Castleman disease variant of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes syndrome: A case report

Abstract

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.

Key Words: Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes syndrome; Castleman disease; M-protein-negative; Demyelinating polyneuropathy; Vascular endothelial growth factor; Plasma cell disorder; Case report

Core Tip: Castleman disease variant of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes syndrome is a rare and challenging multisystem disorder to manage, with atypical variants without detectable M-protein exceptionally rare. This case highlights the importance of recognizing key clinical features and utilizing supportive markers, such as vascular endothelial growth factor and histopathology. To improve functional outcomes, quality of life, and minimize long-term morbidity, early diagnosis enables timely systemic chemotherapy treatment and multidisciplinary supportive care.

INTRODUCTION

Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes (POEMS), is a rare and debilitating multisystem disorder with an estimated prevalence of 0.3 per 100000[1]. It was first described in 1938 following a post-mortem examination of a man with a solitary plasmacytoma, sensorimotor polyneuropathy and skin changes, before it was recognized as a multisystem disorder[2,3]. Its mandatory diagnostic criteria include peripheral neuropathy and monoclonal plasma cell disorder (frequently lambda light chain), while the major criteria include Castleman disease, sclerotic bone lesions, and elevated vascular endothelial growth factor (VEGF) levels[4]. In addition, minor criteria identified are organomegaly, extravascular volume overload, endocrinopathy, skin changes, papilledema and thrombocytosis. A diagnosis of POEMS syndrome would require both mandatory criteria, one of the three major criteria, and at least one of the six minor criteria to be fulfilled[4]. Patients typically present at age 40-60 years, frequently with peripheral numbness or weakness[4,5]. A systematic review by Wang et al[6] on 1946 patients with POEMS syndrome in China from 1986 to 2016 indicated that peripheral neuropathy (796, 60.44%) was commonly the first symptom encountered, followed by extravascular volume overload (207, 15.72%), endocrine abnormalities (130, 9.87%), skin changes (106, 8.05%) and organomegaly (28, 2.13%).

Castleman disease (or angiofollicular lymph node hyperplasia) is a rare lymphoproliferative disorder, diagnosed based on histopathological findings. A retrospective study of 99 patients with POEMS syndrome, showed that 25 of 43 biopsied lymph nodes were diagnostic of Castleman disease, and 84% of these had a hyaline vascular type. Only patients with both peripheral neuropathy and a plasma cell clone can be classified as having classic POEMS syndrome. Those without either characteristic can be classified as having a Castleman disease variant of POEMS syndrome[4,7]. Despite its myriad of symptoms, it is commonly misdiagnosed as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) or other paraproteinemic neuropathies, and it would not be unusual to reach a final diagnosis of POEMS only after 1-2 years from the initial presentation[5].

There have been few published reports on patients presenting with features similar to POEMS syndrome but without any detectable M-protein, a mandatory criterion for its diagnosis. We present an exceptionally rare case of Castleman disease variant of POEMS syndrome to highlight the diagnostic and management issues encountered, with a review of existing literature.

CASE PRESENTATION

Chief complaints

A 56-year-old Malay man presented to the emergency department of a tertiary care center with acute left upper limb weakness and numbness upon awakening.

History of present illness

He woke up with weakness and numbness in his left upper and lower limbs. He could still ambulate with aid as his muscle power progressively improved. There was no associated slurring of speech, facial numbness, headache, vomiting, or giddiness. He was last known to be well the night before going to sleep and presented to the emergency department 12 hours later. Upon further questioning, he reported feeling unwell for the past 4 months, with lethargy, easy fatiguability, unintentional weight loss (18 kg), poor appetite and hyperpigmented skin. Furthermore, he reported progressive leg swelling with peripheral numbness over the past month.

History of past illness

He was recently diagnosed with diabetes mellitus, hypertension and dyslipidemia 4 months prior to presentation. He had no significant past medical or surgical history otherwise.

Personal and family history

He was a reformed smoker, having stopped 20 years ago with a history of 5 pack years. He did not consume alcohol and was a pensioner who previously served in the military. There was no significant medical history or malignancy among his family members.

