Management of Postsurgical Pyoderma Gangrenosum Following Deep Inferior Epigastric Perforator Flap Breast Reconstruction: A Role for a Dermal Regeneration Template

Pyoderma gangrenosum (PG) is a rare necrotizing and ulcerative cutaneous disorder. It most commonly occurs on the lower extremity, although other skin or mucous membranes may also be affected.^1-4 Although PG is often associated with a systemic inflammatory disease, 30% of cases occur following trauma to the skin due to pathergy.⁵ Given its rare occurrence and nonspecific histology, PG is primarily a diagnosis of exclusion. Postsurgical PG, which occurs most often after breast surgery, is particularly challenging to diagnose as it presents similarly to infection.^6,7 Misdiagnosis leads to ineffective treatment with antibiotics and surgical debridement, which further exacerbates disease progression.^5,8,9

The lesions generally respond well to systemic immunosuppressive therapy and a local wound care regimen.^1,10,11 However, reconstruction may be necessary to manage resulting wounds too large to heal by secondary intention or those in esthetically sensitive areas. Although there have been many reports of PG following reduction mammoplasty, very few cases of PG following autologous breast reconstruction have been reported in the literature. Furthermore, clear guidelines are lacking for the timing of and approach to reconstruction for PG-related defects following diagnosis and treatment initiation.

The authors of the current study reviewed the literature and analyzed 15 cases of PG following autologous breast reconstruction: 8 deep inferior epigastric perforator (DIEP) flaps,^5,8,9,12-16 6 transverse rectus abdominis myocutaneous flaps,^17-22 and 1 latissimus dorsi flap.²³ This case report presents the clinical course and management at the authors’ institution of a 62-year-old female with ductal carcinoma in situ who underwent a left breast mastectomy with immediate DIEP flap breast reconstruction complicated by PG. Medical management of PG and the role of surgical intervention are discussed.

A 62-year-old female with hypertension, mild emphysema (former smoker), and obesity (body mass index, 35 kg/m²) presented with ductal carcinoma in situ of the left breast. Of note, the patient did not have a history of inflammatory bowel disease, rheumatoid arthritis, or other systemic inflammatory diseases. The patient underwent left skin-sparing mastectomy with sentinel node biopsy followed by immediate breast mound reconstruction with a DIEP flap. The immediate postoperative course was uneventful.

On postoperative day 4, the patient's body temperature was 102°F. There was evidence of erythema, edema, and bullae involving the mastectomy flaps, sparing the central skin paddle. Given the initial concern for infection, blood cultures were drawn and broad-spectrum antibiotics were started. The following day, the patient remained intermittently febrile despite the antimicrobial regimen acute kidney injury developed. At this point, an infectious diseases specialist was consulted; the continuation of broad-spectrum antibiotics was recommended.

On postoperative day 6, the patient was febrile, with tachycardia and an increasingly edematous and erythematous breast (Figure 1). The patient was taken to the operating room for surgical intervention, during which approximately 20 mL of purulent fluid was drained and cultured (Figure 2). Necrotic skin was debrided and sent for pathologic evaluation. The following day tachycardia persisted, and the patient remained febrile, with a white blood cell count of 33 000/µL, and she underwent another operation. Purulence within the mastectomy dermis was noted. In addition, new pustules and erythema around the center of the lower abdominal incision were present (Figure 3). The flap remained viable, and the skin paddle appeared to be spared from the apparent infection. Initial culture results remained negative, but antibiotics were continued per the recommendation of an infectious diseases specialist.

Because of the unusual presentation and involvement of the abdominal donor site, an atypical process such as PG was suspected. A dermatologist was consulted immediately after the second debridement surgery (7 days after breast reconstruction). Suspicion for PG was high, and the patient was immediately started on 1 mg/kg of prednisone daily for immunosuppressive cover. This regimen was tapered in the hospital as clinical improvement was seen (1 mg/kg to 60 mg/day, then 40 mg/day, then 30 mg/day). Antibiotics were continued since PG is a diagnosis of exclusion, and there were lingering concerns for possible anaerobic infection.

Shortly after initiation of corticosteroids, the fever and tachycardia resolved and leukocytosis improved. Swelling and erythema of the left breast decreased. Antibiotics were discontinued on postoperative day 10, because of improvement on corticosteroids and persistently negative culture results. On postoperative day 13, pathologic results from the intraoperative biopsy of the breast skin returned and were deemed by a dermatologic pathologist to be strongly suggestive of PG. Prior to implementing additional systemic immunosuppressive therapy, the treating physician consulted a hematologist to rule out hematologic malignancy. A serum protein electrophoresis test was ordered to test for a monoclonal gammopathy that could be associated with PG, and monoclonal gammopathy of undetermined significance with elevated light chains and normal kappa/lambda ratio was detected. Per the hematologist, this finding was likely explained by renal dysfunction. Because results were reassuring, the patient was cleared to receive a 5 mg/kg of infliximab infusion on postoperative day 15.

