Rituximab in the Treatment of Epidermolysis Bullosa Acquisita: A Systematic Review.

Objective: Epidermolysis bullosa acquisita (EBA) is a rare dermatosis of the mucous membrane and/or skin. Employing biologic treatment modalities, specifically rituximab (RTX), have become pivotal measure in treating patients with blistering diseases. This study aims to summarize the current evidence on the safety and efficacy of RTX in EBA. Methods: An extensive search was performed in MEDLINE/PubMed, Embase, Scopus, and Web of Science databases until the end of August 19th, 2023. Two independent reviewers screened the papers, and collected data. Two hundred thirty-three studies were screened using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Results: Thirty-one studies were enrolled. The most common reason of RTX administration in patients with EBA was recalcitrant diseases. Clinical response and disease remission was recorded as 92.7 percent (63 patients) and 73.8 percent (45 patients) of the patients, respectively. A relapse rate of 39.5 percent (15 patients) in the mean follow-up of 23.0 months was reported in the studies. Of the patients, 28.2 percent (11 patients) experienced RTX-related side events, mostly mild and transient infusion reactions. Conclusion: The results of this systematic review demonstrated that RTX is safe and effective in patients with EBA. This biological treatment modality can be routinely used in managing EBA.

Lichenoid mycosis fungoides: Report of a case with lichen planus-like histopathologic features.

Key Clinical Message: Mycosis fungoides is a diagnostic challenge. Herein, we report a case with marked lichenoid features in pathology assessments. After several biopsies and clinicopathologic correlation, the diagnosis of lichenoid mycosis fungoides was made. Abstract: Mycosis fungoides (MF) is a great imitator and mimicks other dermatoses clinically and histopathologically. We report a 61-year-old patient with 5-year history of generalized violaceous patches and plaques. His biopsy revealed a marked lichenoid band-like infiltrate of inflammatory cells along the basal layer with basal layer vacuolar changes; the diagnosis of lichen planus was first made histopathologically. Several biopsy specimens, clinicopathologic correlation, and immunohistochemistry findings confirmed the diagnosis of lichenoid MF. Awareness of peculiar histopathologic findings of MF is essential to avoid a potential misdiagnosis. When in doubt, multiple biopsies with other diagnostic methods should be employed.

A systematic review on efficacy, safety and treatment durability of intravenous immunoglobulin in autoimmune bullous dermatoses: Special focus on indication and combination therapy.

Autoimmune bullous diseases (AIBDs) are a group of rare blistering dermatoses of the mucous membrane and/or skin. The efficacy, safety and treatment durability of intravenous immunoglobulin (IVIg) as an alternative treatment should be explored to systematically review the available literature regarding treatment outcomes with IVIg in AIBD patients. The predefined search strategy was incorporated into the following database, MEDLINE/PubMed, Embase, Scopus and Web of Science on 18 July 2022. Sixty studies were enrolled using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The use of IVIg alone or combined with rituximab was reported in 500 patients with pemphigus, 82 patients with bullous pemphigoid, 146 patients with mucous membranes pemphigoid and 19 patients with epidermolysis bullosa acquisita. Disease remission with IVIg therapy and RTX + IVIg combination therapy were recorded as 82.8% and 86.7% in pemphigus, 88.0% and 100% in bullous pemphigoid and 91.3% and 75.0% in mucous membrane pemphigoid, respectively. In epidermolysis bullosa acquisita, treatment with IVIg led to 78.6% disease remission; no data were available regarding the treatment with RTX + IVIg in this group of patients. Among all the included patients, 37.5% experienced at least one IVIg-related side effect; the most common ones were headaches, fever/chills and nausea/vomiting. The use of IVIg with or without rituximab had a favourable clinical response in patients with AIBDs. IVIg has no major influence on the normal immune system, which makes its utilization for patients with AIBDs reasonable.

Drug Adherence and its Association with Health Literacy Among Patients with Autoimmune Bullous Diseases.

