Adrien Bigot

The Clinical Spectrum and Therapeutic Management of Hypocomplementemic Urticarial Vasculitis: Data From a French Nationwide Study of Fifty‐Seven Patients

Hypocomplementemic urticarial vasculitis (HUV) is an uncommon vasculitis of unknown etiology that is rarely described in the literature. We undertook this study to analyze the clinical spectrum and the therapeutic management of patients with HUV.

Pulmonary manifestations of Sjögren's syndrome.

In 9–20% of cases, Sjögrens syndrome is associated with various respiratory symptoms. The most typical manifestations are chronic interstitial lung disease (ILD) and tracheobronchial disease. The most common manifestation of ILD is nonspecific interstitial pneumonia in its fibrosing variant. Other types of ILD, such as organising pneumonia, usual interstitial pneumonia and lymphocytic interstitial pneumonitis, are rare. Their radiological presentation is less distinctive, and definitive diagnosis may require the use of transbronchial or surgical lung biopsy. Corticosteroid therapy is the mainstay of ILD treatment in Sjögrens syndrome, but the use of other immunosuppressive drugs needs to be determined. ILD is a significant cause of death in Sjögrens syndrome. Tracheobronchial disease is common in Sjögrens syndrome, characterised by diffuse lymphocytic infiltration of the airway. It is sometimes responsible for a crippling chronic cough. It can also present in the form of bronchial hyperresponsiveness, bronchiectasis, bronchiolitis or recurrent respiratory infections. The management of these manifestations may require treatment for dryness and/or inflammation of the airways. Airway disease has little effect on respiratory function and is rarely the cause of death in Sjögrens syndrome patients. Rare respiratory complications such as amyloidosis, lymphoma or pulmonary hypertension should not be disregarded in Sjögrens syndrome patients. We present the features, diagnostic tests and treatments of thoracic manifestations of Sjögrens syndrome http://ow.ly/10m8vd

Psychiatric adult-onset of urea cycle disorders: A case-series

Adult onset urea cycle disorders (UCD) may present with psychiatric symptoms, occasionally as the initial presentation. We aimed to describe the characteristics of patients presenting with a psychiatric adult-onset of UCDs, to discuss which signs could suggest this diagnosis in such a situation, and to determine which tests should be conducted. A survey of psychiatric symptoms occurring in teenagers or adults with UCD was conducted in 2010 among clinicians involved in the French society for the study of inborn errors of metabolism (SFEIM). Fourteen patients from 14 to 57 years old were reported. Agitation was reported in 10 cases, perseveration in 5, delirium in 4, and disinhibition in 3 cases. Three patients had pre-existing psychiatric symptoms. All patients had neurological symptoms associated with psychiatric symptoms, such as ataxia or dysmetria, psychomotor slowing, seizures, or hallucinations. Fluctuations of consciousness and coma were reported in 9 cases. Digestive symptoms were reported in 7 cases. 9 patients had a personal history suggestive of UCD. The differential diagnoses most frequently considered were exogenous intoxication, non-convulsive status epilepticus, and meningoencephalitis. Hyperammonemia (180–600 μmol/L) was found in all patients. The outcome was severe: mechanical ventilation was required in 10 patients, 5 patients died, and only 4 patients survived without sequelae. Adult onset UCDs can present with predominant psychiatric symptoms, associated with neurological involvement. These patients, as well as patients presenting with a suspicion of intoxication, must have UCD considered and ammonia measured without delay.

Periprandial administration of inhaled iloprost: a risk factor for digestive bleeding?

