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Kawasaki disease: Clinical features and diagnosis

Kawasaki disease: Clinical features and diagnosis
Author:
Robert Sundel, MD
Section Editors:
Marisa Klein-Gitelman, MD, MPH
Sheldon L Kaplan, MD
Deputy Editor:
Elizabeth TePas, MD, MS
Literature review current through: Dec 2022. | This topic last updated: Jun 29, 2020.

INTRODUCTION — Kawasaki disease (KD, previously called mucocutaneous lymph node syndrome) is one of the most common vasculitides of childhood [1]. KD also occurs rarely in adults. It is typically a self-limited condition, with fever and manifestations of acute inflammation lasting for an average of 12 days without therapy [2]. However, complications such as coronary artery (CA) aneurysms, depressed myocardial contractility and heart failure, myocardial infarction, arrhythmias, and peripheral arterial occlusion may develop and lead to significant morbidity and mortality. (See "Cardiovascular sequelae of Kawasaki disease: Clinical features and evaluation".)

The clinical manifestations and diagnosis of KD are discussed in this topic review. The epidemiology, etiology, treatment, and complications of KD, including cardiac sequelae, are presented separately. Incomplete (atypical) KD and unique features in infants and adults are also reviewed separately. (See "Kawasaki disease: Epidemiology and etiology" and "Kawasaki disease: Initial treatment and prognosis" and "Cardiovascular sequelae of Kawasaki disease: Clinical features and evaluation" and "Incomplete (atypical) Kawasaki disease" and "Kawasaki disease: Complications".)

CLINICAL MANIFESTATIONS — The clinical features of KD reflect widespread inflammation of primarily medium-sized muscular arteries. Diagnosis is based upon evidence of systemic inflammation (eg, fever) in association with signs of mucocutaneous inflammation. The characteristic bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, rash, extremity changes, and cervical lymphadenopathy typically develop after a brief nonspecific prodrome of respiratory or gastrointestinal symptoms [3-8] (see 'Other findings' below). These characteristic clinical signs are the basis for the diagnostic criteria for KD (table 1) [9].

Variations in age have the greatest impact on a patient's likelihood of developing mucocutaneous manifestations of KD. Oral mucous membrane findings are seen in approximately 90 percent of cases of KD, polymorphous rash in 70 to 90 percent, extremity changes in 50 to 85 percent, ocular changes in >75 percent, and cervical lymphadenopathy in 25 to 70 percent [7,10-12].

These findings are often not present at the same time, and there is no typical order of appearance. As an example, some patients have only developed fever and cervical lymphadenopathy by the time of admission (so-called KD with isolated cervical lymphadenopathy, KDiL) [13]. In one case series, these patients tended to be older and to have a more severe course, with increased risk of coronary artery (CA) disease and lack of response to intravenous immune globulin (IVIG). Thus, repeated histories and physical examinations are important both for making a timely diagnosis of KD in children who fail to meet diagnostic criteria, as well as for appropriate consideration of alternative diagnoses. (See 'Diagnosis' below.)

Fever — An elevated body temperature is the most consistent manifestation of KD. Fever is minimally responsive to antipyretic agents, and it typically remains above 38.5ºC (101.3ºF) during most of the illness. On the other hand, fever may be intermittent and may be missed by parents who use tympanic, temporal, axillary, or similar temperature measurement methods that are less reliable than oral or rectal methods. Thus, the diagnosis should be considered in all children with prolonged, unexplained fever ≥5 days but should still be considered in seemingly afebrile children who have other findings consistent with KD. (See "Incomplete (atypical) Kawasaki disease".)

Conjunctivitis — Bilateral nonexudative conjunctivitis is present in more than 90 percent of patients. A predominantly bulbar injection typically begins within days of the onset of fever, and the eyes often have a brilliant erythema, which characteristically spares the limbus (picture 1). Children also are frequently photophobic. In addition, anterior uveitis may develop in up to 70 percent of children with ocular findings [12,14]; therefore, slit-lamp examination may be helpful in ambiguous cases. The presence of uveitis provides further evidence for the diagnosis of KD since it is more commonly seen in KD than in other diseases with similar presentations. (See "Uveitis: Etiology, clinical manifestations, and diagnosis".)

