Introduction

Pustular psoriasis (PP) is a rare immune-mediated form of psoriasis vulgaris characterised by yellowish pus-filled blisters on an erythematous and/or scaly, discoloured base. The pustules can be widespread on the body or localised to a specific area. Pustular psoriasis can be categorised based on the pustule presentation and location, and the subtypes include:^1,2

Generalised

• von Zumbusch subtype – diffuse generalised pustular eruption with associated systemic symptoms like fevers 
• Annular subtype – annular or ring-shaped lesions with pustules along the advancing edge
• Exanthematic subtype – acute pustular eruption lacking systemic symptoms that resolves after a couple of days
• Impetigo herpetiformis – pustular psoriasis appearing during pregnancy

Localised

• Acrodermatitis continua of Hallopeau – pustules impacting the fingers, toes, and nail beds 
• Palmoplantar psoriasis – pustules concerning the palms and soles

Impetigo herpetiformis

Pustular psoriasis can be triggered by pregnancy, low calcium levels (hypocalcemia), or infections during this time, and it is then referred to as impetigo herpetiformis (IH). This condition typically arises in the third trimester of pregnancy and usually resolves after delivery. However, it can also occur in earlier trimesters or postpartum. Importantly, IH can be life-threatening, may occur in birth parents with or without a history of psoriasis, and may even arise in future pregnancies.^3,4

Pathophysiology & triggers

The exact cause of impetigo herpetiformis (IH) has not been proven, but genetics may play a role. Additionally, hormonal and immunologic changes happen during pregnancy. Numerous triggers have also been identified and linked to IH.^3,4

Hormonal influences

A few cases of impetigo herpetiformis have been precipitated by oral contraceptives containing estrogen and progesterone or the intake of these hormones otherwise.^3,5

Immunologic changes during pregnancy

Impetigo herpetiformis is considered to involve immune dysregulation where certain molecular targets and pathways are affected. Interleukins, IL-1 and IL-36, are thought to play a role in disease development since they are associated with neutrophil chemotaxis, which is responsible for the pustule formation.

Additionally, keratinocytes, neutrophils, and monocytes are the most active cell types in generalised pustular psoriasis (GPP). Tumour necrosis factor-α (TNF-α) and IL-17α may also be important in the pathogenesis of GPP and other psoriasis variants.⁶

Genetic predisposition (IL36RN mutations)

From previous studies, it was found that the majority of generalised pustular psoriasis cases without a history of psoriasis vulgaris carried homozygous or compound heterozygous mutation of Interleukin 36 Receptor Antagonist (IL36RN) that encodes IL-36 receptor antagonist.³

Reports also suggest that certain IL36RN mutations are more common and linked to more severe forms of the disease. Currently, 17 mutations associated with GPP have been documented in the literature.⁶

Possible triggers

Several triggers have been linked to impetigo herpetiformis, namely:^3,5,6 

• Hypocalcemia is mostly due to hypoparathyroidism
• Infections
• Stress
• Medications like N-butyl-scopolammonium bromide and ritodrine hydrochloride
• Medication withdrawal (e.g., corticosteroids)

Clinical implications & maternal risks

Pustular psoriasis in pregnancy (PPP) or IH usually presents as erythematous plaques with sterile pustules arranged as rings around the peripheries. New pustules form at the periphery of the main lesion, creating polycyclic lesions. Pustules in the centre of the lesions may dry and become large, yellow-crusted plaques.

Initially, IH is localised to intertriginous areas like the flexures, scalp, and neck before spreading to the extremities, avoiding the face, palms, and soles. Other symptoms include mild itching, fever, malaise, delirium, hypovolemic shock, seizures, painful oral erosions, nail shedding, chills, nausea, vomiting, diarrhoea, and subsequently dehydration.^3,4,5,6 

Electrolyte imbalances, such as hypocalcemia and hypoalbuminemia, occur, and there may be increased erythrocyte sedimentation rate and white blood cell count (leukocytosis). Iron deficiency anaemia, renal failure, and gestational hypertension are possible. Severe, prolonged cases increase the risk of placental insufficiency and potentially lead to life-threatening complications like sepsis.^3,4,5,6

Fetal risks

Increased risk of prenatal complications is likely and previously seen, and common issues include:^3,5,6

• Intrauterine growth restriction (IUGR)
• Premature rupture of membrane (PROM)
• Preterm labour
• Stillbirth
• Neonatal pustular lesions (rare)
• Ondine's curse (rare)

Diagnosis

There are multiple avenues involved in diagnosing pustular psoriasis in pregnancy. These mainly include:^1,2,3,5,6,7

• Clinical assessment – the appearance of the skin disorder is normally widespread erythematous plaques with sterile pustules; sterile, meaning they are due to non-infectious causes.
• Laboratory tests
  • Complete blood count (CBC)
  • Liver and renal function
  • Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
  • Serum calcium
  • Serum vitamin D
• Histological examination
• Skin biopsy 

