Pyoderma gangrenosum

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.

It is characterised by a full-thickness ulcer with blue undermined borders and by pathergy, the appearance of new lesions after local trauma [1].

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 half of those affected by pyoderma gangrenosum have none of the associated risk factors.

Pyoderma gangrenosum associated with inflammatory bowel disease

IBD-associated pyoderma gangrenosum has the following characteristics [5,6]:

• Pyoderma gangrenosum represents the second-most common cutaneous manifestation of IBD (1–3%).
• It is more commonly a complication of ulcerative colitis compared to Crohn disease.
• IBD-associated pyoderma gangrenosum is associated with clinically mild IBD, erythema nodosum, and female sex.
• Underlying bowel disease is active in over half of the patients at the time of an episode of pyoderma gangrenosum
• Pyoderma gangrenosum is most often located on the lower extremity and can be periostomal.
• Ulcerative and pustular types of pyoderma gangrenosum may arise.

What causes pyoderma gangrenosum?

Pyoderma gangrenosum is an autoinflammatory disease (excessive response to an internal antigen) due to some form of neutrophil dysfunction [1]. T lymphocytes and cytokines are involved. There may be a genetic predisposition. 

Drugs are occasionally implicated as triggers of pyoderma gangrenosum, especially cocaine, isotretinoin, propylthiouracil and sunitinib (a protein kinase inhibitor).

What are the 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 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 an 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 another neutrophilic dermatosis, acute febrile neutrophilic dermatosis (Sweet disease).

Pyoderma gangrenosum

Pyoderma gangrenosum

Pyoderma gangrenosum

Pyoderma gangrenosum

Pyoderma gangrenosum

Pyoderma gangrenosum

How is pyoderma gangrenosum diagnosed?

Pyoderma gangrenosum is diagnosed by its characteristic appearance and severe pain. The pathergy test is usually positive (a skin prick test causing a papule, pustule or ulcer). 

• The wound should be swabbed and cultured for micro-organisms, but these are not the cause of pyoderma gangrenosum.
• A biopsy may be necessary to rule out other causes of ulceration. Pyoderma gangrenosum causes a neutrophilic inflammatory infiltrate, but this may be absent when on treatment.
• Mostly, blood tests are not particularly helpful. Some patients may have a positive ANCA (antineutrophil cytoplasmic antibody).

Maverakis criteria

Criteria published after a Delphi consensus exercise in 2018 [2] supersede the Su criteria [3] with a single major criterion required to diagnose pyoderma gangrenosum (a neutrophilic infiltrate). The addition of four or more of the eight minor criteria yields a sensitivity of 86% and a specificity of 90% for pyoderma gangrenosum.

Major criterion

• Histopathology of ulcer edge must show a neutrophilic infiltrate

Minor criteria

• Exclusion of infection
• Pathergy
• History of inflammatory bowel disease or inflammatory arthritis
• History of papule, vesicle, or pustule ulcerating within four days
• Peripheral erythema, undermining border, tenderness at the ulcer site
• Multiple ulcers, at least one on the anterior lower leg
• Cribriform or wrinkled paper scars at the site of the healed ulcer
• Decreased size of the ulcer within one month of initiating immunosuppressive medication.

What is the treatment of pyoderma gangrenosum?

Treatment of pyoderma gangrenosum is mainly 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 before 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 ointment
• Tacrolimus ointment
• Intralesional steroid injections into the ulcer edge
• Ciclosporin solution
• 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 methylprednisolone for 3–5 days
• Ciclosporin [7], which is as effective as prednisone and has differing adverse effects and risks
• Biologic agents: success with infliximab, adalimumab, etanercept and ustekinumab is reported in a small number of cases (used off-label). In New Zealand, adalimumab is funded for pyoderma gangrenosum if certain criteria are met.

Other therapies may include:

• Mycophenolate mofetil
• Dapsone
• Azathioprine
• A tetracycline such as minocycline
• Potassium iodide solution
• Methotrexate
• Cyclophosphamide
• Chlorambucil
• Intravenous immunoglobulins and plasmapheresis.

Expert wound care and pain management are essential. Once the disease is stable and inactive, surgical repair may be considered using a skin flap, skin graft, negative pressure wound therapy, and cultured skin.

Systemic therapy should be tapered slowly over several months.

What is the outlook for pyoderma gangrenosum?

The prognosis for pyoderma gangrenosum is unpredictable. About half of treated patients achieve wound healing on treatment with prednisone or ciclosporin within a year [4,7].

Patients with pyoderma gangrenosum should be very careful to avoid trauma, which can set off a new ulcer.