Perianal fistulizing Crohn's disease (pfCD) represents a severe manifestation of Crohn's disease (CD) that often leads to significant morbidity. Clinical examination alone of perianal fistulae is unlikely to be sufficient in the context of complex pfCD, as patients are likely to have complex disease and are more likely to experience complications, treatment failure, and recurrent disease. Furthermore, the relapsing-remitting nature of Crohn's disease and our limited understanding of the pathogenesis of this potentially destructive disease necessitate regular examination and radiological assessment, often in the form of magnetic resonance imaging (MRI). Recent advancements in diagnostic techniques have enhanced the accuracy and timeliness of pfCD diagnosis, facilitating better patient outcomes. A growing appreciation of isolated perianal Crohn's disease has prompted a recent attempt to develop consensus recommendations on diagnosing and treating this group of patients who would previously not have been offered CD medications. This narrative review aims to summarize current practice and the latest developments in the diagnosis of pfCD, highlighting: 1. Clinical examination and assessment tools 2. Current imaging practices 3. Innovations in imaging and biomarkers 4. The diagnosis of isolated perianal Crohn's disease.

Previous literature suggests that faecal calprotectin (FC) discriminates Crohn's disease perianal fistulas from cryptoglandular fistulas, irrespective of luminal disease. This study aims to prospectively validate this and analyse if increased local fistula calprotectin levels are associated with fistula characteristics.

In this prospective study, all consecutive patients with an active perianal fistula undergoing examination under anaesthesia were included. Faecal and fistula tract scraping calprotectin levels were determined. The primary objective was to analyse whether FC levels could be used to differentiate between Crohn's disease and cryptoglandular perianal fistulas. Secondary outcome parameters were the levels of local calprotectin in fistula scrapings and their correlation with fistula characteristics.

Sixty-three patients were included in this study (perianal Crohn's disease; 45, cryptoglandular; 18). Faecal calprotectin levels were significantly higher in Crohn's disease patients compared with cryptoglandular fistula (354.3 [58.8-1076.3] vs. 47.3 [14.6-233.6] μg/g, p = 0.003). Faecal calprotectin could accurately discriminate Crohn's disease patients with active luminal disease from patients without luminal disease (median [interquartile range]) (1167.0 [557.0-2806.3] vs. 93.0 [47.5-571.6] μg/g, p = 0.001). Faecal calprotectin was not related to calprotectin levels in fistula scrapings. No fistula characteristic was found to be correlated to scraping calprotectin, but a correlation was found with the TOpCLASS classification system, which stratifies fistulas according to disease severity and outcome: class 2a (amenable for repair), class 2b (symptom control) and class 2c (gradually debilitating disease): 140[31.0-149.0]) μg/g versus 706[198.5-1936] μg/g versus 4000[1337-5894] μg/g, p < 0.001). Scraping calprotectin was also related to pronounced hyperintensity of the fistula tract on MRI in Crohn's disease patients: (69.0[30.0-821.0] vs. 1284.0[204.3-4185.5]; p = 0.01)) and cryptoglandular patients: (30.0[13.5-80.5] vs. 3012.0 [923.8-5021.0]; p = 0.002).

Crohn's disease and cryptoglandular perianal fistulas differ in FC levels. Local fistula calprotectin production did not explain this difference, implying FC reflects the luminal condition. A correlation exists between scraping calprotectin levels and Crohn's disease fistula severity, which could be clinically relevant for prognostic cohorts and tailored treatment.

Diagnosis of Crohn's disease (CD) can pose challenges, particularly when perianal fistula is the initial presentation.

To develop and validate a predictive model, establishing a visual web tool for early diagnosis of CD in patients presenting with perianal fistula.

This retrospective, multicentre validation study involved patients diagnosed with either perianal fistulising CD or cryptoglandular fistula who underwent initial perianal fistula surgery subsequent to rectal MRI at three Chinese centres from September 2016 to December 2020. A random forest classification model was trained on the derivation cohort (n = 550), randomly split into training and test sets at a 7:3 ratio. Validation utilised data from two external centres (n = 300). Model interpretation employed the Shapley Addictive explanation (SHAP) framework. The validated model was integrated into a web tool for calculating patient-specific risk.

In the derivation cohort, SHAP analysis highlighted rectal wall ulceration, rectal wall thickening, submucosal fistula, and T2 hyperintensity as risk factors, while age was identified as protective. A random forest classification model developed using these top 5 features achieved an AUROC of 0.9425 (95% CI: 0.8943-0.9906). In the validation cohort, the model performed well with AUROC values of 0.9187 (95% CI: 0.8620-0.9754) and 0.9341 (95% CI: 0.8876-0.9806), respectively. We developed a publicly accessible web-based application.

We have developed a multimodal machine learning model and a web tool that can predict and present CD risk in patients initially presenting with perianal fistula.

Perianal fistulizing Crohn's disease is one of the most disabling phenotypes of Crohn's disease, due to the severe impairment in quality of life including social and personal wellbeing. A multimodal approach with patient-tailored care is the key to optimal management of this condition. Medical therapy is needed to optimize the luminal disease, and surgical intervention is required to control any associated perianal sepsis and attempt palliative or definitive fistula repair. While several medical and surgical options are available, the majority of patients continue to have symptomatic disease. Fortunately, this continues to drive novel innovations which are revolutionizing the treatment and outcomes of perianal fistulizing Crohn's disease. However, there continues to be a need for randomized trials and consistent metrics utilized for classification and treatment outcomes in order to accurately describe optimal treatment outcomes.

Crohn's disease (CD) causes gastrointestinal symptoms (i.e., diarrhea and abdominal pain), systemic symptoms (i.e., fatigue, anemia, weight loss, and fever), and perianal fistulas that produce anal pain. Because of the frequent occurrence of diarrhea and ulcers in the rectum, CD is often exacerbated by perianal abscesses and/or fistulas. Perianal fistulizing CD (PFCD) has an unknown etiology and recurring symptoms such as pain and discharge, which seriously affects the patient's quality of life (QOL). In the past, radical surgery was performed for PFCD, but due to the risk of anal sphincter impairment, conservative therapy using antibiotics and immunosuppressive medications is currently the first treatment option. PFCD management has greatly improved with the use of biologics such as the antitumor necrosis factor alpha (TNF-α) antibodies infliximab and adalimumab. In this review, the results of the administration of anti-TNF-α (certolizumab pegol), anti-interleukin-12/23 (ustekinumab), and anti-α4β7 integrin antibodies (vedolizumab) were evaluated. Our investigation showed that these medications may be effective for maintenance therapy to prevent the recurrence of anal fistulas. In addition to biologics, molecular target drugs and even regenerative medicine using mesenchymal stem cells have been introduced to further expand the treatment options for consideration by medical personnel. We herein discuss the management of PFCD by focusing on studies conducted in the United States and Europe where researchers used recommended guidelines and consensus statements to evaluate the efficacy of each medication and published their findings in peer-reviewed journals.

