Towards a better understanding of adult idiopathic epidermal necrolysis: a retrospective study of 19 cases.

BACKGROUND: Most cases of Stevens-Johnson syndrome and toxic epidermal necrolysis are drug-induced. A small subset of cases remain with unknown aetiology (idiopathic epidermal necrolysis [IEN]). OBJECTIVE: We sought to better describe adult IEN and understand the aetiology. METHODS: This retrospective study was conducted in 4 centres of the French national reference centre for epidermal necrolysis. Clinical data were collected for the 19 adults hospitalized for IEN between January 2015 and December 2019. Wide toxicology analysis of blood samples was performed. Histology of IEN cases was compared with blinding to skin biopsies of drug-induced EN (DIEN, 'controls'). Available baseline skin biopsies were analysed by shotgun metagenomics and transcriptomics and compared to controls. RESULTS: IEN cases represented 15.6% of all EN cases in these centres. The median age of patients was 38 (range 16-51) years; 68.4% were women. Overall, 63.2% (n = 12) of cases required intensive care unit admission and 15.8% (n = 3) died at the acute phase. Histology showed the same patterns of early- to late-stage EN with no difference between DIEN and IEN cases. One toxicology analysis showed unexpected traces of carbamazepine; results for other cases were negative. Metagenomics analysis revealed no unexpected pathological microorganism. Transcriptomic analysis highlighted a different pro-apoptotic pathway in IEN compared to DIEN, with an overexpression of apoptosis effectors TWEAK/TRAIL. CONCLUSIONS: IEN affects young people and is a severe form of EN. A large toxicologic investigation is warranted. Different pathways seem involved in IEN and DIEN, leading to the same apoptotic effect, but the primary trigger remains unknown.

Clinical and microcirculatory effects of transcutaneous CO2 therapy in intermittent claudication. Randomized double-blind clinical trial with a parallel design.

BACKGROUND: This randomized, double blind trial determined the short and long-term clinical and hemodynamic vasodilator effects induced by percutaneous applications of natural CO2 gas in patients with moderate Fontaine stage II. PATIENTS AND METHODS: 62 patients with intermittent claudication (100-500 meters) were randomized to 18 consecutive days of CO2 treatment or placebo (air). The gas fluids were applied at a constant temperature of 30 degrees C on pre-humidified skin. The effects of the treatment were evaluated by total distance walked (primary criterion) and hemodynamic and microcirculatory findings. Patients also answered a quality of life questionnaire. RESULTS: The Strandness test showed a significant increase in total distance walked (+ 131 meters, 66%; p = 0.001) and pain-free distance (+ 81 meters, 73%; p = 0.02) after 18 days of CO2 treatment. The improvement was maintained 3 and 12 months later. The systolic pressure index (ABI) increased by 37% (p = 0.001) 1 minute after treadmill walking and ABI recovery time decreased significantly by 38% (p = 0.002). Microcirculatory findings showed an increase in systolic pressure of the great toe (13%; p < 0.0001), in baseline pO2 (20%; p = 0.01) and in vasomotion (78%; p = 0.001) in the treatment group. The improvement in total walking distance was correlated with the increase in ABI and peripheral cutaneous oxygenation. Patients' subjective assessments corroborated the benefits. No significant change was observed in the placebo group. CONCLUSIONS: This study demonstrates that 18 consecutive days of percutaneous CO2 treatment significantly increases walking distance in patients with moderate intermittent claudication. This effect, which was associated with an increase in peripheral systolic pressure and pO2, is evidence of a better ability to withstand effort.

Evaluation of the organization of the homoionic smectite layers (Na(+) or Ca(2+)) in diluted dispersions using granulometry, microscopy and rheometry.

Smectites are swelling clay materials with pronounced colloidal properties that are widely used in industry. These properties originate in the electrokinetic properties of the smectite layers and their linkage capacities. Thin layers may be dispersed or aggregated according to many parameters, such as concentration, particle size and morphology, exchangeable cation nature and chemical environment (pH, ionic strength). The literature usually provides general rules, like the sodium dispersion contains a lot of small units whereas the calcium dispersion contains a few large units. A volume of water molecules bound to the clay surface is considered as the immobile water phase that behaves like the solid phase obstructing the flow. The water immobilized around layers and trapped inside aggregates cannot participate to the flow. In this study, we evaluated the volume occupied by calcium and sodium units inside the dispersion containing the immobile water phase. First, the smectite was cautiously extracted from a raw bentonite and its physicochemical properties were determined. A large quantity of extracted and saturated smectite (Na-smectite and Ca-smectite) was obtained. Second, the unit size and a shape factor for each sample were evaluated using granulometry and scanning transmission electron microscopy on wet samples (Wet STEM) and some flow curves. Na-smectite dispersions contain 0.13 microm(2) surface units with a shape factor of 50. Ca-smectite dispersions contain 0.32 microm(2) surface units with a shape factor of 3.3. Finally, rheometry allowed us to evaluate the unit occupancy using an adaptation of the Krieger-Dougherty law. We used shape factors and evaluated the concentration from which the entire immobile volume was connected (6.4% for Na-smectite and 11.9% for Ca-smectite). This study explains the evolution of flow properties with increasing concentrations by the evolution of layer interactions at the microscopic scale for homoionic smectite particles in diluted dispersions.

