Generalized pustular psoriasis

checkorphan

Synonyms

GPP,

Overview

Generalized pustular psoriasis (GPP) is a rare, chronic, and severe inflammatory skin disorder characterized by sudden eruption of sterile pustules, often accompanied by systemic inflammation. GPP flares can be life-threatening if untreated, owing to potential serious complications such as sepsis and cardiovascular failure. Diagnosis and clinical measurement of disease severity in GPP are often difficult. Lack of standardized criteria in the international guidelines and the heterogeneity of cutaneous and extracutaneous symptoms make the diagnosis of GPP difficult. Clinical criteria for description and diagnosis of pustular conditions, including GPP, are variable and there is no specific agreement on commonly sustained concepts. Differentiation of GPP from other similar conditions/diseases is important and requires careful assessments. The evidence that supports current topical or systemic therapies is largely based on case reports and small studies. Some biologic agents that target key cytokines involved in the activation of inflammatory pathways have been used as treatments for GPP. Recently, spesolimab, an IL-36R antagonist, has been approved in the USA and Japan for the treatment of GPP flares in adults, but there are no currently approved treatments for GPP in Europe. The IL-36 pathway has recently emerged as a central axis driving the pathogenic inflammatory mechanisms of GPP. Biologic agents that inhibit the IL-36 pathway have shown efficacy and safety in patients with GPP, addressing a generally considered unmet medical need.

Diagnosis

In general, the diagnosis of GPP is mainly clinical. Laboratory tests are helpful for diagnostic confirmation and to assess the level of systemic inflammation and possible systemic complications that may lead to fatal outcomes. Potassium hydroxide direct examinations can also be performed to exclude generalized tinea corporis and disseminated candidiasis, which may cause scaling and pustulosis. Biopsies do not always confirm the diagnosis of GPP (e.g., versus acute generalized exanthematous pustulosis [AGEP]). However, the diagnosis is clinico-pathological and skin biopsies may reinforce the clinical diagnosis of GPP.

At least 29 different primary pustuloses have been described over the years with a wide range of possible associated clinical features. The rarity of these conditions does not allow collecting enough cases to establish diagnostic and differential criteria. The clinical criteria for description and diagnosis of pustular conditions, including GPP, are variable, and it is difficult to reach a commonly accepted agreement. Proposed definitions of pustuloses show several discrepancies on subtypes, localizations, extension, presence of arthritis, pain, systemic inflammation, and other characteristics. Because of that, differential diagnosis in GPP is of paramount importance.

The differential diagnosis of GPP flares vs AGEP represents a clinical challenge and requires a detailed clinical, histopathological, and laboratory evaluation.

Prognosis

In the absence of effective treatment, death can occur in the acute stage. The prognosis is good for subacute annular and circinate generalized pustular psoriasis, and as a consequence, for disease in children. Amongst generalized pustular psoriasis, the prognosis is better when there is a clear trigger, exemplified by generalized pustular psoriasis of pregnancy. Generalized pustular psoriasis developing from acrodermatitis continua of Hallopeau seems to have the worst prognosis.

Treatment

Generalized pustular psoriasis is treated on the following lines:

Conservative Treatment

  • Encourage fluid and protein intake
  • Monitor input/output
  • Treat infection, if any, with antibiotic
  • Terminate pregnancy if there is a risk to maternal life
  • Prevent hypothermia

Topical

  • Bland emollients
  • Diluted corticosteroids

Systemic

First line

  • Acitretin (not given in pregnancy) in dose of 1mg /kg/day
  • Ciclosporin, 3.5 to 5 mg/kg/day
  • Methotrexate, 0.2 to 0.4 mg/kg/day

Second line

  • Infliximab
  • Adalimumab
  • Etanercept
  • Prednisolone (only in special conditions, e.g., complications)

Third line

  • Anakinra