Version May 2024
INTRODUCTION — Pyoderma gangrenosum (PG) is an uncommon inflammatory and ulcerative skin disorder characterized histopathologically by the accumulation of neutrophils in the skin. The most common presentation of PG is the rapid development of one or more painful, purulent ulcers with undermined borders on sites of normal or traumatized skin (picture 1A-C).
Although multiple local and systemic therapies have been utilized for PG, high-quality efficacy studies are lacking for most interventions. Topical corticosteroids, systemic corticosteroids, and cyclosporine are common initial therapies (algorithm 1).
The management and prognosis of PG will be reviewed here. The pathogenesis, clinical features, and diagnosis of PG are reviewed separately. (See "Pyoderma gangrenosum: Pathogenesis, clinical features, and diagnosis".)
TREATMENT PRINCIPLES — In general, after the diagnosis of PG is made, patients are managed with a combination of pharmacologic therapies that suppress the inflammatory process and wound care measures that optimize the environment for wound healing. Although initial signs of improvement may be evident within days of the start of some treatments, weeks to months are often required to achieve complete ulcer healing [1,2].
Major principles of treatment include:
●Importance of confirming the diagnosis – The careful exclusion of causes of cutaneous ulceration (eg, vascular occlusion disorders, venous disease, vasculitis, malignancy, cutaneous infection, trauma, and other ulcerative inflammatory disorders) prior to treatment is critical. Some therapies utilized for PG can be ineffective or harmful in other diseases. (See "Pyoderma gangrenosum: Pathogenesis, clinical features, and diagnosis", section on 'Diagnosis' and "Pyoderma gangrenosum: Pathogenesis, clinical features, and diagnosis", section on 'Differential diagnosis'.)
●Limited efficacy data – Due to a paucity of high-quality data on interventions for PG, definitive guidelines for patient management are lacking. The approach to the treatment of PG is primarily guided by small uncontrolled studies and reports of clinical experience [3]. (See 'Treatment selection' below.)
●Role of disease severity in initial treatment selection – The severity of PG influences our choice of initial therapy. Although topical therapies successfully induce healing in some patients with limited disease, patients with more extensive PG generally require systemic therapy to arrest disease activity. (See 'Limited disease' below and 'More extensive disease and treatment-resistant limited disease' below.)
●Role of adjunctive systemic therapy – Systemic administration of glucocorticoids or cyclosporine is our preferred initial treatment for extensive PG. However, monotherapy can be insufficient, and long-term treatment with these drugs is associated with risk for serious adverse effects. We frequently incorporate other systemic immunomodulatory drugs (eg, infliximab, adalimumab, mycophenolate mofetil) to reduce exposure to systemic glucocorticoids and cyclosporine and promote healing of PG. (See 'Subsequent management' below.)
●Impact of concomitant PG-associated diseases – PG can occur in association with a variety of disorders, such as inflammatory bowel disease, inflammatory arthritis, malignancy, and hematologic disease. The presence of an associated disorder often influences the selection of adjunctive or subsequent treatments for PG, contributing to the selection of treatments that have benefit in both PG and the associated disease. (See 'Prognosis' below and 'Subsequent management' below and "Pyoderma gangrenosum: Pathogenesis, clinical features, and diagnosis", section on 'Associated disorders'.)
●Assessing treatment response – Stabilization of disease progression and reductions in pain and visible signs of inflammation (eg, violaceous discoloration at the wound border) are important early signs of response. Subsequently, the wound base begins to fill with granulation tissue, and the wound diameter progressively shrinks. Documentation of the size, number, and location of ulcers and serial clinical photographs are useful for following the response to therapy.
●Wound management – Wound care is an important component of the management of PG. Key principles include wound dressing, monitoring for infection, avoidance of trauma, and judicious use of surgery. (See 'Wound management' below.)
TREATMENT SELECTION
Limited disease — Limited PG may be considered PG presenting as a single small, superficial (eg, <3 cm) ulcer (picture 1A); a few small, superficial ulcers; or a solitary plaque of vegetative PG. (See "Pyoderma gangrenosum: Pathogenesis, clinical features, and diagnosis", section on 'Subtypes'.)
Initial therapy — Topical corticosteroid therapy is our preferred initial treatment for limited PG (algorithm 1). Wound care and pain management are additional important components of treatment. (See 'Topical corticosteroids' below and 'Wound management' below and 'Pain management' below.)
Topical corticosteroids
●Administration and precautions – We typically utilize a high-potency topical corticosteroid (group 1 or 2 (table 1)), such as clobetasol 0.05% ointment. We instruct patients to apply the topical corticosteroid once or twice daily to the inflamed ulcer periphery. Initial signs of response to topical corticosteroid therapy (eg, stabilization of disease progression and reduced pain) are expected within two to four weeks. If there is a response, treatment is continued until complete healing.
