Coronary aneurysms in infants and young children with acute febrile mucocutaneous lymph node syndrome.

In 1967, Kawasaki, in Japan, first described a new syndrome affecting infants and young children-an acute, febrile illness with mucocutaneous involvement associated with swelling of cervical lymph nodes. The prognosis is usually good but recently it has become evident that 1-2 percent of the patients die suddenly from acute heart failure. Infantile polyarteritis (nodosa-like arteritis) accompained by coronary aneurysm and thrombosis has been noted in postmortem examinations. Twenty patients surviving the illness were examined by coronary angiography; 12 of the 20 had abnormal coronary angiograms; seven patients had coronary aneurysms. Complete regression of the coronary aneurysms was proved in two patients at subsequent angiography. One patient developed mitral regurgitation as a result of papillary muscle dysfunction. One had a coronary aneurysm without symptoms two years after the onset of illness.     

Elevated levels of immunoglobulin E in the acute febrile mucocutaneous lymph node syndrome.

Mucocutaneous lymph node syndrome (MCLS) is a newly recognized disease characterized by fever persisting for more than 5 days, an erythematous skin eruption, conjunctival congestion, dry red fissured lips, reddened tongue, palms, and soles, nonpurulent lymphadenopathy, and sometines diarrhea, arthralgia, and aseptic meningitis. Additional features may include carditis, pericarditis, aneurysmal dilation and thrombosis of coronary arteries, and sudden death. There is a striking similarity of fatal cases to infantile polyarteritis nodosa, a disease recently reported to be associated with elevated levels of serium IgE. Indeed, it is likely that MCLS represents a disease which can progress to polyarteritis nodosa in infants and young children. The paired acute and convalescent serum IgE levels of 20 subjects with acute nonfatal MCLS were studied along with 20 near-age unaffected controls from the same communities in Japan. The results indicate that most if not all subjects with MCLS in the study had an elevation of total serum IgE during the acute phase of the disease (geometric mean 157 IU/ml compared with the control value of 38 IU/ml, P = 0.005). The level appeared to reach a peak 1-2 weeks after onset and declined over the ensuing 1-2 months.     

Morphological observations on the vasculitis in the mucocutaneous lymph node syndrome

Twenty-seven skin biopsies were obtained from the exanthemata of patients in the acute stage of the mucocutaneous lymph node syndrome (MCLS). The three vascular systems of different caliber size—the intrapapillary capillary loops (ICL), the superficial arteriolar or venular plexus (SAP, SVP) and the small subcutaneous vessels—were examined to investigate the characteristics of the vasculitis in MCLS and differentiate it from infantile polyarteritis nodosa (IPN). Significant papillary edema and dilatation of ICL, SAP and SVP were observed on the 4th day after the onset of the illness, and then gradually decreased. In the subcutaneous regions, vasculitis began which endothelial necrosis, and subendothelial edema and degenerative changes in the muscle cells followed. These changes in the small subcutaneous vessels were observed for a longer period than in the ICL, SAP and SVP. Moderate mononuclear cell infiltrations were observed. Both arteries and veins were affected.     

Elucidation on sudden death in children with the mucocutaneous lymph node syndrome

Atrial pacing was carried out in six children aged one year to eleven years with the mucocutaneous lymph node syndrome (MCLS) during cardiac catheterization. The cardiac index (CI) was measured before pacing and at pacing rates of 150 and 180/min. The CI increased in cases which did not show any pathological findings on the coronary artery angiograms. Conversely, CI decreased at a pacing rate of 150/min, in the case which showed arterial stenosis. Atrial pacing with measurement of CI may be a good method for detecting and evaluating coronary artery lesions in children with MCLS.     

