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.     

Crohn's colitis with extraintestinal manifestations: a case report.

The etiopathogenesis of inflammatory bowel disease remains unclear, with various extraintestinal features often found with the disease. Sometimes more than one extraintestinal finding is found in the same patient. In this case report, a patient with more than one extraintestinal manifestation of Crohn's disease is presented. Extensive thrombi in the venous system and pyoderma gangrenosum in the left lower extremity was observed but there was complete recovery following treatment with both systemic and topical agents.     

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.     

Extraintestinal manifestations in patients with diverticulitis

Three patients had diverticulitis and extraintestinal manifestations of arthritis and pyoderma gangrenosum. In each, a mistaken diagnosis of idiopathic inflammatory bowel disease was first made because of extraintestinal complaints associated with the gastrointestinal symptoms of diverticular disease. The joint and skin manifestations were refractory to various treatments, including oral and intradermal steroids, immunosuppressive agents, and hyperbaric oxygen. Segmental resection of the involved colon promptly and completely resolved all symptoms, without recurrence 26 to 38 months after surgery. Microscopic examination of the resected specimens showed only diverticulitis without any evidence of chronic idiopathic inflammatory bowel disease. Patients with diverticulitis may have extraintestinal manifestations as do patients with other inflammatory diseases of the colon. The failure to recognize this relationship may result in misdiagnosis and prolonged medical therapy, whereas segmental colonic resection may be curative.     

Pyoderma gangrenosum and Crohn's disease

Pyoderma gangrenosum is an ulcerative cutaneous lesion of unknown cause that has been associated with chronic diseases. Its association with inflammatory bowel disease has classically been with chronic ulcerative colitis; however, scattered cases have appeared in which pyoderma gangrenosum has accompanied Crohn's disease. Collected series have indicated an incidence varying between 0.16 per cent in the Mayo Clinic series of 1954 to 1.5 per cent in the Cleveland Clinic series of 1975. We have reviewed the records of eight patients with pyoderma gangrenosum and Crohn's disease who were seen at the Lahey Clinic between 1957 and 1980. During this period, 961 patients with Crohn's disease were seen (an incidence of 0.8 per cent). The ages of the patients ranged between 16 and 65 years. In two of the eight patients, the onset of pyoderma gangrenosum was coincident with the onset of the bowel symptoms; in the remaining six patients, the onset of pyoderma gangrenosum averaged 7.3 years after the onset of bowel disease. The diagnosis of Crohn's disease was made histopathologically for five patients; for the rest, the diagnosis was clinical. Lesions of pyoderma gangrenosum were seen on the legs of all eight patients; two patients had additional lesions of the trunk. In five patients, the activity of the skin lesions paralleled that of the bowel disease. Distribution of Crohn's disease in patients with pyoderma gangrenosum is similar to that previously reported—five with ileocolitis, two with colitis, and one with ileitis. Other extraintestinal manifestations of Crohn's disease in this group of patients were perianal disease in two, erythema nodosum in one, arthritis in one, and iritis in one. The diagnosis of pyoderma gangrenosum was confirmed pathologically in only one patient, emphasizing the subjective clinical nature of this diagnosis. This report represents the largest detailed series of patients with pyoderma gangrenosum and Crohn's disease to date.     

Infliximab for treatment of pyoderma gangrenosum associated with inflammatory bowel disease

OBJECTIVES: Pyoderma gangrenosum is an immune-mediated inflammatory condition characterized by ulcerative skin lesions affecting 1-2% of patients with inflammatory bowel disease (IBD). Treatment includes wound care, antibiotics, corticosteroids, and immunomodulators. However, response to therapy varies, and many patients with pyoderma gangrenosum have disease that is refractory to these agents. The aim of this study was to assess the response of medically refractory pyoderma gangrenosum to infliximab. METHODS: This was a multicenter retrospective study of patients with IBD and medically refractory pyoderma gangrenosum treated with infliximab. Data collected included the following: baseline demographics; duration of IBD; history of bowel resection; duration of skin lesions; number, size, and location of pyoderma gangrenosum lesions; prior medications; dose and number of infliximab infusions; bowel activity before and after infliximab; pyoderma gangrenosum activity before and after infliximab therapy; time to response and time to healing of pyoderma gangrenosum lesions; recurrence of pyoderma gangrenosum after infliximab; corticosteroid taper; and adverse reactions to infliximab. RESULTS: There were 13 patients with moderate to severe pyoderma gangrenosum and IBD treated with infliximab. All patients demonstrated complete healing of the skin lesions. Three patients had a complete response to induction infliximab therapy and did not require additional treatment. Ten patients responded to induction infliximab and have maintained pyoderma gangrenosum healing with infusions every 4-12 wk. All patients receiving corticosteroids were able to discontinue them completely after institution of infliximab treatment. Infliximab was well tolerated; the only treatment-related adverse events were sunburn in one patient and an infusion reaction in another. CONCLUSIONS: Infliximab is a safe and effective treatment for IBD-associated pyoderma gangrenosum.     

