11.3 Multisystem & Rheumatologic Diseases

Multisystem & Rheumatologic Diseases: Diagnosis, Treatment, & Critical Care

Systemic Lupus Erythematosus (SLE)

Systemic Lupus Erythematosus is a multi-system autoimmune disease characterized by immune complex deposition and autoantibody production. The diagnostic framework utilizes the EULAR/ACR classification criteria, requiring an entry criterion of an antinuclear antibody (ANA) titer of at least 1:80, followed by additive clinical and immunologic criteria.

• Autoantibody Specificity:
  • ANA: Highly sensitive (> 95%) but poorly specific; a negative test makes SLE highly unlikely.
  • Anti-double-stranded DNA (anti-dsDNA) and Anti-Smith (anti-Sm): Highly specific for SLE. Anti-dsDNA titers correlate with disease activity, particularly lupus nephritis, and track with falling complement levels (C3, C4).
  • Anti-histone: Strongly associated with drug-induced lupus (induced by procainamide, hydralazine, isoniazid, minocycline). Spares the kidneys and central nervous system, and resolves upon discontinuation of the offending agent.
  • Anti-Ro/SSA and Anti-La/SSB: Associated with neonatal lupus (which can cause congenital heart block) and Sjögren's syndrome.
• Lupus Nephritis: A major source of morbidity. Class III (focal) and Class IV (diffuse proliferative) nephritis require aggressive therapy. Renal biopsy is mandatory to guide treatment. Management involves induction therapy with mycophenolate mofetil or cyclophosphamide combined with high-dose corticosteroids, followed by maintenance therapy with mycophenolate or azathioprine.
• Pharmacotherapy: All SLE patients should receive hydroxychloroquine unless contraindicated, as it reduces flares, improves survival, and decreases thrombotic events. Retinal toxicity is a rare but serious side effect requiring annual ophthalmologic screening starting after 5 years of use. Glucocorticoids are used at the lowest effective dose for acute flares.

Rheumatoid Arthritis (RA)

Rheumatoid Arthritis is a chronic, symmetric, inflammatory polyarthritis that characteristically affects the small joints of the hands and feet (metacarpophalangeal and proximal interphalangeal joints), sparing the distal interphalangeal (DIP) joints. It is characterized by morning stiffness lasting more than 1 hour that improves with activity.

• Serology: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are highly specific (> 95%) and predict aggressive, erosive disease. Rheumatoid Factor (RF) is sensitive but less specific. Inflammatory markers (ESR, CRP) are typically elevated.
• Management: Methotrexate is the first-line disease-modifying antirheumatic drug (DMARD) for moderate-to-severe RA. Prior to starting methotrexate, clinicians must check baseline CBC and liver function tests, and counsel patients on avoiding alcohol, the need for daily folic acid supplementation, and strict contraception (highly teratogenic). Alternative DMARDs include sulfasalazine, leflunomide, and hydroxychloroquine.
• Biologic Escalation: For patients who fail non-biologic DMARDs, biologic DMARDs (e.g., TNF-alpha inhibitors like adalimumab, etanercept, infliximab) are initiated. Latent tuberculosis screening with an interferon-gamma release assay (IGRA) or tuberculin skin test, and screening for chronic hepatitis B and C, are mandatory before initiating any biologic therapy to prevent life-threatening reactivation.

Systemic Vasculitides

Vasculitides are inflammatory diseases of blood vessels, classified by the size of the dominant vessels involved.

Large-Vessel Vasculitis

• Giant Cell (Temporal) Arteritis: Affects patients > 50 years, presenting with unilateral headache, jaw claudication, temple tenderness, and visual disturbances (e.g., amaurosis fugax). ESR is markedly elevated (often > 100 mm/hr). Associated with polymyalgia rheumatica (proximal shoulder and pelvic girdle pain/stiffness). If suspected, high-dose systemic glucocorticoids (oral prednisone or IV methylprednisolone if visual loss is active) must be initiated immediately to prevent permanent blindness; temporal artery biopsy is performed subsequently to confirm the diagnosis.
• Takayasu Arteritis: Granulomatous vasculitis of the aorta and its major branches in young Asian females (< 40 years). Presents with constitutional symptoms, upper extremity claudication, discrepant blood pressures between arms (> 10 mmHg), and diminished pulses ("pulseless disease").

