Biological/targeted synthetic DMARDs do not arrest bone loss in patients with rheumatoid arthritis: a multicenter prospective observational study.

OBJECTIVE: To elucidate the differential effects of biological/target synthesized DMARDs (b/tsDMARDs) on bone metabolism in patients with rheumatoid arthritis (RA) in a real-world cohort. METHODS: This was a multicentre prospective observational study of RA patients enrolled at the time of 1st b/tsDMARDs administration. Bone mineral density (BMD) and bone turnover markers (BTMs) were measured during the 52-week observation. The study was designed to enrol all eligible RA patients. The end-points were differences in changes in BMD according to b/tsDMARD type, and the correlation between BMD and BTMs. RESULTS: A total of 1,164 patients were enrolled in this study. b/tsDMARDs improved RA disease activity from mean CDAI 25.5 at baseline to 4.5 at week 26. Patients not receiving anti-osteoporotic agents (anti-OP) at baseline with no history of fracture experienced a significant decrease in both femoral neck (F: mean 0.666-0.655 g/cm3) and radial (R: 0.518-0.514) BMD at week 26. Despite maintaining low CDAI levels during weeks 26-52 (5.3-4.4), there was a continued decline in BMD (F: 0.653, R: 0.509. Weeks 52). None of b/tsDMARDs type preserved BMD. Conversely, patients receiving anti-OP at baseline maintained stable BMD throughout the study (Weeks 0/26/52. F: 0.551/0.551/0.555, R: 0.415/0.416/0.415). Although BTMs were changed by b/tsDMARDs, the changes were unrelated to those in BMD. CONCLUSION: Our study suggested the progression of osteoporosis in RA patients during b/tsDMARDs treatment without anti-OP. BTMs may not reflect BMD change. Regular monitoring of BMD in RA should be considered for early management of osteoporosis.

A case of glucocorticoid-resistant adult Still's disease complicated by pulmonary hypertension and interstitial lung disease.

Adult Still's disease (ASD) is rarely complicated by pulmonary hypertension (PH). A 76-year-old woman experienced ASD relapse with repeated exacerbation of PH and interstitial lung disease. Although she had been treated with immunosuppressive agents and pulmonary vasodilators, the ASD relapsed with fever, rash, increased inflammatory responses and exacerbated interstitial lung disease, and PH. The pathology of PH appeared to encompass groups 1 [pulmonary arterial hypertension (PAH)], 1' [pulmonary veno-occlusive disease (PVOD)], and 3. Remission induction therapy with high-dose glucocorticoid and tocilizumab was administered, and switching or adding pulmonary vasodilators was also attempted. As the disease activity of ASD decreased, the mean pulmonary arterial pressure and pulmonary vascular resistance improved. PH is an extremely rare form of organ dysfunction in individuals with ASD. Like other systemic autoimmune diseases, PH (PAH or PVOD) can determine the prognosis of ASD. Because of PH's rarity, it is important to sufficiently evaluate its pathology, considering the possibility that PH is not clinically classified as PAH (group 1), and to administer immunosuppressive therapy and vasodilators according to the pathology.

A patient with eosinophilic granulomatosis with polyangiitis successfully weaned from corticosteroids through remission induction therapy with mepolizumab.

The patient was a 74-year-old man who was admitted to our hospital for fever, purpura, abdominal pain, and bilateral numbness. Although the patient tested negative for anti-neutrophil cytoplasmic antibody (ANCA), he presented with an elevated peripheral eosinophil count, increased inflammatory responses, duodenitis, cholecystitis, lung lesions, renal disorder, and peripheral neuropathy. The skin biopsy findings revealed vasculitis. Thus, the patient was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA). Given the advanced age of the patient, in addition to the poor general condition and hepatic and renal dysfunction, administration of immunosuppressants was considered to pose a high risk. After obtaining informed consent, remission induction therapy was initiated with mepolizumab (MPZ; 300 mg/M) in combination with high-dose corticosteroid therapy (equivalent to 70 mg/day of prednisolone). After treatment initiation, eosinophil counts and inflammatory responses decreased. Moreover, the abdominal pain and purpura resolved, and renal/hepatic dysfunction and peripheral neuropathy also improved. While the corticosteroid dose was subsequently reduced, no relapse was observed. Approximately 2 years later, the corticosteroid was discontinued. After the discontinuation of the corticosteroid, the patient continued treatment with MPZ alone and has remained in remission for approximately 6 months. Therefore, MPZ may be useful as a remission induction therapy in ANCA-negative EGPA resistant to steroids.

A case of mixed connective tissue disease complicated by pulmonary hypertension and ascites after addition of pulmonary vasodilators.

We present the case of a 54-year-old woman with a long history of pulmonary hypertension associated with mixed connective tissue disease. She was being treated with pulmonary vasodilators, including epoprostenol and bosetan, but her mean pulmonary arterial pressure (mPAP) gradually worsened. Although her mPAP began to improve with adding sildenafil, ascites occurred. Discontinuing newly initiated drugs and starting diuretics improved her ascites. This suggested that an intensification of the treatment with vasodilators might have led to ascites (on a background of a probable arteriovenous shunt formation) in this patient with a long history of pulmonary hypertension.

Two patients with mixed connective tissue disease complicated by pulmonary arterial hypertension showing contrasting responses to pulmonary vasodilators.

Mixed connective tissue disease (MCTD) involves various clinical manifestations, and pulmonary hypertension (PH) is an important organ dysfunction defining the prognosis of MCTD. The pathology of PH is heterogeneous. Here, we present 2 cases of MCTD complicated by PH that had contrasting clinical courses. The first case involved a 54-year-old woman with Raynaud's phenomenon and dyspnoea on exertion. She was diagnosed with MCTD accompanied by pulmonary arterial hypertension (PAH) and was treated with ambrisentan and tadalafil in addition to high-dose glucocorticoid (GC) therapy and rituximab therapy. After treatment, her PH resolved. The second case involved a 64-year-old woman with Raynaud's phenomenon and dyspnoea on exertion. She was similarly diagnosed with MCTD accompanied by PAH and was treated with ambrisentan and tadalafil in addition to high-dose GC therapy and cyclophosphamide pulse therapy. However, she showed exacerbation of her respiratory condition and manifestation of pulmonary veno-occlusive disease (PVOD). Thus, the treatment was discontinued, and subsequently, her condition improved and eventually returned to that before treatment. The findings suggest that the presence or absence of latent PVOD might be an important factor for predicting the therapeutic responsiveness of MCTD-associated PH. Evaluation of chest radiography findings, computed tomography findings, percent vital capacity, and percent carbon monoxide diffusion capacity might be useful for predicting prognosis and might aid in treatment. PVOD could be underlying in patients with CTD-PH. When the complication of PVOD is suggested by chest CT or pulmonary function test, we need a careful introduction with pulmonary vasodilators. So, combination therapy of pulmonary vasodilators should not be applied in all patients with CTD-PH since underlying PVOD could deteriorate the patient's condition.