Pyoderma Gangrenosum

Pyoderma gangrenosum (PG) is a rare and serious condition comprising painful ulceration of the skin. The name relates to the appearance of the ulcers, which have a purulent surface ('pyoderma') and a blue-black edge ('gangrenosum').

PG is rare. The peak incidence is age 20-50, with female preponderance. About 4% of cases are children.¹

This is unknown, however:

• PG may occur in sites of trauma; this phenomenon is called pathergy.
• About half of the cases are associated with other diseases, especially inflammatory bowel disease.
• Associated conditions are:
  • Inflammatory bowel disease (IBD) - Crohn's disease and ulcerative colitis:
    • About 2% of IBD patients develop PG
    • About 30% of PG patients have (or will develop) IBD
  • Arthritis:
    • Usually seropositive rheumatoid arthritis
    • Can occur with seronegative arthritis and spondyloarthropathy
  • LIver disease - chronic active hepatitis, hepatitis C¹ and primary biliary cirrhosis
  • Myeloproliferative disorders, e.g. leukaemia, myeloma, lymphoma, monoclonal gammopathies¹
• Possibly, certain drugs - propylthiouracil, pegfilgrastim and gefinib.¹

The occurence of pyoderma granulosum does not seem to relate to the disease activity in conditions such as IBD and arthritis.

Pyoderma gangrenosum can present in various ways and is not always easy to recognise; however, early recognition and treatment are important.

Classical PG

• Starts as one or more small papules; these soon break down to form a rapidly enlarging ulcer, which is:
  • Usually painful - can be severe pain.
  • A deep ulcer with a purulent surface; the margin is well-defined and blue-violet; the edge is often undermined (eroded).
  • Surrounding skin is pink and indurated.
  • Most often occurs on the legs.
• Patients may be systemically unwell with fever, malaise, myalgia and joint pain.
• Scarring occurs when the ulcer heals.
• Pathergy (ulcers in the site of minor trauma) is common.

Peristomal PG

• PG can occur in skin around stoma sites (any stoma, not only those for inflammatory bowel disease).

Vegetative PG

• Usually is a single lesion in healthy patients
• Is more superficial than classical PG
• Is less aggressive than classical PG; may respond well to topical treatment

Bullous PG

• Occurs mainly with haematological conditions
• Presentation:
  • Concentric bullous areas, rapidly spreading
  • Break down to form ulcers, which are more superficial than in classical PG
  • Affects face and upper limbs more than legs

Pustular PG

• A rare variant of PG, where instead of an ulcer, there is a persistent, painful, pustular lesion.
• Seems to occur only in IBD patients, on the trunk and extensor surfaces of the limbs.

The diagnosis is a clinical one. Investigations are needed to exclude other conditions:

• Blood tests - haematology, inflammatory markers, liver function tests, urine protein and rheumatological investigations may be appropriate to look for associated diseases (as above).
• Swabs - to exclude infection.
• Skin biopsy - there are no specific diagnostic features of PG, but biopsy helps exclude other conditions (see differential diagnosis).

• Infections:
  • Bacterial, including tuberculosis
  • Viral, e.g. herpetic ulcers
  • Parasitic, e.g. syphilis
  • Tropical mycoses, e.g. sporotrichosis
• Vascular:
  • Arterial or venous ulcers
  • Vasculitis, e.g. antiphospholipid syndrome, vasculitic rheumatoid arthritis, systemic lupus erythematosus, Wegener's granulomatosis, Behçet's disease
• Malignancies:
  • Squamous cell carcinoma
  • Cutaneous lymphoma
• Insect or spider bites
• Sweet's syndrome (fever with erythematous papular eruption; can co-exist with PG)

General principles

• Immunosuppression and wound care are the main treatments.
• There are few controlled trials.
• Corticosteroids (high dose) and ciclosporin (low dose) are the most common treatments.
• Most clinicians use a stepwise approach, with a combination of topical and systemic treatments.

Topical treatments

• Wound care - "moist wound management" is important, using dressings such as foam, laminate, alginate or wet compresses.¹
• Potent topical steroids.
  • E.g. triamcinolone injected into ulcer edge.
  • Occasionally used under occlusive dressings.
• Topical tacrolimus.
• Topical sodium cromoglycate has been reported as helpful.^4,5

Systemic treatments

• Corticosteroids, e.g:
  • Oral prednisolone at high doses (60-120 mg)
  • Pulse therapy using intravenous methylprednisolone for 3-5 days
• Ciclosporin at relatively low doses
• Other immunosuppressants used include:^1,6
  • Azathioprine
  • Tacrolimus
  • Mycophenolate mofetil
  • Dapsone
  • Cyclophosphamide pulse therapy¹
  • Thalidomide
• Biological therapies (anti-tumour necrosis factor α treatments)
  • Infliximab - some success reported in recent trials⁷
  • Etanercept - successful in a handful of single case reports⁸
• Other treatments reported as helpful (in case reports) are:
  • Low dose colchicine^1,9
  • Minocycline
  • Intravenous immunoglobulin¹⁰
  • Clofazimine¹
  • Leukophoresis¹
  • Hyperbaric oxygen therapy¹¹

Surgery¹

• Can trigger PG, so used with immunosuppression when in a stage of remission
• Skin grafts or bioengineered skin may be used

• Pain, wound odour and debility.
• Secondary infection.
• Surgery may be needed for large non-healing ulcers (but see above).
• Involvement of other organs: reports include neutrophilic pulmonary involvement¹² and eye involvement.¹³

• The clinical course seems to be variable and difficult to predict.¹
• Some reports suggest that about half of PG patients have recurrence(s).^12,14
• Any underlying disease also affects the prognosis.