What is pyoderma gangrenosum?
Pyoderma gangrenosum presents as a rapidly enlarging, very painful ulcer. It is one of a group of autoinflammatory disorders known as neutrophilic dermatoses.
The name pyoderma gangrenosum is historical. The condition is not an infection (pyoderma), nor does it cause gangrene.
Who gets pyoderma gangrenosum?
Pyoderma gangrenosum is an uncommon disease that affects males and females of any age, but is more common in those aged over 50 years. It is thought to be a reaction to an internal disease or condition. Known associations include:
- Inflammatory bowel disease (ulcerative colitis and Crohn disease)
- Rheumatoid arthritis
- Myeloid blood dyscrasias including leukaemia
- Monoclonal gammopathy (usually IgA)
- Chronic active hepatitis
- Granulomatosis with polyangiitis
- PAPA syndrome
- Use of levamisole-adulterated cocaine
- Miscellaneous less common associations.
About 50% of those affected by pyoderma gangrenosum have none of the associated risk factors.
What causes pyoderma gangrenosum?
Pyoderma gangrenosum is an autoinflammatory disease (excessive response to an internal antigen) due to some form of neutrophil dysfunction. T lymphocytes and cytokines are involved. There may be a genetic predisoposition.
Drugs are occasionally implicated as triggers of pyoderma gangrenosum, especially cocaine, isotretinoin, propylthiouracil and sunitinib.
Clinical features of pyoderma gangrenosum
Pyoderma gangrenosum usually starts quite suddenly, often at the site of a minor injury. It may start as a small pustule, red bump or blood-blister. The skin then breaks down resulting in an ulcer. The ulcer can deepen and widen rapidly. Characteristically, the edge of the ulcer is purple and undermined. Pyoderma gangrenosum is usually very painful. Several ulcers may develop at the same time or over a period of months to years.
Untreated, the ulcers may continue to enlarge, persist unchanged or may slowly heal. Treatment is usually successful in arresting the process, but complete healing may take months. This is particularly true if there is underlying venous disease, another reason for leg ulcers.
Deep ulcers heal with scarring and this is sometimes with a characteristic cribriform or criss-cross pattern. A rare superficial bullous variant of pyoderma gangrenosum may heal without leaving a scar. This may be similar to or confused with acute febrile neutrophilic dermatosis (Sweet disease).
How is pyoderma gangrenosum diagnosed?
Pyoderma gangrenosum is diagnosed by its characteristic appearance. There is no specific test. The wound should be swabbed and cultured for micro-organisms, but these are not the cause of pyoderma gangrenosum. Biopsy may be necessary to rule out other causes of ulceration. Pyoderma gangrenosum characteristically results in a neutrophilic inflammatory infiltrate but this is not always present.
Mostly, blood tests are not particularly helpful. Some patients may have a positive ANCA (antineutrophil cytoplasmic antibody).
The pathergy test is usually positive (a skin prick test causing a papule, pustule or ulcer).
Sue et al proposed that pyoderma gangrenosum can be diagnosed if there are 2 major crtieria and 2 minor criteria as follows, but this is unconfirmed.
- Rapid progression of painful, necrolytic, cutaneous ulcer with an irregular, violaceous and undermined border
- Other causes of cutaneous ulceration have been excluded
- History suggestive of pathergy or clinical finding of cribriform scarring
- Systemic diseases associated with pyoderma gangrenosum
- Histopathological findings (sterile dermal neutrophilia +/- mixed inflammation +/- lymphocytic vasculitis
- Treatment response (rapid response to systemic steroid treatment)
Treatment of pyoderma gangrenosum
Treatment is non-surgical. The necrotic tissue should be gently removed. Wide surgical debridement should be avoided during the active stage of pyoderma gangrenosum because it may result in enlargement of the ulcer. Skin grafting and other surgical procedures may be performed when the active disease phase has settled, with care to minimise trauma.
Often conventional antibiotics such as flucloxacillin are prescribed prior to making the correct diagnosis. These may be continued if bacteria are cultured in the wound (secondary wound infection) or there is surrounding cellulitis (red hot painful skin), but they are not helpful for uncomplicated pyoderma gangrenosum.
Small ulcers are often treated with:
- Potent topical steroid creams
- Tacrolimus ointment
- Intralesional steroid injections
- Special dressings
- Oral anti-inflammatory antibiotics such as doxycycline or minocycline
- If tolerated, careful compression bandaging to reduce swelling.
Systemic treatment for larger ulcers due to pyoderma gangrenosum may include:
- Oral prednisone for several weeks or longer, or intermittent intravenous methyl prednisolone for 3–5 days
- Biologic agents: success with infliximab, adalimumab, etanercept and ustekinumab is reported in a small number of cases (used off-label).
Other therapies may include:
- Mycophenolate mofetil
- Potassium iodide solution
- Intravenous immunoglobulins and plasmapheresis.
Expert wound care is essential.
Outlook or prognosis for pyoderma gangrenosum is unpredictable.