Persistent High Fever Research Articles

Malar rash with pancytopenia

Malar rash with pancytopenia

Multisystem Inflammatory Syndrome in Children Associated with COVID-19 Infection: A Comprehensive Review

AbstractThe Multisystem Inflammatory Syndrome in Children (MIS-C) is a postinfectious syndrome associated with coronavirus disease 2019 (COVID-19) disease in children. The aim of this study is to conduct a thorough review to assist health care professionals in diagnosis and management of this complication of COVID-19 disease in children. A thorough systematic review was conducted through an on-line search based on MIS-C with the primary focus on epidemiology, clinical characteristics, diagnosis, pathophysiology, management, and long-term follow-up. This syndrome is characterized by an exaggerated and uncontrolled release of proinflammatory cytokines involving dysfunction of both innate and adaptive immunity. In this review, a summary of observational studies and case reports was conducted, in which we found that MIS-C generates multiple-organ failure frequently presenting with hemodynamic instability further characterized by Kawasaki-like symptoms (such as persistent high fever, polymorphic rash, and bilateral conjunctivitis) and predominance of gastrointestinal and cardiovascular signs and symptoms. Keys to effective management involve early diagnosis, timely treatment and re-evaluation following hospital discharge. Diagnosis is marked by significant elevation of inflammatory biomarkers, laboratory evidence of COVID-19 infection or history of recent exposure, and absence of any other plausible explanation for the associated signs, symptoms, and presentation. Management includes hemodynamic stabilization, empiric antibiotic therapy (de-escalation if cultures and polymerase chain reaction studies indicate no bacterial co-infection), immunomodulatory therapy (methylprednisolone, intravenous immunoglobulin, anakinra, tocilizumab, siltuximab, Janus kinase inhibitors, tumor necrosis factor-α inhibitors), antivirals (remdesivir), and anticoagulation (acetylsalicylic acid, unfractionated or low-molecular-weight heparin or new oral anticoagulants). In addition, we identified poor prognostic risk factors to include concurrent comorbidities, blood-component consumption and marrow suppression (lymphopenia, thrombocytopenia), depletion of homeostatic components (hypoalbuminemia), and marked evidence of a hyperinflammatory response to include elevated values of ferritin, C-reactive protein, and D-dimer. MIS-C constitutes a postinfectious syndrome characterized by a marked cytokine storm, characterized by fever, bilateral conjunctivitis, and multiple organ dysfunction. Promoting future research and long-term follow-up will be essential for the development of guidelines and recommendations leading to effective identification and management of MIS-C.

A Case of Stentocarditis, Rare Complication of Percutaneous Coronary Intervention

Fever occurs sometimes, usually transiently after coronary catheterization. We report a very rare case that suggests persistent high fever and systemic inflammation caused by stentocarditis induced by percutaneous coronary catheterization in a chronic total occlusion of the right coronary artery. The most important point to remember is that timely detection requires a high index of suspicion and early appropriate treatment is very important in preventing mortality.

Splenic infarction after Epstein\u2013Barr virus infection in a patient with hereditary spherocytosis: a case report and literature review

BackgroundHereditary spherocytosis (HS) complicated by splenic infarction is very rare, and it is even rarer to develop splenic infarction after infectious mononucleosis (IM) as a result of Epstein–Barr virus (EBV) infection. Therefore, misdiagnosis or missed diagnosis is prone to occur.Case presentationA 19-year-old Chinese female previously diagnosed with HS was admitted to our institution with persistent high fever and icterus. On admission, the physical examination showed anemia, jaundice, marked splenomegaly, obvious tenderness in the left upper abdomen (LUA). Peripheral blood film shows that spherical red blood cells accounted for about 6%, and Immunoglobulin M (IgM) antibodies specific to Epstein–Barr virus (EBV) viral capsid antigen were detected. An abdominal CT scan revealed a splenic infarction. The patient was diagnosed with HS with splenic infarction following EBV infection and underwent an emergency laparoscopic splenectomy (LS). Pathological analysis showed a splenic infarction with red pulp expansion, white pulp atrophy and a splenic sinus filled with red blood cells. After two months of follow-up visits, the patient showed no signs of relapse.ConclusionsHS complicated by splenic infarction is very rare and mostly occurs in men under 20 years of age and is often accompanied by other diseases, such as sickle cell traits (SCT) or IM. Although symptomatic management may be sufficient, emergency laparoscopic splenectomy may be safe and effective when conservative treatment is ineffective.