Physical examination

Clinically, he had anasarca, leukonychia, and finger clubbing (Figure 1). He had peripheral sensory loss of a stocking distribution until mid-shin with hyporeflexia over bilateral knees and ankles. Otherwise, muscle power and cranial nerves were grossly normal. He had a palpable 2 cm × 2 cm cervical lymph node, but no organomegaly clinically. Fundoscopy demonstrated bilateral papilledema.

Figure 1  Leukonychia and finger clubbing.

Laboratory examinations

Blood investigation results demonstrated persistent thrombocytosis, with platelet counts ranging from 600 × 10⁹/L to 900 × 10⁹/L, hypoalbuminemia (25-32 g/L), and a reversal of the albumin-globulin ratio (0.7). Serum protein electrophoresis and immunofixation revealed a polyclonal increase in immunoglobulins, with no paraprotein band present. Serum free light chain shows an elevated free Kappa/Lambda ratio of 1.97, while paired urine protein electrophoresis and immunofixation were negative. Serum immunoglobulins showed a modestly elevated immunoglobulin G (IgG) level at 1630 mg/dL, but normal IgA and IgM levels.

Otherwise, his coagulation profile, liver enzymes, renal function and electrolytes were within normal limits. A long Synacthen and thyroid function test performed was suggestive of primary adrenal insufficiency and subclinical hypothyroidism. JAK-2 gene mutation, anticardiolipin, lupus anticoagulant and tumor markers demonstrated negative results. The anti-nuclear antibody (ANA) titer was elevated at 1:320 with a homogenous pattern, but complement levels were normal

Excisional biopsy of the right cervical lymph node was suggestive of Castleman disease of mixed hyaline vascular and plasma cell variant (Figure 2). Furthermore, a bone marrow aspirate smear showed patchy hyper-normocellular marrow with 5% of plasma cells with mild plasmacytosis in the trephine sample, but no kappa and lambda light chain restriction (Figure 3A). Immunohistochemical staining for CD20 demonstrated aggregates of mature B-cells (Figure 3B), rimmed by plasma cells, which were highlighted with CD138 (Figure 3C). The presence of lymphoid nodules rimmed by clusters of plasma cells was suggestive of POEMS. To further support the diagnosis of Castleman disease variant of POEMS syndrome, the VEGF was markedly elevated (> 700 pg/mL).

Figure 2 Hematoxylin and eosin-stained lymph node biopsy with atretic germinal centres. Mantle zones thickened with lymphocytes arranged in layers give an onion skin appearance (white arrow).

Figure 3 Bone marrow trephine sample. A: Hyper-normocellular marrow with 5% plasma cells (orange arrow) and mild plasmacytosis; B: Aggregation of mature B-cells on CD20 immuno-histochemical stains; C: Rimmed clusters of medium to large plasma cells on CD 138 (× 20 magnification).

Imaging examinations

Plain computed tomography (CT) of the brain was done as a first-line radiological investigation. It revealed a well-defined hypodensity at the right frontoparietal lobe, suggestive of a chronic watershed region infarct (Figure 4).

Figure 4  Non-enhanced computed tomography brain (axial view) with well-defined hypodensity at right fronto-parietal lobe, suggestive of a chronic watershed region infarct (orange arrow).

Initial ultrasound of the abdomen showed grade 2 fatty liver with hepatosplenomegaly. The patient further underwent a contrast-enhanced CT (CECT) neck, thorax, abdomen and pelvis, which demonstrated multiple enlarged lymph nodes in the cervical, supraclavicular, axillary, paraaortic and bilateral inguinal regions (Figures 5 and 6). Some of these lymph nodes appeared matted, but without a necrotic center within. An esophagogastroduodenoscopy and colonoscopy showed pangastritis and gastropathy with low-grade tubular adenoma in the colon.

Figure 5 Contrast enhanced computed tomography neck. A: Axial computed tomography (CT) with multiple enlarged cervical and supraclavicular lymph nodes (arrows) and patent bilateral carotid and jugular vessels are highlighted within the blue dotted lines; B: Sagittal CT with similarly enlarged nodes as mentioned (arrows).

Figure 6 Contrast enhanced computed tomography thorax and abdomen. A: Axial view depicting enlarged lymph nodes at bilateral axillary region (arrows); B: Axial view at abdominal level showing lymphadenopathy at paraaortic region (arrow).

