| Knowledge-base field | Eosinophilia-Myalgia Syndrome summary | Ontology suggestions |
|---|---|---|
| Definition/category | Rare, environmentally acquired multisystem inflammatory and fibrosing disorder characterized by severe generalized myalgia, peripheral eosinophilia, and later fasciitis, skin induration, myopathy, or neuropathy; principally associated with contaminated manufactured L-tryptophan. | MONDO:0004941; MeSH:D016603; category: environmental/toxic exposure disease |
| Identifiers | MONDO and MeSH identifiers are established above. No disease-specific OMIM entry is expected because EMS is not Mendelian; Orphanet and dedicated ICD-10/ICD-11 identifiers were not confirmed and should not be inferred. | MONDO:0004941; MeSH:D016603 |
| Trigger | Oral L-tryptophan supplements, especially 1989 lots from one manufacturer containing more than 60 impurities. Epidemiologically associated candidates include EBT (“peak E”), PAA, IMT, PIC, HIT, and AAA, but no single contaminant has been proved to be solely causal. | L-tryptophan—CHEBI:16828; EBT/PAA disease-exposure CHEBI identifiers: not confirmed (pqac-00000005, pqac-00000013) |
| Diagnostic core | Historical CDC surveillance definition: blood eosinophils >1,000/mm³, generalized myalgia severe enough to limit usual activity, and exclusion of infection or neoplasm. The definition was intended for surveillance, not as a stand-alone clinical diagnostic standard; revised 2001 criteria reportedly achieved 97% specificity. | Eosinophilia—HP:0001880; Myalgia—HP:0003326 (pqac-00000015, pqac-00000008) |
| Major acute phenotypes | Myalgia 100%; rash 71%; edema 52%; fever 41%; arthralgia 35%; respiratory manifestations 32% in a summarized outbreak series. A Maryland series reported joint pain 53%, rash and extremity edema 47% each, dyspnea 33%, and fever 27%. Frequencies vary by cohort and ascertainment. | HP:0003326 Myalgia; HP:0000988 Skin rash; HP:0000969 Edema; HP:0001945 Fever; HP:0002829 Arthralgia; HP:0002094 Dyspnea (pqac-00000001, pqac-00000003) |
| Chronic phenotypes | Weight loss 50%, muscle weakness 44%, paresthesia 42%, scleroderma-like skin induration 42%, xerostomia 36%, and alopecia 33%; persistent painful neuropathy, myopathy, fasciitis, contractures, and disability may occur despite normalization of eosinophilia. | HP:0001824 Weight loss; HP:0001324 Muscle weakness; HP:0003401 Paresthesia; HP:0000958 Dry skin/xerosis only if clinically appropriate—not equivalent to xerostomia; HP:0001596 Alopecia; peripheral neuropathy term/ID should be ontology-validated (pqac-00000003, pqac-00000008) |
| Epidemiology | The 1989 epidemic produced more than 1,500 reported US cases; reported deaths vary by surveillance date/source from 27 to approximately 40. Cases were predominantly middle-aged women; one Maryland series was 93% female with median age 51 years. Incidence is now extremely low and no reliable current prevalence is available. | Epidemiologic annotations; no inheritance ontology applicable (pqac-00000000, pqac-00000001, pqac-00000012, pqac-00000015) |
| Genetic susceptibility/protection | No causal gene or pathogenic variant is established. Among L-tryptophan users, HLA-DRB1*03, HLA-DRB1*04, and HLA-DQA1*0601 were susceptibility markers; DRB1*04 had OR 3.93 (95% CI 1.08–16.37). DRB1*07 and DQA1*0501 were protective; among users of implicated lots, the DRB1*07–DQA1*0201 haplotype had OR 0.11 (95% CI 0.02–0.77). Results derive from a small retrospective cohort and are not diagnostic. | HLA gene/allele annotations; inheritance: not applicable; ClinVar/ACMG pathogenic-variant classification: not applicable (pqac-00000019, pqac-00000020) |
| Mechanism | Exposure induces an incompletely defined type-2 inflammatory response involving IL-5/IL-4, eosinophil expansion and tissue degranulation, followed by TGF-β-associated fibroblast activation, extracellular-matrix/collagen deposition, fascial and dermal fibrosis, myocyte injury, and peripheral nerve damage. Kynurenine/quinolinic-acid changes may contribute but remain uncertain. | GO:0043308 Eosinophil activation; GO:0030198 Extracellular matrix organization; GO:0032964 Collagen biosynthetic process; CL:0000771 Eosinophil; CL:0000057 Fibroblast; CL:0000097 Mast cell (pqac-00000006, pqac-00000009, pqac-00000018) |
