hypokalemic paralysis due to primary sjögren syndrome

Case ReportHypokalemic Paralysis due to Primary Sjoumlgren SyndromeCase Report and Review of the Literature

A Garza-Alpirez A C Arana-Guajardo J A Esquivel-ValerioM A Villarreal-Alarcoacuten and D A Galarza-Delgado

Servicio de Reumatologıa Departamento de Medicina Interna Hospital Universitario ldquoDr Jose Eleuterio GonzalezrdquoUniversidad Autonoma de Nuevo Leon Monterrey NL Mexico

Correspondence should be addressed to A C Arana-Guajardo anaaranaggmailcom

Received 29 March 2017 Revised 14 June 2017 Accepted 2 July 2017 Published 1 August 2017

Academic Editor Syuichi Koarada

Copyright copy 2017 A Garza-Alpirez et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

Tubulointerstitial nephritis (TIN) is the main renal involvement associated with primary Sjogren syndrome (pSS) TIN canmanifest as distal renal tubular acidosis (RTA) nephrogenic diabetes insipidus proximal tubular dysfunction and others Wepresent a 31-year-old female with hypokalemic paralysis due to distal RTA (dRTA) She received symptomatic treatment andhydroxychloroquinewith a good responseThere is insufficient information onwhether to perform a kidney biopsy in these patientsor notThe evidence suggests that there is an inflammatory background and therefore a potential serious affection to these patientssuch as hypokalemic paralysis We found 52 cases of hypokalemic paralysis due to dRTA in pSS patients The majority of thosepatients were treated only with symptomatic medication Patients who received corticosteroids had stable evolution even thoughthey did not have another symptomatology With such heterogeneous information prospective studies are needed to assess thevalue of adding corticosteroids as a standardized treatment of this manifestation

1 Introduction

Sjogrenrsquos syndrome is an autoimmune disease with glandular(salivary and lacrimal) and extraglandular (neurologic renalhepatic respiratory vascular and cutaneous) manifestationsTubulointerstitial nephritis (TIN) is the main renal involve-ment associated with primary Sjogren syndrome (pSS) TINcan manifest as distal renal tubular acidosis (RTA) nephro-genic diabetes insipidus proximal tubular dysfunction andothers [1] of which RTA is the main clinical presentation[2] RTA has been reported in 43 to 9 of pSS patients itis more common in middle-aged women and two-thirds ofthem will develop symptoms [2 3] Hypokalemic paralysis isthe initial symptom in seven percent of patients with Sjogrenrsquossyndrome [4] We present a case of paralysis due to RTA in apSS patient and also discuss the treatment in these patients

2 Case Report

A 31-year-old female presented to the emergency roomdue toa 3-day history of progressive weakness and pain of the upper

and lower extremities until walking was impossible Twodays before admission cramps and generalized dysesthesiaswere evidenced On admission the patient presented milddyspnea Her past medical record was significant for pol-yarthralgias in carpal metacarpophalangeal and proximalinterphalangeal joints and dry mouth for the past threemonths She denied use of alcohol illicit drugs or herbalmedicines Her vital signs on admission were a temperatureof 363∘C a heart rate of 54 beats per minute a respiratoryrate of 20 breaths per minute oxygen saturation of 97at room air capillary blood glucose of 103 gdL and bloodpressure of 10060mmHg On physical examination thedeep tendon reflexes were globally diminished her musclestrength both proximal and distal was 35 on Lovettrsquos scaleand her tongue was dry and the infralingual salivary poolingwas absent Remarkable laboratory tests are shown in Table 1A panoramic photo of minor salivary gland biopsy is shownin Figure 1With all lab results a distal RTA (dRTA) diagnosisdue to pSS was made Hypokalemia and metabolic acido-sis were treated with intravenous potassium chloride and

HindawiCase Reports in RheumatologyVolume 2017 Article ID 7509238 7 pageshttpsdoiorg10115520177509238

2 Case Reports in Rheumatology

Table 1 Laboratory investigation

Laboratory investigation ResultCBC Hemoglobin 147 gdL WBC 87 times 103 lymphocytes 0683 times 103 platelets 159 K120583LSerum electrolytes Sodium 1382mmolL potassium 27mmolL chloride 101mmolLSerum chemistry Glucose 123mgdL creatinine 08mgdL urea nitrogen 13mgdLLiver panel AST 19 IUL ALT 13 IUL albumin 42 gdL total bilirubin 07mgdLUrinalysis pH 8 leucocytes 0ndash2HPF erythrocytes 0HPF tubular cells 0HPF

Urinary electrolytes Sodium 114mmolL potassium 32mmolL chloride 573mmolL creatinine318mgdL

Urinary anion gap 76mmolLBlood gas pH 712 HCO

3 11mmolL pO

2 31mmHg pCO

2 37mmHg saturation 37

Serum anion gap 10mEqLThyroid panel TSH 206120583IUmL free T4 094 ngdLAcute phase reactants ESR 31mmh CRP lt 05mgLVirus panel HIV-negative HBV-negative HCV-negativeRheumatoid factor IgM 1557 IUmL IgG 67 IUmL IgA 122 IUmLANAs by IFA 1 5120 fine speckledSSASSB by ELISA 200141967 IUmLUnstimulated whole saliva flow withoutanesthesia 14mL15 minutes

Minor salivary gland biopsylowast Positive focus score of 5Schirmerrsquos test Right eye 7mm left eye 10mmlowastAccording to [5]

Figure 1 A panoramic photo of minor salivary gland biopsy Achronic lymphocyte focal sialadenitis was observed

sodium bicarbonate Then we initiated hydroxychloroquineThe patient was discharged and we followed her up in ourclinic every two months for the next eight months She wasreported to be asymptomatic with the use of potassium citrateonly

