Toxic shock syndrome in children aged 10 years or less. Wiesenthal A M,Todd J K Pediatrics Eight children aged 10 years or less had toxic shock syndrome, and medical records were reviewed for seven of them. There were four boys and three girls, ranging in age from 5 5/12 to 10 8/12 years; all seven met the Centers for Disease Control case definition of toxic shock syndrome. One boy died. The illness was generally characterized by fever, followed by erythroderma, gastrointestinal complaints, and mucous membrane hyperemia. Based on the need for supplemental oxygen or mechanical ventilation, the girls tended to have milder courses than the boys. In four of four cultures performed prior to the institution of antibiotic therapy. Staphylococcus aureus grew from one or more sites. One boy also met the case definition of Kawasaki syndrome and has had multiple coronary artery aneurysms demonstrated in early and late follow-up. Toxic shock syndrome in these children was similar to published descriptions of toxic shock syndrome in series of adult patients, except that, as a group, the children had a greater incidence of respiratory embarrassment.
    Streptococcal superantigens: categorization and clinical associations. Commons Robert J,Smeesters Pierre R,Proft Thomas,Fraser John D,Robins-Browne Roy,Curtis Nigel Trends in molecular medicine Superantigens are key virulence factors in the immunopathogenesis of invasive disease caused by group A streptococcus. These protein exotoxins have also been associated with severe group C and group G streptococcal infections. A number of novel streptococcal superantigens have recently been described with some resulting confusion in their classification. In addition to clarifying the nomenclature of streptococcal superantigens and proposing guidelines for their categorization, this review summarizes the evidence supporting their involvement in various clinical diseases including acute rheumatic fever. 10.1016/j.molmed.2013.10.004
    Staphylococcus aureus isolates from patients with Kawasaki disease express high levels of protein A. Wann E R,Fehringer A P,Ezepchuk Y V,Schlievert P M,Bina P,Reiser R F,Höök M M,Leung D Y Infection and immunity Kawasaki disease (KD) is an acute vasculitis of young children that can be complicated by coronary artery abnormalities. Recent findings suggest that a superantigen(s) may play an important role in stimulating the immune activation associated with the disease, although the origin of this superantigen(s) is unclear. Staphylococcus aureus, isolated from the rectum or pharynx of patients with KD, secretes toxic shock syndrome toxin 1 (TSST-1). The KD isolates express low levels of other exoproteins compared to isolates from patients with toxic shock syndrome (TSS). Thus, it was previously suggested that the KD isolates may be defective in the global regulatory locus agr (for accessory gene regulator), which positively regulates these factors (D. Y. M. Leung et al., Lancet 342:1385-1388, 1993). Here we describe another characteristic of KD isolates. When considered collectively, the KD isolates were found to express higher levels of staphylococcal protein A than the TSS isolates, another characteristic of an agr-defective phenotype. This correlated with a higher level of spa mRNA in these isolates. In contrast, the KD and TSS isolates expressed comparable levels of TSST-1, consistent with previous findings (D. Y. M. Leung et al., Lancet 342:1385-1388, 1993). Analysis of RNAIII transcript levels and nucleotide sequence analysis of the RNAIII-coding region suggested that the KD isolates are not defective in RNAIII, the effector molecule of the agr regulatory system. However, induction of RNAIII transcription in the KD isolates did not result in a dramatic decrease in the amount of spa mRNA, as has been reported for other strains (F. Vandenesch, J. Kornblum, and R. P. Novick, J. Bacteriol. 173:6313-6320, 1991). 10.1128/IAI.67.9.4737-4743.1999
    Toxic shock syndrome or Kawasaki disease. Milgrom H,Palmer E L,Slovin S F,Morens D M,Freedman S D,Vaughan J H Annals of internal medicine 10.7326/0003-4819-94-1-138_1
    The strawberry tongue: What, how and where? Adya Keshavmurthy A,Inamadar Arun C,Palit Aparna Indian journal of dermatology, venereology and leprology 10.4103/ijdvl.IJDVL_57_17
    Association of toxic shock syndrome toxin-secreting and exfoliative toxin-secreting Staphylococcus aureus with Kawasaki syndrome complicated by coronary artery disease. Rowley A H,Shulman S T Pediatric research 10.1203/00006450-199804001-01731
    Staphylococcal scalded skin syndrome, toxic shock syndrome, and Kawasaki disease. Hansen R C Pediatric clinics of North America Three dramatic clinical syndromes have been compared and contrasted. Of these, staphylococcal scalded syndrome is most readily recognized and least likely to have a morbid or fatal outcome. It is easy to confuse toxic shock syndrome and Kawasaki disease. Since the case fatality rate is significant in both of these diseases, and the management so different, proper recognition of the disease by its external features is critical.
    Association of toxic shock syndrome toxin-secreting and exfoliative toxin-secreting Staphylococcus aureus with Kawasaki syndrome complicated by coronary artery disease. Leung D Y,Sullivan K E,Brown-Whitehorn T F,Fehringer A P,Allen S,Finkel T H,Washington R L,Makida R,Schlievert P M Pediatric research Kawasaki syndrome (KS) has been reported to be associated with selective expansion of Vbeta2+ T cells and either staphylococcal toxic shock syndrome toxin-1 or streptococcal pyrogenic exotoxin C in uncomplicated cases. However, there have been no previous studies on the role of superantigens in KS associated with coronary artery disease, the major complication of this illness. The present study characterized bacteria isolated from three acute KS patients who developed coronary artery disease. Staphylococcus aureus secreting either TSST-1 (n = 3) or exfoliative toxin A (n = 1), both known to stimulate expansion of Vbeta2+ T cells, were isolated from all three patients. The percent Vbeta2+ T cells was determined in three patients with coronary artery disease. On presentation, one patient demonstrated reduction, whereas the other two showed expansion, of Vbeta2+ T cells. Repeat analyses of the latter two children showed their percent Vbeta2+ T cells to decrease toward normal. These observations suggest that coronary artery disease in KS may result from superantigenic stimulation of Vbeta2+ T cells. This is also the first demonstration of an association of staphylococcal exfoliative toxin with acute KS. The observation that three different bacterial toxins associated with KS are potent activators of Vbeta2+ T cells suggests an important role for this T cell subset in the pathogenesis of this autoimmune disease. 10.1203/00006450-199709000-00004
    T cells recognize an immunodominant epitope of heat shock protein 65 in Kawasaki disease. Sireci G,Dieli F,Salerno A Molecular medicine (Cambridge, Mass.) BACKGROUND:Kawasaki disease (KD) is an acute systemic vasculitis of infancy and early childhood that is characterized by endothelial cell damage associated with T-cell activation. Lymphocytes infiltrating damaged tissues might be responsible for the disease through secretion of cytokines, such as tumor necrosis factor (TNF)-alpha, that could cause fever, as well as endothelial tissue damage. Debate is growing about the nature of antigen responsible for T-cell activation in KD. Bacillus Calmette Guerin (BCG) and purified protein derivative (PPD) hyperresponsiveness was observed in KD patients and this phenomenon was hypothetically ascribed to cross-reactivity between mycobacterial Heat Shock Protein (HSP) 65 and human homologue HSP63. MATERIALS AND METHODS:CD4+ and CD8+ T-cell clones were obtained from peripheral blood of KD patients in acute phase, or control subjects. The clones were tested for reactivity toward HSP65 and derived peptides. Both proliferation and cytokine production were analyzed. RESULTS:A significant fraction of CD4 and CD8 T-cell clones from KD patients recognized an epitope from HSP65, spanning amino acids 65-85. T-cell clones cross-reacted with the corresponding 90-110 peptide sequence of human HSP-63. CONCLUSIONS:Cross-reactivity between specific epitopes of mycobacterial and human HSP could play a role in the development of the tissue-damage characteristic of KD.