Intralesional injection of corticosteroids (eg, triamcinolone acetonide) has also been used for PG. However, some clinicians, including ourselves, avoid intralesional injections due to concern for the induction of pathergy. Concentrations of triamcinolone between 6 and 40 mg/mL have been utilized [4]. The corticosteroid is injected circumferentially into the ulcer periphery. (See "Intralesional corticosteroid injection" and "Pyoderma gangrenosum: Pathogenesis, clinical features, and diagnosis", section on 'Common features'.)
Cutaneous atrophy, hypopigmentation, and suppression of the hypothalamic-pituitary axis are examples of adverse effects of topical and intralesional corticosteroid therapy. Adverse effects are reviewed in greater detail separately. (See "Topical corticosteroids: Use and adverse effects", section on 'Adverse effects' and "Intralesional corticosteroid injection", section on 'Adverse effects and pitfalls'.)
●Efficacy – Although topical corticosteroids are frequently prescribed as primary and adjunctive therapies in PG, data on the efficacy of local corticosteroid therapy are limited [5-8]. Examples of studies assessing efficacy include:
•A multicenter prospective cohort study that evaluated outcomes of topical therapy in 66 patients with PG supports benefit of topical corticosteroid treatment [7]. Most patients (74 percent) received clobetasol propionate 0.05%; the remaining patients received topical tacrolimus 0.03% or 0.1% ointment. At six months, 28 of the 64 patients (44 percent) for whom information on healing was available had healed on topical therapy alone, including 20 of 47 (43 percent) treated with clobetasol and 5 of 10 (50 percent) treated with topical tacrolimus. The median time to healing was 145 days. Initial ulcer size was a predictor of time to healing.
•In a prospective cohort study that included 49 patients with PG treated with clobetasol propionate 0.05%, 20 (43 percent) achieved healing within six months [7]. The median time to healing was 136 days.
Benefit of intralesional corticosteroid therapy in PG is documented in case reports [6,9-12].
Insufficient response to initial therapy — When topical corticosteroid therapy does not improve limited PG within two to four weeks, we often switch to tacrolimus 0.1% ointment or start oral dapsone or oral minocycline (algorithm 1). Although efficacy data are limited, the relatively favorable adverse effect profiles of these therapies prompt us to try them prior to proceeding to immunosuppressive therapies. (See 'More extensive disease and treatment-resistant limited disease' below.)
Topical tacrolimus
●Administration and precautions – Topical tacrolimus, a topical calcineurin inhibitor, is commercially available as a 0.03% and 0.1% ointment. We typically prescribe tacrolimus 0.1% ointment and instruct patients to apply the ointment to the inflamed ulcer periphery once to twice daily. Signs of improvement may be evident within the first few days to weeks of treatment. However, several weeks to a few months of treatment may be necessary for complete ulcer healing [13-15].
Topical tacrolimus is usually well tolerated; occasionally, patients experience mild burning sensations at the site of application [14].
●Efficacy – Topical tacrolimus in concentrations of 0.03% to 0.3% has demonstrated efficacy for PG in multiple case reports, a few prospective case series, and uncontrolled studies [5,7,13,16]. In one uncontrolled study, a compounded formulation of 0.3% tacrolimus in a carmellose sodium paste appeared to be effective for peristomal PG [8]. Seven of 11 patients treated with the tacrolimus formulation and 5 of 13 patients treated with clobetasol 0.05% lotion or ointment achieved complete healing. In a prospective cohort study that included 10 patients with PG treated with topical tacrolimus, five (50 percent) achieved healing with six months, with a median time to healing of 161 days [7].
Other calcineurin inhibitors may have benefit for PG, but fewer data are available on these agents. A case report documented improvement with pimecrolimus 1% cream [17]. Improvement with topical or intralesional cyclosporine has been described in a few patients [18-21].
Oral dapsone
●Administration and precautions – Our typical target dose for dapsone ranges from 100 to 150 mg per day. We typically start treatment for adults at 50 mg per day and subsequently increase the dose to 100 mg per day after 7 to 10 days (if laboratory tests detect no significant abnormalities).
Signs of improvement usually occur within two to four weeks of an optimal dose. If there is a poor response at 100 mg per day and the patient is tolerating dapsone, we consider increasing the dose to 150 mg per day. If there is no evidence of response within four weeks at this dose, we stop dapsone. Hematologic adverse events can be a limiting factor for increasing the dose of dapsone.
Examples of adverse effects of dapsone include hemolysis, agranulocytosis, methemoglobinemia, dapsone hypersensitivity syndrome, and peripheral neuropathy (table 2). Patients require laboratory monitoring for hematologic and liver toxicity.
Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at increased risk for hematologic toxicity. Screening for G6PD deficiency should precede dapsone therapy. (See "Diagnosis and management of glucose-6-phosphate dehydrogenase (G6PD) deficiency".)
●Efficacy – In case reports and small series, dapsone has been associated with improvements in PG when administered as monotherapy or as a glucocorticoid-sparing agent [9,22-29]. In one retrospective study of 27 patients who received dapsone for at least four weeks as a component of PG therapy, a complete or partial response was documented for 16 and 81 percent of patients, respectively, with an average time to initial response of approximately five weeks [29].
Oral minocycline
●Administration and precautions – Typical dosing for oral minocycline for adults is 100 mg twice daily. Some clinicians utilize doxycycline as an alternative to minocycline because of a more favorable adverse effect profile; however, most published reports of benefit involve use of minocycline [22]. If there is no evidence of response within six to eight weeks, we stop minocycline.
Examples of potential adverse effects of minocycline include dizziness, skin discoloration, photosensitivity, and a lupus-like syndrome. Similar to other tetracyclines, minocycline should not be administered to pregnant individuals or children under the age of nine years due to adverse effects on tooth development.
●Efficacy – Efficacy data for minocycline are limited. Case reports describe improvement in PG when used as monotherapy or as a glucocorticoid-sparing agent [22,30-39].
Refractory limited disease — When limited PG does not respond adequately to topical corticosteroids, topical calcineurin inhibitors, oral dapsone, or oral minocycline, we proceed to interventions utilized for more extensive disease (algorithm 1). (See 'More extensive disease and treatment-resistant limited disease' below.)
More extensive disease and treatment-resistant limited disease — We take a different approach to the treatment of PG that exceeds our description of limited disease (ie, more than a few small [eg, <3 cm] superficial ulcers or a solitary plaque of vegetative PG). This extent of PG generally requires systemic therapy to calm the inflammatory process to allow for wound healing. Systemic therapy is also appropriate for limited PG that responds insufficiently to other treatments. (See 'Limited disease' above.)
Initial treatment — Our preferred initial treatment for extensive PG is a systemic glucocorticoid or oral cyclosporine because of a rapid onset of anti-inflammatory effects (algorithm 1). We select the most tolerable drug based on the patient-specific factors, such as comorbidities. Most often, we begin with a systemic glucocorticoid, reserving cyclosporine for patients who may not tolerate systemic glucocorticoid therapy.
Because long-term treatment with these therapies is often associated with serious adverse effects, we often incorporate other systemic immunosuppressive therapies within the first few weeks of treatment. (See 'Subsequent management' below and "Major adverse effects of systemic glucocorticoids" and "Pharmacology of cyclosporine and tacrolimus", section on 'Side effects'.)
Wound care and pain management are additional important components of treatment. (See 'Wound management' below.)
Topical corticosteroids and topical tacrolimus are often used as adjuncts to systemic treatment. (See 'Topical corticosteroids' above and 'Topical tacrolimus' above.)
Systemic glucocorticoids
●Administration and precautions – Our typical initial regimen for adults is 0.5 to 1.5 mg/kg per day of oral prednisone or its equivalent, with a maximum dose of 60 mg of prednisone per day. In very aggressive or painful disease, intravenous pulse corticosteroids (methylprednisolone 1 g per day for one to five days) can be used as initial treatment [40-42]. Patients are subsequently transitioned to an oral corticosteroid.
The response to systemic glucocorticoids is usually rapid; stabilization of the disease is often evident within the first week [43]. Pain also tends to improve soon after the initiation of treatment.
We aim to taper the glucocorticoid as soon as feasible because of the potential for serious adverse effects with long-term systemic glucocorticoid treatment. For most patients, this prompts us to add an additional systemic agent within the first few weeks of treatment. (See 'Subsequent management' below.)
Systemic glucocorticoid therapy is associated with a wide variety of potential adverse effects (table 3). Systemic glucocorticoid therapy should include consideration of measures to reduce glucocorticoid-associated bone loss. (See "Major adverse effects of systemic glucocorticoids" and "Prevention and treatment of glucocorticoid-induced osteoporosis".)
●Efficacy – Although multiple case reports, case series, and our clinical experience support the use of systemic glucocorticoids for PG [6,22], the findings of a single-blind randomized trial (n = 112) that compared prednisolone monotherapy (initial dose 0.75 mg/kg per day, up to 75 mg per day) with cyclosporine 4 mg/kg per day (up to 400 mg per day) showed that systemic glucocorticoid therapy alone may be insufficient for many patients [44]. After six months, there was only a 47 percent rate of complete ulcer healing in both groups. The pace of improvement during the first six weeks of treatment was similar between the groups, suggesting a comparable time to onset of action. Rates of adverse reactions were also similar in both groups, but serious reactions, notably serious infections, were more frequent in the prednisolone group.