Subsequent positron emission tomography (PET) scan with CT (PET CT) done within 2 weeks from the previous CECT reveals stable multiple supra- and infra-diaphragmatic lymphadenopathies with background metabolism. However, there was a hypermetabolic left thyroid nodule seen, which corresponded to the heterogeneously enhancing left thyroid nodule in CT as depicted in Figure 7. There was also mildly hypermetabolic bone marrow in PET CT without an 18F-fluorodeoxyglucose (FDG)-avid bone lesion, which was of indeterminate clinical significance.

Figure 7 Positron emission tomography/computed tomography (level of the neck). A: Axial view showing hypermetabolic left thyroid nodule (arrows); B: Contrast enhanced computed tomography neck axial showing heterogeneously enhancing left thyroid nodule.

Serial nerve conduction studies demonstrated absent sensory response over bilateral radial and sural nerves, while other tested nerves showed prolonged distal sensory latency with reduced sensory nerve action potential, illustrated in Table 1. The motor response over the left radial and bilateral peroneal was absent. At the same time, the other tested nerves had significantly prolonged distal motor latency and reduced compound muscle action potential with conduction blocks over several nerves, as listed in Table 2, suggesting a generalized sensorimotor demyelinating polyneuropathy with conduction block.

Table 1 Sensory nerve conduction study.

Sensory NCS
Nerve/sites	Rec. site	Latency, ms	Amplitude, µV	Segments	Distance, cm	Vel., m/s
Left median - digit II (antidromic)
Wrist	Index	5.311	2.71	Wrist - index	14	34.9
Right median - digit II (antidromic)
Wrist	Index	5.421	5.61	Wrist - index	15	35.1
Left ulnar - digit V (antidromic)
Wrist	Dig V	4.641	4.41	Wrist - dig V	12	33.9
Right ulnar - digit v (antidromic)
Wrist	Dig V	5.101	4.01	Wrist - dig V	12	31.6
Left radial - superficial (antidromic)
Forearm	Wrist	NR1	NR1	Forearm - wrist	10	NR
Right radial - superficial (antidromic)
Forearm	Wrist	NR1	NR1	Forearm - wrist	10	NR
Left sural - (antidromic)
Calf	Ankle	NR1	NR1	Calf - ankle	14	NR
Right sural - (antidromic)
Calf	Ankle	NR1	NR1	Calf - ankle	14	NR

¹Abnormal results; normal ranges are based on the local population and adjusted for the patient’s height (1.69 m).

NR: No response; NCS: Nerve conduction study; Dig: Digit.

Table 2 Motor nerve conduction study.

Motor NCS
Nerve/sites	Muscle	Latency, ms	Amplitude, mV	Segments	Distance, cm	Velocity, m/s	Dur., ms
Left median – abductor pollicis brevis (APB)
Wrist	APB	5.731	4.01	Wrist - APB	8		8.81
Elbow	APB	16.06	1.8	Elbow - Wrist	24	23	10.52
Right median - abductor pollicis brevis (APB)
Wrist	APB	5.271	5.7	Wrist - APB	8		8.96
Elbow	APB	15.19	2.7	Elbow - Wrist	22	22	10.92
Left ulnar – abductor digiti minimi (ADM)
Wrist	ADM	4.481	4.51	Wrist - ADM	8		10.52
B. elbow	ADM	24.27	0.31	B. elbow - wrist	22	11	18.00
A. elbow	ADM	32.88	0.51	A. elbow - B. elbow	14	16	15.50
Right ulnar – abductor digiti minimi (ADM)
Wrist	ADM	4.501	3.91	Wrist - ADM	8		13.04
B. elbow	ADM	35.27	0.41	B. elbow - wrist	20	6	21.23
A. elbow	ADM	46.10	0.21	A. elbow - B. elbow	14	13	20.42
Left peroneal - extensor digitorum brevis (EDB)
Ankle	EDB	NR1	NR1	Ankle - EDB	8		NR
Right peroneal - extensor digitorum brevis (EDB)
B. fib head	EDB	NR1	NR1	B. fib head - ankle			NR
Left tibial – abductor hallucis (AH)
Ankle	AH	8.311	1.81	Ankle - AH	8		7.15
Knee	AH	26.15	0.91	Knee - ankle	40	22	8.46
Right tibial – abductor hallucis (AH)
Ankle	AH	7.401	1.51	Ankle - AH	8		6.65
Knee	AH	26.29	0.31	Knee - ankle	37	20	8.56
Left peroneal - tibialis anterior (TA)
Fib head	Tib Ant	4.33	2.41	Fib head - tib ant			14.77
Pop fossa	Tib Ant	6.58	2.2	Pop fossa - fib head	10	44
Right peroneal - tibialis anterior (TA)
Fib head	Tib Ant	6.191	2.31	Fib head - tib ant
Pop fossa	Tib ant	8.38	2.0	Pop fossa - fib head	6	27	14.71
Left radial – extensor indicis propius (EIP)
Forearm	EIP	NR1	NR1	Forearm - EIP			NR
Elbow	EIP	NR1	NR1	Elbow - forearm	14	NR	NR
Spiral Gr	EIP	NR1	NR1	Spiral Gr - elbow	13	NR	NR
Right radial – extensor indicis propius (EIP)
Forearm	EIP	3.041	3.5	Forearm - EIP			9.44
Elbow	EIP	6.00	2.2	Elbow - forearm	10	34	9.06
Spiral Gr	EIP	8.69	2.7	Spiral Gr - elbow	10	37	9.52

