Outcome of COVID-19 in patients with autoimmune bullous diseases.

Background Data on outcomes of Coronavirus disease 2019 (COVID-19) infection in autoimmune bullous diseases (AIBDs) patients is scarce. Materials and methods This single-centre survey-based-observational study included patients registered in the AIBD clinic of the Postgraduate Institute of Medical Education and Research, Chandigarh, India. All registered patients were contacted over telephone between June and October 2021. A survey was conducted after obtaining informed consent. Results Among 1389 registered patients, 409 completed the survey. Two hundred and twenty-two (55.3%) patients were females and 187 (45.7%) were males. The mean age was 48.52 ± 14.98 years. Active disease was reported by 34% patients. The frequency of COVID-19 infection in responders was 12.2% (50/409), with a case-fatality ratio of 18% (9/50). Rituximab infusion after the onset of pandemic significantly increased the risk of COVID-19 infection. Active AIBD and concomitant comorbidities were significantly associated with COVID-19 related death. Limitation Relative risk of COVID-19 infection and complications among AIBD patients could not be estimated due to lack of control group. The incidence of COVID-19 in AIBD could not be determined due to lack of denominator (source population) data. Other limitations include telephonic nature of the survey and lack of COVID-19 strain identification. Conclusion Use of rituximab is associated with higher probability of COVID-19 infection, while advanced age, active disease and presence of comorbidities may increase the risk of COVID-19 mortality in AIBD patients.

Indications for Rituximab Use in an Integrated Health Care Delivery System.

BACKGROUND: Rituximab is a top-selling biologic that was first approved by the FDA in 1997 for a non-Hodgkin lymphoma orphan indication. It has since been approved for additional orphan indications, with rheumatoid arthritis as the only FDA-approved, nonorphan indication. Evidence suggests that rituximab is frequently used off-label, but information on its use over time and indications for use in the United States is limited. OBJECTIVE: To assess incident rituximab use over time in an integrated health care delivery system. METHODS: This was a cross-sectional, retrospective study. Data were collected from administrative databases and manual chart reviews. Patients who received their first rituximab infusion between October 1, 2009, and December 31, 2017, and who were not a part of a clinical trial were included. Indication for use (FDA-approved orphan/nonorphan, off-label) was determined. Proportions of use were assessed over time. Multivariable logistic regression modeling was performed to assess factors associated with receiving rituximab for an FDA-approved indication. RESULTS: A total of 1,674 patients were included. The majority (66.4%) of patients had an FDA-approved indication, with lymphoma being the most common approved indication (66.4%). The most common indication for off-label use was neurologic conditions (72.7%), predominantly demyelinating diseases. Off-label indication use increased from 1.2% in 2009 to 55.6% in 2017. Factors associated with rituximab use for an FDA-approved indication included increased age (adjusted odds ratio [AOR] = 1.05, 95% CI = 1.04-1.07) and increased burden of chronic disease (chronic disease score: AOR = 1.07, 95% CI = 1.02-1.12; Charlson Comorbidity Index score: AOR = 3.52, 95% CI = 3.03-4.10). CONCLUSIONS: Off-label use of rituximab grew dramatically over the course of the study. With the recent FDA approval of the rituximab biosimilar and its expected lower price, off-label use will likely continue to rise. Opportunities for cost savings and to ensure appropriate use of these medications should be evaluated. DISCLOSURES: This study was funded by Kaiser Permanente. All authors except Hansen are employed by Kaiser Permanente. Hansen has nothing to disclose. Preliminary results were presented at the Mountain States Conference for Residents and Preceptors in May 2019 in Salt Lake City, UT, and at an encore presentation October 2019 at the American College of Clinical Pharmacy Annual Meeting in New York, NY.

Effectiveness and safety analysis of rituximab in 146 Indian pemphigus patients: A retrospective single-center review of up to 68 months follow-up.

