lupus eritomatose

8/10/2019 lupus eritomatose

1/19

1965 25: 143-160

ROBERT M. LEWIS, ROBERT SCHWARTZ and WILLIAM B. HENRY, JR.Canine Systemic Lupus Erythematosus

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2/19

B L () Q J)

T

h e Jo u rn a l o f H e m ato lo gy

F E B R U A R Y , 1965 V O L . X X V , N O . 2

C an in e S y stem ic L u p u s E ry th em ato su s

B y R O B E R T

M .

L E W IS , R O B E R T S C H W A R T Z

AN D

W I L L I A M

B .

H E N R Y ,

JR .

O

F T H E n um erous investig atio ns o f au to im m u niza tio n , th e co nstruc tion of

an im a l m od e ls h as been p articu la rly in fo rm a tive . S eve ral cla sse s o f

these m o de ls h av e been elabo ra ted : tho se in w hich le sion s a re indu ced by th e

in jectio n of o rgan sp ecif ic an tig en s ( thy ro id itis ,1 en ceph alitis ,2 a spe rm a to -

g en es is3 ); those in w hich lesio ns are indu ced by an tigen -an tibo dy com plexes

(se ru m sickn es s,4 g lo m eru loneph ritis5 ) and tho se in w h ich le sion s a re p rodu ced

by to le rated fo re ign im m uno cy te s (run t d isease 7 ) . In add itio n , the adn un is -

tra tio n o f F reu nds ad juvan t a lon e8 o r o rgan -specif ic he te ro logo us an tisera9 w ill

re su lt in still o th e r types o f im m uno log ic d iso rd ers in labo ra to ry an im a ls . M o re

re n tly , spon tan eo us au to im m u ne d iso rd ers have been desc rib ed in m ice 01

and d ogs .1 2 T he au to im m u ne hem oly tic anem ia o f N Z B m ice has b een of

pa rticu la r in te re st b ecause o f its gene tic backgrou nd and the assoc iated th ym ic

le sio n . W h ile sp on tan eity m ay n o t a lw ay s b e d es irab le u nde r th e co n tro lled

con d ition s o f th e lab ora to ry , th is is an im po rtan t fea tu re o f hu m an au to im -

m un iza tion w ith w hich clin ic ian s m ust dea l. T hus, the ch a rac ter izatio n of

sp on tan eo usly occurr ing au to im m une d isease in low er m am m als m ay pro v ide

in sigh ts uno b ta inab le from m an-m ade m od els .

T h e p urpose o f th is rep o rt is to p resen t the c lin ica l an d pa tho lo g ic fea tu res

o f a m ultisys tem ic d isea se th at w e o bse rv ed in 7 d ogs. T h is co nd itio n is ve ry

sim ilar to sy stem ic lup us e ry them a tosu s in m an . I ts ca rd ina l featu re s a re

au to im m u ne h em oly tic anem ia, th rom bocv to pen ia , and m em bran ous g lom eru -

lo nephrilis . P os itive lupu s p repa ra tio ns and o th e r se ro log ic abn orm a lities foun d

in th ese an im a ls ind ica te the im m un o log ic n atu re o f the d iso rde r.

M E T H O D S

L abo ra to ry tes ts co nsis tin g of w hite b lo od ce ll coun ts (W B C ), p acked cell vo lum e

(P C V ), h em oglob in leve ls (H b), w hite b lood ce ll d iffe ren tia l coun ts , icte rus index , d irec t

an tig lobu lin test, b lood urea n itrogen (B U N ), reticu locy te co un t, u rina lys is , Q u ick pro -

th ro m bm tim e, and serum transam inase va lues (S G O -T , S G P -T ) w ere d ete rm ined by

s tan dard m ethods . P la te le t num b ers w ere es tim ated from th e periph era l b lo od sm ears .

Paper strip e lectro phores is, to ta l se ru m pro te in d ete rm ina tions and H yland rap id s lide

T h is inves tiga tion w as suppo rted in pa rt by R esearch G ra n t G M 0 7621 02 from the N a

tiona l In stitu te o f G enera l M ed ica l Sc iences U . S . P u b lic H ea lth Serv ice and by U . S .

P ub lic H ea lth Serv ice G ran t A M 02037 06 .

F rom the A n ge ll M em oria l A n im a l H osp ita l an d th e B lood R esearch L a bora tory P ra tt

C lin ic N ew E ng land C en ter H o sp ita l B os to n M ass.

Su bm itted F eb . 24 1 96 4; accep ted fo r p ub lica tio n M ay 5 1964 .

14 3

B L O O D V O L .

2 5 , N o. 2 (F E B R uA R Y ), 196 5

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3/19

14 4L E W IS , S C H W A R T Z A N D H E N R Y , JR .

agg lu t ina tion tests fo r rheu m a to id fac to r and a n tithyro id an tib ody w ere p erfo rm ed o n al l

ava ilab le seru m sam ple s o f affe cte d d og s. T hese latte r tw o te sts w e re u sed as sc ree n in g

tests . A pos itiv e te st fo r rh eum ato id facto r requ ire d a seru m dilu t ion o f 1 :20 in g ly cin e-

saline b uffer, w h ere as a pos itiv e te st fo r an tith yro id an tibod y w as reco rde d w he n un-

d ilu ted serum w a s u sed . T itra tio n of seru m w hic h reac ted p osi tive ly to the se sc ree n in g

tests w as no t (lo ne. In a dditio n , cov er slip sm ea rs w e re p rep are d in the m an ner d e-

scribed by M ia le13 an d ex am ine d fo r the prese nce o f the ty p ica l L .E . c ell. A lthou gh

ery th rop hag ocy tos is, nu cle oph ag ocy tos is, ro sette form a tion an d larg e a m o unts of ex tra-

cellu la r pro te in w ere noted , a sm e ar w as c ons ide red p osit ive o n ly w h en the cri teria d e-

sc ribe d by H argra ves14 w ere fu lfi lled .

N orm al V a lu es o f S ele c te d L a b o ra to ry T es ts in D o g s _ _ _ _ _ _

\V hite B lo od C e lls 6 00 0-1 800 0/m m 3

B a nd 0-3%

N eutroph il 6 0-77%

L ym pho cy te 1 2-3 0%

\lon ocy te 3-1 0%

Eosinophil 2-10%

B asop hil rare

P ac ked ce ll vo lum e 4 0-4 5%

H em og lob in 1 2-1 8 G m . %

R eticu locy tes 0 .1 -0 .5 %

Q u ick pro thro m b in tim e 7 .0-1 0 .5 sec ond s

B lo od ure a n itro ge n less than 20 m g . %

S G O -T les s than 2 3 S F units

S G P -T les s th an 27 S F u nits

C a se N u m b e r 1

T his 6-yea r-o ld fe m ale sta nd ard

p 0 0 (1 k

(R 145 11 ) w as a dm itte d to the A nge l M em ori-

a l A nim al H osp ita l in D e cem be r, 1 96 1 , b eca use o f e p is tax is. F in d in gs d uring p hys ica l e x-

am in atio n w ere neg ative exc ep t for the no se b lee d .

In it ia l labo rato ry find ings : W B C 39,000 /m m 3 ; PC V 3 0 pe r c en t; p ro throm bin t im e 7 .3

sec ond s. N e utro ph ilia w ith a left sh ift, m o no cytosis, p o ly chrom atop hil ia , an iso cy to sis ,

m ark ed th rom bo cytope n ia , hyp oc hro m ia a nd 2 nuc lea ted R B C /1 00 W B C w ere se en in

the pe rip heral b lood sm e ar. T he d irect C o om bs test w as 3+ , re tic u lo cy te co unt 2 .1 per

cen t an d B U N 1 3 m g ./1 00 m l. Th e urine w a s n orm al. T he ne x t m orn ing the dog w as se-

verely de pre sse d an d pe tec h iae a nd ec ch ym ose s w ere pre sen t on th e sk in and m u cou s

m e m b ran es. B oth elb ow jo in ts w ere sw ollen an d te nde r. B lo od a nd u rin e sam ple s w e r

sub m itted to the lab ora to ry . P redn iso ne, 10 m g eve ry 24 ho urs , in tram uscu larly , w as

star ted and w ith in 1 w eek th e sym ptom s h ad ab ated . A n L E prepa rat ion do ne a t that t im e

co nta ine d ex trac ellu lar L E b od ies , b u t typ ica l L E cells w e re no t see n .

S he re m ained w ell un t il M arch , 196 2 , w he n lis tle ssn ess , n on spe cif ic la m e ness, a norex ia ,

po lyd ips ia a nd d ark -co lored ur ine dev elo ped . P h ysic al ex am ina tio n rev ealed p allo r, s ligh t

ic teru s, se vere e m a ciat ion , p rostra tion ( the do g w alk ed u nstead ily in to the room , fe ll d ow n

an d co uld no t ris e), su bco nju nct iva l hem o rrha ges , ep ista x is , an d proba b le sp len om ega ly .

