Pyoderma gangrenosum (PG) is a rare and serious skin disease in which a painful nodule or pustule breaks down to form a progressively enlarging ulcer. The name relates to the appearance of the ulcers, which have a purulent surface ('pyoderma') and a blue-black edge ('gangrenosum').

There may be an underlying disorder, such as ulcerative colitis, Crohn's disease, polyarthritis, or gammopathy.

PG comes under the heading of neutrophil dermatoses.

Epidemiology

Pyoderma gangrenosum (PG) is rare. It may occur at any age, but the peak incidence is age 20-50, with female preponderance.¹

Aetiology

The cause is unknown. About half the cases are associated with other diseases, mainly inflammatory bowel disease (IBD), arthritis and lymphoproliferative disorders. Pyoderma gangrenosum (PG) may occur in sites of trauma; this phenomenon is called pathergy.

Associated conditions are:^1,2

• 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 Behçet's disease, seronegative arthritis and spondyloarthropathy.
• Liver disease - chronic active hepatitis, hepatitis C³ and primary biliary cirrhosis.
• Myeloproliferative disorders, e.g. leukaemia, myeloma, lymphoma, monoclonal gammopathies.³
• Other conditions - also reported with paroxysmal nocturnal haemoglobinuria, systemic lupus erythematosus, antiphospholipid syndrome, vasculitis and Wegener's granulomatosis.

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

Possible precipitating factors for PG are:^1,3

• Biopsies, intradermal skin testing, injections, insect bites, etc. (due to pathergy).
• Surgery.
• Certain drugs - propylthiouracil, potassium iodide, granulocyte colony-stimulating factor, isotretinoin and gefitinib.

Presentation^1,2,3

Pyoderma gangrenosum (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.
• Refer urgently if PG is suspected.

Classical PG

• 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:
  1. Explosive onset and rapid spread of lesions, with pain, systemic illness and fever.
  2. 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.

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 inflammatory bowel disease.

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.

Other types

• Rare familial forms of PG have been reported, such as 'PAPA syndrome' (= pyogenic sterile arthritis, pyoderma gangrenosum, and acne).⁴
• PG with oral involvement is also reported.⁵

Investigations^1,2

The diagnosis is a clinical one. Investigations are needed to exclude other conditions and look for associated disease:

• Blood tests:
  • FBC, inflammatory markers, LFTs, urine protein and rheumatological investigations may be appropriate to look for associated diseases (as under 'Aetiology' above).
  • 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 Wegener's granulomatosis.
• 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 diagnosis^1,3,6

• 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.
• Self-inflicted ulceration.
• Sweet's syndrome (acute neutrophilic dermatosis).

Management^1,2,3

General points

• Immunosuppression and wound care are the main treatments.
• There are few controlled trials.
• Treating any associated disease (e.g. IBD) may help.

Topical and local treatments

• Wound care - 'moist wound management' is important, using dressings such as foam, laminate, alginate or wet compresses.
• Potent topical steroids under occlusive dressings.
• Intralesional injection of corticosteroid or ciclosporin.
• Other possible treatments include topical sodium cromoglicate,⁷, topical tacrolimus, benzoyl peroxide, nicotine and 5-aminosalicylic acid. Maggot therapy for the wound was used in one case.⁸

Systemic treatments

• Corticosteroids:
  • These have been the most predictable and effective treatment when delivered in adequate doses. They halt progression and prevent new lesions. High doses (60-200 mg/day) of prednisolone may be needed initially. Pulse therapy using intravenous (IV) methylprednisolone (e.g. 1 g/day for 3-5 days) is used in some departments.
• Sulfa drugs: dapsone, sulfapyridine, and sulfasalazine.
• Immunosuppressant drugs: ciclosporin, azathioprine, cyclophosphamide, tacrolimus, mycophenolate mofetil, 6-mercaptopurine, methotrexate and chlorambucil have been used.
• Biological therapies (anti-tumour necrosis factor alpha treatments):
  • Infliximab - some success reported in recent trials⁹; used in some departments.²
  • Etanercept - successful in a handful of single case reports.¹⁰
  • Adalimumab.¹¹
• Other treatments reported as helpful (in case reports) are:
  • Low-dose colchicine¹²
  • Minocycline
  • IV immunoglobulin¹³
  • Clofazimine
  • Leukophoresis
  • Hyperbaric oxygen therapy¹⁴
  • Alefacept¹⁵

Surgery³

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

Complications³

• Pain, wound odour and debility.
• Scarring of healed lesions.
• Secondary infection.
• Surgery may be needed for large non-healing ulcers (but see 'Surgery' above).
• Involvement of other organs: extracutaneous neutrophilic disease (as above); eye involvement is a rare complication.¹⁶
• Pyoderma gangrenosum (PG) is potentially life-threatening with a significant mortality rate.¹⁷

Prognosis³

• 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.¹
• Some reports suggest that about half of pyoderma gangrenosum (PG) patients have recurrence(s).¹⁷
• Any underlying disease also affects the prognosis.

