Macrophage activation syndrome
disease diseaseOn this page
Also known as MASreactive hemophagocytic lymphohistiocytosis
Summary
Macrophage activation syndrome (MONDO:0015545) is a disease and 17 clinical trials. Top therapeutic interventions include anakinra, emapalumab, and ruxolitinib. A subtype of secondary hemophagocytic lymphohistiocytosis — broader associated-gene and molecular evidence is on the parent page (see Disease family below).
At a glance
- Prevalence: Unknown (Worldwide)
- Phenotypes (HPO): 29
- Clinical trials: 17
Clinical features
Signs & symptoms
Clinical features (HPO)
29 HPO clinical features (Orphanet curated; top 29 by frequency):
| HPO ID | Term | Frequency |
|---|---|---|
| HP:0001410 | Decreased liver function | Very frequent (80-99%) |
| HP:0001873 | Thrombocytopenia | Very frequent (80-99%) |
| HP:0001903 | Anemia | Very frequent (80-99%) |
| HP:0001945 | Fever | Very frequent (80-99%) |
| HP:0002960 | Autoimmunity | Very frequent (80-99%) |
| HP:0003073 | Hypoalbuminemia | Very frequent (80-99%) |
| HP:0003281 | Increased circulating ferritin concentration | Very frequent (80-99%) |
| HP:0003565 | Elevated erythrocyte sedimentation rate | Very frequent (80-99%) |
| HP:0011117 | Abnormal circulating interleukin concentration | Very frequent (80-99%) |
| HP:0011118 | Abnormality of tumor necrosis factor secretion | Very frequent (80-99%) |
| HP:0012156 | Hemophagocytosis | Very frequent (80-99%) |
| HP:0012649 | Increased inflammatory response | Very frequent (80-99%) |
| HP:0025435 | Increased circulating lactate dehydrogenase concentration | Very frequent (80-99%) |
| HP:0030356 | Increased serum interferon-gamma level | Very frequent (80-99%) |
| HP:0030783 | Increased circulating interleukin 6 concentration | Very frequent (80-99%) |
| HP:0031964 | Elevated circulating alanine aminotransferase concentration | Very frequent (80-99%) |
| HP:0040089 | Abnormal natural killer cell count | Very frequent (80-99%) |
| HP:0001744 | Splenomegaly | Frequent (30-79%) |
| HP:0001875 | Decreased total neutrophil count | Frequent (30-79%) |
| HP:0002155 | Hypertriglyceridemia | Frequent (30-79%) |
| HP:0002716 | Lymphadenopathy | Frequent (30-79%) |
| HP:0005681 | Juvenile rheumatoid arthritis | Frequent (30-79%) |
| HP:0011227 | Elevated circulating C-reactive protein concentration | Frequent (30-79%) |
| HP:0011900 | Hypofibrinogenemia | Frequent (30-79%) |
| HP:0031956 | Elevated circulating aspartate aminotransferase concentration | Frequent (30-79%) |
| HP:0001298 | Encephalopathy | Occasional (5-29%) |
| HP:0002240 | Hepatomegaly | Occasional (5-29%) |
| HP:0002725 | Systemic lupus erythematosus | Occasional (5-29%) |
| HP:0012115 | Hepatitis | Occasional (5-29%) |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | macrophage activation syndrome |
| Mondo ID | MONDO:0015545 |
| EFO | EFO:1001806 |
| MeSH | D055501 |
| Orphanet | 158061 |
| NCIT | C114471 |
| SNOMED CT | 430478003 |
| UMLS | C1096155 |
| MedGen | 242753 |
| GARD | 0012124 |
| MedDRA | 10053867 |
| Is cancer (heuristic) | no |
Also known as: MAS · reactive hemophagocytic lymphohistiocytosis
Disease family
This is a subtype of secondary hemophagocytic lymphohistiocytosis. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.
Classification path: disease › human disease › disease by body system or component › syndromic disease › hemophagocytic syndrome › secondary hemophagocytic lymphohistiocytosis › macrophage activation syndrome
Related subtypes (1): acquired hemophagocytic lymphohistiocytosis associated with malignant disease
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
No tiered GWAS variants or ClinVar records for this disease.