Medium-Vessel Vasculitis

• Polyarteritis Nodosa (PAN): Systemic necrotizing vasculitis that classically spares the pulmonary vessels. Strongly associated with active Hepatitis B virus infection. Presents with livedo reticularis, renal insufficiency, abdominal pain (due to mesenteric ischemia), and mononeuritis multiplex (e.g., foot drop). Angiography shows microaneurysms ("string of pearls") in visceral vessels.
• Kawasaki Disease: An acute vasculitis of childhood. Diagnosis requires a fever lasting 5 or more days plus at least 4 of 5 classic clinical criteria: (1) bilateral non-exudative conjunctivitis; (2) oral mucosal changes (strawberry tongue, dry/fissured lips); (3) polymorphous rash; (4) extremity changes (erythema/edema of hands/feet, desquamation); (5) unilateral cervical lymphadenopathy (> 1.5 cm). The primary complication is coronary artery aneurysms. Treatment consists of intravenous immunoglobulin (IVIG) and high-dose aspirin (which is later tapered to low-dose once the fever resolves).

Small-Vessel Vasculitis

• Granulomatosis with Polyangiitis (GPA): Associated with c-ANCA (PR3-ANCA). Triad of upper respiratory tract involvement (chronic sinusitis, saddle nose deformity), lower respiratory tract (hemoptysis, nodules), and necrotizing glomerulonephritis.
• Microscopic Polyangiitis (MPA): Associated with p-ANCA (MPO-ANCA). Similar to GPA with lung and kidney involvement, but lacks granulomatous inflammation and upper respiratory symptoms.
• Eosinophilic Granulomatosis with Polyangiitis (EGPA): Associated with p-ANCA (MPO-ANCA). Characterized by severe asthma, allergic rhinitis, and peripheral eosinophilia.
• Henoch-Schönlein Purpura (IgA Vasculitis): The most common pediatric vasculitis. Tetrad of: (1) palpable purpura on the lower extremities and buttocks without thrombocytopenia; (2) arthritis/arthralgias; (3) abdominal pain (with risk of intussusception); (4) renal disease (identical to IgA nephropathy). Management is supportive with hydration and pain control; systemic corticosteroids are reserved for severe abdominal pain or significant renal involvement.

SIRS and Sepsis Resuscitation Guidelines

Early recognition of sepsis and aggressive resuscitation are critical in reducing mortality.

• SIRS Criteria: Defined by two or more of the following: (1) Temperature > 38.5°C or < 36.0°C; (2) Heart rate > 90/min (or above normal for age in pediatrics); (3) Respiratory rate > 20/min (or above normal for age); (4) WBC count > 12,000/mm³, < 4,000/mm³, or > 10% bands.
• Resuscitation Protocols:
  • Adults (Surviving Sepsis Campaign): Initiate 30 mL/kg of IV crystalloid fluid within the first 3 hours for patients with sepsis-induced hypoperfusion or lactate ≥ 4.0 mmol/L. Obtain blood cultures prior to administering broad-spectrum empiric antibiotics (within 1 hour of presentation).
  • Pediatric Sepsis Resuscitation: Differs from adults in the volume and frequency of fluid administration. Resuscitate with 20 mL/kg boluses of isotonic crystalloid over 5 to 10 minutes. Fluid administration should be titrated to clinical endpoints (mental status, perfusion, capillary refill time < 2 seconds, and urine output) and repeated up to 60 mL/kg or more, monitoring closely for signs of fluid overload (hepatomegaly, rales, or gallop).
  • Vasoactive Support: For fluid-refractory shock, vasoactive agents must be started. In adults, norepinephrine is the first-line vasopressor. In pediatric patients, first-line vasoactive support is tailored to clinical presentation: epinephrine is preferred for cold shock (poor perfusion, delayed capillary refill, low blood pressure), while norepinephrine is preferred for warm shock (bounding pulses, flash capillary refill).