Clinical Study on the Treatment of Complex Anal Fistula by Phased Chinese Herbal Sitz Bath Based on "Fuzheng Quxie" Theory.

Objective: To evaluate the clinical efficacy of a phased Chinese herbal sitz bath for the treatment of complex anal fistula based on the traditional Chinese medicine theory of "Fuzheng Quxie." Methods: We enrolled 200 patients with complex anal fistula who were hospitalized and treated surgically in the Department of Anorectal Medicine of Suining Central Hospital from June 2021 to December 2022. The patients were randomly divided into 2 groups of 100 patients each: sitz bath group 1 (postoperation, the patients used a sitz bath with a self-formulated decoction of "Qingre Zaoshi Zhitong" formula, once in the morning and once in the evening) and sitz bath group 2 (postoperation, the patients used the same decoction as the sitz bath group 1, and when the incision began to heal, the patients then used a sitz bath with a self-formulated decoction of "Yiqi Fuzheng" formula, once in the morning and once in the evening). Both groups were treated for 6 weeks. The assessments included wound symptom score, incision healing time, clinical efficacy after treatment, and serum-related growth factor concentrations and anorectal dynamics indicators before and after treatment. Results: After treatment, sitz bath group 2 had less wound pain, edema, exudate, and granulation growth scores than sitz bath group 1 (P < .05). Postoperative incision healing time was faster in sitz bath group 2 22.96 (1.96) d than in sitz bath group 1 26.19 (2.62) d (t = 9.872, P < .001). The total effective rate after treatment was higher in sitz bath group 2 96% (96/100) than in sitz bath group 1 88% (88/100) (χ2 = 4.4, P = .04). Serum transforming growth factor ß, epidermal growth factor, and basic fibroblast growth factor concentrations were higher in both groups after treatment than before treatment, and the concentrations of the growth factors after treatment were higher for sitz bath group 2 than for sitz bath group 1 (P < .001). Anal rest pressure and anal maximum contraction pressure were higher in both groups after treatment than before treatment, and the pressures after treatment were higher for sitz bath group 2 than for sitz bath group 1 (P < .05). Conclusion: Based on the theory of Fuzheng Quxie, the effectiveness and superiority of a phased Chinese herbal sitz bath for the treatment of complex anal fistula were remarkable, which could promote the improvement of wound symptoms and anal function. This may be related to increases in growth factor concentrations and anorectal dynamics indicators.

Clinical research progress in Traditional Chinese Medicine in treating wound healing after anal fistula surgery.

In the study of the mechanism of wound healing after anal fistula surgery, how to scientifically and efficiently promote wound healing is of great significance. At present, modern medical treatment of wounds after anal fistula surgery mostly focuses on physical therapy intervention, new wound dressing and packing, and external application of growth factors. However, these therapies have many problems, and there is still no consensus on their clinical use. Traditional Chinese Medicine (TCM) has several methods to promote wound healing, such as oral administration, rubbing, and fumigation, which have a long history and obvious efficacy, but research in this area is relatively scattered and lacks classification and summarizing. Therefore, this paper analyzes and summarizes the existing research on TCM for promotion of wound healing after anal fistula surgery, carries out targeted analyses according to different clinical syndromes and treatment methods, and analyzes the defects in current research and anticipates future research trends in order to provide theoretical support for the advantages of TCM in promoting wound healing after anal fistula surgery.

Rates and Predictors of Long-term Clinical Outcomes in Patients With Perianal Crohn's Disease on Biologic Therapy.

