Glatiramer acetate and interferon-beta are approved first-line disease-modifying treatments (DMTs) for multiple sclerosis (MS). DMTs can be associated with cutaneous adverse events, which may influence treatment adherence and patient quality of life. In this systematic review, we aimed to provide an overview of the clinical spectrum and the incidence of skin reactions associated with DMTs. A systematic literature search was performed up to May 2011 in Medline, Embase, and Cochrane databases without applying restrictions in study design, language, or publishing date. Eligible for inclusion were articles describing any skin reaction related to DMTs in MS patients. Selection of articles and data extraction were performed by two authors independently. One hundred and six articles were included, of which 41 (39%) were randomized controlled trials or cohort studies reporting incidences of mainly local injection-site reactions. A large number of patients had experienced some form of localized injection-site reaction: up to 90% for those using subcutaneous formulations and up to 33% for those using an intramuscular formulation. Sixty-five case-reports involving 106 MS patients described a wide spectrum of cutaneous adverse events, the most frequently reported being lipoatrophy, cutaneous necrosis and ulcers, and various immune-mediated inflammatory skin diseases. DMTs for MS are frequently associated with local injection-site reactions and a wide spectrum of generalized cutaneous adverse events, in particular, the subcutaneous formulations. Although some of the skin reactions may be severe and persistent, most of them are mild and do not require cessation of DMT.
BrinkmannVBillichABaumrukerT. Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov2010; 9: 883–897.
4.
Dhib-JalbutSMarksS. Interferon-beta mechanisms of action in multiple sclerosis. Neurology2010; 74Suppl 1: S17–S24.
5.
RackeMKLovett-RackeAEKarandikarNJ. The mechanism of action of glatiramer acetate treatment in multiple sclerosis. Neurology2010; 74Suppl 1: S25–S30.
La MantiaLMunariLMLovatiR. Glatiramer acetate for multiple sclerosis. Cochrane Database Syst Rev2010: CD004678.
8.
WaltherEUHohlfeldR. Multiple sclerosis: side effects of interferon beta therapy and their management. Neurology1999; 53: 1622–1627.
9.
FrohmanEMBrannonKAlexanderS. Disease modifying agent related skin reactions in multiple sclerosis: prevention, assessment, and management. Mult Scler2004; 10: 302–307.
10.
Langer-GouldAMosesHHMurrayTJ. Strategies for managing the side effects of treatments for multiple sclerosis. Neurology2004; 63: S35–S41.
11.
BallNJCowanBJHashimotoSA. Lobular panniculitis at the site of subcutaneous interferon beta injections for the treatment of multiple sclerosis can histologically mimic pancreatic panniculitis. A study of 12 cases. J Cutan Pathol2009; 36: 331–337.
12.
MancardiGLMurialdoADragoF. Localized lipoatrophy after prolonged treatment with copolymer 1. J Neurol2000; 247: 220–221.
13.
MikolDDBarkhofFChangP. Comparison of subcutaneous interferon beta-1a with glatiramer acetate in patients with relapsing multiple sclerosis (the REbif vs Glatiramer Acetate in Relapsing MS Disease [REGARD] study): a multicentre, randomised, parallel, open-label trial. Lancet Neurol2008; 7: 903–914.
14.
Meca-LallanaJEde Mingo-CasadoPAmorin-DiazM. Effects of glatiramer acetate on spasticity in previously interferon-beta-treated and treatment-naive patients with relapsing–remitting multiple sclerosis: a prospective, nonrandomized, open-label, uncontrolled, observational pilot study. Clin Ther2010; 32: 1061–1066.
15.
WolinskyJSNarayanaPAO’ConnorP. Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial. Ann Neurol2007; 61: 14–24.
16.
JohnsonKPBrooksBRCohenJA. Copolymer 1 reduces relapse rate and improves disability in relapsing–remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology1995; 45: 1268–1276.
17.
KorczynADNisipeanuP. Safety profile of copolymer 1: analysis of cumulative experience in the United States and Israel. J Neurol1996; 243: S23–26.
18.
ZwibelHL. Glatiramer acetate in treatment-naive and prior interferon-beta-1b-treated multiple sclerosis patients. Acta Neurol Scand2006; 113: 378–386.
19.
ComiGCohenJAArnoldDL. Phase III dose- comparison study of glatiramer acetate for multiple sclerosis. Ann Neurol2011; 69: 75–82.
