The current pandemic of coronavirus disease 2019 (COVID- 19) poses a bigger challenge to the population in tropical countries where dengue fever is also endemic as both diseases share similar clinical and laboratory features. In COVID-19, hyperferritinaemia is associated with severe disease and clinical outcome while in dengue fever, hyperferritinaemia is a key feature of haemophagocytic lymphohistiocytosis (HLH), which is a complication with high mortality. In this case report, we present a case of coinfection of COVID-19 and dengue with hyperferritinaemia in Queen Elizabeth Hospital, Sabah, Malaysia.
Haemophagocytic syndrome (HPS) should be included in the differential diagnosis of pyrexia of unknown origin (PUO). The hallmark of HPS is the accumulation of activated macrophages that engulf haematopoietic cells in the reticuloendothelial system. We describe a patient with unexplained fever in which a final diagnosis of HPS was established in a bone marrow study.
We present the case of a male infant with congenital tuberculosis in a nonendemic setting complicated by hemophagocytic lymphohistiocytosis, who was treated successfully with antituberculous therapy and corticosteroids. We review the pediatric literature concerning the unusual association of these 2 rare conditions.
Hemophagocytic lymphohistiocytosis (HLH) is a severe and life-threatening condition causing multisystem involvement such as cytopenia, hepatosplenomegaly, and death. Dengue infection is one of the leading causes of HLH. We reviewed three cases of children at HRH Princess Maha Chakri Sirindhorn Medical Center, Faculty of Medicine, Srinakharinwirot University, Nakhon Nayok, Thailand, with dengue fever who subsequently developed HLH, based on the HLH-2004 diagnostic criteria. Following treatment with dexamethasone and intravenous immunoglobulin, there was a dramatic response including defervescence and improvement of cytopenia, hyperfibrinogenemia, and hyperferritinemia. Key features for diagnosis of dengue fever complicated by HLH include a history of prolonged fever exceeding seven days, splenomegaly, and worsening cytopenia. Early recognition and treatment are crucial for a successful outcome.
Infection associated hemophagocytic syndrome is increasingly recognized as a potentially fatal complication of dengue fever. It should be suspected with prolonged fever beyond seven days associated with hepatosplenomegaly, hyperferritinemia, worsening cytopenias and development of multiorgan dysfunction. Surge of similar pro-inflammatory cytokines observed in dengue associated hemophagocytic syndrome and multiorgan dysfunction may indicate they are part of related inflammatory spectrum. A proportion of patients recovered with supportive therapy, however most required interventions with corticosteroids, intravenous immunoglobulin or chemotherapy. We report three cases of dengue associated IAHS with good outcome following early recognition and treatment with dexamethasone and intravenous immunoglobulin.
Haemophagocytic lymphohistiocytosis (HLH) is a potentially fatal disorder resulting from uncontrolled hyperinflammatory response. There had been increase in cases of one of the secondary form of HLH, i.e., infectionassociated haemophagocytic syndrome (IAHS) in severe dengue in recent years. However, the condition remains under diagnosed due to lack of awareness compounded by the lack of validated diagnostic criteria. Severe hepatitis with prolonged cytopenias, severe hyperferritinemia, hypofibrinogenemia and persistent fever were evident in all four cases reported. All the subjects survived with supportive care and adjuvant steroid therapy. Prospective controlled studies are needed to develop diagnostic criteria and management protocol for IAHS in severe dengue.
Hemophagocytic syndrome is a potentially fatal disorder. It is being increasingly reported but remained under-recognized in dengue. Most reported cases were in association with plasma leakage and shock but multi-organ impairment was also observed. We describe the time-lines of 6 cases of confirmed dengue with varying severities of hemophagocytosis. All had persistent fever, cytopenia and elevated transaminases with markedly elevated ferritin levels during and beyond the plasma leakage phase. Acute renal failure and central nervous system manifestation were observed in two patients. Morphological hemophagocytosis was demonstrated in three patients. All survivors showed clinical and biochemical resolution of hemophagocytosis indicating its transient nature. Persistence of fever and cytopenia together with multi-organ dysfunction, out of proportion to and beyond the plasma leakage phase should prompt clinicians to consider this phenomenon.
Hemophagocytic lymphohistiocytosis (HLH) is a disorder characterized by uncontrolled mature histiocyte proliferation, hemophagocytosis, and hypercytokinemia. We describe a previously healthy pregnant patient who presented in the third trimester of pregnancy with HLH.
Haemophagocytic lymphohistiocytosis (HLH) is an uncommon disease with a high fatality rate. Etoposide is an important component of current HLH treatment regimes. Two patients with HLH developed etoposide-related secondary acute myeloid leukemia (sAML) following therapy for HLH. Etoposide, an epipodophyllotoxin, is a topoisomerase II inhibitor that interacts with DNA to potentiate leukaemogenesis. The risk of developing sAML is estimated to be between 1% and 5%, 2-20 years after exposure to etoposide but may also be related to cumulative drug doses, treatment schedules, host factors and co-administration of other antineoplastic agents.
