Secondary Logo

Kawasaki Disease in Adults: Report of 10 Cases

Gomard-Mennesson, Emeline MD; Landron, Cédric MD; Dauphin, Claire MD; Epaulard, Olivier MD, PhD; Petit, Clemence MD; Green, Lisa MD; Roblot, Pascal MD, PhD; Lusson, Jean-René MD, PhD; Broussolle, Christiane MD, PhD; Sève, Pascal MD

doi: 10.1097/MD.0b013e3181df193c
Article
Free
SDC

Kawasaki disease (KD) is an acute multisystemic vasculitis occurring predominantly in children and rarely in adults. Diagnosis is made clinically using diagnostic guidelines; no specific test is available. "Incomplete" KD is a more recent concept, which refers to patients with fever lasting ≥5 days and 2 or 3 clinical criteria (rash, conjunctivitis, oral mucosal changes, changes of extremities, adenopathy), without reasonable explanation for the illness.

To describe the clinical and laboratory features of classical (or "complete") KD, and incomplete KD in adults, we report 10 cases of adult KD, including 6 patients who fulfilled the criteria for incomplete KD, diagnosed either at presentation (n = 4) or retrospectively (n = 2).

At the time of clinical presentation, complete KD was diagnosed in 4 patients, while 4 patients fulfilled the criteria for incomplete KD. For 3 of the 4 patients with incomplete KD, presence of severe inflammation, laboratory findings (hypoalbuminemia, anemia, elevation of alanine aminotransferase, thrombocytosis after 7 days, white blood cell count ≥15,000/mm3, and urine ≥10 white blood cell/high power field), or echocardiogram findings were consistent with the diagnosis. In 2 patients, the diagnosis of KD was made retrospectively in the presence of myocardial infarction due to coronary aneurysms, after an undiagnosed medical history evocative of incomplete KD. Seven patients received intravenous immunoglobulins (IVIG), after a mean delay of 12.5 days, which appeared to shorten the course of the disease.

This relatively large series of adult KD highlights the existence of incomplete KD in adults and suggests that the algorithm proposed by a multidisciplinary committee of experts to diagnose incomplete KD in children could be useful in adults. Further studies are needed to determinate whether prompt IVIG may avoid artery sequelae in adult patients with complete or incomplete KD.

Abbreviations: CRP = C-reactive protein, CT = computed tomography, ESR = erythrocyte sedimentation rate, HIV = human immunodeficiency virus, IVIG = intravenous immunoglobulins, KD = Kawasaki diseases

From Department of Internal Medicine (EGM, CP, LG, CB, PS) Hôtel-Dieu, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Lyon; Department of Internal Medicine (CL, PR), Hôpital Jean Bernard, Poitiers; Department of Cardiology (CD, JRL), Hôpital Gabriel-Montpied, CHU Clermont-Ferrand; and Department of Infectious Diseases (OE), University Hospital, Grenoble, France.

Reprints: Emeline Gomard-Mennesson, MD, Department of Internal Medicine, Hôtel-Dieu, Hospices Civils de Lyon, 1 place de l'Hôpital, 69288 Lyon cedex 02, France (e-mail: e.mennesson@free.fr).

All figures can be viewed online in color at http://www.md-journal.com.

Back to Top | Article Outline

INTRODUCTION

Kawasaki disease (KD) is an acute self-limited vasculitis that usually affects infants and young children. The intense inflammatory process has a predilection for the coronary arteries, resulting in the possible development of aneurysmal lesions, arterial occlusion, or potentially sudden death. First described in Japan in 1967,34 the disease is now known to occur in both endemic and community-wide epidemic forms in children of all races. The etiology remains unknown, although an as-yet unidentified infectious agent might be responsible.65 Adult KD is a rare condition that may remain unrecognized. A literature review by Sève et al69 in 2005 reported 57 cases of adult KD, and 27 new cases have been reported.8,14,17,18,20,22,27,37,47,59,72,82

There is no specific diagnostic test available for KD; the diagnosis is based on the presence of characteristic findings. Diagnosis of KD is classically based on the presence of fever lasting 5 days or more, and at least 4 of the 5 following clinical signs: 1) polymorphic rash, 2) cutaneous changes in the peripheral extremities such as erythema or desquamation, 3) nonexudative bilateral conjunctivitis, 4) involvement of the lips or oral cavity such as injected or fissured lips or strawberry tongue, and 5) cervical adenopathies (Table 1).63

TABLE 1

TABLE 1

More recently, there has been increasing evidence that a number of children with KD do not fulfill classical criteria.85 The term "atypical" or "incomplete" KD has been proposed to refer to this subgroup of patients. Newburger et al53 defined atypical KD as a case in which atypical symptoms or signs, not belonging to the classical criteria, herald the onset of the disease. The term "incomplete" KD is used for children with fever lasting at least 5 days, at least 2 of the clinical criteria for KD, no other explanation for the illness, and laboratory findings consistent with severe inflammation.10 A multidisciplinary committee of experts proposed an algorithm to help clinicians evaluate and manage patients with so-called incomplete KD.53

While cases of incomplete KD are well recognized in children, they are unusual in adults, with only a few cases reported in the medical literature.8,17,22,47,59 In the present work, we describe 10 cases of adult KD, 6 of whom fulfilled the criteria for incomplete KD.

Back to Top | Article Outline

PATIENTS AND METHODS

Ten cases were selected from departments of internal medicine, cardiology, and infectious diseases of 5 university hospitals in France (Lyon, Clermont-Ferrand, Poitiers, Grenoble, and Caen). Patients were considered to have KD if they had fever lasting 5 days or more and 4 clinical criteria (Table 1).63 In acknowledgment of the importance of coronary artery disease in defining KD, it was agreed that in the presence of coronary arterial involvement demonstrated by echocardiography or angiography, fewer than 4 of the remaining 5 clinical criteria were needed to classify a patient as having KD. Similar to the proposed definition of incomplete KD in children, we considered incomplete KD in adults when patients had the following: fever lasting at least 5 days, at least 2 of the clinical criteria for KD, no other explanation for the illness, and laboratory findings consistent with severe inflammation.10 Data from these patients were summarized using a standardized form, including sex, age, main clinical manifestations, cardiac findings, laboratory features, differential diagnosis, treatment, and disease evolution.