¹Abnormal results; normal ranges are based on the local population and adjusted for the patient’s height (1.69 m).

NR: No response; NCS: Nerve conduction study; APB: Abductor pollicis brevis; ADM: Abductor digiti minimi; B: Below; A: Above; EDB: Extensor digitorum brevis; AH: Abductor hallucis; TA: Tibialis anterior; Fib: Fibular; Pop: Popliteal; EIP: Extensor indicis propius; Gr: Groove.

FINAL DIAGNOSIS

A diagnosis of Castleman disease variant of POEMS syndrome, without detectable M-proteins, was made based on the clinical and investigation findings.

TREATMENT

He received melphalan plus dexamethasone, followed by three cycles of cyclophosphamide with dexamethasone while awaiting the availability of lenalidomide. Bortezomib was not administered, considering the existing severe neuropathy. Given that the serum testosterone level was low, testosterone replacement was prescribed monthly. The long-term plan was to proceed with an autologous stem cell transplant (ASCT) once adequate control of the disease was attained.

OUTCOME AND FOLLOW-UP

His treatment was complicated with a new-onset post-infarct seizure requiring antiseizure medication, as well as a left upper limb swelling due to a long-segment basilic vein thrombosis, necessitating anticoagulation. During the ensuing 5 months post-chemotherapy, the patient generally improved, most notably a reduction in skin pigmentation, improved muscle power and resolving fluid retention. Considering his clinical improvement and the cost of tests that require outsourcing (VEGF), we did not arrange for a follow-up study.

Unfortunately, before the planning phase for ASCT, he was admitted with severe sepsis, which was further complicated by a left middle cerebral artery territory stroke, and he succumbed to his illness soon after.

DISCUSSION

Neuropathy-primary symptom

Our patient was admitted with neuropathy with the onset of symptoms dating several months back. Similar to reported literature, he experienced cramps and spasms in his extremities before they progressed proximally[8]. Subsequently, patients develop hyperesthesia and dysesthesia with weakness, experiencing difficulty climbing stairs and reduced grip strength[8,9]. The clinical course of the disease spans from days to weeks or weeks to months[8].

Differential diagnoses

CIDP: CIDP is similar in many aspects, characterized by immune-mediated, motor and sensory, chronic and progressive neuropathy with polyradicular features (distal and proximal involvement) and may be misdiagnosed in 60% of POEMS syndrome cases[10,11]. Several clinical features in favor of Castleman disease variant of POEMS syndrome are the painful and severe neuropathy experienced, with a greater degree of sensorimotor impairment, as the unmyelinated C fibers are commonly well-preserved as opposed to those with CIDP, although this is arbitrary[10,12]. Cranial nerve involvement and dysautonomia are also far less common in patients with this variant of POEMS syndrome. Non-invasively, nerve conduction studies of patients with POEMS syndrome demonstrate conduction slowing predominantly in the intermediate nerve segments than distally, rarely conduction block and a more severe attenuation of lower limb compound muscle action potentials than the upper limbs[11,13]. Histologically, nerve biopsy in POEMS syndrome shows higher rates of axonal degeneration, diffuse myelinated nerve fiber loss and increased numbers of small epineural blood vessels, compared to CIDP showing greater endoneural inflammation, multifocal myelinated fiber loss and onion bulb formations[10].

