Molecular analysis of sarcoidosis lymph nodes for microorganisms: a case–control study with clinical correlates

Robinson, Lary A; Smith, Prudence; SenGupta, Dhruba J; Prentice, Jennifer L; Sandin, Ramon L

Sarcoidosis is a granulomatous disease primarily involving the lungs, lymph nodes and other organs that appears to be the result of an exuberant T cell and macrophage immunologic response to the continued presentation of a poorly degradable antigen. Numerous non-infective agents have been implicated based on epidemiologic basis but none have stood up to scrutiny. 1, 3, 5 The focus over the last two decades has been on infective agents that might trigger sarcoidosis, with the strongest suspects found in the mycobacteria family and the common commensal Propionibacterium acnes. And like classical tuberculosis where up to 90% of people infected with Mycobacterium tuberculosis remain in remission without treatment, 20 sarcoidosis also has a 65-80% spontaneous remission rate without treatment. 1 One may speculate that similar to tuberculosis, the immune system, after its initial response to a triggering microorganism, is successful in eradicating the agent and the immune response subsides. Then in the 20% or so with persistent and progressive sarcoidosis, the organism remains viable and perpetuates the destructive immune response. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 23 Although the classical treatment of Crohn's disease has been with immunosuppressive agents just like with sarcoidosis, many recent studies suggest a much more effective treatment with less side effects may be a triple antibiotic regimen geared toward the putative triggering agent MAP. [24] [25] [26] In fact, many in the field suspect that this intracellular organism (MAP) that resides in the macrophage impairs the normal autophagy that would usually eradicate the organism. 24 Agents that enhance autophagy such as 16α-bromoepiandersterone, 27, 28 currently in human trials, may prove effective along with antibiotics in Crohn's disease. 24 Can some antibacterial/anti-mycobacterial regimen such as that used in Crohn's disease alter the natural history of sarcoidosis in chronically symptomatic patients? Sixty years ago a number of small trials using classical anti-tuberculous drugs (isoniazide, streptomycin, or cortisone) were published with discouraging results. 29 However, atypical mycobacteria (rather than M. tuberculosis) that are more likely to be one of the etiologic agents in sarcoidosis, are almost all resistant to the standard anti-tuberculosis agents such as isoniazid. [30] [31] [32] [33] [34] [35] And if other organisms such as Proprionibacterium acnes or perhaps cell-wall deficient (L-forms) bacteria trigger and perpetuate sarcoidosis in some individuals, then the standard anti-tuberculous drugs would also be ineffective. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 The tetracycline derivatives (minocycline and doxycycline), as well as the anti-malarial drug chloroquine have been shown to be quite effective in treating cutaneous sarcoidosis. 36 Minocycline can produce complete responses in up two-thirds of cases, although it is debated whether this is an anti-microbial effect or an immunomodulating effect. 37 Attention has recently turned to randomized sarcoidosis treatment trials with various anti- 1 2 3