    Analysis of T-cell receptor V-beta 2 in peripheral blood lymphocytes as a diagnostic marker for Kawasaki disease. Reichardt P,Lehmann I,Sierig G,Borte M Infection BACKGROUND:Kawasaki disease (KD) is the most frequent cause of acquired heart disease in children, yet there are no specific diagnostic markers for it. There is controversy whether and by what mechanism selective expansion of T-cell subsets occurs and whether this phenomenon might be helpful for early diagnosis. PATIENTS AND METHODS:To obtain age-related normal values of V-beta 2(+) T-lymphocytes in healthy children and to investigate expansion in KD, we measured expression in 228 children. Peripheral CD3(+) cells were stained with monoclonal antibodies to V-beta 2.1 and the percentage of V-beta 2(+) T-cells was analyzed using flow cytometry. RESULTS:In a control group of 184 healthy subjects (0 to 17 years; median age 6.0 years) we found age-related changes. Levels were highest from 0-2 years (9.02+/-2.80%) and declined towards adolescence (7.56+/-2.42% in 11-15 year olds) (p < 0.001). Results were compared with 24 patients with acute febrile diseases of origin other than KD and with 20 patients with presumed diagnosis KD at admission. Interestingly, while all seven patients whose clinical picture retrospectively confirmed KD showed elevated levels, none of the other children, including none of the patients with initially suspected but not clinically confirmed KD, had levels higher than normal, with the exception of two teenage girls with toxic shock syndrome, a classical superantigen-mediated disease. CONCLUSION:When compared with appropriate age-matched controls, estimation of V-beta 2(+) T-cells might be a valuable tool when making diagnostic decisions suspecting KD. 10.1007/s15010-002-3063-4
    Maternal antibody against toxic shock syndrome toxin-1 may protect infants younger than 6 months of age from developing Kawasaki syndrome. Nomura Yuichi,Yoshinaga Masao,Masuda Kiminori,Takei Syuji,Miyata Koichiro The Journal of infectious diseases The symptoms of Kawasaki syndrome (KS) suggest a possible relationship between KS and superantigen(s). The infrequent occurrence of KS among young infants may be due to a passive maternal antibody. We investigated the antibody titers for superantigens (toxic shock syndrome toxin [TSST]-1, staphylococcal exotoxin B, and streptococcal pyrogenic exotoxins C and A) in 15 patients with KS who were <6 months of age prior to gamma globulin therapy and in 10 mothers of patients with KS <6 months of age. Significant findings were observed for only TSST-1 among the 4 anti-superantigens. The proportion of patients with KS who had high anti-TSST-1 titers was significantly higher than that among infant control subjects (33% vs. 5%, respectively; P=.031). The mean anti-TSST-1 titer for the mothers was significantly lower than that of adult control subjects (P=.021). Among infants <6 months of age, TSST-1 may be related to KS, and a maternal antibody may protect infants from developing KS. 10.1086/340513
    Simultaneous presentation of Kawasaki disease and toxic shock syndrome in an adolescent male. Davies H D,Kirk V,Jadavji T,Kotzin B L The Pediatric infectious disease journal
    Causes of Kawasaki Disease-From Past to Present. Nagata Satoru Frontiers in pediatrics Kawasaki disease (KD) is a multisystem vasculitis that primarily affects the coronary arteries of young children. The causes of KD remain a mystery. It is suspected that some sort of infectious agent is involved because KD has epidemicity and seasonality. That said, the incidence of the disease is high among Japanese people, so it can be speculated that the hosts may have some sort of genetic characteristic that leaves them susceptible to KD. Various theories regarding the etiology have been asserted, such as the infectious vasculitis theory, autoantigen theory, superantigen theory, and RNA virus theory; however, none of them have been able to overcome this epidemicity. Taking into consideration the knowledge gained from previous reports, the best scenario explaining the pathogenesis is "individuals with certain genetic backgrounds are affected by microorganisms which trigger KD." In this article, the pathogenesis of KD is discussed with a focus on the microorganisms mentioned above, along with the previous and current hypotheses as well as my own opinion. 10.3389/fped.2019.00018
    Kawasaki Disease in Children Older Than 10 Years: A Clinical Experience From Northwest India. Jindal Ankur Kumar,Pilania Rakesh Kumar,Guleria Sandesh,Vignesh Pandiarajan,Suri Deepti,Gupta Anju,Singhal Manphool,Rawat Amit,Singh Surjit Frontiers in pediatrics Kawasaki disease (KD) is predominantly seen in young children (<5 years). Diagnosis of KD is often delayed in older children and adolescents, leading to a higher risk of coronary artery abnormalities (CAAs). There is a paucity of literature on KD in older children. Data were collated from a review of records of patients diagnosed with KD who were aged ≥10 years at the time of diagnosis, during the period from January 1994 to June 2019. Eight hundred and sixty five patients were diagnosed with KD during this period. Of these, 46 (5.3%; 26 boys and 20 girls) were aged 10 years or older at the time of diagnosis. The median age at diagnosis was 11 years (range of 10-30 years). The median interval between the of fever and the diagnosis of KD was 12 days (range of 4-30 days). Eight patients (17.4%) presented with hypotensive shock. Coronary artery abnormalities (CAAs) were seen in six patients (13.04%), and three patients had myocarditis. Patients with CAAs were found to have significantly higher median platelet counts and higher median C-reactive protein levels. First-line treatment included intravenous immunoglobulin. Adjunctive therapy was given in five patients (infliximab in four patients and steroids in one patient). The median time between the onset of fever and the administration of IVIg was 13.5 days (range of 6-2). The total duration of follow up is 2,014.5 patient-months. Diagnosis of KD in children older than 10 years is usually delayed, and these patients are thus at a higher risk of CAAs. 10.3389/fped.2020.00024
    Mucocutaneous lymph node syndrome in adults. Differentiation from toxic shock syndrome. Michels T C The American journal of medicine Since infantile mucocutaneous lymph node syndrome was first reported in the United States in 1974, a number of cases of so-called Kawasaki syndrome have been reported in adults. A patient with characteristics of both mucocutaneous lymph node syndrome and toxic shock syndrome is described, and 12 cases reported in the American literature are reviewed in an attempt to clarify the differential diagnosis. Most cases initially reported as Kawasaki syndrome are probably toxic shock syndrome. 10.1016/0002-9343(86)90833-8
    Antibodies to highly conserved peptide sequence of staphylococcal and streptococcal superantigens in Kawasaki disease. Gupta-Malhotra Monesha,Viteri-Jackson Anne,Thomas William,Zabriskie John B Experimental and molecular pathology Superantigen-mediated disease such as toxic shock syndrome is seen in patients who have a weak antibody response to the antigen toxic shock syndrome toxin 1 (TSST-1). We hypothesized that there may be deficiency in antibody production to staphylococcal and streptococcal toxins in Kawasaki disease (KD) children. A peptide was constructed from the homologous portion of the staphylococcal enterotoxins (SE) and streptococcal pyrogenic enterotoxins (SPE), and antibodies to the peptide were made. The anti-peptide antibody immunoblotted several of the SE toxins and SPE toxins. Presence of the peptide antibodies was investigated via ELISA in the sera of acute KD (n = 30), convalescent KD (n = 12), control adults (n = 10), and children (n = 19). The mean anti-peptide antibodies were indistinguishable between control children and KD before treatment with immunoglobulin (P = 0.7) but rose significantly after therapy (P < 0.01). The adults had significantly higher antibodies than the KD, both acute and late (P < 0.0001) and the control children (P < 0.0001). Thus, KD patients do not have a defective serological response against toxins such as SPE/SE/TSST-1. Normal children have significantly lower antitoxin antibody levels to the toxins compared to the adults. 10.1016/j.yexmp.2003.12.003