Multiple myeloma: Castleman Disease variant of POEMS syndrome is associated with underlying plasma cell disorders. Differential diagnosis should include multiple myeloma, which may present with neuropathy as well. Distinguishing between these pathologies is essential as treatment and prognosis differ[4]. Multiple myeloma tends to present with bone pain, anemia, hypercalcemia, extensive infiltration of bone marrow by plasma cells, or renal failure, which is uncommon in the Castleman disease variant of POEMS[14]. Furthermore, imaging would demonstrate the presence of lytic bone lesions instead of sclerotic lesions and without marked elevation in VEGF levels, as seen in POEMS[4].

Paraneoplastic syndrome: Castleman disease variant of POEMS syndrome can closely mimic or coexist with paraneoplastic syndromes, making accurate differentiation essential. Paraneoplastic syndromes present as secondary manifestations of an underlying malignancy mediated by immune mechanisms or ectopic hormone or cytokine production. In contrast, Castleman disease variant of POEMS syndrome represents an underlying plasma cell dyscrasia, with disease biology driven predominantly by VEGF, although inflammatory cytokines may also be elevated[15].

In this context, a diagnosis of Castleman disease variant of POEMS syndrome is favored when imaging demonstrates diffuse, fluorodeoxyglucose-avid lymphadenopathy without evidence of a discrete occult primary tumor, which would otherwise support a paraneoplastic etiology.

Immunoglobulin G4-related disease: Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is another important diagnostic consideration, as it may present with lymphadenopathy and systemic symptoms that overlap with those of Castleman Disease variant of POEMS syndrome. Demographically, IgG4-RD tends to affect older patients, with a mean age in the sixth decade, whereas Castleman disease variant of POEMS syndrome commonly presents earlier, in the fourth to fifth decades of life[15,16]. In contrast to the systemic inflammatory manifestation in Castleman disease variant of POEMS syndrome, IgG4-RD characteristically forms localized inflammatory “pseudotumor” involving organs such as the pancreas, salivary glands, lacrimal glands, and kidneys, and is often associated with atopic or allergic conditions[16]. Castleman disease typically exhibits markedly elevated inflammatory markers, including C-reactive protein, erythrocyte sedimentation rate, and serum IL-6 levels, whereas these markers are comparatively lower in IgG4-RD[15]. Therapeutically, IgG4-RD often responds well to corticosteroid monotherapy, whereas Castleman disease variant of POEMS syndrome generally requires treatment directed at plasma cell disorders to achieve disease control[15].

Amyloid light chain or primary amyloidosis: Amyloid light chain or primary amyloidosis (AL amyloidosis) and Castleman disease variant of POEMS syndrome represent distinct but occasionally overlapping conditions. AL amyloidosis is a clonal plasma cell dyscrasia characterized by tissue deposition of monoclonal light-chain amyloid fibrils[17], while Castleman disease is driven by VEGF-mediated effects rather than primary amyloid deposition. Clinically, patients with AL amyloidosis manifest symptoms related to organ dysfunction caused by amyloid deposition, most commonly affecting the heart, kidneys, or peripheral nerves[17]. Imaging findings further differentiate the two entities: Castleman disease shows diffuse, highly FDG-avid lymphadenopathy on positron emission tomography, whereas AL amyloidosis demonstrates organ-specific infiltration, such as myocardial thickening on echocardiography or cardiac magnetic resonance imaging[17].

Diagnostic challenges

Our patient, however, did not fulfil the mandatory criteria of monoclonal plasma cell disorder, demonstrating a polyclonal gammopathy. This is despite having polyneuropathy and fulfilling 3 major criteria (polyneuropathy, Castleman disease and VEGF elevation) and 6 minor criteria (organomegaly, extravascular volume overload, endocrinopathy, skin changes, papilledema and thrombocytosis). However, our patient did display multiple endocrinopathies as seen in POEMS, involving four major endocrine axes (gonadal, thyroid, glucose and adrenal) necessitating hormonal replacement, as well as recurrent episodes of strokes due to his hypercoagulable state by virtue of the thrombocytosis and plasma cell proliferation.

