SUMMARY Drug-induced liver injury (DILI) to flucloxacillin is rare and is classified as idiosyncratic, as it is dependent on individual susceptibility, unpredictable, and dose-independent. The authors present the case of a 74 - year - old man with a history of monoclonal gammopathy under investigation and alcoholic habits of 24 g/day, with asthenia, anorexia, nausea, abdominal discomfort, and fever with three days of evolution. He was treated with two courses of antibiotic therapy with flucloxacillin to erysipelas previously (3 months and 2 weeks before admission). Lab tests showed serum AST levels of 349 U/L, ALT 646 U/L, alkaline phosphatase 302 U/L, GGT 652 U/L, total bilirubin 3.3 mg/dL and direct bilirubin 2.72 mg/dL. Infectious, autoimmune, and metabolic causes were ruled out. Magnetic resonance cholangiopancreatography showed normal results. Liver biopsy showed mild multifocal (predominantly microvesicular) steatosis; marked changes in the centrilobular areas (sinusoidal dilatation, marked congestion, hemorrhage, and multifocal hepatocyte collapse); expansion of the portal areas with the formation of bridges; proliferated bile ducts and inflammatory infiltrate of variable density, predominantly mononuclear type. The HLA-B*5701 screening test was positive. Hepatic biochemical tests remain abnormal with a significative increase in total bilirubin, which reached levels of 24.1 mg/dL, with the development of jaundice, pruritus, and choluria. DILI was assumed, and the patient was treated with ursodeoxycholic acid. There was favorable evolution, without evidence of blood coagulation dysfunction or encephalopathy. The analytic normalization was, however, slow, with evolution to chronicity. The authors present this case to remind the possibility of moderate/severe drug-induced liver injury to flucloxacillin, an antibiotic commonly used in clinical practice and association with the HLA-B * 5701 allele reported in the literature.

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BackgroundPh3 studies demonstrated clinical efficacy of 2 different once-daily (QD) doses of baricitinib (bari) (2mg and 4mg) in patients (pts) with active rheumatoid arthritis (RA) and an inadequate response (IR) to conventional synthetic DMARDs1 or biologic DMARDs2. In general, larger, more rapid and more consistent treatment effects were observed for the 4mg dose across measures.ObjectivesTo investigate the effects of bari dose step-down in patients who had achieved sustained low disease activity (LDA) or remission with bari 4mg QD.MethodsPts who completed a bari Ph3 Study (RA-BEGIN, RA-BEAM, RA-BUILD, or RA-BEACON) could enter a long-term extension study, RA-BEYOND. In RA-BEYOND, pts who had received bari 4mg for at least 15 months and who had achieved sustained LDA or remission (defined by CDAI score at 2 consecutive visits at least 3 months apart) were re-randomized in a double blind manner to continue receiving bari 4mg or to step down to a 2mg QD dose. Disease activity was assessed at a 12 week (wk) landmark following re-randomization.ResultsAmong pts who achieved satisfactory and sustained disease control with bari 4mg QD, randomized, double blind dose reduction to 2mg QD was associated with modest, statistically significant increases in disease activity across measures at a subsequent 12 wk landmark assessment (Table). However, a large majority of pts (in both the continued 4mg and reduced to 2mg groups) retained the state of LDA or remission that led to their re-randomization.RA-BEAM, RA-BUILD, RA-BEACON combinedEfficacy measure†Continued bari 4 mgStepped down to bari 2 mgWk12(N=147)(N=146)CDAI LDA ≤10§, n (%)136 (92.5)123 (84.2)*CDAI remission ≤2.8§, n (%)57 (38.8)54 (37.0)ΔCDAI0.60 (3.44)2.04 (6.29)*ΔTJC 680.3 (3.0)1.2 (3.8)*ΔSJC 660.1 (1.7)0.8 (2.7)*ΔHAQ-DI0.04 (0.26)0.06 (0.28)ΔPain0.7 (14.7)2.5 (16.4)ΔPtGA1.2 (14.3)2.5 (14.5)ΔPhGA−0.0 (9.6)2.7 (13.6)*ΔCRP0.68 (7.16)1.68 (7.82)ΔDAS28-CRP0.14 (0.70)0.36 (0.77)*ΔDAS28-ESR0.10 (0.73)0.35 (0.89)*ΔSDAI0.69 (3.55)2.19 (6.33)*†Values other than CDAI LDA or remission are mean change from baseline (SD) with missing data imputed using modified last observation carried forward; §Missing data imputed using nonresponder imputation; RA-BEAM = MTX-IR pts; RA-BUILD = csDMARD-IR pts; RA-BEACON = bDMARD-IR pts; Δ = change from baseline; CDAI = Clinical Disease Activity Index; CRP = C-reactive protein; DAS28 = Disease Activity Score modified to include the 28 diarthrodial joint count; ESR = erythrocyte sedimentation rate; HAQ-DI = Health Assessment Questionnaire-Disability Index; PhGA = Physician's Global Assessment of Disease Activity; PtGA = Patient's Global Assessment of Disease Activity; SD = standard deviation; SDAI=Simplified Disease Activity Index; SJC = swollen joint count based on 66 joints; TJC = tender joint count based on 68 joints; *p≤0.05 vs. bari 4 mg.ConclusionsConsistent with completed studies, these data indicate that 4mg QD was the most efficacious dose of bari for pts with RA in clinical studies. Most pts who had achieved sustained disease control ...

A masquerade syndrome is an ophthalmological entity where a neoplasm mimics an inflammatory condition. Ocular melanoma (chiefly uveal) may present with symptoms suggestive of intraocular inflammation such as endogenous endophthalmitis. Ocular melanoma is most commonly found in middle-aged and older caucasian patients. One-third of all uveal melanoma cases present asymptomatically. Early diagnosis facilitates treatment before ocular melanoma reaches metastatic stage IV. Current therapy options for stage IV patients are palliative care and clinical trial participation.eed for clinicians to be aware of rare metastases at the time of diagnosis.

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