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Indian Journal of Dermatology,... 2021Limited evidence is available about effectiveness and choice of immunomodulating treatment modalities for toxic epidermal necrolysis (TEN). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Limited evidence is available about effectiveness and choice of immunomodulating treatment modalities for toxic epidermal necrolysis (TEN).
AIMS
To compare the effectiveness of interventions to reduce mortality in patients of toxic epidermal necrolysis through network meta-analysis.
METHODS
Studies were retrieved using PubMed, Google Scholar and Cochrane Database of Systematic Reviews from inception to September 18, 2018. Only English language articles were considered. Observational and randomized controlled studies having ≥ 5 TEN patients in each intervention arm were included. Two investigators independently extracted study characteristics, intervention details and mortality data. Bayesian network meta-analysis was performed using the Markov chain Monte Carlo (MCMC) approach through the random effect model. The ranking analysis was done to provide a hierarchy of interventions. The consistency between direct and indirect evidence was assessed through node spit analysis. The primary outcome was to compare the mortality [Odds ratio OR (95% credibility interval CrI)] among all treatment modalities of TEN.
RESULTS
Twenty-four studies satisfying the selection criteria were included. The network analysis showed improved survival with cyclosporine as compared to supportive care [OR- 0.19 (95% CrI: 0.05, 0.59)] and intravenous immunoglobulin [OR- 0.21 (95% CrI: 0.05, 0.76)]. The hierarchy of treatments based on "surface under the cumulative ranking curves" (SUCRA) value were cyclosporine (0.93), steroid+intravenous immunoglobulin (0.76), etanercept (0.59), steroids (0.46), intravenous immunoglobulin (0.40), supportive care (0.34) and thalidomide (0.02). No inconsistencies between direct and indirect estimates were observed for any of the treatment pairs.
LIMITATIONS
Evidence is mainly based on retrospective studies.
CONCLUSION
The use of cyclosporine can reduce mortality in TEN patients. Other promising immunomodulators could be steroid+intravenous immunoglobulin combination and etanercept.
Topics: Cyclosporine; Dermatologic Agents; Etanercept; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Stevens-Johnson Syndrome
PubMed: 33871208
DOI: 10.25259/IJDVL_605_19 -
Ticks and Tick-borne Diseases May 2021Alpha-gal syndrome (AGS) refers to a delayed allergic reaction to galactose-α-1,3-galactose (α-Gal) that occurs following the consumption of mammalian meat or exposure...
Alpha-gal syndrome (AGS) refers to a delayed allergic reaction to galactose-α-1,3-galactose (α-Gal) that occurs following the consumption of mammalian meat or exposure to other animal-based foods and products. Increasing evidence suggests that bites from certain tick species can lead to AGS through sensitization of a person's α-Gal specific IgE levels. This systematic review aimed to summarize the published evidence on this topic to understand post-tick exposure AGS epidemiology and health outcomes. A structured search for literature in eight bibliographic databases was conducted in January, 2020. Grey literature and verification searches were also performed. The exposure of interest was tick bites, and the outcome of interest was AGS. All primary research study designs were eligible for inclusion. References were screened for relevance, and data extraction and risk-of-bias assessment were conducted on relevant studies by two independent reviewers. Data were descriptively and narratively summarized. Of 1390 references screened, 102 relevant articles (103 unique studies) were identified (published from 2009 to 2020). Most studies (76.7 %) were case report or series. These 79 studies reported on 236 post-tick exposure AGS cases from 20 different countries, mostly the United States (33.5 %), Spain (19.5 %), Sweden (18.6 %), and France (12.7 %). The mean case age was 51.3 (SD = 16.7, range 5-85, n = 229), while 68.1 % were male (n = 226). The most commonly reported symptom was urticaria (71.2 %); 51.7 % of cases reported anaphylaxis. Twenty-one observational studies were reported, mostly (95.2 %) among clinical allergy patients. The proportion of AGS cases that recalled tick bites was highly variable across these studies. Three challenge studies evaluating tick exposures and α-Gal levels in α-Gal deficient mice were identified. The existing evidence suggests tick bites lead to α-Gal-specific IgE sensitization, which can cause AGS, but further research is needed to clarify if AGS is only attributable to certain tick species and whether other vectors may trigger AGS. Additional research is needed on risk factors for AGS development, evaluation of diagnostic immunoassays, and the epidemiology and distribution of AGS in different populations. Climate change will likely lead to future cases of AGS in new regions worldwide due to the predicted alteration of suitable tick habitats.