    Development of serum IgM antibodies against superantigens of Staphylococcus aureus and Streptococcus pyogenes in Kawasaki disease. Matsubara K,Fukaya T,Miwa K,Shibayama N,Nigami H,Harigaya H,Nozaki H,Hirata T,Baba K,Suzuki T,Ishiguro A Clinical and experimental immunology To serologically determine the association of microbial superantigens and the pathogenesis of Kawasaki disease (KD), we conducted a case-control study. Serum IgG and IgM antibodies against staphylococcal enterotoxin A (SEA), SEB, SEC, toxic shock syndrome toxin-1 (TSST-1), and streptococcal pyrogenic exotoxin A (SPEA) were measured by an enzyme-linked immunosorbent assay in 293 serum samples from 65 KD patients on clinical days 1-28 and 120 control samples. The administration of immunoglobulin products, which contain high concentrations of IgG antibodies against all the superantigens, directly elevated antitoxin IgG antibodies in KD patients. In contrast, antitoxin IgM antibodies were not detected in immunoglobulin products. Actually, we found a significant elevation of IgM antibodies against SEA in KD patients in the first (median titre: 0.020, P < 0.01 versus control), second (0.024, P < 0.001), third (0.030, P < 0.001) and fourth (0.038, P < 0.001) weeks, compared to the controls (0.015). Significant differences of IgM antibodies were also true for SEB, TSST-1, and SPEA throughout the first to fourth weeks, and for SEC throughout the second to fourth weeks. The prevalence of KD patients having high IgM titres (> mean + 2SD of control values) to the 5 superantigens was increased with the clinical weeks, and reached 29-43% of KD subjects at the fourth week. This is the first study that describes kinetics of IgM antibodies against superantigens and clarifies the serological significance throughout the clinical course of KD. Our results suggest that multiple superantigens involve in the pathogenesis of KD. 10.1111/j.1365-2249.2006.03015.x
    Human leukocyte antigen class II transgenic mouse model unmasks the significant extrahepatic pathology in toxic shock syndrome. Tilahun Ashenafi Y,Marietta Eric V,Wu Tsung-Teh,Patel Robin,David Chella S,Rajagopalan Govindarajan The American journal of pathology Among the exotoxins produced by Staphylococcus aureus and Streptococcus pyogenes, the superantigens (SAgs) are the most potent T-cell activators known to date. SAgs are implicated in several serious diseases including toxic shock syndrome (TSS), Kawasaki disease, and sepsis. However, the immunopathogenesis of TSS and other diseases involving SAgs are still not completely understood. The commonly used conventional laboratory mouse strains do not respond robustly to SAgs in vivo. Therefore, they must be artificially rendered susceptible to TSS by using sensitizing agents such as d-galactosamine (d-galN), which skews the disease exclusively to the liver and, hence, is not representative of the disease in humans. SAg-induced TSS was characterized using transgenic mice expressing HLA class II molecules that are extremely susceptible to TSS without d-galN. HLA-DR3 transgenic mice recapitulated TSS in humans with extensive multiple-organ inflammation affecting the lung, liver, kidneys, heart, and small intestines. Heavy infiltration with T lymphocytes (both CD4(+) and CD8+), neutrophils, and macrophages was noted. In particular, the pathologic changes in the small intestines were extensive and accompanied by significantly altered absorptive functions of the enterocytes. In contrast to massive liver failure alone in the d-galN sensitization model of TSS, findings of the present study suggest that gut dysfunction might be a key pathogenic event that leads to high morbidity and mortality in humans with TSS. 10.1016/j.ajpath.2011.02.033
    Elevated anti-alpha-enolase antibody levels in Kawasaki disease. Chun J-K,Lee T J,Choi K M,Lee K H,Kim D S Scandinavian journal of rheumatology OBJECTIVE:By functioning as a heat-shock protein (HSP), alpha-enolase has an important role in the pathophysiology of multivariant vasculitis. Kawasaki disease (KD) is a type of vasculitis occurring primarily in children. The role of alpha-enolase in KD was assessed by measuring anti-alpha-enolase antibody (Ab) titres in patients with KD and the usefulness of anti-alpha-enolase Ab as a diagnostic tool in atypical KD patients was evaluated. METHODS:Anti-alpha-enolase Ab titres were measured by using an enzyme-linked immunosorbent assay (ELISA) in seven normal control patients, nine febrile control patients and 14 KD patients (10 typical KD, four atypical KD). A standard deviation (SD) of 3 above the mean of the normal control group was considered to be positive reactivity. Western blotting using recombinant human alpha-enolase was performed in four KD patients and three normal controls. RESULTS:With the positive reactivity limited to +3 SD over the mean (>0.6), 10 out of 14 patients (71%) were positive at the acute onset and 12 out of 14 patients (85.7%) were positive before discharge. In total, 12 out of 14 patients (85.7%) were positive either at acute onset or before discharge. All four atypical KD patients showed positive reactivity. Specific positive bands against recombinant human alpha-enolase were detected by western blotting in all four KD patients, but no reactivity was seen in three patients with normal controls. CONCLUSION:This is the first study to demonstrate that autoantibodies against the alpha-enolase are present in the sera of KD patients. We suggest that anti-alpha-enolase Ab should be a good candidate for a diagnostic tool in atypical KD. 10.1080/03009740701607075
    Detection of multiple superantigen genes in stools of patients with Kawasaki disease. Suenaga Tomohiro,Suzuki Hiroyuki,Shibuta Shoichi,Takeuchi Takashi,Yoshikawa Norishige The Journal of pediatrics OBJECTIVES:To investigate whether superantigens (SAgs) are involved in the development of Kawasaki disease (KD) by examining SAg genes in the stool of patients with KD. STUDY DESIGN:Stool specimens were obtained from 60 patients with KD and 62 age-matched children (36 children with acute illness and 26 healthy children). Total DNA was extracted from these stool samples. Using polymerase chain reaction, we examined genes of 5 SAgs: streptococcal pyrogenic exotoxin-A (SPE-A), SPE-C, SPE-G, SPE-J, and toxic shock syndrome toxin-1. RESULTS:At least 1 of the 5 SAg genes was detected in 42 (70%) specimens from patients with KD, 14 (38.9%) from the febrile group, and 7 (26.9%) from the healthy group. The detection rate between subjects with and without KD was of at least 1 of the 5 SAg genes (P < .001), and more than 2 SAg genes were significantly different (P = .002). CONCLUSIONS:SAg may be involved in the development of KD; data suggest that multiple SAgs may trigger KD. 10.1016/j.jpeds.2009.03.013
    Adult Kawasaki disease: report of two cases and literature review. Sève Pascal,Stankovic Katia,Smail Amar,Durand Denis Vital,Marchand Guillaume,Broussolle Christiane Seminars in arthritis and rheumatism OBJECTIVES:To describe 2 cases of adult Kawasaki Disease (KD) and to review the medical literature to better define the epidemiological, clinical, laboratory, histopathological, cardiovascular, and therapeutic aspects of adult KD compared with pediatric KD. METHODS:Report of 2 cases, and review of the literature using a Medline search from 1967 to June 2003. RESULTS:Including our 2 cases, there are 57 reports of adult KD, 74% among patients aged 18 to 30 years. Nine cases of KD associated with human immunodeficiency virus (HIV) infection were described, suggesting that an immunocompromised state may predispose to this syndrome. The incidence of specific diagnostic criteria was roughly similar in adults and in children. However, cheilitis, meningitis, and thrombocytosis were observed in a larger percentage of children, while arthralgia, adenopathy, and liver function abnormality were more common in adults. Although adult KD often was diagnosed after the acute phase, when a significant beneficial effect from gammaglobulin infusion could not be expected, this treatment did appear to shorten the course of the disease. Coronary aneurysms were less frequent in adults than in children. Prognosis was more favorable in adults, with less cardiovascular complications and no deaths. CONCLUSIONS:Adult KD is a rare condition, which may go unrecognized. Other known disease processes with similar clinical presentations such as hypersensitivity drug reaction and toxic shock syndrome must be ruled out. For adult KD, exclusion criteria such as absence of hypotension, visceral impairment, staphylococcal infection, and any drug able to induce a drug hypersensitivity reaction are suggestive of the diagnosis, in the presence of the inclusion criteria, rash, conjunctival effusion, oropharynx changes, extremity changes, or adenopathy. 10.1016/j.semarthrit.2005.01.012
