Pemphigus Disease Area Index Research Articles

Safety, Tolerability, and Activity of ALXN1830 Targeting the Neonatal Fc Receptor in Chronic Pemphigus

Pemphigus is a debilitating IgG-mediated autoimmune disease requiring better tolerated, more targeted, and rapid onset therapies. ALXN1830 is a humanized IgG4 antibody that blocks neonatal Fc receptor interactions with IgG. A multicenter, open-label safety and tolerability phase 1b/2 trial (NCT03075904) was conducted in North America from July 2017 to January 2019 and included patients aged ≥18 years with a confirmed diagnosis of pemphigus (vulgaris or foliaceus) and active disease. Dosing included five weekly intravenous doses of ALXN1830 (10 mg/kg) and follow-up through day 112 (study termination). Pharmacokinetics, pharmacodynamics, safety, and efficacy, as evaluated by determining the change in the median pemphigus disease area index, were determined. In this pilot study of eight patients, five weekly infusions of ALXN1830 produced a rapid improvement in the pemphigus disease area index score within 14 days of the first dose. Pemphigus disease area index improvement increased further together with reductions in IgG, circulating immune complexes of IgG, and anti-desmoglein antibodies without affecting albumin, IgM, IgA, or C-reactive protein levels. ALXN1830 was well-tolerated, with headache as the most common adverse event. This study reveals the importance of neonatal Fc receptor in the biology of pemphigus and the potential for use of ALXN1830 in pemphigus treatment.

Correlation of anti-γ/ε nicotinic acetylcholine receptor antibody levels with anti-desmoglein 1,3 antibody levels and disease severity in pemphigus vulgaris.

A role for nondesmoglein antigens in the pathogenesis of pemphigus vulgaris (PV) has been suggested in several studies. Acetylcholine receptors (AchR), are one of the most important groups of these antigens. However, the exact role of both antimuscarinic (m) and nicotinic (n) AchR antibodies (Abs) is still controversial. To evaluate anti-desmoglein (Dsg)1, Dsg 3 and anti-γ/ε nAchR Abs values in patients with PV before and 3months after rituximab (RTX) treatment, and to assess their correlation with disease severity. In total, 75 patients with PV (26 men, 49 women) who were planned to receive RTX were enrolled. Disease activity was assessed by using the Pemphigus Disease Area Index (PDAI). Using ELISA, anti-Dsg1,3 and anti-γ/ε nAchR Abs were determined at baseline and 3months after RTX treatment. At baseline, 53.33% patients had positive values for anti-Dsg1, 89.33% for anti-Dsg3 and 13.33% for anti-γ/ε nAchR Abs. All patients with positive anti-γ/ε nAchR Abs had the mucocutaneous phenotype. PDAI, anti-Dsg1,3 and anti-γ/ε nAchR values were dramatically decreased 3months after RTX infusion (P<0.001). There was a significant positive correlation between disease activity and anti-γ/ε nAchR values at baseline (P=0.04), whereas no significant correlation was observed between anti-Dsg1,3 and anti-γ/ε nAchR values at baseline and 3months after RTX infusion. The reduction in anti-γ/ε nAchR Abs with clinical improvement in this study may suggest a synergic role for anti-γ/ε nAchR Abs with anti-Dsg1,3 Abs, or it could be an epiphenomenon.

Beyond the skin: disease parameters in pemphigus.

Pemphigus represents a group of rare autoimmune bullous diseases that affect the skin and mucous membranes. This group has a chronic course leading to high morbidity and mortality. Because of the painful chronic-recurring blisters and/or erosions on skin and mucosa, pemphigus can impair quality of life (QOL). Therapeutic modalities, anxiety and depression can also have an additional negative impact in the QOL of the pemphigus patients. Since the nature and course of the pathology and the fact that pemphigus worsens the quality of life of affected patients, scoring systems to objectively evaluate the clinical activity of the disease and to correlate that with the QOL are needed. Nowadays the most used global scales to assess the clinical activity of pemphigus are the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS), the Pemphigus Disease Area Index (PDAI) and the Pemphigus Visual Activity Scale (PVAS). To evaluate the patient's generic QOL the most used score is the Dermatology Life Quality Index (DLQI), but all the sponsered clinical trials in pemphigus are using ABQOL this rather than DLQI.