Systemic cyclosporine
●Administration and precautions – Our typical initial regimen for adults is 4 to 5 mg/kg of cyclosporine per day [45]. As with oral glucocorticoids, the response is usually rapid. Pain often improves within a few days, and other signs of improvement are expected within the first four weeks.
We aim to taper cyclosporine as soon as feasible because of concern for adverse effects. For most patients, this prompts us to add an additional systemic agent within the first few weeks of treatment. (See 'Subsequent management' below.)
Examples of adverse effects of cyclosporine include renal toxicity, hypertension, and increased risk for infections and malignancy. Adverse effects are reviewed in greater detail separately. Periodic monitoring of renal function and blood pressure are indicated. Contraindications for cyclosporine include concurrent malignancy, uncontrolled hypertension, uncontrolled infections. (See "Pharmacology of cyclosporine and tacrolimus", section on 'Side effects'.)
●Efficacy – A single-blind randomized trial (n = 112) that compared cyclosporine with prednisolone found complete healing after six months in approximately one-half of patients treated with cyclosporine and a similar time to onset of action between cyclosporine and prednisolone [44]. (See 'Systemic glucocorticoids' above.)
In addition, several retrospective analyses and case reports suggest a beneficial effect of cyclosporine [9,22-24,44,46,47].
Subsequent management
Role and implementation — In our experience, most patients with extensive PG require many months of systemic treatment to achieve healing. Systemic therapies other than glucocorticoids and cyclosporine (eg, infliximab, adalimumab, mycophenolate mofetil) may play an important role in achieving healing of PG and reducing risk for adverse effects related to long-term systemic glucocorticoid or cyclosporine therapy.
●Timing – Many of the immunosuppressive therapies preferred for long-term treatment have a slower onset of action than systemic glucocorticoids and cyclosporine. Therefore, we often add these therapies early, usually within the first few weeks of systemic glucocorticoid or cyclosporine treatment. This supports tapering of glucocorticoids and cyclosporine within a reasonable period.
An occasional exception is the patient who experiences very rapid ulcer healing during the first few weeks of systemic glucocorticoid or cyclosporine therapy. If a need for prolonged systemic treatment (eg, more than two to three months for oral glucocorticoids or more than three to six months for cyclosporine) appears unlikely, we often defer the addition of another systemic treatment.
●Treatment selection – Infliximab, adalimumab, or mycophenolate mofetil are our preferred long-term therapies for PG because of data that suggest efficacy for PG. However, other factors can influence the selection of treatment, such as comorbidities, patient preference, or treatment availability. For example, infliximab or adalimumab may be preferred over mycophenolate mofetil for a patient with Crohn disease or ulcerative colitis because of the benefit of biologic tumor necrosis factor (TNF) inhibitors for inflammatory bowel disease and PG, and contraindications to immunosuppression may lead to the selection of intravenous immune globulin (IVIG) over other therapies. In other scenarios, a biologic interleukin (IL) 17 or IL-23 inhibitor may be preferred because of efficacy for a comorbidity. (See 'Infliximab' below and 'Mycophenolate mofetil' below and 'Other interventions' below.)
●Tapering and discontinuation of systemic glucocorticoids and cyclosporine – For patients receiving a systemic glucocorticoid (or cyclosporine) plus another systemic agent, we typically begin to taper the glucocorticoid or cyclosporine once disease progression has stopped and clear signs of improvement are evident (reductions in pain, visible inflammation, and wound size). For patients receiving a systemic glucocorticoid or cyclosporine alone because of a high likelihood of achieving complete healing relatively quickly, we begin to taper the drug after achievement of complete healing.
We aim to taper and discontinue glucocorticoids within 4 to 10 weeks and monitor patients closely for continued improvement. Tapering glucocorticoids too rapidly may precipitate disease flares [43].
We typically taper cyclosporine over a period that is twice as long as the duration of cyclosporine therapy (eg, taper over five to six months for patients with a three-month duration of cyclosporine therapy).
Infliximab
●Administration and precautions – The treatment regimens for infliximab and the time to response to infliximab vary considerably across case reports and studies [48]. The optimal treatment regimen has not been determined. We typically administer a 5 mg/kg intravenous infusion of infliximab at weeks 0, 2, and 6, followed by infusions every six to eight weeks [45]. In our experience, initial signs of response are usually evident within 8 to 12 weeks.
Potential adverse effects of infliximab include infusion reactions, infections, demyelinating disease, and heart failure. The side effects of TNF-alpha inhibitors are discussed in greater detail separately. (See "Tumor necrosis factor-alpha inhibitors: An overview of adverse effects".)
