{'fraction_non_alphanumeric': 0.020394054614586935, 'fraction_numerical': 0.0076045627376425855, 'mean_word_length': 6.00726392251816, 'pattern_counts': {'":': 0, '<': 1, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Possible suppressive effects of tranilast on NLRP3 inflammasome activation in necrobiosis lipoidica

Dear Editor, Necrobiosis lipoidica is a rare and chronic granulomatous skin disease. A recent study has revealed that an activated nucleotidebinding oligomerization domainlike receptor pyrin domaincontaining3 (NLRP3) inflammasome pathway regulates the development of granulomas in sarcoidosis.1 Herein, we describe a case of necrobiosis lipoidica successfully treated with tranilast and present a pathological analysis about the possible association of an activated NLRP3 pathway. A 69yearold Japanese woman presented to our department with a 6year history of skin rash on her legs. She had been treated with topical steroids, but the skin rash persisted. Physical examination revealed welldemarcated yellowbrown plaques with atrophy of the bilateral lower legs (Figure 1a). Laboratory tests revealed a slightly increased hemoglobin A1c (6.3%, reference <6.2%, National Glycohemoglobin Standardization Program). Histopathological evaluation of the leg skin biopsy showed an altered collagen structure and infiltrating lymphocytes with linear tiers of palisading granulomas in the dermis (Figure 1c,d). Thus, she was diagnosed with necrobiosis lipoidica. She was treated with oral tranilast and continued her medical nutrition therapy for diabetes mellitus. Her skin condition improved on the fourth month of treatment (Figure 1b). Several studies have proposed the possible association of multiple systemic diseases including sarcoidosis, auto immune thyroiditis, and diabetes mellitus. In particular, microangiopathy secondary to deposition of glycoprotein in blood vessel walls in diabetes mellitus has been proposed to be associated with the pathogenesis of necrobiosis lipoidica2; however, the exact details remain unclear. Treatment of necrobiosis lipoidica depends on severity of the disease and may require a combination of topical steroids, phototherapy, and immunosuppressive agents for ulcerated or symptomatic nonulcerated cases.2 Tranilast is an antiallergy medicine used in Asian countries to treat bronchial asthma, keloid, and scars. Several case reports have demonstrated the therapeutic efficacy of tranilast in treating necrobiosis lipoidica.3 Huang et al.4 recently reported that tranilast directly inhibits the NLRP3 inflammasome, which is the most studied inflammasome involved in the pathogenesis of various diseases in vitro and improves disease severity in a mouse model of gouty arthritis and cryopyrinassociated autoinflammatory syndromes in vivo. NLRP3 inflammasome assembly requires two signals, a priming signal activated by lipopolysaccharide or tumor necrosis factorα (TNFα), and a second signal activated by various factors such as adenosine triphosphate, crystalline substances, and reactive nitrogen and oxygen species (ROS). A recent study demonstrated that