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];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:[1][2][3][4][5][6][7]

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[8] - + +/- + + - +/- - 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[9] + + + + + + +/- +/- 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[10] +/- +/- + + +/- +/- + - 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[11] + + + + - - - +/- B19 DNA, ↓Reticulocyte count Anemia ↑ anti–parvovirus B19 IgM - - Hydrops in fetal ultrasonography - - B19 DNA Purpuric rash, Erythema multiforme
Scarlet fever[12] + + +/- + - - - - 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[13] + + + + - - - +/- 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[14] + + + + - - - - 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[15] + + + + +/- - - - 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[16] +/- + +/- + +/- - - - 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[17] +/- + +/- + - - - - 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[18] + + + + - - - - 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[19] + + + + - - +/- +/- 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[20] - + + - - - - +/- 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[21] + + - - - - - +/- 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[22] - - - + +/- - - - 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 

References

  1. ↑ Hartman-Adams H, Banvard C, Juckett G (2014). "Impetigo: diagnosis and treatment". Am Fam Physician. 90 (4): 229–35. PMID 25250996.
  2. ↑ Mehta N, Chen KK, Kroumpouzos G (2016). "Skin disease in pregnancy: The approach of the obstetric medicine physician". Clin Dermatol. 34 (3): 320–6. doi:10.1016/j.clindermatol.2016.02.003. PMID 27265069.
  3. ↑ Moore, Zack S; Seward, Jane F; Lane, J Michael (2006). "Smallpox". The Lancet. 367 (9508): 425–435. doi:10.1016/S0140-6736(06)68143-9. ISSN 0140-6736.
  4. ↑ Ibrahim F, Khan T, Pujalte GG (2015). "Bacterial Skin Infections". Prim Care. 42 (4): 485–99. doi:10.1016/j.pop.2015.08.001. PMID 26612370.
  5. ↑ Ramoni S, Boneschi V, Cusini M (2016). "Syphilis as "the great imitator": a case of impetiginoid syphiloderm". Int J Dermatol. 55 (3): e162–3. doi:10.1111/ijd.13072. PMID 26566601.
  6. ↑ Kimura U, Yokoyama K, Hiruma M, Kano R, Takamori K, Suga Y (2015). "Tinea faciei caused by Trichophyton mentagrophytes (molecular type Arthroderma benhamiae ) mimics impetigo : a case report and literature review of cases in Japan". Med Mycol J. 56 (1): E1–5. doi:10.3314/mmj.56.E1. PMID 25855021.
  7. ↑ CEDEF (2012). "[Item 87--Mucocutaneous bacterial infections]". Ann Dermatol Venereol. 139 (11 Suppl): A32–9. doi:10.1016/j.annder.2012.01.002. PMID 23176858.
  8. ↑ Takahashi K, Oharaseki T, Yokouchi Y (2011). "Pathogenesis of Kawasaki disease". Clin Exp Immunol. 164 Suppl 1: 20–2. doi:10.1111/j.1365-2249.2011.04361.x. PMC 3095860. PMID 21447126.
  9. ↑ Howard T, Ahmad K, Swanson JA, Misra S (2014). "Polyarteritis nodosa". Tech Vasc Interv Radiol. 17 (4): 247–51. doi:10.1053/j.tvir.2014.11.005. PMC 4363102. PMID 25770638.
  10. ↑ Sharma A, Sharma K (September 2013). "Hepatotropic viral infection associated systemic vasculitides-hepatitis B virus associated polyarteritis nodosa and hepatitis C virus associated cryoglobulinemic vasculitis". J Clin Exp Hepatol. 3 (3): 204–12. doi:10.1016/j.jceh.2013.06.001. PMC 4216827. PMID 25755502.
  11. ↑ Heegaard ED, Brown KE (2002). "Human parvovirus B19". Clin Microbiol Rev. 15 (3): 485–505. PMC 118081. PMID 12097253.
  12. ↑ Basetti S, Hodgson J, Rawson TM, Majeed A (2017). "Scarlet fever: a guide for general practitioners". London J Prim Care (Abingdon). 9 (5): 77–79. doi:10.1080/17571472.2017.1365677. PMC 5649319. PMID 29081840.
  13. ↑ Vostral SL (2011). "Rely and Toxic Shock Syndrome: a technological health crisis". Yale J Biol Med. 84 (4): 447–59. PMC 3238331. PMID 22180682.
  14. ↑ Balfour HH, Dunmire SK, Hogquist KA (2015). "Infectious mononucleosis". Clin Transl Immunology. 4 (2): e33. doi:10.1038/cti.2015.1. PMC 4346501. PMID 25774295.
  15. ↑ Levett PN (April 2001). "Leptospirosis". Clin. Microbiol. Rev. 14 (2): 296–326. doi:10.1128/CMR.14.2.296-326.2001. PMC 88975. PMID 11292640.
  16. ↑ Biesiada G, Czepiel J, Leśniak MR, Garlicki A, Mach T (2012). "Lyme disease: review". Arch Med Sci. 8 (6): 978–82. doi:10.5114/aoms.2012.30948. PMC 3542482. PMID 23319969.
  17. ↑ White SJ, Boldt KL, Holditch SJ, Poland GA, Jacobson RM (2012). "Measles, mumps, and rubella". Clin Obstet Gynecol. 55 (2): 550–9. doi:10.1097/GRF.0b013e31824df256. PMC 3334858. PMID 22510638.
  18. ↑ Walker DH (1989). "Rocky Mountain spotted fever: a disease in need of microbiological concern". Clin Microbiol Rev. 2 (3): 227–40. PMC 358117. PMID 2504480.
  19. ↑ Mishra AK, Yadav P, Mishra A (2016). "A Systemic Review on Staphylococcal Scalded Skin Syndrome (SSSS): A Rare and Critical Disease of Neonates". Open Microbiol J. 10: 150–9. doi:10.2174/1874285801610010150. PMC 5012080. PMID 27651848.
  20. ↑ Hoetzenecker W, Mehra T, Saulite I, Glatz M, Schmid-Grendelmeier P, Guenova E; et al. (2016). "Toxic epidermal necrolysis". F1000Res. 5. doi:10.12688/f1000research.7574.1. PMC 4879934. PMID 27239294.
  21. ↑ Chaturvedi S, McCrae KR (2015). "The antiphospholipid syndrome: still an enigma". Hematology Am Soc Hematol Educ Program. 2015: 53–60. doi:10.1182/asheducation-2015.1.53. PMC 4877624. PMID 26637701.
  22. ↑ Espinosa M, Gottlieb BS (July 2012). "Juvenile idiopathic arthritis". Pediatr Rev. 33 (7): 303–13. doi:10.1542/pir.33-7-303. PMID 22753788.

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