| Phenotype category | Specific manifestations/features | Frequency/prevalence among patients | Clinical significance | Suggested HPO terms |
|---|---|---|---|---|
| Polyneuropathy | Symmetrical, sensorimotor, length-dependent, painful demyelinating polyneuropathy/radiculoneuropathy; striking distal weakness of hands/feet; lower-extremity numbness common; neuropathic pain especially in legs; often initially misdiagnosed as CIDP; electrophysiology shows uniform demyelination with marked secondary axonal loss, fewer conduction blocks, more severe lower-limb CMAP loss (pqac-00000000, pqac-00000001, pqac-00000003, pqac-00000005, pqac-00000006) | Mandatory criterion; present in essentially 100% of classic POEMS cohorts in reviewed papers; 42/42 (100%) in Chen et al. cohort; lower-extremity numbness 100%, lower-extremity neuropathic pain 58.8%, lower-extremity weakness 64.7% in Wang et al. cohort (pqac-00000006, pqac-00000009) | Core disabling feature; major cause of diagnostic delay and long-term disability; treatment-resistant “CIDP” should trigger evaluation for POEMS (pqac-00000001, pqac-00000005, pqac-00000010) | HP:0009830 Polyneuropathy; HP:0007104 Demyelinating peripheral neuropathy; HP:0003394 Muscle weakness; HP:0002355 Difficulty walking; HP:0012532 Distal lower limb muscle weakness; HP:0031843 Neuropathic pain |
| Organomegaly | Hepatomegaly, splenomegaly, lymphadenopathy/lymph node enlargement; often identified on imaging rather than palpation (pqac-00000001, pqac-00000003, pqac-00000005) | ~85.7% in Chen et al. cohort; described as a common minor criterion in major reviews (pqac-00000009, pqac-00000003) | Supports multisystem diagnosis; helps distinguish POEMS from CIDP and other paraproteinemic neuropathies (pqac-00000003, pqac-00000005) | HP:0001433 Hepatosplenomegaly; HP:0001744 Splenomegaly; HP:0002240 Hepatomegaly; HP:0002716 Lymphadenopathy |
| Endocrinopathy | Hypogonadism/hypopituitarism most characteristic; thyroid abnormalities and adrenal insufficiency also reported; diabetes/glucose intolerance may occur but are not specific when isolated (pqac-00000001, pqac-00000003, pqac-00000005) | ~84% in review summary; 40/42 (95.2%) in Chen et al. cohort; hypothyroidism 52.9% in Wang et al. series (pqac-00000001, pqac-00000006, pqac-00000009) | Common minor criterion but heterogeneous; combinations of endocrine abnormalities are more diagnostically useful than isolated diabetes or thyroid disease (pqac-00000001) | HP:0000818 Abnormality of the endocrine system; HP:0000824 Hypogonadism; HP:0000821 Hypothyroidism; HP:0000855 Insulin-resistant diabetes mellitus / HP:0005978 Diabetes mellitus |
| Monoclonal gammopathy / plasma cell disorder | Usually low-level monoclonal plasma cell dyscrasia, typically IgAλ or IgGλ; serum paraprotein may be missed by SPEP and requires immunofixation; urine immunofixation and marrow/lesional biopsy may be needed; >95% lambda light-chain restricted in most series (pqac-00000003, pqac-00000005, pqac-00000008, pqac-00000009, pqac-00000010) | Mandatory criterion in classic POEMS; 42/42 (100%) had positive serum or urine immunofixation in Chen et al.; only 64.7% had positive serum immunofixation at presentation in Wang et al.; SPEP positive in as few as 54%, immunofixation 75–92% in review data (pqac-00000005, pqac-00000006, pqac-00000009) | Central pathogenic lesion and treatment target; low tumor burden can obscure diagnosis; marrow plasma cells often <5% (median 1.5% in Chen et al.) (pqac-00000008, pqac-00000009) | HP:0032113 Monoclonal gammopathy; HP:0011897 Abnormal plasma cell morphology/number; HP:0410292 Increased circulating immunoglobulin |
| Skin changes | Hyperpigmentation, hypertrichosis, skin thickening, acrocyanosis, plethora/flushing, white nails, hemangiomas/glomeruloid hemangiomata (pqac-00000001, pqac-00000005) | ~70% in Keddie/Lunn cohort summary; 40/42 (95.2%) in Chen et al.; 13/17 (76.5%) in Wang et al. had skin change (pqac-00000005, pqac-00000006, pqac-00000009) | Common and often visually helpful clue to multisystem disease; contributes to acronym but is not required for diagnosis (pqac-00000001, pqac-00000005) | HP:0000953 Hyperpigmentation of the skin; HP:0002219 Hypertrichosis; HP:0001065 Skin thickening; HP:0000966 Abnormality of the skin; HP:0001101 Acrocyanosis; HP:0001597 Nail abnormality |
