Lincoln S akiara M iyasaka, A ry de A ndrade Junior, C arlos E duardo B ueno, A lvaro N aglb A tallah
R e la p sin g P o ly c h o n d ritis
Internal Medicine Division of Hospital Slio Paulo, Escola Paulista de Medicina of
Universidade Federal de Slio Paulo - Slio Paulo, Brazil
Purpose: This article describes a clinically-diagnosed case of relapsing polychondritis (R P), attended at the H ospital Sao Paulo, and presents a literature review of the subject. Source of research: The literature review w as m ade via M edline (1990-96), Lilacs (1980-96), textbooks of rheum atology, and som e articles about the history of the disease. In M edline, 113 articles from 1990 to 1996 w ere found, and there w ere 23 articles from 1980 to 1996 in Lilacs. R esearch procedure: W e review ed the articles available at BIR EM E (Biblioteca R egional de M edicina) w ith the prim ary focus being on the disease in question. Sum m ary: R P is a rare disease of unknow n etiology described initially by Jackson-W artenhorst in 1923 and characterized by a recurrent and acute inflam m atory process that causes the collapse of the cartilaginous structures and their subsequent replacem ent by fibrous connective tissue. The cartilage m ost com m only attacked is that of the auricle of the ear and nasal septum , w hile the cartilage of the trachea, larynx, epiglottis, ribs, and articulations m ay also be involved. O cular inflam m ations and system ic reactions w ith fever are also described. In 1976, M cAdam presented a com plete prospective study of 23 patients, review ed the 136 cases described up until that tim e, and then proposed diagnostic criteria w hich w ere later expanded by D am iani and Levine. C urrently, m ore than 500 cases have been described. C onclusion: Although a rare disease, better know ledge of it is needed, as R P m ay be lethal w ith tracheal collapse and obstruction of respiratory pathw ays, m aking precise diagnosis and adequate therapeutic intervention necessary.
U N ITER M S: R elapsing polychondritis.
C ASE R EPO R T
A
w h ite B r a z ilia n m a le , a g e d 3 1 , f ir e m a n , n a tiv e o f T e r r a B o a , P a r a n a , a n d r e s id e n t o f P o a , S a o P a u lo , w a s in te r n e d o n J u ly 3 , 1 9 9 6 . T h e p a tie n t c a m e to th e h o s p ita l w ith a h is to r y o f c h e s t p a in f o r o n e m o n th .E le v e n m o n th s b e f o r e th is , w ith n o p r io r s y m p to m s , th e p a tie n t b e g a n to f e e l s ta b b in g p a in s lo c a liz e d in th e r e g io n b e tw e e n th e s h o u ld e r b la d e s , w h ic h w o r s e n e d w ith m o v e m e n t a n d p h y s ic a l f o r c e . T e n m o n th s b e f o r e
A ddress for correspondence:
Lincoln S akiara M iyasaka
R ua T eodoro S am paio, 9 7 2 -casa 18
S ao P aulo/S P - B rasil - C E P 05406-050
dry cough and dyspnea w hen coughing. T he patient denied
having addictions to tobacco or alcohol.
P hysical exam ination
show ed the patient to be in
regular general condition, fever (38°C ), slim m ed, eupneic,
anem ic, H R = 94, arterial blood pressure
11/8
cm of H g.
O n his face, a depression in the nose w as observed
(photo). A decrease of vesicular m urm ur in both lungs
w ithout abnorm al rale w as noted. T here w as no alteration
in the heart, nor in the abdom en. T here w as pain in the
articulations
of the knees,
w rists,
and costo-condral
articulations w ithout local heat or redness.
L A B O R A T O R Y
F IN D IN G S
C reatinin = 0.5
mg/dl;
P otassium = 4.5 m E q/l; sodium
= 143 m E q/l; B ilirrubin T = 0.4, D = 0.2, 1= 0.2 G O T = 9
U Il, G P T = 11U /l; E rythrocyte count = 4.4 x 10
I
m m
3;H b= 12.2
g/dl;
H t = 38% ; M C H = 27.73 pg; M C H C =
32.11 g/dl;
M C V = 86.36; platelet = 394,000; leukocyte
= 14,100 (neut = 76, eos = 3, bas = 0, lim ph = 12, m ono =
9); A lb = 3.1
g/dl;
U rinalysis: pH = 6.5, D = 1020, prot
(-), gluc( -(-), leukocytes =
12,000/ml,
erythrocytes =
800,0001
m l dism orphism
(-), calcium
oxalate
crystals
= few ;
calcium = 284 m g in 1,620 m l urine in 20 h; uric acid =
729 m g in 1,620 m l of urine in 20 h.
