Pustular rash

A pustule is a visible collection of neutrophils within or beneath the epidermis. The key clinical point is whether it is infective or sterile, because the treatment differs completely and because fever with widespread pustules may be an emergency.

Follicular versus nonfollicular. Follicular pustules are centred on a hair follicle, with a hair shaft at the centre (folliculitis, acne). Nonfollicular pustules are not (pustular psoriasis, acute generalised exanthematous pustulosis, candidiasis, impetigo).

Infective versus sterile. Infective pustules contain organisms (Staphylococcus aureus, Pseudomonas, Candida, Malassezia, dermatophytes). Sterile pustules are caused by neutrophilic inflammation driven by interleukin 36, interleukin 17 and related signalling.

Distribution. Localised (face, trunk, folds, palms and soles) or generalised.

Temporal pattern. Acute generalised pustules over days with fever suggest a drug reaction or generalised pustular psoriasis. Relapsing crops on the palms and soles suggest palmoplantar pustulosis.

History

• Onset tempo, fever, systemic symptoms, itch or pain.
• Drugs in the preceding 1 to 3 days (acute generalised exanthematous pustulosis is typically within 48 hours of aminopenicillins, macrolides, quinolones and other antibiotics, as well as calcium channel blockers and hydroxychloroquine), and drugs causing acneiform eruptions: corticosteroids, lithium, phenytoin, isoniazid, anabolic steroids, and EGFR inhibitors.
• Previous psoriasis, recent withdrawal of systemic or potent topical corticosteroids, infection or pregnancy.
• Hot tub or swimming pool exposure 8 to 48 hours before onset (Pseudomonas), shaving, waxing, occlusion, greasy oils.
• Sexual history and joint symptoms (disseminated gonococcal infection).
• Diabetes, HIV, neutropenia, chemotherapy or other immunosuppression.
• Pregnancy and gestation (generalised pustular psoriasis of pregnancy).

Examination

• Vital signs and perfusion.
• Distribution (face, scalp, trunk, folds, palms and soles, genitals), follicular or nonfollicular, background erythema, satellite lesions, erosions.
• Nails: pitting, onycholysis, subungual pustules.
• Joints (psoriatic arthritis), eyes, mucosa, lymph nodes.
• Necrotic black eschar in a sepsis patient (ecthyma gangrenosum).
• Bedside tests: swab from an unroofed pustule for Gram stain; potassium hydroxide microscopy.

Red flags

• Fever, widespread sterile pustules on erythema with hypotension or tachycardia (generalised pustular psoriasis, acute generalised exanthematous pustulosis).
• Pustules or haemorrhagic necrotic lesions in a septic or neutropenic patient (ecthyma gangrenosum, gonococcaemia, meningococcaemia).
• Pustules in pregnancy (generalised pustular psoriasis of pregnancy risks placental insufficiency).
• Pustules involving the eye or nasal tip with zoster.
• Neonates and infants with widespread pustules.
• Painful ulcers developing from pustules (pyoderma gangrenosum).
• Eosinophilic folliculitis with intense itch in HIV.

Special groups

• Neonates: erythema toxicum neonatorum, transient neonatal pustular melanosis and neonatal acne are benign; bacterial infection and herpes need exclusion.
• Pregnancy: avoid oral azoles, doxycycline, ciprofloxacin and acitretin.
• Region specific: tungiasis with secondary infection, HIV associated eosinophilic folliculitis, and staphylococcal infection with overcrowding.

Infective

• Staphylococcal folliculitis, furunculosis and sycosis barbae.
• Impetigo and ecthyma.
• Pseudomonas (hot tub) folliculitis.
• Gram negative folliculitis (prolonged antibiotics for acne).
• Malassezia folliculitis.
• Candidiasis of the skin.
• Tinea barbae, kerion and Majocchi granuloma.
• Demodex folliculitis.
• Scabies (pustules on palms and soles in infants).
• Secondary syphilis, pustular form.
• Disseminated gonococcal infection.
• Meningococcaemia and ecthyma gangrenosum.
• Mpox, varicella and herpes simplex (pustular phase).
• Tungiasis with secondary infection.
• Miliaria pustulosa.

