Pustulose acute generalized exanthematic L27.0

MacMillian, 1973; Tan, 1974; Beylot, 1980

Acute, generalized, often febrile, nonfollicular, sterile, pustular exanthema occurring in association with infections and/or drug use, always accompanied by marked leukocytosis and neutrophilia, and with a tendency to heal spontaneously.

The incidences are given as 0.1-0.5/100,000 inhabitants/year.

Women seem to be affected slightly more often than men.

• Occurrence after viral infections (especially Coxsackie virus B4), possibly in combination with drugs.
• Occurring after medication in > 90% of cases. Triggers described include:
  • Common:
    • Antibiotics (ampicillin, amoxicillin, gyrase inhibitors, pristinamycin).
    • Antimalarials
    • Antimycotics such asterbinafinein particular
    • (hydroxy-)chloroquine
    • Calcium channel blockers (diltiazem)
    • Sulfonamides
  • Rare:
    • Allopurinol
    • Carbamazepine
    • Cephalosporins
    • Doxorubicin
    • Glucocorticoids
    • Ibuprofen
    • Macrolide antibiotics
    • Metamizole
    • metronidazole
    • Nystatin
    • Oxicame
    • Pseudeoephedrine (in flu medicines).
    • Paracetamol.
• An association with HLA-B5, -DR11, and -DQ3 is observed.
• Generalized subcorneal pustulosis may also be a partial symptom of genetic inflammatory systemic diseases (see DIRA - mutation in IL1RN gene below).

A special age disposition does not exist. Children are less frequently affected than adults.

Typical is the infestation of the large flexures (axillary, submammary, inguinal region); but generalized infestation is also possible. AGEP can be accompanied by oedema of the facial skin.

Beginning of the disease with significant impairment of the general condition; often feverish course with temperatures > 38°C.

Typical is the onset in the face and the large joint bends with disseminated, synchronous and relapsing laminar erythema or red swellings on which multiple, constricted, about 0.1 cm large non follicular pustules form. These flow together to form large pustule lakes, whereby the tender cover of pustules can be pushed away from their lower surface (Nikolski phenomenon) and lie on top like a crumpled damp cloth. The pustular exanthema is accompanied by itching or even stinging or burning pain (like a needle prick).

In some cases erythema exudativum may develop multiforme-like cocard-like patterns in which the pustules are usually arranged edge-on, either disseminated or grouped. The pustules exist for a few days; they heal with a racy, raised scaling of thin horny films (see figure).

Involvement of mucous membranes close to the skin (oral mucosa, genitals) is rather rare; if present, clinically mild exfoliating enanthema can be observed.

Notice! The coarse lamellar corneolytic desquamation is diagnostically indicative of a subcorneal pustulation!

In case of an atypical course, a clinically evident pustular formation may be missing in this clinical picture. In this case it is only visible in the histological preparation; but even in these cases a lesional corneolytic scaly ruffle is found when healed.

ESR elevation, CRP elevation, always marked leukocytosis (leukocytes > 10,000-12,000/mm³; sine qua non), marked neutrophilia, usually mild to marked relative lymphopenia, possibly eosinophilia. Elevations of transaminases and alk. phosphatase.

Exocytosis with intraepidermal, immediate subcorneal accumulations of neutrophil granulocytes.

Formation of spongiform to unicompartmental (nonfollicular)pustules.

Focal loss of str. granulosum. Mostly orthokeratotic epithelium. Occasionally, admixtures of eosinophilic granulocytes and erythrocyte extravasations are also present.

Pattern: Superficial perivascular and diffuse neutrophilic dermatitis with subcorneal pustule formation.

In contrast to TEN (subepidermal cleft formation with necrotic epidermis), biopsy in pustulosis acuta generalisata shows subcorneal pustules.

