Cutaneous drug-induced lupus erythematosus: Clinical and immunological characteristics and update on new associated drugs.

Cutaneous drug-induced lupus erythematosus (CDILE) is a lupus-like syndrome related to drug exposure which typically resolves after drug discontinuation. It can present as a systemic or a sole cutaneous form and different drugs may be associated with each form. CDILE pharmacoepidemiology is constantly changing. Indeed, older drugs primarily associated with systemic CDILE are no longer prescribed and new drugs associated with either cutaneous or systemic CDILE have emerged. The present study discusses the clinical and laboratory aspects of CDILE and the postulated pathogenesis, and it provides an update on implicated drugs. We performed a literature review to single out the new drugs associated with CDILE in the past decade (January 2010-June 2020). Among 109 drugs reported to induce CDILE in 472 patients, we identified anti-TNFα, proton-pump inhibitors, antineoplastic drugs, and, in particular, checkpoint inhibitors, as emerging drugs in CDILE. Most of the published studies are cases reports or small case series, and further larger studies as well as the development of validated classification criteria are needed to better understand and characterize their implication in CDILE.

Two pediatric cases of multisystem inflammatory-like syndrome following COVID-19 vaccination.

Multisystem inflammatory syndrome in children (MIS-C) is a novel post-infectious disease occurring in the context of SARS-CoV2 infection. COVID-19 vaccines have been authorized since December 2020, and adverse events including myocarditis have been reported following vaccination. We describe the cases of two pediatric patients presenting with clinical and laboratory features suggestive of MIS-C a few days after receiving their first dose of the Pfizer BNT162b2 vaccine. The outcome was favorable for both patients (after corticosteroid and immunoglobulin administration for one patient). These cases suggest an association between the COVID-19 vaccine and the occurrence of MIS-C.

Hemoglobin level variability in hemodialysis patients treated with epoetin-ß during 1 year.

AIM: This analysis was performed to assess the prevalence and the factors associated with hemoglobin (Hb) variability during treatment with erythropoiesis-stimulating agents (ESA) in France. METHODS: Hb variability was evaluated in a subgroup of hemodialysis (HD) patients of the French cohort DiaNE. Eligible patients had received epoetin-ß at least 6 months before entering DiaNE, 12 months during DiaNE and had no missing monthly Hb measurements. Up and down excursions (Hb variations > 1.5 g/dl with duration > 8 weeks) were assessed. RESULTS: Of the 499 patients evaluated in this analysis, 295 (59%) had Hb levels inside the target range of 11 - 13 g/dl at baseline. The number of patients with constantly stable Hb level inside the target range decreased from baseline to 27.5% at 6 months and 10.8% at 12 months. More than 70% of patients experienced Hb variability. The number of excursions was 1.7 ± 0.8 per patient/year. The amplitude of up excursions was 2.8 ± 1.0 g/ dl with a duration of 14.7 ± 4.7 weeks. The amplitude of down excursions was 2.6 ± 0.9 g/dl with a duration of 14.5 ± 4.6 weeks. The main factors associated with Hb variability were number of epoetin-ß dose changes, adverse events and iron therapy changes. CONCLUSION: Hb variability is frequent in French ESA-treated HD patients and closely related to practices. Further efforts are needed to improve anemia management.

Spontaneous heterotopic triplets - A review of literature.

OBJECTIVE: Spontaneous heterotopic triplets, a tubal ectopic pregnancy and a twin pregnancy, are rare disorders. The study aimed to examine all available evidence regarding signs and symptoms, imaging findings, management and newborn outcome of spontaneous heterotopic triplets. DESIGN: A literature search in Medline and EMBASE databases from 2000 to 2016 was conducted. The following key words were employed: 'spontaneous heterotopic pregnancy', OR 'heterotopic triplets'. Only cases of spontaneous heterotopic triplets without assisted reproduction techniques were included. RESULTS: Six cases were identified and included in the present review. All cases presented with abdominal pain and one case presented in shock. Hemoperitoneum was present in five cases. Laterouterine mass with adnexal gestational sac is not systematically described (3 cases/6), but was a good ultrasonographic sign of heterotopic pregnancy. All patients had tubal rupture, but anyone had vaginal bleeding. The surgical treatment was made by salpingectomy in five cases to ensure successful treatment. The mean and median gestational age at delivery were 29.9 and 37.54 weeks, respectively (range 6-41 weeks). The neonatal outcome was good for 6 newborns. CONCLUSION: Spontaneous heterotopic triplets are rare. Early surgical intervention is the key to successful treatment of heterotopic triplet pregnancy and allows good neonatal outcome.

