Understanding patient perspectives on vaccine decision making in adults with autoimmune bullous diseases: a qualitative study

Abstract

Patients with autoimmune bullous diseases are at an increased risk of infection, both from the underlying skin disease and from immunosuppressive treatments. Limited information is available on vaccine beliefs and behaviors in dermatology patients and adults with autoimmune bullous diseases in particular. To understand vaccine decision making, identify perceived risks and benefits of vaccinations, and discuss individual experiences in patients with autoimmune bullous diseases in the United States. A qualitative study was performed utilizing semi-structured interviews, and analysis was conducted on NVivo. Patterns were identified in the coded data, and representative quotations were recorded for each major theme. Interviews were conducted between February 15, 2022 and September 15, 2022. Twenty patients with a diagnosis of bullous pemphigoid, mucous membrane pemphigoid, pemphigus vulgaris, or pemphigus foliaceous were interviewed. Of the 20 participants, 14 (70%) were female, with a mean (SD, range) age of 64.8 (13.2, 34–83) years. Key themes that emerged from qualitative analysis of the interviews included patient concerns regarding their increased susceptibility to infection, potential exacerbation of skin disease following vaccination, and the effect of immunosuppressive medications on humoral response to vaccines. Lack of appointment availability, difficulty accessing vaccines, and cost were commonly identified barriers to vaccination. These findings provide valuable knowledge for dermatologists in regard to providing counseling specific to patient concerns and to improve communication surrounding vaccination in the dermatology setting.

Introduction

Autoimmune bullous diseases (AIBD) are a group of chronic and potentially lifethreatening diseases characterized by blistering of the skin and mucous membranes. Patients with AIBD are at an increased risk of infection and infection-specific mortality, both from their underlying skin disease and frequent use of immunosuppressive medications [25, 26, 28, 32]. While vaccination has been one of the most successful public health interventions developed, vaccine hesitancy threatens to undermine advances made in the reduction of vaccine-preventable diseases [2, 3]. Studies investigating the patient perspective surrounding vaccines typically examine views of the general population, [10, 39, 40] with limited data available on the beliefs and behaviors of dermatology patients and those with AIBD in particular.

Interest in hesitancy for adult vaccination increased during the coronavirus disease (COVID-19) pandemic, with efficacy, safety, convenience, and cost as concerns reported by the public [10]. Patients with psoriasis and eczema described potential adverse reactions, novelty of the vaccine, and worsening of disease post-vaccination as concerns surrounding COVID-19 vaccination [6, 31]. A crosssectional survey study of 707 International Pemphigus and Pemphigoid Foundation (IPPF) members found that COVID-19 vaccine hesitancy was prevalent in around one-third of participants, although their actual vaccination rate was satisfactory in comparison to the general population [20]. Understanding the patient perspective surrounding vaccine decision making is important to facilitate open conversations between patients and dermatologists and combat misinformation. To expand upon current survey data, the objective of this initial exploratory study was to use qualitative research methods to explore vaccine beliefs and behaviors, understand patient perceptions on susceptibility to and potential severity of contracting an infection, and discuss lived experiences of adults with AIBD in the United States.

Materials and methods

Study design

A convenience sample of twenty patients completed a one-time, virtual, semistructured interview. This study was deemed exempt (Category 2) by the Mass General Brigham Institutional Review Board (Protocol #001856). Verbal consent was obtained from participants prior to participation.

Study participants

Adults over the age of 18 years old with an appointment for an AIBD (including bullous pemphigoid [BP], mucous membrane pemphigoid [MMP], pemphigus vulgaris [PV], and pemphigus foliaceous [PF]) in the dermatology clinics at Brigham and Women’s Hospital (BWH) between 1/1/2020 and 12/1/2021 were invited to participate via the online patient portal. Additional participants were recruited from an IPPF member research email between 8/30/2022 and 9/15/2022. In total, 20 subjects were necessary to reach thematic data saturation.

Measures

Interview questions were intended to explore patient perceptions of their own health and susceptibility to infection, understand vaccine decision making, and discuss risks and benefits of vaccinations. The interview also assessed vaccine knowledge via a free-listing exercise, a qualitative interviewing technique that elicits spontaneous responses around a theme [23].