T h e tem peratu re w as 10 3 .6 F . In tram usc u la r in jec tion s of 1 0 m g. p red n iso ne eve ry 12

hou rs w e re be gun

an d

the do g w as p lac ed in ox yge n .

L abo rato ry fin d in gs w ere : W B C 24 ,00 0/m m 3 ; IT h 5 .3 G m s.; B U N 1 0 m g ./10 0 m l.; L E

pre paratio n , n eg ativ e; d irect C o om bs test 1 + . N eu trop h iia w ith a left sh if t, m o noc yto sis ,

po lyc hro m a top hil ia , a n isocy tos is, hy po chrom ia an d 1 9 n ucle ate d R B C /1 00 W B C w e re

prese n t. D esp ite v igorous th era py w ith co rticos tero ids , b lood tran sfu sio ns an d an tib io t ics,

the do g gra dua lly d eter io rated o ver th e ne x t 7 w eek s w ith the d ev elop m e nt of ex ten sive

purpura , m u ltip le ab sc esse s o f the sk in and subc u ta neo us tissues , pne um onia and a zo-

tem ia, th e b lo od urea n itro ge n leve ls su rpa ssing 1 20 m g . pe r c en t te rm inal ly . T hrom bo-

cy top en ia a nd a nem ia p ers iste d throug hou t the c ou rse . T h e direct C oo m b s test w as in ter-



4/19

C A N IN E SY ST E M I C L U I U S E R Y T H E M A T O SU S

14 5

m itten tly p osi tiv e and 2 o f 1 5 L E ce ll p rep aratio ns w ere pos itiv e. T he antin uc lear an ti-

b ody tes t w as po sit iv e . A red ce ll elu ate p rep are d f rom h er c ells w as show n to sen sitiz e

the ery thro cy tes o f 4 ran dom ly sele cte d n orm al do gs to an in direct an tig lob tilin tes t.

P ost mortem examina tio n:

A dv ance d m in eraliz ation o f the g lom eruli , tu bules, B ow m an s

capsu les and arcuate arteries w e re f oun d in th e k idn ey s . H y alin iz ation an d sclero sis o f

g lom eru li w ere also p rom ine nt. In th e h eart , m ult ip le sm all f o ci o f ne cro sis w e re scatte red

th rou gh out the w all o f the le f t v entricle . R e activ e hy perplasia, charac teriz ed by larg e

n um bers of p lasm a cells, w as th e pro m in en t les ion in the sple en . S eg m e ntal h y aline c han ge

w as prese nt in th e w alls o f ce ntral arteries . M e gak ary ocy tes w ere p rese nt in the bo ne m ar-

row and ly m ph no des w e re h y p erp last ic . S ev e re pu rule nt b ron cho pn eum on ia w as pre sen t.

Summary:

T h is dog had an il lne ss o f 6 m o nth s d uratio n c haracte riz ed b y sev e re thro m b o-

cy top enia an d hem o ly tic ane m ia w ith a p ositiv e antig lob ulin te st w ith ult im ate d ev e lop -

inen t o f ren al f ailure .

T w o L E preparations w ere po sitiv e an d an eluate p repared f rom

her red b loo d cells se nsi tiz e d n orm al can ine re d b loo d ce lls to an ind irec t C oo m b s te st.

Case Number 2

T his 4-y ear-o ld w hite m ale stan dard po odle ( R 1 0 4 9 ) w as ad m itted to the A nge ll

M e m o rial A n im al H osp ital in Jan uary , 196 1, be cau se o f epistax is. A cco rding to the ow ne r,

the an im al be gan to b lee d ex tens iv e ly af ter a do g f ight . Ph y sical ex am in ation rev eale d a

larg e bruise 1)ehind the le f t e ar, m ark e d p allor o f the m uc ou s m em brane s, tach y cardia,

p oly pn ea, w eak ness, an d a tem pe rature of 1 01 F.

In itial lab oratory f indings w ere : \V B C 39 ,O 0 0/m i& PC V 11.5 pe r c en t; icterus ind ex

2 units; d irect C o om bs test 2 +. N eu tro philia w ith a shif t to th e lef t, m o noc y to sis an d

m ark ed th rom bo cy tope nia w ere pre sen t. T h ere w as auto agg lu tination o f th e red blo od

cells. T he u rine had a sp ecif ic grav ity o f 1 .01 2 and trace s of alb um in and i ie w ere

p rese nt. T here w ere n o sig nif icant f ind ing s in th e cen trif uge d urinary sed inw nt.

T he do g w as tre ate d w ith tran sf u sion s o f w h ole b loo d and pre dnison e, 10 m g/d ay , an d

h e g rad ually im prov e d .

A t a f o l low -up ex am inatio n o n Feb ruary 2 3, 1 961 , 2 w eek s af ter return ing hom e, he

app eared in g oo d he alth . T he leu k oc y te cou nt w as 1 0,0 00/m m 3; PC V 37 p er cen t; and

the direct C oom bs te st w as n egativ e. A n iso cy tosis , po ly c hro m atop hil ia, hy poc hro m ia an d

thre e u nclass if ie d ce lls/100 \V B C w e re see n in the p eriphe ral b loo d sm e ar. Pred nison e

therapy w as con tin ued in a ( lose of 2 .5 m g /d ay un til M arc h 1, 19 61. O n M arch 3 , 1 96 1,

the do g w as return ed w ith a te m p erature of 104 F., anorex ia, and a m o ist cou gh . A te nta-

tiv e diagno sis o f acu te bro nch op neu m o nia w as m ade an d tre atm en t w ith 5(X ) m g. c hlo ro-

m y cetin in tram u sc ularly e v e ry h ou rs w as b egu n. Prom pt reco v ery e nsu ed f rom the b ron cho -

pn eum on ia in 5 (lay s .

D esp ite c on tinu ou s predn iso ne therapy , thro inb ocy top en ia persis ted (altho ugh the re w as

no purpu ra) and in M ay , 19 61, a sp len ectom y w as perf orm ed . i lie do g respon ded w ell

and w as discharge d on the th ird ho spital day .

Fo llow in g the o peratio n , the platelet n um be rs w ere no rm al. H o w e v er, 2 w eek s af ter

sp le ne ctom y , w h en th e d ire ct C o om bs tes t w as again f oun d to be p osit iv e , pre dnison e the r-

apy w as r e inSt i t l l t e l . S ix m onths af te r th e sp len ecto m y , ano rex ia, lis tle ssn ess an d v o m iting

re app eared . Ph y sical ex am ination rev eale d pallor, gen eraliz ed ly m ph ade nop ath y , dep res -

s ion , and a m ark ed ly d ry , hy pe rk e rato tic no se. L abo ratory e x am in ation rev ealed: \\B C

16 ,000 /m m 3 ; H ct 27 pe r cen t; d ire ct C o om bs test 2 +. N e utroph ilia w ith a lef t sh i f t, po ly -

c hro m atop hilia, an iso cy tosis, increased platele ts an d 65 nu cle ate d R B C / 100 \V B C w ere

p resent in th e periph eral b loo d sm ear. E ry th roid hy p erp las ia w as see n in the bon e m ar-

row p rep aratio n . T h e u rin e w as un rem ark ab le ex cep t f o r in cre ase d u rob ilin og en. A n L E

p rep aration w as po sitiv e. T reatm en t w ith A C T H an d pre dnison e re sulted in co nsiderable

im pro v e m e nt. O n the nin th hospital (lay he w as b egu n on B W 57 -32 2 (Im uran) , 50 m g ./

day . T he d irec t C oom bs test bec am e neg ativ e an d w ith in 2 w ee k s th e he m atoc rit w as

4 5 p er cen t. T w o w eek s later the d og w as retu rne d to the hospital bec ause o f ep istax is .

Phy sical ex am ination again rev e ale d pallor, de pre ssion and ge neraliz ed w e ak n ess .

L abo ratory f ind ing s at that tim e w e re: \V B C 21,000 /m m 3 ; PC V 3 2 p er c ent; pro -

Th is One



5/19

14 6

L E W IS , S C H W A R T Z A N D H E N R Y , JR .

th rom bin tim e 8. 1 se con ds; ic te rus in dex 1 0 un its ; B U N 24 m gs ./10 0 m l.; S G O -T 45 0 S .F .

un its a nd S G P -T 52 00 S .F . u nits. N eutrop h il ia w ith a le ft sh if t, m on oc yto sis, th ro m b ocy to-

p en ia , p o ly chrom ato philia , h yp och rom ia a nd freq ue n t target c ells w e re ag ain n ote d . T he

urine h ad a spec ific g rav ity o f 1 .009 ; a lbu m in 1 + ; b ile , t rac e; u rob i lino gen 1 + . T he ce n tri -

fug ed ur ina ry se d im en t c on tain ed :

R B C 1-3 ; W B C 0;

c asts 4-8 ; ep ith elia l cel ls 1 -2 per

h igh d ry f ie ld . E uthan asia w as per form ed w ith a leth al do se o f pe n to tha l so d iu m a t the

ow ne rs re que st.