BACKGROUND: Rituximab is being increasingly used for the treatment of pemphigus. Data derived from single-center studies following a uniform treatment protocol are limited. Effect of demography and disease type on treatment response is poorly characterized. OBJECTIVE: Our aim was to assess the effectiveness of biosimilar rituximab in pemphigus patients who had received rituximab as per rheumatoid arthritis protocol (2 doses, 1g each, infused 14 days apart). METHODS: It was a retrospective review of 146 eligible patients to assess the proportion of patients achieving complete remission off treatment, time to achieve complete remission off treatment, proportion of patients who relapsed after achieving complete remission off treatment, time taken to relapse, duration and total cumulative dose of corticosteroids administered after rituximab. Additionally, we tried to find whether a correlation existed between age, gender, total duration of illness before rituximab and pemphigus disease type with the above-mentioned outcome measures. RESULTS: Of 146 patients, 107 (73.3%) attained complete remission off treatment. Mean interval between first dose rituximab administration and complete remission off treatment was 6.6 ± 3.4months. Complete remission off treatment was sustained for a mean duration of 9.1 ± 8.5 months before relapse. Over a mean follow-up duration of 24.9 ± 17.1 months (median 23, maximum 68 months), 75 of 107 patients (76.5%) who had achieved complete remission after first cycle of rituximab relapsed. A mean total cumulative dose of 3496 ± 2496 mg prednisolone was prescribed over a mean duration of 7.2 ± 4.7 months after first cycle of rituximab. Time taken to achieve remission was significantly longer in pemphigus foliaceus and these patients required significantly higher cumulative dose of prednisolone over a longer duration after rituximab. No deaths and long-term complications were recorded. LIMITATIONS: Only clinical parameters were assessed. Immunological parameters including B-cell counts and enzyme-linked immunosorbent assay for anti-desmoglein antibody titers were not carried out. CONCLUSION: This study reinforces the beneficial role of rituximab in pemphigus. Pemphigus foliaceus patients required a higher total cumulative dose of prednisolone over a longer time to achieve remission and the remission lasted longer than that in pemphigus vulgaris.

Low-dose rituximab as an adjuvant therapy in pemphigus.

BACKGROUND: Pemphigus is a chronic autoimmune blistering disease where systemic steroids and immunosuppressants are the mainstay of therapy, but long-term treatment with these agents is associated with many side effects. Rituximab, a chimeric monoclonal anti-CD20 antibody, in low doses has shown efficacy as an adjuvant to reduce the dose of steroids. AIM: To study the clinical efficacy and safety of low-dose rituximab as an adjuvant therapy in pemphigus. METHODS: Fifty patients with extensive pemphigus were selected, who either had recalcitrant pemphigus, were steroid dependent, had relapsed after pulse therapy, had anti-desmoglein levels >20, had contraindications to conventional treatment or wanted to avoid conventional treatment and its side effects. Two doses of rituximab (500 mg) were given 2 weeks apart and patients were regularly followed up every 2 weeks for 3 months and then monthly upto 2 years. Complete blood counts, liver function tests, renal function tests, skin biopsy, direct immunofluorescence and desmoglein levels were checked before and after rituximab administration. Pre-rituximab chest X-ray and electrocardiograph were also obtained. RESULTS: At 3 months, 41 (82%) patients showed complete remission. Nine (18%) patients had partial remission. After 6-12 months, 20 (40% of enrolled patients) continued to be in remission and were off all systemic therapy and the remaining 19 (38%) were continuing to take low doses of steroids with or without other adjuvant immunosuppressants and 2 (4%) had to be given another 2 doses of rituximab and subsequently could be managed with low-dose steroids. Of the 9 patients in partial remission at 3 months, after 6-12 months 5 (10% of the total) were completely off treatment and went into complete remission and 4 (8%) were on additional treatment out of which 2 (4%) had to be given 2 additional doses of rituximab and were in partial remission with low-dose therapy at the end of 12 months. One patient developed urticaria as a side effect. Another developed herpes zoster. CONCLUSION: Our results show that low-dose rituximab is a well-tolerated and beneficial adjuvant therapy in recalcitrant pemphigus which helps reduce both the severity of disease as well as the dose of steroids and immunosuppressants.

