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.     

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.     

Perianal Crohn's disease—Is it all bad news?

PURPOSE: The outcome of treatment of perianal Crohn's disease was assessed in 127 patients. METHODS: A retrospective review of the case notes of 415 patients who were seen in the North East of Scotland between 1985 and 1989 was undertaken. RESULTS: A total of 127 of 415 patients with Crohn's disease had perianal involvement. In 56 patients, perianal disease was the presenting complaint. Ninety-nine of the 127 patients had colonic involvement. Thirtytwo were treated with metronidazole, and 41 were treated with azathioprine, with at least temporary improvement in 91 and 68 percent, respectively. Seventy patients had treatment for fistula-in-ano, and in 50 percent of patients permanent healing was achieved. In general, treatment and outcome were largely related to the extent and severity of gut involvement. Proctectomy was performed in 32 patients (in 11 because of ongoing colonic disease). Only seven patients had proctectomy solely because of perianal disease. Proctectomy was necessary in 32 of 99 patients with colitis and perianal disease but in none of 28 patients without colonic involvement. Primary healing of the perineal wound was obtained in 17 patients, and only one patient has an unhealed perineal wound at the time of reporting. CONCLUSION: Perianal Crohn's disease does not inevitably lead to panproctocolectomy. Cautious surgery for fistula when rectal inflammation is quiescent is worthwhile. Loss of bowel continuity is more likely when colitis coexists with perianal disease. Panproctocolectomy is often indicated because of the combination of colitis and perianal disease rather than for perianal disease alone.     

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.     

Intravenous cyclosporine in refractory pyoderma gangrenosum complicating inflammatory bowel disease

BACKGROUND: Pyoderma gangrenosum complicates inflammatory bowel disease in 2-3% of patients and often fails to respond to antibiotics, steroids, surgical debridement or even colectomy. METHODS: We performed a retrospective chart analysis of 11 consecutive steroid-refractory pyoderma patients (5 ulcerative colitis, 6 Crohn's disease) referred to our practice and then treated with intravenous cyclosporine. Pyoderma gangrenosum was present on the extremities in 10 patients, the face in 2, and stomas in 21. At initiation of intravenous cyclosporine, bowel activity was moderate in 3 patients, mild in 4, and inactive in 4. All patients received intravenous cyclosporine at a dose of 4 mg/kg/d for 7-22 days. They were discharged on oral cyclosporine at a dose of 4-7 mg/kg/d. RESULTS: All 11 patients had closure of their pyoderma with a mean time to response of 4.5 days and a mean time to closure of 1.4 months. All seven patients with bowel activity went into remission. Nine patients were able to discontinue steroids, and nine were maintained on 6-mercaptopurine or azathioprine. One patient who could not tolerate 6-mercaptopurine had a recurrence of pyoderma. No patient experienced significant toxicity. CONCLUSION: Intravenous cyclosporine is the treatment of choice for pyoderma gangrenosum refractory to steroids and 6-mercaptopurine should be used as maintenance therapy.     

Penile Crohn's disease resolved by infliximab

Crohn's disease is a chronic relapsing, granulomatous, and inflammatory bowel disorder. Variable extra-intestinal manifestations may occur, which include erythema nodosum, erythema multiforme, pyoderma gangrenosum, and other non-specific skin lesions. Here, we present a case of metastatic penile Crohn's disease without scrotal involvement, which was initially approached as a balanoposthitis with penile cellulitis, and completely treated with infliximab infusion in a short time.     

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.     

