Kawasaki disease differential diagnosis

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

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, impetigoinsect 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:[1][2][3][4][5][6][7]

Disease Features
Kawasaki disease Commonly presents with high and persistent fever, red mucous membranes in mouth, "strawberry tongue", swollen lymph nodes and skin rash in early disease, with peeling off of the skin of the hands, feet and genital area.
Impetigo  It commonly presents with pimple-like lesions surrounded by erythematous skin. Lesions are pustules, filled with pus, which then break down over 4-6 days and form a thick crust. Impetigo is often associated with insect bites, cuts, and other forms of trauma to the skin.
Insect bites The insect injects formic acid, which can cause an immediate skin reaction often resulting in a rash and swelling in the injured area with the formation of vesicles.
Measles Commonly presents with high fever, coryza and conjunctivitis, with observation of oral mucosal lesions (Koplik's spots), followed by widespread skin rash.
Monkey pox The presentation is similar to small pox, although it is often a milder form, with fever, headache, myalgia, back pain, swollen lymph nodes, a general feeling of discomfort, and exhaustion. Within 1 to 3 days (sometimes longer) after the appearance of fever, the patient develops a papular rash, often first on the face. The lesions usually develop through several stages before crusting and falling off.
Rubella Commonly presents with a facial rash which then spreads to the trunk and limbs, fading after 3 days, low grade fever, swollen glands, joint pains, headache and conjunctivitis. The rash disappears after a few days with no staining or peeling of the skin. Forchheimer's sign occurs in 20% of cases, and is characterized by small, red papules on the area of the soft palate.
Atypical measles The symptoms commonly begin about 7-14 days after infection and present as fever, cough, coryza and conjunctivitis. Observation of Koplik's spots is also a characteristic finding in measles.
Coxsackie virus The most commonly caused disease is the Coxsackie A disease, presenting as hand, foot and mouth disease. It may be asymptomatic or cause mild symptoms, or it may produce fever and painful blisters in the mouth (herpangina), on the palms and fingers of the hand, or on the soles of the feet. There can also be blisters in the throat or above the tonsils. Adults can also be affected. The rash, which can appear several days after a high temperature and painful sore throat, can be itchy and painful, especially on the hands/fingers and bottom of feet.
Acne Acne is typical of teenagers, usually appears on the face and upper neck, but the chest, back and shoulders may have acne as well. The upper arms can also have acne, but lesions found there are often keratosis pilaris, not acne. The typical acne lesions are comedones and inflammatory papules, pustules, and nodules. Some of the large nodules were previously called "cysts"
Syphilis Syphilis commonly presents with gneralized systemic symptoms such as malaise, fatigue, headache and fever. Skin eruptions may be subtle and asymptomatic. Syphilis is classically characterized by:
Molluscum contagiosum
  • The lesions are commonly flesh-colored, dome-shaped, and pearly in appearance. They are often 1-5 millimeters in diameter, with a dimpled center. Generally not painful, but they may itch or become irritated. Picking or scratching the lesions may lead to further infection or scarring. In about 10% of the cases, eczema develops around the lesions. They may occasionally be complicated by secondary bacterial infections.
Mononucleosis
Toxic erythema
  • It is a common rash in infants, with clustered and vesicular appearance.
Rat-bite fever
  • It commonly presents with fever, chills, open sore at the site of the bite and rash, which may show red or purple plaques.
Parvovirus B19
  • The rash of fifth disease is typically described as "slapped cheeks," with erythema across the cheeks and sparing the nasolabial folds, forehead, and mouth.
Cytomegalovirus
Scarlet fever
Rocky Mountain spotted fever
Stevens-Johnson syndrome
  • The symptoms may include fever, sore throat and fatigue. Commonly presents ulcers and other lesions in the mucous membranes, almost always in the mouth and lips but also in the genital and anal regions. Those in the mouth are usually extremely painful and reduce the patient's ability to eat or drink. Conjunctivitis of the eyes occurs in about 30% of children. A rash of round lesions about an inch across, may arise on the face, trunk, arms and legs, and soles of the feet, but usually not on the scalp.
Varicella-zoster virus
  • It commonly starts as a painful rash on one side of the face or body. The rash forms blisters that typically scab over in 7-10 days and clears up within 2-4 weeks.
Chickenpox
  • It commonly starts with conjunctival and catarrhal symptoms and then characteristic spots appearing in two or three waves, mainly on the body and head, rather than the hands, becoming itchy raw pox (small open sores which heal mostly without scarring). Touching the fluid from a chickenpox blister can also spread the disease.
Meningococcemia
Rickettsial pox
Meningitis
Disease Epidemiology Predisposing factors Clinical features Lab abnormalities
Signs Symptoms
Kawasaki