Mucositis — Mucositis often becomes evident as KD progresses. Cracked, red lips (picture 2) and a "strawberry tongue" (picture 3) are characteristic. The latter is a result of sloughing of filiform papillae and denuding of the inflamed glossal tissue. The bumps on the "strawberry" are the remaining fungiform papillae. These manifestations of oral mucositis may occur singly, in a very mild form, or not at all. Discrete oral lesions, such as vesicles or ulcers, and tonsillar exudate are suggestive of a disease process other than KD [6].

Rash — The cutaneous manifestations of KD are polymorphous. The rash usually begins during the first few days of illness, typically as perineal erythema and desquamation, followed by macular, morbilliform, or targetoid skin lesions of the trunk and extremities. Vesicular or bullous lesions generally are not observed, but KD may trigger a psoriasiform eruption in children not previously recognized to have psoriasis [15-19]. Patients may also have redness or crust formation at the site of Bacille Calmette-Guérin (BCG) inoculation. This finding is more useful for increasing the level of suspicion for KD in countries where BCG vaccine is routinely given. (See 'Diagnosis' below.)

Extremity changes — Changes of the extremities are generally the last manifestation to appear. Children develop an indurated edema of the dorsum of their hands and feet (picture 4) and a diffuse erythema of their palms and soles.

The convalescent phase of KD is often characterized by sheet-like desquamation that begins in the periungual region of the hands and feet (picture 5) and by linear nail creases (Beau's lines). The prevalence of periungual desquamation in patients with KD has been reported to vary from 68 to 98 percent [20].

Lymphadenopathy — Cervical lymphadenopathy is the least consistent feature of KD, absent in as many as one-half to three-quarters of children with the disease, especially those under one year of age [11]. When present, lymphadenopathy tends to primarily involve the anterior cervical nodes overlying the sternocleidomastoid muscles [21]. Often, only a single, large node is palpable, although ultrasound imaging of the neck typically reveals numerous discrete nodes arranged like a bunch of grapes [22].

Diffuse lymphadenopathy or other signs of reticuloendothelial involvement (eg, splenomegaly) should prompt a search for alternative diagnoses. (See 'Differential diagnosis' below.)

Cardiovascular findings — Cardiovascular findings are not part of the diagnostic criteria of KD, but they support the diagnosis since most conditions that mimic KD do not involve the heart. Cardiac manifestations during the first week to 10 days of illness may include tachycardia out of proportion to the degree of fever and gallop sounds [2]. These physical exam findings are the result of lymphocytic myocarditis that is ubiquitous in children with KD. In addition, heart sounds may be muffled due to a pericardial effusion, which is detected in approximately 30 percent of children with KD. Such effusions are usually small; significant fluid collections and tamponade are rare.

With improved echocardiographic techniques and better understanding of age and sex norms for CA diameters, approximately 30 percent of patients with KD are found to have CA dilatation at diagnosis [23,24]. Frank aneurysms are usually not seen until after day 10 of illness. Severely ill patients, particularly young infants, may develop fusiform aneurysms of other nonvisceral medium-sized arteries, most characteristically involving the brachial arteries. These are easily palpable or visible in the axillae, although they may be mistaken for enlarged lymph nodes. In addition, young infants may have cold, pale, or cyanotic digits of the hands and feet due to reduced perfusion. Gangrene may, in rare cases, cause loss of fingers or toes during this acute period. The cardiac complications associated with KD are discussed in detail separately. (See "Kawasaki disease: Complications", section on 'Cardiac complications' and "Cardiovascular sequelae of Kawasaki disease: Clinical features and evaluation".)

Arthritis — Arthritis is not included in the diagnostic criteria but has been reported in 7.5 to 25 percent of patients with KD [25,26]. The prevalence of arthritis was 7.5 percent in a retrospective Canadian study of 414 consecutive patients diagnosed with KD [25]. The large joints (ie, knee, ankle, and hip) were primarily involved. Oligoarticular involvement (arthritis of four or fewer joints) occurred in 16 patients and polyarticular involvement (arthritis of five or more joints) in 15 patients. With only very rare exceptions, the arthritis is self-limited and nondeforming. Patients with arthritis were more likely to have increased levels of inflammatory markers (C-reactive protein [CRP] or erythrocyte sedimentation rate [ESR]) and neutrophils. Otherwise, there were no differences in clinical features, response to therapy, or clinical outcomes between patients with or without arthritis.

