Pyoderma gangrenosum

What is pyoderma gangrenosum?¹

Pyoderma gangrenosum is an uncommon neutrophilic dermatosis that usually presents with rapidly growing, painful, undermined, and purulent ulcers that are more likely to develop at areas of trauma. It is associated with underlying systemic diseases in more than half of cases, most commonly with inflammatory bowel disease, but also rheumatoid arthritis, haematological malignancies, chronic active hepatitis or gammopathy.

In neutrophil dermatoses, affected tissue contains a high concentration of neutrophils. Other neutrophil dermatoses include Sweet's syndrome (acute febrile neutrophilic dermatosis), Behcet's disease, neutrophilic dermatosis of the hands and erythema elevatum diutinum.

How common is pyoderma gangrenosum? (Epidemiology)

PG is uncommon. Incidence is estimated to be around 3-10 cases per million population per year worldwide.² A UK study estimated incidence rate to be around 0.91 per 100,000 person-years.³ It may occur at any age, but the peak incidence is over the age of 50, with a slight female preponderance.

What causes pyoderma gangrenosum? (Aetiology)

The cause is unknown. 50-70% of cases are associated with other diseases, mainly inflammatory bowel disease (IBD), arthritis and lymphoproliferative disorders.² PG may occur in sites of trauma; this phenomenon is called pathergy. It often begins in sites of minor injury (reported in 20-30% of cases).

Associated conditions are:^{4 5}

• IBD - Crohn's disease and more frequently 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 Behçet's disease, seronegative arthritis and spondyloarthropathy.

• Liver disease - chronic active hepatitis, hepatitis C and primary biliary cirrhosis.

• Myeloproliferative disorders - eg, leukaemia, myeloma, lymphoma, monoclonal gammopathies.

• Pyogenic sterile arthritis, pyoderma gangrenosum and acne syndrome (PAPA syndrome).⁶

• Other conditions - also reported with paroxysmal nocturnal haemoglobinuria, systemic lupus erythematosus, antiphospholipid syndrome, vasculitis and Granulomatosis with polyangiitis (GPA).⁷

The occurrence of PG does not seem to relate to the disease activity in conditions such as IBD and arthritis.

Possible precipitating factors for PG are:^{4 8}

• Biopsies, intradermal skin testing, injections, insect bites, etc (due to pathergy).

• Surgery.

• Certain drugs - propylthiouracil, the granulocyte colony-stimulating factor pegfilgastrim, isotretinoin and gefitinib.

Pyoderma gangrenosum symptoms (presentation)^{4 5 8}

PG can present in various ways and there are several different forms (listed below). It is not always easy to recognise, although early recognition and treatment are important.

• Consider PG in any non-healing ulcer or wound.

• Lesions can progress rapidly, from pimple to crater within 48 hours.

Classical PG

• This is the most common type.

• This begins as pustule(s) or nodule(s); these soon break down to form a rapidly enlarging ulcer, which has a raised inflammatory border and a boggy, necrotic base. The base may be studded with small abscesses. The ulcer is usually painful and the pain may be severe. It heals with scarring.

• The ulcers are most common on the lower legs and trunk.

• Pathergy (ulcers in the site of minor trauma) is common.

• The clinical course may follow two patterns:
  

  • Explosive onset and rapid spread of lesions, with pain, systemic illness and fever.

  • Indolent and slow-spreading, with spontaneous regression and healing in one area and progression in another.

Peristomal PG

• PG can occur in skin around stoma sites.

• This is particularly common in IBD patients.

• Around 15% of all cases of PG.

Vegetative PG

• This is usually a single lesion in healthy patients; it is a less aggressive form than classical PG. Often there is no systemic disease. It may respond well to topical treatment.

• Lesions are mainly on the head and neck.

• The ulceration is more superficial than classical PG; the ulcer base is usually non-purulent, and there are no undermined borders or surrounding erythema.

