A case of POEMS syndrome comprising of a complicated diagnostic procedure: Case report.

RATIONALE: This article presents the case of a patient with recurrent chronic diarrhea and cachexia who was misdiagnosed, followed by a literature review to summarize the reasons for misdiagnosis of POEMS syndrome and the treatment strategies. PATIENT CONCERNS: The diagnosis and treatment of this patient suggest that with the improvement of M-protein detection levels, the diagnosis of patients with low M-protein levels, such as those with POEMS syndrome, has been greatly aided. DIAGNOSES: POEMS syndrome requires polyneuropathy and monoclonal plasma cell proliferation as mandatory diagnostic criteria. Therefore, patients presenting with polyneuropathy should routinely undergo M-protein testing and consider the possibility of POEMS syndrome. INTERVENTIONS: The patient, in this case, was treated primarily with relatively conservative immunomodulatory agents. OUTCOMES: During follow-up after treatment, the patient's diarrhea and malnutrition showed significant improvement. LESSONS SUBSECTIONS: POEMS syndrome has low clinical specificity and a high rate of misdiagnosis. However, once a definitive diagnosis is made, the treatment outcome is favorable.

Small vessel platelet thrombosis in the peripheral nerves in POEMS syndrome.

INTRODUCTION/AIMS: Vascular thrombosis is prevalent among patients with polyneuropathy, organomegaly, endocrinopathy M-protein, and skin changes (POEMS) syndrome. The endothelial cells in the endoneurium are often hypertrophied and the lumen is frequently occluded. Consequent local hypoxia may increase vascular endothelial growth factor (VEGF), which induces hypercoagulation and vascular permeability. METHODS: This study presents two patients in the fifth decade of life, who had rare nerve biopsy findings of vascular occlusion mainly by platelets. Before the cases presented here, we encountered nine confirmed POEMS patients whose nerve biopsies did not show similar findings. RESULTS: A small artery and a vein were occluded, but no atherosclerotic changes were observed. The endothelial cells that adhered to the packed platelets lost their junctions. DISCUSSION: Platelet aggregation, degranulation, and ischemia may cause a loose endothelial barrier and leak proinflammatory cytokines, such as interleukin-12. This may increase production of VEGF and may cause nerve demyelination. Small vessel platelet thrombosis may contribute to the pathogenesis of this disorder.

POEMS syndrome: an unusual cause of exuberant callus formation.

Several growth factors are expressed in distinct temporal and spatial patterns during fracture repair. Together, they lead to angiogenesis-osteogenesis coupling and hence bone healing by callus formation. Of these growth factors, vascular endothelial growth factor is of particular interest because of its ability to induce neovascularisation (angiogenesis) and osteoclast invasion in soft callus. Hyperplastic callus can be seen in metabolic bone disease, endocrine disease and in patients with traumatic brain injury, but has not been described so far in polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes (POEMS) syndrome. This report is a case of POEMS syndrome with unusual presentation in the form of exuberant callus formation at fracture sites.

Treatment-responsive glycogen storage myopathy in a patient with POEMS syndrome: A new monoclonal gammopathy-associated myopathy.

BACKGROUND: Myopathies associated with monoclonal gammopathy are relatively uncommon and underrecognized, treatable myopathies, and include sporadic late onset nemaline myopathy, light chain amyloid myopathy, and a recently described vacuolar myopathy with monoclonal gammopathy and stiffness (VAMGS). Herein, we report a new subtype of monoclonal gammopathy-associated myopathy (MGAM) in a polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) patient. METHOD: Case report. RESULTS: A 51-year-old woman presented with a 6-month history of progressive bilateral foot drop, lower limb edema, and a 15-lb weight loss. She denied muscle stiffness. Neurologic exam showed severe distal weakness, mild proximal weakness, and length-dependent sensory deficits. Laboratory studies revealed biclonal gammopathy (IgG kappa and IgA lambda), thrombocytosis, and elevated vascular endothelial growth factor. Creatine kinase was normal. Electrodiagnostic studies identified mixed demyelinating and axonal polyradiculoneuropathy and a superimposed proximal myopathy. Gluteus medius biopsy demonstrated scattered fibers with glycogen-filled vacuoles, similar to VAMGS, with additional rare myofibers containing polyglucosan bodies. She was diagnosed with POEMS syndrome and concomitant glycogen storage myopathy. Next-generation sequencing of glycogen storage and polyglucosan body myopathy-related genes was unrevealing. Proximal weakness resolved after autologous stem cell transplant. CONCLUSIONS: This patient expands a spectrum of MGAM. Recognition of this condition and other subtypes of MGAM is of utmost important because they are treatable.

