Pyoderma gangrenosum associated with ulcerative colitis: response to infliximab.

Pyoderma gangrenosum is an extraintestinal manifestation of inflammatory bowel disease that can be therapeutically troublesome. We comment on the case of a patient with clinically inactive ulcerative colitis who progressively developed necrotic lesions on both tibial aspects of his legs, which corresponded both clinically and histologically to pyoderma gangrenosum. Treatment with steroids and azathioprine could not control this complication. A single dose of infliximab 5 mg/kg was given, achieving an impressive response of the skin lesions followed by complete healing 3 months later. Infliximab can be useful in the management of refractory extraintestinal manifestations of inflammatory bowel disease.     

Pyoderma Gangrenosum Associated with Crohn Disease: Effect of TNF- α Blockade with Infliximab

Eight patients with pyoderma gangrenosum associated with Crohn disease were treated with infliximab. All had active mucosal inflammation indicated by endoscopic examination. Within 1-4 months, infliximab treatment resulted in complete healing of the pyoderma gangrenosum in 3 cases (1 parastomal, 2 lower limb), partial healing in 3 (2 parastomal, 1 lower limb) and temporary improvement in 2. Adverse effects such as skin rash, pneumonia and diarrhoea were seen in three patients. Our results imply that infliximab has a therapeutic potential on skin manifestations associated with inflammatory bowel disease, even though successful treatment may require repeat courses of infliximab infusions.     

Pyoderma gangrenosum associated with crohn disease: effect of TNF-alpha blockade with infliximab

Eight patients with pyoderma gangrenosum associated with Crohn disease were treated with infliximab. All had active mucosal inflammation indicated by endoscopic examination. Within 1-4 months, infliximab treatment resulted in complete healing of the pyoderma gangrenosum in 3 cases (1 parastomal, 2 lower limb), partial healing in 3 (2 parastomal, 1 lower limb) and temporary improvement in 2. Adverse effects such as skin rash, pneumonia and diarrhoea were seen in three patients. Our results imply that infliximab has a therapeutic potential on skin manifestations associated with inflammatory bowel disease, even though successful treatment may require repeat courses of infliximab infusions.     

Characteristics and Treatment of Pyoderma Gangrenosum in Inflammatory Bowel Disease

Background

Pyoderma gangrenosum is a serious cutaneous complication seen in approximately 1 % of patients with inflammatory bowel disease (IBD). Oral corticosteroids are the mainstay treatment, although the evidence supporting their use is weak.

Aims

The purpose of this study was to investigate the characteristics of pyoderma gangrenosum associated with Crohn’s disease or ulcerative colitis and which treatments are prescribed in Spanish clinical practice.

Methods

In this retrospective, observational study, the medical records from all patients with IBD and a diagnosis of pyoderma gangrenosum attended by the gastroenterology departments of 12 Spanish hospitals were reviewed. Data on patient demographics and characteristics, underlying IBD and treatment, and pyoderma gangrenosum characteristics, treatment, and outcome were collected and analyzed.

Results

The data from 67 patients were analyzed (41 [61.2 %] women, 41 [61.2 %] with Crohn’s disease, 25 [37.3 %] with ulcerative colitis, and 1 [1.5 %] with indeterminate disease). The underlying disease was in remission in approximately one-third of patients at the time of presentation of pyoderma gangrenosum. Healing was achieved in all patients (in 3 without any systemic therapy). Oral corticosteroids were taken by 51 patients (76.1 %), almost always as first-line treatment, although definitive healing was attained in 19 (28.4 %). Biologic agents such as infliximab and adalimumab were taken by 31 patients (46.3 %) at some point (first-line in 6 patients [9.0 %]), with definitive healing in 29 patients (93.5 %).

Conclusions

Oral corticosteroid therapy remains the most common treatment for pyoderma gangrenosum associated with inflammatory bowel disease. Biologic therapies such as infliximab and adalimumab should also be considered.     

Infliximab for treatment of pyoderma gangrenosum associated with clinically inactive Crohn's disease. A case report

We report the case of a 57-year old female patient with refractory to treatment pyoderma gangrenosum associated with clinically inactive Crohn's disease. Pyoderma gangrenosum was successfully treated with Infliximab, a chimeric monoclonal antibody that inhibits tumour necrosis factor alpha (TNF-alpha). Our case report suggests that Infliximab, a therapeutic agent for refractory and fistulizing Crohn's disease, may also be safe and effective in the treatment of Crohn's disease associated pyoderma gangrenosum, even though the inflammatory bowel disease is clinically inactive and repeated infusions may be required for successful treatment.     

