When Nerves Speak Louder Than Words: Polyneuropathy and Multisystem Involvement in a Teenager.

A case of relapsed systemic multiple myeloma mimicking adenopathy and extensive skin patch overlying a plasmacytoma

Restricted Oligo-Clonal Usage of Monoclonal Immunoglobulin λ Light Chain Germline in POEMS Syndrome.

Polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, skin changes (POEMS) syndrome is a rare disorder that is frequently misdiagnosed due to its heterogeneous presentation and overlap with chronic inflammatory demyelinating polyneuropathy (CIDP). Diagnosis requires the presence of polyneuropathy and a monoclonal plasma cell disorder, along with additional major and minor criteria. We present a 73-year-old woman with progressive weakness, volume overload, and weight loss, initially diagnosed with CIDP. Despite IVIG therapy, her symptoms worsened. Notably, no monoclonal peak was detected on serum protein electrophoresis (SPEP) or immunofixation, complicating the diagnosis. However, markedly elevated vascular endothelial growth factor (VEGF) levels (11.245 pg/mL) and bone marrow biopsy findings of a monoclonal plasma cell disorder confirmed POEMS syndrome. She also developed multiple thromboembolic events, highlighting the syndrome's prothrombotic nature. This case underscores the importance of maintaining high suspicion for POEMS syndrome in the setting of undifferentiated polyneuropathy, even in the absence of a monoclonal peak on SPEP. VEGF measurement and bone marrow biopsy are crucial for diagnosis in such cases. Early recognition and treatment, including plasma cell-directed therapy and anticoagulation, are essential to improving patient outcomes and preventing irreversible complications.

POEMS syndrome is a rare multisystem disorder associated with plasma cell dyscrasia and abnormal cytokine production, including vascular endothelial growth factor (VEGF). The mandatory criterion for its diagnosis includes polyneuropathy and monoclonal plasma cell disorder, along with other major and minor criteria. This case highlights the diagnostic and therapeutic challenges of POEMS syndrome by depicting the case of a 61-year-old male with progressive sensory-motor polyneuropathy, lymphadenopathy, and splenomegaly. The patient presented with a year-long history of bilateral limb weakness and sensory disturbances, accompanied by abdominal distention, weight loss, and other systemic symptoms. Clinical examination revealed skin hyperpigmentation, splenomegaly, and a right axillary lymph node enlargement. Neurological evaluation showed distal limb hypotonia, absent reflexes, and sensory deficits. Diagnostic investigations, including nerve conduction studies, imaging, and bone marrow biopsy, confirmed POEMS syndrome based on polyneuropathy, monoclonal IgG lambda plasma cells, Castleman disease, sclerotic bone lesions, elevated VEGF, and minor criteria, such as endocrinopathy and skin changes. The treatment comprised lenalidomide and dexamethasone, resulting in significant improvement at the three-month follow-up, including normalized VEGF levels and resolution of ascites. This case highlights the necessity of identifying the many presentations of POEMS syndrome for prompt diagnosis and treatment. Despite its rarity and diagnostic complexity, prompt treatment can significantly improve clinical outcomes. POEMS syndrome should be considered in patients with unexplained neuropathy and systemic features, enabling better outcomes through targeted therapies.

Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome is a rare condition defined by monoclonal plasma cell disorder, peripheral neuropathy, and other systemic symptoms. The pathophysiology of POEMS syndrome is unknown, but the overproduction of vascular endothelial growth factor (VEGF) appears to be an important contributory element. The diagnosis of POEMS syndrome requires the presence of both mandatory criteria (ie, polyneuropathy and a monoclonal plasma cell disorder), at least one major criterion (ie, osteosclerotic bone lesions, Castleman disease, or elevated serum or plasma levels of vascular endothelial growth factor), and at least one of the six minor criteria. POEMS syndrome lacks a standard treatment, but patients with limited sclerotic bone lesions are typically treated with radiation therapy. In contrast, those with widespread lesions receive chemotherapy and hematopoietic stem cell transplantation.

Polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes (POEMS) syndrome is a rare multisystem disorder often misdiagnosed due to its wide-ranging manifestations and clinical overlap with common medical conditions. We present a case of a 76-year-old male who initially presented with bilateral lower extremity oedema and fatigue. Despite multiple specialist evaluations and worsening symptoms with characteristic clinical features, including peripheral neuropathy, thrombocytosis, and sclerotic bone lesions, POEMS syndrome was not investigated until the haematology service saw the patient during his hospitalization. Earlier evaluations prior to hospitalization revealed an IgG lambda monoclonal protein, splenomegaly, papilledema, and an elevated vascular endothelial growth factor (VEGF) level of 10,999 pg/ml, confirming the diagnosis of POEMS syndrome.This case underscores the importance of early identification of markers related to POEMS syndrome. The patient’s presentation also fulfilled the PEST acronym (which stands for papilledema, extravascular volume overload, sclerotic bone lesions, and thrombocytosis), a helpful clinical reminder for internists. Due to his poor functional status and age, he was ineligible for an autologous stem cell transplant and was treated with a combination of daratumumab, lenalidomide, and dexamethasone. After 4 months of treatment, he showed significant clinical improvement and a greater than 50% reduction in VEGF levels. This case illustrates the diagnostic challenges of POEMS syndrome and the important role internists can play in early recognition. Prompt VEGF testing, investigation with artificial intelligence tools, and inclusion of POEMS syndrome in the differential can reduce unnecessary consultations and healthcare costs, while enabling timely therapy.LEARNING POINTSWhen a patient has a constellation of symptoms including peripheral neuropathy and monoclonal gammopathy, POEMS syndrome needs to be added to the working diagnoses.Common cognitive biases may delay diagnosis of a rare disease such as POEMS syndrome, leading to adverse clinical outcomes and increased healthcare costs.Earlier screening of the patient’s symptoms via artificial intelligence tools could have prompted an appropriate diagnosis and combat common cognitive biases.

Introduction:Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome is a rare paraneoplastic syndrome that occurs secondary to an underlying plasma cell disorder. The diagnosis of POEMS syndrome is 2 of the mandatory major criteria (polyneuropathy and monoclonal plasma cell disorder), 1 of the other major criteria (Castleman's disease, sclerotic bone lesions, or vascular endothelial growth factor elevation), and at least 1 of the minor criteria (organomegaly, extravascular volume overload, endocrinopathy, skin changes, papilledema, thrombocytosis, or polycythemia). However, some cases do not fully meet the diagnostic criteria, such cases are referred to as incomplete or atypical POEMS syndrome.Patient concerns:A 58-year-old Chinese female was admitted to our department of neurology with weakness of both arms and legs. In addition,it's found that she had skin manifestations, lymphadenopathies, pedal edema, immunoglobin - A-λ restricted paraproteinemia, and elevated vascular endothelial growth factor and other features, but without polyneuropathy.Diagnoses:we made a diagnosis of atypical POEMS syndrome without polyneuropathy.Interventions:Two drug regimens were recommended: VAD (Vincristine, Adriamycin, Dexamethasone) and bortezomib. Finally, the VAD strategy was performed.Outcomes:The patient's limb strength and pain improved and enzyme parameters decreased gradually after 4 weeks. However, the treatment was still not perfect. Conclusion: We reported a rare case of POEMS syndrome without polyneuropathy. We hope similar cases will be reported in the future.

Objective POEMS syndrome is a rare and treatable plasma cell disorder. Although medical advances have improved survival, polyneuropathy – which impairs both sensory and motor function in the limbs – continues to be the predominant contributor to reduced mobility and quality of life. Multidisciplinary teams can offer rehabilitation during the disease progression and recovery, but there is limited guidance on appropriate types, intensity, and timing of intervention. This scoping review aims to answer the question: “What is known about physical recovery and rehabilitation in POEMS syndrome?” Data sources MEDLINE, CINAHL, EMBASE, PEDRO and EMCARE databases. Additional studies were identified from grey literature and handsearching of citations. Review methods A scoping review was conducted. Included papers focused on POEMS syndrome with details on physical outcomes pre and post treatment and rehabilitation intervention. Data was extracted into tables, and a narrative summary was produced for each paper. Results In total 21 papers were included and analysed through narrative summaries across three themes: 1) physical and functional deficits, 2) physical recovery and 3) rehabilitation interventions. There were no studies evaluating rehabilitation intervention and limited detail on intervention specifics and timings. Most studies focused on the outcome of medical intervention on physical impairments, with little attention to disability, function and quality of life. Conclusions There is a need for expert-led recommendations, standardised rehabilitation guidelines and further research into effective interventions including timing, intensity and the patient's preferences.

