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Hemophagocytic lymphohistiocytosis: An unusual complication in disseminated Mycobacterium tuberculosis.

Padhi S, Ravichandran K, Sahoo J, Varghese RG, Basheer A - Lung India (2015 Nov-Dec)

Bottom Line: On univariate analysis (n = 53/63), age >30 years [hazard ratio (HR): 2.79, 95% confidence interval (CI):1.03-7.56, P = 0.03], presence of comorbidities (HR 4.59, CI: 1.08-19.52, P = 0.04), marked hemophagocytosis in bone marrow (HR: 2.65, CI: 1.16-6.05, P = 0.02), and nonusage/delayed usage of antitubercular therapy (ATT) (HR: 3.44, CI: 1.51-7.87, P = 0.003) were associated with decreased survival, though none of these parameters attained statistical significance (P > 0.05) in multivariate analysis.Usage of corticosteroids and/or immunomodulator drugs (HR 1.00, CI: 0.66-3.22, P = 0.35) did not alter the outcome in these patients.Strong clinical suspicion and early usage of ATT might be useful in reducing the morbidity and mortality.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Pondicherry Institute of Medical Sciences, Puducherry, India.

ABSTRACT

Background: Hemophagocytic lymphohistiocytosis (HLH) is an uncommon, potentially fatal, hyperinflammatory syndrome that may rarely complicate the clinical course of disseminated Mycobacterium tuberculosis (MTB). The clinical course of tuberculosis-associated HLH (TB-HLH) has been reported to be unpredictable.

Materials and methods: Here we describe the clinicopathological features, laboratory parameters, management, and outcome data of a patient who satisfied the 2004 diagnostic criteria for HLH secondary to disseminated MTB; we also do a systematic review of the international literature on TB-HLH. The literature review (January 1975-March 2014) found that HLH complicated the clinical course of 63 tuberculosis patients (41 males, 22 females, mean age = 45 ± 23.5 years) with a high mortality rate of 49% (31/63 died). The mean serum ferritin level (n = 44/63) was 5963 ng/mL (range 500-38,539 ng/mL); and a higher proportion (54.2%) of patients had pancytopenia at presentation. On univariate analysis (n = 53/63), age >30 years [hazard ratio (HR): 2.79, 95% confidence interval (CI):1.03-7.56, P = 0.03], presence of comorbidities (HR 4.59, CI: 1.08-19.52, P = 0.04), marked hemophagocytosis in bone marrow (HR: 2.65, CI: 1.16-6.05, P = 0.02), and nonusage/delayed usage of antitubercular therapy (ATT) (HR: 3.44, CI: 1.51-7.87, P = 0.003) were associated with decreased survival, though none of these parameters attained statistical significance (P > 0.05) in multivariate analysis. Usage of corticosteroids and/or immunomodulator drugs (HR 1.00, CI: 0.66-3.22, P = 0.35) did not alter the outcome in these patients.

Conclusion: HLH should be considered as a differential diagnosis in patients with tuberculosis who present with cytopenias, organomegaly, and coagulopathy. Strong clinical suspicion and early usage of ATT might be useful in reducing the morbidity and mortality. The utility of immunosuppressive/immunomodulator therapy lacks general concensus among treating physicians, and warrants further studies.

No MeSH data available.


Related in: MedlinePlus

Diagnostic algorithm of all cases of tuberculosis who presented with hemophagocytic lymphohistiocytosis. +; positive, *; in 3 cases, no information was available. Note: in 33 of 60 cases, the disease was evident in ≥ 2 anatomic sites. Mycobacterium kansasii[21] and Mycobacterium avium intracellulare complex (MAC)[10] were isolated in one case each; and rest cases were attributable to Mycobacterium tuberculosis
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Figure 1: Diagnostic algorithm of all cases of tuberculosis who presented with hemophagocytic lymphohistiocytosis. +; positive, *; in 3 cases, no information was available. Note: in 33 of 60 cases, the disease was evident in ≥ 2 anatomic sites. Mycobacterium kansasii[21] and Mycobacterium avium intracellulare complex (MAC)[10] were isolated in one case each; and rest cases were attributable to Mycobacterium tuberculosis

Mentions: A schematic representation of diagnostic algorithm in all cases with tuberculosis is presented in Flow chart 1. Overall, among 40 of 60 cases where complete data were available (66.6%), the diagnosis of tuberculosis was made at ≥2 different anatomic sites by using either histopathological evaluation (n = 40, 66.6%) or by microbiological methods [demonstration of acid-fast bacilli by the Ziehl–Neelsen stain (n = 36, 60%), isolation by microbial culture (n = 33, 55%), or polymerase chain reaction (PCR) (n = 8, 13.3%)]. On the contrary, clinicoradiological features consistent with tuberculosis were present in only 10 cases (16.7%). On histopathological examination, granulomatous inflammations were demonstrated most commonly in the bone marrow (n = 23), lungs and/or pleura (n = 16), spleen (n = 10), liver (n = 8), and lymph nodes (n = 8). Similarly, among 33 cases where the culture results were positive, the organisms were isolated from 52 different anatomic samples such as the respiratory tract (n = 16), extrapulmonary sites (n = 23) [bone marrow (n = 15), liver (n = 2), spleen (n = 2), and lymph node (n = 4)], and body fluids (n = 13). The isolate was reported as MAC in a sickle cell patient,[10] Mycobacterium kansasii in another case;[21] in the remaining cases it was reported as MTB. Therefore, it can be postulated that cases with disseminated tuberculosis were complicated by the process of HLH.