We conducted a computer-assisted (PubMed, National Library of Medicine, Bethesda, MD) search of publications in English, Spanish, and French from 1967 (when KD was first described) through December 2008 (keywords: Kawasaki disease, adult), in order to identify all cases of adult KD. The reference lists of all the articles were scanned for references not identified in the initial research. Only cases with well-documented clinical summaries and relevant information were included.

Back to Top | Article Outline

CASE REPORTS

Patient 1

A 23-year-old man who had settled in France 3 years earlier was admitted to the cardiac intensive care unit with an inferior non-Q myocardial infarction. Three months earlier, the patient had been admitted to the internal medicine department with a 4-week history of fever, weight loss, and arthralgia. Physical examination had revealed a temperature of 39°C, nonpurulent palpebral conjunctivitis, fissured lips, and numerous small axillary lymph nodes. No eruption or changes to the peripheral extremities were noticed. Laboratory tests revealed an erythrocyte sedimentation rate (ESR) of 85 mm/1st h, and an increased C-reactive protein (CRP) level of 78 mg/L. Blood count and liver enzyme levels were normal. Blood cultures and serologic assays for human immunodeficiency virus (HIV) and hepatotropic viruses were negative. Chest X-ray, abdominal ultrasonography, electrocardiogram, and transthoracic echocardiography were initially normal. Coronary angiography, performed 3 days after the infarction, revealed multiple aneurysms of the left anterior descending coronary and circumflex arteries, distal occlusion of the right coronary artery, and distal stenosis of the interventricular artery (Figure 1).

FIGURE 1

FIGURE 1

KD was then diagnosed. The patient was given aspirin and warfarin chronically to prevent thrombosis. At 2 years' follow-up, his clinical course was quiescent.

Back to Top | Article Outline

Patient 2

A 39-year-old woman presented with a 4-day history of fever, myalgia, and arthralgia, which appeared 12 hours after influenza vaccination. Her previous medical history included Henoch-Schönlein purpura in childhood and diabetes mellitus. Physical examination revealed bilateral wrist arthritis, diffuse erythematous rash, cervical and supraclavicular lymphadenopathy, and splenomegaly. Laboratory studies showed CRP, 315 mg/L; hemoglobin, 108 g/L; platelet count, 122 × 109/L; and albuminemia (28 g/L). The patient's γ-glutamyl transpeptidase level was 12 times the normal level; alkaline phosphatase was 4 times the normal level, and alanine aminotransferase was 15 times normal. Troponin I was slightly increased (0.11 μg/L, normal range < 0.04 μg/L), but myoglobin and creatine phosphokinase-MB were normal. An electrocardiogram showed negative T waves on D3 but a 2-dimensional echocardiogram showed no abnormality or evidence of coronary aneurysms. Blood and urine cultures were negative. Serologic tests were negative for hepatitis A, B, C, HIV, Parvovirus B19, Epstein-Barr virus, cytomegalovirus, herpes simplex virus, Mycoplasma, Legionella, Leptospira, Rickettsia, and Lyme disease. The patient was initially treated with spiramycin, with no effect on clinical symptoms.

Desquamation of the palms and soles occurred the third week, and incomplete KD was suspected. The patient recovered spontaneously within 4 weeks without specific treatment.

Back to Top | Article Outline

Patient 3

A previously healthy 58-year-old man was admitted with a widespread rash, arthralgia, and a high fever (40°C-41°C) which had lasted for 3 days despite steroids and amoxicillin. On admission, physical examination found diffuse exanthema, erythema, and edema of the palms and soles and dry fissured lips. Cardiovascular, abdominal, and neurologic examinations were normal. Laboratory evaluation showed thrombocytopenia (110 × 109/L), leukocytosis (12 × 109/L), high CRP level (309 mg/L), and hyperferritinemia (545 ng/mL). Alanine aminotransferase was twice the normal, natremia was low (130 mmol/L), and proteinuria was positive (0.38 g/24 h). Extensive investigations for infectious diseases were negative. Chest X-ray, transesophageal echocardiography, and coronal computed tomography (CT) scan were normal.

Desquamation of the extremities was observed on the tenth day, suggesting the diagnosis of KD. Intravenous immunoglobulins (IVIG) were administered, followed by apyrexia the next day.

Back to Top | Article Outline

Patient 4

A 37-year-old man, with 4 cardiovascular risk factors, was admitted in 2003 for acute myocardial infarction. Coronary angiography showed occlusion of the distal circumflex artery; multiple stenosis of the left anterior descending artery, first diagonal, and lateral circumflex artery; and multiple coronary aneurysms. The patient underwent a coronary angioplasty with stenting, then a coronary bypass graft. The only noteworthy pathologic history was a hospitalization 9 years earlier for fever of unknown origin, accompanied by arthralgia, conjunctival subicterus, dry cough, and nonpurulent conjunctivitis. At this time, laboratory tests were as follows: leukocytosis, 24 × 109/L with predominance of polymorphonuclear cells (80%); CRP, 539 mg/L; and increased liver enzyme levels (alanine aminotransferase twice the normal level and γ-glutamyl transpeptidase, 5 times normal). Thrombocytosis (883 × 109/L) appeared on the fifteenth day. Treatment with a nonsteroidal antiinflammatory drug was started, and desquamation of the palms and soles occurred at the sixth week. Based on this medical history, the diagnosis of KD was retrospectively made.