Inflammatory bowel disease-related complications are associated with a decreased quality of life, requirement for surgery, and increased morbidity. Endoscopic ultrasound (EUS) is accurate at identifying and characterizing perianal fistulae and abscesses and helps guide treatment decisions. EUS also allows us to accurately assess for mucosal and transmural inflammation and thus can help differentiate Crohn's disease from ulcerative colitis (UC). EUS use can help predict dysplasia in UC, and monitoring transmural inflammation can help assess response to treatment. In addition to diagnostic EUS, therapeutic EUS techniques have been used to endoscopically drain abscesses and bypass strictures in Crohn's disease.

Inflammatory bowel disease refers to a group of non-specific inflammatory illnesses affecting the gastrointestinal tract. According to pathogenic characteristics, it is divided into Ulcerative colitis and Crohn's disease. The exact cause and pathogenic mechanism of these disorders are not yet fully understood. In addition, there is currently no definitive diagnostic method for inflammatory bowel disease, which mainly depends on clinical symptoms, blood testing, imaging investigations, and endoscopic examination, which includes histology. Endoscopic Ultrasonography is a digestive tract examination technique that combines endoscopy and ultrasound. Compared to conventional endoscopy, it can visualize surface and deep lesions of the gastrointestinal wall, as well as provide information on the characteristics of the surrounding layers and nearby lymph nodes. Due to these advantages, Endoscopic Ultrasonography has played a significant role in the evaluation of inflammatory bowel disease in recent years. Through this work, we aim to identify the applications of this method in the case of patients with inflammatory bowel disease.

Perianal fistulas of Crohn's disease (CD) create a significant burden on patients' lives. However, the efficacy and safety of adipose-derived mesenchymal stem cell treatment are contradicting, and real-world evidence is lacking.

To examine the usability of darvadstrocel therapy in managing perianal CD.

We enrolled patients with CD and perianal fistulas in this retrospective multicenter study. The primary outcome was perianal clinical remission (defined as all treated fistulas closed) at weeks 26 and 52. Secondary outcomes were clinical response rates (≥ 1 fistulas closed), perianal activity (PDAI), patient satisfaction, and adverse events. Data were recorded at baseline and weeks 12, 26 and 52. Prediction of primary outcomes was performed by logistic regression.

Overall, among 223 patients (male/female ratio: 0.48), perianal clinical remission was achieved in 78.2% and 62.3% until weeks 26 and 52. Baseline PDAI score (OR 0.75), number of fistulas (OR 0.28) and the number of weeks after preparation for surgery (OR 0.98) were associated with treatment failure. The clinical response rates were 84.8% and 79.8% at weeks 26 and 52. Improvement of subjective perianal symptoms was achieved in 77.8% and 78.4% of patients, respectively. Adverse events occurred in 13.5% of patients; perianal abscesses and proctalgia were the most frequently reported.

Effectiveness data were higher than in clinical trials. The safety profile was reassuring, and patients' satisfaction was high. Appropriate patient selection, fistula preparation and expertise may help to achieve treatment success.

Fistulizing Crohn's Disease (fCD) affects up to 50% of people with Crohn's Disease over their lifetime. Despite this high prevalence, the burden of disease, treatment and natural history in the current biologic era are poorly described. This study explores demographic, disease and treatment factors in a real-world Australasian cohort.

A large real-world cohort of people with inflammatory bowel disease under routine care was interrogated in August 2023. Current fCD was defined as fistula(e) on most recent clinical, radiologic or endoscopic investigation; prior fCD was defined as the resolution of fistula(e) on most recent documentation.

Of 3075 people with Crohn's Disease, 7.4% had current and 10.1% prior fCD (n = 224 & 311). Most patients were in Australia (77%), where 19.3% had current or previous fCD compared to 11% in New Zealand (P < .001). Patients with current or previous fCD were younger compared to those without (P = .003 & P < .001). Males were more commonly affected (P = .021). Current or prior fCD were more likely to be on biologic therapy (P < .001), with anti-tumor necrosis factor agents most frequently utilized. Conversely, those without fCD were more likely on Ustekinumab or Vedolizumab compared to current and prior fCD groups. People with fistulizing disease had higher hospitalization rates, while the prior fCD cohort had longer hospital admissions and more frequently required surgical intervention.

People with fCD used more health-care resources, making this an important area for further research into care gaps to improve outcomes and optimal treatment approaches.

This article discusses the literature review article by Pacheco et al published in July 2024; the authors provided good reviews of perianal Crohn's disease (CD), and challenges faced by clinicians in the management. CD, characterized by its chronic and relapsing nature, is an idiopathic condition that can involve any segment of the gastrointestinal tract. Perianal disease impacts up to 40% of patients with CD, with perianal fistulas constituting up to 80% of perianal lesions. Perianal CD can be highly incapacitating and profoundly diminish the overall well-being of patients. The management focuses on controlling the perianal sepsis and treating luminal CD. Biologics are crucial to the treatment approach, and results have been encouraging. The surgery focuses on controlling the sepsis, with more definitive treatments being fistula surgery, fecal diversion, and proctectomy as the last resort. This manuscript briefly describes the burden of CD, the challenges posed by perianal CD, and the role of different treatment modalities from colorectal surgeon's perspective.

Perianal fistulas are a debilitating complication of Crohn's disease (CD). Due to unknown reasons, CD-associated fistulas are in general more difficult to treat than cryptoglandular fistulas (non-CD-associated). Understanding the immune cell landscape is a first step towards the development of more effective therapies for CD-associated fistulas. In this work, we characterized the composition and spatial localization of disease-associated immune cells in both types of perianal fistulas by high-dimensional analyses.

We applied single-cell mass cytometry (scMC), spectral flow cytometry (SFC), and imaging mass cytometry (IMC) to profile the immune compartment in CD-associated perianal fistulas and cryptoglandular fistulas. An exploratory cohort (CD fistula, n = 10; non-CD fistula, n = 5) was analyzed by scMC to unravel disease-associated immune cell types. SFC was performed on a second fistula cohort (CD, n = 10; non-CD, n = 11) to comprehensively phenotype disease-associated T helper (Th) cells. IMC was used on a third cohort (CD, n = 5) to investigate the spatial distribution/interaction of relevant immune cell subsets.

