Peripheral Neuropathy in Patients with Systemic Lupus Erythematosus

SLE

Peripheral Neuropathy in Patientswith Systemic Lupus Erythematosus

Brandusa Florica MD Ellie Aghdassi PhDdagger Jiandong Su BScdagger

Dafna D Gladman MD Murray B Urowitz MD andPaul R Fortin MDdagger

Objective In patients with systemic lupus erythematosus (SLE) to determine 1) the prevalenceand clinical features of peripheral neuropathies (PN) and whether they were SLE related 2)whether there are associations between other SLE features and PNMethods Patients who met the American College of Rheumatology case definition criteria for SLEperipheral neuropsychiatric syndromes were selected from the University of Toronto Lupus Clinicdatabase Demographic data and SLE-related clinical and laboratory data were extracted Health-related quality of life was assessed using the mental and physical component summary score of theSF-36 questionnaire In a nested case-control study SLE patients with PN were matched bydisease duration and compared with those without PNResults Of 1533 patients in the database 207 (14) had PN Of these 40 were non-SLE-related Polyneuropathy was diagnosed in 56 mononeuritis multiplex in 9 cranial neuropa-thy in 13 and mononeuropathy in 11 of patients Asymmetric presentation was most com-mon (59) and distal weakness occurred in 34 Electrophysiologic studies indicated axonalneuropathy in 70 and signs of demyelination in 20 of patients Compared with patientswithout PN those with PN had significantly more central nervous system involvement higherSLE-disease activity index 2000 and lower SF-36-PCSConclusions The prevalence of PN is relatively high in SLE and occurs more frequently in patientswith central nervous system involvement and high SLE-disease activity index There is a predilec-tion for asymmetric and lower extremities involvement especially peroneal and sural nerves Thismanifestation of the disease has a significant impact on the patientrsquos quality of lifecopy 2011 Elsevier Inc All rights reserved Semin Arthritis Rheum 41203-211

Keywords systemic lupus erythematosus quality of life peripheral neuropathy neuropsychiatric lupus

ossdsntodrp

Division of Rheumatology Department of Medicine The University Health Net-work and University of Toronto Toronto Ontario CanadadaggerDivision of Health Care and Outcome Research Toronto Western Research Insti-tute Toronto Ontario Canada

Dr Paul R Fortin is a Distinguished Senior Investigator of The Arthritis Societywith additional support from the Arthritis Centre of Excellence University of To-ronto Ellie Aghdassi and Jiandong Su are supported by Canadian Network forImproved Outcomes in SLE (CaNIOS) which is supported in part by Lupus CanadaLupus Ontario the Lupus Foundation of Ontario and BC Lupus as well as from theArthritis and Autoimmune Research Centre Foundation The Centre for PrognosticStudies in Rheumatic Disease-University of Toronto Lupus Clinic is supported in partby The Smythe Foundation Lupus Ontario and the Dance for the Cure the Flare forFashion and the Lupus Foundation of Ontario

Address reprint requests to Paul R Fortin MD MPH FRCP(C) Director ofClinical Research Arthritis Centre of Excellence Toronto Western Hospital Room

SMP-10-304 399 Bathurst Street Toronto Ontario Canada M5T 2S8 E-mailpfortinuhnresearchca

0049-017211$-see front matter copy 2011 Elsevier Inc All rights reserveddoi101016jsemarthrit201104001

The frequency of neuropsychiatric manifestationsin patients with systemic lupus erythematosus(NPSLE) is relatively high ranging from 37 to

ver 90 of patients according to different publishedtudies (1-3) These differences are likely a reflection ofelection of different patient populations or of the use ofifferent definitions and criteria to diagnose the nervousystem manifestations Because of this divergence in theomenclature of the nervous system manifestations in sys-emic lupus erythematosus (SLE) the American Collegef Rheumatology (ACR) proposed in 1999 a set of caseefinitions reporting standards and diagnostic testingecommendations for 19 NPSLE syndromes that includeeripheral nervous system manifestations (4)The central nervous system (CNS) manifestations of

LE have received a lot of attention in the last 20 years

203

OApwt

clDa

pdm

204 Peripheral neuropathy in SLE

with many studies reporting on their prevalence clinicalmanifestations and possible pathogenic mechanismsThe peripheral nervous system manifestations have onthe other hand received little attention despite their po-tential significant impact on the patientrsquos quality of life

In the literature studies on the peripheral nervous sys-tem (PN) manifestations are mostly represented by casereports or case series with a small number of patients Inaddition the PN has not been well characterized in SLEin terms of onset severity clinical associations and elec-trophysiological findings and there is no guideline fortheir treatment Therefore the primary objective of ourstudy was to characterize PN in SLE with respect to thepatientrsquos clinical lupus manifestations serologic markersand electrophysiological findings A secondary objectivewas to determine whether any of these characteristics areassociated with the development of PN in SLE

POPULATION AND METHODS

Subjects

Subjects for this study were selected from the Universityof Toronto Lupus Clinic database one of the CanadianNetwork for Improved Outcomes in SLE centers that hascollected clinical and laboratory data prospectively andaccording to a standard protocol since 1970 All patientsfulfilled the ACR classification criteria for SLE or fulfilled3 criteria with either skin or kidney biopsy evidence ofSLE (56) The University of Toronto Lupus Clinic hascontinuous approval from the University Health Net-work Research Ethics Board and informed consent wasobtained from all patients for accessing their data for re-search studies

For an accurate capture and description of the PNmanifestations in SLE the database was searched for pa-tients with distal or proximal weakness andor sensoryloss diagnosed polyneuropathies mononeuritis simple ormultiplex cranial neuropathy plexopathy or radiculopa-thy and abnormal electrophysiology A further chart re-view was performed for the identified patients to confirmclinical findings determine the contributing factors anddocument the diagnostic investigations treatments andoutcome Peripheral neuropathies were defined accordingto the ACR nomenclature and case definitions for neuro-psychiatric syndromes in SLE (4) found online at httpwwwrheumatologyorgpublicationsar1999499

Attribution to SLE was considered when PN was pres-ent in the absence of other more common etiologies andwhen the rheumatologist andor neurologist listed thisattribution as the etiology of the PN The decision wasbased on the clinical evaluation and subsequent investiga-tions included in the ACR nomenclature and case defini-tions for each of the peripheral nervous system syndromesin SLE and after exclusion criteria were considered andassociation factors documented (4) PN secondary to dia-betes mellitus hypothyroidism vitamin B12 deficiency in-

fectious causes Sjoumlgrenrsquos syndrome alcohol abuse drug tox- o

icity compression syndromes and inherited neuropathieswere categorized as ldquonon-SLE-relatedrdquo PN were ldquopossiblySLE-relatedrdquo when SLE remained the more likely etiologydespite concomitant possible other etiologies that were notdeemed as causing the PN

