Introduction
Autoimmune bullous dermatoses encompass a variety of debilitating diseases with serious sequelae that result from autoimmunity against intercellular adhesion molecules in the skin or mucous membranes. Patients affected by these disorders are generally immunosuppressed due to use of steroids and other immunomodulating medications. In the COVID-19 pandemic era, these patients were encouraged to receive vaccination, as immunization seemed to be a safe and practical way to prevent infection in this particularly vulnerable population.1 To this date, however, little is known about the efficacy and safety of the available COVID-19 vaccines in patients affected by autoimmune bullous dermatoses. We present a case of a patient with pemphigus vulgaris who received the first dose of COVID-19 vaccine during a period of remission and subsequently experienced a disease flares.
Case report
A 46-year-old South Asian woman with a history of pemphigus vulgaris, which had been in remission since undergoing 2 rituximab (1g) infusions in July and August of 2019, presented to our dermatology clinic with an acute pemphigus flare. The flare onset occurred 1 week after receiving her first dose of the Moderna COVID-19 vaccine in May 2021. Prior to this, her skin was clear, and she had not been on any immunosuppressive medications. Skin examination revealed numerous flaccid bullae and erosions on her trunk and extremities; yellow-crusted, eroded plaques on her scalp, and erosions of the oral mucosa (Fig 1). Desmoglein 1 and 3 antibodies (Medica Biological Laboratories) were significantly elevated at 123 U/mL and 105 U/mL respectively (positive: >20 U/mL). The patient was started on a prednisone taper at 1 mg/kg/day.
Fig 1.
A, Lesions on the patient’s back in various stages of healing. B, Flaccid bullae on the patient’s buttock. C, Yellow-crusted plaque on the vertex of the scalp. D, Lesion in the buccal mucosa.
At the time of her eruption, there were no other reports of pemphigus vulgaris associated with a COVID-19 vaccine in the literature. Given the uncertainty of whether a second dose of an messenger RNA (mRNA) vaccine could lead to an even more severe flare, the patient did not receive the second dose of the Moderna vaccine. However, the rise of the delta variant of SARS-CoV-2 prompted an in-depth discussion on the possible risks versus benefits of obtaining a vaccine from the alternative provider, Johnson & Johnson. The patient decided to proceed with receiving the Johnson & Johnson vaccine. She tolerated it well with no side effects nor pemphigus flare but remained on prednisone during this time. Although she improved with prednisone, her skin had not completely cleared. Thus, she was treated with rituximab 1 g on day 1 and day 15. She responded well and was able to be tapered off prednisone.
Discussion
Pemphigus vulgaris is a severe autoimmune blistering disorder that affects the skin and mucous membranes. Although the etiology of pemphigus and other related blistering dermatoses remains unclear, it has been established that autoantibodies against desmoglein 1 and desmoglein 3 are responsible for the skin and mucosal lesions. Certain factors, such as drugs and vaccines, may trigger a new onset of pemphigus or exacerbate existing disease. In the current pandemic era, it is important to know how to counsel patients affected by autoimmune bullous diseases on receiving the new COVID-19 vaccines.
In general, patients with autoimmune blistering dermatoses such as pemphigus vulgaris are strongly advised to be vaccinated against preventable infections. However, there are rare cases published of pemphigus induction or exacerbation following vaccination against influenza, hepatitis B, rabies, typhoid, tetanus, anthrax; and, since the timing of our patient’s flare, the novel SARS-CoV2 virus.2, 3, 4 Only 1 case describing the development of new-onset pemphigus vulgaris in a patient who received the Pfizer mRNA vaccine has been reported.2 In this case, a previously healthy patient suffered an outbreak of painful, nonhealing erosions of the oral mucosa and trunk 5 days after the first dose of the vaccine. After the second vaccine dose, the lesions markedly worsened. Two other patients with a history of pemphigus vulgaris in remission who flared soon after their first dose of COVID-19 mRNA vaccinations have recently been reported. However, these 2 patients proceeded to receive the second doses of their vaccines without developing new lesions.3
The patient presented in our case experienced an acute flare of pemphigus vulgaris shortly after receiving her first dose of the Moderna COVID-19 vaccine. However, she denied any adverse reaction to the recombinant adenoviral vector-based Johnson & Johnson vaccine. To our knowledge, the mechanism behind vaccination triggering relapse is unclear. Two ideas have been suggested: The first postulates that certain individuals affected by autoimmune disorders are genetically predisposed to hyperimmune reactions, and administration of a vaccine by nature exacerbates that response. Even though these patients are often on immunosuppressive therapy, stimulation of the immune system after vaccination may disrupt the delicate balance achieved by therapy. Another suggests that there is possible cross-reactivity of vaccine antigens with pemphigus-related/associated antigens.5
This report does not intend to question the safety or efficacy of the new vaccines, but rather highlights the risk of possible relapse when given to this patient population. Although 2 patients have gone on to successfully receive a second dose of their mRNA COVID-19 vaccine, there has been at least 1 patient with new-onset pemphigus vulgaris associated with the first dose that worsened with the second dose.2,3 Therefore, it is difficult to know whether the patient in the present case would have experienced worsening from a second dose of the mRNA COVID-19 vaccine. She went on to receive vaccination from an alternative provider in hopes of minimizing the risk of exacerbating her autoimmune condition. When managing these patients, it is important to consider vaccine-related adverse events when balancing protection against viral infection and preventing exacerbation of previously controlled disease.
Conflicts of interest
None disclosed.
Footnotes
Funding sources: None.
IRB approval status: Not applicable.
References
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