Table 1.

Summary of the data extracted from the primary full articles used in assessing the association of IgE with the severity and clinical phenotype of BP

First author [Ref]	Year	Journal of publication	Type of article	Study design	Setting details	Sample size	Patient demographics	Description of BP diagnosis criteria present	Comorbidities
a
Döpp et al. [18]	2000	J Am Acad Dermatol	Journal article	Cohort	Single centre; University of Würzburg	18	11 males and 7 females; range of age 50–91 years and a median of 72	No	Not discussed
Cozzani et al. [14]	2001	J Eur Acad Dermatol Venereol	Journal article	Cohort	Multi-centre; The Dermatologic Clinic of the University of Genoa and the Division of Dermatology of S. Martino, Galliera, Sampierdarena, Imperia, Savona and La Spezia Hospitals	32	13 males and 19 females; range of age 45–92 years and a mean age of 74	Yes	Discussed
Kelly et al. [35]	2007	J Allergy Clin Immunol	Meeting Abstract	Not clear	Single-centre; University of Utah	140 and 48	No information	No	Not discussed
Ishiura et al. [31]	2008	J Dermatol Sci	Journal Article	Case–Control	Multi-centre; University of Tokyo Hospital and Kanazawa University Hospital	67	35 males and 32 females; range of age 17–93 years and mean of 72.4	Yes	No comorbidities that could affect serum IgE or eosinophil levels
Iwata et al. [32]	2008	Arch Dermatol	Jounral Article	Retrospective case series analysis	Single-centre; Nagasaki University Graduate School of Biomedical Science, Department of Dermatology	37	18 males and 19 females; mean age of 75	Yes	Not discussed
Messingham et al. [39]	2009	J Immunol Methods	Journal Article	Cohort	Single-centre; University of Iowa	43	No information	Yes	Not discussed
Yayli et al. [59]	2011	Br J Dermatol	Journal Article	Retrospective study	None provided	44	23 males and 21 females; range of age 46–94 years and a mean age of 76.5	Yes	Not discussed
Messingham et al. [40]	2014	PLoS One	Journal Article	Case–control study	Single-centre; University of Iowa	48	25 males and 23 females; range of age 59–97 years and a mean of 78.2	Yes	Not discussed
Moriuchi et al. [42]	2015	J Dermatol Sci	Journal Article	Retrospective study	Single-centre; Hokkaido University Graduate School of Medicine, Department of Dermatology	100	47 males and 53 females; range of age 41–99 years and a mean age of 72.2	Yes	Not discussed
Ma et al. [38]	2015	J Dermatol Sci	Letter to Editor	Case–control	Single-centre; University Hospital in China (name not mentioned)	41	19 males and 22 females; mean age of 69.37	Yes	Not discussed
Bing et al. [7]	2015	Arch Dermatol Res	Journal Article	Case–control	Single-centre; Hospital in China (name not mentioned)	37	21 males and 16 females; range of age 29–93 and a mean of 69.08	Yes	Not discussed
Kalowska et al. [34]	2016	Acta Derm Venereol	Journal Article	Retrospective study	Medical University of Warsaw, Department of Dermatology	77	22 males and 55 females; range of age 56–97 years with a mean of 78.6	Yes	Not discussed
Cho et al. [11]	2016	J Dermatol Sci	Letter to Editor	Retrospective study	Single-centre; National Taiwan University Hospital	17	9 males and 8 females; range of age 11–77 years and a mean age of 72	Yes	Not discussed
Hashimoto et al. [26]	2016	Br J Dermatol	Journal Article	Retrospective study	Single-centre; Kurume University	36	8 males and 28 females; range of age 1–90 years and a mean age of 63.6	Yes	Not discussed
van Beek et al. [57]	2016	JAMA Dermatol	Journal Article	Cohort study	Single-centre; University clinic of Lübeck	153 (Cohort 1: 65, Cohort 2: 52, Cohort 3: 36)	Cohort 1 (underwent ELISA for IgE BP180 NC16A aabs): 25 males and 40 females, mean age of 74.6 years; Cohort 2 (underwent BPDAI clinical evaluation): 23 males and 29 females and a mean age of 78.2 years; Cohort 3 (negative for anti-BP180 NC16A IgG and underwent evaluation of the diagnostic importance of serum anti-BP180 IgE): 22 males and 14 females and a mean age of 74.5 years	Yes	Not discussed