Our analyses revealed that activated HLA-DR+CD38+ effector CD4+ T cells with a Th1/17 phenotype were significantly enriched in CD-associated compared with cryptoglandular fistulas. These cells, displaying features of proliferation, regulation, and differentiation, were also present in blood, and colocalized with other CD4+ T cells, CCR6+ B cells, and macrophages in the fistula tracts.

Overall, proliferating activated HLA-DR+CD38+ effector Th1/17 cells distinguish CD-associated from cryptoglandular perianal fistulas and are a promising biomarker in blood to discriminate between these 2 fistula types. Targeting HLA-DR and CD38-expressing CD4+ T cells may offer a potential new therapeutic strategy for CD-related fistulas.

Although observational clinical studies have established an association between Intestinal Diseases (IDS) and Anal Diseases (ADS), the causal relationship is still not fully understood due to the limitations of observational studies. Genome-wide association study (GWAS) statistical data for IDS and ADS were obtained from publicly available databases. To assess the causal effects of IDS on ADS, we conducted Mendelian randomization analysis. The inverse variance weighted method indicated that Inflammatory bowel disease (IBD) had a significant causal relationship with three kinds of ADS: Anorectal abscess (ARB), Haemorrhoidal disease (HEM), and Fissure and fistula of anal and rectal regions (FISSANAL). Crohn's disease (CD) and Ulcerative colitis (UC) also showed significant causal effects with three ADS: ARB, HEM, and FISSANAL. Furthermore, a potential link between CD and BNA(Benign neoplasm of anus and anal canal), Irritable bowel syndrome (IBS) and HEM, Colorectal cancer (CRC) and BNA, and Celiac disease and MNA (Malignant neoplasm of anus and anal canal) was observed. This comprehensive MR analysis highlight the significant and increased risk of common Anal Diseases (ARB, FISSANAL, and HEM) in patients with IBD, CD, and UC. Additionally, potential positive causal associations emerged between IBS and HEM, CRC and BNA, as well as between celiac disease and MNA.

Background: Incidences of perianal fistulas (PAFs) as a first manifestation of Crohn's disease (CD) vary widely in the literature. Aim: To analyse the percentage of patients with a PAF preceding CD diagnosis and assess the time to diagnosis. Methods: A systematic literature search was conducted. Studies reporting on patients with a PAF preceding CD diagnosis were identified. Primary outcomes were the (weighted) percentage of patients with CD with a PAF preceding CD and their time to CD diagnosis. Secondary outcomes were the (weighted) percentage of patients with CD with a PAF preceding CD diagnosis in predefined patient subgroups, including (1) sex (men vs. women), (2) ethnicity (Asian vs. non-Asian), and (3) age (paediatric (0-18 y) and patients with elderly onset CD (>60 y) vs. adult patients (18-60 y)). Results: Seventeen studies were included (34,030 patients with CD). In the overall CD population, a PAF preceded CD in 8.6% [95%CI; 5.72; 12.71] with a weighted mean time to CD diagnosis of 45.9 (31.3) months. No studies reported details on sex differences in patients with a PAF as a manifesting sign of CD. In Asian populations, a PAF preceded CD in 17.66% [95%CI; 11.45; 26.25], which was significantly higher when compared with non-Asians (4.99% [95%CI; 3.75; 6.60], OR:3.99, p < 0.0001). In adolescents, an incidence of 9.17% [95%CI; 5.92; 13.93] was found with significantly lower incidences in paediatric patients (6.38% [95%CI; 1.84; 19.85], OR:0.53, p < 0.0001), and elderly-onset patients (3.77% [95%CI; 1.68; 8.25], OR:0.44, p = 0.0035). Conclusions: This systematic review shows that in the literature, almost 10% of patients present with a PAF as a first manifestation of CD, with a mean time to diagnosis of almost four years. These results emphasise that increased clinical awareness is needed.

Perianal fistulas may affect 15% to 50% of patients with Crohn's disease. Treatment is complex, requiring a multidisciplinary approach. Darvadstrocel (allogenic mesenchymal cells obtained from lipoaspirates) was approved in 2018 by the European and Spanish Agencies of Medicines and Medical Products as a treatment for fistulas in Crohn's disease. Recent guidelines from the European Crohn's and Colitis Organisation and Spanish Working Group on Crohn's Disease and Ulcerative Colitis state that darvadstrocel is effective with a favorable safety profile and a strong level of evidence (n = 2).

Presenting real-world effectiveness data for darvadstrocel in a Spanish population.

Observational retrospective cohort study with prospective data gathering.

The study was conducted at 14 institutions in Spain.

From November 2019 to April 2022, all patients (n = 73) treated with darvadstrocel in these institutions were included, fulfilling the following criteria: 1) complex fistula/s in a patient with Crohn's disease; 2) failure of conventional and antitumor necrosis factor treatment; and 3) the absence of collections of >2 cm confirmed by pelvic MRI at the time of surgery.

Darvadstrocel treatment.

Clinical response (closure of 50% or more of external openings), complete clinical closure (100% of external openings), and radiological closure (no fluid collection >2 cm, edema, or inflammation) evaluated 6 months after treatment.

Clinical response was observed in 63 patients (86.3%), complete clinical closure in 50 patients (68.5%), and radiological closure in 45 patients (69.2%). Combined clinical and radiological response was observed in 41 patients (63.1%). Not all clinically healed patients had radiological closure, and vice versa. No serious adverse events were reported.

Retrospective nature of the study.

Study results were consistent with those reported in previous clinical trials, real-world efficacy findings from the INSPIRE study (assessing darvadstrocel effectiveness in Europe, Israel, Switzerland, United Kingdom, and Japan), and previously published literature. Darvadstrocel was effective and demonstrated a favorable safety profile when used in normal clinical practice for the treatment of fistulas in Crohn's disease. See Video Abstract .