BACKGROUND AND GOALS: Perianal Crohn's disease (pCD) represents an aggressive phenotype with limited studies on long-term outcomes. We evaluated 5-year outcomes of these patients on biologic therapies. METHODS: We performed a retrospective analysis of patients with pCD at a tertiary medical center. We used Kaplan-Meier curves to estimate rates and multivariate logistic regression to identify predictors of long-term outcomes. RESULTS: We included 311 patients with pCD of which 168 patients were started on biologics [138 anti-tumor necrosis factor (TNF) α, 14 vedolizumab, 16 ustekinumab] at the time of diagnosis. Anti-TNF use at the time of diagnosis was associated with decreased rates of perianal abscess recurrence [hazard ratio (HR)=0.48, 95% confidence interval (CI): 0.32-0.74], whereas ustekinumab use was associated with increased rates of perianal fistula closure (HR=3.58, 95% CI: 1.04-12.35) and decreased rates of perianal abscess recurrence (HR=0.20, 95% CI: 0.07-0.56) at follow-up. Among patients who failed their first anti-TNF, switching to another anti-TNF was associated with decreased rates of colectomy (HR=0.20, 95% CI: 0.04-0.90) and permanent diversion (HR=0.16, 95% CI: 0.03-0.94) compared with ustekinumab, whereas vedolizumab use was associated with decreased perianal fistula closure (HR=0.22, 95% CI: 0.05-0.96) compared with ustekinumab. Predictors of colectomy included colonic disease (odds ratio=2.71, 95% CI: 1.36-5.38) and anal stenosis (odds ratio=4.44, 95% CI: 1.59-12.43). CONCLUSION: Type of biologic use at the time of pCD diagnosis or after first anti-TNF failure may be associated with long-term outcomes in patients with pCD.

Approaches in the treatment of perianal fistula in Crohn disease

Perianal fistula is a common complication of Crohn disease, and it is a great burden on the life and psychology of patients, but its treatment is still a difficult problem to face. In recent years, progress in the treatment of Crohn disease has progressed rapidly due to the advent of biological agents, but there has been a lack of research on perianal fistula in Crohn disease, and the direction of research has been scattered; therefore, the author reviews the traditional treatment of perianal fistula in Crohn disease in the context of the available literature and discusses emerging and potential therapeutic approaches. (AU)

The Effect of Qingre Huayu Recipe on Wound Healing after Anal Fistulotomy in Sprague-Dawley Rats.

Anal fistula is a common anorectal disease. At present, most scholars believe that its pathogenesis is related to anal gland infection. Anal fistula cannot heal on its own after the onset and must be treated surgically. The wound of anal fistula surgery is open and polluted, and it belongs to three types of three-stage healing; it is the most difficult to heal among all surgical incisions, with a long course of disease, a lot of exudation, and pain for the patient; traditional Chinese medicine has rich experience in the treatment of postoperative wound healing of anal fistula. The study aimed to evaluate the mechanism of Qingre Huayu (QRHY) Recipe on wound healing after fistulotomy on SD rats. SD rats (n = 72) were randomized into three groups post-anorectal surgery. The rats in the positive control group were given potassium permanganate (PP), treatment group were given QRHY, and trauma model group were given 0.9% normal salinity. The changes in wound secretion, granulated tissue, and epithelium tissue were observed, and wound healing rates were evaluated by the discrepancies in wound area. HE and Masson's staining as well as transmission electron microscopy were also performed. The localization as well as the measurement of Ang1, Src, and VE cadherin expression in each group adopted real-time PCR, western blot, and immunohistochemistry (IHC) assays. Statistically higher wound healing rates were observed in QRHY group on days 3, 7, and 14 compared with other groups. Histological analyses showed highly significant increase in collagen and fibroblasts, less inflammatory cells, and vascular endothelial permeability in QRHY rats. The transmission electron microscopy revealed that the intact structure of tight junctions in endothelial cells and well-organized collagen and VE-cadherin, Ang1, and Tie-2 were upregulated by QRHY, while Src was inhibited. This study showed that QRHY can promote wound healing after anal fistulas.

Treatments for the amelioration of persistent factors in complex anal fistula.