Surgical revascularization for quasi-moyamoya disease associated with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome: a case report and literature review.

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare multisystem disease characterized by plasma cell dyscrasia and overproduction of vascular endothelial growth factor, which is related to disease activity. Recent treatment strategies have improved survival of patients suffering from this disorder; however, ischemic stroke remains a poor prognostic factor. POEMS patients with ischemic stroke frequently develop cerebral large artery stenosis/occlusion, followed by progressive stroke. Post literature review, we present an ischemic stroke case of quasi-moyamoya disease linked with this syndrome that was successfully treated with surgical revascularization. A 41-year-old woman diagnosed with POEMS syndrome developed progressive ischemic stroke due to quasi-moyamoya disease, despite decreased vascular endothelial growth factor level with lenalidomide and dexamethasone treatment. She underwent superficial temporal artery to middle cerebral artery bypass with encephalo-duro-myo-synangiosis bilaterally. The postoperative course was uneventful. Two years and five months after the stroke, neuroimaging demonstrated bypass patency, neovascularization after encephalo-duro-myo-synangiosis, and no recurrence of stroke. Our case is the first to report successful surgical revascularization for a POEMS patient. Surgical revascularization may be a useful treatment option for patients with quasi-moyamoya disease associated with POEMS syndrome, especially for those who develop refractory ischemic stroke despite reduced vascular endothelial growth factor level.

POEMS syndrome presents with a distended abdomen: A case report.

POEMS syndrome is a rare, serious, multisystem disorder and its diagnosis is frequently missed due to its varied clinical presentation. We report here, a 69-year-old woman with initial complaints of distended abdomen, who was misdiagnosed with tuberculosis but failed anti-tuberculosis treatment. Further examinations showed peripheral neuropathy, monoclonal plasma cell disease, sclerotic bone lesions, an elevated serum vascular endothelial growth factor (VEGF) concentration, lymph node hyperplasia, endocrine abnormalities, and skin hyperpigmentation. A diagnosis of POEMS syndrome was made and the patient responded to lenalidomide-based chemotherapy.

Coexistence of primary mediastinal MALT lymphoma and multiple myeloma like POEMS syndrome: A case report and literature review.

RATIONALE: The coexistence of the extranidal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT) and multiple myeloma (MM) is an exceedingly rare situation. The rare situation precludes any evidence-based guidelines for MZL or MM. PATIENT CONCERNS AND DIAGNOSES: We presented a unique case of the coexistence of primary mediastinal MALT lymphoma and MM like polyneuropathy, organomegaly, endocrinopathy, M-protein, skin syndrome. INTERVENTIONS AND OUTCOMES: The patient was first diagnosed with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin syndrome in the department of neurology, then MM in the department of hematology, and the mediastinal MALT simultaneously coexisting with MM was found by biopsy in the department of thoracic surgery. The patient received combination therapy with rituximab and bortezomib followed by lenalidomide maintenance. To understand MZL lymphoma with plasmacytic differentiation better, we analyzed cases of MZL lymphomas with plasma cell neoplasms. Most of these cases were MZL lymphomas with light chain-restricted plasmacytic differentiation. The lymphomas relapsed with plasma cell neoplasms or transformed into plasma cell neoplasms after anti-lymphoma therapy. LESSONS: The case demonstrated clinical complexity and the importance of the detailed assessment. The case and literature review demonstrated the value of detecting light chain-restricted plasmacytic differentiation for the treatment of MZL lymphoma with rituximab plus lenalidomide or bortezomib.