Management strategies 

Multidisciplinary approach

Both the fetus and the birth parent should be monitored closely throughout pregnancy and postpartum to ensure proper management and reduce morbidity and mortality. A team consisting of a dermatologist, an obstetrician, and a neonatologist can collaborate to produce favourable outcomes.⁷

Medical treatment

Systemic corticosteroids

Corticosteroids are the first-line option for pustular psoriasis, and low to high doses of prednisone or prednisolone are normally recommended. However, caution should be exercised at higher doses, as they can lead to reduced fetal reactivity during fetal monitoring. Risks include the possibility of cleft palate if used in earlier trimesters, and potent topical corticosteroids may cause fetal growth restriction. Most birth parents should continue oral corticosteroid therapy until at least delivery, with gradual tapering of the medication, as IH is likely to flare.^3,6,7

Cyclosporine

Cyclosporine has been mainly used for severe and refractory cases, but in 2012, it was approved as first-line therapy for pustular psoriasis in pregnancy. Cyclosporine should not be used during breastfeeding as the amount of infant exposure has not been clarified. Placental transfer of cyclosporine appears to be dose-dependent, and there is a small likelihood of premature rupture of membranes. Birth parents should be monitored for hypertension and renal impairment.^3,6,7

Antibiotics

Antibiotics can be used in mild cases with other therapies. Cephalosporin is typically prescribed, but ampicillin, macrolide, and clofazimine have proven effective in IH.^3,6,7

TNF-alpha inhibitors 

The use of anti-TNF-α drugs such as infliximab and adalimumab is in conflict, as some organisations support it while others oppose it. Notably, the regular use is not approved by the United States Food and Drug Administration (FDA). TNF-α antibodies are pregnancy category B, but there is insufficient human data to demonstrate their safety in pregnancy. Infliximab has successfully cured two cases of pustular psoriasis in pregnancy, as well as refractory cases. Ustekinumab has also been reported to satisfactorily treat a case of recalcitrant severe pustular psoriasis during pregnancy.^3,6

Adjunctive therapies

Calcium & electrolyte correction

The replenishment of calcium, fluids, and electrolytes may be indicated through supplementation.^3,4,6,7

Nutritional support

It may be necessary to implement nutritional supplements like vitamin D and albumin if levels have been affected and reduced.^4,6

Phototherapy

Narrowband UVB (NB-UVB) is a safe additive therapy if an inadequate response to corticosteroids is found. Some studies have reported reduced folate levels during pregnancy due to NBUVB; however, it is not a major concern in the third trimester. Notably, folate deficiency in the first trimester may cause the development of neural tube defects. Photochemotherapy (PUVA) is relatively safe and is not linked to any congenital malformations or infant mortality, but it may lead to low birth-weight infants and is usually reserved for postpartum.^3,6

Pregnancy contraindicated options

Retinoids and methotrexate are contraindicated in pregnancy as they are category X drugs and can cause spontaneous abortions, severe fetal malformations, and complications. Following delivery, retinoids and methotrexate have successfully treated IH.^3,6,7

Prognosis & postpartum considerations

It is crucial to diagnose and initiate the necessary treatment for pustular psoriasis in pregnancy or impetigo herpetiformis (IH) as quickly as possible to improve fetal, maternal, and pregnancy outcomes. Close monitoring plays a vital role in managing this condition as well. Importantly, Maternal mortality is rare, but there is always the risk of fetal death.^6,7

Although IH resolves after delivery, recurrence or flare-ups may occur after delivery. Factors like oral contraceptives, stressful events, and menstrual changes have been connected to these cases. There is also a constant risk of recurrence with successive pregnancies.^5,6

Summary 

Pustular psoriasis (PP) is a rare and severe form of psoriasis characterised by sterile pus-filled pustules on an erythematous base. When it occurs during pregnancy, it is known as impetigo herpetiformis (IH), typically manifesting in the third trimester but potentially appearing earlier or postpartum. IH can be life-threatening, affecting individuals with or without a history of psoriasis, and may recur in future pregnancies.

While the exact cause remains unclear, hormonal changes, immune dysregulation, and genetic predisposition, particularly IL36RN mutations, are thought to play a role. Triggers such as hypocalcemia, infections, stress, and medication withdrawal can exacerbate the condition.

Clinically, IH presents with widespread pustular lesions, often beginning in intertriginous areas before spreading. Symptoms can include fever, malaise, electrolyte imbalances, renal dysfunction, and, in severe cases, sepsis. Fetal risks include intrauterine growth restriction (IUGR), preterm labour, and stillbirth. Diagnosis is primarily clinical but may involve laboratory tests and skin biopsy for confirmation.

Management requires a multidisciplinary approach, with systemic corticosteroids as the first-line treatment. In severe cases, cyclosporine, TNF-alpha inhibitors, and phototherapy may be considered, while supportive therapies such as calcium supplementation and nutritional support help manage complications.

Although IH often resolves after delivery, recurrence is possible, particularly with hormonal fluctuations or subsequent pregnancies. Prompt diagnosis and treatment are crucial for improving maternal and fetal outcomes, as untreated cases can lead to significant morbidity and mortality. Postpartum monitoring remains essential to prevent and manage potential flare-ups.