●Efficacy – The use of infliximab, a chimeric antibody against TNF-alpha, in PG is supported by a placebo-controlled randomized trial of 30 adults with PG, many of whom were concomitantly treated with topical or systemic therapy (most often oral prednisolone) [49]. At the start of the trial, patients were given either a single 5 mg/kg infusion of infliximab (n = 13) or placebo (n = 17). After two weeks, more patients in the infliximab group had clinical signs of improvement (46 versus 6 percent).
Patients in both groups who did not exhibit improvement at week 2 were then given open-label infliximab (a 5 mg/kg single dose). At week 6, 20 of the 29 patients who received infliximab (69 percent) had improved, and 6 patients achieved complete remission (21 percent). There was no significant difference in the response to treatment among patients with (n = 18) and without (n = 11) inflammatory bowel disease. Long-term follow-up was not performed.
In addition to the randomized trial, other studies suggest efficacy of infliximab [50,51]. As an example, a multicenter retrospective study of 13 patients with refractory PG and inflammatory bowel disease treated with 5 mg/kg of infliximab (1 to 24 infusions over zero to four years and in conjunction with other systemic therapies) found that all 13 patients achieved complete healing. The mean times to initial response and complete healing were 11 days (range 2 to 30 days) and 86 days (range 7 to 210 days), respectively [51]. Ten patients required periodic infusions every 4 to 12 weeks to maintain the clinical response. All patients who were taking systemic glucocorticoids were able to discontinue glucocorticoid therapy.
Adalimumab
●Administration and precautions – As with infliximab, adalimumab treatment regimens vary [52-55]. Our typical approach begins with a 40 mg dose of adalimumab every other week. Signs of improvement usually become evident within 8 to 12 weeks. In our experience, a subsequent increase to once-weekly dosing is often required to achieve complete healing.
Potential adverse effects include injection site reactions, infections, demyelinating disease, and heart failure. The side effects of TNF-alpha inhibitors are discussed in greater detail separately. (See "Tumor necrosis factor-alpha inhibitors: An overview of adverse effects".)
●Efficacy – An open-label study of 22 adults with PG treated with adalimumab (at doses of 160 mg at week 0, followed by 80 mg at week 2, and then 40 mg every other week starting at week 4) suggests benefit of adalimumab [56]. Sixteen patients (73 percent) also received oral corticosteroids (≤10 mg per day) for PG or other indications. At week 26, 12 patients achieved complete healing of the target ulcer (55 percent, 95% CI 32-76 percent). The mean time to healing of the target ulcer was 115 days. Adalimumab has also been associated with ulcer healing in reports of individual patients [52-55].
Mycophenolate mofetil
●Administration and precautions – Typical dosing of mycophenolate mofetil for PG in adults is 2 to 3 g per day. Initial signs of response are expected within 8 to 12 weeks.
Examples of adverse effects of mycophenolate mofetil include gastrointestinal symptoms and bone marrow suppression. Adverse effects are reviewed in greater detail separately. (See "Mycophenolate: Overview of use and adverse effects in the treatment of rheumatic diseases", section on 'Adverse effects'.)
●Efficacy – Multiple cases of improvement in PG with mycophenolate mofetil have been reported [9,24,57-62]. Mycophenolate mofetil appeared beneficial in a retrospective study of 26 patients with PG treated with mycophenolate mofetil and prednisolone (with or without other immunomodulatory agents) for at least one month [62]. Improvement in disease severity during treatment was noted in 22 patients (85 percent). Moreover, in a retrospective study of seven patients treated with mycophenolate mofetil for at least two months, four of seven had complete healing, including two patients for whom mycophenolate mofetil was the only systemic therapy given for PG [61].
Refractory disease — When our typical approach to treatment is insufficient, we proceed to other therapies. Because efficacy data are limited, selection of a next-line treatment is primarily based upon consideration of patient comorbidities, patient preference, and treatment availability. (See 'Other interventions' below.)
Cessation of therapy — Once complete healing of lesions has occurred, treatment cessation can be attempted. Systemic therapy should be gradually tapered and stopped over the course of several months rather than abruptly discontinued.
Prolonged treatment is necessary for some patients. In a series of 42 patients with PG who were followed for a median of 26.5 months, 56 percent of the 34 patients who remained alive during the follow-up period required continuing pharmacologic therapy, and 44 percent were able to maintain complete remission without therapy [23].
WOUND MANAGEMENT — The goal of wound care in PG is to create an optimal environment for wound healing.
Local care — Wounds should be cleansed gently with tepid sterile saline or a mild antiseptic prior to dressing changes [2]. Wound dressings that promote a moist wound environment and do not adhere to the wound base are preferred, as they may be beneficial for healing [63]. (See "Basic principles of wound management", section on 'Importance of moisture'.)
The selection of a specific type of wound dressing depends on the nature of the wound and patient and clinician preferences. As an example, patients with wounds that are highly exudative may benefit from the use of more absorptive wound dressings, such as alginates to avoid tissue maceration [64]. (See "Basic principles of wound management", section on 'Wound dressings'.)