Does interleukin-33 level correlate with the activity of Pemphigus vulgaris?: A case-control study.

Pemphigus is a group of immune-mediated blistering diseases of skin and mucus membrane caused by destruction of the intercellular junction (desmosomes) by autoantibodies. Pemphigus vulgaris (PV) is considered the most common type of all pemphigus family. Various cytokines play a major role in pemphigus pathogenesis. Interleukin-33 (IL-33) role has been studied in various autoimmune diseases as; psoriasis and rheumatoid arthritis, yet it has not been studied in Egyptian patients with PV. The study aimed to evaluate the possible role of IL-33 in PV by assessing its level in the serum using ELISA and to detect its correlation with activity score using Pemphigus Disease Area Index (PDAI). Forty-four patients with PV and 36 age and sex-matched healthy controls were enrolled in the study. After full history taking and complete dermatological examination, the severity score was calculated using PDAI, then serum samples were taken from each patient and control subjects and subjected to quantitative measurement of serum IL-33 using ELISA. Serum level of IL-33 is significantly raised in PV patients compared to control subjects (P-value = .007). The level of IL-33 was found to be strongly correlated with the activity of the disease measured by PDAI. IL-33 might have a role in PV pathogenesis as shown by its rising level in PV patients. In addition, serum level of IL-33 is strongly correlated with the activity of PV. Thus, we suspect that IL-33 can be used as marker for monitoring PV severity and measuring treatment efficacy.

15014 Cross-sectional study of the prevalence and predictors of pruritus in pemphigus as compared with bullous pemphigoid

Pemphigus is an autoimmune blistering disease that causes painful erosions, while bullous pemphigoid (BP) is classically known to cause pruritic blisters. Previous reports and anecdotal clinical observations suggest pemphigus patients also experience significant itch; we explored the prevalence and potential predictors of itch in pemphigus patients compared with BP. While the Bullous Pemphigoid Disease Area Index (BPDAI) has a subjective patient itch score (0-10 over 24 hours, week, and month), the Pemphigus Disease Area Index (PDAI) does not, so the BPDAI Pruritus component was administered to both BP and pemphigus patients.

Serum IL-21 level in patients with pemphigus: Before and after treatment.

Interleukin-21 (IL-21) is believed to play a pathogenic role in the development of pemphigus. Our aim was to assess serum IL-21 levels in pemphigus patients before and after treatment. Twenty patients with pemphigus (pemphigus group) and 10 healthy controls (control group) were enrolled. Patients were assessed clinically using the Pemphigus Disease Area Index (PDAI) at presentation and 2 months after treatment. Serum samples were collected to measure serum IL-21 levels by enzyme-linked immunosorbent assay (ELISA), at presentation and after 2 months of treatment. The mean age of the participants was 41.9 ± 13.5 years (7 men and 13 women). The PDAI score at presentation was 37.35 ± 14.206, which decreased significantly after treatment to 11.70 ± 6.729 (P-value <.001). On the other hand, serum IL-21 levels increased after treatment (589.03 ± 131.86 ng/L at first presentation vs 627.10 ± 304.05 ng/L after treatment: P-value .444). No significant correlation was found between the PDAI severity scores and serum IL-21 levels at the first presentation or 2 months after treatment.

Estimated cut-off values for pemphigus severity classification according to pemphigus disease area index (PDAI), autoimmune bullous skin disorder intensity score (ABSIS), and anti-desmoglein 1 autoantibodies

