Introduction

What is PUPPP?

Polymorphic eruption of pregnancy (also known as Pruritic Urticarial Papules and Plaques of Pregnancy, or PUPPP) is an inflammatory skin condition that presents as an itchy rash during the last three months of pregnancy. PUPPP occurs in roughly 1 in 160 pregnancies, however, it is harmless to both the mother and the newborn.¹ While the cause remains somewhat unknown, the chance of developing PUPPP may increase if the mother is:²

• White
• Carrying a male foetus
• Having their first pregnancy
• Carrying twins or triplets

Why perform histopathology?

Histopathology involves the study of a microscopic tissue sample taken from a patient's biopsy, to aid in the accurate diagnosis of a disease. In the case of PUPPP, while histopathology will not diagnose the condition alone, it can contribute to the speed of diagnosis, leading to prompt treatment for the mother and a faster recovery. This article will highlight when histopathology is best performed in PUPPP, the different types of tests that are commonly used, and some real-life examples showcasing the histopathological findings that can help with the timely diagnosis of PUPPP.

Overview of clinical presentation in PUPPP

Who is affected?

Women during their last 3 months of pregnancy are most commonly affected by PUPPP, but more specifically, studies have shown that women with twin and triplet pregnancies are at least six times more likely to develop PUPPP.³

What are the typical symptoms?

The rash in PUPPP typically consists of small papules and plaques that usually begin to present in the stretch marks, however, the rash can spread fairly rapidly once established.⁴ While the appearance of the rash may seem alarming, once treated, it is unlikely to leave any lasting damage or scarring.

Rationale for biopsy

What is the purpose of a skin biopsy in PUPPP?

The appearance of PUPPP can be alarming, and thus the mother will likely benefit from a quick and concise diagnosis for ease of mind. However, in more ambiguous cases, a clinician will often ask to take a skin biopsy. Taking the skin biopsy will allow histopathologists to examine the tissue at a microscopic level, aiming to collect cellular evidence that matches the clinical evidence to reach a correct diagnosis.

When is a biopsy considered?

A biopsy is usually considered when the clinical presentation of PUPPP is unusual. For example, it may appear earlier in pregnancy, or the pattern of the rash may appear atypical or spread rapidly. Additionally, if the mother fails to respond to initial treatment, a biopsy will likely be taken to rule out the possibility of other infectious diseases that may cause more long-term damage.⁵

Goals of histological analysis

Histological analysis is mainly implemented to strengthen the clinical diagnosis of PUPPP, reducing the chance of a misdiagnosis. While harmless, PUPPP doesn’t have any distinguishable histological features, and thus combining the histological findings with clinical findings will allow doctors to be more certain of the diagnosis, leading to earlier treatment.

Histopathological features of PUPPP

Biopsy findings in PUPPP are generally non-specific, meaning they don't point uniquely to this condition, but they can support a clinical diagnosis and exclude other possibilities. The findings are typically mild, with changes more pronounced in the dermis than in the epidermis.

Epidermal findings

Mild Spongiosisthis refers to intercellular oedema in the epidermis, suggesting irritation or inflammation, and is usually limited in extent.

• Focal Parakeratosis -this is the retention of nuclei in the stratum corneum (the outer layer of skin), reflecting a mildly accelerated epidermal turnover
  Exocytosis - occasional migration of inflammatory cells, particularly lymphocytes, into the epidermis may be seen

Dermal findings

• Perivascular Lymphocytic Infiltrate: The most consistent histological feature of PUPPP is a mild to moderate infiltration of lymphocytes around superficial dermal blood vessels
• Eosinophils: These cells are often present within the infiltrate, a feature that may overlap with other conditions but adds to the inflammatory profile of the rash
• Histiocytes and Occasional Neutrophils: These may be present to a lesser extent, contributing to the mixed inflammatory pattern
• Dermal Edema: Mild swelling or fluid accumulation in the dermis is frequently observed and may explain some of the urticarial (hive-like) clinical appearance
• No Blistering or Vasculitis: Importantly, features like subepidermal blistering, necrosis, or vasculitis are absent in PUPPP. Their presence would suggest other diagnoses such as pemphigoid gestationis or cutaneous vasculitis

Differential diagnosis based on histopathology

One of the main values of biopsy in suspected PUPPP cases is in differentiating it from other dermatoses of pregnancy, which may have similar clinical appearances but very different management needs.

Pemphigoid gestationis

• Histology: Subepidermal blister with eosinophilic infiltrate
• Key Differences: Typically involves the periumbilical area (belly button) and may worsen postpartum

Atopic eruption of pregnancy

• Histology:Variable; may show spongiosis and perivascular infiltrate, often without eosinophils
• Key Differences:May present earlier in pregnancy; often associated with a personal or family history of atopy

Polymorphic eruption of pregnancy

These may also mimic PUPPP histologically, but a detailed history, clinical distribution, and review of medications or exposures help clarify the diagnosis.

Conclusion

PUPPP is a common, benign condition that typically requires no invasive testing for diagnosis. However, in uncertain or severe cases, a skin biopsy can provide valuable insight. Histological findings in PUPPP are generally mild and non-specific, showing superficial perivascular lymphocytic infiltrates, eosinophils, and mild epidermal changes. The absence of specific features like blistering or immune deposits helps to rule out more serious conditions.

Ultimately, while histopathology can support the diagnosis of PUPPP, it must be interpreted within the broader clinical picture. By combining histological features with patient history, physical examination, and, when needed, immunofluorescence, healthcare providers can make informed decisions and ensure the best outcomes for both mother and baby.