Other findings — The following nonspecific symptoms commonly occur during the prodrome of the illness, 7 to 10 days before the typical mucocutaneous features develop [2,5]:

Diarrhea, vomiting, or abdominal pain – 61 percent

Irritability – 50 percent (older children with KD more commonly present with lethargy than irritability)

Vomiting alone – 44 percent

Cough or rhinorrhea – 35 percent

Decreased oral intake – 37 percent

Joint pain – 15 percent

Patients with gastrointestinal involvement often have pseudo-obstruction on radiologic studies [27]. The presentation of gastrointestinal symptoms before typical KD features may delay the diagnosis and lead to unnecessary invasive procedures including surgery.

Infants — Infants are at increased risk of CA aneurysms, possibly in part because of delay in treatment due to their lack of complete diagnostic criteria [28-31]. In a retrospective Taiwanese study of 120 patients with KD that included 20 infants ≤6 months of age, for example, the infants were more likely to present with incomplete KD than patients older than six months of age (35 versus 12 percent), have CA involvement (65 versus 19 percent), and receive late immune globulin therapy [30]. Even in infants diagnosed and treated before the 10th day of illness, the incidence of CA abnormalities is significantly higher than it is in older patients. In a retrospective study of 720 children with KD, 88 of whom were <6 months of age, a larger proportion of infants <6 months old had a dilated or aneurysmal CA on the initial echocardiogram compared with those ≥6 months old (43.4 versus 19.5 percent) [32]. Of infants <6 months old who had a normal echocardiogram at diagnosis, 18.6 percent developed a dilated or aneurysmal CA on a subsequent echocardiogram within eight weeks of diagnosis.

Adults — Approximately one-fourth of adult KD cases have occurred in patients with human immunodeficiency virus (HIV) infection [33]. One review found that cervical lymphadenopathy, hepatitis, and arthralgia were all more common in adults with KD than in children, and meningitis, thrombocytosis, and CA aneurysms were less common [34]. A subsequent review of 43 adult patients with KD in France, which excluded cases associated with HIV, found more sobering outcomes [35]. The median time to diagnosis was 13 days, and morbidity was correspondingly high: 26 percent of patients demonstrated CA vasculitis, 19 percent had CA aneurysms, and 9 percent had a myocardial infarction. Patients diagnosed before day 10, however, had outcomes similar to those seen in children. In a separate case report, splenomegaly and elevated serum ferritin levels were reported in one adult patient, most likely due to macrophage activation syndrome (MAS) complicating KD [36]. (See "Kawasaki disease: Complications", section on 'Macrophage activation syndrome'.)

LABORATORY FINDINGS — No laboratory studies are included among the diagnostic criteria for typical KD. However, certain findings may support the diagnosis of KD, particularly in incomplete cases [1] (see 'Diagnosis' below and "Incomplete (atypical) Kawasaki disease", section on 'Laboratory tests'):

Systemic inflammation is characteristic of KD. Typical manifestations include elevation of acute-phase reactants (eg, C-reactive protein [CRP] or erythrocyte sedimentation rate [ESR]), thrombocytosis that generally develops after the seventh day of illness, leukocytosis, and a left-shift (increased immature neutrophils) in the white blood cell (WBC) count.

CRP elevations resolve well before ESR does. However, patients with more severe disease can have persistently high levels of CRP for weeks. Treatment with intravenous immune globulin (IVIG) usually raises the ESR, so this lab test should not be measured after a child receives IVIG. On the other hand, control of inflammation by IVIG accelerates the decrease in CRP, making this a more useful marker of disease activity in a treated child.