Data collection

The Health Belief Model approach was utilized in this qualitative study to guide the development of interview questions [18]. The interview script was additionally developed based on a review of the literature and the expertise of four investigators (JSB, LPC, MHN, AMS). The interview guide was pilot tested with simulated interviews by two research assistants (AJT, MA) and updated based on feedback after each practice interview. Virtual interviews were conducted from 2/15/2022 to 4/27/2022 and 8/30/2022 to 9/15/2022 by a female research assistant with a master’s degree (MA) and lasted 20–30 min. The interviewer received formal training in interview techniques and had no previous relationship to study participants. Participants were aware of the interviewer’s role in the study and interest in the research. Only the interviewer and participant were present during interviews. Interviews were audiorecorded with the participant’s permission, transcribed, and edited for clarity.

Data analysis

After reviewing five transcripts, a codebook was created by two senior members of the team (LPC, MHN) using these transcripts, an a priori set of codes developed from the Health Belief Model, the literature, and preexisting clinic knowledge. Each interview was independently reviewed and coded by two research assistants (AJT, MA) in NVivo in batches of five transcripts. Each round was followed by updating of the codebook with new themes and resolution of coding discrepancies by group consensus between the two coders and a senior team member (MHN).

Patterns and themes were identified in the coded data, and representative quotations with deidentified information were recorded for each major theme (defined as general topics commonly mentioned by participants under which subthemes were categorized). The free-listing exercise was analyzed using a salience index, a measure of importance of an item to study participants [23]. Responses were sorted by salience, with values ranging from 0 (low salience or low recognition) to 1 (high salience or high recognition). This study follows the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines [35].

Results

Participant characteristics

Table 1 summarizes the demographics of study participants. Of the 20 participants, 14 (70%) were female and 6 (30%) were male, with a mean age of 64.8 years (standard deviation: 13.2, range: 34–83 years). The most frequent diagnosis was BP, followed by PV, MMP, and PF. Thirteen patients were recruited from BWH dermatology clinics and seven from IPPF member emails.

Table 1.

Participant characteristics, n = 20

Demographics	n (%)
Age in years, mean (SD)	64.8 (13.2)
[minimum, maximum]	[34, 83]
Female	14 (70)
Male	6 (30)
Diagnosis
Bullous Pemphigoid	7 (35)
Pemphigus Vulgaris	6 (30)
Mucous Membrane Pemphigoid	4 (20)
Pemphigus Foliaceus	3 (15)
Self-Reported Influenza Vaccine History
Yes	13(65)
Sometimes	5 (25)
No	2 (10)
Recruitment Source
Brigham and Women’s Hospital	13(65)
International Pemphigus and Pemphigoid Foundation	7 (35)

Impact of autoimmune bullous diseases on perceived health and medical decision making

The diagnosis of AIBD played a prominent role in many participants’ overall medical decision making and when addressing general health issues (Table 2). Several participants described constantly “feeling very vulnerable to infection,” as a result of immunosuppression from both their skin disease and medications, particularly during the COVID-19 pandemic. A few mentioned how AIBD diagnosis motivates them to receive age-appropriate vaccinations.

Table 2.

AIBD impact, vaccination benefits, risks, and barriers: code frequencies & representative quotations

