18q Deletion Syndrome Presenting with Late-Onset Combined Immunodeficiency.

Patients with chromosome 18q deletion syndrome generally experience hypogammaglobulinemia. Herein, we describe two patients with chromosome 18q deletion syndrome who presented with late-onset combined immune deficiency (LOCID), which has not been previously reported. Patient 1 was a 29-year-old male with 18q deletion syndrome, who was being managed for severe motor and intellectual disabilities at the Yamabiko Medical Welfare Center for 26 years. Although the patient had few infections, he developed Pneumocystis pneumonia at the age of 28. Patient 2, a 48-year-old female with intellectual disability and congenital malformations, was referred to Tokyo Medical and Dental University Hospital with abnormal bilateral lung shadows detected on her chest radiography. Computed tomography showed multiple lymphadenopathies and pneumonia. A lymph node biopsy of the inguinal region revealed granulomatous lymphadenitis, and a chromosomal examination revealed 18q deletion. Array-based genomic hybridization analysis revealed deletion at 18q21.32-q22.3 for patient 1 and at 18q21.33-qter for patient 2. Immune status work-up of the two patients revealed panhypogammaglobulinemia, decreased number of memory B cells and naïve CD4+ and/or CD8+ cells, reduced response on the carboxyfluorescein diacetate succinimidyl ester T-cell division test, and low levels of T-cell receptor recombination excision circles and Ig κ-deleting recombination excision circles. Consequently, both patients were diagnosed with LOCID. Although patients with 18q deletion syndrome generally experience humoral immunodeficiency, the disease can be further complicated by cell-mediated immunodeficiency, causing combined immunodeficiency. Therefore, patients with 18q deletion syndrome should be regularly tested for cellular/humoral immunocompetence.

The safety and effectiveness of HBV vaccination in patients with juvenile idiopathic arthritis controlled by treatment.

OBJECTIVES: To evaluate the safety and effectiveness of hepatitis B virus (HBV) vaccination in patients with juvenile idiopathic arthritis (JIA) controlled by treatment. METHODS: Among 49 patients with juvenile idiopathic arthritis (JIA) at the outpatient clinic of Kagoshima University Hospital, we enrolled 25 who were controlled by treatment. All children were unimmunized and were vaccinated against HBV according to the schedule. Their responses to the vaccine and vaccine adverse events were examined during their visits. RESULTS: Nineteen of the 25 patients with JIA controlled by treatment developed effective antibody responses (76%). All eight patients with JIA below 10 years of age achieved seroconversion. The seroconversion was not influenced by biologics. Five adverse events were observed (6.7%). The rate of all adverse events did not surpass that of a previous report, and all adverse events were immediately resolved. None of the patients with JIA experienced a flare-up or clinical deterioration related to the vaccination. CONCLUSIONS: HBV vaccination is safe and effective. Pediatric rheumatologists should consider HBV vaccination for unimmunized patients with JIA, because the response to HBV vaccine might be influenced by age, and children have a higher risk for potential HBV infection than adults.

Disease activity score in 28 joints at 3 months after the initiation of biologic agent can be a predictive target for switching to the second biologic agent in patients with polyarticular juvenile idiopathic arthritis.

OBJECTIVE: To clarify polyarticular juvenile idiopathic arthritis (pJIA) patients who failed to maintain prolonged remission with the first biologic agent. METHODS: Fourteen pJIA patients were observed for 47.5 months (median) after initiating the first biologic agent. RESULTS: Eight maintained sustained clinical remission (median 47 months) with the first biologic agents, while the six switched to the second one due to lack of efficacy, thereafter. Receiver operating characteristic (ROC) analysis revealed that disease activity score in 28 joints (DAS28) of 2.37 at 3 months could distinguish between the two patient groups (p = 0.001). CONCLUSION: pJIA patients with DAS28 >2.37 at 3 months of the initial biologic therapy may be considered to switch to the second biologics.

Prediction of long-term remission of oligo/polyarticular juvenile idiopathic arthritis with S100A12 and vascular endothelial growth factor.

OBJECTIVES: This study aimed to evaluate the usefulness of S100A12 and vascular endothelial growth factor (VEGF) for predicting the stability of remission for discontinuing methotrexate (MTX) and/or biological agents in Japanese patients with oligo/polyarticular juvenile idiopathic arthritis (JIA). METHODS: Forty-four patients with oligo/polyarticular JIA who received MTX with or without biological agents were enrolled. Serum concentration of both S100A12 and VEGF were simultaneously evaluated by ELISA in active and in remission phase determined by activity markers including DAS-28. RESULTS: S100A12 and VEGF were correlated with DAS-28. Of the 22 patients with oligo/polyarticular JIA in clinical remission, 13 patients with low S100A12 and VEGF concentrations could discontinue treatment without relapse over 2 years. However, nine patients without low S100A12 and VEGF concentrations relapsed afterwards, even though they had been in clinical remission. The cut-off levels of S100A12 and VEGF for division into two groups of the maintenance remission and relapse groups were 177 ng/ml and 158 pg/ml, respectively. CONCLUSIONS: S100A12 and VEGF are useful markers for assessing disease activity of oligo/polyarticular JIA in remission phase. These markers should be kept low when clinicians consider tapering or discontinuing treatments in oligo/polyarticular JIA patients.

A case of planned pregnancy with an interruption in infliximab administration in a 27-year-old female patient with rheumatoid-factor-positive polyarthritis juvenile idiopathic arthritis which improved after restarting infliximab and methotrexate.

We report a 27-year-old case of juvenile idiopathic arthritis (JIA) having been stopped infliximab during pregnancy. She was safely treated by infliximab therapy with premedications for preventing infusin reactions after her delivery, and then improved in the same manner as when she had been treated with infliximab therapy before pregnancy. As a result, it remains unclear whether or not we can use infliximab to control disease activities during pregnancy. In addition, it is also important to clarify whether or not premedications should be used when resuming infliximab treatment in such patients after pregnancy. These problems still remain controversial. More definitive data are needed in order to allow rheumatologists to better select the optimal TNF-alpha inhibitor therapy when treating pregnant JIA patients.