Ferritin is another acute-phase reactant that is elevated in inflammatory conditions such as KD, usually less than five times the upper limit of normal. Much higher values, typically >5000 ng/mL, are seen in macrophage activation syndrome (MAS). This serious but rare complication of KD is associated with an increased resistance to IVIG treatment and an increased risk of CA abnormalities. Elevations of that magnitude are essentially diagnostic of MAS in the setting of KD. (See "Kawasaki disease: Complications", section on 'Macrophage activation syndrome' and "Clinical features and diagnosis of hemophagocytic lymphohistiocytosis", section on 'Rheumatologic disorders/MAS'.)

Lymphocyte numbers typically drop during the acute phase of KD, then rise dramatically during convalescence. Early in the course of disease, a complete blood count with a lymphocytic rather than neutrophilic preponderance is more suggestive of a viral illness. (See 'Differential diagnosis' below.)

Platelet counts generally rise by the second week of illness and may reach 1,000,000/mm3 (reactive thrombocytosis) in the most severe cases. In some studies, the degree of thrombocytosis correlates with the risk of coronary artery (CA) changes in KD. On the other hand, rare children with KD develop thrombocytopenia due to a consumptive coagulopathy. These patients are at significantly increased risk of morbidity and mortality, particularly the development of CA abnormalities [37]. (See "Kawasaki disease: Complications", section on 'Cardiac complications'.)

Thrombocytopenia, high triglycerides, low sodium, elevated liver function tests, and monocytes/macrophages in cerebral spinal fluid (CSF) can all be signs of subclinical MAS and may warrant further diagnostic testing. (See "Kawasaki disease: Complications", section on 'Macrophage activation syndrome'.)

Children with KD often present with a normocytic, normochromic anemia. Hemoglobin concentrations more than two standard deviations below the mean for age are noted in one-half of patients within the first two weeks of illness (table 2).

Urinary microscopy commonly reveals WBCs [38]. Pyuria is usually of urethral origin and therefore may be missed on urinalyses obtained by bladder tap or catheterization [39]. The WBCs are not polymorphonuclear leukocytes and therefore are not detected by dipstick tests for leukocyte esterase. Thus, children with suspected KD should have a clean voided or bagged urine specimen collected for microscopic examination in order to detect this characteristic feature.

In one retrospective series of 259 patients, 45 percent had at least one abnormal liver function test [40]. In a case-control series, approximately 30 percent of 280 patients with KD had mild-to-moderate elevation of transaminases (eg, serum alanine aminotransferase >50 units/L) [6]. The reason for this transaminitis is unclear. In addition, a minority of children develop obstructive jaundice from hydrops of the gallbladder.

CSF may display a mononuclear pleocytosis without hypoglycorrhachia (decreased CSF glucose) or elevation of CSF protein. In a retrospective review, 46 of 520 children with KD underwent lumbar puncture [41]. In this subset of patients, 39 percent had elevated CSF WBC counts. The median count was 22.5 cells/mm3 with 6 percent neutrophils and 92 percent mononuclear cells, although cell counts as high as 320/mm3 with up to 79 percent neutrophils were reported.

Similarly, arthrocentesis of inflamed joints in KD typically demonstrates a pleocytosis, with 125,000 to 300,000 WBCs/mm3, primarily neutrophils [42].

Children with KD develop significant perturbations in serum lipid profiles, including elevated triglycerides and low-density lipoproteins, and depressed high-density lipoproteins [2,43-45], as is often observed in a variety of infectious and inflammatory conditions. A return to normal generally occurs within weeks or months following IVIG therapy, though abnormalities may persist for years in children who are not treated with IVIG [44].

Hyponatremia (serum sodium <135 mEq/L) may be seen and is associated with an increased risk of CA aneurysms [46].

DIAGNOSIS — Diagnosis of KD according to the criteria established by Tomisaku Kawasaki in 1967 [47] requires the presence of fever lasting ≥5 days, combined with at least four of the five following physical findings, without an alternative explanation (table 1) [1,2,48]:

Bilateral bulbar conjunctival injection (picture 1)

Oral mucous membrane changes, including injected or fissured lips (picture 2), injected pharynx, or strawberry tongue (picture 3)

Peripheral extremity changes, including erythema of palms or soles, edema of hands or feet (acute phase) (picture 4), or periungual desquamation (convalescent phase) (picture 5)

Polymorphous rash

Cervical lymphadenopathy (at least one lymph node >1.5 cm in diameter)

Approximately 40 percent of children with KD have a concurrent infection. Ascribing the fever to such an infection or to KD requires clinical judgement.

