Transgenerational impact of topical steroid application on superoxide dismutase activities of hypothalamus-pituitary-adrenal axis in rats.

Topical steroids (TS) have been widely prescribed since the 1950s. This study investigated for the first time the transgenerational effects of TS on the antioxidant mechanism of the hypothalamus-pituitary-adrenal (HPA) axis, both in prenatal and infancy. Three generations (F1, F2, and F3) and prenatal group (P) were investigated in both sexes with two different time points; P45th and P75th day were accepted as puberty and early adulthood, respectively. Clobetasol propionate 0.05% was used as TS. Quantitative real-time PCR was performed to expressional analyses of Sod1, Sod2, and Sod3 genes in the HPA tissues. The Sod mRNA expression of the HPA belonging to P and F1 groups revealed similar results in both genders. The downregulation in the adrenal Sod level was determined in P and F1, F2, and F3 generations in both genders, especially in females (p < 0.05). The Sod activities in the pituitary of all groups were downregulated in female rats (p < 0.05). Interestingly, in male rats, Sod2 and Sod3 were not expressed in the pituitary compared with the control on the day P45, while Sod2 and Sod3 expressions were determined in all the groups on day P75. Sod1 overexpression was found in pituitary and hypothalamus of males in the F3 generation. This study showed that TS applied in infancy had a transgenerational adverse effect on antioxidant defense mechanisms, especially in the adrenal gland.

Inhibition of adenosine deaminase and xanthine oxidase by valproic acid abates hepatic triglyceride accumulation independent of corticosteroids in female rats treated with estrogen-progestin.

Elevated circulating uric acid has been postulated to play an important pathophysiological role in estrogen-progestin combined oral contraceptive (COC)-induced hypertension and endothelial dysfunction. We hypothesized that disruption of glucoregulation and liver triglyceride (TG) accumulation induced by COC use would be abated by valproic acid (VPA) treatment through suppression of adenosine deaminase (ADA) and xanthine oxidase (XO) activities. Female Wistar rats aged 9-10 weeks were treated with a combination of estrogen-progestin COC steroids (1.0 µg ethinylestradiol and 5.0 µg levonorgestrel; p.o.) with or without VPA (100.0 mg/kg; p.o.) daily for 6 weeks. The result shows that the disrupted glucoregulation and associated elevated hepatic ADA activity, plasma and hepatic XO activity, uric acid (UA), TG/HDL-cholesterol, total cholesterol, and malondialdehyde induced by COC treatment were attenuated by VPA treatment. However, VPA did not have any effect on plasma aldosterone, corticosterone, ADA, circulating and hepatic free fatty acid. Our results demonstrate that suppression of plasma and hepatic XO activities, along with hepatic ADA activity and UA by VPA treatment, protects against disrupted glucoregulation and increased liver TG by COC independent of elevated corticosteroids. The findings imply that VPA would provide protection against the development of cardiometabolic disorder via inhibition of the ADA/XO/UA-mediated pathway.

Our experience with wet-wrap treatment.

A wide range of treatments are currently available for severe atopic dermatitis, including systemic therapies such as ciclosporin, corticosteroids, azathioprine, methotrexate, mofetil mycophenolate, and omalizumab. In patients who can no longer take systemic drugs or who need a dose reduction, wet-wrap treatment can be an excellent option. To date, wet wraps have mostly been used in severe cases of childhood atopic dermatitis. We report our experience with wet-wrap treatment in 5 adults with atopic dermatitis and 2 with nodular prurigo. The results were satisfactory and there were few adverse effects.

Pulmonary Manifestation of Granulomatosis With Polyangiitis: A Challenging Case Presentation.

Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, is a rare and potentially life-threatening autoimmune disease characterized by antineutrophil cytoplasmic antibody (ANCA)-associated vasculature inflammation. It presents as a systemic autoimmune disease with necrotizing granulomatous inflammation and pauci-immune small vessel vasculitis. This case initially posed a diagnostic challenge due to its atypical presentation and was misdiagnosed as hypersensitivity pneumonitis. The avian precipitin screening assay was positive in our patient, which may be consistent with bird breeder's lung disease or a non-specific reactivity of the chicken antigen test. However, the presence of positive c-ANCA was pivotal for the GPA diagnosis. Here, we describe in detail the clinical manifestations, diagnostic approach, and treatment of GPA in a 54-year-old female who presented with alveolar hemorrhage, but no renal involvement. Treatment involved the use of high-dose corticosteroids to suppress the autoimmune response. Finally, we discuss the striking response of this unique form of granulomatosis with polyangiitis to corticosteroid treatment and emphasize the importance of early initiation of treatment.

Variations in the treatment of acute peripheral facial paralysis. A nationwide survey.

BACKGROUND: Acute peripheral facial paralysis may be diagnosed and treated by different specialists. OBJECTIVE: The aim of this study was to explore the variability in the treatment of Bell's palsy (BP) and Ramsay Hunt Syndrome (RHS) among different medical specialties. METHODS: An anonymous nationwide online survey was distributed among the Spanish Societies of Otorhinolaryngology (ORL), Neurology (NRL) and Family and Community Medicine (GP). RESULTS: 1039 responses were obtained. 98% agreed on using corticosteroids, ORL using higher doses than NRL and GP. Among all, only 13% prescribed antivirals in BP routinely, while 31% prescribed them occasionally. The percentage of specialists not using antivirals for RHS was 5% of ORL, 11% of NRL, and 23% of GP (GP vs. NRL p = 0.001; GP vs. ORL p < 0.0001; NRL vs. ORL p = 0,002). 99% recommended eye care. Exercises as chewing gum or blowing balloons were prescribed by 45% of the participants with statistically significant differences among the three specialties (GP vs. NRL p = 0.021; GP vs. ORL p < 0.0001; NRL vs. ORL p = 0.002). CONCLUSION: There is general agreement in the use of corticosteroids and recommending eye care as part of the treatment of acute peripheral facial paralysis. Yet, there are discrepancies in corticosteroids dosage, use of antivirals and recommendation of facial exercises among specialties.

Non-surgical treatment of aseptic olecranon bursitis: A systematic review.

OBJECTIVE: Olecranon bursitis (OB), characterized by inflammation and fluid collection in the olecranon bursa is a commonly encountered out-patient condition. The data is heterogeneous regarding a stepwise and standardized approach to aseptic OB treatment and the efficacy of intra-bursal corticosteroid injections (CSI). The objective of this review is to systematically evaluate the non-surgical treatment options for aseptic OB. METHODS: This systematic review was conducted in accordance with PRISMA recommendations. The English and non-English literature search was performed in 5 medical databases to identify studies evaluating the treatment of OB. All included studies were evaluated for risk of bias (RoB) using the revised Cochrane RoB tool for randomized control trials (RCTs) and the Newcastle-Ottawa Scale (NOS) for case-control and cohort studies. RESULTS: For the final analyses, 2 RCTs and 2 observational studies were included. The RoB for the RCTs was high and both failed to demonstrate a significant difference in terms of the resolution of OB and bursal tenderness among various invasive and non-invasive treatment options. Corticosteroid injection (CSI) was associated with a significant decline in the duration of symptoms. However, it was associated with a higher number of complications including bursal infection and skin atrophy. CONCLUSION: Based on the available data, it appears that the clinical resolution of aseptic OB can occur with conservative methods if implemented earlier in the disease course. Although CSI is more effective than other treatments, it should be reserved for refractory cases because of a higher complication rate.

[Management of neurotoxicity following CAR-T cell therapy: Recommendations of the SFGM-TC]. / Prise en charge du syndrome de neurotoxicité associée au traitement par cellules CAR-T chez l'adulte et l'enfant : recommandations de la SFGM-TC.

