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BackgroundEarly-onset sarcoidosis (EOS) and Blau syndrome (BS) are systemic inflammatory granulomatous diseases without visible pulmonary involvement, and are distinguishable from their sporadic and familial forms. The diseases are characterized by a triad of skin rashes, symmetrical polyarthritis, and recurrent uveitis. The most common morbidity is ocular involvement, which is usually refractory to conventional treatment. A gain-of-function mutation in the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) gene has been demonstrated in this disease; however, little is known about the relationship between the activation ofNOD2and the pathophysiology of EOS/BS. Here we describe EOS/BS with a novel mutation in theNOD2gene, as well as detection ofPropionibacterium acnes(P. acnes) in the granulomatous inflammation.Case presentationAn 8-year-old Japanese girl presented with refractory bilateral granulomatous panuveitis. Although no joint involvement was evident, she exhibited skin lesions on her legs; a skin biopsy revealed granulomatous dermatitis, andP. acneswas detected within the sarcoid granulomas by immunohistochemistry withP. acnes-specific monoclonal (PAB) antibody. Genetic analyses revealed that the patient had aNOD2heterozygous D512V mutation that was novel and not present in either of her parents. The mutantNOD2showed a similar activation pattern to EOS/BS, thus confirming her diagnosis. After starting oral prednisolone treatment, she experienced an anterior vitreous opacity relapse despite gradual prednisolone tapering; oral methotrexate was subsequently administered, and the patient responded positively.ConclusionsWe presented a case of EOS/BS with a novel D512V mutation in theNOD2gene. In refractory granulomatous panuveitis cases without any joint involvement, EOS/BS should be considered as a differential diagnosis; genetic analyses would lead to a definite diagnosis. Moreover, this is the first report ofP. acnesdemonstrated in granulomas of EOS/BS. Since intracellularP. acnesactivates nuclear factor-kappa B in aNOD2-dependent manner, we hypothesized that the mechanism of granuloma formation in EOS/BS may be the result ofNOD2activity in the presence of the ligand muramyl dipeptide, which is a component ofP. acnes.These results indicate that recognition ofP. acnesthrough mutantNOD2is the etiology in this patient with EOS/BS.

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE cell-mediated food allergy characterized by repetitive vomiting and other gastrointestinal symptoms. Although little is known about FPIES pathophysiology, some cytokines have been reported to be involved. Since one of the main symptoms is vomiting, which is common to other diseases, it is difficult to distinguish acute FPIES from other conditions such as infectious enterocolitis. Thus, specific biomarkers are required for differential diagnosis. We aimed to identify potential biomarkers distinguishing acute FPIES from infectious enterocolitis and IgE-mediated anaphylaxis, which also cause vomiting. Methods: Seven patients with acute FPIES, nine with IgE-mediated anaphylaxis, and six with infectious enterocolitis were enrolled. The serum concentrations of interleukins (IL)-2, -4, -6, -8, -10, interferon-γ, and tumor necrosis factor-α were measured and compared among the three groups of patients. The serum concentrations of IL-2 and IL-10 were also compared between the symptomatic and asymptomatic stages. Alterations in serum cytokine levels were evaluated in acute FPIES during an oral food challenge test. Results: Serum IL-2 and IL-10 levels were significantly higher in acute FPIES patients than in patients with infectious enterocolitis and IgE-mediated anaphylaxis, whereas no significant differences were detectable in the serum levels of the other cytokines. The IL-2 and IL-10 elevation was only observed in the symptomatic stage of acute FPIES. Conclusion: The elevation in serum levels of IL-2 and IL-10 was specifically observed in symptomatic acute FPIES cases, suggesting that the measurement of IL-2 and IL-10 could be employed for differential diagnosis.

Herein we describe the case of a 6-week-old boy who developed complete Kawasaki disease (KD). The cytokine profile and activation of monocytes and subsequent T cells matched the typical feature of refractory KD. The patient received a total of three courses of i.v. immunoglobulin (IVIG), but did not achieve clinical relief. Adjunctive therapy with oral cyclosporine A (CsA) led to prompt defervescence. This was continued for 7 days without serious adverse events. Coronary artery dilatations regressed within 3 months of follow up. KD infants