Pruritus Is Associated with an Increased Risk for the Diagnosis of Autoimmune Skin Blistering Diseases: A Propensity-Matched Global Study

Ulrike Raap, Maren M. Limberg, Khalaf Kridin, Ralf J. Ludwig

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Autoimmune bullous skin diseases (AIBDs), such as bullous pemphigoid (BP) and pemphigus, are characterized and caused by autoantibodies targeting structural proteins. In BP, clinical experience and recent systematic evaluation identified pruritus to be common and an important cause of impaired quality of life. Furthermore, chronic pruritus may be the sole clinical symptom of BP. In pemphigus, a retrospective study recently documented a high prevalence of pruritus. The temporal relation between pruritus and BP/pemphigus are, however, unknown. Likewise, the presence of pruritus in AIBDs other than BP and pemphigus is unknown. To address this, we performed propensity-matched retrospective cohort studies using TriNetX, providing real-world patient data to (i) assess the risk to develop AIBDs following the diagnosis of pruritus and (ii) vice versa. We assessed this in eight AIBDs: BP, mucous membrane pemphigoid (MMP), epidermolysis bullosa acquisita, dermatitis herpetiformis, lichen planus pemphigoides (LPP), pemphigus vulgaris, pemphigus foliaceous, and paraneoplastic pemphigus (PNP). For all AIBDs, pruritus was associated with an increased risk for the subsequent diagnosis of each of the eight investigated AIBDs in 1,717,744 cases (pruritus) compared with 1,717,744 controls. The observed hazard ratios ranged from 4.2 (CI 3.2–5.5; p < 0.0001) in MMP to 28.7 (CI 3.9–211.3; p < 0.0001) in LPP. Results were confirmed in two subgroup analyses. When restricting the observation time to 6 months after pruritus onset, most HRs noticeably increased, e.g., from 6.9 (CI 6.2–7.9; p < 0.0001) to 23.3 (CI 17.0–31.8; p < 0.0001) in BP. Moreover, pruritus frequently developed following the diagnosis of any of the eight AIBDs, except for PNP. Thus, all AIBDs should be considered as differential diagnosis in patients with chronic pruritus.

Original languageEnglish
Article number485
JournalBiomolecules
Volume13
Issue number3
DOIs
StatePublished - 6 Mar 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Funding

This research was funded by the Cluster of Excellence “Precision Medicine in Chronic Inflammation” (EXC 2167), the Collaborative Research Centre “Pathomechanisms of Antibody-mediated Autoimmunity” (SFB 1526), the research group “Translational Pruritus Research” (PruSearch, FOR 2690, RA-1026/3-2), which are all from the Deutsche Forschungsgemeinschaft, the Schleswig-Holstein Excellence-Chair Program from the State of Schleswig Holstein, an EADV research fellowship grant 2019, and Sinergia Unravel principles of self-organization in injured tissue (CRSII5_202301/1) from the Swiss National Science Foundation.

FundersFunder number
State of Schleswig HolsteinCRSII5_202301/1
Deutsche Forschungsgemeinschaft
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

    Keywords

    • case–control study
    • pemphigoid
    • pemphigus
    • pruritus

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