP hyperextension. , Hitchhiker thumb deformity (Z deformity of the thumb): hyperextension of
the interphalangeal joint with fixed flexion of the MCP joint , Ulnar deviation of the fingers, Piano key sign: dorsal
subluxation of the ulna , Hammer toe or claw toe , Atlantoaxial subluxation (see “Rheumatoid arthritis of the cervical spine”
below)
 Physical examination: compression test (Gaenslen squeeze test)
 Painful compression of hands (or feet) at the level of the MCP joint (metatarsophalangeal joint)
CLINICAL FEATURES ( EXTRAARTICULAR MANIFESTATIONS)

 Constitutional symptoms  Low-grade fever , Myalgia, Malaise, Fatigue , Weight loss, Night sweats
 Rheumatoid nodules Nontender, firm, subcutaneous swellings (2 mm–5 cm) Commonly occur in areas exposed
to higher pressure, e.g., extensor side of the forearm, bony prominences
 Eye: keratoconjunctivitis sicca, scleritis, and episcleritis
 Endocrine and exocrine glands: secondary Sjogren syndrome
 Heart  Pericarditis and myocarditis, Increased risk of myocardial infarction, stroke, CHF, and atrial fibrillation
 Vascular Peripheral vasculitis, manifests as livedo reticularis, Raynaud phenomenon, Purpura, Vasculitic ulcers,
Necrosing fingertips, Peripheral neuropathy
 DIAGNOSTICS

Nonspecific parameters
 ↑ Inflammatory markers
 ↑ CRP and ↑ ESR
 Other acute phase reactants may also be elevated (e.g., ferritin).
 CBC: anemia of chronic disease, thrombocytosis
 TFTs: to rule out an autoimmune thyroid disease, which is common in patients with RA
 Serology: ↑ ANAs in 30–50% of patients with RA

Specific parameters (serological studies)

 Anticitrullinated peptide antibodies (ACPA), e.g., anticyclic citrullinated peptide (anti-CCP)
 Rheumatoid factor (RF): IgM autoantibodies against the Fc region of IgG antibodies
 Serological studies may be negative (i.e., seronegative RA)
While x-ray is recommended as the initial test, ultrasound and MRI might additionally be necessary to assess joint disease severity.
X-ray: initial test- Findings
 Early: soft tissue swelling, osteopenia (juxtaarticular)
 Late: joint space narrowing, marginal erosions of cartilage and bone, osteopenia (generalized), subchondral cysts

Ultrasound
 Indication: If available, perform on affected joints to detect clinical or subclinical synovitis.
 Supportive findings
 Early signs of inflammation: e.g., subclinical synovitis (synovial hyperemia)
 Synovial proliferation (pannus formation)
 Joint effusion: increased fluid (e.g., pus, blood, inflammatory infiltrate) within the synovial compartment of a joint
 Using contrast can increase the sensitivity of detecting inflammation.

MRI of the affected joints (with or without contrast)

 Can help detect early changes in large joints (e.g., subclinical synovitis)
 Consider especially if cervical spine involvement is suspected (see “Atlantoaxial subluxation”).
 TREATMENT

 NSAIDs
 • Steroids
 • Disease-modifying antirheumatic drugs (DMARDs)
 • Protect joints from destruction
 • Methotrexate
 • Azathioprine
 • Cyclosporine
 • Hydroxychloroquine
 • Sulfasalazine
 • Leflunomide
 • TNF-a inhibitors (antibodies against TNF-α)
THANK YOU!