تعليقRecommendation 10.
In patients with tuberculous meningitis, an initial adjuvant corticosteroid therapy with dexamethasone or prednisolone tapered over 6-8 weeks should be used (strong recommendation, moderate certainty of evidence).
Recommendation 11.
In patients with tuberculous pericarditis, an initial adjuvant corticosteroid therapy may be used (conditional recommendation, very low certainty of evidence).
Source of recommendation
These recommendations were first put forward in the guidelines update of 2017 (see mapping of recommendations in Annex). They are copied without modification into this consolidated document and appear exactly as in the 2017 guidelines.
Justification
In patients with tuberculous meningitis, evidence from randomized controlled trials in the systematic review [45-49] showed lower rates of mortality, death or severe disability, and disease relapse when patients were treated with steroids in addition to anti-TB treatment. The benefits in terms of mortality increased with the increasing TB meningitis stage (i.e. increasing severity of disease). Additionally, rates of adverse events and severe adverse events, including severe hepatitis, were lower in the patients receiving steroids.
In patients with tuberculous pericarditis, evidence from studies in the systematic review [50-57] showed a benefit to steroid treatment with regard to death, constrictive pericarditis and treatment adherence. When the studies were considered individually, the largest (1400 patients) and most recent study - the IMPI study [52] - showed no benefit with steroids. However, a complicating factor in these findings is HIV infection. In the IMPI study, 67% of subjects were HIV-positive and only 14% were on ART. This raises the question as to whether immunosuppressed patients may have had a different benefit from steroids when compared to HIV-negative people or persons living with HIV who are on ART. In the IMPI study, a supplemental analysis was done of the HIV-negative patients only and a small mortality benefit was shown with steroid treatment. However, the relationship between HIV infection and steroids is complex. In another smaller study of 58 subjects, all of whom were HIV-positive, steroids were found to reduce mortality [53]. It is of note that the other studies in the review did not address HIV and mortality.
The panel considered that the benefit in preventing constrictive pericarditis outweighed the potential harms of corticosteroid therapy.
Subgroup considerations
Steroids should be given regardless of the severity of meningitis. With regard to the use of steroids in tuberculous pericarditis, in one study an increase in HIV-related cancers (non-Hodgkins' lymphoma and Kaposi sarcoma) was observed [52]. However, this increase appears to be caused by co-administration of immunotherapy (M. indicus pranii).
Implementation considerations
Practitioners should give oral steroids if intravenous formulations are not available.
Monitoring and evaluation
There are no additional recommendations beyond the standard of care.