ANTECEDENTES:Las fístulas perianales pueden afectar entre el 15 y el 50% de los pacientes con enfermedad de Crohn. El tratamiento es complejo y requiere un enfoque multidisciplinario. El darvadstrocel (células mesenquimales alogénicas obtenidas a partir de lipoaspirados) fue aprobado en 2018 por las Agencias Europea y Española de Medicamentos y Productos Sanitarios como tratamiento de las fístulas en la EC. Las recientes directrices de la Organización Europea de Crohn y Colitis y del Grupo de Trabajo Español sobre la Enfermedad de Crohn y Colitis Ulcerosa afirman que darvadstrocel es eficaz con un perfil de seguridad favorable y un sólido nivel de evidencia (2).OBJETIVO:Presentar datos de eficacia real de darvadstrocel en población española.DISEÑO:Estudio de cohorte retrospectivo observacional con recopilación prospectiva de datos.ESCENARIO:14 instituciones.PACIENTES:Desde noviembre de 2019 hasta abril de 2022, se incluyeron todos los pacientes (73) tratados con darvadstrocel en estas instituciones, que cumplieron los siguientes criterios: 1) fístula/s compleja/s en un paciente con enfermedad de Crohn; 2) fracaso del tratamiento convencional y anti factor de necrosis tumoral; 3) ausencia de colecciones > 2 cm confirmada por resonancia magnética pélvica en el momento de la cirugía.INTERVENCIONES:Tratamiento con Darvadstrocel.PRINCIPALES MEDIDAS DE RESULTADO:Respuesta clínica (cierre de ≥50% de las aberturas externas), cierre clínico completo (100% de las aberturas externas) y cierre radiológico (sin acumulación de líquido >2 cm, sin edema ni inflamación) evaluados 6 meses después del tratamiento.RESULTADOS:Se observó respuesta clínica en 63 pacientes (86.3%), cierre clínico completo en 50 pacientes (68.5%) y cierre radiológico en 45 pacientes (69.2%). Se observó respuesta clínica y radiológica combinada en 41 pacientes (63.1%). No todos los pacientes clínicamente curados tuvieron cierre radiológico y viceversa. No hubo eventos adversos graves reportados.LIMITACIONES:Estudio retrospectivoCONCLUSIONES:Los resultados del estudio fueron consistentes con los informados en ensayos clínicos anteriores, los hallazgos de eficacia en el mundo real del estudio INSPIRE (que evalúa la efectividad de darvadstrocel en Europa, Israel, Suiza, el Reino Unido y Japón) y la literatura publicada anteriormente. Darvadstrocel fue eficaz y demostró un perfil de seguridad favorable cuando se utiliza en la práctica clínica habitual para el tratamiento de fístulas en la enfermedad de Crohn. (Traducción-Dr. Jorge Silva Velazco ).

Inflammatory bowel disease remains a difficult disease to effectively treat, especially fistulizing Crohn's disease. Perianal fistulas in the setting of Crohn's disease remain an area of unmet need with significant morbidity in this patient population. Up to one third of Crohn's patients will have perianal fistulizing disease and current medical and surgical interventions are of limited efficacy. Thus, most patients experience significant morbidity, narcotic use, and loss of employment and end up with multiple surgical interventions. Mesenchymal stem cells (MSCs) have shown efficacy in phase 3 clinical trials, but considerable infrastructure challenges make MSCs limited with regard to scalability in clinical practice. Extracellular vesicles, being derived from MSCs and capturing the secretome functionality of MSCs, offer similar physiological utility regarding mechanism, while also providing an off the shelf regenerative medicine product that could be widely used in daily clinical practice.

Pregnant women with active perianal Crohn's disease indicate a cesarean delivery according to the current European Crohn's and Colitis Organisation guidelines. This advice is based on the assumption that vaginal delivery leads to exacerbation of perianal disease and worsening of fecal continence. However, there is no strong evidence to support this.

This study aims to examine the effects of the delivery method on perianal disease progression and fecal incontinence in women with perianal Crohn's disease.

In this retrospective cohort study, 102 women were selected from the 1000 inflammatory bowel disease cohort of a tertiary hospital in the Netherlands. All women are aged >18 years, have perianal Crohn's disease, and have given birth. In addition, all women completed a questionnaire. Fecal continence was scored using the Vaizey score. Using SPSS, descriptive analysis and linear regression analysis were performed, and P values <.05 were considered statistically significant.

The cesarean delivery rate within our cohort was 19.5%. Within the group of women who delivered at least one child vaginally (n=84), 25.5% reported alteration of fecal continence, compared with 13.1% in women who only had cesarean delivery (n=18). After a mean follow-up of 15 years, the median Vaizey score within the cesarean delivery group was 5, compared with 7 in the vaginal delivery group. Within the vaginal delivery group, 18.8% reported perianal disease progression, compared with 22.2% in the cesarean delivery group. No significant relation between mode of delivery and fecal continence or perianal disease progression was found (B, 0,97 [-1,19 to 3,14], P=.38).

Fecal incontinence and perianal disease progression after vaginal delivery in Crohn's disease women with active perianal fistula is not significantly increased in this retrospective cohort. This study opens the discussion for more tailored obstetric advice in women with perianal Crohn's disease.

Mesenchymal stem cells have been administered via direct injection to treat perianal Crohn's fistulizing disease. We herein sought to determine the safety and durability of treatment response to 12 months with 3 individual phase IB/IIA clinical trials of mesenchymal stem cells for refractory perianal, rectovaginal, and ileal pouch fistulas in the setting of Crohn disease.

Three phase IB/IIA randomized placebo-controlled single-blinded clinical trials were performed for (1) perianal fistulas, (2) rectovaginal fistula, and (3) ileal pouch in situ with anovaginal and/or perianal fistulas. Bone marrow-derived mesenchymal stem cells (75 million in 7.5 mL) were injected at the time of exam under anesthesia on day 0 and month 3. Outcome measures were adverse events and combined clinical and pelvic magnetic resonance imaging healing at month 6 and month 12.

Across all 3 trials, 64 patients were enrolled; 49 were treatment and 15 were control. At 6 months, combined clinical and radiographic healing was achieved in 83.3%, 33.3%, and 30.8% of the perianal, rectovaginal, and pouch fistula treatment cohorts, respectively. At 12 months, the treatment response was durable, with 67.7% of perianal, 37.5% of rectovaginal, and 46.2% of peripouch fistulas maintaining complete clinical and radiographic healing. Two patients in the perianal fistula control cohort achieved combined clinical and radiographic healing at 12 months, whereas 0% of rectovaginal and pouch control patients healed.

Bone marrow-derived mesenchymal stem cells offer a safe and effective alternative treatment approach for severe perianal, rectovaginal, and peripouch fistulizing Crohn's disease. Treatment results are durable at 12 months.