3 Discussion

A recent set of classification criteria for pSSwere published bytheACREULAR in 2016 [6] and this applies to the individualthat has a score of ge4 According to this the diagnosis ofthis autoimmune disease was made in our patient (labialsalivary gland with a focus score of ge1 anti-SSA positive andan unstimulated whole saliva flow of less than 01mLmin)Renal involvement in pSS is the result of two distinct patho-physiological processes TIN and glomerulopathy [1] The

tubulointerstitial inflammation is the most common renallesion described by Talal et al [7] dRTAprevalence fluctuatesbetween 5 and 70 according to population studies [4 8 9]dRTA can be classified as complete or incomplete the formeris characterized bymetabolic acidosis withmorning urine pHgt 55 and a positive urinary anion gap The incomplete formpresents with normal serum bicarbonate levels but urinarypH fails to fall to lt53 after ammonium chloride loading[10] The pathogenic mechanism of this complication is notcompletely understood Antibodies to vacuolar H+-ATPaseand anion exchanger 1 as well as antibodies to carbonicanhydrase II have been implicated in the pathogenesis[11ndash13] Another hypothesis is a defective S-phase-kinase-associated protein-1 a component of the regulator of theATPase of vacuolar and endosomal membranes that couldinduce a defective V-ATPase assembly [14] Also a possiblerelation between antibodies anti-SSARo and dRTA has beendescribed as one pathogenicmechanism of development [15]

Hypokalemia is the most common electrolyte abnormal-ity in patients with dRTAThe causes of hypokalemia includedecreased distal tubular Na delivery secondary hyperaldos-teronism defective H-KATPase and bicarbonaturia [16]Hypokalemic paralysis may precede sicca syndrome fromthree months to four years in patients with a final diagnosisof pSS [17 18]

Renal biopsy is not mandatory in these patients [2] butit may help us evidence the inflammatory mechanisms thattrigger the disease As has been demonstrated by Evans et alin twelve patients with TIN secondary to pSS they observedCD4+ T-cell predominance in biopsies similar to those seen

Case Reports in Rheumatology 3

Table2Com

parativ

etreatmentinhypo

kalemicparalysis

duetodistalRT

Ain

Sjogrensynd

romep

atients

Reference

Type

ofstu

dyNum

bero

fpatie

nts

Age

(years)

mean

Extragland

ular

manifesta

tions

besid

esdR

TATreatm

ent

Follo

w-up

Outcome

Goroshi

etal

Case

serie

s13

331

Arthritisarthralgiasvasculitis

Symptom

atic

Extragland

ularH

CQandMTX

28years(05ndash4)

No

improvem

entin

redu

ctionof

HCO3or

Krequ

irements

Khadgaw

atetal

Repo

rtof

cases

2205

No

Symptom

atic

Not

repo

rted

mdash

Soyetal

Case

repo

rt1

39Arthralgiamyalgianephrolith

iasis

Symptom

aticand

methylpredn

isolone

2years

Stableclinical

evolution

Chengetal

Repo

rtof

cases

276

Nephrocalcino

sisSymptom

aticand

prednisolone

5ndash12

mon

ths

Stableclinical

evolution

Kawashimae

tal

Case

repo

rt1

39Oste

omalaciainterstitia

lnephritis

Symptom

aticand

prednisolone

2years

Relapsea

fter

stopp

ing

treatment

Com

eretal

Case

repo

rt1

43No

Symptom

atic

2years

Stableclinical

evolution

Seira

fianetal

Case

repo

rt1

64No

Symptom

atic

prednisoloneand

HCQ

Not

repo

rted

mdash

Vaidya

andGaneshp

ure

Case

repo

rt1

23No

Symptom

atic

15years

Stableclinical

evolution

Sarahetal

Repo

rtof

cases

235

No

Symptom

atic

Not

repo

rted

mdashRa

oetal

Repo

rtof

cases

337

Not

repo

rted

Symptom

atic

Not

repo

rted

mdashNailetal

Case

repo

rt1

65No

Symptom

atic

Not

repo

rted

mdash

Rajagopalaetal

Case

repo

rt1

36

Medullary

neph

rocalcinosis

recurrentC

NSdemyelin

ation

neurom

yelitisop

ticaS

econ

dary

APS

with

thrombo

sis

Symptom

atic

methylpredn

isolone

prednisoloneC

YC

andAZA

3mon

ths

Stableclinical

evolution

Palkar

etal

Case

repo

rt1

58Lo

w-grade

fever

Symptom

atic

Not

repo

rted

Stableclinical

evolution

Dasarietal

Case

repo

rt1

40No

Symptom

aticand

prednisolone

6mon

ths

Stableclinical

evolution

Sing

hvietal

Case

repo

rt1

30No

Symptom

aticand

prednisolone

6mon

ths

Stableclinical

evolution

Changetal

Repo

rtof

cases

210

One

patie

ntcarotid

artery

steno

sisSymptom

atic

3ndash6years

One

patie

nt

four

relapses

Eriksson

etal

Repo

rtof

cases

664

6Not

repo

rted

Norepo

rted

Not

repo

rted

mdashTaylor

andParson

sCa

serepo

rt1

55No

Symptom

atic

Not

repo

rted

mdashCa

rminatietal

Case

repo

rt1

32No

Symptom

atic

Not

repo

rted

mdash


Table2Con

tinued

Reference

Type

ofstu

dyNum

bero

fpatie

nts

Age

(years)

