Blau Syndrome: A Rare Multisystemic Genetic Disease with Distinctive Clinical Manifestations
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Abstract
Blau syndrome is an extremely rare genetic disease characterized by a multisystemic clinical presentation affecting the skin, joints, eyes and nervous system. It is an autosomal dominantly inherited disease caused by mutations in the NOD2/CARD15 gene. This disease predominantly affects children, although adult-onset cases have been reported. The epidemiology of Blau syndrome is limited due to its low prevalence, with fewer than 200 cases reported worldwide. Diagnosis is based on clinical evaluation and molecular genetic testing to identify mutations in the NOD2/CARD15 gene. Treatment focuses on symptom control and reduction of inflammation, using non-steroidal anti-inflammatory drugs, corticosteroids and, in more severe cases, immunosuppressive agents. Multidisciplinary collaboration between different medical specialties is essential for the comprehensive management of patients. Although advances have been made in the understanding of Blau syndrome, more research is still needed to elucidate its pathophysiology, epidemiology and therapeutic options.
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References
I. Borzutzky A, Fried A, Chou J, Bonilla FA, Kim S, Dedeoglu F. NOD2-associated diseases: Bridging innate immunity and autoinflammation. Clin Immunol. 2010;134:251---61.
II. Masel G, Halbert A. Blau syndrome presenting with ichthyosis. Australas J Dermatol. 2005;46:29---32.
III. Punzi L, Furlan A, Podswiadek M, Gava A, Valente M, de Marchi M, et al. Clinical and genetic aspects of Blau syndrome: A 25-year follow-up of one family and a literature review. Autoimmun Rev. 2009;8:228---32.
IV. Stoevesandt J, Morbach H, Martin TM, Zierhut M, Girschick H, Hamm H. Sporadic Blau syndrome with onset of widespread granulomatous dermatitis in the newborn period. Pediatr Dermatol. 2010;27:69---73.
V. Aróstegui JI, Arnal C, Merino R, Modesto C, Antonia Carballo M, Moreno P, et al. NOD2 gene--associated pediatric granulomatous arthritis: clinical diversity, novel and recurrent mutations, and evidence of clinical improvement with interleukin-1 blockade in a Spanish cohort. Arthritis Rheum. 2007;56:3805---13.
VI. Peschke K, Friebe F, Zimmermann N, Wahlicht T, Schumann T, Achleitner M, et al. Deregulated type I IFN response in TREX1--associated familial chilblain lupus. J Invest Dermatol. 2014;134:1456---9.
VII. Shankarappa RK, Ananthakrishna R, Math RS, Yalagudri SD, Karur S, Dwarakaprasad R, et al. Accelerated coronary atherosclerosis and H syndrome. BMJ Case Rep. 2011;2011.
VIII. Molho-Pessach V, Agha Z, Aamar S, Glaser B, Doviner V, Hiller N, et al. The H syndrome: A genodermatosis characterized by indurated, hyperpigmented, and hypertrichotic skin with systemic manifestations. J Am Acad Dermatol. 2008;59:79---85.
IX. McDermott A, Jacks J, Kessler M, Emanuel PD, Gao L. Proteasome--associated autoinflammatory syndromes: Advances in pathogeneses, clinical presentations, diagnosis, and management. Int J Dermatol. 2015;54:121---9.
X. Brehm A, Liu Y, Sheikh A, Marrero B, Omoyinmi E, Zhou Q, et al. Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production. J Clin Invest. 2015;125:4196---211.
XI. Torrelo A, Patel S, Colmenero I, Gurbindo D, Lendínez F, Hernández A, et al. Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome. J Am Acad Dermatol. 2010;62:489---95.
XII. Fuertes L, Santonja C, Kutzner H, Requena L. Immunohistochemistry in dermatopathology: A review of the most commonly used antibodies (part II). Actas Dermosifiliogr. 2013;104:181---203.
XIII. Requena L, Kutzner H, Palmedo G, Pascual M, Fernández-Herrera J, Fraga J, et al. Histiocytoid Sweet syndrome: A dermal infiltration of immature neutrophilic granulocytes. Arch Dermatol. 2005;14:834---42.
XIV. Liu Y, Ramot Y, Torrelo A, Paller AS, Si N, Babay S, et al.Mutations in proteasome subunit type 8 cause chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature with evidence of genetic and phenotypic heterogeneity. Arthritis Rheum. 2012;64:895---907.
XV. Mégarbané A, Sanders A, Chouery E, Delague V, Medlej-Hashim M, Torbey P-H. An unknown autoinflammatory syndrome associated with short stature and dysmorphic features in a young boy. J Rheumatol. 2002;29:1084---7.
XVI. Simonini G, Xu Z, Caputo R, de Libero C, Pagnini I, Pascual V, et al. Clinical and transcriptional response to the long--acting interleukin-1 blocker canakinumab in Blau syndrome--related uveitis. Arthritis Rheum. 2013;65:513---8.
XVII. Lim YW, Sanz LA, Xu X, Hartono SR, Chédin F. Genome-wide DNA hypomethylation and RNA: DNA hybrid accumulation in Aicardi---Goutières syndrome. Elife. 2015;4:e08007.