Pyoderma gangrenosum (also known as PG) is a rare condition that causes large, painful lesions on the skin, which can grow and worsen quickly if left untreated. The exact cause of PG is unknown, though research has shown that the condition is likely to originate from problems in the immune system. A range of first-line treatments has now been developed to target the immune system directly to prevent the formation of the skin lesions. This article will explain two of the main treatments for pyoderma gangrenosum, corticosteroids and immunosuppressive drugs, and their effectiveness at treating the skin condition, as well as any side effects or concerns to look out for when undergoing treatment.

Introduction

What is pyoderma gangrenosum?

Pyoderma gangrenosum is a skin disease which leads to the development of painful, large lesions and ulcers on the skin.¹ The lesions begin as a small bump that grows and develops quickly, usually appearing on the legs. Although the condition appears mainly on the skin, the cause of the pyoderma gangrenosum is usually not due to factors affecting the skin directly, such as infections, but instead from a pre-existing condition or disease affecting the body.

The exact cause of the disease remains unknown, though the disease is often seen in people who have autoimmune conditions.² Some studies suggest that autoimmune disorders may contribute significantly to ulcer formation in pyoderma gangrenosum as the immune system attacks the body’s own tissues.

Who is affected?

The condition most commonly affects individuals between 40 and 60 years old, and often appears alongside autoimmune diseases and inflammatory conditions such as:

• Rheumatoid arthritis
• Ulcerative colitis
• Inflammatory bowel disease
• Systemic lupus erythematosus

Individuals with blood malignancies such as leukaemia, lymphoma, and multiple myeloma are also more susceptible to developing pyoderma gangrenosum lesions.

If pyoderma gangrenosum is left untreated, the ulcers can quickly worsen and enlarge in size. If the ulcers enlarge without treatment, they can become extremely painful, significantly impacting quality of life. Additionally, it is important to begin treatment as soon as possible, as first-line treatment options usually stop the ulcers from enlarging, but do not make the process of healing quicker, which can take multiple months.

Recognising pyoderma gangrenosum

Symptoms and signs to look out for

The main sign of pyoderma gangrenosum is the appearance of large, painful ulcers, though there are some key signs which are important to look out for, such as:

• An exaggerated response to minor skin injuries, such as small cuts or bumps, or the worsening of an existing wound without any clear reason (pathergy)
• Small spots or bumps on the skin, which quickly deepen and widen over the course of a few days into larger, more severe ulcers 
• Pain associated with the ulcers may be out of proportion to the size or appearance of the ulcer itself

The ulcers associated with pyoderma gangrenosum often have a characteristic purple outer edge and don’t appear to heal or improve over time, even with standard treatments such as ointments or creams. If multiple ulcers are present on the skin, they may combine and grow into one larger ulcer.

Diagnosis of pyoderma gangrenosum

As there is no specific test for pyoderma gangrenosum specifically, healthcare professionals will usually rule out any other conditions which have similar symptoms to the condition - this is known as a diagnosis of exclusion. These tests can include:

• Blood tests
• Chest x-rays
• Colon exams
• A skin biopsy may also be conducted, where a portion of the ulcer is removed for testing in a lab³

Doctors may also refer individuals to a dermatologist, a doctor who specialises in skin conditions. The earlier that pyoderma gangrenosum is identified, the easier and more effective treatments can be for stopping and preventing the growth of any ulcers.

Corticosteroids and immunosuppressants: First-line treatments for pyoderma gangrenosum

Although the exact cause of pyoderma gangrenosum is unknown, first-line treatments for the condition mainly aim to reduce inflammation and target the immune system, which is likely the cause of the painful ulcers. Of these treatments, corticosteroids and immunosuppressants are the most common options to stop and reduce the growth of ulcers.

