Bullous pemphigoid and neuropsychiatric medications: An influence of drugs or of underlying conditions?

Kridin, Khalaf; Zelber‐Sagi, Shira; Kridin, Mouhammad; Cohen, Arnon D.

doi:10.1016/j.jaad.2019.03.091

Cited by 6 publications

(8 citation statements)

References 5 publications

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“…This finding is in line with the association of BP with neuropsychiatric medication. 60 In contrast, lower serum anti-BP180 IgG levels were described in DPP4 inhibitorassociated BP, 45,46,61 a finding that could not be confirmed in our study. Furthermore, no association between serum anti-BP180 IgG levels and inhibitors of platelet aggregation or Lthyroxine was revealed in our study.…”

Section: Discussioncontrasting

confidence: 90%

“…When we analysed the association of serum anti‐BP180 NC16A IgG titers with various medications, an association with higher titers was seen in patients using insulin and antipsychotics, respectively. This finding is in line with the association of BP with neuropsychiatric medication 60 . In contrast, lower serum anti‐BP180 IgG levels were described in DPP4 inhibitor‐associated BP, 45,46,61 a finding that could not be confirmed in our study.…”

Section: Discussionsupporting

confidence: 46%

“…22 Differentiating between the impact of the underlying neuropsychiatric disorders and the concomitant antipsychotic medication has been debated previously without conclusive results. 19,[56][57][58][59][60] Our finding of higher levels of anti-BP180 IgG in patients with neuropsychiatric disorders and concomitant antipsychotic medication compared with patients with these disorders but without antipsychotics points to an additional impact of the antipsychotic medication for the induction of BP. Although the association of BP with metabolic and atopic disorders, such as diabetes mellitus, allergic asthma and atopic dermatitis, has been well recognized, 26,29,30,33 no correlation between these comorbidities and serum levels of anti-BP180 NC16A IgG has been observed in the present study.…”

Section: Discussionmentioning

confidence: 84%

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Serum autoantibody reactivity in bullous pemphigoid is associated with neuropsychiatric disorders and the use of antidiabetics and antipsychotics: a large, prospective cohort study

Dikmen

Yilmaz

Benoit

et al. 2022

Acad Dermatol Venereol

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Background Bullous pemphigoid (BP), the by far most frequent autoimmune blistering skin disease (AIBD), is immunopathologically characterized by autoantibodies against the two hemidesmosomal proteins BP180 (collagen type XVII) and BP230 (BPAG1 or dystonin). Several comorbidities and potentially disease‐inducing medication have been described in BP, yet a systematic analysis of these clinically relevant findings and autoantibody reactivities has not been performed. Objective To determine associations of autoantibody reactivities with comorbidities and concomitant medication. Methods In this prospective multicenter study, 499 patients diagnosed with BP in 16 European referral centers were included. The relation between anti‐BP180 NC16A and anti‐BP230 IgG ELISA values at the time of diagnosis as well as comorbidities and concomitant medication collected by a standardized form were analysed. Results An association between higher serum anti‐BP180 reactivity and neuropsychiatric but not atopic and metabolic disorders was observed as well as with the use of insulin or antipsychotics but not with dipeptidyl peptidase‐4 (DPP4) inhibitors, inhibitors of platelet aggregation and L‐thyroxine. The use of DPP4 inhibitors was associated with less anti‐BP180 and anti‐BP230 reactivity compared with BP patients without these drugs. This finding was even more pronounced when compared with diabetic BP patients without DPP4 inhibitors. Associations between anti‐BP180 and anti‐BP230 reactivities were also found in patients using insulin and antipsychotics, respectively, compared with patients without this medication, but not for the use of inhibitors of platelet aggregation, and L‐thyroxine. Conclusion Taken together, these data imply a relation between autoantibody reactivities at the time of diagnosis and both neuropsychiatric comorbidities as well as distinct concomitant medication suggesting a link between the pathological immune mechanisms and clinical conditions that precede the clinically overt AIBD.

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Section: Discussioncontrasting

confidence: 90%

Section: Discussionsupporting

confidence: 46%

Section: Discussionmentioning

confidence: 84%

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Serum autoantibody reactivity in bullous pemphigoid is associated with neuropsychiatric disorders and the use of antidiabetics and antipsychotics: a large, prospective cohort study

Dikmen

Yilmaz

Benoit

et al. 2022

Acad Dermatol Venereol

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“…The I 2 statistic was calculated to assess the statistical heterogeneity between studies, with an I 2 of more than 50% indicating substantial heterogeneity. 39 Because neuropsychiatric diseases per se have been associated with BP, 5 we performed a sensitivity analysis to examine the association of BP with use of psycholeptics and anti-Parkinson medications after excluding studies that did not adjust for the presence of neuropsychiatric diseases. The Review Manager, version 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration) was used for conducting metaanalyses.…”