Managing complex perianal fistulizing Crohn's disease (CD) remains challenging, despite current medical and surgical treatment approaches. Darvadstrocel, a therapy utilizing adipose-derived stem cells, shows promise in promoting tissue regeneration and healing, offering a novel and effective treatment for fistula management.

A systematic literature search was conducted on PubMed and Scopus to identify studies involving patients with complex perianal fistulizing CD treated with darvadstrocel.

In total, 2 randomized controlled trials (RCT), 5 observational studies with retrospective data collection and 2 observational studies with prospective design were included in the final review. Data from the European ADMIRE-CD RCT demonstrated that darvadstrocel is superior to placebo in terms of clinical and imaging improvement over both the short and long term. These findings align with the prospective studies analyzed in this systematic review. The rate of treatment-emergent adverse events in the ADMIRE-CD trial's RCTs was similar in both the darvadstrocel and control groups, with perianal abscess being the most common adverse event up to 52 weeks after drug administration. Retrospective studies indicated no side-effects beyond 52 weeks.

Darvadstrocel appears to be a new, potentially effective and safe treatment option for the management of complex perianal fistulas. However, more randomized clinical trials are needed to evaluate the efficacy and safety profile of the drug.

Crohn's disease is a complex, relapsing and remitting inflammatory disorder of the gastrointestinal tract with a variable disease course. While the treatment options for Crohn's disease have dramatically increased over the past two decades, predicting individual patient response to treatment remains a challenge. As a result, patients often cycle through multiple different therapies before finding an effective treatment which can lead to disease complications, increased costs, and decreased quality of life. Recently, there has been increased emphasis on personalized medicine in Crohn's disease to identify individual patients who require early advanced therapy to prevent complications of their disease. In this review, we summarize our current approach to management of Crohn's disease by identifying risk factors for severe or disabling disease and tailoring individual treatments to patient-specific goals. Lastly, we outline our knowledge gaps in implementing personalized Crohn's disease treatment and describe the future directions in precision medicine.

Perianal fistulizing Crohn's Disease (pCD) affects about 25% of patients with Crohn's Disease (CD). It remains a difficult entity to manage with a therapeutic ceiling of treatment success despite improving medical and surgical management. The refractory nature of the disease calls for an imminent need to better understand its immunopathogenesis and classification to better streamline our treatment options. In this article, we overview the current state of pCD management and discuss where the future of its management may lie.

Fistulizing perianal Crohn's disease poses a treatment challenge, and researchers postulate that this phenotype in young male patients could have a worst outcome.

Thus, the aim of this study was to assess whether sex influences the response to treatment for these patients.

This systematic review (PROSPERO CRD42022319629) was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. We selected articles published in English, Spanish, Portuguese, and Italian between 2010 and 2020 in the PubMed and Science Direct databases. According to the PICO acronym, prospective studies in patients older than 18 years with the objective of treating fistulizing perianal Crohn's disease were selected. Studies in pediatric populations, retrospective, without treatment objectives, and that included only rectovaginal fistulas or a single sex were excluded. Study quality was assessed using the Cochrane risk of bias tool and Newcastle-Ottawa scale.

Of the 1887 articles found, 33 were included. Most studies used anti-TNF drugs as treatment (n=11). Ten studies had subgroup analyses; of them, the two studies reporting sex differences used infliximab and adalimumab as treatment and showed that women had a longer fistula closure time than men.

This systematic review showed that few data corroborate the difference between sexes in the treatment of fistulizing perianal Crohn's disease, possibly having a greater relationship with the phenotype. However, considering the lack of results, further studies with this objective and with standardization of fistulas and response assessment methods are needed.

Perianal fistulas in Crohn's disease (CD) are a poor prognostic phenotype requiring a combination of medical and surgical management. Perianal fistulas in CD are characterized by more complex and multi-branched fistulas, association with skin tags, and frequent presence of proctitis. A comprehensive approach with clinical examination, endoscopic and MR assessment is required, and in particular, MR interpretation provides detailed information on the type of fistula with its internal component and activity, secondary tracts and extension, internal, external openings, associated abscess, and presence of proctitis. Structured reporting of these items would be recommended for further discussion and management planning both at initial diagnosis and for disease monitoring during treatment follow-up. Management strategy would be individualized for each patient, and control of luminal disease activity could be an important determinant in the selection of treatment options. In this review, we provide an overview of the MRI evaluation of perianal fistulas in CD with a proposed structured MR report.

Fistulizing perianal Crohn's disease (CD) is a debilitating condition associated with significant morbidity and reduction in the quality of life. Magnetic resonance imaging (MRI) of the pelvis is the preferred imaging modality for the comprehensive assessment of the perianal fistula. There is a paucity of data from India on the MRI spectrum of complex perianal fistula in CD.

A single-centre cross-sectional analysis of patients with fistulizing perianal CD, who underwent pelvic MRI between January 2020 and December 2021, was performed. The clinical (age, sex, disease duration, disease location and behavior, disease activity [Perianal Disease Activity Index, PDAI] and treatment received) and radiological (number and location of fistulae, extensions, number and location of internal and external openings, fistula activity, presence or absence of perianal abscess and associated proctitis) characteristics of complex perianal fistula (defined according to the American Gastroenterological Association classification) were recorded.

Of total 175 patients with CD who attended the gastroenterology clinic during the study period, 27 (15.42%) (mean age 42±15.5 years, 62.96% females and median disease duration four years) had complex perianal fistula and were included in the analysis. The mean PDAI was 5.48±2.53. The median Van Assche Index was 17 (interquartile range [IQR] 13-19). A majority (96.29%) of the fistulae were trans-sphincteric and four (14.81%) fistulae extended into the supralevator space. All fistulae were active on MRI. Concomitant perianal abscess and proctitis were seen in 59.26% (n=16) and 62.96% (n=17) of patients, respectively. Combination therapy with biologics and antibiotics/immune-suppressants were the most commonly prescribed medical therapy. Six (22.22%) patients underwent combined medical and surgical (non-cutting seton, fistulectomy, fecal diversion) treatment.

The cumulative risk of the development of fistulizing perianal CD in a northern Indian cohort was similar to the western populations. Complex perianal fistulae were predominantly trans-sphincteric and commoner in females. MRI evaluation is pivotal for the delineation of fistula anatomy, assessment of disease extent and activity and the evaluation of concomitant perianal abscess and other complications.

Mesenchymal stem cells have been used for the treatment of perianal Crohn's fistulizing disease by direct injection. However, no studies to date have included patients with proctitis, anal canal involvement, and multiple branching tracts.

