CLINICALLY SPEAKING

Ulceration of Pyoderma Gangrenosum Treated with Negative Pressure Wound Therapy
Stephen M. Geller, DPM* James A. Longton, DPM*
Pyoderma gangrenosum is a skin disease characterized by wounds with blue-to-purple undermined borders surrounding purulent necrotic bases. This article reports on a patient with a circumferential, full-thickness, and partially necrotic lower-extremity ulceration of unknown etiology. Results of laboratory tests and arterial and venous imaging studies were found to be within normal limits. The diagnosis of pyoderma gangrenosum was made on the basis of the histologic appearance of the wound tissue after biopsy as a diagnosis of exclusion. Negative pressure wound therapy was undertaken, which saved the patient’s leg from amputation. Although negative pressure wound therapy has demonstrated efficacy in the treatment of chronic wounds in a variety of circumstances, this is the first documented use of this technique to treat an ulceration secondary to pyoderma gangrenosum. (J Am Podiatr Med Assoc 95(2): 171-174, 2005)

Pyoderma gangrenosum was first described by Brunsting et al1 in 1930. The term pyoderma gangrenosum is actually a misnomer, because the lesions are not infectious or gangrenous.2 The typical lesion is a vesicle, pustule, or papulopustular lesion that ulcerates to form a wound with characteristic blue-to-purple undermined borders surrounded by erythema.2, 3 The lesions are usually painful and may appear anywhere on the body; however, they most often arise on the lower extremities. They vary in that they may have granular or necrotic wound beds with either serous or purulent exudates.2-4

Diagnosis and Histopathology
Diagnosis of pyoderma gangrenosum is a diagnosis of exclusion. There are documented characteristic histologic findings associated with the disorder; however, the diagnosis is conferred only when other
*Podiatry Program, Phoenix Baptist Hospital, Phoenix, AZ. Corresponding author: Stephen M. Geller, DPM, Podiatry Program, Phoenix Baptist Hospital, 1728 W Glendale, Ste 103, Phoenix, AZ 85021.

pathologic processes such as infection, vasculitic syndromes, and neoplasia have been ruled out. Histologically, the lesions vary by site of biopsy from central wound polymorphonuclear leukocyte infiltration with scattered lymphocytes and epidermal and papillary dermal necrosis to lymphocytic vasculitis in the peripheral advancing wound margins.2 Thorough examination is required if pyoderma gangrenosum is suspected, because the diagnosis is associated with comorbidities in approximately 50% of cases. The most common associated illness is inflammatory bowel disease, followed by rheumatoid arthritis, seronegative arthropathies, malignancies, and paraproteinemias.2

Treatment
The treatment of pyoderma gangrenosum is broad but is primarily targeted at systemic control of the inflammatory process. Therapy includes high-dose corticosteroids or other systemic immunosuppressant agents including, but not limited to, cyclosporine, cyclophosphamide, chlorambucil, and azathioprine.5

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Surgical debridement should be judicious, because even minor trauma often causes an increase in the destructive process, a phenomenon known as pathergy.2-5

Negative Pressure Wound Therapy
Negative pressure wound therapy was first described in 1997 by Argenta and Morykwas6 and Morykwas et al7 in porcine animal models and human clinical experimental trials. The V.A.C., or Vacuum Assisted Closure, wound therapy system (KCI, Inc, San Antonio, Texas) is a subatmospheric pressure system that uses foam fit by the applicator to the wound geometry. The foam comes in two varieties, Versafoam (KCI, Inc), a white, hydrophilic, dense polyvinyl-alcohol foam that comes packaged in saline and is used mainly on superficial or extremely painful ulcerations, and a hydrophobic, black polyurethane foam that has larger open cells that enhance exudate removal. Noncollapsible suction tubing connected to a vacuum pump is either embedded directly into a slit cut into the foam by the practitioner or connected to a TRAC pad (KCI, Inc) sitting on top of two layers of foam, depending on the type of wound and the V.A.C. model. The foam dressing and tubing are secured in place by an adhesive drape to maintain an airtight seal. Continuous or intermittent (5 min on, 2 min off) subatmospheric pressure is distributed uniformly across the wound bed through the open foam cells at a manually adjusted pressure of 125 to 175 mm Hg according to the amount of wound drainage. The dressing offers a closed wound environment, which requires less frequent dressing changes than traditional wet-to-dry dressings but requires more skill in application, as the periwound area must be appropriately protected to avoid maceration from excess wound fluids. The physiologic effect of negative pressure wound therapy on soft tissues is compared to the callus distraction theory or the tension/stress effect on bones. In vitro and limited in vivo studies have shown that negative pressure wound therapy may increase local tissue perfusion, increase the rate of granulation tissue formation, and reduce wound bacterial load.7 It has also been theorized that negative pressure wound therapy causes changes in the wound microenvironment by removing interstitial edema and wound exudate containing substances that may impede wound healing, including matrix metalloproteinases.8 These effects are currently being studied to determine whether they can be substantiated with a significant number of patients in randomized controlled trials. Negative pressure wound therapy is also being studied to determine its efficacy in venous stasis and neu-

