Patients with rosacea treated with subantimicrobial-dose (SD), modified-release doxycycline 40 mg experience fewer gastrointestinal diseases (GIDs) compared with conventional-dose (CD), regular-release doxycycline 50 to 100 mg, according to the results of a cross-sectional study published in the Journal of the American Academy of Dermatology.

A total of 71,117 individuals age 30 to 64 with a history of rosacea were included in the study. The investigators analyzed the association between the various doxycycline doses (40 mg, 50 mg, 100 mg) and the prevalence of 10 GIDs: celiac disease; irritable bowel syndrome, small intestinal bacterial overgrowth, Helicobacter pylori infection, gastroesophageal reflux, gastritis, peptic ulcers, ulcerative colitis, Crohn disease, and infectious colitis.

Compared with no doxycycline treatment, CD-doxycycline therapy was associated with a significantly higher risk for overall GID (adjusted odds ratio [aOR] 1.53; 95% CI, 1.48-1.58; P <.0001). SD-doxycycline 40 mg was associated with a significantly lower risk for GID vs CD-doxycycline 100 mg (aOR 0.62; 95% CI, 0.58-0.67; P <.0001) and CD-doxycycline 50 mg (aOR 0.80; 95% CI, 0.73-0.88; P <.0001). The prevalence of GIDs did not differ significantly between treatment with SD-doxycycline and no doxycycline therapy (aOR 1.05; 95% CI, 0.98-1.12; P =.16).

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In a subpopulation analysis of 10,949 individuals that excluded individuals with documented GID in the year prior to initiating doxycycline, patients taking SD-doxycycline were significantly less likely than patients taking CD-doxycycline to experience new-onset GID (1-year cumulative incidence of GID: 8.3% vs 12.0%, respectively; aOR 0.68; 95% CI, 0.61-0.75; P <.0001). Patients with rosacea who received SD-doxycycline experienced fewer overall GIDs compared with patients who received CD-doxycycline.

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The investigators concluded that the results of this study imply that the use of CD-doxycycline may have an impact on the previously reported association between rosacea and GID. This may be due in part to a dose-dependent effect, but it might also be linked to the inherent characteristics of the SD (modified-release) formulation of doxycycline. Longitudinal studies are warranted in order to further define this association.


Lim HG, Fischer A, Rueda MJ, Kendall J, Kang S, Chien AL. Prevalence of gastrointestinal comorbidities in rosacea: Comparison of subantimicrobial, modified release doxycycline versus conventional release doxycycline. J Am Acad Dermatol. 2018;78(2):417-419.