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.     

Extraintestinal manifestations of inflammatory bowel diseases

Inflammatory bowel diseases are associated with extraintestinal manifestations involving almost every organ system in the body. They occur in approximately 20% to 40% of patients with inflammatory bowel diseases. Immune-related and genetic mechanisms play an important role in the pathogenesis of these complications. Peripheral arthritis, erythema nodosum, and episcleritis respond to the treatment of the underlying intestinal inflammation, whereas axial arthropathy, pyoderma gangrenosum, and uveitis do not. Immunomodulator therapy, particularly with biologic agents has been shown to be effective in treating some of the extraintestinal manifestations. Early recognition and treatment are crucial in preventing major morbidity.     

Crohn's disease and systemic lupus erythematosus

A 28-year-old man with inflammatory bowel disease with complex extraintestinal involvement was found to have diagnostic features of both systemic lupus erythematosus and Crohn's disease. Although some of the systemic complications of these diseases may overlap, both diseases may occur as primary disorders. Coexistence of systemic lupus erythematosus should be considered in patients with inflammatory bowel disease and complex extraintestinal manifestations.     

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.     

The joint–gut axis in inflammatory bowel diseases

Inflammatory bowel diseases, Crohn's disease and ulcerative colitis, are associated with a variety of extraintestinal manifestations. The most common extraintestinal manifestation, articular involvement, occurs in 16% to 33% of inflammatory bowel disease patients. These arthropathies may increase morbidity, resulting in a worse quality of life compared with inflammatory bowel disease patients without arthropathies. Thus, arthropathies in inflammatory bowel diseases represent a major medical problem in these patients. Arthritis associated with inflammatory bowel diseases is one of the diseases captured under the umbrella of spondyloarthritis. Spondyloarthritis is a group of inflammatory diseases with overlapping features and is linked to Human Leukocyte Antigen-B27. Arthropathy in inflammatory bowel diseases is clinically divided into peripheral and axial involvement. Peripheral arthritis often flares with relapses of bowel disease resulting in a different treatment approach than axial arthritis in which the course is independent of inflammatory bowel disease activity. Definitions, prevalence, pathophysiology and treatment of the arthropathies commonly seen in inflammatory bowel diseases such as peripheral arthritis, dactylitis, enthesitis, arthralgia, sacroiliitis, inflammatory back pain and ankylosing spondylitis are summarized.     

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.     

Complications of inflammatory bowel disease

Complications in inflammatory bowel disease determine the severity of disease as well as the complexities of medical or surgical treatment opportunities. Therefore, in known inflammatory bowel disease, the prevention, the early detection and the adequate therapeutic response to certain complications are important goals in the follow-up of inflammatory bowel disease patients. Disease complications are separated into intestinal and extraintestinal complications. Intestinal complications are somewhat disease specific, which means that they occur exclusively in either Crohn's disease or ulcerative colitis (e.g., enteric fistulas are particularly found in Crohn's disease and toxic megacolon in ulcerative colitis). Most extraintestinal complications occur in both forms of inflammatory bowel disease (e.g., anemia, thromboembolic events or osteoporosis). The current knowledge on pathogenesis, diagnostic tools, prevention and treatment of certain intestinal and extraintestinal complications is reviewed.     

The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study

OBJECTIVE: The aim of this study was to determine the prevalence of the major extraintestinal manifestations of inflammatory bowel disease (IBD) and their relation to disease diagnosis and gender. METHODS: We used the population-based University of Manitoba IBD Database, which includes longitudinal files on all subjects of all health system contacts identified by International Classification of Diseases, 9th Revision, Clinical Modification codes for visit diagnosis. We extracted a cohort from our database, which included subjects with a known diagnosis of IBD for at least 10 yr. We then determined how many contacts each subject had for each of the following extraintestinal IBD-associated immune diseases: primary sclerosing cholangitis, ankylosing spondylitis, iritis/uveitis, pyoderma gangrenosum, and erythema nodosum. We calculated the prevalence of the extraintestinal diseases using an administrative definition of having at least five health system contacts for the diagnosis in question. This administrative definition has previously been validated in Crohn's disease and ulcerative colitis (UC). RESULTS: A total of 6.2% of patients with IBD had one of six major extraintestinal diseases studied in this report. Only 0.3% of patients had multiple extraintestinal diseases. Iritis/uveitis was the most common extraintestinal disease of all assessed (2.2% of women and 1.1% of men). Iritis/uveitis was more common among women, particularly those with UC (3.8%). Primary sclerosing cholangitis was most common among men with UC (3%). Ankylosing spondylitis was more common among men, and the highest rate was seen among men with Crohn's disease (2.7%). Pyoderma gangrenosum was more common in Crohn's (1.2%) with no gender predilection. Erythema nodosum was similarly present in Crohn's and UC but was more common among women (1.9%). CONCLUSIONS: The associations of immune mediated diseases in extraintestinal sites may help us to further our understanding of IBD pathogenesis, and it may help us in developing a paradigm of disease subsets.     

