REVIEW PAPER
CANDLE syndrome – a narrative review
1
Faculty of Medicine, Wrocław Medical University, Wrocław, Poland
2
V General Surgery Department, J. Gromkowski Regional Specialist Hospital, Wrocław, Poland
3
Department of Internal Medicine and Geriatrics, A. Falkiewicz Specialist Hospital, Wrocław, Poland
4
Clinical Department of Diabetology and Internal Medicine, J. Mikulicz-Radecki University Hospital, Wrocław, Poland
These authors had equal contribution to this work
Submission date: 2024-04-09
Final revision date: 2024-06-20
Acceptance date: 2024-06-20
Publication date: 2024-09-30
Corresponding author
Aleksandra Snopkowska
Faculty of Medicine, Wrocław Medical University, Wrocław, Poland
Faculty of Medicine, Wrocław Medical University, Wrocław, Poland
Pediatr Pol 2024;99(4):335-339
KEYWORDS
TOPICS
ABSTRACT
CANDLE syndrome (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature) is a rare autoinflammatory disorder beginning in early childhood. This narrative review provides an extensive overview of CANDLE syndrome, including its epidemiology, aetiology, clinical manifestations, diagnostic challenges, and current treatment options. The syndrome is associated with gene mutations encoding proteasome or immunoproteasome subunits, particularly PSMB8, contributing to disrupted proteostasis and aberrant type 1 interferon production. The diagnostic criteria remain undefined, necessitating a multidisciplinary approach for accurate diagnosis and management. Despite therapeutic complexities, recent advancements in genetic testing and targeted therapies, notably Janus kinase inhibitors, offer promising avenues for improved patient outcomes. Further research and clinical trials are imperative to enhance understanding and optimise treatment strategies for this rare and debilitating condition.
REFERENCES (40)
1.
Roberts T, Stephen L, Scott C, et al. CANDLE syndrome: orofacial manifestations and dental implications. Head Face Med 2015; 11: 38. DOI: 10.1186/s13005-015-0095-4.
2.
Lachmann HJ. Periodic fever syndromes. Best Pract Res Clin Rheumatol 2017; 31: 596-609.
3.
Boyadzhiev M, Marinov L, Boyadzhiev V, et al. Disease course and treatment effects of a jak inhibitor in a patient with CANDLE syndrome. Pediatr Rheumatol Online J 2019; 17: 19. DOI: 10.1186/s12969-019-0322-9.
4.
Patel PN, Hunt R, Pettigrew ZJ, et al. Successful treatment of chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome with tofacitinib. Pediatr Dermatol 2021; 38: 528-529.
5.
Tüfekçi Ö, Bengoa Ş, Karapinar TH, et al. CANDLE syndrome. J Pediatr Hematol Oncol 2015; 37: 296-299.
6.
Gönül M, Cevirgen Cemil B, Keseroglu HO, et al. New described dermatological disorders. Biomed Res Int 2014; 2014: 616973. DOI: 10.1155/2014/616973.
7.
Torrelo A, Patel S, Colmenero I, et al. Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome. J Am Acad Dermatol 2010; 62: 489-495.
8.
Montealegre Sanchez GA, Jesus AA de, Goldbach-Mansky R. Monogenic autoinflammatory diseases. Rheum Dis Clin North Am 2013; 39: 701-734.
9.
Papendorf JJ, Ebstein F, Alehashemi S, et al. Identification of eight novel proteasome variants in five unrelated cases of proteasome- associated autoinflammatory syndromes (PRAAS). Front Immunol 2023; 14: 1190104. DOI: 10.3389/fimmu.2023.1190104.
10.
Volpi S, Picco P, Caorsi R, et al. Type I interferonopathies in pediatric rheumatology. Pediatr Rheumatol Online J 2016; 14: 35. DOI: 10.1186/s12969-016-0094-4.
11.
Al‐Mayouf SM, AlSaleem A, AlMutairi N, et al. Monogenic interferonopathies: phenotypic and genotypic findings of CANDLE syndrome and its overlap with C1q deficient SLE. Int J Rheum Dis 2018; 21: 208-213.
12.
Kim H, Sanchez GAM, Goldbach-Mansky R. Insights from mendelian interferonopathies: comparison of CANDLE, SAVI with AGS, monogenic lupus. J Mol Med 2016; 94: 1111-1127.
13.
Koska MC, Karadağ AS, Durdu M. Annular neutrophilic dermatoses. Clin Dermatol 2023; 41: 340-354.
14.
Torrelo A, Colmenero I, Requena L. Histologic and immunohistochemical features of the skin lesions in CANDLE syndrome. Am J Dermatopathol 2015; 37: 517-522.
15.
Eleftheriou D, Brogan PA. Genetic interferonopathies: an overview. Best Pract Res Clin Rheumatol 2017; 31: 441-459.
16.
Brehm A, Liu Y, Sheikh A, et al. Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production. J Clin Invest 2015; 125: 4196-4211.
17.
Ghirardo S, Mazzolai M, Di Marco A, et al. Biological treatments and target therapies for pediatric respiratory medicine: not only asthma. Front Pediatr 2022; 10: 837667. DOI: 10.3389/fped.2022. 837667.
18.