In addition to the area of ulceration or erosion, attention should also be paid to the surrounding skin. Use of a barrier cream or ointment, such as zinc oxide paste or petrolatum, may help to prevent skin breakdown at the wound edge [63,64].
Patients should be monitored for clinical signs of wound infection (eg, fever, warmth, swelling, malodor, lymphangitic streaks, increased drainage, or pain) and should be treated appropriately with antibiotics if infection occurs [64].
Avoidance of trauma — Pathergy (exacerbation or new development of lesions at sites of trauma) can occur in PG. Thus, unnecessary traumatic insults to the wound, such as the use of wet to dry dressings and the application of caustic substances (eg, silver nitrate), should be avoided [2,64]. (See "Pyoderma gangrenosum: Pathogenesis, clinical features, and diagnosis".)
If surgery for another indication is necessary in a patient with active PG, we encourage the continuation of PG treatment to the greatest degree feasible and halt tapering of PG therapies in the perioperative period and until the surgical wound has healed. Ideally, elective surgical procedures should be deferred until complete healing of PG has been achieved.
Role of surgery and other interventions — Due to the potential for pathergy, the role of surgery for wound management in PG is controversial [65]. Surgical procedures are considered only in select cases, such as those in which accumulation of necrotic tissue presents a risk for infection or where vital tissues such as tendons or ligaments are exposed in the ulcer bed [6,45].
Although multiple cases in which PG worsened following surgical intervention have been reported [1,66], documentation of cases in which gentle debridement, skin flaps or grafts [67-70], split-thickness grafts with negative pressure wound therapy [71], and the application of bioengineered keratinocyte autografts [58] or allogenic cultured dermal substitutes [72] appeared to be beneficial in PG exists. In a review of the literature that identified cases of surgical intervention in patients with active PG, postoperative disease progression was identified in only 17 percent of patients [65].
If surgery for a PG ulcer will be performed, we advise delaying surgery until a period of good disease control (ie, resolution of erythema or violaceous color at the wound border and cessation of progression of disease). Patients should be concomitantly treated with systemic PG therapy [73].
Although stoma closure can lead to resolution of peristomal PG, recurrence of PG may be common after relocation or revision of a stoma. In a retrospective chart review of 44 patients with peristomal PG, 10 of 15 patients (67 percent) who underwent relocation or revision of a stoma developed recurrent PG [74].
Hyperbaric oxygen has been reported to be of benefit for wound healing in a few patients with PG, but data are insufficient to recommend the routine use of this therapy [75-77].
PAIN MANAGEMENT — Ulcers of PG are often associated with significant pain that appears out of proportion to the clinical appearance of lesions. Although pain may improve during treatment, some patients require the use of narcotic agents to manage discomfort. Consultation with a pain management specialist may be beneficial [63]. (See "Approach to the management of chronic non-cancer pain in adults".)
OTHER INTERVENTIONS — Various other interventions have been utilized for PG, but limited efficacy data, unfavorable adverse effect profiles, cost, or availability generally restrict their use to refractory disease and scenarios in which a particular treatment may provide joint benefit for PG and a comorbidity. Examples of these interventions include other biologic agents (adalimumab, interleukin [IL] 17 inhibitors, IL-23 inhibitors), other conventional immunosuppressants (methotrexate, azathioprine), intravenous immune globulin (IVIG), alkylating agents, and other treatments.
●Other biologic TNF inhibitors – In our experience, infliximab and adalimumab are more efficacious than other tumor necrosis factor (TNF) inhibitors, although benefit of other TNF inhibitors has been reported. Improvement in PG with etanercept (at a dose of 25 to 50 mg twice weekly) has also been reported in a small retrospective series and case report [78,79]. There are case reports describing benefit of other biologic TNF-alpha inhibitors, such as certolizumab pegol [80,81] and golimumab [82].
●Biologic IL-17 and IL-23 inhibitors – Case reports, most describing biologic therapy as an adjunctive treatment for PG in patients with concomitant inflammatory bowel disease, suggest benefit of ustekinumab, an anti-interleukin (IL) 12/23 inhibitor [83-85], as well as the anti-IL-23 biologic agents tildrakizumab [86], guselkumab [87], and risankizumab [88]. The use of anti-IL-17 biologics for PG is uncertain, with both cases of induction and clearance of PG in secukinumab [89,90], ixekizumab [91,92], and brodalumab [93,94].
●Conventional immunosuppressants – Methotrexate [95] and azathioprine [23,96] have appeared beneficial as adjunctive or glucocorticoid sparing in case reports and small case series [97]. Similar to mycophenolate mofetil, these drugs have a delayed onset of action (usually 8 to 12 weeks).