Favorable response to infliximab treatment in a patient with active Crohn disease and pyoderma gangrenosum

Pyoderma gangrenosum is an extraintestinal manifestation of inflammatory bowel disease requiring meticulous medical and/or surgical treatment. We describe a 46-year-old patient who developed harsh pyoderma gangrenosum during a severe flare-up of the underlying Crohn disease of the terminal ileum. The patient responded favorably to treatment with infliximab-the chimeric antibody against tumor necrosis factor-alpha. The drug was administered intravenously at a dose 5 mg/kg/BW at baseline and weeks 2 and 6. Abdominal signs and symptoms as well as the skin lesions improved markedly before the second infusion. The patient is presently on infliximab maintenance regimen at a dose of 5 mg/kg/BW being administered as a 3 dose loading regimen at 0, 2 and 6 weeks with a treatment-free interval of 10 weeks until the next loading dose. The skin lesions remained in remission. Infliximab is a promising therapeutic modality for patients with Crohn disease and pyoderma gangrenosum.     

Management of Peristomal Pyoderma Gangrenosum

PURPOSE This study was designed to evaluate the presentation, management, and outcome of peristomal pyoderma gangrenosum at a specialist colorectal unit and develop a strategy for therapy.METHODS Patients with peristomal pyoderma gangrenosum were identified from a prospectively accrued Institutional Review Board-approved stoma database. Data were collected regarding demographics, disease status, history of illness, time to healing, and treatments used from the database and by chart review.RESULTS Sixteen patients presented between 1997 and 2002 with peristomal ulceration consistent with a diagnosis of peristomal pyoderma gangrenosum. Diagnosis was predominantly clinically based on a classic presentation of painful, undermined peristomal ulceration. The underlying diagnosis was Crohn’s disease in 11 patients, ulcerative colitis in 3, indeterminate colitis in 1, and posterior urethral valves in 1. At the time of development of peristomal pyoderma gangrenosum, the underlying disease was active in 69 percent of patients. Stoma care, ulcer debridement with unroofing of undermined edges, and intralesional corticosteroid injection was associated with a 40 percent complete response rate and further 40 percent partial response rate. Of five patients who received infliximab, four (80 percent) responded to therapy. Complete response after all forms of therapy, including stoma relocation in seven patients, was 87 percent.CONCLUSIONS Local wound management and enterostomal therapy are extremely important for patients with peristomal pyoderma gangrenosum. Infliximab may provide a useful option for those failing other forms of medical therapy. Relocation of the stoma is reserved for persistent ulceration failing other therapies, because peristomal pyoderma gangrenosum may recur at the new stoma site.Reprints are not available.     

Efficacy of infliximab for extraintestinal manifestations of inflammatory bowel disease

Opinion statement Crohn’s disease (CD) and ulcerative colitis (UC), collectively referred to as inflammatory bowel disease (IBD), are associated with extraintestinal manifestations (EIMs) in approximately 40% of patients. Infliximab, a chimeric monoclonal antibody to tumor necrosis factor-α, is effective for induction and maintenance of remission of CD and UC. The role of infliximab for EIMs related to IBD has been less studied, but it is likely as effective. The EIMs may run a course that parallels IBD activity or may present separately. The EIMs that parallel intestinal inflammation (eg, peripheral arthritis, pyoderma gangrenosum, erythema nodosum, and episcleritis) generally respond to infliximab. Therefore, treating patients with IBD who have one of these EIMs will more often than not improve the EIM. The EIMs that run a separate course from IBD are more difficult to treat. Ankylosing spondylitis (AS), uveitis, and primary sclerosing cholangitis (PSC) have variable responses to IBD medications. Infliximab is efficacious for uveitis and is approved by the US Food and Drug Administration for treatment of AS. The efficacy of infliximab for PSC is unknown. The dosing schedule of infliximab for IBD patients with EIMs should be induction doses with 5 mg/kg at 0, 2, and 6 weeks followed by every 8 weeks. Whether long-term infliximab therapy is necessary to maintain remission of EIMs, as in the case of IBD, has not been established.     