Lupus patients with PN were matched by gender andSLE duration (12 months) at the time of PN diagnosisto SLE patients without evidence of PN Attention wasgiven to also match according to whether patients werefrom the University of Toronto Lupus Clinic inceptioncohort defined as first seen in the clinic within 12 monthsof diagnosis of SLE or from the noninception cohort

Data Collection

Demographic clinical and laboratory data were capturedwithin 1 year of the diagnosis of the PN for cases and asimilar reference point for the controls

The cases of PNs identified were further characterizedat the time of neurologic diagnosis in terms of age genderethnicity time from SLE diagnosis to onset of PN andthe period of follow-up For patients with more than onetype of PN the time of first event was recorded as the dateof onset of the PN Data included features of peripheralneurologic event acute versus chronic sensory andormotor involvement of peripheral nerves proximaldistallocation of the neurologic symptoms diffuse or localizedinvolvement and symmetry of the findings The periph-eral nerves affected were specified The electrophysiolog-ical study results were noted when available including thesigns of neuropathic changes denervation axonal neu-ropathy or peripheral nerve demyelination In additionresults of magnetic resonance imaging examination werereviewed for signs of nerve or nerve root enhancement asa marker of inflammatory demyelination and to rule outnerve root compression When available nerve and rele-vant muscle biopsy results were recorded The final neu-rologic diagnosis was also abstracted from the chart re-view

Manifestations of SLE at the time of diagnosis of PNwere recorded using 1982 ACR classification criteria (5)

ther lupus-related variables including the SLE Diseasectivity Index 2000 (SLEDAI-2K) and the Systemic Lu-us International Collaborating Clinics Damage Indexere also recorded within 3 months of PN onset and at

he reference point in time for patients without PN (7-9)Serologic investigations included platelet count anti-

ardiolipin antibodies lupus anticoagulant complementevels C3 and C4 and antibodies to double-stranded

NA at the time PN onset for the cases and at the equiv-lent reference point for the controls

Treatment and medications recorded included steroidulse steroid hydroxychloroquine immunosuppressiverugs cyclophosphamide azathioprine mycophenolateofetil intravenous immunoglobulins plasma exchange

r other relevant treatments were also recorded at the time

tls

R

P

AdCelpraw

1r2(d

P

ApAaampppe2ta(amTm1Swremap

lDpipv(Icv

npr(qnftpc

B Florica et al 205

of PN onset for the cases and at the equivalent referencepoint for the controls

To capture both the physicianrsquos and the patientrsquos as-sessment 2 outcome measures of PN SLE were used Thefirst measure was a physician-generated scale for an indi-vidual PN SLE event comparing the change in neuropa-thy status between the onset of the event and last fol-low-up appointment ldquoImprovedrdquo status was defined bychart review as at least 50 recovery of signs andorsymptoms ldquono responserdquo with less than 50 recovery orldquoworserdquo with progression of the condition

The second measure of the outcome was a patient eval-uation within 3 months of PN diagnosis of the impact ofthe condition on health-related quality of life using theMedical Outcome Study Short Form 36 (SF-36) (10) Itconsists of a self-administered instrument with 36 ques-tions that cover 8 dimensions of well-being physicalfunctioning role limitations due to physical problemsbodily pain vitality general health perceptions socialfunctioning role limitations due to emotional problemsand mental health These 8 scales weighted according tonormative data are scored from 0 to 100 higher scoresreflecting better health-related quality of life (1011)Two psychometrically based summary measures thephysical component summary (PCS) score and the men-tal component summary score (12) were derived fromthe SF-36 questionnaire and scores 48 are consideredimpaired Age- and gender-standardized scores were cal-culated using Canadian normative values (13)

Statistical Analysis

Data were analyzed using SAS statistical program version91 (SAS Institute Inc Cary NC) Descriptive statisticsincluding percentages mean SD or median and inter-quartile range were used Comparisons between demo-graphic and clinical characteristics of patients with SLE(SLE-related and possibly SLE-related) and non-SLEcauses of PN were done using unpaired Studentrsquos t test or2 test

In the case-control study the statistical significance ofhe differences in demographics clinical presentationaboratory markers treatment use and outcome was as-essed using conditional logistic regression test

ESULTS

atientsrsquo Characteristics

total of 1533 patients with SLE were included in theatabase registry of the University of Toronto Lupuslinic between January 1970 and May 2010 After the

lectronic search of the database 215 patients were se-ected for chart review and among those 207 (135)atients were confirmed to have at least 1 peripheral neu-ologic condition as defined by the ACR nomenclaturend case definition of these manifestations Eight patients

ere excluded due to incomplete data Among patients l

03 were part of the inception cohort and thus were en-olled within the first year of their diagnosis of SLE The07 patients with PN were 85 women with a meanSD) age of 445 (151) years and a mean (SD) diseaseuration of 83 (92) years at the time of diagnosis of PN

eripheral Nervous System Manifestations

total of 207 (135) patients experienced at least oneeripheral nervous system manifestation included in theCR nomenclature and case definitions of neuropsychi-tric events in SLE The mean (SD) follow-up periodfter PN diagnosis was 107 (96) years The most com-on PN observed was peripheral polyneuropathy with a

redominance of the sensory form present in 76 (367)atients and the sensory-motor variant in 39 (188)atients The majority of patients with polyneuropathyxperienced chronic peripheral polyneuropathy (40 of07 patients) lasting more than 2 months (14) Twenty-hree (111) patients had a peripheral mononeuropathynd 26 (125) had a cranial neuropathy Nineteen92) patients suffered from mononeuritis multiplexnd only 11 (53) were diagnosed with chronic inflam-atory demyelinating polyradiculoneuropathy (CIDP)wo patients had findings consistent with acute inflam-atory demyelinating polyradiculoneuropathy (AIDP)was SLE-related and the other was non-SLE-related

even patients were diagnosed with radiculopathy and 2ith plexopathy but the events were not considered SLE-

elated We did not observe cases of the remaining periph-ral nervous system manifestations included in ACR no-enclature and case definition there was no documented

utonomic neuropathy or myasthenia gravis among ouratientsAn asymmetric presentation of the peripheral neuro-

ogic manifestation was most commonly seen (593)istal weakness at the onset occurred in 342 of the

atients In the lower extremities the most commonlynvolved nerves were the sural nerve (552) and theeroneal nerve (539) Upper extremity neurologic in-olvements covered most frequently the median nerve373) and the ulnar nerve (304) The cranial nervesII V VI and VII were affected occasionally One patientould have experienced more than 1 peripheral nerve in-olvement at the same time

