Kawasaki disease: Clinical features and diagnosis

INTRODUCTION — 

Kawasaki disease (KD, previously called mucocutaneous lymph node syndrome) is one of the most common forms of systemic vasculitis in children [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].

The most common complication of KD is the development of coronary artery (CA) aneurysms, which can lead to significant morbidity and mortality. Less common but potentially devastating complications include depressed myocardial contractility and heart failure, myocardial infarction, arrhythmias, and peripheral arterial occlusion. (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, and unique features in infants and adults are reviewed separately. (See "Kawasaki disease: Pathogenesis, epidemiology, and etiology" and "Kawasaki disease: Initial treatment and prognosis" and "Cardiovascular sequelae of Kawasaki disease: Clinical features and evaluation".)

CLINICAL MANIFESTATIONS — 

The clinical manifestations of Kawasaki disease (KD) are often not present at the same time, and for most features, there is no typical order of appearance. 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 'Evaluation and diagnosis' below and 'Differential diagnosis' below.)

Inflammatory features — The inflammatory features of KD reflect widespread inflammation of primarily medium-sized muscular arteries.

Fever — High unremitting fevers are the hallmark of KD [3-6]. Children who are afebrile or only briefly febrile are quite unlikely to have KD.

The fever of KD is minimally responsive to antipyretic agents, and it typically remains above 38.5ºC (101.3ºF) during most of the illness. All patients eventually defervesce, even without treatment. The duration of fever is typically between 7 to 12 days, but fevers for >3 weeks have been reported.

Ocular manifestations

●Conjunctivitis – Bilateral nonexudative conjunctivitis is present in more than 90 percent of patients with KD [3-6].

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.

●Uveitis – Anterior uveitis may develop in up to 70 percent of children with ocular findings [6,7]; therefore, slit-lamp examination may be helpful in ambiguous cases. Iridocyclitis (ie, uveitis and inflammation of the adjacent ciliary body) may also occur.

●Other ocular manifestations – Other ocular complications of KD include vitreous opacities, papilledema, and subconjunctival hemorrhage [8,9].

Lymphadenopathy — Cervical lymphadenopathy is present in 25 to 70 percent of patients with KD, making it the least reliable finding associated with this disease [3-6]. Cervical lymphadenopathy is frequently absent in children under one year of age [5].

When present, lymphadenopathy tends to primarily involve the anterior cervical nodes overlying the sternocleidomastoid muscles [10]. 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 [11].

Some patients with KD have only fever and cervical lymphadenopathy at the time of admission (so-called "node first" KD) [12]. These patients tend to be older and to have a more severe course, with increased risk of coronary artery (CA) abnormalities and lack of response to intravenous immune globulin (IVIG).

Mucocutaneous manifestations

Mucositis — Oral mucous membrane findings are seen in approximately 90 percent of patients of KD but may appear only after other features of KD have already presented [3-6].

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.

Rash — A polymorphous rash is present in 70 to 90 percent of patients with KD [3-6].

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. Other cutaneous manifestations include:

●A psoriasiform eruption in children not previously recognized to have psoriasis [13-17].

●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 'Evaluation and diagnosis' below.)

Extremity changes — Extremity changes are present in most patients in both the acute and convalescent phase of KD:

●Acute phase – Children develop an indurated edema of the dorsum of their hands and feet (picture 4) and a diffuse erythema of their palms and soles. These changes occur in 50 to 85 percent of patients with KD but are often the last manifestation to appear [3-6].

●Convalescent phase – 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 [18].

Other manifestations

Arthritis — Arthritis is not included in the diagnostic criteria but has been reported in 7.5 to 25 percent of patients with KD [19,20].

In a study of 414 patients with KD, the most common pattern of joint involvement was an oligoarthritis or polyarthritis of the large joints (ie, knee, ankle, and hip) [19]. With only very rare exceptions, the arthritis was self-limited and nondeforming. A large cohort study in China reported an incidence of arthritis in KD of 10.6 percent, with two-thirds of patients having an oligoarticular course and one-third having a polyarticular course.

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.

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. The most important cardiovascular finding is CA aneurysms.

●Kawasaki disease shock syndrome – KD shock syndrome (KDSS) is an uncommon presentation of KD associated with warm shock and low peripheral vascular resistance. KDSS is discussed in detail elsewhere. (See "Cardiovascular sequelae of Kawasaki disease: Clinical features and evaluation", section on 'KD shock syndrome'.)

