Inflammation is a biological defense mechanism, and the immune system plays a central role in recognizing and eliminating external and internal pathogens. However, oxidative stress due to chronic inflammation accumulates DNA mutations and increases the risk of cancer. The immune system can recognize and eliminate immunogenic cancer cells. Inflammation-related molecules, including cytokines and chemokines, not only promote the malignant transformation, but also accumulate immunosuppressive cells, such as M2-like tumor-associated macrophages and myeloid-derived suppressor cells, in the tumor microenvironment. Tumor cells escape immune attack by placing brakes on the immune cell responses. Immune checkpoint inhibitors activate the immune system by releasing the brake. Although immune checkpoint inhibitors have demonstrated significant therapeutic effects in intractable cancers, the therapeutic effects are limited and overcoming drug resistance is a problem. In order to overcome drug resistance, combined immunotherapy, comprising immune checkpoint inhibitors, angiogenesis inhibitors, and chemotherapeutic agents, is required. In this review, we have outlined the relationship between inflammation and cancer, the roles of cytokines, chemokines, immunosuppressive cells, and current progress in using immune checkpoint inhibitors as a therapeutic.

We report a case of Kawasaki disease (KD) complicated by coronary artery lesions (CALs) with various symptoms other than major items, such as arthralgia and nail lesions.

Case: A 23-month-old girl developed fever. Five out of 6 major items of KD were confirmed on the day of illness 3, and the patient was hospitalized with a diagnosis of KD. She did not respond to the first dose of high-dose immunoglobulin therapy (IVIg). Knee and hip joint pain appeared and orange-brown chromonychia, a characteristic nail finding of KD, was recognized on day 9. After additional IVIg and cyclosporine A (CsA), she developed recurrent fever on day 16, and moderate CALs were observed. The joint pain worsened with fever and were alleviated as the fever improved. Finally, she required 5 doses of IVIg, CsA for 39 days, moderate doses of aspirin for 48 days, and antihypertensive medication. The left anterior descending artery measured a maximum of 4.1 mm (Z score+6.6). She had desquamation of her fingers on day 14, and the joint pain almost disappeared on day 50. She was discharged on day 54. The CALs improved well after 3 months.

Discussion: Systemic juvenile idiopathic arthritis was also considered as a differential diagnosis by the joint pain, but she was finally diagnosed as KD because of BCG inoculation redness, nail findings, membranous desquamation of hand and foot, laboratory test values, and final resolve of fever. In this case, the responsiveness to IVIg and CsA was insufficient. There are several treatment options for IVIg-resistant KD, and it is necessary to establish treatment selection criteria.

Valproate sodium (VPA) -induced hypofibrinogenemia is an underrecognized condition in comparison to thrombocytopenia, which is easily identified by regular blood tests including complete blood count. Here, we report a case of epilepsy with myoclonic-atonic seizures (EMAS) which exhibited valproate-induced mild hypofibrinogenemia with petechiae. A 3-year-old boy with EMAS was referred to our hospital for seizure control. VPA was increased to 40 mg/kg/day with a blood concentration of 128.5 μg/mL (peak value), and epileptic seizures during wakefulness, including myoclonic-atonic seizures, were completely controlled. However, subtle petechiae were repeatedly noted and the blood test showed mild hypofibrinogenemia (112 mg/dL) with normal platelet count, even after decreasing VPA to 30 mg/kg/day (104.3 μg/mL). Therefore, VPA had to be lowered to 25 mg/kg/day (76.3 μg/mL), and hypofibrinogenemia as well as the subtle petechiae eventually resolved. For patients who are taking VPA and are exhibiting bleeding tendencies, it is imperative that a coagulation test be conducted even if VPA is not taken in high doses.