    The role of superantigens of group A Streptococcus and Staphylococcus aureus in Kawasaki disease. Matsubara Kousaku,Fukaya Takashi Current opinion in infectious diseases PURPOSE OF REVIEW:Since the first suggestion of a superantigen hypothesis for Kawasaki disease over a decade ago, debate on the aetiology remains inconclusive. This article reviews recent publications that address the role of superantigens of group A Streptococcus and Staphylococcus aureus in the pathogenesis of Kawasaki disease. RECENT FINDINGS:Over the past few years, new superantigens produced by group A Streptococcus and S. aureus have been increasingly identified, bringing the total known number to more than 30. Several studies on T-cell Vbeta repertoires and seroloepidemiology have demonstrated evidence for the involvement of single or multiple superantigens produced by the two pathogens. The associated superantigens differed in those studies, including streptococcal pyrogenic toxins A and C, staphylococcal enterotoxins A-C, and toxic shock syndrome toxin 1. These disparate findings suggest that the inflammation of Kawasaki disease does not result from a single agent but rather a final common inflammatory pathway in genetically susceptible individuals after numerous infectious agents. SUMMARY:Certain staphylococcal and streptococcal superantigens are suggested to be responsible for the development of Kawasaki disease. A better understanding of the precise role of the causative agents will lead to accurate diagnosis, more targeted therapy and an improvement of coronary outcomes. 10.1097/QCO.0b013e3280964d8c
    A Four-Year-Old with History of Kawasaki Disease Presenting in Acute Shock. Staats Katherine,Tremoulet Adriana H,Harvey Helen,Burns Jane C,Donofrio-Odmann J Joelle Prehospital emergency care : official journal of the National Association of EMS Physicians and the National Association of State EMS Directors We present a case in which emergency medical services (EMS) intervened on a critically ill child with known giant coronary aneurysms as sequela to her severe complicated Kawasaki disease. This patient's severe shock ultimately ended in cardiac arrest and death. We discuss the keys to recognition, and critical importance to early intervention of pediatric shock in prehospital care. We also detail the cardiac ramifications of Kawasaki disease, steps for prompt identification of high risk complaints in these patients, and opportunities for treatment. 10.1080/10903127.2020.1745339
    Levels of intra- and extracellular heat shock protein 60 in Kawasaki disease patients treated with intravenous immunoglobulin. Yin Ji Xu,Kang Mi-Ran,Choi Jong-Sung,Jeon Hak-Soo,Han Heon-Seok,Kim Ji-Yoon,Son Bo-Ra,Lee Young-Min,Hahn Youn-Soo Clinical immunology (Orlando, Fla.) Immune reactivity to autologous heat shock protein 60 (HSP60) has been reported to be associated with a favorable prognosis in autoimmune diseases. To provide a clue for the possible role of HSP60 in Kawasaki disease (KD), we investigated the levels of intra- and extracellular HSP60 in the course of KD. In KD patients, autologous HSP60 was abundantly expressed in CD11c(+) cells during the acute phase and subsequently decreased during the subacute phase. Most of HSP60-expressing CD11c(+) cells observed in the acute phase was composed of CD11c(low) cells instead of CD11c(high) cells, which were dominant in the subacute phase. In contrast, circulating HSP60 levels were higher in the subacute phase than those in the acute phase, reflecting higher level of HSP60 exposure to the immune system of patients during recovery. These changes in the levels of intra- and extracellular HSP60 were not observed in patients with other febrile diseases. The observed features of HSP60 expression in patients with KD are in favor of a role for autologous HSP60 as a regulator for control of inflammation, rather than a proinflammatory mediator in KD. 10.1016/j.clim.2007.05.006
    Epidemiology and management of Kawasaki disease. Luca Nadia J C,Yeung Rae S M Drugs Kawasaki disease (KD) is an acute systemic vasculitis affecting young children and is rising in incidence worldwide. It is most common in children <5 years of age, males and those of Asian ethnicity. It is an important cause of acquired heart disease in children. Standard treatment with high-dose aspirin (acetylsalicylic acid; ASA) and intravenous immune globulin (IVIG) has been shown to decrease the rate of coronary artery aneurysm development. Anti-coagulation has an important place in the management of KD, although guidance based on evidence is lacking. Treatment of refractory KD is an area under intense study and may include IVIG, corticosteroids and/or tumour necrosis factor (TNF)-α inhibitors among immunosuppressive agents. Acute complications of KD include myocarditis/KD shock syndrome and macrophage activation syndrome, which necessitate appropriate awareness in order to initiate proper management. 10.2165/11631440-000000000-00000
    Heat shock proteins and superantigenic properties of bacteria from the gastrointestinal tract of patients with Kawasaki disease. Nagata Satoru,Yamashiro Yuichiro,Ohtsuka Yoshikazu,Shimizu Toshiaki,Sakurai Yumiko,Misawa Shigeki,Ito Teruyo Immunology We previously suggested that gut bacteria may be involved in the onset of Kawasaki disease (KD). In this study, we evaluated the production of heat shock proteins (hsps) and superantigens (sAgs) by microorganisms isolated from the jejunal mucosa of 19 children with KD in the acute phase and from 15 age-matched control children. We identified 13 strains of Gram-negative microbes from patients with KD; these microbes produced large amounts of hsp60 and induced pro-inflammatory cytokine production by peripheral blood mononuclear cells. The Gram-negative microbes also elicited endogenous hsp60 production, leading to the secretion of anti-inflammatory intereukin-10 (IL-10). We also identified 18 strains of Gram-positive cocci that had superantigenic properties and which induced the expansion of Vbeta2 T cells in vitro. All bacteria identified in this study were antibiotic resistant. These data suggest that sAg and hsps produced by gut bacteria might be involved in KD. 10.1111/j.1365-2567.2009.03135.x
    Kawasaki disease in a pediatric intensive care unit: a case-control study. Dominguez Samuel R,Friedman Kevin,Seewald Ryan,Anderson Marsha S,Willis Lisa,Glodé Mary P Pediatrics OBJECTIVES:We conducted a case-control study to ascertain the clinical presentations, risk factors, and clinical outcomes of children who had Kawasaki disease and were admitted to the ICU of our children's hospital. METHODS:We reviewed charts of all children who had a discharge diagnosis of Kawasaki disease and were admitted to the ICU from 1995 through 2007. For each patient, we identified 3 season-matched control subjects who had Kawasaki disease and were not admitted to the ICU. RESULTS:We identified 423 patients with Kawasaki disease. Of those, 14 (3.3%) were admitted to the ICU and met our inclusion criteria. ICU admission diagnoses were most commonly toxic shock or septic shock. Thirteen (92.8%) of 14 patients who were admitted to the ICU met criteria for complete Kawasaki disease before treatment. There was no significant difference in age in ICU patients compared with season-matched control subjects with Kawasaki disease. ICU patients were significantly more likely to be female and to have higher band counts, lower platelet counts, lower albumin levels, and higher C-reactive protein values. Time from admission to treatment with intravenous immunoglobulin was delayed in ICU patients. ICU patients were more likely to have intravenous immunoglobulin-refractory disease and require therapy with a second dose of intravenous immunoglobulin, infliximab, or steroids. CONCLUSIONS:We present a case-control study of patients who had Kawasaki disease and presented severely ill, in shock, and requiring admission to the ICU. These patients frequently were misdiagnosed because of failure to appreciate the full spectrum of disease severity seen in patients with Kawasaki disease. These patients' illnesses was often mistaken for toxic or septic shock, leading to a delay in treatment with intravenous immunoglobulin. Patients who have Kawasaki disease and are admitted to the ICU are at increased risk for intravenous immunoglobulin-refractory disease and may be at risk for development of more severe coronary artery disease. 10.1542/peds.2008-1275
