Beyond the Obstruction: Recognising Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Plasma Cell Disorder, and Skin Changes (POEMS) Syndrome in a Patient With Budd-Chiari Syndrome.

Introduction

Polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes (POEMS) syndrome is a paraneoplastic condition driven by an underlying plasma cell dyscrasia [ 1 ]. Major diagnostic criteria include polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor (VEGF), and Castleman disease, while minor criteria encompass organomegaly, endocrinopathy, characteristic skin changes, papilloedema, extravascular fluid overload, and thrombocytosis [ 1 ]. The diagnosis is established when at least three major criteria are met, including both polyradiculoneuropathy and clonal PCD, along with at least one minor criterion [ 1 ].

POEMS syndrome is extremely rare, with an estimated prevalence of less than 1 per 1,000,000 individuals [ 2 ]. It predominantly affects middle-aged adults, typically in the fourth to sixth decades of life, with a slight male predominance [ 3 ].

Case presentation

A 52-year-old man with no significant past medical history presented with progressive weakness, tingling, and numbness of the lower limbs for the past three months. He also reported significant weight loss of approximately 10 kg over two months, accompanied by worsening fatigue. His mobility gradually declined, eventually requiring the use of a walking frame. Over the past six weeks, he developed increasing abdominal girth with intermittent abdominal pain, bilateral lower limb swelling, and exertional dyspnoea. There was no history of fever, night sweats, or overt bleeding. He also reported altered bowel habits. He was a non-smoker and consumed alcohol only occasionally.

On examination, there was marked abdominal distension with positive shifting dullness on percussion, indicating the presence of ascites. The spleen was palpable, consistent with splenomegaly. Neurological examination revealed bilateral foot drop, reduced lower limb strength (3/5 hip flexors, 4/5 hip extensors, 3/5 knee flexors, 2/5 ankle dorsiflexors), and diminished proprioception below the knees. All reflexes were intact, and bowel and bladder functions were normal. Cranial nerves were intact. He also had mild bilateral gynaecomastia, palmar hyperpigmentation, and bilateral pitting oedema extending up to the mid-thighs. There was no lymphadenopathy or other signs of infection.

These findings indicated multisystem involvement, including neurological (polyneuropathy), endocrine (gynaecomastia), fluid overload (oedema, ascites), organomegaly (splenomegaly), and skin changes (hyperpigmentation). The combination of peripheral neuropathy, organomegaly, endocrinopathy, skin changes, and fluid overload supported a possible diagnosis of POEMS syndrome. Based on these multisystem findings, a clinical suspicion of POEMS syndrome prompted further diagnostic investigations in addition to routine blood tests, the results of which are summarised in Table 1 .

A diagnostic ascitic tap was performed, and the fluid was found to be transudative in nature with no malignant cells. Multiple imaging studies, including CT of the thorax, abdomen, and pelvis, triple-phase CT of the liver (Figure 1 ), MRI of the whole spine (Figure 2 ), bone scan, and PET-CT, were conducted. Nerve conduction studies and biopsies from the liver and bone marrow were also undertaken, and the results are summarised in Table 2 .

The diagnosis of POEMS syndrome in this patient was confirmed based on the fulfillment of the mandatory, major, and minor criteria outlined in Table 3 . The combination of characteristic clinical, radiological, and laboratory findings supports the diagnosis and is consistent with established criteria for this rare multisystem disorder.

He also had Budd-Chiari syndrome, confirmed by imaging and liver biopsy, likely due to the prothrombotic state associated with POEMS.

Management

This complex multisystem diagnosis was discussed in a multidisciplinary team meeting, which included Hepatology, Neurology, Endocrinology, Haematology, Physiotherapy, and Occupational Therapy.

Treatment was commenced with daratumumab, bortezomib, and dexamethasone (Dara-Vd), following advice from the Haematology team. Thalidomide was avoided due to hepatic vein thrombosis. For anticoagulation, the patient was initially treated with therapeutic low-molecular-weight heparin (enoxaparin) and was later switched to warfarin. Management of ascites included fluid restriction and spironolactone (40 mg twice daily), as recommended by the Hepatology team, with ongoing follow-up in their clinic. Hepatitis B prophylaxis was initiated with entecavir. Following Endocrinology advice, thyroid hormone replacement therapy was also started. Physiotherapy was initiated early to support mobility and rehabilitation.

Follow-up

Following initiation of chemotherapy, the patient’s ascites and pleural effusions gradually improved. Neurological symptoms stabilised, although full motor recovery was not observed during the initial phase of treatment. Repeat VEGF testing is planned at six weeks to monitor trends, and CT imaging at three months is scheduled to reassess hepatic vein patency. He remains on long-term anticoagulation and entecavir and continues routine physiotherapy. At discharge, he was able to transfer independently with aids and perform limited self-care. He was referred to a regional Haematology unit for consideration of autologous stem cell transplantation.

