The KD's aetiology is still unknown, and has been hypothesized that it develops in the genetically predisposed patients due to a possibly infectious trigger.
The diagnosis of KD relies on clinical signs and symptoms since no specific diagnostic tests are available. In the classic form the patients are children, and they have fever for more than 5 days and at least 4 out of 5 diagnosis criteria [1,2,3,4]:
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oral lesions such as erythema of oral and pharyngeal mucosa, cracking or fissured lips, strawberry tongue;
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bilateral conjunctivitis without exudate;
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polymorphous rash;
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oedema or erythema of the extremity with a progressing to desquamation of feet and hands;
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cervical lymphadenopathy usually unilateral (≥ 1.5 cm)
The patient we studied presented 3 of these criteria however, some patients show only a few clinical features of the typical clinical picture of KD, defining as incomplete form of KD often underdiagnosed [5] especially in adults [4].
The low diagnostic accuracy for adults onset of KD could be attributed to the several confounding factors [1,2,3,4,5, 8,9,10] such as drug hypersensitivity reactions, toxic shock syndrome, erythema multiforme and Stevens-Johnson syndrome, Scarlet fever, Measles, Rubella, infections to Adenovirus, Parvovirus, Herpesvirus, Epstein-Barr virus, Toxoplasmosis, Leptospirosis, Rocky Mountain spotted fever, Systemic juvenile-onset idiopathic arthritis, rheumatic fever, Reiter syndrome, and mercury poisoning.
Cervical adenopathy, hepatitis and arthralgia are found more common in adults (93%, 65% and 61%, respectively) than in children (15%, 10% and 24–38%, respectively). Children can suffer more frequently of meningitis, thrombocytosis and coronary artery aneurysms than adults (34% vs. 10%, 100% vs. 55%, 18–25% vs. 5%, respectively) [1,2,3,4,5,6, 10].
Less common symptoms of KD include arthritis, jaundice, hepatitis, myocarditis or heart failure, pericarditis, diarrhoea, anterior uveitis, headache and aseptic meningitis [1,2,3,4,5,6].
Common laboratory changes include raised acute phase reactants, hepatic cytolysis, delayed thrombocytosis, hyponatremia and acute kidney injury, eosinophilia and aseptic leukocyturia [6, 10,11,12].
In the present case, we could not detect drug hypersensitivity reactions, toxic shock syndrome, or infectious diseases, and diagnosis of KD was suggested by three well-accepted criteria for diagnosis. However, unusual clinical features were noted:
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(1)
prevalence of KD is much higher in Japan than in Europe, especially in children;
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(2)
the disease occurred in a young adult;
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(3)
abdominal complaints were particularly severe and represented the cause of hospitalization;
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(4)
jaundice was the principal symptom;
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(5)
any cardiovascular involvement was not detected.
Demography, atypical presentation, rapid development of multiorgan failure were the main reasons for delaying diagnosis. Moreover, jaundice could had masked any other cutaneous erythematous manifestation such as polymorphous rash.
In adults with KD gastrointestinal involvement has been reported in 56% of patients, abdominal pain (20–26% of patients), emesis (14%), diarrhea (12–20%), hepatomegaly (14%), jaundice (23%), and splenomegaly (12%) have been described [6, 10, 18, 19].
Hepatobiliary involvement is uncommon in Kawasaki disease, but it is usually described as obstructive jaundice [20]. Abnormalities of liver panel have been documented in 30–45% of cases [10, 18, 19, 21].
This presentation may act as a confounding factor leading to a delay in diagnosis and subsequent treatment [21].
Liver involvement could range from increasing in liver enzymes to a severe cholestatic hepatitis and/or gallbladder hydrops [21, 22].
Obstructive jaundice with hepatic dysfunction due to gallbladder hydrops has been reported in around 13% of case, however being asymptomatic the condition could be more frequent than previously reported [18,19,20,21]. In the majority of cases, hydrops resolves spontaneously without requiring surgical intervention [18,19,20,21]. On the contrary, when laparotomy exploration is performed, it reveals inflamed and edematous gallbladder without stones, and hypertrophic mesenteric lymph nodes. In 1979, it was reported that vascular lesions in KD were histologically similar to systemic vasculitis [23].
As well as in our case, an acute episode of cholestasis, with normal gallbladder and bile ducts preceding general manifestations of KD, has been reported in a 9-year old girl, [24]. Moreover, a 16 years old boy with KD presented with fever, jaundice, and abdominal pain [25].
The mechanism of painful jaundice that occurred in our patient could be related to a distention of the gallbladder, but it spontaneously resolved at the time of ultrasound examination. A vasculitic process in the gallbladder could be supposed to be the cause of an inflammation of the serosa and of obstruction [20]. Abdominal CT in our patient showed enlarged lymph nodes.
In our case, hepatic biopsy found non-specific inflammatory alterations in a particular fragmented liver tissue with accentuated lobular architecture, and lymphocytic inflammatory infiltration, macrophage and mainly granulocyte, several inflammatory infiltrates with a predominant neutrophilic granulocyte component were observed with foci of hepatocytolysis, acidophilic bodies and occasional biliary thrombi. These findings are similar to those described in KD patients with hepatic presentation or in autopsies [18, 20, 26, 27].
Ideal treatment of KD for a child should be administration of both intravenous immunoglobulins and acetylsalicylic acid.
Intravenous immunoglobulins reduce cardiac complications such as myocardial infarction and sudden death [3, 13]; however, the exact mechanisms is not clear, probably immunoglobulins influence T cell differentiation.
Acetylsalicylic acid appears to act on the endothelium, which is known to be dysfunctional in KD. Both Joint Working Group (JCS) and American Heart Association (AHA) [4, 14] recommend antiplatelet agents, primarily acetylsalicylic acid, during the acute phase of disease until aneurysmal pseudo-normalization. The 2017 AHA guidelines note that dual antiplatelet therapy (DAPT) may be considered in some cases, though there are no studies evaluating the efficacy of DAPT in this context.
Nevertheless, in KD acetylsalicylic acid was not reported to reduce development of coronary abnormalities [15].
Therapy in the acute stage of KD includes acetylsalicylic acid in combination with high-dose intravenous immunoglobulins. This treatment could reduce the prevalence of coronary abnormalities, the most serious complication of this disease, but it also favors a rapid reduction of fever and normalization of acute phase reactants.
Corticosteroid treatment appears to be beneficial in patients with severe KD, showing resistance to intravenous immunoglobulins. Combination of corticosteroids and intravenous immunoglobulins is indicated in patients at high risk of unresponsiveness [3, 16, 17].
In the present case intravenous immunoglobulins were not used, because of uncommon presentation, diagnostic delay, lack of experience in similar cases and, above all, because of absence of myocardial and vascular involvement.
Corticosteroid and acetyl salicylic acid were given due to the persistence of cholestasis, high acute phase reactants plasma levels and histological findings.
Our case suggests that atypical KD could be added to the etiological list of painful febrile jaundice in young patients. Physicians should pay attention to the diagnosis of atypical KD in the middle-aged persons and take action as soon as possible to avoid deadly complications.
While adult-onset Kawasaki disease is rare, clinicians should be familiar with the diagnostic criteria to consider them in the differential diagnosis of patients presenting undifferentiated febrile illness. Early treatment should be prescribed to prevent sequelae.
