Dexamethasone-cyclophosphamide pulse therapy outcomes comparing pemphigus vulgaris and pemphigus foliaceus groups in a Brazilian cohort study.

BACKGROUND: Dexamethasone-cyclophosphamide pulse (DCP) and dexamethasone pulse (DP) have been successfully used to treat pemphigus, but DCP/DP outcomes comparing pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are scarce. OBJECTIVE: To compare DCP/DP outcomes in a Brazilian cohort of PV and PF patients according to demographic and clinical data. METHODS: Retrospective analytical cohort study, reviewing medical charts of PV and PF patients (for DCP/DP Phases I‒IV consult Pasricha et al.16‒18). RESULTS: 37 PV and 41 PF patients non responsive to usual treatments were included similarly for DCP or DP therapy. Disease duration was longer among PF before DCP/DP prescription (p < 0.001); PF required a higher number of monthly pulses to acquire remission in Phase I (median 10 and 6 pulses, respectively; p = 0.005). DCP/DP outcomes were similar in both groups: remission in 37.8% of PV and 34.1% of PF after completed DCP/DP cycles following a median of 13 months (1-56 months follow-up); failure occurred in 13.5% of PV and 14.6% of PF in Phase I; relapse in 13.5% of PV and 12.2% of PF, and dropout in 27% of PV and 24.4% of PF in Phases II to IV. Mild side effects were documented. STUDY LIMITATIONS: The severity of PV and PF disease was not assessed by score indexes. CONCLUSIONS: PV and PF patients presented similar DCP/DP outcomes. DCP/DP should be initiated earlier in PF patients due to the longer duration of their disease in order to decrease the number of pulses and the duration of Phase I to acquire remission.

Measurement of pesticides in hair samples from pemphigus foliaceus and pemphigus vulgaris patients in Southeastern Brazil.

BACKGROUND: Pesticides, mainly organophosphates (OP), have been related to increased risk of pemphigus vulgaris (PV) and pemphigus foliaceus (PF), nevertheless, their measurement has not been determined in pemphigus patients. OBJECTIVE: To evaluate pesticide exposure and pesticide measurement, comparing PV, PF and control groups in Southeastern Brazil. METHODS: Information about urban or rural residency and exposure to pesticides at the onset of pemphigus was assessed by questionnaire interview; hair samples from the scalp of PV, PF, and controls were tested for OP and organochlorines (OC) by gas-phase chromatography coupled to mass spectrometry. RESULTS: The minority of PV (2 [7.1%] of 28) and PF (7 [18%] of 39), but none of the 48 controls, informed living in rural areas at the onset of pemphigus (p = 0.2853). PV (33.3%), PF (38.5%), and controls (20%) informed exposure to pesticides (p = 0.186). Twenty-one (14.8%) of 142 individuals tested positive for OP and/or OC: PV (2 [6.3%] of 32) and PF (11 [25.6%] of 43) had similar pesticides contamination as controls (8 [11.9%] of 67) (p = 0.4928; p = 0.0753, respectively), but PF presented higher contamination than PV (p = 0.034). PV did not present any positivity for OP. Three (7%) PF tested positive for both OP and OC. Some PF tested positive for three or four OP, mainly diazinon and dichlorvos. STUDY LIMITATION: Lack of data for some controls. CONCLUSION: Although the frequency of PV and PF patients exposed to pesticides was similar, pesticides were more frequently detected in hair samples from PF compared to PV. The cause-effect relationship still needs to be determined.

Dexamethasone-cyclophosphamide pulse therapy outcomes comparing pemphigus vulgaris and pemphigus foliaceus groups in a Brazilian cohort study

Abstract Background Dexamethasone-cyclophosphamide pulse (DCP) and dexamethasone pulse (DP) have been successfully used to treat pemphigus, but DCP/DP outcomes comparing pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are scarce. Objective To compare DCP/DP outcomes in a Brazilian cohort of PV and PF patients according to demographic and clinical data. Methods Retrospective analytical cohort study, reviewing medical charts of PV and PF patients (for DCP/DP Phases I‒IV consult Pasricha et al.16‒18). Results 37 PV and 41 PF patients non responsive to usual treatments were included similarly for DCP or DP therapy. Disease duration was longer among PF before DCP/DP prescription (p < 0.001); PF required a higher number of monthly pulses to acquire remission in Phase I (median 10 and 6 pulses, respectively; p = 0.005). DCP/DP outcomes were similar in both groups: remission in 37.8% of PV and 34.1% of PF after completed DCP/DP cycles following a median of 13 months (1-56 months follow-up); failure occurred in 13.5% of PV and 14.6% of PF in Phase I; relapse in 13.5% of PV and 12.2% of PF, and dropout in 27% of PV and 24.4% of PF in Phases II to IV. Mild side effects were documented. Study limitations The severity of PV and PF disease was not assessed by score indexes. Conclusions PV and PF patients presented similar DCP/DP outcomes. DCP/DP should be initiated earlier in PF patients due to the longer duration of their disease in order to decrease the number of pulses and the duration of Phase I to acquire remission.

