Clinical and Laboratory Parameters of Autoinflammatory Disorders in Single Tertiary Care Center
-
Roya Sherkat
,
Alireza Rafiei
,
Vida Homayouni
,
Elmira Kalantari
,
Roya Sepahvandi
,
Sahar Memarmontazarin
,
Ali Mosayebian
Abstract
Autoinflammatory diseases (AIDs) are disorders with an inborn error of innate immunity, characterized by recurrent episodes of fever and inflammatory attacks. The spectrum of AIDs is expanding, but there are no standardized clinical criteria for the diagnosis of the patients. This study aims at establishing the first autoinflammatory registry of an Iranian population focusing on the clinical and laboratory features that may help clinicians for a better understanding and diagnosis of these disorders.
Clinical and laboratory characteristics of patients who were clinically and or genetically diagnosed with AIDs were collected during 15 years. The updated version of classification criteria from the Eurofever Registry was used for the clinical diagnosis.
Twenty-eight patients (16 males and 12 females) with the mean±SD age of 28.03±14.49 years (from 2 to 68 years) were entered this study. About 29% were genetically diagnosed. Familial Mediterranean fever (FMF) was the most common diagnosis of the patients. Fever duration episodes were between 1-10 days. Some of the clinical manifestations from the most to the least common were as follows: arthralgia and arthritis (80%), myalgia (76%), coughs and shortness of breath (68%), fatigue (60%), abdominal pain (56%), increased erythrocyte sedimentation rate(ESR) (48%), and splenomegaly (24%).
Here, we presented the most common clinical manifestations of Iranian AIDs who have registered in our AID registry which would be a useful guide for managing the same patients and also designing the future studies.
1. Azizi G, Azarian SK, Nazeri S, Mosayebian A, Ghiasy S, Sadri G, et al. Monogenic Auto-inflammatory Syndromes: A Review of the Literature. Iran J AllergyAsthma Immunol. 2016;12(5):430-44.
2. de Jesus AA, Canna SW, Liu Y, Goldbach-Mansky R. Molecular mechanisms in genetically defined autoinflammatory diseases: disorders of amplified danger signaling. Annu Rev Immunol. 2015;33(8):823-74.
3. Picard C, Al-Herz W, Bousfiha A, Casanova J-L, Chatila T, Conley ME, et al. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. J Clin Immunol. 2015;35(8):696-726.
4. Shwin KW, Lee C-CR, Goldbach-Mansky R. Dermatologic manifestations of monogenic autoinflammatory diseases. Dermatol Clin. 2017;35(1):21-38.
5. Moreira A, Torres B, Peruzzo J, Mota A, Eyerich K, Ring J. Skin symptoms as diagnostic clue for autoinflammatory diseases. An Bras Dermatol. 2017;92(1):72-80.
6. Montazerin SM, Sherkat R, Mosayebian A, Shahrooei M, Homayouni V, Najafi S, et al. Clinical and Laboratory Manifestations of Autoinflammatory Diseases: The Results from the First Iranian Registry. J Clin Immunol. 2019;39(4):S135-S6.
7. Federici S, Sormani MP, Ozen S, Lachmann HJ, Amaryan G, Woo P, et al. Evidence-based provisional clinical classification criteria for autoinflammatory periodic fevers. Ann Rheum Dis. 2015;74(5):799-805.
8. Demirkaya E, Saglam C, Turker T, Koné-Paut I, Woo P, Doglio M, et al. Performance of different diagnostic criteria for familial Mediterranean fever in children with periodic fevers: results from a multicenter international registry. J Rheumatol. 2016;43(1):154-60.
9. Abolhassani H, Kiaee F, Tavakol M, Chavoshzadeh Z, Mahdaviani SA, Momen T, et al. Fourth update on the Iranian national registry of primary immunodeficiencies: integration of molecular diagnosis. J Clin Immunol. 2018;38(7):816-32.
