This study presents effects of intravenous laser blood irradiation (ILBI) in a transient immunodeficiency patient with juvenile idiopathic arthritis (JIA) treated with an interleukin-6 receptor inhibitor (Tocilizumab). Biological agents induce JIA remission, but some patients do not respond favorably to this final therapeutic line of defense. ILBI was performed in a 16-year-old male patient, with JIA and transient immunodeficiency. When ILBI was introduced, the patient was receiving disease-modifying drugs, steroids, tocilizumab, and physical therapy. Because the disease was not well controlled, ILBI was applied in addition to other ongoing therapies. The patient underwent 1 session daily, and 10 successive sessions per month, repeated every 3 months, for 7 months. Patient evaluation was performed before ILBI was started and at 3, 6, 9, and 12 months after ILBI initiation, using the ACR Pediatric response. The outcome was evaluated using Pediatric 50, 70, and 90 responses and compared to initial status, after 3, 6, 9, and 12 months. At the end of study, the titre of IgA and IgG levels returned to normal. Synergistic anti-inflammatory effect of ILBI was evident, if applied additionally in combination with tocilizumab, in a patient with a therapy-resistant severe form of JIA and related subacute transient immunodeficiency. 1. Introduction Juvenile idiopathic arthritis (JIA) is an inflammatory disorder of the connective tissues, characterized by joint swelling, pain, and tenderness. Overproduction of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) is a well-known fact in JIA. Increased levels of these cytokines, both in serum and synovial fluid, induce the production of vascular endothelial factor, triggering angiogenesis in the affected joint. IL-6 is also considered responsible for osteoclast differentiation, followed by joint destruction and osteoporosis [1]. In the last decade, the development of biological agents that target these key inflammatory cytokines or their receptors brought new horizons in JIA treatment. Disease remission became a reachable goal [2]. However, few patients develop a severe chronic rheumatic type of the disease [3]. TNF-α inhibitors are the first-line biological agents used in JIA, if therapy with anti-inflammatory and disease-modifying antirheumatic drugs (DMARDs) proved to be inefficient. IL-6 receptor inhibition with Tocilizumab is a new second-line therapy for anti-TNF-α nonresponding patients, based on the blockade of IL-6-regulated signaling pathways [1, 2]. The main disadvantage
References
[1]
N. Nishimoto, J. Hashimoto, N. Miyasaka et al., “Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an X ray reader-blinded randomised controlled trial of tocilizumab,” Annals of the Rheumatic Diseases, vol. 66, no. 9, pp. 1162–1167, 2007.
[2]
G. Horneff, “Update on biologicals for treatment of juvenile idiopathic arthritis,” Expert Opinion on Biological Therapy, vol. 13, no. 3, pp. 361–376, 2013.
[3]
P. J. Gowdie and S. M. L. Tse, “Juvenile idiopathic arthritis,” Pediatric Clinics of North America, vol. 59, no. 2, pp. 301–327, 2012.
[4]
R. McMahan, L. M. Balfe, and L. Greene, “Summary of AHRQ's comparative effectiveness review of disease-modifying antirheumatic drugs for children with juvenile idiopathic arthritis,” Journal of Managed Care Pharmacy, vol. 18, no. 1, supplement B, pp. 1–16, 2012.
[5]
M. Weber, “The intravenous laser blood irradiation. Introduction of a new therapy,” in Lasers in Medicine, Science and Praxis, Z. Simunovic, Ed., pp. 664–706, Zrinski Printery Publishing House, ？akovec, Croatia, 2009.
[6]
D. A. Chiran, G. Litscher, M. Weber, L. M. Ailioaie, C. Ailioaie, and D. Litscher, “Intravenous laser blood irradiation increases efficacy of etanercept in selected subtypes of juvenile idiopathic arthritis: an innovative clinical research approach,” Evidence-Based Complementary and Alternative Medicine, vol. 2013, Article ID 168134, 9 pages, 2013.