disease

Occurs in children, usually age 1-4 years Interaction of genetic and environmental factors, possibly including an infection in combination with genetic predisposition to an autoimmune mechanism (autoimmune vasculitis) Non-suppurative, painless bilateral conjunctival inflammation (conjunctivitis), strawberry tongue (marked redness with prominent gustative papillae), deep transverse grooves across the nails may develop (Beau’s lines), lymphadenopathy present(acute, non-purulent, cervical), may lead to coronary artery aneurysms. High and persistent fever that is not very responsive to normal treatment with acetaminophen or NSAIDs,  diffuse macular-papular erythematous rash Liver function tests may show evidence of hepatic inflammation and low serum albumin levels, low hemoglobulin and age-adjusted hemoglobulin concentrations, thrombocytosis, anemia. Echocardiographic abnormalities, such as valvulitis (mitral or tricuspid regurgitation) and coronary artery lesions, are significantly more common in Kawasaki disease. [8] Pyuria of uretheral origin.
Toxic shock syndrome Occurs in both adults and children (9:1 female predominance) Occurs in association with vaginitis during menstruation following tampon use (S. aureus); as a complication of soft tissue infections (S. pyogenes or GAS) or in females undergoing medical abortion (C. sordellii). Hypotension, tachycardia, mucous membrane hyperemia (vaginal, oral, conjunctival) Fever, diarrhea, vomiting, diffuse scarlantiform rash Hyponatremia and uremia. Hepatic dysfunction (total bilirubin, serum asparate aminotransferase or serum alanine aminotransferase levels >2 times upper normal limit), leukocytosis with a polymorphonuclear shift to the left. Platelets < 100,000 per mm3 (thrombocytopenia), pyuria of renal origin.
Scarlet fever Distributed equally among both genders. Most commonly affects children between five and fifteen years of age. Occurs after streptococcal pharyngitis/tonsillitis Pastia's sign (puncta and skin crease accentuation of the erythema), strawberry tongue, cervical lymphadenopathy may be present. Scarlet fever appears similar to Kawasaki's disease in some aspects, but lacks the eye signs or the swollen, red fingers and toes Characteristic sandpaper-like rash which appears days after the illness begins (although the rash can appear before illness or up to 7 days later), rash may first appear on the neck, underarm, and groin Leukocytosis with left shift and possibly eosinophilia a few weeks after convalescence. Anti-deoxyribonuclease B, antistreptolysin-O titers (antibodies to streptococcal extracellular products), antihyaluronidase, and antifibrinolysin may be positive.

Kawasaki disease must be differentiated from other causes of fever and rash in infants

