IgG4 producing POEMS syndrome: A rarely recognized subtype.

Serum IgG4 is typically measured for Immunoglobulin G4-related Disease (IgG4-RD), a fibroinflammatory condition associated with polyclonal increase in serum IgG4. Yet, increased IgG4 may still be monoclonal, and little is known about IgG4 POEMS syndrome. We present a case of 40-year-old male with a mass lesion in the left sacral ala. The mass was composed of non-neoplastic fibrous tissue and dense infiltrate of mature plasmacytes with dense eosinophilic cytoplasm and eccentrically placed nuclei that express monoclonal Lambda free light chains and show diffuse positivity for IgG and IgG4. We discuss clinical manifestations and challenges encountered in the diagnosis and treatment of this rare coexistence.

[POEMS Syndrome: Nosographic classification and considerations on a clinical case].

POEMS syndrome is a rare multisystemic disease characterised by the coexistence of two main symptoms, polyneuropathy and monoclonal gammopathy, associated with minor symptoms such as organomegaly, endocrinopathy, and skin changes. We describe a patient who presented with symptoms and signs fulfilling the criteria of POEMS. We have carried out a literature review with particular emphasis on its demographic and polymorphic clinical features.

[Multicentric hyaline vascular Castleman's disease. A POEMS type variant]. / Enfermedad de Castleman multicéntrica hialina vascular. Una variante de POEMS.

BACKGROUND: Castleman's disease is an atypical lymphoproliferative disorder which may be compatible with paraneoplastic manifestations of POEMS syndrome. CLINICAL CASE: a 53 year old man with a history of type 2 diabetes, hypothyroidism and Addison's disease presented with numbness and weakness in limbs, dyspnea, skin hardening, Raynaud's phenomenon, weight loss and fatigue. A physical exam showed tachypnea, generalized cutaneous hyperpigmentation and skin hardening of extremities, muscle weakness, hypoesthesia and hyporeflexia. Laboratory showed hyperprolactinemia, low testosterone, hypothyroidism and Addison's disease. Electrophoresis of proteins showed polyclonal hypergammaglobulinemia. Somatosensory evoked potentials reported peripheral neuropathy and severe axonal polyneuropathy by electromyography. Chest X-rays showed bilateral reticular infiltrates and mediastinal widening. An echocardiogram displayed moderate pulmonary hypertension. Skin biopsy had no evidence of scleroderma. CT reported axillar, mediastinal and retroperitoneal nodes. The mediastinal lesion biopsy reported hyaline vascular Castleman's disease, multicentric variety. He was treated with rituximab. CONCLUSIONS: the case meet criteria for multicentric hyaline vascular Castleman's disease, POEMS variant, treated with rituximab.

Introducción: la enfermedad de Castleman es un trastorno linfoproliferativo atípico en el que pueden existir manifestaciones compatibles con síndrome POEMS. Caso clínico: hombre de 53 años de edad con antecedente de diabetes mellitus tipo 2, hipotiroidismo y enfermedad de Addison. Se iniciaron parestesias y debilidad en las extremidades y, posteriormente, disnea, endurecimiento cutáneo, fenómeno de Raynaud y pérdida de peso. Se identificó taquipnea, hiperpigmentación cutánea generalizada y extremidades con endurecimiento cutáneo, debilidad muscular, hipoestesia e hiporreflexia; así como hiperprolactinemia, testosterona baja, hipotiroidismo y enfermedad de Addison; los anticuerpos antinucleares y antiScl-70 fueron negativos. Los potenciales evocados somatosensoriales indicaron neuropatía periférica y la electromiografía, olineuropatía axonal severa. Radiografía torácica: infiltrado reticular bilateral y ensanchamiento mediastinal. Electrocardiograma: hipertensión arterial pulmonar moderada. Tomografía toracoabdominal: ganglios axilares, mediastinales y retroperitoneales. Con la biopsia se identificó enfermedad de Castleman multicéntrica hialina vascular. El paciente recibió rituximab. Conclusiones: si bien la experiencia con el rituximab aún es limitada, en el caso descrito se observó buena respuesta.

POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) syndrome in China.

