Kawasaki disease differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dildar Hussain, MBBS [2];Eiman Ghaffarpasand, M.D. [3]

Overview

Kawasaki disease must be differentiated from other diseases that cause different rash-like conditions and can be confused with Kawasaki disease. The various conditions that should be differentiated from Kawasaki disease include; infantile polyarteritis nodosa, juvenile idiopathic arthritis, leptospirosis, lyme disease, measles, mercury toxicity, pediatric rocky mountain spotted fever, toxic epidermal necrolysis, staphylococcal scalded skin syndrome, rheumatic fever, impetigo, insect bites, monkey pox, rubella, atypical measles, coxsackie virus, acne, syphilis, molluscum contagiosum, toxic erythema, rat-bite fever, parvovirus B19, cytomegalovirus, scarlet fever, Stevens-Johnson syndrome, varicella-zoster virus, chicken pox, meningococcemia, rickettsial pox, meningitis, toxic shock syndrome, roseola infantum (exanthem subitum), erythema infectiosum (fifth disease), enterovirus, dengue fever, drug - induced rash, infectious mononucleosis, pharyngoconjunctival fever, herpangina, and primary herpetic gingivostomatitis.

Differentiating Kawasaki disease from other diseases

Different rash-like conditions can be confused with Kawasaki disease and are thus included in its differential diagnosis. The various conditions that should be differentiated from Kawasaki disease include:

Abbreviations: ABG= Arterial blood gas, ANA= Antinuclear antibody, ANP= Atrial natriuretic peptide, ASO= Antistreptolysin O antibody, BNP= Brain natriuretic peptide, CBC= Complete blood count, COPD= Chronic obstructive pulmonary disease, CRP= C-reactive protein, CT= Computed tomography, CXR= Chest X-ray, DVT= Deep vein thrombosis, ESR= Erythrocyte sedimentation rate, HRCT= High Resolution CT, IgE= Immunoglobulin E, LDH= Lactate dehydrogenase, PCWP= Pulmonary capillary wedge pressure, PCR= Polymerase chain reaction, PFT= Pulmonary function test.

