Pyoderma gangrenosum is a rare and painful skin condition that causes large, rapidly developing ulcers with distinctive purple or blue edges. Despite its name suggesting infection or gangrene, this disorder is neither infectious nor contagious, but rather stems from problems with the immune system. Understanding this challenging condition can help patients and their families navigate the complex journey from diagnosis to treatment.

Epidemiology

Pyoderma gangrenosum is an uncommon condition that affects approximately 1 in every 100,000 people in the United States each year.^[1] The rarity of this disorder means that many healthcare professionals may never encounter it during their careers, which can contribute to delays in diagnosis and treatment.

The condition can appear at any age, from childhood through elderly years, though it predominantly affects adults. The age range for development extends from about 11 to 89 years, with the highest occurrence in people during their fourth and fifth decades of life.^[2] Most commonly, pyoderma gangrenosum affects women between the ages of 20 and 50 years old.^[3] Despite affecting both sexes, there appears to be a slight female predominance in the overall distribution of cases.

Children account for only 3 to 5 percent of all pyoderma gangrenosum cases, making it extremely rare in pediatric populations.^[2] When it does occur in children, the clinical features and progression of the disease are generally similar to those seen in adults.

Causes

The exact cause of pyoderma gangrenosum remains unknown to medical science. However, researchers believe the condition results from dysfunction in the immune system, particularly involving problems with how neutrophils (a type of white blood cell that fights infection) function and migrate through the body.^[1] This places pyoderma gangrenosum in a category of conditions known as neutrophilic dermatoses, which are characterized by excessive inflammation driven by neutrophils.

Studies have identified several potential mechanisms involved in the disease process. Some lesions show a buildup of clonal T-cells, which are immune cells that normally help protect the body from threats. Additionally, structures called inflammasomes, which are part of the body’s innate immune signaling system, may play a role in attracting neutrophils to the affected areas.^[2] Certain genetic mutations have been associated with pyoderma gangrenosum, including changes in a gene called Janus kinase 2, which is involved in producing various signaling molecules called cytokines.

Research has found elevated levels of inflammatory substances in pyoderma gangrenosum lesions, including interleukin-8, interleukin-1β, interleukin-6, and other immune mediators.^[5] These findings suggest that abnormal cytokine signaling by immune cells is a key component of how the disease develops and progresses.

Some studies suggest that pyoderma gangrenosum may be passed down through families, indicating a possible genetic predisposition.^[1] However, more research is needed to fully understand the hereditary aspects of this condition.

It’s important to understand that despite the misleading name, pyoderma gangrenosum is not caused by infection, and it does not involve actual gangrene (tissue death due to lack of blood supply).^[2] The condition is not contagious and cannot be spread from person to person through skin contact or any other means.

Risk Factors

More than half of people with pyoderma gangrenosum have other underlying health conditions, making certain groups significantly more vulnerable to developing this skin disorder.^[1] Understanding these associations can help healthcare providers identify at-risk patients and maintain appropriate vigilance.

Inflammatory bowel disease represents one of the strongest associations with pyoderma gangrenosum. The condition occurs in 5 to 12 percent of people with ulcerative colitis and in 1 to 2 percent of those with Crohn’s disease.^[2] Interestingly, the development of pyoderma gangrenosum doesn’t always correlate with the severity of the bowel disease, and the skin condition doesn’t necessarily improve when the inflammatory bowel disease is treated. Among patients with inflammatory bowel disease who develop pyoderma gangrenosum, the skin lesions most commonly appear on the lower extremities.

Arthritis conditions also increase the risk of developing pyoderma gangrenosum. Both rheumatoid arthritis and seronegative arthritis (types of inflammatory joint disease) are frequently associated with this skin condition.^[4] In one study of 103 patients with pyoderma gangrenosum, 19 percent had seronegative arthritis.

