RESUMO
Antibiotics are among the most common causes of drug-induced liver injury worldwide. Amoxicillin/clavulanic acid and nitrofurantoin are the most common culprits while tetracyclines are a rare cause of liver injury. Among tetracyclines, minocycline has been reported more frequently than doxycycline, which is an extremely rare cause of drug-induced liver injury. We present a healthy 28-year-old male patient from rural United States who was taking doxycycline for Lyme disease. After five days of therapy, he developed nausea, vomiting, fatigue, and significant transaminitis consistent with a hepatocellular pattern of liver injury. After a thorough workup which ruled out other causes such as infection, autoimmune diseases, liver malignancy, and vascular, structural, and metabolic disorders, his liver injury was attributed to doxycycline. We reached the diagnosis also by demonstrating a consistent temporal association between doxycycline intake and liver injury and the patient recovered completely with the cessation of doxycycline. Recognition of doxycycline as a cause of drug-induced liver injury should be considered in patients utilizing this antibiotic. Doxycycline, unlike minocycline, has a short latency period. Early recognition and discontinuation of doxycycline in our patient resulted in the complete resolution of symptoms and transaminitis preventing further morbidity and mortality.
RESUMO
Hemophagocytic lymphohistiocytosis (HLH) secondary to tick-borne infections is a rare but potentially life-threatening syndrome. We performed a scoping review according to PRISMA guidelines to systematically analyze the existing literature on the topic. A total of 98 patients were included, with a mean age of 43.7 years, of which 64% were men. Most cases, 31%, were reported from the USA. Immunosuppression was present in 21.4%, with the most common cause being previous solid organ transplantation. Constitutional symptoms were the most common, observed in 83.7% of the patients, while fever was reported in 70.4% of cases. Sepsis was present in 27.6%. The most common laboratory abnormalities in this cohort were thrombocytopenia in 81.6% of patients, while anemia, leukopenia, and leukocytosis were observed in 75.5%, 55.1%, and 10.2%, respectively. Liver enzyme elevation was noted in 63.3% of cases. The H-score was analyzed in 64 patients, with the mean value being 209, and bone marrow analysis was performed in 61.2% of patients. Ehrlichia spp. was the main isolated agent associated with HLH in 45.9%, followed by Rickettsia spp. in 14.3% and Anaplasma phagocytophilum in 12.2%. Notably, no patient with Powassan virus infection or Lyme borreliosis developed HLH. The most common complications were acute kidney injury (AKI) in 35.7% of patients, shock with multiple organ dysfunction in 22.5%, encephalopathy/seizure in 20.4%, respiratory failure in 16.3%, and cardiac complications in 7.1% of patients. Treatment included antibiotic therapy alone in 43.9%, while 5.1% of patients were treated with immunosuppressants alone. Treatment with both antibiotics and immunosuppressants was used in 51% of patients. Appropriate empiric antibiotics were used in 62.2%. In 43.9% of cases of HLH due to tick-borne disease, patients received only antimicrobial therapy, and 88.4% of those recovered completely without the need for immunosuppressive therapy. The mortality rate in our review was 16.3%, and patients who received inappropriate or delayed empiric therapy had a worse outcome. Hence, we suggest empiric antibiotic treatment in patients who are suspected of having HLH due to tick-borne disease or in whom diagnostic uncertainty persists due to diagnostic delay in order to minimize mortality.