    New developments in the search for the etiologic agent of Kawasaki disease. Rowley Anne H,Shulman Stanford T Current opinion in pediatrics PURPOSE OF REVIEW:The aim of this article is to review recent developments in the search for the etiologic agent of Kawasaki disease. RECENT FINDINGS:Two recently proposed theories of Kawasaki disease etiology, the toxic shock syndrome toxin-1 hypothesis and the coronavirus NL-63 hypothesis, have been studied extensively and have been disproven. Surprisingly, IgA plasma cells infiltrate inflamed tissues in acute Kawasaki disease, including the coronary artery, and are oligoclonal, or antigen-driven. Synthetic versions of predominant IgA antibodies in acute Kawasaki disease arterial tissue bind to an antigen present in acute Kawasaki disease ciliated bronchial epithelium and in a subset of macrophages in acute inflamed Kawasaki disease tissues. Light and electron microscopic studies of the antigen in acute Kawasaki disease ciliated bronchial epithelium indicate that the Kawasaki disease-associated antigen localizes to cytoplasmic inclusion bodies that are consistent with aggregates of viral protein and associated nucleic acid. SUMMARY:The identification of cytoplasmic inclusion bodies in acute Kawasaki disease ciliated bronchial epithelium has provided direction for future Kawasaki disease etiology studies. Transmission electron microscopic examination of glutaraldehyde-fixed medium-sized bronchi from acute Kawasaki disease fatalities and analysis of the protein and nucleic acid components of the inclusions should provide important information about these inclusion bodies and speed the identification of the specific etiologic agent of Kawasaki disease. 10.1097/MOP.0b013e328012720f
    Nephrotic syndrome in Kawasaki disease: a report of three cases. Krug Pauline,Boyer Olivia,Balzamo Eve,Sidi Daniel,Lehnert Agnès,Niaudet Patrick Pediatric nephrology (Berlin, Germany) BACKGROUND:Renal manifestations are rare in Kawasaki disease (KD). Acute renal failure with tubular necrosis, tubulointerstitial nephritis and renovascular hypertension have been reported in KD, but only one case of a patient with KD associated with nephrotic syndrome (NS) has been reported to date, with the patient improving on steroid therapy but dying from coronary aneurysm. METHODS:We report the cases of three children, aged 4, 4.5 and 8 years, respectively, who presented with typical KD symptoms (high fever, diffuse maculopapular rash, conjunctivitis, peripheral oedema, cervical adenopathies and high C reactive protein levels) and developed NS. RESULTS:Patient 1 had a haemodynamic shock due to cardiac dysfunction and transient renal failure. Ten days later, he developed a NS which spontaneously disappeared 1 week later. Patient 2 had a NS on admission with normal plasma creatinine and no haematuria. Proteinuria disappeared within 10 days. Patient 3 developed NS 5 days after onset with a moderate increase in plasma creatinine. Proteinuria disappeared within 2 weeks. All three patients were treated with intravenous immunoglobulins, antibiotic therapy and aspirin, but none of them received steroid therapy. To date, all three patients have maintained long-term remission. CONCLUSIONS:In conclusion, proteinuria with NS may develop during the acute phase of KD with persistent remission occurring without steroid therapy. 10.1007/s00467-012-2172-2
    Kawasaki disease and toxic shock syndrome--at last the etiology is clear? Curtis Nigel Advances in experimental medicine and biology A decade after the superantigen hypothesis for KD was first suggested, it has still not been either proven or refuted conclusively. Although initial optimism for the hypothesis was quashed by a series of published papers apparently refuting the idea, in the last few years there have been a number of good studies providing evidence in support of the superantigen hypothesis. Whether this renewed enthusiasm is justified will hopefully become clear in the near future. Ultimately, accurate diagnosis, more targeted treatment, and preventative strategies depend on the unraveling of the immunopathogenesis of this disease. 10.1007/978-1-4419-8993-2_26
    Cerebral vasculitis in severe Kawasaki disease: early detection by magnetic resonance imaging and good outcome after intensive treatment. Gitiaux Cyril,Kossorotoff Manoelle,Bergounioux Jean,Adjadj Elias,Lesage Fabrice,Boddaert Nathalie,Hully Marie,Brugel Dominique,Desguerre Isabelle,Bader-Meunier Brigitte Developmental medicine and child neurology Kawasaki disease is an acute vasculitis, that has a classic complication of acquired coronary artery aneurysm. Severe forms with multi-organ involvement or neurological dysfunction are rare. Cerebral vascular involvement has been related to large-vessel injury or cardioembolism, leading to focal brain infarction. A 4-year-old female presented with unusual, rapidly catastrophic Kawasaki disease with refractory shock, acute renal failure, and coma, requiring intensive haemodynamic management. The observation of diffuse micro-haemorrhages (T2*-weighted sequence) associated with white matter injury on brain magnetic resonance imaging (MRI) pointed towards lesions of the medium/small blood vessels. Cerebral vasculitis was suspected and the immunosuppressive treatment was increased Subsequently, the patient's recovery was rapid. On follow-up severe, bilateral vitritis was evident and surgery improved visual outcome. Early recognition of severe or unusual forms of Kawasaki disease could lead to more favourable outcome using appropriate treatment strategies. Diffuse cerebral micro-haemorrhages on T2* brain MRI sequences might be a key sign for the diagnosis of medium or small cerebral vessel involvement. 10.1111/dmcn.12002
    Shock and unresponsiveness to repeated courses of intravenous immunoglobulin in Kawasaki disease: a nationwide database study. Liang Yun-Chieh,Chang Chin-Hao,Lin Ming-Tai,Kao Feng-Yu,Huang San-Kuei,Wu Mei-Hwan Pediatric research BACKGROUND:We aimed to investigate the clinical implications of unresponsiveness to single or repeated courses intravenous immunoglobulin (IVIG) and Kawasaki disease (KD) shock syndrome in patients with KD in an era of a single brand of IVIG. METHODS:Data were collected from National Health Insurance database 2010-2013. Characteristics of the KD patients were analyzed, including age, gender, shock, and associated coronary aneurysms. RESULTS:There were 3043 KD patients (male: 1872) identified. Among them, 46 (1.51%) had KDSS, 261 patients (8.5%) had IVIG unresponsiveness, and 225 patients (7.4%) developed coronary aneurysms. Moreover, 51 patients did not respond to the second course IVIG therapy, i.e., re-IVIG unresponsiveness. KDSS was associated with the occurrence of IVIG unresponsiveness (P < 10) and re-IVIG unresponsiveness (P = 0.02). In addition to male gender and KD shock syndrome, IVIG unresponsiveness (OR: 2.18, 95% CI: 1.48-3.22, P = 0.001) and re-IVIG unresponsiveness (OR: 2.87, 95% CI: 1.40-5.89, P = 0.004) were both independent risk factors for coronary aneurysms. CONCLUSIONS:In a nationwide KD cohort, both IVIG unresponsiveness and re-IVIG unresponsiveness increase the risk of coronary aneurysms. Such observation addresses the importance of refining the treatment for IVIG unresponsiveness, at least in those with KD shock syndrome. 10.1038/s41390-019-0668-1
    What dose of intravenous immunoglobulin should be administered in Kawasaki disease with suspected systemic capillary leak syndrome? Comment on: shock: an unusual presentation of Kawasaki disease (Eur J Pediatr. 2011 Jul; 170(7):941-3). Park Se Jin,Pai Ki Soo,Kim Ji Hong,Shin Jae Il European journal of pediatrics 10.1007/s00431-011-1602-7
    Axillary cellulitis caused by toxic shock syndrome toxin 1-secreting methicillin-resistant Staphylococcus aureus meeting criteria for Kawasaki disease. Zensho Kazumasa,Takemoto Kei,Yamaguchi Mari,Hayashi Hiroaki,Senoh Akemi,Inoue Masaru The Journal of dermatology 10.1111/1346-8138.15167