| Anatomy | Primary sites are skeletal muscle, fascia/perimysium, dermis, subcutis, and peripheral nerves; lungs are commonly involved, while severe disease may affect the heart and other organs. Distribution is generally bilateral/systemic rather than unilateral. | UBERON:0001134 Skeletal muscle organ; UBERON:0002097 Skin of body; fascia/peripheral nerve/lung UBERON identifiers should be ontology-validated before ingestion (pqac-00000004, pqac-00000013) |
| Diagnosis | Exposure history plus CBC with differential and exclusion of parasitic/infectious, allergic, drug-induced, autoimmune, clonal, and malignant eosinophilia. Evaluate organ injury using CK/chemistry, pulmonary and cardiac testing, MRI of muscle/fascia, EMG/nerve-conduction studies, and full-thickness skin–fascia–muscle biopsy when needed. No validated genetic, proteomic, or metabolomic diagnostic test exists. | HPO terms above; LOINC/SNOMED codes should be mapped at test level; genetic testing: not routinely indicated (pqac-00000004, pqac-00000012) |
| Treatment | Immediately discontinue the implicated supplement. Systemic glucocorticoids often reduce acute inflammation and eosinophilia but have inconsistent effects on chronic fibrosis and neuropathy. Mycophenolate, methotrexate, hydroxychloroquine, chlorambucil, or anakinra have only anecdotal/low-quality evidence; pain control and physical/occupational rehabilitation are important. No EMS-specific approved therapy or genotype-guided treatment exists. | NCIT suggestions: Corticosteroid Therapy, Immunosuppressive Therapy, Physical Therapy, Occupational Therapy; exact NCIT identifiers require validation (pqac-00000003, pqac-00000007, pqac-00000008) |
| Prevention | Avoid suspect or unregulated L-tryptophan/5-HTP products; enforce manufacturing controls, lot traceability, impurity testing, adverse-event surveillance, and rapid product withdrawal. A 2023 LC–MS/MS method measured selected impurities with detection limits below 11.2 μg/kg and quantification limits below 35.7 μg/kg in meat matrices. No vaccine, genetic screening, or chemoprophylaxis applies. | CHEBI:16828 L-tryptophan; environmental-exposure and product-quality annotations (pqac-00000000, pqac-00000013) |
| Clinical study | NCT00001918, “L-5-Hydroxy-Tryptophan-Related EMS: Clinical Patient Evaluation,” was a completed NIH/NIMH observational study (planned enrollment 20; July 1999–August 2000), not a therapeutic trial. It evaluated clinical, neurologic, psychiatric, imaging, laboratory, and supplement-impurity findings. | ClinicalTrials.gov:NCT00001918; NCIT: Observational Study—exact code should be validated (pqac-00000012) |
| Models | Induced female C57BL/6 mouse model: daily intraperitoneal EBT caused dermal/subcutaneous inflammation, mast-cell accumulation, progressive fascial fibrosis, and transient myocyte necrosis. After six weeks, fascia measured 168±22 μm versus 43±5 μm with saline, but mice lacked peripheral eosinophilia and did not reproduce the complete human syndrome. Lewis-rat models also show myofascial inflammation/fibrosis. No confirmed naturally occurring veterinary EMS or transmissible/zoonotic form is known. | NCBI Taxon:10090 Mus musculus; NCBI Taxon:10116 Rattus norvegicus; CL:0000097 Mast cell; GO:0030198 Extracellular matrix organization (pqac-00000015, pqac-00000016, pqac-00000017) |


*Table: Compact disease-level summary of eosinophilia-myalgia syndrome, including epidemiology, clinical features, exposure biology, genetics, management, prevention, and experimental models. Ontology mappings are limited to identifiers that can be assigned with reasonable confidence, with uncertain mappings explicitly flagged.*