Differentials
Staphylococcal or streptococcal infection
SIGNS / SYMPTOMS
A positive response to antibiotics; visible skin lesions; purulent tonsils; burns, and signs of pneumonia or septic arthritis.
INVESTIGATIONS
Positive blood culture, throat swab, and skin swab.
Ultrasound of a single lymph node shows that bacterial lymphadenitis is most commonly associated with a single node with a hypoechoic core.[1]
Systemic juvenile idiopathic arthritis (systemic JIA)
SIGNS / SYMPTOMS
Typically presents with fever, rash, and lymphadenopathy. Some patients have arthritis at disease onset, with others developing this during their disease course. Serositis (pericardial effusion or pleural effusion), hepatosplenomegaly and deranged coagulation can occur. Complicating macrophage activation syndrome is common and is associated with increased mortality.
The rash is a fine, evanescent salmon pink, usually appears on the trunk, proximal extremities and, less commonly, on the face. The rash accompanies the spikes of fever and tends to disappear when the fever is down.
These patients do not develop coronary artery aneurysms.
Unlike with other forms of JIA, patients with systemic JIA are usually anemic and have extremely high acute phase markers (erythrocyte sedimentation rate and CRP), as is found in KD.
INVESTIGATIONS
Clinical features can differentiate these conditions.
Scarlet fever
SIGNS / SYMPTOMS
An acute febrile illness caused by group A streptococcus.
The patients usually have evidence of upper respiratory tract infection, mostly pharyngitis, accompanied by a diffuse, fine papular erythematous rash that appears on the trunk, extremities, and face, but with circumoral pallor.
Resolution of the rash is associated with desquamation that starts in the face and progresses downward.
Unlike in KD, in scarlet fever lips are spared and there is no conjunctivitis or conjunctival injection.
INVESTIGATIONS
Positive throat culture, or positive serologic test for group A streptococcus (streptozyme and/or antistreptolysin O), will confirm the diagnosis.
Acute rheumatic fever
SIGNS / SYMPTOMS
An acute illness that occurs 3 to 4 weeks following the onset of group A streptococcal pharyngitis.
These patients develop migratory polyarthritis and more than 50% develop carditis.[39]
Less commonly, the course may be associated with chorea, subcutaneous nodules, and erythema marginatum.
There is no development of coronary artery aneurysms, but untreated patients will eventually develop chronic valvular disease.
INVESTIGATIONS
Positive throat culture or positive serologic test for group A streptococcus (streptozyme and/or antistreptolysin O) will confirm the diagnosis.
Toxic shock syndrome (TSS)
SIGNS / SYMPTOMS
An acute febrile illness that is associated with vomiting, diarrhea, myalgia, strawberry tongue, and erythematous rash with subsequent desquamation.
Many develop acute respiratory distress, hypotension, and shock.
The disease is caused by staphylococcal or group A streptococcal infections.
TSS can follow burns, mild abrasions, or surgery; or it may have no obvious focus.
INVESTIGATIONS
There is no diagnostic test for toxic shock syndrome. The diagnosis is based on clinical grounds.
Isolation of staphylococcus or group A streptococcus serotypes that produce TSS-1 toxin will support the diagnosis.
Staphylococcal scalded skin syndrome
SIGNS / SYMPTOMS
Caused by the staphylococcal epidermolytic toxins A and B.
There is a generalized skin erythema, with development of diffuse, sterile blisters and erosions; prominent circumoral erythema; and radial crusting and fissuring around the eyes, mouth, and nose.
In addition, areas of epidermis may separate in response to gentle force (Nikolsky sign). These changes may lead to secondary infection, sepsis, and electrolyte imbalance.
INVESTIGATIONS
Diagnosis is made on clinical grounds.
Identifications of strains 55 and/or 71 of staphylococci in cultures.
Stevens-Johnson syndrome
SIGNS / SYMPTOMS
A severe bullous form of erythema multiforme, also known as erythema multiforme major.
It is characterized by high fever, pronounced constitutional symptoms, skin rash manifested by diffuse bullae, and mucosal membrane involvement.
The severe explosive mucosal erosions and the widespread bullous skin lesions may differentiate this condition from KD.
There is no development of coronary artery aneurysms, although these patients may benefit from high-dose intravenous immune globulin.
INVESTIGATIONS
There is no diagnostic test for Stevens-Johnson syndrome. The diagnosis is on clinical grounds.
Drug reaction
SIGNS / SYMPTOMS
History of exposure to the drug, presence of oral lesions or ulcers, periorbital edema, and low acute phase markers may help to distinguish it from KD.
INVESTIGATIONS
Diagnosis is made on clinical grounds, although acute-phase markers (such as erythrocyte sedimentation rate and CRP) in KD are significantly higher than in an acute drug reaction.
Rocky Mountain spotted fever
SIGNS / SYMPTOMS
A febrile illness caused by rickettsial infection (Rickettsia rickettsii). The disease is transmitted by a tick bite and characterized by fever, headaches, abdominal pain, vomiting, and diarrhea, followed by severe myalgias.
The hallmark of the disease is the rose-red blanching macular rash that appears first on the extremities, but subsequently spreads to involve the entire body, including palms and soles.
After several days the rash becomes petechial or hemorrhagic, with evidence of a palpable purpura.
In fulminant cases, multiorgan failure may develop, including myocarditis and renal or liver failure.
INVESTIGATIONS
Diagnosis is made on clinical grounds, although confirmation would be achieved using indirect fluorescent antibody technique for R rickettsii.
Measles
SIGNS / SYMPTOMS
Unlike with KD patients, measles manifestations include exudative conjunctivitis, Koplik spots in mouth, rash that typically begins behind the ears.
INVESTIGATIONS
Diagnosis is made on clinical grounds, although acute-phase markers (such as erythrocyte sedimentation rate and CRP) in KD are significantly higher and confirmation of the viral disease would be achieved using antibody titers.
Measles can be confirmed by polymerase chain reaction.
Multisystem inflammatory syndrome in children (MIS-C)
SIGNS / SYMPTOMS
Also known as pediatric multisystem inflammatory system (PMIS).
A rare and severe inflammatory condition has been reported following coronavirus disease 2019 (COVID-19) infection, which shares some clinical features with KD including fever, conjunctival injection, oral mucosal changes (red/cracked lips and strawberry tongue), rash, swollen/red hands and feet, cervical lymphadenopathy, and cardiac sequelae including coronary artery dilations and aneurysms.[40]
MIS-C patients may have more prominent gastrointestinal and neurologic symptoms than KD patients. They may also have more frequent arrhythmias and ventricular dysfunction and be more likely to present in shock.
MIS-C patients typically span a wider age range than KD patients. Younger children present more often with KD-like symptoms and older children with myocarditis and shock. While KD is more common in children of East Asian descent, MIS-C has a higher incidence in children of African, African-Carribean and Hispanic descent, although the reason for this is currently unclear.[41]
INVESTIGATIONS
MIS-C is temporally associated with COVID-19 infection and therefore its likelihood is informed by local COVID-19 prevalence and an epidemiologic link to COVID-19 in the child, e.g., positive COVID-19 PCR or serology test, preceding COVID-19-like illness, or close contact with suspected or confirmed COVID-19 in the past 4 weeks.
There may be a higher CRP in MIS-C, with lower platelet and lymphocyte counts.[41]
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