Corticosteroids: The first choice for fast relief

Corticosteroids are the most commonly prescribed treatment option for individuals with pyoderma gangrenosum.⁴ These drugs work by reducing inflammation in the ulcers, whilst also suppressing the immune system to prevent any further tissue damage caused by any autoimmune conditions.³ Corticosteroids are taken through a variety of routes, including:

• Orally as a pill - this method suppresses the immune system across the entire body, and is usually taken by individuals who have severe or widespread ulcers across their body
• For milder cases where ulcers are smaller or early in development, corticosteroid creams or ointments are applied directly onto the skin - this method avoids affecting the entire immune system and is typically safer than taking corticosteroids orally
• In more severe cases of pyoderma gangrenosum, corticosteroids can be administered as an injection directly into the body- this method provides a very strong anti-inflammatory effect throughout the entire body, and is useful in cases where ulcers are widespread or resistant to other forms of corticosteroid treatment

Typically, individuals see an improvement in their ulcers within 1-2 weeks of taking corticosteroids, though this may vary depending on the severity of the disease.

Immunosuppressants: controlling inflammation beyond steroids

Immunosuppressants are drugs which can prevent the immune system from attacking healthy tissues in the body.⁴ For individuals who do not respond well to corticosteroids or who require long-term treatment to prevent flare-ups, immunosuppressants can be a valuable second-line option. These drugs are often used in combination with corticosteroids to reduce the required steroid dose and minimise side effects.⁴

Immunosuppressants help reduce the growth of ulcers by:

• Dampening the immune response, reducing the risk of any further autoimmune reactions, which could worsen or trigger the formation of ulcers
• Reducing inflammation in the tissues, which can contribute to the pain and tissue damage caused by ulcers
• Allowing the ulcers to heal gradually by preventing any further growth or worsening 

In some cases, especially in severe or treatment-resistant forms of the condition, biologics, a newer class of immunosuppressive drugs, may be considered.⁴ These include drugs such as infliximab or adalimumab, which target specific parts of the immune system involved in inflammation.

Side effects

Corticosteroids and immunosuppressants are effective treatments for pyoderma gangrenosum but come with potential side effects. Both drugs increase the risk of infections by suppressing the immune system. Corticosteroids can cause weight gain, fluid retention, thinning skin, high blood pressure, and osteoporosis with long-term use. They can also lead to mood swings, anxiety, and gastrointestinal issues.

Immunosuppressants can affect liver and kidney function, which could lead to the need for regular blood tests, and also suppress bone marrow, leading to blood disorders. While rare, long-term use can increase the risk of certain cancers. Both medications need careful monitoring to manage these risks and ensure effective treatment.

Conclusion

Pyoderma gangrenosum can be a difficult and distressing condition, but with quick identification, diagnosis and early treatment, the progression of the ulcers can be controlled. Early intervention with first-line treatments such as corticosteroids and immunosuppressants can help prevent severe tissue damage and scarring whilst also relieving pain and inflammation.

Because the disease can recur or flare up over time, especially if underlying conditions are still active, ongoing management by a healthcare professional is key. This may include regular check-ups, adjusting medication dosages, and treating any coexisting autoimmune or inflammatory conditions.

Summary

Pyoderma gangrenosum is a rare condition that causes rapidly expanding ulcers on the skin, often tied to autoimmune disorders. Although the cause isn't fully understood, it is believed to result from immune system irregularities. The main treatments aim to reduce inflammation and regulate immune function, primarily through corticosteroids and immunosuppressants. Corticosteroids, available in oral, topical, or injectable forms, offer quick relief but can lead to side effects like weight gain, high blood pressure, and emotional shifts. Immunosuppressants, used either when corticosteroids are ineffective or for long-term management, reduce immune activity and inflammation. These medications can impact liver and kidney function and may require routine monitoring. Both treatment options are crucial in managing pyoderma gangrenosum, but close monitoring of side effects is important. Prompt treatment is essential to avoid serious complications, and ongoing medical follow-up is key for long-term management.