From the total number of SLE patients with peripheralervous system manifestations 125 (603) patients ex-erienced PN attributed to SLE (76 patients with SLE-elated PN and 49 with possible SLE-related PN) and 82396) patients had non-SLE-related PN The most fre-uent etiologies of non-SLE-related PN were compressiveeuropathy (nerve or root compression) in 35 (426)ollowed by medication toxicity in 23 (28) and hypo-hyroidism in 19 (231) Only 14 (17) patients haderipheral neurologic manifestations attributed to con-omitant diabetes mellitus Other causes of non-SLE-re-

ated PN included ethanol abuse paraproteinemia

sbd

rST


Sjoumlgrenrsquos syndrome uremia and viral hepatitis in a lim-ited number of patients

Demographic and clinical characteristics of patientswith SLE- and non-SLE-related PN are reported in Table1 Patients with SLE-related PN had significantly shorterSLE duration and tended to be younger compared withthose with non-SLE-related PN The ACR classificationcriteria were equally found in both groups of patientsexcept for a trend toward a higher prevalence of arthritis atthe time of neurologic diagnosis in patients with SLE-related PN than those with non-SLE-related PN Serolog-ical markers and the presence of antiphospholipid anti-bodies were similar between the 2 groups Howeverpatients with SLE-related PN had a significantly highermedian SLEDAI-2K (1100 Interquartile range 40-160) than those with non-SLE-related PN (50 Inter-quartile range 20-80 P 0001) When comparingonly definitely SLE-related PN with non-SLE-relatedPN the results were similar (data not shown)

The presentations with polyneuropathy either puresensory or the sensory motor variant were similarly dis-tributed in both SLE-related and non-SLE-related PNMononeuritis multiplex however was always SLE-re-lated in our patients after excluding other possible etiolo-gies Mononeuritis multiplex could occur at any time at

Table 1 Characteristics of Patients with SLE-Related and No

SLE(

Age (yr) 35SLE duration (yr) 6Arthritis [n ()] 4Skin rash [n ()]Central nervous system involvement [n ()] 1Renal [n ()] 4ANA 80 [n ()] 6Ds-DNA-positive (by Farr) [n ()] 4Positive antiphospholipid antibody [n ()] 2SLE-disease activity index [median (IQR)] 11SLICC damage index [median (IQR)] 1Electromyographynerve conduction Study

positive findings [n ()]7

Pure sensory polyneuropathy [n ()] 3Sensory-motor polyneuropathy [n ()] 2Mononeuritis Multiplex [n ()] 1Steroid treatment [n ()] 10Immunosuppressive treatment [n ()] 4Cyclophosphamide [n ()]Outcome-improved [n ()] 8SF-36 physical component summary score 35SF-36 mental component summary score 46

Results are reported as mean SD unless otherwise specified Comand P 005 is considered statistically significant difference

PN peripheral neuropathy SLE systemic lupus erythematosusANA was available in 118125 patients and 7782 patients in eaavailable in 102125 patients and 5282 patients respectively Ov101125 and 7282 patients in each group

the onset of SLE or later during its evolution Assessment r

of the health-related quality of life showed a similar PCSin both SLE and non-SLE-related PN groups (Table 1)

The electrophysiological investigations that were partof PN workup were more often performed in patientswith SLE-related PN and possibly SLE-related PN thanin those with non-SLE-related causes (87 versus 65 ofpatients) Electrophysiological studies were conductedwhen there were clinical signs of weakness but 23 of 61patients with pure sensory deficit on clinical examinationdid not undergo further electrophysiological testing andthe diagnosis was made on clinical grounds alone Themain findings on nerve conduction studies were signs ofaxonal neuropathy in the majority (78) of the patientswith no statistical differences among the SLE-relatedpossibly SLE-related and non SLE-related groups37(74) versus 23 (82) versus 24 (69) of patientsrespectively (Table 2) Only a small number of patients(n 10) underwent nerve biopsy to confirm the diagno-is all patients had perineural inflammatory infiltrate twoiopsies showed axonal degeneration and one biopsy in-icated demyelinationAs expected the treatment with steroids or pulse ste-

oids was used significantly more often for patients withLE-related PN than those with non-SLE-related PNhere was no difference between the two groups with

-Related Peripheral Neuropathy

ed PN Non-SLE-Related PNP Value25) (n 82)

144 386 154 01280 98 102 001

18 (24) 0092 (7) 100

10 (13) 06933 (43) 06134 (44) 03015 (29) 06917 (22) 095

160) 50 (20 80) 0000120) 10 (00 20) 039

34 (81) 020

30 (37) 00710 (12) 015

0 (0) 0000241 (79) 00415 (35) 019

1 (1) 004945 (55) 012

115 340 110 054112 419 130 008

between the 2 groups was done using logistic regression analysis

p within 3 months of PN diagnosis However dsDNA (Farr) wasf we report on ANA positivity since the diagnosis of SLE we have

n-SLE

-Relatn 1

2

4 2 (35)4 (7)8 (15)7 (39)1 (52)5 (44)6 (22)0 (400 (005 (89)

1 (25)5 (20)9 (15)2 (90)8 (47)9 (7)2 (66)4 1

parison

ch grouerall i

espect to the use of immunosuppressive medications and

There

B Florica et al 207

cyclophosphamide (Table 3) According to the physi-cianrsquos assessment the PN improved in 658 of patientswith SLE-related PN and 549 of patients with non-SLE-related PN and this was not significantly differentbetween the two groups

Case-Control Study

In our case-control study we were able to match (bygender and SLE duration) 197 of the SLE patients withPN to 197 control SLE patients without PN The meanSLE duration at the time of PN diagnosis was 87 yearsand the number of ACR criteria for SLE classification wassimilar in both groups (Table 4) In both groups mostpatients were female (863) and the majority were Cau-casian The age at SLE diagnosis was significantly higherin patients with PN and they were more likely to haveCNS involvement (142) compared with patients with-out PN (CNS involvement 66 P 002) Bothgroups had moderate global disease activity and minimalcumulative organ damage according to the median SLE-DAI 2K and Systemic Lupus International CollaboratingClinics Damage Index scores However the SLEDAIscore within three months of diagnosis of PN was bothstatistically and clinically significantly higher in patientswith PN with a median score of 80 versus a score of 60for the patients without PN (P 0007) with an averagedifference of two SLEDAI 2K units A subanalysis of SLE-DAI 2K scores without CNS component indicated nostatistical significant difference between the two groupsbut there was a trend toward a higher disease activity inpatients with PN 60 (40100) compared with those

Table 2 ElectromyographyNerve Conduction Study FindinSLE-Related Peripheral Neuropathy and Non-SLE-Related P

SLE-Related PN(n 54)

Axonal neuropathy N () 37 (74)Demyelinating neuropathy N () 12 (24)Mixed axonal and demyelinating

neuropathy N ()5 (9)

The results in Table 2 are reported as the number and percentagewho underwent EMGNCS (n 54 30 and 42 respectively) Thpatients in each group respectively

PN peripheral neuropathy SLE systemic lupus erythematosus

Table 3 Management and Outcome of Peripheral Neuropa

SLE-Related PN P(n 76)