A ntinuclear antibody (-), anti native D N A antibody
(-), anti E N A antibody (U 1-R N P , anti-S m , anti
SS-AfRo,
anti-S S -B /L a) = (-); C H 50 = 188 U (130-330); R heum atoid
factor (-); cryoglobulin (-); anticardiolipin
antibody (-);
A N C A
(-); C reactive
protein
=
1/16;
L E cels
(-);
M ucoprotein = 5.3; anti streptolisin
0 <200 U I/m l; V D R L
(-); urine protein excretion (-); creatinin clearance = 124
m l/m in/l.73m ;
urine culture (-).
T otal protein = 6.7 (6-8
g/dl),
A lb = 2.91 (3.2 - 5.6);
alpha 1 = 0.21 (0.1 - 0.4); alpha 2 = 1.27 (0.4 - 1.1); beta
= 1.13 (0.1 - 1.2); gam m a = 1.18 (0.5 - 1.6); E rythrocyte
F ig u r e - " S a d d le " a s p e c t o f th e n o s e .
1 6 3 9
T a b le 1
C lin ic a l fe a tu re s in th e c o u rs e o f re la p s in g p o ly c h o n d ritis (6 ): c o m p a ris o n o f 2 s e rie s
sed im en tatio n rate
=
5 3 (1 -7 m m /h ); acid alp h a 1g lu co p ro tein
=
3 9 5 (4 3 -1 3 0 m g /d l).P ro th ro m b in T im e =8 0 .8 (> 7 0 % ); R N I = 1 .1 9 ; P T T
=
1 .0 « 1 .2 5 ); B leed in g T im e=
1 (1 -3 m in ); co ag u latio n tim e=
7 (4 -9 ).X ray ex am in atio n o f facial b o n es sh o w ed th e n asal
b o n e w ith o u t alteratio n , an d cartilag e h ip o p lasia.
O p h th alm o lo g ic ex am in atio n sh o w ed ep iscleritis in th e
left ey e.
R en al b io p sy resu lts w ere: o p tic an d im m u n o flu
-o rescen ce m icro sco p y n o rm al.
E V O L U T IO .N
A u ric u la r C h o n d ritis A rth ritis
N a s a l C h o n d ritis O c u la r M a n ife s ta tio n L a ry n x - T ra c h e a l In n e r E a r C a rd io p a th y V a s c u lo p a th y N e p h ro p a th y
M c A d a m
n
=
15988.60/0
8 1%
72.4%
65.4%
55.90/0
45.9%
11.9%
16.30/0
NR
Is a a k
n
=
1 1 285%
52%
540/0
5 1% 48%
43%
6%
14%
26%
D iag n o sis o f relap sin g p o ly ch o n d ritis (R P ) w as
m ad e clin ically o n Ju ly 9 , 1 9 9 6 , an d treatm en t w ith
p red n iso n e 1 m g /k g (6 0 m g p er d ay ) started . T h ere w as a
p ro m p t su b sid en ce o f articu lar p ain , fev er an d g en eral
co n d itio n , w ith o n ly h o arsen ess rem ain in g .
T h e p atien t is n o w b ein g fo llo w ed u p as an o u tp atien t
receiv in g 4 0 m g o f p red n iso n e p er d ay .
L IT E R A T U R E R E V IE W
Epidemiology
T h e p rev alen ce o f R P is eq u al am o n g m en an d
w o m en . It h as b een d escrib ed in all races b u t is m o re
freq u en t am o n g C au casian s (1 7 ).
Clinical Findings
(6-12)R P is ch aracterized b y acu te in flam ~ ato ry
ep iso d es o f cartilag in o u s stru ctu res th at m ig h t reco v er
sp o n tan eo u sly , b u t th at freq u en tly relap se an d
cu lm in ate w ith th e d estru ctio n o f its stru ctu re. It m ay
p resen t sy stem ic in v o lv em en t w ith fev er, w eig h t lo ss,
an d o th er o rg an s su ch as cen tral n erv o u s sy stem ,
k id n ey s, resp irato ry tract, an d b lo o d v essels.