[7]
Romanian National Health Insurance House, “Approval of the protocol for practice, monitoring and reimbursement for medicines in cases of juvenile idiopathic arthritis for persons who are insured in the national social health insurance system,” Monitorul Oficial al Romaniei, no. 255, part 1, 2007 (Romanian).
[8]
E. H. Giannini, N. Ruperto, A. Ravelli, D. J. Lovell, D. T. Felson, and A. Martini, “Preliminary definition of improvement in juvenile arthritis,” Arthritis and Rheumatism, vol. 40, no. 7, pp. 1202–1209, 1997.
[9]
S. Harirforoosh, W. Asghar, and F. Jamali, “Adverse effects of nonsteroidal antiinflammatory drugs: an update of gastrointestinal, cardiovascular and renal complications,” Journal of Pharmacy & Pharmaceutical Sciences, vol. 16, no. 5, pp. 821–847, 2011.
[10]
F. Aimbire, R. Albertini, M. T. Pacheco et al., “Low-level laser therapy induces dose-dependent reduction of TNFα levels in acute inflammation,” Photomedicine and Laser Surgery, vol. 24, no. 1, pp. 33–37, 2006.
[11]
E. S. Boschi, C. E. Leite, V. C. Saciura et al., “Anti-inflammatory effects of low-level laser therapy (660？nm) in the early phase in carrageenan-induced pleurisy in rat,” Lasers in Surgery and Medicine, vol. 40, no. 7, pp. 500–508, 2008.
[12]
J. M. Bjordal, M. I. Johnson, V. Iversen, F. Aimbire, and R. A. Lopes-Martins, “Low-level laser therapy in acute pain: a systematic review of possible mechanisms of action and clinical effects in randomized placebo-controlled trials,” Photomedicine and Laser Surgery, vol. 24, no. 2, pp. 158–168, 2006.
[13]
H. Shiba, H. Tsuda, M. Kajiya et al., “Neodymium-doped yttrium-aluminium-garnet laser irradiation abolishes the increase in interleukin-6 levels caused by peptidoglycan through the p38 mitogen-activated protein kinase pathway in human pulp cells,” Journal of Endodontics, vol. 35, no. 3, pp. 373–376, 2009.
[14]
M. Reale, C. Orso, M. L. Castellani et al., “Infra-red laser irradiation enhances interleukin-1 receptor antagonist, increases 3H-thymidine incorporation and the release of [3H]arachidonic acid in human monocytes,” Molecular and Cellular Biochemistry, vol. 169, no. 1-2, pp. 51–59, 1997.
[15]
K. Miyazawa, A. Mori, K. Yamamoto, and H. Okudaira, “Transcriptional roles of CCAAT/enhancer binding protein-β, nuclear factor-κB, and C-promoter binding factor 1 in interleukin (IL)-1β-induced IL-6 synthesis by human rheumatoid fibroblast-like synoviocytes,” The Journal of Biological Chemistry, vol. 273, no. 13, pp. 7620–7627, 1998.
[16]
S. Radtke, S. Wüller, X.-P. Yang et al., “Cross-regulation of cytokine signalling: pro-inflammatory cytokines restrict IL-6 signalling through receptor internalisation and degradation,” Journal of Cell Science, vol. 123, no. 6, pp. 947–959, 2010.
[17]
I. Navarro-Millán, J. A. Singh, and J. R. Curtis, “Systematic review of tocilizumab for rheumatoid arthritis: a new biologic agent targeting the interleukin-6 receptor,” Clinical Therapeutics, vol. 34, no. 4, pp. 788–802, 2012.
[18]
F. M. de Lima, A. B. Villaverde, R. Albertini et al., “Dual effect of low-level laser therapy (LLLT) on the acute lung inflammation induced by intestinal ischemia and reperfusion: action on anti-and pro-inflammatory cytokines,” Lasers in Surgery and Medicine, vol. 43, no. 5, pp. 410–420, 2011.