Steroid treatment N () 67 (96)Pulse steroid N () 14 (20)Cyclophosphamide N () 8 (105)Outcomemdashimproved N () 50 (66)

Results are reported as number of patients ()


without PN 40 (2080) P 011 with a difference oftwo SLEDAI 2K units

There was no significant difference in lupus serologysuch as antinuclear antibody anti-double-stranded DNAantibody and antibodies to the extractable nuclear anti-gens (anti-Smith RNP RoSSA and LaSSB) or comple-ment levels between the two groups However specificnervous system antibodies such as anti-ribosomal PNMDA R2 and anti-neural antibodies are not routinelyassessed in our clinic Cases with PN were more likely toreceive treatment with steroids (74) than the controls(594 P 0003) and tended to be more frequently onimmunosuppressive treatment The health-related qual-ity of life measured using age- and gender-standardizedPCS and mental component summary scores revealed astatistically and clinically significantly lower PCS score forpatients with PN compared with patients with no PN(Table 4)

A subgroup analysis including only the definitely SLE-related PN and their controls (74 pairs) gave similar re-sults in terms of significantly higher SLEDAI 2K morefrequent CNS involvement more frequent steroid useand lower PCS score for the cases The only difference wasa statistically significant higher SLEDAI 2K even withoutthe CNS items for the cases (data not shown)

DISCUSSION

Peripheral nervous system involvement in SLE patients isa clinical entity associated with significant morbidity andpoor health-related quality of life Treating physicians areuncomfortable with the diagnosis and management of

Patients with SLE-Related Peripheral Neuropathy Possibleral Neuropathy

ible SLE-Related PN Non SLE-Related PNP Value(n 30) (n 42)

23 (82) 24 (69) 04708 (29) 8 (23) 08606 (20) 4 (10) 0292

nts with SLE-related possible SLE-related and non-SLE related PNNCS was diagnostic in 49 (91) 26 (87) and 34 (81) of

was no statistical difference between the groups of patients

SLE Patients

SLE-Related PN Non-SLE-Related PNP Value(n 49) (n 82)

35 (81) 41 (79) 00131 (3) 2 (4) 0011 (20) 1 (12) 0014

32 (65) 45 (55) 030

gs oferiphe

Poss

of patieis EMG

thy in

ossible

d to c


these manifestations since few studies have reported onthe peripheral nervous system complications of lupusPhysicians are too often left with limited data from a fewcase reports case series or small studies to rely on whentreating persons with lupus who have peripheral neurop-athy and this may delay their diagnosis and treatmentThis study is the first to investigate peripheral nervoussystem manifestations in a large cohort of SLE patientsWhile other studies have presented the prevalence of pe-ripheral neuropathy in SLE as part of NP SLE our studyfocused on PN prevalence its characteristics and its var-ious clinical manifestations

In our cohort 135 of SLE patients had at least onePN event This was a lower prevalence than the 32reported by Brey and coworkers (2) in 128 SLE patientswith mean disease duration of 8 years Most other studieson the prevalence of NPSLE included only a few featuresof peripheral nervous system involvement In an interna-tional multicenter study by Hanly and coworkers (15)158 (28) of 572 patients had NP SLE and only 61 to117 of patients had NP events that were SLE relatedIn that study (15) from a total of 242 NP events 95were presented as peripheral nervous system involvementwhich is consistent with our findings In 2 subsequentstudies (1617) with a larger sample size and in patients

Table 4 Demographic and Clinical Characteristics of PatienManifestations

CharacteristicsPat

Race [n ()]Caucasian 15Black 1Chinese 1Other 2

Age at SLE diagnosis (yr) 3Female [n ()] 17SLE duration (yr)ACR criteriaArthritis [n ()] 6Skin rash [n ()]Central nervous system involvement [n ()] 2Renal disease [n ()] 8SLE-disease activity index [median (IQR)] 8SLICC damage index [median (IQR)] 1Positive ds-DNA (Farr) [n ()] 6low C3 [n ()] 3low C4 [n ()] 3Antiphospholipid antibody [n ()] 4Platelet count 150 [n ()] 2Steroid treatment [n ()] 14Immunosuppressive treatment [n ()] 5SF-36 physical component summary score 3SF-36 mental component summary score 4

Results are reported as mean SD unless otherwise specified P PN peripheral neuropathy SLE systemic lupus erythematosus

Only 197 of 207 patients with PN described in text were matche

with up to 3 yearsrsquo disease duration 335 and 403

experienced at least one NP event of which 236 wasattributed to SLE and only 7 involved peripheral ner-vous system lower than what we observed in our studyThis may partly be explained by the shorter SLE durationof up to three years in these studies as opposed to 107years in our study Furthermore in those studies (15-17)the peripheral neuropathies that did not undergo electro-physiological confirmation study were excluded whichmay also underestimate the prevalence of PN Yet inother studies (1829) when electrophysiological studieswere performed the prevalence of PN in SLE was docu-mented as being as high as 21 with more symptomsversus 6 in healthy controls In another study McNich-oll and coworkers (19) reported nerve conduction abnor-malities in 33 of SLE patients at baseline and in 56 ofpatients at 2-yearsrsquo follow-up Both of these studies hadrelatively small sample sizes which makes them suscepti-ble to selection and ascertainment biases

The limitations of our study include the retrospectivereview of the characteristics of the peripheral neuropathywith the possibility of missing important information forthe accurate diagnosis of PN However all the data usedwere recorded prospectively in a predefined format andthe attribution to SLE or non-SLE was establishedthrough an additional detailed chart review Another lim-

h SLE with or without Peripheral Neurologic

ith PN Patients without PNP Value97) (n 197)

) 156 (80) 06811 (6)14 (7)15 (8)

149 317 141 00004) 170 (86) 10089 85 88 05620 55 19 084

) 45 (23) 01211 (12) 048

) 13 (7) 002) 90 (46) 030 140) 60 (20 90) 001 20) 00 (00 10) 018

) 62 (38) 089) 39 (21) 068) 39 (22) 089) 40 (20) 062) 19 (10) 034) 117 (59) 0002) 39 (20) 009113 383 112 004119 468 126 088

is considered statistically significant differencemerican College of Rheumatology

ontrol patients without PN

ts wit

ients w(n 1

9 (817 (9)3 (7)7 (4)65 0 (8687 55 0 (316 (7)8 (140 (41

0 (40

0 (000 (398 (207 (233 (225 (135 (743 (2750 47

005ACR A

itation is the fact that almost one half of the patients used

B Florica et al 209

in our analysis were not part of the inception cohort andnot seen from the onset of SLE So part of their diseasehistory may be missing including the PN initial eventsWe tried to account for this limitation by performing acase-control subanalysis and by matching patients fromeach category for the analysis of patients with or withoutPN A subgroup analysis of these patients gave similarfinal results in terms of clinical characteristics Finallythere was a possibility that the associated features in thosepatients with PN definitively due to SLE compared withthose due to other causes might have been unduly influ-enced by instances of PN designated as possibly due toPN However a subgroup analysis including only thedefinitely SLE-related PN and their controls gave similarresults Despite these limitations to our knowledge thisstudy is the only large study solely focused on the descrip-tion of peripheral neuropathy in SLE

