Introduction

What is Pyoderma Gangrenosum?

Pyoderma Gangrenosum (PG) is one of medicine’s trickiest skin conditions that can mimic deadly infections, autoimmune diseases, or even surgical emergencies. Pyoderma Gangrenosum is essentially a painful, non-infectious and non-healing pus-filled ulcer which progressively enlarges to variable depths and sizes. It is a rare condition affecting around 3 to 10 people per million each year, commonly affecting age groups above 50 years, with women being more often affected than men.^2,6 However, Pyoderma Gangrenosum can occur at any age, starting from infancy.^,8,10

This condition falls under a category of skin conditions called “neutrophilic dermatoses”, where the immune system utilises its defence cells(neutrophils) without any known trigger. The result? Red, swollen, painful, or blistered skin.³

Challenges in differentiating Pyoderma Gangrenosum from other serious conditions

Akin to many dermatological conditions, Pyoderma Gangrenosum can often be mistaken for other serious conditions such as infections, vasculitis, and necrotising fasciitis, due to its non-specific and variable clinical presentations. This poses a significant diagnostic challenge to physicians, leading to inappropriate treatments like surgical removal of the dead tissues in a process called surgical debridement, often resulting from misdiagnosis.⁴

Pyoderma Gangrenosum overview

Clinical features

Pyoderma Gangrenosum has various subtypes, the most common being the Classic ulcerative Pyoderma Gangrenosum.²It begins as a pustule, red bump or a small wound, which rapidly enlarges to a painful wound with raised, irregular red-purple edges, surrounded by a peripheral red halo.⁷ Pyoderma Gangrenosum occurs most commonly on the lower legs preferably right over the shin bone (also called the tibia), but can occur on other areas of the body as well, including breast, hand, trunk, head and neck.

These ulcers appear with undermined borders, where the tissue at the edges of an ulcer or wound appears to be eroded or "scooped out".This is when the deeper layers are more extensively destroyed below the outer edges of the ulcers, forming a cave-like effect. This feature is characteristic of Pyoderma Gangrenosum and helps differentiate it from other ulcerative conditions.

Pathophysiology

Pyoderma Gangrenosum is caused by genetic alterations of the immune system, neutrophil dysfunction, and abnormal inflammatory responses mediated by a protein called Tumour necrosis factor-alpha(TNF-α). These findings imply that in susceptible individuals, Pyoderma Gangrenosum is an overactive inflammatory reaction to inflammatory, traumatic, or malignant events.³

While the exact mechanism of development of Pyoderma Gangrenosum is not fully understood, it is linked to a phenomenon called “Pathergy” where ulcer formation, or worsening of pre-existing ulcers, is triggered following a minor skin injury, be it a needle-prick or surgery. This phenomenon occurs in up to 25-50% of affected individuals and is also the basis behind the aggravation of Pyoderma Gangrenosum following surgical debridement.^1,2

In up to 75% of cases, it is often associated with systemic diseases, most commonly Inflammatory Bowel Disease(IBD), followed by Rheumatoid arthritis, and, less frequently, blood-related cancers. Pyoderma Gangrenosum shares genetic similarities with IBD and is the second most common cutaneous manifestation of IBD, accounting for 0.5% of all cases.¹¹

How is it diagnosed?
Pyoderma Gangrenosum is diagnosed mainly based on the clinical picture and by exclusion of other causes with the use of diagnostic tools such as wound cultures, imaging and biopsy along with screening for Pyoderma Gangrenosum-associated diseases.

Key differential diagnoses

Differentiating Pyoderma Gangrenosum from infections

Common infectious mimics

• Bacterial cellulitis-A bacterial infection of skin and subcutaneous tissue.
• Cutaneous abscess
• Fungal or atypical mycobacterial infections
• Viral Infections-human immunodeficiency virus (HIV)

Cutaneous infections manifest with local signs of inflammation, such as pain, redness, warmth caused by bacteria, viruses, or fungi. This clinical picture overlaps with that of Pyoderma Gangrenosum, making it difficult to differentiate between the two conditions based on clinical examination alone.

