We present a case of a 69-year-old woman, with a previous history of arterial hypertension and dyslipidemia. Her medication included amlodipine 5 mg, candesartan 8 mg, hydrochlorothiazide 12.5 mg and nebivolol 5 mg. She presented with a 1-year history of left-side supraclavicular swelling associated with progressive fatigue, anorexia, and weight loss (body weight: 74 to 63 kg). Cervical ultrasound documented multiple cervical lymphadenopathies with the largest lymph node (measuring 3.1 × 1.7 cm) being localized on the left supraclavicular region; and she was referred to the Department of General Surgery. A left supraclavicular lymph node excisional biopsy was performed. The histopathological examination of the specimen was consistent with the diagnosis of herpes virus-8-positive CD (HHV-8 CD, ).\nShe was then forwarded to the Department of Internal Medicine upon lymph node biopsy showed CD. Additional clinical history inquiry was attempted and revealed that, during the last few months, she noted progressive diffuse skin darkening and symmetrical paresthesia of the lower limbs. She denied fever, night sweats, gastrointestinal or respiratory complaints. Neurologic review of symptoms was negative for dysphagia, dysarthria, ocular changes, and bowel and bladder dysfunctions. She had no history of smoking, alcohol abuse, or illicit-drug use. She had no contact with animals or any sick person and did not have any recent travel outside Portugal. She had no family history of neurologic or oncologic diseases.\nOn physical examination, she was afebrile. Her blood pressure was 151/77 mm Hg and heart rate 62 beats/min, and peripheral oxygen saturation was 97% while on room air. She had diffuse cutaneous hyperpigmentation and palpable lymph nodes in her cervical and supraclavicular regions, with the largest measuring 3 × 2 cm. Abdominal examination revealed an enlarged liver and no other abnormality. She had bilateral edema of lower limbs. Neurological examination revealed hypoesthesia below the ankles and tendon hyporreflexia; her muscle strength was decreased in upper and lower extremities with muscle strength grade 4-/5 proximal and grade 4+/5 distal.\nBlood tests showed normal complete blood count, coagulation tests, serum bilirubin (total and conjugated), aspartate and alanine aminotransferases and lactate dehydrogenase. Erythrocyte sedimentation rate and C-reactive protein were within normal range. Renal function, serum calcium and total serum protein were normal. Endocrine screening showed normal thyroid function, a normal glycemic profile (fasting plasma glucose and hemoglobin A1c), and a normal cortisol dosage. Hepatitis B and C, toxoplasmosis, tuberculosis, human immunodeficiency virus (HIV), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections were ruled out. Auto-immune screening (antinuclear antibodies (ANA), anti-double-stranded deoxyribonucleic acid (dsDNA) and rheumatoid factor) was negative with no complement consumption. Albumin was 3.2 g/dL (reference range (RR): 3.4 - 5) and serum protein electrophoresis (SPEP) with immunofixation demonstrated a monoclonal immunoglobulin G (IgG)/kappa peak with IgG level of 2,120 mg/dL (RR: 650 - 1,600). Serum free light chains ratio was normal. Bence-Jones proteins were not detected. Bone marrow biopsy showed the presence of reactive-appearing lymphocytes B and T and 5% of plasma cells ().\nPlasma vascular endothelial growth factor (VEGF) measurement was elevated (644 pg/mL, RR: < 115). Human herpes virus-8 (HHV8) was not detected in peripheral blood by polymerase chain reaction.\nThoraco-abdominopelvic computed tomography scan revealed small bilateral pleural effusion, multiple enlarged supra and infra-diaphragmatic lymphadenopathies, hepatosplenomegaly and multiple osteosclerotic lesions (). On transthoracic echocardiography there was a normal systolic function without pulmonary hypertension or pericardial effusion. Electromyography was consistent with sensorimotor peripheral polyneuropathy.\nThus, our patient meets the criteria for the diagnosis of POEMS syndrome in association with CD.\nShe was referred to the Hematology Department, and she started treatment with a combination of bortezomib, cyclophosphamide, and dexamethasone.\nAfter the first cycle, she noticed improvement of paresthesia and IgG level reduced from 2,120 to 960 mg/dL (RR: 650 - 1,600). She has tolerated treatment well without any clinically significant adverse effect.
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.