Genes & proteins
No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).
Function
No pathway enrichment — requires an associated-gene cohort.
Therapeutics
Drugs indicated or in trials for this disease
No drug has an approved disease-direct ChEMBL indication for this disease.
5 drugs in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.
| Drug | Highest phase |
|---|---|
| Emapalumab | Phase 3 |
| Methylprednisolone | Phase 3 |
| Ruxolitinib | Phase 3 |
| Anakinra | Phase 2 |
| Tocilizumab | Phase 2 |
Clinical trials & evidence
Clinical trials
Clinical trials: 17.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 8 |
| PHASE2 | 4 |
| PHASE3 | 2 |
| PHASE1/PHASE2 | 2 |
| PHASE1 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT05001737 | PHASE3 | COMPLETED | Evaluate Efficacy, Safety and Tolerability, PK and PD of Emapalumab in Children and Adults With MAS in Still’s or SLE |
| NCT05137496 | PHASE3 | UNKNOWN | Ruxolitinib and Methylprednisolone as a First-line Treatment for Macrophage Activation Syndrome |
| NCT01966367 | PHASE1/PHASE2 | ACTIVE_NOT_RECRUITING | CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation |
| NCT05611710 | PHASE2 | ACTIVE_NOT_RECRUITING | Anakinra in Dengue With Hyperinflammation ( AnaDen ) |
| NCT02569463 | PHASE1/PHASE2 | UNKNOWN | Low-dose IL-2 ( Interleukin-2) Treatment in Macrophage Activation Syndrome（MAS） |
| NCT03311854 | PHASE2 | COMPLETED | A Study to Investigate the Safety and Efficacy of Emapalumab, an Anti-IFN-gamma mAb in Patients With Systemic Juvenile Idiopathic Arthritis (sJIA) or Adult-onset Still’s Disease (AOSD) Developing Macrophage Activation Syndrome/Secondary HLH (MAS/sHLH) |
| NCT03332225 | PHASE2 | COMPLETED | A Trial of Validation and Restoration of Immune Dysfunction in Severe Infections and Sepsis |
| NCT04339712 | PHASE2 | COMPLETED | Personalised Immunotherapy for SARS-CoV-2 (COVID-19) Associated With Organ Dysfunction |
| NCT02780583 | PHASE1 | TERMINATED | Treatment of Macrophage Activation Syndrome (MAS) With Anakinra |
| NCT03827343 | Not specified | ACTIVE_NOT_RECRUITING | Retrospective Study of Immunotherapy Related Toxicities and Factors Impacting Outcomes in Children and Adults With Cancer |
| NCT06339177 | Not specified | RECRUITING | Hemophagocytic Lymphohistiocytosis (HLH) Evaluation and Research of Clinical, ImmUnoLogic and TranscriptomE Study |
| NCT07491926 | Not specified | NOT_YET_RECRUITING | MASKd: a Study on Kawasaki Disease (KD) Complicated by Macrophage Activation Syndrome (MAS) |
| NCT01095146 | Not specified | UNKNOWN | New Candidate Criteria for Diagnosis of Macrophage Activation Syndrome |
| NCT02854943 | Not specified | COMPLETED | Investigation of Ferritin in Critically Ill Patients With Hemophagocytic Lymphohistiocytosis |
| NCT03721809 | Not specified | COMPLETED | Characterization of the Inflammatory Profile of Patients With Macrophage Activation Syndrome Secondary to Bacterial Sepsis |
| NCT06405152 | Not specified | COMPLETED | Assessment of Macrophage Activation syndromE in STill’s Disease |
| NCT06992505 | Not specified | COMPLETED | Assessment of Macrophage Activation syndromE in STill’s Disease in Italy |
Drugs tested across these trials (top 30)
| Molecule | Max phase | Trials referencing |
|---|---|---|
| ANAKINRA | 4 | 2 |
| EMAPALUMAB | 4 | 2 |
| RUXOLITINIB | 4 | 1 |
| CHEMBL5220618 | 0 | 2 |
| CHEMBL4637163 | 0 | 1 |
Related Atlas pages
- Drugs: Anakinra, Emapalumab, Ruxolitinib