Redness or crust formation at the site of Bacille Calmette-Guérin (BCG) inoculation is also suggested as a useful sign in several diagnostic guidelines [2,9]. In one series of 15,524 patients with KD and a history of BCG vaccination, 50 percent had this finding compared with none of the 53 children admitted with respiratory syncytial virus or rotavirus infection who served as the control group [19].

Rash and conjunctival injection are seen with many illnesses, but other KD features, such as red, cracked lips and redness and swelling of the hands and feet, are unusual in the illnesses in the differential diagnosis and should increase the suspicion for KD. (See 'Differential diagnosis' below.)

Typical versus incomplete KD — As with all clinical criteria, these are imperfect guidelines with less than 100 percent sensitivity and specificity. In addition, Dr. Kawasaki published his guidelines before cardiac involvement was recognized in this disease, so they were never intended to identify children at risk for developing coronary artery (CA) abnormalities. Thus, it is not surprising that at least 10 percent of children who develop CA aneurysms never meet criteria for KD [49]. Incomplete KD should be suspected in patients less than six months of age with unexplained fever ≥7 days, even if they have no clinical findings of KD, and in patients of any age with unexplained fever ≥5 days and only two or three clinical criteria. An algorithmic approach can help identify such cases (algorithm 1) [2] and thereby significantly decrease the number of children who develop CA abnormalities despite not meeting criteria for the disease. (See "Incomplete (atypical) Kawasaki disease".)

Laboratory evaluation — As noted above, Dr. Kawasaki identified the first 50 cases of "mucocutaneous lymph node syndrome" on the basis of clinical findings rather than laboratory or imaging studies [47]. Thus, no laboratory values are included in the classical diagnostic criteria, but they nonetheless may support a diagnosis of KD in ambiguous cases. In fact, some laboratory tests are explicitly included in the algorithm for diagnosis of atypical KD (algorithm 1) [2]. (See "Incomplete (atypical) Kawasaki disease", section on 'Laboratory tests'.)

The following blood tests are typically obtained on children in whom a diagnosis of KD is being considered:

Complete blood counts with differential white blood cell (WBC) counts

Liver function tests including aspartate transaminase (AST), alanine transaminase (ALT), and albumin

C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)

Urinalysis

Elevated WBC and platelet counts, transaminases, and acute-phase reactants, as well as anemia and pyuria, are suggestive of KD.

In addition, when specific mimics of KD are strongly suspected, studies that are more specific for these alternative diagnoses may help confirm the diagnosis. These can include rapid viral testing (eg, adenovirus), serologic testing for leptospirosis and other bacterial infections, and blood cultures. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with an emerging syndrome (multisystem inflammatory syndrome in children [MIS-C]) of persistent fever, systemic inflammation, and multiorgan failure children with some features of KD [50]. Polymerase chain reaction (PCR) testing for SARS-CoV-2 should be performed in children who present with features of MIS-C, particularly if there is evidence of coronavirus disease 19 (COVID-19) exposure. (See "COVID-19: Multisystem inflammatory syndrome in children (MIS-C) clinical features, evaluation, and diagnosis".)

Echocardiography — Echocardiography should be performed in all patients with KD as soon as the diagnosis is suspected in order to establish a reference point for longitudinal follow-up (algorithm 1) and treatment efficacy. In addition, initial CA diameter is a factor in identifying patients at high risk of developing a coronary aneurysm and therefore warranting augmentation of initial intravenous immune globulin (IVIG) therapy (see "Kawasaki disease: Complications", section on 'Coronary artery abnormalities' and "Cardiovascular sequelae of Kawasaki disease: Clinical features and evaluation", section on 'Risk factors'). Finally, CA diameters are useful for identifying patients who should be treated with IVIG despite failing to meet classical diagnostic criteria for KD. Echocardiographic evaluation for KD is discussed in greater detail separately. (See "Cardiovascular sequelae of Kawasaki disease: Clinical features and evaluation", section on 'Initial evaluation' and "Incomplete (atypical) Kawasaki disease", section on 'Echocardiography'.)

