Clinical Meetings at RH Year 2003

2003 Dec - Abnormal blood picture in patient with pulmonary disease

Dr. CW Lo, Department of Medicine, Yan Chai Hospital Case History Kan C was a 61-year-old man who is an ex-smoker and lived alone. He had known history of hypertension, gouty arthritis and chronic renal impairment. He presented this time with decrease in appetite for one week associated with cough, sputum and subjective weight loss. Initial CXR was shown as follows:





Bacteriological studies confirmed active pulmonary tuberculosis and anti-TB treatment was then commenced. However, this patient developed type I respiratory failure two days later and was transferred to ICU for mechanical ventilation. The disease course was complicated by acute on chronic renal failure, septic shock and disseminated intravascular coagulopathy requiring renal replacement therapy and inotropic support.

Subsequent blood test showed pancytopenia and leucoerythroblastic picture. Bone marrow examination (Fig.3) confirmed reactive hemophagocytic syndrome and trephine showed the presence of tuberculous granuloma. The condition of the patient further deteriorated and finally died despite the use of intravenous methylprednisolone.



The final diagnosis was disseminated tuberculosis with reactive hemophagocytic syndrome.

Discussion
Reactive hemophagocytic syndrome is a reactive condition in which there is systemic proliferation of non-neoplastic histiocytes engaged in phagocytosis of hemopoietic cells, associated with otherwise unexplained blood cytopenia, and fever.1 The exact pathogenesis of reactive hemophagocytic syndrome remains unknown. The systemic activation of histiocytes in hemophagocytic syndrome associated with lymphoma probably occurs as a result of macrophage activating lymphokines released from neoplastic lymphocytes.2 There has been no controlled treatment trial on tuberculosis-associated hemophagocytic syndrome. The rationale for use of high dose steroid and intravenous immunoglobulin (IVIG) in those extremely severe clinical conditions is to interfere with phagocytosis and suppress lymphocyte activation. Gill et al reported 3 adult cases of hemophagocytic syndrome treated successfully with high dose IVIG alone 3, however, the optimal treatment protocol remained uncertain. There was a recently reported case of disseminated tuberculosis associated hemophagocytic syndrome and multiple organ dysfunction syndrome successfully treated by plasma exchange and continuous haemodiafiltration.4

Hemophagocytic syndrome is shown to be a cytokine-mediated disease, characterized by hypercytokinemia, as a result of an inappropriately or excessively mounted immunological reaction in susceptible hosts, giving rise to unregulated and overstimulated histiocytic proliferation resulting in up-regulated cytokine production and hemophagocytosis.

References

1. Chan JK, Ng CS, Law CK, Ng WF, Wong KF. Reactive hemophagocytic syndrome: a study of 7 fatal cases. Pathology 1987;19:43-50.
2. Jaffe ES, Costa J, Fauci AS, Cossman J, Tsokos M. Malignant lymphoma and erythrophagocytosis simulating malignant histiocytosis.Am J Med 1983;75:741-749.
3. Gill DS, Spencer A, Cobcroft RG. High dose gamma-globulin therapy in the reactive haemophagocytic syndrome. Br J Haematol 1994;88:204-206.
4. Goto S, Aoike I, Shibasaki Y, Morita T, Miyazaki S, Shimizu T, Suzuki M. A successfully treated case of disseminated tuberculosis-associated hemophagocytic syndrome and multiple organ dysfunction syndrome. Am J Kidney Dis 2001;38: E19.