In March 2017, a 60-year-old man was admitted with progressive fatigue and numbness in the lower extremities.\nBefore his presentation to our institution, he had been diagnosed with cerebral infarction at the left basal ganglia at a local hospital in August 2016. Based on an elevated fasting serum glucose concentration, he was diagnosed with diabetes mellitus and treated with oral hypoglycemic agents. As a result, his serum blood glucose concentration gradually declined. After the acute phase of cerebral infarction, he developed progressive fatigue and numbness in his lower extremities. These symptoms worsened during the next several months until he had difficulty walking and using the stairs. He also developed weight loss with a decreased appetite, constipation, dry skin, reduced sweating, and insomnia. In March 2017, he presented with progressive fatigue in the lower extremities and was admitted to the Third Affiliated Hospital of Soochow University.\nThe patient took aspirin intermittently because of his history of cerebral infarction. He had quit smoking 10 years previously. His personal history contained nothing remarkable. He had no family history of related hereditary diseases.\nPhysical examination revealed generalized hyperpigmentation of the skin, enlarged hands, and coarsened skin (). Superficial lymph nodes were not palpable. The breath sounds in the lower lungs were slightly weakened, and the heart sounds were normal. He had hypoesthesia to light touch and reduced pin-prick sensation below the knees as well as lack of knee and ankle reflexes. His muscle strength grade was 4/5 in the upper extremities and 4/5 in the lower extremities.\nThe patient’s cardiac, liver, and renal functions were normal. His glycosylated hemoglobin concentration was 7.0% (reference range, <6.5%), and his fasting serum glucose concentration was 7.55 mmol/L (reference range, 3.9–6.1 mmol/L), indicating mild glucose control. The patient had a high serum estradiol concentration (158 pg/dL; reference range, <40 pg/dL) with normal luteinizing hormone and follicle-stimulating hormone concentrations. Thyroid examination showed a decreased free T3 concentration (8.93 pmol/L; reference range, <10 mg/dL), which indicated the possibility of low T3 syndrome and other consumptive diseases. His 24-hour concentrations of urinary cortisol, serum cortisol (8:00–16:00), and corticotropin (8:00–16:00) were normal, and his cortisol concentration was suppressed in response to an overnight 1-mg dexamethasone suppression test, which ruled out Cushing’s syndrome. Because of his enlarged hands and coarsened skin, a growth hormone suppression test was performed. The growth hormone concentration at 0, 30, 60, 90, and 120 minutes was 0.98, 1.37, 1.34, 1.22, and 1.02 ng/mL, respectively; insulin-like growth factor 1 (IGF-1) was negative.\nCranial magnetic resonance imaging (MRI) was performed to rule out the possibility of acromegaly. Cranial MRI showed an ischemic cavity in the left frontal lobe, brain atrophy, and segmental stenosis of the left posterior cerebral artery. Electromyography showed severe multiple peripheral neuropathy affecting both the upper and lower extremities. A vibration perception threshold test showed that the patient’s superficial sense was almost normal but that his deep sense was abnormal, indicating a high risk of neuropathic ulcers. A positron emission tomography–computed tomography (PET-CT) scan showed hypermetabolic foci in the T5–6, T8, and T11–L4 vertebral bodies and the 4th, 7th, and 10th left ribs; thus, sclerosing bone disease and an old infarction in the left thalamus were considered (). Abdominal CT showed a small amount of fluid in the pericardial cavity, a small amount of fluid in the right pleural cavity, and multiple stones in the gallbladder. Color Doppler echocardiography showed no abnormalities.\nThe patient was initially diagnosed with diabetes, diabetic peripheral neuropathy, and cerebral infarction sequelae. For treatment of the diabetic peripheral neuropathy, the patient began pharmacologic therapy comprising α-lipoic acid, aldose reductase inhibitors, mecobalamin, and pancreatic kininogenase enteric-coated tablets. His clinical condition improved after the pharmacologic therapy. However, the patient gradually lost interest in most activities, including sex and sports, and he experienced sleep disturbances. He was given sleeping pills and antidepressants because of insomnia and depression, and his symptoms were gradually relieved. Within 3 months after discharge from the hospital, he gradually developed pain in his lower limbs. He experienced difficulty standing on his heels and unsteadiness while walking. He eventually required a walking stick, and he continued losing weight and had a poor appetite.\nThe patient visited the neurologic department of Beijing Union Medical College Hospital. During his stay there, his serum protein electrophoresis results were suggestive of monoclonal gammopathy. His serum IgG level was positive with λ light chain restriction. His serum light chain κ concentration was 1500 mg/dL (reference range, 598–1329 mg/dL), and his light chain λ concentration was 960 mg/dL (reference range, 298–665 mg/dL). His urine light chain κ concentration was 12.9 mg/dL (reference range, 0.0–5.1 mg/dL). He underwent lumbar puncture, and a bone marrow biopsy revealed megakaryocyte hyperplasia and clustering. Oligoclonal IgG bands were positive in the cerebrospinal fluid, whereas no M protein was found via serous protein electrophoresis. Unfortunately, VEGF measurement was not available in Beijing Union Medical College Hospital at the time.\nThis patient met both mandatory major criteria for POEMS syndrome (polyradiculoneuropathy and monoclonal plasma cell proliferative disorder), one of the three other major criteria (sclerotic bone lesions), and three of the six minor criteria (endocrinopathy, skin changes, and extravascular volume overload). The patient was diagnosed with POEMS syndrome, diabetes, and cerebral infarction sequelae.\nThe patient was treated with alkylator therapy and a peripheral blood stem cell transplant. During hospitalization, he gradually stopped using oral hypoglycemic drugs. Aspirin was prescribed after discharge.\nAfter discharge, the patient’s fatigue and numbness gradually improved, and he experienced no further difficulties walking and climbing stairs. Furthermore, the patient stopped losing weight and his appetite increased. His blood glucose concentration remained within the reference range during follow-up. After 5 months, the hyperpigmentation in the lower extremities gradually resolved. One year later, his glycosylated hemoglobin concentration was 5.9% (reference range, <6.5%), and his fasting serum glucose concentration was 5.7 mmol/L (reference range, 3.9–6.1 mmol/L). Thyroid examination showed no abnormalities. The patient still had a high serum estradiol concentration (72 pg/dL; reference range, <40 pg/dL).
