High Efficiency of Kanakinumabum for a Patient with a Late Diagnosed Chronic Infantile Neurological Cutaneous Articular Syndrome (CINCA)

The article presents the monitoring of a severe course of CINCA/NOMID syndrome diagnosed at late stages. The use of monoclonal antibodies to IL 1 — kanakinumabum — in a patient with chronic neurological cutaneous and articular syndrome was successful: fever, cutaneous and pain syndromes were completely stopped, joint contractures decreased after one week of therapy. Laboratory parameters of the child’s disease activity (ESR and CRP) became normal after 8 weeks of treatment. Movements in the affected joints recovered completely after 24 weeks; the audiologist noted an improvement in hearing. The above clinical example demonstrates the high efficiency of kanakinumabum for a patient with chronic neurological cutaneous and articular syndrome, and shows the perspective of therapeutic application of IL 1 blocker for patients with CINCA syndrome including advanced stages of the disease. No adverse effects were noted during kanakinumabum therapy.

1. Гатторно М. Аутовоспалительные заболевания у детей. Вопросы современной педиатрии. 2014; 13 (2): 55–64.

2. Agostini L., Martinon F., Burns K., McDermott M. F., Hawkins P. N., Tschopp J. NALP3 forms an IL-1-beta processing inflammasome with increased activityin Muckle–Wells auto-inflammatory disorder. Immunity. 2004; 20: 319–25.

3. URL: https://www.printo.it/eurofever/eurofever_results.asp 4. Kitley J. L., Lachmann H. J., Pinto A., Ginsberg L. Neurologic manifesta-tions of the cryopyrin-associated periodic syndrome. Neurology. 2010; 74: 1267–70.

4. Hedrich C. M., Bruck N., Paul D., Hahn G., Gahr M., Rosen-Wolff A. «Mutationnegative» familial cold autoinflammatory syndrome (FCAS) in an 8-year-oldboy: clinical course and functional studies. Rheumatol Int. 2012; 32: 2629–36.

5. Hoffman H. M., Mueller J. L., Broide D. H., Wanderer A. A., Kolodner R. D. Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nature Genet. 2001; 29: 301–305.

6. Arostegui J. I., Lopez Saldana M. D., Pascal M., Clemente D., Aymerich M., Balaguer F., Goel A., Fournier del Castillo C., Rius J., Plaza S., Lopez Robledillo J. C., Juan M., Ibanez M., Yague J. A somatic NLRP3 mutation as a cause of sporadic case of chronic infantile neurologic, cutaneous, articularsyndrome/neonatal-onset multisystem inflammatory disease: Novel evidence of the role of lowlevel mosaicism as the pathophysiologic mechanism underlying mendelian inherited diseases. Arthritis Rheum. 2010 Apr; 62 (4): 1158–66.

7. Tanaka N., Izawa K., Saito M. K. et al. High incidence of NLRP3 somatic mosaicism in patients with chronic infantile neurologic, cutaneous, articular syndrome: results of an International Multicenter Collaborative Study. Arthritis Rheum. 2011; 63: 3625–3632.

8. Saito M., Fujisawa A., Nishikomori R., Kambe N., Nakata-Hizume M., Yoshimoto M. et al. Somatic mosaicism of CIAS1 in a patient with chronic infantile neurologic, cutaneous, articular syndrome. Arthritis Rheum. 2005; 52: 3579–85.

9. Gattorno M., Piccini A., Lasiglie D., Tassi S., Brisca G., Carta S. et al. The pattern of response to anti-interleukin-1 treatment distinguishes two subsets of patients with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum. 2008; 58: 1505–15.

10. Gattorno M., Tassi S., Carta S., Delfino L., Ferlito F., Pela gat ti M. A. et al. Pattern of interleukin-1beta secretion in response to lipopolysaccharide and ATP before and after interleukin-1 blockade in patients with CIAS1 mutations. Arthritis Rheum. 2007; 56: 3138–48.

11. Goldbach-Mansky R., Dailey N. J., Canna S. W., Gelabert A., Jones J., Rubin B. I. et al. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. N Engl J Med. 2006; 355: 581–92.

12. Lachmann H. J., Kone-Paut I., Kuemmerle-Deschner J. B., Leslie K. S., Hachulla E., Quartier P. et al. Use of canakinumab in the cryopyrin-associated periodicsyndrome. N Engl J Med. 2009; 360: 2416–25.

13. Kitley J. L., Lachmann H. J., Pinto A., Ginsberg L. Neurologic manifesta-tions of the cryopyrin-associated periodic syndrome. Neurology. 2010; 74: 1267–70.

14. Kone-Paut I., Lachmann H. J., Kuemmerle-Deschner J. B., Hachul la E., Leslie K. S., Mouy R. et al. Sustained remission of symptoms and improved health-relatedquality of life in patients with cryopyrin-associated periodic syndrometreated with canakinumab: results of a double-blind placebo-controlled ran-domized withdrawal study. Arthritis Res Ther. 2011; 13: R202.

15. Kuemmerle-Deschner J. B., Ramos E., Blank N., Roesler J., Felix S. D., Jung T. et al. Canakinumab (ACZ885, a fully human IgG1 anti-IL-1beta mAb) induces sus-tained remission in pediatric patients with cryopyrin-associated periodicsyndrome (CAPS). Arthritis Res Ther. 2011; 13: R34.

16. Kuemmerle-Deschner J. B., Hachulla E., Cartwright R., Hawkins P. N., Tran T. A., Bader-Meunier B. et al. Two-year results from an open-label, multicentre, phase III study evaluating the safety and efficacy of canakinumab in patientswith cryopyrin-associated periodic syndrome across different severity phen-otypes. Ann Rheum Dis. 2011; 70: 2095–102.

17. Ahmadi N., Brewer C. C., Zalewski C., King K. A., Butman J. A., Plass N. et al. Cryopyrin-associated periodic syndromes: otolaryngologic and audiologicmanifestations. Otolaryngol Head Neck Surg. 2011; 145: 295–302.

18. Klein A. K., Horneff G. Improvement of sensoneurinal hearing loss in apatient with Muckle–Wells syndrome treated with anakinra. Klin Padiatr. 2011; 222: 266–8.

19. Ait-Abdesselam T., Lequerre T., Legallicier B., Francois A., Le Loet X., Vittecoq O. Anakinra efficacy in a Caucasian patient with renal AA amyloidosis sec-ondary to cryopyrin-associated periodic syndrome. Joint Bone Spine. 2011; 77: 616–7.

20. Kuemmerle-Deschner J. B., Tyrrell P. N., Koetter I., Wittkowski H., Bialkowski A., Tzaribachev N. et al. Efficacy and safety of anakinra therapy in pediatric andadult patients with the autoinflammatory Muckle-Wells syndrome. Arthritis Rheum. 2011; 63: 840–9.

21. Thornton B. D., Hoffman H. M., Bhat A., Don B. R. Successful treatment of renal amy-loidosis due to familial cold autoinflammatory syndrome using an interleukin1 receptor antagonist. Am J Kidney Dis. 2007; 49: 477–81.