Pyoderma gangrenosum

Pyoderma gangrenosum is an uncommon cause of very painful skin ulceration. It may affect any part of the skin, but the lower legs are the most common site. Pyoderma gangrenosum is classified as a neutrophilic dermatosis and is considered a reaction to an internal disease or condition. It affects males and females of any age, but is more common in those aged over 50 years.

The name pyoderma gangrenosum is historical. The condition is not an infection (pyoderma), nor does it cause gangrene.

Pyoderma gangrenosum

What are neutrophilic dermatoses?

Neutrophilic dermatoses are skin conditions characterised by dense infiltration of inflammatory cells (neutrophils) in the affected tissue. They arise in reaction to some underlying systemic illness. A neutrophilic dermatosis may be seen in isolation or more than one type may occur in the same individual.

Neutrophilic dermatoses often arise at the site of injury such as a needle prick, biopsy or insect bite. This reaction to injury is known as Koebner phenomenon, pathergy or isomorphic response.

Other neutrophilic dermatoses include:

• Sweet syndrome
• Neutrophilic dermatosis of the hands
• Neutrophilic eccrine hidradenitis
• Erythema elevatum diutinum
• Behcet disease
• Bowel bypass syndrome (bowel-associated dermatitis-arthritis syndrome)

Who is at risk of pyoderma gangrenosum?

Pyoderma gangrenosum often affects a person with an underlying internal disease such as:

• Inflammatory bowel diseases (ulcerative colitis and Crohn disease)
• Rheumatoid arthritis
• Myeloid blood dyscrasias
• Chronic active hepatitis.
• Wegener granulomatosis
• PAPA syndrome
• Miscellaneous less common associations.

However, about 50% of those affected by pyoderma gangrenosum have none of the associated risk factors.

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 as it enlarges. It is usually very painful. Several ulcers may develop at the same time.

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 Sweet disease, a related inflammatory skin condition.

Investigations in pyoderma gangrenosum

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).

Treatment of pyoderma gangrenosum

Treatment is non-surgical. The necrotic tissue should be gently removed. Wide surgical debridement should be avoided because it may result in enlargement of the ulcer.

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 infection) or there is surrounding cellulitis (red hot painful skin), but they are not helpful for uncomplicated pyoderma gangrenosum.

Small ulcers are best treated with:

• Potent topical steroid creams
• Intralesional steroid injections
• Special dressings eg. silver sulfadiazine cream or hydrocolloids.
• Oral anti-inflammatory antibiotics such as dapsone or minocycline.
• If tolerated, careful compression bandaging for swollen legs
• Potassium iodide solution
• Short-term nicotine as 0.5% in cetomacrogol cream, gum, patches, snuff

More severe disease requires immunosuppressive therapy:

• Tacrolimus ointment is an immune modulating drug that inhibits calcineurin and has been reported to improve pyoderma gangrenosum. It is not yet available in New Zealand (2012).
• Oral steroids. These have important side effects and should be taken carefully according to the doctor's instructions. They may be required for several months in high dose.
• Ciclosporin. This does not have PHARMAC funding in New Zealand for this indication. It also has important side effects.
• Methotrexate.
• Cyclophosphamide .
• Mycophenolate mofetil.
• Intravenous immunoglobulins and plasmapheresis

Treatment with the biological agent infliximab has also been reported to be effective in a small clinical trial of patients with pyoderma gangrenosum.

Outlook or prognosis for pyoderma gangrenosum is unpredictable.