An important contribution of our study was to charac-terize patients with different manifestation of PN Inkeeping with previous data (20) the most common clin-ical presentation of PN was a distal axonal sensory orsensory-motor polyneuropathy with acute or subacuteonset Most patients presented with late and relativelymild decreased sensation that initially involved the lowerextremities In our cohort of patients an asymmetricalinvolvement of the extremities was the most frequent pre-sentation and this is also consistent with previous reportsSural peroneal and median nerves were the most fre-quently involved

Mononeuropathies single or multiplex were the sec-ond most common presentation In most cases the onsetwas dramatic with sudden weakness in different nerveterritories Martinez-Taboada and coworkers (21) de-scribed 2 SLE patients with severe mononeuritic multi-plex secondary to necrotizing vasculitis of small- and me-dium-size vessels One patient presented with neurologicinvolvement at the onset of the disease and the other laterin the course of the disease after discontinuation of steroidand chloroquine treatment Matsuki and coworkers (22)reported a 61-year-old patient with weakness of the lowerextremities concomitant to onset of SLE and diagnosedwith mononeuritis multiplex

CIDP was another severe form of PN present in ourstudy The clinical impairment was even more severe withinability to walk due to proximal weakness Vina andcoworkers (23) reviewed a total of 13 patients with CIDPreported in the literature from 1950 to 2004 A majority(913) presented with their CIDP before or at the onset ofSLE 10 of 13 had weakness in both upper and lowerextremities and also had dermatological and arthriticmanifestations of SLE Hantson and coworkers (24) re-ported a severe form of CIDP presenting with a Guillain-Barreacute syndrome-like picture in one patient who devel-oped rapidly progressive quadriplegia and acuterespiratory failure AIDP an ascending motor radiculo-neuropathy that resembles Guillain-Barreacute syndrome was

a relatively rare condition in our cohort observed in only

two patients AIDP in SLE is only presented in the liter-ature as case reports (24-26)

A major challenge to clinicians is whether one can at-tribute these neurologic events to SLE or not With theexception of the association between antiphospholipidantibodies and cerebrovascular events most of NPSLEmanifestations do not have specific immunopathogenicetiologies or mechanisms and alternative etiologies shouldbe considered and ruled out before attributing them toSLE The ACR nomenclature and case definition ofNPSLE is helpful in this direction (4) Hanly and cowork-ers (15-17) in an international multicenter inception co-hort of SLE patients classified all PNs as not attributableto SLE if there was no electrophysiologic confirmationHowever ACR recommends that the diagnosis should bebased on clinical findings andor electrophysiological test-ing This may explain why their reported prevalence ofPN was lower than the prevalence in our study and may beunderestimated However the process of attribution ofneurologic events to SLE or not is not always an easyclear-cut process For example compression or entrap-ment neuropathies frequent causes of PN may be theresult of local inflammation involving the adjacent jointstructures and although not the direct result of autoim-mune process they could still be considered attributableto SLE PN could also present as complications of otherorgan involvement in SLE (renal failure liver failure)nutritional deficiency or even as side effects of differentdrugs (steroid-induced diabetes antimalarial drugs aza-thioprine)

A close analysis of patients with SLE-related versusnon-SLE-related PNs indicated shorter disease durationat the time of neurologic diagnosis in patients with SLE-related PN As expected mononeuritic multiplex wasmore likely to be SLE-related and patients with SLE-related PN were more likely to have active disease at thetime of diagnosis of the PN but there was no differencebetween the two groups with respect to SLE immunemarkers platelets count or presence of antiphospholipidantibodies This was consistent with the findings of Hanlyand coworkers (27) Psychosis was the only manifestationassociated with antiribosomal P antibody and ischemiccerebrovascular disease was associated with the presenceof lupus anticoagulant (27)

In our patients there were also no significant differ-ences between electrophysiological findings in the pre-specified groups of patients demonstrating the difficultyof differentiating the attribution to SLE or other causesbased on nerve conduction studies The most frequentfindings were signs of axonal neuropathy The same ax-onal neuropathies signs were reported as the most fre-quent occurrence by Brey and coworkers (2) and Huynhand coworkers (28)

Although peripheral neuropathy in SLE may be verydisabling affecting the quality of life of relatively youngpeople there are no large randomized controlled trials to

evaluate this potentially treatable condition In this study


PN resulted in impaired quality of life especially in thephysical component regardless of the attribution to SLEor non-SLE A previous study reporting the NPSLE over-all found a better outcome for the events attributed toSLE (16) However the mean study follow-up period ofthese patients was relatively short (21 months) In termsof treatment Barile-Fabris and coworkers (29) random-ized 32 patients with NPSLE to receive oral prednisoneand methylprednisolone IV or oral prednisone and cyclo-phosphamide IV The response rate for all NPSLE man-ifestations was significantly higher in the cyclophosph-amide group Only 7 of these patients presented withperipheral nerves involvement and the response was betterin this very small group for patients who received cyclo-phosphamide The treatment of vasculitic peripheral neu-ropathies severe neurologic manifestations of primaryvasculitis and connective tissue diseases was analyzed in aretrospective study by Mathew and coworkers (30) From106 cases 94 used a corticosteroid-based treatment and54 patients received cyclophosphamide One-year sur-vival was 903 and 72 of the patients had a goodoutcome with subsequent improvement of their periph-eral neuropathy Ten percent of the patients relapsed withtheir PN within 1 year but only 1 of them had been oncyclophosphamide treatment

In our case-control study comparing patients with andwithout PN patients with PN were older at the time ofSLE diagnosis had more frequent CNS involvement hadhigher disease activity score and were more likely to betreated with steroids and immunosuppressive medica-tions The age difference at diagnosis may have contrib-uted to accumulation of comorbid conditions and thedevelopment of PN In addition SLE patients are atgreater risk of developing diabetes renal abnormalitiesand malabsorption leading to nutritional deficiencies thatcould all contribute to the development of PN A morefrequent CNS involvement and a higher disease activityin patients with PN suggest an autoimmune etiology forthe PN manifestations in SLE with a predilection of theimmune response toward neurological tissue It remainsto be determined whether any of these clinical character-istics could predict the onset of PN in SLE

CONCLUSION

Although the ACR criteria for classification of SLE do notinclude PN they are recognized as manifestations of thedisease and included in ACR case definitions for neuro-psychiatric syndromes in SLE In our cohort of SLE pa-tients PN was a prevalent condition in 135 of ourpatients and was most often seen in those with an olderage at SLE diagnosis and with CNS manifestation and anactive disease at the time of the diagnosis of the PNRegardless of the attribution to SLE or non-SLE-relatedfactors the patients with peripheral neuropathies have animpaired quality of life reflected mainly by a significantly

low physical component score of the SF-36 health-related

quality-of-life questionnaire Large randomized controlledtrials are needed to determine which treatments should beused to treat peripheral neuropathic manifestations in SLEand to improve the quality of life and long-term outcome ofthese patients