T h e m o st freq u en t clin ical featu res o f 2 literatu re
rev iew s w ith 1 5 9 an d 1 1 2 cases w ere su m m arized b y
A n d res J P o liti (T ab le 1 ).
T h e m o st freq u en t clin ical featu re in b o th series is
au ricu lar ch o n d ritis. T h e au ricu lar p av ilio n is sw o llen ,
n
=
n u m b e r o f p a tie n tsp ain fu l an d an g ry -red in co lo u r. In 9 5 % o f cases it is
b ilateral. It m ay p ro v o k e th e n arro w in g o f th e ex tern al
au d itiv e can al. T h e ear lo b e is p reserv ed . T h e p ro cess m ay
su b sid e sp o n tan eo u sly , o r it m ay d estro y th e cartilag e,
leav in g a "cab b ag e-lik e" ap p earan ce. It m ay p resen t as a
p o ly o r o lig o arth ritis.
N asal ch o n d ritis lead s to th e d estru ctio n o f th e
cartilag in o u s p o rtio n o f th e n asal sep tu m , g iv in g th e n o se
a "sad d le-lik e" ap p earan ce.
T h e o cu lar alteratio n s are u n sp ecific, su ch as
co n ju n ctiv itis, u v eitis, retin o p ath ies, o p tical n eu ritis,
p alp eb ral ed em a, an d p ro p to sis. E p iscleritis is th e m o st
freq u en t, o ccu rrin g in 3 9 p er cen t o f cases (2 1 ).
R esp irato ry m an ifestatio n s are h o arsen ess,
d y sp n ea, a ch o k in g sen satio n , w h eezin g , an d p ain in
th e lary n g o trach eal articu latio n s. T h ese can p ro v o k e
o b stru ctio n th ro u g h th ree m ech an ism s: ed em a o f th e
g lo ttis, trach ea an d b ro n ch i; fo rm atio n o f a fib ro u s m ass
in th e airw ay s; an d co llap se o f th e trach eal cartilag e.
T h e o b stru ctio n is co m p licated b y in fectio n .
H earin g lo ss m ay b e ex p erien ced d u e to o b stru ctio n
o f th e ex tern al au d ito ry can al, m id d le ear o titis, o r b y
afflictio n o f th e au d ito ry b ran ch o f th e V III cran ial n erv e
d u e to v ascu litis. N au sea, d izzin ess, v o m itin g , an d atax ia
. b y n eu ritis o f th e co ch lear b ran ch d u e to v ascu litis m ay
also b e p resen t.
V ascu litis is also fo u n d in so m e cases o f R P .
A cco rd in g to M ich et, sy stem ic v ascu litis is th e m o st
freq u en t asso ciated in flam m ato ry sy n d ro m e (1 7 ) b u t th is
w as n o t P o liti's fin d in g in h is su m m ary o f 2 7 1 cases o f
p o ly ch o n d ritis (6 ). T h ere are cases d escrib ed o f ao rtal an d
Associated Diseases
Complementary
Exams
T a b le 2
D is e a s e s a s s o c ia te d w ith r e la p s in g p o ly c h o n d r itis
A p p ro x im a te ly 2 5 p e rc e n t o fR P c a se s a re a sso c ia te d
w ith o th e r d ise a se s, w ith th e fo llo w in g b e in g th e m o st
c o m m o n a c c o rd in g to P o liti.
Etiopathogenesis
T h e e tio p a th o g e n e sis is n o t c le a r, b u t th e re a re in d
i-c a tio n s o f a u to -im m u n e in v o lv e m e n t. R P is a sso c ia te d
w ith a u to -im m u n e d ise a se s in
250/0
o f c a se s; im m u n o g lo-b u lin s a n d le sio n c o m p le m e n ts a re e n c o u n te re d , a s a re
ty p e II a n tic o lla g e n a n tib o d ie s in th e se ru m o f p a tie n ts
w ith a c tiv e R P . C lin ic a l im p ro v e m e n t o c c u rs w ith im m u
-n o su p p re ssio -n th e ra p y .
Histopathology
T h e h isto p a th o lo g ic a l fin d in g s a re d ia g n o stic .
