A rare case of hemophagocytic lymphohistiocytosis triggered by disseminated tuberculosis

Hemophagocytic lymphohistiocytosis (HLH) is an uncommon, life threatening hyperinflammatory syndrome caused by severe hypercytokinemia due to highly stimulated but ineffective immune process, leading to phagocytosis of erythrocytes, leukocytes, platelets and their precursors in bone marrow and other tissues by macrophages. There are two types, which are primary HLH and secondary HLH. HLH is a potentially treatable condition which is often missed due to lack of suspicion, variable and nonspecific presentations and inability to fulfill all the diagnostic criteria. Prompt initiation of immunochemotherapy is essential but timely diagnosis may be challenging, because of rarity of HLH. We report a case of secondary HLH in 62-year-old female, triggered by disseminated tuberculosis.


introduction
Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and life-threatening syndrome of excessive immune activation. It most frequently affects infants from birth to 18 months of age, but the disease is also observed in children and adults of all ages. HLH can occur as a familial or sporadic disorder and it can be triggered by a variety of events that disrupt immune homeostasis. Infection is a common trigger both in those with a genetic predisposition and in sporadic cases [1].

Case report
62-years-old female, presented with shortness of breath, cough, fever for one month duration, history of weight loss (5 kg) & loss of appetite, no hemoptysis, no chest pain, no abdominal pain, no malena, no genitourinary symptoms. History of Left pleural effusion-tubercular one year back, taken

Discussion
Hemophagocytic lymphohistiocytosis (HLH) is a rare, aggressive, life threatening syndrome of excessive inflammation and tissue destruction due to abnormal immune activation. There are two types: primary (Genetic) HLH -due to known and unknown genetic defects (Familial HLH) and immune deficiency syndromes (Chediak Higashi syndrome, Griscelli syndrome, X linked Immunoproliferative syndromes). Secondary HLH(acquired) describes patient with HLH phenotype in absence of known genetic cause, typically occurs in setting of infections, autoimmune & malignant diseases, immunosuppression/ organ transplantation [2,3].
Normally natural killer cells (constitutes 10-15% of lymphocytes) and cytotoxic lymphocytes (activated T lymphocytes) regulates and eliminate damaged, infected host cells such as macrophages bearing foreign antigen. In HLH these two fails to eliminate activated macrophages, this lack of normal feedback regulation leads to excess macrophage activity & elevated levels of cytokines [4,5] [9,10].
In our case, patient had disseminated kochs, sepsis, so started on antibacterial and anti-tubercular therapy. Cytopenias, hepatosplenomegaly raised the suspicion of HLH, so further evaluated. 6 out of 8 findings in diagnostic criteria for HLH were positive, diagnosed to have secondary HLH due to disseminated tuberculosis.

Conclusion
Though in our case -tuberculosis sepsis, a rare complication of disseminated tuberculosis is the differential diagnosis, presence of classical features such as hemophagocytosis in bone marrow, cytopenias, splenomegaly, hyperferritinemia, hypertriglyceredemia strongly suggest hemophagocytic lymphohistiocytosis. Making the correct diagnosis is crucial, because treatment differs from sepsis, as HLH needs immunosuppressive therapy. Prompt initiation of immunochemotherapy is essential but timely diagnosis may be challenging because of rarity of HLH.