Generalised pustular psoriasis

Synonyms: acute generalised pustular psoriasis of von Zumbusch, pustular psoriasis von Zumbusch variant

What is generalised pustular psoriasis?

Pustular psoriasis defines a heterogeneous group of skin inflammatory diseases, which have in common the presence of aseptic pustules. Genetically distinct from psoriasis vulgaris, they have been shown to be related to mutations in any of 3 genes of the skin immune system, respectively called IL36RN, CARD14 and AP1S3.¹

The different variants include acute generalised PP (GPP), PP of pregnancy (impetigo herpetiformis), annular (and circinate) PP, infantile/juvenile PP, palmoplantar PP/palmoplantar pustulosis, and acrodermatitis continua of Hallopeau (ACH).²

Acute erythema is seen with a rapid spread of multiple sterile pustules over the body, concentrated in the flexures, genital regions and fingertips. It is a medical emergency that requires urgent hospital referral.

The 2017 European guidelines established the diagnostic criteria for GPP, including the presence of primary, sterile, non-follicular, and macroscopic pustules affecting the non-acral skin. It may or may not occur in the presence of plaque psoriasis, and classified as being recurrent (more than one episode) or persistent (lasting more than three months).³

Generalised pustular psoriasis needs to be distinguished from a localised form of pustular psoriasis known as palmoplantar pustulosis (PPP).

How common is generalised pustular psoriasis? (Epidemiology)

It is a rare condition: precise prevalence figures for the UK are not available. Prevalence is 7 per 1 million in Japan.⁴ The average age of those affected is 50 but the range is wide.

Recognised triggers^{5 6}

• Systemic steroid withdrawal.

• Drugs: salicylates, iodine, lithium, phenylbutazone, oxyphenbutazone, trazodone, penicillin, hydroxychloroquine, calcipotriol, interferon alfa and recombinant interferon-beta injection.

• Topical medications causing irritation: coal tar, anthralin, steroids under occlusive dressing and zinc pyrithione in shampoos.

• Infections.

• Sunlight or phototherapy.

• Cholestatic jaundice.

• Hypocalcaemia.

No cause is identified in many patients.

Generalised pustular psoriasis symptoms (Presentation) ⁷

• The skin becomes very red and tender.

• Clusters of pustules appear within hours. Multiple, small (2-3 mm), yellowish pustules develop on an erythematous background and may spread rapidly to a generalised pattern. Over about 24 hours, the pustules coalesce, dry and desquamate in sheets. Further crops of pustules may appear over days to week, leaving the patient uncomfortable and exhausted.

• The flexural and anogenital regions are most commonly affected. Facial lesions are less common.

• Pustules may occur on the tongue and under the nails, causing dysphagia and loss of nails respectively.

• Patients are usually systemically unwell with symptoms including headache, fever, chills, arthralgia, malaise, anorexia and nausea. On examination, there is maybe a fast respiratory rate, tachycardia and pyrexia suggesting a toxic state. The tongue is dry and cracked.

• As the pustules remit, most systemic symptoms ebb but the patient can be left with erythroderma or with residual lesions of ordinary psoriasis.

While children and infants can develop a generalised pustular psoriasis of the adult form, a circinate or annular type is more usual, which tends to run a subacute/chronic course and to be more benign:

• There are recurrent episodes of annular or circinate erythematous plaques, with pustules on the periphery.⁸

• They are mostly over the trunk but also involve the extremities.

• They expand peripherally whilst healing in the centre.

• Systemic symptoms are mild or absent.

• Spontaneous remissions are frequent.

Differential diagnosis

• Drug eruptions.

• Sepsis.

Investigations

• FBC - typical raised white cell count with a marked rise in neutrophils and fall in lymphocytes.

• Elevated inflammatory markers.

• Hypoalbuminaemia.

• Abnormal LFTs.⁹

• Abnormal renal function parameters due to acute kidney injury or tubular necrosis.

• No microbial growth from cultures of pustules and blood.

Generalised pustular psoriasis treatment and management^{7 10 11}

• The extent and severity of generalised pustular psoriasis requires prompt intervention, hospitalisation, and not infrequently, intensive care unit support.

• Intensive nursing and supportive therapy with attention to hydration, fluid balance, nutrition and temperature regulation.

• Bland topical compresses and saline or oatmeal baths assist in soothing and debriding affected areas.

• Treatment options include acitretin, methotrexate, infliximab, adalimumab, etanercept, and ustekinumab (anti-IL-12/IL-23). Various other biological agents have shown promise, including anti-IL-17, anti-IL-23, anti-IL-1 and anti-IL-36 receptor agents.

• There is no evidence to recommend the use of phototherapy during the flare-up (acute phase) of GPP. There have been reports on the efficacy of PUVA phototherapy during the maintenance period, after the acute flare-up had been controlled.

Complications⁶

• Secondary bacterial infection of the skin may occur.

• Hair loss with telogen effluvium is possible.

• With subungual involvement, nails will be lost.

• Hypoalbuminaemia may result from loss of plasma protein into tissues.

• Reduced circulating volume may cause renal tubular necrosis.

• Poor circulation and general toxicity may cause liver damage.

• Malabsorption and malnutrition.

• Death due to cardiac failure, sepsis or acute respiratory distress syndrome.

Prognosis¹¹

• Generalised pustular psoriasis has a variable and unpredictable course and most patients have recurrent disease. The time interval between crises varies, and there may or may not be complete regression of the lesions between them. The severity of the crises can also vary in the same patient.

• The emergence of pustules can occur without major signs of systemic inflammation or be associated with intense inflammatory conditions, with rapid progression and risk of death, requiring admission to an intensive care unit.

• Data on mortality rates are limited and between 3% and 7% of mortality have been reported.

• Identification of infection is often difficult due to the intense inflammatory process, making it a challenge to decide on the balance between the use of immunosuppressants and antibiotics.

• The careful monitoring of symptoms and clinical evolution is essential for early intervention, in an attempt to avoid severe complications.