The role of inhaled iloprost should be suspected in cases of gastro-intestinal haemorrhage in patients suffering from pulmonary hypertension (PH) receiving this treatment, and the way the drug is administered should possibly be changed. n nClinical, functional and haemodynamic deterioration of systemic scleroderma-PH in a 73-year-old Caucasian woman without any other past medical history, led to the introduction of aerosolized iloprost 5 µg six times a day in addition to her existing treatment of sitaxentan 100 mg once daily, sildenafil 20 mg three times daily, furosemide 40 mg once daily, bromazepam 6 mg one to two times daily, calcium 1000 mg once daily, cholecalciferol 880 IU once daily, monosodic alendronate 70 mg weekly, fluindione 20 mg once daily with an international normalized ratio (INR) maintained between 2 and 3. In the past, she had had occasional melaena, once a month, generally the day following alendronate ingestion. Two months after beginning aerosolized iloprost, the frequency of her melaena increased, becoming continuous, after each aerosolization (INR = 2.18). An oesogastroduodenal endoscopy revealed digestive angiomatosis, and the hypothesis that iloprost could play a role in causing this lesion to bleed was raised. As reassessment of pulmonary hypertension suggested the benefit of inhaled iloprost, it was decided to reduce the regimen to five aerosols a day, avoiding the first post-prandial hour. The frequency of melaena decreased and abdominal meteorism stopped completely. Reducing the dose of aerosols did not have any effect on the PH at the next reassessment. n nIn a 79-year-old Caucasian man with a past medical history of ischaemic cardiomyopathy, inhaled iloprost aerosol 5 µg six times a day was initiated following deterioration of a PH secondary to a chronic obstructive pulmonary disease, in association with previous treatment with sildenafil 20 mg three times daily, bosentan 125 mg two times daily, fluindione 20 mg once daily (INR between 2 and 3 throughout follow-up), furosemide 40 mg once daily, amiodarone 200 mg once daily, pravastatin 40 mg once daily, ramipril 5 mg once daily, clopidogrel 75 mg once daily, tiotropium bromide 1 inhalation day−1, molsidomine 2 mg three times daily and potassium chloride 600 mg day−1. n nOne month earlier, anaemia with iron deficiency had been diagnosed and treated by blood transfusion and ferrous sulphate supplements (80 mg two times daily). Oesogastroduodenal endoscopy had revealed millimetric bleeding angiodysplasias in the duodenal cap, which had been treated by argon plasma coagulation. Four months after beginning inhaled iloprost, haemoglobinaemia was 85 g l−1 with iterative digestive haemorrhages requiring several blood transfusions, despite ongoing ferrous supplementation. A colonoscopy found a 3 mm caecal angiodysplasia and two colic polyps requiring argon plasma coagulation therapy and polypectomy. In spite of this digestive procedure, gastro-intestinal haemorrhage continued and consequently clopidogrel was stopped and iloprost reduced to 5 aerosols a day, avoiding the immediate post-prandial period. There was no recurrence of digestive bleeding and haemoglobin stabilized. At the next reassessment, there had been no worsening of PH. n nThese two cases suggest a possible link between digestive haemorrhage and iloprost aerosols. There was a temporal relationship between inhalation of iloprost and the onset or worsening of bleeding, and between the reduced dose of iloprost inhalation and improvement of bleeding symptoms. The digestive haemorrhage did not recur after the iloprost dosage was reduced and inhalation was avoided after meals. The role of fluindione can be excluded because the INR did not increase and because bleeding symptoms improved despite the continuation of fluindione treatment. In the second patient, stopping clopidogrel may have had a beneficial effect on gastro-intestinal haemorrhage, but the symptoms worsened when iloprost was started, requiring blood transfusion. The role of other drugs can be ruled out as bleeding symptoms improved despite the continuation of these drugs. Neither of these patients had any history of liver disease. n nThe evidence for the effect of inhaled iloprost on digestive bleeding is strong and possibly multifactorial. Iloprost is an analogue of epoprostenol. Besides its vasodilatory effect, it inhibits platelet function in a dose-related manner and platelet aggregability returns to baseline levels after the end of the infusion [1]. Because its absolute bioavailability is approximately 80% [2], inhaled iloprost may induce sufficiently high serum concentrations to produce adverse systemic effects. Splanchnic blood flow increases after iloprost administration [3], which could promote the bleeding of an angioma. This pharmacodynamic effect could also explain why bleeding symptoms improved when iloprost was no longer inhaled close to meals. It is possible that part of the aerosolized iloprost is swallowed rather than truly inhaled and could have a direct action on the digestive cell wall. Prostaglandins inhibit secretion of histamine and pancreastatin by enterochromaffin-like cells of the gastric epithelium and therefore decrease gastric acidity, making the hypothesis that digestive haemorrhage is related to gastro-duodenal ulcers highly improbable [4]. n nIn conclusion, these observations suggest that patients with a risk of digestive bleeding should avoid inhaled aerosols during peri-prandial periods as far as possible, and that patients with a history of digestive bleeding should be monitored clinically and biologically during the months following the introduction of inhaled iloprost.