This study aimed to determine safety and efficacy of mesenchymal stem cells for refractory perianal Crohn's disease.

Phase IB/IIA randomized controlled trial.

Tertiary IBD referral center.

Adult Crohn's disease patients with perianal fistulizing disease.

Seventy-five million mesenchymal stem cells were administered with a 22-G needle by direct injection after curettage and primary closure of the fistula tract. A repeat injection of 75 million mesenchymal stem cells at 3 months was given if complete clinical and radiographic healing were not achieved.

Adverse and serious adverse events occurred at postprocedure day 1, week 2, week 6, month 3, month 6, and month 12. Clinical healing, radiographic healing per MRI, and patient-reported outcomes were collected at the same time points.

A total of 23 patients were enrolled and treated; 18 were treatment patients and 5 were control. There were no adverse or serious adverse events reported related to mesenchymal stem cell therapy. At 6 months, 83% of the treatment group and 40% of the control group had complete clinical and radiographic healing. The perianal Crohn's disease activity index, Wexner incontinence score, and VanAssche score had all significantly decreased in treatment patients at 6 months; none significantly decreased in the control group.

Single institution and single blinded.

Bone marrow-derived mesenchymal stem cells offer a safe and effective alternative treatment approach for severe perianal fistulizing Crohn's disease. See Video Abstract at http://links.lww.com/DCR/C128 .

ANTECEDENTES:Las células madre mesenquimales se han utilizado para el tratamiento de la enfermedad fistulizante de Crohn perianal mediante inyección dirigida. Sin embargo, ningún estudio hasta la fecha ha incluido pacientes con proctitis, afectación del canal anal y vías de ramificación múltiples.OBJETIVO:Determinar la seguridad y eficacia de las células madre mesenquimales para la enfermedad de Crohn perianal refractaria.DISEÑO:Ensayo de control aleatorizado de fase IB/IIA.AJUSTES:Centro de referencia de enfermedad inflamatoria intestinal terciaria.PACIENTES:Pacientes adultos con enfermedad de Crohn con enfermedad fistulizante perianal.INTERVENCIÓN:Se administraron 75 millones de células madre mesenquimales con una aguja 22G mediante inyección directa después del legrado y cierre primario del trayecto de la fístula. Se administró una inyección repetida de 75 millones de células madre mesenquimales a los 3 meses si no se lograba una curación clínica y radiográfica completa.PRINCIPALES MEDIDAS DE RESULTADOS:eventos adversos y adversos graves en el día 1, la semana 2, la semana 6, el mes 3, el mes 6 y el mes 12 después del procedimiento. Curación clínica, curación radiográfica por imagen de resonancia magnética y resultados informados por el paciente en los mismos puntos de tiempo.RESULTADOS:Un total de 23 pacientes fueron reclutados y tratados; 18 fueron de tratamiento y 5 de control. No se informaron eventos adversos o adversos graves relacionados con la terapia con células madre mesenquimales. A los seis meses, el 83 % del grupo de tratamiento y el 40 % del control tenían una curación clínica y radiográfica completa. El índice de actividad de la enfermedad de Crohn perianal, la puntuación de incontinencia de Wexner y la puntuación de VanAssche habían disminuido significativamente en los pacientes de tratamiento a los seis meses; ninguno disminuyó significativamente en el grupo de control.LIMITACIONES:Institución única y simple ciego.CONCLUSIONES:Las células madre mesenquimales derivadas de la médula ósea ofrecen un d tratamiento alternativo seguro y eficaz para la enfermedad de Crohn fistulizante perianal grave. Consulte Video Resumen en http://links.lww.com/DCR/C128 . (Traducción-Dr Yolanda Colorado ).

Many patients with inflammatory bowel disease (IBD) have persistent symptoms and disease activity despite the best available medical or surgical treatments. These patients are commonly referred to as having difficult-to-treat IBD and need additional therapeutic strategies. However, the absence of standard definitions has impeded clinical research efforts and comparisons of data. Under the guidance of the endpoints cluster of the International Organization for the Study of Inflammatory Bowel Disease, we held a consensus meeting to propose a common operative definition for difficult-to-treat IBD. 16 participants from 12 countries voted on 20 statements covering various elements of difficult-to-treat IBD, such as failure of medical and surgical treatments, disease phenotypes, and specific complaints from patients. "Agreement" was defined as at least 75% consensus. The group agreed that difficult-to-treat IBD is defined by the failure of biologics and advanced small molecules with at least two different mechanisms of action, or postoperative recurrence of Crohn's disease after two surgical resections in adults, or one in children. In addition, chronic antibiotic-refractory pouchitis, complex perianal disease, and comorbid psychosocial complications that impair disease management also qualified as difficult-to-treat IBD. Adoption of these criteria could serve to standardise reporting, guide enrolment in clinical trials, and help identify candidates for enhanced treatment strategies.

This study compared disease burden, experiences, and health-related quality of life (HRQoL) between patients with Crohn's perianal fistulas (CPFs) and those with Crohn's disease (CD) without perianal fistulas (PFs; non-PF CD).

This cross-sectional, observational study was conducted in 3 cohorts of US patients aged 18-89 years with self-reported, physician-diagnosed CD: (1) non-PF CD; (2) CPF without PF-related surgery; and (3) CPF with PF-related surgery. Data on medical and surgical interventions, CD-specific symptoms, HRQoL (assessed using the Short Inflammatory Bowel Disease and 5-dimension EuroQol questionnaires), and fecal incontinence (assessed using Revised Faecal Incontinence Scale and Fecal Incontinence Quality of Life questionnaires) were collected via a web-enabled questionnaire.

In total, 403 patients with CD completed the questionnaire (non-PF CD, n = 300; CPF without surgery, n = 51; CPF with surgery, n = 52). A high symptom burden was seen across cohorts. More patients with CPF underwent ≥1 CD-related surgery and experienced ≥1 failure of CD-related surgery (79% and 20%) vs non-PF CD (53% and 9%; P < .001). Overall HRQoL outcomes were worse for patients with CPF vs non-PF CD, with significantly worse Short Inflammatory Bowel Disease and 5-dimension EuroQol questionnaire scores for those without PF-related surgery (P < .01). Across all cohorts, 58% of patients reported experiencing fecal incontinence, which had a greater negative impact (higher Revised Faecal Incontinence Scale scores; lower Fecal Incontinence Quality of Life scores) in patients with CPF vs non-PF CD.