20.
MillerASpadaVBeerkircherD. Long-term (up to 22 years), open-label, compassionate-use study of glatiramer acetate in relapsing–remitting multiple sclerosis. Mult Scler2008; 14: 494–499.
21.
O’ConnorPFilippiMArnasonB. 250 microg or 500 microg interferon beta-1b versus 20 mg glatiramer acetate in relapsing–remitting multiple sclerosis: a prospective, randomised, multicentre study. Lancet Neurol2009; 8: 889–897.
22.
JohnsonKPBrooksBRCohenJA. Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disability. Copolymer 1 Multiple Sclerosis Study Group. Neurology1998; 50: 701–708.
23.
FlechterSKottESteiner-BirmannsB. Copolymer 1 (glatiramer acetate) in relapsing forms of multiple sclerosis: open multicenter study of alternate-day administration. Clin Neuropharmacol2002; 25: 11–15.
24.
FlechterSVardiJPollakL. Comparison of glatiramer acetate (Copaxone) and interferon beta-1b (Betaferon) in multiple sclerosis patients: an open-label 2-year follow-up. J Neurol Sci2002; 197: 51–55.
25.
DebouverieMMoreauTLebrunC. A longitudinal observational study of a cohort of patients with relapsing–remitting multiple sclerosis treated with glatiramer acetate. Eur J Neurol2007; 14: 1266–1274.
26.
Placebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis. European Study Group on interferon beta-1b in secondary progressive MS. Lancet1998; 352: 1491–1497.
27.
GottesmanMHFriedman-UrevichS. Interferon beta-1b (betaseron/betaferon) is well tolerated at a dose of 500 microg: interferon dose escalation assessment of safety (IDEAS). Mult Scler2006; 12: 271–280.
28.
BrochetBLemaireGBeddiafA. Reduction of injection site reactions in multiple sclerosis (MS) patients newly started on interferon beta 1b therapy with two different devices. Revue Neurologique2006; 162: 735–740.
29.
DurelliLVerdunEBarberoP. Every-other-day interferon beta-1b versus once-weekly interferon beta-1a for multiple sclerosis: results of a 2-year prospective randomised multicentre study (INCOMIN). Lancet2002; 359: 1453–1460.
30.
NeilleyLKGoodinDSGoodkinDE. Side effect profile of interferon beta-1b in MS: results of an open label trial. Neurology1996; 46: 552–554.
31.
KapposLPolmanCHFreedmanMS. Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurology2006; 67: 1242–1249.
32.
Neutralizing antibodies during treatment of multiple sclerosis with interferon beta-1b: experience during the first three years. The IFNB Multiple Sclerosis Study Group and the University of British Columbia MS/MRI Analysis Group. Neurology1996; 47: 889–894.
33.
HurwitzBJJefferyDArnasonB. Tolerability and safety profile of 12- to 28-week treatment with interferon beta-1b 250 and 500 microg QOD in patients with relapsing–remitting multiple sclerosis: a multicenter, randomized, double-blind, parallel-group pilot study. Clin Ther2008; 30: 1102–1112.
34.
KapposLFreedmanMSPolmanCH. Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial. Lancet Neurol2009; 8: 987–997.
35.
RioJMarzoMETintoreM. [Profile of efficacy and safety in the treatment of remittent-recurrent multiple sclerosis with interferon beta-1b] Perfil de eficacia y seguridad en el tratamiento de la esclerosis multiple remitente-recurrente con interferon beta-1b. Neurologia1998; 13: 422–426.
36.
MontalbanXSastre-GarrigaJTintoreM. A single-center, randomized, double-blind, placebo-controlled study of interferon beta-1b on primary progressive and transitional multiple sclerosis. Mult Scler2009; 15: 1195–1205.
37.
RederATEbersGCTraboulseeA. Cross-sectional study assessing long-term safety of interferon-(beta)-1b for relapsing–remitting MS. Neurology2010; 74: 1877–1885.
38.
JacobsLDCookfairDLRudickRA. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol1996; 39: 285–294.
39.
HavrdovaEZivadinovRKrasenskyJ. Randomized study of interferon beta-1a, low-dose azathioprine, and low-dose corticosteroids in multiple sclerosis. Mult Scler2009; 15: 965–976.
40.