Back to Top | Article Outline

Patient 5

A 39-year-old woman presented with a fever lasting 6 days, associated with successive appearance of asthenia, dry cough, erythematous maculopapular rash, changes in the lips, chest pain, and tachycardia (140 beats per minute). Laboratory studies revealed CRP, 190 mg/L; serum albumin, 16.4 g/L; and sterile leukocyturia (70 cells/μL). Troponin was slightly elevated (0.2 μg/L). Investigations for infectious diseases were negative. Thrombocytosis (811 × 109/L) was noted on the third week. On day 11, echocardiography showed pericardial effusion and left coronary artery perivascular brightness. A diagnosis of KD was then considered, and the patient received IVIG (0.4 g/kg for 5 d) and aspirin (75 mg/d for 6 wk). Within 1 day of treatment, the fever disappeared and other clinical and laboratory aspects started to normalize rapidly. Repeated echocardiography showed no abnormalities. Three months later, she remained well. Coronary angiography revealed normal coronary arteries with no ectasia or aneurysms. Low-dose aspirin was continued.

Back to Top | Article Outline

Patient 6

A 21-year-old otherwise healthy woman was admitted for the assessment of a 6-day-long high fever (39°C-40°C) and widespread eruption. Physical examination found diffuse polymorphic exanthema, erythema, and edema of the palms; dry fissured lips, and conjunctival subicterus. Important laboratory values included CRP, 300 mg/L; white blood cell count, 21 × 109/L with predominance of polymorphonuclear cells; hemoglobin, 92 g/L; platelet count, 1000 × 109/L; and albuminemia (22 g/L). Liver enzyme tests disclosed signs of liver cytolysis: alanine and aspartate aminotransferase levels of, respectively, 256 and 208 IU/L (normal <50 IU/L) and γ-glutamyl transpeptidase of 1008 IU/L (normal < 32 IU/L). Sterile pyuria was also noted (58/μL). Echocardiography revealed a slight pericardial effusion and right coronary artery perivascular brightness. Faced with such manifestations, KD was diagnosed on day 7, and the patient was treated with a single dose of IVIG 2 g/kg and aspirin. With this treatment, clinical and laboratory improvement was obtained within 3 days. Peeling of the skin, beginning in the hyponychium and progressing to platelike desquamation of the palms and soles, developed from the third through the fourth week. Low-dose aspirin was maintained for 2 months.

Back to Top | Article Outline

Patient 7

A previously healthy 25 year-old man was admitted to the department of internal medicine for a 14-day history of fever up to 39°C, knee arthralgia, and widespread rash. Results of initial physical examination were remarkable for a diffuse erythematous eruption, edema, and erythema of the palms and soles; oropharyngeal changes including "strawberry" tongue, cheilitis, and pharyngitis; and bilateral nonsuppurative conjunctivitis. Abnormal laboratory results were as follows: ESR, 84 mm/1st h; CRP, 400 mg/L; leukocytosis, 16.1 × 109/L with predominance of polymorphonuclear cells; alanine aminotransferase, 190 IU/L; serum albumin, 28.4 g/L; and sterile leukocyturia, 340 cells/μL). Blood cultures were sterile. Serologic assays for HIV, hepatitis A, B, C, Parvovirus B19, Epstein-Barr virus, Cytomegalovirus, herpes simplex virus, human herpesvirus 8, Leptospira, and syphilis were negative. Electrocardiogram, chest X-ray, and 2 transthoracic echocardiograms were normal. On day 14, a clinical diagnosis of KD was made, and the patient received a single dose of IVIG of 2 g/kg and high-dose aspirin (1 g/6 h) for 8 weeks. Fever disappeared over the following 24 hours, with a reduction of oral changes and conjunctivitis within 1 week. Peeling started on day 11.

Back to Top | Article Outline

Patient 8

A 30-year old man came to the emergency room with a 1-day fever, myalgia, and diffuse morbilliform exanthema. No significant information could be gathered from the personal and family history. During the examination, he looked ill with a temperature of 39.5°C. He had injected conjunctivae, icterus, strawberry tongue, and edema of the palms and soles. Investigations revealed the following: white blood count, 17.2 × 109/L with predominance of polymorphonuclear cells; CRP, 79 mg/L; alanine aminotransferase, 623 IU/L; total bilirubin, 69 μmol/L (normal < 5 μmol/L). Differential diagnosis including serologic tests for viruses (HIV, Cytomegalovirus, Epstein-Barr virus, herpes simplex virus, hepatotropic virus), toxoplasmosis, and bacteria (Rickettsia, Chlamydia, and leptospirosis) were negative. Blood and throat cultures were negative. Abdominal ultrasonography and electrocardiogram were normal. Echocardiography showed mild pericardial effusion and a dilatation of the proximal right coronary artery. Faced with such manifestations, KD was diagnosed on day 8 and the patient was treated with oral aspirin (3000 mg/d for 9 d) and IVIG (2 g/kg). With this treatment, the patient showed defervescence within 4 days, and desquamation of the hands and feet started on day 17. Echocardiography repeated 8 days later showed a small aneurysm of the right coronary artery. Coronography or CT coronary angiography were not performed. Echocardiography 7 months later revealed coronary artery perivascular brightness, whereas electrocardiogram stress test was normal.

Back to Top | Article Outline

Patient 9

An 18-year-old man was admitted to the hospital because of fever lasting 16 days and diarrhea. He had a past history of asthma. On admission, he was febrile (40°C), and physical examination revealed the following: a diffuse maculopapular rash; erythema and edema of hands and palms; conjunctivitis; oropharyngeal changes with strawberry tongue and erythematous dry fissured lips (Figure 2). Laboratory tests disclosed leukocytosis, 16.2 × 109/L with predominance of polymorphonuclear cells (78%); and CRP, 259 mg/L. Blood, urine, and throat cultures were negative. Serologic tests were negative for HIV, Parvovirus B19, and for antistreptolysin test O. Electrocardiogram showed complete right bundle branch block but subsequent echocardiography, CT coronary angiography, and electrocardiogram stress test were normal. On day 21, a diagnosis of KD was made and the patient was treated with aspirin (4000 mg/d for 7 d) and IVIG (0.5 g/kg for 4 d). With this treatment, the patient showed defervescence within 1 day, and desquamation of the hands and feet started on day 22 (Figure 3).

