Emerging Cases of Pemphigus Vulgaris Following COVID-19 Infection

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As of April 2023, the global impact of the coronavirus disease 2019 (COVID-19) pandemic is staggering, with over 676 million confirmed cases and a tragic toll of more than 6.8 million deaths reported worldwide.[1] The pandemic has revealed varying degrees of case severity, influencing nearly every country in the world.

This article delves into the intricate relationship between COVID-19 and autoimmune diseases, particularly Pemphigus Vulgaris (PV), shedding light on emerging cases and potential connections between the two.

The COVID-19 Pandemic Landscape

COVID-19, primarily transmitted through respiratory droplets and close contact, has exhibited fluctuating waves of infection rates, with spikes and subsequent drops over time. Factors such as population density, healthcare facilities provision, and public health measures have played crucial roles in determining the severity and impact of the pandemic.[2,3]

Autoimmune Diseases and COVID-19

Emerging evidence suggests a potential influence of COVID-19 on the onset of autoimmune diseases, as highlighted by a systematic review linking COVID-19 to various autoimmune conditions.[4,5] Studies have indicated that the new onset of autoimmune diseases may occur post-COVID-19 diagnosis, with the severity of immune-related manifestations possibly correlating with the intensity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.[6]

Autoantibodies found in COVID-19 patients further support the association between the infection and autoimmune diseases, indicating shared clinical manifestations, immune responses, and pathogenic mechanisms.[7,8]

Understanding Pemphigus Vulgaris

Pemphigus Vulgaris (PV) is a mucocutaneous autoimmune disease characterized by widespread bullae and ulceration on the skin and mucosa. The disease results from the production of autoantibodies against desmoglein-1 and desmoglein-3, leading to intraepithelial acantholysis and damage to the keratinocyte layer of the epithelium.[9] Several risk factors, including genetics, drugs, viral infections, allergens, and psychological stress, have been identified as potential triggers for PV.[9,10]

Emerging Cases of Oral PV Post-COVID-19

This manuscript focuses on the emerging cases of oral PV following COVID-19 infection, highlighting the critical need to identify this life-threatening condition early in post-COVID-19 patients. Individuals with oral PV may experience impaired physiological function due to extensive ulceration and prolonged pain.[11] The link between COVID-19 and oral PV serves as a crucial area of exploration for healthcare professionals and researchers.

Discussion
The emergence of oral pemphigus vulgaris (PV) in the aftermath of COVID-19 infection raises intriguing questions about the potential links between viral infections and the onset of autoimmune diseases. The presented case series, encompassing four individuals diagnosed with PV approximately one to five months following COVID-19 infection, underscores the need for a comprehensive understanding of the consequences of SARS-CoV-2 infection on the immune system and the subsequent development of autoimmune conditions.

COVID-19 and Oral Ulceration
The association between oral ulceration and COVID-19 infection remains a complex and relatively uncharted territory.[12–14] The clinical manifestations of COVID-19, particularly in the oral cavity, can mimic those of various oral diseases, including autoimmune conditions. Individuals with a history of autoimmune diseases, such as PV and oral lichen planus, may experience recurrent episodes and heightened severity of illness, as observed in the presented cases.[12]

The Case Series
The presented case series, authored by Gunardi et al. and published in the Journal of Oral and Maxillofacial Pathology in July-September 2023, details the experiences of four patients who developed oral and skin lesions diagnosed as PV following a recent history of COVID-19 infection.[12] The patients, aged between 33 and 57, demonstrated diverse clinical presentations and treatment responses.

Autoimmune Diseases and COVID-19
Autoimmune diseases involve abnormal immune responses directed against self-antigens. More than 80 categories of autoimmune disorders exist, and while their etiologies are not fully understood, factors such as genetics, age, environment, and viral infections have been implicated.[15] Notably, prior studies have associated herpesviruses, cytomegalovirus, and varicella zoster with PV.[16,17] The study by Gunardi et al. contributes to this body of knowledge, suggesting a potential link between SARS-CoV-2 infection and the development of PV.[18–21]

Mechanisms of Autoimmunity Triggered by Viruses
The proposed mechanisms of autoimmunity triggered by viruses, including SARS-CoV-2, involve molecular mimicry, bystander activation, and epitope spreading.[29] The high expression of angiotensin-converting enzyme 2 (ACE2) receptors, identified as the key functional receptor for SARS-CoV-2, in skin keratinocytes and oral mucosa is noteworthy.[22–25] The cases presented by Gunardi et al. indicate a consistent pattern of initial oral lesions followed by skin involvement, aligning with the distribution of ACE2 receptors.

Limitations and Future Directions
While the case series provides valuable insights, limitations exist, primarily stemming from the reliance on medical records for COVID-19 data. The lack of specific information regarding the SARS-CoV-2 virus type and the medications administered during COVID-19 treatment poses challenges in pinpointing potential factors contributing to PV development.

Conclusion
In conclusion, the discussion surrounding the emergence of oral PV post-COVID-19 infection offers a nuanced exploration of potential connections between viral infections and autoimmune diseases. The presented cases emphasize the importance of heightened vigilance among clinicians regarding the possibility of autoimmune reactions following the COVID-19 pandemic. As researchers continue to unravel the mechanisms underlying PV induced by SARS-CoV-2, further investigations are warranted to elucidate the intricate interplay between viral infections, genetic predispositions, and the onset of autoimmune diseases. The study by Gunardi et al. contributes to the growing body of literature in this field, prompting a call for ongoing research and a deeper understanding of the complex relationships between viral infections and autoimmune pathologies.


reference link : https://journals.lww.com/jpat/fulltext/2023/27030/the_emerging_concern_of_oral_pemphigus_vulgaris.26.aspx

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