Low bone mineral density and peripheral blood monocyte activation profile in calcium stone formers with idiopathic hypercalciuria.

Calcium stone formers (CaSF) with idiopathic hypercalciuria (IH) have been shown to have decreased bone mineral density (BMD). The mechanism of their bone loss remains obscure. Monokines like interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor-alpha (TNF-alpha), and granulocyte macrophage stimulating factor (GM-CSF) are involved in bone remodeling, but only IL-1 excess has been incriminated in the bone loss of CaSF with IH. Therefore, to more precisely delineate the role of monocyte activation in the pathogenesis of bone loss in these patients, we studied the production of IL-1 beta, IL-6, TNF-alpha, and GM-CSF by unstimulated or lipopolysaccharide (LPS)-stimulated cultured peripheral blood monocytes in 15 CaSF with IH, in 10 CaSF with dietary calcium-dependent hypercalciuria (DH), and in 10 healthy controls (C). Cytokines were measured in the culture medium by sensitive enzyme-linked immunosorbent assay and vertebral BMD by single energy computed tomography. The decrease of vertebral BMD in IH compared with DH, was confirmed (Z score: -1.2 +/- 0.2 vs. -0.5 +/- 0.2; P = 0.04; Mann-Whitney). In the supernatant of unstimulated peripheral blood monocytes, IL-1 beta and TNF-alpha levels were higher in IH than in C (respectively, 40 +/- 21 vs. 7 +/- 1 pg/mL, P = 0.008 and 236 +/- 136 vs. 39 +/- 23 pg/mL, P = 0.03); those of GM-CSF were greater in IH than in DH and C (respectively, 52 +/- 27 vs. 6 +/- 2, P = 0.04 and 6 +/- 2 pg/mL, P = 0.01) and those of IL-6 were not significantly different among the groups. After in vitro stimulation by LPS (10 micrograms/mL), the levels of the various monokines were not significantly different. In IH patients, the post-LPS levels of IL-6 were negatively correlated to vertebral BMD (n = 15, Z = -1.97, P = 0.04; Spearman), whereas those of GM-CSF were positively related to vertebral BMD (n = 15, Z = 2.01, P = 0.04). In this study, calcium stone formers with IH have bone mineral decrease and a particular profile of peripheral blood monocytes activation. This latter is characterized by a spontaneously increased synthesis of IL-1 beta, TNF-alpha, and GM-CSF. Furthermore, post-LPS levels of IL-6 and GM-CSF are correlated with vertebral BMD. These results suggest that monocyte activation may be involved in the bone loss of calcium stone formers with IH.

Serial measurements of antineutrophil cytoplasmic autoantibodies in patients with systemic vasculitis.

