title: Oral antimycobacterial therapy in chronic cutaneous sarcoidosis: a randomized, single-masked, placebo-controlled study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  A randomized, placebo-controlled, single-masked trial on 30 patients with symptomatic chronic cutaneous sarcoidosis lesions deemed to require therapeutic intervention.
  
  
  METHODS
  A tertiary referral dermatology center in Nashville, Tennessee.
  
  
  METHODS
  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.
  
  
  METHODS
  Participants were monitored for absolute change in lesion diameter and decrease in granuloma burden, if present, on completion of therapy.
  
  
  METHODS
  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) mm in the placebo group (P = .02).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01074554.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee2Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Wonder P
authors.initials: WP
authors.lastname: Drake
authors.forename: Kyra
authors.initials: K
authors.lastname: Oswald-Richter
authors.forename: Bradley W
authors.initials: BW
authors.lastname: Richmond
authors.forename: Joan
authors.initials: J
authors.lastname: Isom
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Burke
authors.forename: Holly
authors.initials: H
authors.lastname: Algood
authors.forename: Nicole
authors.initials: N
authors.lastname: Braun
authors.forename: Thyneice
authors.initials: T
authors.lastname: Taylor
authors.forename: Kusum V
authors.initials: KV
authors.lastname: Pandit
authors.forename: Caroline
authors.initials: C
authors.lastname: Aboud
authors.forename: Chang
authors.initials: C
authors.lastname: Yu
authors.forename: Naftali
authors.initials: N
authors.lastname: Kaminski
authors.forename: Alan S
authors.initials: AS
authors.lastname: Boyd
authors.forename: Lloyd E
authors.initials: LE
authors.lastname: King
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017963:Azithromycin / Q000008:administration & dosage / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002908:Chronic Disease; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D064704:Levofloxacin; D008297:Male; D008875:Middle Aged; D015242:Ofloxacin / Q000008:administration & dosage / Q000627:therapeutic use; D012293:Rifampin / Q000008:administration & dosage / Q000627:therapeutic use; D012507:Sarcoidosis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D012720:Severity of Illness Index; D016037:Single-Blind Method; D012871:Skin Diseases / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D059467:Transcriptome; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D017963:Azithromycin; D004977:Ethambutol; D015242:Ofloxacin; D012293:Rifampin