Is HLH a potential complication of scrub typhus?

Question

Hello doctor,

My 27-year-old son, a geologist, was mapping caves when he developed a high fever and intense muscle pain. He now has black eschar marks on his neck and chest, along with a spreading rash. The local hospital confirmed scrub typhus, but his case is complicated by hemophagocytic lymphohistiocytosis (HLH). His ferritin levels are astronomically high (greater than 10,000), and he is developing multi-organ failure. He has been started on Doxycycline and Rifampicin, but his condition is deteriorating rapidly. The doctors mentioned the possibility of genetic susceptibility to severe scrub typhus. His coagulopathy is making invasive treatments risky, and he had severe bleeding after central line placement. Two other team members are also showing symptoms. Should we consider plasmapheresis? What about immunosuppression for HLH? I am also concerned because he was taking immunosuppressants for his ulcerative colitis.

Please help.

Thank you.

Answer 1

Hello,

Welcome to icliniq.com.

I understand your concern.

I am sorry to hear about your son's condition. It sounds very complicated, but I will try to provide some insights to help you navigate through this.

Scrub Typhus with HLH: Scrub typhus (caused by Orientia tsutsugamushi) can trigger an inflammatory response that, in some patients, leads to hemophagocytic lymphohistiocytosis (HLH). HLH is a severe systemic inflammatory syndrome and can worsen the prognosis of scrub typhus, especially with very high ferritin levels and multi-organ failure.

Treatment Considerations:

Doxycycline and Rifampicin: These are the mainstays of treatment for scrub typhus, and continuing them is important. However, they may not be sufficient alone when HLH complicates the course. Scrub typhus is also known to sometimes require adjunctive therapies in the setting of HLH, including immunosuppressive treatments.
Immunosuppressive therapy for HLH: HLH treatment typically involves steroids (e.g., Dexamethasone) to dampen the hyper-inflammatory response, and in more severe cases, other immunosuppressants (like Cyclosporine, Etoposide, or intrathecal Methotrexate) can be used. However, there is a risk that immunosuppression may allow the scrub typhus infection to worsen, so this needs careful balancing. Given the coagulopathy (which may result from both HLH and the ongoing infection), the decision for immunosuppression should be made by the critical care team and immunologists who can assess the potential benefit versus risk.
Plasmapheresis: Plasmapheresis is generally considered for patients with HLH when there is severe hyperinflammation or life-threatening organ dysfunction due to the massive cytokine release, as seen in your son's case. However, the presence of coagulopathy complicates this decision especially since he had bleeding complications after a central line placement. If bleeding is still an issue, plasmapheresis might pose significant risks, so this should be weighed carefully by specialists in both hematology and critical care. Some centers use plasmapheresis selectively to try and remove pro-inflammatory cytokines or other mediators.
Immunosuppressants for ulcerative colitis: Immunosuppressants for ulcerative colitis (e.g., Mesalazine, corticosteroids, biologics like TNF (tumor necrosis factor) inhibitors) may potentially make your son more susceptible to infections. Given that he is already immunocompromised, the critical issue is whether his ongoing ulcerative colitis treatment is contributing to his vulnerability to scrub typhus or HLH. The treating team may need to review his medications, adjust them, and consider the potential for drug interactions and immune system modulation during his current illness.
Invasive treatments and coagulopathy: The coagulopathy and bleeding tendencies from HLH and scrub typhus must be managed very carefully. Invasive procedures, such as placing a central line, are risky in this scenario. The team may want to prioritize non-invasive monitoring and supportive care, such as using blood products to address the coagulopathy (fresh frozen plasma, platelets), and considering the risk of bleeding before attempting any further invasive treatments.
Multidisciplinary team: Ensure a multidisciplinary team of experts in infectious disease, hematology, immunology, and critical care is involved in the decision-making.

Supportive care: Given the multi-organ involvement, supportive care (e.g., mechanical ventilation, renal replacement therapy, vasopressors) is critical in stabilizing his condition.

HLH protocols: If HLH is confirmed, try to initiate HLH-directed therapy as soon as possible, but carefully consider how it may interact with his ongoing scrub typhus treatment.

Given the complexity of this case, including the bleeding issues, decisions must be made with close monitoring of his vital signs, organ function, and coagulopathy status. Time is critical, but caution is necessary to avoid exacerbating his coagulopathy or infection.

I hope this helps.

Kindly follow up if you have more concerns.

Thank you.