DIFFERENTIAL DIAGNOSIS — KD is most commonly confused with infectious exanthems of childhood [2,51,52]. Early in the course, KD is often mistaken for more routine childhood illnesses, such as viral gastroenteritis, viral upper respiratory tract infection, or pneumonia, depending upon the other presenting symptoms, such as vomiting or cough. Concurrent viral infections are common, and, therefore, the presence of respiratory symptoms or positive respiratory viral polymerase chain reaction (PCR) testing does not exclude the diagnosis of KD [53]. Meningitis is sometimes suspected due to irritability.

Infectious diseases and other mimics of KD may have the following clinical features not commonly found in KD [2]:

Exudative conjunctivitis (eg, adenovirus)

Exudative pharyngitis (eg, streptococcal pharyngitis)

Discrete intraoral lesions (eg, Koplik spots in measles)

Bullous or vesicular rash (eg, Stevens-Johnson syndrome [SJS])

Generalized lymphadenopathy (eg, Epstein-Barr virus [EBV] infection)

The presence of any of these findings and/or the absence of fever should suggest a diagnosis other than KD. Of note, concurrent infections (both viral and bacterial) are common in patients with KD, found in up to 33 percent of children in one study [54]. In this retrospective analysis of 129 consecutive children seen with KD in Toronto, infection at the time of diagnosis did not affect response to therapy or outcome. In any event, diagnosis of an infectious condition does not preclude a concurrent diagnosis of KD.

The differential diagnosis of KD includes (table 3):

Measles, echovirus, adenovirus [55], and EBV – These viral illnesses may share many of the signs of mucocutaneous inflammation, but they typically have less evidence of systemic inflammation and generally lack the extremity changes seen in KD. In addition, EBV typically causes a polyclonal gammopathy while serum immunoglobulin G (IgG) in KD is usually low or low normal [56]. (See "Measles: Clinical manifestations, diagnosis, treatment, and prevention" and "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention" and "Pathogenesis, epidemiology, and clinical manifestations of adenovirus infection" and "Clinical manifestations and treatment of Epstein-Barr virus infection".)

Toxin-mediated illnesses, especially group A streptococcal infections (eg, scarlet fever and toxic shock syndrome) – These usually lack the ocular and articular involvement typical of KD, though patients with staphylococcal toxic shock syndrome occasionally have conjunctival erythema. Patients with toxic shock often have generalized edema. The edema is rarely confined to the hands and feet, as it is in children with KD. Patients with scarlet fever may have periungual desquamation. (See "Invasive group A streptococcal infection and toxic shock syndrome: Epidemiology, clinical manifestations, and diagnosis" and "Staphylococcal toxic shock syndrome" and "Invasive group A streptococcal infections in children", section on 'Clinical manifestations'.)

Rocky Mountain spotted fever and leptospirosis – Headache and gastrointestinal complaints typically are prominent features of these infections. (See "Clinical manifestations and diagnosis of Rocky Mountain spotted fever" and "Leptospirosis: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

Drug reactions such as SJS or serum sickness – These may mimic KD but with subtle differences in the ocular and mucosal manifestations, such as keratitis in SJS rather than uveitis in KD. Further, laboratory markers of inflammation are generally normal or only mildly elevated. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis".)

Systemic juvenile idiopathic arthritis (JIA) – Children with this condition generally lack the conjunctival and oral findings of KD. Lymphadenopathy also is generalized, and it may be accompanied by splenomegaly, unlike in KD. While systemic JIA is not generally associated with cardiac involvement other than pericarditis, several case reports have documented moderate coronary involvement (Z-score <3.0) in children with systemic JIA [57]. (See "Systemic juvenile idiopathic arthritis: Clinical manifestations and diagnosis".)

