POEMS syndrome
| POEMS syndrome | |
|---|---|
| Other names | Crow–Fukase syndrome, Osteosclerotic myeloma, PEP syndrome, Polyneuropathy-endocrinopathy-plasma cell dyscrasia syndrome, Takatsuki syndrome. |
| Treatment | Corticosteroids, low-dose alkylators, peripheral blood stem cell transplantation, high-dose chemotherapy.[6] |
| Medication | Thalidomide, lenalidomide, bortezomib, bevacizumab.[5] |
| Prognosis | Median survival of 13.8 years.[8] |
| Frequency | Rare |
POEMS syndrome (also termed osteosclerotic myeloma, Crow–Fukase syndrome, Takatsuki disease, or PEP syndrome) is a
The signs and symptoms of most
POEMS syndrome typically begins in middle age – the average age at onset is 50 – and affects up to twice as many men as women.
Signs and symptoms
The signs and symptoms of POEMS syndrome are highly variable. This often leads to long delays (e.g. 13–18 months) between the onset of initial symptoms and diagnosis.
Common features
The more common features of the disease are summarized in the acronym POEMS:
Pathogenesis
While the main features of this
Diagnosis
The diagnosis of POEMS syndrome is based on meeting its two mandatory criteria, meeting at least one of its 3 other major criteria, and meeting at least one of its 6 minor criteria.[4]
Mandatory Criteria
Polyneuropathy
Plasma cell dyscrasia
Plasma cell dyscrasias are a group of monoclonal gammopathies in which normal plasma cells in the bone marrow and soft tissues become altered. POEMS syndrome is often associated with an IgA or IgG lambda limited plasma cell dysfunction. On iliac crest biopsies, patients with POEMS syndrome often have few monoclonal plasma cells. In patients with localized illness, iliac crest biopsies may be normal. Other common findings were megakaryocyte hyperplasia and clustering, as well as unusual megakaryocyte appearances. Atypical plasma cells invade normal marrow in osteosclerotic lesions, causing sclerosis of the bony lamellae.[11]
Major Criteria
Castleman's disease
Castleman's disease (CD) is a rare heterogeneous lymph node disorder characterized by elevated interleukin-6 levels. Neuropathy can occur in CD patients with or without POEMS syndrome.[11] CD and POEMS tend to overlap, with roughly 15–24% of POEMS syndrome patients also having CD, with the majority having hyaline vascular type.[5]
Sclerotic bone lesions
Vascular endothelial growth factor
Minor Criteria
Organomegaly
POEMS syndrome has been associated with hepatomegaly, splenomegaly, and lymphadenopathy in 50–78% of patients. Organomegaly is usually minimal, and bulky disease is uncommon.[5]
Extravascular volume overload
80% of POEMS patients are reported to have extravascular volume overload including, peripheral edema, ascites, pleural effusion, and pericardial effusion. Ascites and peripheral edema are more prevalent than pleural or pericardial effusions. Extravascular volume overload can cause significant morbidity and corresponds with a lower survival rate.[5]
Endocrinopathy
Approximately 84% of POEMS syndrome patients have characteristics of several endocrinopathies. Hypogonadism is the most prevalent endocrine disorder, followed by thyroid anomalies, glucose metabolism defects, and adrenal insufficiency.[4] Men frequently experience impotence and gynecomastia. Amenorrhea tends to be common in women.[6] The cause of endocrinopathy is unknown, however VEGF may have a role.[5]
Skin changes
About 90–100% of those with POEMS syndrome will experience skin changes. The most common manifestations are hyperpigmentation and haemangiomas. Other skin abnormalities include thickening, hypertrichosis, acquired facial lipoatrophy, and infiltrating livedo reticularis with necrosis. POEMS syndrome can also cause Vascular-type skin changes including acrocyanosis, flushing, hyperaemia, and Raynaud's phenomenon. Nail changes consist of leukonychia and clubbing.[11]
Papilledema
Papilledema is often one of the earliest signs of POEMS disease and is usually bilateral.[5] Patients tend to be asymptomatic, however, they may report headaches, brief obscurations of vision, scotomata, large blind spots, and gradual visual field constriction.[8] Papilledema has been noted in 29–64% of patients and is associated with an unfavorable prognosis.[5]
Hematological alterations
50% of POEMS patients have thrombocytosis and polyglobulia develops in 15% of patients. Those with thrombocytosis and erythrocytosis are often misdiagnosed with chronic myeloproliferative disease before POEMS syndrome is identified.[5]
Laboratory findings
In addition to tests corresponding to the above findings, such as
Differential diagnosis
Patients diagnosed as having
Treatment
As reported by Dispenzieri et al.
Other treatment regimens are being studied.
Since VEGF plays a central role in the symptoms of POEMS syndrome, some have tried bevacizumab, a monoclonal antibody directed against VEGF. While some reports were positive, others have reported capillary leak syndrome suspected to be the result of overly rapid lowering of VEGF levels. It therefore remains doubtful as to whether this will become part of standard treatment for POEMS syndrome.[12]
History
R. S. Crow, working in Bristol, first described the combination of osteosclerotic myeloma, polyneuropathy and various unusual features (such as pigmentation and clubbing) in two patients aged 54 and 67.[13]
References
- ^ a b c d "POEMS syndrome — About the Disease — Genetic and Rare Diseases Information Center". rarediseases.info.nih.gov. Retrieved 2023-08-14.
- ^ PMID 21035860.
- ^ S2CID 31324035.
- ^ S2CID 128361561.
- ^ PMID 28894560.
- ^ a b c d e f "POEMS Syndrome: Background, Pathophysiology, Etiology". 16 October 2021.
{{cite journal}}: Cite journal requires|journal=(help) - ^ "POEMS Syndrome — Symptoms, Causes, Treatment — NORD". rarediseases.org. Retrieved 2023-08-16.
- ^ PMID 16304404. Retrieved 15 August 2023.
- ^ PMID 27866585.
- ^ PMID 12456500.
- ^ PMID 30498913.
- PMID 18024383.
- PMID 13364332.