Can vulvar edema be the presenting sign of Crohn's disease? A case series.

Vulvar involvement as an extraintestinal manifestation of Crohn's disease (CD) is a challenging diagnosis considering that vaginal findings may precede gastrointestinal symptoms. The aim of this study is to describe the clinical presentation, radiological findings, and treatment of vulvar Crohn's disease (VCD). We reviewed the time from initial presentation to diagnosis, presenting symptoms, radiological findings, gastrointestinal Crohn's disease Paris classification, and treatment response of five female pediatric patients. All the patients had radiological findings of vulvar inflammation on magnetic resonance imaging. Vaginal symptoms preceded gastrointestinal disease in two of the patients, which correlated with a delay in diagnosis. All patients had active disease on colonoscopy, with three of them having significant colorectal inflammation. Four of the patients were treated with infliximab, while one patient received ustekinumab with a resolution of their symptoms. In conclusion, VCD can precede gastrointestinal symptoms and is easily miss-diagnosed, leading to a delayed Crohn's disease diagnosis and treatment.

Thalidomide use and outcomes in pediatric patients with Crohn disease refractory to infliximab and adalimumab.

OBJECTIVE: The aim of the study was to evaluate thalidomide as rescue therapy for pediatric patients with severe refractory Crohn disease (CD) who failed to respond to antitumor necrosis factor (TNF) biologic agents. PATIENTS AND METHODS: A computerized database was used to identify children with CD who had failed conventional immunosuppression therapy and received thalidomide rescue therapy. Twelve patients, mean age at diagnosis 10 years, were identified. Eight children had disease localized to the ileum and colon and 4 to the gastroduodenal area and colon. Five cases were complicated by strictures and 7 by fistulae. Previous drug therapy included azathioprine/6-mercaptopurine (11/12), methotrexate (7/12), and anti-TNF biologics (12/12). Outcome measures were Harvey-Bradshaw Index, change in prednisone dose, hospitalizations, bowel resections, and incision and drainage procedures. Laboratory evaluations were calculated before and after 1 to 6 months of thalidomide. RESULTS: Mean Harvey-Bradshaw Index score improved from 11.8 to 3.9 (P = 0.0004), mean prednisone dose decreased from 13.9 to 2.3  mg/day (P = 0.001), mean number of hospitalizations decreased from 6.3 to 1.3 (P = 0.002), and erythrocyte sedimentation rate decreased from 35 to 14  mm/h (P = 0.02). The surgery rate pre-thalidomide was 0.031 and on thalidomide was 0.004. Of the 7 patients with fistulae, 5 had complete fistula closure, 1 had partial closure, and 1 showed no improvement. Adverse reactions that resulted in discontinuation of thalidomide are as follows: 42% peripheral neuropathy, 17% worsening of the CD, 8% dizziness, and 8% allergic reaction. All 5 patients who developed peripheral neuropathy had clinical resolution of the neurologic symptoms within 2 to 3 months after stopping thalidomide. CONCLUSIONS: Thalidomide is a potentially effective rescue therapy for severe refractory CD in children who fail to respond to anti-TNF medications.

Hypersensitivity Reaction to Ustekinumab in Pediatric and Young Adult Inflammatory Bowel Disease Patients: A Case Series.

Ustekinumab (UST) is a human IgG1K monoclonal antibody that binds to the p40 receptor subunit bound by cytokines IL-12 and IL-23. It is indicated in both Crohn's disease and ulcerative colitis as a second-line agent. The safety and efficacy of UST in children and young adults has not been thoroughly studied. We report a case series of six pediatric patients and young adults who developed hypersensitivity reactions during intravenous infusion with UST. These reactions ranged from mild allergic reactions to anaphylaxis, with no detectable antibodies if tested. We hypothesize the reaction could be secondary to ethylenediaminetetraacetic acid, which is present solely in the intravenous preparation. Patients who experience hypersensitivity reactions during their UST infusion may safely receive subcutaneous preparations of UST, as demonstrated by some patients who received it based on physician discretion. Further investigation is required to establish the etiology of infusion reactions.

