A novel inflammatory bowel disease phenotype, named UC2CD, was recently described and is characterized by the transformation from ulcerative colitis (UC) to the Crohn’s disease (CD) phenotype, with distinct clinical, serologic, and genetic features. In our case series, we describe the clinical characteristics of 8 patients presenting with this new phenotype, treated at the Inflammatory Bowel Disease Clinic of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ).
Recientemente se describió un nuevo fenotipo de la Enfermedad Inflamatoria intestinal denominada UC2CD (por sus siglas en inglés), caracterizada por la transformación de la Colitis Ulcerosa Crónica Idiopática (CUCI) hacía fenotipo de la Enfermedad de Crohn (EC), identificando características clínicas, serológicas y genéticas especiales. Se reporta una serie de 8 pacientes con este nuevo fenotipo atendidos en la Clínica de Enfermedad Inflamatoria Intestinal del Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ) en donde describimos las características clínicas de dichos pacientes.
Inflammatory bowel disease (IBD) is a diagnostic challenge, given that there are no isolated clinical, biochemical, imaging, endoscopic, or histopathologic data that confirm the condition.1,2 There are 2 well-described primary phenotypes of IBD: Crohn’s disease (CD) and ulcerative colitis (UC), each with different clinical characteristics.3 When a subtype of the disease cannot be classified, it is called unclassified IBD, and when there is a colectomy specimen and data of UC and CD overlap, it is known as indeterminate colitis.1 In this case series, we present a novel IBD phenotype recently proposed by Li et al., known as ulcerative colitis to Crohn’s disease (UC2CD), corresponding to patients initially diagnosed with UC who then develop characteristics of CD.4
Materials and methodsDemographic and clinical characteristics were collected from the clinical records of patients identified with this new phenotype, within the time frame of 2017 to the present, who were treated at the Inflammatory Bowel Disease Clinic of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán.
ResultsEight patients presented with this novel IBD phenotype, characterized by having an initial diagnosis of UC that later was consistent with CD. The 8 patients were 6 women and 2 men. Five of the 8 patients were diagnosed with UC before reaching 40 years of age and 7 of the 8 patients lived in urban zones. Regarding disease characteristics, all the cases presented with pancolitis (E3), with a 5 to 29-year range of progression for transforming to CD. Three of the 8 patients presented with a fistulizing phenotype. Four of the 8 patients had extraintestinal manifestations (EIMs), such as arthralgias, spondyloarthritis, osteopenia, and osteoporosis, one in each patient, respectively. Table 1 describes the medical treatment. Of the 8 patients, initial or baseline treatment was conventional in 6 of them and only 2 received adalimumab. After the transformation to CD, 4 of the 8 patients were treated with biologic therapy, 2 with adalimumab, and 2 with ustekinumab. These last 2 were refractory cases before the transformation.
Demographic, clinical, biochemical, and radiologic characteristics of the Mexican patients with UC2CD.
| Case | Sex | Age at DX (years) | Age at transf (years) | Disease duration | TX before transf | Globulins before transf g/dL | ESR before transf mm/h | TX after transf | Globulins after transf g/dl | ESR after transf mm/h | Radiologic findings |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | F | 22 | 43 | 21 | MSZ + AZA | 3.1 | 7 | MSZ + AZA | 2.4 | 3 | Stricture in the distal and terminal ileum |
| 2 | M | 23 | 28 | 5 | MSZ + enemas + prednisone | 3.1 | 3 | MTX + suppositories | 2.76 | 3 | Stricture in the terminal ileum |
| 3 | F | 39 | 49 | 10 | MSZ + suppositories | 3.68 | 37 | MTZ + enemas | 3.65 | 33 | Entero-enteric fistulas + stricture in the distal ileum |
| 4 | M | 28 | 57 | 26 | Ciprofloxacin | 3.1 | 8 | ADA + sulfasalazine + MTX | 4.65 | 27 | Perianal fistulas + stricture in the distal ileum |
| 5 | F | 45 | 62 | 17 | ADA | 3.43 | 3 | USTE + sulfasalazine | 2.84 | 36 | Stricture in the terminal ileum |
| 6 | F | 14 | 40 | 29 | ADA | 3.81 | 3 | USTE | 3.39 | 3 | Perianal fistulas + stricture in the terminal ileum |
| 7 | F | 40 | 57 | 18 | MSZ + AZA + enemas + suppositories | 3.05 | 3 | ADA + AZA + MSZ | 3.61 | 19 | Rectovaginal and transsphincteric fistulas |
| 8 | F | 42 | 53 | 11 | Sulfasalazine | 2.24 | 10 | MTX | 4.25 | 12 | Not performed |
ADA: adalimumab; AZA: azathioprine; DX: diagnosis; ESR: erythrocyte sedimentation rate; F: female; M: male; MSZ: mesalazine; MTX: methotrexate; transf: transformation; TX: treatment; USTE: ustekinumab.
Surgical treatment was required in 6 of the 8 patients. Proctocolectomy was performed on 5 patients and subtotal colectomy on one patient; 5 cases required surgery due to medical treatment refractoriness, and one patient because of perforation.
DiscussionIn their study, Li et al. proposed the novel phenotype, UC2CD, highlighting the description of a new IBD subtype with typical clinical and serologic characteristics, as well as refractoriness to tumor necrosis factor-alpha (TNF-α) biologic therapy and a greater risk for presenting with EIMs. They also proposed a predictive model based on globulins, erythrocyte sedimentation rate, OmpC, ASCA-IgA, and CBir-1.4
Notably, in our clinical practice in Mexico, measurement of serologic markers focused on microbial antibodies is limited, with only globulins and erythrocyte sedimentation rate determined routinely. In our study, 7 of the 8 patients had globulin levels above 2.5 g/dL, according to the cutoff point proposed by Li et al. and only one patient had an erythrocyte sedimentation rate above 30 mm/h before the transformation.
Coinciding with the study by Li et al., we observed that, indeed, patients were anti-TNF-α-refractory and required surgical treatment, as well as having globulin levels above 2.5 mg/dL. Fifty percent of our patients presented with EIMs, which is in the upper limit of prevalence of EIMs reported in the literature.5,6
In conclusion, our case series provides relevant characteristics for this new IBD phenotype, called UC2CD, such as early age below 40 years at diagnosis, the presence of pancolitis, EIMs, elevated globulin levels, medical and anti-TNF treatment refractoriness, and the need for surgical treatment. More studies with a larger number of patients are necessary for appropriately characterizing this new phenotype.
Ethical considerationsNo patient data were used and so obtaining informed consent was not necessary. Likewise, because no intervention or maneuver was performed and data were not managed, the study was considered low-risk and required no review or approval by the local ethics committee. Even so, it meets the current research regulations, preserving the confidentiality of personal identification data and guaranteeing participant anonymity (all were healthcare workers who participated voluntarily).
Financial disclosureNo financial support was received in relation to this article.
The authors declare that there is no conflict of interest.
