Topical management
In mild cases, topical measures such as dressings, topical agents or intralesional injections may be sufficient to control the disease process (Table 1). Daily wound care should be performed through close liaison with a wound-care specialist. Moisture-retentive dressings appear to be superior to desiccative gauzes, in that they provide better pain control, induce collagen production, facilitate autolytic debridement and promote angiogenesis [58]. Furthermore, these occlusive dressings are useful as a means to avoid contaminating PPG with effluent. Cleansing of the wound with sterile saline is helpful, while the application of antibacterial agents—such as hydrogen peroxide or benzoyl peroxide—may also be useful [51, 59, 60]. Topical steroids and tacrolimus 0.3% preparations may be beneficial but care must be taken to exclude the possibility of concomitant infection [16, 61]. Patients whose diseases are in remission can try topical human platelet-derived growth factor if the process of re-epithelialization is slow [62, 63]. Intralesional injection of triamcinolone hexacetonide or cyclosporine has also been shown to be effective [64–66]. In general, the periphery of the lesion is injected, but the ulcer base may be injected too. Other topical therapies that may be used in controlling the inflammation and promoting wound healing include benzoyl peroxide, disodium cromoglycate, chlormethine, nicotine and 5-aminosalicylic acid [59, 62, 67–72].
Although PPG is a non-infectious disease in origin, the ulcer can harbor superimposed bacterial infection. If infection is suspected, swabs for bacterial and fungal smear and culture should be taken and empiric antibiotic treatment that covers coliforms should be given immediately [48]. Surgical intervention for PPG—such as debridement—should be avoided, as pathergy can coincide in 25–50% cases of PG. The risk of developing recurrent and more refractory PG may be high [5].
Systemic management
In patients who do not respond to topical or local therapies, who have a severe, rapid course, or who have active underlying disease (i.e. IBD), systemic management should be considered. Although there is no single therapy that can be efficacious in all cases, oral prednisone has been shown in the literature to be the most consistently successful agent for the treatment of PG [48]. Therapy with oral prednisone (1 mg/kg per day) is usually effective in controlling PG (Table 1) [73, 74]. The treatment should be continued until the lesions show evidence of healing and prolonged low-dose maintenance therapy is usually necessary in recurrent cases. Intravenous corticosteroid therapy (hydrocortisone 100 mg four times daily or methylprednisolone 1 g/day [pulse therapy]) for up to 5 days has also been reported to be successful (Table 1) [52, 75, 76]. Patients exposed to long-term use of prednisone are at risk of related side-effects: protecting agents, such as calcium, vitamin D and bisphosphonates can be used concomitantly [77]. Oral minocycline 100 mg twice daily may be of some benefit, usually as an adjunct to oral corticosteroid [2].
There are alternative ‘step-up’ therapies, the main purposes of which are twofold: (i) to reduce dependence on corticosteroids and (ii) to treat refractory disease. Dapsone and minocycline are the most frequently prescribed agents to provide a steroid-sparing effect [34, 54–56]. Oral dapsone 100–300 mg per day or minocycline 100 mg twice daily appear to be efficacious (Table 1). The mechanisms of action of these agents in the treatment of PG are not fully understood but they are related to its anti-microbial activity or anti-inflammatory effect. When corticosteroids fail, the most widely used alternative is cyclosporin [28, 74]. Several case reports and small case series demonstrate that most patients show clinical improvement within three weeks with a dose of 3–5 mg/kg per day and cyclosprin has been shown to be considerably more efficacious in the treatment of PG than azathioprine and methotrexate [26, 78, 79]. Other reported effective agents are tacrolimus, 6-mercaptopurine, cyclophosphamide, colchicine, clofazimine and chlorambucil [80–85].
Infliximab, an antibody against tumor necrosis factor α, has been shown to be efficacious in the management of PG. A randomized double blind, placebo-controlled trial by Brooklyn et al. compared 13 PG patients treated with infliximab with a group of 17 controls [3]. At 2 weeks, 46% of the infliximab group had responded, compared with 6% of the control group. Concerns about side-effects of infliximab, such as sepsis, have also been raised [48]. However, the benefits of infliximab outweigh the risks of its use and the agent has become the drug of choice in steroid-refractory PG. Although there are reports of refractory cases [86–88], adalimumab and etanercept are also thought to be effective biologic agents for PG[89–92]. Uses of plasma exchange, human immunoglobulin infusion and interferon-a therapy are also reported in more refractory PG (Table 1) [93–95].
General management
Because of the persistent and recurrent nature of PG, a long-term maintenance therapy may be required. As a general measure, pain relief, correction of anemia, nutrition and management of associated disease are important. Stoma care, including use of an appropriate stoma appliance and prevention of leaks, also deserves attention (Table 1) [5]. Relocation of stoma should be contra-indicated except for other indications, such as parastomal herniation or stoma dysfunction.