P o st m o rtem exam ina tion : H isto log ic ex am ina tio n o f the sp lee n fo llo w in g its re m o val in

1 96 2 reve aled con ges tio n , a tro phy of ly m p ho id fo l lic les, ex tram ed ulla ry h em ato poiesis w ith

la rge num be rs of m ega ka ryo cy te s, and se gm ental hy aline c ha nge s in so m e cen tral arte rie s.

P e riar teria l fib osis w as n ot fou nd . In th e k id ne ys, g lom eru lo scle ros is w as n ot pro m inen t,

bu t m a ny g lom eru li con tained tw o o r th ree w ide ly d ila ted ca p il lary loo ps w hic h stoo d

op en , a lth oug h em pty , a nd w ere re la t ively th in -w alled . M ult ip le sm all sh arp ly d elin eated

foci of ne cro sis w e re sc atte red throug ho ut the l ive r. H ya line deg ene rat ion o f a rte rio les an d

ex tram ed ulla ry hem ato po ies is w ere no ted in th e ly m p h n od es. T h e m eg aka ryo cy tes in th e

fe m o ral m a rro w ha d a fib ril lar cy top lasm an d th eir nu clei w e re p ykn otic . F ib rou s th ic ken -

in g o f th e v isc era l p leura w a s p rese n t.

Sum m ar y :

A 4-y ear -o ld m ale p ood le sim ultan eou sly d eve lop ed th rom bo cy top en ia and

h em o ly tic ane m ia w ith a pos itiv e an tig lob u lin test. P red n iso ne w as on ly part ia l ly e ffe ctiv e

an d a sp len ec tom y w as per form ed . T h e ope rat ion w a s fo llo w ed b y an in crea se in p late -

le ts to n orm al, bu t th ere w a s soon an ex ace rba tion o f the hem oly tic ane m ia , du rin g w hich

th e LE tes t w a s pos itiv e . F u rth er tre atm en t w ith p red n iso ne and an an tim eta bo lite re-

su lte d in im prov em e nt, b u t sig ns of ex ten sive h ep atit is a pp eared tog eth er w ith a relap se

o f the thro m b ocy top en ia . R e nal and hep atic le sion s w ere p rom in en t at n ecro psy .

C a s e N u m b e r 3

T h is 5-y ea r-o ld m a le c oc ker sp an ie l (P 1 293 6) w as ad m itted to the A n ge l M em orial

A nim al H o sp ita l on N ov em be r 2 1 , 1 96 1 , b ec ause o f w ea kn ess a nd ano rex ia . T he an im al

ha d be en treated in the ou t-pa tie n t clin ic w ith salic y la tes fo r a n ob scu re lam ene ss 11

m onths prev ious ly . H e ha d otherw ise be en in go od h ealth u n ti l the day b efo re e n try w h en

he b eca m e very list les s a nd refuse d to eat . O n th e d ay of a dm ission , the dog v om ited and

pa sse d d ark urine. P h ysical ex am ina tio n reve aled sev ere ic teru s, po lyp ne a, w eak nes s a nd

sp lenomegaly .

In itia l lab ora to ry find ing s: W B C 25 ,00 0/m m 3; H b 6 .3 G m .; B U N 67 m g ./1 00 m l.;

(li rec t C oom bs tes t 2+ ; ic ter ic ind ex 2 50 ; ret icu loc y te c oun t 4 .4 p er c en t . N e utroph iia w ith

a sh ift to th e lef t, m o noc yto sis , th rom boc yto pe n ia , an isoc y to sis, p o ly chrom ato philia an d 23

nuc lea ted R B C /1 00 W B C w ere pre sen t in the p eriphe ral b lo od sm e ar. A n L E pre pa ration

w a s p os itiv e . U rin aly sis: C lou dy am ber ; sp ecific grav i ty 1 .037 ; alb um in 4+ ; b ile 4 + ; uro -

b i lino ge n 4+ . T he ce n tri fug ed u rina ry sed im ent c on tain ed W B C 1 -2 ; R B C 0; c asts 0-1 ;

b il irub in crysta ls 2 an d large am ou nts of ye llow a m o rph ou s m a ter ia l pe r h igh d ry f ie ld .

O n the se con d hosp ita l d ay predn iso ne w a s be gun in a d osa ge of 5 m g. e very 12 hou rs.

O n the th ird d ay m ark ed he patom ega ly w a s fo un d and the do g w as un able to sta nd . T h e

hem og lob in le vel co n tinue d to fall, rea ch ing 3 .8 G m . on the six th hosp ita l d ay a t w hic h

t im e p red n isone w as increased to 10 m g. e ve ry 12 ho urs . T he fo llow ing d ay he b eg an to

eat , c ou ld ris e , and w an ted to p lay . T h e ur ine w as no rm a l in c o lo r fo r th e fir st tim e on the

sev en th ho sp ita l d ay . O n the n in th h osp ita l day , he w as p ut on a de cre asin g do se of oral

p re dn ison e. L ab ora to ry f ind ing s a t tha t t im e w e re as fo llow s: W B C 33,0 00 /m m 3 ; H b 7 .8

G m .; d irec t C oo m b s test, neg ative; re t icu locy te cou nt 1 2 .9 pe r ce n t; B U N 16 m g./10 0 m l.;

S G O -T 4 0

S .F .

u nits; S G P -T 56

S .F .

u nits. N eu tro ph ilia , sh ift to th e le ft, m on oc yto sis,

a n isocy tos is, po lyc hro m a top hil ia , h yp och rom ia, target ce lls, a nd 5 nuc lea ted R B C /1 00

W B C w ere pre sen t in th e p erip he ral b lood sm e ar. U rina lys is: spec ific g rav ity 1 .0 25 ; a lbu m in

4 +; b ile , u rob ilin og en 1 . T he c en trifu ged ur ina ry sed im ent con tained R B C 0; W B C 5-7 ;

ca sts , rarely see n ; e p ith elia l c ells 2 -5 pe r h igh dry f ie ld . T es ts fo r a n tithy ro id a n tibod y

a nd a ntinuc lea r a n tib od y w e re p osi tiv e .



6/19

C A N IN E S Y S T E M IC L T JP U S E R Y T H E M A T O S U S

14 7

T he dog im prov ed and w as d isch arged on D ecem b er 8 , 1961 , w ith instruct ion s for the

o w n er to co ntinu e trea tm ent w ith pre dn iso ne for on e m on th . O n D ec em ber 28 , 1961 , he

re tu rned w ith severe pneum on ia w hich respo nded rap id ly to an tib io tic s . O n M arch 8 ,

1 962 , he ag ain w as re tu rned w ith genera lized h air loss , obes ity and gray -p ink h yperkera t-

otic sk in

le s io ns on the face and under the ch in . A biop sy of th is erup tion show ed acan tho-

sis , particu la rly inv o lv ing the ha ir fo llicles , foca l hyp erkera to sis, foca l telang iec tasis in the

papil lary lay er w hich a lso con ta ined aggreg ations of p lasm a cells and lym p hocy tes. T here

w ere sm all co llec tions of m ast ce lls a roun d the d erm al cap illa rie s and a few cap illa rie s

w ith h yal in iz ed w alls w ere seen . T he

o w n e r

re la ted that sim ila r lesions h ad b een se en

p rio r to th e h em o ly t ic cris is, b u t subsequ en tly d isapp eared w itho u t trea tm ent . T h e obe sity

an d g ene ralized h air lo ss w a s th oug ht to be d ue to p ro lon ged c ort ico stero id therapy . A s

of Ju ly 1 , 196 3 , the ha ir ha d g row n ba ck an d th e sk in le sio ns o n th e face ha d ag ain d isa p-

p ea red ; how ev er, h e re m a ined qu ite ob ese an d

has persis ten t a lb um inurla .

S u m m a r y T his

m a le c ock er sp an iel d eve lop ed thro m b ocy top en ia , he m o ly tic ane m ia w ith

a pos itive an tig lobu lin tes t, azo tem ia an d pro te inur ia .

A b o u t

1 year p rio r to th e o nse t o f

these d istu rban ces h e had lam eness w hich resp onded to sa licy lates .

T he he m ato log ic

abn orm alitie s resp ond ed to predn iso ne, b u t p ro tein uria pe rsis ted . A sk in ra sh invo lv ing

the fac e sh ow ed his top ath o lo g ic lesio ns c om patib le w ith h um an d isco id lupu s. T he L E

prepara tion w as pos itive .

