Pyoderma Gangrenosum : A Review of Orthopedic Case Reports

Pyoderma gangrenosum (PG) is an uncommon disease characterized by necrotic ulcers that are often associated with underlying systemic disease. PG can occur at the surgical site following surgery, including orthopedic surgery, and may be commonly mistaken for postoperative infection, delaying diagnosis and resulting in wound deterioration and subsequent sequelae. Previously, 20 case reports of PG have been reported after orthopedic surgery. We reviewed these cases and found the majority (60%) were women. Forty percent had underlying evidence of systemic disease. Debridement was performed in 70%. Development of satellite lesions led to diagnosis of PG in 35%. These cases underscore the difficulty in diagnosis of PG and the use of inappropriate treatment, thereby highlighting the need for better awareness, diagnostic criteria, and clinical management of this disease.


Introduction
PG was first described by Brocq [1] in 1916 and then by Brunsting et al. [2] in 1930.PG is a noninfectious neutrophilic dermatosis that manifests clinically as papules and pustules that enlarge and become undermined, painful necrotic ulcers with a bluish border and surrounding erythema and edema (Figure 1).The necrotic ulcers must be distinguished from bacterial infection, and this can be challenging as the ulcers may become secondarily infected and develop a purulent exudative cover.The peak incidence of disease is between the ages of 20 to 50 years with women being more often affected than men [3].It is estimated that the disease affects somewhere between 3 and 10 patients per million [4].In 50-70% of patients, PG occurs in association with an underlying systemic disease such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA) or seronegative arthritis, and hematologic disorders [3,5,6].PG can develop in response to various medications or as a pathergic response at sites of skin damage after trauma and surgery [3].
We present an analysis of cases of PG reported in the orthopedic literature, and a review of the important clinical features of disease.The purpose of this report is to educate more health care providers on

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inability to reconstruct the affected foot, and a partial toe amputation in another due to compromised blood supply.Systemic steroids were used in the treatment of all cases.Four patients required skin grafts.One patient required a latissimus dorsi myocutaneous flap in addition to a skin graft for reconstruction, while another patient required a free fasciocutaneous anterolateral thigh flap and gastrocnemius flap for closure.One other patient required a free flap and rotational flap for closure of a large shoulder defect.This highlights the ability to perform uncomplicated surgery if accurate diagnosis and appropriate treatment is employed prior to surgery.