Anal fistulae are abnormal hollow connections between the wall of the anal canal and the perianal skin around the anus that have remained a burden on the medical sector for centuries. The complexity of this disease is attributed to a number of factors such as the degree of associated sphincter muscle, concomitant illnesses, existence of multiple fistulous tracts and the number of previous interventions. Persistence of a complex anal fistula can cause a decline in patient's physical quality of life as well as impact on the psychological status of patients who often suffer from anxiety and depression. Surgical intervention remains the gold standard for treatment, however; the risk of incontinence and high recurrence potential has led to interest into developing alternative treatment approaches such as the use of biologics, bioactives and biomaterials. One potential reason for these varied outcomes could be the multifactorial interplay between genetic, immune-related, environmental, and microbial persistence factors on tissue regeneration. Recent observations have proposed that adverse inflammatory mediators may contribute more than microbial factors. The moderate to high success rates of biotechnological advances (mesenchymal stem cells and biomaterial scaffolds) show promise as therapies for the amelioration of adverse persistent factors while facilitating a means to closing the fistula tract. The purpose of this review is to outline recent advances in biologics and combination therapies to treat persistent factors associated with complex anal fistula.

Antimicrobial photodynamic and photobiomodulation adjuvant therapies for the treatment of perianal abscess.

Although the treatment and management options for perianal abscess vary considerably, most cases require incision and drainage. Whatever the clinical approach selected, it is imperative to monitor patients to identify postoperative signs and symptoms which suggest treatment failure or further complications, such as sepsis, recurrent abscess, and fistula formation. Considering the debate on the role of postoperative antibiotic therapy for patients with perianal abscess and the significant discomfort caused by the infection, the present study aimed to report a clinical case in which antimicrobial photodynamic therapy (aPDT) and photobiomodulation therapy (PBMT) were used after incision and drainage of a simple perianal abscess. Within 5 days, there was no sign or symptom of both infection and inflammation, and after 3 months, no fistulous pathways or perianal collections were present. According to the current case report, the combination of aPDT and PBMT following incision and drainage of perianal abscess may be a smart strategy for infection resolution and prevention of late complications.

Effectiveness of the Aloe Vera extract in the treatment of fistula-in-ano / Eficácia do extrato de Aloe Vera no tratamento da fístula anal

Abstract Rationale: Considering that anal fistulae are still challenging regarding their treatment due to the risk of fecal incontinence in the most complex cases and the increasing use of phytotherapeutic drugs such as Aloe Vera in medicine, even with proven healing effectiveness, there is interest in researching this drug in the treatment of anal fistulae. Objective: To evaluate the efficacy of Aloe Vera extract in the treatment of anal fistulae in rats. Method: Thirty male Wistar rats weighing 250-300 g were submitted to anal fistula and after 30 days were divided into three groups: Control Group (GCo) (n = 5), Carbopol Group (GCa) (n = 5), and Aloe Vera Group (GAV) (n = 10). In the GCo no treatment was performed, while in the others a daily infusion of 0.3 mL of solution (Carbopol only in GCa and Carbopol plus Aloe Vera extract in the GAV) was performed through the external orifice of the fistula for 30 days. Afterwards, euthanasia was performed and specimens were removed for histological study. It was evaluated the closure of the fistulous tract, the area of the remaining tract, the inflammatory infiltrate and the degree of vascular congestion. The results were submitted to statistical treatment by Kruskall-Wallis test, considering p<0.05. Results: There was no complete closure of the fistulous tract in any of the animals. The mean area of the remaining tract was 847.2 µm in the GCo, 565.6 µm in the GCa and 377.8 µm in the GAV (p<0.05). The mean of the inflammatory infiltrate score was 2.4 in the GCo, 2.4 in the GCa and 2.3 in the GAV (p<0.05), while in the evaluation of vascular congestion, we observed a mean of 1.6 in the GCo, 1.4 in GCa and 1.1 in GAV (p<0.05). Conclusion: The extract of Aloe vera was able to reduce the lumen of the fistulous tract and reduce the degree of vascular congestion; however, it did not allow the complete closure of the fistulous tract nor diminished the inflammatory process.