Patients with CPF experience substantial HRQoL burden, reflecting the impact of symptoms and medical/surgical interventions. These results may help to inform comprehensive care strategies to improve patient HRQoL.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is becoming increasingly prevalent in Saudi Arabia. However, there is limited data on the characteristics and manifestations of IBD in this population. This study aimed to establish a multi-center database of patients with IBD in the Qassim region of Saudi Arabia to better understand the demographics, prevalence, and manifestations of IBD in this population.

This retrospective study included patients diagnosed with IBD at three healthcare facilities in the Qassim region of Saudi Arabia. The patient's demographic and clinical characteristics, disease location and behavior, age at diagnosis, medication use, related surgeries, and extraintestinal manifestations were recorded based on the Montreal classification. A total of 257 patients with IBD were included in the study, of which 126 had UC and 131 had CD.

Of the 257 patients with IBD, 134 (52.2%) were male and 123 (47.8%) were female. The mean age of patients with CD and UC were 28.74 (range 15-67) and 38.79 (range 15-75) years, respectively. There was a significant difference between all age groups (p < 0.005), with more patients aged over 40 years being diagnosed with UC. UC was most commonly classified as left-sided UC (E2) (60; 47.6%), while the most common location of CD was the ileocolon (L3) (76; 58%). Non-stricturing and non-penetrating CD was the most common behavior (B1) (70; 53.8%). Approximately one-third of the patients with Crohn's disease developed perianal disease (70; 27.2%), with fistulizing Crohn's being the most prevalent manifestation (40; 30.5%), followed by abscess formation (10; 7.6%) and fissures (9; 6.8%). The most common extraintestinal manifestation was arthropathy (15; 5.8%). Significant p-values were detected for UC and CD (p = 0.036).

This study provides crucial insights into the demographics, patterns, and manifestations of IBD in Saudi Arabia. The findings highlight the need for improved diagnosis, management, and treatment strategies for IBD in this population. The establishment of a multi-center database will help to facilitate future research and improve patient care in Saudi Arabia.

We aimed to develop criteria for treatment intensification in patients with (1) luminal Crohn's disease (CD), (2) CD with perianal disease and/or fistula, (3) CD with small bowel stenosis, (4) in the postoperative setting, and (5) for discontinuing or reducing the dose of treatment in patients with CD.

PubMed and Embase were searched for studies published since 1998 which may be relevant to the five defined topics. Results were assessed for relevant studies, with preference given to data from randomized, controlled studies. For each question, a core panel of 12 gastroenterologists defined the treatment target and developed statements, based on the literature, current guidelines, and relevant additional studies. The evidence supporting each statement was graded using the Oxford Centre for Evidence-Based Medicine: Levels of Evidence (March 2009). A modified Delphi process was used to refine statements and gain agreement from 54 Japanese specialists at in-person and online meetings conducted between October 2020 and April 2021.

Seventeen statements were developed for treatment intensification in luminal CD (targeting endoscopic remission), six statements for treatment intensification in perianal/fistulizing CD (targeting healing of perianal lesions and complete closure of the fistula), six statements for treatment intensification in CD with small bowel stenosis (targeting resolution of obstructive symptoms), seven statements for treatment intensification after surgery (targeting endoscopic remission), and five statements for discontinuing or reducing the dose of treatment in patients with CD.

These statements provide guidance on how and when to intensify or de-intensify treatment for a broad spectrum of patients with CD.

Perianal fistulas are defined as pathological connections between the anorectal canal and the perianal skin. Most perianal fistulas are cryptoglandular fistulas, which are thought to originate from infected anal glands. The remainder of the fistulas mainly arises as complications of Crohn's disease (CD), trauma, or as a result of malignancies. Fistulas in CD are considered as a consequence of a chronic and transmural inflammatory process in the distal bowel and can, in some cases, even precede the diagnosis of CD. Although both cryptoglandular and CD-associated fistulas might look similar macroscopically, they differ considerably in their complexity, treatment options, and healing rate. Therefore, it is of crucial importance to differentiate between these two types of fistulas. In this review, the differences between CD-associated and cryptoglandular perianal fistulas in epidemiology, pathogenesis, and clinical management are discussed. Finally, a flow chart is provided for physicians to guide them when dealing with patients displaying their first episode of perianal fistulas.

There are limited real-world data characterizing perianal fistulae in patients with Crohn's disease (CD).

To describe characteristics of patients with CD with and without perianal fistulae.

In this cross-sectional study, characteristics, treatment history, and health outcomes of patients with CD enrolled in the CorEvitas IBD Registry were described according to perianal fistula status (current/previous or none).

Eight hundred and seventy-eight patients were included. Compared with patients with no perianal fistulae (n = 723), patients with current/previous perianal fistulae (n = 155) had longer disease duration since CD diagnosis (mean 16.5 vs 12.3 years; difference 4.3 years; 95% CI, 2.0, 6.6) and fewer had Harvey-Bradshaw Index scores indicative of remission (0-4, 56.8% vs 69.6%; difference - 12.9%; 95% CI, - 21.6, - 4.2). More patients with current/previous fistulae reported a history of IBD-related emergency room visits (67.7% vs 56.1%; difference 11.6%; 95% CI, 3.4, 19.8), hospitalizations (76.1% vs 58.4%; difference 17.7%; 95% CI, 10.1, 25.4), and surgeries (59.4% vs 27.7%; difference 31.7%; 95% CI, 23.3, 40.1), and a history of treatment with tumor necrosis factor inhibitors (81.3% vs 60.7%; difference 20.6%; 95% CI, 13.5, 27.7), immunosuppressants (51.6% vs 31.2%; difference 20.4%; 95% CI, 11.9, 29.0), and antibiotics (50.3% vs 23.7%; difference 26.6%; 95% CI, 18.2, 35.1) than patients without perianal fistulae.

Patients with CD with current/previous perianal fistulae have more symptomatic experiences of disease, higher medication use, hospitalization rates, and emergency room visits than patients without perianal fistulae. Interventions to prevent/reduce risk of developing fistulae may help improve outcomes in CD.

Perianal fistulas are among the most severe complications of Crohn disease, but limited data regarding their outcomes are available in children. Our objective was to determine predictors of perianal fistula healing among pediatric patients newly diagnosed with Crohn disease.

This single-center retrospective study followed patients with perianal fistulas at Crohn disease diagnosis until fistula healing. Time to healing was analyzed using Cox proportional hazard regression models considering relevant covariates including patient demographics, disease characteristics, medical therapies [no anti-tumor necrosis factor (TNF)α therapy, anti-TNFα therapy ±therapeutic drug monitoring], and perianal surgical procedures including fistulotomy, fistulectomy, removal of perianal lesions, seton placement, and incision and drainage.