First author [Ref]	Year	Variable X; IgE	Method of measurement	Variable Y	Method of measurement	Intervention/s	Duration	Control/comparison	Outcome
b
Döpp et al. [18]	2000	Anti-BP180 NC16A aabs	Immunoblotting and ELISA	Disease Activity	No method given	Oral prednisolone + dapsone or doxycycline + nicotinamide	8 weeks	50 healthy controls; no matching mentioned	Serum concentrations of anti-BP180 IgE aabs parallel disease activity
Cozzani et al. [14]	2001	Total serum IgE	IIF	Disease activity and phenotype	Serum IgE via IIF; clinical symptoms	Treatment for BP; no drug mentioned	6 months	No mention	Total serum IgE does not correlate with disease activity; more correlation with bullous and not urticarial phenotype
Kelly et al. [35]	2007	Total serum IgE	ELISA	Disease activity	No method given	Non-interventional study	–	No mention	Serum IgE highly correlated with disease activity; serum IgE levels increased as BP180 and BP230 ELISA levels increased
Ishiura et al. [31]	2008	anti-BP180/230 aabs	ELISA	Disease activity	% of skin covered with lesions (disease severity), disease duration, serum IgE levels, serum and local eosinophil count	Non-interventional study	–	36 healthy controls; 18 males and 18 females; range of age 51–85 years and a mean of 70.1; age and sex matched	Affected areas negatively correlated with anti-BP230 IgE aabs
Iwata et al. [32]	2008	anti-BP180/230 aabs + total serum IgE	ELISA	Disease activity	Scale of 1 (remission)—4 (highest activity) au	Non-interventional study	–	26 healthy controls; age and sex matched; 6 pemphigus vulgaris and 5 pemphigus foliaceus disease comparison patients	Anti-BP180 IgE aabs associated with broader skin lesions, % of skin with lesions, required steroid dosage, longer duration of treatment necessary for remission and more intensive therapies (immunosuppressive agents). Thus, anti-BP180 IgE aabs parallels disease activity and causes a severe form of BP (anti-BP230 IgE do not correlate with disease activity)
Messingham et al. [39]	2009	Anti-BP180 NC16A aabs	ELISA + western blot	Disease activity	Scale of 1–4 (from least to most severe)	Treatment for BP; no drug mentioned	–	55 healthy controls; age and sex matched; 6 disease comparisons with epidermolysis bullosa acquisita (EBA) and 21 disease comparisons with SLE	Anti-BP180 NC16A IgE aabs decrease over the treatment course with improvement in disease severity and vice versa
Yayli et al. [59]	2011	IgE deposits in biopsy specimen	DIF microscopy	Disease phenotype	Presence of specific clinical symptoms	Non-interventional study	–	13 MMP disease comparison patients; 4 males and 9 females; range of age 44–84 years and a mean age of 68.7	5/18 of patients with linear (unspecified) IgE deposits along the BM zone had urticarial papules and flakes and increased pruritus
Messingham et al. [40]	2014	anti-BP180 NC16A aabs + total serum IgE	ELISA	Disease severity	BP index scaled from 1 to 6 (remission to severe disease) and/or the BPDAI criteria scaled from 0 to 120 (least to most severe)	Non-interventional study	–	58 healthy control and 25 disease comparisons (dermatology patients with other autoimmune diagnoses); age and sex matched	Correlation between anti-BP180/230 aabs and disease activity BPDAI
Moriuchi et al. [42]	2015	IgE aabs at BM zone	ELISA and IIF	Disease severity and phenotype	Presence of specific clinical symptoms	Non-interventional study	–	None mentioned	No correlation between anti-BP180/230 IgE aabs and disease severity; predominant IgE deposition to BM zone alters the pattern of clinical manifestations of BP, e.g. development of erythrodermic BP or pemphigoid nodularis (a rare form of BP)