BackgroundPemphigus is a potentially fatal disease if left untreated. Valid scoring systems and defined cut-off values for classification of patients would help with better management through specified pharmaceutical and non-pharmaceutical treatments.MethodsIn this study, pemphigus patients who were receiving immunosuppressive treatments and had recent disease relapse were recruited for examination of pemphigus disease area index(PDAI), autoimmune bullous skin disorder intensity score (ABSIS), physician global assessment (PGA), autoimmune bullous disease quality of life (ABQoL), anti-desmoglein 1 (anti-Dsg1), and anti-Dsg3 autoantibody titers from December-2017 to February-2018. Cut-off values were estimated using model-based clustering classification and the 25th and 75th percentiles approach, performed separately for the exclusive cutaneous, exclusive mucosal, and mucocutaneous groups.ResultsIn the 109 included patients, the 25th and 75th percentiles cut-offs were 6.2 and 27 for PDAI score, and 4 and 29.5 for ABSIS score. The model-based analysis resulted in two groups (cut-point:15) for PDAI score, and three groups (cut-points:6.4 and 31.5) for ABSIS score. The groups were significantly different for the PDAI, ABSIS, PGA, and ABQoL values. Based on anti-Dsg1 autoantibody values, the model-based analysis cut-point was 128 and the 25th and 75th percentiles cut-offs were 98 and 182. Anti-Dsg3 autoantibody values did not differentiate between pemphigus severity classes.ConclusionsEstimated cut-off values based on the anti-Dsg1 level, PDAI, and ABSIS scoring systems could be used to classify patients into different severity grades for better management and prognosis.

Intralesional injection of biosimilar rituximab in recalcitrant mucocutaneous lesions of patients with pemphigus vulgaris: A pilot study.

The efficacy of intravenous rituximab (RTX) in patients with pemphigus have been shown in the previous studies. The study aimed to investigate the effectiveness of intralesional injection of RTX in the healing of pemphigus lesions, with lower doses and probable better safety profile than intravenous RTX. Eleven Pemphigus patients with recalcitrant lesions received two intralesional injections of biosimilar RTX, 5 mg/cm2 . During 6 months follow-up, Pemphigus Disease Area Index, the patients' satisfaction, quality of life, the disease activity, the number and size of lesions, the anti-desmoglein (Dsg) 1 and 3 antibodies and the count of CD4+ and CD19+ cells were assessed. All patients were in partial remission on therapy. The absolute count of CD19+ B cells showed a statistically significant decline (P = .006). The percentage of CD4 + T lymphocytes increased 2 weeks after injection and decreased 2 weeks later (P = .01). The average number and size of lesions decreased. The concentration of anti-Dsg 3 antibody decreased insignificantly during the study. The severe pain during the injection was considered as the main complication. At the end of the study, two patients were in complete remission on therapy, and the other nine remained in partial remission on therapy. Few side effects resulting from intralesional injection of RTX and enhanced quality of life of the patients were considered as the valuable achievements of this study. The results showed that although a low dose of RTX leads to a significant decrease of CD19+ B lymphocytes, it did not show parallel clinical effectiveness.

Serum levels of soluble PD1 in pemphigus vulgaris: A useful marker for disease severity.

Pemphigus vulgaris (PV) is a life-threatening autoimmune blistering disease targeting the skin and mucous membranes. Programmed cell death protein 1 (PD1) is an immune checkpoint which binds to two ligands, PDL1 and PDL2 resulting in negative regulation of antigen receptor signaling, thus, play a critical role in the immune regulation of autoimmune diseases. In this work we aimed to assess serum levels of soluble PD1 (sPD1) in patients with active PV and in patients in remission in an attempt to evaluate its effect on disease severity. In this case-control study, 60 pemphigus vulgaris patients (30 clinically active and 30 in a clinical remission) and 30 age matched healthy control subjects were included. Severity of PV was assessed using pemphigus disease area index (PDAI) score. Serum levels of sPD1 were measured by ELISA for both patients and healthy control. Serum levels of sPD1 were significantly lower in PV patients than in controls (P<.001) and significantly lower in patients with active disease than in those in remission (P<.001). Serum sPD1 correlated negatively with the severity of the disease (P<.001, r=-0.4). A defect in PD1 pathway is suggested in PV patients, and this defect plays a substantial role in determining the severity of the disease. Thus, sPD1 could be considered a useful marker for disease severity and targeting PD1 pathway could be a potential aim for future therapies of PV.

