UVEI TI S I N SARCOI D OSI S
D r . N URCH ALI ZA H . SI REGAR
Ba gia n I lm u Pe n ya k it M a t a Fa k u lt a s Ke dok t e r a n Un ive r sit a s Su m a t e r a Ut a r a
UVEI TI S I N SARCOI D OSI S
Sarcoidosis, first recognised as a derm at ological rarit y in lat er relat ed t o a w idely dissem inat ed inv olm ent of t he ret iculo- endhot elial syst em ( benign lym phogranulom at osis) , is an affect ion, or perhaps a group of affect ion of unknow n aet iology w hich m ay inv olve alm ost every organ in t he body . ( 1)
Sarcoidosis is a com m on, idiopat hic, m ult ist st em disorder charact erized by t he presence of non- caseat ing granulom at a w ich m ay affec virt ually any single or com binat ion of organs in t he body ( 2,3,4,6)
Hist ologically, t he lesion consist of non- caseat ing t ubercle com prised of accum ulat ion of ephit heloid cell w it h giant cells. Clinically it m ay be sym pt om less but usually it t ends t o pursue an indolent course for m any y ears, oft en w it h exacerbat ions and rem issions, som et im es show spont aneous recovery but occasionally t o be progressiv e w it h a fat al t erm inat ion. ( 1)
Uv eit is is t he m ost frequent ocular inflam m at ion in sarcoidosis. Bet w een 25% and 50% of pat ient s w it h syst em ic sarcoidosis exhibit ocular inflam m at ory disease. Sarcoidosis ia 10 t im es m ore frquent am ong Am erican black s t han am ong Whit e. Person of all age can be affect ed, alt hough occurrence is m ost com m on bet w een t he age 20 and 50 y ears.( 3,4,5,6)
PATH OGEN ESI S
Granulom at ous disease is m ediat ed by ant igen- st im ulat ed act iv at ed T- helper cells, w hich secret e lym phok ines t hat at t ract , arrest , and act iv at e m onocyt es and cause t hem t o different iat e int o epit heloid and m ult i nucleat ed giant cells. Sarcoidosis seem s t o reflect an im m une response t o a st ill unident ified ant igen ( or ant igens) , probably air- borne because of t he high frequency of hilar lym padenopat hy involvem ent at t he on set .
t uberculin and ot her ubiquit ous ant igens, or t hey lose t heir posit iv e react iv it y if t hey dev elop sarcoidosis.
This anergy is rest ored aft er t he sarcoidosis resolves. How ever, persons w it h sarcoidosis do not m anifest am paired rej ect ions of hom ograft s or increased suscept ibilit y t o m alignant neoplasem s or infect ion ( provided t hat t hey are not receiving long- t ernm high- dose cort icost eroid t heraphy) .
A peridheral blood T- cells lym phopenia occurs in sarcoidosis, apparent ly due t o t he ext rav ascular pooling of T- lym phocyt es in t issue rat her t han because of im m une deficiency.( 4)
The lungs are affect ed in about 90% of cases. The init ial present at ion m ay vary dram at ically, and t he cl; inical course m ay be acut e, subacut e or chronic.
1. Acut e disease usually affect s pat ient s during t he t hird decade. I t dev elops over a few and present in one of t he follow ing w ays :
a. Lofgren syndrom e,w hich is charact erized by fever, eryt hem a nodosum , bilat eral hilar lym phadenopat hy and frequent ly art hralgia.
b. Heerfordt syndrom e ( unv eoparot id fev er) w hich is charact erized by fev er, parat oid enlargem ent and uv eit is.
c. Sevent h nerve palsy w it h ot her neurological involvem ent m ay be present .