10. Procopio V, Manti S, Bianco G, Conti G, Romeo A, Maimone F, et al. Genotype-phenotype correlation in FMF patients: a “non classic” recessive autosomal or “atypical” dominant autosomal inheritance?. Gene. 2018;641(23):279-86.
11. Tunca M, Akar S, Onen F, Ozdogan H, Kasapcopur O, Yalcinkaya F, et al. Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine. 2005;84(1):1-11.
12. Battal F, Silan F, Topaloğlu N, Aylanç H, Yıldırım Ş, Binnetoğlu FK, et al. The MEFV gene pathogenic variants and phenotype-genotype correlation in children with familial Mediterranean fever in the Çanakkale population. BJMG. 2016;19(2):23-8.
13. Kilic A, Varkal MA, Durmus MS, Yildiz I, Yıldırım ZNY, Turunc G, et al. Relationship between clinical findings and genetic mutations in patients with familial Mediterranean fever. Pediatr. Rheumatol. 2015;13(1):59.
14. Papa R, Doglio M, Lachmann HJ, Ozen S, Frenkel J, Simon A, et al. A web-based collection of genotype-phenotype associations in hereditary recurrent fevers from the Eurofever registry. Orphanet J Rare Dis. 2017;12(1):167.
15. Kishida D, Nakamura A, Yazaki M, Tsuchiya-Suzuki A, Matsuda M, Ikeda S-i. Genotype-phenotype correlation in Japanese patients with familial Mediterranean fever: differences in genotype and clinical features between Japanese and Mediterranean populations. Arthritis Res Ther. 2014;16(5):439-43.
16. Erten S, Altunoglu A, Keskin H, Ceylan G, Dalgaci A, Uyanık G, et al. Increased frequency of MEFV gene mutations in patients with primary dysmenorrhea. Mod Rheumatol. 2013;23(5):959-62.
17. Kasifoglu T, Cansu DÜ, Korkmaz C. Frequency of abdominal surgery in patients with familial Mediterranean fever. Intern Med. 2009;48(7):523-6.
18. Ait-Idir D, Djerdjouri B, Bouldjennet F, Taha RZ, El-Shanti H, Sari-Hamidou R, et al. The M694I/M694I genotype: a genetic risk factor of AA-amyloidosis in a group of Algerian patients with familial Mediterranean fever. Eur J Med Genet. 2017;60(3):149-53.
19. Dogan H, Bayrak OF, Emet M, Keles M, Gulluoglu S, Gul Z, et al. Familial Mediterranean fever gene mutations in north-eastern part of Anatolia with special respect to rare mutations. Gene. 2015;568(2):170-5.
20. Tchernitchko DO, Gérard-Blanluet M, Legendre M, Cazeneuve C, Grateau G, Amselem S. Intrafamilial segregation analysis of the p. E148Q MEFV allele in familial Mediterranean fever. Ann Rheum Dis. 2006;65(9):1154-7.
21. Ben‐Chetrit E, Lerer I, Malamud E, Domingo C, Abeliovich D. The E148Q mutation in the MEFV gene: Is it a disease‐causing mutation or a sequence variant?. Hum Mutat. 2000;15(4):385-6.
22. Migita K, Hisanaga S, Izumi Y, Kawahara C, Shigemitsu Y, Iwanaga N, et al. Protracted arthritis in a Japanese patient with familial Mediterranean fever. Mod Rheumatol. 2017;27(5):905-9.
23. Jarjour RA, Dodaki R. Arthritis patterns in familial Mediterranean fever patients and association with M694V mutation. Mol Biol Rep. 2011;38(3):2033-6.
24. Cekin N, Akyurek ME, Pinarbasi E, Ozen F. MEFV mutations and their relation to major clinical symptoms of Familial Mediterranean Fever. Gene. 2017;6269(24):9-13.
25. Kümpfel T, Gerdes L, Wacker T, Blaschek A, Havla J, Krumbholz M, et al. Familial Mediterranean fever-associated mutation pyrin E148Q as a potential risk factor for multiple sclerosis. Mult Scler. 2012;18(9):1229-38.