mean

Extragland

ular

manifesta

tions

besid

esdR

TATreatm

ent

Follo

w-up

Outcome

Muthu

krish

nanetal

Case

repo

rt1

39No

Symptom

aticand

prednisolone

2years

Stableclinical

evolution

Prakashetal

Case

repo

rt1

49No

Symptom

atic

methylpredn

isolone

prednisolone

16days

Died

Skalovae

tal

Case

repo

rt1

16No

Symptom

atic

methylpredn

isolone

CYL

Not

repo

rted

Stableclinical

evolution

Liao

etal

Case

repo

rt1

49Not

repo

rted

Symptom

atic

Not

repo

rted

mdash

Seng

uletal

Case

repo

rt1

48No

Symptom

atic

prednisoloneH

CQNot

repo

rted

mdash

Yilm

azetal

Case

repo

rt1

53No

Symptom

atic

methylpredn

isolone

HCQ

AZA

10days

Stableclinical

evolution

LoganandAhm

edCa

serepo

rt1

36No

Symptom

aticH

CQ3years

Stableclinical

evolution

Fujim

otoetal

Case

repo

rt1

27Kidn

eylithiasis

Symptom

atic

4mon

ths

Stableclinical

evolution

Mugun

dhan

etal

Case

repo

rt1

38Nephrocalcino

sisSymptom

aticand

prednisolone

Not

repo

rted

mdash

Garza-Alpire

zetal

Case

repo

rt1

31Po

lyarthralgias

Symptom

aticH

CQ8mon

ths

Stableclinical

evolution

Symptom

aticp

otassiu

m(K

)and

bicarbon

ate(H

CO3)HCQ

hydroxychloroqu

ineMTX

metho

trexateC

YCcycloph

osph

amideAZA

azathioprineMMm

ycop

heno

late

mofetil

CYL

cyclospo

rineAA

PS

antip

hospho

lipid

synd

romeextragland

ular

manifesta

tion

arthritis

arthralgiaand

vasculitis


in lip salivary glands [19] Also similar lymphocytic infiltratesaround renal tubules have been observed [20] More datafrom prospective studies of pSS biopsies are needed in orderto enhance knowledge in these subsets of patients and also todetermine the best treatment

dRTA treatment includes potassium restitution beforealkali therapy because the last might aggravate hypokalemiaby enhancing the shift of potassium into cells and bicarbona-turia [21] In the beginning hydroxychloroquine was startedin the suspicion of a secondary cause of Sjogrenrsquos syndromebut it was later discontinued

RTA is not a usual indication for immunomodulatorytherapy in pSS even though it is an extraglandular mani-festation [22] Steroid therapy in cases that are nonrespon-sive to replacement therapy and in those with recurringhypokalemic paralysis attacks is indicated [23]

We searched in MEDLINE IMBIOMED and GoogleScholar for clinical cases of hypokalemic paralysis due topSS We included only articles written in English or SpanishIn Table 2 we describe each one of them number ofcases age of patients extraglandular manifestations besidesdRTA treatment and outcome We found fifty-two cases foranalysis but we included only cases with a complete reportof treatment [15 21ndash47] We observed the highest frequencyof this clinical presentation in young adults of the femalegender It is important to note that in some cases dRTAwas present before the diagnosis of pSS All patients receivedsymptomatic treatment We noted that 25 (1352) receivedcorticosteroids Of these patients 61 (813) did not reportextraglandular manifestations besides dRTA The outcomes(at different duration) were clinically stable in 61 (813) 8(113) had a relapse after treatmentwas stopped 8 (113) diedfrom an infectious cause and 23 (313) did not report theoutcome

On the other hand 326 (1752) received only symp-tomatic treatmentOf these patients 41 (717) did not reportextraglandular manifestations Only in six (35) patients wasthe outcome reported of whom 83 (56) were clinicallystable and in 17 (16) four relapses occurred

In the early diagnosis era of autoimmune diseases (likein rheumatoid arthritis) the importance of recognizingkidney involvement before glandular symptoms appear hasbeen observed previously [21 25 28] Also we consider itimportant to determine whether some factors can triggerthe beginning of this manifestation This association hasbeen observed by Logan and Ahmed They described ina patient the use of Echinacea as a trigger of pSS [45]Perhaps this means that the immunological tolerance isalready lost and some infections or substances can precipitatethe clinical diseaseWe agree with the recommendation givenby Francois and Mariette to screen all pSS patients accordingto manifestations every six to twelve months [10]

With such heterogeneous information prospective stud-ies are needed to assess the value of adding corticosteroids asa standardized treatment of this manifestation We may con-sider that in cases of hypokalemic paralysis in which there isa potentially life-threatening presentation the treatment withcorticosteroids could be justified

Conflicts of Interest

The authors declare that there are no conflicts of interestregarding the publication of this article

References

[1] R Evans A Zdebik C Ciurtin and S B Walsh ldquoRenalinvolvement in primary Sjogrenrsquos syndromerdquo Rheumatologyvol 54 no 9 pp 1541ndash1548 2015

[2] M Ramos-Casals P Brito-Zeron R Seror et al ldquoCharac-terization of systemic disease in primary Sjogrenrsquos syndromeEULAR-SS Task Force recommendations for articular cuta-neous pulmonary and renal involvementsrdquo Rheumatology vol54 no 12 pp 2230ndash2238 2015

[3] M Ramos-Casals P Brito-Zeron R Solans et al ldquoSystemicinvolvement in primary Sjogrenrsquos syndrome evaluated by theEULAR-SS disease activity index Analysis of 921 spanishpatients (GEAS-SS registry)rdquo Rheumatology (United Kingdom)vol 53 no 2 Article ID ket349 pp 321ndash331 2014

