Is it Atypical Kawasaki Disease or Evolving Systemic JIA?

Incomplete Kawasaki disease (KD) occurs in patients with fever lasting five or more days and with two or three of the classical findings (exanthema, conjunctivitis, changes in the extremities, erythema of oral mucosa and lips, cervical lymphadenopathy) [1]. It is difficult to define its real incidence. However the association between bilateral conjunctival bulbar injection and perineal erythema, with early desquamation in a patient with platelet count > 450.000 after 7 days of fever is indicative of incomplete KD. The definition “atypical KD” should be reserved for patients who have clinical manifestations such as renal impairment, unilateral peripheral facial nerve palsy, testicular swelling, pulmonary nodules and/or infiltrates, pleural effusions, diarrhea, vomiting and abdominal pain, acute surgical abdomen, hemophagocytic syndrome that generally are not seen in Kawasaki disease [1]. The “classical” clinical criteria have low sensitivity and specificity and therefore, other clinical and laboratory features may be helpful in establishing the diagnosis, especially for atypical or incomplete KD. In the last years many studies highlighted clinical and/or laboratory findings useful to obtain a precocious diagnosis in atypical and incomplete KD, because coronary artery lesions (CAL) occur in 15-25% of untreated KD and approximately in 5% of KD who received intravenous immunoglobulin (IVIG) treatment before 10 days of fever [2,3]. Relief of hyponatremia, hypoalbuminemia, increased D-Dimer are biochemical findings useful for diagnosis [4]. The association of more parameters, also considering AST, ALT, gamma-GT, leukocytes, percentage of neutrophils, platelet counts, CRP, ESR can be a help in the labyrinth of KD. In fact a precocious diagnosis and a timely treatment with IVIG significantly improve prognosis and reduce the risk of CAL. However the doubt of an atypical KD requests electrocardiography and echocardiography, to exclude CAL, pericardial effusion, valvular insufficiency, arrhythmia, prolonged PR interval, nonspecific ST and T wave changes in patients with FUO. Although aneurysms are rare before day 10 of fever, perivascular brightness, coronary arteries ectasia in the acute stage, indicate coronary arteritis before the aneurysms develop. incomplete KD should be considered in all children with unexplained fever for ≥5 days associated with 3 or less of the clinical criteria. incomplete KD is more common in young infants, who have a higher risk to develop CAL. Young infants may present with incomplete KD: echocardiography should be considered in infants younger than 6 months with fever for ≥7 days, laboratory evidence of systemic inflammation, no other explanation of the disease.

Introduction: Infants with atypical Kawasaki Disease always posed a diagnostic difficulty to cardiologist and literature has suggested that infants with Kawasaki Disease had a higher complication rate. A retrospective review of atypical Kawasaki disease from July 1994 to June 2000 was carried out to study the incidence and coronary complication rate among patients with atypical Kawasaki Disease. Methods: The hospital records of patients with Kawasaki diseases diagnosed between July 1994 to June 2000 were reviewed by members of Hong Kong Kawasaki Disease Study Group. Patients were identified as atypical Kawasaki disease if they have less than five of the diagnostic criteria after having excluded other possible causes. Results: A total of 72 cases of atypical Kawasaki disease were diagnosed from July 1994 to June 2000. Forty-five are males. Twenty-seven were females. M: F ratio 1.7: 1. Age of onset range from 0.2yr to 12.8yrs (mean 2.1yr; median 2.2yr). 39 of them are infants (54%; p< 0.0001). 56 (79%) received IVIG therapy (p =0.01). Coronary artery aneurysm developed in 25 cases (34.7%) of atypical Kawasaki Disease (p<0.0001). 15 (60%) of them were infants. 20 of the atypical cases with coronary aneurysm received IVIG therapy. Conclusion: We conclude that patients with atypical Kawasaki disease had a higher rate of coronary complication. Infants were associated with a higher rate of atypical presentation and coronary complication. Male sex and use of IVIG contribute no statistical significance in the development of coronary complication in atypical Kawasaki disease. However, patients with atypical Kawasaki disease had a significant lower incidence of receiving IVIG therapy when compared with typical Kawasaki presentation. This may be due to delay in diagnosis and treatment. A high index of suspicion and clinical assessment by cardiologist is recommended in the diagnosis and treatment of atypical Kawasaki disease especially among infants.

