Abstract
Macrophage activation syndrome (MAS) is a rare phenomenon that occurs either primarily or secondary to a multitude of conditions, including juvenile rheumatoid arthritis most commonly, and other infections like enteric fever and tuberculosis. It has been reported as an extremely rare complication of scrub typhus with no cases presented from India. We report three cases of scrub typhus presenting with confirmed MAS between January 2007 and December 2007 to a tertiary care hospital in South India. All three patients had clinical and laboratory evidence for scrub typhus and MAS. All the patients responded promptly to antibiotics and made an uneventful recovery. These three patients are presented to highlight the importance of considering scrub typhus in patients with MAS following acute febrile illnesses.
Introduction
Macrophage activation syndrome (MAS) is a severe, potentially life-threatening complication of several systemic disorders characterized by uncontrolled proliferation and activation of T-lymphocytes leading to overproduction of inflammatory cytokines. 1 Histiocytes with ingested haemopoetic cells or cellular elements are the pathognomonic findings on bone marrow aspiration. MAS is classified into primary and secondary types. Secondary MAS has been described with infections, malignancies and collagen vascular diseases. 2 Common infections described in association with MAS are typhoid, TB and leishmaniasis. 3 There are few case reports associating scrub typhus and the development of MAS. 4 We report three cases of MAS secondary to scrub typhus infection from a tertiary care hospital in South India.
Case history
Case 1
A 35-year-old farmer presented to the emergency department (ED) with high grade fever, myalgias and dry cough for 10 days. On examination, he was febrile, pulse was 96/min, blood pressure was 110/70 mmHg and respiratory rate was 18/min. A 2×3 cm eschar was detected on the left posterior chest wall. Abdominal examination revealed mild hepatosplenomegaly. The laboratory profile is presented in Table 1. Bone marrow aspiration smear revealed marked haemophagocytosis. Blood and bone marrow cultures, and serologies for leptospira, typhoid, spotted fever, hantavirus and dengue fever were negative. IgM Scrub typhus ELISA was positive. He was diagnosed with scrub typhus, due to the telltale presence of an eschar, with secondary MAS. He was started on doxycycline 100 mg twice daily and parenteral ceftriaxone 1g every 12 h along with platelet and fresh frozen plasma transfusions, as well as colony stimulating factors due to severe neutropenia. The patient was afebrile within 96 h of hospitalization and improved gradually within 10 days.
Laboratory profile of cases 1, 2 and 3
Case 2
A 61-year-old labourer presented with high-grade fever for 20 days associated with oliguria and pedal oedema for 3 days prior to admission. He was febrile, his pulse was 100/min, blood pressure 106/60 mmHg and respiratory rate 17/min. He had a few palpable cervical lymph nodes and hepatosplenomegaly. Bone marrow aspiration smear showed haemophagocytosis. Blood and serologies were negative as for Case 1. Scrub typhus IgM ELISA was positive. He became afebrile within 72 h of initiating doxycyclin.
Case 3
A 23-year-old male student presented with fever, vomiting and myalgias of 5 days' duration. On examination, he was afebrile, pulse rate was 88/min, blood pressure was 106/68 mmHg and respiratory rate was 16/min. He had a few palpable cervical and axillary lymph nodes with mild splenomegaly. Blood cultures and other serologies were negative like the first two cases. Scrub typhus IgM ELISA was positive and bone marrow examination showed haemophagocytosis. He was started on doxycycline alone and he defervesced within 48 h of hospitalization.
Discussion
These patients were diagnosed to have MAS based on the diagnostic criteria proposed by the Familial Haemophagocytic Lymphohistiocytosis (FHL) Study Group of the Histiocyte Society for MAS. 5 Patients with scrub typhus present with an acute febrile illness and multiple system involvement usually in the cooler months. All the patients presented to the ED with an acute febrile illness with positive scrub typhus serology and MAS that was conclusively proven by bone marrow examination.
Prompt treatment of the underlying condition is pivotal in the management of secondary MAS. In our case series, all the patients responded well to antibiotics and made uneventful clinical recoveries.
Conclusion
Secondary MAS is a rare yet serious complication of scrub typhus. Scrub typhus will have to be borne in mind while treating patients presenting with a short febrile illness and MAS.