Pemphigus Oral Lesions Intensity Score (POLIS): A Novel Scoring System for Assessment of Severity of Oral Lesions in Pemphigus Vulgaris

Background: Many patients with pemphigus vulgaris (PV) in India present with predominant/exclusive oral mucosal lesions. Current validated scoring systems for pemphigus do not adequately represent the clinical variability of oral lesions.Objective: To develop and validate a novel scoring system exclusively for oral lesions in PV.Methods: In this cross-sectional study, the Delphi method was used to build an initial scale that was administered in 115 patients with PV. Exploratory factor analysis was used to examine the underlying factor structure of the new scale. The psychometric properties of the new scale were studied. Correlations between the new scale and Autoimmune Bullous Skin Disorder Intensity Score (ABSIS), Pemphigus Disease Area Index (PDAI), and Physician Global Assessment (PGA) were also assessed.Results: Content validity of the initial scale was established with an average content validity index (CVI) of 0.8. Exploratory factor analysis resulted in a 3-factor structure with a total of 9 items. Corrected item-total correlation, a measure of data quality, was more than 0.30 for all items in the new oral mucosal scale—Pemphigus Oral Lesions Intensity Score (POLIS). Significant correlations were observed between POLIS and oral ABSIS (r = 0.85, p < 0.001), mucosal PDAI (r = 0.70, p < 0.001), and PGA (r = 0.60, p < 0.001). POLIS was also reliable with good internal consistency (Cronbach's α = 0.86) and strong inter-rater agreement.Limitations: The study cohort included participants from a single center. Usability and time taken to administer the scale were not assessed.Conclusions: The new scale, POLIS, has adequate validity and reliability. It includes both quality of life and clinical disease severity parameters, assessing disease severity holistically. Further studies evaluating the scale's responsiveness to change are in progress.

Treatment of Pemphigus Vulgaris and Foliaceus with Adjuvant Rituximab Compared to Immunosuppression Alone: Real-Life Experience

Introduction: In a randomized prospective trial, adjuvant rituximab was more efficacious than corticosteroids alone in the treatment of pemphigus; however, real-life data are limited. Rituximab treatment for pemphigus has only recently been introduced to the Israeli health basket. Previously, patients received rituximab if they paid out of pocket or through private insurance, separating patients into 2 treatment groups, mostly based on economic capability. Methods: A retrospective cohort study of the 12-month clinical response of pemphigus vulgaris/foliaceus patients. We compared patients after a single cycle (1,000 mg on days 0 and 15 or weekly 375 mg/m² for 4 weeks) of adjuvant rituximab with systemic corticosteroids ± steroid-sparing agents, to patients who were prescribed rituximab, could not obtain it, and received systemic corticosteroids ± steroid-sparing agents. Results: Forty-five patients were included (adjuvant rituximab, n = 29; immunosuppression alone, n = 16). At baseline, rituximab patients had a higher mean pemphigus disease area index (PDAI) (p = 0.07) and higher mean daily dosages of prednisone (1.51 vs. 1.16 mg/kg, p = 0.39). All patients but 1 in the rituximab group continued systemic steroids, and 31% in the rituximab group versus 50% in the immunosuppression-alone group received systemic adjuvants. At 12 months, partial or complete remission rates (on or off maximum 40 mg/day prednisone equivalent) were nonsignificantly higher in the rituximab group (62 vs. 50%, p = 0.53); however, patients on rituximab showed faster remissions (3.4 ± 1.9 vs. 5.9 ± 3.6 months; p = 0.03) with a trend for a greater PDAI reduction (p = 0.051). Adverse events were comparable. Conclusions: In this real-life study, a single cycle of rituximab achieved more remissions and sooner compared to conventional immunosuppression, but the differences were not significant, probably due to a small sample size and severe baseline disease in the rituximab group. Future real-life studies on larger groups are needed.

