Oral Antimycobacterial Therapy in Chronic Cutaneous Sarcoidosis A Randomized, Single-Masked, Placebo-Controlled Study

被引:62
作者
Drake, Wonder P. [1 ,2 ]
Oswald-Richter, Kyra [2 ]
Richmond, Bradley W. [3 ]
Isom, Joan [1 ]
Burke, Victoria E. [4 ]
Algood, Holly [1 ]
Braun, Nicole [1 ]
Taylor, Thyneice [1 ]
Pandit, Kusum V. [5 ]
Aboud, Caroline [5 ]
Yu, Chang [6 ]
Kaminski, Naftali [5 ]
Boyd, Alan S. [7 ]
King, Lloyd E. [7 ]
机构
[1] Vanderbilt Univ, Sch Med, Dept Med, Div Infect Dis,Med Ctr North, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Sch Med, Dept Med, Div Allergy Pulm & Crit Care Med, Nashville, TN 37232 USA
[4] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA
[5] Univ Pittsburgh, Sch Med, Dorothy P & Richard P Simmons Ctr Interstitial Lu, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA
[6] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37232 USA
[7] Vanderbilt Univ, Sch Med, Dept Med, Div Dermatol, Nashville, TN 37232 USA
基金
美国国家卫生研究院;
关键词
MYCOBACTERIUM-TUBERCULOSIS; PROPIONIBACTERIUM-ACNES; MOLECULAR ANALYSIS; IMMUNE-RESPONSES; STATEMENT; PROTEINS; ANTIGEN; SAFETY; TISSUE;
D O I
10.1001/jamadermatol.2013.4646
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
IMPORTANCE Sarcoidosis is a chronic granulomatous disease for which there are limited therapeutic options. This is the first randomized, placebo-controlled study to demonstrate that antimycobacterial therapy reduces lesion diameter and disease severity among patients with chronic cutaneous sarcoidosis. OBJECTIVE To evaluate the safety and efficacy of once-daily antimycobacterial therapy on the resolution of chronic cutaneous sarcoidosis lesions. DESIGN AND PARTICIPANTS A randomized, placebo-controlled, single-masked trial on 30 patients with symptomatic chronic cutaneous sarcoidosis lesions deemed to require therapeutic intervention. SETTING A tertiary referral dermatology center in Nashville, Tennessee. INTERVENTIONS Participants were randomized to receive either the oral concomitant levofloxacin, ethambutol, azithromycin, and rifampin (CLEAR) regimen or a comparative placebo regimen for 8 weeks with a 180-day follow-up. MAIN OUTCOMES AND MEASURES Participants were monitored for absolute change in lesion diameter and decrease in granuloma burden, if present, on completion of therapy. OBSERVATIONS In the intention-to-treat analysis, the CLEAR-treated group had a mean (SD) decrease in lesion diameter of -8.4 (14.0) mm compared with an increase of 0.07 (3.2) mm in the placebo-treated group (P=.05). The CLEAR group had a significant reduction in granuloma burden and experienced a mean (SD) decline of -2.9 (2.5) mm in lesion severity compared with a decline of -0.6 (2.1) mmin the placebo group (P=.02). CONCLUSIONS AND RELEVANCE Antimycobacterial therapy may result in significant reductions in chronic cutaneous sarcoidosis lesion diameter compared with placebo. These observed reductions, associated with a clinically significant improvement in symptoms, were present at the 180-day follow-up period. Transcriptome analysis of sarcoidosis CD4+ T cells revealed reversal of pathways associated with disease severity and enhanced T-cell function following T-cell receptor stimulation.
引用
收藏
页码:1040 / 1049
页数:10
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