Topics: Anaphylaxis; Animals; Food Hypersensitivity; Humans; Mice; Tick Bites; Urticaria
PubMed: 33529984
DOI: 10.1016/j.ttbdis.2021.101674 -
Sarcoidosis, Vasculitis, and Diffuse... 2020Sarcoidosis typically presents with peribronchovascular and perilymphatic nodules on high-resolution computed tomography (HRCT); a miliary pattern is reported but not...
BACKGROUND AND OBJECTIVES
Sarcoidosis typically presents with peribronchovascular and perilymphatic nodules on high-resolution computed tomography (HRCT); a miliary pattern is reported but not well described.
DESIGN SETTING
We describe four patients with miliary sarcoidosis and results of a systematic review of all previously reported cases from 1985 onwards.
RESULTS
We identified only 27 cases of "miliary" sarcoidosis in the HRCT era. These patients were older (85.2% older than 40 years), had more co-morbidities (72.7%) and were symptomatic compared to "typical" sarcoidosis. Respiratory symptoms were present in 61.9% at diagnosis. Hypercalcemia was seen in 28.5%. On review of HRCT images, only 34.6% (9/26) had a "true miliary" pattern without fissural nodules. In our series, prominent perivascular granulomas were seen on histopathology in all. 44.4% (12/27) had tuberculosis preceding or concurrent to miliary sarcoidosis. Of the eight true associations, tuberculosis preceded sarcoidosis by 52 (median, IQR 36) weeks in six and occurred concurrently in another two. The diagnosis of tuberculosis was clinical in all with concurrent diagnosis of tuberculosis and sarcoidosis. Treatment with steroids had 100% response and 14.2% relapse.
CONCLUSIONS
A true miliary pattern in the HRCT era is very rare in sarcoidosis and subtle perilymphatic pattern is nearly always seen; this should be labeled "pseudo-miliary". Prominent perivascular granulomas are associated with true miliary pattern. Miliary sarcoidosis patients are older and symptomatic, needing treatment at diagnosis. "Miliary" sarcoidosis may follow treatment for tuberculosis; concurrent cases possibly indicate the difficulty in differentiating both or a "tuberculo-sarcoid" presentation. .
Topics: Adult; Aged; Antitubercular Agents; Bacteriological Techniques; Biopsy; Diagnosis, Differential; Female; Humans; Lung; Male; Middle Aged; Predictive Value of Tests; Recovery of Function; Recurrence; Sarcoidosis, Pulmonary; Steroids; Tomography, X-Ray Computed; Treatment Outcome; Tuberculosis, Miliary
PubMed: 33093769
DOI: 10.36141/svdld.v37i1.7837 -
Journal of the American Academy of... Feb 2021Prolonged wear of facial protective equipment can lead to occupational dermatoses.
BACKGROUND
Prolonged wear of facial protective equipment can lead to occupational dermatoses.
OBJECTIVE
To identify important causes of occupational dermatoses from facial protective equipment.
METHODS
A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed using PubMed and Embase databases. Articles were included if they reported occupational dermatoses caused by surgical/procedure masks or N95 respirators, or both.
RESULTS
We identified 344 articles, and 16 were suitable for inclusion in this review. Selected articles focused on facial occupational dermatoses in health care workers. Allergic contact dermatitis to the elastic straps, glue, and formaldehyde released from the mask fabric was reported. Irritant contact dermatitis was common on the cheeks and nasal bridge due to pressure and friction. Irritant dermatitis was associated with personal history of atopic dermatitis and prolonged mask wear (>6 hours). Acneiform eruption was reported due to prolonged wear and occlusion. Contact urticaria was rare.
