Diagnosis

Systemic lupus erythematosus

Etiology

Cause [sgp]

• Unknown

• Multiple factors are associated:

  • Genetic: associated with HLA-A1, HLA-B8, HLA-DR3, twins, Klinefelter syndrome

  • Epigenetic

  • Ethnic

  • Immunoregulatory

  • Hormonal: females, estrogen (contraceptives, hormone replacement therapy)

  • Environmental: EBV-antibodies, drugs (procainamide, hydralazine), UW exposure

Pathophysiology [e9b][sgp]

1. Genetically susceptible individuals + environmental trigger --> autoimmunity

2. Infection or environmental factor --> cell damage

3. Defect in apoptosis --> cell-surface display of cytoplasmic and nuclear antigens --> immune system exposed to self-antigens

4. Dysregulated (intolerant) T and B lymphocytes targets normally protected intracellular antigens --> chronic self-aimed immune response:

   • Cytokine release

   • Complement activation

   • Autoantibody production

   • Organ damage

5. Clinical presentation:

   • General: Fatigue, fever, arthralgia, myalgia, lymphadenopathy, splenomegaly

   • Dermatologic: Lupus-specific lesions

     • Acute cutaneous lupus: localized, malar/butterfly, and generalized rash

     • Subacute cutaneous lupus: annular and papulosquamous rash

     • Chronic cutaneous lupus: discoid lupus, hypertrophic/verrucous, lupus panniculitis/profundus, lupus tumidus, chilblains lupus, mucosal discoid lupus, and lichenoid discoid lupus

   • Mucosa: Oral and nasal ulcers, Sjogren syndrome, keratoconjunctivitis sicca

   • Renal failure: Lupus nephritis

   • Psychiatric: depression, anxiety, psychosis

   • CNS: headache, stroke, seizure, aseptic meningitis, demyelinating syndrome (optic neuritis, myelitis), chorea, cognitive dysfunction, neuropathy, mononeuritis multiplex, autonomic neuropathy, Guillain-Barré syndrome, Myasthenia gravis

   • Pulmonary: Pneumonitis, pleuritis, pleural effusion, pulmonary hypertension, pulmonary embolism

   • Gastrointestinal: Nausea, dyspepsia, abdominal pain, esophageal dysmotility, mesenteric vasculitis, lupus enteritis, peritonitis, ascites, protein-losing enteropathy, pancreatitis, lupoid hepatitis, Budd-Chiari syndrome, mesenteric vessel thrombosis

   • Cardiac: Pericarditis, myocarditis, Libman-Sacks endocarditis

   • Vasculitis

   • Thrombotic microangiopathy

   • Hematologic: Leukopenia, lymphopenia, anemia, thrombocytopenia

   • Obstetric: Risk of spontaneous abortions and fetal loss, pre-eclampsia, and maternal thrombosis

   • Ocular: retinal vasculitis, optic neuritis, uveitis, scleritis, peripheral ulcerative keratitis, episcleritis, glaucoma or cataract

   • Sudden sensorineural hearing loss

Complications [sgp]

• Accelerated atherosclerosis --> coronary artery disease

• Kidney failure

• Anxiety and depression

• Pregnancy-related complications: fetal loss, pre-eclampsia/eclampsia

• Long-term use of corticosteroid therapy: avascular necrosis, glaucoma, cataract, weight gain, and poor control of Diabetes mellitus

Epidemiology

Incidence per 100.000 [htu][3nw][dk2][wnv][mwy][zvs][bs6][pao][q4p][ush]

Approach

• Blood test: ANA, anti-dsDNA antibody, anti-Smith antibody, Anti-Ro/SSA antibody

• Blood gas

• Urine microscopy

• Chest x-ray

• CT thorax

• ECG

• Echocardiography

• MR caput

• MR cor

• Arthrocentesis

• Lumbar puncture

• Renal biopsy

• Skin biopsy

SOAP BRAIN MD:

• Serositis (pleuritis, pericarditis, peritonitt)

• Oral ulcers

• Arthritis

• Photosensitivity

• Blood disorders (hemolytic anemia, leukopenia, thrombocytopenia)

• Renal involvement (proteinuria and cellular casts)

• Antinuclear antibodies (ANA)

• Immunologic phenomena (anti-dsDNA/Smith/phospholipid antibody)

• Neurologic disorder

• Malar rash

• Discoid rash

Rule out infections and drug reactions (procainamide, hydralazine, and isoniazid).

Treatment

Goal of treatment: induction of remission, consolidation of remission, and remission maintenance [yc9]

1. Cutaneous/musculoskeletal/serositis SLE: milder disease [e9b][yc9]

   • NSAIDs

   • Hydroxychloroquine

   • Low-potency immunosuppressive medications

   • Short courses of corticosteroids

2. Involvement of vital organs: [yc9][nhv]

   • Prednisone

   • Hydroxychloroquine

   • Azathioprine

   • Methotrexate

   • Mycophenolate Mofetil

   • Calcineurin inhibitors

   • Cyclophosphamide

   • Biologic: Rituximab, Belimumab, Anifrolumab

   • Other (plasmaferesis, intravenous immunologlobulins)

Differential diagnoses

Acute pancreatitis, Antiphospholipid syndrome, Behcet's disease, Cytomegalovirus, Drug side effects, Endocarditis, Erysipelas, Fibromyalgia, Guillain-Barre syndrome, Heart failure, HIV, Interstitial lung disease, Leukemia, Lyme disease, Lymphoma, Meningitis, Mixed connective tissue disease, Mononeuropathy, Mononucleosis, Myocarditis, Parvovirus B19, Pericarditis, Pneumonia, Polymyositis, Primary biliary cirrhosis, Primary sclerosing cholangitis, Psoriasis, Pulmonary embolism, Raynaud phenomenon, Renal failure, Rheumatoid arthritis, Rosacea, Sarcoidosis, Scleroderma, Seborrheic dermatitis, Sjogren syndrome, Still disease, Stroke, Thrombotic thrombocytopenic purpura, Ulcer disease, Viral hepatitis