Extraintestinal complications of inflammatory bowel disease

Recent studies of extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) have demonstrated the importance of genetic predisposition in the etiology of musculoskeletal and cutaneous manifestations. In addition, small studies have shown infliximab to be effective in treating troublesome EIMs, particularly in pyoderma gangrenosum. Other trials have examined the safety of cyclooxygenase-2-specific nonsteroidal inflammatory drugs in IBD. Further work has been done on osteoporosis in IBD, and the American Gastroenterological Association has published a technical review and management guidelines for osteoporosis in a range of gastrointestinal disorders. However, despite further publications, debate remains concerning whether IBD patients with osteoporosis have a significant increase in fracture risk, and whether the bone loss is related to the disease or to its treatment.     

Pyoderma gangrenosum: an update

Pyoderma gangrenosum (PG) can be differentiated into classic and atypical forms. The classic form is characterized by ulcers and the atypical form by deep erosions with bullous blue-gray margins. Pathergy, the development of cutaneous lesions at sites of trauma, is a common feature of both forms of PG. Approximately 50% of patients who have PG have underlying systemic diseases, most commonly inflammatory bowel disease, myeloproliferative disorders, and various forms of inflammatory arthritis. The diagnosis of PG is one of exclusion. The management of this disorder begins with treatment of any underlying disease and local or systemic glucocorticoids or immunomodulating therapies.     

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.     

Selected Rheumatologic and Dermatologic Manifestations of Inflammatory Bowel Disease

This review focuses on the behavior and pathogenesis of selected dermatologic and rheumatologic manifestations of inflammatory bowel disease. Erythema nodosum, the most common skin lesion, correlates with activity of the bowel disease but not with its duration or extent. Resolution occurs with therapy of inflammatory bowel disease. Pyoderma gangrenosum, the most severe skin lesion, bears little relationship to the activity or extent of the colitis. Therapy is usually supportive, but dapsone and steroids appear promising. Immune and vasculitic mechanisms have been postulated for both skin lesions. Peripheral arthritis usually has its onset with or after the development of colitic symptoms. It worsens with exacerbation of bowel inflammation and responds to treatment of the bowel disease. Immune mechanisms are likely. Spondyloarthropathy usually occurs before the onset of overt intestinal disease. Its course is unrelated to the bowel inflammation, it does not respond to treatment of bowel disease, and it is associated with HLA B27.     

Chronisch-entzündlichen Darmerkrankungen

Inflammatory bowel diseases (IBD) are associated with a number of extraintestinal manifestations and complications. Extraintestinal manifestations have to be distinguished from extraintestinal complications, such as gall or kidney stones and disease-specific complications, such as osteoporosis and thromboembolic complications. The most frequent extraintestinal manifestations involve the joints, skin (e.g. erythema nodosum and pyoderma gangrenosum), eyes and the hepatobiliary tract. Extraintestinal manifestations are observed in up to 70% of patients with Crohn’s disease and ulcerative colitis. More than 25% of IBD patients will suffer from more than one extraintestinal manifestation. The etiology and pathogenesis of extraintestinal manifestations in IBD are largely unknown, but it is thought that luminal antigens lead to a systemic response due to an increased intestinal permeability.     

Management of extraintestinal manifestations and other complications of inflammatory bowel disease

The past 18 months have seen many studies of the prevalence, pathogenesis, and treatment of the extraintestinal manifestations of inflammatory bowel disease (IBD). Inhibitors of tumor necrosis factor alpha have shown effectiveness in randomized trials for the treatment of spondyloarthropathies and ocular manifestations. Open-label studies suggest that these agents may be effective for pyoderma gangrenosum as well. The epidemiology of primary sclerosing cholangitis (PSC), and its relationship to IBD, is becoming clearer. Colorectal neoplasia in PSC remains an important clinical problem. Osteoporosis occurs more commonly in IBD, but the relative importance of corticosteroid use versus underlying chronic bowel inflammation as risk factors remains controversial. Chromoendoscopy may be an important means to improve detection of colorectal neoplasia in IBD. Observational studies suggest that prolonged use of aminosalicylates is associated with decreased risk of neoplasia, but data are conflicting. A randomized trial of ursodeoxycholic acid in PSC showed decreased risk of colorectal neoplasia in patients receiving the drug relative to those on placebo.