Overview

Pyoderma gangrenosum (PG) is a dermatosis characterized by sterile inflammation primarily involving neutrophils. It is characterized by recurring skin ulcers that produce mucopurulent or hemorrhagic exudate. These excruciating sores appear with indented bluish edges and redness around them. PG is often linked to conditions such as inflammatory bowel disease, rheumatic disorder, or neoplasia.¹

It can occur on any body part – beginning without warning or after surgery. Pyoderma Gangrenosum lesions on the leg may take longer to heal because wounds in the leg tend to heal slower than other body parts, especially when lower leg swelling is present. PG can cause a lot of pain and worsen quickly, so receiving the right diagnosis and treatment plan is crucial.²

The specific cause for pyoderma gangrenosum is multifactorial. The state is non-infectious and non-contagious. It is frequently linked to conditions like ulcerative colitis, Crohn's disease, and arthritis, which are autoimmune diseases. It has possibly been linked to genetic factors.³

Moreover, pyoderma gangrenosum frequently occurs following skin injury (pathergy), such as trauma or surgery. At times, pyoderma gangrenosum can develop close to a surgical incision (for example, a stoma site). 

Risk factors

Pyoderma gangrenosum is a rare disease affecting males and females of any age but is more common in those aged over 50 years. It is often linked to an existing disease or condition within the body. Its known associations include:

1. Ulcerative colitis and Crohn's disease (inflammatory bowel disease)
2. Rheumatoid arthritis
3. Myeloid blood dyscrasias including leukaemia
4. Monoclonal gammopathy (usually IgA)
5. Chronic active hepatitis
6. Granulomatosis with polyangiitis
7. PAPA (an abbreviation for Pyogenic Arthritis, Pyoderma gangrenosum, and Acne) syndrome
8. Behçet disease
9. Use of levamisole-adulterated cocaine
10. Miscellaneous less-common associations

Roughly 50% of individuals with pyoderma gangrenosum do not have any of the related risk factors.

Classification

The most prevalent type of PG is typically seen as a quickly advancing ulcer, often causing severe pain, and is characterised by a purple edge that is eroded.⁶

Bulbous PG

This form manifests as quickly developing shallow blisters, often painful, and large blisters appearing in clusters, often merging on the arms. From a histological perspective, this shows resemblances to Sweet's syndrome. A search for a haematological malignancy should be conducted as they are found in as many as 70% of cases.

Pustular PG

This form is frequently observed in cases of inflammatory bowel disease flare-ups, and is characterized by painful pustules usually found on the extensor surfaces.

Granulomatus superficial PG

Also referred to as vegetative pyoderma gangrenosum, this type typically advances at a slower pace and manifests with, ulcerated sores. These patients typically do not have a systemic condition and generally do not need systemic treatment as a result.

Peristomal PG 

This particular form likely occurs due to a pathergic reaction to trauma caused by fecal irritation or as a result of devices on the skin and is most commonly observed in individuals with inflammatory bowel disease who possess a stoma.

Malignant pyoderma

This is a significant yet infrequent clinical subtype characterized by destructive ulceration mainly impacting the upper torso, head, and neck. Lesions lack the purple border seen in classical PG and the condition is not linked to systemic illness.

Clinical features

PG is most frequently found on the lower legs, particularly in the pretibial region. PG has also been seen in various other body locations such as the breast, hand, trunk, head and neck, and peristomal skin. Manifestations outside the skin involve the mucosa of the upper airway, eye, and genital area, sterile pulmonary neutrophilic infiltrates, spleen infiltrates, and neutrophilic myositis. Another extracutaneous manifestation of the disease is sterile cortical osteolysis observed near PG ulcers.⁷

Pyoderma gangrenosum typically begins abruptly, frequently at the location of a small wound.

It could begin as a tiny pimple, crimson lump, or blood-filled sore, frequently mistaken for a bug bite. An ulcer is formed as a result of the breakdown of the skin. The ulcer may quickly become wider and deeper. Typically, the border of the ulcer appears purple and sunken. It usually results in significant discomfort.