Ma et al. [38]	2015	anti-BP180 aabs	ELISA	Disease severity	% area of skin lesions, dosage of prednisone and duration of treatment for remission	Non-interventional study	–	30 healthy controls and 16 disease comparisons with pemphigus vulgaris	No positive correlation between IgE anti-BP180 aabs with disease severity; however, correlated slightly with broader areas of skin lesions larger prednisone dosage and a longer duration of treatment for a more effective control
Bing et al. [7]	2015	Anti-BP180 NC16A in serum and dermal infiltrate	ELISA	Disease activity	Scale of 1–5 (least to most skin eruptions/blisters) au; one extra point for mucosal involvement	Non-interventional study	–	28 healthy controls; 13 males and 15 females; range of age 60–82 years and a mean of 67.32; 18 patients with pemphigus vulgaris and 1 with Stevens–Johnson syndrome as disease comparisons; 12 males and 7 females, range of age 33–86 years and a mean age of 54.05	Anti-BP180 NC16A IgE levels reflected disease severity generally; however, Spearman test showed −ve r between disease activity scores in the initial 1–2 months (early stage of BP) and anti-BP180 NC16A IgE aab titres
Kalowska et al. [34]	2016	Anti-BP180 NC16A aabs + total serum IgE	ELISA + chemiluminescence	Disease activity	% of body surface area affected	Non-interventional study	–	29 healthy controls with no parasitic infections, autoimmune diseases or allergic reactions; 21 males and 8 females; range of age 62–87 years and a mean of 70.5	+ve Pearson r test between anti-BP180 NC16A IgE aabs + total serum IgE and disease severity in the active stage of BP; significant correlation between clinical remission of BP and serum IgE
Cho et al. [11]	2016	Anti-BP180/230 aabs	ELISA	Disease severity	BPDAI scale	Non-interventional study	–	None mentioned	High serum anti-BP180 IgE aabs correlated with high BPDAI scores; also correlation with urticaria/erythema scores, but not eruptions/blister scores
Hashimoto et al. [26]	2016	IgE anti-BP180/230 aabs	ELISA	Disease severity and phenotype	Developed their own criteria of disease severity and phenotype; disease severity score of 1–2, BP phenotypes included bullous, erythematous, bullous/erythematous, nodular	Non-interventional study	–	None mentioned	ELISA values of anti-BP180 IgE aabs correlated with severity scores 1 and 2, but there was no statistical significance of such correlation regarding anti-BP230 IgE aabs; no significant association between BP180/230 and the bullous/erythematous or erythematous phenotypes, but statistically significant association with nodular phenotype
van Beek et al. [57]	2016	Anti-BP180 NC16A	ELISA	Disease activity and phenotype	BPDAI score for severity; clinical presentation determined by the total BPDAI score (0-200 points) [= BPDAI blister/erosion + BPDAI urticaria/erythema]	Non-interventional study	2008–2014 (6 years)	30 disease comparisons with pemphigus vulgaris or pemphigus foliaceus (14 males and 16 females with a mean age of 54.4 years); 49 healthy controls with non- inflammatory dermatoses (21 males and 28 females with a mean age of 81.6 years) and 127 healthy controls undergoing allergy testing for IgE levels	47/117 patients tested positive for anti-BP180 NC16A serum IgE aabs and there was correlation with their disease activity (BPDAI score); no correlation between BP180 NC16A IgE aabs with urticarial or erythematous lesions or the classic phenotype of blisters and eruptions; total serum IgE correlated with the BPDAI score of pruritus