FIGURE 2

FIGURE 2

FIGURE 3

FIGURE 3

Back to Top | Article Outline

Patient 10

A 22-year-old man presented with a 5-day history of conjunctivitis, fever up to 40.5°C, and rash. Results of the initial examination were remarkable for diffuse exanthema, erythema, and edema of the palms and soles; and oropharyngeal changes with prominent papillae (strawberry tongue) and dry, fissured lips. Skin biopsy showed no specific inflammatory infiltrate. Initial laboratory evaluation revealed CRP, 157 mg/L; leukocytosis, 28.8 × 109/L with predominance of polymorphonuclear cells (88%); alanine aminotransferase level, 125 IU/L; alkaline phosphatase level, 119 IU/L. Blood and urine cultures were sterile. Serologic tests were negative for HIV, Cytomegalovirus, Epstein-Barr virus, hepatitis B, Parvovirus B19, and Rickettsia. Chest radiographs, electrocardiogram, initial echocardiography studies, and abdomen ultrasonography were normal. Two days after admission, a clinical diagnosis of KD was made, and the patient received IVIG (1 g/kg for 2 d) and aspirin (3000 mg/d for 5 d). With this treatment, the patient showed defervescence within 1 day, and diffuse desquamation started on day 10. Low-dose aspirin was continued for 6 weeks. Control echocardiography studies were normal.

Back to Top | Article Outline

RESULTS

In the 10 patients reported here, the mean age at KD was 27.3 years. The diagnostic characteristics and cardiac findings of the 10 patients are summarized in Table 2. Laboratory data are shown in Table 3. The search for infectious agents was negative in all patients.

TABLE 2

TABLE 2

TABLE 3

TABLE 3

Four of our patients (Patients 7-10) fulfilled the criteria for classical, or complete, KD. The mean delay for the diagnosis was 12 days in those cases. Four cases (Patients 2, 3, 5, 6) fulfilled the criteria for incomplete KD. Two of these patients (Patients 5, 6) have been reported elsewhere.17 The mean delay for the diagnosis was 10 days for these cases. Three of these 4 patients had laboratory criteria (thrombocytosis, anemia, hypoalbuminemia, sterile pyuria, elevation of transaminases) (Patients 2, 5, 6), while 2 patients had echocardiography findings consistent with the diagnosis (Patients 5, 6). The diagnosis of KD was made retrospectively in 2 patients (Patients 1, 4), in the presence of symptomatic coronary obstruction due to coronary aneurysms and coronary occlusion, related to a medical history suggestive of incomplete KD as an adult. One of these patients (Patient 4) has been reported elsewhere17 and had laboratory criteria consistent with the diagnosis.

Three patients were treated with low-dose aspirin (Patients 1, 5, 6), or nonsteroidal inflammatory drug (Patient 4), while 4 patients received high-dose aspirin (Patients 7, 8, 9, 10). Seven of our patients received IVIG after a mean delay of 12.5 days following the beginning of the disease; for 2 patients, treatment was begun because of abnormalities on the echocardiography, with a successful course; for the third patient, IVIG was administrated after desquamation of the extremities had started. However, IVIG appeared to shorten the course of the disease.

Back to Top | Article Outline

DISCUSSION

KD is an acute multisystemic vasculitis affecting predominantly medium-sized arteries. In developed countries, it is the most common cause of acquired heart disease in young children.83 Clinical, epidemiologic, and pathologic studies that were performed in the 1970s and 1980s quickly led to the hypothesis that an infectious disease agent was the cause of KD. Multiple agents have previously been suspected, including various bacteria, Rickettsia, Coronavirus, and even dust mite antigens.67 However, to date, extensive cultures and serologic studies have not been successful, and none of the proposed agents has been confirmed.65

By examining tissue samples from fatal cases of KD, researchers have recently made progress in understanding KD etiology and pathogenesis.65 These studies revealed that oligoclonal IgA plasma cells infiltrate inflamed tissues, including coronary arteries. Synthetic versions of these oligoclonal KD antibodies bind to an antigen in acute-KD-inflamed ciliated bronchial epithelium. Microscopy studies have demonstrated that the antigen is localized in cytoplasmic inclusion bodies in tissues inflamed by acute KD.66 Based on these results, Rowley et al65 proposed a model of KD pathogenesis in which the etiologic agent of KD enters through the respiratory tract and infects ciliated bronchial epithelium, where it forms intracytoplasmic inclusion bodies. The agent might enter the bloodstream via macrophages before being carried to its target tissues, particularly coronary arteries, other arterial tissue, and ductal tissues. Antigen-specific IgA plasma cells and CD8+ T lymphocytes infiltrate the targeted tissues to combat the pathogen and contain the infection, but the coronary arteries might be damaged by the products of activated macrophages and lymphocytes, such as metalloproteinases. On the other hand, genetic studies have identified single nucleotide polymorphisms in several genes that are related to an immune response, such as interleukin-4, chemokine receptor 5, and the inositol 1,4,5-triphosphophate 3_kinase C, that are associated with KD susceptibility and also with an increased risk of coronary artery lesions. These findings provide new insights that could unlock the mysteries of KD.55,65

Classical KD is unusual in adults, with 81 cases, including our 4 cases, reported in the literature14,17,18,20,25,27,37,69,72,82 (Table 4). In a 2005 review, Sève et al69 summarized the differences between children and adults: adults present more frequently with cervical adenopathy (93% of adults vs. 75% of children), hepatitis (65% vs. 10%, respectively) and arthralgia (61% vs. 24%-38%, respectively) compared with children, while adults are less frequently affected by meningitis (10% vs. 34%, respectively), thrombocytosis (56% vs. 100%, respectively) and coronary aneurysms (5% vs. 20%, respectively) compared with children.

TABLE 4

TABLE 4

Four of our patients fulfilled the criteria for classical KD. Conversely to previous reports, none of these patients had cervical adenopathy. It is noteworthy that only 1 of these patients had arthralgia, 3 had hepatic cytolysis, while only 1 had thrombocytosis. In 1 patient, echocardiography performed at the acute phase showed a small aneurysm of the right coronary artery. Overall these data suggest that adult KD would not be a benign disease.