Multiple ulcers can occur simultaneously or gradually over months to years. If left untreated, the ulcers can either grow bigger, stay the same, or heal gradually. Therapy often effectively halts the progression, although full recovery may require several months. This is especially the case when there is an undiscovered venous disorder, another cause of leg ulcers. Deep wounds may recover with scarring, occasionally displaying a distinct cribriform or atrophic look.⁸

The following are the characteristics of pyoderma gangrenosum associated with inflammatory bowel disease:

• Pyoderma gangrenosum is the second most frequently seen skin condition with Inflammatory Bowel Disease (IBD), affecting 1-3% of patients
• It occurs more frequently as a complication of ulcerative colitis than in Crohn's disease
• IBD-related pyoderma gangrenosum is linked to mildly symptomatic IBD, erythema nodosum, and being female
• More than 50% of patients experiencing pyoderma gangrenosum have an active underlying bowel disease
• Pyoderma gangrenosum is commonly found on the lower limb and can also occur around a stoma site
• Pyoderma gangrenosum can manifest as ulcerative or pustular forms

Diagnosis

1. Pyoderma gangrenosum is identified by its distinct appearance and intense pain. Typically, the pathergy test results in a positive outcome, showing a papule, pustule, or ulcer when the skin is pricked. Swab the wound and send for microbial culture, although microorganisms are not responsible for pyoderma gangrenosum
2. A biopsy might be needed to eliminate other potential reasons for ulceration. While undergoing treatment, the neutrophilic inflammatory infiltrate associated with Pyoderma gangrenosum may not be present
3. In general, blood tests are not very useful. Certain individuals may test positive for ANCA (antineutrophil cytoplasmic antibody)⁸
4. Other tests: bone marrow sampling, Proctoscopy, Colonoscopy⁹

The maverakis standards or guidelines

The standards established through a Delphi consensus process in 2018 replaced the Su criteria, now only requiring a single primary criterion for diagnosing pyoderma gangrenosum (neutrophilic infiltrate). Having four or more out of the eight minor criteria results in an 86% sensitivity and a 90% specificity for diagnosing pyoderma gangrenosum.⁸

Major characteristics

The ulcer edge should exhibit a neutrophilic infiltrate on histopathological examination.

Minor characteristics

1. Prevention of infection
2. A phenomenon known as pathergy
3. The past of either inflammatory bowel disease or inflammatory arthritis
4. The history of a sore developing a papule, vesicle, or pustule and then ulcerating in four days
5. Redness around the wound, a border that is eroded, and sensitivity at the site of the ulcer
6. Several ulcers, with at least one located on the front part of the lower leg
7. Creased or wrinkled marks on paper-like tissue at the location where the ulcer has healed
8. The ulcer reduced in size after starting immunosuppressive medication for one month

Treatment

Management of pyoderma gangrenosum primarily involves non-surgical approaches. Gently remove the necrotic tissue. It is recommended to refrain from wide surgical debridement when pyoderma gangrenosum is active as it could cause the ulcer to expand. Skin grafting and other surgeries can be done once the acute phase of the illness has passed, taking precautions to reduce injury.

Frequently, traditional antibiotics like flucloxacillin are given before an accurate diagnosis is made. If bacteria grow in the wound (resulting in a secondary wound infection) or if there is cellulitis in the surrounding area (skin that is red, hot, and painful), the treatments may need to be continued. However, they are not effective for treating uncomplicated cases of pyoderma gangrenosum.⁸

Other treatments include:

1. For initial or mild pyoderma gangrenosum cases:
   • Corticosteroids are drugs that have anti-inflammatory properties. They could come in the form of a cream or an ointment that is applied directly to your ulcers, or as pills or tablets that are ingested with water. Some examples are cortisone and prednisone. Potential side effects include enhanced hunger, increased weight gain, alterations in mood, skin breakouts, and difficulty sleeping⁹
   • Nonsteroidal anti-inflammatory drugs (NSAIDs) are oral medications taken with water to alleviate aches and pains. Some examples are aspirin and ibuprofen. Possible side effects include flatulence and discomfort, a swollen abdomen, stomach ache,nausea and vomiting, and changes in bowel movements
   • Silver sulfadiazine cream is an antibiotic ointment prescribed for the treatment of second or third-degree burns as well as for the prevention and treatment of severe infections. Possible side effects can consist of itching, fever, chills, skin rashes, and heightened susceptibility to the sun or ultraviolet (UV) light
2. In cases of severe pyoderma gangrenosum
   • Medications that suppress the immune system: These drugs decrease the ability of your immune system to attack your own body. Some examples are mycophenolate and cyclosporine
   • Biological agents: These drugs are aimed at specific inflammatory proteins. Some examples are infliximab, adalimumab and ustekinumab
   • Hyperbaric oxygen therapy involves providing 100% oxygen in a specialized chamber to treat wounds and other medical issues. As you inhale, it enables you to take in more oxygen, aiding in the healing process of your body tissues

Summary

In short, pyoderma gangrenosum is a rare skin condition characterized by recurring ulcers that produce mucopurulent or hemorrhagic exudate. It is linked to inflammatory conditions and can cause severe pain. Medication is typically used to inhibit the immune system during treatment. Timely identification and treatment are crucial for effectively managing the situation.