    Kawasaki disease: an unexpected etiology of shock and multiple organ dysfunction syndrome. Gatterre Pauline,Oualha Mehdi,Dupic Laurent,Iserin Franck,Bodemer Christine,Lesage Fabrice,Hubert Philippe Intensive care medicine OBJECTIVE:Severe forms of Kawasaki disease (KD) associated with shock have recently been reported in which a greater number of coronary artery abnormalities (CAA) were observed. In this study, we analyzed organ involvement not restricted to cardiovascular aspects in severe KD and assessed whether their outcome is different than in common forms. DESIGN:Retrospective study. SETTING:A 12-bed pediatric intensive care unit (PICU) in a university hospital setting. PATIENTS:All patients managed in the PICU with a diagnosis of KD from 1 January 2001 to 30 April 2009. RESULTS:Eleven patients were admitted because of moderate febrile shock without initial KD diagnosis. Median age was 75 months (6-175) with a male:female ratio of 1.4. KD was diagnosed and treated after a delay of 1 day (0-2), for a total of 7 days (5-9) after fever onset. Seven patients (63%) developed CAA after 21 days (6-30) with complete regression within a delay of 120 days (18-240). Nonspecific encephalopathy (n = 6) as well as acute kidney injury (n = 10) were also observed. Multiple organ dysfunction syndrome (MODS) occurred in eight patients. Although predicted mortality according to the PELOD score [21 (10-43)] ranged from 20% to up to 50%, all 11 children survived with no sequelae. CONCLUSION:Moderate shock is the main reason for PICU admission in children suffering from KD. These forms can be associated with surprising MODS. Despite the severity of symptoms, all patients survived without any sequelae, hence the need for proper diagnosis and rapid treatment of these unusual severe forms. 10.1007/s00134-012-2473-8
    Shock: an unusual presentation of Kawasaki disease. Thabet Farah,Bafaqih Hend,Al-Mohaimeed Suleiman,Al-Hilali Mariam,Al-Sewairi Wafaa,Chehab May European journal of pediatrics UNLABELLED:Kawasaki disease (KD) is a common acute systemic vasculitis of childhood. Although KD has wide spectrum of clinical features, shock is not one of its common presentation form. We describe a 5-month-old female infant with severe shock syndrome requiring fluid resuscitation, inotropic support, and PICU admission. She was diagnosed retrospectively to have KD complicated by coronary artery aneurysms in spite of receiving early course of IV immunoglobulin. CONCLUSION:Diagnosis of KD could be missed in the pediatric intensive care unit because of its atypical presentation and the wide array of associated clinical symptoms. Subsequently, intensivists and emergency room physicians should maintain a high index of suspicion not to miss it or diagnose it at an advanced stage of the illness. 10.1007/s00431-011-1426-5
    Characteristics of children with Kawasaki disease requiring intensive care: 10 years' experience at a tertiary pediatric hospital. Kuo Ching-Chia,Lee Yu-Shin,Lin Ming-Ru,Hsia Shao-Hsuan,Chen Chih-Jung,Chiu Cheng-Hsun,Hwang Mao-Sheng,Huang Yhu-Chering Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi BACKGROUND/PURPOSE:Kawasaki disease (KD) is a febrile systemic vasculitis, and some patients may develop serious complications requiring intensive care. We aim to ascertain the clinical presentations and outcomes of these patients. METHODS:From October 2004 to October 2014, children with KD who had stayed in the pediatric intensive care unit (ICU) for acute stage treatment were defined as case patients; for each case, three age/sex-matched patients with KD but without ICU stay, if identified, were selected as control patients. Clinical data were retrospectively collected and analyzed. RESULTS:Among the total of 1065 KD patients, we identified 26 case patients and 71 controls for statistical analysis. ICU patients had a longer fever duration, and tended to have hemoglobin level < 10 g/dL, platelet count < 150 × 10/L, band cell percentage > 10%, peak serum C-reactive protein level > 200 mg/L, serum albumin value < 3 g/dL, and often presented with multiorgan system involvement. Time from symptom onset to the diagnosis of KD was similar between the two groups, but ICU patients were less likely to have KD as a leading admission diagnosis. Shock (73.1%, n = 19) was the most common reason for ICU admission. ICU patients were more likely to receive antibiotics, albumin infusion, and require a second dose of intravenous immunoglobulin or steroid therapy. No in-hospital mortality was observed. CONCLUSION:Patients with KD requiring ICU admission are significantly associated with multiorgan involvement, abnormal hematological and biochemistry biomarkers, KD recognition difficulty at the time of admission, and intravenous immunoglobulin-refractory KD. 10.1016/j.jmii.2016.06.004
    Extracorporeal Membrane Oxygenation Support for Cardiac Dysfunction Due to Kawasaki Disease Shock Syndrome. Zhang Han,Xie Lijian,Xiao Tingting Frontiers in pediatrics Kawasaki disease (KD) is usually characterized as an inflammatory vasculitis during early childhood, which predominantly involves medium-sized arteries and is treated with intravenous γ-globulin (IVIG) and oral aspirin. KD with hemodynamic instability, characterized by systolic blood pressure decreasing by more than 20% below the normal range, is defined as Kawasaki disease shock syndrome (KDSS). The pathogenesis of KDSS is still not comprehensively understood. Life-threatening cardiogenic shock can occur during the acute phase of KDSS, while the mechanism of cardiac dysfunction due to KDSS is still controversial, and such cases are rarely reported. Here, we present the application of veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) for cardiac function support of a child with KDSS. By doing so, it will be a reminder that KDSS can cause severe cardiac dysfunction, and we should stay vigilant at the early stage of the disease to distinguish KDSS from toxic septic shock in the first place and initiate the appropriate treatment at the right moment, in order to prevent such patients from having irreversible outcomes. 10.3389/fped.2019.00221
    Kawasaki Disease Shock Syndrome with Retrograde Diastolic Aortic Flow. Flynn Elise,Kowalski Remi,Burgner David The Journal of pediatrics 10.1016/j.jpeds.2015.11.013
    Population-based study of Kawasaki disease shock syndrome in Taiwan. Lin Ming-Tai,Fu Chun-Min,Huang San-Kuei,Huang Shin-Chung,Wu Mei-Hwan The Pediatric infectious disease journal By using a National Health Insurance database, we investigated the occurrence of Kawasaki disease (KD) shock syndrome in Taiwan. KD shock syndrome occurred most frequently in winter, and the incidence was 1.45 per 100 patients with KD. Compared with KD patients without shock, KD shock syndrome patients were older, more likely to develop coronary lesions (15.9% vs. 7.0%) and had longer hospitalization duration. 10.1097/INF.0b013e31829efae6
    Recognition of a Kawasaki disease shock syndrome. Kanegaye John T,Wilder Matthew S,Molkara Delaram,Frazer Jeffrey R,Pancheri Joan,Tremoulet Adriana H,Watson Virginia E,Best Brookie M,Burns Jane C Pediatrics OBJECTIVE:We sought to define the characteristics that distinguish Kawasaki disease shock syndrome from hemodynamically normal Kawasaki disease. METHODS:We collected data prospectively for all patients with Kawasaki disease who were treated at a single institution during a 4-year period. We defined Kawasaki disease shock syndrome on the basis of systolic hypotension for age, a sustained decrease in systolic blood pressure from baseline of > or =20%, or clinical signs of poor perfusion. We compared clinical and laboratory features, coronary artery measurements, and responses to therapy and analyzed indices of ventricular systolic and diastolic function during acute and convalescent Kawasaki disease. RESULTS:Of 187 consecutive patients with Kawasaki disease, 13 (7%) met the definition for Kawasaki disease shock syndrome. All received fluid resuscitation, and 7 (54%) required vasoactive infusions. Compared with patients without shock, patients with Kawasaki disease shock syndrome were more often female and had larger proportions of bands, higher C-reactive protein concentrations, and lower hemoglobin concentrations and platelet counts. Evidence of consumptive coagulopathy was common in the Kawasaki disease shock syndrome group. Patients with Kawasaki disease shock syndrome more often had impaired left ventricular systolic function (ejection fraction of <54%: 4 of 13 patients [31%] vs 2 of 86 patients [4%]), mitral regurgitation (5 of 13 patients [39%] vs 2 of 83 patients [2%]), coronary artery abnormalities (8 of 13 patients [62%] vs 20 of 86 patients [23%]), and intravenous immunoglobulin resistance (6 of 13 patients [46%] vs 32 of 174 patients [18%]). Impairment of ventricular relaxation and compliance persisted among patients with Kawasaki disease shock syndrome after the resolution of other hemodynamic disturbances. CONCLUSIONS:Kawasaki disease shock syndrome is associated with more-severe laboratory markers of inflammation and greater risk of coronary artery abnormalities, mitral regurgitation, and prolonged myocardial dysfunction. These patients may be resistant to immunoglobulin therapy and require additional antiinflammatory treatment. 10.1542/peds.2008-1871