Background: Despite the emergence of novel medications, poor drug adherence is an obstacle toward disease management in patients with autoimmune bullous dermatoses (AIBDs). Objectives: We sought to evaluate medication adherence among patients with AIBDs and determine the impact of health literacy on adherence. Methods: We performed a cross-sectional survey of patients with AIBDs who attended Razi Hospital from May to October 2021. Drug adherence and health literacy were assessed using the Morisky Medication Adherence Scale-8 (MMAS-8; scored 0-8) and Health Literacy for Iranian Adults (HELIA; scored 0-100) questionnaires, respectively. Multivariable ordinal regression, including the covariates age, sex, education level, and annual income, were employed for analyses. Results: Two hundred participants with a mean±standard deviation (SD) age of 50.3±13.5 years were recruited. The female:male ratio was 1.2. About half (53%) of the patients reported good adherence (MMAS-8 score of 8) to their AIBD medications. Moreover, limited health literacy, with a mean±SD score of 57.8±25.8, was noted. Multivariable ordinal regression indicated that literacy score was significantly associated with good drug adherence (odds ratio [OR]: 0.11 per 1 score of health literacy increase, 95% confidence interval [CI]: 0.09-0.14). Conclusion: These findings showed suboptimal drug adherence and health literacy of patients with AIBDs. Improving patient health literacy might be a way to increase drug adherence.

Perception of timbre in adult Cochlear implant users: Comparison of Iranian and Western musical instruments.

OBJECTIVES: Cochlear implants (CI) have dramatically improved speech perception for patients with sensorineural hearing impairment. However, listening to music is a great challenge for them. This study examined the perception and appraisal of Iranian musical instruments comparing with similar Western instruments. METHODS: Eleven adult CI users and 25 normal hearing (NH) individuals participated in this study. Musical stimuli of three commonly heard instrument pairs were prepared. Participants were asked to identify the instruments and rate their appraisal on a ten-point Likert scale (0 = dislike very much, 10 = like very much). RESULTS: The instrument recognition rate was 40.6% among the CI users, and the mean appraisal score was 5.2 ± 2.7. NH listeners had none significant higher scores on both tasks with a recognition rate of 50.0% and the mean appraisal score of 6.9 ± 1.5. Iranian instruments were more recognized in both groups. Regarding their appraisal, the mean score for both types was almost equal in the NH group, while CI users more appraised Iranian instruments. CONCLUSION: In addition to better recognition of Iranian instruments, they were particularly better appraised in the CI group. Iranian instruments provide suitable musical pieces for CI recipients that can be considered in rehabilitation programs.

Burden of pemphigus vulgaris with a particular focus on women: A review.

Pemphigus vulgaris is a chronic autoimmune mucocutaneous blistering disorder. Apart from the disease itself, other aspects of patients' life, including psychological, social, and financial, can be affected. Women are particularly more disposed to the impact of the disease due to their physiological characteristics, the specific periods of pregnancy and lactation as well as their social and familial role. In this review, we summarized the burden of pemphigus vulgaris on various aspects of women's lives. It is essential to understand these problems and provide appropriate support for patients with such a burdensome disease.

Applicability of glucocorticoid toxicity index in pemphigus: Comparison between two groups of rituximab-treated and rituximab-naïve patients.

Rituximab (RTX) combined with short-term glucocorticoids (GC) is an effective therapeutic option for pemphigus. The newly developed Glucocorticoid Toxicity Index (GTI) tool provides the possibility to measure GC toxicities over time. To compare 1-year GTI between two groups of RTX-treated and RTX-naïve patients with pemphigus. The responsiveness of the GTI was also investigated. A prospective cohort of 129 adults with newly diagnosed pemphigus was conducted. GC-related toxicities were assessed at 3-month intervals according to Composite and Specific lists of the GTI. Of the patients, 76.7% (n = 99) received RTX. Throughout the time intervals, RTX-treated patients had lower GTI compared to RTX-naïve ones (p = 0.036). The mean GTI at 1-year was 34.3 in the RTX-treated group and 50.8 in the RTX-naïve group (p = 0.04). The most commonly observed GC-related toxicity was neuropsychiatric manifestations for 34% (224 events). The relapse rate of RTX-treated patients (1%) was significantly lower than RTX-naïve patients (10%) (p = 0.037). The GTI showed no correlation with cumulative GC consumption in both groups (p > 0.05, both). Patients treated with GC alone had remarkably higher GTI than patients treated with GC plus RTX. The GTI is an applicable tool to quantitatively capture GC toxicities at the patient level in pemphigus.