Itch-related quality of life impact across 3 autoimmune blistering diseases: a retrospective cohort study

Introduction: Autoimmune blistering diseases (AIBD) produce a range of debilitating symptoms potentially greatly impacting quality of life (QoL). We sought to compare the disease-related and itch-related QoL impact between AIBD including pemphigus, bullous pemphigoid (BP), and mucous membrane pemphigoid (MMP). Methods: We performed a retrospective cohort study of patients attending a specialty Autoimmune Blistering Disease Clinic at a single academic center between July 2017 and April 2019. Patients with an established histopathologic or serological diagnosis of pemphigus, BP or MMP with mucosal and/or cutaneous lesions on clinical examination, or patient-reported QoL impact in the past week were recruited to participate. Patients completed Autoimmune Blistering Disease Quality of Life (ABQoL), Treatment of Autoimmune Blistering Disease Quality of Life (TABQoL), and ItchyQoL survey instruments, and disease severity was assessed using the Pemphigus Disease Area Index (PDAI) (pemphigus), Bullous Pemphigoid Disease Area Index (BPDAI) (BP), and Mucous Membrane Pemphigoid Disease Area Index (MMPDAI) (MMP). Statistical analyses were performed using IBM SPSS 26. Results: BP and pemphigus demonstrated similar itch-related QoL impact, greater than that of MMP. Disease severity was significantly associated with itch-related QoL in BP and pemphigus, as was use of biological/targeted therapies in BP alone. Discussion: Itch is a significant symptom in both BP and pemphigus and can negatively affect QoL. Disease severity and treatment type play a role in itch-related QoL in pemphigus and BP. Additional studies are needed to elucidate the mechanisms for itch in AIBD, particularly in pemphigus where this symptom has only recently been described.

Correlation of IgG autoantibodies against acetylcholine receptors and desmogleins in patients with pemphigus treated with steroid sparing agents or rituximab.

IntroductionAutoantibodies (autoAbs) against desmoglein-1 (DSG1) and desmoglein-3 (DSG3) have conventionally been studied and well accepted in the pathogenesis of pemphigus vulgaris (PV) and foliaceus (PF). Recent studies have suggested that non-DSG autoAbs may contribute to the pathogenesis of pemphigus, including autoAbs directed at acetylcholine receptors (AChR) and thyroid peroxidase (TPO). The purpose of this study is to retrospectively analyze PV and PF patient sera to better understand the relationship between anti-AChR and -TPO Abs to disease activity and DSG reactivity between patients treated with prednisone and steroid sparing agents (SSA; n = 22) or prednisone and rituximab (n = 21).MethodsPatients were evaluated at 2 time points, T1 and T2, for disease activity using the Pemphigus Disease Area Index (PDAI), and sera were tested for the presence of TPO, DSG1, DSG3, muscarinic (M3) and nicotinic (n) AChR IgG autoAbs, as well as antibodies against Varicella Zoster Virus (VZV) by ELISA.ResultsDisease activity significantly decreased in patients from T1 to T2 (p < .0001). A significant difference was seen in IgG anti-DSG1 (p < .0001) and anti-DSG3 (p = .0049) levels when T1 was compared to T2 in both treatment groups. A significant increase was found between pemphigus patients and normal subjects with nAChR (p < .0001) at T1 but not with m3AChR, TPO or VZV Abs. No significant difference was seen between T1 and T2 values in patients with pemphigus for the non–desmoglein Abs TPO (p = .7559), M3AChR (p = .9003), nAChR (p = .5143) or VZV (p = .2454). These findings demonstrate that although an increase in IgG anti-nAChR autoAbs was found in PV and PF subjects, these Abs did not decrease with treatment. No other non-DSG Abs were increased or significantly changed over time in patients with pemphigus. This suggests that anti -AChR and -TPO Abs may not play a direct role in the pathogenesis of most patients with pemphigus, but does not rule out a role for non-DSG auto antibodies in distinct subsets of pemphigus patient.

