Kawasaki Disease: Differential Diagnosis and Diagnostic Approaches

Kawasaki disease (KD), also known as mucocutaneous lymph node syndrome, is an acute systemic vasculitis primarily affecting medium-sized arteries, with a significant predilection for the coronary arteries. As the leading cause of acquired heart disease in children in developed countries, and increasingly in developing nations, prompt diagnosis and treatment are crucial to prevent serious cardiac complications. This article provides an in-depth review of Kawasaki disease, emphasizing its differential diagnosis and the critical steps in evaluation for healthcare professionals.

Understanding Kawasaki Disease Etiology and Epidemiology

While the exact etiology of Kawasaki disease remains elusive, research suggests a potential link to an environmental trigger, possibly a wind-borne or water-borne pathogen, in genetically predisposed individuals. Genetic susceptibility is indicated by the increased incidence in siblings and associations with specific genetic markers like HLA-B51 and HLA-Bw22j2 serotypes. Despite ongoing investigations, no single causative agent, bacterial or viral, has been definitively identified, although respiratory viruses are frequently detected in KD patients. It’s important to emphasize that Kawasaki disease is not contagious.

Epidemiologically, KD predominantly affects children under five years of age, with a peak incidence in toddlers, but it can occur across all age groups, including adults. Males are slightly more affected than females, and boys tend to experience more severe outcomes. Infants under four months are rarely diagnosed, possibly due to protection from maternal antibodies. Notably, Kawasaki disease has a higher prevalence in children of Asian descent, particularly Japanese ethnicity, and is less common in Caucasian children. Seasonal patterns also exist, with increased incidence observed during winter and spring.

Pathophysiology and Histopathology of Kawasaki Disease

The pathogenesis of Kawasaki disease is characterized by an aberrant immune response, likely triggered by an infectious agent entering through the respiratory tract. This triggers the activation of lymphocytes, pro-inflammatory cytokines (TNF-α, IL-1, IL-4, IL-6), and matrix metalloproteinases (MMP3 and MMP9). Oligoclonal IgA plasma cells are believed to play a key role in the development of coronary arteritis, with respiratory mucosa involvement suggesting a respiratory portal of entry.

This inflammatory cascade leads to myocarditis and arteritis, initiating fibrinoid necrosis of the internal elastic lamina of blood vessels. Neutrophil invasion weakens the vessel wall, predisposing it to aneurysm formation. Atypical monocyte and macrophage activation are central to the unique vascular lesions in KD, indicating an innate immune system malfunction. Over time, coronary aneurysms can thicken, leading to stenosis and thrombus formation, with risks of myocardial infarction (MI), rupture, arrhythmias, and sudden death. Thrombocytosis during the subacute phase further elevates thrombotic risk. Small coronary aneurysms can spontaneously regress in approximately 60% of cases as inflammation subsides during convalescence.

Histopathological examination, though rarely performed for diagnosis, reveals early neutrophilic infiltration and destruction of the vessel media. Granulomatous inflammation, a hallmark of coronary arteritis in KD, develops within 6-8 days, affecting all vessel layers. As the disease progresses, inflammatory infiltrates shift to lymphocytes, monocytes, and fibroblasts, leading to arterial remodeling. Intriguingly, cytoplasmic inclusion bodies containing RNA have been observed in the majority of fatal cases, suggesting a persistent viral presence or post-infectious inflammatory process.

Clinical Presentation and Diagnostic Criteria: Differentiating Kawasaki Disease

Children with Kawasaki disease typically present with a constellation of signs and symptoms following several days of fever and malaise. A thorough medical history is essential, as diagnostic criteria may emerge at different points during the illness. The disease course is classically divided into three phases: acute, subacute, and convalescent.

The acute phase is marked by abrupt onset of high fever, often exceeding 38.5°C (101.3°F), lasting 1-2 weeks or longer if untreated. Concurrently, patients develop rash, bilateral non-exudative conjunctivitis, and myocarditis. The subacute phase begins with fever resolution and extends to weeks 4-6. Desquamation of hands and feet, thrombocytosis, and the development of coronary artery aneurysms are characteristic of this phase. The convalescent phase, typically within 3 months of onset, sees resolution of clinical signs, although cardiac abnormalities may persist. New coronary aneurysms after 8 weeks are uncommon.

