Original ArticleAssociation between bullous pemphigoid and hypovitaminosis D in older inpatients: Results from a case–control study
Introduction
Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease mainly affecting older adults (i.e., ≥ 70 years) with an incidence of around 20 new cases per 1,000,000 persons per year [1], [2]. BP is a severe disease because of the high mortality rate in older patients with a high comorbidity burden (i.e., a high number of chronic or acute diseases other than BP index-disease) [2], [3]. It justifies developing prevention strategies of BP. However, such an objective cannot be achieved without first understanding the immunopathogenic mechanisms of BP, which remain to date not fully elucidated. Among the biological determinants likely to influence autoimmunity in older adults, serum 25-hydroxyvitamin D (25OHD) concentration, which is considered the best indicator of vitamin D supply from cutaneous synthesis and diet, could be a candidate. Hypovitaminosis D (i.e., serum 25OHD concentration < 50 nmol/L) is highly frequent in older adults with a prevalence estimated around 70% over 70 years of age [4], [5]. The clinical relevance is that hypovitaminosis D effects are not restricted to bone, but target a large number of non-bone processes including the immune system and the maintenance of self-tolerance [6], [7], [8]. As an illustration, higher vitamin D status has been associated with risk reduction and clinical improvement of autoimmune disorders such as lupus, multiple sclerosis [9], [10]. Thereby, hypovitaminosis D may trigger or exacerbate autoimmunity, and hypovitaminosis D is associated with the incidence and/or severity of various autoimmune disorders [6], [7], [8]. We hypothesized that these mixed results could be explained by an interaction between hypovitaminosis D and a high comorbidity burden, hypovitaminosis D being associated with BP only in older patients with a high comorbidity burden.
This study aims to 1) compare serum vitamin D status in older inpatients with BP and matched-controls without BP, and 2) examine whether hypovitaminosis D, a high comorbidity burden or their combination were associated with BP.
Section snippets
Participants
Using a case–control design, 90 consecutive older inpatients (31 consecutive inpatients with a de novo diagnosis of active BP and 59 matched-control inpatients without BP) hospitalized in the Department of Dermatology of Angers University Hospital (France) between November 2012 and February 2014, were recruited for this study. Controls were consecutively recruited in the same ward in the Department of Dermatology of Angers University Hospital, France, and during the same period of inclusion as
Results
There was no significant difference between older inpatients with and without BP (Table 1). The diagnoses in the control group were skin diseases (n = 41, 69.5%) including the management of chronic wounds (n = 10); skin infections (n = 9) including erysipelas (n = 7), varicella (n = 1) and ecthyma (n = 1); tumors (n = 9) including squamous cell carcinoma (n = 1), extramammary Paget disease (n = 1), Kaposi disease (n = 1), Merkel cell carcinoma (n = 1), mycosis fungoides (n = 5); pruritus (n = 8) including eczema (n = 2),
Discussion
The findings showed that BP was significantly associated with hypovitaminosis D in older inpatients only in the case of high comorbidity burden, suggesting a more complex interplay between hypovitaminosis D and BP than suggested to date.
There is growing epidemiological evidence of a beneficial effect of higher vitamin D status in the onset and progression of autoimmune disorders [18]. Only three studies [19], [20], [21] focused specifically on the association between low serum 25OHD
Learning points
- •
Bullous pemphigoid is an autoimmune subepidermal blistering disease mainly affecting adults aged over 70 years.
- •
Hypovitaminosis D is associated with a greater incidence and/or severity of different autoimmune disorders.
- •
The association between hypovitaminosis D and BP is still open to debate, some studies showing an association, while others have failed to find any association.
- •
BP was significantly associated with hypovitaminosis D in older inpatients solely in the case of a high comorbidity
Author's contributions
- −
MES has full access to the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analyses.
- −
Study concept and design: MES, LM, OB and CA.
- −
Acquisition of data: MES and LM.
- −
Analysis and interpretation of data: MES and OB.
- −
Drafting of the manuscript: MES and OB.
- −
Critical revision of the manuscript for significant intellectual content: LM, EL and CA.
- −
Funding obtained: MES.
- −
Statistical expertise: OB.
- −
Administrative, technical, and material support: LM.