Clinical efficacy of rituximab in the treatment of pemphigus: A retrospective study.

BACKGROUND: Pulsed corticosteroids have been used successfully for the management of pemphigus. However, prolonged use of glucocorticoids may be associated with adverse effects and some patients show a poor response to conventional therapy. Biologics have shown a promising role in such cases; however, there is limited data from the Indian subcontinent. OBJECTIVE: The primary objective was to assess the efficacy and adverse effects of rituximab in pemphigus. The secondary objective was to measure the cumulative doses of corticosteroids required for these patients. METHODS: We undertook a retrospective review of records of 25 pemphigus patients (pemphigus vulgaris: 21, pemphigus foliaceus: 4) who had received rituximab infusion (rheumatoid arthritis protocol in 21 patients, modified in 4). Oral prednisolone was administered in dosages up to 0.5 mg/kg of body weight and tapered over the next 3-4 months according to the disease activity. However, other immunosuppressive agents such as cyclophosphamide and azathioprine were continued for one year after clinical remission was achieved. RESULTS: Complete remission was observed in 22 (88%) patients. The mean time to disease control and complete remission was 1.10 and 4.36 months, respectively. Four (16%) patients experienced relapse after a mean duration of 11.75 months. The mean total dose of oral steroids administered was equivalent to 3535.64 mg of prednisolone. Exacerbation of disease was noted in two patients after the first dose of rituximab and infectious complications, pneumonia and cellulitis, developed in one patient each. LIMITATIONS: A small sample size, the retrospective nature of the study and unavailability of follow-up anti-desmoglein autoantibodies levels were limitations. CONCLUSION: Rituximab is an effective agent in the treatment of pemphigus. The use of rituximab enabled use of a lower initial dose of oral prednisolone in pemphigus and hence reduced its total cumulative dose. Severe side effects were rare.

Non HCV-related infectious cryoglobulinemia vasculitis: Results from the French nationwide CryoVas survey and systematic review of the literature.

In patients with infectious cryoglobulinemia vasculitis (CryoVas) in the absence of hepatitis C virus infection, data on presentation, therapeutic management and outcome are lacking. We conducted a nationwide survey that included patients with HCV-negative CryoVas. We describe here the presentation, therapeutic management and outcome of 18 patients with non-HCV infectious CryoVas and 27 additional patients identified form a systematic review of the literature. We included 18 patients, mean age 57.9±13.5 years. Infectious causes were viral infections in 8 patients [hepatitis B virus (HBV) in 4, and cytomegalovirus, Epstein Barr virus, parvovirus B19 and human immunodeficiency virus in one case each], pyogenic bacterial infection in 6 patients, parasitic infection in 2 patients, and leprosy and candidiasis in one case each. Baseline manifestations were purpura (78%), glomerulonephritis (28%), arthralgia (28%), peripheral neuropathy (22%), skin necrosis (22%), cutaneous ulcers (17%), and myalgia (11%). Cryoglobulinemia was type II in 2/3 of cases. Most cases received specific anti-infectious therapy as first-line therapy, sometimes associated with corticosteroids, achieving sustained remission in the majority of cases. Refractory or relapsing patients, frequently related to HBV infection, showed a complete remission after rituximab in addition to antiviral therapy. In contrast, corticosteroids and/or immunosuppressive agents used in the absence of anti-infectious agents were frequently associated with refractory CryoVas. Viral and pyogenic bacterial infections represent the main causes of non-HCV infectious CryoVas. Antimicrobial therapy is commonly associated with sustained remission. Immunosuppressive agents should be considered only as a second-line option in patients with refractory vasculitis.

Use of rituximab in pemphigus patients with chronic viral hepatitis: report of three cases.