Beyond the classic features, less frequent manifestations can include abdominal pain, vomiting, diarrhea, hepatitis, parotitis, intussusception, and arthralgia, particularly in large joints. Neurological symptoms like headache, irritability, seizures, and aseptic meningitis can occur. Respiratory symptoms (rhinorrhea, cough), aortic aneurysms, valvular insufficiency, and genitourinary involvement (epididymitis, orchitis, urethritis) are also reported. Crucially, purulent conjunctivitis or exudative pharyngitis should prompt consideration of alternative diagnoses.

The American Heart Association (AHA) criteria, updated in 2014, are the cornerstone of KD diagnosis. However, cardiac abnormalities detected by echocardiogram in patients not fully meeting criteria are still diagnostic of KD. The diagnostic criteria mandate fever for five or more days plus at least four of the following five clinical features:

Bilateral bulbar conjunctival injection: Painless redness of the conjunctiva, sparing the limbus, and without exudate.
Mucous membrane changes: Erythema of the mouth and pharynx, strawberry tongue, or red, cracked lips.
Extremity changes: Edema or erythema of hands and feet in the acute phase, followed by desquamation, particularly periungual peeling, in the subacute phase, and nail changes (Beau’s lines).
Polymorphous rash: A generalized, non-vesicular rash, which can be maculopapular, morbilliform, or scarlatiniform, primarily on the trunk and extremities, typically appearing within 5 days of fever onset, and lacking pruritus.
Cervical lymphadenopathy: Enlarged cervical lymph node, usually unilateral and greater than 1.5 cm in diameter.

Mnemonic aids like “Warm CREAM” (Fever, Conjunctivitis, Rash, Extremity changes, Adenopathy, Mucous membranes) and “FEBRILE” (Fever, Enanthem, Bulbar conjunctivitis, Rash, Internal organ involvement, Extremity changes) can assist in recalling the diagnostic criteria. The sequential appearance of these symptoms aids in differentiating KD from other febrile illnesses.

Evaluation and Differential Diagnosis of Kawasaki Disease

The diagnosis of Kawasaki disease is primarily clinical. However, in cases of incomplete Kawasaki disease or when differentiating KD from other conditions, specific laboratory and imaging studies become crucial.

Table: Differential Diagnosis of Kawasaki Disease

Condition	Key Differentiating Features from Kawasaki Disease
Viral Infections	Exudative conjunctivitis (adenovirus), generalized vesicular rash (varicella), Koplik spots (measles), lack of full KD criteria, shorter fever duration in some viral illnesses.
Bacterial Infections	Exudative pharyngitis (streptococcal pharyngitis), localized cellulitis (preseptal cellulitis), purulent lymphadenitis, specific bacterial cultures positive.
Scarlet Fever	Pastia’s lines, sandpaper rash, circumoral pallor, exudative pharyngitis, lacks conjunctivitis and extremity changes of KD.
Toxic Shock Syndrome	Hypotension, diffuse macular rash (sunburn-like), multisystem organ involvement, lacks typical KD conjunctivitis and extremity changes.
Staphylococcal Scalded Skin Syndrome (SSSS)	Blistering rash with epidermal shedding, Nikolsky’s sign positive, lacks conjunctivitis and mucous membrane changes of KD.
Toxic Epidermal Necrolysis (TEN)	Mucosal involvement, widespread bullae and skin detachment, severe systemic illness, often drug-induced, lacks typical KD features in early stages.
Rheumatic Fever	Migratory polyarthritis, carditis (different pattern than KD), erythema marginatum, subcutaneous nodules, chorea, elevated ASO titers, responds to penicillin.
Juvenile Idiopathic Arthritis (JIA)	Chronic arthritis, uveitis (anterior), lacks acute febrile phase and rash of KD, specific JIA subtypes have distinct features.
Systemic Lupus Erythematosus (SLE)	Butterfly rash, photosensitivity, renal involvement, serositis, positive ANA, anti-dsDNA, other autoantibodies, chronic course, different cardiac manifestations.
Drug Hypersensitivity Reactions	Temporal association with new medication, pruritic rash, eosinophilia, lacks fever pattern and other specific KD criteria, rash morphology varies.
Meningitis	Nuchal rigidity, altered mental status, photophobia, Kernig’s and Brudzinski’s signs, CSF pleocytosis (may be present in KD but usually less pronounced).
Rocky Mountain Spotted Fever	Tick bite history, petechial rash (starts peripherally), headache, myalgia, elevated transaminases, specific serology.
Lyme Disease	Erythema migrans (bulls-eye rash), arthritis (later stage), cranial nerve palsies, heart block, exposure to tick-borne areas, specific serology.
Leptospirosis	Exposure to contaminated water, conjunctival suffusion (prominent conjunctival redness without exudate), jaundice, renal dysfunction, specific serology.