Measurement of pesticides in hair samples from pemphigus foliaceus and pemphigus vulgaris patients in Southeastern Brazil

Abstract Background Pesticides, mainly organophosphates (OP), have been related to increased risk of pemphigus vulgaris (PV) and pemphigus foliaceus (PF), nevertheless, their measurement has not been determined in pemphigus patients. Objective To evaluate pesticide exposure and pesticide measurement, comparing PV, PF and control groups in Southeastern Brazil. Methods Information about urban or rural residency and exposure to pesticides at the onset of pemphigus was assessed by questionnaire interview; hair samples from the scalp of PV, PF, and controls were tested for OP and organochlorines (OC) by gas-phase chromatography coupled to mass spectrometry. Results The minority of PV (2 [7.1%] of 28) and PF (7 [18%] of 39), but none of the 48 controls, informed living in rural areas at the onset of pemphigus (p = 0.2853). PV (33.3%), PF (38.5%), and controls (20%) informed exposure to pesticides (p = 0.186). Twenty-one (14.8%) of 142 individuals tested positive for OP and/or OC: PV (2 [6.3%] of 32) and PF (11 [25.6%] of 43) had similar pesticides contamination as controls (8 [11.9%] of 67) (p = 0.4928; p = 0.0753, respectively), but PF presented higher contamination than PV (p = 0.034). PV did not present any positivity for OP. Three (7%) PF tested positive for both OP and OC. Some PF tested positive for three or four OP, mainly diazinon and dichlorvos. Study limitation Lack of data for some controls. Conclusion Although the frequency of PV and PF patients exposed to pesticides was similar, pesticides were more frequently detected in hair samples from PF compared to PV. The cause-effect relationship still needs to be determined.

Bullous pemphigoid and milia: prevalence and clinical laboratory findings in a Brazilian sample

Abstract Background: Bullous pemphigoid (BP) associated with milia lesions has been increasingly reported, but its prevalence has not been reported in a Brazilian BP population yet. Objectives: To describe the occurrence and clinical-laboratorial findings of BP-milia association in a southeastern Brazilian sample. Methods: A descriptive study based on the medical charts of 102 BP patients was accomplished. Clinical and laboratory data of BP-milia patients were compiled. Total serum IgE measurements, immunoblot assays based on basement membrane zone antigens, and HLA-DQ alleles typing were performed. Results: Milia was evident in 8 (7.8%) BP patients, five males, aged between 46 and 88 years. Increased total IgE levels were determined in 7 (87.5%) of the eight patients. In five of eight patients, immunoblotting showed IgG reactivity against the BP180-NC16a domain but not against collagen VII or laminin-332; it also revealed reactivity against the BP180 C-terminal domain or LAD-1, or both in four of them. The HLA-DQB1*03:01 and HLA-DQA1*05:05 alleles were identified in three of five BP-milia patients. Moreover, three of five cases presented the HLA-DQB1*06 allelic group. Study limitations: HLA determination was performed in five patients. Conclusions: Milia formation in BP patients seems to be less uncommon than previously admitted. Laboratory data revealed increased IgE; autoantibodies against the BP180 C-terminal domain or LAD-1, or both; and the HLA-DQB1*06 allelic group, described for the BP-milia association. Careful determination of antibodies against basement membrane zone molecules and HLA characterization in different populations may provide further insights into this association. © 2022 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/).

Bullous pemphigoid and milia: prevalence and clinical laboratory findings in a Brazilian sample.

BACKGROUND: Bullous pemphigoid (BP) associated with milia lesions has been increasingly reported, but its prevalence has not been reported in a Brazilian BP population yet. OBJECTIVES: To describe the occurrence and clinical-laboratorial findings of BP-milia association in a southeastern Brazilian sample. METHODS: A descriptive study based on the medical charts of 102 BP patients was accomplished. Clinical and laboratory data of BP-milia patients were compiled. Total serum IgE measurements, immunoblot assays based on basement membrane zone antigens, and HLA-DQ alleles typing were performed. RESULTS: Milia was evident in 8 (7.8%) BP patients, five males, aged between 46 and 88 years. Increased total IgE levels were determined in 7 (87.5%) of the eight patients. In five of eight patients, immunoblotting showed IgG reactivity against the BP180-NC16a domain but not against collagen VII or laminin-332; it also revealed reactivity against the BP180 C-terminal domain or LAD-1, or both in four of them. The HLA-DQB1*03:01 and HLA-DQA1*05:05 alleles were identified in three of five BP-milia patients. Moreover, three of five cases presented the HLA-DQB1*06 allelic group. STUDY LIMITATIONS: HLA determination was performed in five patients. CONCLUSIONS: Milia formation in BP patients seems to be less uncommon than previously admitted. Laboratory data revealed increased IgE; autoantibodies against the BP180 C-terminal domain or LAD-1, or both; and the HLA-DQB1*06 allelic group, described for the BP-milia association. Careful determination of antibodies against basement membrane zone molecules and HLA characterization in different populations may provide further insights into this association.