Immunohistology: Immunoglobulins (IgG) and complement factors (C3) in the vessel walls of the capillaries of the stratum papillare and in the basement membrane zone

The "AGEP validation score" from the EuroSCAR study group (Sidoroff et al. 2001) is helpful for the validation of the diagnosis. A score of 8-12 pts speaks for the diagnosis:

AGEP validation score of EuroSCAR study group (Sidoroff A et al. 2001)

Symptom Score

• Pustule
  • Typical +2
  • Compatible +1
  • Non-compatible 0
• Erythema
  • Typical +2
  • Compatible +1
  • Non-compatible 0
• Distribution patterns
  • Typical +2
  • Compatible +1
  • Non-compatible 0
• Postpustular desquamation
  • Typical +1
  • Non-compatible 0
• Mucous membrane infestation
  • Yes +1
  • No 0
• Acute course (<10 days)
  • Yes +1
  • No 0
• Healing (<15 days)
  • Yes +1
  • No 0
• Fever
  • Yes +1
  • No 0
• Neutrophil leukocytosis (>7,000)
  • Yes +1
  • No 0

• Clinical differential diagnoses:
  • Pyoderma (microbiological detection of the purulent cocci)
  • Psoriasis pustulosa generalisata (anamnesis; chronic recurrent course, recurrences without fever symptoms and without the severe general symptoms of AGEP)
  • Dermatosis, acute febrile neutrophils (Sweet-Syndrome) (analogous acute and general symptoms, but primarily reddish-livid, succulent papules, nodules and plaques. Intralesional, grafting pustular formation possible. Pustules, however, not in the density as in AGEP.
  • Hand-foot-mouth disease (few acral localized painful blisters; only moderate or no disturbance of the AZ)
  • Erythema exsudativum multiforme (not pustular)
  • Lyell syndrome (large-area exfoliative, not pustular)
  • Subcorneal pustulose (chronic recurrent course; similar clinical morphology! The occurrence of larger and flaccid pustules - hypopyon formation is indicated). Entity is increasingly disputed!
  • Impetigo herpetiformis (occurrence in the last trimester of pregnancy)
  • Pityrosporum folliculitis (always follicular papules and pustules; no severe course of the disease).
• Histological differential diagnoses:
  • Psoriasis pustulosa generalisata (no reliable histological differentiation; medical history)
  • Pustular tinea (subcorneal pustular formation possible; detection of hyphae in the PAS preparation; in the upper dermis dense diffuse, sometimes perivasally accentuated lymphocytic infiltrate with few neutrophils and eosinophil granulocytes)
  • Impetigo contagiosa (subcorneal pustule; detection of bacteria)
  • Impetiginized eczema (eczema picture with broad-based acanthosis and extensive parakeratosis, broad spongiosis; focal penetration of the epithelium with neutrophil granulocytes).

Stopping the triggering medication.

Healing is usually described 10-14 days after discontinuation of the triggering drug. Until then symptomatic therapy, e.g. with dimetindene or other H1-blockers.

Important: control of protein and electrolyte balance.

Internal steroid medication can be initiated in the eruption phase of the disease: Initially 250-150 mg prednisolone/day i.v.; reduce by 50 mg daily depending on the acuity, oralize from 50 mg and reduce in 5 mg steps.

Spontaneous healing after 10-28 days

The disease also heals spontaneously after discontinuation of the triggering drugs. The extent to which glucocorticoid therapy is useful currently remains open.

In individual cases, a positive epicutaneous test against causative drugs can be obtained after the clinical manifestations have subsided (the non-irritative concentration of the drug in epicutaneous drug testing varies).

• Findings: Patients in clearly reduced, feverish (38.7 °C) AZ. On the trunk and extremities in diffuse distribution dense exanthema of 0.2-0.5 cm large, red, partly isolated papules and plaques, partly confluent to larger areas. Particularly on the confluent plaques, isolated pustules of barely 0.1 cm in size, which in places have confluated to form larger pus puddles, can hardly be seen. Oral mucosa o.B. No hepatosplenomegaly, no lymph node swelling.
• Histology: Intraepidermal, superficial, spongiform to single chambered pustules. Laboratory: CRP 65 mg/l; leucocytosis (16.400/µl), neutrophilia (87%), lymphopenia (1.200/ul), GGT(54 U/l).
• Therapy: Systemic glucocorticoids (prednisolone 250 mg/day i.v. with dose reduction of 50 mg in decreasing doses. Additional sedative antihistamine ( Dimetinden 2 times/day 4 mg i.v.). Local therapy with thin application of Lotio alba or Lotio alba aquosa skin-coloured (NRF 11.22.).
• Course: After 2 days of defibrillation, after 4 days of paling of the lesions, coarse lamellar desquamation first on the trunk and significantly later on the lower extremity. After 7 days CRP 35 mg/l, leucocytosis at 11,400 µ/l. After 14 days extensive restitutio. The patient was allowed to take lukewarm showers in each phase of the disease.

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