Fournier's gangrene complicating ulcerative pancolitis

Fournier gangrene is a very rare and a rapidly progressing, polymicrobial necrotizing faciitis or myonecrosis of the perineal, perianal and genital regions, with a high mortality rate. Infection is associated with superficial traum, urological and colorectal diseases and operations. The most commonly found bacteria are Escherichia coli followed by Bacteroides and streptococcal species. Diabetes mellitus, alcoholism, and immunosuppression are perpetuating co-factors.Fournier's gangrene complicating inflammatory bowel disease has been reported in three patients so far, two with Crohn's disease.A 78-year-old man diagnosed with ulcerative pancolitis was referred for fever, and painful perianal and scrotal swelling after perianal surgery for a horseshoe-type perianal abscess. Since bowel disease diagnosis, patient was on mesalazine and achieved long-term remission. Perianal abscess occurred suddenly one week before perianal surgery without any evidence of pre-existing fistula or other abnormalities. Physical examination showed extensive edema and crepitus of perineum and genitalia and patient had symptoms of significant toxicity.The diagnosis of Fournier's gangrene was made and patient underwent emergency surgery with extensive surgical debridement of the scrotal and perianal area and Hartman procedure with a diverting colostomy. In addition, patient started on therapy with mesalazine 3gr, methylprednisolone 16 mg, parenteral nutrition and broad spectrum of antibiotics. Two days after the first operation the patient needed a second operation for perianal debridement. On the fourth day, blood cultures showed E. coli. Patient had an uneventful recovery and was discharged after 34 days of hospitalization. On follow up, disease review is scheduled and colostomy closure is planned.     

Recurrent posterior scleritis and orbital myositis as extra-intestinal manifestations of Crohn's disease: Case report and systematic literature review

BackgroundOcular episcleritis and uveitis are well-recognised extra-intestinal manifestations of Crohn's disease. Orbital myositis is rare: to our knowledge it has been associated with Crohn's disease in thirteen cases. Posterior scleritis, orbital myositis and Crohn's disease have been reported as coexisting in only two cases.Methods and resultsWe describe a third case, that of a 31-year old female with Crohn's colitis for 8 years, complicated by enteropathic arthritis and pyoderma gangrenosum. She presented with intense and intractable periorbital pain, particularly at night and worse on eye movements. B-scan ultrasonography confirmed posterior scleritis and treatment with high dose oral steroids (up to 60 mg prednisolone) was initially effective, but subsequently failed to control the inflammation. There was only a partial response to infliximab. Five months after presentation, diplopia developed, with failure of abduction of the left eye. MRI scan of the orbits confirmed orbital myositis involving the left lateral and medial rectus muscles. Pulsed intravenous methylprednisolone and six cycles of intravenous cyclophosphamide over a three month period resulted in complete resolution of inflammatory symptoms.ConclusionsThis case highlights a rare combination of ocular abnormality secondary to Crohn's disease and reports successful resolution with aggressive immunosuppressive therapy.     

Trauma and the pyoderma gangrenosum of inflammatory bowel disease

In five patients with inflammatory bowel disease (three with ulcerative colitis, two with Crohn's disease), pyoderma gangrenosum developed on a lower extremity at the site of trauma. In these subjects, the pyoderma was not clearly correlated with disease activity.     

Risk factors that predict the requirement of aggressive therapy among Chinese patients with Crohn's disease

OBJECTIVES: Crohn's disease is now increasingly considered as a disabling disease. Conventionally, the disease is managed by step‐up therapy. In recent years, the top‐down strategy has been proposed and is thought to benefit the patients in whom the condition is likely to rapidly deteriorate toward disabling. However, this strategy has severe adverse effects which have to be weighed against its benefits. The aim of this study is to identify the risk factors that can predict the requirement of top‐down therapy among Chinese patients. METHODS: We included 207 Chinese patients who had histories of Crohn's disease for ≥5 years, or those who had Crohn's disease for <5 years and at least one criterion of disabling disease. The risk factors related to the 5‐year disabling course and the 2‐year disabling course of Crohn's disease were separately analyzed in the same cohort by logistic regression. RESULTS: Among the 207 patients, the rate of disabling disease was 80.19% for 5‐year, and 71.01% for 2‐year. The risk factors of age <40 years at diagnosis, steroids requirement for treating acute exacerbation, and presence of perianal disease at diagnosis were significantly associated with a 5‐year disabling course. In the same cohort, the risk factors related to 2‐year disabling course were likewise steroids requirement for treating acute exacerbation and presence of perianal disease at diagnosis. CONCLUSION: The risk factors associated with disabling Crohn's disease, which entails the requirement of top‐down therapy in Chinese patients, are requirement of steroids for treating acute exacerbation and the presence of perianal disease at diagnosis.     

