Chilblains as a Diagnostic Sign of Aicardi-Goutières Syndrome

Abstract

Aicardi-Goutières syndrome (AGS) is a genetically heterogeneous disorder showing variability in age of onset and clinical features. Chilblain lesions have been described in AGS patients and recent papers have discussed the clinical, molecular and cutaneous histopathological overlap with chilblain lupus. Here we report on 2 unrelated children with AGS and chilblain lesions, whose clinical histories and examination findings well illustrate the wide phenotypic variability that can be seen in this pleiotropic disorder. Although both patients show remarkable similarity in the histopathology of their associated skin lesions, with thrombi formation, fat necrosis and hyalinization of the subcutaneous tissue, we note that the histopathology reported in other AGS cases with chilblains does not necessarily demonstrate this same uniformity. Our findings highlight the significant role of the characteristic chilblain skin lesions in the diagnosis of AGS, and variability in the associated histopathology which may relate to the stage and severity of the disease.

Insights from Mendelian Interferonopathies: Comparison of CANDLE, SAVI with AGS, Monogenic Lupus

“…Photosensitive rashes, positive LE band on skin biopsy, glomerulonephritis, and positive anti-dsDNA and anti-Sm antibodies are seen in patients with monoSLE, but rarely in patients with CANDLE ( n = 3 with anti-dsDNA, n = 1 with anti-SmB antibody), SAVI ( n = 2 with anti-dsDNA, none with anti-Sm antibody reported), and AGS ( n = 1 with anti-dsDNA and none with anti-Sm antibody reported). Interestingly, IgM deposition at the basement membrane or dermal-epidermal junction consistent with a LE band has been described with chilblain lesions in AGS patients [37, 46] as noted above. Other disease manifestations are as follows:…”

“…Out of 7 chilblain cases assessed in AGS, 4 were noted to have IgM deposition in the basement membrane (positive in 1 with mutated TREX1 and 1 with mutated RNASEH2B , and 2 not genetically analyzed, one of whom was noted to have anti-C1q antibodies which raises the possibility of cofactors [36]; negative in 2 with mutated SAMHD1 (at least 1 AR) and 1 with AR TREX1 mutations) [37]. Chilblain-like vasculopathy is also seen in SAVI, but not CANDLE.…”

Mutations in ADAR1 cause Aicardi-Goutières syndrome associated with a type I interferon signature

“…The skin lesions typical of DSH have not been described in AGS (they are distinct from AGS-related chilblains) 30 , and none of the ADAR1 mutation–positive AGS cases included in our study had obvious features of DSH. Of note, DSH has only very rarely been reported outside of Japan and China.…”

Aicardi–Goutieres syndrome in children with idiopathic epilepsy

“…Формы с началом в неонатальном периоде имеют более тяжелое клиническое течение и связаны с высокой смертностью -до 34% боль-ных на первом году жизни [8]. Формы с дебютом по-сле первых месяцев жизни ребенка ассоциируются с повышенной продолжительностью жизни больных с лучшим интеллектуальным потенциалом и более низкой смертностью (8%) [8,14,15]. Таким обра-зом, клинически выделяют две формы синдрома -с ранним (около 20% случаев) и поздним началом, что определяет тяжесть неврологических нарушений и соответственно обусловливает прогноз.…”