Inflammatory and sterile

• Acne vulgaris, acne conglobata and acne fulminans.
• Papulopustular rosacea and perioral dermatitis.
• Generalised pustular psoriasis (von Zumbusch).
• Palmoplantar pustulosis.
• Acrodermatitis continua of Hallopeau.
• Acute generalised exanthematous pustulosis.
• Subcorneal pustular dermatosis (Sneddon-Wilkinson).
• IgA pemphigus.
• Pyoderma gangrenosum, pustular onset.
• Behcet disease.
• Sweet syndrome, pustular variant.
• SAPHO syndrome.
• Hidradenitis suppurativa.
• Folliculitis decalvans.
• Pseudofolliculitis barbae.

Drug and immune related

• Steroid acne and other acneiform drug eruptions (lithium, phenytoin, isoniazid, EGFR inhibitors, anabolic steroids).
• Eosinophilic folliculitis (HIV associated).
• Pustular drug eruptions.

Neonatal

• Erythema toxicum neonatorum.
• Transient neonatal pustular melanosis.
• Neonatal acne.

Step 1. Exclude sepsis and widespread skin failure. Check vital signs, cultures and bloods in any febrile patient with widespread pustules.

Step 2. Classify. Follicular or not, localised or generalised, and acute or relapsing. Match to the drug and exposure history.

Step 3. First line tests

• Pustule swab: Gram stain, bacterial culture (request MRSA), potassium hydroxide microscopy and fungal culture, herpes simplex, varicella zoster and mpox PCR if indicated. A culture may show colonisers; correlate with Gram stain.
• Full blood count: neutrophilia over 7 x 10^9/L supports acute generalised exanthematous pustulosis and generalised pustular psoriasis; eosinophilia may occur in drug reactions.
• CRP, ESR, urea and creatinine, liver tests, calcium and albumin (hypocalcaemia and hypoalbuminaemia occur in generalised pustular psoriasis), glucose.
• Blood cultures if febrile.
• HIV test; syphilis serology; urine nucleic acid test and genital swabs for gonorrhoea and chlamydia.

Step 4. Targeted tests

• Skin punch biopsy (4 mm). Psoriasis shows spongiform subcorneal pustules with Kogoj features and acanthosis. Acute generalised exanthematous pustulosis shows subcorneal or intraepidermal spongiform pustules, papillary dermal oedema, eosinophils and focal keratinocyte necrosis. Direct immunofluorescence for IgA pemphigus.
• Patch testing for the suspected drug after the eruption has resolved (6 weeks or more), at specialist centres.
• IL36RN gene testing in recurrent generalised pustular psoriasis in selected cases.
• Acute generalised exanthematous pustulosis diagnosis: acute pustular eruption, fever over 38 C, neutrophils over 7 x 10^9/L, typical biopsy, short interval from drug to rash (usually under 48 hours), and resolution within 15 days.

Limits. Early lesions may be sterile before secondary infection. Biopsy cannot always separate pustular psoriasis from the drug reaction, and history decides.

Immediate. Stabilise unwell patients: intravenous fluids, oxygen, analgesia and temperature control. Admit patients with fever and widespread pustules. Stop the suspected drug.

General measures. Warm saline compresses, gentle cleansing with soap substitutes, avoid occlusion, avoid picking, avoid shaving over active lesions, and remove the trigger.