Microcirculatory and clinical effects of serial percutaneous application of carbon dioxide in primary and secondary Raynaud's phenomenon.

BACKGROUND: A randomized double-blind monocentric trial was conducted at the spa of Royat, France, in patients with mild Raynaud's phenomenon (one or two attacks a day during the autumn and winter months). Hemodynamic changes were quantified by laser Doppler flow (LDF) and computerized chronothermometric test (CT) during local application of CO2 and compared with the usual clinical parameters. PATIENTS AND METHODS: Patients were randomized to 18 days of CO2 (group 1) or 9 days of air + 9 days of CO2 (group 2). The gas was applied at a constant temperature to previously humidified skin on the forearm. Effects of the active treatment were measured by LDF and continuing benefits by computerized chronothermometric test (CT test). Clinical assessment was made on four occasions (before, in the middle and at the end of treatment, and three months afterwards) on the basis of the number of daily attacks and the duration and severity of the attacks. RESULTS: LDF showed a significant increase in digital blood flow (+ 41%) and in vasomotion (+ 42%) during CO2 treatment but no change on placebo treatment. CT test showed a comparable response to cold in the two groups during treatment. Three months later, however, warming time was significantly decreased (by 7 minutes: 25%) and warming rate increased (+ 22.4%) in group 1 (intergroup difference: p = 0.02). There was no difference between groups in the weekly number of attacks during treatment periods. In contrast there was a moderate increase in both groups in the winter months. There was no increase in the severity of the attacks nor in their duration. CONCLUSION: In this clinical trial, LDF evidenced positive effects of percutaneous application of natural CO2 gas on vasomotricity and vasomotion while CT test showed that patients who had received 18 days of CO2 adapted more easily to exposure to cold. Clinical improvement seems to be masked by winter weather conditions.

[Evaluation of atherogenic risk in homozygous sickle cell disease: study of lipid and apolipoprotein AI and B plasma levels]. / Evaluation du risque athérogène chez le drépanocytaire homozygote: étude des taux plasmatiques des lipides et apolipoprotéines AI et B.

The main clinical use of measurements of Apo Al and Apo B is to determine a patient's risk status for the development of ischemic heart disease. Apo B is generally accepted as a contributory cause of coronary artery disease, while Apo Al apparently has a protective effect. The present study reports the plasma change of Apo Al and B in sickle cell anaemic subjects. Immunochemical findings revealed that Apo Al and B levels were found to be lower in sickle cell patients as compared with normal subjects (HbAA). The atherogenicity index given by Apo B/Apo Al remained in the normal range during periods of steady state (0.64 +/- 0.28), while subjects in painful crisis had high index values (0.95 +/- 0.35). Therefore, we concluded that epidemiological studies on a large sample of patients are needed to confirm this relationship between painful crisis and risk of developing coronary artery disease.

[Severe urinary tract and cutaneous lesions after umbilical cord artery puncture and direct injection of hypertonic sodium bicarbonate to the newborn in the delivery room. Report of three cases (author's transl)]. / Lésions urinaires et cutanées par ponction d'une artère du cordon ombilical et injection à la serinque de soluté bicarbonaté hypertonique chez le nouveau-né en salle d'accouchement. A propos de trois observations.

Three cases of necrotizing and calcifying lesions of low urinary tract, buttock and adjacent perineum are reported. These lesions have been induced by direct syringe injection into an umbilical artery of 42% sodium bicarbonate solution at the dose of 5 to 6 ml/kg of body weight. Radiographic examinations are very important to study the urinary tract lesions. These have been surgically controlled in two cases. The follow up ranges from 10 to 21 1/2 months. On the bladder initial necrotizing lesions are followed by calcification and parietal retraction. These bladder lesions induce a more or less important ureterohydronephrosis. To these constant lesions are variably associated urethral calcifications and stenosis, distal ureter calcifications. These lesions seem to be related to the sodium bicarbonate hyperosmolality, to the injection conditions, and to the local hemodynamic features.