Laboratory Studies: While not mandatory for complete KD diagnosis, certain lab tests are valuable, particularly in incomplete KD and differential diagnosis.

Complete Blood Count (CBC): Mild to moderate normocytic anemia is common in the acute phase. Thrombocytosis is characteristic of the subacute phase. Thrombocytopenia, though less frequent, may indicate higher risk of coronary artery aneurysms. Elevated white blood cell count (WBC > 15,000/mm³) can be seen.
Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP): Acute phase reactants are almost always elevated, indicating inflammation. CRP > 30 mg/L and/or ESR > 40 mm/hr are significant in incomplete KD assessment.
Serum Albumin: Hypoalbuminemia can be present and correlates with disease severity. Serum albumin ≤ 3.0 g/dL is a criterion in incomplete KD.
Liver Function Tests: Elevated alanine aminotransferase (ALT) and hyperbilirubinemia may occur due to hepatic congestion.
Urinalysis: Sterile pyuria (WBC > 10/high-power field) is typical.
Pro-B-type Natriuretic Peptide (Pro-BNP): Elevated levels may correlate with increased risk of coronary artery aneurysms and IVIG resistance, particularly in infants.
Blood Cultures, Stool Cultures, ANA, RF, ASO Titers: These are typically negative in KD and help rule out other conditions.

Echocardiogram: Echocardiography is a critical imaging modality in KD.

Acute Phase Echocardiogram: Should be performed in the acute phase to assess for coronary artery aneurysms (CAA), myocarditis, pericardial effusion, valvular dysfunction, and aortic root dilation. Proximal left anterior descending and right coronary arteries are most commonly affected.
Follow-up Echocardiograms: Typically repeated at 2 weeks and 6-8 weeks after illness onset to monitor coronary artery status and aneurysm evolution. In patients with incomplete KD, echocardiogram is crucial for diagnosis and to guide treatment decisions.

Advanced Imaging: In certain situations, advanced imaging modalities may be considered:

Coronary Computed Tomography Angiography (CTA): CTA offers detailed visualization of coronary arteries, especially mid and distal segments, and can quantify lesions precisely. However, radiation exposure in children is a concern.
Magnetic Resonance Angiography (MRA): MRA is radiation-free and more sensitive for small lesions and intimal hyperplasia, making it a valuable alternative to CTA, particularly for follow-up.
Electron Beam CT: May be used to assess coronary artery calcifications as a long-term marker for future cardiac events.
Coronary Angiography: Reserved for complex coronary artery lesions to assess stenosis, typically delayed until 6-12 months after initial presentation.

Electrocardiogram (ECG): ECG can reveal myocardial damage and repolarization abnormalities, such as prolonged PR interval, deep Q waves, ST-T changes, and arrhythmias, supporting cardiac involvement in KD.

Treatment and Management Strategies

The primary goals of Kawasaki disease treatment are to reduce coronary artery inflammation and prevent coronary artery aneurysm formation. Treatment should be initiated promptly, ideally within 10 days of fever onset.

First-line therapy:

Intravenous Immunoglobulin (IVIG): A single high dose of IVIG (2 g/kg) infused over 10-12 hours is the cornerstone of treatment. IVIG significantly reduces the risk of coronary artery aneurysms.
Aspirin: High-dose aspirin (80-100 mg/kg/day divided every six hours) is administered initially for its anti-inflammatory effects. Once the patient is afebrile for 48-72 hours, aspirin is continued at a low dose (3-5 mg/kg/day) for its antiplatelet properties until cardiac risk is resolved, typically 6-8 weeks, or longer if coronary abnormalities persist.

IVIG Resistance: Approximately 10-20% of patients are IVIG-resistant, defined by persistent fever ≥ 36 hours after IVIG infusion. For these patients, retreatment strategies include:

Repeat IVIG infusion: A second dose of IVIG (2 g/kg).
Infliximab: A TNF-alpha inhibitor (5 mg/kg) has shown efficacy in IVIG-resistant KD, leading to faster fever resolution and reduced inflammation.
Corticosteroids: Prednisolone or methylprednisolone may be considered in IVIG-resistant cases, or as adjunctive therapy in high-risk patients. Studies suggest corticosteroids may reduce CAA formation and shorten fever duration, but their routine use is still debated.
Cyclophosphamide or Plasma Exchange: In refractory cases, these therapies may be considered, although evidence is limited.