Typical adult dosing for methotrexate is 10 to 30 mg per week; azathioprine is usually prescribed at doses ranging from 100 to 300 mg per day [45]. Thiopurine methyltransferase (TPMT) enzyme activity guides appropriate dosing for azathioprine. Both drugs have the potential for serious adverse effects. (See "Major side effects of low-dose methotrexate" and "Pharmacology and side effects of azathioprine when used in rheumatic diseases", section on 'Adverse effects' and "Thiopurines: Pretreatment testing and approach to therapeutic drug monitoring for adults with inflammatory bowel disease", section on 'Assessing TPMT enzyme activity'.)
●IVIG – Intravenous immune globulin (IVIG) is typically given as a total dose of 2 g/kg every four weeks. The total dose is divided and administered over the course of two to five days.
Efficacy data for IVIG for PG are limited. A systematic review of cases and case series documenting treatment of refractory PG with IVIG (often in conjunction with systemic glucocorticoids) found complete responses in 26 of 49 patients (53 percent) and complete or partial responses in 43 of 49 patients (88 percent) [98]. The mean time to initial response was 3.5 weeks, and patients were treated for an average of 5.9 months. Limitations of the review included potential publication bias given that most data were derived from case reports and a paucity of long-term, follow-up data in the included patients. Moreover, failures to respond to retreatment with IVIG upon disease relapse have occurred. Well-designed prospective trials are necessary to clarify the efficacy of IVIG for PG. (See "Overview of intravenous immune globulin (IVIG) therapy".)
●Cyclophosphamide and chlorambucil – Although a few case reports and uncontrolled studies document improvement in refractory PG with pulsed intravenous cyclophosphamide [99-101] or chlorambucil [102-104], concern for myelosuppression and other severe adverse effects limits the use of these alkylating agents. In an uncontrolled study of nine patients with PG treated with monthly infusions of cyclophosphamide (at a dose of 500 mg/m2 for up to six treatments), seven patients achieved complete remission, one achieved partial remission, and one failed to respond to therapy [99]. Four patients achieved complete healing prior to the third treatment. Two patients relapsed within three months after the cessation of therapy.
Chlorambucil appeared to be effective for recalcitrant PG in an uncontrolled study of six patients who were treated with chlorambucil (at a dose of 2 to 4 mg per day) with or without prednisone therapy [102]. Improvement was noted in six to eight weeks, and healing of ulcers occurred within 2 to 10 months in all patients. All patients who were also receiving prednisone for PG were able to discontinue prednisone therapy. Prolonged remissions (four to nine years) were sustained in four patients who discontinued chlorambucil after 6 to 24 months of therapy.
●Other agents – Multiple other interventions have been reported to be of benefit in individual patients. Examples of topical therapies include sodium cromoglycate [9,105,106], nicotine [107-109], benzoyl peroxide [110,111], 5-aminosalicylic acid [112], nitrogen mustard [113], and platelet-derived growth factor [114,115].
Other biologic agents with reports of apparent benefit include the IL-1 inhibitor anakinra [116], the IL-1-beta inhibitor canakinumab [117], the IL-36 receptor antagonist spesolimab [118], and the IL-6 inhibitor tocilizumab [119]. Janus kinase (JAK) inhibitors with reports of apparent benefit include baricitinib [120,121] and tofacitinib [122-125].
Additional systemic agents that may be beneficial include clofazimine [23,126], colchicine [127,128], interferon alfa [129], melphalan [130], mercaptopurine [131], metronidazole [132], potassium iodide [133], sulfasalazine [24], tacrolimus [134], and thalidomide [22,135,136]. Apheresis of leukocytes [137-141] and plasmapheresis [101] have also been used for treatment.
PROGNOSIS — Follow-up studies of patients with PG suggest that with treatment, more than 50 percent of patients achieve complete wound healing within one year:
●In an Australian series of 26 patients hospitalized for PG, 6 of 12 patients available for follow-up six months after hospital discharge had complete ulcer healing [142].
●In a series with 64 patients with classic PG and 22 patients with bullous (atypical) PG, the mean time to complete remission (wound healing and absence of active disease) was 11.5±11.1 months in patients with classic PG and 9±13.7 months in patients with bullous PG [1]. Overall, 68 percent of patients achieved complete remission within six months, and 95 percent were in remission within three years.
The effect of treatment of associated underlying medical disorders on disease activity in patients with PG is variable, as the course of PG does not always parallel that of the related underlying disease [9]. Improvement in PG has been reported in some patients following proctocolectomy for inflammatory bowel disease [143]. However, PG may also occur peristomally or in other locations following proctocolectomy [9,144-148].
PG typically heals with scars, which can be disfiguring. New lesions may develop during or after healing of other lesions. Relapses can appear after long periods of disease quiescence [149].
