Objective
This study aimed to investigate the risk factors of hydroxychloroquine (HCQ)-induced hypersensitivity in patients with systemic lupus erythematosus (SLE) and to propose a simple ...dose-escalation regimen in cases of mild HCQ-induced hypersensitivity.
Methods
We identified patients with SLE who started HCQ between 2009 and 2018 and cases of HCQ-induced hypersensitivity by reviewing the electronic medical charts. A simple dose-escalation regimen, starting at 40 mg/day with weekly increments of 40 mg/day to 200 mg/day, was used in patients with HCQ-induced hypersensitivity who did not require hospitalization or systemic steroid therapy. We then compared the clinical parameters of patients with and without HCQ-induced hypersensitivity and evaluated the success of our dose-escalation regimen.
Results
We enrolled 302 patients with SLE and identified 25 cases of HCQ-induced eruption (8.3%). The mean Naranjo score of these patients was 5.1 ± 1.4 (min 3, max 8), and all 25 patients received a ‘possible’ (9) or ‘probable’ (16) score. A mild, generalized, maculopapular rash occurred in 24 patients, and urticaria occurred in one patient at 24 days (interquartile range 15–40 days) after the start of treatment. The proportion of cyclophosphamide use, glucocorticoid consisting of prednisolone 20 mg/day or more, and initiation of SMX-TMP within 28 days were higher in patients with skin eruptions. On multivariate analysis, only cyclophosphamide use was identified as a risk factor of HCQ-induced hypersensitivity (odds ratio = 12.3 (95% confidential interval 1.4–14.3)). Thirteen of the 14 patients on the dose-escalation regimen (92.9%) tolerated continued HCQ treatment. One patient re-experienced eruptions on day 10 day after starting HCQ.
Conclusions
Mild late reactions are common in HCQ-induced hypersensitivity. A simpler dose-escalation regimen enables safe and easier reintroduction of HCQ but should not be applied to patients with immediate reactions or moderate late reactions.
Adipose-derived stem cells (ASCs) are found in a location within the adipose tissue known as the stem cell niche. The ASCs in the niche are maintained in the quiescent state, and upon exposure to ...various microenvironmental triggers are prompted to undergo proliferation or differentiation. These microenvironmental triggers also modulate the extracellular matrix (ECM), which interacts with the cells through the cytoskeleton and induces downstream events inside the cells that bring about a change in cell behaviour. In response to these changes, the cells remodel the ECM, which will differ according to the type of tissue being formed by the cells. As the ECM itself plays an important role in the regulation of cellular differentiation, this study aims to explore the role of the cell-secreted ECM at various stages of differentiation of stem cells in triggering the differentiation of ASCs. To this end, the ASCs cultured in proliferation, osteogenic and adipogenic media were decellularized and the secreted ECM was characterized. Overall, it was found that osteo-differentiated ASCs produced higher amounts of collagen and glycosaminoglycans (GAG) compared to the undifferentiated and adipo-differentiated ASCs. The two types of differentiated ECMs were subsequently shown to trigger initial but not terminal differentiation of ASCs into osteo- and adipo-lineages respectively, as indicated by the upregulation of lineage specific markers. In addition, integrin subunits alpha (α) 6 and integrin beta (β) 1 were found to be produced by ASCs cultured on cell-secreted ECM-coated substrates, suggesting that the integrins α6 and β1 play an instrumental role in cell-ECM interactions. Taken together, this study demonstrates the importance of the ECM in cellular fate decisions and how ECM-coated substrates can potentially be used for various tissue engineering applications.
Objectives: The aim of this study was to assess the use of muscle biopsy for histopathological confirmation of small vessel vasculitis (SVV) or medium vessel vasculitis (MVV).
Method: Muscle biopsies ...were performed for all consecutive cases of suspected SVV or MVV seen at Tokyo Metropolitan Tama Medical Centre between February 2012 and May 2014 except those for which a skin or renal biopsy was indicated.
Results: Forty-nine patients underwent muscle biopsies. All patients were followed for a minimum of 6 months. Diagnosis of SVV or MVV was made in 35 patients. An unrelated condition was diagnosed in 11 patients and no diagnoses were made in three patients. Of the 35 patients in whom SVV or MVV was diagnosed, positive muscle biopsies were obtained in 20 patients 15 microscopic polyangiitis (MPA), three polyarteritis nodosa (PAN), and two eosinophilic granulomatosis with polyangiitis (EGPA), while other findings led to the same diagnosis in 15 (seven MPA, four GPA, three PAN, and one rheumatoid vasculitis). The sensitivity of the muscle biopsy was 57% 20/35; 95% confidence interval (CI) 50-57. Of 13 patients presenting with peripheral neuropathy, the muscle biopsy demonstrated vasculitis in nine patients, with 75% sensitivity (9/12; 95% CI 69-75). There were no complications in the procedure apart from delayed wound healing in one patient.
Conclusions: Muscle biopsy is a safe method that offers a high diagnostic yield for SVV or MVV, especially in patients with vasculitic neuropathy.
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