Incomplete KD is very rare in adults who have been reported.8,17,22,47,59 The term "incomplete" KD is preferable to "atypical" KD and is reserved for patients with fever, at least 2 of the clinical criteria for KD, and laboratory data showing systemic inflammation. We describe here 6 cases. In 2 of these patients, diagnosis of KD was made in the presence of myocardial infarction due to coronary aneurysms, after an undiagnosed medical history evocative of incomplete KD as an adult. Including the current case reports, 10 cases of incomplete adult KD have been reported (Table 5). Of note, Pérez-Rodon et al59 described a 28-year-old man who presented with exertional angina due to severe diffuse disease of the entire coronary vasculature after a 6-month earlier undiagnosed history of incomplete KD, while Bonté et al8 reported a case of incomplete adult-onset KD that presented as a prolonged fever of unknown origin with subsequent development of coronary aneurysms and peripheral gangrene of the lower limbs.

TABLE 5

TABLE 5

As with classical KD, diagnosis of incomplete KD requires that there be no other reasonable explanation for the illness. In adults, the main differential diagnoses are drug hypersensitivity reaction and toxic shock syndrome.69 Other diseases include streptococcal infection (scarlet fever), leptospirosis, Mycoplasma and Rickettsiae diseases, adenovirus and other viral illnesses (measles, rubella, Epstein-Barr virus infection, fifth disease), toxoplasmosis, rheumatologic disorders (Reiter syndrome, juvenile rheumatoid arthritis), and mercury poisoning (acrodynia). All our patients had an extensive workup which was not contributory for these diagnoses.

The potentially severe outcome of coronary involvement in children has emphasized the importance of early identification of all patients, especially those with incomplete KD. The lack of a specific and sensitive diagnostic test remains a major obstacle to correctly identifying all patients with KD.36 In 2004, a multidisciplinary committee of experts proposed an algorithm to aid clinicians in deciding which children with fever for ≥5 days and <4 classical criteria should undergo echocardiography, receive IVIG treatment, or both for KD.53 For these patients, if the clinical characteristics are compatible with KD, laboratory tests including CRP and ESR should be obtained. In patients with compatible features and elevated CRP levels or ESR, supplemental laboratory tests including measures of serum albumin and transaminase levels, complete blood cell count, and urinalysis should be performed. If 3 or more laboratory criteria are present, patients should have echocardiography and be treated. These criteria include albumin ≤3.0 g/dL, anemia, elevation of alanine aminotransferase, platelets after 7 days ≥450,000/mm3, white blood cell count ≥15,000/mm3, and urine ≥10 white blood cells/high power field. If fewer than 3 laboratory abnormalities are present but abnormalities are noted on the echocardiogram, the child should be treated. For cases in which clinical assessment indicates that treatment is unnecessary, patients should be followed closely, with serial laboratory testing, if needed. It is noteworthy that 4 of our patients had 3 or more supplemental criteria consistent with KD.

To detect coronary abnormalities in children's KD, 2D imaging is the preferred imaging modality. The sensitivity and specificity are considered as high for detecting abnormalities of the proximal left main coronary artery and right coronary artery. High-frequency transducers are used to search for signs of KD; that is, aneurysms, ectatic arteries, lack of normal tapering, or perivascular echogenicity of "brightness."53 Other information includes depressed left ventricular contractility and pericardial effusion. As previously described,17 echocardiography presents limits in adults because it is more difficult to visualize coronary arteries as the body size increases. The fact that some exams were performed by echocardiographers experienced in children's KD may explain our results. New noninvasive methods of coronary imaging (multidetector row CT and magnetic resonance angiography) may offer new perspectives for the diagnosis of coronary aneurysms in adults KD.26,71 Overall, despite these limitations, our study supports the use of the algorithm proposed in children to diagnose incomplete KD in adults.

The consensus recommendation for the treatment of KD in children is high-dose aspirin therapy (80-100 mg/kg per d) for 14 days, followed by a lower dose (3-5 mg/kg) combined with IVIG infusions. Aspirin is continued for 6-8 weeks, or until evidence of inflammation has subsided, and after checking the absence of coronary abnormality by echocardiography. Yet it has not been proven that aspirin reduces the incidence of coronary artery aneurysms or their associated complications. The effectiveness of IVIG has been well demonstrated in multicenter, randomized trials.21,52 In a 1984 study, Furusho et al21 randomized 40 children treated by aspirin and IVIG (400 mg/kg per d for 4 d) and 45 children treated by aspirin alone. Coronary arteriography confirmed lesions noted in echocardiographic studies in 24% of the aspirin monotherapy group and in 2.5% of the IVIG group, suggesting a significant decrease in the incidence of coronary artery aneurysms with IVIG therapy. A more recent trial reported in 1991 suggested that a single infusion of IVIG (2 g/kg) might accelerate resolution of inflammation compared to the 4-day regimen.52 Patients receiving 400 mg/kg per day for 4 days were almost twice as likely to have coronary artery aneurysms than those receiving a single 2 g/kg dose (14 of 252 patients vs. 6 of 254 patients, respectively; p =.067). A meta-analysis confirmed that high-dose IVIG, 2 g/kg, administrated before day 10 is the optimal therapeutic regimen.54

Most of the patients in the current study received IVIG more than 10 days after the beginning of the disease, when it was theoretically too late to expect significant benefit from immunoglobulins. However, IVIG appeared to shorten the course of the disease in most of our cases. These data are similar to what Sève et al69 described in their literature review, where the disease was often diagnosed after the acute phase, and IVIG showed a benefit.