Bullous PG

• Presents with concentric, painful bullous areas, rapidly spreading. These break down to form ulcers, which are more superficial than in classical PG. It affects the face and upper limbs more than the legs.

• It has been reported in association with haematological disease.

Pustular PG

• There are multiple sterile pustules surrounded by an erythematous halo and associated with fever and arthralgias.

• It often improves with treatment of the underlying IBD.

Genital PG

• Typical PG ulcers located on the vulva, penis or scrotum.

• Behçet's disease should be considered as a differential diagnosis.

Extracutaneous neutrophilic disease

• Sterile neutrophilic infiltrates - usually in the lungs, but can also occur in the heart, central nervous system, gastrointestinal tract, eye, liver, spleen and lymph nodes.

• Symptoms reflect the location of the lesions.

• Oral involvement has also been reported.⁹

Investigations^{2 5}

The diagnosis is clinical, and a diagnosis of exclusion. Investigations are needed to exclude other conditions and look for associated disease. Infection, vascular disorders and malignancies in particular need to be excluded.

• Blood tests for any underlying systemic condition include:
  

  • FBC, inflammatory markers, LFTs, urine protein and rheumatological investigations may be appropriate.

  • Autoantibodies - patients with PG are often p-ANCA (perinuclear) positive, particularly if inflammatory bowel disease is present. The presence of c-ANCA (cytoplasmic) may indicate GPA.

  • Endoscopy may be required to confirm or exclude inflammatory bowel disease.

• Swabs and cultures of the ulcer.

• Biopsy of the lesion - often indicated to exclude other causes, although there are no specific diagnostic features of PG. Biopsy may sometimes cause extension of the ulcer.

Differential diagnosis⁴

• Infections:
  

  • Bacterial, including tuberculosis.

  • Viral - eg, herpetic ulcers.

  • Parasitic - eg, syphilis.

  • Tropical mycoses - eg, sporotrichosis.

• Vascular:
  

  • Arterial or venous ulcers.

  • Vasculitis - eg, antiphospholipid syndrome, vasculitic rheumatoid arthritis, systemic lupus erythematosus, GPA, Behçet's disease.

• Malignancies:
  

  • Squamous cell carcinoma.

  • Cutaneous lymphoma.

• Insect bites or spider bites.

• Self-inflicted ulceration.

• Sweet's syndrome (acute neutrophilic dermatosis).

Pyoderma gangrenosum treatment and management^{10 11}

Management can be challenging. In addition to medical therapy, wound care with appropriate dressings and pain control are essential.

• Refer urgently to a dermatologist for diagnosis and treatment.

• Immunosuppression and wound care are the main treatments.

• There are few controlled trials.

• Treating any associated disease may help.

Treatment options include:¹²

• Topical or intralesional treatments:

  • Super-potent topical steroids - eg Dermovate® (clobetasol), with or without tacrolimus.

  • Intralesional Adcortyl® (triamcinolone).

• Moderate to severe cases:

  • Prednisolone: high doses may be required initially, lower doses for maintenance.

  • High-dose tetracyclines, eg lymecycline.

• Other treatment options include colchicine, ciclosporin, sulfasalazine and infliximab.

For extensive wounds with or without necrosis, surgical therapy may be necessary for debridement and/or obtaining coverage.

Complications⁸

• Pain, wound odour and debility.

• Scarring of healed lesions.

• Secondary infection.

• Involvement of other organs: extracutaneous neutrophilic disease (as above); eye involvement is a rare complication.¹³

Prognosis⁴

• The clinical course is variable and difficult to predict. There may be spontaneous resolution, a quiescent phase for months or years or flare-ups following minimal trauma or for no apparent cause.

• Any underlying disease significantly affects the prognosis.²

• Male sex, older age, bullous variety and association with haematological malignancy are associated with poorer prognosis.

• A UK-based study found that people with PG had a three times higher risk of death than the general population.³