Refractory parastomal ulcers: a multidisciplinary approach

Chronic parastomal ulcers in patients with ileostomy or colostomy stomas are unusual. Previous reports have implicated infections, fistulas, recurrent inflammatory bowel disease (IBD), pyoderma gangrenosum, and trauma. Over the past 8 years we have evaluated 10 cases of such refractory parastomal ulcers that occurred at a mean of 11 years after stomal surgery. Eight patients had had an ileostomy for IBD while two had undergone colostomy for colon cancer. Five patients with IBD were diagnosed as having pyoderma gangrenosum ulcerations. They required systemic treatment for a mean of 25 weeks to effect ulcer healing. The other five patients had either parastomal ulcers on the basis of dermatoses (contact dermatitis, eczema, or bullous pemphigoid) or contact ulcers due to face-plate pressure and parastomal dermatitis. These patients received topical treatment with healing of ulcers in a mean of 4 weeks. We conclude that parastomal ulcers occurring in patients without IBD or IBD patients without classic pyoderma gangrenosum require early dermatologic evaluation as they respond relatively quickly to appropriate local therapy.     

Pyoderma gangrenosum associated with inflammatory bowel disease. Report of two cases with good response to infliximab

Among the extraintestinal manifestations of inflammatory bowel disease (IBD), pyoderma gangrenosum (PG) often poses a therapeutic challenge. We describe two cases of PG associated with inflammatory bowel disease, who responded to treatment with Infliximab.     

Successful therapy of refractory pyoderma gangrenosum and periorbital phlegmona with tacrolimus (FK506) in ulcerative colitis

We describe two male patients with ulcerative colitis and refractory pyoderma gangrenosum including periorbital phlegmona in one case. Both patients were successfully managed with low dose oral tacrolimus (0.1 mg/kg bodyweight per day). Serum trough levels were closely monitored and maintained between 4 and 6 ng/mL. A rapid response was noted in both cases. Complete non-scarring skin restitution without side effects was accomplished in both cases. Low dose oral tacrolimus provides a valuable alternative treatment option for IBD patients with refractory pyoderma gangrenosum.     

Atypical auricular pyoderma gangrenosum simulating fungal infection

We describe a patient with a highly unusual appearance of pyoderma gangrenosum. The pyoderma was located on the auricular region and preceded other manifestations of inflammatory bowel disease by 11 years. There was no correlation between the course of the pyoderma and the clinical activity of the associated bowel disease. Mycotic superinfections masked and delayed the diagnosis in our patient for several years. Only when typical pyoderma gangrenosum lesions developed on the legs at the site of trauma and responded dramatically to systemic corticosteroids was the correct diagnosis established. Pyoderma gangrenosum with secondary fungal infection was thus distinguished from deep ulcerated skin fungal infection simulating pyoderma.     

Significance of erythema nodosum and pyoderma gangrenosum in inflammatory bowel diseases: a cohort study of 2402 patients

Erythema nodosum and pyoderma gangrenosum are the most common cutaneous manifestations in inflammatory bowel diseases (IBD). We conducted the current study to assess the cumulative prevalence of erythema nodosum and pyoderma gangrenosum in patients with IBD and to appraise their association with demographic, clinical, and prognostic factors related to IBD. Between 2000 and 2005, data for all patients with IBD at our gastroenterology department were prospectively and systematically collected using a standardized protocol. Among 2402 patients (1521 diagnosed with Crohn disease [63.3%] and 744 with ulcerative colitis [31.0%]), 140 (5.8%) had at least 1 skin manifestation. The most frequent dermatologic symptoms were erythema nodosum (4.0%) and pyoderma gangrenosum (0.75%). In multivariate analyses, erythema nodosum was significantly and independently associated with a diagnosis of Crohn disease (p < 0.001), female sex (p < 0.001), eye and joint involvement (p < 0.001), and pyoderma gangrenosum (p < 0.0001). Among patients with Crohn disease, erythema nodosum was associated with isolated colonic involvement (p = 0.0001). Pyoderma gangrenosum was significantly and independently associated with black African origin (p = 0.003), familial history of ulcerative colitis (p = 0.0005), uninterrupted pancolitis as the initial location of IBD (p = 0.03), permanent stoma (p = 0.002), eye involvement (p = 0.001), and erythema nodosum (p < 0.0001). It is noteworthy that the association between pyoderma gangrenosum and permanent stoma persisted after exclusion of patients with peristomal pyoderma gangrenosum (p = 0.07). In conclusion, neither erythema nodosum nor pyoderma gangrenosum was significantly associated with the severity criteria in IBD; however, their occurrence may reflect a peculiar phenotype among affected patients.     