In conclusion, we describe herein a relatively large series of adult KD. At the time of clinical presentation, complete KD was diagnosed in 4 cases, while 4 patients fulfilled the criteria for incomplete KD. In 2 patients, diagnosis of KD was made in the presence of myocardial infarction due to coronary aneurysms, after an undiagnosed medical history evocative of incomplete KD as an adult. Four of the patients with incomplete KD had either extra laboratory findings or echocardiogram findings consistent with KD. Overall, our data suggest that the algorithm proposed to diagnose incomplete KD in children could be useful in adults. As with children's KD, transthoracic echocardiography performed by an expert must screen for lesions of the right coronary artery, completed by complementary imaging modalities such as CT scan if the results seem insufficient. Given the findings of serious cardiovascular damage in some patients in the current study and in the literature, we suggest that adult patients with features suggestive of incomplete KD may benefit from prompt IVIG. Larger international studies, to collect data on clinical, laboratory, and cardiovascular features and treatment of adults with KD, are necessary to confirm our hypothesis.

Back to Top | Article Outline

REFERENCES

1. Bachmeyer C, Turc Y, Curan D, Duval-Arnould M. Anterior uveitis as the initial sign of adult Kawasaki syndrome (mucocutaneous lymph node syndrome). Am J Ophthalmol. 2000;129:101-102.
2. Ball SC. Kawasaki-like disease in an HIV-infected patient. AIDS Read. 2005;15:414-416.
3. Barabe P, Mbaye E, Peghini M, Brullard B, Gueye PM. [First Senegalese case of Kawasaki's disease]. Presse Med. 1987;16:1977-1978.
4. Barbaro G, Di Lorenzo G, Barbarini G. Kawasaki-like syndrome in an HIV-infected adult. Rheumatology (Oxford). 2003;42:1427-1429.
5. Barbour AG, Krueger GG, Feorino PM, Smith CB. Kawasaki-like disease in a young adult. Association with primary Epstein-Barr virus infection. JAMA. 1979;241:397-398.
6. Bayrou O, Phlippoteau C, Artigou C, Haddad T, Leynadier F. Adult Kawasaki syndrome associated with HIV infection and anticardiolipin antibodies. J Am Acad Dermatol. 1993;29:663-664.
7. Blanchard JN, Powell HC, Freeman WR, Letendre S, Blanchard D, Shimizu C, Burns JC. Recurrent Kawasaki disease-like syndrome in a patient with acquired immunodeficiency syndrome. Clin Infect Dis. 2003;36:105-111.
8. Bonte I, Mahr A, Laroche L, Guillevin L, Robineau M. Peripheral gangrene in adult-onset Kawasaki disease. Scand J Rheumatol. 2005;34:71-73.
9. Brinchault G, Noyon V, Roussel M, Gacouin A, Michelet C. [Kawasaki's disease in adults: a case report]. Presse Med. 2003;32:165.
10. Burns JC, Glode MP. Kawasaki syndrome. Lancet. 2004;364:533-544.
11. Burstein F, Metson R, Colman MF, Canalis RF. Kawasaki disease in adults. An otolaryngologist's perspective. Arch Otolaryngol. 1984;110:543-545.
12. Butler DF, Hough DR, Friedman SJ, Davis HE. Adult Kawasaki syndrome. Arch Dermatol. 1987;123:1356-1361.
13. Caputo AE, Roberts WN, Yee YS, Posner MP. Hepatic artery aneurysm in corticosteroid-treated, adult Kawasaki's disease. Ann Vasc Surg. 1991;5:533-537.
14. Chang C, Wood JC, Strickling WA, Walsh DS. Kawasaki disease in a US army soldier highlights surveillance. Int J Dermatol. 2006;45:83-84.
15. Chavanet P, Portier H, Escalier F, Courtois B. Intravenous gammaglobulin for adult Kawasaki disease. Lancet. 1985;2:1184-1185.
16. Couilliet D, Grange F, Guillaume JC. [A case for diagnosis: Kawasaki disease in the adult]. Ann Dermatol Venereol. 1994;121:905-906.
17. Dauphin C, Motreff P, Souteyrand G, Laurichesse H, Gourdon F, Lesens O, Lamaison D, Beytout J, Cassagnes J, Lusson JR. [Kawasaki disease is also a disease of adults: report of six cases]. Arch Mal Coeur Vaiss. 2007;100:439-447.
18. El Karoui K, Servais A, Fadel F, Jablonski M, Fakhouri F, Lesavre P, Hummel A. Acute renal failure and febrile rash-infectious or not? Adult Kawasaki disease (KD). Nephrol Dial Transplant. 2007;22:949-951.
19. Everett ED. Mucocutaneous lymph node syndrome (Kawasaki disease) in adults. JAMA. 1979;242:542-543.
20. Fason JT, Fry YW, Smith D. Kawasaki disease in a postpartum patient. J Natl Med Assoc. 2004;96:1499-1502.
21. Furusho K, Kamiya T, Nakano H, Kiyosawa N, Shinomiya K, Hayashidera T, Tamura T, Hirose O, Manabe Y, Yokoyama T, et al. High-dose intravenous gammaglobulin for Kawasaki disease. Lancet. 1984;2:1055-1058.
22. Galempoix JM, Kaeppler E, Lanoux P, Belaida A, Aboutara M, Penalba C. [Kawasaki adult disease: case report]. Rev Med Interne. 2006;27:646-649.
23. Glanzer JM, Galbraith WB, Jacobs JP. Kawasaki disease in a 28-year-old man. JAMA. 1980;244:1604-1606.
24. Gomberg R, Hamm P, Martin A. Mucocutaneous lymph node syndrome (Kawasaki disease) in an adult. West J Med. 1981;135:406-408.
25. Granel B, Serratrice J, Ene N, Igual JP, Habib G, Disdier P, Weiller PJ. Painful jaundice revealing Kawasaki disease in a young man. J Gastroenterol Hepatol. 2004;19:713-715.