BACKGROUND/AIM: The clinical characteristics of POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) syndrome in China are largely unknown. This work thus studied the clinical manifestations of POEMS syndrome in China. METHODS: We retrospectively reviewed the medical records of 82 patients with POEMS syndrome in our hospital and made a comparison with those reported outside China. RESULTS: There were 82 patients. Forty (49%) were 45 years old or younger. Sensorimotor deficits were the common initial symptoms. The clinical manifestations are as follows: (i) peripheral neuropathy and abnormal electromyogram were seen in all patients (100%); (ii) organomegaly was present in 72 patients (88%); 61 of them (74%) had splenomegaly; (iii) endocrinopathy was present in 74 cases (90%); hypothyroidism was seen in 51 of 70 patients (73%); (iv) 60 patients (73%) had monoclonal plasmaproliferative disorder; only 22 of 40 (55%) had M-protein; (v) skin changes were seen in 71 patients (87%); (vi) 68 patients (83%) had oedema and effusions; of these, hydropericardium was seen in 23 patients (28%); (vii) 35 of 55 patients (64%) had abnormal electrocardiogram and only 21 of 46 (46%) had bone lesions in X-ray. CONCLUSIONS: POEMS syndrome in China has its own distinctive features, parts of which are commoner in the young people, the higher frequency of splenomegaly, hypothyroidism, hydropericardium and abnormal electrocardiogram, as well as the lower M-protein and bone lesions in X-ray.

POEMS syndrome: failure of newly suggested diagnostic criteria to anticipate the development of the syndrome.

POEMS syndrome is a unique clinical entity. Although it's a diagnosis of exclusion, it was previously described by the presence of several typical characteristics as paraproteinemia, polyneuropathy, organomegaly, endocrinopathy, and skin changes. Recently, new criteria were proposed, and the presence of two major and one minor criterion was claimed to suffice for a diagnosis. Both methods considered other important characteristics germane to the syndrome unessential for diagnosis. Retrospective evaluation of patients with lymphoproliferative disease was carried out to reveal the presence of the syndrome according to these different methods. Patients' clinical progression during follow-up will be used to validate the criteria's sensitivity and specificity. Six hundred twenty-nine consecutive files of patients with paraproteinemia who were followed-up at a tertiary medical center were reviewed. Of 12 patients who fulfilled the new criteria for diagnosis of POEMS, 3 remain stable during long-term follow-up and only 5 finally developed the full-blown syndrome. Four patients developed other diseases that accounted for their clinical findings. Patients presenting with neuronal vasculitic changes on biopsy, kappa light-chain monoclonal gammopathy, and cryoglobulinemia were unlikely to develop POEMS syndrome, even though they fulfilled the newly suggested criteria. Although they are not in the criteria, sclerotic bone lesions were found only in patients who eventually developed the full syndrome. The diagnosis of POEMS syndrome according to the newly suggested criteria should not be definitive in the presence of atypical clinical features of the syndrome.

POEMS syndrome: experience with fourteen cases.

The POEMS syndrome, also known as Crow-Fukase disease, is a rare multisystem disorder, which may take several years to evolve fully. The combination of symptoms and signs is highly complex and some of the features are detected at sub-clinical level requiring high level of suspicion. The clinical data on POEMS is still evolving with only a few case reports from India. Herein, we report a series of 14 cases with POEMS syndrome at our centre over the past 8 years, which were analysed retrospectively for their clinical features, response to therapy and treatment outcome. Presence of plasma cell dyscrasia (PCD) was essential for inclusion in this study. Confirmation of PCD was done by positive "M" spike in serum and/or urine, bone marrow plasmacytosis or presence of plasmacytoma on biopsy. In addition, the diagnosis of POEMS syndrome needed the presence of at least two of the following features: polyneuropathy, organomegaly, endocrinopathy and/or skin changes. Patients were excluded from study if there was a secondary cause of polyneuropathy like amyloidosis, drugs like vincristine, nerve root or spinal cord compression. Two patients had complete form (all five features) of the syndrome, whereas 12 had incomplete form. Median age was 48 years (range 32-65). Peripheral neuropathy was seen in 13 (92.85%) cases, organomegaly 10 (71.42%), endocrinal involvement 7 (50%) and skin changes 9 (64.28%). An association with Castleman's disease and vasculitis was also noted. With different chemotherapy protocols, all treated patients (n = 12), had significant symptomatic improvement with or without objective improvement at median follow up of 48 months (range 6-120). In conclusion, high level of suspicion is required to detect this rare entity.

The AESOP (adenopathy and extensive skin patch overlying a plasmacytoma) syndrome: report of 4 cases of a new syndrome revealing POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) syndrome at a curable stage.

We describe an easily recognizable and previously not individualized clinical syndrome that can reveal solitary plasmacytoma of bone. We report 4 patients with a slowly extending violaceous skin patch overlying a solitary plasmacytoma of bone, associated with enlarged regional lymph nodes. Biopsies of the cutaneous lesion and the lymph nodes were not specific, although increased dermal mucin deposition and vascular proliferation were present in all skin specimens. Three patients had associated polyneuropathy. One patient had POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, and Skin changes) syndrome at the time the plasmacytoma was diagnosed. Another patient developed POEMS syndrome, from which he died, 4 years after excision of the plasmacytoma. The 3 other patients were treated either with irradiation or with a combination of irradiation and surgery, and recovered completely, including from the associated neuropathy and/or POEMS syndrome. We suggest calling this unique and distinctive clinical presentation the for

[POEMS syndrome--a case report]. / Das POEMS Syndrom--Ein Fallbericht.