ropathic ulcers. The significance of these studies has not yet been determined.6, 9, 10 The therapy has shown promise in other uses such as securing skin grafts after transplantation and for reepithelialization of donor sites.11, 12 Although negative pressure wound therapy is useful in many clinical situations, it is contraindicated in certain settings. It should not be used on necrotic tissue with eschar present. Wounds with associated osteomyelitis must be treated with appropriate debridement and antibiotic therapy. It is also not appropriate in the presence of neoplasm because of its effect on tissue proliferation. Other contraindications include organ or body cavity fistulas and placement in proximity to vessels.13

Case Report
An otherwise healthy 82-year-old woman presented to the Wound Care and Hyperbaric Medicine Clinic at Paradise Valley Hospital, Phoenix, Arizona, by referral after a 2-month history of a progressively enlarging, painful ulceration on the posterior aspect of her right lower extremity. The patient first noticed a brownish discoloration in the area, which opened a few days later with a moderate amount of yellowish, watery exudate. The patient initially applied 1% hydrocortisone cream to the wound area, and the wound grew larger and ulcerated. The patient’s primary-care physician then performed a swab culture of the wound and began administration of oral cephalexin. Local wound care was managed with triple antibiotic ointment and nonadherent dressing. After 6 weeks of cephalexin therapy with no improvement, the patient was referred to a vascular surgeon, who discontinued the cephalexin and prescribed oral ciprofloxacin and metronidazole. The patient was also prescribed venous duplex ultrasound and referred to our clinic for further evaluation. The patient’s medical and social histories were noncontributory, with no chronic illnesses or medications other than the ciprofloxacin and metronidazole. Review of systems revealed no history of dependent edema of the lower extremities, varicose veins, trauma, prior ulceration, or known insect bites. The patient had no appreciable foot deformities or burning, tingling, numbness, weakness, or cramping sensations. Upon initial evaluation at our clinic, the patient’s right lower leg was markedly edematous from the knee to the toes. The wound was circumferential, extending from the inferior aspect of the gastrocnemius muscle belly to just proximal to the malleoli and measuring 15 cm at its greatest width (Fig. 1). There was

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Figure 1. Initial appearance of circumferential necrotizing calf wound that was diagnosed as pyoderma gangrenosum.

a bridge of necrotic skin on the anterior tibial crest. The wound base was black eschar with yellow, necrotic, gelatinous slough. The wound edges appeared hyperemic with purplish discoloration. Also noted were periwound serous fluid–filled vesicles. Dorsalis pedis and posterior tibial pulses were palpable. There was no associated lymphangitis. Homans’ sign was absent. The patient’s right upper thigh exhibited no appreciable warmth, tenderness, or erythema. The wound was cleansed with normal saline, and deep tissue was taken from the wound base and sent for gram stain, culture, and sensitivity testing. Additionally, a pie-shaped specimen including both healthy and involved tissue was taken from the proximal wound margin for appropriate biopsy. The initial histopathologic examination revealed nonspecific findings of acute and chronic inflammation. Specific tests for acid-fast organisms and fungi were found to be negative. The specimen obtained contained no evidence of vasculitis or neoplasm. A diagnosis of pyoderma gangrenosum was suggested on subsequent reexamination of the slide preparations. Lower-extremity vascular testing was expanded to include arterial and venous duplex Doppler studies, which revealed adequate arterial circulation and no evidence of thrombophlebitis. A complete blood count with differential count, comprehensive metabolic panel, and rheumatoid factor were obtained and found to be within normal limits. The patient’s erythrocyte sedimentation rate was elevated at 70 mm/h.