Of 485 patients identified, 107 (22%) had a perianal fistula at Crohn disease diagnosis. Multivariate analysis identified that perianal fistulotomy, fistulectomy, and lesion removal [hazard ratio (HR) 0.46; P = 0.028], non-White race (HR 0.30, P < 0.01), and male sex (HR 0.42; P = 0.02) were associated with delayed fistula healing. Faster fistula healing was associated with treatment with anti-TNFα with therapeutic drug monitoring (HR 1.78, P = 0.009). There were no other differences in healing by treatment.

Fistulotomy, fistulectomy, and perianal lesion removal as well as non-White race were associated with delayed fistula healing. Anti-TNFα therapy was associated with faster fistula healing when combined with therapeutic drug monitoring, compared to all other medical treatment groups, including anti-TNFα therapy without therapeutic drug monitoring.

Optimal management of inflammatory bowel disease (IBD) relies on a clear understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This article provides concise guidelines for the management of IBD in adults, based on the most up-to-date information at the time of writing and will be regularly updated. These guidelines were developed by the Saudi Ministry of Health in collaboration with the Saudi Gastroenterology Association and the Saudi Society of Clinical Pharmacy. After an extensive literature review, 78 evidence-and expert opinion-based recommendations for diagnosing and treating ulcerative colitis and Crohn's disease in adults were proposed and further refined by a voting process. The consensus guidelines include the finally agreed on statements with their level of evidence covering different aspects of IBD diagnosis and treatment.

Perianal fistulizing disease is a common complication of Crohn's disease (CD), for which new therapies are urgently needed. To assist design of clinical trials for novel therapeutics, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to quantify placebo rates and identify factors influencing them in perianal CD.

We searched MEDLINE, EMBASE and CENTRAL from inception to June 2021. Eligible studies were placebo-controlled trials of pharmacological interventions for perianal CD (pCD). Placebo fistula response and remission rates for induction and maintenance trials were extracted and pooled using a random-effects model. Mixed-effects meta-regression was used to evaluate the impact of patient and study-level characteristics on point estimates.

In 17 RCTs (13 induction, 5 maintenance) the pooled placebo fistula response and remission rate for induction trials was 25% (95% CI 17-36%) and 17% (95% CI 11-25%), respectively. For maintenance trials, the pooled placebo fistula response and remission rate was 23% (95% CI 17-32%) and 19% (95% CI 14-25%), respectively. Trials enrolling patients with less disease activity and a higher proportion with ileal predominant disease were associated with significantly higher placebo response rates. Trials originating in Europe (compared to North America), therapies requiring perianal injection and a longer timepoint to measure remission were associated with higher placebo remission rates.

Placebo response and remission rates in pCD trials are influenced by patient and disease-related factors, as well as the type of intervention being studied. These contemporary rates will inform trial design for novel therapeutics.

Perianal Crohn's disease is associated with decreased quality of life, high morbidity, and high health care use. Treatment goals are to provide infection control, stop fistula drainage, and heal fistula tracts while preserving the anorectal sphincter. Treatment includes a combination of medical and surgical intervention, but new techniques are using interventional endoscopy to act as either a bridge to surgery or to decrease the need for surgical intervention. The decision on which approach to pursue requires knowledge of prior surgery, altered anatomy, prior fistula treatment, and imaging and endoscopic evaluation of fistula complexity, mucosal involvement, and associated stricture or abscess.

Interventional inflammatory bowel disease (IBD) or endoscopic therapy for IBD or IBD surgery-associated complications has emerged as a main treatment modality bridging medical and surgical treatment. It delivers therapy more definitive than medical therapy and less invasive than surgical treatment. The main applications of interventional IBD are strictures, fistulas, abscesses, bleeding, foreign bodies, postoperative complications, and colitis-associated neoplasia. The major endoscopic treatment modalities are balloon dilation, stricturotomy, strictureplasty, fistulotomy, sinusotomy, septectomy, banding ligation, incision and drainage, polypectomy, endoscopic mucosal resection, and endoscopic submucosal dissection.

Standard endosonographic examination of the rectal area is usually performed with radial endoscopic ultrasound (EUS). However, in recent years, widespread availability of linear EUS for assessing various anatomical regions in the gastrointestinal tract has facilitated its use in the assessment of anorectal disorders. Currently, many rectal and anal diseases, including perianal abscesses, fistulae, polyps, and neoplastic lesions, can be well-visualized and evaluated with linear EUS. The aim of this review is to shed light on the anatomy and systematic examination of the anorectal region with linear EUS and clinical implications for different anorectal pathologies.

Management of perianal fistulas differs based on fistula type. We aimed to assess the ability of diagnostic strategies to differentiate between Crohn's disease (CD) and cryptoglandular disease (CGD) in patients with perianal fistulas.

We performed a diagnostic accuracy systematic review and meta-analysis. A systematic search of electronic databases was performed from inception through February 2021 for studies assessing a diagnostic test's ability to distinguish fistula types. We calculated weighted summary estimates with 95% confidence intervals for sensitivity and specificity by bivariate analysis, using fixed effects models when data were available from 2 or more studies. The Quality Assessment of Diagnostic Accuracy Studies tool was used to assess study quality.

Twenty-one studies were identified and included clinical symptoms (2 studies; n=154), magnetic resonance imaging (MRI) characteristics (3 studies; n=296), ultrasound characteristics (7 studies; n=1003), video capsule endoscopy (2 studies; n=44), fecal calprotectin (1 study; n=56), and various biomarkers (8 studies; n=440). MRI and ultrasound characteristics had the most robust data. Rectal inflammation, multiple-branched fistula tracts, and abscesses on pelvic MRI and the Crohn's ultrasound fistula sign, fistula debris, and bifurcated fistulas on pelvic ultrasonography had high specificity (range, 80%-95% vs 89%-96%) but poor sensitivity (range, 17%-37% vs 31%-63%), respectively. Fourteen of 21 studies had risk of bias on at least 1 of the Quality Assessment of Diagnostic Accuracy Studies domains.

Limited high-quality evidence suggest that imaging characteristics may help discriminate CD from CGD in patients with perianal fistulas. Larger, prospective studies are needed to confirm these findings and to evaluate if combining multiple diagnostic tests can improve diagnostic sensitivity.