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.