The use of oral antibiotics in treating acne vulgaris: a new approach.

Although acne is not an infectious disease, oral antibiotics have remained a mainstay of treatment over the last 40 years. The anti-inflammatory properties of oral antibiotics, particularly the tetracyclines, are efficacious in treating inflammatory acne lesions. Common prescribing practices in Dermatology exert significant selection pressure on bacteria, contributing to the development of antibiotic resistance. Antibiotic use for acne not only promotes resistance in Propionibacterium acnes, but also affects other host bacteria with pathogenic potential. This review will summarize the commonly used treatments for acne vulgaris, and how they should be combined as rational treatment. The indications for using oral antibiotics in acne will be highlighted. Strategies described in the literature to conserve the utility of oral antibiotics will be summarized. These include limiting the duration of antibiotic therapy, concomitant use of a topical non-antibiotic agent, use of subantimicrobial dose doxycycline, and the introduction of topical dapsone.

Emerging therapies in rosacea.

Rosacea is a common skin disorder with multiple symptoms. The emergence of research that furthers understanding of pathophysiological mechanisms has created new targets for disease treatment. Specifically, there is a need for new treatments that address the various erythematic symptoms associated with rosacea. Systemic and topical therapies have both yielded positive results in treating rosacea with various medications. Subantimicrobial-dose doxycycline is one such promising treatment. Development of novel products in the near future should help achieve more satisfactory outcomes for patients.

Adjunctive Effects of a Sub-Antimicrobial Dose of Doxycycline on Clinical Parameters and Potential Biomarkers of Periodontal Tissue Catabolism.

OBJECTIVES: The aim of the present randomized, double-blind, placebo-controlled, parallel-arm study was to examine the effectiveness of a sub-antimicrobial dose of doxycycline (SDD) in combination with nonsurgical periodontal therapy, compared to nonsurgical periodontal therapy alone, on potential gingival crevicular fluid (GCF) biomarkers of periodontal tissue catabolism related to the clinical outcomes over a 12-month period. Materials and Methods: GCF was collected and clinical parameters were recorded from 30 periodontitis patients randomized either to an SDD or placebo group. The SDD group received SDD (20 mg) b.i.d for 3 months plus scaling and root planing (SRP), while the placebo group was given placebo capsules b.i.d for 3 months plus SRP. The patients were evaluated every 3 months during the 12-month study period. At each visit, clinical parameters and GCF sampling were repeated. Matrix metalloproteinase (MMP)-8, MMP-9, MMP-13, myeloperoxidase (MPO), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase-5 (TRAP-5) were determined by IFMA and ELISA. Results: Significant improvements were observed in all clinical parameters in both groups over 12 months (p < 0.0125) while the SDD group showed significantly better reduction in gingival index (GI) and pocket depth and a gain in clinical attachment compared to the placebo group (p < 0.05). GCF MMP-8 and OPG levels significantly reduced in the SDD group compared to baseline (p < 0.05). GCF MMP-9 significantly decreased in both groups compared to baseline (p < 0.05). GCF MPO significantly decreased at 3 and 9 months in the SDD group, while it significantly decreased at 6 months in the placebo group (p < 0.05). TRAP and MMP-13 could be detected in none of the samples. Conclusions: The present results indicate that three months of adjunctive usage of SDD to nonsurgical periodontal therapy compared to nonsurgical periodontal therapy alone in periodontitis patients results in further improvement of clinical periodontal parameters and GCF markers of periodontal tissue breakdown over a 12-month period. Beneficial effects of adjunctive SDD therapy is likely to be related to the reduced levels of two major periodontitis-associated MMPs, MMP-8 and -9, and their potential oxidative activator MPO.

Subantimicrobial Dose Doxycycline Worsens Chronic Arthritis-Induced Bone Microarchitectural Alterations in a Mouse Model: Role of Matrix Metalloproteinases?