sure wound therapy was ordered after careful consideration yielded no contraindications. Three days after the initial examination, the wound was debrided of necrotic tissue using pulsed lavage and dressed with Mesalt sodium chloride–impregnated dressing (Mölnlycke Health Care AB, Göteborg, Sweden). The following week, the wound was reexamined and dressed with four-layer compressive wrap to help control edema. Negative pressure wound therapy was begun 1 week later. Initially, the white polyvinylalcohol foam was used because the wound was painful at a suction power of 175 mm Hg (Fig. 2). After the pain persisted and was eventually linked to the high pressures needed for the polyvinyl-alcohol sponge, a transition was made to the black polyurethane foam. Mepitel (Mölnlycke Health Care AB) was used as a nonadherent dressing with the black foam to facilitate pain-free dressing changes and limit the aggressive nature of this open-cell foam. The wound showed signs of progressive healing, including a decrease in size (Fig. 3). The large wound epithelialized to form two separate wounds that became progressively smaller. The patient concurrently began a course of corticosteroid therapy, with slow tapering from 40 to 20 mg/day, and was referred to a rheumatologist for evaluation and management of the systemic immunologic component of the disease. The negative pressure wound therapy was discontinued after 7 months of treatment, when only a small island of granulation tissue remained in the area of the original wound (Fig. 4). The wound was then managed with a series of absorptive primary dressings secured with a three- or four-layered compressive wrap to control edema. For a short period, the wound was com-

Course of Treatment
Therapy focused first on reduction of the leg edema and absorption of the wound exudate. Negative pres-

Figure 2. Depiction of negative pressure wound therapy. Two TRAC pads (KCI, Inc) were used to ensure equal distribution of negative pressure. Note the Yconnector at left.

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Figure 3. Appearance of wound 3 weeks after the start of negative pressure wound therapy. Note the emerging skin islands and the absence of necrotic tissue.

Figure 4. Appearance of wound at 31 weeks.

pletely epithelialized and the patient was fitted for graduated compression stockings. However, the patient remains on a low dose of corticosteroids and continues to be followed by the rheumatologist, who is considering other immunosuppressive therapies. Small serous fluid–filled vesicular lesions that continue to open and close are managed weekly in our clinic with absorptive and compressive dressings.

Conclusion
Negative pressure wound therapy has demonstrated efficacy in the treatment of chronic wounds in diverse circumstances. Appropriate indication and contraindication criteria should be evaluated as with any wound treatment algorithm. In this case, a nearly circumferential lower-extremity wound secondary to pyoderma gangrenosum was treated successfully with negative pressure wound therapy using white polyvinyl-alcohol and then black polyurethane foam.

References
1. BRUNSTING LA, GOECKERMAN WH, O’LEARY PA: Pyoderma (ecthyma) gangrenosum: clinical and experimental observations in five cases occurring in adults. Arch Dermatol 22: 655, 1930. 2. BENNETT ML, JACKSON JM, JORIZZO JL, ET AL: 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 79: 37, 2000. 3. POWELL FC, SCHROETER AL, SU WP, ET AL: Pyoderma gangrenosum: a review of 86 patients. Q J Med 55: 173, 1985. 4. CALLEN JP: Pyoderma gangrenosum and related disorders. Med Clin North Am 73: 1247, 1989. 5. HAFNER J, TRUEB RM: Management of vasculitic leg ulcers and pyoderma gangrenosum. Curr Probl Dermatol 27: 277, 1999. 6. ARGENTA LC, MORYKWAS MJ: Vacuum-assisted closure: a new method for wound control and treatment: clinical experience. Ann Plast Surg 38: 563, 1997. 7. MORYKWAS MJ, A RGENTA LC, SHELTON -B ROWN EI, ET AL: Vacuum-assisted closure: a new method for wound control and treatment: animal studies and basic foundation. Ann Plast Surg 38: 553, 1997. 8. M ORYKWAS MJ, A RGENTA LC: Nonsurgical modalities to enhance healing and care of soft tissue wounds. J South Orthop Assoc 6: 279, 1997. 9. JOSEPH E, HAMORI CA, BERGMAN S, ET AL: A prospective randomized trial of vacuum assisted closure versus standard therapy of chronic nonhealing wounds. Wounds 12: 60, 2000. 10. MCCALLON SK, KNIGHT CA, VALIULUS JP, ET AL: Vacuumassisted closure versus saline-moistened gauze in the healing of postoperative diabetic foot wounds. Ostomy Wound Management 46: 28, 2000. 11. S CHNEIDER AM, M ORYKWAS MJ, A RGENTA LC: A new and reliable method of securing skin grafts to the difficult recipient bed. Plast Reconstr Surg 102: 1195, 1998. 12. G ENECOV DG, S CHNEIDER AM, M ORYKWAS MJ, ET AL : A controlled subatmospheric pressure dressing increases the rate of skin graft donor site reepithelialization. Ann Plast Surg 40: 219, 1998. 13. M ENDES -E ASTMAN S: Negative pressure wound therapy. Plast Surg Nurs 18: 27, 1998.

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