Case Number 4

T his 4 -y ear-o ld fem ale toy fox te rrier (N 46 20 ) e n te red the A n gell M em or ial A n im al

H osp i ta l

on M arch

30 , 1 9 6 0 , because of purpura . Sh e w as firs t seen in the ou t-pa tien t

clin ic in Ja nua ry , 19 60 , fo r a bdo m inal d is ten t ion , p o ly d ip sia , a du ll d ry co at, and a lopec ia.

N o treatm e nt w as g ive n a nd these sig ns su bsid ed w ith in a fe w w ee ks. T h e p rese n t illn ess

b egan on the day prio r to en try w h en the ow ner no tic ed b lood in th e an im a ls bed .

Th e

p hys ica l exam ina tio n revea led pe tech iae an d ecch ym oses of the sk in and m u cous m em -

branes. T h e gum s w ere b leed in g

ac tiv ely . T h e tem pe ratu re w as 1 03 F . M ele na an d sligh t

per iph era l lym pha den op ath y w e re no ted .

In it ia l la bo rato ry w ork w as : W B C 17 ,00 0/m m :i; H b 6 .8 G m . per cen t; p ro th rom bin

t im e 7 .8 sec ond s (n orm al 6-9

second s); d irec t C oom b s tes t

3 . S ev ere th rom boc yto pen ia ,

m o d er a t e

an isoc y to sis , po lych rom atoph ilia a nd 4 nu cle ate d R B C /100 W B C w ere foun d .

T h e leuk ocy te d iffe ren tia l fo rm ula w as norm al. U rina lysis : clea r ye llow ; specific g rav ity

1 .0 23 ; album in 4+ ; b ile and in d ic an , trac e. T h e c en trifu ged u rina ry sed im en t show ed R .B C

1-3 ; W B C 10 -20 ; cas ts 0-1 ; e p ithelia l cells 1 -3 p er h igh dry fie ld .

O n the se con d h osp ita l d ay , the dog a ppe are d ve ry w eak a nd had a b lood y v aginal d is-

charg e. S he w as g iven 16 0 m l. o f w hole b lo od , 10 m g. p redn iso ne in tram uscu lar ly , and

2 .5 m g. p red n isone o rally eve ry 6 ho urs . B y the fifth h osp ita l d ay she sho w e d m arked im -

p rovem ent, and the periphera l b lood sm ear n ow con ta in ed norm al n um bers o f p la te lets .

H ow ever, 4+ a lbum inur ia w as still p resen t.

S he w as d ischarged on the sev en th hosp ita l day o n m ain tenance dose of p redn isone fo r

tw o w eeks . T he dog rem ain ed asym ptom atic fo r

6 m on th s, b u t in O cto be r, 19 60 , ex te ns ive

s lc in and m u co us m em bran e b leed ing and th ro m bocy topen ia aga in appeared . T he P C V

w as 34 per cen t an d the d irec t C o om bs tes t w as n eg ative . T rea tm en t w ith predn isone w as

re inst i tu ted

an d d uring th e nex t w eek the dog grad ua lly im prov ed . D esp ite con tinu ous

p red n ison e the rapy , th ro m b ocy top en ia p ersiste d an d in Jan ua ry , 1 96 1 , a sp le nec tom y w a s

p erfo rm ed . P o sto pera tiv ely , th e d og m a in tain ed n orm al p late le t num be rs w ith ou t m e dic a-

t ion

an d w as

free of p urp ura . H o w e ver , on Ju ne 16 , 1 96 1 ,

she re tu rned w ith hem orrhag ic

en te r itis and

w as su bsequ en tly trea ted fo r th is d iso rd er four tim es w ith in the nex t 2

m on ths . O n A ug ust 23 , 1 96 1 , she en tere d

th e hosp ita l w ith a h isto ry of an orex ia fo r 4

d ays , po lyd ips ia , p o ly ur ia , vo m iting a nd m ele na. L abo rato ry w o rk re vea led a hem og lob in

lev el of 1 0 .5 G m ., B U N

15 4

m g./1 00 m l. and n orm al p late le ts. T h e ur ine no w h ad a

specif ic grav i ty of 1 .0 11 , a lbu m in 1-f-, an d 0-2 h ya line casts w ere seen per h ig h dry f ie ld .

T he do g w as trea ted fo r u rem ia and d ischarg ed on th e e ig h th ho sp ita l day .



7/19

14 8 L E W I S S C H W A R T Z A N D H E N R Y J R .

O n F ebruary 2 7 , 19 62 , the d og en tered th e h osp ita l w ith sev ere u rem ia . T he B U N w as

253 m g./100 m l. and an L E p repara tion w as pos itive . T h e tes t fo r an ti-thy ro id an tibody

w as pos itiv e. T h e an im al w as sacrificed w ith an overd ose of pen to tha l sod ium .

Post mortem findings : N e crop sy rev ealed sm a ll c on trac ted k idn eys of une qu al s ize . B o th

k id ney s con tained he ale d infarcts. O utside th e w edg e-shap ed areas o f in farc tio n the g lom er-

u lar cap illar ie s and sm all a rter io les w ere th ickened and hya lin ized , an d a genera lized

m ono nuc lear in te rtub u lar ex uda te w as ev iden t. T he sp leen , w h ich w as ex am ined fo llow ing

the sp le nec tom y in Ja nu ary , 1 961 , w as se verely c on ges ted , con tained h ype rp last ic lym ph oid

fo llic les and m ild ex tram edu llary h em atop o iesis. S egm enta l th icken ing and hya lin ization

o f th e w alls of cen tra l ar teries w as fo und , b u t per iar teria l fib ros is w as ab sen t. D iffuse fatty

in filtra tion of the live r w as presen t. T he lym p ho id fo llic les in the bod y lym ph nod es w ere

hyp erp las tic and n o ev idence of ex tram edu lla ry hem ato po iesis

w a s seen .

Summary:

T his to y fo x terr ier d eve lop ed seve re th ron iboc y to pe n ia a nd hem oly tic a nem ia

w ith a p os itiv e a ntig lo bu lin tes t w hich w ere treated at fi rst w ith co rtic ostero ids a nd later

by sp len ectom y. R em ov al of the sp leen resu lted in an 8-m o nth rem iss ion . H ow ev er, 2 3

m onths af te r th e in itial sym ptom s of her d isease, she d eve lo ped pro gress ive urem ia . T he

L .E . ce ll te st w as pos itive an d an ti-thy ro id an tib od ies w ere foun d in her se rum . G lom eru lo -

sc le ros is w ith w ire lo op les ions w as presen t a t au to psy .

Case Number 5

O n Jan uary 25 , 1 96 1 , th is 4-y ear-o ld sp aye d fem ale G erm an sh eph erd (R 7 05 ) w as

p resen ted to A ng ell M e m o ria l A nim al H osp ita l w ith a h is to ry o f w eakness o f th e h ind

leg s, an orex ia , m alaise , po lyd ip sia an d sporad ic vo m iting . T hese s igns had been presen t

fo r 6 day s. P hys ical ex am ina tion revea led a tem pera tu re o f 102 F ., ex trem e pa llo r, tachy-

ca rd ia and po lypn ea. Fo llow ing th e phy sica l exam ina tion , the dog co llapsed an d w as

hosp i tal ized .

Spec ific trea tm en t co nsis ted of w hole b loo d an d predn isone , 2 .5 m g. every

8 ho urs.

In itia l labora to ry find in gs w ere: W B C 54 ,000/nun3; P C V 20 per cen t; d irec t C o o m b s

test 2+ . N eu troph ilia w ith a le ft sh if t, m on ocy tos is , m arked polychromatophil ia , an isocy-

tosis, m ac roc y to sis , hy po chrom ia, an d 1 3 nu cle ated R B C /10 0 W B C w e re seen in th e

periphera l b lood sm ear.

U rina lys is: c lo ud y y ello w ; spe cific g rav i ty 1 .028 ; alb um in 1 + ; b ile , tra ce; u rob ilinog en ,

trace.

T he cen trifug ed urina ry sed im en t con ta in ed no R B C ; 0-2

W B C an d rare g ran u la r

cas ts per h ig h dry

f ield .

B y the fou rth hosp ita l d ay , th e d og h ad re ga ined her a ppe tite a nd w a s br igh t, a le rt, a nd

a ctive in he r c age . S he w as d isc harged on F ebruary 3 , 196 1 , the n in th ho sp i ta l da y , an d

a t th is tim e h ad a P C V of 38 per cen t, W B C 2 0 , 0 0 / m m 3 ; d irec t C #{ 244} onub stest 1+ . H om e

m ed ica tio n c on sisted o f a dec rea sing do se o f p red n isone for a 2 -w eek p erio d , m ult ip le

v itam ins, a nd an o ral he m a tin ic (P erih em in Jun ior -W in th rop ). O n F e bru ary 1 5 , 1 96 1 , a fter

12 da ys a t h om e, the dog w a s retu rne d to th e hosp ita l w ith a h isto ry o f progress ive a no-

rex ia , vom iting , w ea kne ss a nd polypn ea. P h ysical ex am ina tion re ve aled p allo r, he pato n iega ly ,

ta chy card ia , po lypn ea a nd a tem pe ratu re of 10 4 F . T h e la borato ry fin d in gs w ere: W B C

3 0 ,000 /m m 3; PC V 2 0 per cen t; d irec t C oo m bs tes t 2 . N eu troph ilia , m ono cy to sis , po ly -

ch ro m atop h ilia , an isocy tosis , m acrocy to sis and 22 nuc lea ted R B C /10 0 W B C w ere p resen t .