Development of Polyneuropathy, Organomegaly, Endocrinopathy, M Protein, and Skin Changes Syndrome after Conversion from Plasmacytoma of Bone to Multiple Myeloma.

A 36-year-old man developed polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome after conversion from solitary plasmacytoma of bone to multiple myeloma. Twenty-four days following the neurological onset, he lost his independent walking ability. The level of serum vascular endothelial growth factor (VEGF) at diagnosis was 5,250 pg/mL. Three months after initiating treatment, he regained his independent walking ability in line with a reduction in the elevated serum VEGF level. Due to their genomic instability gained during conversion, myeloma cells may overproduce humoral factors and cytokines, possibly contributing to the development of neuropathy as well as the production of VEGF.

Chronic diarrhea - The poetic masquerade.

Chronic diarrhea, by definition, is the passage of loose/liquid stools, with increased frequency (more than three times/day), or an output of over 200 g/day, lasting for a duration of four or more weeks. The clinical approach to identify the cause of chronic diarrhea generally depends on the local socioeconomic status. In high-income countries, systemic causes such as irritable bowel syndrome (IBS), inflammatory bowel disease, malabsorption syndromes (lactose intolerance/coeliac disease) are primarily considered. In mid- to low-income countries, infective causes like chronic bacterial, mycobacterial, fungal infections, HIV, bowel cancer are considered before systemic causes/malabsorption syndromes. Amyloidosis, more accurately, reactive amyloidosis is one of the rarer causes of chronic/persistent diarrhea. Inflammatory colitis secondary to POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) as a cause for chronic diarrhea has been reported only in a handful of cases and is often missed. We present such a case of chronic diarrhea in a middle-aged man, who was eventually diagnosed to have POEMS syndrome.

Vitamin B6 deficiency as a cause of polyneuropathy in POEMS syndrome: rapid recovery with supplementation in two cases.

BACKGROUND: The etiology of POEMS syndrome and its associated polyneuropathy have not been fully elucidated. The clinical picture of POEMS-associated polyneuropathy and nutritional polyneuropathy due to vitamin B6 (VB6) deficiency are strikingly similar, both being typically sensorimotor, symmetrical, stocking and glove distribution, and more severe in the lower extremities. CASE PRESENTATION: We report two consecutive POEMS patients with VB6 deficiency who showed unusual rapid and drastic recovery of polyneuropathies within 6-8 weeks after oral VB6 supplementation. Case 1 was supplemented with VB6 from time of autologous stem cell transplantation. Polyneuropathy began to improve within one week, and he became walker-free and could walk unaided with a cane within 6 weeks. Case 2 was supplemented with VB6 from time of stem cell harvest, and he became cane-free and his gait almost normalized within two months. Nerve conduction studies were also confirmatory of neurologic recovery in both cases. CONCLUSIONS: Objective physical improvement of POEMS-associated polyneuropathy has been reported to typically require approximately a year after autologous stem cell transplantation, and together with our observations of VB6 deficiency and supplementations leading to accelerated recoveries of polyneuropathy, VB6 deficiency most probably contributes to POEMS-associated polyneuropathy. VB6 acts as a coenzyme in approximately 150 biochemical reactions. VB6 has been reported to inhibit the hypoxia-inducible factor/vascular endothelial growth factor (VEGF) pathway, and VEGF levels are known to corollate with disease activity of POEMS syndrome. Therefore, VB6 deficiency may contribute not only to POEMS-associated polyneuropathy, but also to the etiology of POEMS syndrome itself.

POEMS Syndrome Diagnosis in a Patient with Mixed Polyneuropathy: Case Report.

