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Anais Brasileiros de Dermatologia 2022Epidermolysis bullosa acquisita is a rare autoimmune disease, characterized by the synthesis of anti-collagen VII autoantibodies, the main component of hemidesmosome...
Epidermolysis bullosa acquisita is a rare autoimmune disease, characterized by the synthesis of anti-collagen VII autoantibodies, the main component of hemidesmosome anchoring fibrils. The antigen-antibody binding elicits a complex inflammatory response, which culminates in the loss of dermo-epidermal adhesion of the skin and/or mucous membranes. Skin fragility with bullae, erosions, and milia in areas of trauma characterizes the mechanobullous form of the disease. In the inflammatory form of epidermolysis bullosa acquisita, urticarial inflammatory plaques with tense bullae, similar to bullous pemphigoid, or mucosal lesions can determine permanent scars and loss of functionality in the ocular, oral, esophageal, and urogenital regions. Due to the similarity of the clinical findings of epidermolysis bullosa acquisita with other diseases of the pemphigoid group and with porphyria cutanea tarda, the diagnosis is currently confirmed mainly based on the clinical correlation with histopathological findings (pauci-inflammatory subepidermal cleavage or with a neutrophilic infiltrate) and the demonstration of the presence of anti-collagen VII IgG in situ by direct immunofluorescence, or circulating anti-collagen VII IgG through indirect immunofluorescence and/or ELISA. There is no specific therapy for epidermolysis bullosa acquisita and the response to treatment is variable, usually with complete remission in children and a worse prognosis in adults with mucosal involvement. Systemic corticosteroids and immunomodulators (colchicine and dapsone) are alternatives for the treatment of mild forms of the disease, while severe forms require the use of corticosteroid therapy associated with immunosuppressants, intravenous immunoglobulin, and rituximab.
Topics: Adult; Autoantibodies; Autoimmune Diseases; Blister; Child; Epidermolysis Bullosa Acquisita; Humans; Immunoglobulins, Intravenous; Pemphigoid, Bullous
PubMed: 35701269
DOI: 10.1016/j.abd.2021.09.010 -
American Journal of Clinical Dermatology May 2021Dermatitis herpetiformis (DH), presenting with an intense itch and blistering symmetrical rash, typically on the elbows, knees, and buttocks, is a cutaneous... (Review)
Review
Dermatitis herpetiformis (DH), presenting with an intense itch and blistering symmetrical rash, typically on the elbows, knees, and buttocks, is a cutaneous manifestation of celiac disease. Though overt gastrointestinal symptoms are rare, three-fourths of patients with DH have villous atrophy in the small bowel, and the rest have celiac-type inflammatory changes. DH affects mostly adults and slightly more males than females. The mean age at onset is about 50 years. DH diagnosis is confirmed by showing granular immunoglobulin A deposits in the papillary dermis. The DH autoantigen, transglutaminase 3, is deposited at the same site in tightly bound immune complexes. At present, the DH-to-celiac disease prevalence is 1:8. The incidence of DH is decreasing, whereas that of celiac disease is increasing, probably because of improved diagnostics. In DH, the treatment of choice for all patients is a gluten-free diet (GFD) in which uncontaminated oats are allowed. At onset, most patients need additional dapsone to rapidly control the rash and itching. Dapsone can be stopped after a mean of 2 years, and a strict lifelong GFD alone is required. Dietary adherence offers an excellent long-term prognosis for patients with DH, with a normal quality of life and all-cause mortality.