T h e urine w as dark am ber in co lo r an d had a spec ific g rav ity o f 1 .037 ; b ile 2 +; u rob ilin o -

gen 3+ . T h e cen trifu ged u rina ry sed im en t co n ta in ed R B C 20-3 0 ; W B C 1-2 ; and n o cas ts

p er h igh dry fie ld . T rea tm en t cons is tin g o f 5 m g . p redrm isone every 8 h ours w as s ta rted . B y

th e fif th h osp ita l day the dog had aga in rega ined her ap pe tite and appeared brigh t an d

a le rt. S he w as d ischarged on F eb ruary 25 , 196 1 , the ten th hosp ital day , w ith

instruct ions

fo r th e o w n er to g ive decreasing d oses o f p redn isone fo r 3 w eek s. T he d irec t C oom b s tes t

w as s till p ositive a t the tim e of d ischarge and 144 n uc lea ted R B C /100 W B C w ere presen t

in the periphera l b loo d . A fte r ten days a t ho m e, the d og aga in deve lo ped vom iting , w eak-

n ess, m ala ise an d p allo r an d w a s adm itted to th e h osp ita l fo r the th ird tim e . In a dditio n ,

the d og w as jaund iced a t th is tim e and sp lenom eg aly w as de tected . T he la borato ry find -



8/19

C A N I N E SY ST E M I C L U P U S E R Y T H E M A T O SU S 14 9

in g s co n s isted o f W B C 5 4 ,0 0 0 /m m 3 ; PC V 1 6 p er cen t; d irec t C o o m n b s tes t 3 +. N eu tro -

phil ia

w ith a sh if t to th e le f t, m o n o cy to sis, p o ly ch ro m ato p h ilia, an iso cy to sis , h y p o ch ro m ia,

m acro cy to sis, targ e t ce lls an d 8 5 n u c leated R B C /1 0 0 W B C w ere ag ain n o ted . T h e d o g

w as treated

w ith 1 0 m g . p red n iso n e in tran iu scu larly ev ery 1 2 h o u rs f o r 7 d ay s , at w h ich

tim e m ark ed c lin ical im p ro v em en t w as ev id en t. T h ree h u n d red m l. o f co m p atib le w h o le

bloo d w as

g iv en in trav en o u s ly o n M arch 1 3 ,

19 61 , and

rep eated o n M arch 1 5 , at w h ich

tim e a

sp len ec to m y w as p erf o rm ed . A n u n ev en tf u l reco v ery f ro m su rg ery f o llo w ed an d

th e

d o g w as d isch arg ed o n M arch 2 3 ,

19 61 . A

d ecreas in g d o se o f p red n iso n e w as p re -

sc rib ed f o r 1 w eek . A t th e tim e o f d isch arg e, th e lab o rato ry f in d in g s w ere : W B C 5 2 ,0 0 0 /

m m 3 ; PC V

2 8 p er cen t; d irec t C o o m b s tes t 2 . T h e p erip h eral b lo o d sm ear s till rev ealed

ne utroph ilia, m on oc y to sis an d 82 nuc leated R B C / 1 00 W B C . Period ic e x am in atio ns , c orn -

m en c in g o n M arch 3 1 , d isc lo sed a co n s isten tly ne gativ e direct C o om bs tes t, an d lack of

an y c lin ical sig n s o f ex acerb atio n . In th e d if f eren tial sm ears , h o w ev er, p o ly ch ro n u ato p h ilia,

anisocytos is , p o ik ilo cy to sis, H o w e ll Jo lly b o d ie s, h y p o ch ro n u ia an d an o ccasio n al n u c leated

R B C

w ere seen . E x am in atio n in A u g u s t, 1 9 6 2 , rev ealed a

ret icu loc y te cou nt o f 1 .4 p er

cent an d a B U N o f 2 1 m g ./1 0 0 m l. A n L E ce ll p rep aratio n w as p o s itiv e . T h e L E p rep ara-

tion w as again po sitiv e in Jan uary , 1 96 3, an d m ild alb u m in u ria w as d e tec ted .

H isto log ic ex am ination of the spleen f o llo w in g its surgic al renu ov al rev e ale d sev e re ex tra-

m e dullary hem atopo ies is an d hem no sid ero sis . Periarte rial f ib ros is w as abse nt, b ut m an y of

the ce ntral arterie s c ontain ed seg m e ntal de po sits o f hy aline m aterial w ith in their w alls.

Summary: T h is f em ale G erm an shep herd w as f oun d to hav e sev ere h em o ly tic an em ia

w ith a p o sitiv e an tig lo b u lin te st w h ich ev en tu ally req u ired sp len ec to m y . T h e o p eratio n

re su lted in a p ro m p t am e lio ratio n o f th e h em o ly tic an en u ia an d th e d irec t C o o m b s te st

bec am e neg ativ e. Fo llo w -u p ex am ination s f o r

2 0 m o n th s af te r sp len ec to m y f o u n d th e d o g

in ap paren t g ood health , b u t w ith p o s itiv e L E te sts an d alb u m in u ria.

Case Number 6

T h is 5 -y ear-o ld o v ario h y ste rec to m iz ed h m ale te rrie r (P 1 2 4 1 1 ) en te red th e A n g e ll

M em o rial A n im al H o sp ital o n A p ril 1 5 , 1 9 6 1 ,

b ecause of w e ak n ess , le thargy an d an ore x ia.

T h e o w n er related th at

3 m o nth s be f ore the do g h ad be en tre ate d at an oth er h ospital f o r

pn eum on ia w hic h w as f o llow ed by rapid reco v ery .

T he p hy s ical e x am inatio n at adm iss ion to th e h osp ital re v ealed sev ere pallor, tachy cardia,

ex trem e w eak n ess an d a tem p eratu re o f 1 0 3 F.

In itial lab o rato ry f in d in g s

w ere : \V B C 24,000 /m nnm 3; PC V

1 3 p er cen t; H em o g lo b in 4 .1

C m . per c ent; B U N 25 m gs./100 nil .; icte rus ind ex 15 un its ; d irec t C oom bs test 2 +; auto -

ag glu tin atio n of th e R B C w as o bserv ed . N eu trop hil ia w ith a shif t to the le f t, m ono cy tos is,

20 nuc leated R B C /100 W B C , an iso cy to sis , an d po ly c hro nu asia w e re see n in the p erip he ral

b lo od sm ear. T h e p latelets w e re dec reased in num be r, larg e in siz e an d o f te n in odd f o rm s.

U rinaly sis : c lear y ello w ; spec if ic grav ity 1 .01 7; album in 3; bile 1+; n o u rob ilin og en. T he

ce ntri f ug ed urin ary se dim en t had 0- 2 R B C ; 1 -2 W B C ; 0- 2 cas ts and 1-2 sm all ep ithe lial

ce lls p er h igh d ry f ield . T he do g w as tre ate d w ith 1 20 m l. w hole blo od and p red rm iso ne,

1 0 m g. e v ery 1 2 ho urs . S h e im pro v ed co ns iderably an d w as disch arge d on the elev e nth

hospital day w ith a m aintenance do se of p red nisone . T w o day s f o llo w ing disch arg e, she

re turn ed w ith e pistax is. T o pical ad ren alin an(l co ld p ack s sto pp ed the hen iorrhage an d the

o w n er w as instructed to c on tinu e th e p red nisone the rap y f o r 1 m o nth .