Resumo Racional: Considerando que o tratamento das fístulas anais tem risco de incontinência fecal e o crescente uso do Aloe Vera na medicina, há interesse em se pesquisar este fármaco. Objetivo: Avaliar a eficácia do extrato de Aloe vera no tratamento das fístulas anais em ratos. Método: Utilizou-se 30 ratos Wistar, os quais foram submetidos à criação de fístula anal e após 30 dias distribuídos em três grupos: Controle (GCo), Carbopol (GCa) e Aloe Vera (GAV). No GCo nenhum tratamento foi realizado, enquanto nos outros realizou-se infusão diária de 0,3 mL de Carbopol GCa e Carbopol mais extrato de Aloe Vera no GAV por 30 dias. Foram retirados os espécimes para estudo histológico, avaliou-se o fechamento do trajeto fistuloso, a área do trajeto remanescente, o infiltrado inflamatório e o grau de congestão vascular. Resultados: Não houve fechamento completo do trajeto fistuloso em nenhum dos animais. A média da área do trajeto remanescente foi 847,2 µm no GCo; 565,6 µm no GCa e 377,8 µm no GAV (p<0,05). A média do escore de infiltrado inflamatório foi 2,4 no GCo; 2,4 no GCa e 2,3 no GAV (p<0.05), enquanto na avaliação da congestão vascular observou-se média 1,6 no GCo; 1,4 no GCa e 1,1 no GAV (p<0,05). Conclusão: O extrato de Aloe Vera foi capaz de diminuir o lumen dos trajetos fistulosos e reduzir o grau de congestão vascular, porém, não permitiu o fechamento completo dos trajetos fistulosos nem diminuiu o processo inflamatório.

Patients with perianal Crohn's fistulas experience delays in accessing anti-TNF therapy due to slow recognition, diagnosis and integration of specialist services: lessons learned from three referral centres.

AIM: Crohn's anal fistula should be managed by a multidisciplinary team. There is no clearly defined 'patient pathway' from presentation to treatment. The aim of this study was to describe the patient route from presentation with symptomatic Crohn's anal fistula to starting anti-tumour necrosis factor (anti-TNF) therapy. METHOD: Case note review was undertaken at three hospitals with established inflammatory bowel disease services. Patients with Crohn's anal fistula presenting between 2010 and 2015 were identified through clinical coding and local databases. Baseline demographics were captured. Patient records were interrogated to identify route of access, and clinical contacts during the patient pathway. RESULTS: Seventy-nine patients were included in the study, of whom 54 (68%) had an established diagnosis of Crohn's disease (CD). Median time from presentation to anti-TNF therapy was 204 days (174 vs 365 days for existing and new diagnosis of CD, respectively; P = 0.019). The mean number of surgical outpatient attendances, operations and MRI scans per patient was 1.03, 1.71 and 1.03, respectively. Patients attended a mean of 1.49 medical clinics. Seton insertion was the most common procedure, accounting for 48.6% of all operations. Where care episodes ('clinical events per 30 days') were infrequent this correlated with prolongation of the pathway (r = -0.87; P < 0.01). CONCLUSION: This study highlights two key challenges in the treatment pathway: (i) delays in diagnosis of underlying CD in patients with anal fistula and (ii) the pathway to anti-TNF therapy is long, suggesting issues with service design and delivery. These should be addressed to improve patient experience and outcome.

Root extractive from Daphne genkwa benefits in wound healing of anal fistula through up-regulation of collagen genes in human skin fibroblasts.

Wound healing is the main problem in the therapy of anal fistula (AF). Daphne genkwa root has been traditionally used as an agent to soak sutures in operation of AF patients, but its function in wound healing remains largely unclear. The aim of the present study was to illuminate mechanisms of D. genkwa root treatment on AF. In the present study, 60 AF patients after surgery were randomly divided into two groups, external applied with or without the D. genkwa extractive. Wound healing times were compared and granulation tissues were collected. In vitro, we constructed damaged human skin fibroblasts (HSFs) with the treatment of TNF-α (10 µg/ml). Cell Count Kit-8 (CCK-8) and flow cytometry analysis were used to determine the effects of D. genkwa root extractive on cell viability, cell cycle and apoptosis of damaged HSFs. Furthermore, protein levels of TGF-ß, COL1A1, COL3A1, Timp-1, matrix metalloproteinase (MMP)-3 (MMP-3) and MEK/ERK signalling pathways were investigated both in vivo and in vitro Results showed that D. genkwa root extractive greatly shortens the wound healing time in AF patients. In granulation tissues and HSFs, treatment with the extractive significantly elevated the expressions of COL1A1, COL3A1, Timp-1, c-fos and Cyclin D1, while reduced the expression of MMP-3 Further detection presented that MEK/ERK signalling was activated after the stimulation of extractive in HSFs. Our study demonstrated that extractive from D. genkwa root could effectively improve wound healing in patients with AF via the up-regulation of fibroblast proliferation and expressions of COL1A1 and COL3A1.