GhezziAAmatoMPCapobiancoM. Treatment of early-onset multiple sclerosis with intramuscular interferonbeta-1a: long-term results. Neurol Sci2007; 28: 127–132.
41.
SchwidSRThorpeJShariefM. Enhanced benefit of increasing interferon beta-1a dose and frequency in relapsing multiple sclerosis: the EVIDENCE Study. Arch Neurol2005; 62: 785–792.
42.
Sandberg-WollheimMBeverCCarterJ. Comparative tolerance of IFN beta-1a regimens in patients with relapsing multiple sclerosis. The EVIDENCE study. J Neurol2005; 252: 8–13.
43.
HerndonRMRudickRAMunschauerFE3rd. Eight-year immunogenicity and safety of interferon beta-1a-Avonex treatment in patients with multiple sclerosis. Mult Scler2005; 11: 409–19.
44.
LearySMMillerDHStevensonVL. Interferon beta-1a in primary progressive MS: an exploratory, randomized, controlled trial. Neurology2003; 60: 44–51.
45.
PanitchHGoodinDSFrancisG. Randomized, comparative study of interferon beta-1a treatment regimens in MS: The EVIDENCE Trial. Neurology2002; 59: 1496–1506.
46.
PhillipsJTRiceGFrohmanE. A multicenter, open-label, phase II study of the immunogenicity and safety of a new prefilled syringe (liquid) formulation of Avonex in patients with multiple sclerosis. Clin Ther2004; 26: 511–521.
47.
FreedmanMSFrancisGSSandersEA. Randomized study of onceweekly interferon beta-1la therapy in relapsing multiple sclerosis: three-year data from the OWIMS study. Mult Scler2005; 11: 41–45.
48.
AndersenOElovaaraIFarkkilaM. Multicentre, randomised, double blind, placebo controlled, phase III study of weekly, low dose, subcutaneous interferon beta-1a in secondary progressive multiple sclerosis. J Neurol Neurosurg Psychiatry2004; 75: 706–710.
49.
OgerJFrancisGChangP. Prospective assessment of changing from placebo to IFN beta-1a in relapsing MS: the PRISMS study. J Neurol Sci2005; 237: 45–52.
50.
Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Lancet1998; 352: 1498–1504.
51.
GoldRRieckmannPChangP. The long-term safety and tolerability of high-dose interferon beta-1a in relapsing–remitting multiple sclerosis: 4-year data from the PRISMS study. Eur J Neurol2005; 12: 649–656.
52.
BaumK. Safety and tolerability of a ‘refrigeration-free’ formulation of interferon beta-1b–results of a double-blind, multicentre, comparative study in patients with relapsing–remitting or secondary progressive multiple sclerosis. J Int Med Res2006; 34: 1–12.
53.
GiovannoniGBarbarashOCasset-SemanazF. Safety and immunogenicity of a new formulation of interferon beta-1a (Rebif New Formulation) in a Phase IIIb study in patients with relapsing multiple sclerosis: 96-week results. Mult Scler2009; 15: 219–228.
54.
LugaresiADurastantiVGasperiniC. Safety and tolerability in relapsing–remitting multiple sclerosis patients treated with high-dose subcutaneous interferon-beta by Rebiject autoinjection over a 1-year period: the CoSa study. Clin Neuropharmacol. 2008; 31: 167–172.
55.
DevonshireVArbizuTBorreB. Patient-rated suitability of a novel electronic device for self-injection of subcutaneous interferon beta-1a in relapsing multiple sclerosis: an international, single-arm, multicentre, Phase IIIb study. BMC Neurology2010; 10.
56.
EdgarCMBrunetDGFentonP. Lipoatrophy in patients with multiple sclerosis on glatiramer acetate. Can J Neurol Sci2004; 31: 58–63.
57.
BallNJCowanBJMooreGR. Lobular panniculitis at the site of glatiramer acetate injections for the treatment of relapsing–remitting multiple sclerosis. A report of two cases. J Cutan Pathol2008; 35: 407–410.
58.
SoosNShakeryKMrowietzU. Localized panniculitis and subsequent lipoatrophy with subcutaneous glatiramer acetate (Copaxone) injection for the treatment of multiple sclerosis. Am J Clin Dermatol2004; 5: 357–359.
59.