Kawasaki disease (KD) is an acute febrile vasculitis primarily affecting medium-sized arteries in children under 5 years. Infants under 6 months represent a diagnostic challenge due to atypical or incomplete presentations, increasing the risk of coronary artery lesions and complications such as aneurysms. Early diagnosis and treatment with intravenous immunoglobulin (IVIG) and aspirin are crucial to prevent long-term cardiac sequelae. We report a rare case of KD in a 5-month-old Bangladeshi girl presenting with prolonged fever, rash, and sterile pyuria. Initial evaluations pointed to partially treated meningitis, delaying KD diagnosis. Subsequent symptoms included edema, osteoarthritis, and persistent inflammation, leading to an echocardiographic detection of a small coronary aneurysm. Treatment with IVIG, aspirin, and corticosteroids resulted in the resolution of symptoms and normalization of cardiac findings. Infants below 6 months often present with incomplete KD, complicating diagnosis and delaying treatment. This case underscores the importance of considering KD in febrile infants with persistent inflammation, even in the absence of classic symptoms. Echocardiography and laboratory markers remain essential for early detection and management. Increased awareness and timely intervention in atypical and incomplete KD presentations are critical for reducing complications, particularly in high-risk groups like infants under 6 months.

Kawasaki Disease is multisystem vasculitis affecting young children and infants. While the diagnosis of a typical form of Kawasaki Disease is obvious, there are some patients who do not fulfill the classic diagnostic criteria for the disease which is termed as 'incomplete Kawasaki Disease' or 'Atypical Kawasaki Disease'. We present a case of a 6 months old child with fever who after failing to respond to IV antibiotics showed considerable improvement after administering aspirin and Intravenous Immunoglobulin thus diagnosed as Atypical Kawasaki Disease. Moreover, due to sharing of similar features by both Kawasaki Disease and Multiple Inflammatory Syndrome in Children, the case posed a diagnostic dilemma.

Kawasaki disease (KD) is the most common pediatric vasculitis with coronary involvement feared as the most serious complication. The reported case describes a child presenting initially with atypical KD and coronary artery aneurysms. He was treated with intravenous immunoglobulin and aspirin. In spite of adequate compliance and no clinical recurrence, serial echocardiography revealed nonregression of aneurysm and new-onset moderate aortic regurgitation (AR) in the subacute phase produced by prolapse of noncoronary cusp of the aortic valve. AR without aortic root dilatation from persistent inflammation of the valve leaflets in KD is a rare phenomenon. This case demonstrates unusual cardiac manifestations of KD and reoriented our protocol for long-term surveillance in infantile KD.

Kawasaki disease is an acute febrile condition seen in children. However, it is also well recognized that some patients do not fulfill the classic diagnostic criteria for the diagnosis of kawasaki disease. The incomplete form of kawasaki disease is termed as ‘Incomplete KD’ or ‘Atypical KD’. We present a case of a 6 year old child with a history of prolonged fever, periorbital, oral and lip changes, changes in the extremities and an erythamatous, maculopapular rash. Based on the physical exam and her echocardiogram that showed right coronary artery dilatation, Intravenous immune globulin was administered in this patient. This patient was refractory to two doses of intravenous immune globulin and therefore was started on methylprednisolone, to which she responded dramatically. The diagnostic dilemma primarily arose when this child presented with joint pain a day after her discharge from the hospital and a positive laboratory workup. So, was this a case of incomplete Kawasaki refractory to intravenous immuno globulin therapy or systemic juvenile idiopathic arthritis? We suggest that physicians should be cognizant of the fact that they must individualize every patient’s management to the best of their knowledge and judgment, rather than merely going by the guidelines.

Atlantoaxial rotatory fixation (AARF) is a rare complication of acute Kawasaki disease (KD). Early diagnosis and intervention are important for AARF because delayed diagnoses may incur neurological sequelae. However, previous studies on AARF associated with KD are limited, and its clinical characteristics and course are unknown. This study aimed to examine the clinical features and treatment course of KD with AARF using a Japanese national inpatient database. Using the Diagnosis Procedure Combination database, we identified KD patients who received intravenous immunoglobulin (IVIG) treatment between July 2010 and March 2020. The clinical characteristics of KD patients with AARF and their risk factors were evaluated using multivariable logistic regression analysis. We also examined the relationship between AARF, the proportion of coronary artery abnormalities (CAAs), IVIG resistance, length of stay and medical costs. We identified 71,913 patients with KD, 166 of whom had AARF. The AARF group had older age, heavier bodyweight and atypical KD. In multivariable analysis, AARF was associated with older age [odds ratio (OR): 1.24; 95% confidence interval (CI): 1.19-1.29], lower body mass index (OR: 0.89; 95% CI: 0.82-0.96) and atypical KD (OR: 1.95; 95% CI: 1.12-3.40). AARF was not associated with CAAs (OR: 0.73; 95% CI, 0.23-2.32) and IVIG resistance (OR: 1.05; 95% CI, 0.74-1.49). However, AARF was associated with higher medical costs (difference, US$1064; 95% CI: 346-1781) and longer hospital stay (difference, 3.1 days; 95% CI: 1.7-4.4). AARF in patients with acute KD should be considered if cervical symptoms present in older patients with atypical KD.