Development and Application of RAA Nucleic Acid Test Strip Assay and Double RAA Gel Electrophoresis Detection Methods for ASFV and CSFV.

African swine fever (ASF) is an acute, severe and hemorrhagic infectious disease caused by African swine fever virus (ASFV) infecting domestic pigs and wild boars. Since the outbreak of the disease in China in 2018, it has brought a great impact on China’s pig industry. Classical swine fever (CSF) is an acute contact infectious disease of pigs caused by classical swine fever virus (CSFV) infection. Clinically, acute CSF usually shows persistent high fever, anorexia, extensive congestion and bleeding of the skin and mucosa, which are similar to ASF. It is of great significance to prevent, control and accurately detect ASF and CSF in pig farms. In this study, Recombinase aided amplification (RAA) technology combined with a nucleic acid test strip (RAA-strip) was established for simple and specific detection of ASFV/CSFV. The sensitivity and preliminary clinical application results showed that the RAA test strip established in this study could detect recombinant plasmids containing ASFV/CSFV gene fragments as low as 103 copies/µL. The minimum detection limits of virus DNA/cDNA were 10 and 12 pg respectively, and there was no cross-reaction with other porcine viruses. The specificity of the method was good. We used 37–42 clinical samples to evaluate the performance of our established method, and the positive concordance rates with conventional PCR were 94.1 and 57.1%, respectively. In addition, ASFV and CSFV double RAA agarose gel electrophoresis detection methods were established. The results showed that the method had good specificity. The detection limit of this method is 106 copies for ASFV p72 gene recombinant plasmid and 105 copies for CSFV NS5B Gene recombinant plasmid. The use of this method for clinical material detection was consistent with the PCR method. In summary, the developed method of RAA-strip assay for ASFV and CSFV realized the visual detection of pathogens, and the developed method of dual RAA agarose gel electrophoresis assay for ASFV and CSFV realized the simultaneous detection of two pathogens in one reaction, with good specificity, high sensitivity and rapid reaction rate, which was expected to be clinically feasible for the differential diagnosis of ASF and CSF provided technical support.

Splenic abscess – unusual cause of fever in an infant

Splenic abscess in children is a rare entity and it usually oc­curs after local dissemination or hematogenous spread, es­pe­cial­ly in immunocompromised patients. Because of its rarity and nonspecific symptoms and signs, the splenic abs­cess is difficult to diagnose. We report the case of a 14-month-old girl with splenic abscesses. She was admitted to the hospital for persistent high fever, aphthous lesions and an ulcerative malleolar lesion. The laboratory tests showed leukocytosis, anemia, thrombocytosis, elevated C-reactive protein and D-dimers levels, with normal pro­cal­ci­to­nin levels. The blood culture and the culture from the lesion were negative. The abdominal ultrasound showed two hypoechogenic lesions in the spleen. She was suc­ces­sful­ly treated with wide-broad antibiotic therapy for six weeks, with a total resolution of the lesions. The pro­longed antibiotic therapy and hospitalization can lead to complications such as dysbiosis and superficial vein throm­bo­sis. This case illustrates that splenic abscess should be considered in unknown-focus fever, even in infants with no underlying conditions. Conservative therapy should be the first-line therapy for splenic abscesses in children, con­si­de­ring the importance of the immunological functions of the organ.

Symmetrical Polyarthropathy and Hepatosplenomegaly as a Manifestation of Parvovirus B-19: A Case Report

This case was of a 35-years old Egyptian lady, who works as a primary school teacher, who presented to the OPD with complaints of persistent high fever for two days. Along with this fever, she also had severe pain in multiple joints of both hands, wrists, knees, and ankles. In addition, the woman also complained of having developed a rash on both her legs, which was so painful that she was unable to stand without pain. The pain was agonizing and it prevented her from performing her usual jobs as normal. But that was the extent of her symptoms. She did not complain of a cough, shortness of breath, chest pain, back pain, abdominal pain, or any other pain for that matter. In a summary, none of the factors and symptoms that could have pointed towards the patient suffering from a case of COVID19 were present. Moreover, there was no recent history of travel. She also had not contracted any gastrointestinal or genitourinary infections in the preceding few days. The clinical examination of the patient revealed no abnormalities at all. The only thing worth noting was remarkable swelling and tenderness over the metacarpophalangeal and proximal interphalangeal joints. The following series of events are discussed in detail in the subsequent section, and it was concluded that the woman might be suffering from the parvovirus B19 infection. She had several favorable causative factors that pointed toward this diagnosis, with the most important one being her in close contact with primary school children, who are most the likely age group, between five and twenty years, to carry this infection and also contract it. Adults can contract the infection from children, but the range of symptoms varies from person to person. In this case of the woman, further evaluations and investigations were needed to confirm the diagnosis, which was likely due to the obvious risk factors present in this case.