Complement and protease inhibitors in the mucocutaneous lymph node syndrome

Total hemolytic activity of serum (CH50), complement components C3 and C4, alpha 1antitrypsin (alpha 1AT), alpha 1antichymotrypsin (alpha 1X), antithrombin III (AT III), alpha 2 macroglobulin (alpha 2M), and inter-alpha-inhibitor (I-alpha-I) were measured in 23 Japanese and 19 European children with the Mucocutaneous Lymph node Syndrome (MCLS) during the acute phase of disease. Second sera, obtained after day 20 were available from 18 Japanese and 10 European children. In 28 out of 31 children with mild disease, as assessed by the coronary risk score of Asai and Kusakawa, complement was normal or elevated during the acute phase. In 10 out of 11 children with high risk scores, CH50 was below the normal range. One child in this group had ECG changes during the acute phase, one patient died and two others developed coronary aneurysms. C1I was elevated in all 42 cases, alpha 1AT in 40, and alpha 1X in 38 patients. alpha 1AT was depressed in two children, one of whom developed an aneurysm. One of the four children with depression of alpha 1X died of myocardial infarction. Decreased concentrations of AT III, alpha 2M and I-alpha-I were frequent and tended to mark the more severe courses of the disease. A third group of 20 children was evaluated 5 weeks to 6 months after the acute illness. Mean concentrations of all five protease inhibitors were completely normalized in this group. The results of this study indicate that consumption of complement and of protease inhibitors occurs in many cases of MCLS during the acute phase. Determination of CH50 appears to be useful to identify high risk patients early in the course of their illness. Transient deficiency of substances for control of inflammation may in part be responsible for the severe vascular lesions seen in some patients.     

Antibiotic prophylaxis and therapy of febrile aplastic children with acute leukemia

One hundred and twenty-one febrile episodes (FE) were studied in 58 aplastic children with acute leukemia. All patients received a prophylactic regimen of trimethoprim-sulfamethoxazole (TS) and colistin sulfate orally, and amphotericin B locally from the beginning of their antineoplastic therapy. Eighty episodes were analysed retrospectively. Forty-one episodes in 24 patients were treated prospectively with a standard regimen of gentamicin + cefotaxime. The results show that the prophylactic regimen does not eradicate potentially pathogenic organisms from the throat, urine, or stools. Sixty-three per cent of FE were of unknown origin (FUU). 40.5% of all isolated organisms were TS resistant. In the prospective group, 9 of 41 FE (22%) responded to gentamicin + cefotaxime with lysis of fever within 48 hours, and 63% required no further antibiotics. Defeverescence occurred in the whole group within 5 +/- 4 days. No patients were lost to infectious complications. The combination of gentamicin + cefotaxime as initial therapy of a febrile episode must be supplemented within 48 to 72 hours by additional antibiotics in the absence of clinical improvement.     

Immunologic studies of lymph node lymphocytes in the generalized lymphadenopathy syndrome

A generalized lymphadenopathy syndrome (GLS) occurs in persons at high risk for development of acquired immunodeficiency syndrome (AIDS). The natural history and immunologic status of patients with GLS are not fully known, although in some persons GLS may progress to full AIDS. We present the clinical and immunologic findings in two children with severe hemophilia A with nonprogressive GLS for 18-24 months. The functional activity in vitro of lymphocytes from both peripheral blood and biopsied lymph nodes were compared. The peripheral blood lymphocytes responded normally to both mitogens and antigens; lymph node lymphocytes failed to respond to antigens, but did respond to mitogens. The implications of these abnormalities for understanding the pathogenesis of GLS are discussed.     

