Pyoderma gangrenosum

Byoderma gangrenosum (PG) is a rare condition first identified by Brocq in 1916.1 The condition's characteristic chronic ulceration with violaceous undermined borders was more completely described in 1930 and, since then, the course of the disease has been revealed.2-5

The term pyoderma gangrenosum is a misnomer. The condition is neither infectious nor gangrenous; rather, it is an inflammatory process of unknown etiology, leading to painful skin ulcers.

Pyoderma gangrenosum primarily affects adults, typically those between 40 and 60 years old. It consists of recurring destructive ulcers that begin as pustules and resolve as cribriform scars.6- Several clinical variants of PG have been identified, including ulcerative, pustular, bullous, vegetative, and peristomal types (Table 1, Figures 1 and 2).3,9,10 The typical PG lesion has inflamed, undermined borders and is found on the lower leg. Because no diagnostic test for PG exists and a number of other conditions resemble PG, diagnosis relies on the clinical presentation and exclusion of other causes. Pyoderma gangrenosum is associated with other conditions in up to 75% of patients, and the type of clinical presentation may suggest an underlying systemic disease.5 Associated conditions include inflammatory bowel disease, arthritis (rheumatoid or seronegative), monoclonal gammopathy, and hematologic malignancies.5 After PG is diagnosed, the underlying condition or conditions should be determined.11

Pathophysiology

The mechanism by which PG lesions develop is unknown; however, it is believed that pathergy plays a role.7 Pathergy is the development of lesions in areas of trauma. In susceptible people, even minimal trauma or irritation to the skin can result in the production of PG lesions. Debridement is one traumatic event that may result in PG pustules or ulcers. They may also occur at skin graft harvest sites and stoma placement sites or at surgical wounds or scars.

It has been suggested that interleukin-8 (IL-8), a proinflammatory cytokine, may play a role in the pathogenesis of PG.12 Interleukin-8 is chemotactic for neutrophils and is not normally detected in human skin. However, IL-8 is overexpressed in certain chronic skin conditions, including PG. One laboratory study showed that PG ulcers developed after IL-8 was injected into human skin xenografts that were grafted onto mice.12

Diagnosis

No single diagnostic test is available for PG. Pyoderma gangrenosum is a clinical diagnosis of exclusion. Histologic and laboratory evaluation in patients with PG are based largely on excluding other causes and evaluating a patient for underlying systemic disease. Pyoderma gangrenosum may resemble both infectious and inflammatory conditions, such as vasculitis, vasculopathy, mycobacterial or bacterial infections, or collagen vascular diseases (Table 2).2,3,9

Because PG is associated with many systemic diseases and malignancies, including inflammatory bowel disease, arthritis, and hematologic malignancies, a careful search for associated conditions should be undertaken when evaluating a patient; these conditions may impact treatment (Table 3).4 This can be accomplished with a variety of blood, urine, and radiographic tests, such as complete blood counts, renal and hepatic function, sigmoid or colonoscopy, chest radiograph, and, if necessary, bone marrow biopsy (Table 4).1,3,4

Treatment

There is no specific treatment for PG, although corticosteroids are usually helpful.1 The goals for managing PG are pain control, wound healing, and prevention of infection. The treatment should be tailored to the patient's type of lesions, extent of disease, duration of disease, severity of disease, lifestyle, other associated systemic diseases, age, gender, prior treatments, and the practitioner's preference.

For limited or mild disease, topical or intralesional steroids may be used (Table 5).1-3,6,9 For more severe or widespread disease, a variety of systemic therapies can be used. Antibiotics with anti-inflammatory properties, such as minocycline or dapsone, are often used as first-line therapies. Systemic steroids given in an oral, intravenous, or pulsed fashion are generally effective, although their adverse effects limit longterm use. A variety of immunosuppressive agents have been found effective for treating PG, including cyclosporine, mycophenylate mofetil, methotrexate, and chlorambucil. Thalidomide, granulocyte-macrophage colony-stimulating factor, and nicotine patches represent other therapeutic options.

In summary, PG is an inflammatory process resulting in ulceration of unknown etiology. It is associated with systemic disorders in a significant percentage of patients and treatment is aimed at the underlying inflammatory process.

References

1. Bennett ML, Jackson JM, Jorizzo JL, Fleischer AB, White WL, Callen JR Pyoderma gangrenosum: a comparison of typical and atypical forms with an emphasis on time to remission. Case review of 86 patients from 2 institutions. Medicine 2000;79:37-46.

2. Chow RK, Ho VC. Treatment of pyoderma gangrenosum. J Am Acad Dermatol 1996;34:1047-60.

3. Powell FC, Collins S. Pyoderma gangrenosum. Clin Dermatol 2000;18:28393.

4. Callen JP Pyoderma gangrenosum. Lancet 1998;351:581-5.

5. Litvak D, Kirsner RS, Pakdaman NN, Federman DG. Pyoderma gangrenosum and myelodysplastic syndrome. South Med J 2000;93:923-5.

6. Powell RJ, Holbrook MR, Stevens A. Pyoderma gangrenosum and its treatment. Lancet 1997;350:1720-1.

7. Hughes AP, Jackson JM, Callen JR Clinical features and treatment of peristomal pyoderma gangrenosum.JAMA 2000;284:1546-8.

8. Hurwitz RM, Haseman JH. The evolution of pyoderma gangrenosum. A clinicopathologic correlation. Am J Dermatopathol 1993;15:28-33.

9. Powell FC, Su WP, Perry HO. Pyoderma gangrenosum: classification and management. Am Acad Dermatol 1996;34:395-409.

10. Lyon CC, Smith AJ, Heck MH, Wong GA, Griffiths CE. Parastomal pyoderma gangrenosum: clinical features and management. J Am Acad Dermatol 2000;42:992-1002.

11. von den Driesch P Pyoderma gangrenosum: a report of 44 cases with follow-up. Br J Dermatol 1997;137:1000-5.

12. Oka M, Berking C, Nesbit M, et al. Interleukin-8 overexpression is present in pyoderma gangrenosum ulcers and leads to ulcer formation in human skin xenografts. Lab Invest 2000;80:595-604.

Jennifer T Trent, MD, and Robert S. Kirsner, MD

Jennifer T. Trent MD, is a Research Associate in the University of Miami School of Medicine, Miami, FL. Robert S. Kirsner, MD, is an Associate Professor in the Department of Dermatology and Cutaneous Surgery and in the Department of Epidemiology and Public Health at the University of Miami School of Medicine, Miami, FL.

Copyright Springhouse Corporation May/Jun 2001
Provided by ProQuest Information and Learning Company. All rights Reserved