Differential Diagnosis of Measles. Table adapted from CDC Pinkbook.[9]
Disease Agent Typical Season Typical Age Prodrome Fever Duration of the rash (days) Rash Other Signs & Symptoms
Kawasaki disease Unknown Winter - Spring < 5 years 3 days of abrupt fever High; fever of 5 days is a diagnostic criteria 5 - 7 Erythematous, morbilliform, maculopapular or scarlatiniform, central distribution; erythematous, indurated palms and soles Acute: dry, fissured and injected lips, strawberry tongue; irritability; cervical lymphadenopathy; conjunctival injection; peripheral edema; Subacute: finger-tip desquamation; Complications: arthritis, carditis
Measles Paramyxovirus
Measles virus
Winter - Spring 1 to 20 years 2-4 days of cough, conjunctivitis, and coryza High 5 - 6 Erythematous, irregular size, maculopapular; starts on temples and behind ears; progresses down from face; fades to brownish Koplik's spots: C blue-white papules (salt grains) on bright red mucosa opposite premolar teeth
Roseola Infantum (exanthem subitum) Human herpes virus type 6 Any season 6 months to 2 years None High 1-2; it follows defervescence Discrete erythematous macules, rarely involves face, begins as fever ends Lymphadenopathy, irritability
Rubella Togavirus Spring 7 months to 29 years 0 - 4 days; mild malaise, fever; absent in children Low grade 1 - 3 Discrete, rose-pink, diffuse, maculopapular; progresses downward from face, may change quickly Arthralgia (usually in adults), tender posterior cervical and suboccipital lymphadenopathy, malaise, petechiae on soft palate
Scarlet Fever ß-hemolytic streptococci Winter > 2 years 0 - 6 day, marked Low to high 2 - 7 Scarlet "sunburn" with punctate papules "sandpaper", circumoral pallor, increased intensity in skin folds, blanches stars face/head, upper trunk and progresses downward Sore throat, exudative tonsillitis, vomiting, abdominal pain, lmphadenopathy, white then red strawberry tongue
Erythema Infectiosum (Fifth Disease) Human parvovirus type B19 Spring 5 - 10 years None, usually in children, may occur in adults None to low-grade 2 - 4 Starts as “slapped cheek”, maculopapular; progresses to reticular (lacy) pattern; can recur with environmental changes such as sunlight exposure Arthralgia/arthritis in adults, adenopathy
Enterovirus Echovirus
Coxsackie virus
Summer - Fall Mainly childhood 0 - 1 day fever and myalias Low to high 1 - 5 Fine, pink, always affects face; variant is Boston exanthem (large ~ 1 cm, discrete maculopapules) Sore throat, headache, malaise, no lymphadenopathy, gastroenteritis
Dengue Fever Flavivirus
Dengue virus types 1 - 4
None High 1 - 5 Generalized maculopapular rash after defervescence; spares palms and soles Headache, myalgia, abdominal pain, pharyngitis, vomiting
Drug induced rash Many Any Any Possible due to underlying illness Possible Varies Typically diffuse but may be concentrated in diaper area, typically no progression, erythema multiform rash can progress over a few days Possibly due to underlying illness or complications
Infectious Mononucleosis Epstein-Barr Virus None 10 - 30 years 2 - 5 days of malaise and fatigue Low to high 2 - 7 Trunk and proximal extremities. Rash common if Ampicillin given Pharyngitis, lymphadenopathy, splenomegaly, malaise
Pharyngoconjunctival Fever Adenovirus types 2, 3, 4, 7, 7a Winter - Spring < 5 years Low to high 3 - 5 Starts on face and spreads down to trunk and extremities Sore throat, conjunctivitis, headache, anorexia

The following table is a list of differential diagnosis oral lesions presenting similar to measles:

Disease Presentation Risk Factors Diagnosis Affected Organ Systems Important features Picture
Coxsackie virus
  • Symptomatic treatment
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Chicken pox <figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline>
Measles <figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline>
Herpangina
  • Attendance at a kindergarten/child care center
  • Contact with herpangina cases
  • Residence in rural areas
  • Overcrowding
  • Poor hygiene
  • Low socioeconomic status
  • Skin
  • Oral Cavity
  • Characteristic enanthem- Punctate macule which evolve over a period of 24 hours to 2-4mm erythematous papules which vesiculate, and then centrally ulcerate.
  • The lesions are usually small in number, and evolve rapidly. The lesions are seen more commonly on the soft palate and uvula. The lesions can also be seen on the tonsils, posterior pharyngeal wall and the buccal mucosa.
Erythema, vesicles and ulcerating lesions in herpangina
Erythema, vesicles and ulcerating lesions in herpangina
Primary herpetic gingivoestomatitis[12]
  • Oral cavity
  • Mucous membranes
  • Ulcers are common on lips, gums, throat, front of tongue, inside of the cheeks and roof of the mouth
  • Treatment is with antiviral agents such as Valacyclovir and Famciclovir

<figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline>

Koplik spots must be differentiated from other diseases causing oral lesions such as leukoplakia and herpes simplex virus infection.