A lth ou gh p red nison e w as co ntin ue d , the dog c ontinu ed to h av e thro nub oc y to pen ia an d

purpura, an d in Ju n e , 1 9 6 1 , a sp len ec to m y w as per formed. Fo l lo win g th e o p eratio n th e

blood f in d in g s w ere, f o r th e f irst tim e since the on set o f her illness, n orm al. H o w e v er, urin-

aly sis co ntinue d to sh ow se v ere p rote inu ria. S ix tee n m on ths af ter sp le nec tom y the do g

w as read m itted to th e ho spital b ecause of an ore x ia and leth arg y . Phy sic al ex am ination re-

v ealed p allo r, he pato m e galy an d a tem pe ratu re o f 1 03 F. T he lab oratory f ind ing s w ere :

W B C 55 ,00 0/m m 3; H b. 5 .5 G m .; d irec t C o om bs tes t, n egativ e ; re ticu loc y te co unt 1 .6 p er

ce nt; B U N 24 m g s./1 00 m l. N eu trop hil ia w ith a sh if t to th e lef t, po ly c hro m atop hilia, aniso -

c y to sis , p oik ilo cy tosis , hy poc hro m ia, th rom bo cy tope nia, and 30 nu cle ated R B C /1 00 W B C



9/19

15 0 L E W I S , S C H W A R T Z A N D H E N R Y JR .

w ere seen in the periph eral b lood sm ear . U rina lys is : c loudy bro w n ; spec ific g rav ity 1 .040 ;

a lb um in 4+ ; b ile , trace and u rob ilinogen 2+ . T he cen tr ifuged u rina ry sed im en t con ta ined

1 3-1 5 R B C ; 25 -30 W B C ; 1 -2 cas ts p er h ig h dry fie ld . A n L E prepa ration w as negat ive,

bu t tests fo r rheum ato id facto r , an tith y ro id an tib ody and an t inu cle ar an tibo dy

w er e

pos i -

tiv e . P re dn ison e, 10 m g e very 8 ho urs, w a s s tar ted on e n try .

Af ter

in i t ial

signs of im provem ent, th e dog becam e ic teric , b ega n v om itin g b lood -tinge d

fro th and had a subno rm al tem pera tu re . T he ic terus be cam e m ore prono un ced

and the

vo m itin g co ntinue d . T h e B U N rap id ly rose to 200 m g./1 00 m l. an d the S G O -T and SG P -T

w e re fou nd to be m a rke d ly ele va ted (29 60 and 1 56 0 S .F . un its respec tive ly .) S he d e-

velope d C hey ne-S to kes re sp ira tion a nd died on the eigh th ho sp i ta l da y .

Post mortem examina tio n:

H isto lo g ic exa m ination of th e sp leen fo llow ing its re m o val

re vea led c on ges tion , h em osidero sis , ex tram ed ullary h em ato poiesis an d h yal in iz ation of

som e o f the ce n tra l a rte ries . T he re w as no p eriarte ria l f ib ro sis .

T he k id ney s w e re foun d to h ave hy alin iz ed an d scle ro t ic g lom eru li, th icke ne d hy alin ize d

B o w m an s cap su les an d p erig lom eru la r in fil tra t ion s of p lasm a cel ls. A sm a ll hem orrha g ic

in fa rct w a s p resen t in on e k idn ey . T he liv er con tained la rge co nflu en t are as of ne cro sis .

A n o cclud ing th rom bu s w as pre sen t in a m usc u la r b ran ch of the left c oro na ry artery an d

m u ltip le sm all in fa rcts w ere p rese n t th rou gh out the m yoc ard ium of bo th ven tric les . L a rge

nu m b ers of p lasm a c ells an d a pa uci ty of lym ph ocy tes w ere p rese n t in th e ly m p h n od es.

T h e fe m o ral m arrow w as a deq ua tely ce llu lar; h ow eve r, fe w m eg aka ryo cy tes w e re prese n t.

Summary:

A 5 -y ear-o ld fem ale te rrie r de velope d th rom bo cy top en ia an d hem oly tic ane -

m ia w ith a pos itiv e an t ig lo bu lin tes t. P ro teinur ia w as fou nd at th e o nse t of h er d isea se .

P re dn ison e h ad on ly a par tia l ef fec t on th e h em ato log ic ab no rm a lities, b u t sp len ecto m y w a s

fo llo w ed by a 1 6-m on th renu iss ion . T he term in al ep isod e w as ch ara cte rize d by su dde n a p-

pea ran ce of hep atic a nd re nal fa ilu re w ith th rom bo cytope n ia . A n L .E . tes t w as ne gat ive ,

bu t an t inu cle ar a nd a n ti thy ro id a n tibod ies a nd rheu m a to id fa cto r w e re fou nd in h er

se rum.

Case Number 7

T his 2 -year-o ld m ale w ire -ha ired fox te rrie r (T 49 1) w as adm itted to th e A ng e ll M em ori-

a l A nim al H o sp ita l in Janu ary , 196 2 , becau se of anorex ia , m ala ise , dia rrh ea, da rk red u rin e

and a lam eness o f the h ind lim b . T hese sign s h ad been ap paren t fo r 3 days . P a llo r, depres -

sion , sp len om ega ly , and a tem pera tu re o f 103 F . w ere no ted o n the phys ical exam ina tion .

F o llow in g a 4-d ay cou rse of p en ic illin the laborato ry f in d ings w ere : W B C 46 ,000 /m m 3 ;

PC V 26 per cen t; re ticu locy te coun t 11 .2 per cen t; ic te rus ind ex 5 u n its; B U N 7 mg./100

m l.; d irec t C oom bs test 2 + ; SG O -T 2 6 S .F . units an d S G P-T 19 S .F . u n its . N eu tro ph ilia

w ith a le ft sh ift, th rom bo cy top en ia , p o lych rom ato ph ilia , a n iso cy tos is a nd 3 nu cle ate d R B C /

10 0 W B C w ere p resen t in the d iffe ren tia l sm ear. U rina lys is : c lo udy am b er ; specific g rav ity

1 .045 ; alb um in , trace ; b ile 4+ ; u ro b ilin ogen 2+ . T he cen trifuged urina ry sed im en t con -

tained : R B C 1-2 ; W B C 1-3 an d gran u lar c asts 0-2 per h ig h dry f ie ld .

Pred n isone w as sta rted a t th is tim e and a prom pt recovery fo llow ed . T he do g w as d is-

ch arged o n the e leven th hosp ital day w ith a W B C o f

1 8 , 0 0 0 / m m 3 ;

P C V 34 p er cen t;

re ticu locy te coun t 1 .2 per cen t; and a w eak ly pos itive d irec t C oom bs test. P red n ison e w as

presc ribed fo r 2 w eek s a t hom e. Ph ysica l exam ina tion 6 w eek s

af ter d is cha rge

revea led

th e do g to be in apparen t good hea lth . T he hem ato log ic and urina ry find ing s w ere unre -

m arkab le , and the d irec t C oom b s test w as n eg a tive a t th is tim e . H ow ever, the L E prepara -

tio n , an tith y ro id an tibody test, an d la tex f ix ation tes t fo r rheum ato id facto r w ere pos itiv e.

T he se ro log ic test fo r syph ilis w as nega tive . U p to th is w riting , the dog has rem ained in

ap paren t go od hea lth .

D I S C U S S I O N

T h e d isease a ffec ting these an im als o ccu rred in a va riety o f b reed s: 2

p oo d le s, 1 co cke r sp an ie l, 1 fo x terrie r , 1 G erm an sheph erd , 1 w ire -ha ired



10/19

C A N I N E SY ST E M I C L U P U S E R Y T H E M A T O SU S 15 1

Table 1 .-Prominent F inding s in Dogs with Systemic Lupus Erythematosus

CASE NO .

HEMO LYT IC AN EM IA

I

+

2

+

3[ 4

+ j+

5

+

6

+

7

AN T IG LOBU LIN TE ST

+

+ + + +

+

+

THROMBOCYTOPEN IA

+

+

+ +

0

+ +

RET ICULOCYTOS IS

+

-

+

-

+ +

+

-

-

+

-

+

-

-

JAUNDICE

+

-

+

-

-

AZOTEM IA

+

+ + +

0

+

-

ALBUMINURIA

-

BIL IRUB INURIA

..

LEG END + {149}PRESEN T

{149}BSENT

0 {149}NO T DE TER MINE D

te rrie r, and 1 m o ngre l. T h e do gs ranged in age f rom 4 to 6 y ears (ro ugh ly

equ iv alen t to 3 0-40 y ears in m an). T w o of the 4 f em ales h ad b een ov ario -

hy ste rec tom iz ed and o nly 1 o f these 4 h ad b orn e a litte r. N one o f the dog s

had receiv ed an y m ed icatio n p rior to th e o nse t o f illness and , as far as is

k no w n, no ne w ere ex p osed to tox ic chem ical ag en ts. In 6 o f th e do gs th e onset

o f the d isease occurred du rin g the w in ter m onth s (N ov em ber, D ecem b er,

Janu ary and M arch) an d in th e sev en th dog , p urp ura f irst appeared in A pril.

E ach d og h ad been v acc inated ag ain st can in e d is tem per and the in terv al

be tw een the v acc ination and th e appearance o f th is d iso rder w as at least 3 { 189 }

years.

T hese 7 do gs had a s im ilar patte rn o f d isease : h em oly tic anem ia, throm bo-

cy top en ia an d neph ritis (tab le 1). T he d isord er f irs t b ecam e c lin ically ev id en t

as a resu lt o f th e hem ato log ic abno rm alitie s, bu t in 3 o f th e an im als, pro -

tein uria w as n o ted at th e f irst ex am inatio n . S ev eral o ther ab norm alities w ere

also fou nd in c lud in g in term itten t lam eness o f u nk n ow n cause in 2 dog s,

alop ecia in 2 an d an erup tio n on the bu tte rf ly area o f the f ace in 1 do g .