Long-term Management: Long-term follow-up and management are crucial, particularly for patients with coronary artery involvement.

Cardiology Follow-up: Regular cardiology evaluations, including echocardiograms and cardiac stress testing, are recommended.
Antiplatelet Therapy: Low-dose aspirin is typically continued long-term for patients with coronary artery aneurysms. Dual antiplatelet therapy (aspirin plus clopidogrel or dipyridamole) or anticoagulation (warfarin or low-molecular-weight heparin) may be necessary for large aneurysms to prevent thrombosis.
Lifestyle Modifications: Focus on cardiovascular risk reduction, including healthy diet and exercise.

Prognosis and Complications of Kawasaki Disease

The prognosis of Kawasaki disease is largely dependent on the presence and severity of cardiac complications. Early diagnosis and treatment significantly improve outcomes. Mortality is rare in treated KD, primarily due to cardiac complications such as myocardial infarction or sudden cardiac death, typically occurring within the first 15-45 days of illness onset.

Complications of Kawasaki Disease:

Coronary Artery Aneurysms (CAA): The most serious complication, occurring in up to 25% of untreated children, but reduced to 3-5% with IVIG. Giant aneurysms (>8mm) have a higher risk of thrombosis and myocardial infarction.
Myocarditis: Common in the acute phase, but long-term cardiac dysfunction is less frequent.
Valvulitis: Mitral or aortic regurgitation can occur.
Pericarditis and Pericardial Effusion.
Myocardial Infarction (MI) and Sudden Cardiac Death.
Premature Atherosclerosis: Even with aneurysm resolution, vessel wall thickening can increase the risk of future coronary artery disease.

Risk Factors for Coronary Artery Aneurysms:

Prolonged fever (>8 days)
IVIG resistance
Male sex
Asian or Hispanic ethnicity
Younger age of onset (< 6 months) or older age (> 9 years)
Elevated inflammatory markers (CRP, ESR, Pro-BNP)
Lower serum IgG levels
Thrombocytopenia at presentation
Incomplete Kawasaki disease

Conclusion

Kawasaki disease presents a diagnostic challenge due to its varied clinical manifestations and overlap with other pediatric illnesses. A high index of suspicion, particularly in young children with prolonged fever and characteristic mucocutaneous findings, is essential. Prompt recognition and treatment with IVIG and aspirin are critical to minimize the risk of coronary artery complications and improve long-term cardiovascular outcomes. Understanding the differential diagnosis of Kawasaki disease, utilizing diagnostic mnemonics, and employing appropriate laboratory and imaging studies are crucial for timely and accurate diagnosis, leading to improved care and prognosis for affected children. Continued research into the etiology and optimal management strategies for Kawasaki disease remains vital to further enhance patient outcomes.

