Strategic use of levofolinic acid for methotrexate-induced side effects in juvenile idiopathic arthritis: a prospective observational study

Objective: To evaluate the efficacy of levofolinic acid (LVF) administered 48 h before methotrexate (MTX) in reducing gastrointestinal side effects without interference with drug efficacy. Methods: A prospective observational study was performed including patients with Juvenile Idiopathic Arthritis (JIA) reporting significant gastrointestinal discomfort after MTX despite taking a dose of LVF 48 h after MTX. Patients with anticipatory symptoms were excluded. A LVF supplemental dose was added 48 h before MTX and patients were followed every 3–4 months. At each visit data on gastrointestinal symptoms, disease activity (JADAS, ESR, CRP values) and treatment changes were collected. Friedman test for repeated measures analyzed differences between these variables over time. Results: Twenty-one patients were recruited and followed for at least 12 months. All patients received MTX subcutaneously (mean 9.54 mg/m2) and LVF 48 h before and after MTX (mean 6.5 mg/dose), 7 received a biological agent too. Complete remission of gastrointestinal side effects was reported in 61.9% of study patients at first visit (T1) and increased over time (85.7%, 95.2%, 85.7% and 100% at T2, T3, T4, T5, respectively). MTX efficacy was maintained as showed by significant reduction of JADAS and CRP (p = 0.006 and 0.008) from T1 to T4 and it was withdrawn for remission in 7/21. Conclusions: LVF given 48 h before MTX significantly reduced gastrointestinal side effects and did not reduce drug’s efficacy. Our results suggest that this strategy may improve compliance and quality of life in patients with JIA and other rheumatic diseases treated with MTX

Sacro-Caudal Dysgenesis in Two Boxer Dogs: Clinical Presentation, Diagnostic Investigations and Outcome

Two female Boxer dogs from the same litter were presented at 2-months of age for urinary and fecal incontinence. Both dogs had an abnormal tail consisting of a small stump, an atonic anal sphincter and absent perineal reflex and sensation. Electrodiagnostic evaluation showed suspect neurotmesis of pudendal nerves. Radiology and CT scan of the spine displayed similar findings in both dogs: 6 lumbar vertebrae followed by a lumbosacral transitional vertebra, lacking a complete spinous process, and a hypoplastic vertebra carrying two hypoplastic sacral transverse processes as the only remnant of the sacral bone; caudal vertebrae were absent. At MRI, one dog had a dural sac occupying the entire spinal canal and ending in a subfascial fat structure. In the other dog, the dural sac finished in an extracanalar, subfascial, well-defined cystic structure, caudal to the spine and likely communicating with the subarachnoid space, consistent with meningocele. The owners declined surgical treatment. During the 18-months follow-up, the dogs did not show changes in clinical signs except for recurrent cystitis. Sacro-caudal dysgenesis is a malformation of the sacrum, caudal vertebrae and the corresponding spinal cord segments. Similar findings are described in humans in the Currarino syndrome, characterized by a triad of congenital anomalies that are not consistently present together: anorectal malformations, sacrococcygeal osseous defects, and various types of presacral masses (meningocele, enteric cysts or teratomas). To the Authors’ knowledge, this is the first report describing sacro-caudal dysgenesis in dogs. Investigations are underway to identify the genetic basis of this condition