H em oly tic anem ia w as th e m os t prom in en t f eature o f the d isease in these

dog s (f ig . 1 ). It w as ch aracteriz ed b y h em oglo b in lev e ls as low as

3. 5

G m .

per cen t, re ticu locy to sis , n orm oblastem ia and uro b ilinu ria. Jaun d ice and

spherocy tosis w ere v ariab le f in d ing s. T here w as hy perp lasia o f the ery thro id

e lem ents in the bon e m arrow . In each case , the d irec t an tig lob u lin test w as

pos itiv e ; the stren g th o f th e reac tion v aried be tw een 1+ an d 3+. T h us, th ese



11/19

.

1 f.

V

I

152

L E W IS S C H W A R T Z A N D H E N R Y JR.

iip .

Fig. 1.-Peripheral blood from a dog with systemic lupus erythematosus and

autoimmune hemolytic anemia. N I acrocvtosis, spherocvtosis and polvchroniatophil ia

are present. \V right-G iemsa)

dogs had the typical features of autoimmimuc liemolytic anemia as seen in man.

A n eluate PrePar from the red cells of dog number R 14511 sensitized

normal

canine erythrocytes, further substantiating the presence of an eryth-

rocyte autoantihody. A lthough each dog

responded initially to prednisone

therapy, 4

had recurrent hemolytic episodes and eventually underwent

splenectomy. T hereafter, anemia was not a major problem until azotemia ap-

peared. I n contrast to w hat is usually found in human beings with this con-

litiofl, the direct antiglobulin test in these clogs always became negative

shortly after the institution of therapy. T he reappearance of a positive anti-

globulin test in those clogs which were in remission was soon followed by a

recurrent attack of hemolytic anemia.

T he next most common feature of this canine disease w as thrombocytopenia.

T his abnormality was

found in 6 animals and w as associated w ith an overt

hemorrhagic tendency in four. T he bleeding manifestations were char-

acterized by easy bruising, ecchymoses, petechiae, and active bleeding from

mucous membranes. Bone marrow aspirates of 2 of these thrombocytopenic

dogs contained normal numbers of megakaryocytes. T his finding, together

with

the

prompt response to corticosteroicis suggests that the thrombocyto-

Penia in these dogs is analogous to the idiopathic IT P) variety seen in man.



12/19

I,

.,

{149}

C A N IN E S Y S T E M IC L U P U S E R Y T H E M A T O S U 5

i 4

I,

. :

4

.4

153

Fig .

2.-Skin

biopsy f rom m alar eruption of Case N o. 3. H perkeratosi s, para-

k eratosi s, tel angiectasi s of vessel s

in

the papi l l ary l ayer of the

derm is and accum ul a-

ti ons of

m ononuclear i nf l am m atory cel l s

i n the derm i s are present.

Hematoxvlin-

eosin)

T he sim ul taneous occurrence of idiopathi c thrombocy topenic purpura and

autoim m une hem oly ti c anem ia descri bed in m an Evan s syndrom e)1 i s as-

sociated w i th a high inci dence of sy stem ic l upus ery them atosus.

Fi ve of these dogs al so m ani f ested signs of renal i nvolv em ent dur ing som e

phase of thei r i l l ness. I n three, m arked protei nuri a w as f ound at the outset

and renal f ai lure w as the cause of death i n 4 dogs of th is seri es. Cor ti co-

steroids f ai l ed to im prov e the nephri t i s.

Of parti cular i nterest w as the dev elopm ent of a dry scal y eruption invol v -

ing the butterf l y area of the f ace in dog num ber P 12936. Cl i ni cal l y , th is

l esi on bore a resem blance to the erupti on of l upus in m an onl y because of

i ts l ocation. H i stol ogical l y , how ev er, there w as a stri k i ng resem blance to

hum an discoid lupus f i gs. 2,

3). T hi s dog had had tw o bouts of thi s rash-

one

of

w hich antedated the onset

of

the

autoimm une hem oly ti c anem ia.

I t should be noted that thi s anim al had, al so, sal i cy l ate- responsi ve l am e-

ness 1 year to the hem atologi c di sorder. T hus, thi s dog ex hibi ted the se-

quential developm ent of arthri ti s, butterf l y rash, autoim m une hem oly ti c ane-

m ia, i di opathi c throm bocy topenia and f inal l y , nephr i t i s, w i thi n a peri od of

approx im ately 1 year.

T he prom inent gross f i ndi ngs at necropsy w ere rel ated to anem ia, urem ia,

or term inal bacteri al i nf ecti on, such as bronchopneum onia. H i stol ogi cal l y ,

chronic membranous glom erulonephr i ti s w i th w i re i oop lesions w as a con-

sistent f i nding f i g. 4). Ex tramedul lary hem atopoiesi s including num erous

m egakaryocy tes w as a uni f orm f i nding in these dogs. I n addi ti on, hepati c



13/19

8

Fig . 3 .-S k in biop sy f rom m alar eru p tion o f C ase N o. 3 . T he ch an ges p resen t

here are acan th osis, te lang iec tasis

of v e sse ls in p apil lary lay er of the de rm is and

p eriv ascu lar accu m u latio n o f p lasm a ce lls an d ly m p h o cy tes . (H em ato x y lin -eo s in )

15 4

L E W IS S C H W A R T Z A N D H E N R Y JR .

necros is w as ob serv ed in 2 do gs, and m y o card ial in f arc tion resu ltin g f ro m

throm b osis o f sm all m uscu lar coronary arterie s w as fo und in 2 o th er dog s.

Periarte rial f ib ro sis (on ion sk in lesion s)

in

the sp leen w as sp ec if ically

sou gh t, b u t n o t f ou nd . H ow ev er, f ib rin o id necro sis, w h ich w as seg m ental in

n atu re , w as o b serv ed in th e w alls o f cen tral arterie s in th e sp leen s o f 5 d o g s

(f ig . 5 ) . Furth erm o re , hem atox y lin b od ies w ere no t recogn iz ed in the tis-

sues stu d ied f ro m these do gs.

T here has been renew ed in terest in au to im m une d iseases in recen t y ears,

an d n um erous d isorders o f obscu re cause are curren f ly b ein g consid ered as

due to au to im m u niz atio n . T he v alid ity o f som e of these assertions m ust

aw ait th e accum u latio n o f m ore data. T he w id esp read use o f im m u nolo g ic



14/19

\.

,

* *

*

+ t,

L i1

I

C NI NE SY ST EM I C L UPUS ERY T H EM TOSUS

155

Fig. 4.-Chrom e m em branous glom erulonephri t i s i n a dog w i th system ic l upus

ery them atosus. W ire l oop lesi ons, hval i ni zati on of gl om erular tuf ts, and adhe-

si ons of gl om erular tuf ts to B ow m an s capsule w ere f ound. Peri odi c aci d-Schi f f )

tests has di scl osed the presence of ci rcul ati ng anti bodies in m any diseases

not hi therto thought to have an im m unologi c com ponent. I t is thus di f f i cul t

to render a precise w ork ing def i ni t i on of an autoim .rnune di sorder. M acK ay

and B urnet 6 hav e l i sted six features or mark ers of autoimm unization w hich

seem to be acceptable guidel i nes in deal i ng w i th thi s problem. T hese are

hyperglobul i nem ia, the presence of autoantibodies in the serum, the deposi -

ti on of denatured gam ma globul i n or i ts deri v ati v es in ti ssues, accumulati ons

of l y mphocy tes and plasma cel l s in dam aged ti ssues, benef i t f rom corti co-

steroids, and the coex istence of mul ti ple autoimmune disorders in the sam e

indiv idual . T ak en by themselves, none of these mark ers are conclusi v e;

how ever, w hen each of them occurs at one tim e or another during the course

of an i l l ness, they are of considerable im portance. A s f ar as i s know n at

l )resent, the only process w hich could giv e r i se to thi s constel l ati on of

m arkers is an immunologic one.

M ost of these markers of autoim munization w ere f ound in the canine

disorder descr ibed in thi s report. A utoantibodies, such as rheum atoid f actor,

L E f actor f i g. 6), anti thy roid antibody and posi ti ve antiglobul i n tests w ere

demonstrable in v arious combinations in every case table 2). A ccumulati ons

of plasm a cel l s w ere found not only in damaged ti ssue, but in the lymph

nodes and spleens as w el l f i g. 7). I n each case there w as a prom pt ini ti al re-

sponse to corti costeroids, but

4 dogs ev entual l y underw ent splenectom y be-



15/19

Fig . 5 .-Cen tral arte ry in sp leen o f C ase N o . 2 . T here a re segm enta l fib rin o id

changes in th e tun ica m e dia and he m o sid ero sis. (P e riod ic a cid -S c h if f)

# {1 76 }S inc e s ub m ission of th is re por t, 8 m ore d ogs w ith S L E h ave b een stud ied . T hree o f

these an im als had hyperg lob u lin em ia .