BACKGROUND Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes (POEMS) syndrome is a rare plasma cell neoplasm with associated paraneoplastic syndrome. Castleman disease variant of POEMS syndrome, lacking detectable M-protein is uncommon and presents substantial diagnostic and therapeutic challenges. We illustrate a case of Castleman disease variant of POEMS syndrome and the complexity of its clinical management. CASE SUMMARY A 56-year-old man presented with limb weakness, sensory neuropathy, weight loss, and hyperpigmentation. He was diagnosed with Castleman disease variant of POEMS syndrome, having fulfilled 3 major criteria (polyneuropathy, Castleman disease, and vascular endothelial growth factor elevation) and 6 minor criteria (organomegaly, extravascular volume overload, endocrinopathy, skin changes, papilledema, and thrombocytosis). He received melphalan plus dexamethasone, followed by three cycles of cyclophosphamide while planning for an autologous stem cell transplant, but suffered from seizures and thrombotic episodes throughout the course of his treatment. He gradually improved over 5 months, with improvement in limb strength, reduced pigmentation, and reduced fluid retention, but eventually succumbed to his illness due to sepsis. CONCLUSION Although a monoclonal plasma cell disorder is a mandatory diagnostic criterion for POEMS syndrome, it may be minimal or undetectable in some patients with the Castleman disease variant who otherwise fulfil diagnostic criteria.

Durable Responses with Autologous Hematopoietic Stem Cell Transplantation in Patients with POEMS Syndrome

Polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes (POEMS) syndrome is a rare multisystemic paraneoplastic disorder caused by an underlying plasma cell dyscrasia. Its diagnosis isbased on the presence of two mandatory criteria and at least one major and one minor criterion. We report a case of a 52-year-old female patient who presented with complaints of acrocyanosis, night sweats, scaly skin, and swelling on the left side of the neck. She was a known case of hypothyroidism, antiphospholipid syndrome, and cerebral venous thrombosis, and hadother comorbidities as well. She also exhibited weakness and paresthesia of the limbs and muscle wasting in the hands. All necessary examinations and investigations were performed and the patient was eventually diagnosed with POEMS syndrome. She underwent chemotherapy along with immunotherapy initially, but as the disease relapsed, she was referred for high-dose therapy (HDT) and autologous stem cell transplantation.

Background: POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes) is characterized by the presence of a monoclonal plasma cell disorder, peripheral neuropathy, and one or more of the following features: osteosclerotic myeloma, Castleman disease, increased levels of serum vascular endothelial growth factor (VEGF), organomegaly, endocrinopathy, edema, typical skin changes, and papilledema. Clinical Case: 45 year old male with no chronic medical issues presented initially to the orthopedic clinic with right hip pain, pelvic MRI showed a right iliac crest lesion. CT Guided biopsy was done and showed plasmacytoma. SPEP showed elevated IgG lambda level in the gamma zone. In the meantime he was complaining of ascending numbness and weakness in hands and feet and he progressively became wheelchair bound. During his treatment and follow ups with Hematology/Oncology he was noted to have elevated blood sugars in the 500s. Hemoglobin A1C was elevated at 9.5 which confirmed the diagnosis of new onset diabetes. He was also noted to have splenomegaly which confirmed the diagnosis of POEMS syndrome. He was started on insulin and he managed to achieve good diabetes control with insulin and dietary changes. He is currently status post stem cell transplantation with a good response and the weakness and polyneuropathy improved with PT and OT. POEMS syndrome has major and minor criteria for diagnosis, mandatory major criteria includes polyneuropathy, monoclonal plasma cell proliferative disorder (almost always lambda). Additional major criteria are sclerotic bone disease, castleman disease, elevated VEGF. Minor criteria are organomegaly, extravascular volume load, endocrinopathy, and skin changes. In order to diagnose the syndrome, mandatory major criteria, and one major and one minor criteria need to be clinically present. Endocrinopathy includes the adrenal, pituitary, thyroid, gonadal, parathyroid, and pancreatic glands. Two-thirds of patients had at least one endocrine abnormality at presentation. Endocrine abnormalities can also develop later, during the course of the disease. Hypogonadism is the most common endocrine abnormality. Elevated levels of follicle stimulating hormone in the absence of primary hypogonadism levels have been reported, hence history and physical examination is crucial to detect the development of endocrinopathies in POEMS syndrome. There are no current guidelines or recommendations about the frequency of screening for endocrinopathies but it is suggested to obtain a baseline of thyroid function test, pituitary, gonadal, and adrenal axis. In addition to baseline parathyroid hormone level, close monitoring of calcium and blood glucose levels once the diagnosis is confirmed in patients with suggestive symptoms. Conclusion: POEMS syndrome is a rare condition that involves multiple endocrine organs, currently there are no guidelines or recommendations to obtain baseline endocrine labs once the diagnosis is confirmed, but it might be appropriate if there is a high clinical suspicion.

POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal plasma cell disorder, Skin changes) syndrome is a rare paraneoplastic disorder driven by a λ-restricted plasma cell clone. Cutaneous manifestations are common but typically limited to hyperpigmentation, hemangiomas, and sclerodermoid changes. We herein report the first case of POEMS syndrome presenting with skin lesions closely resembling those of Vibrio vulnificus infection. A 65-year-old woman was admitted with malignant hypertension, refractory ascites, symmetrical thigh ecchymoses evolving into tense hemorrhagic bullae, and progressive sensorimotor polyneuropathy. Laboratory workup revealed thrombocytosis, hypoalbuminemia, acute kidney injury, an IgA-λ monoclonal band on serum immunofixation, and a markedly elevated VEGF level (729.7 pg./mL, reference range: 9-86 pg./mL). Electromyography confirmed a demyelinating neuropathy. Infectious, autoimmune, hepatic, renal, and malignant etiologies were systematically excluded. A multidisciplinary team reached the diagnosis of POEMS syndrome based on two mandatory criteria (polyneuropathy and monoclonal plasma cell disorder), one major criterion (elevated VEGF), and multiple minor criteria (extravascular volume overload, endocrinopathy, skin changes, thrombocytosis, organomegaly). The patient received bortezomib plus dexamethasone, leading to gradual resolution of skin lesions, improvement of neuropathic symptoms, and reduction of VEGF levels. After six cycles, ascites resolved and neurological function partially recovered. This case expands the spectrum of POEMS-associated skin changes to include V. vulnificus-like bullous lesions. "V. vulnificus-like" refers purely to morphological similarity and not microbiological confirmation. Awareness of such atypical presentations is essential for early recognition. Clinicians should consider POEMS syndrome in patients with unexplained multisystem involvement and vascular skin changes. VEGF measurement and immunofixation electrophoresis are essential tools for timely diagnosis.

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) is a rare paraneoplastic disorder due to an underlying plasma cell dyscrasia. The diagnosis of POEMS syndrome requires a chronic polyneuropathy and a monoclonal lambda plasma cell-proliferative disorder (mandatory criteria), and various systematic symptoms such as sclerotic bone lesions, Castleman's disease, organomegaly, endocrinopathy, skin changes, papilloedema and biological abnormalities such as elevated vascular endothelial growth factor (VEGF), thrombocytosis or polycythaemia. We describe an observation of a patient with recurrent thrombosis with thrombocytosis that, after excluding a myeloproliferative neoplasm, proved to be due to POEMS syndrome. This case is unusual compared to the foreground thrombotic symptomatology. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) is a rare multi-systematic paraneoplastic disorder due to an underlying plasma cell disorder. The diagnosis of POEMS syndrome requires the presence of both mandatory criteria (a chronic polyneuropathy and a monoclonal plasma cell-proliferative disorder, always lambda restricted); at least one major (among sclerotic bone lesions, Castleman's disease, elevated VEGF (vascular endothelial growth factor)) and one minor criterion (among organomegaly, endocrinopathy, skin changes (haemangiomas, hypertrichosis, hyperpigmentation), papilloedema and thrombocytosis or polycythaemia. We describe an unusual observation of a young patient with recurrent thrombosis with thrombocytosis that, after excluding a myeloproliferative neoplasm, proved to be due to POEMS syndrome.

POEMS syndrome is defined by the presence of peripheral neuropathy (P), organomegaly (O), endocrinopathy (E), a monoclonal plasma cell disorder (M) and skin changes (S). We report a case of POEMS syndrome in a 34-year-old female who presented with three month history of back pain, pain in lower limbs, weakness, numbness and edema in both lower limbs. Patient was unable to walk and bed ridden with worsening general condition, shortness of breath and fever for three days. Further clinical examinations (hyperpigmentation), systemic examination (hepato-splenomegaly), laboratory investigation (hypothyroidism), CT showed sclerosis in sacral bone and left acetabular lytic lesion, which on biopsy and immunohistochemistry showed plasma cell dyscrasia and confirmed by increased plasma cells in bone marrow biopsy and presence of M band in immunofixation study. Here we describe, in detail, an unusual clinical presentation of this rare paraneoplastic syndrome with multisystemic involvement which needs multidisciplinary approach with strong clinico-pathological & radiological correlation to diagnose this rare entity.
 J MEDICINE JAN 2020; 21 (1) : 55-58