D u rin g th e a c tiv e p h a se , th e re is a lo ss o f c a rtila g e
m e ta c ro m a sis, c h o n d ra l a n d p e ric h o n d ra l n e c ro sis,
in filtra tio n b y th e p o ly m o rp h o n u c le a r n e u tro p h ils,
p la sm a c y te s, ly m p h o c y te s, a p o p to tic b o d ie s, a n d
p e ric h o n d ra l h e m o rrh a g e . In th e a d v a n c e d sta g e , th e re is
c ic a tric a l re p a ir w ith ly m p h o h istio c y tic in filtra tio n ,
fib ro sis, d e p o sit o f h e m o sid e rin a n d lo ss o f e la stic tissu e .
S tu d ie s w ith d ire c t im m u n o flu o re sc e n c e re v e a le d
p o sitiv ity fo r Ig A , Ig M , Ig G a n d C 3 , su g g e stin g th e
p re se n c e o f c irc u la tin g im m u n e c o m p le x e s (2 2 ,2 3 ).
Differential Diagnosis
C o n sid e rin g th e g e n e ra l c lin ic a l situ a tio n , th e m o st
d iffic u lt d iffe re n tia l d ia g n o sis is w ith W e g e n e r's
g ra n u lo m a to sis (W G ) a n d o th e r sy ste m ic v a sc u litis. W G
is m a n ife ste d a s a sy ste m ic v a sc u litis w ith c o lla p se o f th e
n a sa l w a ll, a rth ritis, a n d a fflic tio n o f th e re sp ira to ry
sy ste m . W G c a n b e d iffe re n tia te d b y th e p re se n c e o f
g ra n u lo m a s, in v o lv e m e n t o f lu n g s a n d k id n e y s, a n d th e
la c k o f a u ric u la r p a v ilio n in v o lv e m e n t.
T h e " sa d d le " n o se c a n a lso b e fo u n d in W G a n d
le ish m a n io sis, a d v a n c e d c o n g e n ita l sy p h ilis, lu p u s,
sa rc o id o sis, th e le p ro m a to u s ty p e o f le p ro sy , b a so c e llu la r
e p ith e lio m a s, c o c a in e in h a la tio n , a sp e rg ilo sis a n d
p a ra c o c c i d i o i d o m i c o si s. 5 %
3 .1%
1 .2 5 %
1 .2 5 %
1 .2 5 %
1 .2 5 % 5 %
1 .8 8 %
1 .2 5 %
1 .2 5 %
0 .6 2 %
3 .1%
6 .9 % R h e u m a to id A r th r itis
S jo g r e n 's S y n d r o m e
S y s te m ic L u p u s E r ith e m a to u s
S y s te m ic S c le r o d e r m ia
P s o r ia tic A r th r itis
R a y n a u d 's S y n d r o m e
T h y r o id itis
U lc e r a tiv e C o litis
G lo m e r u lo n e p h r itis
D is g a m m a g lo b u lin e m ia
P e r n ic io u s A n e m ia
N e o p la s m
O th e r
In a re v ie w o f 1 2 9 p a tie n ts w ith R P , 2 9 p re se n te d
a ffe c te d k id n e y s. M e sa n g ia l e x p a n sio n , c e llu la r
p ro life ra tio n , a n d n e c ro tiz in g g lo m e ru lo n e p h ritis w e re
o b se rv e d . E le c tro n m ic ro sc o p y d e te c te d d e n se d e p o sits
a t th e m e sa n g i-a l le v e l, a n d d ire c t im m u n o flu o re sc e n c e
re v e a le d C 3 a n d Ig M in th e m e sa n g io ( 0 ) .
N e u ro lo g ic a l m a n ife sta tio n s in c lu d e o p h th a lm ic
n e u ritis o f th e o c u lo m o to r, fa c ia l a n d a u d itiv e -v e stib u la r
n e u ritis, h e a d a c h e s, e n c e p h a lo p a th y , c o n v u lsio n s,
h e m ip a re sia s a n d a ta x ia s.
N o c o m p le m e n ta ry e x a m is d ia g n o stic fo r R P ; a ll
a re o n ly slig h tly se n sitiv e a n d sp e c ific . T h e ir u tility is o n ly
to d isc a rd o th e r p a th o lo g ie s a n d re c o g n iz e o th e r a ilm e n ts.