Document references

1. Ruocco E, Sangiuliano S, Gravina AG, et al; Pyoderma gangrenosum: an updated review. J Eur Acad Dermatol Venereol. 2009 Sep;23(9):1008-17. Epub 2009 Mar 11. [abstract]
2. Brooklyn T, Dunnill G, Probert C; Diagnosis and treatment of pyoderma gangrenosum. BMJ. 2006 Jul 22;333(7560):181-4.
3. Wollina U; Pyoderma gangrenosum--a review. Orphanet J Rare Dis. 2007 Apr 15;2:19. [abstract]
4. Touitou I; Pyogenic arthritis - pyoderma gangrenosum - acne. Orphanet, October 2006
5. Paramkusam G, Meduri V, Gangeshetty N; Pyoderma gangrenosum with oral involvement - case report and review of the Int J Oral Sci. 2010 Jun;2(2):111-6. [abstract]
6. Weenig RH, Davis MD, Dahl PR, et al; Skin ulcers misdiagnosed as pyoderma gangrenosum. N Engl J Med. 2002 Oct 31;347(18):1412-8. [abstract]
7. Tamir A, Landau M, Brenner S; Topical treatment with 1% sodium cromoglycate in pyoderma gangrenosum. Dermatology. 1996;192(3):252-4. [abstract]
8. Hunter S, Langemo D, Thompson P, et al; Maggot therapy for wound management. Adv Skin Wound Care. 2009 Jan;22(1):25-7.
9. Brooklyn TN, Dunnill MG, Shetty A, et al; Infliximab for the treatment of pyoderma gangrenosum: a randomised, double blind, placebo controlled trial.; Gut. 2006 Apr;55(4):505-9. Epub 2005 Sep 27. [abstract]
10. Rogge FJ, Pacifico M, Kang N; Treatment of pyoderma gangrenosum with the anti-TNFalpha drug - Etanercept. J Plast Reconstr Aesthet Surg. 2008;61(4):431-3. Epub 2007 Jan 23. [abstract]
11. Traczewski P, Rudnicka L; Adalimumab in dermatology. Br J Clin Pharmacol. 2008 Nov;66(5):618-25. Epub 2008 Jul 11. [abstract]
12. Kontochristopoulos GJ, Stavropoulos PG, Gregoriou S, et al; Treatment of Pyoderma gangrenosum with low-dose colchicine. Dermatology. 2004;209(3):233-6. [abstract]
13. Hagman JH, Carrozzo AM, Campione E, et al; The use of high-dose immunoglobulin in the treatment of pyoderma gangrenosum. J Dermatolog Treat. 2001 Mar;12(1):19-22. [abstract]
14. Tutrone WD, Green K, Weinberg JM, et al; Pyoderma gangrenosum: dermatologic application of hyperbaric oxygen therapy. J Drugs Dermatol. 2007 Dec;6(12):1214-9. [abstract]
15. Foss CE, Clark AR, Inabinet R, et al; An open-label pilot study of alefacept for the treatment of pyoderma gangrenosum. J Eur Acad Dermatol Venereol. 2008 Aug;22(8):943-9. Epub 2008 Apr 1. [abstract]
16. Saito N, Yanagi T, Akiyama M, et al; Pyoderma Gangrenosum of the Eyelid: Report of Two Cases and Review of the Dermatology. 2010 Aug 17. [abstract]
17. von den Driesch P; Pyoderma gangrenosum: a report of 44 cases with follow-up. Br J Dermatol. 1997 Dec;137(6):1000-5. [abstract]

Internet and further reading

• DermNet NZ, Pyoderma granulosum - pictures and information
• Jackson JM et al; Pyoderma Gangrenosum, eMedicine, Mar 2010
• Miller J, Yentzer BA, Clark A, et al; Pyoderma gangrenosum: a review and update on new therapies. J Am Acad Dermatol. 2010 Apr;62(4):646-54. [abstract]

Acknowledgements