15 6

L E W I S S C H W A R T Z A N D H E N R Y J R .

cause o f recu rren t m an ife sta tion s o f the hem a to log ic com p onen ts o f th is d is-

ease. M u ltip le le sio ns invo lv ing th e red ce lls , p la tele ts , k idneys , sk in , and

o th er o rg an s, w ere fou nd . N o te sts fo r the d epositio n o f gam m a glo bu lin in

dam aged tissue w ere m ad e, so th is m arke r cann o t be eva lua ted . A lth oug h

hyp ergam m ag lobu linem ia w as no t foun d in these do gs, its ab sence do es no t

ru le o u t an im m u no lo g ic d is tu rbance.*

T he va lid ity o f the various se ro log ic p rocedures w as tes ted in o ur labora -

to ry in the fo llo w in g m ann e r: S e rum sam ples from 25 ran do m ly se lected dog s

in appa ren t goo d health w ere used as con tro ls fo r th e la tex fixa tion and an ti-

th y ro id an tibod y te sts , to ta l s erum pro te in lev els , and se rum pape r str ip

elec tro pho re sis . N o con tro l serum sam ples reacted in the tests fo r rheum a to id

fac to r o r an tithy ro id an tibo dy . T h e am o un t o f gam m a glo bu lin p re sen t in

th e con tro l serum sam ples ranged fro m 4 .8 to 2 8 .8 p e r cen t. T h is v ariab ility

in th e am oun t o f gam m a g lobu lin p re sen t in dog serum co inc ides w ith p re -

v io us repo rts on th e incons isten cy 7 of re su lts o f se ru m e lectrop hore sis in

health y and d iseased d ogs . O ur recen t observa tion of w e ll-de fin ed hyp e r-

gam m ag lobu linem ia on ly during the p rod rom a l stage o f au to im m un e h em oly t-

ic an em ia in a d og m ay in d ica te th a t th e tim e o f sam ple co llec tion fro m af-

fec ted d ogs is ex trem ely im po rtan t in th e de tec tion of ab norm a lly h igh serum

lev els o f gam m a glob u lin . A te st fo r an tinuc lear an tib ody w as p erfo rm ed on

th e se ru m of 5 o f these d ogs. A pos itiv e te st w as reco rd ed in 3 and in the

asy m pto m a tic dau gh te r o f C ase N um b er 1 . H o w ev er , du e to the lack of ade -



16/19

F ig . 6 .-L .E .

ce lls from d ogs w ith sy stem ic lup us ery th em a to sis . (W rig h t-G iem sa )

C A N IN E S Y S T E M IC L UPUS E R Y T H E M A T O S U S

15 7

q ua te po sitive co n tro l se ra o f can ine o rig in , th is p rocedu re is u nde r fu r the r

study and w ill n o t be dea lt w ith fu rth er .

T hus, usin g th e b roadest p ath o log ic an d c lin ical c rite r ia it is ev iden t th at

th ese dog s had an im m un o log ic d iso rde r o f th e au to im m un e type . T h is w as

n o t a con d ition con fined to one o rg an as is H ash im oto s d isea se , fo r ex am ple ,

bu t w as a gene ra lized process w hich a ttack ed tw o p rin cip al sy stem s-b loo d

ce lls and b loo d v essels . T h e im m u no lo g ic cond ition of m an w h ich ex em plif ies

th is m ultisystem ic invo lvem en t is sy stem ic lu pus ery th em ato sus. T he re are

m an y reasons fo r b eliev in g tha t a nea rly iden tica l d iso rde r h as been fou nd in

these dog s.

T h ere a re m an y sim ila ritie s an d som e d iffe rences be tw een can ine and

h um an lup us. T he sim ila ritie s inc lud e the on set in Y oun g adu lts ; the p re sence



17/19

15 8 L E W i S

S C H W A R T Z

A N I H E N R Y JR .

T ab l e

2 .-Sero log ic Abnorma litie s in D og s with Systemic Lupus Erythemato sus

CASE NO

I 2 3

4

5

6

{ 49 }T

L E FACTOR

RHEUMATO ID

FACTOR

-

0

ANT ITHYRO ID

ANT IBODY

-

0

HYPER

-

GAMMAGLOBUL INEMIA

LEGEND I { 1 49 }PRESENT

- { 149 } SENT

O

{ 149 }NOT DETERMINED

o f m u ltip le au to an tibod ie s , in clu d ing the L E fac to r ; th e hem a to lo g ic , rena l,

de rm a to log ic and ca rd iac le sion s; and th e sequen tia l dev elo pm en t o f o ne ab -

n orm ality su pe rim p osed o n ano the r. T he d iffe ren ces in c lude th e absence of

any d iscern ib le ph o to sen sitiv ity ; the lack of on ion sk in lesio ns in th e sp leen ;

the absen ce of hem ato xy lin bo d ie s in tissu e sec tion s; the str ik in g hepa tic

n ec rosis th at w as seen in tw o cases ; and the lack of hy pe rg iobu linem ia . T h ese

d ifferences m ay sim p ly rep re sen t sp ec ie s va ria tio ns. In an y even t, w e do n o t

b elieve they de trac t fro m th e b road re sem b lan ces be tw een the tw o fo rm s o f

the d isea se . H ope fu lly , fu r the r stu d ie s o n can ine lu pu s w ill y ie ld in fo rm a tion

u sefu l in un de rs tan d ing h um an lup us.

S U M M A R Y

A n atu ra lly occu rr ing im m u no lo g ic d isease , cha rac te rized by au to im m u ne

h em oly tic an em ia, id iopa th ic th ro m bo cy top en ic purpu ra and nephritis , is

d esc r ibed in seven do gs. T he d isea se p rim arily a ffec ted fo rm ed e lem en ts in

th e b lo od , g lom eru li an d b lood vesse ls . A b norm a l se rum pro te ins, inc lud ing

th e L E fac to r , rh eu m a to id fac to r and an tith y ro id an tibo dy w ere fou nd in

affec ted dog s. C o rticoste ro ids and sp len ec tom y w ere effec tive in con tro lling

the h em ato log ic co m p onen ts o f th e d isease, b u t ap pa ren tly h ad n o e ffec t o n

th e rena l le sion s. R ecurrence w as frequen t and the p rog nosis w as g rave . A d -

d itiona l ab norm a litie s , inc lud in g m a la r e rup tio n , in te rm itten t lam en ess an d

a lop ec ia w ere occas io na lly fou nd as an in teg ral pa rt in the sequ en tial in -

v o lvem en t o f seve ra l tissues d urin g the cou rse o f th e d isease.

A C K N O W L E D G M E N T S

W e are in deb ted to M iss

Jane

R e insboroug h fo r tech n ic al a ssis tan ce, D r. W . A . B a rda w il

fo r per forming

th e an tinuc lear an tibo dy te sts ,

and D r. T . C . Jones fo r a id in preparing th e

manuscr ip t .



18/19

C A N I N E SY ST E M I C L U P U S E R Y T H E M A T O SU S

15 9

F ig . 7 . L ym ph

no de f rom a dog w ith sy stem ic lup us ery them atosu s. L arge ac-

cu m ulation s o f p lasm a ce lls are w ith in th e s inu soids. (H e m atox v lin -eo sin )

SU M M A R IO IN IN T E R L IN G U A

E s describ ite sep te casos can in d e tin n atu ralm en te o ccurren te m o rb o

im m uno log ic ch arac terisate per au to im m u n anem ia h em oly tic , id io path ic

purpura th rom bocy to pen ic , e nephritis . L e m o rb o af f icev a prim arim en te Ic

f orm ate e lem entos de l san gu in e, le g lo m enilos , e le

va so s

sang u inee . A no rm al

pro tein as seral- inc luse le fac tor de L E , fac tor rheum ato ide , e an ticorpore

an tithy ro idee -essev a trov ate in af f ic ite canes. C ortico ste ro ides e sp lenee tom ia

essev a e f f icace in com batter le com p onen tes h em ato log ic de l m orho , sed iste

m esuras parev a hab er nu lle e f f ec to sup er le les iones renal. R ecurren tias e -ssev a

f requ en te, e le prog nose essev a grav e . A lte re anorm alitates-eru p tion m alar,

claud ication in term itten te , e alo pec ia-essev a occasion alm en te tro v ate co m o

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Robert S. Schwartz M.D . Assistant Pro fes sor o f Medic ine

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William B. Henry Jr. D .V.M. Staff Member Artge ll Memoria l

Anima l H ospita l Bo sto n M ass.


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