C-reactive protein (CRP) is an acute-phase protein whose requests have been growing exponentially in several countries, including Brazil. In this study, the use of CRP in several clinical situations was reviewed by a group of physicians comprised by specialists in internal medicine, medical emergencies, intensive care, screening, and laboratory medicine, aiming to analyze the applicable literature and to propose guidelines for a more rational use of this laboratory test. The result was the creation of flowcharts guiding CRP request, adjusted to four different healthcare environments, namely, intensive care units, emergency room, wards, and outpatient clinics. These flowcharts, as well as a more detailed discussion on several clinical recommendations for the test, are presented in this study.

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Objectives It is unknown if hydroxychloroquine blood level dynamics impact flare rates in lupus nephritis patients. We prospectively evaluated hydroxychloroquine levels to determine which blood-based patterns are more associated with disease activity. Methods In total, 82 lupus nephritis patients under a prescribed hydroxychloroquine dose of 4–5.5 mg/kg actual body weight (maximum 400 mg/day) for ≥3 months were evaluated at baseline and 7 months. Hydroxychloroquine blood levels were determined by liquid chromatography-tandem mass spectrometry. Flare was defined as increase ≥3 in the Systemic Lupus Erythematosus Disease Activity Index 2000 score and/or a change or increase in therapy. Results Overall, 9/82(11%) patients had flares during follow-up and had lower baseline hydroxychloroquine blood levels than those without flares (220.4 (53.5–1471.1) vs. 1006.3 (53.5–2137.8) ng/ml, p = 0.013). The hydroxychloroquine blood level cut-off that best predicted flares was 613.5 ng/ml (odds ratio = 8.67, 95% confidence interval: 1.66–45.18, p = 0.006). For 77 (94%) patients, the 7-month hydroxychloroquine level dynamics was evaluated and revealed: 59/77 (77%) had a persistent pattern of adequate (41/77(53%)) or fluctuating (18/77 (23%)) levels, with a low and comparable risk of flares (2/41 (5%) vs. 1/18 (5%), p = 1.000). The remaining group had persistent low levels (18/77 (23%)) and their flare frequency was significantly higher than the adequate group (5/18 (28%) vs. 2/41 (5%), p = 0.023). The frequencies of adequate/inadequate hydroxychloroquine blood levels in patients were comparable at baseline and 7 months (McNemar’s test, p = 0.480). Conclusion We provide novel evidence that hydroxychloroquine blood-level patterns (persistently low, adequate, or intermittent) have distinct impacts on flare rates in lupus nephritis patients. These findings reinforce the need of routine hydroxychloroquine measurements to maintain the appropriate blood levels.

Objective Low hydroxychloroquine (HCQ) blood levels are predictors of flare in adult lupus. Childhood-onset systemic lupus erythematosus (cSLE) has high morbidity with renal involvement in up to 80% of cases. The aim of this study is to determine the HCQ cut-off levels which predicts flare in childhood-onset lupus nephritis (LN). Methods Sixty LN patients on HCQ use for at least 6-months were prospectively evaluated at baseline (BL) and about 6-months later for cSLE flare and HCQ blood levels (ng/mL) measured by liquid chromatography-tandem mass spectrometry. Results There were 19 patients (32%) with flare, during the study with median SLEDAI increase of 4 (0–8). Median (IQR) BL HCQ levels of the flare group were lower compared to stable patients [557.5 (68.6–980.3) vs. 1061.9 (534.8–1590.0 ng/mL); p=0.012]. ROC curve analysis demonstrated that HCQ levels≤1075 ng/mL were associated with a 5.08 (95%CI 1.28-20.13; p=0.021) times increased risk of flare. Six-month HCQ levels revealed that most patients 24/54 (44%) had persistently low levels (≤1075) during follow-up. Among those, 11/24 (46%) had flare. Multiple logistic regression analysis including prednisone use, baseline SLEDAI-2K, adherence based on pharmacy refill and BL HCQ blood levels as possible predictors of flare revealed that only HCQ blood level was independently associated with flare (OR 0.999, 95%CI 0.998-1.0, p=0.013). Conclusions We demonstrated that HCQ blood cut-off level under 1075 ng/mL predicts flare in childhood-onset LN patients under prescribed HCQ dose of 4.0–5.5 mg/kg/day. We further observed that most of these patients have compliance issues reinforcing the need for a close surveillance particularly in those with levels below the defined cut-off.

Introduction In 2016 the American Academy of Ophthalmology(2016-AAO) recommended a maximum daily HCQ use of 5.0 mg/kg real body weight(RBW) taking into consideration minimizing eye toxicity. Retinopathy in systemic lupus erythematosus(SLE) patients was recently associated with obesity and this condition is progressively more common in these patients. However, the impact of obesity in HCQ blood levels remains controversial. Objective To determine if the 2016-AAO recommendation based on RBW with and without maximum daily dose restriction results in adequate and safe blood levels in obese lupus nephritis(LN) patients. Methods A cross-sectional study was performed with 108 LN patients under the prescribed 2016-AAO dose for at least 3 months. LN patients were assessed for demographic characteristics, body mass index(BMI), disease parameters, HCQ dose, concomitant treatment and HCQ blood levels measured by liquid chromatography-tandem mass spectrometry. Obesity was defined as BMI ≥30kg/m2. Results Obesity was identified in 35/108(32%) LN patients. The calculation of HCQ daily dosage revealed that obese patients were under a lower prescribed daily dose according to the real body weight (RBW) [4.4(2.9-5.4) vs. 4.9(4-5.5)mg/Kg/day, p < 0.001] due to the maximum limit used. Regardless of that the median of HCQ blood levels was significantly higher in obese compared to non-obese patients (1562 ± 548.6 vs. 1208 ± 448.9 ng/mL, p = 0.002). Further analysis of patients under the 20016-AAO recommendation by RBW without the restriction of maximum daily dose confirmed that in spite of comparable daily dose in 14 obese patients and 61 non-obese patients [4.8 (4.5-5.4) vs. 5.0(4.5-5.5) mg/kg, p = 0.312], the median of HCQ blood levels was significantly higher in obese patients than in non-obese (1734 ± 457.3 vs. 1189 ± 449.4 ng/mL, p < 0.001). Conclusion Obese patients under the 2016-AAO prescribed dose of HCQ based on RBW with and without maximum daily dose restriction have a very high HCQ blood levels compared to non-obese patients, with a potential increased risk of ocular toxicity. The use of 2016-AAO dose of HCQ according to the ideal body weight for this group of patients should be considered.Clinicaltrials.gov #NCT0312243.