The immune effector cell-associated syndrome (ICANS) has been described as the second most frequent specific complication following CAR-T cell therapy. The median time to the onset of neurological symptoms is five days after CAR-T infusion. ICANS can be concomitant to cytokine release syndrome but often follows the resolution of the latter. However, 10 % of patients experience delayed onset after 3 weeks of CAR-T cell infusion. The duration of symptoms is usually short, around five days if an early appropriate treatment is given. Symptoms are heterogeneous, ranging from mild symptoms quickly reversible (alterations of consciousness, deterioration in handwriting) to more serious forms with seizures or even a coma. The ICANS severity is currently based on the ASTCT score. The diagnosis of ICANS is clinical but EEG, MRI and lumbar punction can help ruling out alternative diagnoses. The first line treatment consists of high-dose corticosteroids. During the twelfth edition of practice harmonization workshops of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), a working group focused its work on updating the SFGM-TC recommendations on the management of ICANS. In this review we discuss the management of ICANS and other neurological toxicities in patients undergoing of CAR-T cell therapy. These recommendations apply to commercial CAR-T cells, in order to guide strategies for the management neurological complications associated with this new therapeutic approach.

[Management of cytokine release syndrome and macrophage activation syndrome following CAR-T cell therapy: Guidelines from the SFGM-TC]. / Prise en charge du syndrome de relargage cytokinique et du syndrome d'activation macrophagique après traitement par CAR-T cells : recommandations de la SFGM-TC.

The use of chimeric antigen receptor T cells (CAR-T) has increased since their approval in the treatment of several relapsed/refractory B cell malignancies. The management of their specific toxicities, such as cytokine release syndrome (CRS), tends to be better understood and well-defined. During the twelfth edition of practice harmonization workshops of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), a working group focused its work on the management of patients developing CRS following CAR-T cell therapy. A special chapter has been allocated to macrophage activation syndrome (MAS), a rare but life-threatening complication post-CAR-T. In addition to symptomatic measures and preemptive broad-spectrum antibiotics, immunomodulators such as tocilizumab and corticosteroids remain the corner stone for the treatment of CRS. Tocilizumab/corticosteroids-resistant CRS associated with haemophagocytosis markers (spleen and liver enlargement, hyperferritinaemia>10,000ng/mL, hypofibrinogenemia…) should direct the diagnosis towards an overlapping CRS/MAS. An adapted treatment will be based on high-dose IV anakinra and corticosteroids and chemotherapy with etoposide at late refractory stages. These complications and others delignate the need of close collaboration with an intensive care unit.

Corticodependent bilateral trochleitis.

Trochleitis is usually a transient and non-disabling inflammation of the trochlea of superior oblique. The case is presented of a difficult to manage bilateral trochleitis in a 29-year-old woman. After an exhaustive aetiological study with neuro-imaging tests, as well as an analysis of autoimmunity and infection, no underlying cause was found. Multiple injections of corticosteroids were required in both eyes, with a partial effect. Surgical intervention was finally decided in order to visually examine the trochlea, take biopsies, and inject methylprednisolone. These were effective in relieving the symptoms. This case is exceptional due to it involving both eyes and its severity, and represented a therapeutic challenge for the clinical team.

Corticodependent bilateral trochleitis. / Trocleítis bilateral corticodependiente.

Trochleitis is usually a transient and non-disabling inflammation of the trochlea of superior oblique. The case is presented of a difficult to manage bilateral trochleitis in a 29-year-old woman. After an exhaustive aetiological study with neuro-imaging tests, as well as an analysis of autoimmunity and infection, no underlying cause was found. Multiple injections of corticosteroids were required in both eyes, with a partial effect. Surgical intervention was finally decided in order to visually examine the trochlea, take biopsies, and inject methylprednisolone. These were effective in relieving the symptoms. This case is exceptional due to it involving both eyes and its severity, and represented a therapeutic challenge for the clinical team.

[Strategies for prescription of inhaled corticosteroids in mild-to-moderate asthma]. / Stratégies de prescription des corticoïdes inhalés dans l'asthme léger à modéré.