Efficacy and safety of oral pioglitazone in the management of lichen planopilaris in comparison with clobetasol: A randomized clinical trial.

Lichen planopilaris (LPP) is a scarring alopecia for which no treatment with remarkable effect has been identified. Pioglitazone has been reported as a possible therapeutic option. To compare the efficacy and safety of pioglitazone with clobetasol in LPP. This randomized, double-blind, parallel-group was conducted at Razi hospital. Patients were treated either with pioglitazone 15 mg/daily or clobetasol lotion 0.05% once at night for 6 months. Patients were visited every 2 months to assess the lichen planopilaris activity index (LPPAI) and record probable adverse events. Forty patients (mean age: 43.6 years; 62.5% female) were randomized 1:1. The mean of LPPAI at baseline and last session were 4.68 ± 1.97 and 2.59 ± 0.97 in the clobetasol group and 5.01 ± 1.71 and 3.04 ± 1.36 in the pioglitazone group, respectively. Both treatments significantly decreased the LPPAI over the two-month interval visits (p < 0.001). No significant difference in the LPPAI reduction was detected between groups. Regarding the safety profile, three clobetasol-treated patients developed folliculitis, and two in the pioglitazone group developed mild headaches. Pioglitazone effectively controlled the signs and symptoms of the LPP with no serious side effects. It can be considered a treatment option for LPP, although it was not superior to clobetasol.

Exacerbation of Autoimmune Bullous Diseases After Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination: Is There Any Association?

Background and Aim: There have been concerns regarding the potential exacerbation of autoimmune bullous diseases (AIBDs) following vaccination against COVID-19 during the pandemic. In the current study, vaccine safety was evaluated in patients with AIBDs. Methods: In this study, patients with AIBDs were contacted via face-to-face visits or phone calls. Patient demographics, vaccine-related information, pre- and post-vaccine disease status, and complications were recorded. The exacerbation was considered either relapse in the remission/controlled phase of the disease or disease worsening in the active phase. The univariate and multivariate logistic regression tests were employed to determine the potential risk factors of disease exacerbation. Results: Of the patients contacted, 446 (74.3%) reported receiving at least one dose of vaccine injection (54.7% female). Post-vaccine exacerbation occurred in 66 (14.8%) patients. Besides, there were 5 (1.1%) patients with AIBD diagnosis after vaccination. According to the analysis, for every three patients who received vaccines during the active phase of the disease one experienced disease exacerbation. The rate of disease exacerbation increased by three percent with every passing month from the last rituximab infusion. Active disease in the past year was another risk factor with a number needed to harm of 10. Conclusion: Risk of AIBD exacerbation after the COVID-19 vaccine is not high enough to prevent vaccination. This unwanted side effect, can be reduced if the disease is controlled at the time of vaccination.

A Young Boy with Brittle Hair.

Trichothiodystrophy (TTD) is a rare multisystem disorder with an autosomal recessive mode of inheritance. TTD presentations vary from only hair abnormalities like brittle, fragile hair to physical and mental retardation. Mutations of DNA repair genes have been identified as responsible for the disease. A 5-year-old boy presented with sparse, short, and brittle hair to our clinic. He was born to consanguineous parents. Trichoscopy and light microscopy revealed broken hairs with no specific shaft defect. Due to the inaccessibility of the polarized microscopy, a bedside technique was employed. We used a polarized dermatoscope and a mirror in order of achieving transillumination of the hair shafts, which revealed striking bright and dark bands. These bands are referred to as "tiger tail," which is the pathognomonic sign of TTD. Subsequent polarizing microscopy also confirmed the clinical diagnosis. This highlighted a feasible method for observing the tiger tail, which expanded the known clinical diagnostic tools of TTD.

Does topical minoxidil at concentrations higher than 5% provide additional clinical benefit?

Minoxidil solution is used for the treatment of androgenetic alopecia (AGA). Minoxidil 5% solution has been shown to have superior efficacy to minoxidil 2% solution, it is unknown whether concentrations of minoxidil > 5% provide additional clinical benefit. We performed a review of the literature to examine the evidence on the efficacy and safety of higher concentrations of minoxidil in AGA. A search of the PubMed database was performed using the keywords 'minoxidil', 'androgenic alopecia' and 'pattern hair loss'. Relevant articles, including clinical trials, other clinical studies, case series and case reports published in English were considered for review. In addition, relevant references from the bibliography section of the retrieved articles were also reviewed.

