Efficacy of Antituberculous Therapy in Management of Sarcoidosis
Condition: Sarcoidosis; Tuberculosis
MeSH terms: Tuberculosis; Sarcoidosis
Study type: Interventional

Summary: 
      From the time sarcoidosis has been described, there has always been a belief that the disease
      is in some way related to tuberculosis. If indeed tuberculosis is a causal factor in
      sarcoidosis, then the hypothesis can be further reinforced, if anti-tubercular therapy (ATT)
      is useful in treatment of sarcoidosis. Very few trials have been conducted in the past but
      the results of these trials have been discouraging. These trials were generally small studies
      and limited by time bias and used older regimens based on isoniazid, amino-salicylic acid and
      streptomycin. In our experience nearly one third of patients who are finally diagnosed to
      have sarcoidosis, have received ATT for variable length of time, but its impact of final
      outcome of sarcoidosis has not been studied. The aim of this prospective randomized
      controlled trial (RCT) is to evaluate the efficacy and safety of Rifampicin and Isoniazid
      along with prednisolone compared to prednisolone alone in treatment of Sarcoidosis.
    

Detailed description: 
      Sarcoidosis has evolved from the position of a disease of relative obscurity in the tropics,
      towards an increasing recognition and reporting from India and around. From the time
      sarcoidosis has been described, there has always been a belief that the disease is in some
      way related to tuberculosis. However, the inability to identify mycobacteria by histologic
      staining or culture from pathologic tissues continues to be one of the strongest arguments
      against a potential role for mycobacteria. Of late, molecular analysis (such as polymerase
      chain reaction [PCR] techniques) for nucleic acids of the putative agents serves as an
      alternative method for isolating fastidious organisms. A recent meta-analysis suggested a 30%
      prevalence rate of mycobacterial DNA in sarcoid samples but the individual studies reported
      detection rates from 0-50%. Moreover, most of these studies were published from countries
      with low prevalence for tuberculosis. If indeed mycobacteria are etiologically linked to
      sarcoidosis then the detection rates for mycobacterial DNA in sarcoid samples would be higher
      in countries with high prevalence of TB. In a recent prospective case-control study aimed at
      detection of mycobacterial DNA in patients with sarcoidosis from India, reinforced the
      hypothesis by showing mycobacterial DNA with PCR for 65 kDa protein gene in 48% of samples
      (BAL or biopsy) from freshly diagnosed patients of sarcoidosis.

      There are numerous factors that favor mycobacteria being a trigger for sarcoidosis. These
      include histopathological appearances of the granulomas 15, reports of mycobacterial disease
      either existing coincidentally, succeeding or antedating sarcoidosis and the finding of
      mycobacteria in occasional granulomas of sarcoidosis.Passage experiments have also suggested
      that mycobacteria with characteristics of M. tuberculosis may be the incriminating
      agent.Recent studies on humoral immunity to mycobacterial antigens from sarcoidosis patients
      have renewed interest in a potential of mycobacteria in sarcoidosis. It has been shown that
      mycobacterial ESAT-6 and katG are recognized by sarcoidosis CD4+ T cells when presented by
      known sarcoidosis susceptibility allele, DRB1*1101. It is possible that the presence of
      mycobacterial infection or BCG vaccination in genetically predisposed host may be involved in
      the development of autoimmunity.It has also been suggested that the organism might exist in a
      cell wall deficient L-form and may be difficult to isolate.

      This possible link not only has implications in the differential diagnosis of the two common
      conditions, it may also have some therapeutic implications. Reactivation of tuberculosis
      after cortico-steroid treatment is instituted for sarcoidosis is a genuine concern, given the
      high prevalence of latent infection in our country. If indeed tuberculosis is a causal factor
      in sarcoidosis, then the hypothesis can be further reinforced, if anti-tubercular therapy
      (ATT) is useful in treatment of sarcoidosis. Very few trials have been conducted in the past
      but the results of these trials have been discouraging. These trials were generally small
      studies and limited by time bias and used older regimens based on isoniazid, amino-salicylic
      acid and streptomycin. In our experience nearly one third of patients who are finally
      diagnosed to have sarcoidosis, have received ATT for variable length of time, but its impact
      of final outcome of sarcoidosis has not been studied.

      The aim of this prospective randomized controlled trial (RCT) is to evaluate the efficacy and
      safety of Rifampicin and Isoniazid along with prednisolone compared to prednisolone alone in
      treatment of Sarcoidosis.
    

Intervention name(s): Antituberculous therapy along with steroids
Intervention type(s): Drug
Intervention description(s): INH (300 mg/day) plus Rifampicin (450 mg/day if wt.<50 kg and 600 mg/day if wt. >50 kg) for six months Prednisolone 1 mg/kg/day for 6 weeks (maximum 80 mg) Prednisolone 0.75 mg/kg/day for 6 weeks (maximum 60 mg) Prednisolone 0.5 mg/kg/day for 3 months (maximum 40 mg) Prednisolone 0.25 mg/kg/day for 3 months (maximum 20 mg) Taper over the next three months Prednisolone 0.25 mg/kg EOD for 15 days Prednisolone 0.125 mg/kg EOD for 15 days Then taper by 5 mg every 15 days to complete one year
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Sarcoidosis; Tuberculosis