Febrile palpebral edema

Febrile palpebral edema

ROLE OF PIROXICAM IN CONTROLLING FEVER IN COVID 19 - AN OBSERVATIONAL CASE SERIES STUDY

INTRODUCTION- COVID 19 pandemic is creating havoc in medical infrastructure. Further misery is created by the fact that there is no proven treatment of COVID 19 infection. Most of the drugs given currently in COVID 19 is for symptomatic management of infection. Updated protocols released on time to time basis have drugs which are based more on clinical observations rather than experimental ones. These drugs consists mainly repositioned drugs already approved by FDA for other disease treatment. METHOD- In our study, we have used Piroxicam polyhedral crystals sublingually for control of fever in COVID 19 pneumonia which was not controlled by Paracetamol and steroids combination. It was advised in patients progressing to severe disease category or developing pneumonia. RESULT- Our case series with limited data shows that cases have responded well to Piroxicam in control of fever. They became normothermic after single dose of drug. Further, patients' blood oxygen levels have also improved with therapy; however, with limited data, a cause-effect relationship could not be determined. CONCLUSION- At present, Piroxicam can be advised in COVID 19 infection under medical supervision for control of persistent high fever. In future, randomised studies are needed to further consolidate above claim that Piroxicam is helpful in controlling fever as well as improving blood oxygen saturation of cases

P053 Fulminant purpura in a patient with SARS-CoV-2

Background/Aims According to available data children with SARS-CoV-2 has asymptomatic or a milder clinical course, but there are known cases of multisystem inflammatory syndrome. Methods we observed a case of fulminant purpura in a boy with SARS-CoV-2. A three years old boy had febrile fever, vomiting, abdominal pain for no apparent reason. On the 2nd day this boy had joint pain, petechial rashes, fever and abdominal pain persisted. The patient was hospitalized in the pediatric Department, where he was diagnosed with hemorrhagic vasculitis, there was prescribed therapy with glucocorticosteroids (1 mg/kg per day), dipyridamole (2.5 mg/kg per day), oral cephalosporin. Against the background of ongoing therapy, the child's condition became worth. On the 5th day of the disease appeared necrosis in the area of the ankle joints, heels, and toes, patient was transferred to the pediatric Department of Children's Clinical Regional Hospital. Results at the time of hospitalization, the child's condition was severe: the boy had persistent high fever, petechial rash on the torso and legs, necrosis in the area of the left ankle, outer surface of the right ankle and in the area of both heels, edema of the feet and hands. The boy was in a forced position, couldn’t not walk and had intense pain in the shoulders, elbows, wrists, hips, knees and ankles. Blood tests revealed anemia (HGB 73 g/l), thrombocytopenia (PLT 120 x 109/L), leukocytosis (WBC 23 x 109/L), ESR 60 mm/h; in the clinical analysis of urine - proteinuria. In the blood test was detected significantly increased levels of CRP (129 mg/L), ferritin (637 ng/mL), triglycerides (1.39 mm/L), hypoproteinemia (48 g/L), hypoalbuminemia (31 g/L); the level of ALT, AST, LDH was normal. The level of D-dimer was 4792ng/mL, fibrinogen - 8.8 g/L, antithrombin III - 156%, protein C - 64%, coagulation Factor IX activity - 150 %, coagulation Factor VIII activity 289%. An increase of antinuclear antibodies, cardiolipins, phospholipids and ANCA were excluded. A nasopharyngeal swab was negative for SARS-CoV-2 (was made on the 5th day of the disease). On 14th illness day we detected IgM antibodies directed toward SARS-CoV-2 in this patient (IgG antibodies directed toward SARS-CoV-2 were absent). An echocardiogram showed no coronary artery abnormalities, echocardiogram was normal, a chest CT and MRI of the brain also were normal. The diagnosis was fulminant purpura in a patient with SARS-CoV-2. This boy received heparin, IVIG 2 g/kg, dexamethasone 10 mg per meter of body surface a day, antibiotic therapy was continued. As a result fever, petechial rash and necrosis regressed. After 4 weeks we detected IgG antibodies directed toward SARS-CoV. Conclusion the current case demonstrates the possibility of developing a multi-system inflammatory syndrome like fulminant purpura in patients who had SARS-CoV-2. Disclosure N. Tsurikova: None. S. Rodionocskaya: None. E. Ligostaeva: None. V. Avdeenko: None. N. Kobzeva: None. I. Tsiganok: None.

Pattern of Co-infection with Dengue Fever: An Observational Study

Background: Dengue fever is a major public health problem in Bangladesh. Suspicion, attention, and early tests are necessary to identify concurrent illnesses with dengue. This study was assessed to find out the other infections associated with Dengue fever to minimize morbidity and mortality.
 Materials & Methods: Hospitalized patients with fever were initially selected. After clinical and laboratory evaluation, fever with dengue NS1 or IgM positive cases were included. Among the 175 dengue patients; during follow-up, some patients had a persistent high fever, cough, dysuria, appearance/deepening of jaundice,and other toxic features that could not correlate with dengue. Relevant investigations were done to find out the co-infections among them.
 Results: Co-infection was found in 13.1% cases, among 5to 13 years of age group with female predominance. Dengue NS1 was found positive in 39.1% and IgM positive in 60.9% of cases. Typhoid fever 39.1%, paratyphoid fever 4.3%, rickettsial fever 13%, HAV infection 26%, HEV infection 8.7%, UTI 4.3%, and bacterial pneumonia 4.3% were found among the cases of dengue fever as co-infection.
 Conclusion: The study shows that dengue patients are at a higher risk of having other infections. Thirteen percent of the dengue patients were found associated with different co-infection.
 Bangladesh J Child Health 2020; VOL 44 (3) :157-160

Haemophagocytic syndrome and COVID-19.

Primary and secondary haemophagocytic lymphohistiocytosis (HLH) are hyperferritinaemic hyperinflammatory syndromes with a common terminal pathway triggered by different etiopathogenetic factors. HLH is characterised by a decreased capacity of interferon gamma production with an activated NK phenotype profile similar to other hyperinflammatory syndromes. Viruses are closely linked to the development of HLH as infectious triggers, and the break of tolerance to self-antigens is considered a critical mechanism involved in the development of immune-mediated conditions triggered by viral infections. Emerging studies in patients with COVID-19 are suggesting a key role of monocytes/macrophages in the pathogenesis of this viral infection, and there is a significant overlap between several features reported in severe COVID-19 and the features included in the HLH-2004 diagnostic criteria. Therefore, SARS-Cov-2, as other respiratory viruses, may also be considered a potential etiological trigger of HLH. The frequency of HLH in adult patients with severe COVID-19 is lower than 5%, although this figure could be underestimated considering that most reported cases lacked information about some specific criteria (mainly the histopathological criteria and the measurement of NK cell function and sCD25 levels). Because HLH is a multi-organ syndrome, the diagnostic approach in a patient with severe COVID-19 in whom HLH is suspected must be carried out in a syndromic and holistic way, and not in the light of isolated clinical or laboratory features. In COVID-19 patients presenting with persistent high fever, progressive pancytopenia, and hepatosplenic involvement, together with the characteristic triad of laboratory abnormalities (hyperferritinaemia, hypertriglyceridaemia, and hypofibrinogenaemia), the suspicion of HLH is high, and the diagnostic workup must be completed with specific immunological and histopathological studies.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10067-020-05569-4.

Deep Septic Pelvic Thrombophlebitis – a Life-Threatening Condition in Postpartum Period

SUMMARYDeep septic pelvic thrombophlebitis is a rare but potentially devastating complication in the puerperium. Early diagnosis and aggressive treatment of this postpartum complication is essential. We report a case of a 23-year-old multipara, who presented with persistent high fever and abdominal pain two days after delivery. Diagnosis of deep septic pelvic thrombophlebitis was suspected and confirmed by using contrast-enhanced computerized tomography. Upon admission in the intensive care unit, she developed shortness of breath together with hypoxemia, which was attributed to septic pulmonary emboli. Streptococcus pyogenes group A was cultured from cervical swab. Treatment consisted of broad spectrum antibiotic therapy and low molecular weight heparin. She was dismissed for home care symptom-free fourteen days after delivery and referred to hematologist to diagnose the possible causes of thrombophilia.

Doença de Kawasaki atípica associada à síndrome colestática: relato de caso

OBJECTIVES: To report the case of a child with atipical Kawasaki disease associated with cholestatic syndrome. Kawasaki disease is an inflammatory syndrome that affects small and medium-sized vases, which cause is unknown. The diagnostic is clinical and based in classic criterions, which are commonly reported symptoms, does not including cholestatic jaundice nor hepatomegaly because they are un-usual findings. CASE REPORT: 6-year-old female presented persistent high fever, rash and gastrointes-tinal symptoms. She developed with conjunctival injection, strawberry tongue, and cracked lips, with-out improvement of the fever after the empiric antibiotic treatment. In elapsing of the disease, the rash got improvement and appeared cholestatic syndrome and classic symptoms of the disease of complete Kawasaki (unilateral cervical lymphadenopaty, conjunctival injection, and hand desquama-tion), that it made possible her diagnosis and treatment, with improvement of cholestatic syndrome, without aneurysm appearance. CONCLUSIONS: This paper shows the importance of including Kawasaki disease as differential diagnosis in cases of jaundice feverish syndromes, allowing their treatment in skilled time end prevent complications.

COVID-19 in children

COVID-19 disease is of mild severity in most children. The common symptoms include fever, sore throat, cough, nasal congestion, diarrhea, and vomiting. Prompt testing of suspect cases with rapid antigen test and/or reverse transcription–polymerase chain reaction in nasopharyngeal swabs is recommended. The routine use of computed tomography (CT) scan should be discouraged. For children with mild disease, only symptomatic therapy is required. Red flag signs include persistent high fever, breathlessness, drowsiness, and hypoxia. For children with moderate/severe disease, oxygen, steroids, and anticoagulation are standard of care. Vaccination of children against COVID-19 is not a priority at this time. The indirect effects of COVID-19 vastly outnumber the direct effects.

Rapid Progression of Kaposi\u2019s sarcoma complicated with hemophagocytic syndrome in a severely immunosuppressed patient with HIV-infection: a case report

BackgroundAIDS-related KS generally involves cutaneous lesions, that slowly progress over months to years. Neither rapidly progressing of KS nor KS complicated with hemophagocytic syndrome (HPS) has rarely been reported.Case presentationWe report a rare case of rapid progression of Kaposi’s sarcoma complicated with hemophagocytic syndrome in a severely immunosuppressed patient with HIV-infection. The symptoms of this patient were atypical, showing only persistent high fever and rapid progressed to hemophagocytic syndrome. This patient was successfully treated with antiretroviral therapy combined with liposomal doxorubicin.ConclusionsThe condition of the KS patient could deteriorate rapidly over a period of days and even developeded into HPS, which was life-threatening. However, chemotherapy initiated in a timely manner might improve prognosis.

Diagnostic histologique de lymphome intravasculaire guidé par une hyperfixation corticale rénale à la tomographie par émission de positons : à propos d’un cas

Intravascular large B cell lymphoma is a rare non-Hodgkin large B cell lymphoma disease, with heterogeneous clinical manifestation and difficult pathological diagnosis. Positron emission tomography may be helpfull in this context and has already been reported. A 45-year-old woman was admitted for persistent high fever, inflammatory syndrome and unexplained haemophagocytic syndrome. Bilateral cortical renal hypermetabolism at positron emission tomography initially misled to pyelonephritis diagnosis and secondarily led to kidney biopsy, which showed intravascular large B cell lymphoma. Renal involvement in intravascular large B cell lymphoma is rare and is usually characterized by acute renal failure and proteinuria. Global hypermetabolism at positron emission tomography has already been described in this context, but cortical hypermetabolism has never been associated with pathological findings. In front of persistent high fever without etiology, this positron emission tomography feature must lead to intravascular large B cell lymphoma suspicion and to kidney biopsy to obtain pathological proof.