Index of suspicion.

Background: Kawasaki disease (KD) is described as a life-threatening vasculitis, which mostly develops in children below five years of age and is diagnosed according to clinical criteria. It is also a common rheumatologic disorder in Iran. Objectives: The present study aimed at determining the clinical and demographic characteristics of KD patients in Iran. Methods: We retrospectively assessed 69 cases of KD in an Iranian pediatric population from March 2014 to March 2018. The Japanese Kawasaki Disease Research Committee guidelines were used as the diagnostic criteria for typical KD. Incomplete or atypical KD was diagnosed in patients with coronary artery changes, but without all the criteria for KD. Results: In this study, 69 patients were recruited, with a male-female ratio of 1:8. Overall, 64% (n, 44) and 36% of children met the criteria for typical and atypical KD, respectively. Also, echocardiographic abnormalities were reported in eight patients (12%). Coronary artery aneurysm was found in 2% of patients, while other cardiac abnormalities were found in 12% of patients. The male-female ratio of coronary artery anomalies and other cardiac abnormalities was 3:1. Polymorphic exanthema was the most common clinical manifestation. The erythrocyte sedimentation rate ≥ 40 mm/h was the most common laboratory finding, while skin desquamation was the most common complication in other organs. Conclusions: KD is not uncommon in Markazi Province, Iran. In this study, distribution of demographic characteristics was not similar to reports from other countries. Also, clinical findings, age and gender distribution, laboratory findings, and complications in other organs were not similar to previous reports. The incidence of typical and atypical KD was different in this region, especially in terms of complications, such as cardiac and gastrointestinal complications.

Kawasaki Disease is a spectrum of idiopathic, self-limited fever disease affecting childrenunder 5 years old. This disorder can be challenging to be diagnosed by a pediatrician since thereis no specific diagnostic laboratory test. One atypical Kawasaki Disease case presented withgastrointestinal symptoms, a two-year-old girl was hospitalized with fever, accompanied by non-hemorrhagic diarrhea three days before admission. Physical examination revealed unilateralcervical lymph enlargement and mild-moderate dehydration. Initial laboratory examinationresult showed thrombocytosis, leukocytosis (shift to the left), and normal routine fecal analysis.The patient was initially diagnosed with acute diarrhea with mild-moderate dehydration. She wastreated with a rehydration regimen and antibiotic, but her fever persisted. On the third day ofhospitalization, she fulfilled 3 of the classic Kawasaki Disease criteria (conjunctivitis, crackedlips with strawberry tongue, and lymphadenopathy). Further blood work resulted in increased C-reactive protein 43.35 mg/L and ESR 72 mm/hour, while chest X-ray and electrocardiographwere within normal limit. This patient was proceed to Hasan Sadikin General Hospital for furtherexamination and therapy. Atypical Kawasaki Disease can be a puzzling diagnosis due to itsuncommon presentations. Clinicians should importantly keep it in mind as a differential diagnosisin patients with prolonged fever.&#x0D; Keywords: atypical Kawasaki disease; diarrhea; prolonged fever

Kawasaki disease (KD) is a type of systemic vasculitis of unknown etiology. Atypical Kawasaki disease is defined as that where there are signs and symptoms not corresponding to the classical criteria for this nosological entity. Children with atypical Kawasaki disease may present with acute abdominal symptoms, meningeal irritation, pneumonia or renal failure. We describe 4 children with ages ranging from 2 to 12 years who had atypical Kawasaki disease, with neurological and gastrointestinal symptoms as part of the systemic presentation of the disease. Treatment consisted of immunoglobulin and corticosteroids with good evolution. KD is a systemic vasculitis that can involve many territories. Atypical manifestations can mislead the clinician and delay diagnosis. Pediatricians and sub-specialists should be aware of these neurological manifestations in order to provide adequate and opportune treatment.

