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A 40-year-old male was hospitalized with renal impairment and severe hypercalcemia. His concentration of serum IgG4 was high, but serum whole PTH, 1-25(OH) vitamin D3 and PTHrP were not elevated. Computed tomography showed swelling of the bilateral lacrimal glands and systemic lymphadenopathy. The histological findings of lacrimal gland biopsy fulfilled the diagnostic criteria of IgG4-related ophthalmic disease (IgG4ROD). Bone scintigraphy showed increased ectopic uptake in the stomach, heart, lungs, and kidneys. He died on day 16 of admission, although the therapies for hypercalcemia were continued. Autopsy results showed an increase of osteoclasts in the bone marrow and metastatic calcification in multiple organs, and excluded from the differential diagnosis other disorders which present lymph-node swelling and hypercalcemia such as cancer, lymphoma, Castleman's disease, and sarcoidosis. He was given a diagnosis of IgG4ROD with osteolytic hypercalcemia.

BackgroundTakayasu arteritis (TAK) is a rare disease that mostly affects young females and causes inflammation, stenosis and dilatation of the aorta and its main branches. Although glucocorticoids are effective, relapses occur frequently [1]. Recently, the efficacy of biologics has been reported in refractory TAK. HLA-B*52 is a major genetic risk factor and associated with the severity [2]. Our group reported a SNP in the regions of IL12B gene associated with the onset of TAK, and the patients with risk alleles at the SNP showed significantly severer symptoms [3].ObjectivesTo evaluate the efficacy and safety of biologics in the treatment of refractory TAK, we analyzed the clinical profiles and genetic information of patients treated with biologics in our institute.MethodsWe searched for TAK patients who used biologics in 163 TAK cases treated in Kyoto University Hospital from 2000 to 2016. From medical records, we extracted information of classifications, symptoms, complications, ESR, CRP, dose of prednisolone (PSL), use of immunosuppressive agents (IS), and adverse events at 0, 1, 6 12 months after the initiation of biologics.ResultsOf 163 cases, 12 (7.4%) were treated with biologics. Two were excluded because biologics were used for coexisting rheumatoid arthritis. Remaining 10 cases were treated with infliximab (IFX, 3–5 mg/kg div. bimonthly, N=4), tocilizumab (TCZ, 8 mg/kg div. monthly, N=3) or ustekinumab (UST, 45 mg s.c. trimonthly, N=3). Sex ratio was 1:9. The age of onset was 29.4±12.2 y.o. (mean±S.D.). According to Hata's classification [4], they were categorized into types I (N=3), IIa (2) and V (5). Three patients had aortic regurgitation. The number of IS used in the past was 1.7±0.8 per patient. B*52 was positive in 7 (70%) patients. All the cases had risk-type alleles (A vs. C) of IL12B SNP (AA: AC: CC =4: 6: 0). ESR was significantly decreased (p=0.009) and CRP showed a tendency to decrease after 12 mo. (Table 1). Dose of PSL was significantly decreased from 10.6±1.9 to 7.7±2.4 mg/day after 12 mo. (p=0.018). We could not find significant improvements in imaging modalities such as MR and ultrasonography. Overall duration of treatments with biologics was 39±22 months. Two cases discontinued IFX due to occurrence of breast cancer and infusion reaction, respectively. Chronic heart failure was exacerbated in a case treated with TCZ. Two of 3 patients treated with UST exhibited steroid- sparing effects and none of them discontinued UST in the mean observation period of 31 mo.Table 1.Changes after the treatment with biologicsBefore1 mo.6 mo.12 mo. P (before vs. 12 mo.) ESR (mm /h)31±1614±914±1212±120.009CRP (mg/L)15±198±134±52±40.075PSL (mg/day)10.6±1.910.5±2.09.0±2.37.7±2.40.018ConclusionsBiologics showed steroid-sparing effects in refractory TAK. Besides, there was a tendency that patients who used biologics had B*52 and the risk-type allele of IL12B SNP, implicating the refractory courses of them.References Maksimowicz-McKinnon K, Clin Exp Rheumatol 25:S58–9, 2007.Numano F, Jpn Circ J 46(2):184–9, 1982...

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