Discussion

POEMS syndrome is an uncommon, multisystem paraneoplastic disorder secondary to an associated monoclonal plasma cell neoplasm [ 2 , 3 ]. It is distinct from classical multiple myeloma, as it is associated with sclerotic rather than lytic bone lesions, demyelinating polyneuropathy, and a constellation of endocrinopathies including hypogonadism, thyroid dysfunction, and diabetes mellitus [ 2 , 3 ]. Patients often present with extravascular fluid overload, such as ascites, pleural effusions, and peripheral oedema, mediated by elevated VEGF levels [ 4 , 5 ]. VEGF overexpression is a characteristic feature of the syndrome and leads to vascular hyperpermeability, angiogenesis, and a prothrombotic state, contributing to complications such as Budd-Chiari syndrome, pulmonary hypertension, and thrombotic events [ 4 , 6 , 7 ]. The underlying pathophysiology involves a clonal PCD, most commonly secreting lambda light chains, which triggers a cascade of cytokine release, including VEGF, IL-6, and TNF-alpha, resulting in diverse systemic manifestations [ 4 , 6 ].

Early recognition of neuropathic presentations is crucial, as they may be preceded by systemic manifestations by several months to years [ 3 , 6 ]. Electrophysiology typically demonstrates symmetric sensorimotor demyelinating patterns, as observed in our patient. Early treatment can halt disease progression and improve functional outcomes [ 3 , 5 ].

Management of POEMS syndrome primarily focuses on suppression of the underlying plasma cell clone using targeted therapies.

In patients who are not candidates for transplantation or have diffuse disease, proteasome inhibitors (e.g., bortezomib), immunomodulatory drugs (e.g., lenalidomide or thalidomide), and monoclonal antibodies (e.g., daratumumab) are increasingly used [ 7 , 8 ]. These agents are typically combined with low-dose corticosteroids, such as dexamethasone, to optimise efficacy and tolerability. Recent case series indicate that daratumumab-containing regimens are effective in relapsed or refractory POEMS, leading to rapid haematologic responses and decreased VEGF levels [ 7 ]. Supportive care is also essential and includes management of fluid overload, anticoagulation for prothrombotic complications, physiotherapy for neuropathy, and endocrine replacement therapy [ 2 , 3 ]. VEGF can serve as a biomarker for disease activity, treatment response, and therapeutic decision-making [ 4 ]. Long-term follow-up is recommended, as relapse can occur, and early intervention strongly influences prognosis [ 3 ]. The multisystem nature of POEMS favors a multidisciplinary approach, involving haematology, neurology, endocrinology, hepatology, and rehabilitation services [ 5 , 9 ]. Complications such as Budd-Chiari syndrome, although rare, reflect the prothrombotic state induced by VEGF and cytokine imbalance and require prompt recognition and anticoagulation [ 9 ]. Prognosis has improved significantly over the past two decades due to advances in therapy and supportive care, with five-year survival rates exceeding 70%-80% in recent cohorts [ 5 , 7 ].

Conclusions

POEMS syndrome should be suspected in cases of unexplained neuropathy accompanied by a multisystem presentation. Budd-Chiari syndrome may occur as a vascular complication due to thrombosis. Elevated VEGF levels are both diagnostic and predictive of disease activity. Investigations (including VEGF levels; full blood count; liver, renal, and thyroid function tests; skeletal surveys; follow-up imaging; and nerve conduction studies) should be monitored routinely. Regular follow-up is essential to assess treatment response, disease progression, and symptom improvement. Early targeted therapy is associated with favourable outcomes, although the long-term sequelae of neuropathy in POEMS remain uncertain. This case highlights the complex diagnostic overlap among haematology, neurology, and hepatology encountered in acute settings. It emphasises the importance of maintaining a broad differential diagnosis and considering rare, potentially life-threatening diseases in multisystem presentations. The key take-home messages are the importance of early recognition of POEMS syndrome and awareness of its potential vascular complications.

Disclosures

Human subjects: Informed consent for treatment and open access publication was obtained or waived by all participants in this study.

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following:

Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work.

Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work.

Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Author Contributions

Concept and design: Shadman Sakib Rahman, Kh Imranul Alam, Nusrat A. Chowdhury, Md Al Amin Sarkar, Usman Ul Haq, Sumaiya Kamal

Acquisition, analysis, or interpretation of data: Shadman Sakib Rahman, Kh Imranul Alam, Nusrat A. Chowdhury, Md Al Amin Sarkar, Usman Ul Haq, Sumaiya Kamal, James Alegbeleye

Drafting of the manuscript: Shadman Sakib Rahman, Kh Imranul Alam, Md Al Amin Sarkar, Usman Ul Haq, Sumaiya Kamal

Critical review of the manuscript for important intellectual content: Shadman Sakib Rahman, Nusrat A. Chowdhury, James Alegbeleye

Supervision: Shadman Sakib Rahman, Kh Imranul Alam, James Alegbeleye

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