Pregnancy outcomes in women with pemphigus exposed to rituximab before or during pregnancy.

Rituximab (RTX) is an effective treatment for pemphigus; however, the drug labeling recommends not to use RTX within 1 year before conception. Objectives: To report pregnancy outcomes of patients with pemphigus who were treated with RTX before or during pregnancy. Methods: We identified 19 pregnancies with RTX exposure before or during pregnancy. All had previously been advised not to get pregnant within 1 year of RTX administration. The cases were categorized into 3 groups of exposure of within 6 months (group A), between 6 and 12 months (group B), and longer than 12 months of conception (group C). The pregnancy outcomes of different RTX exposure intervals were compared. Results: Group A included 9 pregnancies, of which 3 had received RTX accidentally after conception. Group B and C included 4 and 6 pregnancies, respectively. There was no significant difference between the groups regarding pregnancy outcomes. Overall, there were 17 live births, 1 spontaneous abortion, and 1 termination. Of the live births, 3 preterm deliveries and 4 low-birth-weight neonates were noted. Moreover, 1 neonate was hospitalized due to early-onset neonatal sepsis, and 1 had hydronephrosis. Disease flare-up occurred in 5 patients during pregnancy (4 minor and 1 major relapses) and in 5 patients after delivery (3 minor and 2 major relapses). Conclusions: Except for 1 case of neonatal sepsis which survived following medical treatment, no serious relevant adverse pregnancy outcome that could be attributed to RTX exposure before and during early pregnancy in women with pemphigus was detected. Nevertheless, RTX should not be administered within 1 year before planned pregnancy, as not enough data is available yet.

Music Appreciation of Cochlear Implant Users versus Normal Hearing Individuals.

Introduction: Cochlear implants (CI) provide speech perception for patients with sensorineural hearing impairment; nonetheless, listening to music is a daunting challenge for them. The present study aimed to compare Iranian CI users and normal hearing (NH) controls in terms of musical habits and appreciation and investigate the possible effect of background variables. Materials and Methods: A total of 37 CI users who underwent surgery at least 18 months before the study and 59 NH listeners were enrolled in this study. The participants were assigned to two age groups: group A (patients ≥15 years old) and group B (patients <15 years old). They were asked to complete the questionnaires to assess their music engagement. Results: In group A, the mean score of music importance was significantly higher in CI users (8.7±2.1), as compared to that in NH subjects (5.8±2.3) (P=0.005). Participation in professional musical training and singing with music was not significantly different between the groups. In group B, the mean score of desire for music was not significantly different between CI users (8.2±1.8) and NH subjects (7.7±2.0). They participated in professional musical training and had a reaction to music almost equally. Singing with music was significantly less common in the CI group (CI 16[61.5%], NH (40[85.1%]) (P=0.023). Selected background variables had no significant effect on the music tendency and habits of CI users. Conclusions: Iranian CI users tended to have a high level of music appreciation in both adult and children groups. Moreover, CI users and NH controls did not significantly differ in the importance of music, devoted time, participation in musical activities, and musical habits.

Adverse outcome and severity of COVID-19 in patients with autoimmune bullous diseases: A historical cohort study.

The ongoing COVID-19 pandemic has raised concerns regarding the outcome of this infection in patients with autoimmune bullous dermatoses (AIBDs) due to effect of drugs used to treat these disorders. This investigation was performed from the onset of the pandemic to June 1, 2021. Patients with AIBDs who contracted COVID-19 were evaluated. A generalized linear model was employed to find the predictors of severe COVID-19 among patients with AIBDs. Ninety-three patients with AIBDs with a mean age of 50.3 years were evaluated. The most COVID-19 related symptoms were tiredness (76.3%) myalgia (69%), and cough (63.4%). During follow-up, the rate of hospitalization and death were 45.2% and 4.3%, respectively. Previous comorbidities (ß = 0.61) and mean prednisolone dosage above 10 mg/day in the last 3 months (ß = 1.10) significantly increased COVID-19 severity. Also, vaccination against SARS-CoV-2 (ß = -1.50) and each passing month from the last rituximab dose decreased severity (ß = -0.02). Notably, 19.3% of the patients developed AIBD flare-ups following COVID-19 infection. Higher prednisone dose and the shorter interval from the last rituximab infusion were determinants of severe COVID-19. Physicians should assess the risk versus the benefits when prescribing the medications. Moreover, vaccination could successfully attenuate COVID-19 severity.