26. Rigante D, Federico G, Ferrara P, Maggiano N, Avallone L, Pugliese AL, et al. IgA nephropathy in an Italian child with familial Mediterranean fever. Pediatr Nephrol. 2005;20(11):1642-4.
27. Topaloglu R, Ozaltin F, Yilmaz E, Ozen S, Balci B, Besbas N, et al. E148Q is a disease-causing MEFV mutation: a phenotypic evaluation in patients with familial Mediterranean fever. Ann Rheum Dis. 2005;64(5):750-2.
28. Hung T, Pratt G, Sundararaman B, Townsend M, Chaivorapol C, Bhangale T, et al. The Ro60 autoantigen binds endogenous retroelements and regulates inflammatory gene expression. Science. 2015;350(6259):455-9.
29. Boccitto M, Wolin SL. Ro60 and Y RNAs: structure, functions, and roles in autoimmunity. Crit Rev Biochem Mol Biol. 2019;54(2):133-52.
30. Xue D, Shi H, Smith JD, Chen X, Noe DA, Cedervall T, et al. A lupus-like syndrome develops in mice lacking the Ro 60-kDa protein, a major lupus autoantigen. Proc Natl Acad Sci U S A. 2003;100(13):7503-8.
31. Coşku S, Kurtgöz S, Keskin E, Sönmez F, Bozkurt G. Frequency of mutations in Mediterranean fever gene, with gender and genotype–phenotype correlations in a Turkish population. J Genet. 2015;94(4):629-35.
32. Ben-Zvi I, Herskovizh C, Kukuy O, Kassel Y, Grossman C, Livneh A. Familial Mediterranean fever without MEFV mutations: a case–control study. Orphanet J Rare Dis. 2015;10(1):34-41.
33. Stella A, Cortellessa F, Scaccianoce G, Pivetta B, Settimo E, Portincasa P. Familial Mediterranean fever: breaking all the (genetic) rules. Rheumatology (Oxford). 2019;58(3):463-7.
34. Asgardoon MH, Azizi G, Yazdani R, Sohani M, Pashangzadeh S, Kalantari A, et al. Monogenic primary immunodeficiency disorder associated with common variable immunodeficiency and autoimmunity. Int Arch Allergy Immunol. 2020;181(9):706-14.
35. Erten S, Erzurum C, Altunoglu A. Three family members with familial Mediterranean fever carrying the M694V mutation showed different clinical presentations. Intern Med. 2012;51(13):1765-8.
36. Saulsbury FT, Wouters CH, Martin TM, Austin CR, Doyle TM, Goodwin KA, et al. Incomplete penetrance of the NOD2 E383K substitution among members of a pediatric granulomatous arthritis pedigree. Arthritis Rheum. 2009;60(6):1804-6.
37. Caso F, Galozzi P, Costa L, Sfriso P, Cantarini L, Punzi L. Autoinflammatory granulomatous diseases: from Blau syndrome and early-onset sarcoidosis to NOD2-mediated disease and Crohn's disease. RMD open. 2015;1(1):e000097.
38. Pugazhendhi S, Santhanam S, Venkataraman J, Creveaux I, Ramakrishna BS. NOD2 gene mutations associate weakly with ulcerative colitis but not with Crohn's disease in Indian patients with inflammatory bowel disease. Gene. 2013;512(2):309-13.
39. Shoham NG, Centola M, Mansfield E, Hull KM, Wood G, Wise CA, et al. Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway. PNAS. 2003;100(23):13501-6.
40. Maggio MC, Ceccherini I, Grossi A, Gattorno M, Corsello G. PAPA and FMF in two siblings: possible amplification of clinical presentation? A case report. Ital J Pediatr. 2019;45(1):111-9.
41. Schellevis MA, Stoffels M, Hoppenreijs EP, Bodar E, Simon A, van der Meer JW. Variable expression and treatment of PAPA syndrome. Ann Rheum Dis. 2011;70(6):1168-70.