[4] H Ren W M Wang X N Chen W Zhang X L Pan Wanget al ldquoRenal involvement and followup of 130 patients withprimary Sjogrenrsquos syndromerdquoThe Journal of Rheumatology vol35 pp 278ndash284 2008

[5] D M Chisholm and D K Mason ldquoLabial salivary gland biopsyin Sjogrenrsquos diseaserdquo Journal of Clinical Pathology vol 21 no 5pp 656ndash660 1968

[6] C H Shiboski S C Shiboski R Seror et al ldquo2016 AmericanCollege of RheumatologyEuropean League Against Rheuma-tism classification criteria for primary Sjogrenrsquos syndromeA consensus and data-driven methodology involving threeinternational patient cohortsrdquoAnnals of the Rheumatic Diseasesvol 76 no 1 pp 9ndash16 2016

[7] N Talal E Zisman and P H Schur ldquoRenal tubular acidosisglomerulonephritis and immunologic factors in Sjogrenrsquos syn-dromerdquo Arthritis and Rheumatology vol 11 no 6 pp 774ndash7861968

[8] SMaripuri J P Grande T GOsborn et al ldquoRenal involvementin primary sjogrenrsquos syndrome a clinicopathologic studyrdquoClinical Journal of the American Society of Nephrology vol 4no 9 pp 1423ndash1431 2009

[9] N Bossini S Savoldi F Franceschini et al ldquoClinical and mor-phological features of kidney involvement in primary Sjogrenrsquossyndromerdquo Nephrology Dialysis Transplantation vol 16 no 12pp 2328ndash2336 2001

[10] H Francois and X Mariette ldquoRenal involvement in primarySjogren syndromerdquo Nature Reviews Nephrology vol 12 no 2pp 82ndash93 2016

[11] B Bastani L Haragsim S Gluck and K C SiamopoulosldquoLack of h-atpase in distal nephron causing hypokalaemic distalrta in a patient with sjogrenrsquos syndromerdquo Nephrology DialysisTransplantation vol 10 no 6 pp 908-909 1995

[12] F Takemoto J Hoshino N Sawa et al ldquoAutoantibodies againstcarbonic anhydrase II are increased in renal tubular acido-sis associated with Sjogren syndromerdquo American Journal ofMedicine vol 118 no 2 pp 181ndash184 2005

[13] P E DeFranco L Haragsim P G Schmitz B Bastani and JP Li ldquoAbsence of vacuolar H+-ATPase pump in the collectingduct of a patient with hypokalemic distal renal tubular acidosisand Sjogrenrsquos syndromerdquo Journal of the American Society ofNephrology vol 6 no 2 pp 295ndash301 1995


[14] P Sandhya and D Danda ldquoRole of vacuolar ATPase and Skp1in Sjogrenrsquos syndromerdquo Medical Hypotheses vol 82 no 3 pp319ndash325 2014

[15] P Eriksson T Denneberg S Enestrom B Johansson FLindstrom and T Skogh ldquoUrolithiasis and distal renal tubularacidosis preceding primary Sjogrenrsquos syndrome A retrospectivestudy 5-53 years after the presentation of urolithiasisrdquo Journal ofInternal Medicine vol 239 no 6 pp 483ndash488 1996

[16] S-H Lin S Cheema-Dhadli M Gowrishankar E B MarlissK S Kamel and M L Halperin ldquoControl of excretion ofpotassium lessons from studies during prolonged total fastingin human subjectsrdquo American Journal of PhysiologymdashRenalPhysiology vol 273 no 5 pp F796ndashF800 1997

[17] R Shioji T Furuyama S Onodera H Saito H Ito and YSasaki ldquoSjogrenrsquos syndrome and renal tubular acidosisrdquo TheAmerican Journal of Medicine vol 48 no 4 pp 456ndash463 1970

[18] K-K Pun C-K Wong E Y-L Tsui S C-F Tam A W-CKung and C C-LWang ldquoHypokalemic periodic paralysis dueto the Sjogren syndrome in Chinese patientsrdquoAnnals of InternalMedicine vol 110 no 5 pp 405-406 1989

[19] R D R Evans C M Laing C Ciurtin and S B WalshldquoTubulointerstitial nephritis in primary Sjogren syndromeclinical manifestations and response to treatmentrdquo BMC Mus-culoskeletal Disorders vol 5 no 17 p 2 2016

[20] N Talal ldquoSjogrenrsquos syndrome lymphoproliferation and renaltubular acidosisrdquo Annals of Internal Medicine vol 74 no 4 pp633-634 1971

[21] C-J Cheng J-S Chiu C-C Chen and S-H Lin ldquoUnusualcause of hypokalemic paralysis in agedmen Sjogren syndromerdquoSouthern Medical Journal vol 98 no 12 pp 1212ndash1215 2005

[22] MGoroshi S Khare T Jamale andN Shah ldquoPrimary Sjogrenrsquossyndrome presenting as hypokalemic paralysis a case seriesrdquoJournal of Postgraduate Medicine vol 63 no 2 p 128 2016

[23] M Soy O N Pamuk M Gerenli and Y Celik ldquoA primarySjogrenrsquos syndrome patient with distal renal tubular acido-sis who presented with symptoms of hypokalemic periodicparalysis report of a case study and review of the literaturerdquoRheumatology International vol 26 no 1 pp 86ndash89 2005

[24] R Khadgawat N Tandon D Khandelwal S Bhattacharya SKaur and A Ammini ldquoHypokalemic paralysis as a presentingmanifestation of primary Sjogren1015840s syndrome a report of twocasesrdquo Indian Journal of Endocrinology and Metabolism vol 16no 5 pp 853ndash855 2012

