Mediterranean fever gene variants modify clinical phenotypes of idiopathic multi-centric Castleman disease.

Four cases of idiopathic multi-centric Castleman disease (iMCD) reportedly have variants in hereditary autoinflammatory disease-related genes; however, the frequency and role of these variants in iMCD is still unknown. We therefore investigated such gene variants among patients with iMCD and aimed to reveal the relationship between iMCD and autoinflammatory disease-related genes. We reviewed 14 Japanese iMCD patients who were recruited between January 2015 and September 2019. All patients met both the Japanese tentative diagnostic criteria for Castleman disease and the international consensus diagnostic criteria for iMCD. We performed genetic analyses for 31 autoinflammatory disease-related genes by targeted next-generation sequencing. The MEFV gene variants were observed in 10 of 14 patients with iMCD. Although iMCD had a high percentage of exons 2 or 3 variants of MEFV, comparison of data from healthy Japanese subjects indicated that there was no significant difference in the percentage between healthy Japanese subjects and patients with iMCD. Variants of uncertain significance (VUS) in the TNFRSF1A and CECR1 genes were observed in two of the patients, respectively. We divided patients into two groups-those with MEFV variants (excluding E148Q variants) and those without MEFV variants-and compared the clinical characteristics between these two groups. Patients with MEFV variants, excluding E148Q variants, exhibited a significantly higher likelihood of fever and significantly lower levels of hemoglobin than those lacking MEFV variants. Our results indicated that patients with iMCD tended to have a high frequency of MEFV gene variants and the presence of such variants can affect iMCD clinical phenotypes.

New bone-like tissue formation in calcific tendinopathy: A case report.

Currently, the pathogenesis of nontraumatic heterotopic ossification (HO), e.g., bone-like tissue in calcific tendinopathy remains unclear. Here, we report a 75-year-old, right-handed Japanese woman who had been on hemodialysis for 3 years and was admitted to our hospital to evaluate pain and swelling of the right forearm. She worked as a cook, and her main job over the 3 most recent years had been the frequent and continuous shredding of cabbage. A radiograph showed the highly radiopaque material on the dorsal aspect of the right wrist and in the right shoulder. The biopsy of this radiopaque material revealed HO with marrow, as well as calcified material. Histomorphometric analysis of the HO identified a severe type of osteitis fibrosa with a fibrous tissue volume to total volume of 19.8% (>0.5% required for diagnosis) and an osteoid volume to bone volume of 20.0% (>15% required for diagnosis). We found more woven bone-like tissue than lamellar bone-like tissue. However, the intact parathyroid hormone level was 3-times the normal upper limit with 203 pg/mL, but histomorphometric analysis of the right iliac crest revealed normal bone structure. These findings indicate that the frequent and continuous shredding action with the right hand contributed to the nontraumatic HO localized on the dorsal aspect of the right wrist.

Diaphyseal femoral fracture due to severe vitamin D3 deficiency and low parathyroid hormone levels on long-term hemodialysis: a case report.

INTRODUCTION: Currently, there are no reports of diaphyseal femoral fracture equivalent to atypical femoral fractures (AFFs) in patients receiving long-term hemodialysis (HD). CASE REPORT: A 56-year-old Japanese man receiving long-term HD for 34 years was admitted to our hospital due to a delay in postoperative healing. The patient began maintenance hemodialysis at 22 years of age. The patient then underwent surgical parathyroidectomy (PTX) for secondary hyperparathyroidism at 43 years of age, which resulted in decreased levels of parathyroid hormone (PTH). Thereafter, this patient's serum 1,25(OH)2 D3 level was very low because active vitamin D3 derivative was not administered. At 54 years of age, a transverse fracture of the femoral shaft equivalent to AFF occurred. Surgery with open reduction and internal fixation using intramedullary nailing was performed; however, the delay of postoperative healing continued for 16 months. A left iliac crest bone biopsy was performed and showed osteoid-like lesion and an increase of woven bone. The patient received active vitamin D3 derivative and recombinant human PTH (1-34) derivative. Twenty-nine months after the first surgery, a reoperation was performed. Simultaneously, a right iliac crest bone biopsy was performed. Bone morphometrical improvement was confirmed. Six months after resurgery, the bone union was achieved. Severe vitamin D3 deficiency and decreased levels of PTH may induce a higher osteoid state and an increase of woven bone, which may then attribute to the development of diaphyseal femoral fracture and impairment of postoperative bone healing. It is hypothesized that treatment with active vitamin D3 and teriparatide acetate may be a therapeutic option via the accelerated formation of lamellar bone for refractory diaphyseal femoral fracture of long-term dialysis.

Incidence and risk factors of new-onset hypertrophic pachymeningitis in patients with anti-neutrophil antibody-associated vasculitis: using logistic regression and classification tree analysis.

OBJECTIVES: Hypertrophic pachymeningitis (HP) is a rare complication in patients with anti-neutrophil antibody-associated vasculitis (AAV); its clinical features, incidence, and risk factors remain unknown. We aimed to clarify the prevalence, clinical features, and factors associated with new-onset HP in patients with AAV. METHOD: A retrospective cohort study involving 93 patients with AAV was conducted. HP incidence between patients with granulomatosis with polyangiitis (GPA) and those with microscopic polyangiitis (MPA) was compared to investigate risk factors associated with HP. We performed only univariate analysis using logistic regression and classification tree (CART) analysis due to the small number of HP cases. RESULTS: Among the 93 patients (76 with MPA and 17 with GPA), only 6 patients developed HP (1 with MPA, 5 with GPA) over an average observation period of 4 years; all patients who developed HP were positive for myeloperoxidase anti-neutrophil antibody. HP incidence was significantly higher in patients with GPA than in those with MPA (60.2 versus 3.3 persons per 1000 person-years, respectively, P = 0.002). The univariate analysis revealed that otitis media (P < 0.001) and sinusitis (P = 0.014) were associated with new-onset HP. Univariate CART analysis grouped the patients into patients with HP who have otitis media (33%) and patients with HP who have sinusitis (21%). The odds ratio of otitis media adjusted by age and first diagnosis of AAV was 38.1 (95% confidence interval, 3.08-331.4; P = 0.004). CONCLUSIONS: Although only in the univariate analysis, otitis media was the most discriminating factor to predict new-onset HP in patients with AAV.