Discussion:
ES is an autoimmune disorder characterized by the combination of AIHA
and immune thrombocytopenia [1]. Although the worldwide incidence of
ES has not been reported in the literature, a French national
observational study done in 265 patients with AIHA showed that 37% of
the patients had ES, while Pui et al. reported that 73% in a cohort of
15 children with AIHA had ES [4][5].
The pathophysiology underlying ES is not clearly defined but is most
likely related to a generalized dysregulation of the immune system,
involving both the cellular and humoral immunity [6][7].
Downregulation of the T cell control over the autoreactive B cell clones
results in a deranged Th1/Th2 ratio with subsequent increased production
of IL-10 and INF-γ, and decreased generation of TGF-β. The increased
secretion of INF- γ (a Th1 cytokine) stimulates the autoimmune B cell
clones to produce autoantibodies against red cell-specific and
platelet-specific antigens [8]. ES is also seen in the background of
autoimmune lymphoproliferative syndrome (ALPS), common variable
immunodeficiency (CVID), 22q11.2 deletion syndrome, and IgA deficiency,
indicating immunodeficiency as a possible predisposing factor for this
autoimmune phenomenon [9-11].
Few case reports have described the co-occurrence of TB and ES
[12-14]. Sharma et al. reported a case of ES presumed to be
secondary to TB. The authors hypothesize that the occurrence of ES in a
TB patient may be due to production of antibodies against the blood
cells by lymphocytes in response to the tubercular pathogen. Molecular
mimicry involving unknown antigens of tubercular bacilli and platelet
surface antigens could be responsible for thrombocytopenia seen in ES
patients with TB [13]. Kim et al. reported a case of tuberculosis
cutis orificialis in a patient with pre-existing ES. They discussed the
possibilities of impaired cellular immunity and the long-term use of
immunosuppressive medications in ES as predisposing factors for TB
[14]. Hence, ES could predispose to TB and vice versa. In our case,
the patient presented with symptoms of TB and ES concurrently. It is
possible that a common, yet to be determined pathophysiological
denominator could be responsible for the co-existence of these two
seemingly disparate conditions.
Frequent relapses characteristic of ES makes its treatment an uphill
task. There have been no randomized controlled trials comparing the
effectiveness of different modalities of treatments for ES.
Corticosteroids have been the mainstay of treatment based on studies
from small cohorts, although frequent relapses have been reported. Pui
et al., in his study cohort, reported remission with corticosteroid
therapy in all six children who required treatment. However, relapse was
reported during viral infections or on tapering of the corticosteroid
dose [5]. Those who fail to respond or require a high dose of
corticosteroids have reportedly been treated with IVIG [15]. Other
treatment options that have been used for refractory cases include
immunosuppressants, blood transfusion, splenectomy, and hematopoietic
stem cell transplant [2].
Further research is needed to unravel the pathophysiology behind the
concurrence of ES and TB so that common pathophysiological culprit, if
any, could be targeted. As mentioned above, there are no well-validated
guidelines for the treatment of ES and, by extrapolation, for concurrent
ES and TB. The coincidence of TB with ES adds a layer of complexity as
the treatment of ES exacerbates TB. Furthermore, the manner in which
anti-tubercular medications, with their nuclear targets, affect the
course of ES remains to be studied. Thus, there is a significant
knowledge gap in our understanding of this condition. The impetus for
research, the locus of which is primarily situated in developed
countries, could be dampened as TB is mostly a third world problem.
Furthermore, the cost-effectiveness of therapy should also be an
important consideration while devising therapeutic interventions for
concurrent TB and ES.