PEP Syndrome

At a glance

Acronym that stands for Plasma cell dyscrasia, Endocrinopathy, Polyneuropathy. A paraneoplastic syndrome due to an underlying plasma cell neoplasm that causes multisystem disorders, including neuropathy, organ overgrowth, endocrine dysfunctions, and skin changes.

Synonyms

Polyneuropathy Organomegaly Endocrine Monoclonal Protein Skin Lesions Syndrome; POEMS Syndrome; Osteosclerotic Myeloma; Shimpo Syndrome; Crow-Fukase Syndrome.

Incidence

Mainly affects adults in the 45-to 65-year-old age range.

Genetic inheritance

No genetic inheritance demonstrated. Probably an inflammatory disease.

Pathophysiology

Pathophysiology is not well understood. Chronic inflammatory process with high circulating cytokines (interleukin [IL]-1, IL-6, tumor necrosis factor) and coagulation activator levels. Vascular endothelial growth factor (VEGF), originally known as vascular permeability factor (VPF), correlates best with disease activity.

Diagnosis

Association of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein plasma cell dyscrasia, and skin changes. Diagnosis based on monoclonal plasma cell demonstration in bone marrow biopsy and clinical features. Mandatory major criteria include i) polyneuropathy and ii) monoclonal plasma cell-proliferative disorder (almost always lambda). In addition, one of the three other major criteria (Castleman disease, sclerotic bone lesions disease, and VEGF elevation) and one of the six minor criteria (organomegaly, edema or ascites, endocrinopathy, skin changes, papilledema and thrombocytosis/polycythemia) must be met.

Clinical aspects

The clinical picture is dominated by a demyelinating polyneuropathy with motor disability and sclerotic skeletal lesions. Cranial nerves and autonomic nervous system usually unaffected. Hepatomegaly and sometimes splenomegaly and lymph node enlargement. Endocrine involvement mainly affects gonadotrophins and androgens. Hemostasis studies show procoagulant activity and thrombocytosis. Rarely associated with fractures and renal involvement. If localized sclerotic lesions are found, radiotherapy may improve systemic polyneuropathy and if widespread chemotherapy (melphalan and steroids) is helpful. Survival at 5 years is 60%. Other treatment options include neoadjuvant chemotherapy and anti VEGF treatments. Treatment progression can be monitored using VEGF concentrations.

Precautions before anesthesia

Mainly dominated by a potentially severe pulmonary hypertension and recurrent cerebrovascular insults. Check coagulation tests before and define anticoagulation strategy. Check plasma calcium. Obtain preoperative neurologic evaluation.

Anesthetic considerations

Because of vascular abnormalities and potential organ ischemia, avoid hypotension. Specific considerations in presence of severe pulmonary hypertension must apply. Regional anesthesia is possible.

Pharmacological implications

Interaction between anesthetic medications and cerebroinvasive and antihypertensive medications will be considered. Prolonged actions of neuromuscular blocking drugs have been described.

Other conditions to be considered

• ☞Castleman Disease: Uncommon lymphoproliferative disorder. Unicentric Castleman disease is localized and carries an excellent prognosis, whereas multicentric Castleman disease is a systemic disease occurring most commonly in the setting of human immunodeficiency ...