Introduction

The skin, being the largest organ of the human body, is susceptible to a variety of medical conditions, including acne, scarring, pigmentation, redness, inflammation, sunburn, and freckles. These skin conditions can arise from multiple factors, including poor dietary habits, environmental pollution, prolonged sun exposure, certain medications, hormonal imbalances, and underlying health conditions. 

Our skin cells follow a well-regulated turnover cycle. When this cellular discipline is disrupted, conditions like psoriasis can arise, where the skin renews itself too quickly, leading to inflammation and scaling. There are certain skin conditions which can mimic psoriasis. Therefore, it is necessary to recognise psoriasis based on histopathological parameters, the characteristics of a tissue sample under the microscope, to aid the treatment protocol.

How would you feel if you had plaques and blisters on your body? Painful, embarrassed, debilitating? In this article, we will discuss the autoimmune skin disorder psoriasis, including its incidence, causes, triggering factors, assessment, diagnosis, microscopic findings, and treatment.

Overview of psoriasis

Definition

Psoriasis is a chronic, relapsing and remitting disease, which manifests as well-demarcated reddened papules and plaques covered with silvery white scales. It affects skin, nails and joints. This disease is characterised by acute flares that are emotionally and physically debilitating.¹ 

Variants of psoriasis

• Plaque psoriasis: the most common form, commonly seen on elbows and knees
• Guttate psoriasis: silvery scales covered tiny, reddened papular eruptions are seen
• Erythrodermic psoriasis: the confluent plaques cover the whole body, except the central face
• Pustular psoriasis: pus-filled lesions on the skin, nails, bones and oral mucosa
• Scalp psoriasis: the skin behind the ear and posterior upper neck gets covered with well-demarcated plaques
• Annular/figurate psoriasis: as suggested by the name, ring-like lesions of psoriasis with central clearing appear
• Oral psoriasis: reddened, ulcerated or pus-filled lesions appear on the tongue and gingiva¹ 

Pustular psoriasis

The 2017 consensus diagnostic criteria by the European Rare and Severe Psoriasis Expert Network (ERASPEN) define generalised pustular psoriasis (GPP) as the presence of primary, visible, sterile pustules (pimples containing a yellow pus) occurring beyond just the palms, soles, or existing psoriatic plaques. These pustules may appear with or without systemic inflammation, and follow either a relapsing or persistent course lasting more than three months.²

Causes

It is an immune-mediated disorder involving T cells and their interactions with the cells involved in keratin production. Genetically, pustular psoriasis is associated with mutations in any of 3 genes of the skin immune system, i.e. IL36RN, CARD14 and AP1S3.^3,4

Triggering factors

• Withdrawal of systemic corticosteroids
• Infections 
• Medications (e.g., lithium, antimalarials)
• Pregnancy
• Hypocalcemia (low calcium levels)
• Stress⁵

Types of pustular psoriasis  

Localised pustular psoriasis 

Palmoplantar pustular psoriasis (PPP) 

PPP affects people assigned female at birth more frequently than people assigned male at birth. It begins as sterile pustules accompanied by redness, thickened skin, and scaling on the palms and soles. The pustular lesions may resolve, leaving behind brown discolouration.⁵

Acrodermatitis continua of Hallopeau (ACH)

This predominantly involves the fingertips and nails of the hands and/or feet. ACH presents as sterile pustules, which are often painful, and the destruction of nails takes place.⁶

Generalised pustular psoriasis (GPP)

It is a severe and potentially life-threatening form characterised by an acute onset of rapidly disseminating skin eruptions, covered with aseptic pustules (without bacterial infection). It includes acute generalised pustular psoriasis, pustular psoriasis of pregnancy, and infantile and juvenile pustular psoriasis.^4,5

The condition is excruciating as the affected skin is covered with sterile pustules, and any contact with clothing or bedding often causes staining with blood and pus. The risk of infection increases owing to the loss of the protective action of the skin.^5,7 

Signs of pustular psoriasis

• Koebner phenomenon: When trauma is given on the skin of susceptible individuals, new psoriatic papules appear at that particular site⁸
• Auspitz sign: Pinpoint bleeding points form when silvery white scales are removed⁸ 
• Woronoff ring: A ring-like area of blanching appears around resolving psoriatic plaques⁹

Diagnosis of pustular psoriasis 

When clinical findings are insufficient for diagnosing GPP, genetic testing and histopathological analysis, the characteristics of a tissue sample under the microscope of skin biopsies can aid in making a definitive diagnosis. Additional tests include X-ray if joints are affected and laboratory tests, including complete blood count, liver function tests, and renal function tests.^10,11

