Risk of infections in patients with pemphigus treated with rituximab vs. azathioprine or mycophenolate mofetil: a large-scale global cohort study.

BACKGROUND: The risk of infectious complications among patients with pemphigus managed by rituximab is yet to be precisely elucidated. OBJECTIVES: To evaluate the risk of infections in patients with pemphigus managed by rituximab vs. first-line corticosteroid-sparing agents [azathioprine and mycophenolate mofetil (MMF)]. METHODS: A global population-based cohort study compared patients with pemphigus initiating rituximab (n = 963) vs. azathioprine or MMF (n = 963) regarding the risk of 26 different infections. Propensity score matching was conducted to optimize comparability. RESULTS: During the initial 12 months following treatment, patients under rituximab experienced elevated risk of COVID-19 [hazard ratio (HR) 1.82, 95% confidence interval (CI) 1.06-3.14; P = 0.028], parasitic diseases (HR 3.22, 95% CI 1.04-9.97; P = 0.032) and cytomegalovirus (CMV) infection (HR 1.63, 95% CI 1.04-2.58; P = 0.033). When evaluating infections developing ≥ 12 months after drug initiation, rituximab was associated with greater risk of pneumonia (HR 1.45, 95% CI 1.00-2.10; P = 0.047), COVID-19 (HR 1.87, 95% CI 1.49-2.33; P < 0.001), osteomyelitis (HR 2.42, 95% CI 1.11-5.31; P = 0.023), herpes simplex virus (HR 2.06, 95% CI 1.03-4.11; P = 0.037) and CMV (HR 1.63, 95% CI 1.07-2.49; P = 0.023) infections. CONCLUSIONS: Within the first 12 months after treatment, patients under rituximab experience an elevated risk of COVID-19, parasitic and CMV infections. Rituximab is associated with pneumonia, osteomyelitis and viral diseases even beyond the first year after therapy. Pneumococcal vaccine and suppressive antiviral therapy should be considered even 1 year following therapy. There is no signal for elevated risk of tuberculosis, hepatitis B virus reactivation, Pneumocystis jiroveci pneumonia and progressive multifocal leukoencephalopathy.

COVID-19 severity and SARS-Cov-2 vaccine safety in pemphigus patients.

There are safety concerns in the treatment of pemphigus patients with immunosuppressants, particularly rituximab (RTX), in times of the COVID-19 pandemic. In the beginning, the reports were more pessimistic. However, few reports have recently pointed to manageable courses in this patient group. Therefore, we investigated the disease characteristics and demographic features of pemphigus patients in the period of the COVID-19 pandemic. We aimed to investigate the impact of immunosuppressants on the course of COVID-19 in pemphigus patients. Also, we tried to find out the rate of flares due to COVID-19 and SARS-Cov-2 vaccines. This multicenter study included 247 patients with pemphigus from three tertiary dermatology clinics with the specialized outpatient clinic for autoimmune blistering diseases. Patients were asked standardized questions in person or via telephone calls. Also, demographic data were collected from patients' files. Two hundred forty-four of 247 patients took the survey between August and September 2021. The data of three patients were obtained from the National Health System. We collected the data of all pemphigus patients who visited the clinics at least once in the past 3 years. Among 51 patients having COVID-19, 40 had a non-serious disease, whereas 11 required hospitalization. One patient died because of COVID-19 infection. The number of patients is limited, and data depends mainly on patients' statements. RTX treatment does not require additional safety cautions than other immunosuppressives.

Autoimmune mucocutaneous blistering diseases after SARS-Cov-2 vaccination: A Case report of Pemphigus Vulgaris and a literature review.

BACKGROUND: Cases of severe autoimmune blistering diseases (AIBDs) have recently been reported in association with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. AIMS: To describe a report of oropharyngeal Pemphigus Vulgaris (OPV) triggered by the mRNABNT162b2 vaccine (Comirnaty®/ Pfizer/ BioNTech) and to analyze the clinical and immunological characteristics of the AIBDs cases reported following the SARS-CoV-2 vaccination. METHODS: The clinical and immunological features of our case of OPV were documented. A review of the literature was conducted and only cases of AIBDs arising after the SARS-CoV-2 vaccination were included. CASE REPORT: A 60-year old female patients developed oropharyngeal and nasal bullous lesions seven days after the administration of a second dose of the mRNABNT162b2 vaccine (Comirnaty®/ Pfizer/BioNtech). According to the histology and direct immunofluorescence findings showing the presence of supra-basal blister and intercellular staining of IgG antibodies and the presence of a high level of anti-Dsg-3 antibodies (80 U/ml; normal < 7 U/ml) in the serum of the patients, a diagnosis of oropharyngeal Pemphigus Vulgaris was made. REVIEW: A total of 35 AIBDs cases triggered by the SARS-CoV-2 vaccination were found (including our report). 26 (74.3%) were diagnosed as Bullous Pemphigoid, 2 (5.7%) as Linear IgA Bullous Dermatosis, 6 (17.1%) as Pemphigus Vulgaris and 1 (2.9%) as Pemphigus Foliaceus. The mean age of the sample was 72.8 years and there was a predominance of males over females (F:M=1:1.7). In 22 (62.9%) cases, the disease developed after Pfizer vaccine administration, 6 (17.1%) after Moderna, 3 (8.6%) after AstraZeneca, 3 (8.6%) after CoronaVac (one was not specified). All patients were treated with topical and/or systemic corticosteroids, with or without the addition of immunosuppressive drugs, with a good clinical response in every case. CONCLUSION: Clinicians should be aware of the potential, though rare, occurrence of AIBDs as a possible adverse event after the SARS-CoV-2 vaccination. However, notwithstanding, they should encourage their patients to obtain the vaccination in order to assist the public health systems to overcome the COVID-19 pandemic.

