Differentiating AGEP from Pustular Psoriasis
AGEP is an acute, self-limiting drug reaction that resolves rapidly within days to weeks after stopping the offending medication, whereas generalized pustular psoriasis (GPP) is a chronic inflammatory disease requiring long-term systemic therapy—the key distinguishing features are timing of onset, drug history, clinical course, and specific histopathologic findings. 1
Clinical Timing and Onset
Rapid onset strongly favors AGEP:
- AGEP typically develops within 24-48 hours after drug exposure, with pustules appearing acutely 2
- GPP develops more gradually, either evolving from chronic plaque psoriasis or presenting acutely but with a slower progression 1
- AGEP resolves spontaneously within 1-2 weeks after drug withdrawal, whereas GPP persists and requires ongoing systemic treatment 1, 3
Drug History
A clear temporal relationship with medication use is the hallmark of AGEP:
- AGEP is predominantly drug-induced, most commonly by beta-lactam antibiotics, followed by other antibiotics, antifungals, NSAIDs, and various other medications 3, 2
- Document all medications started within 48 hours of symptom onset 2
- GPP may be triggered by drug withdrawal (especially systemic corticosteroids) or certain medications like lithium, chloroquine, or beta-blockers, but lacks the acute temporal relationship seen in AGEP 4
Distribution and Morphology
Look for these specific clinical patterns:
- AGEP frequently involves mucosal surfaces (oral and genital erosions), which is uncommon in GPP 5, 6
- AGEP can present with targetoid lesions, purpura, and erythema multiforme-like features—findings not typical of GPP 5
- GPP characteristically shows pustules on an erythematous background with evidence of classic plaque psoriasis elsewhere on the body 1, 4
- Facial edema is more prominent in AGEP 5
Histopathologic Differentiation
Biopsy reveals subtle but consistent differences:
- Favoring AGEP: presence of eosinophils, necrotic keratinocytes, mixed interstitial and mid-dermal perivascular infiltrate, and absence of tortuous or dilated blood vessels 7
- Favoring GPP: prominent epidermal psoriatic changes (especially in chronic GPP), tortuous dilated blood vessels, and absence of eosinophils 7
- Vasculitis may be present in AGEP but is not specific 7, 3
- Both conditions show subcorneal pustules with neutrophilic infiltration, making this feature non-discriminatory 4, 7
Systemic Features
Severity and organ involvement differ:
- AGEP presents with high fever and may involve organs (cholestasis, nephritis, lung, bone marrow involvement) in less than one-third of cases 2
- GPP presents with fever, systemic toxicity, and risk of metabolic complications requiring hospitalization 1
- GPP carries higher mortality risk and requires more aggressive systemic management 1
Personal and Family History
Background psoriasis complicates but doesn't exclude AGEP:
- A personal history of psoriasis occurs more frequently in AGEP patients than expected by population prevalence, but histopathology shows no significant differences from AGEP patients without psoriasis history 7
- Family history of psoriasis or personal history of chronic plaque psoriasis favors GPP but does not rule out AGEP 7
Response to Treatment
Therapeutic response confirms the diagnosis:
- AGEP resolves rapidly (days to weeks) after drug discontinuation, with or without topical/systemic corticosteroids 3, 2
- GPP requires long-term systemic therapy with agents like spesolimab, acitretin, cyclosporine, or biologics 1, 4
- Recurrence with re-challenge of the same drug confirms AGEP 3
Critical Pitfall to Avoid
Never use systemic corticosteroids as primary therapy for suspected GPP, as withdrawal can precipitate severe flares, erythrodermic psoriasis, or fatal deterioration 8. However, systemic corticosteroids are appropriate for AGEP 3, 2. If the diagnosis is uncertain and the patient is severely ill, prioritize drug withdrawal and supportive care while awaiting histopathology confirmation before initiating definitive therapy.