Oral antimycobacterial therapy in chronic cutaneous sarcoidosis: a randomized, single-masked, placebo-controlled study

JAMA Dermatol. 2013 Sep;149(9):1040-9. doi: 10.1001/jamadermatol.2013.4646.

Abstract

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) mm in 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.

Trial registration: clinicaltrials.gov Identifier: NCT01074554.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / therapeutic use*
  • Azithromycin / administration & dosage
  • Azithromycin / therapeutic use
  • CD4-Positive T-Lymphocytes / metabolism*
  • Chronic Disease
  • Drug Therapy, Combination
  • Ethambutol / administration & dosage
  • Ethambutol / therapeutic use
  • Female
  • Follow-Up Studies
  • Humans
  • Levofloxacin
  • Male
  • Middle Aged
  • Ofloxacin / administration & dosage
  • Ofloxacin / therapeutic use
  • Rifampin / administration & dosage
  • Rifampin / therapeutic use
  • Sarcoidosis / drug therapy*
  • Sarcoidosis / microbiology
  • Sarcoidosis / pathology
  • Severity of Illness Index
  • Single-Blind Method
  • Skin Diseases / drug therapy*
  • Skin Diseases / microbiology
  • Skin Diseases / pathology
  • Transcriptome
  • Treatment Outcome
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Levofloxacin
  • Azithromycin
  • Ethambutol
  • Ofloxacin
  • Rifampin

Associated data

  • ClinicalTrials.gov/NCT01074554