Kawasaki Disease: Unusual Presentation with Retropharyngeal Involvement

Background Kawasaki disease is an acute febrile generalized vasculitic syndrome of childhood of unknown ethology. The most severe complication may involve the hearth and include acute myocarditis with hearth failure, arrythmia, and coronary artery aneurism. The typical clinical symptoms are fever, conjunctivitis, rash, cervical lymphadenopathy, and mucocutaneous changes, and the diagnosis is made by the clinical criteria. Early use of aspirin and immunoglobuline improves symptoms and prevent heart complications. Case Presentation. A 4-year-old male presented to our attention for multiple unilateral laterocervical lymphadenopathies, odynophagia, and neck stiffness, initially treated with IV antibiotic therapy with partial resolution of symptoms. After four months he made a new ER access for cervicalgia, tonsils asymmetry, trismus, stiff neck, lameness, and phalanx hyperaemia and increase in the size of cervical lymph nodes. Radiology showed increase of lymphnodes dimension and retropharyngeal space asymmetry. The same day heart murmur appeared, so the patient underwent cardiological evaluation that documented dilation of the coronary arteries. This sign made it possible to place the diagnostic suspicion of Kawasaki disease and to start IV immunoglobulins and acetylsalicylic acid administration with prompt response. Conclusions Kawasaki disease presents with a range of symptoms which, taken individually, are very common in childhood. One of these symptoms is represented by the swollen of neck lymph nodes. It is only clinical reasoning that leads to the correct diagnosis, and therefore, to the correct setting of the therapy, reducing the risk of complications.


Introduction
Kawasaki disease (KD) is a childhood's acute febrile generalized vasculitis syndrome, frst reported in 1967 in Japan by its namesake, Dr. Tomisaku Kawasaki [1]. While its cause is currently unknown, multiple theories have been proposed, ranging from genetic and environmental factors to an infectious etiology.
KD, as a multisystem disorder, involves predominantly medium and small-sized vessels, causing coronary artery aneurysms (CAA) thrombosis, stenosis, and even sudden death, making it one of the leading causes of acquired heart disease in developed countries. Occurring in young children, mostly below 5 years of age, with 1.5-times higher risk in boys than girls [2], KD is diagnosed by clinical criteria, reported in Table 1 [3].
It must be kept in mind that KD goes into diferential diagnosis with many other diseases such as: toxic shock syndrome, Henoch-Schönlein purpura, exanthematous diseases such as measles, b-hemolytic streptococcus infection, toxic shock syndrome, Stevens-Johnson syndrome, and systemic juvenile idiopathic arthritis [4].
Retropharyngeal oedema is a rare presentation of KD that can be misdiagnosed as retropharyngeal abscess, leading to a wrong therapeutic attitude. Lameness occurs in about 33% of all cases, especially in the lower limbs and involving small joints [5]. Moreover, in some cases KD can be diagnosed as "incomplete" while referring to patients without enough diagnostic criteria in association with the typical fever or as "atypical" if concerning patients presenting early symptoms other than typical manifestations of KD (e.g., renal involvement, slowly resolving pneumonia, acute pancreatitis, and facial paralysis), in association to the disease's characteristic fever [6].
Te most frequent blood count alterations associated with KD are represented by thrombocytosis and increased infammatory indexes such as white blood cells and CRP.
Timely institution of treatment with intravenous immunoglobulin (IVIG) and high dose aspirin as early as possible after diagnosis causes rapid improvement of the disease and reduces the risk of CAA, while 10-20% of patients not treated in time develop these complications [7].