Very Early-Onset Inflammatory Bowel Disease (VEO-IBD) Presenting with Recurrent Leukocytoclastic Vasculitis Preceded by Streptococcal Pharyngitis.

Inflammatory bowel disease (IBD) that presents in children <6 years of age is known as very early-onset IBD (VEO-IBD). Extraintestinal manifestations in IBD, such as erythema nodosum (EN), pyoderma gangrenosum (PG), and, less likely, leukocytoclastic vasculitis (LV), are more commonly present in Crohn's disease. Association between LV and ulcerative colitis (UC) is not commonly seen. We report a case of a 6-year-old female with a VEO-IBD UC phenotype presenting with multiple episodes of leukocytoclastic vasculitis, each preceded by streptococcal pharyngitis. Prior to the diagnosis of VEO-IBD, a skin biopsy was obtained and had shown leukocytoclastic vasculitis with a negative IgA stain. Initial laboratory results were remarkable for leukocytosis and increased anti-strep O and anti-DNase B titers. Gastrointestinal panel PCR demonstrated Clostridium difficile toxin A/B. Treatment for LV consisted of methylprednisolone IV 20 mg for four days with a weaning schedule of prednisolone for two weeks and naproxen 250 mg BID for three days. Clostridium difficile was treated with metronidazole 250 mg TID for ten days. She remained stable for three years until she presented with continuous bloody stools, newly onset chest pain, and shortness of breath. Computed tomography angiogram (CTA) was normal. Stool calprotectin was elevated at 658 mcg/gm. Abdominal magnetic resonance enterography (MRE), esophagogastroduodenoscopy, and colonoscopy confirmed a VEO-IBD ulcerative colitis phenotype. She was started on infliximab 10 mg/kg every four weeks after infliximab titers, and antibodies were obtained. Currently, the patient remains on clinical and biochemical remission, with no recent LV episodes or recurrence of streptococcal pharyngitis. Our patient is unique as no case report has been published with multiple episodes of leukocytoclastic vasculitis in association with a VEO-IBD UC phenotype.

Antitumor Necrosis Factor-Alpha (TNF-α) Infliximab-Induced Pleural Effusion and Pericarditis in Crohn's Disease.

Crohn's disease (CD) is a chronic inflammatory disease that can be associated with intestinal and extraintestinal manifestations. Some patients are treated with infliximab, an antitumor necrosis factor-alpha (TNF-α) agent, to help them achieve and maintain clinical and biochemical remission. However, some patients with CD can present severe adverse effects such as drug-induced lupus and rarely present with pleural space and pericardium involvement. We report a case of an 18-year-old Hispanic male with CD who acquired anti-TNF-α-induced lupus after infliximab therapy presenting with pleural effusion and pericarditis. The patient presented with a 2-week history of pleuritic chest pain. Initial laboratory workup was remarkable for leukocytosis and increased inflammatory markers. Imaging and cardiovascular studies were consistent with pericarditis and pleural effusions. Serositis was initially thought to be reactive secondary to the current Mycoplasma pneumoniae infection. He was treated with colchicine 0.6 mg PO TID for six weeks and azithromycin 500 mg PO for seven days. Pain improved after discharge but resurfaced on the day of infliximab infusion. Imaging and cardiovascular studies demonstrated the persistence of pleural effusions and pericarditis. Ultrasound-guided thoracentesis was consistent with exudative pleural effusions. Rheumatological workup was remarkable for increased antihistone antibodies, consistent with drug-induced lupus. Infliximab-induced pericarditis and pleural effusions are rarely reported in the literature. It is thought that infliximab may have a proinflammatory activity or have a delayed type III hypersensitivity reaction. The first line of therapy of anti-TNF-α-induced lupus is the withdrawal of the offending drug. Our patient is unique as few cases of anti-TNF-α-induced pleural effusion and pericarditis in CD are reported. After discontinuing the offending drug, ustekinumab was started, and maintaining a steroid and colchicine regimen, the patient's chest pain improved. Antihistone antibodies have returned to normal one month after starting ustekinumab.