KD patients almost always have marked eosinophilia and elevated serum IgE levels. Some studies have reported that blood eosinophil counts in KD patients are correlated with lesion size, that is, larger lesions are associated with higher eosinophil count . Common symptoms of KD include the head and neck region, and CT and MRI show a wide range of lesions and multiple enlarged lymph nodes . Orbital involvement, including eyelid swelling, has also been reported [8–12], but is uncommon. Furthermore, most KD cases with orbital involvement were adults from Asian countries, and, to our knowledge, the case reported here is the youngest case of KD with orbital involvement. Additionally, our patient developed a lesion in his left arm as a result of his condition. The patient opted for surgical excision of the left arm mass because, other than itchiness, the lesion was asymptomatic. The involvement of the arm of a KD patient is rare but not unique, as Lam et al. have previously reported a case of KD affecting the anterolateral aspect of the upper arm . In that earlier case, the skin lesion specimen did not show characteristic findings of KD; however, this could be attributed to the fact that only surface tissue was obtained by biopsy. However, similarities in clinical features of our case and that reported by Lam et al., i.e. an itchy left arm mass and similar MRI findings, suggest involvement of KD.
Our patient exhibited elevated eosinophil and IgE levels as the swelling of the eyelids worsened. Unfortunately, definitive diagnosis was delayed, although a related disease was initially suspected, which delayed initiation of appropriate therapeutic intervention. Clinically, the differential diagnosis of KD may include IgG4-related diseases, Hodgkin’s lymphoma, Castleman’s disease, Langerhans cell histiocytosis, angiolymphoid hyperplasia with eosinophilia (ALHE), drug reactions, and allergies. These histological features may overlap with those of idiopathic orbital inflammation [8, 12] or ALHE [1, 2]. Notably, some cases of KD occurring in the left lacrimal gland with increased serum levels of IgG4, mimicking IgG4-related disease, have been reported [14, 15]. In the current case, we made a differential diagnosis of IgG4-related disease, despite normal IgG4 levels and lack of IgG4 expression in the lacrimal gland specimen. In the literature, the most common misdiagnosis of KD is ALHE, although patients with ALHE have normal IgE levels and no renal complications [4, 10, 16, 17]. In our case, there were no signs of renal disorders. Histologically, Warthin-Finkeldey cells were not observed in the first biopsy, but were detected in the lacrimal gland tissue following the second operation. A Warthin-Finkeldey cell is a giant multinucleate cell found in hyperplastic lymph nodes early in the course of measles and also in HIV-infected individuals, neoplastic and non-neoplastic lymph node disorders, and in KD [18–20]. Collectively, the clinical features and other histopathological findings ultimately indicated a definitive diagnosis of KD.
No standard treatment for KD has been established. Suggested therapeutic options include oral or intralesional corticosteroids, surgical removal, and radiotherapy. In most cases, oral corticosteroids are effective as an initial treatment, but relapses have been frequently reported after surgery or withdrawal of oral steroids [21, 22]. Other agents, including CsA, have been reported to induce and/or maintain remission, and there are several reports of treatment with cyclosporine [21–23]. Cyclosporine acts to reduce IL-2 synthesis, resulting in inhibition of T-lymphocyte proliferation and attenuation of the immune response. Sato et al. reported an 11-year-old boy with cervical lymphadenopathy who was successfully treated with steroids and CsA . Similarly, Shin et al. reported an 8-year-old boy with right upper eyelid swelling who was diagnosed with KD and was effectively treated with steroids, CsA, and azathioprine .
Nephrotic syndrome (NS) has been reported as a complication of KD [21, 25, 26]. Among 11 Japanese KD patients with NS, 2 were treated with CsA . Katagiri et al. explained that mRNA levels of cytokines and eosinophils were suppressed when the blood concentration of CsA was > 75 ng/mL in an adult patient with KD . Marked eosinophilia and elevated serum IgE were associated with regulation of Th2 cell cytokines, such as IL-4, IL-5, IL-13, and interferon-g mRNA [27, 28], and CsA efficacy may be improved by the suppression of these activities in KD . Although sIL-2R levels were normal in the current case, IL-4, peripheral eosinophil counts, and IgE levels were elevated. As in previous reports, administration of CsA improved clinical features, including laboratory findings, and was maintained. NS complications during the clinical course of KD with a lacrimal gland mass have been reported previously . Given the high rate of recurrence and reported association with lymphoma , careful long-term follow-up in is recommended for our case.
In summary, we have described a case of KD with rare or possibly unique clinical manifestations in a patient that would not normally be considered to be at risk of KD. Indeed, the incongruence with the clinical presentations initially determined in this case led to inexact diagnoses that delayed initiation of effective therapeutic intervention for several years. The details of this case provide valuable information about the range of clinical presentations that can be associated with KD, which can aid timely diagnosis and increase the efficacy of therapies.