Abstract

Pyoderma gangrenosum is a condition that causes tissue to become necrotic, causing deep ulcers that usually occur on the legs. When they occur, they can lead to chronic wounds. Ulcers usually initially look like small bug bites or papules, and they progress to larger ulcers. Though the wounds rarely lead to death, they can cause pain and scarring.

The disease was identified in 1930. It affects approximately 1 person in 100,000 in the population. Though it can affect people of any age, it mostly affects people in their 40s and 50s.

Types

There are two main types of pyoderma gangrenosum:

- the 'typical' ulcerative form, which occurs in the legs

- an 'atypical' form that is more superficial and occurs in the hands and other parts of the body

Other variations are:

- Peristomal pyoderma gangrenosum comprises 15% of all cases of pyoderma

- Bullous pyoderma gangrenosum

- Pustular pyoderma gangrenosum

- pyoderma gangrenosum

Causes

Though the cause is not well understood, the disease is thought to be due to immune system dysfunction, and particularly improper functioning of neutrophils. In support of an immune cause, a variety of immune mediators such as IL-8, IL-1β, IL-6, interferon (IFN)-γ, G-CSF, TNF, matrix metallopeptidase (MMP)-9, MMP-10, and Elafin have all been reported to be elevated in patients with pyoderma gangrenosum.

Also in support of an immune cause is the finding that at least half of all pyoderma gangrenosum patients suffer from immune-mediated diseases. For instance, ulcerative colitis, rheumatoid arthritis, and multiple myeloma (MM) have all been associated with pyoderma gangrenosum. It can also be part of a syndromes such as PAPA syndrome.

One hallmark of pyoderma gangrenosum is pathergy, which is the appearance of new lesions at sites of trauma.

Causes | Associations

The following are conditions commonly associated with pyoderma gangrenosum:

- Inflammatory bowel disease:

- Ulcerative colitis

- Crohn's disease

- Arthritides:

- Rheumatoid arthritis

- Seronegative arthritis

- Hematological disease:

- Myelocytic leukemia

- Hairy cell leukemia

- Myelofibrosis

- Myeloid metaplasia

- Monoclonal gammopathy

- Autoinflammatory disease:

- Pyogenic sterile arthritis, pyoderma gangrenosum, and acne syndrome (PAPA syndrome)

- Granulomatosis with polyangiitis

Diagnosis

Often a diagnosis of exclusion, skin biopsy shows a neutrophillic inflammatory infiltrate.

Treatment

First-line therapy for disseminated or localized instances of pyoderma gangrenosum is systemic treatment by corticosteroids and ciclosporin. Topical application of clobetasol, mupirocin, and gentamicin alternated with tacrolimus can be effective.

Pyoderma gangrenosum ulcers demonstrate pathergy, that is, a worsening in response to minor trauma or surgical debridement. Significant care should be taken with dressing changes to prevent potentially rapid wound growth. Many patients respond differently to different types of treatment, for example some benefit from a moist environment, so treatment should be carefully evaluated at each stage.

Papules that begin as small "spouts" can be treated with Dakins Solution to prevent infection and wound clusters also benefit from this disinfectant. Wet to dry applications of Dakins can defeat spread of interior infection. Heavy drainage can be offset with Coban dressings. Grafting is not recommended due to tissue necrosis.

If ineffective, alternative therapeutic procedures include systemic treatment with corticosteroids and mycophenolate mofetil; mycophenolate mofetil and ciclosporin; tacrolimus; thalidomide; infliximab; or plasmapheresis.

There is currently a phase III trial for the use of the IL-1B modulating agent gevokizumab in treating the ulcers of pyoderma gangrenosum.