2. I nsidious- onset disease t y pically present s during t he fift h decade w it h fat igue, dy spnoea and art hralgia.
CLI N I CAL FEATURES ( 1 ,2 ,3 ,4 ,5 ,6 )
1. Lung inv olvem ent is t he hallm ark of t hese disease, and st aging is based on radiological assessm ent of bot h parenchy m al and lym phat ic inv olvem ent as follow s :
a. St age 1 : Bilat eral hilar lynphadenopat hy
b. St age 2 : Bilat eral hilar lynphadenopat hy and ret iculonodullar parenchym al infilt rat es.
c. St age 3 : Ret iculonodular infilt rat es alone
d. St age 4 : Progressiv e pulm onary fibrosis w it h bullae form at ion and
bronchiet asis 3. Skin lesions
a. Ery t hem a nodosum is by far t he m ost com m on. I t is charact erized by red, t ender nodules on t he ant erior surface of t he bot h legs and occasionally on t he but t ocks and arm s.
b. Cut aneous granulom at a, w hich m ay be m aculopapular, raised or nodular, m ay be seen on t he face, but t ocka and ext rem it ies.
c. Lupus pernio ( purple lupus) is t he classical cut aneous granulom aous m anifest at ion w hich is charact erized by chronic, indurat ed, purple- blue lesions
4. CNS lesions occur in 5% pat ient s and are associat ed w it h significant m orbidit y and m ort alit y .
a. Cranial nerve palsies, w hich m ay affect any cranial nerve, are t he m ost com m on CNS m anifest at ion. The facial nerve is m ost frequent ly affect ed
b. Ot her lesions include m eningeal infilt rat ion, seizures and personalit y dist uebance.
OCULAR FEATURES
The eye is involve in about 30% pat ient s w it h sarcoidosis. Ocular involvem ent m ay occur in pat ient s w it h few , if any , const it ut ional sym pt om s, as w ell as in t hose w it h inact ive syst em disease.
The post erior segm ent is inv olved in about 25% of pat ient s w it h ocular sarcoid and is usually associat ed w it h ant erior uveit is.
1. Ant erior segm ent lesions m ay inv olve t he conj unct iv e, episleraa and rarely, t he sclera.
2. Kerat oconj unct ivit ies sicca m ay occur as a result of lacrim al gland involvem ent .
3. Ant erior uv eit is is usually bilat eral and m ay be eit her acut e or chronic. a. Acut e iridocy lit is t y pically y oung pat ient s w it h acut e sarcoidosis.
b. Chronic granulom at ous iridocylit is usually affect s older pat ient s w it h chronic lung fibrosis in w hom t he ssyst em ic disease m ay be inact ive. The int raocular inflam m at ion, m ay be difficult t o cont rol t he com plicat ions such as band kerat ophat y, com plicat ed cat aract . Koeppe and Busacca iris nodules and w hit e clups of cells ( snow balls) in t he inferior ant erior v it reous are t y pical findings. Num m ular corneal infilt rat es, inferior corneal endot helial opacificat ion, and large iris granulom as also occur. Post erior synechiae can be ext ensive and m ay lead t o iris bom be and large angle- closure glaucom a. Peripheral ant erior synechiae m ay be ax t ensive, encom passing t he ent ire angle, 3600 in advanced cases. Secondary glaucom a m ay be severe, part icularly w hen aggressive st eroid t heraphy reverses ciliary body hyposecret ion. The iridocycilit is m ay vary and at t im e can be indist inguishable from acut e nongranulom at ous disease.
4. Vit reous changes are eit hw r in t he form of diffuse v it rit is or, less frequent ly, “ cot t on ball” opacit ies.
5. Periphlebit is is t he m ost com m on feat ure of post erior segm ent sarcoidosis. I t is m ost frequent ly m ild, alt hough rarely adv anced peprphlebit is giv es rise t o t he charact erist ic periv ascular “ candle- w ax drippings” . Alt hough acut e lesions m ay resolve spont aneously or w it h t he use of syst em ic st eroids, vascular sheat ing, once est ablished, usually persist s.
6. Ret inal and preret inal granulom at a are uncom m on. The let t er are t y pically discret e,grey- w hit e and locat ed inferior and ant erior t o equat or ( Lander sign) . 7. Choroidal granulom at a are com m on and charact erized by bilat eral, m ult iple,
sm all, pale- yellow elevat ed lesion, usually m ost num erous inferiorly. Rarely a choroidalgranulom a m ay be solit ary and large and m ay be m ist ak en for an am elanot ic m elanom a.
8. Acut e sarcoid ret inopat hy is charact erized by com binat ion of v it reous haze, “ candlew ax drippings” , ret inal and preret inal granulom at a and ret inal haem orrhages.
