1. Systemic Lupus Erythematosus (SLE)

Etiology 

Pathophysiology

Constitutional Symptoms

• Fatigue - common in 80%

• Fever - rule out infection

• Weight changes

• Myalgia

Musculoskeletal Manifestations

• Joint involvement is the most common manifestation in SLE

• Arthritis a common feature typical not erosive nor deforming 

  • Involves fingers, wrists, and knees

• Arthralgia, myalgias

Cutaneous/Skin Manifestation 

• Up to 93% of patients with SLE have skin involvement

• Discoid lupus: sores/lesions on face, ear, scalp that scar

• Malar (butterfly) rash: photosensitive rash that develops over bridge of nose and cheeks 

Renal manifestation and Lupus Nephritis

• 25-50% present with lupus nephritis at diagnosis

• Characterized by proteinuria

• Can lead to end stage renal disease and significant reductions in 10-year survival

Antiphospholipid Syndrome

• Antiphospholipid syndrome is a completely separate autoimmune disease

• SLE is a common cause of secondary antiphospholipid syndrome

• Present clinically as thrombosis; will need anticoagulation 

  • Warfarin used 

more manifestation

Agents

BLyS inhibitor

• Belimumab (Benlysta)

• Monoclonal antibody against BLyS (B lymphocyte stimulator protein; no BLyS bining to B cells → inhibition of autoreactive B cell survival)

  • BLyS appears to be overexpressed in SLE, and contributes to increased autoreactive B cells

Cyclophosphamide 

• Immunosupressant and chemotherapeutic agents

• Known as alkylating agent: binds to DNA making it impossible for cells to function → leads to cell death 

  • Cyclophosphamide seems to have selectivity for T cells, which helps in its immunosuppression 

Cyclophoshamide ADE/warning

• Cyclophosphamide can lead to hemorrhagic cystitis

• Prevent by giving mesna, which detoxifies acrolein (the toxic metabolite), and with frequent hydration 

Calcineurin Inhibitors

• Cyclosporine (Gengrad), Tacrolimus (Prograf), and Voclosporin (Lupkynis)

• Blocks T-cell proliferation by inhibiting calcineurin leading to a decrease in the production of IL-2 and other cytokines

  • Like IL-2 inhibitors

Antimetabolite - mycophenolate  

• Mycophenolate mofetil (CellCept) and Mycophenolate sodium-enteric coated (Myfortic)

• Reduces lymphocyte proliferation by binding to a key enzyme (inosine monophosphate dehydrogenase) responsible for nucleotide synthesis 

  • Can inhibit synthesis of all cells, but is more sensitive for the version of the enzyme on T and B cells 

• Other antimetabolites: azathioprine and methotrexate