3 | Discussion
O. tsutsugamushi being a mite-borne bacterium poses the risk of a serious disease called Scrub Typhus. Rodents function as animal reservoirs for O. tsutsugamushi, however, the microorganism also can be maintained among mite colonies through  transovarial transmission.(4) Studies show scrub typhus is an evolving public health problem with numerous outbreaks since 2015 in Nepal. Scrub typhus is a neglected tropical disease, is one of the important causes of undifferentiated treatable fever in Asia.(5)
Scrub typhus is associated with the eschar, which is a pathognomonic lesion. It’s the first lesion that appears after being bitten by a chigger (Leptotrombidium mite). Because eschar is where O. tsutsugamushi is multiplying and a huge number of organisms are found there, it has been demonstrated to be a superior sample for PCR test than blood.(6) Scrub typhus is defined by small vessel vasculitis, which affects the lungs, heart, brain, and kidneys in particular. Scrub typhus has non-specific clinical signs, and patients frequently report to the physician with a generalized fever of uncertain etiology. Severe symptoms of MOF, ARDS, shock, and DIC, on the other hand, may develop.(7)
Primary HLH occurs due to hereditary immune conditions, while on the contrary secondary HLH occurs in settings such as infection, malignancy, autoimmune disease, post-allogeneic hematopoietic stem cell transplantation, and drug hypersensitivity.(5) Interconnection between HLH and infection is vital as both familial and sporadic cases are commonly provoked by infectious diseases. HLH imitates infectious diseases concealing the identification of a causative agent leading to serious health problems.(8)
Patients with HLH die because of bleeding in visceral organs, opportunistic infection secondary to neutropenia, or Multiple organ failure within 2 months which accounts for more than 10% of cases.(4)
With an increasing number of cases documented in the last ten years, HLH is a potentially serious consequence of scrub typhus. However, the majority of instances recorded thus far have been single cases or case series with limited sample size. As a result, the clinical symptoms and prognosis of individuals with HLH linked with scrub typhus are mostly unknown.(2)
In the present case, the patient had a high-grade intermittent fever with eschar which was not responding to broad-spectrum antibiotics. During the initial work, the patient was diagnosed with a case of Scrub typhus not responding to Doxycycline and Ciprofloxacin. For this reason, an extensive workup was carried out to rule out other etiologies of fever which failed to establish the cause. Bi-cytopenia and Hyperactive macrophages with erythrophagocytosis in bone marrow biopsy suggested the possibility of HLH. Similarly, in line with HLH, biochemical parameters met the criteria for diagnosis of HLH. The patient initially responded well to the treatment but eventually, his condition deteriorated due to multi-organ failure leading to death.