What are Stevens-Johnson syndrome and DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) in a 67-year-old male patient with a history of gout (hyperuricemia) taking allopurinol?

Stevens-Johnson Syndrome and DRESS Syndrome

Stevens-Johnson Syndrome (SJS)

Stevens-Johnson syndrome is a severe, life-threatening cutaneous adverse reaction characterized by epidermal detachment involving less than 10% of body surface area, with mucosal involvement and a mortality rate of 5-15%. 1

Key Clinical Features of SJS

• **SJS presents with skin detachment affecting <10% of body surface area**, distinguishing it from toxic epidermal necrolysis (TEN) which involves >30% BSA 1
• The condition typically manifests with erythema multiforme-like lesions that progress to epidermal necrosis and sloughing 2
• Mucosal involvement (oral, ocular, genital) is a hallmark feature that helps differentiate SJS from other drug reactions 1
• In the context of allopurinol use, SJS typically develops within 8 days of drug initiation, though timing can vary 3

Allopurinol-Specific Risk

• Allopurinol is one of the leading causes of SJS, particularly in patients with the HLA-B*58:01 genetic marker 4
• The FDA drug label explicitly warns that skin reactions to allopurinol "can be severe and sometimes fatal," including Stevens-Johnson syndrome 2
• The active metabolite oxypurinol, rather than allopurinol itself, drives the T-cell mediated immune response that causes SJS 4

DRESS Syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms)

DRESS syndrome is a rare, potentially life-threatening drug-induced hypersensitivity reaction characterized by a morbilliform rash involving >30% of body surface area, fever >38°C, eosinophilia >700/μL, lymphadenopathy, and multi-organ involvement that typically occurs 2-6 weeks after drug exposure. 5

Defining Clinical Features of DRESS

• The characteristic latent period of 2-6 weeks after drug initiation distinguishes DRESS from immediate drug reactions and from SJS 5, 6
• The most common cutaneous finding is a confluent morbilliform (maculopapular) rash covering >30% of body surface area 5, 7
• Fever >38°C accompanied by constitutional symptoms including rigors, myalgias, and arthralgias 5, 6
• Eosinophilia is a hallmark feature, defined as >700/μL or >10% of white blood cells 5
• Lymphadenopathy is commonly present 5

Multi-Organ Involvement in DRESS

• Hepatitis is the most common organ manifestation, with ALT >2 times the upper limit of normal 5
• Kidney involvement presents as nephritis with creatinine >1.5 times baseline 5
• Cardiac involvement can include myocarditis and pericarditis 5, 6
• Pulmonary involvement may manifest as pneumonitis 7

Pathophysiology Unique to DRESS

• The syndrome involves reactivation of herpes family viruses (particularly EBV and HHV-6) and activation of lymphocytes, leading to T-cell immune-directed toxicity 5, 7
• Genetic predisposition through HLA-B*58:01 is strongly associated with allopurinol-induced DRESS 5, 6
• The FDA label confirms that DRESS syndrome has been reported with allopurinol use and is "potentially life-threatening and fatal" 2

Critical Distinctions Between SJS and DRESS

DRESS syndrome can be distinguished from SJS by the presence of eosinophilia, longer latency period (2-6 weeks vs. days), and prominent internal organ involvement rather than primarily mucosal and epidermal detachment. 5

Diagnostic Differentiation

• SJS presents with epidermal detachment and mucosal involvement, while DRESS presents with a morbilliform rash without significant epidermal necrosis 5, 7
• DRESS has marked eosinophilia (>700/μL), which is not a feature of SJS 5
• DRESS has a 2-6 week latency period, while SJS typically occurs within days to 2 weeks 5, 3
• DRESS prominently involves internal organs (liver, kidney, heart), while SJS primarily affects skin and mucous membranes 5, 1

Overlapping Presentations

• True overlapping cases of DRESS and SJS are very rare when using strict RegiSCAR diagnostic criteria, though they have been reported with allopurinol 8
• When overlap occurs, it represents a diagnostic and therapeutic challenge requiring careful clinical assessment 8

Management Differences Critical for the 67-Year-Old Patient

Immediate Actions for Both Conditions

• Immediate discontinuation of allopurinol is the first and most crucial step for both SJS and DRESS 5, 7
• Prompt dermatology consultation is mandatory 5, 7

Treatment Divergence

• For DRESS: Systemic corticosteroids are first-line therapy (IV methylprednisolone 1-2 mg/kg/day) with weaning over at least 4 weeks required due to T-cell immune-directed toxicity 5, 7
• For SJS/TEN: Corticosteroid use is debated and probably deleterious in late forms, with management focused on intensive supportive care in burn units 1
• Unlike in SJS, corticosteroids are not contraindicated in DRESS syndrome 5

Severity-Based Care

• Severe SJS cases require admission to burn unit or ICU with specialized wound care 5, 1
• DRESS cases with life-threatening systemic impairment require ICU-level care with multi-organ monitoring 7, 1

Prognosis

• SJS has a mortality rate of 5-15% 1
• DRESS has a mortality rate of approximately 10%, with relapse occurring in approximately 12% of cases 7, 1

Specific Considerations for Allopurinol in This Patient

Risk Factors

• Renal insufficiency increases the risk of allopurinol-induced skin reactions due to decreased clearance of the active metabolite oxypurinol 2, 9
• Concomitant use of thiazide diuretics decreases oxypurinol clearance and increases risk 9
• The HLA-B*58:01 genetic marker strongly predisposes to allopurinol-induced SCAR 5, 4

Critical Pitfall to Avoid

• Treatment with allopurinol should be discontinued immediately if any rash develops, as the FDA label explicitly states that skin reactions "can be severe and sometimes fatal" 2
• Drug challenge with allopurinol is contraindicated except in extreme circumstances 5
• Patch testing or delayed intradermal testing should not be performed until at least 6 months after complete resolution and at least 4 weeks after discontinuing systemic steroids 5

Alternative Therapy

• Febuxostat shows no cross-reactivity with allopurinol in patients who developed allopurinol-SCAR, making it a potential alternative for gout management after recovery 4