42. Hong J-B, Su Y-N, Chiu H-C. Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome (PAPA syndrome): report of a sporadic case without an identifiable mutation in the CD2BP1 gene. J Am Acad Dermatol. 2009;61(3):533-5.
43. Demidowich A, Freeman A, Kuhns D, Aksentijevich I, Gallin J, Turner M. Genotype, phenotype, and clinical course in five patients with pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome. Arthritis Rheum. 2011;64(8):2022-7.
44. Lindwall E, Singla S, Davis WE, Quinet RJ, editors. Novel PSTPIP1 gene mutation in a patient with pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome. Semin Arthritis Rheum; 2015: Elsevier.
2. de Jesus AA, Canna SW, Liu Y, Goldbach-Mansky R. Molecular mechanisms in genetically defined autoinflammatory diseases: disorders of amplified danger signaling. Annu Rev Immunol. 2015;33(8):823-74.
3. Picard C, Al-Herz W, Bousfiha A, Casanova J-L, Chatila T, Conley ME, et al. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. J Clin Immunol. 2015;35(8):696-726.
4. Shwin KW, Lee C-CR, Goldbach-Mansky R. Dermatologic manifestations of monogenic autoinflammatory diseases. Dermatol Clin. 2017;35(1):21-38.
5. Moreira A, Torres B, Peruzzo J, Mota A, Eyerich K, Ring J. Skin symptoms as diagnostic clue for autoinflammatory diseases. An Bras Dermatol. 2017;92(1):72-80.
6. Montazerin SM, Sherkat R, Mosayebian A, Shahrooei M, Homayouni V, Najafi S, et al. Clinical and Laboratory Manifestations of Autoinflammatory Diseases: The Results from the First Iranian Registry. J Clin Immunol. 2019;39(4):S135-S6.
7. Federici S, Sormani MP, Ozen S, Lachmann HJ, Amaryan G, Woo P, et al. Evidence-based provisional clinical classification criteria for autoinflammatory periodic fevers. Ann Rheum Dis. 2015;74(5):799-805.
8. Demirkaya E, Saglam C, Turker T, Koné-Paut I, Woo P, Doglio M, et al. Performance of different diagnostic criteria for familial Mediterranean fever in children with periodic fevers: results from a multicenter international registry. J Rheumatol. 2016;43(1):154-60.
9. Abolhassani H, Kiaee F, Tavakol M, Chavoshzadeh Z, Mahdaviani SA, Momen T, et al. Fourth update on the Iranian national registry of primary immunodeficiencies: integration of molecular diagnosis. J Clin Immunol. 2018;38(7):816-32.
10. Procopio V, Manti S, Bianco G, Conti G, Romeo A, Maimone F, et al. Genotype-phenotype correlation in FMF patients: a “non classic” recessive autosomal or “atypical” dominant autosomal inheritance?. Gene. 2018;641(23):279-86.
11. Tunca M, Akar S, Onen F, Ozdogan H, Kasapcopur O, Yalcinkaya F, et al. Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine. 2005;84(1):1-11.
12. Battal F, Silan F, Topaloğlu N, Aylanç H, Yıldırım Ş, Binnetoğlu FK, et al. The MEFV gene pathogenic variants and phenotype-genotype correlation in children with familial Mediterranean fever in the Çanakkale population. BJMG. 2016;19(2):23-8.
13. Kilic A, Varkal MA, Durmus MS, Yildiz I, Yıldırım ZNY, Turunc G, et al. Relationship between clinical findings and genetic mutations in patients with familial Mediterranean fever. Pediatr. Rheumatol. 2015;13(1):59.
14. Papa R, Doglio M, Lachmann HJ, Ozen S, Frenkel J, Simon A, et al. A web-based collection of genotype-phenotype associations in hereditary recurrent fevers from the Eurofever registry. Orphanet J Rare Dis. 2017;12(1):167.
