What is the treatment for fever with pustules over the body?

Treatment of Fever with Pustules Over the Body

The immediate priority is to identify whether this represents drug-induced acute generalized exanthematous pustulosis (AGEP), generalized pustular psoriasis (GPP), or infection in an immunocompromised host, as each requires fundamentally different management—discontinue any recently started medications immediately, obtain bacterial cultures if infection is suspected, and initiate supportive care while pursuing definitive diagnosis. 1, 2, 3

Critical Initial Assessment and Differential Diagnosis

The combination of fever and widespread pustules demands urgent evaluation for three distinct entities:

Drug-Induced AGEP (Most Common)

• Presents with sudden onset of hundreds of sterile, nonfollicular pustules on erythematous, edematous skin, accompanied by fever >38°C and neutrophilia 1, 2, 4
• Typically occurs 7-10 days after antibiotic exposure (especially beta-lactams, clindamycin, or piperacillin/tazobactam) 1, 2
• Pustules often coalesce into large bullae, particularly in intertriginous areas and body flexures 1, 4
• Immediate withdrawal of the causative agent is the mainstay of treatment—lesions heal spontaneously within 2 weeks after discontinuation 3
• Supportive care only; no specific antimicrobial therapy needed as pustules are sterile 3

Generalized Pustular Psoriasis

• Characterized by diffuse erythema, swelling of extremities, and multiple sterile pustules accompanied by high fever and general malaise 5
• For severe GPP with extensive body surface area involvement, infliximab 5 mg/kg demonstrates rapid efficacy and is the preferred biologic 6, 7
• Systemic corticosteroids (prednisone 0.5-1 mg/kg for 7 days) can be used as bridge therapy, though they risk disease flare upon discontinuation 8, 6
• Critical pitfall: Never use systemic corticosteroids as primary long-term therapy—they precipitate severe flares and can trigger erythrodermic transformation 6, 7
• Acitretin 0.1-1 mg/kg/day is effective for pustular variants but requires mandatory contraception counseling (contraindicated in pregnancy and 2 years post-treatment in women) 6

Infection in Immunocompromised/Neutropenic Patients

• In cancer patients with fever and neutropenia, hospitalization and empiric vancomycin plus antipseudomonal antibiotics (cefepime, carbapenem, or piperacillin-tazobactam) are required immediately 8
• Pustular lesions may represent ecthyma gangrenosum from Pseudomonas, Candida, Aspergillus, or other opportunistic pathogens 8
• Obtain bacterial, viral, and fungal cultures before initiating therapy, but do not delay treatment 8
• When infection is suspected (painful lesions, pustules on arms/legs/trunk, yellow crusts, discharge), antibiotics must be administered for at least 14 days based on sensitivities 8

Specific Treatment Algorithms

For Drug-Induced AGEP

1. Discontinue all recently started medications immediately 3
2. Provide supportive care with topical emollients and antipyretics 3
3. No antibiotics needed—pustules are sterile 3
4. Monitor for spontaneous resolution within 2 weeks 3

For Suspected GPP (Non-Drug-Related)

1. If covering >30% body surface area with systemic symptoms: Start infliximab 5 mg/kg IV 6
2. Consider short-course prednisone 0.5-1 mg/kg as bridge therapy only 8
3. For maintenance after acute control: Acitretin 0.1-1 mg/kg/day or ustekinumab 90mg 6, 7
4. Avoid TNF antagonists if palmoplantar pustulosis is present—they may exacerbate this specific variant 6

For Neutropenic Fever with Pustules

1. Immediate hospitalization and empiric vancomycin PLUS cefepime (or meropenem or piperacillin-tazobactam) 8
2. Obtain blood cultures and biopsy/aspiration of pustules for bacterial, fungal, and viral studies 8
3. If no response after 4-7 days, add antifungal coverage (liposomal amphotericin B 5-10 mg/kg/day or isavuconazole) 8
4. Continue antibiotics for at least 14 days based on culture sensitivities 8

Critical Pitfalls to Avoid

• Never assume pustules are infectious without cultures—AGEP and GPP have sterile pustules that worsen with unnecessary antibiotics 1, 3
• Do not use systemic corticosteroids as primary therapy for pustular psoriasis—they cause severe rebound flares 6, 7
• In drug-induced AGEP, continuing the offending medication can lead to life-threatening progression 3
• In neutropenic patients, delaying empiric broad-spectrum antibiotics increases mortality from gram-negative sepsis 8
• Lithium, chloroquine, and beta-blockers may precipitate or worsen pustular psoriasis 6

Monitoring Requirements

• Serial complete blood counts to assess for neutrophilia (AGEP/GPP) versus neutropenia (infection) 1, 2, 8
• Daily temperature monitoring and assessment of pustule progression 1, 5
• For patients started on systemic therapy: baseline and ongoing liver function tests, renal function, and lipid panels 6
• Blood pressure and serum creatinine monitoring if cyclosporine considered 6