Autoantibodies against desmoglein 2 are not pathogenic in pemphigus

Abstract Background Anti-desmoglein 1 and 3 autoantibodies justify acantholysis in pemphigus; however, the pathogenesis of anti-desmoglein 2 is hypothetical. Objective To compare the participation of desmogleins 1, 2 and 3 through the production of serum autoantibodies, and protein and gene expression in the skin/mucosa of patients with pemphigus foliaceus and pemphigus vulgaris. Methods The autoantibodies were titrated by ELISA in 202 samples of pemphigus foliaceus, 131 pemphigus vulgaris, 50 and 57 relatives of patients with pemphigus foliaceus and pemphigus vulgaris, respectively, and 114 controls. Protein and gene expressions were determined by immunohistochemistry and qPCR in the skin/mucosa of 3 patients with pemphigus foliaceus and 3 patients with pemphigus vulgaris. Results Higher titers of anti-desmoglein 2 (optical density) resulted in pemphigus foliaceus and pemphigus vulgaris, when compared to controls (0.166; 0.180; 0.102; respectively; p < 0.0001). There was a correlation between anti-desmoglein 2 and anti-desmoglein 1 titers in pemphigus foliaceus (r = 0.1680; p = 0.0206). There was no cross-reaction of anti-desmoglein 2 with desmoglein 1 and 3. Protein overexpression of desmoglein 2 was observed in intact and lesional skin of patients with pemphigus compared to the skin of controls. Internalization granules of desmoglein 1 and 3, but not of desmoglein 2, were observed in lesions of pemphigus foliaceus and pemphigus vulgaris, respectively. Gene overexpression of desmoglein 2 was observed in the mucosa. Study limitations Small sample size for the statistical analysis of protein and gene expression. Conclusion Autoantibodies against desmoglein 2 are not pathogenic in pemphigus; protein and gene overexpression of desmoglein 2 in the skin and mucosa may be involved in acantholysis repair.

Autoantibodies against desmoglein 2 are not pathogenic in pemphigus.

BACKGROUND: Anti-desmoglein 1 and 3 autoantibodies justify acantholysis in pemphigus; however, the pathogenesis of anti-desmoglein 2 is hypothetical. OBJECTIVE: To compare the participation of desmogleins 1, 2 and 3 through the production of serum autoantibodies, and protein and gene expression in the skin/mucosa of patients with pemphigus foliaceus and pemphigus vulgaris. METHODS: The autoantibodies were titrated by ELISA in 202 samples of pemphigus foliaceus, 131 pemphigus vulgaris, 50 and 57 relatives of patients with pemphigus foliaceus and pemphigus vulgaris, respectively, and 114 controls. Protein and gene expressions were determined by immunohistochemistry and qPCR in the skin/mucosa of 3 patients with pemphigus foliaceus and 3 patients with pemphigus vulgaris. RESULTS: Higher titers of anti-desmoglein 2 (optical density) resulted in pemphigus foliaceus and pemphigus vulgaris, when compared to controls (0.166; 0.180; 0.102; respectively; p < 0.0001). There was a correlation between anti-desmoglein 2 and anti-desmoglein 1 titers in pemphigus foliaceus (r = 0.1680; p = 0.0206). There was no cross-reaction of anti-desmoglein 2 with desmoglein 1 and 3. Protein overexpression of desmoglein 2 was observed in intact and lesional skin of patients with pemphigus compared to the skin of controls. Internalization granules of desmoglein 1 and 3, but not of desmoglein 2, were observed in lesions of pemphigus foliaceus and pemphigus vulgaris, respectively. Gene overexpression of desmoglein 2 was observed in the mucosa. STUDY LIMITATIONS: Small sample size for the statistical analysis of protein and gene expression. CONCLUSION: Autoantibodies against desmoglein 2 are not pathogenic in pemphigus; protein and gene overexpression of desmoglein 2 in the skin and mucosa may be involved in acantholysis repair.