Concept	Representative quotation	n (%)
Theme: Impact of Autoimmune Bullous Diseases on Perceived Health and Medical Decision Making
General health	“Let’s say I have some other health issue, I may think, “How will this impact my pemphigus or will pemphigus impact this?”	10 (50)
Concern about infection	“I know that being on medication for active pemphigoid makes my immune system out of whack, and the bullous pemphigoid makes my immune system out of whack. This makes me unsure that I could fight a disease off … as well as I might have without having pemphigoid.”	8 (40)
Motivation for vaccination	“My [pemphigoid] has encouraged me to get the vaccines I need as a senior, like the pneumococcal vaccine and T-DaP booster …I never thought about getting the pneumonia vaccine when I reached the age that I should, but now I embrace all vaccines appropriate for my age.ȍ	3 (15)
Theme: Benefits of Vaccination
Personal	“On a personal level, the benefit is to minimize the likelihood of getting certain diseases.”	19 (95)
Societal	“It also is preventative for the common good. You get herd immunity.”	17 (85)
Travel	“We recently traveled to Canada and if I had not been fully vaccinated, I would not have been able to go since the Canadian government was very careful about having us fill out a questionnaire and copying my vaccine card for COVID.”	2 (10)
Theme: Risks of Vaccination
Effect of immunosuppressive medication on vaccine efficacy	“The [treatments] they gave me have lowered my immune system so it would stop attacking my skin, and I have to wait a certain amount of time before I can get vaccines.”	12 (60)
Exacerbation of chronic diseases	“The long-term effect… in the back of my mind [is] if it’s going to reactivate my pemphigus.”	9 (45)
Local and/or mild side effects (sore arm, flulike symptoms)	“I expect to get a little sick and not feel good.”	9 (45)
Serious side effects (thrombosis, cardiovascular damage)	“It’s assumed that some portion, some number of people are going to have an untoward effect from medications and everything else, so I take that into account, but also I hope that I’m not going to be in that .001% of people who get blood clotting problems and platelet issues from whatever vaccine I get.”	7 (35)
Effect of altered immune system on vaccine efficacy	“When I look at things that could affect my immune system, such as getting my next COVID vaccination or Shingrix vaccine, I am very reluctant to have one of those based on … my concern about if my immune system going into overdrive.”	6 (30)
Allergic reaction	“You could also be allergic to some of the elements of the vaccine and that could also be bad.”	5 (25)
Guillain-Barre Syndrome	“Well, many years ago there was a friend of the family who got Guillain-Barre Syndrome from some vaccine so that would probably be the worst-case scenario.”	3 (15)
Not effective	“The vaccine could have limited efficacy and you could think that you’re immune from something when you are actually not.”	3 (15)
General safety concerns	“I was concerned about the unintended consequences of[vaccines] and the long-term side effects…”	2 (10)
Theme: System-Level and Cultural Barriers to Vaccination
Availability of Appointments	“I would say that the biggest barrier for me would have to be access because I'm very busy and my doctor is not around the corner.”	11 (55)
Access to vaccine	“If they didn’t make enough of the vaccine, then people couldn’t get it.”	10 (50)
Cost	“I would say that the biggest barrier is whether your insurance covers it, so being able to afford it.”	10 (50)
Lack of information about vaccines	“There are definitely awareness barriers ofpeople being aware of vaccines and their availability.”	5 (25)
Lack of time	“I can go on my lunch break since the place is just 10 minutes away, but if your doctor’s office or pharmacy only has appointments during a time that doesn’t work with your schedule, that would be a barrier.”	4 (20)
Misinformation	“I believe that this time around one of the greatest scourges of our lifetime was all of the misinformation that came out regarding these vaccines, and we have social media to thank for this.”	4 (20)
Distance	“Another barrier is that the location is not a very accessible place for you.”	3 (15)
Concerns about safety/side effects	“Well, I do worry about having any of the reactions that are severe now that I feel my immune system may not be up to snuff.”	2 (10)
Lack of Trust (in vaccine ingredients, physicians, and science/clinical trials)	“… historical medical mistrust in certain populations.”	1 (5)
Religious reasons	“There was one teammate that for religious reasons they didn’t want to get the vaccine.”	1 (5)

Benefits and risks of vaccinations

In describing potential benefits of vaccinations, most participants discussed both personal and societal benefits, while some noted fulfillment of travel requirements (Table 2). When asked about risks of vaccinations, the majority of participants described concern regarding potential interaction between a vaccine and an immunosuppressive medication prescribed for their AIBD, with one mentioning, “If I’m not in remission then I’m going to be on an immunosuppressant and then I’m not sure… whether [the vaccine] would be effective or not.” Several also described feeling “terrified” about vaccination causing exacerbation or relapse of their chronic skin disease. Some mentioned the potential for a short duration of mild side effects, including local reactions and flulike symptoms, in addition to more serious side effects they were aware of but recognized were uncommon, such as thrombosis and cardiovascular damage. Some reported unease regarding the effect of their altered immune system, as a result of their autoimmune skin condition, on vaccine efficacy. Allergic reactions, Guillain-Barre syndrome, general safety concerns, and the vaccine being ineffective were mentioned by few.