    Hyponatremia Is a Feature of Kawasaki Disease Shock Syndrome: A Case-Control Study. Schuster Jennifer E,Palac Hannah L,Innocentini Nancy,Rowley Anne H,Young Luciana T,Shulman Stanford T Journal of the Pediatric Infectious Diseases Society Kawasaki disease (KD) shock syndrome (KDSS) is hypotension with KD. We compared children with KDSS and matched control children with KD. Children with KDSS more often were female, had a lower platelet count and sodium concentration, had a condition refractory to immunoglobulin, and had abnormal echocardiography results. KDSS is a unique subset of KD. 10.1093/jpids/piw081
    Innate immune responses following Kawasaki disease and toxic shock syndrome. Chen Katherine Y H,Messina Nicole,Germano Susie,Bonnici Rhian,Freyne Bridget,Cheung Michael,Goldsmith Greta,Kollmann Tobias R,Levin Michael,Burgner David,Curtis Nigel PloS one The pathogenesis of Kawasaki disease (KD) remains unknown and there is accumulating evidence for the importance of the innate immune system in initiating and mediating the host inflammatory response. We compared innate immune responses in KD and toxic shock syndrome (TSS) participants more than two years after their acute illness with control participants to investigate differences in their immune phenotype. Toxic shock syndrome shares many clinical features with KD; by including both disease groups we endeavoured to explore changes in innate immune responses following acute inflammatory illnesses more broadly. We measured the in vitro production of interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-1 receptor antagonist (IL-1ra), and IL-10 following whole blood stimulation with toll-like receptor and inflammasome ligands in 52 KD, 20 TSS, and 53 control participants in a case-control study. Analyses were adjusted for age, sex, and unstimulated cytokine concentrations. Compared to controls, KD participants have reduced IL-1ra production in response to stimulation with double stranded RNA (geometric mean ratio (GMR) 0.37, 95% CI 0.15, 0.89, p = 0.03) and increased IL-6 production in response to incubation with Lyovec™ (GMR 5.48, 95% CI 1.77, 16.98, p = 0.004). Compared to controls, TSS participants have increased IFN-γ production in response to peptidoglycan (GMR 4.07, 95% CI 1.82, 9.11, p = 0.001), increased IL-1β production to lipopolysaccharide (GMR 1.64, 95% CI 1.13, 2.38, p = 0.01) and peptidoglycan (GMR 1.61, 95% CI 1.11, 2.33, p = 0.01), and increased IL-6 production to peptidoglycan (GMR 1.45, 95% CI 1.10, 1.92, p = 0.01). Years following the acute illness, individuals with previous KD or TSS exhibit a pro-inflammatory innate immune phenotype suggesting a possible underlying immunological susceptibility or innate immune memory. 10.1371/journal.pone.0191830
    Clinical manifestations associated with Kawasaki disease shock syndrome in Mexican children. Gámez-González Luisa Berenise,Murata Chiharu,Muñoz-Ramírez Mireya,Yamazaki-Nakashimada Marco European journal of pediatrics UNLABELLED:Recently, there have been increasing reports of severe forms of Kawasaki disease (KD) associated with shock that have been managed in pediatric intensive care units. It has been suggested that KD is more severe in the Hispanic population. We conducted a study to determine the frequency of Kawasaki disease shock syndrome (KDSS) in our population and compared characteristics between patients with KD without shock and patients with KDSS. Data from 214 patients with KD treated in a tertiary pediatric hospital were collected during a 12-year period. We compared clinical and laboratory features of KD patients without shock and KDSS patients. Of 214 consecutive patients with KD, 11 (5 %) met the definition for KDSS. All of these patients received fluid resuscitation, seven (64 %) required inotropic treatment, and six (54 %), ventilatory support. On admission, seven of these patients (64 %) had an incomplete presentation of the disease, whereas in the group of patients without shock, the relative frequency of an incomplete presentation was 29 %. Twenty percent (3/11) of patients with KDSS presented giant coronary aneurysms versus none of 203 KD patients without shock (p = 0.001); myocardial infarction, 27 % (3/11), versus 1 % (2/203) (p = 0.001); and intravenous immunoglobulin (IVIG) resistance, 60 % (6/11), versus 12 % (24/203). Gastrointestinal manifestations in the acute phase occurred in 91 % of KDSS patients versus 30 % patients without shock (p = 0.001). CONCLUSION:Patients with KD presenting in shock seem to have an increase in gastrointestinal manifestations, incomplete presentation, IVIG resistance, and worse cardiac outcomes. Larger, prospective, multicentre studies should be carried out to corroborate these findings. 10.1007/s00431-012-1879-1
    Describing Kawasaki shock syndrome: results from a retrospective study and literature review. Taddio Andrea,Rossi Eleonora Dei,Monasta Lorenzo,Pastore Serena,Tommasini Alberto,Lepore Loredana,Bronzetti Gabriele,Marrani Edoardo,Mottolese Biancamaria D'Agata,Simonini Gabriele,Cimaz Rolando,Ventura Alessandro Clinical rheumatology Kawasaki shock syndrome (KSS) is a rare manifestation of Kawasaki disease (KD) characterized by systolic hypotension or clinical signs of poor perfusion. The objectives of the study are to describe the main clinical presentation, echocardiographic, and laboratory findings, as well as the treatment options and clinical outcomes of KSS patients when compared with KD patients. This is a retrospective study. All children referred to two pediatric rheumatology units from January 1, 2012, to December 31, 2014, were enrolled. Patients were divided into patients with or without KSS. We compared the two groups according to the following variables: sex, age, type of KD (classic, with less frequent manifestations, or incomplete), clinical manifestations, cardiac involvement, laboratory findings, therapy administered, response to treatment, and outcome. Eighty-four patients with KD were enrolled. Of these, five (6 %) met the criteria for KSS. Patients with KSS had higher values of C-reactive protein (p = 0.005), lower hemoglobin levels (p = 0.003); more frequent hyponatremia (p = 0.004), hypoalbuminemia (p = 0.004), and coagulopathy (p = 0.003); and increase in cardiac troponins (p = 0.000). Among the KSS patients, three had a coronary artery involvement, but none developed a permanent aneurysm. Intravenous immunoglobulin resistance was more frequent in the KSS group, although not significantly so (3/5, 60 % vs. 23/79, 30 %, P = NS). None of the five cases was fatal, and all recovered without sequelae. KSS patients are more likely to have higher rates of cardiac involvement. However, most cardiovascular abnormalities resolved promptly with therapy. 10.1007/s10067-016-3316-8
    Early Differentiation of Kawasaki Disease Shock Syndrome and Toxic Shock Syndrome in a Pediatric Intensive Care Unit. Lin Ying-Jui,Cheng Ming-Chou,Lo Mao-Hung,Chien Shao-Ju The Pediatric infectious disease journal BACKGROUND:Kawasaki disease shock syndrome (KDSS) and toxic shock syndrome (TSS) can present as shock and fever with skin rash, but the management of these 2 groups of patients is different. This report proposes to help clinicians earlier distinguish these 2 diseases and expedite institution of appropriate therapy. METHODS:We retrospectively reviewed the medical records of patients admitted to the pediatric intensive care unit with the diagnosis of KDSS or TSS from January 2000 through December 2010. Clinical, laboratory and echocardiographic data were collected for analysis of differences between them. RESULTS:Seventeen patients met the inclusion criteria of KDSS and 16 had a confirmed diagnosis of TSS. The mean age of the KDSS group was significantly younger than that of the TSS group (36.8 ± 41.1 vs. 113.3 ± 55.6 months, P < 0.001). Significantly lower hemoglobulin and age-adjusted hemoglobulin concentrations were noted in the KDSS group [Hb, age-adjusted Z score, -1.88 (range, -3.9 to 3.9) vs. 0.89 (range, -6.4 to 10.8), P = 0.006]. The median platelet count of the KDSS group was nearly twice that of the TSS group [312 × 10³ per μL (range, 116-518) vs. 184.5 × 10³ per μL (range: 31-629), P = 0.021]. Echocardiographic abnormalities, such as valvulitis (mitral or tricuspid regurgitation) and coronary artery lesions, were significantly more common in the KDSS group (P = 0.022). CONCLUSIONS:Echocardiography, anemia and thrombocytosis are useful early differentiating features between KDSS and TSS patients. 10.1097/INF.0000000000000852
