Pyoderma Gangrenosum: Signpost of Underlying Disease

April 1, 2006

Pyoderma gangrenosum is frequentlyassociated with systemic diseases,such as ulcerative colitis and Crohn’sdisease (Table). The occurrence of theskin ulcers does not necessarily correlatewith the activity of the underlyingdisorder.

Pyoderma gangrenosum is frequentlyassociated with systemic diseases,such as ulcerative colitis and Crohn'sdisease (Table). The occurrence of theskin ulcers does not necessarily correlatewith the activity of the underlyingdisorder.

 Table - Systemic diseases associated with pyoderma gangrenosum
Ulcerative colitis Crohn’s disease Monoclonal gammopathy Seronegative arthritis associated with inflammatory bowel disease Seronegative symmetrical small-joint polyarthritis Rheumatoid arthritis Ankylosing spondylitis Acute myelomonocytic leukemia Hairy cell leukemia Adenocarcinoma of the colon Multiple myeloma Chronic active hepatitis Primary biliary cirrhosis Behçet syndrome Wegener granulomatosis HIV infection 

Pyoderma gangrenosum doesnot appear to be an infectious disease.Pathergy, or the development of lesionsfollowing trivial trauma, is oftenassociated with this condition.

In this article, I describe the identifyingcharacteristics of pyodermagangrenosum and review the treatmentoptions. Brief case histories andphotographs that illustrate the variousmanifestations of the disease begin onpage 460.

CLINICAL TYPES

The 4 clinical variants of pyodermagangrenosum are:

  • Ulcerative. This form is by far themost prevalent. It is associated withactive inflammatory bowel disease.
  • Pustular. The typical presentation isin the mucous membranes, axillae,and genital areas.
  • Bullous. This is apparently one of theleast aggressive variants.
  • Vegetative. This variant is most commonlyencountered with myelodysplasticand lymphoproliferative diseases.

PRESENTATION
Pyoderma gangrenosum oftenbegins as a small pustule that rapidlyexpands to a large, deep ulcer. Multiplepustules and multiple areas of ulcerationalso are common, especiallywith leg lesions. The usually welldefinededge of the ulcer is blue orpurplish; necrosis may undermine thesubcutaneous tissue beneath the border.Necrotic tissue and exudate developin the center of the lesion, whichis usually surrounded by a halo or areolaof erythema.

Lesions most commonly arise onthe lower legs but can occur anywhereon the body. Early stages of theinflammatory skin condition may beconfused with cellulitis. Althoughbiopsy results often are not specific topyoderma gangrenosum, the biopsymay exclude other causes of skinulceration, including malignancy.Lymphocytic infiltrates and fibrinoidnecrosis of vessel walls are frequentlyseen in peripheral biopsy speci-mens, whereas polymorphonuclearleukocytic infiltrations and dermalnecrosis are often encountered in centralbiopsy specimens.

WORKUP
Generally, this skin disorder isidentified on the basis of its characteristicappearance; there are no tests orpathognomonic histopathologic featuresthat routinely confirm the diagnosis.The goal of laboratory testing isto exclude other disorders or to identifydiseases that are associated withpyoderma gangrenosum. The workupmay include serum protein electrophoresis,complete blood cell count,erythrocyte sedimentation rate, rheumatoidfactor, perinuclear or cytoplasmicantineutrophil cytoplasmic antibody(p-ANCA or c-ANCA) testing,skin biopsy, culture of the ulcer base,and evaluation of the colon. Becausedeep mycosis, tuberculosis, and tropicalulcers can mimic pyoderma gangrenosum,these infectious disordersneed to be ruled out.

TREATMENT
Although various therapies havebeen advocated, treatment can be difficult;it may take many months for thelesions to resolve. Counsel patients totry to avoid skin trauma, which can impedehealing. Dressings, compresses,rest, and washing with hydrogen peroxideare simple interventions to promotere-epithelialization. The affectedarea can be cleansed gently and coveredwith saline dressings.

Local therapy is most helpful forpatients with early disease. Topical orintralesional corticosteroids have beenwidely used with success. If injectionsare given, administer 1 mL of triamcinoloneacetonide (5 mg/mL) or triamcinolonehexacetonide (10 mg/mL)below the rim of the ulcer. Topical applicationof 1% or 4% solution of cromolynsodium has also been effectivewith early lesions.

Systemic corticosteroids are consideredby many practitioners to bethe mainstay of therapy. Large dosesand prolonged administration of prednisone(40 to 120 mg/d) often are necessaryto induce remission.

Immunosuppressive drugs,such asazathioprine, tacrolimus, or cyclosporine,have been tried. While azathioprinehistorically has been the immunosuppressiveagent administeredmost often for pyoderma gangrenosum,the therapeutic response takes aminimum of 6 to 8 weeks, and clearancerates are low. Tacrolimus (0.15mg/kg bid) is used for atopic dermatitisand may be a promising therapy forpyoderma gangrenosum.

Antileprosy drugs, such as dapsoneand clofazimine, also have been usedfor ulcerative disease.

Surgical therapy for pyodermagangrenosum has been limited by thetendency for new lesions to develop orpreexisting ones to expand at the siteof trauma. Several recent reports suggestthat radical surgery can be used toclear severe disease on the extremities;amputation also may be appropriate.Surgical resection of inflammatory intestinehas been attempted to treat pyodermagangrenosum, but the resultshave been mixed. Medical therapy appearsto be superior in this setting.

FOR MORE INFORMATION:

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  • Duguid CM, Powell FC. Pyoderma gangrenosum.Clin Dermatol. 1993;11:129-133.
  • Elgart G, Stover P, Larson K, et al. Treatment ofpyoderma gangrenosum with cyclosporine: resultsin seven patients. J Am Acad Dermatol. 1991;24:83-86.
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  • Habif TP. Clinical Dermatology: A Color Guide toDiagnosis and Therapy. 3rd ed. St Louis: Mosby-YearBook; 1996:591-593.

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