Infective

• Staphylococcal folliculitis or impetigo: chlorhexidine 4% wash daily and mupirocin 2% ointment three times daily for 5 days (or fusidic acid 2% three times daily for 5 to 7 days; avoid prolonged use because of resistance). Extensive or recurrent disease: flucloxacillin 500 mg orally four times daily for 7 days (children 25 to 50 mg/kg daily in 4 doses). Penicillin allergy: clarithromycin 250 to 500 mg orally twice daily for 7 days, or doxycycline 100 mg orally twice daily for 7 days in adults.
• MRSA: doxycycline 100 mg orally twice daily for 5 to 10 days, or co-trimoxazole 960 mg orally twice daily for 5 to 10 days (halve the dose if creatinine clearance is 15 to 30 mL/min; avoid under 15 mL/min; monitor potassium and creatinine; avoid in G6PD deficiency and late pregnancy; interacts with warfarin and ACE inhibitors).
• Recurrent staphylococcal folliculitis: decolonise with mupirocin 2% to the nostrils twice daily for 5 days and chlorhexidine 4% body wash daily for 5 to 7 days; treat household contacts if recurrent.
• Pseudomonas hot tub folliculitis: self limiting over 7 to 14 days. Severe or immunocompromised: ciprofloxacin 500 mg orally twice daily for 7 days (reduce for creatinine clearance under 30 mL/min; avoid in pregnancy and under 18 years; tendon and QT warnings).
• Malassezia folliculitis: ketoconazole 2% shampoo to the affected skin daily for 5 to 7 days, or itraconazole 200 mg orally once daily with food for 7 days (monitor liver tests; avoid in heart failure; many CYP3A4 interactions; not in pregnancy).
• Cutaneous candidiasis: clotrimazole 1% cream two to three times daily for 2 to 4 weeks, with drying of folds.
• Scabies: permethrin 5% cream, whole body from the neck down, left for 8 to 12 hours and repeated after 7 days, with simultaneous treatment of contacts; ivermectin 200 micrograms/kg orally with food, repeated after 7 days (not for children under 15 kg or pregnancy).
• Secondary syphilis: benzathine benzylpenicillin 2.4 million units intramuscularly once.
• Disseminated gonococcal infection: ceftriaxone 1 g intravenously or intramuscularly once daily for 7 days, plus azithromycin 1 g orally once.
• Ecthyma gangrenosum or sepsis with pustules: admit and give piperacillin with tazobactam 4.5 g intravenously every 6 hours (or cefepime 2 g every 8 hours) with an aminoglycoside initially; adjust for kidney function; biopsy and culture.
• HIV associated eosinophilic folliculitis: start antiretroviral therapy; topical corticosteroid (mometasone furoate 0.1% once daily) and cetirizine 10 mg orally once daily.

Acne and rosacea. Inflammatory acne: benzoyl peroxide 2.5 to 5% once daily plus adapalene 0.1% at night; moderate disease adds doxycycline 100 mg orally once daily for 8 to 12 weeks (not in pregnancy or under 12 years). Isotretinoin is for specialists (teratogenic, pregnancy prevention required).

Sterile pustulosis

• Acute generalised exanthematous pustulosis: withdraw the drug; supportive care; emollients; clobetasol propionate 0.05% once daily for 5 to 7 days. Most cases settle in 1 to 2 weeks with desquamation. Systemic corticosteroids have unclear benefit; prednisolone 0.5 to 1 mg/kg orally daily for a short course is used in severe cases. Record the drug allergy.
• Generalised pustular psoriasis: admit if unwell. Specialist options: acitretin 25 to 50 mg orally daily (teratogenic; contraception for 3 years after stopping; monitor liver tests and lipids), ciclosporin 2.5 to 5 mg/kg orally daily in 2 doses (monitor blood pressure and creatinine; stop if creatinine rises over 30% from baseline), methotrexate 7.5 to 25 mg orally weekly with folic acid 5 mg weekly on a different day (monitor full blood count, liver tests, creatinine), infliximab 5 mg/kg intravenously, or spesolimab 900 mg intravenously as a single dose with a repeat dose after 1 week if the flare persists. Avoid abrupt withdrawal of systemic corticosteroids. In pregnancy: prednisolone, ciclosporin or certolizumab, with obstetric surveillance.
• Palmoplantar pustulosis: smoking cessation; potent topical corticosteroid under occlusion; phototherapy; acitretin for refractory disease.
• Subcorneal pustular dermatosis: dapsone 50 to 100 mg orally daily after G6PD testing.

Monitoring. Temperature, haemodynamics, fluid balance, skin involvement, white cell count, calcium, albumin, creatinine and liver tests in generalised disease. Drug level and toxicity monitoring for each specialist agent.

Referral and escalation. Urgent dermatology for generalised pustular eruptions and suspected pustular psoriasis. Obstetric and dermatology review within 24 hours for generalised pustules in pregnancy. Infectious diseases for sepsis, disseminated gonococcal infection and ecthyma gangrenosum. Allergy review for drug eruptions.

Admission criteria. Fever with widespread pustules, haemodynamic instability, suspected sepsis, neutropenia, pregnancy with generalised pustules, hypocalcaemia, or inability to manage at home.

Discharge and follow up. Review at 1 to 2 weeks. Safety net advice: return for fever, spreading redness, new widespread pustules, joint swelling or pain, reduced foetal movements, or eye involvement.