Oshima K, Inage E, Toriumi S, Oishi K, Yamada H , et al.
The Tohoku journal of experimental medicine •
Cimetidine is effective for treating periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, primarily in children, and is covered by public insurance in Japan. However, as demand for gastric ulcer treatment declines, cimetidine production has been restricted, raising concerns about supply for pediatric patients. We analyzed Japanese prescription trends in adults and children using publicly available data. Specifically, national reimbursement data were used to assess annual cimetidine prescription volumes by age group and pediatric share. Chronological changes were examined based on original formulation supply. In the database, 11 and 6 cimetidine products (including discontinued stock) were available for outpatient and in-hospital dispensing, respectively. Annually, 1.01 million and 80,000 cimetidine tablets (200-mg equivalents) were dispensed for patients under 15 years in outpatient and in-hospital settings, respectively. No inpatient prescriptions were recorded. Pediatric prescriptions peaked at ages 5-9 years, differing from adult trends, and accounted for 2.5% of total prescriptions. Although overall dispensing volumes are declining, pediatric prescriptions are increasing. Despite overall demand decreasing, approximately 1 million 200-mg cimetidine tablets are needed annually for use in children, and pediatric demand is increasing. Therefore, securing production of this new indication is essential.
Nakamura H, Kikuchi A, Sakai H, Kamimura M, Watanabe Y , et al.
Frontiers in pediatrics •
Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA syndrome), and Kawasaki disease (KD) are both considered to be disorders of the innate immune system, and the potential role of inflammasome activation in the immunopathogenesis of both diseases has been previously described. Herein, we report the clinical courses of three patients who presented a rare combination of PFAPA syndrome and KD. Two patients who presented KD later developed the PFAPA syndrome, of whom one developed recurrent KD 2 years after the initial diagnosis. The third patient developed KD one year after the onset of PFAPA syndrome. The presence of both of these conditions within individual patients, combined with the knowledge that inflammasome activation is involved in both PFAPA syndrome and KD, suggests a shared background of inflammatory dysregulation. To elucidate the mechanism underlying shared inflammatory dysregulation, we investigated the roles of Nod-like receptors (NLRs) and their downstream inflammasome-related genes. All the patients had a frameshift variant in (CARD8-FS). A previous study demonstrated a higher frequency of CARD8-FS, whose product loses CARD8 activity and activates the NLRP3 inflammasome, in patients with the PFAPA syndrome. Additionally, the NLRP3 inflammasome is known to be activated in patients with KD. Together, these results suggest that the CARD8-FS variant may also be essential in KD pathogenesis. As such, we analyzed the variants among patients with KD. However, we found no difference in the variant frequency between patients with KD and the general Japanese population. We report the clinical courses of three patients with a rare combination of PFAPA syndrome and KD. All the patients had the CARD8-FS variant. However, we could not find a difference in the variant frequency between patients with KD and the general Japanese population. As the frequency of KD is much higher than that of PFAPA among Japanese patients, and the cause of KD is multifactorial, it is possible that only a small portion of patients with KD harbor CARD8-FS as a causative gene.