POEMS syndrome with undetectable M-protein: a case report and literature review.

BACKGROUND: Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a rare plasma cell (PC) neoplasm with associated paraneoplastic syndrome. According to the current diagnostic criteria, peripheral polyneuropathy and monoclonal PC proliferative disorder represent two mandatory criteria. CASE PRESENTATION: We report a 54-year-old male with peripheral neuropathy of bilateral lower limbs, sclerotic bone lesions, elevated vascular endothelial growth factor (VEGF) levels, splenomegaly, extravascular volume overload, endocrinopathy, and skin hemangiomas. Of note, serum and urine protein electrophoresis (PEP) and immunofixation electrophoresis (IFE) of this patient indicated undetectable M-protein and the normal ratio of free light chains κ and λ (FLC-R (κ/λ)). No monoclonal PCs were found in bone marrow examinations or biopsy of diseased bones. However, his clinical manifestations matched most of the diagnostic criteria. After excluding other diseases that are easily confused with POEMS syndrome, the diagnosis of variant POEMS syndrome with undetectable M-protein was proposed. The patient obtained clinically significant improvement and elevated VEGF returned to normal after 6 months of treatment with lenalidomide plus dexamethasone. CONCLUSIONS: Monoclonal PC dyscrasia (M-protein) while being a mandatory criterion for POEMS syndrome is undetectable in a considerable amount of patients that otherwise demonstrate typical symptoms. Here, we reported a case of variant POEMS syndrome with featured clinical manifestations, elevated VEGF levels, and good response to therapies targeting PCs but no evidence of M-protein. Therefore, negative results in M-protein and monoclonal PCs aren't enough to reject the diagnosis of POEMS syndrome. It is imperative to recognize the variant form of POEMS syndrome.

Distribution and clinical features of primary immunodeficiency diseases in Chinese children (2004-2009).

Two hundred and one patients have been diagnosed with primary immunodeficiency diseases (PIDs) in our center from January 2004 to December 2009. The male-to-female ratio was 5.29:1. Spectrums of PIDs were as follows: predominantly antibody deficiency disease was the most common category (94 patients, 48.2%), followed by other well-defined immunodeficiency syndromes (40 patients, 20.5%), combined T and B cell immunodeficiencies (33 patients, 16.9%), congenital defects of phagocyte number and/or function (21 patients, 10.8%), and diseases of immune dysregulation (six patients, 3.1%). Agammaglobulinemia was the most frequent disease type. The median of diagnosis lag was 18.0 months. Pneumonia was the most common manifestation of PID patients. Some manifestations were prone to concentrate in certain diseases. As for therapy, 99 patients (50.8%) received intravenous immunoglobulin replacement therapy; 13 patients received hematopoietic stem cell transplantation and nine of them were still alive. In this study, we sought to describe and analyze the distribution, clinical features, and therapy methods of PIDs among children diagnosed in our country and to compare with reports from other countries and regions.

[Overview of clinical occurrence of primary immunodeficiency disorders in children].

OBJECTIVE: More than one hundred primary immunodeficiency disorders have been discovered so far. But the incidence of these disorders in our country is still not clear, so we analyzed the clinical data of 93 children with primary immunodeficiency disorders seen in our hospital in recent 30 years to understand the occurrence of primary immunodeficiency disorders in children, to promote the clinicians to become familiar with these disorders, to improve the nationwide registry system and to establish the basis for the treatment and prevention in future. METHODS: To analyze the constituent ratio of the 93 children with primary immunodeficiency disorders seen in our hospital from 1974 to 2003, diagnostic and classification criteria were set by taking the proposal by International Union of Immunological Societies (IUIS) PID classification committee in 2003 into account. All the data were analyzed retrospectively. RESULTS: In the 93 children with primary immunodeficiency disorders, antibody deficiencies were the most frequent (39.8%) finding, followed by combined immunodeficiency, combined T- and B-cell disorders (22.6%), and T lymphocytic deficiencies alone (14.0%). Immunodeficiency with other major defects accounted for 12.9%, phagocytic disorders 9.7%, and complement deficiencies 1.1%. Thus, there seemed to be a tendency that the incidence increased with time. The incidence of these disorders has increased significantly as shown by 50 diagnosed cases in children with these disorders since 1996. Sixteen children died, with the highest mortality occurred with combined immunodeficiency. Seven children developed bronchiectasis. Two children suffered from persistent diarrhea while one of the two was complicated with persistent intestinal fistula. One child developed juvenile rheumatoid arthritis, another one with granulocytopenia and iridocyclitis, and the other with allergic purpura. The boys: girls ratio for all disorders was 3:1. The age of onset ranged from 10 days to 37 years of age. CONCLUSIONS: There are vast variety of primary immunodeficiency disorders in our area and antibody deficiency is the most common abnormality. Combined immunodeficiency has early onset age and high mortality rate. With the great improvement of the diagnostic techniques, these disorders have become a group of important disorders and all the clinicians should pay great attention to these disorders.

[Mechanism of inhibitory effect of intravenous immunoglobulin on neonatal umbilical cord blood lymphocytes].