Efficacy of anti-tumor necrosis factor therapy in patients with ulcerative colitis

OBJECTIVES: Tumor necrosis factor-alpha (TNF-alpha) is an important cytokine involved in the pathogenesis of inflammatory bowel disease. The monoclonal antibody to TNF-alpha, infliximab, is effective in treating Crohn's disease. Preclinical studies suggest the importance of TNF-alpha in treating ulcerative colitis (UC). We report the effectiveness of infliximab for UC and examine factors predictive of response to medication. METHODS: Data from all UC patients receiving infliximab at four institutions were analyzed. Disease activity was determined by the Disease Activity Index. RESULTS: A total of 27 patients with active UC received inpatient (37%) and outpatient (63%) infliximab as single (52%) or multiple (two to 15) infusions (48%). Twelve patients (44%) achieved remission and six patients (22%) had partial response. Nine patients had no response; five subsequently underwent total colectomy. The median time to achieve response and remission was 4 days and the median duration 8 wk. Nine of the 18 patients who responded experienced 19 relapses; 18 of these relapses (95%) were successfully treated with repeat infusions. Steroid-refractory patients were less likely to respond to infliximab therapy than were steroid-responsive patients (33% vs 83%; p = 0.026). No other factors were predictive of response to infliximab. Two patients developed serious adverse events, including death in one case. CONCLUSIONS: Preliminary evidence suggest effectiveness of infliximab in the treatment of UC, including medically refractory severe disease. Individuals who are refractory to corticosteroids, however, may be unlikely to respond to infliximab. A randomized controlled trial is necessary to further investigate the efficacy of infliximab in patients with UC.     

Biologic therapy in the management of extraintestinal manifestations of inflammatory bowel disease

The inflammatory bowel diseases (IBD), notably Crohn's disease (CD) and ulcerative colitis (UC), are systemic inflammatory diseases primarily involving the gastrointestinal tract. Twenty percent to 40% of patients with IBD develop extraintestinal inflammation and symptoms, known as extraintestinal manifestations (EIMs).1-7 The most common EIMs affect the joints, skin, eyes, and biliary tract. The EIMs associated with IBD bear a negative impact on patients with UC and CD. Thus, the successful treatment of EIMs is essential for improving the quality of life of IBD patients. For most EIMs, their resolution often parallels that of the active IBD in both timing and therapy required. However, some EIM such as axial arthritis, pyoderma gangrenosum, uveitis, and primary sclerosing cholangitis run a clinical course independent of IBD disease activity. The advent of biologic response modifiers, e.g., tumor necrosis factor-alpha (TNF) inhibitors, has improved the treatment of IBD and its associated EIMs. This article reviews the therapeutic experiences of the 2 most widely used anti-TNF neutralizing antibodies, infliximab and adalimumab, for immune-mediated EIM of IBD.     

Use of infliximab in a patient with pyoderma gangrenosum and rheumatoid arthritis

Abstract

Pyoderma gangrenosum (PG) is characterized by ulcerative skin lesions. Infliximab (IFX) may promote PG healing in patients with inflammatory bowel disease, but whether IFX is effective for treating PG in patients with rheumatoid arthritis (RA) has not reported. We report the case of a 53-year-old woman with PG complicated by RA who was treated using IFX therapy. This case suggests that IFX therapy might offer effective treatment for such patients.     

Use of infliximab in a patient with pyoderma gangrenosum and rheumatoid arthritis

Pyoderma gangrenosum (PG) is characterized by ulcerative skin lesions. Infliximab (IFX) may promote PG healing in patients with inflammatory bowel disease, but whether IFX is effective for treating PG in patients with rheumatoid arthritis (RA) has not reported. We report the case of a 53-year-old woman with PG complicated by RA who was treated using IFX therapy. This case suggests that IFX therapy might offer effective treatment for such patients.     

