Tuberculosis-Associated Hemophagocytic Lymphohistiocytosis: A Review of Current Literature

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a condition of immune dysregulation and hyperinflammation, leading to organ failure and death. Malignancy, autoimmune conditions, and infections, including Mycobacterium tuberculosis (TB), are all considered triggers of HLH. The aim of this study was to review all reported cases of TB-associated HLH in English literature, and to summarize the epidemiology, diagnostics, treatment, and mortality in patients with concomitant HLH and TB. A systematic review of described cases with TB-associated HLH, via a structured literature search in the medical database PubMed, is presented. Additional articles were included through cross-referencing with existing review articles. Articles were reviewed based on a predetermined set of criteria. A total of 116 patients with TB-associated HLH were identified with a male:female ratio of about 3:2. The age at presentation ranged from 12 days to 83 years. Malignancy, autoimmunity, and renal failure were the most common comorbid conditions. Most patients received both tuberculostatic and specific immunomodulating treatment, which was associated with a 66% (48/73) survival rate compared to 56% (15/27) in those receiving only tuberculostatic treatment, and 0% (0/13) in those receiving only immunomodulating treatment. The survival rate was 55% overall. The overlapping presentation between disseminated TB and HLH poses challenging diagnostics and may delay diagnosis and treatment, leading to increased mortality. TB should be considered as a potential trigger of HLH; clinicians’ knowledge and awareness of this may result in the appropriate investigations needed to ensure diagnosis and proper treatment.

Tuberculosis-associated hemophagocytic lymphohistiocytosis: diagnostic challenges and determinants of outcome

“…All (18/18) patients not on antituberculosis treatment died, while in hospital mortality was only 27.8% (28/97) in patients started on antituberculosis treatment (p < 0.001). Time from hospital admission to death was 13 days (IQR [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] in patients who did not receive antituberculosis treatment (reported for 14/18 patients) and 31 days (IQR 13-42, p = 0.007) who did receive antituberculosis treatment (reported for 22/28 patients).…”

“…Our study is the first PRISMA-compliant, individual patient level meta-analysis, bringing together all reported adult HIV-negative TB-HLH patients. We overlap 73 adult cases but have added an additional 42 adult cases to those in the most recent review that comprised 116 cases, including 43 that we excluded because they were pediatric, HIV-positive or had missing data [7]. This allowed a priori specified subgroup comparisons and multivariate outcome analyses.…”

“…Currently, understanding of optimal diagnostic strategies and therapeutic approaches in TB-HLH is limited because data is largely confined to case reports and small case series. A recent review on clinical characteristics of TB-HLH included a heterogenous patient population including children and lacked pre-defined patient categorization or multivariate assessment of the determinates of outcomes [7].…”

Tuberculosis-Associated Hemophagocytic Lymphohistiocytosis: Diagnostic Challenges and Determinants of Outcome

“…Our study is the first PRISMA-compliant, individual patient–level meta-analysis bringing together all reported adult cases of HIV-negative TB-HLH. We overlap 73 adult cases but have added an additional 42 to those in the most recent review that comprised 116 cases, including 43 that we excluded because they were pediatric or HIV positive or they had missing data [ 7 ]. This allowed a priori–specified subgroup comparisons and multivariate outcome analyses.…”

“…Currently, understanding of optimal diagnostic strategies and therapeutic approaches in TB-HLH is limited because data are largely confined to case reports and small case series. A recent review on clinical characteristics of TB-HLH included a heterogenous patient population including children and lacked predefined patient categorization or multivariate assessment of the determinates of outcomes [ 7 ]. This limits the ability to draw firm conclusions on how to best identify patients with TB-HLH, the investigations with greatest diagnostic yield, and the interventions that most affect survival.…”