Pharmacological evaluation for improvement of Kanazawa Sutra, medicinal thread for anal fistula.

Kanazawa Sutra (KanS) is a medicinal thread that is used for the treatment of anal fistula. It is used as a substitute for Kshara Sutra (KS) which is used in Ayurvedic medicine. KanS is composed of Ficus carica latex (FCL), Capsicum annuum tincture (CAT), Achyranthes fauriei Kshara (which is processed ash from the whole plant) and powdered Curcuma longa rhizome (CLR). In this study, we evaluated the ingredients of KanS by measuring nitric oxide (NO) production in murine macrophage-like cell line J774.1 as well as examining cytotoxicity to rat skeletal muscle myoblasts (L6) and L6 differentiation, with a view to improving its pharmacological effect. We focused on Mallotus japonicus bark (MJB), which is described in the Japanese Pharmacopeia and belongs to the Euphorbiaceae family. Its biological activities were evaluated in a similar manner to the evaluation of KanS ingredients. We found that MJB extracts showed similar biological activity to Euphorbia neriifolia latex (ENL), an ingredient of KS. We conclude that the NO inhibitory activity of KanS is mainly due to CLR, and its cytotoxicity to L6 and inhibitory activity on L6 differentiation are mainly due to CLR and FCL. As CAT has no characteristic activity, the biological activity and the anal fistula treatment ability of KanS would be improved by substituting MJB for CAT.

Adalimumab combined with ciprofloxacin is superior to adalimumab monotherapy in perianal fistula closure in Crohn's disease: a randomised, double-blind, placebo controlled trial (ADAFI).

OBJECTIVE: To assess whether a combination of adalimumab and ciprofloxacin is superior to adalimumab alone in the treatment of perianal fistulising Crohn's disease (CD). DESIGN: Randomised, double-blind, placebo controlled trial in eight Dutch hospitals. In total, 76 CD patients with active perianal fistulising disease were enrolled. After adalimumab induction therapy (160/80 mg week 0, 2), patients received 40 mg every other week together with ciprofloxacin 500 mg or placebo twice daily for 12 weeks. After 12 weeks, adalimumab was continued. Follow-up was 24 weeks. Primary endpoint (clinical response) was defined as 50% reduction of fistulas from baseline to week 12. Secondary endpoints included remission (closure of all fistulas), Perianal Crohn's Disease Activity Index, Crohn's Disease Activity Index (CDAI) and Inflammatory Bowel Disease Questionnaire (IBDQ). RESULTS: Clinical response was observed in 71% of patients treated with adalimumab plus ciprofloxacin and in 47% treated with adalimumab plus placebo (p=0.047). Likewise, remission rate at week 12 was significantly higher (p=0.009) in the combination group (65%) compared with adalimumab plus placebo (33%). Combination treatment was associated with a higher mean CDAI change and mean IBDQ change at week 12 (p=0.005 and p=0.009, respectively). At week 24, no difference in clinical response between the two treatment groups was observed (p=0.22). No difference in safety issues was observed. CONCLUSIONS: Combination therapy of adalimumab and ciprofloxacin is more effective than adalimumab monotherapy to achieve fistula closure in CD. However, after discontinuation of antibiotic therapy, the beneficial effect of initial coadministration is not maintained. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00736983.

Clinical characteristics of non-perianal fistulating Crohn's disease in China: a single-center experience of 184 cases.

