Freddy Caldera

Overlap of Juvenile Polyposis Syndrome and Cowden Syndrome Due to De Novo Chromosome 10 Deletion Involving BMPR1A and PTEN: Implications for Treatment and Surveillance

We describe a patient with a severe juvenile polyposis phenotype, due to a de novo deletion of chromosome 10q22.3‐q24.1. He was initially diagnosed with Juvenile polyposis syndrome (JPS) at age four after presenting with hematochezia due to multiple colonic juvenile polyps. He then re‐presented at 23 years with recurrent hematochezia from juvenile polyps in his ileoanal pouch. He is one of the earliest reported cases of JPS associated with a large deletion of chromosome 10. Since his initial diagnosis of JPS further studies have confirmed an association between JPS and mutations in BMPR1A in chromosome band 10q23.2, which is in close proximity to PTEN. Mutations in PTEN cause Cowden syndrome (CS) and other PTEN hamartoma tumor syndromes. Due to the chromosome 10 deletion involving contiguous portions of BMPR1A and PTEN in our patient, he may be at risk for CS associated cancers and features, in addition to the polyps associated with JPS. This case presents new challenges in developing appropriate surveillance algorithms to account for the risks associated with each syndrome and highlights the importance of longitudinal follow‐up and transitional care between pediatric and adult gastroenterology for patients with hereditary polyposis syndromes.

Reactivation of latent tuberculosis in a Crohn's patient after TB prophylaxis treated with adalimumab.

Reactivation of Latent Tuberculosis in a Crohns Patient After TB Prophylaxis Treated With Adalimumab

Lower Sustained Diphtheria and Pertussis Antibody Concentrations in Inflammatory Bowel Disease Patients

BackgroundPatients with inflammatory bowel disease (IBD) are often immunosuppressed, and those patients receiving anti-tumor necrosis factor α (TNF) therapy can have lower antibody responses to vaccines. Pertussis cases are at their highest levels in the post-vaccine era. There is little data regarding responses to the Tdap (tetanus, diphtheria, and acellular pertussis) vaccine in IBD patients.AimsThe aim of this study was to compare sustained vaccine-induced Tdap antibody concentrations in a cohort of IBD patients stratified by medication regimens with healthy controls (HC) who had received an adult Tdap booster.MethodsWe performed a cross-sectional study evaluating antibody responses to Tdap vaccine among IBD patients compared to HC. Our study consisted of three patient groups: adults with IBD stratified by maintenance medication regimen: (1) thiopurine monotherapy; (2) anti-TNF monotherapy; and (3) combination therapy (anti-TNF and immunomodulator (thiopurine or methotrexate)).ResultsNinety IBD patients and 20 HC participated. Pertussis pertactin antibody concentrations were significantly lower in IBD patients (p = 0.021) compared to HC, and those on anti-TNF agents (monotherapy or combination) had lower antibody concentrations compared to those on thiopurine monotherapy (p = 0.028). Diphtheria antibody concentrations were also lower in IBD patients (p < 0.001), and those on anti-TNF agents (monotherapy or combination) had lower antibody concentrations compared to the thiopurine monotherapy group (p < 0.001).ConclusionIBD patients on anti-TNF agents had lower antibody concentrations to diphtheria and pertussis. These findings suggest a need for different Tdap booster schedules for IBD patients on anti-TNF therapy.Clinical Trials Registry NCT02434133.

Infliximab Therapy for Corticosteroid-Resistant Ipilimumab-Induced Colitis.

A 56 year old man presenting with stage III melanoma was treated with ipilimumab therapy. After his second cycle of ipilimumab he developed severe abdominal cramping and non-bloody diarrhea. Colonoscopy revealed diffuse moderate inflammation (erosions, erythema, granularity, loss of vascularity) from transverse colon to the rectum (Fig. 1). Biopsy results revealed colonic mucosa with patchy, lymphoplasmacytic infiltrate within the lamina propria, cryptitis, apoptotic bodies, and damaged surface epithelium (Fig. 2). He was treated with intravenous corticosteroids followed by prednisone 60 mg daily for ipilimumab-induced colitis. His symptoms persisted; therefore a single dose of infliximab 5 mg/ kg was given. He clinically responded to infliximab and was able to be tapered off prednisone. Ipilimumab is an anticytotoxic T-lymphocyte antigen-4 antibody, FDA approved for unresectable or metastatic melanoma. Ipilimumab-induced colitis is well recognized and can present 5-10 weeks after an infusion. Presenting symptoms include diarrhea, abdominal pain, hematochezia, ileus, and bowel perforation. In patients in whom disease proves steroid refractory, treatment with infliximab is recommended [1]. Ipilimumab activates T cells and the production of cytokines; infliximab counters this by suppression of cytokines interleukin 1 and 6. In patients in whom symptoms resolve after infliximab, steroids IMAGE OF THE ISSUE

Reactivation of Latent Tuberculosis After Treatment With Biologic Therapy: P-1 YI