Hemogram and bone marrow morphology in children with chronic aplastic anemia and myelodysplastic syndrome

Background  Aplastic anemia (AA) and myelodysplastic syndrome (MDS) are both acquired disorders in which bone marrow fails to produce or release sufficient blood cells. Anemia, infections and thrombocytopenia are common signs of such diseases. Clinically, it is difficult to distinguish chronic aplastic anemia (CAA) from MDS, especially from MDS without splenomegaly. As prognosis and treatment of AA and MDS are different, it is extremely important to make a differential diagnosis for the two diseases. Methods  The medical records of 31 patients with CAA and 17 patients with MDS were retrospectively reviewed. Hemogram, bone marrow smear and biopsy for those patients were analyzed. Results  The mean counts of monocytes and platelets in the peripheral blood of the CAA patients were significantly lower than those of the MDS patients. Bone marrow smear showed a reduction of cellularity in CAA patients. The mean counts of myeloblasts+promyelocytes, myeloblasts+proerythroblasts, and megakaryocytes in the bone marrow of CAA patients were markedly lower than those in MDS patients. But the mean lymphocyte count was reversed. Bone marrow cells showed morphological abnormalities in MDS. Hematopoietic tissue in the bone marrow biopsy decreased obviously in more than 96% of the patients with CAA. Adipose tissue in the bone marrow of CAA patients increased obviously. A reduction or deficiency (<2 cell/piece) of megakaryocytes was noted in 28 patients with CAA. Fibrous tissue in the bone marrow was detected in 5 patients with CAA. Bone marrow biopsy results showed hypercellular changes in 12 MDS patients. Ten patients showed aggregated erythroblasts which were in the same stage of development, and 15 patients had abnormal localization of immature precursors (ALIP). Conclusions  Blood cell counts can be decreased in addition to the reduction of cellularity in the bone marrow without dyshematopoiesis in CAA patients. Peripheral blood monocytes, fibrous tissue and cellularity in bone marrow are increased in MDS. Dyshematopoiesis and ALIP may appear characteristically in the children with MDS. Histology of bone marrow is important in the differential diagnosis of MDS and CAA.     

A two-year survey of mucocutaneous lymph node syndrome in northeastern Italy. Epidemiological and clinical findings

A two-year retrospective survey of cases of mucocutaneous lymph node syndrome (MLNS, Kawasaki disease) was conducted by a collaborative research group in Northeastern Italy (Friuli Venezia-Giulia) by reviewing the records of all patients admitted in the paediatric wards of this area from January 1, 1981 to December 31, 1982. 19 cases of MLNS were identified representing an overall incidence in the two-year period of 14.7 cases per 100,000 children younger than 5 years of age. Seasonal clustering of cases was observed, 17 out of 19 cases occurring either in spring or autumn (P = 0.0004, binomial distribution) and 11 out of 19 cases occurring in spring alone (P = 0.0023). No evidence for direct contact between cases or common source exposure emerged, and no risk factors were identified. The clinical spectrum of the disease was similar to that described elsewhere, carditis, uveitis, arthritis and urethritis being the most frequent complications. One infant died, and in this case coronary artery aneurysms were demonstrated by two-dimensional echocardiography. In the remaining cases recovery was complete without sequelae. This study suggests that MLNS is more frequent than expected and that the real incidence of the disease is probably underestimated. The evidence of seasonal clustering of cases strongly suggests the presence of a yet unidentified exogenous factor playing a role in the etiology of the disease.     

儿童慢性再生障碍性贫血与骨髓异常增生综合征的临床特点比较

目的：对儿童慢性再生障碍性贫血（CAA）与骨髓异常增生综合征（MDS）的临床特点进行比较分析,探讨两种疾病之间的差异,帮助临床鉴别诊断。方法：回顾性分析2007年9月至2010年9月收治的23例CAA患儿和9例MDS患儿的临床资料,对所有病例的血常规、网织红细胞计数、乳酸脱氢酶、血清铁蛋白等水平及骨髓细胞学检查、骨髓CD34+计数、骨髓染色体检查、骨髓荧光原位杂交（FISH）检查结果进行对比分析。结果：MDS组中性粒细胞、网织红细胞、血清铁蛋白、乳酸脱氢酶水平均高于CAA组;MDS组骨髓原始细胞计数及三系血细胞的病态造血现象与CAA组差异有显著性;MDS组骨髓CD34+细胞计数水平较CAA组高,FISH异常的检出率亦较CAA组高。结论：CAA和MDS患儿实验室检查、骨髓细胞形态学、细胞遗传学检查结果存在显著不同,三者联合检测对鉴别CAA与MDS有重要意义。     