LIMITATIONS
Only publications listed in PubMed or Embase were included. Most publications were case reports and retrospective studies.
CONCLUSION
This systematic review from members of the American Contact Dermatitis Society highlights cases of occupational dermatitis to facial protective equipment, including potential offending allergens. This work may help in the diagnosis and treatment of health care workers with facial occupational dermatitis.
Topics: Allergens; Dermatitis, Allergic Contact; Dermatitis, Irritant; Dermatitis, Occupational; Facial Dermatoses; Health Personnel; Humans; Infectious Disease Transmission, Patient-to-Professional; Masks; N95 Respirators
PubMed: 33011325
DOI: 10.1016/j.jaad.2020.09.074 -
Respiratory Medicine Oct 2020Regular physical activity is strongly recommended to prevent chronic respiratory diseases, including asthma. On the other hand, vigorous physical training may trigger...
Regular physical activity is strongly recommended to prevent chronic respiratory diseases, including asthma. On the other hand, vigorous physical training may trigger airway symptoms and bronchoconstriction. The transient airway narrowing occurring because of exercise is named exercise-induced bronchoconstriction (EIB). Despite management according to guidelines, a significant proportion of patients experiences uncontrolled EIB, which thus represents a relevant unmet medical need. In particular, although prevention and treatment of EIB are effectively based on the use of beta-2 bronchodilator drugs, high heterogeneity in individual responses has been reported. Furthermore, even though beta-2 adrenergic drugs remain the mainstay of EIB management, occurrence of tolerance and side effects, as well as doping concerns have been reported with their use. In regard to this, inhaled antimuscarinics could represent an alternative or additional effective and safe bronchodilator therapeutic option for achieving optimal EIB control and minimize adverse events. The present systematic review aims to collect and provide the most updated and evidence-based literature findings on the efficacy and safety of short- and long-acting inhaled anti-muscarinic drugs for the preventive treatment of EIB in both children and adults. Take-Home Message: Anti-muscarinic drugs are effective and safe in preventing EIB, despite response variability is reported. Further studies should focus on long-acting molecules, chronic administration and phenotype-driven effects.
Topics: Administration, Inhalation; Adolescent; Adult; Bronchoconstriction; Bronchodilator Agents; Child; Delayed-Action Preparations; Female; Humans; Male; Muscarinic Antagonists; Physical Conditioning, Human; Respiratory Hypersensitivity; Young Adult
PubMed: 32911137
DOI: 10.1016/j.rmed.2020.106128 -
Scientific Reports Jun 2020Serious cutaneous adverse drug reactions [i.e., SJS/TEN with severe ocular complications (SOC)] associated with cold medicine (CM) were reported in several studies. To... (Meta-Analysis)
Meta-Analysis
Serious cutaneous adverse drug reactions [i.e., SJS/TEN with severe ocular complications (SOC)] associated with cold medicine (CM) were reported in several studies. To assess the risks of CM-induced SJS/TEN with SOC, systematic review and meta-analysis were employed. Studies investigating associations between HLA genotypes and CM-induced SJS/TEN with SOC were systematically searched in PubMed, Scopus and the Cochrane Library. Overall odds ratios (ORs) with 95% CIs were calculated using a random-effects model to determine these associations. An initial search of the databases identified 24,011 articles, of which 6 studies met the inclusion criteria. In total from all studies, associations between 81 different HLA genotypes and CM-induced SJS/TEN with SOC (i.e., 22 different HLA-A genotypes, 40 different HLA-B genotypes and 19 different HLA-C genotypes) were investigated. Risk factors to develop SJS/TEN with SOC in patients who used CM were identified from our meta-analysis. HLA-A*0206 (OR = 3.90; 95% CI = 1.96-7.77), HLA-A*3303 (OR = 2.28; 95% CI = 1.31-3.97), HLA-B*4403 (OR = 3.27; 95% CI = 1.52-7.03) and HLA-C*0501 (OR = 2.55; 95% CI = 1.19-5.44) were associated with CM-induced SJS/TEN with SOC. With our results demonstrating a significant association between using of CMs and the severe ADR, a genetic testing can be helpful. However, the CMs are commonly used as an over-the-counter drug in practically almost of people in populations worldwide, the genetic screening prior to use of the CMs might not be cost-effective. Nonetheless, for people with a family history of developing the ADRs with a possible involvement of CMs, a genetic screening may be beneficial.