REFERENCES

1 Ainiala H Hietaharju A Loukkola J Peltola J Korpela MMetsaumlnoja R et al Validity of the new American College of Rheu-matology criteria for neuropsychiatric lupus syndromes a popu-lation-based evaluation Arthritis Rheum 200145419-23

2 Brey RL Holiday SL Saklad AR Navarrete MG Hermosillo-RomoD Stallworth CL et al Neuropsychiatric syndromes in lupus prev-alence using standardized definitions Neurology 2002581214-20

3 Hanly JG McCurdy G Fougere L Douglas JA Thompson KNeuropsychiatric events in systemic lupus erythematosus attribu-tion and clinical significance J Rheumatol 2004312156-62

4 The American College of Rheumatology nomenclature and case def-initions for neuropsychiatric lupus syndromes Arthritis Rheum199942(4)599-608

5 Tan EM Cohen AS Fries JF Masi AT McShane DJ RothfieldNF et al The 1982 revised criteria for the classification of sys-temic lupus erythematosus Arthritis Rheum 1982251271-7

6 Hochberg MC Updating the American College of Rheumatologyrevised criteria for the classification of systemic lupus erythemato-sus Arthritis Rheum 199740(9)1725

7 Bombardier C Gladman DD Urowitz MB Caron D ChangCH Derivation of the SLEDAI A disease activity index for lupuspatients The Committee on Prognosis Studies in SLE ArthritisRheum 199235630-40

8 Gladman D Ginzler E Goldsmith C Fortin P Liang M UrowitzMB The development and initial validation of the Systemic Lu-pus International Collaborating ClinicsAmerican College ofRheumatology damage index for systemic lupus erithematosusArthritis Rheum 199639363-9

9 Gladman DD Ibantildeez D Urowitz MB Systemic lupus erythemato-sus disease activity index 2000 J Rheumatol 200229(2)288-91

10 Ware JE Sherbourne CD The MOS 36-item short-form healthsurvey (SF-36) I Conceptual framework and item selection MedCare 199230473-83

11 Wachtel T Piette J Mor V Quality of life in persons with HIVinfection measurement by the Medical Outcomes Study instru-ment Ann Intern Med 1992116129-37

12 Ware JE Jr Kosinski M SF-36 physical and mental health sum-mary scales A manual for users of Version 1 2nd ed Lincoln RIQuality Metric Incorporated 2001

13 Hopman WM Towheed T Anastassiades T Tenenhouse APoliquin S Berger C et al and The Canadian Multicentre Os-teoporosis Study Research Canadian normative data for theSF-36 health survey CMAJ 2000163(3)1

14 Leger JM Diagnosis of chronic neuropathy J Neurol 1999 246(3)156-61

15 Hanly JG Urowitz MB Sanchez-Guerrero J Bae SC Gordon CWallace DJ et al Neuropsychiatric events at the time of diagnosisof systemic lupus erythematosus An international inception co-hort study Arthritis Rheum 200756265-73

16 Hanly JG Urowitz MB Su L Sanchez-Guerrero J Bae SCGordon C et al Short-term outcome of neuropsychiatricevents in systemic lupus erythematosus upon enrollment intoan international inception cohort study Arthritis Rheum200859721-9

17 Hanly JG Urowitz MB Su L Bae SC Gordon C Wallace DJ etal for the Systemic Lupus International Collaborating Clinics(SLICC) Prospective analysis of neuropsychiatric events in aninternational disease inception cohort of patients with systemic

lupus erythematosus Ann Rheum Dis 201069529-35

2

2

2

2

2

3

B Florica et al 211

18 Omdal R Mellgren SI Husby G Salvesen R Henriksen OATorbergsen T A controlled study of peripheral neuropathy insystemic lupus erythematosus Acta Neurol Scand 199388(1)41-6

19 McNicholl JM Glynn D Mongey AB Hutchinson M Bresni-han B A prospective study of neurophysiologic neurologic andimmunologic abnormalities in systemic lupus erythematosusJ Rheumatol 199421(6)1061-6

20 Rosenbaum R Neuromuscular complications of connective tissuediseases Muscle Nerve 200124154-69

21 Martinez-Taboada VM Blanco Alonso R Armona J Fernandez-Sueiro JL Gonzales Vela C Rodriguez-Valverde V Mononeuritismultiplex in systemic lupus erythematosus response to pulse in-travenous cyclophosphamide Lupus 1996574-6

22 Matsuki Y Hidaka T Matsumoto M Fukushima K Suzuki KSystemic lupus erythematosus demonstrating anti-GM 1 anti-body with sudden onset of drop foot as the initial presentationIntern Med 1999 38(9)729-32

23 Vina ER Fang AJ Wallace DJ Weisman MH Chronic inflamma-tory demyelinating polyneuropathy in patients with SLE prognosisand outcome Semin Arthritis Rheum 200535(3)175-84

24 Hantson P Kevers L Fabien N Van den Bergh P Acute-onset

chronic inflammatory demyelinating polyneuropathy with cranial

nerve involvement dysautonomia respiratory failure andautoantibodies Muscle Nerve 2010 41(3)423-426

5 Agarwal AK Goel A Rohtagi A Dudeja RK Kumar A Kalra SAcute inflammatory polyneuropathy in systemic lupus erythema-tosus JIACM 20056(4)334-6

6 Hsu TY Wang SH Kuo CF Chiu TF Chang YC Acute inflam-matory demyelinating polyneuropathy as the initial presentationof lupus Am J Emerg Med 200927(7)900e3-5

7 Hanly JG Urowitz MB Siannis F Farewell V Gordon C BaeS et al Autoantibodies and neuropsychiatric events at the timeof systemic lupus erythematosus diagnosis results from an in-ternational inception cohort study Arthritis Rheum 200858843-53

8 Huynh C Ho S Fong K Cheung RTF Mok C Lau C Periph-eral neuropathy in systemic lupus erythematosus J Clin Neuro-physiol 199916(2)164-8

9 Barile-Fabris L Ariza-Andraca R Olguiacuten-Ortega L Jara LJFraga-Mouret A Miranda-Limoacuten JM et al Controlled clinicaltrial of IV cyclophosphamide versus IV methyl-prednisolone insevere neurological manifestations in systemic lupus erythemato-sus Ann Rheum Dis 200564620-5

0 Mathew L Talbot K Love S Puvanarajah S Donaghy M Treat-ment of vasculitic peripheral neuropathy a retrospective analysis

of outcome QJM 2007100(1)41-51

OApwt

clDa

pdm


with many studies reporting on their prevalence clinicalmanifestations and possible pathogenic mechanismsThe peripheral nervous system manifestations have onthe other hand received little attention despite their po-tential significant impact on the patientrsquos quality of life