T h e e ry th ro c y te se d im e n ta tio n ra te a n d re a c tiv e C
p ro te in a re th e b e st e x a m s to a c c o m p a n y th e e v o lu tio n o f
th e d ise a se . T a d a k i e t a l stu d ie d th e c o m p o sitio n o f u rin a ry
g lu c o sa m in o g lic a n a n d fo u n d a n e le v a tio n o f d e rm a ta n
su lp h a te a n d h y a lu ro n ic a c id , b o th o f sk in o rig in in th e
a c tiv e p h a se s o f th e d ise a se a n d n o t th e 4 -6 su lp h a te
c o n d ro i tin th a t w o u ld b e e x p e c te d in c a se s o f c a rtila g e
d e stru c tio n (2 4 ).S o fu rth e r stu d ie s a re n e c e ssa ry in th is a re a .
A n tib o V d ie s to ty p e II c o lla g e n h a v e b e e n re p o rte d to
c o rre la te w ith th e a c tiv ity o f th e d ise a se (2 0 ).
Prognosis
T h e fiv e -y e a r su rv iv a l ra te is 7 4 p e r c e n t (1 4 ). T h e
m o st fre q u e n t re a so n fo r d e a th is in fe c tio n o f th e '
re sp ira to ry tra c t, se c o n d a ry to th e b ro n c h ia l o b stru c tio n
a n d th e u se o f c o rtic o ste rio d s. O th e r c a u se s a re sy ste m ic
v a sc u litis, a c u te re sp ira to ry in su ffic ie n c y d u e to
re sp ira to ry c o lla p se , a n d re n a l in su ffic ie n c y d u e to
g lo m e ru lo n e p h ritis.
Treatment
T h e tre a tm e n t o f R P c o n sists o f th e u se o f
n o n ste rio d a n ti-in fla m m a to rie s a n d lo w d o se
1641
co rtico stero id s in situ atio n s o f m ild au ricu lar/n asal ch o n d ritis o r arth ritis. F o r cases w ith serio u s m an ifestatio n s su ch as lary n g o trach eal o r o cu lar sy m p to m s, in n er ear in flam m atio n , sev ere au ricu lar o r n asal ch o n d ritis, sy stem ic v ascu litis, ao rtitis o r g lo m eru lo n ep h ritis, p red n iso n e at a d o se o f 1 m g /k g / d ay is in d icated . T h e u se o f im m u n o su p p resso rs su ch as azath io p rin e an d cy clo p h o sp h o am id e is reserv ed fo r th o se p atien ts refracto ry to stero id th erap y (1 3 ). T h e u se o f d ap so n a, co lch icin a (1 5 ), an ti-C D 4 m o n o clo n al
an tib o d y , D -p en icillam in e an d an tim alarials" h as also b een d escrib ed . T h e in creasin g n u m b er o f su ccessfu l rep o rts o f cy clo sp o rin A in a d o se o f 1 5 m g /k g /d ay su g g ests th at it m ay b e th e b est to lerated an d p o ten tially m o st reliab le d ru g fo r th e co rtico stero id -resistan t p atien t (1 4 ,1 6 ). N eb u lized racem ic ep h ed rin e is an o p tio n
u sed su ccessfu lly in cases o f acu te su b g lo tic ed em a (1 9 ). C o n tin u o u s p o sitiv e airw ay p ressu re m ask s m ay p ro v id e relief o f sev ere d y sp n eic sy m p to m s (1 7 ).
D I S C U S S I O N
R P is a rare d isease seld o m d escrib ed in th e literatu re. O n ly 5 0 0 cases h av e b een p u b lish ed w o rld w id e u p u n til n o w . In B razil, o n ly fo u r articles w ere en co u n tered fro m 1 9 9 0 -9 6 (search b y L ilacs).