According to the Japanese diagnostic criteria established in 2018, a definitive diagnosis of generalised pustular psoriasis (GPP) requires the presence of all four of the following features:

1. Systemic symptoms such as fever and fatigue
2. Widespread erythematous skin lesions covered with numerous sterile pustules, which may coalesce into lakes of pus
3. Histopathological confirmation of neutrophilic subcorneal pustules, specifically Kogoj’s spongiform pustules
4. Recurrence of the clinical and histological findings

The diagnosis is definitive if all four parameters are present, and a suspected diagnosis if only two or three parameters are met.^10,11

Microscopic findings

For understanding the histopathology of pustular psoriasis, let’s take a look at the normal composition of skin under a microscope. Normal skin is composed of the following layers from top to bottom:

• Epidermis
• Epidermal basement membrane
• Papillary and reticular dermis, with related adnexa like hair follicles, sweat glands and sebaceous(oil-secreting) glands
• Subcutaneous fat

The layers of the epidermis, arranged from the deepest to the most superficial, are as follows:

1. Basal layer (stratum basale)
2. Prickle cell layer (stratum spinosum)
3. Granular layer (stratum granulosum)
4. Keratin layer (stratum corneum)

The epidermis has downgrowths called rete ridges, which penetrate the upper dermis to provide stronger tethering. Normally, the cells in the epidermis mature from basal cells to form keratin in 50-60 days, but in psoriasis, this is significantly shortened to about 7 days. In psoriasis, the maturation process is so fast that there is insufficient time for the development of a proper granular layer. Instead of normal keratin, there is the formation of an opaque white scale composed of a mixture of keratin and debris of the keratinocytes (cells producing keratin). The rapidly proliferating epidermis is thickened to produce raised red patches under the white scale.³

Let's throw light on some terms which are used to describe the findings observed microscopically.^5,7

• Pustule: A pus-filled raised lesion is termed a pustule
• Parakeratosis: Normally, the cells in the upper layer of epidermis, i.e. stratum corneum, lose their nuclei upon keratin formation. However, if there is abnormal retention of nuclei, it’s called parakeratosis
• Hyperplasia: an increase in the number of layers of cells
• Hyperkeratosis: hyperplasia of the stratum corneum
• Acanthosis: diffuse epidermal hyperplasia

The lesions of psoriasis undergo several morphological changes as they evolve from early to advanced stages.^5,7

Early stage

The epidermis is quite normal. The changes occur in the papillary dermis. The blood vessels become dilated and tortuous, with accumulation of neutrophils in their lumen. Lymphocytic infiltrate appears around blood vessels (perivascular cuffing).^5,7

After that, the epidermis layer starts proliferating due to a markedly shortened cell turnover time. Normally, keratinocytes lose their nuclei as they proliferate and mature, but in this stage, they aberrantly retain intact nuclei and release few extracellular lipids that are responsible for the adhesion of epidermal cells. These poorly adherent cells form the characteristic scales of psoriatic lesions. Scattered neutrophils are seen at the edge of parakeratosis.^5,7

Advanced stage

Characterised by:

1. Acanthosis, i.e. thickening of the stratum spinosum
2. There is regular elongation of the rete ridges associated with epidermal hyperplasia
3. Thinning of suprapapillary plates
4. Marked mitotic activity 
5. Parakeratosis comes together with the loss of the  granular layer
6. There is transmigration of inflammatory cells through epidermis into parakeratotic scale, resulting in collections of neutrophils in the stratum corneum to form characteristic “Munro microabscesses”
7. When the inflammatory cells accumulate in the  stratum spinosum, they form “spongiform pustule of Kogoj”
8. In pustular psoriasis, the subcorneal abscesses become prominent 

Munro microabscesses and spongiform pustule of Kogoj are diagnostic of psoriasis, but they are not always present in the histological sections.^5,7

Treatment

The main aim of the treatment is the management of acute flares, complete disease clearance, minimising disease severity, duration of complications, and decreasing the disease burden for the patient.^5,7 

Summary

Pustular psoriasis is a chronic, debilitating skin disorder characterised by relapsing and remitting episodes, and it can lead to significant morbidity and even mortality if left untreated. Patient awareness of this condition is crucial, as early diagnosis and appropriate treatment can significantly improve both the quality and duration of life. Several other skin conditions can mimic pustular psoriasis. Therefore, the expertise of a trained pathologist plays a vital role in establishing an accurate diagnosis.