Factors Associated With Short-term Relapse in Patients With Pemphigus Who Receive Rituximab as First-line Therapy

Rituximab and short-term corticosteroid therapy are the criterion standard treatments for patients with newly diagnosed moderate to severe pemphigus. To examine factors associated with short-term relapse in patients with pemphigus treated with rituximab. This post hoc analysis of a randomized clinical trial (Comparison Between Rituximab Treatment and Oral Corticosteroid Treatment in Patients With Pemphigus [RITUX 3]) conducted from January 1, 2010, to December 31, 2015, included patients from 20 dermatology departments of tertiary care centers in France from the RITUX 3 trial and 3 newly diagnosed patients treated according to the trial protocol. Data analysis was performed from February 1 to June 30, 2019. Patients randomly assigned to the rituximab group in the RITUX 3 trial and the 3 additional patients were treated with 1000 mg of intravenous rituximab on days 0 and 14 and 500 mg at months 12 and 18 combined with a short-term prednisone regimen. Baseline (pretreatment) clinical and biological characteristics (Pemphigus Disease Area Index [PDAI] score, ranging from 0-250 points, with higher values indicating more severe disease) and changes in anti-desmoglein (DSG) 1 and anti-DSG3 values as measured by enzyme-linked immunosorbent assay during the 3 months after rituximab treatment were compared between patients with disease relapse and those who maintained clinical remission during the first 12 months after treatment. The positive and negative predictive values of these factors were calculated. Among 47 patients (mean [SD] age, 54.3 [17.0] years; 17 [36%] male and 30 [64%] female) included in the study, the mean (SD) baseline PDAI score for patients with relapsing disease was higher than that of the patients with nonrelapsing disease (54 [33] vs 28 [24]; P = .03). At month 3, 7 of 11 patients with relapsing disease (64%) vs 7 of 36 patients with nonrelapsing disease (19%) had persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher (P = .01). A PDAI score of 45 or higher defining severe pemphigus and/or persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher at month 3 provided a positive predictive value of 50% (95% CI, 27%-73%) and a negative predictive value of 94% (95% CI, 73%-100%) for the occurrence of relapse after rituximab. The findings suggest that initial PDAI score and changes in anti-DSG antibody values after the initial cycle of rituximab might help differentiate a subgroup of patients with high risk of relapse who might benefit from maintenance rituximab infusion at month 6 from a subgroup of patients with low risk of relapse who do not need early maintenance therapy. NCT00784589.

Therapeutic outcomes of pemphigus in a referral service in Northern Brazil: a retrospective study of 32 patients

Background Pemphigus are rare chronic autoimmune blistering disorders with challenging therapeutic management. Objective To investigate the therapeutic outcomes of pemphigus patients admitted to a dermatology referral service in northern Brazil. Materials and methods We conducted a retrospective analysis of 32 patients with histopathological diagnosis of pemphigus between 2010 and 2016. Clinical and epidemiological data were collected. Therapeutic outcome was evaluated according to the criteria proposed by the International Pemphigus Committee. Pemphigus Disease Area Index (PDAI) was used to quantify disease severity. Results Of the 32 patients, 68.75% had pemphigus vulgaris (PV) and 31.25% had pemphigus foliaceus (PF). Female-to-male ratio was 1:1. The average age was 49.5 years. All patients received oral prednisone as the first-line therapy. Adjuvant immunosuppressive drugs were gradually added in refractory and/or severe cases. After 24 months of treatment, disease control and complete remission rates were 37.5% and 25%, respectively. The mortality rate was 9.37%. PDAI score was significantly lower at 24 months of therapeutic follow-up (p < .0001). Conclusion Therapeutic management with corticosteroids and/or immunosuppressive drugs was able to induce disease control/complete remission in most of patients. PDAI was a useful tool for objective assessment of disease severity during therapeutic follow-up.

Comparative retrospective evaluation of efficacy of rituximab therapy with dexamethasone cyclophosphamide pulse therapy in patients of pemphigus vulgaris at a tertiary care hospital