Section: Discussionmentioning

confidence: 99%

“…3,4 Bullous pemphigoid has been associated with neuropsychiatric diseases including cerebrovascular disease and dementia. 5,6 The annual incidence of BP was estimated to range from 2.4 to 21.7 per million population in different populations worldwide. [7][8][9][10][11][12][13][14] Various studies have shown an increase in the incidence of BP of 1.9-to 4.3-fold compared with that previously reported over the past 2 decades.…”

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confidence: 99%

Association Between Medication Use and Bullous Pemphigoid

2020

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IMPORTANCEThe association between the use of medications and the development of bullous pemphigoid (BP) is unclear.OBJECTIVE To assess the associations between previous exposure to certain medications and BP.DATA SOURCES For this systematic review and meta-analysis, PubMed, the Cochrane Central Register of Controlled Trials, and Embase were searched for relevant studies from inception to February 20, 2020.STUDY SELECTION Case-control or cohort studies and randomized clinical trials that examined the odds or risk of BP in patients with previous medication use were included. No geographic or language limitations were imposed. DATA EXTRACTION AND SYNTHESISThe Meta-analysis of Observational Studies in Epidemiology (MOOSE) guideline was followed. The Newcastle-Ottawa Scale was used to evaluate the risk of bias of included observational studies; Cochrane Collaboration's tool was used for randomized clinical trials. Aggregate data were used to conduct a random-effects model meta-analysis if the included studies were sufficiently homogenous. Subgroup analyses were performed for use of various medications of the same category. MAIN OUTCOMES AND MEASURESOdds ratio (OR), hazard ratio, and risk ratio of bullous pemphigoid in association with medication use. RESULTSThis meta-analysis included 13 case-control studies, 1 cohort study, and 1 randomized clinical trial with a total of 285 884 participants. The meta-analysis of case-control studies showed a significant association of BP with previous use of aldosterone antagonists (pooled OR, 1.75; 95% CI, 1.28-2.40), dipeptidyl peptidase 4 inhibitors (pooled OR, 1.92; 95% CI, 1.55-2.38), anticholinergics (pooled OR, 3.12; 95% CI, 1.54-6.33), and dopaminergic medications (pooled OR, 2.03; 95% CI, 1.34-3.05). One cohort study found an increased risk of BP among patients receiving dipeptidyl peptidase 4 inhibitors (hazard ratio, 2.38; 95% CI, 1.16-4.88; P = .02). One trial found a higher occurrence of BP in patients with diabetes receiving linagliptin (0.2% in diabetes group vs 0% in the placebo group). CONCLUSIONS AND RELEVANCEThe findings of this systematic review and meta-analysis suggest that aldosterone antagonists, dipeptidyl peptidase 4 inhibitors, anticholinergics, and dopaminergic medications are associated with BP. These medications should be judiciously prescribed, particularly in high-risk patients who are elderly and have disabling neurologic disorders.

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The effect of dipeptidyl peptidase‐4 inhibitor on incidence and clinical course in bullous pemphigoid patients in a tertiary medical center

Hsu,

Yang,

Huang

et al. 2023

The Kaohsiung J of Med Scie

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Several studies have reported an association between dipeptidyl peptidase 4 inhibitor (DPP4i), a commonly prescribed second‐line oral antihyperglycemic drug, and bullous pemphigoid (BP). However, the benefits of DPP4i withdrawal in patients with BP remain controversial. This study primarily aimed to evaluate the clinical severity of DPP4i‐associated BP by comparing it to those without Type 2 diabetes mellitus (DM). The secondary objective was to determine whether cessation of DPP4i is necessary for all patients with BP. This retrospective case–control study included 83 patients. The participants were divided into three groups according to their diabetic status and the status of discontinuance or continuance of DPP4i. The 12‐month follow‐up of the monthly dosage of systemic steroids per body weight (kg) and the percentage of systemic steroid off‐therapy in these participants were recorded since the diagnosis of BP. Compared to patients with BP without DM, the 1st, 3rd, and 12th systemic prednisolone doses were significantly lower in the DPP4i group (p = 0.01684, 0.02559, and 0.009336, respectively). The 12th systemic prednisolone dose was significantly lower in patients who discontinued DPP4i (p = 0.0338). Nevertheless, several spontaneous remissions with systemic steroid off‐therapy were also noted in the DPP4i‐continuance group within 12 months of follow‐up. This article supports the favorable impact of DPP4i withdrawal in patients with BP and shows that DPP4i may incite or aggravate BP, resulting in a milder disease course.

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Bullous pemphigoid and neuropsychiatric medications: An influence of drugs or of underlying conditions?

Cited by 6 publications

References 5 publications

Serum autoantibody reactivity in bullous pemphigoid is associated with neuropsychiatric disorders and the use of antidiabetics and antipsychotics: a large, prospective cohort study

Serum autoantibody reactivity in bullous pemphigoid is associated with neuropsychiatric disorders and the use of antidiabetics and antipsychotics: a large, prospective cohort study

Association Between Medication Use and Bullous Pemphigoid

The effect of dipeptidyl peptidase‐4 inhibitor on incidence and clinical course in bullous pemphigoid patients in a tertiary medical center

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