Pemphigus vulgaris relapse during the coronavirus disease pandemic.

Pemphigus vulgaris (PV) is the most common type of pemphigus group of autoimmune skin diseases. The treatment of PV relapse is challenging especially during the coronavirus disease (COVID-19) pandemic. In this prospective study, we aimed to evaluate the treatment of patients with relapsing PV during the pandemic. Twelve patients with PV who experienced relapse from March 2020 to January 2022 were included. The patients were asked whether they experienced COVID-19 symptoms and the pemphigus disease area index (PDAI) was measured. PCR for COVID-19, chest computed tomography, routine investigations, and electrocardiography were performed for the admitted patients. The mean PDAI of the patients during relapse was 23.6 ± 14.8 (range 5-60). Seven patients received azathioprine; one patient received mycophenolate mofetil; and six patients received 1000 mg of rituximab (RTX) twice at an interval of 14 days. None of the 12 patients had COVID-19-suggestive symptoms. Only 1 patient relapsed after receiving the COVID-19 vaccine. The six admitted patients who received RTX were negative for COVID-19 based on the PCR testing results. Out of the 12 patients, eight achieved complete remission, while four achieved partial remission. No major adverse effects were observed. In conclusion, the treatments with systemic steroids, immunosuppressive drugs, and rituximab were well tolerated by the patients with relapsing PV, provided that there was no contact with individuals with COVID-19. These treatments can then be provided to patients with PV during the pandemic with careful follow-up.

Can rituximab be used in the treatment of pemphigus vulgaris during the COVID-19 pandemic?

Rituximab is a monoclonal antibody that targets CD20, a B-lymphocyte antigen; that leads to a decline in the B-cell counts for at least a year. The patients who have received rituximab treatment in the previous 5 years with the diagnosis of pemphigus group of diseases at Cerrahpasa Medical Faculty were questioned for COVID-19 infection. A total of 48 patients were included in this study; only one male patient had COVID-19 infection which had a mild course. There is no significant difference in the total number of lymphocytes between patients who have received rituximab within the previous 5 years or last year. The number of lymphocytes is independent of the number of courses of rituximab treatment received. Therefore, we suggest that all pemphigus patients who have received rituximab treatment within the previous 5 years should be careful of the preventive measures against the COVID-19 infection irrespective of the number of treatment courses or the number of years which has passed since the treatment. The disease course was mild in the only infected patient. Thus, rituximab may be used in the treatment of pemphigus vulgaris during the COVID-19 pandemic if its use is necessary.

Rituximab as the treatment of pemphigus vulgaris in the COVID-19 pandemic era: A narrative review.

Pemphigus vulgaris (PV), an autoimmune blistering disease is treated with immunosuppressive medications. As the immunosuppressive effect of rituximab, the first-line therapy of PV, lasts more than 6 months, many concerns have raised due to the ongoing novel coronavirus disease (COVID-19) pandemic. With this background, our objective was to review the currently available literature as well as important websites for the evidence related to rituximab, PV and COVID-19, adverse effects associated with drugs, and relevant guidelines. "PubMed" and "Google Scholar" database were systematically searched for retrieving all articles related to anti-CD20 therapy in pemphigus vulgaris and COVID-19 published up to 14 July 2020. A total of seven clinical studies are performed with anti-CD20 therapy in COVID-19, three of which are performed on pemphigus patients, and have shown concerns employing rituximab in patients with COVID-19. Evidence for treating PV patients with rituximab in COVID-19 pandemic is limited. Until sufficient evidence or guideline for pemphigus and COVID-19 treatment is available, we advocate caution commencing rituximab in patients with pemphigus, due to the reported adverse outcomes.