- −
Study
Funding
The study was supported financially by SVR. The sponsor had no role in the design or carrying out of the study, in the collection, management, analysis, or interpretation of the data, or in the preparation, review, or approval of the manuscript.
Conflict of interest disclosures
The authors have no conflicts of interest to report.
References (21)
- et al.
A comparison of two regimens of topical corticosteroids in the treatment of patients with BP: a multicenter randomized study
J Invest Dermatol
(2009) Vitamin D regulation of immune function
Vitam Horm
(2011)- et al.
Vitamin D: modulator of the immune system
Curr Opin Pharmacol
(2010) - et al.
Increased risk of bullous pemphigoid in male and very old patients: a population-based study on incidence
J Am Acad Dermatol
(1999) Incidence of bullous pemphigoid and pemphigus vulgaris
BMJ
(2008)Vitamin D deficiency
N Engl J Med
(2007)- et al.
Vitamin D and cognitive performance in adults: a systematic review
Eur J Neurol
(2009) - et al.
Vitamin D and ageing: neurological issues
Neuropsychobiology
(2010) - et al.
Extraskeletal effects of vitamin D: facts, uncertainties, and controversies
Joint Bone Spine
(2011) - et al.
Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis
JAMA
(2006)
Cited by (12)
Psoriasis and other skin disorders
2023, Feldman and Pike's Vitamin D: Volume Two: Disease and TherapeuticsNutrition and bullous diseases
2022, Clinics in DermatologyCitation Excerpt :Case control trials have shown patients with BP have significantly lower serum vitamin D levels than their healthy counterparts and higher rates of hypovitaminosis D, despite having similar sun exposure scores.19,20 Similarly, a cohort study found patients with rickets, osteomalacia, and vitamin D deficiency to have a rate ratio of 2.7 for pemphigoid21; however, the inverse relationship between vitamin D status and pemphigoid has been contested by case control studies that showed similar serum vitamin D levels in patients with BP as healthy controls.22,23 To our knowledge, there have been no large epidemiologic trials to substantiate claims that vitamin D is protective against BP, although low serum albumin on admission for BP has been associated with a higher risk of a lethal outcome.24
Calcitriol Treatment Ameliorates Inflammation and Blistering in Mouse Models of Epidermolysis Bullosa Acquisita
2018, Journal of Investigative DermatologyCitation Excerpt :More recently, the role of vitamin D has also been investigated in autoimmune bullous diseases. Accumulating evidence suggests an increased frequency of hypovitaminosis D in patients with pemphigus and pemphigoid (El-Komy et al., 2014; Joshi et al., 2014; Marzano et al., 2012, 2015; Moravvej et al., 2016; Sarre et al., 2016; Tukaj et al., 2013; Zarei et al., 2014), although some studies found no difference in the vitamin D status compared to healthy subjects due to concomitantly observed suboptimal 25-hydroxyvitamin D serum levels also in the corresponding control cohorts (Joshi et al., 2014; Moravvej et al., 2016; Sarre et al., 2016; Tukaj et al., 2013). Importantly, serum concentrations of 25-hydroxyvitamin D have been reported to be inversely associated with clinical disease severity in these patients, pointing toward a possible causative role of hypovitaminosis D in the disease process (Marzano et al., 2015; Moravvej et al., 2016; Zarei et al., 2014).
Association between serum 25-hydroxyvitamin D concentration and severity of first-diagnosed bullous pemphigoid in older adults
2019, Archives of Gerontology and GeriatricsCitation Excerpt :Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease mainly affecting adults aged ≥70years. A few studies have focused on the link between vitamin D and BP, and have reported lower serum 25-hydroxyvitamin D (25OHD) concentrations amongst patients with BP (Marzano, Trevisan, & Eller-Vainicher, 2012; Sarre, Annweiler, Legrand, Martin, & Beauchet, 2016; Tukaj, Schmidt, & Recke, 2013). Given the clinical improvement observed with vitamin D in other autoimmune diseases, we hypothesized that serum 25OHD could have an effect on the severity of BP.
Comorbidity in bullous pemphigoid: up-date and clinical implications
2023, Frontiers in ImmunologyEnvironmental factors in autoimmune bullous diseases with focusing on seasonality: new insights
2023, Dermatology Reports