1 Two A.M.

Wu W.

Gallo R.L.

et al. Rosacea: part I. Introduction, categorization, histology, pathogenesis, and risk factors. 2 Parodi A.

Paolino S.

Greco A.

et al. Small intestinal bacterial overgrowth in rosacea: clinical effectiveness of its eradication. , 3 Weinstock L.B.

Steinhoff M. Rosacea and small intestinal bacterial overgrowth: prevalence and response to rifaximin. To the Editor: We read with interest the review by Two et althat reports the microorganisms known to trigger or worsen rosacea such as Demodex folliculorum, Staphylococcus epidermidis, Helicobacter pylori, and Bacillus oleronius with no mention of the role of small intestinal bacterial overgrowth (SIBO).

2 Parodi A.

Paolino S.

Greco A.

et al. Small intestinal bacterial overgrowth in rosacea: clinical effectiveness of its eradication. Our study observed SIBO in 46% of patients with rosacea with improvement after rifaximin.

2 Parodi A.

Paolino S.

Greco A.

et al. Small intestinal bacterial overgrowth in rosacea: clinical effectiveness of its eradication. SIBO may trigger rosacea by increasing circulating cytokines, especially tumor necrosis factor-alpha.Recently, we completed the study with a 3-year follow-up to investigate the role of SIBO in rosacea.

4 Wilkin J.

Dahl M.

Detmar M.

et al. Standard grading system for rosacea: report of the National Rosacea Society Expert Committee on the Classification and Staging of Rosacea. Table I Demographic and clinical characteristics of the whole sample with small intestinal bacterial overgrowth and evaluation of differences between healthy subjects and patients with rosacea who completed the 3-year follow-up Total

(N = 88) Rosacea patients

(N = 48) Control group

(N = 40) P value

OR [95%IC] Males 31 (35.2%) 16 (33.3%) 15 (37.5%) 0.86 Age (yr) 53.8 ± 14.7 49.9 ± 14.3 58.4 ± 13.9 0.014 Small intestinal bacterial overgrowth at baseline 22 (25.0%) 20 (41.7%) 2 (5.0%) <0.001

OR: 13.6 [2.9 – 62.9] Small intestinal bacterial overgrowth at 3-year follow-up 5 (5.7%) 5 (10.4%) 0 (0.0%) 0.10 Fig. 1 Frequency of small intestinal bacterial overgrowth in rosacea patients after therapy and controls Sixty Caucasian patients with first diagnosis of rosacea and 40 healthy controls were enrolled consecutively in 6 months after obtaining informed consent ( Table I Fig 1 ). Subtype II rosacea (persistent central facial erythema with transient papules and/or, pustules)was significantly prevalent in these patients (88.3%), while the remaining 11.7% were subtype I ( Table I ).

Table II Differences in small intestinal bacterial overgrowth distribution between patients with subtype I and subtype II rosacea who completed 3-year follow up (n = 48) Subtype I rosacea Subtype II rosacea P value Small intestinal bacterial overgrowth at baseline 1 (8.3%) 19 (52.8%) .018* OR:12.3 [1.4-105.5] ∗P < .05. Differences in SIBO distribution between patients with subtype I and subtype II rosacea who completed the 3-year follow-up were analyzed with statistical analysis software (n = 48, 80%) ( Table II ).

All patients underwent lactulose hydrogen breath test (LHBT) and glucose breath test (GBT) at baseline and after 3 years to verify the presence of SIBO.

3 Weinstock L.B.

Steinhoff M. Rosacea and small intestinal bacterial overgrowth: prevalence and response to rifaximin. Patients were assigned in a 1:1 computer-generated blind randomization to receive rifaximin 400 mg every 8 hours (n = 20) or placebo (n = 20) for 10 days.

3 Weinstock L.B.

Steinhoff M. Rosacea and small intestinal bacterial overgrowth: prevalence and response to rifaximin. Thirty days later, another LHBT/GBT was performed and patients in the placebo group were switched to the rifaximin group for ethical reasons.

At this first LHBT/GBT follow-up, 58.3% of patients with rosacea had normal intestinal flora ( Fig 1 ) and remission of rosacea, that is, absence of papules and pustules and no or slight erythema.

All 40 patients completed one cycle of a 10-day rifaximin treatment and were re-evaluated with LHBT/GBT and clinically every 6 months for 3 years. At the 3 year follow-up, only 5.7% of patients had positive LHBT/GBT.

Frequencies and odds ratio throughout the follow-up are described in Table II . At the 3-year follow-up, rosacea was still in remission in the 64.5% of patients who completed treatment and were re-evaluated after 3 years.

To our knowledge, this is the first study with a 3-year follow-up assessing the clinical manifestations and investigations to define the role of SIBO in rosacea.

5 Powell F.C. Clinical practice: rosacea. Our study revealed interesting outcomes. First, treatment of SIBO determined clinical remission in all patients, which persisted in the majority throughout follow-up. This is remarkable because frequent relapses are often observed with traditional therapies.

Furthermore, patients with rosacea were 13 times more likely to have SIBO compared with controls ( Table I ); moreover, patients with subtype II rosacea were 12 times more likely to have SIBO ( Table II ).

2 Parodi A.

Paolino S.

Greco A.

et al. Small intestinal bacterial overgrowth in rosacea: clinical effectiveness of its eradication. 6 Gravina A.G.

Federico A.

Ruocco E.

et al. Helicobacter pylori infection but not small intestinal bacterial overgrowth may play a pathogenic role in rosacea. , 7 Culp B.

Scheinfeld N. Rosacea: a review. , 8 Van Zuuren E.J.

Kramer S.

Carter B.

Graber M.A.

Fedorowicz Z. Interventions for rosacea. Finally, SIBO is determinant in maintaining inflammation in rosacea and may have a relevant pathogenic role. In fact, rifaximin induced remission in our patients with SIBO due to its activity on the intestinal bacteria, and since poorly absorbable, with small if any interference on the cutaneous microfloraor any anti-inflammatory activity.

In conclusion, SIBO seems to play a role in triggering rosacea, especially subtype II, and when present, its treatment is crucial for rosacea improvement and in maintaining clinical remission.

Article Info Footnotes Funding sources: None. Conflicts of interest: None declared. Identification DOI: https://doi.org/10.1016/j.jaad.2016.01.059 Copyright © 2016 by the American Academy of Dermatology, Inc. ScienceDirect Access this article on ScienceDirect