References

McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, Baker AL, Jackson MA, Takahashi M, Shah PB, Kobayashi T, Wu MH, Saji TT, Pahl E., American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; and Council on Epidemiology and Prevention. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association. Circulation. 2017 Apr 25;135(17):e927-e999. PubMed: 28356445
Saguil A, Fargo M, Grogan S. Diagnosis and management of kawasaki disease. Am Fam Physician. 2015 Mar 15;91(6):365-71. PubMed: 25822554
Vervoort D, Donné M, Van Gysel D. Pitfalls in the diagnosis and management of Kawasaki disease: An update for the pediatric dermatologist. Pediatr Dermatol. 2018 Nov;35(6):743-747. PubMed: 30338568
JCS Joint Working Group. Guidelines for diagnosis and management of cardiovascular sequelae in Kawasaki disease (JCS 2013). Digest version. Circ J. 2014;78(10):2521-62. PubMed: 25241888
Turnier JL, Anderson MS, Heizer HR, Jone PN, Glodé MP, Dominguez SR. Concurrent Respiratory Viruses and Kawasaki Disease. Pediatrics. 2015 Sep;136(3):e609-14. PubMed: 26304824
Sundel RP. Kawasaki disease. Rheum Dis Clin North Am. 2015;41(1):63-73, viii. PubMed: 25399940
Matsubara T. Infliximab for the treatment of Kawasaki disease. Pediatr Int. 2018 Sep;60(9):775. PubMed: 30255976
Kim DS. Kawasaki disease. Yonsei Med J. 2006 Dec 31;47(6):759-72. PMC free article: PMC2687814 PubMed: 17191303
Takahashi K, Oharaseki T, Yokouchi Y. Pathogenesis of Kawasaki disease. Clin Exp Immunol. 2011 May;164 Suppl 1(Suppl 1):20-2. PMC free article: PMC3095860 PubMed: 21447126
Rowley AH, Baker SC, Shulman ST, Garcia FL, Fox LM, Kos IM, Crawford SE, Russo PA, Hammadeh R, Takahashi K, Orenstein JM. RNA-containing cytoplasmic inclusion bodies in ciliated bronchial epithelium months to years after acute Kawasaki disease. PLoS One. 2008 Feb 13;3(2):e1582. PMC free article: PMC2216059 PubMed: 18270572
Lang B. Recognizing Kawasaki disease. Paediatr Child Health. 2001 Nov;6(9):638-43. PMC free article: PMC2805967 PubMed: 20084135
Marchesi A, Tarissi de Jacobis I, Rigante D, Rimini A, Malorni W, Corsello G, Bossi G, Buonuomo S, Cardinale F, Cortis E, De Benedetti F, De Zorzi A, Duse M, Del Principe D, Dellepiane RM, D’Isanto L, El Hachem M, Esposito S, Falcini F, Giordano U, Maggio MC, Mannarino S, Marseglia G, Martino S, Marucci G, Massaro R, Pescosolido C, Pietraforte D, Pietrogrande MC, Salice P, Secinaro A, Straface E, Villani A. Kawasaki disease: guidelines of the Italian Society of Pediatrics, part I – definition, epidemiology, etiopathogenesis, clinical expression and management of the acute phase. Ital J Pediatr. 2018 Aug 30;44(1):102. PMC free article: PMC6116535 PubMed: 30157897
Rowley AH, Shulman ST. Kawasaki syndrome. Clin Microbiol Rev. 1998 Jul;11(3):405-14. PMC free article: PMC88887 PubMed: 9665974
Jindal AK, Indla RT, Pilania RK, Singh S. Non-Exudative Conjunctival Injection With Limbal Sparing: A Pathognomonic Clinical Sign of Kawasaki Disease. J Clin Rheumatol. 2020 Apr;26(3):e59-e60. PubMed: 30247222
Beken B, Unal S, Cetin M, Gümrük F. The relationship between hematological findings and coronary artery aneurysm in kawasaki disease. Turk J Haematol. 2014 Jun;31(2):199-200. PMC free article: PMC4102053 PubMed: 25035683
Suddleson EA, Reid B, Woolley MM, Takahashi M. Hydrops of the gallbladder associated with Kawasaki syndrome. J Pediatr Surg. 1987 Oct;22(10):956-9. PubMed: 3316594
Sun Q, Zhang J, Yang Y. Gallbladder Hydrops Associated With Kawasaki Disease: A Case Report and Literature Review. Clin Pediatr (Phila). 2018 Mar;57(3):341-343. PubMed: 28952362
Reddy S, Forbes T, Chintala K. Cardiovascular involvement in Kawaski Disease. Images Paediatr Cardiol. 2005 Apr;7(2):1-9. PMC free article: PMC3232573 PubMed: 22368648
Tsuda E, Singhal M. Role of imaging studies in Kawasaki disease. Int J Rheum Dis. 2018 Jan;21(1):56-63. PubMed: 29115035
Kahn AM, Budoff MJ, Daniels LB, Jimenez-Fernandez S, Cox AS, Gordon JB, Burns JC. Calcium scoring in patients with a history of Kawasaki disease. JACC Cardiovasc Imaging. 2012 Mar;5(3):264-72. PMC free article: PMC4188432 PubMed: 22421171
