Baricitinib as a novel treatment for bullous pemphigoid: a case series report (preprint)

Bullous pemphigoid (BP) is an autoimmune blistering disorder occurring mostly in the elderly. The standard treatment of BP patients with systemic corticosteroid have some potential serious side effects. Up till now, there is still lack of novel treatment for BP patients. Baricitinib, a selective Janus kinase (JAK) 1 and 2 inhibitor, has been used to treat rheumatoid arthritis, alopecia areata, and COVID-19. Successful treatment of refractory BP by JAK inhibitors has been reported in sporadic cases. In this study, we reported 8 BP patients treated with baricitinib. The patients after treatment were followed up for 3-24 months, with an average of 9.1 months. All 8 cases achieved disease control and the mean disease control period was 3 weeks (1-6 weeks). The bullous pemphigoid disease area index total (21.2 ± 13.0 to 2.5 ± 4.3, p<0.01), erosion/blister (6.0 ± 7.7 to 0.2 ± 0.5, p<0.05), urticaria/erythema (10.2 ± 11.9 to 0.0 ± 0.0, p=0.06), mucosal erosion/blister (10.0 ± 6.4 to 4.5 ± 5.1, n=4, p=0.25) and itching NRS (3.6 ± 3.5 to 0.0 ± 0.0, p=0.06) scores were all reduced after 2 months’ treatment. Seven of 8 patients achieved complete remission during tapering at month 3 and did not experience relapse during the follow-up period. The serum levels of anti-BP180 autoantibodies (IgG) were reduced significantly (77.1 ± 47.8U/mL to 40.1 ± 37.1U/mL, n=6, p<0.05) after 3 months’ treatment. During the follow-up period, only one patient experienced mild elevation of serum creatinine level after 3 months’ treatment of baricitinib, which returned to normal through discontinuation of the medication. In conclusion, this study demonstrated that low-dose, short-term administration of baricitinib is effective and safe for treating BP patients.

A nationwide study of 331 rare diseases among 58 million individuals: prevalence, demographics, and COVID-19 outcomes (preprint)

Background: The Global Burden of Disease study has provided key evidence to inform clinicians, researchers, and policy makers across common diseases, but no similar effort with single study design exists for hundreds of rare diseases. Consequently, many rare conditions lack population-level evidence including prevalence and clinical vulnerability. This has led to the absence of evidence-based care for rare diseases, prominently in the COVID-19 pandemic. Method: This study used electronic health records (EHRs) of more than 58 million people in England, linking nine National Health Service datasets spanning healthcare settings for people alive on Jan 23, 2020. Starting with all rare diseases listed in Orphanet, we quality assured and filtered down to analyse 331 conditions with ICD-10 or SNOMED-CT mappings clinically validated in our dataset. We report 1) population prevalence, clinical and demographic details of rare diseases, and 2) investigate differences in mortality with SARs-CoV-2. Findings: Among 58,162,316 individuals, we identified 894,396 with at least one rare disease. Prevalence data in Orphanet originates from various sources with varying degrees of precision. Here we present reproducible age and gender-adjusted estimates for all 331 rare diseases, including first estimates for 186 (56.2%) without any reported prevalence estimate in Orphanet. We identified 49 rare diseases significantly more frequent in females and 62 in males. Similarly we identified 47 rare diseases more frequent in Asian as compared to White ethnicity and 22 with higher Black to white ratios as compared to similar ratios in population controls. 37 rare diseases were overrepresented in the white population as compared to both Black and Asian ethnicities. In total, 7,965 of 894,396 (0.9%) of rare-disease patients died from COVID-19, as compared to 141,287 of 58,162,316 (0.2%) in the full study population. Eight rare diseases had significantly increased risks for COVID-19-related mortality in fully vaccinated individuals, with bullous pemphigoid (8.07[3.01-21.62]) being worst affected. Interpretation: Our study highlights that National-scale EHRs provide a unique resource to estimate detailed prevalence, clinical and demographic data for rare diseases. Using COVID-19-related mortality analysis, we showed the power of large-scale EHRs in providing insights to inform public health decision-making for these often neglected patient populations.