PG may be associated with increased risk for death. In a retrospective cohort study that included 3386 patients with PG and over 67,000 controls, all-cause mortality was higher in patients with PG (adjusted hazard ratio 2.122, 95% CI 1.971-2.285) [150]. Increased mortality rates were also observed for diseases within a wide variety of organ systems.
Various factors may contribute to increased mortality in patients with PG, and death may occur due to underlying associated disorders, particularly in patients with malignancy, or due to complications directly related to ulcers or immunosuppressive therapy (eg, sepsis) [23,151]. Other potential contributory factors, such as effects related to an underlying chronic inflammatory state, have also been proposed [150].
Due to the association between bullous PG and hematologic disease, patients with bullous PG who present without an identifiable underlying hematologic disorder should be followed closely [45].
PREVENTION — There are no specific measures that have been shown to prevent the initial development of PG. In patients with an existing diagnosis, avoidance of trauma may help to reduce the development of new lesions. If patients with PG require surgery for other indications, wound closure with subcuticular stitches and close postoperative follow-up with a dermatologist are suggested.
Some authors have suggested that administering systemic glucocorticoids during and for two weeks or more after surgery may help to prevent the development of new lesions in patients with aggressive PG [2]. However, the impact of this intervention has not been formally studied.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pyoderma gangrenosum".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Pyoderma gangrenosum (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Disease overview – Pyoderma gangrenosum (PG) is an uncommon inflammatory and ulcerative disorder that may occur independently or in association with a variety of systemic diseases (picture 1A-C). (See 'Introduction' above.)
●Treatment principles – The approach to the treatment of PG involves consideration of various factors, such as disease severity and comorbidities. Topical and systemic therapies that suppress the inflammatory response are the mainstays of treatment. Wound care and pain management are additional important components of treatment. The role of surgery in PG is controversial. (See 'Treatment principles' above and 'Wound management' above and 'Pain management' above and 'Role of surgery and other interventions' above.)
●Response assessment – The response to PG therapy is assessed clinically. Typical early signs of response are the stabilization of disease progression, reduced visible signs of inflammation (eg, violaceous discoloration of the wound border), and reduced pain. Subsequently, the wound base begins to fill with granulation tissue, and the wound diameter progressively shrinks. Documentation of the size, number, and location of ulcers and serial clinical photographs are useful for following the response to therapy. (See 'Treatment principles' above.)
●Approach to treatment – Efficacy data on treatments for PG are limited. The severity of PG influences the initial approach to treatment (algorithm 1).
•Limited disease
-Initial treatment – For patients with limited PG (a single or few small [eg, <3 cm], superficial ulcers or a solitary plaque of vegetative PG), we suggest initial treatment with a super high-potency or high-potency topical corticosteroid (group 1 or 2 (table 1)) (Grade 2C). (See 'Limited disease' above.)
-Subsequent management of limited disease – For limited disease that responds well to topical corticosteroid therapy, treatment is continued until complete healing. For limited disease that does not respond sufficiently to topical corticosteroids, we suggest topical tacrolimus 0.1% ointment, oral minocycline, or oral dapsone for next-line treatment rather than systemic immunosuppressive therapies (Grade 2C). If the response remains insufficient, we proceed to therapies for extensive disease. (See 'Insufficient response to initial therapy' above and 'Refractory limited disease' above.)
•Extensive disease
-Initial treatment – For patients with more extensive PG, we suggest initial treatment with oral prednisone (Grade 2C). Oral cyclosporine is a reasonable alternative for patients who are less likely to tolerate systemic glucocorticoid therapy. (See 'More extensive disease and treatment-resistant limited disease' above.)
-Subsequent management of patients receiving a systemic glucocorticoid or cyclosporine – Treatment with prednisone or cyclosporine alone is not sufficient for many patients, and long-term treatment with prednisone or cyclosporine is associated with risk for serious adverse effects. For most patients, we suggest the addition of infliximab, adalimumab, or mycophenolate mofetil during the first few weeks of prednisone or cyclosporine treatment (Grade 2C). Tapering of prednisone or cyclosporine may begin once disease progression has stopped and clear signs of improvement are evident. If the response is inadequate, we proceed to other treatments. (See 'Subsequent management' above and 'Other interventions' above.)
Some patients may benefit from a different approach (eg, addition of a different systemic agent that may also improve a particular PG-associated comorbidity or avoidance of immunosuppression due to comorbidities). In addition, PG that responds very rapidly to prednisone or cyclosporine and appears likely to heal completely within several weeks may not require the addition of another systemic agent. (See 'Other interventions' above and 'Subsequent management' above.)
●Prognosis – It is estimated that with treatment, more than one-half of patients with PG achieve wound healing within one year, and almost all patients achieve remission with longer follow-up. However, relapses can occur after long periods of disease remission. (See 'Prognosis' above.)
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