Asthma is a common respiratory condition characterized by chronic inflammation of the airways. Most asthmatics have a mild-to-moderate form of the disease, but are still at risk of severe exacerbations and significantly impaired quality of life. This article reviews the strategies for prescription of inhaled corticosteroids in patients with mild-to-moderate asthma. The definition of asthma severity, the goals of asthma management and the adjustment of therapeutics are successively addressed. The major changes proposed by the GINA group in 2019 are also discussed.

Giant cell arteritis with ocular involvement successfully treated with tocilizumab and very short-course glucocorticoids: A case report.

PURPOSE: To report the case of a patient with arteritic anterior ischemic optic neuropathy (AAION) with a history of glucocorticoids (GC) hypersensitivity treated with monthly intravenous tocilizumab (IV TCZ) and short course of GC. CASE REPORT: A 71-year-old Caucasian patient presented with AAION related to giant cell arteritis (GCA) confirmed by temporal artery biopsy. Past medical history was significant for GC hypersensitivity proven by allergy evaluation and the patient was managed with IV TCZ and very short-course GC. CONCLUSION: TCZ therapy with very short-course GC could be effective in GCA with ophthalmic involvement as a first-line strategy. Clinical trials are needed for thorough evaluation of the efficiency of TCZ as a first-line treatment to induce and maintain remission in patients with GCA and ocular involvement.

Consensus Document on the Diagnosis and Treatment of Chronic Bronchial Infection in Chronic Obstructive Pulmonary Disease. / Documento de consenso sobre el diagnóstico y tratamiento de la infección bronquial crónica en la enfermedad pulmonar obstructiva crónica.

Although the chronic presence of microorganisms in the airways of patients with stable chronic obstructive pulmonary disease (COPD) confers a poor outcome, no recommendations have been established in disease management guidelines on how to diagnose and treat these cases. In order to guide professionals, the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) has prepared a document which aims to answer questions on the clinical management of COPD patients in whom microorganisms are occasionally or habitually isolated. Since the available scientific evidence is too heterogeneous to use in the creation of a clinical practice guideline, we have drawn up a document based on existing scientific literature and clinical experience, addressing the definition of different clinical situations and their diagnosis and management. The text was drawn up by consensus and approved by a large group of respiratory medicine experts with extensive clinical and scientific experience in the field, and has been endorsed by the SEPAR Scientific Committee.

[Rhabdomyolysis in patients treated by corticosteroids for acute asthma in intensive care unit]. / La corticothérapie, une cause de rhabdomyolyse chez les asthmatiques en réanimation.

INTRODUCTION: Acute muscle involvement is an infrequent complication of corticosteroids, characterized by muscle weakness and a rhabdomyolysis, rapidly regressive after withdrawal of corticosteroids. CASE REPORT: We report the case of a woman admitted in intensive care unit for acute severe asthma, treated with high doses of methylprednisolone. Serum CPK level raised with a peak at 28,160 UI/L (n<250 UI/L) at day 15, suggesting acute rhabdomyolysis with renal failure. CPK rapidly normalized when corticosteroids were discontinued. Other causes of rhabdomyolysis were ruled out. CONCLUSION: This necrosing myopathy under high doses of corticosteroids has been described in patients with severe acute asthma. The mechanism of the muscle damage results from a combination of corticosteroids toxicity, respiratory acidosis and mechanic ventilation.

[Evaluation of conjunctival inflammation among prosthesis wearers]. / Évaluation de l'inflammation conjonctivale chez les porteurs de prothèse oculaire.

