Juvenile Idiopathic Arthritis With Associated Inflammatory Bowel Disease and CARD8 Mutation.

Juvenile idiopathic arthritis is a common chronic childhood disease, with a prevalence of ∼1 per 1000 children. Arthritis can also be a manifestation of other inflammatory conditions, such as inflammatory bowel disease (IBD). Studies suggest a genetic influence in IBD, including mutations in CARD8. CARD8 is a negative regulator of the NLRP3 inflammasome, and mutations in this gene are hypothesized to induce gastrointestinal inflammation. However, few studies have evaluated this association and most have included a limited number of patients. We present a case of a pediatric patient with IBD-associated arthritis and a CARD8 mutation. Our patient is a 7-year-old female who was initially evaluated by rheumatology for right leg pain and an intermittent rash. She had clinically active arthritis on exam and was started on methotrexate with only slight improvement. Additional workup revealed sacroiliitis by imaging, elevated inflammatory markers, no anemia, and a variant of unknown significance in CARD8. Adalimumab was recommended but before medication initiation, our patient's symptoms progressed to worsening joint pain, fatigue, fevers, nausea, vomiting, diarrhea, and hematochezia. Infectious testing was negative. Fecal calprotectin was >8000 µg/g. A colonoscopy revealed IBD most consistent with Crohn's disease. Adalimumab was ultimately added, and she has responded well to combination therapy. This case report highlights the association between CARD8 mutations and IBD, especially in the setting of IBD-associated arthritis.

Relations between disease status and body composition in pediatric inflammatory bowel disease.

To evaluate the effect of remission status on physical activity and body composition in pediatric patients with inflammatory bowel disease (PIBD) and healthy peers. Single-center cohort study, including 54 PIBD patients and 33 healthy peers. During the initial study visit, a brief demographic questionnaire, physical activity questionnaire completed by participants, and instructions on recording dietary intake were given. Physicians completed the Physician Global Assessment (PGA) for disease severity. Medical chart abstraction was done to obtain disease variables of interest. DEXA scan completed 1 week later to obtain information on body composition. Variables of interest were compared between the three groups (IBD-Remission, IBD-Active, and healthy controls) using an ANOVA or Chi-square test as appropriate. IBD patients were older than controls, reported lower quality of life (73.9 vs. 80.9), and engaged in less MVPA (195.4 versus 361.1). The IBD-Active group had a significantly lower lean body mass, bone mineral density, and time spent in MVPA compared to the IBD-Remission group and healthy controls. IBD-Remission group had a significantly lower percentage of biologic use (55% vs. 87%) and comorbidities (26% vs. 44%) compared to IBD-active group. IBD-remission group also had a lower fat mass percentage. In this study, we report significantly favorable LBM, BMD, and time spent in MVPA in patients with IBD in remission compared to those not in remission with the former demonstrating a body composition resembling that of healthy peers.Conclusion: While an improvement in BMD was observed with remission, the scores were still lower than controls. What is Known: • Body composition deficits in pediatric inflammatory bowel disease are common and some persist despite achievement of remission leading to long term outcomes including osteopenia and osteoporosis. • Weight restoration in patients with pediatric IBD is primarily explained by gains in fat mass without similar gains in lean mass. What is New: • While an improvement in bone mineral density was observed, the achievement of remission significantly improves affects physical activity and body composition in pediatric inflammatory bowel disease. • However, some parameters of body composition do not reach levels comparable to healthy peers.

Conceptual Model of Lean Body Mass in Pediatric Inflammatory Bowel Disease.

Youth with inflammatory bowel disease (IBD) demonstrate deficits in lean mass (LM) placing them at increased risk for future health problems, including reduction of bone mass and impaired bone architecture. Research suggests that deficits in LM are multifactorial, including influences from the disease and its treatment, and health behaviors such as diet and physical activity. Based on a systematic literature review examining factors related to LM deficits in IBD, this article presents a conceptual model to explain the development of LM in youth with IBD. The model considers predictors of LM across 4 domains: demographic; medical; diet; and physical activity. Much existing research is cross-sectional, but suggests multiple factors work together to promote or inhibit LM accrual in youth with IBD. The conceptual model, developed based on empirical findings to date, can be used to understand and further elucidate the process through which LM is developed and maintained, to inform the development of empirically supported clinical interventions, and to guide future research objectives and priorities.

Cryptosporidial infection in children with inflammatory bowel disease.

BACKGROUND AND AIMS: Cryptosporidiosis is usually a self-limiting illness in healthy patients. However, it can cause severe life threatening complications in immunocompromised patients. The effect of cryptosporidial infection on inflammatory bowel disease (IBD) has not been well studied and available literature is largely restricted to adult case reports. The purpose of this study is to describe the clinical characteristics of cryptosporidial infection in children with IBD. METHODS: Stool studies from children with IBD presenting with presumed relapse during the period 2005-2011 were reviewed retrospectively. Cryptosporidial infection was diagnosed by stool enzyme immunoassay. An age matched control group of IBD patients without cryptosporidial infection was used for comparison. RESULTS: Medical records of 170 IBD patients were reviewed and a total of 149 presumed relapses were identified. Cryptosporidial infection was found in seven of the 39 patients with positive stool studies (four ulcerative colitis/three Crohn's disease) presenting with relapse. The median age was 13 years (range: 3-17) and five patients were female. The median duration of the IBD was 18 months (range 2-48 months). All but one patient had stable disease prior to acquiring infection. Five patients required hospitalization due to significant dehydration. Three of the five patients treated with nitazoxanide had significant clinical improvement in 3 days. All patients had complete resolution of symptoms by three weeks and no infection related complications were noted. In comparison to patients with cryptosporidial infection, the control group required an increased need for escalation of therapy (71% vs. 0.0%, p=001) and higher re-hospitalization rates (24% Vs.0.0%, p=0.54) within 6 months following indexed relapse. CONCLUSION: In IBD patients, cryptosporidiosis can cause significant illness leading to increased need for hospitalization. In the absence of appropriate stool studies, cryptosporidiosis can be misdiagnosed as disease relapse and lead to inappropriate therapy. Nitazoxanide appears to be effective along with supportive therapy.

Mycophenolate mofetil-related enterocolitis and weight loss: a pediatric case series.

Mycophenolate mofetil (MMF) is an immunosuppressive medication utilized in the management of both autoimmune and solid organ transplant patients. Diarrhea is a common gastrointestinal side effect of MMF, but more severe forms of GI symptoms are described in renal transplant patients with a distinct pattern of histopathologic change, similar to graft-versus-host disease or Crohn's disease. This rare entity, commonly referred to as "MMF-related enterocolitis," has been described in adult patients, mostly in renal transplant patients, and in only two pediatric renal transplant patients. In previously reported cases, symptoms and abnormal histopathology improve with dose reduction of MMF. We describe a series of three pediatric patients with varied underlying disease process who presented with severe diarrhea and histopathologic findings characteristic of MMF-related enterocolitis, who share a novel finding of weight loss as a complication of MMF-related enterocolitis in pediatric patients.