[25] M Kawashima T Amano Y Morita M Yamamura and HMakino ldquoHypokalemic paralysis and osteomalacia secondaryto renal tubular acidosis in a case with primary Sjogrenrsquossyndromerdquo Modern Rheumatology vol 16 no 1 pp 48ndash512006

[26] D M Comer A G Droogan I S Young and A P MaxwellldquoHypokalaemic paralysis precipitated by distal renal tubularacidosis secondary to Sjogrenrsquos syndromerdquo Annals of ClinicalBiochemistry vol 45 no 2 pp 221ndash225 2008

[27] S Seirafian M Shafie A Abedini B Pakzad and PRoomizadeh ldquoRecurrent attacks of hypokalemic quadriparesisan unusual presentation of primary Sjogren syndromerdquo InternalMedicine vol 55 no 13 pp 1797ndash1800 2016

[28] G Vaidya and S Ganeshpure ldquoSjogrenrsquos syndrome with distalrenal tubular acidosis presenting as hypokalaemic paralysisrdquoBMJ Case Reports vol 19 2012

[29] S Sarah G Lijo E Sukanya andD Rajasekaran ldquoRenal tubularacidosis due to Sjogrenrsquos syndrome presenting as hypokalemic

quadriparesis a report of two casesrdquo Indian Journal of Nephrol-ogy vol 25 no 6 pp 386-387 2015

[30] N Rao M John N Thomas S Rajaratnam and MS Seshadri ldquoAetiological clinical and metabolic profile ofhypokalaemic periodic paralysis in adults a single-centre expe-riencerdquoNationalMedical Journal of India vol 19 no 5 pp 246ndash249 2006

[31] M Nail T Bhat M Naqash et al ldquoHypokalemic quadriparesisin an elderly femalerdquo Indian Journal of Nephrology vol 22 no5 pp 402-403 2012

[32] S Rajagopala G Danigeti and D Subrahmanyan ldquoAn unusu-ally dry storyrdquo Indian Journal of Critical Care Medicine vol 19no 9 pp 550ndash553 2015

[33] A V Palkar S Pillai and G C Rajadhyaksha ldquoHypokalemicquadriparesis in Sjogren syndromerdquo Indian Journal of Nephrol-ogy vol 21 no 3 pp 191ndash193 2011

[34] S Dasari K Naha G Vivek V Acharya and M Hande ldquoPri-mary presentation with acute flaccid quadriparesis in Sjogrenrsquossyndrome sans siccardquo BMJ Case Reports vol 2013 2013

[35] J Singhvi A Ganguli and B Kaur ldquoPrimary Sjogrenrsquos syn-drome presenting as Acute Flaccid Quadriplegiardquo Annals ofNeurosciences vol 17 no 2 2010

[36] Y-C Chang C-C Huang Y-Y Chiou and C-Y Yu ldquoRetaltubular acidosis complicated with hypokalemic periodic paral-ysisrdquo Pediatric Neurology vol 13 no 1 pp 52ndash54 1995

[37] I Taylor and M Parsons ldquoHypokalemic paralysis revealingSjogrenrsquos syndromerdquo Journal of Clinical Neuroscience vol 11 no3 pp 319ndash321 2004

[38] G Carminati A Chena J M Orlando S Russo S Salomonand J A Carena ldquoDistal renal tubular acidosis with rhabdomy-olysis as the presenting form in 4 pregnant womenrdquo Nefrologiavol 21 no 2 pp 204ndash208 2001

[39] J Muthukrishnan S Dawra V Marwaha and C S NarayananldquoSjogrenrsquos syndrome presenting as hypokalemic paralysisrdquoMed-ical Journal Armed Forces India vol 71 pp S172ndashS174 2015

[40] E B S Prakash M E Fernando M Sathiyasekaran R MBhoopathy J J Jayanth and J Samuel ldquoPrimary Sjogrenrsquossyndrome presenting with distal renal tubular acidosis andrhabdomyolysisrdquo Journal of Association of Physicians of Indiavol 54 pp 949-950 2006

[41] S Skalova L Minxova and R Slezak ldquoHypokalaemic paralysisrevealing Sjogrenrsquos syndrome in a 16-year old girlrdquo GhanaMedical Journal vol 42 pp 124ndash128 2008

[42] C-Y Liao C-CWang I-H Chen J-C Shiang M-Y Liu andM-K Tsai ldquoHypokalemic paralysis as a presenting manifesta-tion of primary Sjogrenrsquos syndrome accompanied by vitaminD deficiencyrdquo Internal Medicine vol 52 no 20 pp 2351ndash23532013

[43] E Sengul F Bunul A Yazici et al ldquoAn unusual initial pre-sentation of Sjogrenrsquos syndrome severe hypokalemic paralysissecondary to distal renal tubular acidosisrdquo Eurasian Journal ofMedicine vol 45 no 3 pp 218ndash221 2013

[44] H Yilmaz M Kaya M Ozbek K Ureten and S I SafaYildirim ldquoHypokalemic periodic paralysis in Sjogrenrsquos syn-drome secondary to distal renal tubular acidosisrdquoRheumatologyInternational vol 33 no 7 pp 1879ndash1882 2013

[45] J L Logan and J Ahmed ldquoCritical hypokalemic renal tubularacidosis due to Sjogrenrsquos syndrome association with the pur-ported immune stimulant echinaceardquo Clinical Rheumatologyvol 22 no 2 pp 158-159 2003


[46] T Fujimoto H Shiiki Y Takahi and K Dohi ldquoPrimarySjogrenrsquos syndrome presenting as hypokalaemic periodic paral-ysis and respiratory arrestrdquo Clinical Rheumatology vol 20 no5 pp 365ndash368 2001