Background: Popular treatment modalities for pemphigus vulgaris are dexamethasone cyclophosphamide pulse (DCP) therapy and rituximab. However, no previous studies are available which have compared the efficacy of the two modalities. Aim: This study aims to study the response of pemphigus vulgaris to DCP and rituximab therapy and to compare the efficacy and safety of the two modalities over a period of 1½ years. Materials and Methods: This was an observational retrospective study. The medical records of a total of 14 pemphigus vulgaris patients from July 2016 to July 2018 were retrieved for analysis who were treated with either DCP therapy or rituximab (7 in each group). Patients treated with any other modality except DCP/rituximab were excluded from the study. The pemphigus disease area index (PDAI) scores at baseline, 1 month, 6 months, 12 months, and 18 months were analyzed using statistical software (Stata Corp. 2013. Stata Statistical Software: Release 13. College Station, TX, Stata Corp. LP, Texas, USA). Outcome Measures: Time to achieve the end of consolidation phase, improvement in PDAI scores, adverse effects, and relapse. Results: Rituximab group achieved early remission; however, there was no statistically significant difference in the two groups in the time when they reached the end of consolidation phase. Repeated measure anova showed significant difference in PDAI scores within the two groups over time. One patient in DCP group relapsed following discontinuation of cyclophosphamide due to complications. Overall, the scoring of disease severity was markedly reduced in both the groups. Conclusion: Both DCP therapy and rituximab were found to be extremely and equally effective in inducing and maintaining remission.

Evaluation of methicillin-resistant Staphylococcus aureus infections in pemphigus vulgaris patients: cross-sectional study

Background Pemphigus vulgaris (PV) is a potentially fatal autoimmune vesiculobullous disease. Staphylococcus aureus is the most common cause of cutaneous bacterial infection in pemphigus. Methicillin-resistant S. aureus (MRSA) is a common multidrug-resistant bacterium. MRSA infection is high among dermatology inpatients and vesiculobullous diseases patients are the commonest infected.Objective This study aimed at determining the causative organisms of the secondary bacterial skin infections in PV patients, identifying MRSA, doing antibiotic sensitivity pattern for MRSA, and determining the risk factors for acquiring MRSA infection among PV patients in the locality.Patients and methods This cross-sectional study included 54 PV patients. All patients were subjected to history taking, general, and dermatological examinations. Pemphigus disease area index score was calculated. Three swabs for bacterial culture and antibiotic sensitivity testing were obtained (one from vesicle or bulla, one from pustule, and the third from the nose).Results In all, 51 (94.4%) patients showed positive cultures for S. aureus either as nasal carrier, skin colonization, or skin infection. There was overlap as some patients showed more than one type of positive culture at the same time. Of the patients, 19 out of 51 patients (37.25%) had positive cultures for MRSA. All MRSA strains were sensitive to vancomycin. Also, they had good sensitivity to trimethoprim–sulfamethoxazole, amikacin, ciprofloxacin, and erythromycin, while all MRSA strains were resistant to cefoxitin and ampicillin. Hospitalization, previous antibiotics use in the last 4 weeks prior to this study, length of hospital stay, history of hospital-acquired infections, and community-acquired infections were significantly higher among MRSA-positive patients.Conclusion There is high MRSA infection/colonization among PV patients. MRSA responds to cheap antibiotics as trimethoprim–sulfamethoxazole, amikacin, and ciprofloxacin.

Phosphorylated p38 mitogen-activated kinase in patients with pemphigus vulgaris: a case–controlled study

Background Although the exact pathogenic mechanisms leading to blister formation in pemphigus vulgaris (PV) have not been fully elucidated, intracellular signaling following antibody binding has been found to be necessary for inducing cell-cell dissociation. The phosphorylated p38 mitogen-activated protein kinase (P38 MAPK) signaling pathway plays a major role in the modulation of immune-mediated inflammatory responses and therefore has been linked with several autoimmune diseases. Studies showed that activation of P38 MAPK plays a role in the acantholytic process in PV through changes in the quaternary structure and cytoskeletal rearrangements. Objective To determine the levels of p38 MAPK and its substrate [MAP kinase-activated protein kinase 2 (MAPKAPK2)] in the peripheral blood mononuclear cells of patients with PV in relation to both the clinical score and the antidesmoglein 3 antibodies. Patients and methods This study included 25 Egyptian patients with PV and 25 healthy controls, who were recruited from Cairo University Hospitals. Detailed history was documented, and the severity of the diseases was determined by pemphigus disease area index score in each patient. Blood samples were obtained from all participants. Then, determination of the expression of p38 MAPK and its substrate MAPKAPK2 on peripheral mononuclear cells was done using flow cytometry, with measurement of antidesmoglein 3 antibody using enzyme-linked immunosorbent assay technique. Results We detected that P38 MAPK and MAPKAPK2 were upregulated in patients with PV in comparison with controls (P=0.024 and P=0.002, respectively). There was a positive correlation between the anti-Dsg3 antibodies and P38 MAPK (r=0.591, P=0.004) and between disease severity (pemphigus disease area index score) and P38 MAPK (r=0.617, P=0.002) as well. Conclusion This study concluded that P38 MAPK and its substrate MAPKAPK2 have a role in the pathogenesis of PV. Moreover, P38 MAPK can be used as a marker for disease activity follow-up, as it was correlated with both disease severity and autoantibody level.

