What causes pruritic urticarial papules and plaques of pregnancy (PUPP)?

What Causes PUPP?

The exact cause of PUPP (Pruritic Urticarial Papules and Plaques of Pregnancy) remains unknown, but the condition is strongly associated with abdominal skin distension from pregnancy, particularly in primigravidas, multiple gestations, and excessive maternal weight gain. 1, 2

Proposed Pathophysiologic Mechanisms

While the precise etiology is elusive, several theories have been proposed:

Mechanical Distension Theory

• Abdominal skin stretching appears to be the primary trigger, with lesions characteristically beginning in striae gravidarum on the abdomen 3
• This explains why PUPP predominantly affects:
  • Primigravidas (70%) - experiencing maximal skin distension for the first time 3
  • Multiple gestation pregnancies (13%) - greater abdominal distension 3
  • Women with excessive maternal weight gain (78%) - increased skin stretching 3

Immunologic Mechanisms

• Recent cytokine profiling suggests an upregulated Th2 immune response, including elevated IL-9 and IL-33 4
• Possible reaction against skin-resident bacteria and fungi may contribute 4
• Damage to connective tissue from stretching may convert non-antigenic molecules into antigenic ones, triggering an immune response 5

Hormonal Factors

• Hormonal alterations during pregnancy have been proposed but not definitively proven 2, 5
• Placental products may play a role 5

Key Clinical Context

Important distinction: PUPP is fundamentally different from intrahepatic cholestasis of pregnancy (ICP). While ICP is mentioned in the guidelines [6-6] as part of the differential diagnosis of pruritus in pregnancy, PUPP is characterized by:

• Pruritic urticarial papules and plaques on the abdomen and proximal thighs 6
• Presence of a visible rash (unlike ICP which has pruritus without rash)
• No systemic risks to mother or fetus 1, 2

Risk Factor Summary

The strongest associations with PUPP development are:

• Primigravidity (first pregnancy)
• Multiple gestation pregnancies
• Excessive maternal weight gain
• High maternal BMI 7
• Third trimester onset (83% of cases, mean onset 34 weeks) 3

Bottom line: PUPP appears to result from mechanical skin distension triggering an inflammatory immune response in genetically susceptible individuals, though the complete pathophysiologic pathway remains incompletely understood.