H isto lo g ical d iag n o sis is m ad e w ith d ifficu lty b ecau se cartilag e m aterial can n o t b e o b tain ed fo r an aly sis,
o r b ecau se fin d in g s are u n ch aracteristic, p rin cip ally in th e ad v an ced stag es w h en th ere is d estru ctio n o f th e stru ctu res an d th eir rep lacem en t b y fib ro sis. W h en th ere is n o p o ssib ility o f a h isto lo g ical d iag n o sis, it m u st b e m ad e clin ically . A cco rd in g to D am ian i an d L ev in e, th is clin ical d iag n o sis can b e co n firm ed b y :
1 ) T h ree o f M cA d am 's criteria: b ilateral au ricu lar ch o n d ritis, p o ly ch o n d ritis, n asal ch o n d ritis, o cu lar in flam m atio n (co n ju n ctiv itis, scleritis, ep iscleritis, u v eitis o r q u eratitis), ch o n d ritis o f th e resp irato ry tract o r in v o lv em en t o f th e V II cran ial n erv e, ev en w ith o u t h isto lo g ical co n firm atio n ;
2 ) O n e o r m o re o f M cA d am 's criteria w ith h isto lo g ical co n firm atio n ;
3 ) T w o o r m o re affected sites w ith resp o n se to treatm en t w ith co rtico id s o r d ap so n a.
T h e case in q u estio n p resen ts fo u r o f M cA d am 's criteria: n asal ch o n d ritis, p o ly ch o n d ritis, ep isceritis, an d ch o n d ritis o f th e resp irato ry tract, in ad d itio n to th e im m ed iate resp o n se to co rtico th erap y . In sp ite o f n o t h av in g h isto lo g ical co n firm atio n , w e w ere ab le to m ak e th e d iag n o sis clin ically . T h e h em atu ria w ith n eg ativ e d y sm o rp h ism an d elev ated u rin ary calciu m w as in terp reted as b ein g d u e to u rin ary m icro calcu li, w h ich im p ro v es th e p ro g n o sis.
REFERENCES
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1 9 6 0 ;2 6 3 :5 1 - 5 8 .
2 . K a y e R L , S o n e s D A . R e la p s in g P o ly c h o n d r itis . C lin ic a l a n d P a th o lo g ic F e a tu r e s in F o u r te e n C a s e s . A n n a ls o f I n te r n a l M e d ic in e 1 9 6 4 ;6 0 ( 4 ) :6 5 3 - .6 6 4 .
3 . D o la n D L , L e m m o n G B , T e ite lb a u m S L . R e la p s in g P o ly c h o n d r itis . A n a ly tic a l L ite r a tu r e R e v ie w a n d S tu d ie s o n P a th o g e n e s is . A m e r ic a n J o u r n a l o f M e d ic in e 1 9 6 6 ;4 1 :2 8 5 - 2 9 7 .
4 . R e ta m a r R A , L e o n A R , S p in e r R E , M a g n in P H . E s ta d o A c tu a l d e la P o lic o n d r itis C r o n ic a s R e c u r r e n te d o s N u v e a s O b s e r v a c io n e s . R e v A r g D e r m 1 9 9 3 ;7 4 :8 5 - 9 6 .
5 . M ic h e t C J . V a s c u litis a n d R e la p s in g P o ly c h o n d r itis . R h e u m a tic D is e a s e C lin ic s o f N o r th A m e r ic a 1 9 9 0 ; .
1 6 ( 2 ) :4 4 1 - 4 4 4 .
6 . P o liti A J . P o ly c o n d r itis R e c id iv a n te s R e v is io n C r f tic a . A r c h iv o s A r g e n tin o s d e D e r m a to lo g f a 1 9 9 3 ;T .X L I I I :7 3 - 9 1 . 7 . P e r e ir a M D , A r a u jo C M , S ilv a R C , A z e v e d o J R G M , F e r r e ir a M A T , R e s e n d e P S , A m a r a l M J C S , P e d r o s o E R P . A s s o c ia ~ a o e n tr e P o lic o n d r ite R e c id iv a n te e T u b e r c u lo s e T r a ta d a c o m C o r tic o id e e C ic lo f o s f a m id a - R e la to d e U rn C a s o . R e v M 6 d M in a s G e r a is 1 9 9 4 ;4 ( 4 ) :5 8 - 6 0 .
8 . S e lf J , H a m m a r s te n J F , L y n e B , P e te r s o n D A , P a u l S T . R e la p s in g P o ly c h o n d r itis . A r c h I n te r n M e d 1 9 6 7 ;
1 2 0 : 1 0 9 - 1 1 2 .
9 . P a r r o c h ia E B . P o lic o n d r itis A tr o f ia n te . B o l H o s p S J d e D io s 1 9 9 4 ;4 1 ( 5 ) :3 3 0 - 3 3 1 .
