PM&R News   •   December 2020

A 16-year-old black female presents to her primary care physician with symptoms of fatigue, musculoskeletal pain, and a facial rash. On examination she is noted to be thin with malar skin changes. No other abnormality is found.

Description

• Autoimmune disorder – systemic autoantibodies
• Multiple phenotypic presentations
• Remitting and relapsing course is common

Anatomy: Dependent on phenotypes expressed: any organ system can be involved

Pathophysiology

• Increased predisposition → cell damage (2/2 environment or infections) secondary to self-antigens → immune activation of T & B cells → immunity mediator release (cytokines, complement system, autoantibody activation) and ultimately tissue damage

Epidemiology

• U.S.: 20-150/100,000
  • Females: 164 (Caucasians) – 406 (African Americans)/100,000
• Risk factors
  • Female (10x > males): estrogen and prolactin encourage autoimmunity
    • Child-bearing age: 16-55 (65%)
    • (Androgens are protective)
  • Genetics potentially have a role
  • Klinefelter: 14x greater risk
  • Drugs: > 100 triggers
  • Ethnicity: African Americans > Asians & Hispanics > Caucasians

Differential Diagnoses:Rheumatoid Arthritis, Mixed connective tissue disease (SLE + systemic sclerosis + polymyositis), Undifferentiated connective tissue disease, Systemic sclerosis, Sjögren’s, Vasculitis, Behçet syndrome, Dermatomyositis and polymyositis , Adult Still’s disease, Kikuchi disease, Serum sickness, Fibromyalgia, Multiple sclerosis, Infections, Malignancies, and Thrombotic thrombocytopenic purpura.

Presentation/ Clinical Manifestations

• Symptoms
  • Constitutional (90%): commonly initial presentation (fatigue, fever, weight loss)
  • Photosensitivity* (90%): abnormal skin reaction that lasts weeks-months
    • MC: malar rash or discoid lesion
  • Brittle, broken hair
  • MSK Issues (80-90%): polyarthritis/arthralgias   (typically small joints and symmetrical)
    • This is an early symptom
  • Neuro Issues: MC → Intractable Headaches (50%)
    • Also: delirium, psychosis, seizures, cognitive dysfunction
  • Pleuritis (MC pulm manifestation)
  • Raynaud Phenomenon*
  • Joint pain/swelling*
  • Pericarditis/serositis symptoms*
  • Inquiry of drug reactions* (see table at end for a comprehensive list)

• Physical Exam findings
  • Mucocutaneous lesions (80%): Acute/Subacute/Chronic cutaneous lupus erythematosus (A/S/CCLE)  malar (butterfly) rash/photosensitive, widespread rash/ MC form: Discoid lupus erythematosus (DLE) ; respectively
    • Malar: cheeks/bridge of nose: erythematous, raised, and pruritic
  • Oral/Nasal ulcers*: typically painless
  • Rheumatoid nodules
  • Anemia: 50%
  • CV: Pericarditis + exudative effusions(MC cardio manifestation)
    • Also affects valves, pericardium/myocardium, conductive system, coronary arteries
  • GI issues (dysmotility → ascites → pancreatitis)
  • Ocular issues (keratoconjunctivitis sicca (dry eye syndrome) → optic neuritis)
  • Renal involvement (50%)
  • Hair loss*: “patchy or frontal/peripheral”

*Up to date notes most commonly observed findings when suspecting SLE

Diagnosis

• Labs:
  • CBC with diff
  • Serum, creatinine
  • UA
  • ESR/CRP levels
  • urine protein:creatinine ratio
  • Antinuclear antibodies (ANA): diagnostic hallmark; (+) in 97%; seen in other disorders
    • Gold standard: Immunofluorescence assay
    • If Positive, proceed with the below testing:
  • Anti-Ds-DNA antibodies (95% Sp): 60-70%
    • Gold standard: Farr radioimmunoassay test
  • Anti-Smith antibodies (99% Sp): <30%
  • Antiphospholipid antibodies
  • Complements C3 and C4: ↓; indicative of depletion and potential estimates of severity
• Imaging and biopsy: dependent on involved organs and clinical presentation

• Definitive Diagnosis: “…no single clinical feature or lab abnormality can confirm a diagnosis of SLE. SLE is diagnosed based on the constellation of signs, symptoms and appropriate laboratory workup.”

  • Up to date recommends referral to experienced rheumatologist:
    • Exclude other diagnoses + fulfills the 1997 American College of Rheumatology (ACR) criteria OR
    • the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria
  • Probable dx: 2-3 ACR or SLICC criteria + 1 of the following:
    • Optic neuritis, aseptic meningitis
    • Glomerular hematuria
    • Pneumonitis, pulmonary hemorrhage, or pulmonary hypertension, interstitial lung disease
    • Myocarditis, verrucous endocarditis (Libman-Sacks endocarditis)
    • Abdominal vasculitis
    • Raynaud phenomenon
    • Elevated acute phase reactants (eg, ESR and CRP)

Treatment

• Goals: Improve morbidity, decrease mortality, reduce the risk of organ damage, ↑ QOL, patient education
• Individualized and dependent on manifestations
• Pharmacologic:  hydroxychloroquine or chloroquine
  • Mild: +/- NSAIDs ; +/- short-term glucocorticoids (low dose; ie: prednisone <5mg qd)
  • Mod (constitutional, cutaneous, MSK, or hematologic): + short-term prednisone (5-15 mg)
  • Severe: immunosuppressive therapy → systemic glucocorticoids (high-doses): 1-2 mg/kg/day of prednisone +/- other immunosuppressive agents
• Monitoring: CBC, ESR, CRP, spot urine protein and creatinine, serum creatinine, eGFR, anti-double-stranded deoxyribonucleic acid (dsDNA), and C3 & C4.

Complications

• Increased risk for: seizures, strokes, fibromyalgia (20%), aseptic meningitis, demyelinating syndrome, movement disorders, cranial/peripheral neuropathies, depression/anxiety/psychosis, lupus nephritis (proteinuria Sx’s: HTN, hematuria, proteinuria, LE edema, ↑Creatinine), CAD (2/2 coronary vasculitis or atherosclerosis), spontaneous abortions (more so with AP antibodies), and non-Hodgkin lymphoma

Prognosis

• Poor if any of the following present: renal disease, HTN, male sex, extremes of age at presentation, low SES, black race, and/or Antiphospholipid antibodies.
• 2-5x higher mortality

Patient Education

• Triggers for flare-ups: Estrogen (OCPs and hormone replacement therapy), UV light, sulfa-based drugs, smoking (dose-dependent), silica exposure, viral infections, vitamin D deficiency, alfalfa sprouts, and canavanine containing foods.
  • Sun protection
  • Diet and exercise
  • Smoking cessation
  • Immunizations (see chart at end)
  • Avoiding certain meds
  • Pregnancy/contraception counseling

References:

1. https://emedicine.medscape.com/article/332244-overview
2. https://www.ncbi.nlm.nih.gov/books/NBK535405/
3. https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-systemic-lupus-erythematosus-in-adults
4. https://www.uptodate.com/contents/overview-of-the-management-and-prognosis-of-systemic-lupus-erythematosus-in-adults?topicRef=4668&source=see_link
5. https://www.uptodate.com/contents/epidemiology-and-pathogenesis-of-systemic-lupus-erythematosus?topicRef=4668&source=see_link
6. Vignette

Photo by Mustafa Omar on Unsplash