The prevalence of inflammatory bowel disease in an Israeli Arab population

AimsTo determine the prevalence of inflammatory bowel disease among the 1.5 million Arab residents in Israel who represent 20% of the total population.MethodsFamily physicians in all Arab towns and villages were contacted to obtain information on patients with inflammatory bowel disease. Relevant clinical data were retrieved and updated to December 31, 2009.ResultsInformation was obtained from 23/71 municipalities approached (representing 200,000 out of 1.5 million Arabs). There were 64 confirmed cases of Crohn's disease indicating a prevalence rate of 32/100,000. The rate of smoking within this cohort was lower than in the general population (1.5% vs. 40%; P < 0.001). There were 44 confirmed cases of ulcerative colitis with a prevalence rate of 22/100,000. The percentage of active smokers in this cohort was 18%. Clinical remission or mild activity was observed in 75% of patients in both cohorts at the time of the survey. Fourteen patients (21%) had undergone surgery for Crohn's disease, whereas none had undergone surgery for ulcerative colitis. Twenty-eight (42%) patients with Crohn's disease and 20 (45%) with ulcerative colitis were on maintenance therapy with 5-aminosalicylic acid. Only 18% with Crohn's disease and 6.8% with ulcerative colitis had received anti-tumor necrosis factor. The most prevalent extra-intestinal manifestations were perianal disease (18%) in Crohn's disease, and arthralgia or arthritis (6.8%) in ulcerative colitis.ConclusionsWe found a low prevalence rate of inflammatory bowel disease in the Israeli Arab population.     

A family report of Crohn's disease in three children immigrating from Albania to Greece and review of the literature

Cases of immigrant families affected by IBD have rarely been reported and seem to be of exceptional interest towards a better understanding of disease aetiopathogenesis.The first case of Crohn's disease in a family of immigrants from Albania to Greece with three offspring is described herein. A family with three children, one 22 year-old male and two 18-year-old twin females immigrated from southern Albania to northwest Greece ten years ago. The whole family lived in the same house and had no previous history of bowel or other chronic diseases. Two years ago the boy complained of diarrhoea, perianal pain and loss of weight. Subsequent investigation revealed ileal and perianal Crohn's disease. One year after Crohn's disease was diagnosed in the boy, one of the twins was diagnosed with ileal Crohn's disease. Six months afterwards, the second twin underwent emergency appendectomy due to acute appendicitis; four months later she was diagnosed with ileal Crohn's disease.Genetically predisposed individuals seem to be vulnerable to a continuous pressure of a still unknown environmental factor(s). In addition, lifestyle modification seems to represent a predisposing factor toward inflammatory bowel disease in immigrants.     

Oral cyclosporin in refractory inflammatory bowel disease

Background: The role of cyclosporin in patients with severe, refractory inflammatory bowel disease is unclear. Methods: A seven year retrospective review of patients treated with oral cyclosporin for inflammatory bowel disease refractory to conventional medical therapy was undertaken. Results: Twenty-eight patients (13 ulcerative colitis and 15 Crohn's disease) received oral cyclosporin for a mean of nine months (range 0.25–27 months). Within four weeks of starting cyclosporin, a complete clinical response occurred in 15 patients (nine with ulcerative colitis and six with Crohn's colitis), in whom conventional maintenance treatment was instituted concurrently. The clinical response was sustained during cyclosporin treatment in ten, but maintained after cyclosporin withdrawal in only five patients (18% of entire study group). Four of the five patients who relapsed after cyclosporin withdrawal had failed previously to respond to azathioprine. None of the five patients with continuing remission after cyclosporin withdrawal had received azathioprine in the past. There were three clinically significant infections and 14 cases of impaired renal function during treatment. Conclusions: Oral cyclosporin induces remission in some patients with severe ulcerative colitis or Crohn's colitis, but its benefits in cases refractory to azathioprine are overshadowed by a high frequency of relapse after drug withdrawal. (Aust NZ J Med 1998; 28: 179–183.)     

Serum lysozyme,serum proteins,and immunoglobulin determinations in nonspecific inflammatory bowel disease

The serum levels of lysozyme, serum electrophoresis, and serum immunoglobulins were determined prospectively in 101 patients with ulcerative colitis, ulcerative proctitis, Crohn's disease, or nonclassifiable nonspecific inflammatory bowel disease. Although the mean serum lysozyme concentration of patients with Crohn's disease (10.5±6.8 μg/ml) and ulcerative colitis (9.6±4.1 μg/ml) performed by a standardized lysoplate method was significantly greater than normal controls (6.0±1.5 μg/ml), the results did not correlate with the diagnosis nor with the degree of disease activity. Individually separated protein fractions and serum immunoglobulins also did not correlate with the serum lysozyme levels. This study indicates that measurement of the level of serum lysozyme in individual patients is not helpful in determining the cause or degree of activity of non-specific inflammatory bowel disease.     

