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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 27, No 6, November/December 2016
350
AFRICA
A prospective investigation into the effect of colchicine
on tuberculous pericarditis
Jurgens Jacobus Liebenberg, Catherine Jane Dold, Lourens Rasmus Olivier
Abstract
Introduction:
Tuberculous (TB) pericarditis carries significant
mortality and morbidity rates, not only during the primary
infection, but also as part of the granulomatous scar-forming
fibrocalcific constrictive pericarditis so commonly associated
with this disease. Numerous therapies have previously been
investigated as adjuvant strategies in the prevention of peri-
cardial constriction. Colchicine is well described in the treat-
ment of various aetiologies of pericarditis. The aim of this
research was to investigate the merit for the use of colchicine
in the management of tuberculous pericarditis, specifically to
prevent constrictive pericarditis.
Methods:
This pilot study was designed as a prospective,
double-blinded, randomised, control cohort study and was
conducted at a secondary level hospital in the Northern Cape
of South Africa between August 2013 and December 2015.
Patients with a probable or definite diagnosis of TB pericardi-
tis were included (
n
=
33). Study participants with pericardial
effusions amenable to pericardiocentesis underwent aspira-
tion until dryness. All patients were treated with standard TB
treatment and corticosteroids in accordance with the South
African Tuberculosis Treatment Guidelines. Patients were
randomised to an intervention and control group using a web-
based computer system that ensured assignment concealment.
The intervention group received colchicine 1.0 mg per day for
six weeks and the control group received a placebo for the
same period. Patients were followed up with serial echocardi-
ography for 16 weeks. The primary outcome assessed was the
development of pericardial constriction. Upon completion of
the research period, the blinding was unveiled and data were
presented for statistical analysis.
Results:
TB pericarditis was found exclusively in HIV-positive
individuals. The incidence of pericardial constriction in our
cohort was 23.8%. No demonstrable benefit with the use of
colchicine was found in terms of prevention of pericardial
constriction (
p
=
0.88, relative risk 1.07, 95% CI: 0.46–2.46).
Interestingly, pericardiocentesis appeared to decrease the inci-
dence of pericardial constriction.
Conclusion:
Based on this research, the use of colchicine in
TB pericarditis cannot be advised. Adjuvant therapy in the
prevention of pericardial constriction is still being investigat-
ed and routine pericardiocentesis may prove to be beneficial
in this regard.
Keywords:
pericarditis, colchicine, tuberculosis, constrictive peri-
carditis
Submitted 6/10/15, accepted 16/3/16
Cardiovasc J Afr
2016;
27
: 350–355
www.cvja.co.zaDOI: 10.5830/CVJA-2016-035
South Africa, a land of stark contrasts, contains a diverse natural
beauty that can easily be compared with some of the world’s
most majestic outdoor scenes. One of the new seven wonders
of the natural world, Table Mountain, parades its splendour to
the capital of South Africa, Cape Town. Unfortunately, South
Africa is also considered by many to be one of the tuberculosis
(TB) capitals of the world. The incidence of TB in South Africa
is estimated to have increased by over 400% in the past 15
years. This is confounded by a staggering co-infection rate of
approximately 73% with the human immunodeficiency virus
(HIV).
1
One of the most dreaded complications of TB pericarditis
is pericardial scar formation. Due to scarring, the pericardium
becomes calcified and contracts over the cardiac chambers,
thereby encasing the heart in a fibrocalcific skin that impedes
diastolic filling.
2
Constrictive pericarditis (CP) is the natural
consequence of about 17 to 40% of cases of TB pericardial
infection.
3
The definitive treatment of CP is surgical removal of
the pericardium, a procedure with a significant peri-operative
mortality rate of approximately 15%.
4
South Africa is on the forefront of research on TB heart
disease and has recently published the large, multi-centre IMPI
trial.
5
One of the goals of the IMPI trial was to assess the impact
of corticosteroids in the management of TB pericarditis. The
major findings of the study included (1) corticosteroids had
no impact on mortality rates in patients with TB pericarditis,
(2) corticosteroids decreased the incidence of pericardial
constriction by 46%, and (3) HIV-positive patients who received
corticosteroids had a significantly increased risk of developing
HIV-associated malignancies.
In established TB, early and effective treatment with short-
course anti-TB therapy is the mainstay of management. Various
strategies have been investigated as adjuncts to anti-TB drugs
in the prevention of pericardial constriction. The ongoing
discussions and numerous investigations into a wide array of
agents as possible ‘magic bullets’ in the prevention of pericardial
constriction (post-TB infection) illustrates both the interest
in the field, and also the lack of a satisfying solution to this
problem. The following strategies have previously been evaluated:
Mycobacterium indicus pranii
immunotherapy,
5
corticosteroids,
5
pericardiocentesis,
6
open surgical drainage (pericardial window),
7
thalidomide,
8
instilling intrapericardial fibrinolytic therapies,
9-11
and a wide array of non-steroidal anti-inflammatory medication.
Not one of these therapies has, to date, been internationally
Worcester Hospital, Worcester, South Africa
Jurgens Jacobus Liebenberg, MB ChB,
liebjurg@gmail.comHanover Park Day Hospital, Cape Town, South Africa
Catherine Jane Dold, MB ChB
Medi-Clinic Hospital, Durbanville, South Africa
Lourens Rasmus Olivier, MMed (Int), DTMH (Wits)