Can DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) syndrome cause septic shock in patients?

Can DRESS Syndrome Cause Septic Shock?

DRESS syndrome does not directly cause septic shock, but it can present with a sepsis-like clinical picture that mimics septic shock, and patients with DRESS are at significantly increased risk of developing true septic shock as a secondary complication due to immunosuppression from the disease itself and from corticosteroid treatment. 1, 2

DRESS as a "Septic Shock Mimicker"

DRESS syndrome has earned the moniker "the great clinical mimicker" because its presentation frequently resembles severe sepsis or septic shock 1, 3:

• Fever >38°C is a hallmark feature, occurring in nearly all cases 4, 5
• Hemodynamic instability can occur, with labile blood pressures documented in severe cases 1
• Multi-organ dysfunction develops in up to 90% of patients, affecting liver, kidneys, lungs, and heart—mimicking the organ failure seen in septic shock 3, 4
• Systemic inflammatory response with constitutional symptoms including rigors, myalgias, and arthralgias closely resembles sepsis 5, 6

The latency period of 2-6 weeks after drug exposure distinguishes DRESS from immediate drug reactions, but this delayed presentation often leads clinicians to initially suspect infection rather than drug hypersensitivity 4, 5, 1.

True Septic Shock as a Complication of DRESS

The critical distinction is that patients with DRESS are highly vulnerable to developing actual septic shock as a secondary complication:

Mechanisms of Infection Risk

• Immunosuppression from DRESS itself: The dysregulated immune response and T-cell dysfunction create susceptibility to opportunistic infections 4
• Corticosteroid therapy: Systemic corticosteroids (methylprednisolone 1-2 mg/kg/day for minimum 4 weeks) are first-line treatment but significantly increase infection risk 4, 6
• Skin barrier disruption: Extensive rash involving >30% body surface area provides portal of entry for pathogens 4, 6

Documented Cases of Secondary Sepsis

• A case report documented a patient with phenytoin-induced DRESS who developed "signs and symptoms of severe sepsis" that was initially treated as infection before DRESS was recognized 1
• Another case described a 10-year-old with DRESS who developed true sepsis, progressing to ARDS and ultimately dying from septic complications 2
• MRSA infections (clavicular osteomyelitis, septic arthritis) have been documented as complications during DRESS treatment with corticosteroids 7

Critical Diagnostic Pitfalls

The most dangerous clinical error is misdiagnosing DRESS as sepsis and continuing the culprit drug while treating with antibiotics:

• 45% of DRESS cases with pulmonary involvement were initially misdiagnosed as pneumonia and treated with empiric antimicrobials 3
• Clinicians should have a "high index of suspicion for DRESS syndrome in patients being treated with aromatic anticonvulsants who develop a sepsis-like syndrome" 1
• All cultures revealing no growth in a patient with apparent sepsis should trigger consideration of DRESS 1

Key Distinguishing Features

When evaluating a patient with suspected sepsis:

• Check eosinophil count: Eosinophilia >700/μL or >10% strongly suggests DRESS rather than infection 4, 5
• Review medication timeline: Onset 2-6 weeks after starting allopurinol, anticonvulsants (phenytoin, carbamazepine, phenobarbital), sulfonamides, or vancomycin 4, 6, 1
• Assess for rash: Morbilliform confluent rash involving >30% BSA is present in DRESS but not typical sepsis 4, 6
• Evaluate liver function: ALT >2× upper limit of normal occurs in DRESS hepatitis 5, 6

Management When Sepsis Cannot Be Excluded

When true infection versus DRESS remains uncertain:

• Immediately discontinue suspected culprit drug—this is the single most important intervention 4, 6
• Obtain blood cultures and urinalysis before starting antibiotics 5
• Initiate broad-spectrum antibiotics if sepsis cannot be ruled out, following Surviving Sepsis Campaign guidelines for empiric coverage 8
• Start systemic corticosteroids (methylprednisolone 1-2 mg/kg/day IV) once DRESS is suspected, as corticosteroids are NOT contraindicated in DRESS unlike in Stevens-Johnson syndrome 6
• Provide hemodynamic support with fluid resuscitation targeting MAP 65-70 mmHg and norepinephrine as first-line vasopressor if shock develops 8

Monitoring for Secondary Infection

Once DRESS is confirmed and corticosteroids initiated:

• Consider antibiotic prophylaxis if prolonged immunosuppression is required 8
• Maintain high vigilance for new fever or clinical deterioration suggesting superimposed infection 7, 2
• Avoid fluid overload which can worsen organ edema and increase intra-abdominal pressure 8

Prognosis and Long-term Considerations

• Mortality risk: DRESS carries significant mortality, particularly when complicated by ARDS (31% of pulmonary DRESS cases) or true sepsis 2, 3
• Relapse occurs in 12% of cases, particularly with premature steroid taper (<4 weeks) 4, 6
• Long-term sequelae: Autoimmune disorders and organ failure can develop as chronic complications 9