BACKGROUND: There is little information of non-perianal fistulating Crohn's disease in the consensus published by the European Crohn's and Colitis Organization in 2006 and 2010. This study was designed to demonstrate the clinical characteristics of non-perianal fistulating Crohn's disease among homogenous Chinese population. METHODS: One-hundred-and-eighty-four patients were retrospectively collected. All of these patients were diagnosed of Crohn's disease between February 2001 and April 2011. RESULTS: The male-to-female ratio was 2.7:1. The most common symptoms at onset were abdominal pain (88.0%), diarrhea (34.7%), and fever (28.3%). The most common disease location and behavior at diagnosis were small bowel (56.0%) and penetrating (51.6%). Among 324 non-perianal fistulae, the most common types were ileocolonic anastomotic (30.9%), terminal ileocutaneous (19.7%), and enteroenteric anastomotic (11.4%). One-hundred-and-thirty- eight (75.0%) patients received antibiotics, and ß-lactam (85.5%) and metronidazole (67.4%) are most frequently used. One-hundred-and-seventy-eight (96.7%) patients suffered 514 surgical operations, and the cumulative surgical rates after 1, 3, and 5 years were 38.0%, 52.2%, and 58.7% respectively. Nine patients died during the follow-up period, and the cumulative survival rates after 1, 3, and 5 years were 97.8%, 96.7%, and 96.2% respectively. CONCLUSIONS: This study displayed the clinical characteristics of non-perianal fistulating Crohn's disease in our center. Large population-based studies are required for further investigation in China.

Clinical study of external application of Qiyu oil gauze for promoting post-operational healing in patients with anal fistula.

OBJECTIVE: To observe the effects of the external application of Qiyu oil gauze (QYOG) for promoting post-operational healing in patients with anal fistula and to explore its mechanism of action so as to provide a beneficial scientific basis for its wide use. METHODS: Sixty patients with anal fistula scheduled to receive simple low anal fistulectomy were equally assigned, according to the sequence of hospitalization, to the tested group and the control group, and their wounds were classified according to longitudinal diameter into three grades (Grade I with a diameter below 2 cm; Grade II, 2-5 cm; and Grade III, over 5 cm). After the operation was completed and the operational wound was sterilized with benzalkonium bromide, the wound substratum was packed with QYOG in the test group and with vaseline gauze in the control group. The packing gauze was changed every day till the wound was healed. The healing time of the patients was observed, and the number of capillaries and positive cell percentages of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) in wound granulation tissues were counted on the 5th day after the operation. RESULTS: The wound healing time was 17.80+/-5.46 days in the test group, which was significantly shorter than that in the control group (21.90+/-6.32 days, P<0.01). The number of capillaries and positive cell percentages of VEGF and bFGF in wound granulation tissues on the 5th day in the tested group were higher than those in the control group (P<0.01), though the difference in EGF between the two groups was insignificant (P>0.05). CONCLUSION: QYOG could shorten the wound healing time after anal fistulectomy, which suggests that it participates in the stimulation of wound granulation tissues to produce VEGF and bFGF, and thus promotes capillary genesis and improves blood circulation in wounds so as to promote wound healing.

Ciprofloxacin or metronidazole for the treatment of perianal fistulas in patients with Crohn's disease: a randomized, double-blind, placebo-controlled pilot study.

BACKGROUND: Although metronidazole and ciprofloxacin are used to treat perianal Crohn's disease (CD), no placebo-controlled trials have been performed. METHODS: We performed a placebo-controlled pilot trial to evaluate the efficacy and safety of metronidazole and ciprofloxacin in patients with perianal CD. Twenty-five patients with CD and actively draining perianal fistulas were randomized to receive ciprofloxacin 500 mg, metronidazole 500 mg, or placebo twice daily for 10 weeks. Remission and response of perianal fistulas were defined as closure of all fistulas and closure of at least 50% of fistulas that were draining at baseline, respectively. The primary endpoint was remission at 10 weeks. RESULTS: Ten patients were randomized to ciprofloxacin, 7 to metronidazole, and 8 to placebo. Remission at week 10 occurred in 3 patients (30%) treated with ciprofloxacin, no patients (0%) treated with metronidazole, and 1 patient (12.5%) treated with placebo (P = 0.41). Response at week 10 occurred in 4 patients (40%) treated with ciprofloxacin, 1 patient (14.3%) treated with metronidazole, and 1 patient (12.5%) treated with placebo (P = 0.43). Termination of the trial prior to week 10 occurred in 1 patient (10%) treated with ciprofloxacin, 5 patients (71.4%) treated with metronidazole, and 1 patient (12.5%) treated with placebo (P < 0.02). No serious adverse events occurred. CONCLUSION: Remission and response occurred more frequently in patients treated with ciprofloxacin but the differences were not significant in this pilot study. Ciprofloxacin was well tolerated.