Background: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease hallmarked by irreversible damage of cartilage and bone. Matrix metalloproteinases (MMPs) involved in connective tissue remodeling play an important role in this process. Numerous MMPs have been examined in humans and animals, but their functions are still not fully understood. Therefore, we investigated the role of MMPs in the K/BxN serum-transfer model of RA with the broad-spectrum MMP inhibitor subantimicrobial dose doxycycline (SDD) using complex in vivo and in vitro methodolgy. Methods: Chronic arthritis was induced by repetitive i.p. injections of K/BxN serum in C57BL/6J mice. SDD was administered daily in acidified drinking water (0.5 mg/mL, 80 mg/kg) during the 30 days experimental period. Mechanonociceptive threshold of the paw was evaluated by aesthesiometry, grasping ability by grid test, arthritis severity by scoring, neutrophil myeloperoxidase activity by luminescence, vascular hyperpermeability and MMP activity by fluorescence in vivo imaging and the latter also by gelatin zymography, bone structure by micro-computed tomography (micro-CT). Plasma concentrations of doxycycline were determined by liquid chromatography-mass spectrometry analysis. Results: K/BxN serum induced significant inflammatory signs, mechanical hyperalgesia, joint function impairment, increased myeloperoxidase activity and vascular hyperpermeability. Significant increase of MMP activity was also observed both in vivo and ex vivo with elevation of the 57-60, 75, and 92 kDa gelatinolytic isoforms in the arthritic ankle joints, but neither MMP activity nor any above described functional parameters were influenced by SDD. Most importantly, SDD significantly reduced bone mineral density in the distal tibia and enhanced the Euler number in the ankle. Arthritis-induced microarchitectural alterations demonstrating increased irregularity and cancellous bone remodeling, such as increased Euler number was significantly elevated by SDD in both regions. Conclusion: We showed increase of various MMP activities in the joints by in vivo fluorescence imaging together with ex vivo zymography, and investigated their functional significance using the broad-spectrum MMP inhibitor SDD in the translational RA model. This is the first demonstration that SDD worsens arthritis-induced bone microarchitectural alterations, but it appears to be independent of MMP inhibition.

The Link Between Periodontitis and Rheumatoid Arthritis: A Periodontist's Perspective.

In this review, we critically evaluate the case-control studies examining the relationship between rheumatoid arthritis (RA) and periodontitis, two common chronic inflammatory diseases with a similar host-mediated pathogenesis. We review the "two-hit" periodontitis model that our group previously proposed, in which we elucidate how a systemic disease such as RA can potentially exacerbate or initiate periodontitis. Furthermore, we discuss adjunctive host modulation therapy, originally developed for periodontitis (i.e., subantimicrobial-dose doxycycline alone or in combination with an anti-inflammatory agent), to simultaneously mitigate RA and periodontitis. Finally, we review studies describing periodontal treatment effects on both RA disease activity measures and systemic inflammation. Current evidence suggests that an association exists between periodontitis and RA. Well-designed multicenter longitudinal clinical trials and studies with sufficient sample sizes are needed to ascertain the temporal relationship between these two diseases and whether periodontal treatment can reduce the severity of RA or prevent its onset.

Imunomodulação do hospedeiro com dose subantimicrobiana de doxiciclina no tratamento coadjuvante da periodontite crônica – revisão da literatura / Host Immunomodulation with Subantimicrobial Dose Doxycycline as Adjunctive Treatment of Chronic Periodontitis – Literature Review

A Terapia de Modulação do Hospedeiro (TMH) com dose subantimicrobiana de Doxiciclina (DSD) tem o objetivo de complementar o tratamento periodontal convencional atuando na diminuição dos processos destrutivos da resposta imunoinflamatória e no aumento dos processos protetivos e regenerativos. O objetivo desta revisão da literatura é descrever os principais aspectos da TMH e avaliar, sob o ponto de vista clínico, a eficácia da DSD como tratamento coadjuvante à terapia periodontal convencional em pacientes portadores de periodontite crônica. Para tanto, foram realizadas buscas na base de dados PubMed e foram incluídos artigos indexados a partir do ano 2000 que abordavam o tema proposto. Para avaliação da eficácia clínica foram selecionados 6 estudos clínicos duplo-cegos, randomizados, placebo-controlados, com grupos paralelos, em pacientes com periodontite crônica e sem condições sistêmicas que pudessem influenciar o curso da doença periodontal. Os estudos clínicos selecionados mostraram uma capacidade superior da TMH com DSD na melhoria dos parâmetros clínicos e dos marcadores biológicos da periodontite quando comparados com o tratamento convencional sozinho

The Host Modulation Therapy (HMT) with subantimicrobial dose Doxycycline (SDD) is intended to complement the conventional periodontal treatment acting on reducing destructive processes of the immunoinflammatory response and increasing protective and regenerative processes. The purpose of this review is to describe the main aspects of HMT and evaluate, from a clinical point of view, the efficacy of SDDas an adjunct to conventional periodontal therapy in patients with chronic periodontitis. For this purpose, searches were conducted in PubMed database and articles indexed from 2000 that addressed the proposed theme were included. To evaluate the clinical efficacy, 6 double-blind, randomized, placebo-controlled, parallel-group clinical trial sin patients with chronic periodontitis and without systemic conditions that could influence the course of the periodontal disease, were selected. The selected clinical studies showed a superior ability of HMT with SDD in improving clinical parameters and biological markers of periodontitis when compared to conventional treatment alone.