PURPOSE: To assess the value of serial determinations of antineutrophil cytoplasmic autoantibodies (ANCA) for monitoring disease activity in patients with systemic vasculitis. PATIENTS AND METHODS: Forty-three patients with histologically proven vasculitis (21 with Wegener's granulomatosis, 17 with microscopic polyangiitis, and 5 with renal-limited vasculitis) were studied for a median follow-up of 22 months. Disease activity was prospectively assessed and quantified by the Birmingham Vasculitis Activity Score. A total of 347 sera were analyzed for ANCA determination. RESULTS: Relapses occurred in 23 (54%) of 43 patients. Diagnostic category (Wegener's granulomatosis vs micropolyangiitis and renal-limited vasculitis), severity of initial symptoms (mean vasculitis activity score, mean number of organs involved), and ANCA pattern [cytoplasmic-ANCA (c-ANCA) vs perinuclear-ANCA (p-ANCA)] did not significantly differ between relapsers and nonrelapsers. Lung involvement was more frequent at onset among relapsers [16 of 23 (70%) vs 6 of 20 (30%); P = 0.02]. Relapses were slightly, but not significantly, more frequent in patients with Wegener's granulomatosis or a c-ANCA pattern. The percentage of relapsers was greater in patients with persistently positive ANCA than in patients with negative or decreasing ANCA titers (86% vs 20%, P = 0.0001). However, the predictive value of an increase in ANCA titers for the occurrence of a subsequent relapse was only 28% (4 of 14) for c-ANCA, 12% (2 of 17) for anti-proteinase 3-ANCA, and 43% (6 of 14) for anti-myeloperoxidase-ANCA. An increase in ANCA occurred before or during relapse in 33% (10 of 30) of cases for c-ANCA/anti-proteinase 3 antibodies, and 73% (11 of 15) of cases for anti-myeloperoxidase antibodies. CONCLUSION: The persistence of ANCA positivity is strongly associated with relapses. However, an increase in ANCA titers has a poor value for the early prediction of a subsequent relapse and should not be used as a sole parameter for therapeutic intervention. In addition, our results suggest that serial anti-myeloperoxidase determination may be useful as a prognostic marker in patients who are p-ANCA positive.

[Transperineal repair of rectocele with prosthetic mesh. A prospective study]. / Traitement de la rectocèle par voie périnéale avec prothèse. Une étude prospective.

PURPOSE: To assess the long term results of a transperineal repair of rectocele with a prosthetic mesh and the criteria for selecting the patients. METHODS: Twenty-five consecutive patients (median age: 60 years) with a symptom-giving rectocele have been operated upon. Indication for surgery was: an obstructed defecation (N = 22); a fecal incontinence (N = 1); a pelvic heaviness with dyspareunia (N = 1) or a severe rectal syndrome (N = 1). Patients were evaluated by physical examination and, preoperatively, by defecography and anorectal manometry. The rectovaginal septum was repaired, through a perineal approach, with an absorbable (N = 5) or non absorbable (N = 20) prosthetic mesh. Long term results were assessed after a median follow-up of 45 (range 12-120) months by physical examination and a standardized questionnaire. The presence of the following three symptoms was evaluated: feeling of incomplete emptying, prolonged and unsuccessful straining at stool, digital assistance. Outcome was considered as successful when none of these symptoms were present, as good when minor emptying difficulties persisted, as moderate when emptying difficulties were associated with straining, as a failure when the symptomatic triad was unchanged. A general satisfaction score was established. RESULTS: All the patients had the defect of the rectovaginal septum corrected. Four patients had a low residual rectocele associated, in two cases, with a rectal prolapse subsequently treated by a Delorme's operation. Outcome in patients complaining of obstructed defecation was considered excellent or good in 80% of patients, moderate in 9% and poor in 9%. Subjective scoring showed a significantly better result in cases of success. Among 11 incontinent patients, seven (63.5%) improved or regained full continence. Dyspareunia in three cases was corrected. Age, parity, digital assistance, previous gynecologic surgery, use of laxatives, size of rectocele, type of mesh, anatomical result of repair had no significant prognostic value. On the other hand, in patients with obstructed defecation, clinical and manometric signs of anal hyperactivity of the pelvic floor or anismus (N = 4) were significantly related to a poor result (P < 0.001). CONCLUSION: Surgical repair with a prosthetic mesh is an efficient therapy in patients with obstructed defecation and/or incontinence caused by a rectocele. Clinical and defecographic parameters have no influence on outcome. Preoperative manometric data may help in selecting patients. In case of anal hyperactivity or anismus, given the risk of functional failure, behavioral retraining must be considered as first-line treatment.

[Renal and hypertensive complications of extracorporeal lithotripsy]. / Complications rénales et hypertensives de la lithotritie extracorporelle: les patients à risque.