Topics: Adult; Age Factors; Celiac Disease; Combined Modality Therapy; Dapsone; Dermatitis Herpetiformis; Dermis; Diet, Gluten-Free; Female; Humans; Immunoglobulin A; Intestinal Mucosa; Intestine, Small; Male; Patient Compliance; Prevalence; Prognosis; Quality of Life; Risk Factors; Sex Factors; Treatment Outcome
PubMed: 33432477
DOI: 10.1007/s40257-020-00584-2 -
International Journal of Molecular... Oct 2022Dapsone (DDS), Rifampicin (RIF) and Ofloxacin (OFL) are drugs recommended by the World Health Organization (WHO) for the treatment of leprosy. In the context of leprosy,... (Meta-Analysis)
Meta-Analysis Review
Dapsone (DDS), Rifampicin (RIF) and Ofloxacin (OFL) are drugs recommended by the World Health Organization (WHO) for the treatment of leprosy. In the context of leprosy, resistance to these drugs occurs mainly due to mutations in the target genes (Folp1, RpoB and GyrA). It is important to monitor antimicrobial resistance in patients with leprosy. Therefore, we performed a meta-analysis of drug resistance in Mycobacterium leprae and the mutational profile of the target genes. In this paper, we limited the study period to May 2022 and searched PubMed, Web of Science (WOS), Scopus, and Embase databases for identified studies. Two independent reviewers extracted the study data. Mutation and drug-resistance rates were estimated in Stata 16.0. The results demonstrated that the drug-resistance rate was 10.18% (95% CI: 7.85-12.51). Subgroup analysis showed the highest resistance rate was in the Western Pacific region (17.05%, 95% CI:1.80 to 13.78), and it was higher after 2009 than before [(11.39%, 7.46-15.33) vs. 6.59% (3.66-9.53)]. We can conclude that the rate among new cases (7.25%, 95% CI: 4.65-9.84) was lower than the relapsed (14.26%, 95 CI%: 9.82-18.71). Mutation rates of Folp1, RpoB and GyrA were 4.40% (95% CI: 3.02-5.77), 3.66% (95% CI: 2.41-4.90) and 1.28% (95% CI: 0.87-1.71) respectively, while the rate for polygenes mutation was 1.73% (0.83-2.63). For further analysis, we used 368 drug-resistant strains as research subjects and found that codons (Ser, Pro, Ala) on RpoB, Folp1 and GyrA are the most common mutation sites in the determining region (DRDR). In addition, the most common substitution patterns of Folp1, RpoB, and GyrA are Pro→Leu, Ser→Leu, and Ala→Val. This study found that a higher proportion of patients has developed resistance to these drugs, and the rate has increased since 2009, which continue to pose a challenge to clinicians. In addition, the amino acid alterations in the sequence of the DRDR regions and the substitution patterns mentioned in the study also provide new ideas for clinical treatment options.
Topics: Humans; Rifampin; Dapsone; Leprostatic Agents; Ofloxacin; Drug Resistance, Bacterial; Mycobacterium leprae; Leprosy; Mutation; Amino Acids; Microbial Sensitivity Tests
PubMed: 36293307
DOI: 10.3390/ijms232012443 -
Journal of Palliative Medicine Feb 2023Death anxiety is powerful, potentially contributes to suffering, and yet has to date not been extensively studied in the context of palliative care. Availability of a... (Randomized Controlled Trial)
Randomized Controlled Trial
Death anxiety is powerful, potentially contributes to suffering, and yet has to date not been extensively studied in the context of palliative care. Availability of a validated Death Anxiety and Distress Scale (DADDS) opens the opportunity to better assess and redress death anxiety in serious illness. We explored death anxiety/distress for associations with physical and psychosocial factors. Ancillary to a randomized clinical trial (RCT) of Dignity Therapy (DT), we enrolled a convenience sample of 167 older adults in the United States with cancer and receiving outpatient palliative care (mean age 65.9 [7.3] years, 62% female, 84% White, 62% stage 4 cancer). They completed the DADDS and several measures for the stepped-wedged RCT, including demographic factors, religious struggle, dignity-related distress, existential quality of life (QoL), and terminal illness awareness (TIA). DADDS scores were generally unrelated to demographic factors (including religious affiliation, intrinsic religiousness, and frequency of prayer). DADDS scores were positively correlated with religious struggle ( < 0.001) and dignity-related distress ( < 0.001) and negatively correlated with existential QoL ( < 0.001). TIA was significantly nonlinearly associated with both the total DADDS ( = 0.007) and its Finitude subscale ( ≤ 0.001) scores. There was a statistically significant decrease in Finitude subscale scores for a subset of participants who completed a post-DT DADDS ( = 0.04). Findings, if replicable, suggest that further research on death anxiety and prognostic awareness in the context of palliative medicine is in order. Findings also raise questions about the optimal nature and timing of spiritual and psychosocial interventions, something that might entail evaluation or screening for death anxiety and prognostic awareness for maximizing the effectiveness of care.