Diseases		Clinical manifestations								Para-clinical findings									Gold standard	Additional findings
		Symptoms					Physical examination
										Lab Findings				Imaging				Histopathology
		Headache	Fever	Weight loss	Arthralgia	Claudication	Bruit	HTN	Focal neurological disorder	Biomarker	CBC	ESR	Other	CT scan	Angiography	Ultrasound/ Echocardiography	Other
Kawasaki disease		-	+	+/-	+	+	-	+/-	-	NT-proBNP, Meprin A, Filamin C	Normochromic anemia, ↑WBC with a left shift, Thrombocytosis	↑	Acute-phase reactants, ↓Cholesterol, ↓HDL, ↓ApolipoA	Coronary artery calcifications	Coronary artery aneurysms, stenosis or occlusion	Coronary artery anomaly in echocardiography	Electron beam CT (EBCT)	Acute destruction of the media by neutrophils, with loss of elastic fibers	History and physical examination	Diarrhea, Vomiting
Polyarteritis nodosa		+	+	+	+	+	+	+/-	+/-	LAMP-2 protein autoantibodies	Leukocytosis, Normochromic anemia, Thrombocytosis	↑	↑ Cr or BUN, ↑ ALT or AST, Proteinuria	Focal regions of infarction or hemorrhage	Multiple microaneurysms, Hemorrhage due to focal rupture, Occlusion	Aneurysms and renal arteriovenous fistula in color Doppler sonography	-	Necrotizing inflammatory lesions	Angiography	Sudden weight loss, Abdominal pain
Hepatitis B virus-associated polyarteritis nodosa		+/-	+/-	+	+	+/-	+/-	+	-	HBsAg	Leukocytosis, Normochromic anemia, Thrombocytosis	↑	↑ ALT or AST	Focal regions of infarction or hemorrhage	Microaneurysms in mesenteric artery	Aneurysms and renal arteriovenous fistula in color Doppler sonography	-	Necrotizing inflammatory lesions	Angiography	Peripheral neuropathy, Livedo reticularis
Infectious disease	Parvovirus B19 infection	+	+	+	+	-	-	-	+/-	B19 DNA, ↓Reticulocyte count	Anemia	↑	anti–parvovirus B19 IgM	-	-	Hydrops in fetal ultrasonography	-	-	B19 DNA	Purpuric rash, Erythema multiforme
	Scarlet fever	+	+	+/-	+	-	-	-	-	Antistreptolysin-O (ASO) titers	Leukocytosis	↑	↑CRP	Thickened pulmonary markings if pneumonia	-	-	-	Sparse neutrophilic perivascular infiltrate	History and physical examination	Sand-paper rashes, Sore throat
	Toxic shock syndrome	+	+	+	+	-	-	-	+/-	Procalcitonin	Leukocytosis with left shift	↑	Myoglobinuria, Sterile pyuria	Acute respiratory distress syndrome	-	-	-	Necrolysis of keratinocytes in epidermis, Perivascular lymphocytic infiltrate	Clinical criteria	Peeling or rashes, Organ dysfunction
	Mononucleosis	+	+	+	+	-	-	-	-	EBV DNA	Atypical lymphocyte	↑	Heterophile antibodies	CNS involvement	-	Splenomegaly	Encephalitis in MRI	Lymphoproliferative response in oropharynx, Lymphocytic infiltration in spleen	Heterophile antibody test	Splenomegaly, Palatal petechiae
	Leptospirosis	+	+	+	+	+/-	-	-	-	IL-6, IL-8 and IL-10	Anemia	-	↑Cr or BUN, ↑ALT or AST, Proteinuria	Diffuse alveolar hemorrhage	-	-	-	Toxin-mediated break down of endothelial cell membranes of capillaries	Culture and the microscopic agglutination test	Red eyes, Skin rash
	Lyme Disease	+/-	+	+/-	+	+/-	-	-	-	CXCL9 (MIG), CXCL10 (IP-10) and CCL19 (MIP3B)	Leukopenia, Thrombocytopenia	-	Microscopic hematuria, Proteinuria, ↑ALT or AST	Punctate lesions in periventricular white matter in brain SPECT	-	-	-	Acrodermatitis chronica atrophicans	Serologic tests	Erythema migrans
	Measles	+/-	+	+/-	+	-	-	-	-	Measles IgM	Leukopenia, Lymphocytosis, Thrombocytopenia	-	↑ALT or AST	Pneumonia	-	-	CXR	Spongiosis and vesiculation in the epidermis with scattered dyskeratotic keratinocytes	PCR	Generalized rash, Cough, Coryza, or Conjunctivitis
	Rocky Mountain Spotted Fever	+	+	+	+	-	-	-	-	R rickettsii serology	Thrombocytopenia, Anemia	-	↑ALT or AST, Hyponatremia	Infarction, edema, and meningeal enhancement	-	Myocardial or conduction abnormalities in echocardiography	-	Immunofluorescent or immunoperoxidase staining of R rickettsii	Clinical criteria and tick exposure	Rash on the palms and soles
	Staphylococcal Scalded Skin Syndrome	+	+	+	+	-	-	+/-	+/-	Anti exfoliatin and anti alpha-toxin antibodies	Leukocytosis with left shift	↑	Blood culture	Pneumonia	-	-	-	Intraepidermal blister, dense superficial perivascular lymphohistiocytic infiltrate	Blood culture and clinical findings	Widespread skin erythema, fluid-filled blisters
	Toxic Epidermal Necrolysis	-	+	+	-	-	-	-	+/-	MicroRNA-124	Normochromic normocytic anemia, Eosinophilia	↑	Fluid loss and electrolyte abnormalities	Tracheobronchial inflammation	-	-	-	Necrotic keratinocytes with full-thickness epithelial necrosis	Histopathology and clinical findings	Erythematous macular rash with purpuric centers
Systemic disease	Antiphospholipid Syndrome	+	+	-	-	-	-	-	+/-	Antiphospholipid antibodies	Thrombocytopenia, Hemolytic anemia	-	Lupus anticoagulant (LA)	Stroke, Pulmonary embolism, Budd-Chiari syndrome	Thrombus in major vessels	Valve thickening, vegetations, or insufficiency in echocardiography	-	Noninflammatory bland thrombosis without perivascular inflammation	Hx of thrombosis and antiphospholipid antibodies	Miscarriage, Pulmonary hypertension
	Juvenile Idiopathic Arthritis	-	-	-	+	+/-	-	-	-	Rheumatoid factor (RF), S100A12	Lymphocytosis, Thrombocytopenia	↑	Myeloid-related proteins 8/14 (MRP8/14)	Synovial hypertrophy, Joint effusions	Cerebral vasculitis	Inflamed synovium	Bone scanning	Vascular congestion, RBC extravasation, Venular lumen occlusion	Conventional radiography	Evanescent rash, Dactylitis