NOD2/CARD15 gene variants are linked to failure of antibiotic treatment in perianal fistulating Crohn's disease.

OBJECTIVES: The Crohn's disease (CD) susceptibility gene, nucleotide-binding oligomerizetion domain 2 (NOD2)/caspase recruitment domain 15 (CARD15), is linked to the innate immune response associated with altered epithelial bacterial defense. Its relevance in antibiotic therapy of perianal fistulating CD remains elusive. The aim of the study was to explore systematically the association between NOD2/CARD15 variants and clinical response of perianal fistulas in patients using antibiotic therapy. METHODS: Fifty-two patients (median age 36 yr) with draining perianal fistulas were treated with ciprofloxacin (N = 49) or metronidazole (N = 3) for a median duration of 7 wk. Complete response was defined as the absence of any draining fistula despite gentle finger compression. Genotyping for NOD2/CARD15 variants and human beta (beta)-defensin 2 (HBD-2) copies was performed by 5' nuclease assays (Applied Biosystems, Foster City, CA). The examiners and laboratory investigators were blinded. The Fisher exact test and Wilcoxon signed rank test were used for statistical analysis. RESULTS: Ciprofloxacin was discontinued in one patient due to diarrhea after 2 wk. Complete fistula response was observed in 13 of 39 patients with NOD2/CARD15 wild-type (33.3%) compared with none in patients carrying NOD2/CARD15 variants (0%, P= 0.02). The median number of HBD-2 gene copies between responders and partial/nonresponders was similar. CONCLUSIONS: The study result suggests a substantial contribution of NOD2/CARD15 to the antibiotic treatment outcome of perianal fistulating CD. NOD2/CARD15 variants may predispose to an altered intestinal microflora in perianal fistulas that is less responsive to antibiotic treatment.

Clinical and endosonographic effect of ciprofloxacin on the treatment of perianal fistulae in Crohn's disease with infliximab: a double-blind placebo-controlled study.

BACKGROUND: Ciprofloxacin is effective in perianal Crohn's disease but after treatment discontinuation symptoms reoccur. Infliximab is effective but requires maintenance therapy. AIM: To evaluate the effect of combined ciprofloxacin and infliximab in perianal Crohn's disease. METHODS: A double-blind placebo-controlled study was conducted. Patients were randomly assigned to receive 500-mg ciprofloxacin twice daily or a placebo for 12 weeks. All patients received 5-mg/kg infliximab in week 6, 8 and 12 and were followed for 18 weeks. Primary end-point was clinical response, defined as a 50% or greater reduction from baseline in the number of draining fistulae. Secondary end-points were the change in Perianal Disease Activity Index and hydrogen peroxide enhanced three-dimensional endoanal ultrasonography findings. Analysis was by intention-to-treat. RESULTS: Twenty-four patients were included but two discontinued treatment. At week 18, response was 73% (eight of 11) in the ciprofloxacin group and 39% (five of 13) in the placebo group (P = 0.12). Using logistic regression analysis patients treated with ciprofloxacin tended to respond better (OR = 2.37, CI: 0.94-5.98, P = 0.07). The Perianal Disease Activity Index score only improved (P = 0.008) in the ciprofloxacin group. Three-dimensional endoanal ultrasonography improved in three patients with a clinical response. CONCLUSIONS: A combination of ciprofloxacin and infliximab tended to be more effective than infliximab alone.