●Early manifestations – 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 examination findings are the result of lymphocytic myocarditis that is ubiquitous in children with KD, which may be associated with mild to moderate ventricular dysfunction that typically resolves with treatment.

In addition, small pericardial effusions may occur. However, significant fluid collections and tamponade are rare.

●Coronary artery aneurysms – CA aneurysms are defined as follows:

•Dilation – Z-score 2 to <2.5

•Small aneurysm – Z-score ≥2.5 to <5

•Medium aneurysm – Z-score ≥5 to <10 and absolute dimension <8 mm

•Large aneurysm – Z-score ≥10 or absolute dimension ≥8 mm

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 (Z-score of 2) at diagnosis [21,22].

Medium- or larger-sized aneurysms are usually not seen until after day 10 of illness. 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) [23], highlighting the greater risk for aneurysms in this age group. In addition, 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.

The cardiac complications associated with KD are discussed in detail separately. (See "Cardiovascular sequelae of Kawasaki disease: Clinical features and evaluation".)

Nonspecific symptoms — The following nonspecific symptoms commonly occur during the prodrome of the illness, 7 to 10 days before the typical mucocutaneous features develop [2,24]:

●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

Lack of awareness that KD may present with nonspecific symptoms initially before the development of the typical mucocutaneous features may lead to delays in diagnosis, misdiagnosis, and unnecessary interventions.

Less common manifestations

●Peripheral vascular – Peripheral arterial obstruction can lead to ischemia and gangrene. This complication generally accompanies other manifestations of severe disease, such as giant CA aneurysms and aneurysms in peripheral arteries [25].

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.

●Central nervous system – Irritability is a feature of the acute illness and is thought to be related to the cerebral spinal fluid pleocytosis seen in up to 40 percent of children with KD. Data regarding potential long-term behavioral problems have been mixed [26,27].

In general, direct vasculitic effects on the brain in KD are unusual, and autopsy studies before the introduction of IVIG treatment showed minimal central nervous system involvement [28].

●Urinary abnormalities and kidney disease – With the exception of sterile pyuria, urinary abnormalities and kidney disease are uncommonly associated with KD.

Among the kidney complications noted in selected cases are acute interstitial nephritis, mild proteinuria, and acute kidney injury (AKI) [29-31]. AKI is a rare complication of KD and has been reported in association with hemolytic uremic syndrome, immune complex-mediated glomerulonephritis, and acute interstitial nephritis [30,31].

As with all unusual manifestations of KD, other diagnoses must be seriously entertained when organs other than the heart are involved. (See "Acute kidney injury in children: Clinical features, etiology, evaluation, and diagnosis" and "Clinical manifestations and diagnosis of Shiga toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome in children" and "Intravenous immune globulin: Adverse effects", section on 'Complications affecting the kidney'.)

●Gastrointestinal findings — Gastrointestinal manifestations, including the following, may rarely occur in conjunction with KD:

•Hydrops of the gallbladder [32]

•Cholestasis [32]

•Paralytic ileus [32]

•Vasculitis of the appendix [32]

•Gastrointestinal obstruction [33]

•Pseudoobstruction [34,35]

•Intussusception [36]

•Pancreatitis [37,38]

•Bile duct stenosis [38]

Hydrops of the gallbladder is the most common of these findings but is uncommon overall, perhaps because most children do not have abdominal ultrasonography in the acute phase of illness. It occurs in the acute phase of KD and generally resolves rapidly after IVIG. Other gastrointestinal manifestations are considerably less common, and alternate diagnoses should be considered prior to attributing these findings to KD. (See 'Differential diagnosis' below.)

●Sensorineural hearing loss – Sensorineural hearing loss can occur during the acute illness. Most patients will have complete resolution of hearing loss after several months [39]. However, up to 30 percent of patients will have hearing loss that persists past six months [40]. Risk factors for persistent sensorineural hearing loss include delayed use of IVIG and prolonged thrombocytosis, anemia, and an elevated ESR.