Case Report
A 4-year-old male presented to our attention referring left submandibular swelling accompanied by odynophagia and left fexion of the head, in absence of rhinitis or nasal obstruction. Te patient was taken to the emergency room where blood chemistry tests were performed showing an increased level of WBC, CRP, and fbrinogen and normal levels of ALT, AST, and LDH. Te SARS-COV-2 nasal swab test resulted negative. Te neck ultrasound revealed multiple increased size lymph nodes in left II, III, and IV areas, with well recognizable hilum and no colliquation areas. Te clinical examination highlighted a laterocervical mesoadenia and inspection of the oral cavity showed tonsils asymmetry (left > right), lateral oropharynx wall swelling and nasopharynx purulent discharge.
CT scan was performed in the clinical suspicion of parapharyngeal abscess, showing nasopharyngeal airspace asymmetry and multiple oval lymphadenopathies along the laterocervical stations bilaterally. Having evaluated both the clinical and radiological evidence, the multidisciplinary team decided to avoid surgery and proceed with IV antibiotic therapy.
In view of an echographic increase in the lymphadenopathies size after medical therapy, a neck MRI was performed under sedation, confrming the persistence of obliteration on the left deep parapharyngeal and carotid spaces with left retropharyngeal lymphadenopathies ( Figure 1).
Te hospital's diagnostic protocol for pediatric lymphadenopathies was therefore applied, performing multiple tests to identify possible pathogens (blood culture, nasal secretion culture, intradermal Mantoux reaction, and serologies for EBV), which gave negative results.
Serology for Bartonella henselae resulted weakly positive (1 : 256) and the patient therefore perform an abdominal US that was within limits. Pharyngeal swab resulted positive for Group A beta-hemolytic Streptococcus pyogenes (GABHS).
During the patient's hospital stay, gradual reduction of the left cervical lymphadenopathies was documented, with symptoms abate and improvement of infammatory indexes, except for persistence of a mild platelets level increase and the patient was then discharged at home with clarithromycin therapy.
After 4 months from the hospital discharge, the patient experienced a laterocervical swelling relapse, with left cervicalgia, stif neck, trismus, and fever. At the same time, pain and swelling of the hands appeared, with polymorphous rush at the level of phalanx, foot-plant and lumbar region, and unilateral lameness in the absence of osteoarticular swellings. Tese symptoms then regressed spontaneously after some days. Te SARS-COV-2 nasal swab test resulted negative, blood chemistry tests showed an increase in WBC, CRP, platelets, and fbrinogen, while blood cultures and throat swab cultures gave negative results. Concomitantly, a new antibiotic IV therapy was started and continued for 15 days. PCR and serology for Bartonella, Brucella, Borrelia, Toxoplasma, CMV, and Francisella were performed, all resulting negative. Te neck US and MRI showed numerical and dimensional increase of the previously known laterocervical lymph nodes, with evidence of colliquation areas and retropharyngeal space asymmetry. No septic or meningeal signs were found at the clinical examination and the MRI did not highlight meningeal pathology, so it was not deemed necessary to assay cerebrospinal fuid.
Fibrolaryngoscopy revealed adenoid hypertrophy and a minimal asymmetry of the pharyngeal region without macroscopic swelling, with maintained airways patency.
Contextually, the patient experienced strawberry tongue (Figure 2), conjunctival hyperemia and heart murmur. For this reason, cardiological evaluation and echocardiogram were performed, documenting coronary arteries dilation, wider at the level of the common trunk and the proximal right coronary artery (Z score 4.7 and 3.7, respectively).
Suspecting a potential KD diagnosis, the patient started the administration of intravenous immunoglobulins and acetylsalicylic acid at an anti-infammatory dose. Fever for more than fve days (four days if treatment with IVIG eradicates fever) plus at least four of the following clinical signs not explained by another disease process (1) Bilateral conjunctival injection (2) Changes in the oropharyngeal mucous membranes (including >1 of the following symptoms: injected and/or fssured lips, strawberry tongue, injected pharynx) (3) Changes in the peripheral extremities, including erythema of the hands and feet (acute phase) or periungual desquamation (convalescent phase) (4) Polymorphous rash, primarily truncal; nonvesicular (5) Cervical lymphadenopathy: anterior cervical lymph node at least >1.5 cm in diameter Tis therapy led to a prompt clinical and radiological response as follows: gradual improvement of the symptoms and the thermal curve, reduction in the caliber of the coronary arteries (Z score of 3.1 for the common trunk, 2.3 for the right coronary artery), reduction in the lymphadenopathies dimension at MRI (Figure 3), improvement of platelets level, and reduction of the CRP.
Te patient continued IV antibiotic therapy for a total of 14 days and was then discharged in good clinical conditions on the 20 th day after the admission. Tree months later the cardiologic control showed no cardiological sequelae and cardioaspirin therapy was stopped.
In this case report, the pediatric-ENT protocol for management of cervical lymphadenopathies was applied, establishing the steps to follow to reach the diagnosis and start the adequate therapy.
In view of the pandemic period, the child was tested for SARS-COV-2 and resulted negative. Tis fnding turns out to be relevant in view of the fnal diagnosis of KD for which the causes are not yet known.
Te patient then underwent further investigations due to a nonresponse to antibiotic therapy: complete blood count, CRP, LDH, ALT/AST, EBV serology, neck ultrasound, CT scan, and MRI. Mantoux intradermal test resulted negative, with no change in injection site.
Due to the nonspecifc results of these tests, second level diagnostic investigations were also performed, including serological investigations for Toxoplasma Gondii, Francisella Tularensis, Borrelia Burgdorferi, Brucella, and CMV. Te patient tested positive at low titer for Bartonella H. Infection and had a positive pharyngeal swab for GABHS that warranted the clinical presentation on initial admission.

Case Reports in Pediatrics
In addition to conjunctivitis, strawberry tongue, cutaneous rash, fever, and mesoadenia the patient manifested a cardiological symptomatology that allowed the diagnosis of Kawasaki disease. Te blood count showed thrombocytosis, which frequently appears 15 days after the beginning of symptoms. Moreover, the patient manifested lameness, a symptom that, according to literature, may be present in 33% of KD cases [4].
In addition to classic KD symptoms, the patient also manifested stif neck and retropharyngeal oedema, a quite rare symptom that could be misdiagnosed as retropharyngeal abscess leading to wrong therapeutic attitude [4].
Literature describes other cases of KD with retropharyngeal involvement, such as radiological fndings at CT scan of increased density areas in the retropharyngeal space.
In view of the latency of 4 months between the two hospital accesses and considering that no other cases of KD with two episodes (with this temporal distance) are described in the literature, we do not exclude that the frst episode may not be attributable to KD but instead to upper respiratory tract infections. However, the second episode presents the criteria for the diagnosis of KD and for these reasons we report this clinical case as relevant. Tese articles concluded that, in children presenting with fever and cervical lymphadenopathies that also display retropharyngeal low-density areas extending into deeper neck spaces, as well as changes in adjacent soft tissue, the hypothesis of KD should be considered [8].

Conclusion
Te patient presented with a vague range of symptoms, such as persistent febrile cervical lymphadenopathies, stif neck, lameness, and a radiological fnding of retropharyngeal oedema.
To date, there are no specifc tests to diagnose KD, hence, the importance to exclude other illnesses and make a differential diagnosis through frst and second level tests, for which a clear protocol is necessary, in addition to a multidisciplinary evaluation of the clinical case. Te interpretation of radiological analyses is also essential to defne the correct therapeutic procedure and avoid unnecessary surgical procedures.