A 45-year-old man, Caucasian, was referred to an urgent internal medicine clinic in 2014 for assessment of recent onset peripheral edema and hematologic abnormalities. His medical history was notable for alcoholism (with a prior episode of pancreatitis), untreated chronic hepatitis C infection, depression, and vitamin B12 deficiency. Neuropathy, described as the sensation of “pins and needles”, was reported 1 year before presentation.\nNerve conduction studies in patients with POEMS syndrome show slowing of nerve conduction that is more predominant in the intermediate than distal nerve segment. The sensation in the knee and distal weakness were reduced. He presented normal cardiac, liver and renal function. He could not use a prosthesis due to edema of the leg. The skeletal survey was normal and the computed tomography for the chest, abdomen and pelvis showed splenomegaly, borderline lymphadenopathy.\nAn episode of necrotizing fasciitis leading to right below elbow amputation and left Symes amputation was also performed. He was living on the street and in shelters. His left foot prosthesis had broken several months previously. When he was assessed for a replacement prosthesis, he was noted to have peripheral edema that prevented prosthesis fitting. Routine laboratory investigations showed hypogonadism, polycythemia, thrombocytosis, and neutrophilia. In the internal medicine clinic, the patient complained of paraesthesias, subjective sensory loss, and a tingling, burning pain in his distal extremities. Moderate peripheral edema and hepatosplenomegaly were found on examination. Abdominal ultrasound showed hepatosplenomegaly with the spleen measuring 13.4 cm. The patient did not have a biopsy or a Fibroscan to determine his fibrosis status. Bilirubin levels were in the normal range for the entire period of time. Alanine aminotransferase (ALT) fluctuated 26–30 IU, and aspartate aminotransferase (AST) fluctuated 36–39 IU. Hepatitis C viral load was 2.1 × 106.\nAn echocardiogram revealed normal biventricular function. The skeletal survey was normal.\nLaboratory investigations were remarkable for hemoglobin 190g/L, platelets 687 × 109/L, neutrophils 37.4 × 109/L, total testosterone 2.2 nmol/L (normal range, 5.5–25.2), and prolactin 24.3 mcg/L (<15). Blood film examination showed normal morphology. Electrolytes, creatinine, alanine and aspartate aminotransferases, bilirubin, C-reactive protein, and urinalysis were normal. Serum protein electrophoresis demonstrated polyclonal gammopathy. Analysis of peripheral blood for JAK2 mutation and BCR-ABL fusion product was negative. The immunofixation-revealed <1 gm/L amount of lambda light chain.\nPOEMS syndrome was considered despite the normal results of the serum protein electrophoresis. Computed tomography of the chest, abdomen, and pelvis confirmed hepatosplenomegaly and showed prominent retroperitoneal lymph nodes. Electromyography showed a demyelinating polyneuropathy. Lumbar puncture was performed; albumin-cytologic dissociation was seen on analysis of cerebrospinal fluid. Bone marrow aspiration and biopsy revealed hypercellular marrow with 5% plasma cells.\nSerum protein electrophoresis was repeated, again showing polyclonal gammopathy; the kappa/lambda ratio in peripheral blood was normal. Serum protein electrophoresis was repeated with immunofixation and instructions to look carefully for a low-titer monoclonal protein. An IgA M-protein with lambda light chain was identified, with a titer of less than 1 g/L. A 24-h urine collection for protein electrophoresis was not feasible given the patient’s homelessness and mobility impairment.\nVEGF level was markedly elevated at 2800 pg/mL (normal 30–90). Due to the diagnostic value of VEGF, the patient was referred to the malignant hematology clinic with a new diagnosis of POEMS syndrome. The treatment with dexamethasone and lenalidomide was initiated. Eight months later, his edema and neuropathic symptoms had improved somewhat and his VEGF level had decreased to 1828 pg/mL despite some non-adherence with treatment. At 17 months from diagnosis, his VEGF level had further decreased to 1022 pg/mL, although his edema and symptoms of polyneuropathy did not show further improvement.\nStem cell harvest was performed at 20 months from diagnosis. At 22 months from diagnosis, he was admitted to hospital with bilateral infected leg ulcers. He improved quickly with antibiotics but refused to restart dexamethasone and lenalidomide. His VEGF level fell to 540 pg/mL at 29 months from diagnosis despite a 7-month gap in treatment; however, his peripheral edema had worsened to the point that his left foot prosthesis once again did not fit, and his neuropathic pain had become less responsive to analgesics. At this point, he was not taking his medication. In addition, he also began drinking heavily. This fact led to a remission of POEMS. The levels of VEGF increased to 3480 pg/mL. This fact clearly demonstrates the link between the clinical and laboratory manifestation of POEMS syndrome and alcohol misuse.