Discussion
PG is a neutrophilic dermatosis characterized by papules and pustules that rapidly progress to undermined necrotic ulcerations that can occur following surgery [3,5].Several clinical variants of PG have been described in the literature: ulcerative, pustular, bullous percent of patients had a significant past medical history including arthritis, myelodysplastic syndrome, and a vague history of wound complication.One patient had a history of both Crohn's disease and RA and another had a prior history of PG following a dog bite.
In the postoperative period, PG can easily be confused with wound infection, delaying diagnosis and contributing to significant patient morbidity.Patients will often receive multiple treatments by debridement for suspected wound infection that exacerbate the progression of disease due to pathergy, an aberrant immune response characterized by development of new lesions in response to trauma or surgery [5].Among the cases of PG following orthopedic surgery, 70% received at least one wound debridement before PG was accurately diagnosed, and 50% received multiple treatments by debridement.The development a satellite lesion distant to the site of surgery aided in the correct diagnosis in 35%.A delay in diagnosis led to a subsequent below-the-knee amputation in one patient due to an and vegetative [3,5,6].Ulcerative type classically presents on the legs, although it can occur anywhere and is associated with IBD and arthritis.The evolution of ulcerative PG involves pustules that enlarge and necrose, forming ulcers with a blue, damaged border and surrounding erythema.Pustular type commonly presents on the limbs as discrete, superficial pustules that coalesce and ulcerate, and is commonly associated with IBD.Bullous type typically occurs in association with hematologic malignancy and is characterized by painful vesicles that enlarge into bullae with a necrotic center.
Vegetative type typically presents on the trunk with a superficial, solitary ulcer.Vegetative PG is considered to be less aggressive and is usually not associated with an underlying systemic disease [5].
Pathogenesis is multifactorial and thought to involve abnormalities in neutrophil function and inflammatory mediators as well as a genetic predisposition [4].Defects in neutrophil migration, chemotaxis, and phagocytosis have been reported in patients with PG.Increased activity of neutrophils is thought to contribute to pathergy, an aberrant immune response to skin antigens altered by surgery or trauma responsible for causing PG in about 20-30% of patients.Various pro-inflammatory cytokines and other inflammatory mediators have also been implicated in pathogenesis.Immunohistochemical studies have demonstrated high levels of IL-8, a chemoattractant for neutrophils, in PG ulcers.Studies have also shown that IL-17, IL-23, TNF-alpha, and matrix metalloproteinases are overexpressed in PG lesions and that there is an imbalance of T-regulatory cells and Th17 cells in patients with PG.A number of genetic mutations have been reported, and in some cases a constellation of diseases occur in concert with PG.PAPASH syndrome is characterized by pyogenic arthritis, PG, hidradenitis suppurativa, and acne as a result of a mutation in the PSTPIP-1 gene.Genetic mutations implicated in IBD susceptibility have also been correlated with the development of PG [4].
Diagnosis is based predominantly on clinical findings.Obtaining a detailed past medical history of PG or an underlying systemic illness may help lead to the appropriate diagnosis.Diagnosis is made challenging by the fact that there is no laboratory parameter diagnostic of PG and biopsies of skin lesions demonstrate non-specific acute inflammatory changes with a preponderance of neutrophils [3,7] (Figure 2).Additionally, PG may mimic infection.Important clues to the diagnosis include sterile wound cultures, failure of ulcerative lesions to respond to antibiotic therapy, and provocation of disease after wound debridement [7].In practice, the development of satellite lesions distant to the site of surgery has proven to aid diagnosis.Major and minor diagnostic criteria have been proposed and may serve as a useful tool to the clinician when considered together [26,27].Major criteria include: 1) a rapidly progressing, painful, and necrolytic cutaneous ulcer, 2) exclusion of other cutaneous diseases.Minor criteria include: 1) a history of pathergy, 2) presence of an underlying systemic disease associated with PG, 3) characteristic histopathologic findings, 4) rapid response to steroids [27].
Approach to treatment involves both local and systemic therapies [5,28].Local therapy is centered on proper wound care and prevention of secondary infection.Topical corticosteroids may also be used alone or as an adjunct to systemic therapy [6].Skin grafting is typically unsuccessful and has been associated with the formation of new lesions at the donor site [19].However, in this review we found surgery was performed successfully after appropriate treatment had been employed.Options for systemic therapy include corticosteroids such as oral prednisone at a dose of 1mg/kg/day until lesions significantly improve followed by a taper.Intravenous pulse administration of high dose methylprednisolone can be used for rapid relief in refractory cases.Other systemic treatment options include TNF-alpha antagonists such as infliximab (which has the highest level of evidence), adalimumab, or etanercept, and calcineurin inhibitors such as cyclosporine, antimicrobials such as dapsone, and chemotherapeutic agents such as cyclophosphamide and methotrexate [19,27].
In conclusion, prompt identification and treatment of PG is imperative to decrease patient morbidity.This comprehensive analysis of individual case reports of PG in the orthopedic literature highlights the challenge of diagnosis in the postoperative period and the need for increased education amongst clinicians.In cases where cutaneous lesions develop postoperatively, PG should be considered in the differential, especially among patients with strong risk factors.Efforts to increase awareness of this disease should be taken to prevent misdiagnosis of infection and aggressive treatment by debridement that only exacerbates this condition.

Figure 1 :
Figure 1: PG ulcer with an undermined bluish border and surrounding erythema and edema.

Table 1 :
Cases of Pyoderma Gangrenosum Following Orthopedic Surgery.