Disease Presentation Risk Factors Diagnosis Affected Organ Systems Important features Picture
Diseases predominantly affecting the oral cavity
Oral Candidiasis
  • Denture users
  • As a side effect of medication, most commonly having taken antibiotics. Inhaled corticosteroids for the treatment of lung conditions (e.g, asthma or COPD) may also result in oral candidiasis which may be reduced by regularly rinsing the mouth with water after taking the medication.
  • Clinical diagnosis
  • Confirmatory tests rarely needed
Localized candidiasis

Invasive candidasis

Tongue infected with oral candidiasis - By James Heilman, MD - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=11717223.jpg
Herpes simplex oral lesions
  • Stress
  • Recent URTI
  • Female sex
  • The symptoms of primary HSV infection generally resolve within two weeks
Oral herpes simplex infection - By James Heilman, MD - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=19051042.jpg
Aphthous ulcers
  • Painful, red spot or bump that develops into an open ulcer
  • Physical examination
  • Diagnosis of exclusion
  • Oral cavity
  • Self-limiting , Pain decreases in 7 to 10 days, with complete healing in 1 to 3 weeks
Apthous ulcer on the lower surface of the tongue - By Ebarruda - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=7903358
Squamous cell carcinoma
Squamous cell carcinoma - By Luca Pastore, Maria Luisa Fiorella, Raffaele Fiorella, Lorenzo Lo Muzio - http://www.plosmedicine.org/article/showImageLarge.action?uri=info%3Adoi%2F10.1371%2Fjournal.pmed.0050212.g001, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=15252632
Leukoplakia
  • Vulvar lesions occur independent of oral lesions
Leukoplakia - By Aitor III - Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=9873087
Melanoma
Oral melanoma - By Emmanouil K Symvoulakis, Dionysios E Kyrmizakis, Emmanouil I Drivas, Anastassios V Koutsopoulos, Stylianos G Malandrakis, Charalambos E Skoulakis and John G Bizakis - Symvoulakis et al. Head & Face Medicine 2006 2:7 doi:10.1186/1746-160X-2-7 (Open Access), [1], CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=9839811
Fordyce spots
Fordyce spots - Por Perene - Obra do próprio, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=19772899
Burning mouth syndrome
Torus palatinus
Torus palatinus - By Photo taken by dozenist, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=846591
Diseases involving oral cavity and other organ systems
Behcet's disease
Behcet's disease - By Ahmet Altiner MD, Rajni Mandal MD - http://dermatology.cdlib.org/1611/articles/18_2009-10-20/2.jpg, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=17863021
Crohn's disease
Agranulocytosis
Syphilis[16]
oral syphilis - By CDC/Susan Lindsley - http://phil.cdc.gov/phil_images/20021114/34/PHIL_2385_lores.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=2134349
Coxsackie virus
  • Symptomatic treatment
Coxsackie virus stomatitis - Adapted from Dermatology Atlas.[17]
Chicken pox
Chickenpox - By James Heilman, MD - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=52872565
Measles
  • Unvaccinated individuals[10][11]
  • Crowded and/or unsanitary conditions
  • Traveling to less developed and developing countries
  • Immunocompromized
  • Winter and spring seasons
  • Born after 1956 and never fully vaccinated
  • Health care workers
Koplick spots (Measles) - By CDC - http://phil.cdc.gov/PHIL_Images/20040908/4f54ee8f0e5f49f58aaa30c1bc6413ba/6111_lores.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=824483


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  16. title="By Internet Archive Book Images [No restrictions], via Wikimedia Commons" href="https://commons.wikimedia.org/wiki/File:A_manual_of_syphilis_and_the_venereal_diseases%2C_(1900)_(14595882378).jpg"
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