26. Greil GF, Stuber M, Botnar RM, Kissinger KV, Geva T, Newburger JW, Manning WJ, Powell AJ. Coronary magnetic resonance angiography in adolescents and young adults with Kawasaki disease. Circulation. 2002;105:908-911.
27. Hattori T, Matsukawa Y, Takei M, Yamaguchi K, Yamazaki T, Sawada U, Sawada S, Horie T, Ayusawa M, Noto N, Harada K. Adult Kawasaki disease unrelated to Epstein-Barr virus and group A Streptococcus. Intern Med. 2005;44:1182-1184.
28. Heenen M, Lorent A, Song M. [3 cases of Kawasaki syndrome]. Dermatologica. 1982;165:472-476.
29. Herrero JB, Ornia N, Serrano O, Pinilla E, Fernandez Capitan C, Camacho J, Arnalich F. [Kawasaki's syndrome in the adult and bilateral sacroiliitis]. An Med Interna. 1995;12:549-5.
30. Hicks JT, Korenyi-Both A, Utsinger PD, Baran EM, McLaughlin GE. Neuromuscular and immunochemical abnormalities in an adult man with Kawasaki disease. Ann Intern Med. 1982;96:607-610.
31. Huong DL, Gatfosse M, Papo T, Barjonet G, Lacombe P, Godeau P. Symptomatic splenic infarction complicating adult Kawasaki disease. Br J Rheumatol. 1995;34:579-580.
32. Jackson JL, Kunkel MR, Libow L, Gates RH. Adult Kawasaki disease. Report of two cases treated with intravenous gamma globulin. Arch Intern Med. 1994;154:1398-1405.
33. Johnson RM, Little JR, Storch GA. Kawasaki-like syndromes associated with human immunodeficiency virus infection. Clin Infect Dis. 2001;32:1628-1634.
34. Kawasaki T. [Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children]. Arerugi. 1967;16:178-222.
35. Keim DE, Geltner JW. Mucocutaneous lymph node syndrome in an adult, with lymph node biopsy correlation. South Med J. 1985;78:872-874.
36. Kim DS. Kawasaki disease. Yonsei Med J. 2006;47:759-772.
37. Kogulan P, Mbualungu E, Villanueva E, Coe MD, Lucey DR. Kawasaki syndrome in an adult: case report and review of the literature in adolescents and adults. J Clin Rheumatol. 2001;7:194-198.
38. Leclerc G, Begin P, Laramee P, Genest P. Transient heart failure in an adult with Kawasaki disease. Clin Cardiol. 1986;9:128-130.
39. Lee TJ, Vaughan D. Mucocutaneous lymph node syndrome in a young adult. Arch Intern Med. 1979;139:104-105.
40. Liebmann LI, Mikelic V, Joh MM, Wilson FM. Hydrops of the gallbladder in an adult with Kawasaki disease. JAMA. 1982;247:827-829.
41. Lucht F, Fresard A, Bonnefille E, Lamaud C, Rousset H. [Aseptic purulent meningitis in Kawasaki syndrome in an adult]. Presse Med. 1988;17:1763-1764.
42. Machet L, Vaillant L, Goutal H, Lanternier G, Khallouf R, Chagnon JL, Lorette G. Kawasaki disease in a young adult with a perineal rash. Br J Dermatol. 1990;123:413-414.
43. Mahr A, Triaire A, Charniot JC, Guillevin L, Robineau M. Coronary aneurysms in Kawasaki's disease of the adult. Ann Med Interne (Paris). 1999;150:448.
44. Marcella JJ, Ursell PC, Goldberger M, Lovejoy W, Fenoglio JJ Jr, Weiss MB. Kawasaki syndrome in an adult: endomyocardial histology and ventricular function during acute and recovery phases of illness. J Am Coll Cardiol. 1983;2:374-378.
45. Martinez-Escribano JA, Redondo C, Galera C, Sanchez-Pedreno P, Abel JL, Frias JF. Recurrent Kawasaki syndrome in an adult with HIV-1 infection. Dermatology. 1998;197:96-97.
46. McIlroy MA, Fisher EJ, Saravolatz LD, Hardwicke MB, Wilson FM. Aseptic meningitis complicating adult Kawasaki disease: case report and review of the literature. Am J Med. 1989;87:106-110.
47. McMahon MA, Wynne B, Murphy GM, Kearns G. Recurrence of Kawasaki disease in an adult patient with cholecystitis. Ir Med J. 2007;100:400-401.
48. Michels TC. Mucocutaneous lymph node syndrome in adults. Differentiation from toxic shock syndrome. Am J Med. 1986;80:724-728.
49. Milgrom H, Palmer EL, Slovin SF, Morens DM, Freedman SD, Vaughan JH. Kawasaki disease in healthy young adult. Ann Intern Med. 1980;92:467-470.
50. Montagnac R, Czertok G, Lesavre P, Schillinger F. [Kawasaki syndrome in a young adult. Dermatologic and immunologic study]. Sem Hop. 1982;58:2538-2542.
51. Muniain-Ezcurra M, Bueno-Mariscal C, Rodriguez-Bano J, Dominguez-Castellano A, Balonga-Tomas B, Rios-Villegas MJ, Borobio-Enciso MV, Perez-Cano R. Kawasaki disease and parvovirus B19 infection in an adult HIV-1-infected patient. Clin Microbiol Infect. 1998;4:609-610.
52. Newburger JW, Takahashi M, Beiser AS, Burns JC, Bastian J, Chung KJ, Colan SD, Duffy CE, Fulton DR, Glode MP, et al. A single intravenous infusion of gamma globulin as compared with four infusions in the treatment of acute Kawasaki syndrome. N Engl J Med. 1991;324:1633-1639.
53. Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC, Shulman ST, Bolger AF, Ferrieri P, Baltimore RS, Wilson WR, Baddour LM, Levison ME, Pallasch TJ, Falace DA, Taubert KA. Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Circulation. 2004;110:2747-2771.
54. Oates-Whitehead RM, Baumer JH, Haines L, Love S, Maconochie IK, Gupta A, Roman K, Dua JS, Flynn I. Intravenous immunoglobulin for the treatment of Kawasaki disease in children. Cochrane Database Syst Rev. 2003;(4):CD004000.