Debridement of the necrotic mastectomy flaps resulted in a large defect (170 cm²). Because of concern that healing by secondary intention would result in wound contraction that would cause further deformity and that skin grafting at that point could produce pathergy, a bilayer wound matrix was used for the defect. Steroids were tapered to 10 mg daily. On postoperative day 22, the bilayer wound matrix was applied to the breast wound (Figure 4). Four weeks later, a split-thickness skin graft was applied to the collagen layer (Figure 5). Negative pressure wound therapy (NPWT) was used as a bolster. The patient was maintained on prednisone 20 mg per day during the perioperative period and vitamin A for improved wound healing. The prednisone was tapered and discontinued 3 months after diagnosis of PG. The skin graft healed uneventfully (Figure 6). Ten months after mastectomy and DIEP flap reconstruction, the patient had acceptable breast shape. Even so, the authors offered the option of tissue expansion and excision of the grafted skin for an improved esthetic outcome.

Pyoderma gangrenosum is a rare necrotizing and ulcerative cutaneous disorder. It manifests clinically as pustules that quickly enlarge to painful ulcers with undermined, violaceous borders and surrounding erythema, followed by necrosis of the skin and subcutaneous tissue. Pyoderma gangrenosum occurs following trauma to the skin, including surgery due to pathergy, and is also associated with systemic inflammatory diseases such as inflammatory bowel disease, rheumatic disease, hematologic disorders, and malignancy.^1-4

Diagnosis of postsurgical PG can be challenging given its unknown pathogenesis, nonspecific histology, and similarity in clinical presentation to wound infection and ischemia.⁹ However, certain clinical clues may increase suspicion for postsurgical PG. Postsurgical PG often presents with edema, erythema, marginal necrosis, and undermining of the wound edge, followed by dehiscence and blistering of adjacent skin. The bullae and necrosis may affect all surgical sites but spare the nipple-areolar complex in breast reduction cases.⁷ Interestingly, the central DIEP flap skin paddle was spared in the patient reported in this study. The authors’ literature review of postsurgical PG after autologous breast reconstruction shows that the mastectomy skin and abdominal incisions are initially affected and that the flap skin is often affected in a delayed fashion. The onset of symptoms varies from 1 day to 6 weeks postoperatively.^6,7 Of the 15 cases of PG following autologous breast reconstruction, the median time to initial presentation of symptoms was 3.5 days, and a correct diagnosis of PG was reached after a median of 10.5 days (Table Part 1 and Part 2).

Early clinical suspicion of PG is critical. Misdiagnosis can be detrimental as further surgical intervention can provoke pathergy and lead to worsening of the condition. Of the reviewed case reports of postsurgical PG after autologous breast reconstruction, 85% of patients (11/13) underwent surgical debridement prior to the correct diagnosis of PG, often resulting in significant disfigurement.^5-8,21 Schintler et al²¹ reported a case in which repeated debridement resulted in flap loss and a significant donor site defect. Early consideration of PG may allow for a conservative approach to debridement while confirming the diagnosis. Singh et al⁹ reported a case of PG following DIEP flap reconstruction in which care was taken to minimize aggressive debridement because of early suspicion of PG. Complete healing of the lesions was achieved by 2 months postoperatively, with cosmetically acceptable results. In addition to the apparent infectious presentation, progressive edema and patchy, violaceous discoloration can be mistaken as signs of flap venous congestion and lead to unnecessary surgical interventions.^13,18 In one such patient, venous augmentation was performed 2 days postoperatively, resulting in ulcerations at the donor site of the saphenous vein graft.¹⁸

No official guidelines concerning the medical management of PG have been established. Typical treatment involves local wound care in conjunction with 1 mg/kg daily to 3 mg/kg daily of systemic corticosteroids to halt inflammation and disease progression.^1,10,11 Although there is no established wound care management, wet-to-dry dressings, application of petroleum jelly, and NPWT all have been reported in the literature.⁸ The authors of the current study recommend against wet-to-dry dressings to avoid further pathergy. Cyclosporine A is widely documented as an effective second-line therapy combined with steroids or after initial steroid use. Unfortunately, acute kidney injury from the administration of broad-spectrum antibiotics developed in the current case study; thus, cyclosporine was contraindicated. Cytotoxic drugs, sulfa drugs, oral tacrolimus, and anti-tumor necrosis factor alpha therapy such as infliximab are less commonly used but have proven effective in various cases.^1,10,11 Of the 15 cases reviewed, 13 patients (86.7%) received intravenous or oral steroids. Six patients (40%) received cyclosporine A. Notably, 1 patient was treated with topical tacrolimus in addition to intravenous steroids. Topical therapy reduces the risk of secondary infection and may be considered in conjunction with systemic therapy to allow earlier tapering of corticosteroids.^1,24 However, topical therapy is typically used for patients with more limited, indolent disease.²⁵