[Situs inversus and long-term bronchopneumopathies, existing since the neonatal period]. / Situs inversus et bronchopneumopathies au long cours, dès la période néonatale.

Four boys are described who developed respiratory difficulties and broncho-pulmonary disease in the neonatal period. Three had situs inversus, and one situs ambiguus (Ivemark's syndrome). The symptoms continued for several months or years and in three children progressed to bronchiectasis. The other child is recovered. Two the children were brothers and a third sib. presented with bronchopulmonary disease at birth that continued for 17 months. He did not have situs inversus.

[Alpha chain disease. Report of a case (author's transl)]. / A propos d'un cas de maladie des chaînes alpha.

A young patient, with alpha chain disease, is in good clinic condition, a little more than 4 years after the diagnosis. She received, during 1 year, antibiotics of tetracycline type, then antimitotics during 2 years. 9 months after antimitotics treatment was achieved, histologic signs remained unmodified, without evidence of degenerescence. Immunoelectrophoresis which was normal at the end of chemotherapy is always normal after 15 months without treatment.

[Glutaric aciduria. 1 new case]. / Acidurie glutarique. Une nouvelle observation.

A 4 year old girl with mild mental retardation presented with convulsions, coma and hepatomegaly. She died rapidly. The main biochemical findings were hypoglycaemia, metabolic acidosis, generalised aminoaciduria, elevation of the plasma and urine alpha-amino adipic acid, massive urine excretion of glutaric and glutaconic acids with traces of alpha-hydroxyglutaric acid. The diagnosis of glutaric aciduria was confirmed by the low activity of glutaryl CoA dehydrogenase in liver tissue. This diagnosis should be considered in children with progressive neurological disorders (dystonia, choreoathetosis) and in children with an illness similar to Reye's syndrome.

Hyperthyroidism, diabetes mellitus and the congenital rubella syndrome.

A male patient born to a mother who developed rubella during the tenth week of gestation presented a typical congenital rubella syndrome with mental retardation, neuro-sensory deafness, hypoplasia of the dental enamel and chorioretinitis. Hyperthyroidism occurred at the age of 3 10/12 years and was treated successfully with propylthiouracil for 4 years. The course was complicated by premature craniosynostosis and a craniectomy was performed at the age of 7 years. Overt diabetes mellitus developed at 17 years and was well controlled by insulin therapy. Histocompatilibity (HLA) antigens were A2, B8, B40. Diabetes mellitus and thyroid disorders have previously been reported after congenital rubella, and recently after congenital cytomegalovirus infection. Our patient had both endocrinopaties. It is possible that HLA B8 antigens might be responsible for increased susceptibility to rubella infection.

[Prevention of septicemia caused by gastrointestinal tract organisms in patients with granulopenia. Comparison of three gastrointestinal tract decontamination treatments]. / Prévention des septicémies d'origine digestive chez les granulopéniques: comparaison de trois traitements de décontamination digestive.

Three gastrointestinal tract decontamination regimens were tested in patients with granulopenia: vancomycin 250 mg, tobramycin 75 mg, and colistin 1 million international units (regimen A); vancomycin 125 mg, tobramycin 75 mg, and colistin 1 million IU (regimen B); and colistin 1 million IU (regimen C); nystatin was added to all three regimens. Effectiveness was evaluated by stool organism counts and blood cultures to detect bacterial translocation (passage of bacteria from the intestinal tract to the bloodstream). Regimen C proved insufficiently effective. Regimen A was found to be poorly tolerated by the digestive mucosa. Regimen B was the best treatment since the low dosage of vancomycin proved effective. Nystatin satisfactorily eliminated yeasts.

[Bacterial endocarditis due to Corynebacterium diphtheriae (author's transl)]. / Endocardite infectieuse à Corynebacterium diphtheriae.

A case of bacterial endocarditis with unusual features in a 5 year-old boy is reported. There was no underlying heart disease or provocating factor. The organism was a non toxigenic Corynebacterium diphtheriae which was difficult to classify. It appeared to be close to the JK group of Corynebacterium described by the Center for Disease Control and considered as possibly responsible for severe infections. However, it was sensitive to penicillin. The course of the disease was complicated by the destruction of coronary valves and by splenic infarctus. Replacement of the aortic valve with a prosthesis was necessary. The boy was finally cured but the outcome remains uncertain.