Body Mass Index, Fatty Liver Index and Other Metabolic Disturbances Differentially Affect Albuminuria and Glomerular Filtration Rate in the General Population

Objective: Obesity and diabetes mellitus increase the risk of chronic renal disease. However, whether body mass index (BMI) and metabolic disturbances are associated with renal dysfunction and affect similarly albuminuria and estimated glomerular filtration rate (eGFR) are less clear. Hence, the aim of this study was to describe these associations in the general French population. nMethods: We realised a large cross-sectional study of 118,314 subjects aged ≥ 40 years undergoing a medical examination in 11 French regional health centers. Results: Renal dysfunction ((abnormal albuminuria (≥ 30 mg/g) and/or low eGFR ( 40: 7.35 [5.89-9.15]) had a greater risk of abnormal albuminuria than subjects with normal weight. In contrast, the relationship between BMI - or other metabolic disturbances- and low eGFR was continuous. Metabolic disturbances increased the risk of abnormal albuminuria to a greater extent than the risk of abnormal eGFR. High fatty liver index and high calculated risk of developing diabetes were risk factors for both abnormal albuminuria and low eGFR. nConclusion: There is a J-curve relationship between BMI and abnormal albuminuria, in contrast to the continuous association between other metabolic disturbances and abnormal eGFR. All metabolic disturbances are associated with abnormal albuminuria, but the association with abnormal eGFR is less clear, suggesting a stronger relationship with endothelial than renal dysfunction. Abnormal albuminuria and eGFR may precede the onset of diabetes.

Liver involvement in urea cycle disorders: a review of the literature

Urea cycle disorders (UCDs) are inborn errors of metabolism of the nitrogen detoxification pathway and encompass six principal enzymatic deficiencies. The aging of UCD patients leads to a better knowledge of the long-term natural history of the condition and to the reporting of previously unnoticed manifestations. Despite historical evidence of liver involvement in UCDs, little attention has been paid to this organ until recently. Hence, we reviewed the available scientific evidence on acute and chronic liver dysfunction and liver carcinogenesis in UCDs and discuss their pathophysiology. Overall, liver involvement, such as acute liver failure or steatotic-like disease, which may evolve toward cirrhosis, has been reported in all six main UCDs. Excessive glycogen storage is also a prominent histologic feature, and hypoglycemia has been reported in citrin deficiency. Hepatocarcinomas seem frequent in some UCDs, such as in citrin deficiency, and can sometimes occur in non-cirrhotic patients. UCDs may differ in liver involvement according to the enzymatic deficiency. Ornithine transcarbamylase deficiency may be associated more with acute liver failure and argininosuccinic aciduria with chronic liver failure and cirrhosis. Direct toxicity of metabolites, downstream metabolic deficiencies, impaired tricarboxylic acid cycle, oxidative stress, mitochondrial dysfunction, energy deficit, and putative toxicity of therapies combine in various ways to cause the different liver diseases reported.

Strong heterogeneity of outcome reporting in systematic reviews

OBJECTIVESnThe Core Outcome Measures in Effectiveness Trial initiative aims at developing core outcome set (COS) for research. Consensus on a COS for renoprotection research is lacking. We performed a systematic review (SR) of SRs of renoprotection to identify outcomes used in renoprotection research and to assess how frequently these outcomes could be meta-analyzed in the SRs.nnnSTUDY DESIGN AND SETTINGnWe searched for SRs with meta-analyses of renoprotection treatments in the Database of Abstracts of Reviews of Effects and in MEDLINE and collected outcomes that were meta-analyzed. For each outcome and SR, we assessed the proportion of trials/patients that could be meta-analyzed.nnnRESULTSnWe retrieved 66 SRs. A total of 609 outcomes were extracted for 20 distinct renoprotection outcomes. The median (interquartile range) proportion of SRs in which these outcomes had been meta-analyzed was 8% (2%, 27%) (range 2-50%). The proportion of trials that had been aggregated was >75% for only 36% of the outcomes.nnnCONCLUSIONnThe outcomes meta-analyzed in renoprotection trials are heterogeneous, with a low proportion of trials or patients pooled for each outcome and each SR. A COS is needed in renoprotection research to limit this waste of research. The outcomes identified in the present work could be a basis for this COS.

Letter to the Editor: Central Nervous System Involvement in Relapsing Polychondritis, a Rare and Difficult Diagnosis: a Case Report

Graphical Abstract