COVID-19 and autoimmune bullous diseases: Lessons learned.

Both COVID-19 and autoimmune bullous diseases represent potentially life-threatening conditions. Autoimmunity has been a special focus during the COVID-19 pandemic considering the possible detrimental mutual influence between COVID-19 and autoimmune disorders as well as their supposed induction or triggering by SARS-CoV-2 vaccines. There is a growing need to assess the impact of the current pandemic particularly in patients with autoimmune bullous diseases requiring potent and long-term immunosuppressive treatments. This review provides the relevant state-of-the-art knowledge, including our own research, about immunobullous diseases in relation to COVID-19 and summarizes expert perspectives on their management throughout the pandemic.

SARS-CoV-2 vaccine-triggered conversion from systemic lupus erythematosus (SLE) to bullous SLE and dipeptidyl peptidase 4 inhibitors-associated bullous pemphigoid.

Bullous systemic lupus erythematosus (BSLE) is a rare blistering disease in patients with SLE. BSLE is a heterogenous disease caused by autoantibodies to the basement membrane, mainly type VII collagen. The pathogenesis of the development of autoantibodies in BSLE remains unknown. We report a case of SLE taking dipeptidyl peptidase 4 inhibitors (DPP4i) who developed tense blister lesions after administration of SARS-CoV-2 vaccine. Initial erythematous lesion before administration of SARS-CoV-2 vaccine had not shown IgG deposition at basement membrane both direct and indirect immunofluorescence (IIF). However, the result of those examinations became positive after the administration of SARS-CoV-2 vaccine. Furthermore, IIF test results using NaCl split skin had shown positive against epidermal side. These observations suggest that SARS-CoV-2 vaccination triggered production of autoantibodies that cause bullous SLE. The present case fulfills the diagnostic criteria for both BSLE and DPP4i-associated bullous pemphigoid. Skin lesions were cleared after withdrawal of DPP4i. Therefore, physicians should ask patients who develop blisters after the vaccination whether they are taking DPP4i.

A new eruption of bullous pemphigoid following mRNA COVID-19 vaccination.

The rapid development and implementation of COVID-19 vaccines throughout the global population has given rise to unique, rare, adverse skin reactions. This case report describes an elderly man with new-onset bullous pemphigoid following the second dose of the Pfizer-BioNTech (mRNA) COVID-19 vaccine.

Erythema multiforme-like bullous pemphigoid following COVID-19 mRNA vaccine (preprint)

Cases of bullous pemphigoid following Covid-19 vaccines have been recently reported. We describe herein an atypical case of acral bullous pemphigoid after Pfizer BionTech vaccine. Clinicians should be aware of this reaction and encourage full vaccination as the disease displays a rapid improvement treatment.

A case of acquired hemophilia A and bullous pemphigoid following SARS-CoV-2 mRNA vaccination.

Acquired hemophilia is a rare disease resulting from autoantibodies against endogenous factor VIII (FVIII), which associates with bleeding and a high mortality rate. The pathophysiology is still unclear. Recent studies suggest genetic and environmental factors trigger the breakdown of immune tolerance. We report a 77-year-old Taiwanese man presented with multiple ecchymoses and some hemorrhagic blisters three weeks after SARS-CoV-2 mRNA (Moderna) vaccination. Isolated activated partial thromboplastin time (aPTT) prolongation was found. Acquired hemophilia A (AHA) was confirmed by low factor VIII (FVIII) activity and high titer of FVIII inhibitor. The pathohistology of skin biopsy further supported the concomitant diagnosis of bullous pemphigoid. To date, 6 cases of acquired hemophilia A following SARS-CoV-2 mRNA vaccination were reported worldwide. We reviewed and summarized the characteristics of these cases. We also discussed the rare finding of concomitant acquired hemophilia A and bullous pemphigoid. Bullous pemphigoid results from autoantibody against epithelial basement membrane zone of skin. In this article, we proposed possibility of SARS-CoV-2 mRNA vaccine associated autoimmunity against FVIII and epithelial basement membrane zone.