Topics: Female; Humans; Aged; Male; Palliative Care; Acedapsone; Hospice and Palliative Care Nursing; Quality of Life; Anxiety; Neoplasms
PubMed: 36067074
DOI: 10.1089/jpm.2022.0052 -
Frontiers in Immunology 2020Monogenic autoinflammatory diseases are rare conditions caused by genetic abnormalities affecting the innate immunity. Previous therapeutic strategies had been mainly... (Review)
Review
Monogenic autoinflammatory diseases are rare conditions caused by genetic abnormalities affecting the innate immunity. Previous therapeutic strategies had been mainly based on results from retrospective studies and physicians' experience. However, during the last years, the significant improvement in their genetic and pathogenic knowledge has been accompanied by a remarkable progress in their management. The relatively recent identification of the inflammasome as the crucial pathogenic mechanism causing an aberrant production of interleukin 1β (IL-1β) in the most frequent monogenic autoinflammatory diseases led to the introduction of anti-IL-1 agents and other biologic drugs as part of the previously limited therapeutic armamentarium available. Advances in the treatment of autoinflammatory diseases have been favored by the use of new biologic agents and the performance of a notable number of randomized clinical trials exploring the efficacy and safety of these agents. Clinical trials have contributed to increase the level of evidence and provided more robust therapeutic recommendations. This review analyzes the treatment of the most frequent monogenic autoinflammatory diseases, namely, familial Mediterranean fever, tumor necrosis factor receptor-associated periodic fever syndrome, hyperimmunoglobulin D syndrome/mevalonate kinase deficiency, and cryopyrin-associated periodic syndromes, together with periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis syndrome, which is the most common polygenic autoinflammatory disease in children, also occurring in adult patients. Finally, based on the available expert consensus recommendations and the highest level of evidence of the published studies, a practical evidence-based guideline for the treatment of these autoinflammatory diseases is proposed.
Topics: Animals; Autoimmune Diseases; Biological Therapy; Colchicine; Dapsone; Evidence-Based Medicine; Fever; Humans; Immunotherapy; Lymphadenitis; Pharyngitis; Randomized Controlled Trials as Topic; Stomatitis, Aphthous; Syndrome; Thalidomide
PubMed: 32655539
DOI: 10.3389/fimmu.2020.00865 -
Journal of the American Academy of... Oct 2022Panniculitis represents a rare and potentially lethal manifestation of alpha-1 antitrypsin deficiency (AATD). Evidence regarding management is limited to case reports... (Review)
Review
BACKGROUND
Panniculitis represents a rare and potentially lethal manifestation of alpha-1 antitrypsin deficiency (AATD). Evidence regarding management is limited to case reports and small case series. We sought to clarify typical features and investigation of AATD-associated panniculitis and assess the evidence regarding therapeutic options.
SEARCH METHODOLOGY
Articles and abstracts published between 1970 and 2020 were identified by searches of MEDLINE, PubMed, and secondary searches of references from relevant articles using the search terms "panniculitis," "alpha-1," "antitrypsin," "deficiency," and "Weber-Christian."
FINDINGS
We identified 117 cases of AATD-associated panniculitis. In 1 series, AATD was present in 15% of all cases of biopsy-proven panniculitis. Failure to achieve clinical response was seen in all instances of systemic steroid use. Dapsone, although effective and accessible, is frequently associated with failure to achieve remission. In these instances, intravenous AAT augmentation therapy generally resulted in response.
CONCLUSIONS
AATD may be more prevalent among patients presenting with panniculitis than previously thought. Patients presenting with panniculitis and systemic illness show high mortality risk. Although most cases are associated with the severe ZZ-genotype, moderate genotypes may also predispose to panniculitis. Dapsone remains the most cost-effective therapeutic option, whereas intravenous AAT augmentation remains the most efficacious. Finally, glucocorticoids appear ineffective in this setting.
Topics: Dapsone; Glucocorticoids; Humans; Panniculitis; alpha 1-Antitrypsin; alpha 1-Antitrypsin Deficiency
PubMed: 33516773
DOI: 10.1016/j.jaad.2021.01.074