[47] K Mugundhan M C Mayan Vasif P D Nidhin et alldquoHypokalemic paralysis in Sjogrenrsquos syndrome secondary torenal tubular acidosisrdquo Journal of Association of Physicians ofIndia vol 64 p 72 2016

Submit your manuscripts athttpswwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014


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The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

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Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


Table 1 Laboratory investigation

Laboratory investigation ResultCBC Hemoglobin 147 gdL WBC 87 times 103 lymphocytes 0683 times 103 platelets 159 K120583LSerum electrolytes Sodium 1382mmolL potassium 27mmolL chloride 101mmolLSerum chemistry Glucose 123mgdL creatinine 08mgdL urea nitrogen 13mgdLLiver panel AST 19 IUL ALT 13 IUL albumin 42 gdL total bilirubin 07mgdLUrinalysis pH 8 leucocytes 0ndash2HPF erythrocytes 0HPF tubular cells 0HPF

Urinary electrolytes Sodium 114mmolL potassium 32mmolL chloride 573mmolL creatinine318mgdL

Urinary anion gap 76mmolLBlood gas pH 712 HCO

3 11mmolL pO

2 31mmHg pCO

2 37mmHg saturation 37

Serum anion gap 10mEqLThyroid panel TSH 206120583IUmL free T4 094 ngdLAcute phase reactants ESR 31mmh CRP lt 05mgLVirus panel HIV-negative HBV-negative HCV-negativeRheumatoid factor IgM 1557 IUmL IgG 67 IUmL IgA 122 IUmLANAs by IFA 1 5120 fine speckledSSASSB by ELISA 200141967 IUmLUnstimulated whole saliva flow withoutanesthesia 14mL15 minutes

Minor salivary gland biopsylowast Positive focus score of 5Schirmerrsquos test Right eye 7mm left eye 10mmlowastAccording to [5]

Figure 1 A panoramic photo of minor salivary gland biopsy Achronic lymphocyte focal sialadenitis was observed

sodium bicarbonate Then we initiated hydroxychloroquineThe patient was discharged and we followed her up in ourclinic every two months for the next eight months She wasreported to be asymptomatic with the use of potassium citrateonly

3 Discussion

A recent set of classification criteria for pSSwere published bytheACREULAR in 2016 [6] and this applies to the individualthat has a score of ge4 According to this the diagnosis ofthis autoimmune disease was made in our patient (labialsalivary gland with a focus score of ge1 anti-SSA positive andan unstimulated whole saliva flow of less than 01mLmin)Renal involvement in pSS is the result of two distinct patho-physiological processes TIN and glomerulopathy [1] The

tubulointerstitial inflammation is the most common renallesion described by Talal et al [7] dRTAprevalence fluctuatesbetween 5 and 70 according to population studies [4 8 9]dRTA can be classified as complete or incomplete the formeris characterized bymetabolic acidosis withmorning urine pHgt 55 and a positive urinary anion gap The incomplete formpresents with normal serum bicarbonate levels but urinarypH fails to fall to lt53 after ammonium chloride loading[10] The pathogenic mechanism of this complication is notcompletely understood Antibodies to vacuolar H+-ATPaseand anion exchanger 1 as well as antibodies to carbonicanhydrase II have been implicated in the pathogenesis[11ndash13] Another hypothesis is a defective S-phase-kinase-associated protein-1 a component of the regulator of theATPase of vacuolar and endosomal membranes that couldinduce a defective V-ATPase assembly [14] Also a possiblerelation between antibodies anti-SSARo and dRTA has beendescribed as one pathogenicmechanism of development [15]

Hypokalemia is the most common electrolyte abnormal-ity in patients with dRTAThe causes of hypokalemia includedecreased distal tubular Na delivery secondary hyperaldos-teronism defective H-KATPase and bicarbonaturia [16]Hypokalemic paralysis may precede sicca syndrome fromthree months to four years in patients with a final diagnosisof pSS [17 18]

Renal biopsy is not mandatory in these patients [2] butit may help us evidence the inflammatory mechanisms thattrigger the disease As has been demonstrated by Evans et alin twelve patients with TIN secondary to pSS they observedCD4+ T-cell predominance in biopsies similar to those seen


Table2Com

parativ

etreatmentinhypo

kalemicparalysis

duetodistalRT

Ain

Sjogrensynd

romep

atients

Reference

Type

ofstu

dyNum

bero

fpatie

nts

Age

(years)

mean

Extragland

ular

manifesta

tions

besid

esdR

TATreatm

ent

Follo

w-up

Outcome

Goroshi

etal

Case

serie

s13

331


Symptom

atic

Extragland

ularH

CQandMTX

28years(05ndash4)

No

improvem

entin

redu

ctionof

HCO3or

Krequ

irements

Khadgaw

atetal

Repo

rtof

cases

2205

No

Symptom

atic

Not

repo

rted

mdash

Soyetal

Case

repo

rt1


iasis

Symptom

aticand

methylpredn

isolone

2years

Stableclinical

evolution

Chengetal

Repo

rtof

cases

276

Nephrocalcino

sisSymptom

aticand

prednisolone

5ndash12

mon

ths

Stableclinical

evolution

Kawashimae

tal

Case

repo

rt1

39Oste

omalaciainterstitia

lnephritis

Symptom

aticand

prednisolone

2years

Relapsea

fter

stopp

ing

treatment

Com

eretal

Case

repo

rt1

43No

Symptom

atic

2years

Stableclinical

evolution

Seira

fianetal

Case

repo

rt1

64No

Symptom

atic

prednisoloneand

HCQ

Not

repo

rted

mdash

Vaidya

andGaneshp

ure

Case

repo

rt1

23No

Symptom

atic

15years

Stableclinical

evolution

Sarahetal

Repo

rtof

cases

235

No

Symptom

atic

Not

repo

rted

mdashRa

oetal

Repo

rtof

cases

337

Not

repo

rted

Symptom

atic

Not

repo

rted

mdashNailetal

Case

repo

rt1

65No

Symptom

atic

Not

repo

rted

mdash

Rajagopalaetal

Case

repo

rt1

36

Medullary

neph

rocalcinosis

recurrentC

NSdemyelin

ation

neurom

yelitisop

ticaS

econ

dary

APS

with

thrombo

sis

Symptom

atic

methylpredn

isolone

prednisoloneC

YC

andAZA

3mon

ths

Stableclinical

evolution

Palkar

etal

Case

repo

rt1

58Lo

w-grade

fever

Symptom

atic

Not

repo

rted

Stableclinical

evolution

Dasarietal

Case

repo

rt1

40No

Symptom

aticand

prednisolone

6mon

ths

Stableclinical

evolution

Sing

hvietal

Case

repo

rt1

30No

Symptom

aticand

prednisolone

6mon

ths

Stableclinical

evolution

Changetal

Repo

rtof

cases

210

One

patie

ntcarotid

artery

steno

sisSymptom

atic

3ndash6years

One

patie

nt

four

relapses

Eriksson

etal

Repo

rtof

cases

664

6Not

repo

rted

Norepo

rted

Not

repo

rted

mdashTaylor

andParson

sCa

serepo

rt1

55No

Symptom

atic

Not

repo

rted

mdashCa

rminatietal

Case

repo

rt1

32No

Symptom

atic

Not

repo

rted

mdash


Table2Con

tinued

Reference

Type

ofstu

dyNum

bero

fpatie

nts

Age

(years)

mean

Extragland

ular

manifesta

tions

besid

esdR

TATreatm

ent

Follo

w-up

Outcome

Muthu

krish

nanetal

Case

repo

rt1

39No

Symptom

aticand

prednisolone

2years

Stableclinical

evolution

Prakashetal

Case

repo

rt1

49No

Symptom

atic

methylpredn

isolone

prednisolone

16days

Died

Skalovae

tal

Case

repo

rt1

16No

Symptom

atic

methylpredn

isolone

CYL

Not

repo

rted

Stableclinical

evolution

Liao

etal

Case

repo

rt1

49Not

repo

rted

Symptom

atic

Not

repo

rted

mdash

Seng

uletal

Case

repo

rt1

48No

Symptom

atic

prednisoloneH

CQNot

repo

rted

mdash

Yilm

azetal

Case

repo

rt1

53No

Symptom

atic

methylpredn

isolone

HCQ

AZA

10days

Stableclinical

evolution

LoganandAhm

edCa

serepo

rt1

36No

Symptom

aticH

CQ3years

Stableclinical

evolution

Fujim

otoetal

Case

repo

rt1

27Kidn

eylithiasis

Symptom

atic

4mon

ths

Stableclinical

evolution

Mugun

dhan

etal

Case

repo

rt1

38Nephrocalcino

sisSymptom

aticand

prednisolone

Not

repo

rted

mdash

Garza-Alpire

zetal

Case

repo

rt1

31Po

lyarthralgias

Symptom

aticH

CQ8mon

ths

Stableclinical

evolution

Symptom

aticp

otassiu

m(K

)and

bicarbon

ate(H

CO3)HCQ

hydroxychloroqu

ineMTX

metho

trexateC

YCcycloph

osph

amideAZA

azathioprineMMm

ycop

heno

late

mofetil

CYL

cyclospo

rineAA

PS

antip

hospho

lipid

synd

romeextragland

ular

manifesta

tion

arthritis

arthralgiaand

vasculitis











References
























































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table2Com

parativ

etreatmentinhypo

kalemicparalysis

duetodistalRT

Ain

Sjogrensynd

romep

atients

Reference

Type

ofstu

dyNum

bero

fpatie

nts

Age

(years)

mean

Extragland

ular

manifesta

tions

besid

esdR

TATreatm

ent

Follo

w-up

Outcome

Goroshi

etal

Case

serie

s13

331


Symptom

atic

Extragland

ularH

CQandMTX

28years(05ndash4)

