Dataset Information

A blistering new era for bullous pemphigoid: A scoping review of current therapies, ongoing clinical trials, and future directions.

ABSTRACT: Bullous pemphigoid (BP) is a severe autoimmune blistering skin disorder that primarily causes disease in the older population and is the most prevalent subepidermal variant of the pemphigoid diseases. It manifests as exquisitely pruritic vesiculobullous eruptions and is associated with significant morbidity and mortality. Studies are reporting an increase in prevalence, and, among the elderly, BP is no longer considered to be as rare as previously thought. The pathogenesis involves autoantibodies directed against proteinaceous components of hemidesmosomes, with consequent autoimmune destruction of the dermal-epidermal junction. In recent times, more complex elements of the underlying inflammatory orchestra have been elucidated and are being used to develop targeted immunotherapies. The primary treatment modalities of BP include the use of topical and systemic corticosteroids, certain non-immunosuppressive agents (tetracyclines, nicotinamide, and sulfone), and immunosuppressants (methotrexate, azathioprine, cyclophosphamide, and Mycophenolate). However, in the long term, most of these agents are associated with substantial toxicities while recurrence rates remain high. Such egregious prospects led to significant efforts being directed towards developing newer targeted therapies which work by attenuating specific newly discovered pillars of the inflammatory pathway, and these efforts have garnered hope in providing safer alternatives. Our review focuses on presenting the various therapeutic options that are currently in trial since December 2019, as well as on summarizing presently established treatment guidelines to provide readers with the latest exciting updates.

SUBMITTER: Khalid SN

PROVIDER: S-EPMC8435812 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BACKGROUND:Bullous pemphigoid (BP) is the most common autoimmune blistering disease in the West. Oral steroids are the standard treatment.This is an update of the review published in 2005. OBJECTIVES:To assess treatments for bullous pemphigoid. SEARCH STRATEGY:In August 2010 we updated our searches of the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (Clinical Trials), MEDLINE, EMBASE, and the Ongoing Trials registers. SELECTION CRITERIA:Randomised controlled trials of treatments for participants with immunofluorescence-confirmed bullous pemphigoid. DATA COLLECTION AND ANALYSIS:At least two authors evaluated the studies for the inclusion criteria, and extracted data independently. MAIN RESULTS:We included 10 randomised controlled trials (with a total of 1049 participants) of moderate to high risk of bias. All studies involved different comparisons, none had a placebo group. In 1 trial plasma exchange plus prednisone gave significantly better disease control at 1 month (0.3 mg/kg: RR 18.78, 95% CI 1.20 to 293.70) than prednisone alone (1.0 mg/kg: RR 1.79, 95% CI 1.11 to 2.90), while another trial showed no difference in disease control at 6 months.No differences in disease control were seen for different doses or formulations of prednisolone (one trial each), for azathioprine plus prednisone compared with prednisone alone (one trial), for prednisolone plus azathioprine compared with prednisolone plus plasma exchange (one trial), for prednisolone plus mycophenolate mofetil or plus azathioprine (one trial), for tetracycline plus nicotinamide compared with prednisolone (one trial). Chinese traditional medicine plus prednisone was not effective in one trial.There were no significant differences in healing in a comparison of a standard regimen of topical steroids (clobetasol) with a milder regimen (RR 1.00, 95% 0.97 to 1.03) in one trial. In another trial, clobetasol showed significantly more disease control than oral prednisolone in people with extensive and moderate disease (RR 1.09, 95% CI 1.02 to 1.17), with significantly reduced mortality and adverse events (RR 1.06, 95% CI 1.00 to 1.12). AUTHORS' CONCLUSIONS:Very potent topical steroids are effective and safe treatments for BP, but their use in extensive disease may be limited by side-effects and practical factors. Milder regimens (using lower doses of steroids) are safe and effective in moderate BP. Starting doses of prednisolone greater than 0.75 mg/kg/day do not give additional benefit, lower doses may be adequate to control disease and reduce the incidence and severity of adverse reactions. The effectiveness of adding plasma exchange, azathioprine or mycophenolate mofetil to corticosteroids, and combination treatment with tetracycline and nicotinamide needs further investigation.