Hemophagocytic lymphohistiocytosis: An unusual complication in disseminated Mycobacterium tuberculosis.

Padhi S, Ravichandran K, Sahoo J, Varghese RG, Basheer A - Lung India (2015 Nov-Dec)

Diagnostic algorithm of all cases of tuberculosis who presented with hemophagocytic lymphohistiocytosis. +; positive, *; in 3 cases, no information was available. Note: in 33 of 60 cases, the disease was evident in ≥ 2 anatomic sites. Mycobacterium kansasii[21] and Mycobacterium avium intracellulare complex (MAC)[10] were isolated in one case each; and rest cases were attributable to Mycobacterium tuberculosis
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663863&req=5

Figure 1: Diagnostic algorithm of all cases of tuberculosis who presented with hemophagocytic lymphohistiocytosis. +; positive, *; in 3 cases, no information was available. Note: in 33 of 60 cases, the disease was evident in ≥ 2 anatomic sites. Mycobacterium kansasii[21] and Mycobacterium avium intracellulare complex (MAC)[10] were isolated in one case each; and rest cases were attributable to Mycobacterium tuberculosis
Mentions: A schematic representation of diagnostic algorithm in all cases with tuberculosis is presented in Flow chart 1. Overall, among 40 of 60 cases where complete data were available (66.6%), the diagnosis of tuberculosis was made at ≥2 different anatomic sites by using either histopathological evaluation (n = 40, 66.6%) or by microbiological methods [demonstration of acid-fast bacilli by the Ziehl–Neelsen stain (n = 36, 60%), isolation by microbial culture (n = 33, 55%), or polymerase chain reaction (PCR) (n = 8, 13.3%)]. On the contrary, clinicoradiological features consistent with tuberculosis were present in only 10 cases (16.7%). On histopathological examination, granulomatous inflammations were demonstrated most commonly in the bone marrow (n = 23), lungs and/or pleura (n = 16), spleen (n = 10), liver (n = 8), and lymph nodes (n = 8). Similarly, among 33 cases where the culture results were positive, the organisms were isolated from 52 different anatomic samples such as the respiratory tract (n = 16), extrapulmonary sites (n = 23) [bone marrow (n = 15), liver (n = 2), spleen (n = 2), and lymph node (n = 4)], and body fluids (n = 13). The isolate was reported as MAC in a sickle cell patient,[10] Mycobacterium kansasii in another case;[21] in the remaining cases it was reported as MTB. Therefore, it can be postulated that cases with disseminated tuberculosis were complicated by the process of HLH.

Bottom Line: On univariate analysis (n = 53/63), age >30 years [hazard ratio (HR): 2.79, 95% confidence interval (CI):1.03-7.56, P = 0.03], presence of comorbidities (HR 4.59, CI: 1.08-19.52, P = 0.04), marked hemophagocytosis in bone marrow (HR: 2.65, CI: 1.16-6.05, P = 0.02), and nonusage/delayed usage of antitubercular therapy (ATT) (HR: 3.44, CI: 1.51-7.87, P = 0.003) were associated with decreased survival, though none of these parameters attained statistical significance (P > 0.05) in multivariate analysis.Usage of corticosteroids and/or immunomodulator drugs (HR 1.00, CI: 0.66-3.22, P = 0.35) did not alter the outcome in these patients.Strong clinical suspicion and early usage of ATT might be useful in reducing the morbidity and mortality.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Pondicherry Institute of Medical Sciences, Puducherry, India.

ABSTRACT

Background: Hemophagocytic lymphohistiocytosis (HLH) is an uncommon, potentially fatal, hyperinflammatory syndrome that may rarely complicate the clinical course of disseminated Mycobacterium tuberculosis (MTB). The clinical course of tuberculosis-associated HLH (TB-HLH) has been reported to be unpredictable.

Materials and methods: Here we describe the clinicopathological features, laboratory parameters, management, and outcome data of a patient who satisfied the 2004 diagnostic criteria for HLH secondary to disseminated MTB; we also do a systematic review of the international literature on TB-HLH. The literature review (January 1975-March 2014) found that HLH complicated the clinical course of 63 tuberculosis patients (41 males, 22 females, mean age = 45 ± 23.5 years) with a high mortality rate of 49% (31/63 died). The mean serum ferritin level (n = 44/63) was 5963 ng/mL (range 500-38,539 ng/mL); and a higher proportion (54.2%) of patients had pancytopenia at presentation. On univariate analysis (n = 53/63), age >30 years [hazard ratio (HR): 2.79, 95% confidence interval (CI):1.03-7.56, P = 0.03], presence of comorbidities (HR 4.59, CI: 1.08-19.52, P = 0.04), marked hemophagocytosis in bone marrow (HR: 2.65, CI: 1.16-6.05, P = 0.02), and nonusage/delayed usage of antitubercular therapy (ATT) (HR: 3.44, CI: 1.51-7.87, P = 0.003) were associated with decreased survival, though none of these parameters attained statistical significance (P > 0.05) in multivariate analysis. Usage of corticosteroids and/or immunomodulator drugs (HR 1.00, CI: 0.66-3.22, P = 0.35) did not alter the outcome in these patients.

Conclusion: HLH should be considered as a differential diagnosis in patients with tuberculosis who present with cytopenias, organomegaly, and coagulopathy. Strong clinical suspicion and early usage of ATT might be useful in reducing the morbidity and mortality. The utility of immunosuppressive/immunomodulator therapy lacks general concensus among treating physicians, and warrants further studies.

No MeSH data available.


Related in: MedlinePlus