HISTOLOGICAL AND FUNCTIONAL CONSEQUENCES OF ESWL: Extracorporeal shock wave litotripsy is now used for the treatment of about 90% of stones. Because of the nonpunctual delivery of energy into the stone, a small volume of renal parenchyma is injured, giving rise to a fibrous scar which can be visualized by morphological techniques such as magnetic nuclear resonance. Isotopic techniques point out a 15% reduction of renal plasma flow on the side of the litotripsy. For a majority of patients, this alteration is transient. HYPERTENSION: In a few cases, abrupt onset of transient hypertension has been reported in clear relation with a compressive perirenal hematoma. The causal effect of ESWL on late occurrence of permanent hypertension is however still uncertain, probably because of the difficulty to show that this occurrence is not related to the older age of the patient alone. The FDA sponsored multicentric study begun in 1993 should solve this issue in the future. PATIENTS AT RISK: Recent articles suggest that altered renal function prior to ESWL would predict late occurrence of hypertension and worsening of renal failure. Furthermore, age and the resistance index of arcuate or interlobular renal arteries (measured by Doppler) could help to screen the patients at risk of developing hypertension. Practical attitude: In practice, renal function and blood pressure should be carefully monitored in patients aged over 60 and/or who have a serum creatinine > 300 mumol/l.

[Physiopathology, exploration and treatment of calcium lithiasis]. / Physiopathologie, exploration et traitement de la lithiase calcique.

The main risk factors for calcium urolithiasis that are clinically detectable are low diuresis, hypercalciuria, hyperruricuria, alkaline urinary pH, hyperoxaluria, hypomagnesuria, hypocitraturia. They should be evaluated, all the more precisely that the disease is active, under both the urological and metabolic points of view, using 24 hour urine collection made at home on a free diet with a dietary record. In the majority of the cases the calcic urolithiasis is idiopathic, i.e. not related to a cause of secondary hypercalciuria like primary hyperparathyroidism, or to a hyperroxaluria either primary or of digestive or toxic origin. Its treatment if mainly dietary with high fluid intake (diuresis greater than 2 1/24 h), normoclacic diet (800-1000h mh/24 h) with meat but not dairy product restriction, oxalate salts, carbohydrate and alcohol restriction. These dietary recommendations should be controlled by measuring the above cited parameters in the 24 hour urine samples and by measuring urea excretion which should not exceed 0.33 g/kg of body weight. When diet fails, drugs may be added mainly allopurinol, thiazides and potassium citrate.

Phenotype-genotype correlation and follow-up in adult patients with hypokalaemia of renal origin suggesting Gitelman syndrome.

INTRODUCTION: Gitelman syndrome (GS) is a tubulopathy caused by SLC12A3 gene mutations, which lead to hypokalaemic alkalosis, secondary hyperaldosteronism, hypomagnesaemia and hypocalciuria. AIM: The aim of this study was to assess the prevalence of SLC12A3 gene mutations in adult hypokalaemic patients; to compare the phenotype of homozygous, heterozygous and non-mutated patients; and to determine the efficiency of treatment. METHODS: Clinical, biological and genetic data were recorded in 26 patients. RESULTS: Screening for the SLC12A3 gene detected two mutations in 15 patients (six homozygous and nine compound heterozygous), one mutation in six patients and no mutation in five patients. There was no statistical difference in clinical symptoms at diagnosis between the three groups. Systolic blood pressure tended to be lower in patients with two mutations (P=0.16). Hypertension was unexpectedly detected in four patients. Five patients with two mutated alleles and two with heterozygosity had severe manifestations of GS. Significant differences were observed between the three groups in blood potassium, chloride, magnesium, supine aldosterone, 24 h urine chloride and magnesium levels and in modification of the diet in renal disease. Mean blood potassium levels increased from 2.8 ± 0.3, 3.5 ± 0.5 and 3.2 ± 0.3 before treatment to 3.2 ± 0.5, 3.7 ± 0.6 and 3.7 ± 0.3 mmol/l with treatment in groups with two (P=0.003), one and no mutated alleles respectively. CONCLUSION: In adult patients referred for renal hypokalaemia, we confirmed the presence of mutations of the SLC12A3 gene in 80% of cases. GS was more severe in patients with two mutated alleles than in those with one or no mutated alleles. High blood pressure should not rule out the diagnosis, especially in older patients.