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).
The authors observed a 66-year-old woman with a previous history of paresthesia of distal prevalence in the upper limbs and the lower right limb associated with pain in the palmar and plantar region, with onset 1 year before, followed by reduction in strength, mainly in hands and feet, of slow and progressive evolution. During this period the patient noted diffuse skin darkening and appearance of papular lesions on the cervical and right infraclavicular region, abdomen and dorsum. She suffered a 20-kg weight loss during evolution of the picture, besides diabetes mellitus and hypothyroidism. Examination showed diffuse cutaneous hyperpigmentation, atrophy of the interosseous muscles (fig. , fig. ), sclerodermiform cutaneous thickening and normochromic, papular lesions (fig. ) in the cervical region, abdominal and right infraclavicular region. At dermatoscopy of the infraclavicular lesions there was presence of red lakes (fig. ). Neurological examination showed grade 3 strength of distal prevalence in the upper and lower limbs and hypopallesthesia in ‘glove’ and in ‘boot’. These alterations were suggestive of sensorimotor polyneuropathy.\nOphthalmological examination did not reveal presence of papillary edema. Concerning laboratory examinations, thrombocytosis was noted, with rheumatoid factor <10; anti-nuclear factor, VDRL, anti-HIV, anti-HTLV and serology for hepatitis B and C were negative. Prolactin and cortisol dosages were within normal range. Electroneuromyography was compatible with polyneuropathy with predominance of demyelination and axonal degeneration. Bone marrow aspirate presented medullary plasmacytosis (9% plasmacytes). Serous protein electrophoresis demonstrated a monoclonal peak in the gamma fraction and in immunofixation examination: monoclonal IgG/lambda peak.\nSkeleton radiography revealed a lithic lesion with sclerotic borders in the left femur (fig. ); histopathologic examination confirmed it to be a plasmocytoma. Histopathologic examination of the right infraclavicular lesion showed an exophytic lesion containing dispersed vascular connective structures (fig. ), and increased magnification showed both thick- and thin-walled vascular structures, compatible with arteriovenous hemangioma (fig. ). The lesion on the dorsum presented histopathologic characteristics of hemangioma in tufts and the lesion on the abdomen cherry hemangioma.\nThe patient was treated with radiotherapy of the femur due to the osteosclerotic lesions and showed improvement of the neurological picture as well as of hyperpigmentation and weigh loss.