Project description:Glucocorticoids are the most effective anti-inflammatory therapy for asthma yet are relatively ineffective in chronic obstructive pulmonary disease. Glucocorticoids suppress inflammation via several molecular mechanisms. Glucocorticoids suppress the multiple inflammatory genes that are activated in chronic inflammatory diseases, such as asthma, by reversing histone acetylation of activated inflammatory genes through binding of ligand-bound glucocorticoid receptors (GR) to co-activator molecules and recruitment of histone deacetylase-2 to the activated inflammatory gene transcription complex (trans-repression). At higher concentrations of glucocorticoids GR homodimers interact with DNA recognition sites to activate transcription through increased histone acetylation of anti-inflammatory genes and transcription of several genes linked to glucocorticoid side effects (trans-activation). Glucocorticoids also have post-transcriptional effects and decrease stability of some pro-inflammatory mRNA species. Decreased glucocorticoid responsiveness is found in patients with severe asthma and asthmatics who smoke, as well as in all patients with chronic obstructive pulmonary disease. Several molecular mechanisms of glucocorticoid resistance have now been identified which involve post-translational modifications of GR. Histone deacetylase-2 is markedly reduced in activity and expression as a result of oxidative/nitrative stress so that inflammation becomes resistant to the anti-inflammatory actions of glucocorticoids. Dissociated glucocorticoids and selective GR modulators which show improved trans-repression over trans-activation effects have been developed to reduce side effects, but so far it has been difficult to dissociate anti-inflammatory effects from adverse effects. In patients with glucocorticoid resistance alternative anti-inflammatory treatments are being investigated as well as drugs that may reverse the molecular mechanisms of glucocorticoid resistance.

Project description:Bullous pemphigoid (BP) is a rare autoimmune skin blistering disease, characterized by the presence of autoantibodies against hemidesmosomal autoantigens. Cytokine expression is altered in BP patients, and several of these differently expressed cytokines, including IL-1α, IL-1β, IL-8, and TNF-α, contribute to disease pathogenesis. Since genetic polymorphisms in the genes of these cytokines might be implicated in susceptibility to BP disease, we aimed at testing this implication in susceptibility to BP in an Iranian cohort. Blood samples were collected from the subjects and genomic DNA was extracted. To detect the single nucleotide polymorphisms (SNPs), IL-1α (rs1800587), IL-1β (rs1143627, rs16944, rs1143634), IL-8 (rs4073), and TNF-α (rs1799964, rs1800630, rs1799724, and rs361525) genes were genotyped in BP patients and healthy controls as well as IL-8 (rs4073) in pemphigus vulgaris (PV) patients. Quantitative gene expression was evaluated by RT-PCR analysis. A significant difference was observed in the distribution of genotypes or alleles of IL-8 SNP between the BP patients and controls. The A-allele of IL-8 SNP is significantly more prevalent in the control individuals compared to the BP patient. To further validate this observation, we included PV patients as an additional control. Again, the A-allele of IL-8 SNP is significantly more prevalent in the PV compared to the BP patients. While we observed a trend toward significant differences regarding alleles of TNF-α rs1799724 as well as alleles of TNF-α rs1799964, this difference was, however, not evident after correction for multiple analysis. There was no significant difference in all other studied SNPs. In contrast to IL-1α, IL-1β, and TNF-α, IL-8 gene expression levels were significantly higher in the patients than that of controls. The minor allele in IL-8 SNP might play a protective role in susceptibility to BP in Iranian patients. Although higher expression levels of IL-8 gene was found in the patients compared with healthy controls, these levels, however, suggest no association with the examined polymorphism. Moreover, further investigation revealed an elevation in gene expression between wild and polymorphic genotypes of IL-1α rs1800587 and TNF-α rs361525 in the patient group and these SNPs are therefore associated with altering the levels of gene expression.

Dataset Information

A blistering new era for bullous pemphigoid: A scoping review of current therapies, ongoing clinical trials, and future directions.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure