Signs parents may notice
- High fever that persists despite treatment of the infection
- Enlarged liver or spleen, or a swollen abdomen
- Rash
- Yellowing of the eyes or skin (jaundice)
- Easy bruising or bleeding
- Swelling of the body
- Drowsiness, irritability or seizures
Tests that may be used
- Complete blood count (CBC)
- Ferritin, triglycerides and fibrinogen
- Liver function tests and LDH
- Clotting tests
- Tests to find the trigger, such as infection screening
- Bone marrow examination in some children
- Genetic tests if an inherited form is suspected
What are hyperinflammation syndromes?
The immune system normally switches on to fight an infection and then switches off again. In hyperinflammation syndromes, the immune response becomes excessive and does not switch off properly. Immune cells release large amounts of chemical messengers called cytokines, a situation sometimes described as a “cytokine storm”. This can cause persistent fever and affect the blood counts, liver, clotting system and other organs.
Hemophagocytic lymphohistiocytosis (HLH) is the medical name for this pattern. When it happens in a child with a rheumatic condition, such as systemic juvenile idiopathic arthritis or lupus, it is usually called macrophage activation syndrome (MAS).
What can trigger it?
- Infections: viral infections including dengue and other respiratory or viral illnesses, as well as bacterial infections such as enteric (typhoid) fever.
- Rheumatic conditions: especially systemic JIA and lupus.
- Inherited (familial) HLH: a rare genetic form, usually in infants and young children.
- Other causes, which doctors also check for during evaluation.
Dr. Ravali’s published research includes work on severe dengue as a cytokine storm syndrome, infection-associated hyperinflammation, and HLH following enteric fever.
How is it diagnosed?
Hyperinflammation is suspected when a child remains unwell with fever despite treatment, and blood tests show a characteristic pattern: falling blood counts, a very high ferritin, abnormal liver tests and changes in clotting. Doctors use established criteria to make the diagnosis and look carefully for the trigger. A bone marrow examination or genetic tests may be needed in some children.
How is it treated?
Children with hyperinflammation need care in hospital, often in a high-dependency unit or pediatric intensive care unit (PICU), with close monitoring.
- The trigger is treated, for example with antibiotics for a bacterial infection.
- Medicines that calm the immune system, such as steroids, IVIG, ciclosporin or biological therapies, are used depending on the severity and cause.
- Inherited HLH requires specialised treatment protocols and, usually, a stem cell transplant at a specialist centre.
Recognising hyperinflammation early and starting appropriate treatment promptly makes an important difference. Care is usually shared between the pediatric rheumatology, PICU, haematology and infectious diseases teams.
After recovery
Once the illness settles, follow-up visits check blood counts and liver tests, monitor the effects of medicines as they are tapered, and look after the underlying condition if there is one. Your doctor will also advise on vaccinations and on when your child can return to school.
Treatment options that may be considered
- Treatment of the trigger, such as an infection
- Supportive care, often in a high-dependency unit or PICU
- Steroids
- IVIG
- Ciclosporin
- Biological therapies in selected children
- Specialist protocols and referral for stem cell transplant in inherited HLH
When to seek medical help urgently
- Fever that is not settling, or a child who is getting worse despite treatment for an infection
- Drowsiness, confusion or a seizure
- Bleeding, bruising or jaundice
- Breathing difficulty or passing very little urine
Questions parents often ask
Is HLH a type of cancer?
No. HLH is a condition in which the immune system becomes overactive. Some of the medicines used in severe or inherited cases are also used in cancer care, which can cause confusion, but HLH itself is not cancer.
Does every child with dengue develop this?
No. Most children with dengue recover with careful supportive care. Only a small number of children with severe illness develop hyperinflammation, and doctors look for it when the course is not as expected.
Can it happen again?
When hyperinflammation is triggered by an infection and the trigger is treated, it usually does not recur. In children with a rheumatic condition such as systemic JIA, MAS can occur again during a flare, so close follow-up is important. Inherited forms need specialised long-term treatment.
Is it inherited?
Most cases in children are triggered by infections or rheumatic conditions. An inherited (familial) form is considered in infants, in children with repeated episodes, or when there is a family history, and genetic testing can help.
This page is general information and not a substitute for a consultation. Every child is different, and the right treatment depends on an individual assessment. Please do not start, stop or change any medicine without speaking to your child's doctor.