Assessing the Correlation Between Disease Severity Indices and Quality of Life Measurement Tools in Pemphigus.

Pemphigus, an autoimmune blistering disease that affects the skin and mucous membranes, adversely impacts patients' quality of life (QOL). While there are various QOL measurement tools that can be used in this disease, few studies have assessed how a patient's change in disease severity can affect their QOL. This study aims to identify which disease severity index correlates best with the change in QOL. Fifty pemphigus patients completed QOL surveys with disease severity scored over two visits. QOL was assessed with the Autoimmune Bullous Disease Quality of Life (ABQOL), Dermatology Life Quality Index (DLQI), Skindex-29, and Short Form Survey 36 (SF-36). Disease severity was scored with the Pemphigus Disease Area Index (PDAI) and Autoimmune Bullous Skin Disorder Intensity Score (ABSIS). Correlations between the change in QOL scores and change in disease severity were analyzed using Spearman's coefficient (r). The change in PDAI showed a strong correlation (r = 0.60–0.79) with changes in the ABQOL, Skindex-29 symptoms (Skindex-S), and Skindex-29 functioning (Skindex-F) subscales for all patients (n = 50). For patients with mucosal disease (n = 24), the change in PDAI showed a strong correlation with changes in the ABQOL and Skindex-S subscale. For patients without mucosal disease, the change in PDAI showed a strong correlation with the Skindex-S. The change in ABSIS showed a strong correlation with Skindex-S for all patients and patients with no mucosal involvement, but showed no strong correlations for patients with mucosal involvement. The changes in PDAI always had a stronger correlation than the changes in ABSIS scores to changes in the ABQOL, DLQI, and Skindex-29 subscales, except where the PDAI and ABSIS scores were about the same for the Skindex-S subscale in patients with no mucosal involvement (r = 0.76 and r = 0.77, respectively). PDAI is superior to ABSIS in its correlation with validated QOL tools. The QOL tools that appear to be of most use in clinical trials and patient management are the Skindex-S and ABQOL.

The use of rituximab as an adjuvant in the treatment of oral pemphigus vulgaris.

Pemphigus vulgaris patients with exclusive oral involvement (OPV) treated with conventional immunosuppressive therapy may be non-responders or experience severe side effects and/or relapses. In such cases, rituximab could be used as an adjuvant in recalcitrant OPV patients. A retrospective single-center study on patients with oral pemphigus vulgaris treated with RTX at a dose of 375mg/m2 was performed, evaluating the complete clinical and immunological remission, side effects of RTX, and possible correlation between anti-desmoglein (Dsg) 3 antibodies and clinical remission. We treated 10 OPV patients, of which 60% had a moderate and 40% mild disease severity before therapy with RTX. Complete clinical remission (CCR) was achieved in 100% of OPV patients, of which 20% developed side effects and 20% experienced a relapse in a mean time of 15.2±10.2weeks. The mean time for CCR was achieved in 19.8±10.3weeks, whereas the duration of the CCR consisted in 37.4±33.5weeks. OPV patients underwent a mean follow-up of 57.2±37.7weeks. In all patients, the mean of pemphigus disease area index (PDAI) decreased from 20.3±14.1 to 0.4±0.0, whereas the mean Dsg3 value dropped from 157.1±40.6 to 67.0±26.6 after therapy with RTX. However, no correlation was found between PDAI and anti-Dsg3 antibodies before and after therapy with RTX (P>.05). RTX represents a valid and safe alternative as an adjuvant in OPV patients with low rate of relapses and side effects.