Periarteriitis nodosa in children and mucocutaneous lymph node syndrome as causes of multifocal convulsions (propulsive petit-mal) (author's transl)

On an infant with the classical signs of Kawasaki-disease (MLNS), in whom after a few days began to show distal demarcations on all four extremities due to arterial malperfusion. Parts of these extremities had to be resected. Histologic evaluation showed an infantile type of periarteriitis nodosa. Later on the child developed multifocal convulsions. The similarities of MLNS and IPN are discussed as well as cerebral vasculitis.     

ATG-F治疗儿童再生障碍性贫血疗效研究

目的探索抗人T-细胞兔免疫球蛋白(ATG-F,德国Fresenius)治疗儿童再生障碍性贫血(简称再障)的临床疗效。方法采用ATG-F联合环孢菌素A(CSA)的联合免疫抑制疗法(IST)治疗儿童再障共31例,其中极重型再障(VSAA)4例,重型再障(SAA)16例,依赖输血型非重型再障(NSAA)11例。实施ATG相关不良反应综合防治措施,并动态监测ATG-F治疗期间与治疗后外周血淋巴细胞绝对计数(ALC)。结果参照国际Camitta再障疗效标准,总有效率为71.0%(22/31例),其中SAA/VSAA和NSAA的总有效率分别为65.0%(13/20例)和81.8%(9/11例),总有效率差异无显著性。ATG-F相关类过敏反应、血清病和感染等不良反应发生率分别为35.5%(11例)、32.3%(10例)和16.1%(5例),均得以及时控制,无治疗相关死亡。动态监测显示,ATG-F治疗期间ALC下降幅度达到70%~80%,并可持续较长时间,直至治疗后90d仍未恢复到治疗前ALC计数水平的50%。结论本研究显示,ATG-F通过大幅度清除ALC以达到抑制异常T细胞之效应,治疗儿童再障疗效显著;采用审慎实施与防护措施,可有效防治ATG相关不良反应。ATG-F可以作为儿童再障IST治疗的ATG剂型选择之一。     

再生障碍性贫血患儿C-kit基因表达及其意义

目的　探讨C kit基因与再生障碍性贫血 (再障 )发病的关系。方法　应用免疫细胞化学方法和核酸原位杂交技术检测儿童再障C kit、C kitmRNA表达的变化。结果　 1.C kit阳性细胞表达值 (A值 )在慢性再障 (CAA)组、重型再障 (SAA)组和正常对照组分别为 0 .5 2± 8.81、0 .4 6± 2 .18、0 .5 8± 7.94 ,CAA、SAA组与正常对照组比较差异无显著性 (P均 >0 .0 5 )。 2 .C kitmRNA阳性细胞表达值 (A值 )CAA、SAA组和正常对照组分别为 0 .4 7± 6 .0 2、0 .77± 8.0 9、0 .6 1± 3.71。CAA、SAA组与正常对照组比较差异无显著性 (P均 >0 .0 5 )。结论　儿童再障骨髓造血衰竭并非C kit及C kitmRNA低表达所致     

State of lipid peroxidation processes and cyclase system components in lymphocytes and blood plasma of children with aplastic anemia]

Lipid peroxidation, antioxidant defence enzymes in lymphocytes and the content of cyclonucleotides in blood plasma were examined in children (3 groups) with aplastic anemia. The groups were formed depending on the disease stages in the examined. Disorders in the distribution of the activity of antioxidant defence enzymes, in the content of hydroperoxides and malonic aldehyde were discovered, with these disorders being diverse and dependent on the disease stage. The cAMP/cGMP in blood plasma was changed towards considerable rise of the cAMP level. During a remission, a majority of the characteristics did not return to normal.