Topics: Eye; Female; Genetic Predisposition to Disease; Genotype; HLA Antigens; Histocompatibility Antigens Class I; Humans; Male; Multi-Ingredient Cold, Flu, and Allergy Medications; Ocular Physiological Phenomena; Odds Ratio; Risk Factors; Stevens-Johnson Syndrome
PubMed: 32601360
DOI: 10.1038/s41598-020-67610-5 -
BMC Pediatrics Jun 2020Early antibiotic exposure may be contributing to the onset of childhood allergies. The main objective of this study was to conduct a systematic review on the...
BACKGROUND
Early antibiotic exposure may be contributing to the onset of childhood allergies. The main objective of this study was to conduct a systematic review on the relationship between early life antibiotic exposure and childhood asthma, eczema and hay fever.
METHODS
Pubmed and Embase were searched for studies published between 01-01-2008 and 01-08-2018, examining the effects of (1) prenatal antibiotic exposure and (2) infant antibiotic administration (during the first 2 years of life) on childhood asthma, eczema and hay fever from 0 to 18 years of age. These publications were assessed using the Newcastle Ottawa Scale (NOS) and analysed narratively.
RESULTS
(1) Prenatal antibiotics: Asthma (12 studies): The majority of studies (9/12) reported significant relationships (range OR 1.13 (1.02-1.24) to OR 3.19 (1.52-6.67)). Three studies reported inconsistent findings. Eczema (3 studies): An overall significant effect was reported in one study and in two other studies only when prenatal antibiotic exposure was prolonged. (2) Infant antibiotics: Asthma (27 studies): 17/27 studies reported overall significant findings (range HR 1.12 (1.08-1.16) to OR 3.21 (1.89-5.45)). Dose-response effects and stronger effects with broad-spectrum antibiotic were often reported. 10/27 studies reported inconsistent findings depending on certain conditions and types of analyses. Of 19 studies addressing reverse causation or confounding by indication at least somewhat, 11 reported overall significant effects. Eczema (15 studies): 6/15 studies reported overall significant effects; 9 studies had either insignificant or inconsistent findings. Hay fever (9 studies): 6/9 reported significant effects, and the other three insignificant or inconsistent findings. General: Multiple and broad-spectrum antibiotics were more strongly associated with allergies. The majority of studies scored a 6 or 7 out of 9 based on the NOS, indicating they generally had a medium risk of bias. Although most studies showed significant findings between early antibiotic exposure and asthma, the actual effects are still unclear as intrapartum antibiotic administration, familial factors and confounding by maternal and child infections were often not addressed.
CONCLUSIONS
This review points to a moderate amount of evidence for a relationship between early life antibiotics (especially prenatal) and childhood asthma, some evidence for a relationship with hay fever and less convincing evidence for a relationship with eczema. More studies are still needed addressing intra-partum antibiotics, familial factors, and possible confounding by maternal and childhood infections. Children exposed to multiple, broad-spectrum antibiotics early in life appear to have a greater risk of allergies, especially asthma; these effects should be investigated further.
Topics: Anti-Bacterial Agents; Asthma; Child; Eczema; Female; Humans; Hypersensitivity; Infant; Parturition; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 32593308
DOI: 10.1186/s12887-020-02042-8 -
European Respiratory Review : An... Mar 2020Many sarcoidosis patients experience a reduction in health-related quality of life (HRQoL) and a majority of patients report fatigue. Historically, drug trials in...
AIMS
Many sarcoidosis patients experience a reduction in health-related quality of life (HRQoL) and a majority of patients report fatigue. Historically, drug trials in sarcoidosis have focused on changes in chest radiographs, lung function parameters and biomarkers, while HRQoL and fatigue have not been the main outcomes examined. We performed a systematic review of the literature to evaluate the existing evidence on the effects of pharmacological interventions on HRQoL and fatigue outcomes.
