Polyclonal hypergammaglobulinaemia: towards definition of a threshold.

BACKGROUND: Polyclonal hypergammaglobulinaemia (PH) represents a classic diagnosis problem in internal medicine. However, there is no consensus threshold for PH. The aim of this study was to define a threshold for PH. METHODS: We conducted a retrospective multicentric study using laboratory biological databases between 1 January 2016 and 31 December 2016 in two university hospitals and one non-university hospital. All patients 18 years old or over and with at least one serum protein electrophoresis (SPE) available in 2016 were included. Exclusion criteria were monoclonal, biclonal, or oligoclonal spikes or, in case of hypogammaglobulinaemia, proven free light chain gammopathy. The main endpoint was to define the threshold values for PH in this population. Another objective was to define the 95th percentile of the distribution. RESULTS: 20 766 SPEs were included in this cohort. The PH threshold on 95th percentile was 18.9 g/L. The threshold varied according to geographical areas. CONCLUSIONS: This is the first study to scientifically define a PH threshold. The main limitation is that our threshold is only biological. The study was not designed to associate this threshold with a clinically active disease. In conclusion, while the 19 g/L cut-off seems the most relevant threshold, but it will need to be validated by prospective studies.

Anti-PM-Scl antibodies-positive patients encompass three different groups with distinct prognoses.

OBJECTIVE: To help identify homogeneous subgroups among patients with anti-PM-scleroderma-antibodies (PM-Scl-Abs) positive auto-immune diseases regardless of diagnostic classifications. MATERIAL AND METHODS: This multicentric (four hospitals) retrospective study collected all consecutive patients (from 2011 to 2021) with positive testing for anti-PM-Scl-Abs in a context of CTD. Subgroups of patients with similar clinico-biological phenotypes were defined using unsupervised multiple correspondence analysis and hierarchical clustering analysis of the features recorded in the first year of follow-up. RESULTS: One hundred and forty-two patients with anti-PM-Scl-Abs were evaluated and 129 patients were included in the clustering analysis and divided into three clusters. Cluster 1 (n = 47) included patients with frequent skin thickening, digestive involvement and interstitial lung disease (ILD) with non-specific interstitial pneumonia (NSIP). They were more likely to develop progressive fibrosing ILD. Cluster 2 (n = 36) included patients who all featured NSIP with frequent organizing pneumonia-associated pattern and mechanic's hands. This subgroup had increased risk of relapse and ILD was characterized by a good functional outcome. Cluster 3 (n = 46) was characterized by predominant or isolated musculoskeletal involvement and frequently matched UCTD criteria. Although very frequent among anti-PM-Scl-Abs positive patients, muscle involvement was less discriminating compared with skin thickening and ILD pattern to classify patients into subgroups. CONCLUSION: Anti-PM-Scl-Abs associated auto-immune diseases are segregated into three subgroups with distinct clinical phenotype and outcomes. Skin thickening and NSIP are determinant predictors in segregation of theses populations.

Polyclonal hypergammaglobulinaemia: towards definition of a threshold.

BACKGROUND: Polyclonal hypergammaglobulinaemia (PH) represents a classic diagnosis problem in internal medicine. However, there is no consensus threshold for PH. The aim of this study was to define a threshold for PH. METHODS: We conducted a retrospective multicentric study using laboratory biological databases between 1 January 2016 and 31 December 2016 in two university hospitals and one non-university hospital. All patients 18 years old or over and with at least one serum protein electrophoresis (SPE) available in 2016 were included. Exclusion criteria were monoclonal, biclonal, or oligoclonal spikes or, in case of hypogammaglobulinaemia, proven free light chain gammopathy. The main endpoint was to define the threshold values for PH in this population. Another objective was to define the 95th percentile of the distribution. RESULTS: 20 766 SPEs were included in this cohort. The PH threshold on 95th percentile was 18.9 g/L. The threshold varied according to geographical areas. CONCLUSIONS: This is the first study to scientifically define a PH threshold. The main limitation is that our threshold is only biological. The study was not designed to associate this threshold with a clinically active disease. In conclusion, while the 19 g/L cut-off seems the most relevant threshold, but it will need to be validated by prospective studies.

Isavuconazole Kinetic Exploration for Clinical Practice.

BACKGROUND: Isavuconazole is a new antifungal prodrug for the treatment of invasive aspergillosis and mucormycosis. As no clear pharmacokinetic-pharmacodynamic relationship has been established for patients, therapeutic drug monitoring is not currently required. However, as isavuconazole is a new drug, clinicians are sometimes sceptical about the exposure achieved in their patients and seek pharmacokinetic exploration. A minimal response consists of determining that the patient's pharmacokinetic profile agrees with profiles reported by Desai et al. using concentrations from the SECURE study. METHODS: Based on one concentration and Desai et al.'s population-pharmacokinetic model, it is possible to estimate a patient's most likely pharmacokinetic profile. If a patient's pharmacokinetic profile is close to the profiles reported by Desai et al., therapeutic drug monitoring is not required. In contrast, when the pharmacokinetic profile differs from the Desai et al. profiles, isavuconazole concentration monitoring and pharmacokinetic profile modeling are the only methods for obtaining information on a patient's exposure and the efficacy of isavuconazole. RESULTS: Four patients presented with surprising pharmacokinetic profiles, unexplained by drug interactions or cytochrome P450 3A4/5 polymorphisms. For two of them, a drug dosage adjustment was proposed and applied by clinicians, together with a check for a new pharmacokinetic profile a few days later. CONCLUSIONS: Collecting one blood sample just before the first maintenance dose to make an early estimation of the patient's most likely pharmacokinetic profile is one method of identifying patients with outlier pharmacokinetic behavior.