LABORATORY FINDINGS — 

A diagnosis of Kawasaki disease (KD) is established on clinical grounds. However, certain laboratory findings may support the diagnosis of KD, particularly in incomplete cases [1]. (see 'Evaluation and diagnosis' below):

●Acute phase reactant elevation – Elevated levels of acute phase reactants (eg, C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], ferritin) are common among patients with KD.

Of these tests, the CRP may be a better marker of disease activity (see "Acute phase reactants", section on 'Discrepancies between acute phase reactant levels'):

•CRP changes in response to inflammation faster than the ESR or ferritin

•Treatment with intravenous immune globulin (IVIG) leads to a false-positive elevation in the ESR

KD is unlikely if the CRP is less than 3 mg/dL or the ESR is less than 40 mm/hour [2]

●Hematologic abnormalities

•Lymphocytes – Lymphocyte numbers typically decrease during the acute phase of KD, then rise dramatically during convalescence.

•Platelets

-Thrombocytosis – 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 [41].

-Thrombocytopenia – Rarely, 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 [42].

•Anemia – 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 1).

●Pyuria – Urinary microscopy commonly reveals macrophages [43]. Children with suspected KD should have a clean voided or bagged urine specimen collected for microscopic examination:

•Pyuria is usually of urethral origin and therefore may be missed on urinalyses obtained by bladder tap or catheterization [44].

•The white blood cells (WBCs) are not polymorphonuclear leukocytes and therefore are not detected by dipstick tests for leukocyte esterase.

●Transaminitis – In one retrospective series of 259 patients, 45 percent had at least one abnormal liver function test [45]. 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) [46]. The reason for this transaminitis is unclear. In addition, a minority of children develop obstructive jaundice from hydrops of the gallbladder.

●Serum lipids – Children with KD develop significant perturbations in serum lipid profiles, including elevated triglycerides and low-density lipoproteins as well as depressed high-density lipoproteins [2,47-49], as is often observed in a variety of infectious and inflammatory conditions.

Serum lipids generally return to normal within weeks or months following IVIG therapy, although serum lipid abnormalities may persist for years in children who are not treated with IVIG [48].

●Hyponatremia – Hyponatremia (serum sodium <135 mEq/L) may be seen in severe illness and is associated with an increased risk of CA aneurysms [50].

●Hypoalbuminemia – Hypoalbuminemia (serum albumin ≤ 3 g/dL) may also be seen in severe illness and is a component of the laboratory evaluation for incomplete KD.

●Cerebrospinal pleocytosis – Cerebrospinal fluid (CSF) may display a mononuclear pleocytosis without decreased CSF glucose or elevation of CSF protein. In a retrospective review, 46 of 520 children with KD underwent lumbar puncture [51]. 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 cells/mm³ with up to 79 percent neutrophils were reported.

●Synovial fluid pleocytosis – Arthrocentesis of inflamed joints in patients with KD typically demonstrates a pleocytosis, with 125,000 to 300,000 WBCs/mm³, primarily neutrophils [52].

EVALUATION AND DIAGNOSIS

Importance of early diagnosis — Because early treatment decreases the long-term morbidity of Kawasaki disease (KD), it is important to maintain a high level of suspicion for this diagnosis. Treatment with intravenous immune globulin (IVIG) within the first 10 days of illness, and ideally before day 7 of illness, reduces the prevalence of coronary artery (CA) aneurysms fivefold compared with children not treated with IVIG [53,54].

Delays in diagnosis are associated with the following factors: [55].

●Age below six months

●Incomplete KD

●Greater distance from a tertiary center

●Limited local expertise with KD

By contrast, socioeconomic status was not associated with a delay in diagnosis [56].

In whom to suspect

Children — KD should be considered in all children with unexplained fever, lasting for at least five days, particularly when associated with one or more of the following:

●Uveitis

●Red, cracked lips

●Redness and swelling of the hands and feet

●Redness or crust formation at the site of Bacille Calmette-Guérin (BCG) inoculation [2,57].

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 [17].

Classically, children present with bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, rash, extremity changes, and cervical lymphadenopathy following a brief nonspecific prodrome of respiratory or gastrointestinal symptoms [3,24,46,58-60]. However, children with KD may lack some or all of these features. Both infants and adults are less likely to meet formal criteria for KD, leading to delays in diagnosis [61-64].