System-level and cultural barriers to vaccination

The most commonly identified barriers to successful vaccination included lack of available vaccine appointments, limited access to the vaccine, and cost—all concerns that surfaced in the general population during the initial release of the COVID-19 vaccine (Table 2). Several participants described technological difficulties in scheduling appointments and challenges in coordinating transportation for elderly patients. The recombinant zoster vaccine was most frequently mentioned as a vaccine AIBD participants desired but experienced difficulty obtaining due to limited coverage by insurance. Some mentioned lack of information about vaccines, lack of time to attend appointments, misinformation, and distance to vaccine clinics as additional barriers. Concerns about safety and side effects, lack of trust, and religious reasons were reported by few.

Vaccine knowledge and annual influenza vaccine practices

In addition to answering questions about vaccination beliefs and behaviors, participants were also asked to list all recommended vaccines for adults in the United States to the best of their knowledge (Table 3). Herpes zoster was the most frequently mentioned vaccine, and thus demonstrated the highest salience index (0.60), followed by pneumococcal, influenza, tetanus, COVID-19, human papillomavirus, and hepatitis. The median number of vaccines mentioned by participants was 4 (interquartile range: 3–4). When prompted with, “Do you typically get the flu shot?,” 13 (65%) participants reported yes, 2 (10%) reported no, and 5 (25%) reported sometimes. Most participants described personal benefits as a factor influencing their decision to receive an annual influenza vaccine, while some mentioned physician recommendation, fulfilling a requirement, and benefit to society (Table 4). Factors that affected participants’ decisions not to receive an annual influenza vaccine included perception of the vaccine being unnecessary and potential contraindications to the vaccine.

Table 3.

Free-listing of vaccines recommended for adults in the united states

Vaccine	Total (n = 20) n (%)	Salience Index
Zoster	17 (85)	0.60
Pneumococcal	16 (80)	0.55
Influenza	13 (65)	0.44
Tetanus (including T-DaP & Td)	9 (45)	0.27
COVID-19	10 (50)	0.25
Human papillomavirus	3 (15)	0.11
Hepatitis (including A & B)	2 (10)	0.03

Table 4.

Influenza and development of new vaccines: code frequencies & representative quotations

Theme: Factors that affect your decision to receive an annual influenza vaccine
Personal health benefit	“Getting the flu at my age would probably not be a good thing because you could die from it, so it S better to get the flu shot.”	14 (70)
Physician recommendation	“My oncologist told me that I needed to get my flu shot every year to keep myself healthy, and so I did and I never stop getting it ever since.”	3 (15)
Requirement	“I have gotten the flu shot because it was required by my work.”	3 (15)
Benefit to society	“I don’t want to give it to anybody else, and I don’t want to get it from anybody.”	2 (10)
Theme: Factors that affect your decision NOT to receive an annual influenza vaccine
Unnecessary	“I thought I didn’t need the flu shot because I never really got sick.”	4 (20)
Contraindications	“I had Guillain-Barre in 1977 … and because of that I was told that it was contraindicated to get a flu vaccine, and this is why I've never gotten the flu vaccine.”	2 (10)
Theme: Benefits of New Vaccines, including COVID-19
High level of testing/new beneficial technology	“So it’s just different technology that’s used to create these drugs and the fact that we’ve been able to come up with the COVID-19 vaccine so quickly using a brand-new technology, I don’t really see an issue with that.”	13 (65)
Approved by experts	“I mean, I know there’s a whole medical establishment that dedicate their lives to trying to solve the world’s problems.”	2 (10)
Theme: Negative Aspects of New Vaccines, including COVID-19
Lack of long-term data	“I think with anything new you just never know what the long-term effects will be, so I will never say to somebody that there’s no risk to something new. ”	8 (40)
Lack of trust (funding source)	“I have some concerns about the motivation for certain approaches. For instance, by making pharma companies such a prominent presence in the way that we dole out medical care. Pharma is a billion-dollar sector yet there is unwillingness to be more equitable in their distribution and that makes me less comfortable about the products, it makes me think, ‘What is the motive?’”	1 (5)