Haemophagocytic lymphohistiocytosis (HLH) is rare. Although Kawasaki disease (KD) has been reported as a precursor to HLH, coronary arteritis occurring at the onset of secondary HLH, not in association with KD, has not been reported. An 8-year-old girl presented with virus-induced secondary HLH associated with a giant aneurysm and ectasia of the coronary arteries which was detected incidentally at onset of the disease. She did not fulfill the criteria for diagnosis of KD. The coronary lesions improved after 6 months of treatment with dexamethasone and etoposide. Echocardiography early in the course of HLH is a useful tool to detect the unusual finding of coronary arteritis which may carry significant clinical sequelae.
Introduction: Secondary Hemophagocytic Lymphohistiocytosis (HLH) is a condition seen in severe dengue that can be potentially fatal. Timely management using HLH-directed treatment such as steroids or etoposide have been seen to improve the outcome of patients however there is no protocol on how to manage the disease. Two criteria commonly used to guide the direction of treatment are namely the HLH-2004 criteria and the Hscore; with the latter being used more often. The best cut-off H score is 169 corresponding to a sensitivity of 93%, specificity of 86% and accurate classification of 90% of the patients. We described of five patients diagnosed with severe dengue compli-cated with HLH. Methods: 5 cases that were diagnosed with severe dengue with secondary HLH and received dexa-methasone were reviewed retrospectively and clinical data extracted. Results: All patients had fever beyond critical or leaking phase. Four out of five cases had Hscore higher than 169 and had a mean score of 181 with only one bone marrow performed. Three patients had concurrent leaking and bleeding and three patients had fast progression of se-vere transaminitis during the critical phase. The mean peak ferritin level was 21077 micro/L. The only bone marrow aspiration done revealed increased macrophages and hemophagocytic activity. All patients received a short course of dexamethasone and discharged well. Conclusion: Short course dexamethasone is effective in treatment of HLH in dengue despite the concerns of administration of steroids in bleeding dengue patient. Secondary HLH in dengue remains a clinical diagnosis with no conclusive diagnostic criteria. It should be suspected in a severe dengue patient with hyperferritinemia and persistent fever. Technical difficulty of performing bone marrow during severe dengue makes conclusive diagnosis remains elusive.
An 18-year-old male adolescent presented with prolonged high spiking temperature, photosensitive rash, oral ulcers and reduced hearing bilaterally of recent onset. Examination revealed malar rash, vasculitis rash over bilateral palms and soles, oral and buccal ulcers, palpable posterior auricular and inguinal lymph nodes, and reduced hearing bilaterally. His further investigations noted pancytopaenia, elevated transaminases, hyperferritinaemia, low C3 and C4 levels, positive antinuclear antibody, double-stranded DNA and direct Coombs test, while bone marrow aspiration revealed active phagocytic activity suggestive of hemophagocytic syndrome. We made a diagnosis of systemic lupus erythematosus with macrophage activation syndrome. We treated him with pulse intravenous methylprednisolone and his condition improved drastically. Temperature resolved on the next day after intravenous methylprednisolone; bilateral sensorineural hearing loss improved to near-normal hearing after treatment. He remained well during follow-up with a tapering dose of prednisolone.
It is often a challenge and a dilemma for clinicians encountering patients with pyrexia of unknown origin. Numerous tests performed to determine the underlying cause often give inconclusive results. We present a 52-year-old man with undulating fever for more than 10 months with persistent hyperferritinaemia, and negative immunological and serological markers. Despite corticosteroids, disease modifying anti-rheumatic agents and immune-modulator therapy, he succumbed to the illness. A diagnosis of refractory Adult onset Still's disease complicated by haemophagocytic lymphohistiocytosis was made.
Dengue is known to cause high morbidity and mortality worldwide. In recent years, there have been increasing cases of dengue fever associated with a rare complication: hemophagocytic syndrome (HPS), which is a dangerous disorder that carries high mortality. It is associated with infections, autoimmune disorders, and malignancies. Prolonged duration of fever and cytopenia together with multi-organ dysfunction out of proportion to the plasma leakage phase should alert clinicians to consider this condition. In this case study, we highlight a 45-year-old woman with underlying diabetes who was admitted due to dengue fever with warning signs. Her conditions deteriorated quickly: she had spontaneous bleeding, evidence of plasma leakage, severe hepatitis, and coagulopathy on the 11th day of illness. With the support of other blood results, such as raised serum ferritin and lactate dehydrogenase, she was diagnosed with severe dengue with hemophagocytosis syndrome. She responded well to intravenous dexamethasone and recovered on the 19th day of illness.