HashimotoSBallNTremlettH. Progressive lipoatrophy after cessation of glatiramer acetate injections: a case report. Mult Scler2009; 15: 521–522.
60.
BeiskeAGMyhrKM. Lipoatrophy: a non-reversible complication of subcutaneous interferon-beta 1a treatment of multiple sclerosis. J Neurol2006; 253: 377–378.
61.
O’SullivanSSCroninEMSweeneyBJ. Panniculitis and lipoatrophy after subcutaneous injection of interferon beta-1b in a patient with multiple sclerosis. J Neurol Neurosurg Psychiatry2006; 77: 1382–.
62.
Soares AlmeidaLMRequenaLKutznerH. Localized panniculitis secondary to subcutaneous glatiramer acetate injections for the treatment of multiple sclerosis: a clinicopathologic and immunohistochemcal study. J Am Acad Dermatol2006; 55: 968–974.
63.
WebsterGFKnoblerRLLublinFD. Cutaneous ulcerations and pustular psoriasis flare caused by recombinant interferon beta injections in patients with multiple sclerosis. J Am Acad Dermatol1996; 34: 365–367.
64.
ElgartGWSheremataWAhnYS. Cutaneous reactions to recombinant human interferon beta-1b: the clinical and histologic spectrum. J Am Acad Dermatol1997; 37: 553–558.
65.
OzdenMGErelAErdemO. Dermal fibrosis and cutaneous necrosis after recombinant interferon-beta1a injection in a multiple sclerosis patient. J Eur Acad Dermatol Venereol2005; 19: 112–113.
66.
CasoniFMerelliEBedinR. Necrotizing skin lesions and NABs development in a multiple sclerosis patient treated with IFNbeta 1b. Mult Scler2003; 9: 420–423.
67.
YangCHChenCHChanHL. Skin necrosis following a recombinant interferon-beta-1b injection. Chang Gung Med J2002; 25: 774–777.
68.
GarciaFVMDaudenESanchezJ. Local reactions associated with subcutaneous injections of both beta-interferon 1a and 1b. Acta Derm Venereol2001; 81: 152.
69.
AlbaniCAlbaniG. A case of cutaneous necrosis during interferon-beta 1b (B-IFN) therapy in multiple sclerosis. J Neurol Neurosurg Psychiatry1997; 62: 418.
70.
CreangeALefaucheurJP. Focal neuropathy associated with cutaneous necrosis at the site of interferon-beta injection for multiple sclerosis. J Neurol Neurosurg Psychiatry2000; 68: 395.
71.
SheremataWATaylorJRElgartGW. Severe necrotizing cutaneous lesions complicating treatment with interferon beta-1b. N Engl J Med1995; 332: 1584.
FeldmannRLow-WeiserHDuschetP. Necrotizing cutaneous lesions caused by interferon beta injections in a patient with multiple sclerosis. Dermatology1997; 195: 52–53.
74.
WeinbergJMWolfeJTSoodS. Cutaneous necrosis associated with recombinant interferon injection. Report of three cases with interferon beta-1b and review of the literature. Acta Derm Venereol1997; 77: 146–148.
75.
RadziwillAJCourvoisierS. Severe necrotising cutaneous lesions complicating treatment with interferon beta-1a. J Neurol Neurosurg Psychiatry1999; 67: 115.
76.
BoscaIBoscaMBelenguerA. Necrotising cutaneous lesions as a side effect of glatiramer acetate. J Neurol2006; 253: 1370–1371.
77.
KoontzDAlshekhleeA. Embolia cutis medicamentosa following interferon beta injection. Mult Scler2007; 13: 1203–1204.
78.
FeldmannRSchierlMRauschkaH. Necrotizing skin lesions with involvement of muscle tissue after subcutaneous injection of glatiramer acetate. Eur J Dermatol2009; 19: 385.
79.
HardeVSchwarzT. Embolia cutis medicamentosa following subcutaneous injection of glatiramer acetate. J Dtsch Dermatol Ges2007; 5: 1122–1123.
80.
GaudezCRegnierSAractingiS. [Livedo-like dermatitis (Nicolau’s syndrome) after injection of Copolymer-1 (Glatiramer acetate)] Dermite livedoide de Nicolau apres injection de Copolymere-1 (acetate de Glatiramer). Rev Neurol (Paris)2003; 159: 571–573.
81.
