Serum interleukin-18 level as a possible early diagnostic marker of systemic juvenile idiopathic arthritis.

Early diagnosis of systemic juvenile idiopathic arthritis (s-JIA) is a prerequisite for therapeutic efficacy. However, it is often challenging because most patients with s-JIA do not show arthritis at disease onset and are simply diagnosed with fever of unknown origin. Serum ferritin levels have commonly been used to diagnose s-JIA because they increase in patients with this condition by more than 5 times their normal value. However, there are no definite biomarkers for s-JIA, which makes the clinical diagnosis of s-JIA difficult. We report a case of s-JIA in which interleukin (IL)-18 elevation was observed before ferritin elevation at the early phase of s-JIA. We propose serum IL-18 levels as a more useful biomarker for the early diagnosis of s-JIA compared to serum ferritin levels.

Mild progressive osseous heteroplasia overlap syndrome with PTH and TSH resistance appearing during adolescence and not early childhood.

PURPOSE: Progressive osseous heteroplasia (POH), a genetic disorder, is associated with Albright's hereditary osteodystrophy (AHO), pseudohypoparathyroidism, and primary osteoma cutis and has common features of superficial ossification and GNAS-inactivating mutations. Disorders due to GNAS-inactivating mutations are classified as "inactivating parathyroid hormone (PTH)/PTHrP signaling disorder type 2." This study reports a case of mild POH overlap syndrome to improve understanding of genotype-phenotype correlations. METHODS: A 13-year and 6-month-old Japanese boy was referred to our hospital with a chief complaint of the lower limb length difference. He underwent clinical, biochemical, radiological, and genetic studies. RESULTS: He showed sporadic GNAS mutation, deep ectopic ossification, small for gestational age (SGA), congenital tooth defect, and lack of AHO features; he met the diagnostic criteria for POH, and mild PTH and TSH resistance was detected. He had constant hyperphosphatasemia and hypocalciuria. At the age of 10 years, he occasionally experienced high iPTH levels. The pituitary stimulation test showed a normal response of all hormones at 3 years of age, but TSH response was decreased (previously 0.770, peak value 4.144 µIU/mL) in the TRH loading test at age 13 years and 6 months. DNA analysis showed a heterozygous p.D189MfsTer14 mutation of GNAS. The parents did not carry this mutation. CONCLUSION: We report a rare case of POH overlap syndrome with PTH/TSH resistance that appeared in adolescence rather than early childhood. Cases diagnosed with POH in early childhood also require reassessment during adolescence. Further studies of the GNAS heterozygous mutation p.D189MfsTer14 may reveal factors involved in POH overlap syndrome.