The likelihood of a person having an infection before conducting any tests is high if they present with an ulcerative skin condition and elevated inflammatory parameters.⁹ Wound cultures and special stains remain as the mainstay diagnostic methods required to rule out infection. If the ulcer responds to antibiotics, and the wound culture test reveals positive to infectious organisms, it is more likely to be a skin infection. Simultaneously, if the ulceration is progressive despite adequate antibiotic therapy and tissue cultures are negative, Pyoderma Gangrenosum should be suspected.⁹

Key differences

Differentiating Pyoderma Gangrenosum from vasculitis

Vasculitis is the inflammation of the small blood vessels in the skin, often triggered by infections, medications, or autoimmune conditions. Wegener's granulomatosis is a form of vasculitis, which most frequently presents with a clinical picture of ulceration which closely resembles Pyoderma Gangrenosum.

Vasculitis mimics

• Cutaneous small vessel vasculitis (CSVV)-Wegener's granulomatosis
• ANCA-associated vasculitis
• Cryoglobulinemia

Key differences

Most diagnostic challenges faced in differentiating vasculitis are due to the overlap of the histological features of vasculitis and Pyoderma Gangrenosum. Therefore, guidelines such as the Delphi criteria prove as a good tool in the exclusion of vasculitis with a specificity of 90.48%.

Differentiating Pyoderma Gangrenosum from necrotising fasciitis

 Overview of necrotising fasciitis

NF is a severe, rapidly progressing soft tissue infection caused by Staphylococcus aureus. It is often called a “flesh-eating disease” due to the rapid necrosis of subcutaneous fat, superficial fascia, and deep fascia. It initially presents as cellulitis or induration, which progresses to patchy skin discolouration, followed by tense oedema and bullae formation.

One may also experience extreme pain which is out of proportion to the local skin changes, accompanied by early signs of systemic toxicity such as fever, tachycardia, leukocytosis and elevated creatinine kinase. NF can sometimes become fulminant and rapidly escalate to sepsis, requiring aggressive management with antibiotics and extensive surgical debridement.

Key differences

NF is a severe, rapidly progressing soft tissue infection caused by Staphylococcus aureus. It is often called a “flesh-eating disease” due to the rapid necrosis of subcutaneous fat, superficial fascia, and deep fascia. It initially presents as cellulitis or induration, which progresses to patchy skin discolouration, followed by tense oedema and bullae formation.

One may also experience extreme pain which is out of proportion to the local skin changes, accompanied by early signs of systemic toxicity such as fever, tachycardia, leukocytosis and elevated creatinine kinase. NF can sometimes become fulminant and rapidly escalate to sepsis, requiring aggressive management with antibiotics and extensive surgical debridement.

Distinguishing features

The fact that tissue necrosis and induration happen quickly, in hours as opposed to days, may aid in differentiating NF from Pyoderma Gangrenosum ⁸

Histopathology-NF presents with a collection of two types of immune cells called lymphocytes and histiocytes within the skin, along with necrosis, pus collections and oedema of superficial fascia, while Pyoderma Gangrenosum is predominantly characterised by neutrophil accumulation.

These findings are further supported by imaging modalities such as CT/MRI findings of gas and fluid collection within tissues, along with inflamed fascia. The gold standard for diagnosis of NF is direct inspection of fascial oedema and necrosis at surgery, which is absent in Pyoderma Gangrenosum.

Summary of key differences between Pyoderma Gangrenosum and its mimics

Summary

Pyoderma Gangrenosum is a rare disease that continues to be challenging due to its diagnostic and therapeutic pitfalls. It is crucial to maintain a systematic diagnostic approach. Therefore, Pyoderma Gangrenosum is a condition which prompts high clinical suspicion and careful exclusion, to prevent the physical, psychological, and social repercussions of misdiagnosis and inappropriate treatment. This can be achieved by visiting your dermatologist at the earliest, to ensure a smooth progress towards healing.