9.5 Dermatologic and Immunologic Conditions in the ICU

Dermatologic and Immunologic Conditions in the ICU

Severe Cutaneous Adverse Reactions

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)

SJS/TEN are mucocutaneous drug reactions with <10% and >30% body surface area (BSA) epidermal detachment, respectively. Mortality approaches 30% in TEN.

Common culprits: allopurinol, anticonvulsants (lamotrigine, carbamazepine, phenytoin), sulfonamide antibiotics, NSAIDs (oxicam class), nevirapine.

Management:

1. Immediate withdrawal of all suspect drugs (highest yield intervention).
2. Burn-unit transfer for TEN >10% BSA; wound care, fluid resuscitation using burn formulas (Parkland), electrolyte monitoring.
3. Nutritional support (enteral preferred; high protein).
4. IVIG 2-3 g/kg over 3-4 days historically used; meta-analyses conflicting; not standard of care.
5. Corticosteroids controversial; brief pulse methylprednisolone may be used early in SJS overlap; avoid in extensive TEN due to infection/sepsis risk.
6. Cyclosporine 3-5 mg/kg/day for 7-10 days shows some mortality benefit in small studies.
7. Antibiotic prophylaxis only for documented infection; semi-occlusive dressings with silver sulfadiazine (avoid if sulfonamide allergy).

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Onset 2-8 weeks after culprit drug (aromatic anticonvulsants, allopurinol, sulfonamides, minocycline). Features: rash, fever, lymphadenopathy, eosinophilia, hepatitis, nephritis.

Treatment: Stop culprit; prednisone 1 mg/kg/day taper over weeks-months; topical corticosteroids. Reactivation of human herpesvirus-6, CMV, EBV contributes; monitor.

Erythema Multiforme Major

Herpes simplex or Mycoplasma-triggered; target lesions; mucosal involvement possible. Treatment: HSV prophylaxis (acyclovir 400 mg BID), supportive care.

Drug-Induced Angioedema

Histamine-mediated (allergic): urticaria + angioedema; responds to epinephrine, H1/H2 blockers, corticosteroids.

Bradykinin-mediated (ACE inhibitor, hereditary/acquired): NO urticaria; does NOT respond to epinephrine or antihistamines.

• ACE inhibitor angioedema: Stop ACE inhibitor permanently. For severe airway involvement: icatibant 30 mg SC (bradykinin B2 antagonist), C1-esterase inhibitor concentrate (Berinert 20 IU/kg), fresh frozen plasma 2-4 units, or ecallantide 30 mg SC (kallikrein inhibitor).
• Hereditary angioedema: C1-INH concentrate, icatibant; long-term prophylaxis with lanadelumab (300 mg SC q2w) or berotralstat (150 mg PO daily).

Immunology in the ICU

Immunosuppressed Patient Empiric Coverage

Immunoparalysis and Prolonged Critical Illness

After ~7-10 days of critical illness, monocyte HLA-DR expression drops, marking immunoparalysis. Patients develop secondary infections (fungemia, VAP) and reactivation of latent viruses (CMV, HSV). Strategies:

• Monitor trends; consider immune monitoring in transplant recipients.
• Avoid prolonged broad-spectrum antibiotics; de-escalate per culture data.
• Prophylaxis: acyclovir/valganciclovir per protocol; PJP prophylaxis if prolonged steroids.
• Reassess immunosuppressive regimen with transplant team; reduce maintenance doses when safe.

Hypersensitivity Reactions in the ICU

Anaphylaxis: IM epinephrine 0.3-0.5 mg (1:1000) q5-15 min; supine with legs elevated; H1/H2 blockers and corticosteroids adjunctive; fluid resuscitation; bronchodilators. Refractory anaphylaxis may require an IV epinephrine infusion (0.05-0.5 mcg/kg/min) and glucagon (1-5 mg IV over 5 min then 5-20 mcg/min infusion) in beta-blocked patients. Trypsase peaks 1-2 hours; serial levels confirm mast-cell degranulation.

Beta-lactam allergy: Cross-reactivity between penicillin and cephalosporin/carbapenem is low (<2% for third/fourth gen cephalosporins, <1% carbapenems). Use skin testing, graded challenge, or alternative agent per severity.

Vancomycin infusion reaction (red man syndrome): rate-dependent histamine release; slow infusion, antihistamines; not a true allergy (can resume with rate adjustment).

Immune Reconstitution Inflammatory Syndrome (IRIS)

IRIS occurs within days to weeks of starting antiretroviral therapy (HIV), stopping immunosuppression after transplant, or antimicrobial treatment of opportunistic infection. The recovering immune system mounts an exaggerated inflammatory response against latent or subclinical infection (TB, MAC, CMV, cryptococcus, PJP) or self-antigens (sarcoidosis, autoimmune thyroiditis). Presentation: fever, lymphadenopathy, worsening pulmonary infiltrates, meningitis. Treatment is mostly supportive; short-course corticosteroids (prednisone 1-2 mg/kg/day taper) are used for severe inflammatory disease; do not stop ART once started.

Biologic and Targeted Therapy Complications

The ICU increasingly admits patients on biologics (TNF inhibitors, rituximab, anti-IL-6, JAK inhibitors) for autoimmune disease or malignancy. Complications include:

• Cytokine release syndrome (CRS): fever, hypotension, hypoxia after CAR-T or blinatumomab; grade by ASTCT criteria; treat with tocilizumab (anti-IL-6) 8 mg/kg IV for grade ≥2, plus corticosteroids for grade ≥3.
• Immune checkpoint inhibitor toxicity: ipilimumab, nivolumab, pembrolizumab cause immune-related adverse events (irAEs): pneumonitis, colitis, hepatitis, hypophysitis, myocarditis. First-line is high-dose corticosteroids (methylprednisolone 1-2 mg/kg/day); infliximab or mycophenolate for refractory colitis/hepatitis.
• TNF inhibitor infection risk: reactivation of latent TB, HBV, histoplasmosis; screen before initiation.
• Rituximab: HBV reactivation risk; prolonged B-cell depletion; PJP prophylaxis if combined with steroids.

Clinical Scenario

A 64-year-old male on lisinopril presents with acute tongue and lip swelling over 6 hours, no urticaria. He has used no new medications. Airways threatened. What pharmacotherapy is indicated?

Answer: This is bradykinin-mediated ACE inhibitor angioedema. Discontinue lisinopril immediately. Administer icatibant 30 mg SC or C1-esterase inhibitor concentrate (Berinert 20 IU/kg IV); alternative is fresh frozen plasma 2 units IV. Conventional epinephrine/antihistamines/corticosteroids are ineffective. Prepare for fiberoptic intubation or surgical airway if progression continues.