Anti-tumor necrosis factor (TNF) therapy is associated with increased infectious risk including reactivation of latent tuberculosis infection (LTBI). It is recommended that patients with risk factors for tuberculosis (TB) be evaluated for LTBI prior to initiation of anti-TNF therapy. Patients with evidence of LTBI undergo treatment before initiation of biologic therapy. The risk of disseminated TB after treatment and initiation of biologic therapy is not well characterized in patients with inflammatory bowel disease. We present a patient who developed disseminated TB as a complication of anti-TNF therapy after completing appropriate treatment for LTBI Case Report: A 52 yo Sri Lankan male with clinical and pathologic evidence of Crohn colitis is found to have asymptomatic LTBI. Treatment with isoniazid (INH) was initiated. After 6 weeks of therapy he was started on infliximab. The patient had a good initial response to therapy but required intermittent prednisone for control of his symptoms. After a viral URI, infliximab was discontinued and not restarted. He completed a 9-month course of INH and was feeling well on no anti-TB treatment. The patients Crohn disease flared and he was initiated on adalimumab after a colonoscopy confirmed active disease. Three months after adalimumab initiation and 4 months after completion of INH for LTBI he had a febrile illness, diarrhea and weight loss. A CT abdomen/pelvis was obtained and showed multiple lesions throughout the spleen and liver. The adalimumab was stopped and he was admitted to hospital for further work-up. After an extensive work-up including evaluation for fungal etiologies and a spleen biopsy he was initiated on empiric anti-TB treatment. After several weeks the AFB smear from both sputum and spleen were positive for pan-susceptible TB. While undergoing treatment for active TB he has been maintained on mesalamine based therapy with marginal control of his Crohn disease. Discussion: Prior to initiation of anti-TNF treatment patients with IBD should be evaluated for active and latent TB1. The risk of disseminated TB after treatment for LTBI and initiation of biologic therapy is unknown. If evidence of LTBI is found, treatment is recommended prior to starting biologic therapy2,3. Recommendations from the ATS and BTS vary from 1-9 months of treatment prior to starting anti-TNF therapy, even though chemoprophylaxis is only effective 70% of the time after 9 months. 4,5 We present the case of a patient with Crohn disease, found to have LTBI and initiated on therapy. After completion of LTBI treatment anti-TNF therapy was instituted. He became ill and was admitted to hospital where he was found to have disseminated TB. Though this patients TB presented after completion of therapy for LTBI most cases of disseminated TB are discovered early in the treatment course of anti-TNF therapy. Close monitoring for reactivation is warranted even if patients have undergone treatment, since treatment is not always effective. We present a case report of a patient with Crohn disease and treated LTBI who developed disseminated disease after completion of treatment and initiation of a biologic agent.

Methotrexate Reduces DNA Integrity in Sperm From Men With Inflammatory Bowel Disease

There are few data on the effects of methotrexate on reproductive capacity in men with inflammatory bowel diseases (IBDs). We performed a case-control study to determine the effects of methotrexate on sperm quality and genetic integrity. We compared sperm samples from 7 men with IBD who had been exposed to methotrexate for at least 3 months with sperm samples collected from 1912 age-matched men at fertility centers (controls) where sperm parameters would be expected to be worse than those of the general population. Sperm were evaluated by basic semen analysis and advanced sperm integrity testing. In samples from men with IBD, all basic semen analysis parameters were within normal limits. However, these samples had reduced sperm integrity, based on significant increases in levels of DNA fragmentation and damage from oxidative stress compared with controls. Our findings indicate that methotrexate can reduce DNA integrity in sperm and cause damage via oxidative stress.

Symptomatic Microscopic Colitis Atop Quiescent Inflammatory Bowel Disease: A Case Series

Microscopic colitis (MC) has rarely been described to be the cause of watery diarrhea in those with established inflammatory bowel disease (IBD), and instead has been presented as a herald syndrome to eventual IBD or incidentally found in asymptomatic IBD patients. We report a case series of 7 patients with IBD who presented with a watery diarrheal exacerbation due to new-onset MC. We propose that new-onset MC should be considered in the differential diagnosis of watery diarrhea occurring in patients with long-standing IBD and that evaluation should include colonoscopy with biopsies obtained throughout the colon.

Comparing guideline-based care quality for inflammatory bowel disease and rheumatoid arthritis patients within a medical home

ABSTRACT Background: Rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) patient populations face similar risks of chronic immunosuppression including corticosteroid use. We compared the receipt of preventive services between IBD and RA populations according to published quality metrics. Methods: We defined a single-center cohort of patients with IBD or RA receiving specialty and primary care. Electronic health record abstraction assessed quality metrics, sociodemographics, comorbidity, and utilization. Comparisons used multivariate odds ratios and Student’s t-tests. Results: 218 RA and 190 IBD patients were included. In multivariate analysis, IBD patients were less likely to receive pneumococcal vaccination (OR=0.29, 95% CI: 0.11-0.85), while RA patients underwent glucocorticoid-induced osteoporosis screening more often (100% vs. 82.5%, p = 0.023). Conclusions: Gastroenterologists can improve care quality for IBD patients by assuming greater responsibility for preventive care in IBD patients and/or collaborating with primary care and health systems to improve preventive care delivery.