In the literature studies on the peripheral nervous sys-tem (PN) manifestations are mostly represented by casereports or case series with a small number of patients Inaddition the PN has not been well characterized in SLEin terms of onset severity clinical associations and elec-trophysiological findings and there is no guideline fortheir treatment Therefore the primary objective of ourstudy was to characterize PN in SLE with respect to thepatientrsquos clinical lupus manifestations serologic markersand electrophysiological findings A secondary objectivewas to determine whether any of these characteristics areassociated with the development of PN in SLE

POPULATION AND METHODS

Subjects

Subjects for this study were selected from the Universityof Toronto Lupus Clinic database one of the CanadianNetwork for Improved Outcomes in SLE centers that hascollected clinical and laboratory data prospectively andaccording to a standard protocol since 1970 All patientsfulfilled the ACR classification criteria for SLE or fulfilled3 criteria with either skin or kidney biopsy evidence ofSLE (56) The University of Toronto Lupus Clinic hascontinuous approval from the University Health Net-work Research Ethics Board and informed consent wasobtained from all patients for accessing their data for re-search studies

For an accurate capture and description of the PNmanifestations in SLE the database was searched for pa-tients with distal or proximal weakness andor sensoryloss diagnosed polyneuropathies mononeuritis simple ormultiplex cranial neuropathy plexopathy or radiculopa-thy and abnormal electrophysiology A further chart re-view was performed for the identified patients to confirmclinical findings determine the contributing factors anddocument the diagnostic investigations treatments andoutcome Peripheral neuropathies were defined accordingto the ACR nomenclature and case definitions for neuro-psychiatric syndromes in SLE (4) found online at httpwwwrheumatologyorgpublicationsar1999499

Attribution to SLE was considered when PN was pres-ent in the absence of other more common etiologies andwhen the rheumatologist andor neurologist listed thisattribution as the etiology of the PN The decision wasbased on the clinical evaluation and subsequent investiga-tions included in the ACR nomenclature and case defini-tions for each of the peripheral nervous system syndromesin SLE and after exclusion criteria were considered andassociation factors documented (4) PN secondary to dia-betes mellitus hypothyroidism vitamin B12 deficiency in-

fectious causes Sjoumlgrenrsquos syndrome alcohol abuse drug tox- o

icity compression syndromes and inherited neuropathieswere categorized as ldquonon-SLE-relatedrdquo PN were ldquopossiblySLE-relatedrdquo when SLE remained the more likely etiologydespite concomitant possible other etiologies that were notdeemed as causing the PN

Lupus patients with PN were matched by gender andSLE duration (12 months) at the time of PN diagnosisto SLE patients without evidence of PN Attention wasgiven to also match according to whether patients werefrom the University of Toronto Lupus Clinic inceptioncohort defined as first seen in the clinic within 12 monthsof diagnosis of SLE or from the noninception cohort

Data Collection

Demographic clinical and laboratory data were capturedwithin 1 year of the diagnosis of the PN for cases and asimilar reference point for the controls

The cases of PNs identified were further characterizedat the time of neurologic diagnosis in terms of age genderethnicity time from SLE diagnosis to onset of PN andthe period of follow-up For patients with more than onetype of PN the time of first event was recorded as the dateof onset of the PN Data included features of peripheralneurologic event acute versus chronic sensory andormotor involvement of peripheral nerves proximaldistallocation of the neurologic symptoms diffuse or localizedinvolvement and symmetry of the findings The periph-eral nerves affected were specified The electrophysiolog-ical study results were noted when available including thesigns of neuropathic changes denervation axonal neu-ropathy or peripheral nerve demyelination In additionresults of magnetic resonance imaging examination werereviewed for signs of nerve or nerve root enhancement asa marker of inflammatory demyelination and to rule outnerve root compression When available nerve and rele-vant muscle biopsy results were recorded The final neu-rologic diagnosis was also abstracted from the chart re-view

Manifestations of SLE at the time of diagnosis of PNwere recorded using 1982 ACR classification criteria (5)

ther lupus-related variables including the SLE Diseasectivity Index 2000 (SLEDAI-2K) and the Systemic Lu-us International Collaborating Clinics Damage Indexere also recorded within 3 months of PN onset and at

he reference point in time for patients without PN (7-9)Serologic investigations included platelet count anti-

ardiolipin antibodies lupus anticoagulant complementevels C3 and C4 and antibodies to double-stranded

NA at the time PN onset for the cases and at the equiv-lent reference point for the controls

Treatment and medications recorded included steroidulse steroid hydroxychloroquine immunosuppressiverugs cyclophosphamide azathioprine mycophenolateofetil intravenous immunoglobulins plasma exchange

r other relevant treatments were also recorded at the time

tls

R

P

AdCelpraw

1r2(d

P


lDpipv(Icv

npr(qnftpc

B Florica et al 205







ESULTS
















sbd

rST






SLE(












144 386 154 01280 98 102 001

18 (24) 0092 (7) 100

10 (13) 06933 (43) 06134 (44) 03015 (29) 06917 (22) 095

160) 50 (20 80) 0000120) 10 (00 20) 039

34 (81) 020

30 (37) 00710 (12) 015

0 (0) 0000241 (79) 00415 (35) 019

1 (1) 004945 (55) 012

115 340 110 054112 419 130 008



n-SLE

-Relatn 1

2

4 2 (35)4 (7)8 (15)7 (39)1 (52)5 (44)6 (22)0 (400 (005 (89)

1 (25)5 (20)9 (15)2 (90)8 (47)9 (7)2 (66)4 1

parison

ch grouerall i


There

B Florica et al 207


Case-Control Study
















DISCUSSION




23 (82) 24 (69) 04708 (29) 8 (23) 08606 (20) 4 (10) 0292



SLE Patients


35 (81) 41 (79) 00131 (3) 2 (4) 0011 (20) 1 (12) 0014

32 (65) 45 (55) 030

gs oferiphe

Poss

of patieis EMG

thy in

ossible

d to c





CharacteristicsPat










) 156 (80) 06811 (6)14 (7)15 (8)

