The use of immunoglobulin is a therapeutic option with increasing evidence of efficacy for different rheumatologic autoimmune systemic diseases. Some studies concerning immunoglobulin use in systemic sclerosis have been published with encouraging results. We present the case of a young woman diagnosed with rapidly progressive diffuse cutaneous systemic sclerosis, refractory to therapy with methotrexate and rituximab, which presented a relevant skin improvement after one year of subcutaneous immunoglobulin (2 g/kg cumulative monthly dose, refracted in weekly administrations). Furthermore, a narrative literature review of the evidence for alternative treatments with a focus on immunoglobulin use for systemic sclerosis skin involvement was carried out.
AsanoY.The pathogenesis of systemic sclerosis: an understanding based on a common pathologic cascade across multiple organs and additional organ-specific pathologies. JCM2020; 9(9): 2687.
van den HoogenFKhannaDFransenJ, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism Collaborative Initiative. Ann Rheum Dis2013; 72(11): 1747–1755.
4.
Kowal-BieleckaOFransenJAvouacJ, et al. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis2017; 76(8): 1327–1339.
5.
MedsgerTAJr.Natural history of systemic sclerosis and the assessment of disease activity, severity, functional status, and psychologic well-being. Rheum Dis Clin North Am2003; 29(2): 255–273, vi.
CutoloMSulliASecchiME, et al. The contribution of capillaroscopy to the differential diagnosis of connective autoimmune diseases. Best Pract Res Clin Rheumatol2007; 21(6): 1093–1108.
8.
CutoloMPizzorniCSecchiME, et al. Capillaroscopy. Best Pract Res Clin Rheumatol2008; 22(6): 1093–1108.
9.
CutoloMPizzorniCTuccioM, et al. Nailfold videocapillaroscopic patterns and serum autoantibodies in systemic sclerosis. Rheumatology2004; 43(6): 719–726.
10.
BoselloSLDe LucaGRuccoM, et al. Long-term efficacy of B cell depletion therapy on lung and skin involvement in diffuse systemic sclerosis. Semin Arthritis Rheum2015; 44(4): 428–436.
11.
SantiagoTSantosERuaroB, et al. Ultrasound and elastography in the assessment of skin involvement in systemic sclerosis: a systematic literature review focusing on validation and standardization—WSF Skin Ultrasound Group. Semin Arthritis Rheum2022; 52: 151954.
12.
SobolewskiPMaślińskaMZakrzewskiJ, et al. Applicability of shear wave elastography for the evaluation of skin strain in systemic sclerosis. Rheumatol Int2020; 40(5): 737–745.
13.
AllanoreYMatucci-CerinicMDistlerO.Treatment of systemic sclerosis: is there any hope for the future? Table 1. RMD Open2016; 2(2): e000260.
14.
LeeJJPopeJE.Emerging drugs and therapeutics for systemic sclerosis. Expert Opin Emerg Drugs2016; 21(4): 421–430.
15.
WynnTA.Cellular and molecular mechanisms of fibrosis. J Pathol2008; 214(2): 199–210.
16.
AgarwalPSchulzJNBlumbachK, et al. Enhanced deposition of cartilage oligomeric matrix protein is a common feature in fibrotic skin pathologies. Matrix Biology2013; 32(6): 325–331.
17.
PattanaikDBrownMPostlethwaiteBC, et al. Pathogenesis of Systemic Sclerosis. Front Immunol2015; 6: 272.
18.
Van den HoogenFHBoerboomsAMSwaakAJ, et al. Comparison of methotrexate with placebo in the treatment of systemic sclerosis: a 24 week randomized double-blind trial, followed by a 24 week observational trial. Br J Rheumatol1996; 35(4): 364–372.
19.
PopeJEBellamyNSeiboldJR, et al. A randomized, controlled trial of methotrexate versus placebo in early diffuse scleroderma. Arthritis Rheum2001; 44(6): 1351–1358.
20.
JohnsonSRFeldmanBMPopeJE, et al. Shifting our thinking about uncommon disease trials: the case of methotrexate in scleroderma. J Rheumatol2009; 36(2): 323–329.
21.
De Figueiredo CaldasMMVde AzevedoKPMde França NunesAC, et al. Is rituximab effective for systemic sclerosis? A systematic review and meta-analysis. Adv Rheumatol2021; 61(1): 15.
22.
CohenSBEmeryPGreenwaldMW, et al. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum2006; 54(9): 2793–2806.
23.
KraaijMDvan LaarJM.The role of B cells in systemic sclerosis. Biologics2008; 2(3): 389–395.
24.
BerghenNVulstekeJBWesthovensR, et al. Rituximab in systemic autoimmune rheumatic diseases: indications and practical use. Acta Clin Belg2019; 74(4): 272–279.
25.