Adults — KD rarely presents in adults. As in children, KD should be considered in patients with persistent, unexplained fever, particularly among patients with human immunodeficiency virus (HIV) infection. Approximately one-fourth of adult KD cases have occurred in patients with HIV [65].

Adults may present with a different spectrum of features than those classically associated with KD in children. One review found that cervical lymphadenopathy, hepatitis, and arthralgias were all more common in adults with KD than children [66].

Many adult patients will be diagnosed only after having developed complications associated with CA aneurysms. A review of 43 adult patients with KD in France, which excluded cases associated with HIV, found that at the time of diagnosis, 26 percent of patients demonstrated CA vasculitis, 19 percent had CA aneurysms, and 9 percent had a myocardial infarction [67].

Apply diagnostic criteria — Diagnosis of KD according to the criteria established by Tomisaku Kawasaki in 1967 [68] requires the presence of fever lasting ≥5 days, combined with at least four of the five following physical findings, without an alternative explanation (table 2) [1,2,69]:

●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)

However, many patients with KD will have "incomplete" KD, which fails to meet epidemiologic case definition.

Consider incomplete Kawasaki disease — Incomplete KD should be suspected in the following scenarios:

●Patients less than six months of age with unexplained fever ≥7 days, even if they have no clinical findings of KD

●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.

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 CA abnormalities. Thus, it is not surprising that at least 10 percent of children who develop CA aneurysms never meet criteria for complete KD [70]. 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 [63].

Laboratory evaluation for ambiguous cases — In most cases, KD is diagnosed based on clinical features alone [68]. When the diagnosis cannot be established clinically, laboratory testing may be used to help support a diagnosis of incomplete KD (algorithm 1) [2].

Laboratory findings suggestive of KD include the following [2]:

●Elevated acute-phase reactants (C-reactive protein [CRP] ≥3 mg/dL [≥30 mg/L] or erythrocyte sedimentation rate [ESR] ≥40 mm/hour)

●White blood cell (WBC) count ≥15,000/microL

●Normocytic, normochromic anemia for age (table 1)

●Platelet cell count ≥450,000/microL after seven days of illness

●Non-neutrophilic (sterile) pyuria due to urethritis in KD (≥10 WBCs/high-power field)

●Serum alanine aminotransferase level >50 units/L

●Serum albumin ≤3 g/dL

Elevated WBC and platelet counts, transaminases, and acute phase reactants, as well as anemia and pyuria, are suggestive of KD. (See 'Laboratory findings' above.)

In addition, when specific mimics of KD are strongly suspected, we perform tests to establish an alternate diagnosis. These may include (see 'Infectious etiologies' below):

●Rapid viral testing (eg, adenovirus)

●Serologic testing for leptospirosis and other bacterial infections

●Blood cultures

●Polymerase chain reaction (PCR) testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Echocardiography for all patients — Echocardiography should be performed in all patients as soon as a diagnosis of KD is suspected in order to establish a reference point for longitudinal follow-up and treatment efficacy (algorithm 1).

In addition, initial CA diameter is one of the most predictive risk factors for developing a CA aneurysm and therefore high baseline Z-scores warrant augmentation of initial IVIG therapy. (See "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. The following echocardiographic abnormalities are suggestive of KD [2]:

●CAs with Z-scores of the left anterior descending coronary artery (LAD) or right coronary artery (RCA) of ≥2.5; or

●CA aneurysms of arteries other than the proximal LAD or RCA; or

●Three of the following findings:

•Findings consistent with coronary arteritis (eg, Z-score of the LAD or RCA ≥2.0 to 2.5)

•Decreased left ventricular contractility

•Mild valvular regurgitation (primarily mitral valve)

•Pericardial effusion

None of these findings are pathognomonic for KD, but significantly dilated CAs are unusual in other conditions.

Echocardiographic evaluation for KD is discussed in greater detail separately. (See "Cardiovascular sequelae of Kawasaki disease: Clinical features and evaluation", section on 'Initial evaluation'.)

DIFFERENTIAL DIAGNOSIS — 

An overview of the differential diagnosis of Kawasaki disease (KD) is presented in the table (table 3):

Features that suggest alternate diagnoses

The following clinical features are not commonly found in KD and are suggestive of alternative diagnoses [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)

●Splenomegaly (eg, EBV)

●Discrete oral lesions (eg, vesicles or ulcers)

Additionally, a complete blood count with a lymphocytic (rather than neutrophilic) preponderance early in the disease course is more consistent with a viral infection rather than KD.