9. Periperal ret ina neovasculat izat ion m ay occur in associat ion w it h capillary drop- out on fluorescein angiography . I n black pat ient s it m ay be a confused w it h sickle- cell ret inopat hy .
10. Opt ic nerve lesions m ay be of t he follow ing t y pes :
a. Focal granulom at a m ay inv olve t he opt ic nerve but do not usually affect visual acuit y.
b. Papilloedem a is usually secondary t o CNS involem ent and m ay occur in t he absence of t he ot her ocular lesions.
d. Persist ent disc oedem a of unknow n cause is frequent finding in pat ient s w it h ret inal or v it reous inv olvem ent .
D I AGN OSTI C TEST ( 2 ,3 ,4 ,5 ,6 )
Alt hough t he diagnost ic is oft en easy, in som e pat ient s of feat ures are m issing and t he follow ing special invest igat ion m ay be useful :
1. Chest radiographs are abnorm al in over 90% of pat ient s. 2. Biopsy
a. Lung biopsy is accurat e in diagnosing sarcoidosis in about 90% of pat ient s.
b. Conj uct iv al biopsy is posit iv e in about 90% pat ient s pat ient s irrespect ive of t he precence of eye involvem ent .
c. Lacrim al gland biopsy by t ransj unct iv al rout e m ay be considered in pat ient s w it h suspect ed sarcoidosis, part iculary if t he lacrim al glands are enlarged or if t hey dem onst rat ed increased gallium upt ake. Biopsies are posit iv e in 25% of pat ient s non- enlarged and in 75% enlarged glands.
3. The Kv eim Silzbach t est is posit iv e in 85- 90% in pat ient s w it h early or act iv e syst em at ic disease but sensit ive decreases w it h chronicit y.
4. Serum angiot ensis- convert ing enzym e ( ACE) is usually elevat ed in pat ient s w it h act iv e sarcoidosis and norm al during rem ission. I n pat ient s w it h suspect ed neut osarcoid, ACE should be m easured in t he cerebrospinal fluid. 5. Calcium assays show abnorm al m et abolism . Hypercalciuria is com m on but
hypercalcaem ia is unsual.
6. Gallium - 67 scan of t he head, neck and t horax frequent ly show s increased upt ak e in pat ient s w it h act iv e sarcoidosis.
7. Bronchoalveolar lavage show s a raised proport ion of act ivat ed T- helper lym phocyt es.
TREATM EN T ( 2 ,3 ,5 )
Topical periocular, and syst em at ic cort icost eroids are variable necessary. Cycloplegia is required for com fort and for prevent ion of synechiae. When syst em at ic disease is present ,cooperat ion bet w een t he opht halm ologist and int ernist is required t o dev ice an opt im alt herapeut ic plan.
Pat ient s diagnosed and t reat ed early hav e a fav orable out com e and are left w it h lit t le residual ocular disabilit y. Topical st eroids are not alw ays adequat e, and periocular st eroid inj ect ion of 20- 40 m g of depom et t hy lprednisolone m ay be needed t o supplem ent drops for ant erior nodular irit is and glaucom a. Sy st em ic cort icost eroids in high init ial doses are oft en necessary as w ell as, e.g. prednisone 40- 60 m g PO qd w it h t aper over sev eral w eeks. Cy cloplegics ( at ropine, hom ot ropine) are cont inued t hroughout t he st eroid course. Cyclosporine A has been used successfully in recalcit rant cases, but no regim en has been est ablished. Cy t ot ox ic agent s such as azat hioprine or cyclophospham ide offer no advant age.
REFEREN CES
1. Am erican Academ y of Opht halm ology, I nt raocular I nflam m at ion and Uveit is, Basic And Clinical Science Course 1997- 1998, page 122- 124
2. Elder- Duke, Sir St ew art , Syst em of Opht halm ology, Disease of t he Uveal t ract , The C.V Mosby Com pany , 1970 page 517- 531
4. Kanski, Jack J, Clinical Opht halm ology, A Syst em at ic Approach, Fourt h Edit ion But t erw ort h- Heinem ann, 1999 page 273- 279.
5. Khurana, A.K, Opht halm ology, New Age I nt ernat ional ( P) Lim it ed, Publishers,1998, page 182.