Opinions on new vaccines

Given the novelty of the COVID-19 vaccine and heightened discussion regarding immunizations, participants were questioned about their thoughts on new vaccines, including the COVID-19 vaccine (Table 4). Most participants identified high levels of testing and new technology as benefits of new vaccines, while some mentioned approval by experts. Some participants expressed concerns regarding lack of longterm data in new vaccines, while a minority mentioned lack of trust in the funding source.

Discussion

The results of this qualitative study highlight the multitude of ways AIBD diagnoses uniquely impact patients’ medical and vaccine decision making that differ from the general population. Most participants described personal and societal benefits to vaccinations, similar to the public, however concerns about overall increased risk of infection, effect of immunosuppressive medications on vaccine efficacy, and exacerbation of bullous disease following vaccination were recognized as novel themes specific to AIBD patients. By conducting and analyzing individual interviews, our study captures participants’ lived experiences with AIBD and offers insight into opportunities for patientcentered vaccination education within dermatology.

An important theme that emerged from participant interviews was the concern regarding increased risk of infection specific to AIBD, resulting in mental preoccupation and social isolation. Patients with AIBD are uniquely at risk of infection due to compromise of the skin and mucocutaneous barriers and subsequent loss of protective functions, with prior studies demonstrating an increased risk of developing pneumonia and infections requiring hospitalization or contributing to death [26–28]. AIBD patients additionally experience an increased risk of infection from iatrogenic immunosuppression. In 2018, rituximab received U.S. Food and Drug Administration approval for moderate to severe PV and has since become first-line therapy [1]. In addition to rituximab, other immunosuppressive treatments including mycophenolate mofetil and azathioprine have also been associated with increased risk of bacterial and viral infections in pemphigus patients [24, 38]. Our study participants expressed concerns regarding their increased susceptibility to infection and, as a result, approach daily activities with great caution. With infection as a significant contributor of morbidity and mortality in AIBD, dermatologists should educate patients on the importance of timely vaccination while recognizing the mental toll this concern may take on AIBD patients. These patients may also find additional information on infection prevention, including hand washing, mask wearing, and travel precautions, helpful to alleviate some of their fears.

Beyond risk of infection, patients with AIBD reported concern about immunosuppressive medications affecting their ability to mount an immune response to vaccinations, with rituximab most frequently mentioned. A recent course of rituximab therapy has been associated with reduced humoral response to COVID-19, influenza, pneumococcal, and tetanus diphtheria vaccines [7, 9, 13, 17, 34, 36]. Given this concern, vaccination recommendations should be included in pre-treatment counseling for any immunosuppressive medication in dermatology but especially for rituximab, considering its profound effect on antibody response during treatment and for 6–12 months post-treatment [30, 37]. For non-live vaccines, the American College of Rheumatology recommends timing vaccination for when the next rituximab dose is due and holding rituximab for 2 weeks after vaccination, continuing methotrexate and other immunosuppressive medications, and deferring vaccination for prednisone only if the dosage is ≥ 20 mg daily [5] Study participants repeatedly described feeling anxious about vaccine efficacy while on a medication prescribed for their AIBD, underscoring the need for clear communication regarding timing of vaccinations in relation to immunosuppressive medications.