Assessing quality of life in patients with autoimmune bullous diseases using the Persian version of Treatment of Autoimmune Bullous Disease Quality of Life questionnaire finds similar effects in women as men.

In autoimmune bullous diseases (AIBDs), autoantibodies loosen molecular adhesions in the skin and/or mucosa and lead to blisters and erosions. Immunosuppressive drugs reduce mortality of the AIBD; therefore, patients will have to live longer with comorbidities. Objective: This study aims to determine the quality of life of AIBD patients undergoing systemic treatment while investigating the survey's relationship with various factors. Methods: In this 2-step cross-sectional study, we initially included 53 consecutive pemphigus patients to investigate reliability and validity of the Persian version of Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL) questionnaire. Then, we conducted the study on 119 AIBD patients, currently under treatment at an AIBD clinic in Iran. Results: The mean TABQOL score for our patients was 13.87 ± 7.51. The highest TABQOL was for epidermolysis bullosa acquisita (24 ± 8.485) followed by pemphigus foliaceus (20.5 ± 14.181) and the lowest for pemphigus vulgaris (13.24 ± 6.54). There was no significant difference between patients' TABQOL scores and their gender, history of rituximab injection, and disease severity scores. We only found a positive correlation between TABQOL and prednisolone dose. Conclusion: Treatments of AIBD considerably impact the quality of life of patients and an impairment in quality of life is correlated to higher doses of prednisolone.

Comparison of the efficacy and safety of 308-nm excimer laser with intralesional corticosteroids for the treatment of alopecia areata: A randomized controlled study.

BACKGROUND: Corticosteroids have been the mainstay of treatment for alopecia areata (AA). Recently, the 308-nm excimer laser has been proposed for treating AA. OBJECTIVES: To compare the efficacy and safety of excimer laser with intralesional corticosteroid (ILCS) in AA. METHODS: Patients with at least two alopecic patches were randomly assigned to receive weekly excimer laser treatments or monthly injections of ILCS. Photographs and trichoscopy images were examined at baseline, the last treatment session, and after one month of follow-up. The hair regrowth score was evaluated on a 6-point scale. RESULTS: Sixteen patients with 99 alopecic patches completed the study. At the last treatment session, the mean score of hair regrowth for the laser was significantly lower than the ILCS (p = 0.003). However, after a month of follow-up, the difference was not statistically significant (p = 0.148). Positive response in hair regrowth (≥50%) was achieved in 47% of laser-treated patches and 66% in ILCS-treated ones. Four (25%) and 8 (50%) patients experienced severe adverse events of laser and ILCS, respectively. CONCLUSIONS: The excimer laser was safe and effective in AA. The effect of laser on hair regrowth might be delayed as compared with ILCS.

Rituximab in childhood and juvenile autoimmune bullous diseases as first-line and second-line treatment: a case series of 13 patients.

BACKGROUND: Little data are available concerning the outcome of rituximab (RTX) therapy in pediatric patients with autoimmune bullous diseases (AIBDs). OBJECTIVE: We sought to evaluate safety and efficacy of RTX administration in pediatric patients with AIBDs and to assess first-line RTX therapy in pemphigus patients. METHODS: AIBD patients consisting of 12 pemphigus patients and a patient with bullous pemphigoid who received RTX before the age of 18 were enrolled. Detailed information regarding patients' outcome after the first RTX cycle was assessed. RESULTS: The mean age of the patients at RTX infusion was 15 ± 2 years. Six patients in the pemphigus group received RTX as first-line therapy. In pemphigus patients: complete remission (on minimal therapy) was achieved by seven patients, partial remission (on minimal therapy) and complete remission (off therapy) were achieved by three patients and one, respectively. Relapse occurred in nine patients, which were mostly mild. Likewise, the BP patient received RTX with a good clinical response. The observed adverse events were mostly mild infusion reactions and a case of sepsis. CONCLUSION: Rituximab is safe and effective in childhood/juvenile patients with AIBDs. Furthermore, RTX can be used as first-line treatment in pediatric patients with pemphigus.