Lopez-LermaIIranzoPHerreroC. New-onset psoriasis in a patient treated with interferon beta-1a. Br J Dermatol2009; 160: 716–717.
82.
NavneJEHedegaardUBygumA. [Activation of psoriasis in patients undergoing treatment with interferon-beta] Aktivering af psoriasis hos patienter i interferon-beta-behandling. Ugeskr Laeger2005; 167: 2903–2904.
83.
SzilasiovaJGdovinovaZJautovaJ. Cutaneous vasculitis associated with interferon beta-1b treatment for multiple sclerosis. Clin Neuropharmacol2009; 32: 301–303.
84.
CohenBAGreenbergerPASainiS. Delayed occurrence of a severe cutaneous reaction in a multiple sclerosis patient taking interferon beta-1b. Allergy Asthma Proc1998; 19: 85–88.
85.
Debat ZoguerehDBoucrautJBeau-SalinasF. [Cutaneous vasculitis with renal impairment complicating interferon-beta 1a therapy for multiple sclerosis]. Rev Neurol (Paris)2004; 160: 1081–1084.
86.
CicekDKandiBOguzS. An urticarial vasculitis case induced by glatiramer acetate. J Dermatolog Treat2008; 19: 305–307.
87.
GilMChizzoliniCKayaG. Erythema elevatum et diutinum, multiple sclerosis and interferon beta. Dermatology2004; 209: 75–76.
88.
HeinzerlingLDummerRBurgG. Panniculitis after subcutaneous injection of interferon beta in a multiple sclerosis patient. Eur J Dermatol2002; 12: 194–197.
NakamuraYKawachiYFurutaJ. Severe local skin reactions to interferon beta-1b in multiple sclerosis-improvement by deep subcutaneous injection. Eur J Dermatol2008; 18: 579–582.
91.
SoriaAMaubecEHenry-FeugeasMC. [Panniculitis induced by interferon beta-1a vascular toxicity]. Ann Dermatol Venereol2007; 134: 374–377.
ConroyMSewellLMillerOF. Interferon-beta injection site reaction: review of the histology and report of a lupus-like pattern. J Am Acad Dermatol2008; 59: S48–49.
94.
ArrueISaizAOrtiz-RomeroPLRodriguez-PeraltoJL. Lupus-like reaction to interferon at the injection site: report of five cases. J Cutan Pathol2007; 34Suppl 1: 18–21.
SomaniAKSwickARCooperKD. Severe dermatomyositis triggered by interferon beta-1a therapy and associated with enhanced type I interferon signaling. Arch Dermatol2008; 144: 1341–1349.
97.
ThouvenotEHillaire-BuysDBos-ThompsonMA. Erythema nodosum and glatiramer acetate treatment in relapsing–remitting multiple sclerosis. Mult Scler2007; 13: 941–944.
98.
KumarNRodriguezM. Scleromyxedema in a patient with multiple sclerosis and monoclonal gammopathy on interferon beta-1a. Mult Scler2004; 10: 85–86.
99.
GonoTMatsudaMShimojimaY. Lupus erythematosus profundus (lupus panniculitis) induced by interferon-beta in a multiple sclerosis patient. J Clin Neurosci2007; 14: 997–1000.
100.
KocerBNazlielBOztasM. Vitiligo and multiple sclerosis in a patient treated with interferon beta-1a: a case report. Eur J Neurol2009; 16: e78–79.
101.
NoldenSCasperCKuhnA. Jessner-Kanof lymphocytic infiltration of the skin associated with glatiramer acetate. Mult Scler2005; 11: 245–248.
102.
Sanchez-LopezJdel RioPRCases-OrtegaB. Allergy workup in immediate-type local reactions to glatiramer acetate. J Investig Allergol Clin Immunol2010; 20: 521–523.
103.
BatistaJPonceVHierroB. Transient exacerbation of cholinergic urticaria during concomitant treatment with glatiramer acetate. Allergy2010; 65: 246.
104.
BayerlCBohlandPJungEG. Systemic reaction to glatiramer acetate. Contact Dermatitis2000; 43: 62–63.
105.
RauschkaHFarinaCSatorP. Severe anaphylactic reaction to glatiramer acetate with specific IgE. Neurology2005; 64: 1481–1482.
106.
AlavaCTorneroPPrietoA. Anaphylaxis with glatiramer acetate and delayed urticarial reaction to interferon beta-1a in a multiple sclerosis patient with chronic urticaria. Allergy2010; 65: 242.