Blood disorders constitute another major risk category. Approximately 20 percent of patients with pyoderma gangrenosum have hematologic disorders, including various types of leukemia (such as myelocytic leukemia and hairy cell leukemia), myelofibrosis, myeloid metaplasia, and monoclonal gammopathy.^[2] Both solid tumors and hematologic malignancies have been linked to the development of pyoderma gangrenosum.

Other systemic conditions associated with increased risk include chronic active hepatitis, granulomatosis with polyangiitis, Behçet disease, and a rare genetic condition called PAPA syndrome (pyogenic arthritis, pyoderma gangrenosum and acne syndrome).^[4] PAPA syndrome is associated with mutations in a specific gene called PSTPIP1.

About half of people who develop pyoderma gangrenosum have none of these identified risk factors, meaning the condition can appear in previously healthy individuals with no apparent predisposing conditions.^[4]

Symptoms

Pyoderma gangrenosum typically begins suddenly, often catching patients off guard with its rapid progression. The condition usually starts with a small bump, spot, pustule (pus-filled bump), red bump, or blood blister on the skin.^[3] Many people initially mistake this early lesion for an insect bite, such as a spider bite or mosquito bite, because of its similar appearance.

Within days, this small lesion can transform dramatically. The skin breaks down, creating an opening that rapidly expands into a large, painful open sore called an ulcer. This ulcer can deepen and widen at an alarming rate, sometimes growing significantly larger in just a matter of days.^[4] The speed of this progression is one of the hallmark features that distinguishes pyoderma gangrenosum from other types of skin ulcers.

The appearance of pyoderma gangrenosum ulcers has distinctive characteristics that help with diagnosis. The edge of the ulcer typically looks purple or blue, creating what doctors call a “violaceous” border. On white skin, this purple or blue coloration is quite visible, while on brown or black skin, the area around the ulcer may simply appear darker than the surrounding skin.^[6] The border of the ulcer is often described as “undermined,” meaning it has an overhanging edge that extends beyond the visible wound.

Pain is a dominant and distressing symptom for most patients with pyoderma gangrenosum. The ulcers are usually very painful, and this severe pain can significantly disrupt sleep and daily activities.^[4] The intensity of the pain often seems disproportionate to what might be expected from the appearance of the wound alone.

While the legs are the most common location for pyoderma gangrenosum ulcers, the condition can appear anywhere on the body, including the arms, chest, genitals, neck, and face.^[3] The number of ulcers can vary considerably. Mild cases may have just one ulcer, while severe cases can develop multiple ulcers. Sometimes, if two or more ulcers are close together, they may grow and merge into one larger ulceration.

The ulcers typically leak fluid or pus, which can make wound care challenging and increase the risk of secondary infection. Beyond the skin manifestations, some patients experience additional symptoms including stiff joints, aching and painful muscles, and fever.^[6] These systemic symptoms reflect the inflammatory nature of the condition and its connection to immune system dysfunction.

A particularly troubling feature of pyoderma gangrenosum is a phenomenon called pathergy, which occurs in about 30 percent of affected patients.^[8] Pathergy means that new ulcers can develop at sites where the skin experiences trauma or injury. This can include seemingly minor injuries, surgical incisions, or even sites where skin biopsies were taken. Sometimes pyoderma gangrenosum appears around surgical openings, such as a stoma site (where part of the bowel is brought through an opening in the abdomen), creating what’s known as peristomal pyoderma gangrenosum.

Prevention

Because the exact cause of pyoderma gangrenosum remains unclear, there is no guaranteed way to prevent the first occurrence of the condition. However, for people who have already been diagnosed with pyoderma gangrenosum, certain preventive strategies can help reduce the risk of developing new ulcers.^[1]

The most important preventive measure involves protecting the skin from injury and trauma. Given the pathergy phenomenon—where new lesions develop at sites of skin injury—avoiding cuts, scrapes, bumps, and other forms of skin trauma becomes crucial for people with pyoderma gangrenosum. This means taking extra care during daily activities and being mindful of situations that could lead to skin injury.