Increased Serum Levels of Vascular Endothelial Growth Factor in Patients with Inflammatory Bowel Disease

Background: Vascular endothelial growth factor (VEGF) is a potent angiogenic, vascular permeability-enhancing, and calcium-dependent enzyme-modulating cytokine with overexpression in various pathologic disorders, including granulomatous inflammation, tissue repair, delayed hypersensitivity reactions, rheumatoid arthritis, and tissue ischemia. The present study investigates the role of VEGF in chronic inflammatory bowel disease. Methods: Thirty-one patients with Crohn's disease, 15 patients with ulcerative colitis, and 9 healthy volunteers were studied. VEGF serum levels were measured with a solid-phase enzyme-linked immunosorbent assay. Results: Significantly increased VEGF serum levels were observed in both active Crohn's disease and active ulcerative colitis when compared with healthy controls. Patients with active Crohn's disease and active ulcerative colitis showed significantly higher VEGF serum levels than patients with quiescent disease. No difference was observed between inactive disease and healthy controls. In addition, strongly increased VEGF serum levels were found in patients with Crohn's disease with fistulas in the absence of clinical, endoscopic, histologic, and laboratory findings of disease activity. Conclusions: Significantly increased VEGF serum levels were observed in patients with active Crohn's disease and ulcerative colitis, which suggests that VEGF has an important role in chronic inflammatory bowel disease. Its possible association with fistulas has yet to be determined.     

Management of inflammatory bowel disease in France: A nationwide survey among private gastroenterologists

BackgroundData on the current management of inflammatory bowel disease are scarce.MethodsThis was a nationwide survey among 65 private gastroenterologists treating patients with inflammatory bowel disease in France in 2012.ResultsA total of 375 inflammatory bowel disease patients were analysed: 48% had ulcerative colitis. One third of inflammatory bowel disease patients had a history of hospitalisation, and 40% of Crohn's disease patients had prior surgery. Two thirds of inflammatory bowel disease patients had active disease. Significantly fewer ulcerative colitis patients were treated with anti-tumour necrosis factor therapy than Crohn's disease patients (18.9% vs. 38.9%; p < 0.0001). Among patients treated with anti-tumour necrosis factor, only 4.5% were receiving concomitant immunomodulators. Half of inflammatory bowel disease patients had undergone a colonoscopy within the past year. For colorectal cancer screening, random biopsies and chromoendoscopy were performed in 75% and 40% of cases, respectively. An endoscopic score was used for only 10% of inflammatory bowel disease patients. About one third of inflammatory bowel disease patients had imaging studies within the past year (magnetic resonance enterography in 65%). An abdominal computed tomography scan was prescribed for 12% of inflammatory bowel disease patients.ConclusionsMany patients still have active disease in the biologics era, and the number of patients receiving combination therapy is low in private practice. Chromoendoscopy and endoscopy scores are not often used.     

Hyperbaric oxygenation in severe perineal Crohn's disease

PURPOSE: Perineal involvement in Crohn's disease is a common and distressing condition, often refractory to medical or surgical treatments. Recent reports suggest the efficacy of hyperbaric oxygenation (HBO) in the healing of perineal lesions. We evaluated HBO in severe patients with perineal Crohn's disease. METHODS: Ten consecutive patients (8 women, 2 men; mean age, 30 years) were studied. There were four superficial fissures, four cavitating ulcers, six low or superficial fistulas, two high fistulas, and one irreversible anal stenosis. All patients had received one or more medical treatments without healing the perineal lesions, and all had had previous surgery for perineal lesions. RESULTS: Two patients discontinued HBO after a few sessions and did not complete treatment. Eight patients completed at least 30 HBO sessions and were evaluable. At the end of the procedure, six of eight patients treated were healed, three completely and three partially. All patients who healed completely received HBO as an additional treatment to local perineal surgery. CONCLUSION: HBO might be useful as a last resort treatment of chronic perineal Crohn's disease, resistant to other treatments or as a complement to surgery.     

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.