The patient reported herein first presented with symptoms 4 days after breast reconstruction, consistent with the median of 3.5 days calculated from the articles reviewed (Table Part 1 and Part 2). Initially, a necrotizing infection was suspected and managed with surgical debridement and broad-spectrum antibiotics. The similarity in presentation to infection made it difficult to reach a prompt diagnosis of PG. In breast reconstruction, undermining lesions, although among the classic signs of PG, are challenging to identify in light of surgically created mastectomy skin flaps. Over the course of a few days in this case, however, negative cultures, involvement of the abdominal donor site, and an unusually high white blood cell count were supportive of a diagnosis of PG.

The role of reconstructive surgical intervention after diagnosis of PG remains controversial. Many physicians regard it as futile and advocate for medical management alone to avoid worsening the condition.^5,15,26 However, surgical reconstruction may accelerate recovery in cases of persistent nonhealing lesions or significant defects. In the literature review conducted for this study, 8 of the 15 patients underwent surgery within 3 months of PG diagnosis. Skin grafting was used in 5 of these cases at an average of 62 days postoperatively. Synergistic approaches of surgical debridement complemented by NPWT also have been successful.¹¹ When surgery is considered, the use of immunosuppressive cover is imperative, and the disease must be quiescent prior to planned surgeries.²⁷

The authors of this study proceeded with the application of a bilayer wound matrix as an intermediate reconstruction for several reasons. First, applying a bilayer wound matrix theoretically reduces the risk of pathergy because there is no donor site to produce an injury stimulus. Second, it allows additional time for medical management to control the process before further operations. Wound care is facilitated because applying the bilayer wound matrix produces a closed sterile wound that protects the tissue from desiccation and eliminates the need for frequent dressing changes. Last, the bilayer wound matrix should improve esthetic outcomes because skin grafts applied to a bilayer wound matrix undergo less contracture than split-thickness skin grafts applied directly to granulating tissue. A similar approach was reported by Goshtasby et al²⁸ in the management of PG following reduction mammoplasty. A bilayer wound matrix was placed after 3 months of medical management and local wound care. The authors of the current study highlight the success of bilayer wound matrix placement in a patient within just 2 weeks of starting systemic steroid treatment, which is earlier than other reports in the literature. Through this approach, the patient achieved satisfactory wound healing and reasonable esthetic outcome without recurrence of PG.

In the case reported herein, early consultation with specialists in infectious diseases and dermatology resulted in a timely diagnosis of PG. Suspicion for PG is based on the clinical course as well as nonspecific histopathology. Involvement of the mastectomy skin and/or abdominal donor site with sparing of the transferred flap skin should raise the suspicion for PG. Diagnosis is made after excluding other possible disorders. In this case, a hematologist was consultated. Consultation with a gastroenterologist for a colonoscopy should also be considered to rule out inflammatory bowel disease. A multidisciplinary approach to clinical management is critical for effective and safe treatment.

Limitations of this study include the retrospective nature of the review and the fact that it is a case report. Timing and dosing of medical management and surgery may not apply to all patients. More research is needed, however challenging, given the rarity of the disease.

Although PG is an exceedingly rare complication, it should be considered in cases of atypical infectious presentations following autologous breast reconstruction. Early recognition and multidisciplinary management are critical to successful treatment and prevention of further morbidity. Early placement of a bilayer wound matrix followed by skin grafting is an option for reconstruction and may be performed safely earlier than previously reported in the literature.

Authors: Aishu Ramamurthi, BS¹; Karri A Adamson, MD¹; Kai J Yang, MD¹; James Sanger, MD¹; Justin P Ling-LeBlanc, MD¹; Barbara Wilson, MD²; and John A LoGiudice, MD¹

Affiliations: ¹Department of Plastic Surgery, Medical College of Wisconsin, Milwaukee, WI; ²Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI

Correspondence: Karri A Adamson, MD, Department of Plastic Surgery, Medical College of Wisconsin, 1155 N Mayfair Rd, Wauwatosa, WI 53226; kadamson@mcw.edu

Disclosure: The authors disclose no financial or other conflicts of interest.