One rare case of POEMS syndrome is presented. In a 39-year-old male patient a progressive numbness in hands and feet developed within 5 years. Admission with increasing dyspnoea and lower leg edema. In swollen inguinal lymph nodes a lymphadenopathy with angiofollicular hyperplasia and vascular-plasmacellular proliferation was diagnosed and classified as Castleman-like histologic features. In os ilium an osteosclerotic plasmocytoma with restriction of kappa light chains was found. Potential pathomechanism of POEMS syndrome are discussed.

[POEMS syndrome]. / Le POEMS syndrome.

POEMS syndrome is an acronym defined by Bardwick (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal component and Skin changes). Other various clinical and biological features are reported: edema, cachexia, microangiopathic glomerulopathy, most rarely pulmonary hypertension, cutaneous necrosis. Thrombocytosis or polycythemia may be a prominent feature. POEMS syndrome is sometimes associated with lymphoproliferative disorder. Castelman-like disease is frequently observed as pathologic findings on lymph nodes. Distinction between POEMS syndrome and osteosclerotic myeloma is delicate. The rate of the monoclonal protein is modest-always less than 30 g/L-and is almost of the lambda light chain class. In contrast to multiple myeloma this syndrome is rarely associated with hypercalcemia, skeletal fracture, renal involvement and increasing of M component during evolution. Bone marrow plasmocytosis is usually less than 15% and the kinetic phenotype and genetic characteristics of the plasma cell remain those found in monoclonal gammopathy of undetermined significance. The pathophysiology of this syndrome remains largely unknown but overproduction of pro-inflammatory cytokines are reported, especially TNF alpha, IL-6 and IL-1 beta. Some clinical manifestations seem to be cytokine related. Polyneuropathy and cachexia are the main cause of death. A part corticosteroid and cure of solitary bone lesion, treatment is disappointing and survival is 60% at five years.

Síndrome de Poems

Una forma poco común de discrasia de células plasmáticas asociada a polineuropatía, organomegalia, endocrinopatía, proteína monoclonal y cambios de piel ha recibido el nombre de POEMS. Informamos un caso de una paciente con mieloma múltiple asociado a amiloidosis y hallazgos clínicos de polineuropatía, hepatoesplenomegalia, intolerancia a los carbohidratos, pico monoclonal e hiperpigmentación que configuran el diagnóstico del síndrome de POEMS. Es el primer caso descrito en nuestro país y el cuarto en Latinoamérica.

Plasma-cell dyscrasia with polyneuropathy. The spectrum of POEMS syndrome.

BACKGROUND: The POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome and osteosclerotic myeloma (polyneuropathy and sclerotic bone lesions) may both be manifestations of plasma-cell dyscrasia, but the interrelation of these diseases is not clear. We therefore set out to define the clinical spectrum of disease in patients with plasma-cell dyscrasia and polyneuropathy who have the complete or incomplete form of the POEMS syndrome or osteosclerotic myeloma. METHODS: Among 2714 patients with plasma-cell dyscrasia who were identified between 1973 and 1989, we reviewed the cases of those with polyneuropathy and plasma-cell dyscrasia who fulfilled the criteria for the POEMS syndrome or osteosclerotic myeloma. RESULTS: Thirty-eight patients (1.4 percent) with a median age of 51 years were identified, 22 of whom were male. By definition, all had polyneuropathy (37 combined sensorimotor, and 1 primarily motor). Other findings included osteosclerotic bone lesions (82 percent), skin abnormalities (58 percent), lymphadenopathy (42 percent), papilledema (37 percent), peripheral edema (29 percent), hepatomegaly (24 percent), splenomegaly (21 percent), and ascites (11 percent). Thirty-three patients (87 percent) had an abnormal M protein in serum or urine (17 had IgA lambda, and 12 IgG lambda). Five patients fulfilled all the criteria for the POEMS syndrome. The estimated five-year survival in the 38 patients was 60 percent, which was significantly better than the 20 percent survival in 869 patients with multiple myeloma (P < 0.05). The clinical course was similar among the patients with the complete form of the POEMS syndrome and those with the incomplete form. CONCLUSIONS: Plasma-cell dyscrasia with polyneuropathy is a rare multisystem disease that often presents with osteosclerotic bone lesions. The differentiation of the POEMS syndrome from so-called osteosclerotic myeloma with peripheral neuropathy appears to have no clinical value.