Burns JC, Capparelli EV, Brown JA, Newburger JW, Glode MP. Intravenous gamma-globulin treatment and retreatment in Kawasaki disease. US/Canadian Kawasaki Syndrome Study Group. Pediatr Infect Dis J. 1998 Dec;17(12):1144-8. PubMed: 9877364
Durongpisitkul K, Gururaj VJ, Park JM, Martin CF. The prevention of coronary artery aneurysm in Kawasaki disease: a meta-analysis on the efficacy of aspirin and immunoglobulin treatment. Pediatrics. 1995 Dec;96(6):1057-61. PubMed: 7491221
Kim HK, Oh J, Hong YM, Sohn S. Parameters to guide retreatment after initial intravenous immunoglobulin therapy in kawasaki disease. Korean Circ J. 2011 Jul;41(7):379-84. PMC free article: PMC3152732 PubMed: 21860639
Yamazaki-Nakashimada MA, Gámez-González LB, Murata C, Honda T, Yasukawa K, Hamada H. IgG levels in Kawasaki disease and its association with clinical outcomes. Clin Rheumatol. 2019 Mar;38(3):749-754. PubMed: 30343342
Fabi M, Corinaldesi E, Pierantoni L, Mazzoni E, Landini C, Bigucci B, Ancora G, Malaigia L, Bodnar T, Di Fazzio G, Lami F, Valletta E, Cicero C, Biasucci G, Iughetti L, Marchetti F, Sogno Valin P, Amarri S, Brusa S, Sprocati M, Maggiore G, Dormi A, Lanzoni P, Donti A, Lanari M. Gastrointestinal presentation of Kawasaki disease: A red flag for severe disease? PLoS One. 2018;13(9):e0202658. PMC free article: PMC6122791 PubMed: 30180185
Nolan BE, Wang Y, Pary PP, Luban NLC, Wong ECC, Ronis T. High-dose intravenous immunoglobulin is strongly associated with hemolytic anemia in patients with Kawasaki disease. Transfusion. 2018 Nov;58(11):2564-2571. PubMed: 30265742
Newburger JW. Kawasaki disease: Medical therapies. Congenit Heart Dis. 2017 Sep;12(5):641-643. PubMed: 28580631
Burns JC, Hoshino S, Kobayashi T. Kawasaki disease: an essential comparison of coronary artery aneurysm criteria. Lancet Child Adolesc Health. 2018 Dec;2(12):840-841. PubMed: 30337184
Miyata K, Kaneko T, Morikawa Y, Sakakibara H, Matsushima T, Misawa M, Takahashi T, Nakazawa M, Tamame T, Tsuchihashi T, Yamashita Y, Obonai T, Chiga M, Hori N, Komiyama O, Yamagishi H, Miura M., Post RAISE group. Efficacy and safety of intravenous immunoglobulin plus prednisolone therapy in patients with Kawasaki disease (Post RAISE): a multicentre, prospective cohort study. Lancet Child Adolesc Health. 2018 Dec;2(12):855-862. PubMed: 30337183
Denby KJ, Clark DE, Markham LW. Management of Kawasaki disease in adults. Heart. 2017 Nov;103(22):1760-1769. PubMed: 28751537
Williams RV, Wilke VM, Tani LY, Minich LL. Does Abciximab enhance regression of coronary aneurysms resulting from Kawasaki disease? Pediatrics. 2002 Jan;109(1):E4. PubMed: 11773572
McCandless RT, Minich LL, Tani LY, Williams RV. Does abciximab promote coronary artery remodeling in patients with Kawasaki disease? Am J Cardiol. 2010 Jun 01;105(11):1625-8. PubMed: 20494673
Suzuki H, Terai M, Hamada H, Honda T, Suenaga T, Takeuchi T, Yoshikawa N, Shibuta S, Miyawaki M, Oishi K, Yamaga H, Aoyagi N, Iwahashi S, Miyashita R, Onouchi Y, Sasago K, Suzuki Y, Hata A. Cyclosporin A treatment for Kawasaki disease refractory to initial and additional intravenous immunoglobulin. Pediatr Infect Dis J. 2011 Oct;30(10):871-6. PubMed: 21587094
Kuijpers TW, Biezeveld M, Achterhuis A, Kuipers I, Lam J, Hack CE, Becker AE, van der Wal AC. Longstanding obliterative panarteritis in Kawasaki disease: lack of cyclosporin A effect. Pediatrics. 2003 Oct;112(4):986-92. PubMed: 14523200
Gupta-Malhotra M, Gruber D, Abraham SS, Roman MJ, Zabriskie JB, Hudgins LC, Flynn PA, Levine DM, Okorie U, Baday A, Schiller MS, Maturi J, Meehan D, Dyme J, Parker TS, Wittkowski KM, Gersony WM, Cooper RS. Atherosclerosis in survivors of Kawasaki disease. J Pediatr. 2009 Oct;155(4):572-7. PubMed: 19595365
Gordon JB, Kahn AM, Burns JC. When children with Kawasaki disease grow up: Myocardial and vascular complications in adulthood. J Am Coll Cardiol. 2009 Nov 17;54(21):1911-20. PMC free article: PMC2870533 PubMed: 19909870

Figure: Classic strawberry tongue appearance in Kawasaki Disease. This is due to the inflammation of the mucous membranes in the oral cavity, a key diagnostic criterion.