Treatment of Pyoderma Gangrenosum with Infliximab in Crohn's Disease

Pyoderma gangrenosum (PG) is an ulcerating noninfectious disease of the skin seen in 1 to 5% of patients with inflammatory bowel disease. The pathogenesis of PG has yet to be determined but may be related to abnormal T cell responses and the production of TNF-alpha, a powerful proinflammatory cytokine. Infliximab, a chimeric monoclonal antibody to TNF-alpha, has been approved for the treatment of Crohn's disease. We present four patients with PG treated with Infliximab for fistulizing Crohn's in whom complete healing of PG was achieved. Four patients with active fistulizing Crohn's disease and PG were treated. All patients were females ranging in age from 48 to 60 years, with a mean age of 54 years. Three of four patients had PG lesions located on the lower extremities; one patient had peristomal disease. All patients had at least colonic involvement of their Crohn's. The patients received either a single infusion or a series of three 5 mg/kg Infliximab infusions. All four patients demonstrated rapid healing of PG within 4 weeks of the first infusion of Infliximab. PG healing followed improvement in bowel disease. Complete resolution without recurrence was noted in all patients. Rapid resolution of PG was noted in four female patients with fistulizing Crohn's disease treated with Infliximab. Healing was complete, without recurrence. The anti-TNF-alpha properties of Infliximab suggest that healing may be mediated by the drug's effect on cytokine pathways, perhaps by blunted T cell activation early in the inflammatory cascade. We suggest an independent effect of Infliximab on PG.     

Prolonged duration of response to infliximab in early but not late pediatric Crohn's disease

OBJECTIVES: Tumor necrosis factor-alpha plays a central role in chronic intestinal inflammation of Crohn's disease. Targeting this cytokine with the chimeric monoclonal antibody infliximab has emerged as an effective form of therapy in adult Crohn's disease patients. We sought to determine whether infliximab treatment would benefit pediatric patients with medically refractory Crohn's disease. We also assessed the duration of response, comparing children with early disease to children with long-standing (late) Crohn's disease. METHODS: Fifteen consecutive children (mean age 12.8 +/- 3.2 yr) with medically refractory Crohn's disease were enrolled in a prospective, open-label trial of a single, 5-mg/kg infliximab intravenous infusion. Medically refractory disease was defined as an inability to taper steroids, lack of response to immunomodulator therapy over 4 months, and active disease as measured by the Pediatric Crohn's Disease Activity Index (PCDAI). Primary endpoints included measurements of disease activity (PCDAI), steroid use, and duration of clinical response. RESULTS: In all, 14/15 children (94%) improved after infliximab infusion, with a significant decrease of both PCDAI and daily steroid use by 4 wk. Ten patients (67%) achieved complete remission by 10 wk. Among the 14 patients who responded, three of six children (50%) with early disease maintained clinical response through the 12-month trial period, compared to none of eight children with late disease. There were no serious complications associated with the use of infliximab in any of the patients. CONCLUSIONS: Infliximab is safe and effective in the short-term treatment of medically refractory pediatric Crohn's disease. More importantly, there is a remarkably prolonged duration of response after infliximab therapy in children with early compared to late Crohn's disease.     

Parastomal pyoderma gangrenosum in inflammatory bowel disease

PURPOSE: Parastomal pyoderma gangrenosum is uncommon and its association with inflammatory bowel disease is unclear. This is a review of five patients with parastomal pyoderma gangrenosum. METHODS: A retrospective review of five patients with ulcerative colitis (two patients) or Crohn's disease (three patients) who have been seen in one surgical unit was conducted. RESULTS: All patients were females and each presented within nine months of abdominal surgery and stoma construction. All had active proctitis (n=3) or perianal Crohn's disease (n=2). Both patients with perianal Crohn's disease had a mild clinical course with healing of parastomal pyoderma gangrenosum when treated with steroids with and without low-dose cyclosporin A. They both had curettage of the perineal wound as well. In the remaining three patients with active proctitis, the parastomal lesions failed to resolve despite high-dose systemic steroids. By contrast, the parastomal pyoderma gangrenosum healed promptly in two of these patients following proctectomy for active proctitis. CONCLUSION: The variable clinical outcome of parastomal pyoderma gangrenosum may be related to the activity of the underlying inflammatory bowel disease or possibly to low-grade perineal sepsis.