The age, mobility, social support networks, pain threshold, extent and severity of disease, and ability to comply with therapeutic measures should be evaluated for each patient and the treatment adapted accordingly. The patient should be given realistic expectations of the speed of recovery likely in this disease. Thus, although lesions develop and evolve within days, the healing process usually takes weeks or even months. Adequate bed rest, efficient pain relief, correction of anemia, and appropriate therapy of any associated disease are pivotal in the overall management strategy of a patient with PG.12 If other systemic illnesses are present, cooperation with an internal medicine specialist is important, and if surgery is anticipated appropriate measures (such as the use of subcuticular sutures and systemic steroid cover) should be adopted to avoid precipitating new postoperative PG lesions.
The location, morphology, size, and outline of each lesion should be recorded (by photography and by using a calibrated transparent plastic sheet placed over lesions on which the outline is traced) on presentation and subsequent review.
The cutaneous lesions of PG are usually extremely tender so cleansing should be carried out daily with tepid sterile saline or a mild antiseptic solution. Potassium permanganate solution diluted 1:2,000 is helpful if there is marked exudation. Silver sulphadiazine 1% cream is usually soothing when applied to the ulcerated lesions of PG and may facilitate granulation tissue formation as well as inhibiting bacterial growth. A nonadhesive dressing should be applied over the lesion and held in place with a crêpe elasticized bandage wound firmly, but not tightly, over it. Some patients, particularly those with superficial lesions, obtain significant relief with the use of hydrocolloid dressings, which can be left on for 2–3 days and “melt” into the lesion. Careful instruction to the patient and nurse is important to ensure compliance and to avoid the use of irritants such as chemical desloughing agents, caustics (such as silver nitrate), or dressings (such as gauze impregnated with soft paraffin and/or antibacterial agents which may adhere to the ulcer base) or pressure dressings as are sometimes prescribed for patients with ulcers due to venous insufficiency. A variety of bacteria may be cultured from the wound surface, but these usually represent contaminants and directed antibiotic therapy is not required unless there are clinical signs of incipient cellulitis around the wound.
Topical treatments are important adjuncts to the systemic treatment needed for the management of most PG patients, and may be sufficient to bring the condition under control in those who have vegetative or mild ulcerative PG. Potent topical corticosteroids applied to the periphery of an active PG lesion can reduce inflammation and may be sufficient to heal vegetative or peristomal ulcerative PG.13 Although topical disodium cromoglycate (with or without occlusion), benzoyl peroxide, nicotine cream or patches, hyperbaric oxygen, and radiotherapy have all been reported as being helpful in individual patients with PG, their effectiveness has not been established. Clinical impression suggests that topical tacrolimus (with or without occlusion) is particularly effective for isolated pustular lesions and for the superficial ulcerations of peristomal PG.
Intralesional triamcinolone acetonide (5–10 mg/mL) injected twice weekly into the border of a vegetative or peristomal PG lesion may lead to healing and can also be useful in a patient with ulcerative PG if one section of the ulcer is proving recalcitrant to other therapies. Intralesional cyclosporine and tacrolimus have also been reported to be effective in some PG patients.
Because PG is a rare disease, most systemic treatment recommendations are based on experience gained from small series of patients studied.14 The main systemic treatments used for PG with their suggested dosages are listed in Box 33-2. As experience with newer agents is gained, it is likely these recommendations will change.15 The initiation of systemic therapy is based on the variant of PG (ulcerative and bullous PG usually require systemic therapy), the rapidity of its evolution, the extent of cutaneous involvement, and the general medical status of the patient.
Box 33-2 Systemic Treatments for Pyoderma Gangrenosum
Systemic corticosteroid treatment is probably the initial treatment of choice for most patients with PG. It is important to initiate systemic steroids at a sufficiently high dose to control the disease. Rapid diminution of pain is often recorded by the patient after initiation of therapy and steroids should be continued at this dosage until lesions show evidence of healing, after which gradual tapering of the dose can be undertaken. A steroid-sparing agent should be added as soon as possible, as well as bone protective measures to diminish the risk of osteoporosis because prolonged therapy can be anticipated in most patients. Intravenous corticosteroids in pulsed doses have been used to induce PG remission, but serious potential adverse effects limit their use to exceptional circumstances. Dapsone has been traditionally used in the treatment of PG and remains a useful drug, particularly when used in conjunction with systemic corticosteroids. Dapsone is generally well tolerated, but hematological complications (including agranulocytosis, hemolysis, hemolytic anemia, and methemoglobulinemia) as well as other potentially serious side effects may occur. Other antimicrobial agents reported as successful in the treatment of PG patients include rifampicin, tetracyclines, vancomycin, mezlocillin, clofazimine, and minocycline. These have usually been prescribed in combination with other systemic therapies and seem to work in PG patients by mechanisms other than their antibacterial properties. Most experience has been with clofazimine and minocycline (100–200 mg daily). The latter agent is well tolerated and often allows for a reduction in systemic corticosteroid dosage and appears to prolong remission in some patients.
Cyclosporine is an alternative first-line therapy of PG16 or may be used in combination with systemic corticosteroids to achieve rapid control of disease. Doses of 3 to 5 mgs/kg/day have shown efficacy and continued treatment is usually required for 3–4 months. Less risk of serious side effects (such as impairment of renal function and hypertension) is seen at these low doses, but careful monitoring of patients is required and attention should paid to the possibility of other drugs interacting with this medication.
Tacrolimus (FK-506) and mycophenolate mofetil have also been used successfully in the treatment of PG either as monotherapies or in combination with systemic corticosteroids or cyclosporine.17 Both drugs cause significant immunosuppression with resultant susceptibility of the patient to infection and malignant disease and can have other potentially serious side effects. Infliximab, an antitumor necrosis factor antibody, has been used successfully to treat patients with inflammatory bowel disease and has been reported to be effective in some patients with PG.18 Other similar drugs that have been reported to be efficacious in the treatment of patients with PG include etanercept and adalimumab. The role of these agents in the management of PG has yet to be fully defined and susceptibility to reactivation of tuberculosis infection and other significant side effects remain a concern. Anakinra, an IL-1 receptor antagonist has been reported to be effective in treating PG of the PAPA syndrome and suggests another possible treatment for this condition.5 The use of thalidomide in the treatment of PG has probably been superseded by the development of these other agents. Other drugs which have been reported to be helpful in the treatment of PG include azathioprine (thiopurine methyl transferase levels should be checked pretreatment), colchicine,19 cyclophosphamide, chlorambucil, and melphalan. These agents can have toxic effects and evidence of their efficacy is limited.
Other modalities which have been reported to be useful in the management of individual patients or small series of patients with PG include human intravenous immunoglobulin,20 interferon-α, nicotine,21 potassium iodide, leukocytapheresis,22 and plasma exchange. Skin grafting should be avoided if possible because of the risk of inducing new PG lesions at the donor sites, but cultured tissue allografts/autografts and the use of bovine collagen matrix have been reported to be useful in patients in whom the disease is controlled but reepithelialization incomplete.23
The unpredictable nature of PG and its variable aggressiveness in individual patients mean that a flexible approach to treatment is required and the use of therapeutic agents have to be adapted to the patient's physiologic state (childhood, pregnancy, old age). By whichever modality control of PG is achieved, maintenance therapy should be continued until there is complete wound healing. In addition, patients with ulcerative PG have a significant risk of relapse, so long-term follow-up is required.