Reply to: Comment on "Bullous pemphigoid and neuropsychiatric medications: An influence of drugs or of underlying conditions?"

To the Editor: We thank Kridin et al1Kridin K. Zelber-Sagi S. Kridin M. Cohen A.D. Bullous pemphigoid and neuropsychiatric medications: an influence of drugs or of underlying conditions?.J Am Acad Dermatol. 2023; 88: e137Abstract Full Text Full Text PDF Scopus (4) Google Scholar for their interest in our recent publication2Varpuluoma O. Jokelainen J. Försti A. et al.Drugs used for neurological and psychiatric conditions increase the risk of bullous pemphigoid: a case-control study.J Am Acad Dermatol. 2019; 81: 250-253Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar concerning the risk of bullous pemphigoid (BP) presented by drugs used for neurologic and psychiatric conditions. Neurologic and psychiatric conditions have been well established as major risk factors for BP, but the pathomechanism behind this association is largely unknown.3Försti A. Huilaja L. Schmidt E. et al.Neurological and psychiatric associations in bullous pemphigoid–more than skin deep?.Exp Dermatol. 2017; 26: 1228-1234Crossref PubMed Scopus (46) Google Scholar Only a minority of patients with neurologic and psychiatric diseases get BP; therefore, it is important to study whether there are also other factors that influence risk of BP in these patients. Before our recent work, the largest epidemiologic study that addressed neurologic and psychiatric drugs as BP risk factors included 201 patients.4Bastuji-Garin S. Joly P. Lemordant P. et al.Risk factors for bullous pemphigoid in the elderly: a prospective case-control study.J Invest Dermatol. 2011; 131: 637-643Abstract Full Text Full Text PDF PubMed Scopus (228) Google Scholar However, in small study populations, the number of individuals receiving a particular drug or class of drug may be too low to detect any associated risk. Therefore, it is essential to use larger unselected cohorts to examine such potential risks. A previous study found neuroleptic drugs with an aliphatic side chain to be associated with an increased risk of BP,4Bastuji-Garin S. Joly P. Lemordant P. et al.Risk factors for bullous pemphigoid in the elderly: a prospective case-control study.J Invest Dermatol. 2011; 131: 637-643Abstract Full Text Full Text PDF PubMed Scopus (228) Google Scholar and our recent publication confirmed this association.2Varpuluoma O. Jokelainen J. Försti A. et al.Drugs used for neurological and psychiatric conditions increase the risk of bullous pemphigoid: a case-control study.J Am Acad Dermatol. 2019; 81: 250-253Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar It is also noteworthy that in our study, not all the agents used for certain diseases (eg, anti-Parkinson drugs or neuroleptics) were associated with an increased risk of BP despite the common indication. Given the registry-based design of our study, we did not have access to the patients' detailed clinical data and therefore could not verify the exact indication for every medication used. Kridin et al1Kridin K. Zelber-Sagi S. Kridin M. Cohen A.D. Bullous pemphigoid and neuropsychiatric medications: an influence of drugs or of underlying conditions?.J Am Acad Dermatol. 2023; 88: e137Abstract Full Text Full Text PDF Scopus (4) Google Scholar comment that our findings concerning the association between neuropsychiatric medications and BP should be interpreted with great caution owing to the possible presence of residual confounders. To avoid this possibility, we agree that future studies of the same topic could use the propensity score method. However, in our unpublished work on similar national data sets, use of the propensity score method appeared to yield results similar to those of the multivariate analysis method. As suggested by Kridin et al,1Kridin K. Zelber-Sagi S. Kridin M. Cohen A.D. Bullous pemphigoid and neuropsychiatric medications: an influence of drugs or of underlying conditions?.J Am Acad Dermatol. 2023; 88: e137Abstract Full Text Full Text PDF Scopus (4) Google Scholar it would be interesting to compare the prevalence of these medications between patients with concurrent neuropsychiatric disease and BP and those with neuropsychiatric disease, but not BP. Finally, we conclude, similarly to our recent research letter,2Varpuluoma O. Jokelainen J. Försti A. et al.Drugs used for neurological and psychiatric conditions increase the risk of bullous pemphigoid: a case-control study.J Am Acad Dermatol. 2019; 81: 250-253Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar that additional studies in different populations are required to study the potential association between drugs affecting the nervous system and the onset of BP. Bullous pemphigoid and neuropsychiatric medications: An influence of drugs or of underlying conditions?Journal of the American Academy of DermatologyVol. 88Issue 3PreviewTo the Editor: We read with great interest the study performed by Varpuluoma et al1 in which the authors aimed to estimate the frequency of exposure to drugs used to manage neuropsychiatric diseases among patients with bullous pemphigoid (BP) relative to matched control subjects during the 2 years preceding the diagnosis of BP. The nationwide case-control study revealed a significant association between administration of 29 different therapeutic agents and subsequent development of BP. Of note, all the constituent drugs belonging to the classes butyrophenone derivatives and antidementia anticholinesterases were significantly associated with an increased risk of BP. Full-Text PDF