Macrophage activation syndrome

What it is

From: Orphanet

A rare hemophagocytic syndrome characterized by excessive activation and proliferation of macrophages and T cells occurring in the context of a variety of diseases, including infections, neoplasms, rheumatic disorders, and leading to sudden onset of persistent fever, lymphadenopathy, and hepatosplenomegaly. Complications include profound depression of one or more blood cell lines with coagulopathy and pancytopenia, and impaired liver and renal function. Bone marrow examination reveals numerous well differentiated macrophages actively phagocytosing hematopoietic elements.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal circulating interleukin concentration · Very frequent (99-80%)

The concentration of an interleukin (a class of cytokines) is outside the limits of normal.

Abnormal natural killer cell count · Very frequent (99-80%)

Abnormal increase or decrease of total natural killer (NK) cells, commonly characterized as CD3-CD19- and CD16+ or CD56+ lymphocytes, in the blood, per microlitre, or altered NK cell phenotype, compared to a reference range for a given sex and age-group, measured ex vivo.

Abnormality of tumor necrosis factor secretion · Very frequent (99-80%)

An abnormality in the production or cellular release of tumor necrosis factor.

Anemia · Very frequent (99-80%)

A reduction in erythrocytes volume or hemoglobin concentration.

Autoimmunity · Very frequent (99-80%)

The occurrence of an immune reaction against the organism's own cells or tissues.

Decreased liver function · Very frequent (99-80%)

Reduced ability of the liver to perform its functions.

Elevated circulating alanine aminotransferase concentration · Very frequent (99-80%)

An abnormally high concentration in the circulation of alanine aminotransferase (ALT).

Elevated erythrocyte sedimentation rate · Very frequent (99-80%)

An increased erythrocyte sedimentation rate (ESR). The ESR is a test that measures the distance that erythrocytes have fallen after one hour in a vertical column of anticoagulated blood under the influence of gravity. The ESR is a nonspecific finding. An elevation may indicate inflammation or may be caused by any condition that elevates fibrinogen.

Fever · Very frequent (99-80%)

Body temperature elevated above the normal range.

Hemophagocytosis · Very frequent (99-80%)

Phagocytosis by macrophages of erythrocytes, leukocytes, platelets, and their precursors in bone marrow and other tissues.

Hypoalbuminemia · Very frequent (99-80%)

The concentration of albumin in the blood circulation is below the lower limit of normal.

Increased circulating ferritin concentration · Very frequent (99-80%)

Increased concentration of ferritin in the blood circulation.

Increased circulating interleukin 6 concentration · Very frequent (99-80%)

The concentration of interleukin-6 in the blood circulation is above the upper limit of normal.

Increased circulating lactate dehydrogenase concentration · Very frequent (99-80%)

An elevated level of the enzyme lactate dehydrogenase in the blood circulation.

Other findings in the same source

From: Orphanet

Additional reported features include Increased inflammatory response (Very frequent (99-80%)); Increased serum interferon-gamma level (Very frequent (99-80%)); Thrombocytopenia (Very frequent (99-80%)); Decreased total neutrophil count (Frequent (79-30%)); Elevated circulating C-reactive protein concentration (Frequent (79-30%)); Elevated circulating aspartate aminotransferase concentration (Frequent (79-30%)); Hypertriglyceridemia (Frequent (79-30%)); Hypofibrinogenemia (Frequent (79-30%)); Juvenile rheumatoid arthritis (Frequent (79-30%)); Lymphadenopathy (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Adolescent; Adult; Childhood

Which doctor should you see?

The suggested department for discussing Macrophage activation syndrome is Rheumatology, with a rheumatologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Are the findings inflammatory, structural or due to another mechanism?
• Is there evidence that other organs need assessment?
• How will function and any treatment-related risks be monitored?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Macrophage activation syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.