POEMS syndrome is a rare condition of paraneoplasic origin characterized by the presence of a sensorimotor polyneuropathy associated with the presence of a proliferative disorder of plasmatic monoclonal cells and overproduction of vascular endothelial growth factor. The acronym "POEMS" represents multisystem findings including polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder and skin changes; nevertheless, clinical presentation is heterogeneous. We describe a clinical case, the diagnostic and therapeutic approach in a patient with sensorimotor polyneuropathy in whom POEMS syndrome was diagnosed; to understand this pathology, its clinical and paraclinical manifestations in order to make a diagnosis or to avoid a delayed one and to provide an adequate treatment.

POEMS Syndrome with Biclonal Gammopathy and Renal Involvement.

Polyneuropathy, Organomegaly, Endocrinopathy, M-protein and Skin changes (POEMS) syndrome manifests as elevated levels of vascular endothelial growth factor (VEGF) and monoclonal gammopathy. We treated a case of POEMS syndrome showing monoclonality in both IgA-λ and IgG-κ. Serial renal biopsies before treatment and after normalization of the VEGF levels suggested that glomerular microangiopathy had developed due to VEGF, while biclonal gammopathy was not eliminated. The renal pathology, proteinuria, and renal function all clearly improved. Although severe polyneuropathy limited activities of daily living and enforced a bedridden state, the patient dramatically regained his motor function, achieving crutch walking after induction of remission. This case is highly notable due to the presence of biclonality and repeated biopsies.

Efficacy of novel agents in patients with nephropathy associated with POEMS syndrome.

OBJECTIVE: To evaluate the clinical characteristics and outcomes of patients with nephropathy associated with POEMS syndrome who received novel agents in combination with dexamethasone therapy, and renal pathological changes based on repeat biopsy in some patients after these novel-agent-based therapies. METHODS: The records of patients with nephropathy associated with POEMS syndrome in a single hospital from May 2017 to February 2021 were retrieved and studied in detail. All the patients received four cycles of initial novel-agent-based regimens such as bortezomib and dexamethasone (BD) or thalidomide plus dexamethasone (TD) or lenalidomide plus dexamethasone (RD) treatment. We further evaluated the pathological efficacy of these novel agents by repeat renal biopsy. RESULTS: Twelve patients with an average age of 48.6 ± 8.3 years diagnosed with nephropathy associated with POEMS syndrome were enrolled in this study. The duration from disease onset to renal biopsy was 28(8.3 ~ 54.5) months. All patients achieved good clinical responses in different degree after four cycles of initial novel agents in combination with dexamethasone therapy. After the treatment with novel-agent-based regimens, the levels of proteinuria decreased in most patients and were negative in five patients. The levels of serum creatinine (SCr) decreased in ten patients. Serum M protein was negative in four patients and still positive in the other eight patients. The levels of serum vascular endothelial growth factor (VEGF) were detected in seven patients, which were all decreased. The levels of interleukin-6 (IL-6) were detected in eight patients, which were also decreased. Repeat biopsies were performed after four cycles of novel-agent-based therapies in four patients who were all treated with BD treatment. Mesangiolysis, mesangial cells proliferation, endothelial cells proliferation, subendothelial space widening and acute renal tubulointerstitial lesions improved, the chronic renal tubulointerstitial lesions were stable. CONCLUSIONS: Novel agents improved clinical manifestations in patients with nephropathy associated with POEMS syndrome. In addition, novel-agent-based regimens such as BD treatment improved renal pathological manifestations, which suggested that novel agents could improve renal prognosis of the patients from the perspective of renal pathology.

A 65-Year-Old Man With Weight Loss, Peripheral Neuropathy, and Lower Extremity Swelling.

CASE PRESENTATION: A 65-year-old man with no past medical history sought treatment at the hospital with lower extremity swelling, pain, tingling in a stocking-glove distribution, and syncope. He reported a 23-pound unintentional weight loss. He felt unsteady walking with a couple of falls, and his exercise tolerance was limited to several hundred feet. He did not report vision changes, dysphagia, bowel or bladder problems, tremor, orthopnea, lightheadedness, or chest pain. He did not report any history of substance misuse, high-risk sexual behavior, or concerning exposures. The patient was admitted for further workup.