Adenovirus pneumonia with hemophagocytic lymphohistiocytosis in children: a clinical analysis of 7 children

To study the clinical features of children with adenovirus pneumonia and hemophagocytic lymphohistiocytosis (HLH). A retrospective analysis was performed on the mediacal data of 7 children with adenovirus pneumonia and HLH from March to September, 2019. The age of these children ranged from 11 months to 5 years, and among these children, 5 were aged <2 years and 5 were boys. None of these children had underlying diseases. All children were hospitalized due to persistent high fever and cough, and the peak temperature of fever was 39°C to 41°C. With disease progression, 7 children developed hepatomegaly and 6 developed splenomegaly. Routine blood test results showed reductions in two or three lineages of blood cells, with increases in serum ferritin (SF), C-reactive protein (CRP), procalcitonin (PCT), and lactate dehydrogenase (LDH). Phagocytosis of blood cells was observed in 6 children. Radiological examination of lungs showed pneumonia changes. All 7 children were diagnosed with human adenovirus type 7 infection based on pathogenic metagenome detection. No abnormality was found by HLH gene detection and the children were diagnosed with secondary HLH. All children received intravenous immunoglobulin. Among these children, 4 received dexamethasone and etoposide chemotherapy, 3 received dexamethasone alone, and 4 received plasma exchange. Of the 7 children, 2 died and 5 were recovered. Compared with those who survived, the children who died had significantly greater reductions in the three lineages of blood cells and significantly greater increases in serum levels of CRP, PCT, SF, and LDH. The children with adenovirus pneumonia and HLH have main clinical features of persistent high fever, progressive reductions in two or three lineages of peripheral blood cells, and involvement of other organ systems, including hepatosplenomegaly. Significant increases in serum levels of CRP, PCT, SF, and LDH may suggest a poor prognosis.

Recent advances in treatment of viral pneumonia using Chinese patent medicine

Viral pneumonia is caused by a spreading of lung infection caused by respiratory viruses. Some virus infections were found to be highly aggressive, leading to lung inflammation and severe damage in respiratory system with high fatality rate. Currently, there is no effective therapeutic drugs in the clinic. The common clinical symptoms of viral pneumonias include fever, rhinitis, runny nose, nonproductive cough, fatigue, myalgias and headaches after the immune system being tricked by driving cytokines and overactivated immune response induced by cytokine storms. Patients with severe symptoms could get persistent high fever, dysfunctional breathing, consciousness disorders and even respiratory failure, post-inflammatory pulmonary fibrosis, multi-organ damages, shock and so on. Most clinical treatments are used to inhibit virus replication, relieve symptoms, inhibit excessive inflammatory response, regulate immune balance and protect organs. Both applied and basic research demonstrate that Chinese patent medicine has certain anti-viral effects, effectively inhibiting viral pneumonia transiting from mild to severe, rapid relieving of patient symptoms because of their multi-component and multi-target integrated roles. This review has summarized the reports on the treatment of viral pneumonia. Based on the pathogenic characteristics of viral pneumonia, this paper summarizes the diverse roles of the marketed Chinese patent medicine, such as their effects in inhibiting the progress of viral replication and overactivated inflammatory response, regulating immune balance, attenuating pulmonary fibrosis and so forth. Our paper summarizes the advantages of Chinese patient medicine in the treatment of viral pneumonia, based on which improvements of clinical therapy are expected to be made soon.

Hemophagocytic lymphohistiocytosis: An update on pathogenesis, diagnosis, and therapy.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening state of immune hyperactivation that arises in the setting of genetic mutations and infectious, inflammatory, or neoplastic triggers. Sustained, aberrant activation of cytotoxic CD8+ T cells and resultant inflammatory cytokine release are core pathogenic mechanisms. Key clinical features include high persistent fever, hepatosplenomegaly, blood cytopenia, elevated aminotransferase and ferritin levels, and coagulopathy. HLH is likely under-recognized, and mortality remains high, especially in adults; thus, prompt diagnosis and treatment are essential. Familial forms of HLH are currently treated with chemotherapy as a bridge to hematopoietic stem cell transplantation. HLH occurring in rheumatic disease (macrophage activation syndrome) is treated with glucocorticoids, IL-1 blockade, or cyclosporine A. In other forms of HLH, addressing the underlying trigger is essential. There remains a pressing need for more sensitive, context-specific diagnostic tools. Safer, more effective therapies will arise with improved understanding of the cellular and molecular mechanisms of HLH.