M-protein negative variant

Although the presence of a monoclonal plasma cell disorder is a mandatory criterion for the diagnosis of POEMS syndrome, rare cases have been reported in the literature where patients exhibit typical clinical and laboratory features (polyneuropathy, elevated VEGF, multiple major and minor criteria) but lack a demonstrable monoclonal gammopathy[18]. There were recent cases of M-protein-negative variants that demonstrated successful management with lenalidomide and dexamethasone (RD), similar to the classic M-protein-positive entity. For instance, Du et al[19] described two patients in their 60s and 70s who presented with hallmark POEMS symptoms but lacked monoclonal protein; both achieved clinical and laboratory remission following RD treatment. Similarly, a 2024 report by Ji et al[20] documented a patient with a comprehensive constellation of symptoms, including polyneuropathy, organomegaly, and sclerotic bone lesions, who showed significant improvement on the same regimen despite the absence of a detectable M-protein. These atypical cases may pose diagnostic challenges due to low tumor burden or plasma cell clones below the threshold for detection. These cases should be frequently monitored and treated as POEMS based on their clinical picture, especially when VEGF levels are significantly elevated, and other causes of neuropathy have been excluded[21]. It also highlights the need for longitudinal studies to monitor for future monoclonal protein development and the necessity of re-evaluating current diagnostic nomenclature and criteria.

Role of VEGF

In the Castleman disease variant of POEMS, VEGF links the plasma cell disorder and its diverse manifestations. VEGF overproduction represents the dominant pathogenic mediator rather than an interleukin-6–driven cytokine storm. Pathophysiologically, VEGF acts as a potent pro-angiogenic factor that increases vascular permeability, directly leading to extravascular fluid overload, as evidenced by edema, ascites, and organomegaly. Furthermore, it causes endoneural edema, leading to polyneuropathy[4]. As this variant lacks a detectable M-protein, elevated serum VEGF remains the most reliable biomarker for confirming the diagnosis and monitoring the efficacy of treatment.

Treatment and management

There’s currently no standard therapy for the Castleman disease variant of POEMS syndrome[20]. The principle of treatment is based on the degree of plasma cell infiltration[5,9,22]. Targeted radiotherapy is favored for isolated sclerotic bone lesions (up to 3) without marrow involvement, and is associated with a 10-year survival rate of 70%[5,9,22]. Extensive osteoporotic lesions or bone marrow involvement would require systemic chemotherapy. High-dose melphalan in combination with ASCT, and lenalidomide with dexamethasone are examples of effective systemic regimes. Two prospective studies of lenalidomide with dexamethasone achieved a remission rate of over 70% and a 3-year progression-free survival rate of 60%-75%[23,24]. Other treatment regime may include thalidomide and bortezomib, which are agents with anti-VEGF and anti-TNF effects[4,22].

Supportive therapy such as physical therapy, continuous positive airway pressure, analgesics for neuropathic pain, psychological support as well as orthotics, positively influence overall long-term outcomes and wellbeing[4,22]. Endocrinopathies may require hormone replacement therapy, with thyroxine or steroids, as in our case, to address hypothyroidism and adrenal insufficiency. Subsequent follow-up should include an echocardiogram and diffusing capacity for carbon monoxide every six months for those receiving systemic chemotherapy to monitor its side effects. PET CTs could be used to assess for relapses based on availability of facility[4,22].

Disease outcome

Castleman disease variant of POEMS syndrome leads to a significant deterioration in quality of life through neuropathy, fluid retention, thromboembolic events and cachexia. Patients frequently succumb to the illness due to respiratory and circulatory failure, progressive malnutrition, infection and kidney failure. Good prognostic factors include albumin > 3.2 g/dL, attaining complete hematological response, and a younger onset of disease[4,22]. Poor prognostic factors include age greater than 50 years, presence of pleural effusion, severe renal impairment and pulmonary hypertension[4,22].

CONCLUSION

Castleman disease variant of POEMS syndrome remains a diagnostic and therapeutic challenge. We highlight this case to raise awareness of prompt full diagnostic work-up and a multidisciplinary approach in order to reduce long-term irreversible morbidity and mortality.

ACKNOWLEDGEMENTS

The authors would like to take this opportunity to extend our thanks to the patient and his caregivers for granting us permission to publish his case for the benefit of the medical community.