METHODS
The systematic search was performed in Medline and Embase and yielded 15 records covering seven randomised controlled trials and seven single-arm open label studies, which were included in a qualitative synthesis (the results of one study were included in two publications). 12 studies evaluated immunosuppressive and/or immunomodulatory therapies and two studies evaluated stimulants.
RESULTS
Nine out of the 14 studies observed positive treatment effects from the interventions on HRQoL and/or fatigue, exceeding the minimal important difference. The risk of bias was generally high with only three studies rated as having a low risk of bias. The results suggest a potential for improvement in HRQoL and/or fatigue in patients with active disease who are either untreated or treated but not yet fully stabilised or therapy refractory.
CONCLUSION
More randomised, double-blind and placebo-controlled trials are needed to expand the evidence base on these important outcome parameters.
Topics: Fatigue; Functional Status; Humans; Lung; Quality of Life; Recovery of Function; Sarcoidosis, Pulmonary; Treatment Outcome
PubMed: 31996355
DOI: 10.1183/16000617.0057-2019 -
Frontiers in Immunology 2019Despite the large number of performed studies, the etiology and pathogenesis of sarcoidosis still remain unknown. Most researchers allude to the possible autoimmune or...
Despite the large number of performed studies, the etiology and pathogenesis of sarcoidosis still remain unknown. Most researchers allude to the possible autoimmune or immune-mediated genesis of the disease. This review attempts an integral analysis of currently available information suggesting an autoimmune genesis of sarcoidosis and is divided into four categories: the evaluation of clinical signs described both in patients with sarcoidosis and "classic" autoimmune diseases, the role of triggering factors in the development of sarcoidosis, the presence of immunogenic susceptibility in the development of the disease, and the analysis of cellular and humoral immune responses in sarcoidosis. Studying the etiology and pathogenesis of sarcoidosis will improve diagnostic procedures as well as the prognosis and patients' quality of life.
Topics: Animals; Autoimmune Diseases; Humans; Immunity, Cellular; Immunity, Humoral; Sarcoidosis
PubMed: 31969879
DOI: 10.3389/fimmu.2019.02933 -
Allergy May 2020Drug hypersensitivity reactions (DHRs) are associated with high global morbidity and mortality. Cutaneous T cell-mediated reactions classically occur more than 6 hours...
Drug hypersensitivity reactions (DHRs) are associated with high global morbidity and mortality. Cutaneous T cell-mediated reactions classically occur more than 6 hours after drug administration and include life-threatening conditions such as toxic epidermal necrolysis, Stevens-Johnson syndrome, and hypersensitivity syndrome. Over the last 20 years, significant advances have been made in our understanding of the pathogenesis of DHRs with the identification of human leukocyte antigens as predisposing factors. This has led to the development of pharmacogenetic screening tests, such as HLA-B*57:01 in abacavir therapy, which has successfully reduced the incidence of abacavir hypersensitivity reactions. We have completed a PRISMA-compliant systematic review to identify genetic associations that have been reported in DHRs. In total, 105 studies (5554 cases and 123 548 controls) have been included in the review reporting genetic associations with carbamazepine (n = 31), other aromatic antiepileptic drugs (n = 24), abacavir (n = 11), nevirapine (n = 14), trimethoprim-sulfamethoxazole (n = 11), dapsone (n = 4), allopurinol (n = 10), and other drugs (n = 5). The most commonly reported genetic variants associated with DHRs are located in human leukocyte antigen genes and genes involved in drug metabolism pathways. Increasing our understanding of genetic variants that contribute to DHRs will allow us to improve diagnosis, develop new treatments, and predict and prevent DHRs in the future.
Topics: Carbamazepine; Drug Hypersensitivity; Drug Hypersensitivity Syndrome; HLA-B Antigens; Humans; Pharmaceutical Preparations; Stevens-Johnson Syndrome; T-Lymphocytes
PubMed: 31899808
DOI: 10.1111/all.14174