Use of rituximab in patients with chronic viral hepatitis can worsen pre-existing hepatitis or reactivate occult infection. There are no reports of use of rituximab in pemphigus patients with co-existing viral hepatitis. Herein, we report three pemphigus patients with co-existing chronic viral hepatitis (hepatitis C (n = 2), hepatitis B (n = 1)), who were treated successfully with rituximab under close supervision and concurrent antiviral drug administration. There was no derangement of the liver function tests or increase in viral load in any of the patients. By incorporating good collaboration with a hepatologist and close follow-up, such patients can be managed successfully with biologic therapies when the conventional treatment modalities have failed.

Intermediate doses of rituximab used as adjuvant therapy in refractory pemphigus.

BACKGROUND: Rituximab, a monoclonal anti-CD20 antibody, has been used with encouraging results in pemphigus. We describe herein refractory cases of pemphigus vulgaris (n = 23) and pemphigus foliaceus (n = 1) treated with rituximab in addition to steroids and immunosuppressants. AIMS: To assess the response to treatment, the duration of clinical remission, serology of the response and adverse effects of rituximab in pemphigus patients. METHODS: We recorded observations of 24 patients with pemphigus having either refractory disease in spite of high dose of steroids and immunosuppressants, corticosteroid-dependent disease, strong contraindications to corticosteroids, or severe disease. The patients were treated with infusions of one injection per week for three consecutive weeks of 375 mg of rituximab per m ² of body-surface area. One similar infusion was repeated after 3 months of 3 rd dose. We observed the clinical outcome after 6 months of 3 rd dose of rituximab and looked for complete healing of cutaneous and mucosal lesions (complete remission). OBSERVATIONS: After follow-up of 7-24 months, five patients showed only partial improvement while 19 of 24 patients had a complete remission 3 months after rituximab. Of these 19 patients, 12 patients achieved complete remission and are off all systemic therapy, and the rest are continuing with no or low dose of steroids with immunosuppressants. Two patients relapsed after initial improvement; one was given moderate dose of oral steroids and immunosuppressant and the other was given repeat single dose of rituximab to control relapse. CONCLUSION: Rituximab is able to induce a prolonged clinical remission in pemphigus after a single course of four infusions. The high cost and limited knowledge of long term adverse effects are limitations to the use of this biologic agent.

Childhood pemphigus vulgaris successfully treated with rituximab.

Pemphigus is a potentially fatal autoimmune epidermal bullous disorder. Rituximab is a novel therapy for the treatment of refractory pemphigus. However, there is limited clinical data on safety and efficacy of rituximab in pediatric age group. Herein, we report an 11-year-old boy of childhood pemphigus vulgaris who failed to respond to dexamethasone pulse therapy and was subsequently treated with rituximab and achieved complete remission.

[Treatment of skin ulcers in collagen vascular diseases].

The causes of skin ulcers in collagen vascular diseases are complicated, and involve peripheral vascular complications, vasculitis, and thrombosis. It is necessary to determine the treatment, such as oral medication, infusion, ointment and surgery after careful consideration of its causes. This review shows skin manifestations of various collagen vascular diseases and the causes of skin ulcers in these diseases.

Multiple capillary hemangiomas: a distinctive lesion of multicentric Castleman's disease and POEMS syndrome.

A diagnosed case of Castleman's disease, proven by biopsy from enlarged inguinal lymph nodes, presented with multiple, asymptomatic, erythematous papules and nodules prevalent since nine years over the trunk and extremities. The lesions had been gradually increasing in number and size. The patient had had plasmacytoma of the lower thoracic vertebra 12 years ago, for which he was adequately treated with chemotherapy and local radiotherapy. Dermatological examination revealed erythematous papules and nodules on the face, trunk, and extremities that were diagnostic of capillary hemangiomas. Histopathology of the erythematous, soft papule was suggestive of capillary hemangioma. Contrast-enhanced computerized tomography of the abdomen and pelvis showed multiple retroperitoneal nodes suggestive of Castleman's disease along with multiple osteolytic lesions in the pelvic girdle and vertebrae. The patient was treated with injection rituximab and is currently under follow-up. We report this case to highlight a rare association between Castleman's disease and POEMS syndrome.