Generalised pustular psoriasis (GPP)

Last Updated: 2021-10-18

Author(s): Navarini

Zumbusch (1910)

  • DITRA
  • Psoriasis pustulosa gravis Zumbusch
  • Psoriasis pustulosa of the Zumbusch type
  • Generalized pustular psoriasis
  • Generalized pustular psoriasis
  • GPP
  • PPG
  • Severe pustular psoriasis
  • In pregnancy: impetigo herpetiformis

Rare, severe skin disease which forms white, sterile, multiple disseminated, sometimes confluent, sterile pustules. The general condition may be impaired. A lethal course is possible without therapy. Familial and acquired forms are known. Formerly misclassified as psoriasis.

  • Can occur at any age, in genetic forms (e.g. in homozygous IL36RN mutation) the onset is earlier
  • Very rare, 1:100,000 to 2:1,000,000, nevertheless always remember!
  • M:F = 1:1
  • Frequent in Japan and other Asian regions and North Africa due to higher allele frequency of IL36RN mutations
  • Initiation is earlier in patients without psoriasis vulgaris than in those without psoriasis vulgaris
  • In affected children, genetics as well as infections play a role

Generalised pustular psoriasis (GPP) is defined as primary, sterile, macroscopically visible pustules on non-acral skin (excluding cases where pustulation is confined to psoriatic plaques).

GPP can

  • with or without systemic inflammation
  • occur with or without psoriasis vulgaris (PV) (with PV in 33-70%) and may
  • be either a relapsing (>1 episode) or persistent (>3 months) condition

GPP is part of the DITRA (Mlack of interleukin-36 receptor antagonist) syndrome. IL-36Ra is an inhibitory protein of IL-36, which belongs to the IL-1 cytokine family. Keratinocytes and other epithelial cells produce the proinflammatory cytokines IL-36α, IL-36β and IL-36γ. These are key to the development of GPP. Patients show infiltration of the epidermis by neutrophilic granulocytes. The cytokine environment attracts these to the upper epidermis and triggers the inflammation.

Various trigger factors are known:

  • Pregnancy
  • Rapid corticosteroid withdrawal (considered somewhat less important due to a recent publication which recorded no pustular psoriasis relapse after approximately 2000 steroid withdrawals)
  • Hypocalcaemia
  • Bacterial and viral (especially EBV) infections
  • Drugs especially lithium, salicylates, iodine preparations, progesterone and propanolol
  • Patients have a higher incidence of HLA-B 27.
  • In familial GPP and in 80% of sporadic cases without psoriasis vulgaris, a mutation is found in the gene encoding the IL-36 receptor antagonists.
  • In familial GPP, a gain-of-function mutation in CARD14 was detected.

Acute onset with febrile episodes and non-specific general symptoms such as malaise, erythroderma, muscle stiffness, joint pain. Afterwards, cutaneous symptoms appear with macroscopic, white, sterile pustules, which appear within hours after the onset of fever, first intertriginally, then increasingly on the trunk and extremities. Confluence of the pustules is possible. After the pustules burst, weeping or dried areas remain. If the oral mucosa is also affected, acute stomatitis with wipeable plaques and exfoliatio areata linguae.

 

Blood: Often but not always neutrophilia, hypocalcaemia, hypoalbuminemia, BSR, CRP, transaminase and alkaline phosphatase elevation.

In the course of the disease, there are recurrent attacks of fever and pustules with increasing general symptoms and even death due to secondary complications. These episodes can alternate with those of psoriasis vulgaris

  • Anamnesis
  • Biopsy of the pustule
  • Clinical: Establish diagnosis according to ERASPEN criteria. At first relapse AGEP cannot be ruled out clinically, therefore first treatment is analogous to AGEP and thereafter chronic therapy is started in case of persistence > 3 months or relapse.
  • Lab: Mostly leucocytosis > 12'000/ul, mostly neutrophilia >80%, CRP > 50mg/l, ESR > 40nm/h, sometimes hypocalcaemia, hypoalbuminemia, transaminase and alkaline phosphatase elevation. Attention - clinical diagnosis, systemic inflammation is not always found.

By definition, the pustules occur disseminated on non-acral skin. The number of pustules can vary. It is not yet known whether there are also milder forms of GPP. Initially, the pustules appear intertriginally and then spread further to the trunk, extremities (incl. plantar and palmar), oral mucosa, upper respiratory tract mucosa and genital mucosa.

Inquire about the following points:

  • Localisation
  • Inquire about general symptoms, especially fever
  • Infections (Trichophyton rubrum, Streptococcus, VZV, EBV, CMV) and other pathogens
  • Pregnancy
  • Skin diseases, especially pre-existing psoriasis vulgaris
  • Family history
  • Medications

Aggregates of neutrophils in the sense of spongiform pustules according to Kogoj. Large pustules are found in the epidermis, matched by an exocytosis of neutrophil granulocytes into the epidermis. Acanthosis, parakeratosis, in the late stage a psoriasiform hyperplasia, tortuous capillaries.

  • Infections, especially bronchopneumonia
  • Death
  • Liver metabolic disorders
  • Iron deficiency
  • Malabsorption and malnutrition
  • Abortion
  • Hair loss
  • Nail loss
  • Hypoalbuminemia
  • Tubular necrosis of the kidney

Avoid trigger factors and change medication if necessary

.

Without treatment, the disease is potentially life-threatening, especially because of the complications, and sometimes ends up being lethal.

In treated children, the prognosis is good.

Generally, the prognosis is better in sporadic GPP with manifestations of psoriasis vulgaris.

There is no curative therapy yet, but the symptoms can be completely suppressed

The following options can be chosen depending on the severity of the disease:

General measures:

  • Discontinue provoking medication
  • Treat infection if necessary
  • Initiate intensive care measures immediately if severe, depending on body surface area, also treat in burn intensive care unit
    • Sulphadiazine-silver cream
    • Put antibiotics (Bactigras) on the gauze grid to cover the erosions
    • Mouth hygiene with astringent fluids
    • Eye hygiene several times a day with astringent and disinfecting eye drops (Solan eye drops)
    • Dexpanthenol-containing eye ointment
  • If relapsing activity stops, continue local therapy with hydrophilic ointments to reduce irritation of the skin

Systemic therapy:

  • Acitretin 0.5-1.0mg/kg bw/day is traditionally the most commonly given therapy. The onset of action is slow and the drug produces a number of side effects incl. teratogenicity.
  • Infliximab has been used off-label several times in severe cases with good success
  • IL-17 and IL-23 antagonists are also used off-label. The IL-23 antagonist guselkumab is registered in Japan for pustular psoriasis
  • Prednisone, methotrexate, cyclosporine are also traditionally used
  • PUVA or bath PUVA as an adjunct

Comment:

  • IL-36R antagonists are still in clinical trials, currently not registered.
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