For patients with pyoderma gangrenosum, surgical procedures require special consideration. Surgery itself can trigger new ulcers at the surgical site, making it important for patients to inform their surgical team about their condition before any planned procedures. In some cases, preventive treatment with immunosuppressive medications may be recommended before and after surgery to reduce the risk of pathergy.^[9]

Managing underlying associated conditions may help prevent or reduce flares of pyoderma gangrenosum. If you have inflammatory bowel disease, rheumatoid arthritis, or another condition linked to pyoderma gangrenosum, working with your healthcare team to keep that condition well-controlled may potentially reduce the likelihood of developing skin problems. However, it’s important to note that controlling the associated disease doesn’t always prevent pyoderma gangrenosum from occurring or recurring.

People with pyoderma gangrenosum should also be aware of medications that can potentially trigger the condition. If you need to take a drug that has been associated with pyoderma gangrenosum, discuss this with your doctor so appropriate monitoring can be arranged.

Regular follow-up with a dermatologist or other healthcare provider familiar with pyoderma gangrenosum is valuable for people with a history of this condition. Early detection of new lesions allows for prompt treatment, which may prevent the ulcers from becoming as large or severe as they might otherwise become.

Pathophysiology

The pathophysiology of pyoderma gangrenosum—meaning how the disease process unfolds in the body—involves complex interactions between genetic factors, immune cells, and inflammatory signaling pathways. While researchers continue to uncover new details, the current understanding points to this being primarily an autoinflammatory disease, meaning it results from an excessive inflammatory response to internal triggers rather than external pathogens.

At the cellular level, pyoderma gangrenosum involves significant dysfunction of neutrophils, the white blood cells that normally help fight infections. In people with this condition, neutrophils behave abnormally, accumulating in large numbers in the skin and contributing to tissue damage rather than tissue healing. When doctors examine tissue samples from pyoderma gangrenosum lesions under a microscope, they typically find an abundance of these neutrophils infiltrating the affected area.

The immune system’s signaling molecules, called cytokines, play a central role in the disease process. Abnormal cytokine production and signaling by T cells (a type of immune cell) and macrophages (cells that normally help clear debris and fight infection) drive the inflammatory cascade seen in pyoderma gangrenosum.^[2] Specifically, elevated levels of several inflammatory mediators have been found in pyoderma gangrenosum lesions, including interleukin-23, various matrix metalloproteinases, and other pro-inflammatory substances.

Some cases of pyoderma gangrenosum involve genetic mutations that affect immune function. For example, mutations in the Janus kinase 2 gene can alter the production of multiple cytokines, potentially setting the stage for the inflammatory dysregulation seen in this condition. In PAPA syndrome, mutations in the PSTPIP1 gene lead to a hereditary form of autoinflammation that includes pyoderma gangrenosum as one of its features.

The phenomenon of pathergy—where trauma triggers new lesions—provides insight into the disease mechanism. Normal wound healing involves a carefully orchestrated inflammatory response that ultimately leads to tissue repair. In pyoderma gangrenosum, the inflammatory response becomes dysregulated and excessive, causing tissue destruction rather than healing. When injury occurs to the skin of someone with pyoderma gangrenosum, instead of triggering normal healing, it can paradoxically initiate the destructive inflammatory cascade that creates a new ulcer.

The characteristic appearance of pyoderma gangrenosum ulcers—with their purple, undermined borders and rapid expansion—reflects the intense inflammatory process occurring at the edges of the wound. The purple coloration results from inflammation and altered blood flow in the area, while the undermined border develops as the inflammatory process extends beneath the surface of apparently normal-looking skin adjacent to the visible ulcer.

Some patients with pyoderma gangrenosum develop involvement of organs beyond the skin, demonstrating that the inflammatory process can be systemic. Sterile neutrophilic infiltrates (accumulations of neutrophils without actual infection) have been found in the lungs, heart, central nervous system, gastrointestinal tract, eyes, liver, spleen, bones, and lymph nodes of some affected individuals.^[8] This highlights that pyoderma gangrenosum is not simply a skin disease but rather part of a more generalized inflammatory condition.