15. Kishida D, Nakamura A, Yazaki M, Tsuchiya-Suzuki A, Matsuda M, Ikeda S-i. Genotype-phenotype correlation in Japanese patients with familial Mediterranean fever: differences in genotype and clinical features between Japanese and Mediterranean populations. Arthritis Res Ther. 2014;16(5):439-43.
16. Erten S, Altunoglu A, Keskin H, Ceylan G, Dalgaci A, Uyanık G, et al. Increased frequency of MEFV gene mutations in patients with primary dysmenorrhea. Mod Rheumatol. 2013;23(5):959-62.
17. Kasifoglu T, Cansu DÜ, Korkmaz C. Frequency of abdominal surgery in patients with familial Mediterranean fever. Intern Med. 2009;48(7):523-6.
18. Ait-Idir D, Djerdjouri B, Bouldjennet F, Taha RZ, El-Shanti H, Sari-Hamidou R, et al. The M694I/M694I genotype: a genetic risk factor of AA-amyloidosis in a group of Algerian patients with familial Mediterranean fever. Eur J Med Genet. 2017;60(3):149-53.
19. Dogan H, Bayrak OF, Emet M, Keles M, Gulluoglu S, Gul Z, et al. Familial Mediterranean fever gene mutations in north-eastern part of Anatolia with special respect to rare mutations. Gene. 2015;568(2):170-5.
20. Tchernitchko DO, Gérard-Blanluet M, Legendre M, Cazeneuve C, Grateau G, Amselem S. Intrafamilial segregation analysis of the p. E148Q MEFV allele in familial Mediterranean fever. Ann Rheum Dis. 2006;65(9):1154-7.
21. Ben‐Chetrit E, Lerer I, Malamud E, Domingo C, Abeliovich D. The E148Q mutation in the MEFV gene: Is it a disease‐causing mutation or a sequence variant?. Hum Mutat. 2000;15(4):385-6.
22. Migita K, Hisanaga S, Izumi Y, Kawahara C, Shigemitsu Y, Iwanaga N, et al. Protracted arthritis in a Japanese patient with familial Mediterranean fever. Mod Rheumatol. 2017;27(5):905-9.
23. Jarjour RA, Dodaki R. Arthritis patterns in familial Mediterranean fever patients and association with M694V mutation. Mol Biol Rep. 2011;38(3):2033-6.
24. Cekin N, Akyurek ME, Pinarbasi E, Ozen F. MEFV mutations and their relation to major clinical symptoms of Familial Mediterranean Fever. Gene. 2017;6269(24):9-13.
25. Kümpfel T, Gerdes L, Wacker T, Blaschek A, Havla J, Krumbholz M, et al. Familial Mediterranean fever-associated mutation pyrin E148Q as a potential risk factor for multiple sclerosis. Mult Scler. 2012;18(9):1229-38.
26. Rigante D, Federico G, Ferrara P, Maggiano N, Avallone L, Pugliese AL, et al. IgA nephropathy in an Italian child with familial Mediterranean fever. Pediatr Nephrol. 2005;20(11):1642-4.
27. Topaloglu R, Ozaltin F, Yilmaz E, Ozen S, Balci B, Besbas N, et al. E148Q is a disease-causing MEFV mutation: a phenotypic evaluation in patients with familial Mediterranean fever. Ann Rheum Dis. 2005;64(5):750-2.
28. Hung T, Pratt G, Sundararaman B, Townsend M, Chaivorapol C, Bhangale T, et al. The Ro60 autoantigen binds endogenous retroelements and regulates inflammatory gene expression. Science. 2015;350(6259):455-9.
29. Boccitto M, Wolin SL. Ro60 and Y RNAs: structure, functions, and roles in autoimmunity. Crit Rev Biochem Mol Biol. 2019;54(2):133-52.
30. Xue D, Shi H, Smith JD, Chen X, Noe DA, Cedervall T, et al. A lupus-like syndrome develops in mice lacking the Ro 60-kDa protein, a major lupus autoantigen. Proc Natl Acad Sci U S A. 2003;100(13):7503-8.