No

improvem

entin

redu

ctionof

HCO3or

Krequ

irements

Khadgaw

atetal

Repo

rtof

cases

2205

No

Symptom

atic

Not

repo

rted

mdash

Soyetal

Case

repo

rt1


iasis

Symptom

aticand

methylpredn

isolone

2years

Stableclinical

evolution

Chengetal

Repo

rtof

cases

276

Nephrocalcino

sisSymptom

aticand

prednisolone

5ndash12

mon

ths

Stableclinical

evolution

Kawashimae

tal

Case

repo

rt1

39Oste

omalaciainterstitia

lnephritis

Symptom

aticand

prednisolone

2years

Relapsea

fter

stopp

ing

treatment

Com

eretal

Case

repo

rt1

43No

Symptom

atic

2years

Stableclinical

evolution

Seira

fianetal

Case

repo

rt1

64No

Symptom

atic

prednisoloneand

HCQ

Not

repo

rted

mdash

Vaidya

andGaneshp

ure

Case

repo

rt1

23No

Symptom

atic

15years

Stableclinical

evolution

Sarahetal

Repo

rtof

cases

235

No

Symptom

atic

Not

repo

rted

mdashRa

oetal

Repo

rtof

cases

337

Not

repo

rted

Symptom

atic

Not

repo

rted

mdashNailetal

Case

repo

rt1

65No

Symptom

atic

Not

repo

rted

mdash

Rajagopalaetal

Case

repo

rt1

36

Medullary

neph

rocalcinosis

recurrentC

NSdemyelin

ation

neurom

yelitisop

ticaS

econ

dary

APS

with

thrombo

sis

Symptom

atic

methylpredn

isolone

prednisoloneC

YC

andAZA

3mon

ths

Stableclinical

evolution

Palkar

etal

Case

repo

rt1

58Lo

w-grade

fever

Symptom

atic

Not

repo

rted

Stableclinical

evolution

Dasarietal

Case

repo

rt1

40No

Symptom

aticand

prednisolone

6mon

ths

Stableclinical

evolution

Sing

hvietal

Case

repo

rt1

30No

Symptom

aticand

prednisolone

6mon

ths

Stableclinical

evolution

Changetal

Repo

rtof

cases

210

One

patie

ntcarotid

artery

steno

sisSymptom

atic

3ndash6years

One

patie

nt

four

relapses

Eriksson

etal

Repo

rtof

cases

664

6Not

repo

rted

Norepo

rted

Not

repo

rted

mdashTaylor

andParson

sCa

serepo

rt1

55No

Symptom

atic

Not

repo

rted

mdashCa

rminatietal

Case

repo

rt1

32No

Symptom

atic

Not

repo

rted

mdash


Table2Con

tinued

Reference

Type

ofstu

dyNum

bero

fpatie

nts

Age

(years)

mean

Extragland

ular

manifesta

tions

besid

esdR

TATreatm

ent

Follo

w-up

Outcome

Muthu

krish

nanetal

Case

repo

rt1

39No

Symptom

aticand

prednisolone

2years

Stableclinical

evolution

Prakashetal

Case

repo

rt1

49No

Symptom

atic

methylpredn

isolone

prednisolone

16days

Died

Skalovae

tal

Case

repo

rt1

16No

Symptom

atic

methylpredn

isolone

CYL

Not

repo

rted

Stableclinical

evolution

Liao

etal

Case

repo

rt1

49Not

repo

rted

Symptom

atic

Not

repo

rted

mdash

Seng

uletal

Case

repo

rt1

48No

Symptom

atic

prednisoloneH

CQNot

repo

rted

mdash

Yilm

azetal

Case

repo

rt1

53No

Symptom

atic

methylpredn

isolone

HCQ

AZA

10days

Stableclinical

evolution

LoganandAhm

edCa

serepo

rt1

36No

Symptom

aticH

CQ3years

Stableclinical

evolution

Fujim

otoetal

Case

repo

rt1

27Kidn

eylithiasis

Symptom

atic

4mon

ths

Stableclinical

evolution

Mugun

dhan

etal

Case

repo

rt1

38Nephrocalcino

sisSymptom

aticand

prednisolone

Not

repo

rted

mdash

Garza-Alpire

zetal

Case

repo

rt1

31Po

lyarthralgias

Symptom

aticH

CQ8mon

ths

Stableclinical

evolution

Symptom

aticp

otassiu

m(K

)and

bicarbon

ate(H

CO3)HCQ

hydroxychloroqu

ineMTX

metho

trexateC

YCcycloph

osph

amideAZA

azathioprineMMm

ycop

heno

late

mofetil

CYL

cyclospo

rineAA

PS

antip

hospho

lipid

synd

romeextragland

ular

manifesta

tion

arthritis

arthralgiaand

vasculitis











References
























































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table2Con

tinued

Reference

Type

ofstu

dyNum

bero

fpatie

nts

Age

(years)

mean

Extragland

ular

manifesta

tions

besid

esdR

TATreatm

ent

Follo

w-up

Outcome

Muthu

krish

nanetal

Case

repo

rt1

39No

Symptom

aticand

prednisolone

2years

Stableclinical

evolution

Prakashetal

Case

repo

rt1

49No

Symptom

atic

methylpredn

isolone

prednisolone

16days

Died

Skalovae

tal

Case

repo

rt1

16No

Symptom

atic

methylpredn

isolone

CYL

Not

repo

rted

Stableclinical

evolution

Liao

etal

Case

repo

rt1

49Not

repo

rted

Symptom

atic

Not

repo

rted

mdash

Seng

uletal

Case

repo

rt1

48No

Symptom

atic

prednisoloneH

CQNot

repo

rted

mdash

Yilm

azetal

Case

repo

rt1

53No

Symptom

atic

methylpredn

isolone

HCQ

AZA

10days

Stableclinical

evolution

LoganandAhm

edCa

serepo

rt1

36No

Symptom

aticH

CQ3years

Stableclinical

evolution

Fujim

otoetal

Case

repo

rt1

27Kidn

eylithiasis

Symptom

atic

4mon

ths

Stableclinical

evolution

Mugun

dhan

etal

Case

repo

rt1

38Nephrocalcino

sisSymptom

aticand

prednisolone

Not

repo

rted

mdash

Garza-Alpire

zetal

Case

repo

rt1

31Po

lyarthralgias

Symptom

aticH

CQ8mon

ths

Stableclinical

evolution

Symptom

aticp

otassiu

m(K

)and

bicarbon

ate(H

CO3)HCQ

hydroxychloroqu

ineMTX

metho

trexateC

YCcycloph

osph

amideAZA

azathioprineMMm

ycop

heno

late

mofetil

CYL

cyclospo

rineAA

PS

antip

hospho

lipid

synd

romeextragland

ular

manifesta

tion

arthritis

arthralgiaand

vasculitis











References
























































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


























References
























































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


























































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















hypokalemic paralysis due to primary sjögren syndrome

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