Concern for exacerbation or reactivation of skin disease was also distinctly recognized by AIBD patients as a potential risk to vaccination, with participants reporting feeling distress about a vaccine causing flare or relapse of their bullous disease. While new-onset and flares of BP and pemphigus have been reported following SARSCoV-2 vaccination, [15, 16] a large retrospective cohort study examining COVID-19 vaccines and a systematic review examining case reports of administration of any vaccine both found insufficient evidence to suggest an association between vaccinations and increased risk of AIBD [8, 22]. While case reports and case series can indicate “signals” of potentially important drug or vaccine-induced adverse events and may notably impact patient perceptions of risk, randomized placebo-controlled trials and large epidemiologic studies (e.g. cohort and casecontrol studies) are required to establish causation [11]. This highlights the importance of directly addressing patient concerns to help increase vaccination rates. While exacerbation of AIBD is a potential risk of vaccination, the benefits of protection against disease outweigh these risks in most cases, with studies showing COVID-19 vaccines to be safe in patients with AIBD or systemic autoimmune or inflammatory disorders, and similar conclusions determined for more established vaccinations, including the influenza and human papillomavirus vaccines [19, 21, 22, 33]. Despite the known benefits, our study participants confirmed that AIBD patients feel “terrified” about the potential for exacerbation of skin disease. Dermatologists should provide honest answers regarding what is known or unknown about disease flare and relapse following vaccination, such that patients are provided with information specific to their concerns.

With appointment availability and access to vaccine as commonly mentioned barriers to vaccination, dermatology offices may consider administering vaccines to provide additional and convenient sites for patients, particularly for older patients who may struggle with the technology required to schedule vaccine appointments. Private insurance reimbursements for the zoster vaccine have even been found to be financially feasible in supporting healthcare providers and offices in procuring and administering the zoster vaccine [29]. Additional research is critical to understand the most efficient and effective way to administer vaccines in dermatology clinics. Participants further described cost as a barrier, primarily due to lack of coverage by insurance, with the zoster vaccine most frequently mentioned. Beginning in 2023, the Inflation Reduction Act in the United States requires all adult vaccines recommended by the Center for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) to be covered under Medicare Part D [12]. This eliminates out-of-pocket costs for vaccines including the zoster vaccine, which can cost patients over $370 for both doses, [4] and is especially important for AIBD patients who are typically over the age of 50. However, 24.6% of the 65 million patients covered by Medicare in 2022 were not enrolled in Part D plans, [14] emphasizing the need for additional efforts to increase access and coverage of vaccines. Dermatologists should be well informed of policy-level changes in order to help patients accurately understand their vaccine coverage.

While this study expands upon existing survey data in the literature to explore vaccine-related beliefs and behaviors in adults with AIBD, there are limitations to qualitative research. Patients were recruited from an academic practice setting and the IPPF community, thus results may not be generalizable to all patients with AIBD. Complete demographic information, including education level and socioeconomic level, and details regarding disease severity, duration, and treatment, which may have influenced participant responses, could not be collected. Nonetheless, this study provides insight into AIBD patient experiences in making decisions around vaccines, which can help to inform clinical discussions as well as the development of educational materials, including by the IPPF. Further qualitative research and large population-based studies are needed to enable development of patient-centered interventions to improve vaccination rates in the context of dermatologic conditions and immunosuppressive treatments. Results from this initial exploratory study will inform additional qualitative research focused on eliciting AIBD patient perspectives on specific vaccines, stratified by disease severity and therapeutics.

In summary, the key themes identified from this qualitative study underscore the patient perspective and concerns around vaccinations specific to adults with AIBD. Notably, participants mentioned concerns regarding increased susceptibility to infection, risks of disease flare or relapse following vaccination, and fears surrounding vaccine efficacy in relation to dermatology treatments. Patients with AIBD and those who are prescribed immunosuppressive medications for skin disease increasingly turn to dermatologists with questions. While dermatology clinics are often fast-paced and patients present with a wide breath of skin concerns, every clinic visit is an opportunity for dermatologists to provide individualized vaccine guidance to normalize immunizations and encourage uptake, specifically in patients whose skin disease and/or treatment put them at an increased risk of infection.

Abbreviations

ACIP

Advisory Committee on Immunization Practices

AIBD

Autoimmune bullous diseases

BP

Bullous pemphigoid

BWH

Brigham and Women’s Hospital

CDC

Center for Disease Control and Prevention

COVID-19

Coronavirus disease

IPPF

International Pemphigus and Pemphigoid Foundation

MMP

Mucous membrane pemphigoid

PF

Pemphigus foliaceous

PV

Pemphigus vulgaris

Data availability

The datasets generated during and/or analyzed during the current study are not publicly available due to privacy concerns associated with qualitative research but are available from the corresponding author on reasonable request.