Torrelo A. CANDLE syndrome as a paradigm of proteasome-related autoinflammation. Front Immunol 2017; 8: 927. DOI: 10.3389/fimmu.2017.00927.
19.
Gedik KC, Lamot L, Romano M, et al. The 2021 European Alliance of Associations for Rheumatology/American College of Rheumatology points to consider for diagnosis and management of autoinflammatory type i interferonopathies: CANDLE/PRAAS, SAVI and AGS. Ann Rheum Dis 2022; 81: 601-613.
20.
De Jesus AA, Brehm A, VanTries R, et al. Novel proteasome assembly chaperone mutations in PSMG2/PAC2 cause the autoinflammatory interferonopathy CANDLE/PRAAS4. J Allergy Clin Immunol 2019; 143: 1939-1943.e8. DOI: 10.1016/j.jaci.2018.12.1012.
21.
Symmank D, Borst C, Drach M, et al. Dermatologic manifestations of noninflammasome-mediated autoinflammatory diseases. JID Innov 2022; 3: 100176. DOI: 10.1016/j.xjidi.2022.100176.
22.
Kunimoto K, Kimura A, Uede K, et al. A New infant case of Nakajo- Nishimura syndrome with a genetic mutation in the immunoproteasome subunit: an overlapping entity with JMP and CANDLE syndrome related to PSMB8 mutations. Dermatology 2013; 227: 26-30.
23.
Goldbach-Mansky R. Immunology in clinic review series; focus on autoinflammatory diseases: update on monogenic autoinflammatory diseases: the role of interleukin (IL)-1 and an emerging role for cytokines beyond IL-1. Clin Exp Immunol 2012; 167: 391-404.
24.
Wang H, Das L, Tan Hung Tiong J, et al. CANDLE syndrome: an extended clinical spectrum. Rheumatology 2014; 53: 2119-2120.
25.
Gomes AV. Genetics of proteasome diseases. Scientifica (Cairo) 2013; 2013: 637629. DOI: 10.1155/2013/637629.
26.
Liu Y, Ramot Y, Torrelo A, et al. Mutations in proteasome subunit β 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.
27.
McDermott A, Jacks J, Kessler M, et al. Proteasome‐associated autoinflammatory syndromes: advances in pathogeneses, clinical presentations, diagnosis, and management. Int J Dermatol 2015; 54: 121-129.
28.
Cavalcante MPV, Brunelli JB, Miranda CC, et al. CANDLE syndrome: chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature – a rare case with a novel mutation. Eur J Pediatr 2016; 175: 735-740.
29.
Gómez-Arias PJ, Gómez-García F, Hernández-Parada J, et al. Efficacy and safety of Janus kinase inhibitors in type i interferon-mediated monogenic autoinflammatory disorders: a scoping review. Dermatol Ther (Heidelb) 2021; 11: 733-750.
30.
Yamazaki-Nakashimada M, Santos-Chávez E, de Jesus A. Systemic autoimmunity in a patient with CANDLE syndrome. J Investig Allergol Clin Immunol 2019; 29: 75-76.
31.
Yu Q, Mehta A, Zou J, et al. Human induced pluripotent stem cells generated from chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome patients with a homozygous mutation in the PSMB8 Gene (NIHTVBi016-A, NIHTVBi017-A, NIHTVBi018-A). Stem Cell Res 2022; 62: 102820. DOI: 10.1016/j.scr.2022.102820.
32.
Poli MC, Ebstein F Nicholas SK, et al. Heterozygous truncating variants in POMP escape nonsense-mediated decay and cause a unique immune dysregulatory syndrome. Am J Hum Genet 2018; 102: 1126-1142.
33.
Tripathi SV, Leslie KS. Autoinflammatory diseases in dermatology. Dermatol Clin 2013; 31: 387-404.
34.
Jabbari A, Dai Z, Xing L, et al. Reversal of alopecia areata following treatment with the JAK1/2 inhibitor baricitinib. EBioMedicine 2015; 2: 351-355.
35.
McKenna GJ, Ziada HM. Periodontal manifestations of chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome in an 11‐year‐old patient. Clin Adv Periodontics 2015; 5: 153-158.
36.
Ohmura K. Nakajo-Nishimura syndrome and related proteasome-associated autoinflammatory syndromes. J Inflamm Res 2019; 12: 259-265.
37.
Papa R, Picco P, Gattorno M. The expanding pathways of autoinflammation: a lesson from the first 100 genes related to autoinflammatory manifestations. Adv Protein Chem Struct Biol 2020; 120: 1-44.
38.
Maccora I, Marrani E, Mastrolia MV, et al. Ocular involvement in monogenic autoinflammatory disease. Autoimmun Rev 2021; 20: 102944. DOI: 10.1016/j.autrev.2021.102944.
39.
Kanazawa N, Kunimoto K, Ishii N, et al. Is CANDLE the best nomenclature? Br J Dermatol 2014; 171: 659-660.
40.
Kanazawa N, Ishii T, Takita Y, et al. Efficacy and safety of baricitinib in Japanese patients with autoinflammatory type i interferonopathies (NNS/CANDLE, SAVI, And AGS). Pediatr Rheumatol Online J 2023; 21: 38. DOI: 10.1186/s12969-023-00817-8.
Share
RELATED ARTICLE
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