31. Coşku S, Kurtgöz S, Keskin E, Sönmez F, Bozkurt G. Frequency of mutations in Mediterranean fever gene, with gender and genotype–phenotype correlations in a Turkish population. J Genet. 2015;94(4):629-35.
32. Ben-Zvi I, Herskovizh C, Kukuy O, Kassel Y, Grossman C, Livneh A. Familial Mediterranean fever without MEFV mutations: a case–control study. Orphanet J Rare Dis. 2015;10(1):34-41.
33. Stella A, Cortellessa F, Scaccianoce G, Pivetta B, Settimo E, Portincasa P. Familial Mediterranean fever: breaking all the (genetic) rules. Rheumatology (Oxford). 2019;58(3):463-7.
34. Asgardoon MH, Azizi G, Yazdani R, Sohani M, Pashangzadeh S, Kalantari A, et al. Monogenic primary immunodeficiency disorder associated with common variable immunodeficiency and autoimmunity. Int Arch Allergy Immunol. 2020;181(9):706-14.
35. Erten S, Erzurum C, Altunoglu A. Three family members with familial Mediterranean fever carrying the M694V mutation showed different clinical presentations. Intern Med. 2012;51(13):1765-8.
36. Saulsbury FT, Wouters CH, Martin TM, Austin CR, Doyle TM, Goodwin KA, et al. Incomplete penetrance of the NOD2 E383K substitution among members of a pediatric granulomatous arthritis pedigree. Arthritis Rheum. 2009;60(6):1804-6.
37. Caso F, Galozzi P, Costa L, Sfriso P, Cantarini L, Punzi L. Autoinflammatory granulomatous diseases: from Blau syndrome and early-onset sarcoidosis to NOD2-mediated disease and Crohn's disease. RMD open. 2015;1(1):e000097.
38. Pugazhendhi S, Santhanam S, Venkataraman J, Creveaux I, Ramakrishna BS. NOD2 gene mutations associate weakly with ulcerative colitis but not with Crohn's disease in Indian patients with inflammatory bowel disease. Gene. 2013;512(2):309-13.
39. Shoham NG, Centola M, Mansfield E, Hull KM, Wood G, Wise CA, et al. Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway. PNAS. 2003;100(23):13501-6.
40. Maggio MC, Ceccherini I, Grossi A, Gattorno M, Corsello G. PAPA and FMF in two siblings: possible amplification of clinical presentation? A case report. Ital J Pediatr. 2019;45(1):111-9.
41. Schellevis MA, Stoffels M, Hoppenreijs EP, Bodar E, Simon A, van der Meer JW. Variable expression and treatment of PAPA syndrome. Ann Rheum Dis. 2011;70(6):1168-70.
42. Hong J-B, Su Y-N, Chiu H-C. Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome (PAPA syndrome): report of a sporadic case without an identifiable mutation in the CD2BP1 gene. J Am Acad Dermatol. 2009;61(3):533-5.
43. Demidowich A, Freeman A, Kuhns D, Aksentijevich I, Gallin J, Turner M. Genotype, phenotype, and clinical course in five patients with pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome. Arthritis Rheum. 2011;64(8):2022-7.
44. Lindwall E, Singla S, Davis WE, Quinet RJ, editors. Novel PSTPIP1 gene mutation in a patient with pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome. Semin Arthritis Rheum; 2015: Elsevier.
| Files | ||
| Issue | Vol 21 No 2 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v21i2.9227 | |
| Keywords | ||
| Cryopyrin-associated periodic syndromes Familial Mediterranean fever Hereditary autoinflammatory diseases | ||
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How to Cite
1.
Sherkat R, Rafiei A, Homayouni V, Kalantari E, Sepahvandi R, Memarmontazarin S, Mosayebian A. Clinical and Laboratory Parameters of Autoinflammatory Disorders in Single Tertiary Care Center. Iran J Allergy Asthma Immunol. 2022;21(2):197-206.