149 317 141 00004) 170 (86) 10089 85 88 05620 55 19 084

) 45 (23) 01211 (12) 048

) 13 (7) 002) 90 (46) 030 140) 60 (20 90) 001 20) 00 (00 10) 018

) 62 (38) 089) 39 (21) 068) 39 (22) 089) 40 (20) 062) 19 (10) 034) 117 (59) 0002) 39 (20) 009113 383 112 004119 468 126 088



ts wit

ients w(n 1

9 (817 (9)3 (7)7 (4)65 0 (8687 55 0 (316 (7)8 (140 (41

0 (40

0 (000 (398 (207 (233 (225 (135 (743 (2750 47

005ACR A


B Florica et al 209















CONCLUSION




REFERENCES



















2

2

2

2

2

3

B Florica et al 211

















tls

R

P

AdCelpraw

1r2(d

P


lDpipv(Icv

npr(qnftpc

B Florica et al 205







ESULTS
















sbd

rST






SLE(












144 386 154 01280 98 102 001

18 (24) 0092 (7) 100

10 (13) 06933 (43) 06134 (44) 03015 (29) 06917 (22) 095

160) 50 (20 80) 0000120) 10 (00 20) 039

34 (81) 020

30 (37) 00710 (12) 015

0 (0) 0000241 (79) 00415 (35) 019

1 (1) 004945 (55) 012

115 340 110 054112 419 130 008



n-SLE

-Relatn 1

2

4 2 (35)4 (7)8 (15)7 (39)1 (52)5 (44)6 (22)0 (400 (005 (89)

1 (25)5 (20)9 (15)2 (90)8 (47)9 (7)2 (66)4 1

parison

ch grouerall i


There

B Florica et al 207


Case-Control Study
















DISCUSSION




23 (82) 24 (69) 04708 (29) 8 (23) 08606 (20) 4 (10) 0292



SLE Patients


35 (81) 41 (79) 00131 (3) 2 (4) 0011 (20) 1 (12) 0014

32 (65) 45 (55) 030

gs oferiphe

Poss

of patieis EMG

thy in

ossible

d to c





CharacteristicsPat










) 156 (80) 06811 (6)14 (7)15 (8)

149 317 141 00004) 170 (86) 10089 85 88 05620 55 19 084

) 45 (23) 01211 (12) 048

) 13 (7) 002) 90 (46) 030 140) 60 (20 90) 001 20) 00 (00 10) 018

) 62 (38) 089) 39 (21) 068) 39 (22) 089) 40 (20) 062) 19 (10) 034) 117 (59) 0002) 39 (20) 009113 383 112 004119 468 126 088



ts wit

ients w(n 1

9 (817 (9)3 (7)7 (4)65 0 (8687 55 0 (316 (7)8 (140 (41

0 (40

0 (000 (398 (207 (233 (225 (135 (743 (2750 47

005ACR A


B Florica et al 209















CONCLUSION




REFERENCES



















2

2

2

2

2

3

B Florica et al 211

















sbd

rST






SLE(












144 386 154 01280 98 102 001

18 (24) 0092 (7) 100

10 (13) 06933 (43) 06134 (44) 03015 (29) 06917 (22) 095

160) 50 (20 80) 0000120) 10 (00 20) 039

34 (81) 020

30 (37) 00710 (12) 015

0 (0) 0000241 (79) 00415 (35) 019

1 (1) 004945 (55) 012

115 340 110 054112 419 130 008



n-SLE

-Relatn 1

2

4 2 (35)4 (7)8 (15)7 (39)1 (52)5 (44)6 (22)0 (400 (005 (89)

1 (25)5 (20)9 (15)2 (90)8 (47)9 (7)2 (66)4 1

parison

ch grouerall i


There

B Florica et al 207


Case-Control Study
















DISCUSSION




23 (82) 24 (69) 04708 (29) 8 (23) 08606 (20) 4 (10) 0292



SLE Patients


35 (81) 41 (79) 00131 (3) 2 (4) 0011 (20) 1 (12) 0014

32 (65) 45 (55) 030

gs oferiphe

Poss

of patieis EMG

thy in

ossible

d to c





CharacteristicsPat










) 156 (80) 06811 (6)14 (7)15 (8)

149 317 141 00004) 170 (86) 10089 85 88 05620 55 19 084

) 45 (23) 01211 (12) 048

) 13 (7) 002) 90 (46) 030 140) 60 (20 90) 001 20) 00 (00 10) 018

) 62 (38) 089) 39 (21) 068) 39 (22) 089) 40 (20) 062) 19 (10) 034) 117 (59) 0002) 39 (20) 009113 383 112 004119 468 126 088



ts wit

ients w(n 1

9 (817 (9)3 (7)7 (4)65 0 (8687 55 0 (316 (7)8 (140 (41

0 (40

0 (000 (398 (207 (233 (225 (135 (743 (2750 47

005ACR A


B Florica et al 209















CONCLUSION




REFERENCES



















2

2

2

2

2

3

B Florica et al 211

















There

B Florica et al 207


Case-Control Study
















DISCUSSION




23 (82) 24 (69) 04708 (29) 8 (23) 08606 (20) 4 (10) 0292



SLE Patients


35 (81) 41 (79) 00131 (3) 2 (4) 0011 (20) 1 (12) 0014

32 (65) 45 (55) 030

gs oferiphe

Poss

of patieis EMG

thy in

ossible

d to c





CharacteristicsPat










) 156 (80) 06811 (6)14 (7)15 (8)

149 317 141 00004) 170 (86) 10089 85 88 05620 55 19 084

) 45 (23) 01211 (12) 048

) 13 (7) 002) 90 (46) 030 140) 60 (20 90) 001 20) 00 (00 10) 018

) 62 (38) 089) 39 (21) 068) 39 (22) 089) 40 (20) 062) 19 (10) 034) 117 (59) 0002) 39 (20) 009113 383 112 004119 468 126 088



ts wit

ients w(n 1

9 (817 (9)3 (7)7 (4)65 0 (8687 55 0 (316 (7)8 (140 (41

0 (40

0 (000 (398 (207 (233 (225 (135 (743 (2750 47

005ACR A


B Florica et al 209















CONCLUSION




REFERENCES



















2

2

2

2

2

3

B Florica et al 211

















d to c





CharacteristicsPat










) 156 (80) 06811 (6)14 (7)15 (8)

149 317 141 00004) 170 (86) 10089 85 88 05620 55 19 084

) 45 (23) 01211 (12) 048

) 13 (7) 002) 90 (46) 030 140) 60 (20 90) 001 20) 00 (00 10) 018

) 62 (38) 089) 39 (21) 068) 39 (22) 089) 40 (20) 062) 19 (10) 034) 117 (59) 0002) 39 (20) 009113 383 112 004119 468 126 088



ts wit

ients w(n 1

9 (817 (9)3 (7)7 (4)65 0 (8687 55 0 (316 (7)8 (140 (41

0 (40

0 (000 (398 (207 (233 (225 (135 (743 (2750 47

005ACR A


B Florica et al 209















CONCLUSION




REFERENCES



















2

2

2

2

2

3

B Florica et al 211

















B Florica et al 209















CONCLUSION




REFERENCES



















2

2

2

2

2

3

B Florica et al 211




















CONCLUSION




REFERENCES



















2

2

2

2

2

3

B Florica et al 211

















2

2

2

2

2

3

B Florica et al 211

















Documents

Peripheral Neuropathy in Patients with Systemic Lupus Erythematosus