A diagnosis of an infectious condition does not preclude a concurrent diagnosis of KD. Concurrent infections (both viral and bacterial) are found in up to 33 percent of children with KD [71,72] and should be treated appropriately.

Infectious etiologies

●Viral infections – Measles, echovirus, adenovirus, and EBV all present with mucocutaneous inflammation, which may be mistaken for KD [73]. Adenovirus is a particularly common mimicker of KD, and polymerase chain reaction (PCR) testing should be considered in the seasons that adenovirus circulates widely.

However, these viral illnesses 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 can be low or low normal [74].

These diagnoses are discussed in detail elsewhere. (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 infections" and "Clinical manifestations and treatment of Epstein-Barr virus infection".)

●Bacterial infections

•Rocky Mountain spotted fever and leptospirosis – Rocky Mountain spotted fever and leptospirosis both present with an acute febrile illness accompanied by lymphadenopathy and rash, which may be mistaken for KD.

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

•Scarlet fever – Patients with scarlet fever may have periungual desquamation in addition to fever, erythema of the oropharynx, and rash.

However, appropriate treatment with antibiotics should lead to rapid defervescence. (See "Complications of streptococcal tonsillopharyngitis", section on 'Scarlet fever' and "Invasive group A streptococcal infections in children", section on 'Treatment'.)

•Toxic shock syndrome – Patients with staphylococcal toxic shock syndrome occasionally have conjunctival erythema and edema.

However, they usually lack the ocular and articular involvement typical of KD. Additionally, unlike KD, the edema of toxic shock syndrome is not confined to the hands and feet. (See "Staphylococcal toxic shock syndrome", section on 'Diagnosis' and "Invasive group A streptococcal infection and toxic shock syndrome: Epidemiology, clinical manifestations, and diagnosis", section on 'Toxic shock syndrome'.)

●Multisystem inflammatory syndrome in children – Multisystem inflammatory syndrome in children (MIS-C) is characterized by persistent fever, systemic inflammation, and multiorgan failure children and shares some clinical features of KD [75].

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".)

Noninfectious etiologies

●Drug reactions – SJS and serum sickness may mimic KD.

However, there are 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 – While systemic juvenile idiopathic arthritis (sJIA) is not generally associated with cardiac involvement other than pericarditis, several case reports have documented coronary involvement (Z-score <3) in children with systemic JIA [76].

However, 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. (See "Systemic juvenile idiopathic arthritis: Clinical manifestations and diagnosis".)

●Macrophage activation syndrome – Macrophage activation syndrome (MAS) is a life-threatening complication of rheumatic diseases. Although it occurs most frequently in patients with systemic JIA, it may also occur in patients with KD.

Leukopenia, thrombocytopenia, high triglycerides, low sodium, elevated liver function tests, and monocytes/macrophages in cerebrospinal fluid (CSF) can all be signs of subclinical MAS and may warrant further diagnostic testing.

A ferritin >5000 ng/mL in a patient with KD may be suggestive of MAS. When this occurs in association with KD, it is associated with an increased resistance to IVIG treatment and an increased risk of coronary artery (CA) abnormalities. (See "Clinical features and diagnosis of hemophagocytic lymphohistiocytosis", section on 'Rheumatologic disorders'.)

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 5^th to 6^th 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 10^th to 12^th 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) 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 as well as extremity changes (picture 4 and picture 5), and cervical lymphadenopathy (table 2). 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 complete KD. However, the presence of compatible laboratory features strongly supports the diagnosis. (See 'Laboratory findings' above.)

●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 criteria, without any other explanation (table 2 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 'Evaluation and diagnosis' above.)

●Incomplete Kawasaki disease and delayed diagnosis in infants and adults – Infants and possibly adults are more likely to present with incomplete KD (ie, KD that does not meet diagnostic criteria). Infants are at greater risk for cardiovascular sequelae, possibly due in part to a delay in diagnosis and intervention although they may have inherently more severe disease. Thus, infants six months of age or younger with unexplained fever for at least seven days need to 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 'Children' 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 (algorithm 1). (See 'Differential diagnosis' above.)

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges Robert Sundel, MD, who contributed to earlier versions of this topic review.