| Extravascular volume overload | Peripheral edema, ascites, pleural effusion, pericardial effusion; can accompany pulmonary hypertension, cardiac insufficiency, renal dysfunction; may worsen during stem-cell mobilization/transplant periods (pqac-00000001, pqac-00000003, pqac-00000005, pqac-00000009) | Peripheral edema 71.4%, ascites 40.5%, pleural effusion 35.7%, pericardial effusion 54.8% in Chen et al.; edema 82.4% in Wang et al. cohort (pqac-00000006, pqac-00000009) | Important minor criterion; associated with worse overall survival in reviews; major determinant of clinical acuity and transplant fitness (pqac-00000003, pqac-00000005) | HP:0000969 Edema; HP:0001541 Ascites; HP:0012378 Pleural effusion; HP:0001698 Pericardial effusion |
| Bone lesions | Usually osteosclerotic lesions; can be densely sclerotic, lytic with sclerotic rim, or mixed “soap-bubble” lesions; often multiple and small; FDG-PET/CT helps identify active lesions and biopsy targets (pqac-00000001, pqac-00000005, pqac-00000007) | Approximately 95% in one review summary; 18/42 (42.9%) in Chen et al. genomic cohort; prevalence varies by cohort and imaging modality (pqac-00000001, pqac-00000009) | One of the major diagnostic criteria; determines local vs systemic therapy decisions, including radiotherapy for ≤3 lesions without diffuse marrow disease (pqac-00000003, pqac-00000005) | HP:0002792 Abnormality of the skeletal system; HP:0030934 Osteosclerosis; HP:0002758 Osteolysis |
| Papilledema | Optic disc edema/papilledema, sometimes with preserved vision initially; may reflect vascular leak and raised intracranial/optic disc fluid dynamics rather than primary optic nerve disease (pqac-00000001, pqac-00000003, pqac-00000005) | ~50% during 10-year follow-up in two cohorts summarized by Cerri et al.; 5/42 (11.9%) in Chen et al. cohort (pqac-00000001, pqac-00000009) | Minor criterion; reported as an independent adverse prognostic factor for overall survival in prior cohort data summarized by reviews (pqac-00000001) | HP:0001085 Papilledema |
| Thrombocytosis / polycythemia | Thrombocytosis more common than polycythemia; part of prothrombotic diathesis; often accompanies stroke risk and hypercoagulability (pqac-00000001, pqac-00000003, pqac-00000005) | Thrombocytosis present in ~55% in review data; recognized minor criterion in all major diagnostic frameworks discussed (pqac-00000001, pqac-00000003) | Helpful discriminator from CIDP; linked to ischemic stroke/thrombotic complications and may affect treatment choices such as lenalidomide thromboprophylaxis (pqac-00000003, pqac-00000005) | HP:0001873 Thrombocytosis; HP:0001901 Polycythemia |
| Other neurologic/systemic features | Castleman disease overlap; ischemic stroke (often watershed distribution); pulmonary hypertension; restrictive lung disease; renal dysfunction; heart failure; pachymeningeal involvement; depression reported in prior cohorts; Castleman-associated cases may have mild or absent neuropathy (pqac-00000001, pqac-00000003, pqac-00000005, pqac-00000013) | Castleman disease in ~11–30% of patients in review summaries; ischemic stroke ~10%; male predominance ~2.5:1 and onset most often in 5th–6th decade (pqac-00000001, pqac-00000002, pqac-00000003) | Expands differential diagnosis and affects prognosis/management; cardiopulmonary involvement influences transplant candidacy and survival (pqac-00000002, pqac-00000005) | HP:0002664 Castleman disease; HP:0001297 Stroke; HP:0002092 Pulmonary hypertension; HP:0000077 Abnormality of the kidney; HP:0001635 Congestive heart failure; HP:0100840 Pachymeningitis |


*Table: This table summarizes the major clinical phenotypes of POEMS syndrome, including characteristic manifestations, approximate frequencies from the retrieved literature, their diagnostic or prognostic relevance, and suggested HPO mappings. It is useful for structuring disease knowledge base entries and phenotype annotation.*