Delayed diagnosis — Treatment with intravenous immune globulin (IVIG) within the first 10 days of illness reduces the prevalence of coronary artery (CA) aneurysms fivefold compared with children not treated with IVIG [58,59]. Thus, it is desirable to diagnose KD as soon as possible after the onset of symptoms in order to initiate treatment and reduce the risk of CA lesions [60]. However, timely identification is challenging because the diagnosis is based upon nonspecific clinical signs and there is no definitive diagnostic test. Thus, the clinicians in a medical facility with the most experience taking care of patients with KD should be consulted as early as possible in the course of the evaluation of suspected KD. These clinicians may include pediatric rheumatologists, infectious disease specialists, cardiologists, and/or hospitalists, depending upon the institution.

In a retrospective study of 562 patients diagnosed with KD at eight North American centers, 92 cases (16 percent) were diagnosed after the first 10 days of illness (ie, late diagnosis) [61]. Predictors of a delay in diagnosis of KD included age below six months, clinical presentation of incomplete KD, greater distance from a tertiary center, and variability between clinical centers. In contrast, socioeconomic status was not associated with a delay in diagnosis.

These findings suggest that practice variation in confirming a diagnosis of KD may in part contribute to a delayed diagnosis. The results of this study underscore the need for a high index of suspicion of KD, especially in young infants and patients who present with incomplete KD, in order to identify and treat patients in a timely manner. (See "Incomplete (atypical) Kawasaki disease".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Kawasaki disease".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Kawasaki disease (The Basics)")

SUMMARY AND RECOMMENDATIONS

Overview – Kawasaki disease (KD, also called mucocutaneous lymph node syndrome) is one of the most common vasculitides of childhood. KD occurs only rarely in adults. It is typically a self-limited condition, with fever and manifestations of acute inflammation lasting for an average of 12 days without therapy. (See 'Introduction' above.)

Clinical manifestations – KD is characterized by systemic inflammation manifested by fever and mucocutaneous involvement, including bilateral nonexudative conjunctivitis (picture 1), erythema of the lips and oral mucosa (picture 2 and picture 3), polymorphous rash, extremity changes (picture 4 and picture 5), and cervical lymphadenopathy (table 1). These findings are often not present at the same time. Thus, repeated histories and physical examinations are important in making a timely diagnosis of KD in children with fever and signs of mucocutaneous inflammation. (See 'Clinical manifestations' above.)

Laboratory findings – No laboratory studies are included among the diagnostic criteria for typical KD. However, the presence of compatible laboratory features strongly supports the diagnosis. (See 'Laboratory findings' above and "Incomplete (atypical) Kawasaki disease", section on 'Laboratory tests'.)

Diagnosis – The diagnosis of KD according to classical criteria requires the presence of fever ≥5 days, combined with at least four of the other five signs of mucocutaneous inflammation, without any other explanation (table 1 and algorithm 1). A significant proportion of children with KD have a concurrent infection; therefore, ascribing the fever to such an infection or to KD requires clinical judgment. Additional clinical and laboratory features are often used to guide diagnosis in children who have fewer than five criteria for KD (incomplete KD). (See 'Diagnosis' above and "Incomplete (atypical) Kawasaki disease".)

Incomplete KD and delayed diagnosis in infants and adults Infants and possibly adults are more likely to present with incomplete KD. Infants are at greater risk for cardiovascular sequelae, possibly due in part to a delay in diagnosis and intervention. Thus, infants six months of age or younger with unexplained fever for at least seven days should be evaluated for KD, even if they have no clinical findings of KD. Adults with delayed diagnosis also have a higher rate of morbidity. (See 'Infants' above and 'Adults' above.)

Differential diagnosis – KD is most commonly confused with infectious exanthems of childhood. The presence of clinical features not commonly found in KD, including exudative conjunctivitis, exudative pharyngitis, discrete intraoral lesions, bullous or vesicular rash, splenomegaly, and/or generalized lymphadenopathy, suggest another diagnosis (table 3). Nonetheless, KD is sufficiently pleomorphic that none of these findings can definitively exclude the diagnosis. Children with KD can have concurrent infections, particularly with viruses circulating in the community at the time of their diagnosis. (See 'Differential diagnosis' above.)

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