National Center For Child Health and Development

Cimetidine for Pediatric Use in Japan: Rising Prescriptions for a New Indication.

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.

Can the effectiveness of tonsillectomy for PFAPA syndrome be predicted based on clinical factors.

To evaluate the clinical factors associated with the outcome of tonsillectomy in children with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, thereby clarifying who would most likely benefit from that surgery. This was a case-control study of 53 PFAPA patients who underwent tonsillectomy and were divided into a complete-resolution group and a postoperative-fever group. Logistic regression analyses were performed using 17 clinical factors as variables to identify factors associated with the surgical outcome. Hierarchical cluster analysis was also performed to evaluate for relationships between phenotypes and surgical outcomes. Thirty-nine (73.6%) patients had complete resolution after tonsillectomy. In simple logistic regression analysis, the surgical outcome showed significant positive trends with late-onset (odds ratio [OR] 7.1, P = 0.02) and presence of headache (OR 6.5, P = 0.01). In stepwise multiple logistic regression analysis adjusted for age at onset, presence of headache was significantly associated with complete resolution (OR 6.5, P = 0.01). The complete resolution rates for each combination of headache status and age at onset were as follows: presence of headache/age at onset ≥36 months, 100% (14/14); presence of headache/age at onset <36 months, 76.9% (10/13); absence of headache/age at onset ≥36 months, 75.0% (6/8); and absence of headache/age at onset <36 months, 43.8% (7/16). In hierarchical cluster analysis, complete resolution, age at onset, and headache were in the same cluster. PFAPA patients with headache and late onset responded well to tonsillectomy. The mechanisms underlying this association may warrant further investigation.

Transcriptome analysis reveals two distinct endotypes and putative immune pathways in tonsils from children with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome.

[Tonsillectomy in Cases with Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome].

The periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is an autoinflammatory disease, characterized, as its name suggests, by periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis. This syndrome is the most common cause of recurrent fever in children, however the rate of recognition of this syndrome is still low. Tonsillectomy has been suggested as an effective treatment, even though the precise, pathophysiology underlying this syndrome remains unknown. In this study, we investigated the outcomes in patients who underwent tonsillectomy. In particular, we examined the surgical outcomes and clinical features of the patients who underwent tonsillectomy. A total of 19 patients with PFAPA syndrome underwent tonsillectomy at our hospital from July 2013 to May 2016. Before the surgery, while all the patients had received medications, none showed complete resolution of the syndromes. However, of the 19 patients, 15 showed complete resolution of the syndrome immediately after the surgery. Four patients had fever even after the surgery. Three patients showed partial remission, with the frequency and duration of the episodes decreasing after the surgery. However, in one patient, the fever persisted as before the surgery. There were no significant differences in the clinical characteristics, such as the age at onset, fever episodes, associated symptoms, or age at surgery among the three groups. However, we observed a trend towards a higher frequency of a family history in patients with persistent symptoms after surgery. Tonsillectomy was highly effective against PFAPA syndrome, however, some patients failed to respond to the procedure. Therefore, it is important to carefully evaluate the risks and benefits in each case. The indications for tonsillectomy have not yet been clearly established. It is essential to continue further investigations to establish effective therapeutic strategies for this syndrome.