107.
MazzeoLRicciardiLFazioMC. Severe urticaria due to recombinant interferon beta-1a. Br J Dermatol2003; 148: 172.
108.
Fusun KalpakliogluABaccioglu KavutAErdemogluAK. Desensitization in interferon-beta1a allergy: a case report. Int Arch Allergy Immunol2009; 149: 178–180.
109.
GuijarroCBenito-LeonJBermejo-ParejaF. Widespread urticaria due to intramuscular interferon beta-1a therapy for multiple sclerosis. Neurol Sci2011; 32: 309–311.
110.
DimovVSandhuMBewtraA. Repeat desensitizations in interferon beta-1a and beta-1b allergy: a case report. Ann Allergy, Asthma Immunol2009; 103: A83.
111.
BrownDLLoginISBorishL. An urticarial IgE-mediated reaction to interferon beta-1b. Neurology2001; 56: 1416–1417.
CohenJABarkhofFComiG. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med2010; 362: 402–415.
114.
FrulandJESandermannSSnowSN. Skin necrosis with subsequent formation of squamous cell carcinoma after subcutaneous interferon beta injection. J Am Acad Dermatol1997; 37: 488–489.
115.
TaiYJTamM. Fixed drug eruption with interferon-beta-1b. Australas J Dermatol2005; 46: 154–157.
116.
SerarslanGOkuyucuEMelekI. Widespread maculopapular rash due to intramuscular interferon beta-1a during the treatment of multiple sclerosis. Mult Scler2008; 14: 259–261.
117.
MehtaCLTylerRJCrippsDJ. Granulomatous dermatitis with focal sarcoidal features associated with recombinant interferon beta-1b injections. J Am Acad Dermatol1998; 39: 1024–1028.
118.
ZieglerVRKrankeBSoyerP. [Extensive cutaneous–subcutaneous infiltration as a side-effect of interferon-beta injection]. Hautarzt1998; 49: 310–312.
119.
MacbethAEKendallBRSmithA. Calcified subcutaneous nodules: a long-term complication of interferon beta-1a therapy. Br J Dermatol2007; 157: 624–625.
KlugerNThouvenotECamuW. Cutaneous adverse events related to glatiramer acetate injection (copolymer-1, Copaxone). J Eur Acad Dermatol Venereol2009; 23: 1332–1333.
122.
ButtmannMGoebelerMToksoyA. Subcutaneous interferon-beta injections in patients with multiple sclerosis initiate inflammatory skin reactions by local chemokine induction. J Neuroimmunol2005; 168: 175–182.
123.
NielsenNMFrischMRostgaardK. Autoimmune diseases in patients with multiple sclerosis and their first-degree relatives: a nationwide cohort study in Denmark. Mult Scler2008; 14: 823–829.
124.
Langer-GouldAAlbersKBVan Den EedenSK. Autoimmune diseases prior to the diagnosis of multiple sclerosis: a population-based case-control study. Mult Scler2010; 16: 855–861.
125.
LebrunCDebouverieMVermerschP. Cancer risk and impact of disease-modifying treatments in patients with multiple sclerosis. Mult Scler2008; 14: 399–405.
126.
Sandberg-WollheimMKornmannGBischofD. The risk of malignancy is not increased in patients with multiple sclerosis treated with subcutaneous interferon beta-la: analysis of data from clinical trial and post-marketing surveillance settings. Mult Scler2011; 17: 431–440.
127.
BaumgartDCGrittnerUSteingraberA. Frequency, phenotype, outcome, and therapeutic impact of skin reactions following initiation of adalimumab therapy: experience from a consecutive cohort of inflammatory bowel disease patients. Inflamm Bowel Dis2011; 17: 2512–2520.
128.
KaiserCKnightANordstromD. Injection-site reactions upon Kineret (anakinra) administration: experiences and explanations. Rheumatol Int2011.
129.
JollyHSimpsonKBishopB. Impact of warm compresses on local injection-site reactions with self-administered glatiramer acetate. J Neurosci Nurs2008; 40: 232–239.
130.
PardoGBoutwellCConnerJ. Effect of oral antihistamine on local injection site reactions with self-administered glatiramer acetate. J Neurosci Nurs2010; 42: 40–46.
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