    Clinical manifestations of Kawasaki disease shock syndrome: a case-control study. Chen Pei-Shin,Chi Hsin,Huang Fu-Yuan,Peng Chun-Chih,Chen Ming-Ren,Chiu Nan-Chang Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi BACKGROUND:Kawasaki disease shock syndrome (KDSS) is a severe condition related to Kawasaki disease (KD), and sometimes it is difficult to diagnose. This is a case-control study to ascertain the clinical presentations, risk factors, and clinical outcomes of children who had KDSS. MATERIALS AND METHODS:Children who were hospitalized during 2001-2011 with the diagnosis of KD combined with hypotension, sepsis, or shock were retrospectively reviewed and were defined as case patients. For each case patient, three season-matched patients diagnosed as having KD with normal blood pressure were identified to serve as control patients. Demographic characteristics, clinical presentations, laboratory features, therapies, and outcomes were analyzed. RESULTS:Nine KDSS patients and 27 control patients were identified. The average age of patients with KDSS was 3.2 ± 3.2 years. Compared with controls, KDSS patients were less likely to have a diagnosis of KD at admission (22.2% vs. 66.7%) and had a higher risk of coronary artery dilatation (77.8% vs. 11.1%). Risk factors for KDSS included higher neutrophil counts and proportions of bands, higher C-reactive protein (CRP), and lower platelet counts. All case patients received aspirin therapy; eight patients received intravenous immunoglobulin therapy, with two receiving more than one course. Seven KDSS patients required fluid resuscitation, and eight patients required vasoactive infusions. CONCLUSION:Patients with KDSS may have uneven clinical course and may be misdiagnosed in the beginning. They may have more prominent inflammatory markers in the early phase and higher risk of coronary artery dilatation. 10.1016/j.jmii.2013.06.005
    Kawasaki disease shock syndrome: clinical characteristics and possible use of IL-6, IL-10 and IFN-γ as biomarkers for early recognition. Li Yandie,Zheng Qi,Zou Lixia,Wu Jianqiang,Guo Li,Teng Liping,Zheng Rongjun,Jung Lawrence Kwok Leung,Lu Meiping Pediatric rheumatology online journal BACKGROUND:As an acute febrile and inflammatory disease, Kawasaki disease (KD) could develop Kawasaki disease shock syndrome (KDSS) sometimes. However its pathogenesis was still not well known. This study was to learn more about the clinical features and evaluate the role of cytokines in the pathogenesis of KDSS. METHODS:We collected clinical and laboratory data retrospectively for all patients with KDSS(KDSS, n = 27)who were hospitalized at our hospital from Jan 2014 to Oct 2017. For patient with KDSS, we randomly identified 43 patients with KD as control subjects (KD, n = 43). Clinical features, laboratory evaluations were collected. Cytokines IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ in serum were assayed using flow cytometric bead array. RESULTS:The patients with KDSS were older age (43.41 ± 31.42 vs 28.81 ± 21.51 months, P < 0.05), longer duration of fever (10.63 ± 5.12 vs 6.98 ± 2.45 days, P < 0.05), higher WBC count, neutrophils, CRP, ESR, PCT and D-dimer, and lower hemoglobin and albumin, more severe hyponatremia and hypokalemia, more refractory to IVIG therapy, more coronary artery abnormalities (CAAs), aseptic meningitis, and longer duration of hospitalization than patients with KD (all P < 0.05). The levels of serum IL-6 [184.1 (27.7-2577.3) vs 54.1 (4-425) pg/ml], IL-10 [42.6 (5-236.7) vs 9.4 (3-94) pg/ml], TNF-α [2.6 (1.0-23.4) vs 2.1 (1-6) pg/ml] and IFN-γ [18.3 (4.5-94.4) vs 6.7 (2-56) pg/ml] in KDSS patients were significant higher than KD patients (all P < 0.05). ROC curves showed that 66.7 pg/ml of IL-6, 20.85 pg/ml of IL-10 and 8.35 pg/ml of IFN-γ had sensitivity and specificity for identifying KDSS as 85.2 and 62.8%; 66.7 and 83.7%; 74.1 and 74.4% respectively. No fatality was recorded in this series. CONCLUSIONS:KDSS were characteristic as more cytokine production and prone to developing IVIG non-responsiveness and CAAs. KD patients with IL-6 above 66.7 pg/ml, IL-10 above 20.85 pg/ml, and IFN-γ above 8.35 pg/ml suggested higher risk for KDSS. 10.1186/s12969-018-0303-4
    Unusual manifestations of Kawasaki disease with retropharyngeal edema and shock syndrome in a Taiwanese child. Fang Li-Ching,Shyur Shyh-Dar,Peng Chun-Chih,Jim Wai-Tim,Chu Szu-Hung,Kao Yu-Hsuan,Chen Chen-Kuan,Liu Ling-Chun Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi We report a 3-year-old girl with Kawasaki disease who presented with retropharyngeal edema and shock syndrome. This is the first reported case in Taiwan. The patient initially presented with fever, cough, and pyuria followed by rapidly progressive enlarged bilateral cervical lymphadenopathy. On the third day of the fever, computed tomography for airway compression sign found widening of the retropharyngeal space mimicking a retropharyngeal abscess. Later, an endotracheal tube was inserted for respiratory distress. A skin rash over her trunk was also noted. On the fifth day of the fever, the clinical course progressed to hypotension and shock syndrome. Because of more swelling of bilateral neck lymph nodes, computed tomography was arranged again and revealed partial resolution of the edematous changes in the retropharyngeal space. Edema of the hands and feet, bilateral bulbar conjunctivitis, and fissured lips were subsequently found. The diagnosis of Kawasaki disease was confirmed on the eighth day of fever. There was no evidence of bacterial infection. She was administered intravenous immunoglobulin (2 mg/kg) and high dose aspirin (100 mg/kg/day). One day later, the fever subsided, and her blood pressure gradually became stable. Heart echocardiography on the Day 13 revealed dilated left coronary artery and mitral regurgitation. Follow-up echocardiography six months later showed normal coronary arteries. To date, the patient has not experienced any complications. This case illustrates that retropharyngeal edema and shock syndrome can be present in the same clinical course of Kawasaki disease. Clinicians and those who work in intensive care units should be aware of unusual presentations of Kawasaki disease to decrease rates of cardiovascular complications. 10.1016/j.jmii.2012.01.017
    Kawasaki shock syndrome complicating a recurrence of Kawasaki disease. Tissandier Côme,Lang Matthieu,Lusson Jean René,Bœuf Benoit,Merlin Etienne,Dauphin Claire Pediatrics We describe a case of recurrent Kawasaki disease (KD) in a non-Asian 6-year-old boy who had been diagnosed with typical KD without cardiac involvement at age 3 years. He was admitted to the PICU 3 years later for heart failure, hypotension, and deterioration of his general condition. Ultrasonography revealed left ventricular dysfunction with a 44% ejection fraction and grade I mitral valve failure without coronary artery involvement. Subsequent observation of hyperemic conjunctiva, bilateral cervical adenopathies with erythematous skin (normal neck ultrasound and computed axial tomography findings), peeling of the fingertips at day 8 of the illness, and occurrence of an inflammatory syndrome led to a diagnosis of incomplete recurrent KD with a clinical picture of Kawasaki shock syndrome (KSS). Clinical improvement was rapidly obtained after intravenous immunoglobulin and intravenous corticosteroid therapy (30 mg/kg per day for 3 subsequent days). Left ventricular function gradually improved, with ultrasound returning to normal after 3 months. Diagnosis was difficult to establish because of the recurrence of the disease and the incomplete clinical picture, with clinical features of KSS. Physicians need to be aware of these pitfalls in the management of patients with clinical signs of KD. 10.1542/peds.2014-0004