Additional features including villous atrophy and crypt hyperplasia are the other findings in other Marsh stages of coeliac disease.Antibodies associated with coeliac disease were reported in around 11% of cases. These IgA endomysial antibodies and anti-transglutaminase antibodies are very sensitive and specific for coeliac disease implying that this proportion of duodenal lymphocytosis cases has definite coeliac disease. Around 33% of cases have the HLA-DQ2 allele, which is found in over 90% of people with coeliac disease. Absence of HLA-DQ2 (and the rarer HLA-DQ8) makes coeliac disease most unlikely. As antibody-negative coeliac disease is recognised, HLA status, persistence or progression of the duodenal IEL numbers following a gluten challenge, followed by symptomatic improvement on a gluten-free diet, has been used to be more certain about the diagnosis, which was made in 22% of one series of over 200 adult cases. Helicobacter infection is a common finding at endoscopy and although duodenal IEL counts were found to be slightly higher with this infection, this was not considered to be a meaningful cause in children. Other infections, including Cryptosporidiosis and Giardiasis can also be associated with an increase in IELs. Management
The management is that of any identified associated disorder such as a gluten free diet for cases with coeliac disease or treatment of associated infections. Prognosis
When duodenal lymphocytosis is associated with other features of coeliac disease, in particular positive antibodies, or HLA-DQ2/8 and a family history, treatment with a gluten-free diet produces an improvement in IEL numbers.
It was developed and marketed by Melinta Therapeutics (formerly Rib-X Pharmaceuticals), which subsequently merged with Cempra.Key clinical trials for delafloxacin have been performed by Melinta regarding indications for skin and skin structure infections as well as complicated bacterial infections and uncomplicated gonorrhea. The trial on gonorrhea was terminated before data was released.Delafloxacin was approved by the FDA in June 2017, after it was noninferior to vancomycin plus aztreonam in two trials on 1042 patients with acute bacterial skin and skin structure infection. New Drug Applications (NDA) for delafloxacin (Baxdela) 450 mg tablets and 300 mg injections were approved by the FDA in June 2017.The FDA obligated Melinta to conduct further studies as follows:
a 5-year surveillance study to determine if resistance emerges, with the final report due in December 2022
a study of the IV form in pregnant rats to determine distribution to the reproductive tract, due June 2018, with further studies required if there is significant distribution.Melinta merged with Cempra in August, 2017.Melinta has entered into commercialization and distribution agreements with both Menarini Therapeutics (March 2017) and Eurofarma Laboratórios (January 2015) for international commercialization of delafloxacin. The agreement with Menarini allows them to commercialize and distribute in 68 countries, including Europe, China, and South Korea among others. A similar agreement with Eurofarma allows for commercialization in Brazil. References
External links
"Delafloxacin". Drug Information Portal. U.S. National Library of Medicine. "Delafloxacin meglumine". Drug Information Portal. U.S. National Library of Medicine.