ABSTRACT
COVID-19 is to date a global pandemic that can affect all age groups; gastrointestinal symptoms are quite common in patients with COVID-19 and a new clinical entity defined as Multisystem Inflammatory Syndrome in Children (MIS-C) has been described in children and adolescents previously affected by COVID-19. Presenting symptoms of this new disease include high fever and severe abdominal pain that can mimic more common causes of abdominal pain; patients can rapidly deteriorate presenting severe cardiac dysfunction and multiorgan failure. Some fatalities due to this serious illness have been reported. We describe the case of a ten-year-old patient presenting with persistent high fever associated with continuous and worsening abdominal pain. Various hypotheses were performed during his diagnostic workup and an initial appendectomy was performed in the suspect of acute appendicitis. As his clinical picture deteriorated, the child was subsequently diagnosed and successfully treated as a case of MIS-C. The objective of this case report and brief review of abdominal pain in children throughout the age groups is to provide the emergency pediatrician with updated suggestions in diagnosing abdominal pain in children during the COVID-19 pandemic.
Subject(s)
Abdominal Pain/etiology , COVID-19/complications , Pediatric Emergency Medicine/statistics & numerical data , Systemic Inflammatory Response Syndrome/diagnosis , Abdominal Pain/diagnosis , Acute Disease , Appendectomy/methods , Appendicitis/diagnosis , Appendicitis/surgery , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/pathology , COVID-19/therapy , COVID-19/virology , Combined Modality Therapy , Conjunctivitis/etiology , Dyspnea/diagnosis , Dyspnea/therapy , Fever/diagnosis , Fever/etiology , Humans , Immunoglobulins, Intravenous/administration & dosage , Immunoglobulins, Intravenous/therapeutic use , Male , Mucositis/etiology , Oxygen/therapeutic use , Pediatric Emergency Medicine/trends , Platelet Aggregation Inhibitors/therapeutic use , SARS-CoV-2/genetics , Steroids/therapeutic use , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/pathology , Systemic Inflammatory Response Syndrome/therapy , Treatment OutcomeABSTRACT
Vaginal ulcers can be associated with a number of different diseases. We describe two girls who presented genital ulcers as a persistent symptom of PFAPA (periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis) syndrome. The possibility of considering this clinical manifestation as a clue for the diagnosis of PFAPA is discussed.
Subject(s)
Fever/diagnosis , Lymphadenitis/diagnosis , Pharyngitis/diagnosis , Skin Ulcer/etiology , Stomatitis, Aphthous/diagnosis , Tonsillitis/diagnosis , Vulvar Diseases/etiology , Adolescent , Female , Humans , SyndromeABSTRACT
Collagenase-3 mRNA is initially detectable when osteoblasts cease proliferation, increasing during differentiation and mineralization. We showed that this developmental expression is due to an increase in collagenase-3 gene transcription. Mutation of either the activator protein-1 or the runt domain binding site decreased collagenase-3 promoter activity, demonstrating that these sites are responsible for collagenase-3 gene transcription. The activator protein-1 and runt domain binding sites bind members of the activator protein-1 and core-binding factor family of transcription factors, respectively. We identified core-binding factor a1 binding to the runt domain binding site and JunD in addition to a Fos-related antigen binding to the activator protein-1 site. Overexpression of both c-Fos and c-Jun in osteoblasts or core-binding factor a1 increased collagenase-3 promoter activity. Furthermore, overexpression of c-Fos, c-Jun, and core-binding factor a1 synergistically increased collagenase-3 promoter activity. Mutation of either the activator protein-1 or the runt domain binding site resulted in the inability of c-Fos and c-Jun or core-binding factor a1 to increase collagenase-3 promoter activity, suggesting that there is cooperative interaction between the sites and the proteins. Overexpression of Fra-2 and JunD repressed core-binding factor a1-induced collagenase-3 promoter activity. Our results suggest that members of the activator protein-1 and core-binding factor families, binding to the activator protein-1 and runt domain binding sites are responsible for the developmental regulation of collagenase-3 gene expression in osteoblasts.
Subject(s)
Collagenases/genetics , DNA-Binding Proteins/metabolism , Gene Expression Regulation, Developmental , Gene Expression Regulation, Enzymologic , Osteoblasts/enzymology , RNA, Messenger/genetics , Transcription Factor AP-1/metabolism , Animals , Base Sequence , Binding Sites , Cell Differentiation , DNA Primers , Drosophila Proteins , Matrix Metalloproteinase 13 , Nuclear Proteins , Osteoblasts/cytology , Promoter Regions, Genetic , Proto-Oncogene Proteins c-fos/genetics , Proto-Oncogene Proteins c-jun/genetics , Rats , Transcription FactorsABSTRACT
It is well documented that steroid hormones modulate cytokine gene expression. In some tissues estrogens are known to suppress cytokine production while in other tissue types, cytokine expression is enhanced by the hormone. This study was conducted to investigate the regulatory mechanisms which underlie the modulation of the interleukin-1beta (IL-1beta) gene at the transcription level. To accomplish this, the macrophage cell line RAW264.7, which appeared insensitive to 17beta-estradiol (E2) treatment, was stably transfected with the human estrogen receptor (ER) and an IL-1beta promoter-CAT reporter construct. E2 markedly enhanced LPS-induced IL-1beta promoter-driven CAT activity in an E2 dose dependent manner. This responsiveness was estrogen specific since no synergism was observed between LPS and the sex steroids testosterone or progesterone while the estrogen analogue 17alpha-estradiol stimulated only at 10 to 100 times the amount required for 17beta-E2. Several antiestrogens, H1285, ICI 182 780, and tamoxifen inhibited the estrogen stimulated enhancement of IL-1beta promoter activity in a dose-dependent manner, indicating that this effect was indeed mediated through the ER in a ligand dependent manner. The estrogenic effect appeared to be indirect and time dependent since the addition of E2 was required hours prior to LPS stimulation; addition of E2 and LPS at the same time resulted in a greatly reduced estrogenic effect. The estrogen metabolites 17-epiestriol and 16-keto-17beta-E2 displayed an estrogenic response virtually indistinguishable from E2. 4-Hydroxyestradiol displayed activity only at 100-fold the concentration of E2 while 2-hydroxyestrone showed no activity at any of the concentrations tested. Overall the results demonstrate that E2 and some metabolites of E2 synergize with LPS to markedly enhance IL-1beta promoter activity through ER mediated processes.
