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.
A 40-year-old male presented with progressive weakness, tingling and numbness in lower limbs for 2 years. He noted lower limbs swelling and skin changes over the face, hands and feet for 1 year. He also gave a history of erectile dysfunction and loss of libido for past 6 months. There was no history of bone pain or drug abuse. He had no previous history of tuberculosis, diabetes mellitus or hypertension.\nOn physical examination, bilateral pedal edema was present (Fig. a and b). Skin was thickened and hyperpigmented over the face, fingers of the hands and shin (Fig. a–d). Bilateral gynecomastia and testicular atrophy were also present. Abdominal examination showed hepatomegaly and ascites. Higher mental functions were normal. Examination of the fundi revealed bilateral papilledema, but otherwise cranial nerve examination was unremarkable. Muscle power in upper limbs was normal and predominant distal weakness [Medical Research Council (MRC) grade 4/5 at hip joints and 4-/5 at ankle joints] was present in lower limbs. Deep tendon reflexes in the upper limb were diminished (+1) including biceps, triceps and supinator and absent in lower limbs (knee and ankle). All modalities of sensations including pain, touch, temperature, vibration and joint position senses were impaired below knees. Romberg's sign was positive.\nFull blood count, liver and renal function tests, muscle enzymes (creatine phosphokinase), serum ferritin and vitamin B12 level were normal. Serum total protein was 7.1 g/dl, albumin 3 g/dl, globulin 4.1 g/dl and A : G ratio 1 : 1.3. Fasting and postprandial blood sugar levels were normal. Thyroid function tests revealed hypothyroidism (TSH level: 16.62 mIU/l and normal TSH level 0.4–4 mIU/l). Luteinizing hormone and testosterone levels were 15 (1.8–8.6 IU/l) and 111 (300–1000 ng/dl), respectively. Antinuclear antibody, rheumatoid factor, enzyme-linked immunosorbent assay test for human immunodeficiency virus, serology for hepatitis B and C were negative. Abdominal ultrasonography showed hepatomegaly (16 cm), moderate ascites and multiple enlarged mesenteric lymph nodes along the iliac vessels. Fine-needle aspiration cytology of mesenteric lymph node was inconclusive. Ascitic fluid was an exudate (SAAG < 1.1). Ascitic fluid adenosine deaminase level was normal and no malignant cells were observed. Nerve conduction studies showed sensorimotor demyelinating and axonal type polyneuropathy in both upper (median and ulnar nerves) and lower limbs (peroneal, tibial and sural nerves). Cerebrospinal fluid (CSF) analysis was normal. X-ray of the pelvis showed multiple osteosclerotic lesions involving head of left femur and right iliac crest (Fig. ). X-ray of the skull and spine was normal. The serum protein electrophoresis showed gamma globulinemia with no monoclonal M spike. Immunoelectrophoresis using the immunofixation method revealed a monoclonal IgG lambda band. The bone marrow biopsy from right iliac crest showed large atypical plasma cells in the range of 6–8% (Fig. ). The patient was diagnosed with POEMS syndrome. He was given radiotherapy, followed by a combination therapy of melphalan (16 mg/m2) and dexamethasone. At 6 months and 1-year follow-up, the patient has no worsening of symptoms.