PURPOSE: To define the best methods of evaluating conjunctival inflammation in patients with ocular prostheses. METHODS: The level of conjunctival inflammation and the patients' complaints were evaluated by several quantitative and qualitative methods : clinical grading, Schirmer's test, self-evaluation analogic scale of secretions, and a quality of life survey derived from the OSDI score (Ocular Surface Disease Index), initially designed for dry eye syndrome and modified to be relevant among this population. In order to test for consistency, the patients were re-evaluated for inflammation at the conclusion of 1 month of dexamethasone treatment, using the same methodology. The progression of each parameter under treatment was measured, searching for a correlation between improvement in the criteria and the patient's satisfaction. RESULTS: Twenty five patients were evaluated. The Schirmer's test did not change significantly with treatment. The clinical inflammation grade decreased significantly with treatment (p<0.0001) but was not correlated with patient satisfaction (p=0.63). The modified OSDI score and the self-evaluation analogic scale of secretions were both significantly improved (p<0.0001) and correlated with patient satisfaction (p=0.0048 for the OSDI, p<0.0001 for the analog scale). CONCLUSION: In our study, the most relevant tools to evaluate treatment efficacy for conjunctival inflammation in prosthetic eye wearers were the modified OSDI score and the self-evaluation analogic scale of secretions. The clinical grading scale is probably a good indicator for the biological effect of a treatment on the conjunctiva but may be unrelated to the patient's symptoms.

Clinical, Dermoscopic and Histologic Features of Recurrent Cutaneous Eosinophilic Vasculitis Cases. / Características clínicas, dermatoscópicas e histológicas de varios casos de vasculitis eosinofílica recurrente cutánea.

Primary recurrent cutaneous eosinophilic vasculitis is a rare condition characterized by pruritic, erythematous, purpuric plaques associated to edema. We compared and analyze the clinical, dermoscopic and histological features of the disease in 4 patients from our hospital and 13 patients published in the literature. Seventeen patients were included, with a median age of 56yo, a median duration of disease of 6 months. Lesions were most frequently generalized (47%) or localized in lower limbs (41%). The most frequent features were purpuric color (71%), local edema (65%), necrotizing vasculitis (94%) and eosinophil infiltration (100%) in histology. Most of the patients (82.4%) were given oral steroids with a median dose of 30mg. Primary recurrent cutaneous eosinophilic vasculitis might be an infra-diagnosed condition. The analysis of the patients allowed us to propose diagnostic criteria for the definition of this disease. We suggest a therapeutic strategy with high-potency steroids and dapsone, which might be considered as first-line treatment.

The impact of asthma and its treatment on growth: an evidence-based review.

OBJECTIVES: To assess the impact of asthma and its treatment (inhaled corticosteroids and other control medications) on growth. DATA SOURCES: The authors searched PubMed (up to August 24, 2018) and screened the reference lists of retrieved articles. Systematic reviews and meta-analysis were selected. If there was no such article, the authors selected either randomized clinical trials or observational studies. DATA SYNTHESIS: A total of 37 articles were included in this review. The findings from 21 studies suggest that asthma per se, especially more severe and/or uncontrolled cases, can transitorily impair child's growth. Two Cochrane reviews of randomized clinical trials showed a small mean reduction in linear growth (-0.91cm/year for beclomethasone, -0.59cm/year for budesonide, and -0.39cm/year for fluticasone) in the first year of treatment with inhaled corticosteroids in prepubertal children with persistent asthma. The effects were likely to be molecule- and dose-dependent. A recent review showed that most of "real-life" observational studies had not found significant effects of inhaled corticosteroids on growth in asthmatic children. Fifteen studies showed that the maintenance systemic corticosteroids could cause a dose-dependent growth suppression in children with severe asthma, but other controllers (cromones, montelukast, salmeterol, and theophylline) had no significant adverse effects no growth. CONCLUSIONS: Severe and/or uncontrolled asthma can transitorily impair child's growth. Regular use of inhaled corticosteroids may cause a small reduction in linear growth in children with asthma, but the well-established benefits of inhaled corticosteroids in controlling asthma outweigh the potential adverse effects on growth. Use of the minimally effective dose of inhaled corticosteroids and regular monitoring of child's height during inhaled corticosteroids therapy are recommended.

Treatment of Persistent Cutaneous Atrophy After Corticosteroid Injection With Fat Graft.

Subcutaneous fat atrophy and hypopigmentation are potential adverse side effects of local corticosteroid injection that may resolve spontaneously within 1-2 years. This report shows that fat grafting provides a simple, effective and safe correction of corticosteroid induced cutaneous atrophy with very satisfying esthetic and functional results.