SmithVVan PraetJTVandoorenB, et al. Rituximab in diffuse cutaneous systemic sclerosis: an open-label clinical and histopathological study. Ann Rheum Dis2010; 69(1): 193–197.
26.
LafyatisRKissinEYorkM, et al. B cell depletion with rituximab in patients with diffuse cutaneous systemic sclerosis. Arthritis Rheum2009; 60(2): 578–583.
27.
BoselloSDe SantisMLamaG, et al. B cell depletion in diffuse progressive systemic sclerosis: safety, skin score modification and IL-6 modulation in an up to thirty-six months follow-up open-label trial. Arthritis Res Ther2010; 12(2): R54.
28.
GiuggioliDLumettiFColaciM, et al. Rituximab in the treatment of patients with systemic sclerosis: our experience and review of the literature. Autoimmun Rev2015; 14(11): 1072–1078.
29.
ZhuJLBlackSMChenHW, et al. Emerging treatments for scleroderma/systemic sclerosis. Fac Rev2021; 10: 43.
30.
CantariniLRiganteDVitaleA, et al. Intravenous immunoglobulins (IVIG) in systemic sclerosis: a challenging yet promising future. Immunol Res2015; 61(3): 326–337.
31.
GomesJPSantosLShoenfeldY.Intravenous immunoglobulin (IVIG) in the vanguard therapy of systemic sclerosis. Clin Immunol2019; 199: 25–28.
32.
QuillinanNPDentonCP.Disease-modifying treatment in systemic sclerosis: current status. Curr Opin Rheumatol2009; 21(6): 636–641.
33.
PoelmanCLHummersLKWigleyFM, et al. Intravenous immunoglobulin may be an effective therapy for refractory, active diffuse cutaneous systemic sclerosis. J Rheumatol2015; 42(2): 236–242.
34.
SangesSRivièreSMekinianA, et al. Intravenous immunoglobulins in systemic sclerosis: data from a French nationwide cohort of 46 patients and review of the literature. Autoimmun Rev2017; 16(4): 377–384.
35.
KudoHJinninMYamaneK, et al. Intravenous immunoglobulin treatment recovers the down-regulated levels of Th1 cytokines in the sera and skin of scleroderma patients. J Dermatol Sci2013; 69(1): 77–80.
36.
BallowM.Mechanisms of action of intravenous immune serum globulin in autoimmune and inflammatory diseases. J Allergy Clin Immunol1997; 100(2): 151–157.
37.
MannhalterJWEiblMM.Down regulation of Fc receptors by IVIgG. Int Rev Immunol1989; 5(2): 173–179.
38.
SinghJCohenSMehendirattaV, et al. Effects of scleroderma antibodies and pooled human immunoglobulin on anal sphincter and colonic smooth muscle function. Gastroenterology2012; 143(5): 1308–1318.
39.
KumarSSinghJKedikaR, et al. Role of muscarinic-3 receptor antibody in systemic sclerosis: correlation with disease duration and effects of IVIG. Am J Physiol-Gastrointest Liver Physiol2016; 310(11): G1052–G1060.
40.
AmitalHRewaldELevyY, et al. Fibrosis regression induced by intravenous gammaglobulin treatment. Ann Rheum Dis2003; 62(2): 175–177.
41.
ChizzoliniCRaschiERezzonicoR, et al. Autoantibodies to fibroblasts induce a proadhesive and proinflammatory fibroblast phenotype in patients with systemic sclerosis. Arthritis Rheum2002; 46(6): 1602–1613.
42.
ChinniahKJModyGM.Recovery from severe dysphagia in systemic sclerosis—myositis overlap: a case report. Afr Health Sci2017; 17(2): 593–596.
43.
KameiRYamaokaTIkinagaK, et al. Successful treatment of a refractory dysbiotic intestinal pseudo-obstruction in a patient with systemic sclerosis-polymyositis overlap syndrome by intravenous immunoglobulin administration possibly related to gut flora normalisation. Clin Exp Rheumatol2017; 35(Suppl. 106(4)): 214–215.
44.
ClarkKEEtomiODentonCP, et al. Intravenous immunogobulin therapy for severe gastrointestinal involvement in systemic sclerosis. Clin Exp Rheumatol2015; 33(4 Suppl. 91): S168–S170.
45.
RajaJNihtyanovaSIMurrayCD, et al. Sustained benefit from intravenous immunoglobulin therapy for gastrointestinal involvement in systemic sclerosis. Rheumatology2016; 55(1): 115–119.
46.
ScarponeRMeierKGhoreschiK, et al. Intravenous immunoglobulins in a series of 32 rare and recalcitrant immune dermatoses. Acta Derm Venereol2020; 100(17): adv00298.
47.
NacciFRighiAConfortiML, et al. Intravenous immunoglobulins improve the function and ameliorate joint involvement in systemic sclerosis: a pilot study. Ann Rheum Dis2007; 66(7): 977–979.