1 0 . G ib s o n G J . R a r e R h e u m a tic D is o r d e r s . R e la p s in g P o ly c h o n d r itis . B a illie r e s C lin R h e u m a to I 1 9 9 3 ;7 : 1 7 9 - 1 8 1 . 1 1 . F r e e d m a n S F , A m e d e e R G . R e la p s in g P o ly c h o n d r itis . J L a
S ta te M e d S o c 1 9 9 2 ;1 4 4 :1 3 1 - 1 3 3 .
1 2 . P e r e z M S , L a r io A B , L o p e z A J , V a ld in e ls o A J L . A c ta O to r r in o la r in g o l E s p 1 9 9 2 ;4 3 :2 1 - 2 6 .
1 3 . K a r p m a n W J . A r th r itis a n d A llie d C o n d itio n . A T e x tb o o k o f R h e u m a to lo g y , 1 3th
e d . 1 9 9 6 ; 1 5 9 5 - 1 6 0 3 .
1 4 . K lip p e l J H , D ie p p e P A . R h e u m a to lo g y , 1 9 9 4 ;6 .3 1 .1 - 6 .3 1 .4 . 1 5 . G o ih m a n - Y a h r M . R e la p s in g P o ly c h o n d r itis R e s p o n d in g
to C o lc h in e . I n t J D e r m a to lo g y 1 9 9 4 ;3 3 ( 6 ) :4 4 8 - 9 . 1 6 . O r m e r o d A D , C la r k L J . R e la p s in g P o ly c h o n d r itis
-tr e a tm e n t w ith c y c lo s p o r in A . B r itis h J o u r n a l o f D e r m a to lo g y 1 9 9 2 ; 1 2 7 :3 0 0 - 3 0 1 .
1 7 . M ic h e t C J . R e la p s in g P o ly c h o n d r itis o f K o o p m a n W J A r th r itis a n d A llie d C o n d itio n s . A T e x tb o o k o f R h e u m a to lo g y , 1 3th
e d . 1 9 9 7 ;8 2 :1 5 9 5 - 1 6 0 3 .
1 8 . V a le n z u e la R , C o o p e r r id e r P A , G o z a te P , e t a l. R e la p s in g P o ly c h o n d r itis . H u m a n P a th o l 1 9 8 0 ; 1 1 : 1 9 - 2 2 .
1 9 . G a f f n e y R J , H a r r is o n M , P a th P R C , B la y n e y A W . N e b u liz e d R a c e m ic E p h e d r in e in th e T r e a tm e n t o f A c u te E x a c e r b a tio n o f L a r y n g e a l R e la p s in g P o ly c h o ~ d r itis . J L a r y n g O to l
1 9 9 2 ; 1 0 6 :6 3 - 6 4 .
2 0 . F o id a r t J M , A b e S , M a r tin G R e t a l. A n tib o d ie s to ty p e I I c o lla g e n in r e la p s in g p o ly c o n d r itis . N e w E n g la n d J o u r n a l o f M e d ic in e 1 9 7 8 ;2 9 9 :1 2 0 3 - 1 2 0 7 .
2 1 . I s s a k B L , L ie s e g a n g T J , M ic h e t C J . O c u la r a n d S y s te m ic F in d in g s in R e la p s in g P o ly c h o n d r itis . O p h th a lm o lo g y 1 9 8 6 ;9 3 :6 8 1 - 6 8 9 .
2 2 . F o id a r t J M , K a tz S J . S u b tle c lu e s to d ia g n o s is b y im m u n o p a th o lo g y : r e la p s in g p o ly c h o n d r itis . A m J D e r m a th o p a th o l 1 9 7 9 ; 1 :2 5 7 - 2 6 0 .
2 3 . B e r g f e ld W F . R e la p s in g P o ly c h o n d r itis w ith p o s itiv e d ir e c t im m u n o f lu o r e s c e n c e . A r c h D e r m a to I 1 9 7 8 ;1 1 4 :1 2 7 . 2 4 . T a d a k i T , A ib a S , I g a r a s h i M , T a g a m i H . A n a ly s is o f
in c r e a s e d u r in a r y a c id g ly c o s a m in o g lic a n s in a p a tie n t w ith r e la p s in g p o ly c h o n d r itis . A c ta D e r m V e n e r e o l 1 9 8 7 ; 6 7 :4 4 1 - 4 4 5 .