OBJECTIVE: The expression of CD25, CD45RA, CD45RO on umbilical cord blood mononuclear cells (CBMCs) and CD3(+) T lymphocytes was investigated to explore the mechanism of immunosuppressive effects of intravenous immunoglobulin on neonatal immune function. METHODS: Umbilical cord blood mononuclear cells and CD3(+) T lymphocytes isolated from 8 neonates were studied. The expression of CD25, CD45RA, CD45RO on umbilical cord blood mononuclear cells (CBMCs) and CD3(+) T lymphocytes induced with various stimuli of different combinations of IVIG and phytohemagglutinin (PHA) including (1) control group, (2) PHA activation group, (3) IVIG pre-inhibition group, (4) PHA pre-activation group, (5) PHA+IVIG group was measured with four-color immunofluorescence antibodies staining-flow cytometric technique. The results were also compared with peripheral blood mononuclear cells of 8 adults (PBMCs). RESULTS: IVIG inhibited the PHA-induced proliferation of CBMCs as reflected by the decreased expression of CD25 and CD45RO. The amounts of CD25(+) and CD4(+)CD45RO(+) CBMCs reached 77.52% +/- 2.31% and 64.29% +/- 3.09% after PHA use. But a decreased response in CD25(+) (7.66% +/- 1.20% and 7.78% +/- 1.46%) and CD4(+)CD45RO(+) CBMC (3.18% +/- 1.90% and 3.11% +/- 0.08%) was observed when IVIG was added in both IVIG pre-inhibition group and PHA+IVIG group. As compared with PBMCs, IVIG failed to induce the increase of the expression of CD45RA in CBMCs whereas CD45RA(+) PBMCs increased from 54.93% +/- 3.63% to 72.77% +/- 0.39% in IVIG pre-inhibition group. Moreover, IVIG inhibited the expression of CD25 and CD45RO on cord blood CD3(+) T lymphocytes no matter whether they were activated with PHA or not. The amounts of CD25(+) and CD4(+)CD45RO(+) CD3(+) T lymphocytes reached 97.92% +/- 2.19% and 80.41% +/- 5.57% after PHA use. But a decreased response in CD25(+) CBMCs (77.29% +/- 0.63%, 51.48% +/- 1.85% and 62.73% +/- 1.24%) and CD4(+)CD45RO(+) CD3(+) T lymphocytes (35.47% +/- 2.55%, 40.14% +/- 1.16% and 36.41% +/- 2.96%) was observed when IVIG was added in IVIG pre-inhibition group, PHA pre-activation group and PHA+IVIG group, and the degree of inhibition of IVIG on cord blood CD3(+) T lymphocytes was much lower than that of CBMCs. CONCLUSIONS: Cord blood T lymphocytes activation was inhibited by IVIG through the inhibition of CD25(+) CBMCs expression and the prevention of transformation from CD4(+)CD45RA(+) cells into CD4(+)CD45RO(+) cells. This IVIG-mediated suppression of activation in cord blood T cells may be derived from the indirect effect of other immune cells or molecules other than the direct effects on T cells. IVIG failed to induce the increase of expression of CD45RA in CBMCs, which may be related to the fact that majority of CBMCs were CD45RA(+) cells, but this may not rule out that the immunosuppressive effect of IVIG could be accomplished by the increase of CD45RA(+) cells in adult peripheral blood mononuclear cells. The suppressive effect of IVIG on CD4(+)CD45RO(+) T lymphocytes may account for its inhibitory effect on immunoglobulin production of neonates' B cells. Considering that naïve CD45RA(+) cells dominate in neonates and IVIG can inhibit transformation from CD4(+)CD45RA(+) cells into CD4(+)CD45RO(+) cells, it is recommended that IVIG should be used properly in neonates, otherwise it may deteriorate their poor immune function especially when it is used for prophylaxis or as a treatment of neonatal non-infectious diseases, and its immunosuppressive action will increase the susceptibility of neonates to infection.

[Reactivity and antigenic cross-reactivity of latex in children with allergic disorders].

OBJECTIVE: To explore the relationship between latex allergen and clinical presentation as well as allergenic cross-reactivity between latex and other allergens, to know the incidence of latex allergy in Chinese children and elucidate the allergenic cross-reactivity of latex with other allergens. METHODS: Totally 265 children with allergic disorders were assayed with 13 international standard allergen agents by means of SPT. RESULTS: In 79 children with latex allergenic SPT position, 53 were boys and 26 were girls with an average age of 5.6 years, and 14 cases had episodes occurred in winter, 14 cases in spring, 24 cases in summer, and 27 cases in autumn. Of them, 66 cases presented as asthma, 5 cases atopic skin disorders, 1 case anaphylactoid purpura, 1 case hives and 6 cases only had mild cough. Statistical analysis showed that the positive percentage of the latex SPT had no obvious relation with sex and age, but was higher in summers and autumns than in winters and springs (P < 0.01). Children with allergic symptoms had higher positive rate in latex allergenic SPT than those without them, that is, the positive percentage of the latex SPT significantly increased among children presenting with some allergic symptoms, such as asthma, hives and atopic skin disorders (P < 0.01). All the children with latex allergenic SPT position had cross-reactivity with acarid allergen, 62.0% approximately 43.0% with animal protein allergens including milk, cats, shrimp, dogs, eggs in the order of decreasing cross-reaction rate, and 10.1% - 3.8% with mold and plant farina allergens. But the cross-reactivity between latex and mold or tree farina I were not statistically significant. CONCLUSION: Thirty percent of the children with allergic disorders were latex allergenic SPT positive. Latex allergenic SPT positive results were significantly correlative to allergic clinical presentation and season, while were not relative to sex and age. The cross-reactivity of latex with acarid was most common, followed by animal protein allergens, while the cross-reactivity with mold and plant farina allergen was rare.