55. Onouchi Y, Gunji T, Burns JC, Shimizu C, Newburger JW, Yashiro M, Nakamura Y, Yanagawa H, Wakui K, Fukushima Y, Kishi F, Hamamoto K, Terai M, Sato Y, Ouchi K, Saji T, Nariai A, Kaburagi Y, Yoshikawa T, Suzuki K, Tanaka T, Nagai T, Cho H, Fujino A, Sekine A, Nakamichi R, Tsunoda T, Kawasaki T, Nakamura Y, Hata A. ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms. Nat Genet. 2008;40:35-42.
56. Paira SO, Roverano S. Kawasaki syndrome in a young adult. J Rheumatol. 1992;19:488-490.
57. Patrick AL, Barton EN, Vincente JB. Kawasaki disease in an adult Trinidadian male. Trop Geogr Med. 1988;40:254-256.
58. Pavese P, Brion JP, Meusnier T, Stahl JP. [Kawasaki syndrome in adults: treatment with polyvalent intravenous immunoglobulins]. Ann Med Interne (Paris). 1997;148:287-288.
    59. Perez-Rodon J, Aboal J, Morales M, Masia R. [Kawasaki disease with coronary artery lesions in adults]. Rev Esp Cardiol. 2006;59:1203-1204.
    60. Phillips WG, Marsden JR. Adult Kawasaki syndrome. Br J Dermatol. 1993;129:330-333.
    61. Porneuf M, Sotto A, Barbuat C, Ribou G, Jourdan J. Kawasaki syndrome in an adult AIDS patient. Int J Dermatol. 1996;35:292-294.
    62. Porwancher RB. Adult Kawasaki disease in HIV-infected patients. 8th International Conference on AIDS. Vol. 8. Amsterdam: International AIDS Society; 1992: pp. B227.
      63. Rauch AM, Hurwitz ES. Centers for Disease Control (CDC) case definition for Kawasaki syndrome. Pediatr Infect Dis. 1985;4:702-703.
      64. Reynaud-Mendel B, Lemann M, David F, Menasche S, Bachelez H, Dubertret L. Adult Kawasaki disease complicated by pancreatitis. Am J Gastroenterol. 1997;92:1239-1240.
      65. Rowley AH, Baker SC, Orenstein JM, Shulman ST. Searching for the cause of Kawasaki disease-cytoplasmic inclusion bodies provide new insight. Nat Rev Microbiol. 2008;6:394-401.
      66. 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;3:e1582.
      67. Satou GM, Giamelli J, Gewitz MH. Kawasaki disease: diagnosis, management, and long-term implications. Cardiol Rev. 2007;15:163-169.
      68. Saxe N, Horak A, Goldblatt J. Mucocutaneous lymph node syndrome in a young adult. A case report. S Afr Med J. 1980;58:1011-1013.
      69. Seve P, Stankovic K, Smail A, Durand DV, Marchand G, Broussolle C. Adult Kawasaki disease: report of two cases and literature review. Semin Arthritis Rheum. 2005;34:785-792.
      70. Shelleh HH, Khan SA, Khan LA, Al-Hateeti H, Iqbal S, Saleh AF. Adult Kawasaki disease. Saudi Med J. 2000;21:1078-1080.
      71. Sohn S, Kim HS, Lee SW. Multidetector row computed tomography for follow-up of patients with coronary artery aneurysms due to Kawasaki disease. Pediatr Cardiol. 2004;25:35-39.
      72. Stankovic K, Miailhes P, Bessis D, Ferry T, Broussolle C, Seve P. Kawasaki-like syndromes in HIV-infected adults. J Infect. 2007;55:488-494.
      73. Struillou L, Magadur-Joly C, Barrier JH. Adult Kawasaki syndrome. Report of five cases and literature review. Eur J Intern Med. 1995;6:5-12.
        74. Takagi S, Oshimi K, Sumiya M, Gonda N, Kano S, Takaku F, Miyata K, Yaginuma T. Adult onset mucocutaneous lymph node syndrome with coronary aneurysm. Am Heart J. 1981;101:852-853.
        75. Takamoto T, Niwa A, Taniguchi K, Takeuchi J. Acute febrile mucocutaneous lymph node syndrome (Kawasaki disease) in an adult. Clin Cardiol. 1982;5:555-559.
        76. Thompson AC, Lamey PJ. Kawasaki syndrome in an adult. J Laryngol Otol. 1990;104:37-38.
        77. Tomiyama J, Hasegawa Y, Kumagai Y, Adachi Y, Karasawa K. Acute febrile mucocutaneous lymph node syndrome (Kawasaki disease) in adults: case report and review of the literature. Jpn J Med. 1991;30:285-289.
        78. Velez AP, Menezes L, Crespo A. Kawasaki-like syndrome possibly associated with immune reconstitution inflammatory syndrome in an HIV-positive patient. AIDS Read. 2006;16:464-466.
        79. Viraben R, Dupre A. Kawasaki disease associated with HIV infection. Lancet. 1987;1:1430-1431.
        80. Weir WR, Bouchet VA, Mitford E, Taylor RF, Smith H. Kawasaki disease in European adult associated with serological response to Coxiella burneti. Lancet. 1985;2:504.
        81. Wolf CV II, Wolf JR, Parker JS. Kawasaki's syndrome in a man with the human immunodeficiency virus. Am J Ophthalmol. 1995;120:117-118.
        82. Wolff AE, Hansen KE, Zakowski L. Acute Kawasaki disease: not just for kids. J Gen Intern Med. 2007;22:681-684.
        83. Wood LE, Tulloh RM. Kawasaki disease in children. Heart. 2009;95:787-792. [Epub 2008 Aug 12.]
        84. Yoganathan K, Goodman F, Pozniak A. Kawasaki-like syndrome in an HIV positive adult. J Infect. 1995;30:165-166.
        85. Zilberman MV, Goya G, Witt SA, Glascock B, Kimball TR. Dobutamine stress echocardiography in the evaluation of young patients with Kawasaki disease. Pediatr Cardiol. 2003;24:338-343.
        © 2010 Lippincott Williams & Wilkins, Inc.