It was previously reported from Italy that all patients with Kawasaki disease had a positive tuberculin intradermal test. In this study from Seattle, WA, nine patients with Kawasaki disease showed no reaction to intradermal tuberculin. The difference in results might be caused by the different tuberculin products.

Objective: By functioning as a heat‐shock protein (HSP), α‐enolase has an important role in the pathophysiology of multivariant vasculitis. Kawasaki disease (KD) is a type of vasculitis occurring primarily in children. The role of α‐enolase in KD was assessed by measuring anti‐α‐enolase antibody (Ab) titres in patients with KD and the usefulness of anti‐α‐enolase Ab as a diagnostic tool in atypical KD patients was evaluated.Methods: Anti‐α‐enolase Ab titres were measured by using an enzyme‐linked immunosorbent assay (ELISA) in seven normal control patients, nine febrile control patients and 14 KD patients (10 typical KD, four atypical KD). A standard deviation (SD) of 3 above the mean of the normal control group was considered to be positive reactivity. Western blotting using recombinant human α‐enolase was performed in four KD patients and three normal controls.Results: With the positive reactivity limited to +3 SD over the mean (>0.6), 10 out of 14 patients (71%) were positive at the acute onset and 12 out of 14 patients (85.7%) were positive before discharge. In total, 12 out of 14 patients (85.7%) were positive either at acute onset or before discharge. All four atypical KD patients showed positive reactivity. Specific positive bands against recombinant human α‐enolase were detected by western blotting in all four KD patients, but no reactivity was seen in three patients with normal controls.Conclusion: This is the first study to demonstrate that autoantibodies against the α‐enolase are present in the sera of KD patients. We suggest that anti‐α‐enolase Ab should be a good candidate for a diagnostic tool in atypical KD.

To compare the clinical and laboratory features of children with Kawasaki disease with those with acute adenoviral infection, which may mimic Kawasaki disease. We retrospectively compared the medical records of children with Kawasaki disease and atypical Kawasaki disease with those of children with acute adenoviral infection. All children included were initially evaluated because their primary care physicians were concerned that they might have Kawasaki disease. The utility of a rapid direct fluorescent antigen test for adenovirus was evaluated. Thirty-six children with Kawasaki disease (23 with classic and 13 with atypical presentations) and 7 patients with acute adenoviral infection were studied. A tertiary care pediatric hospital. Children with Kawasaki disease were more likely to have conjunctivitis (36 of 36 vs 4 of 7), strawberry) tongues (23 of 36 vs 1 of 7), perineal peeling (19 of 36 vs 0 of 7), and distal extremity changes (22 of 36 vs 0 of 7) than those with acute adenoviral infection. Children with acute adenoviral infection were more likely to have purulent conjunctivitis (3 of 7 vs 1 of 36) and exudative pharyngitis (3 of 7 vs 1 of 35). In addition to pyuria (13 of 26 vs 0 of 6), patients with Kawasaki disease had higher mean white blood cell counts (15.3 +/- 3.5 vs 11.5 +/- 6.0 x 10(9)/L), erythrocyte sedimentation rates (56 vs 42 mm/h), platelet counts (426 vs 259 x 10(9)/L), and levels of alanine aminotransferase (101 vs 18 U/L) than those with acute adenoviral infection. Children with Kawasaki disease had lower mean albumin levels (32 vs 36 g/L). A rapid antigen test for adenovirus had a specificity and sensitivity of 100% compared with viral culture. Kawasaki disease and acute adenoviral infection can present with many of the same clinical characteristics. A rapid direct fluorescent antigen assay for adenovirus may be a helpful adjunctive test for distinguishing acute adenoviral infection from Kawasaki disease.

The diagnosis of incomplete or atypical Kawasaki disease (KD) is challenging. Children presenting with febrile illnesses may have few of the classical diagnostic criteria, yet develop clinical, laboratory and echocardiographic findings compatible with the condition. Early recognition and prompt treatment of KD is essential for better outcomes. This is particularly the case for infants who are at a greater risk of developing complications such as coronary artery aneurysms. This may be partly attributed to late diagnosis or initiation of therapy. This report discusses the case of a febrile infant with atypical Kawasaki disease presenting with aseptic meningitis and coronary artery aneurysm. The case highlights the importance of considering atypical Kawasaki disease in any infant with prolonged fever (more than seven days), following exclusion of infectious causes and in the absence of classical diagnostic criteria.