MULTIMODAL IMAGING OF RECURRENT CYSTOID MACULAR EDEMA ASSOCIATED WITH POEMS SYNDROME RESPONSIVE TO INTRAVITREAL DEXAMETHASONE IMPLANT.

PURPOSE: To describe the multimodal imaging findings of cystoid macular edema (CME) in POEMS syndrome and to demonstrate the effectiveness of the dexamethasone intravitreal implant in this condition. METHODS: A case report of a patient with POEMS syndrome. Multimodal imaging, including optical coherence tomography and ultra-wide field fluorescein angiography, was used to evaluate the CME and its response to treatment. RESULTS: A 66-year-old man with a history of POEMS syndrome in clinical remission after chemotherapy presented with blurry vision in the left eye. Vitreomacular traction and CME were noted on optical coherence tomography. After pars plana vitrectomy, the patient had persistent CME in the left eye and developed new CME in the right eye, which worsened over the next year. Visual acuities at this time were 20 of 60 in both eyes. The CME was unresponsive to topical ketorolac and prednisolone acetate and intravitreal bevacizumab but partially response to intravitreal and sub-Tenon's triamcinolone acetate injections. Intravitreal dexamethasone implant was given bilaterally with full resolution and visual acuities improvement to 20 of 40 in the right eye and 20 of 30 in the left eye. However, CME recurred after 3 months. Ultra-wide field fluorescein angiography demonstrated bilateral CME and diffuse peripheral vascular leakage. Serum vascular endothelial growth factor levels were normal. CONCLUSION: Cystoid macular edema may develop in POEMS syndrome in the absence of systemic findings, elevated serum vascular endothelial growth factor, or optic nerve edema. Previously unreported peripheral vascular leakage was demonstrated on ultra-wide field fluorescein angiography. Dexamethasone implant was the most effective of used therapies to treat CME.

Moyamoya Disease-like Cerebrovascular Stenotic Lesions Are an Important Phenotype of POEMS Syndrome-associated Vasculopathy.

A 41-year-old woman was diagnosed with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome based on polyneuropathy, hepatosplenomegaly, sclerotic bone lesions, IgA-λ M-protein, and an elevated level of serum vascular endothelial growth factor. One month after the initiation of lenalidomide-dexamethasone with prophylactic aspirin, she developed facial paralysis, dysarthria, and left hemiplegia. Multiple cerebral infarctions and internal carotid artery stenosis were detected. Five months after switching to pomalidomide-dexamethasone, she again developed cerebral infarction. Progressed stenotic lesions in the bilateral internal carotid artery terminal portions were detected, showing a moyamoya disease-like appearance. Quasi-moyamoya disease can be an important phenotype of systemic vasculopathies of POEMS syndrome.

Improvement in the Symptoms and VEGF Levels after Resection of an Extrame Dullary Spinal Tumor and Additional Chemotherapy in a Patient with Multiple Myeloma Complicated with POEMS Syndrome.

We herein report a case of multiple myeloma and polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes (POEMS) syndrome. The patient experienced exacerbated gait disturbance due to weakness and numbness in the lower limbs. Thoracic magnetic resonance imaging revealed an extramedullary tumor with spinal compression that required surgical resection. Plasmacytoma was diagnosed based on a biopsy. Radiation, betamethasone, and chemotherapy were therefore administered. Surgical removal of extramedullary tumors improved his symptoms, motor conduction velocity, and amplitude of the muscle action potential in the peroneal and tibial nerves, as shown by the nerve conduction study. Surgery also decreased the serum vascular endothelial growth factor levels. The patient required additional chemotherapy due to multiple myeloma and showed better outcomes nine months after discharge. The benefits of some treatments remain controversial due to the small number of patients. However, our findings reveal that an early diagnosis and comprehensive treatment may result in better outcomes in such patients.