R ev ista d a S o c ie d ad e B r as ile ir a d e M e d ic in a T r o p ic al 2 8 ( 4 ) :4 0 5 - 4 0 7 , ou t- dez , 1 9 9 5 .
RELA TO D E CA SO
D IA BETES M ELU TU S A SSO CIA TED W IT H PEN TA M ID IN E
ISETH IO N A TE IN D IFFU SE CU TA N EO U S LEISHM A N IA SIS
Jack son M auricio Lopes Costa, M arta Solange C. M oraes, A na Cristina R. Saldanha, A ldina Barral and M arcelo N. Burattini
The a u th ors re po rt a case o f a m a le p a tie n t fro m B acab a l, M A w ith d iffus e cu ta n e o u s leis hm a nias is ( D C L ) , f o r a t least n in e y ears, w ith 168 lesions o n his body. These w ere tu m o u r- like n od ule s w ith s om e u lce ra tm i. H e u s e d p e n ta v a le n t a n tim o n ia l C glu ca n tim e® ) a n d a n a s s ocia tion o f g a m m a in te rfe ro n p lu s g lu ca n tim e w ith im p ro v e m e n t o f the les ions b u t relaps ed later. Recently , p e n ta m id in e is e thion ate ( p e n ta ca rin a t® ) w as g iv e n a dos age o f 4mg/ kg/ w eight/ day on a lte rn a te day s f o r 2 0 a pplica tion s . A fte r 3 m on ths a s im ila r cou rs e o f 10 a pp lica tio n w as giv e n 2 times . La te r he d e v e lope d d ia b e tic signs w ith w eight loss o f 10kg, poly d y ps ia, p o ly u ria a n d xe ros tom ia . The low e r lim b s les ions s how ed s igns o f activ ity . B lo o d glu cos e levels n o rm a lis e d a n d re m a in like this a t m om e n t. A tte n tio n is d ra w n to the fa c t that p e n ta m id in e is e thion a te s h ou ld b e us ed as a therapy op tion w ith care, ob e y ng rigo ro u s
la b o ra to ry co n tro ls in clu d in g a glu co s e tole ra n ce test.
Key - w ords : D iffu s e cu ta n e ou s leis hmanias is . P e n ta m id in e is e thionate . D iab ete s m ellitus . M a ra n h ã o State.
D iffuse cutaneo us leishm aniasis (DCL) is a rare fo rm o f cutaneo us leishm aniasis in w hich cellular immunity to leishm ania antigens is ab sent and w hich sho w s a p o o r resp o nse to antileishm anial agents. A cco rd ing to Silva12, w ho o riginally d escribed the d isease in Brazil, initial lesio ns are macular, p ap ular o r no d ular co ntaining abund ant p arasites. Reg io nal lym p had eno p athy and m uco sal lesio ns are unco m m o n and visceral lesio ns unrep o rted 5.
The d isease beg ins as a no d ule, to spread lo cally and d istally to the rest o f the skin. A ltho ugh the M o ntenegro skin test is negative, in d ic atin g a lac k o f c e llu lar im m u nity to leishm ania antigens, DCL patients d o respo nd to unrelated skin test antigens such as PPD and cand id in3 5.
Bry ceso n4 used v ario us treatm ent regimens o f d rug in 24 DCL p atie n ts, p en tam id ine m e s y la te ( 4m g / k g / d aily ) re s u lte d in im p ro v em ent in all 24 p atients, but relapsed . Pen to stam (lO m g / sbV / kg fo r 5-30 d ay s) resulted in initial im p ro v em ent. O ne o f 6
D epartamento de Patologia da Faculdade de M edicina da Universidade Federal do M aranhão, São Luis,. MA, Universidade Federal da Bahia, Salvador, BA e Escola Paulista de M edicina/EPM , São Paulo, SP,Brasil.
Endereço para coirespondência: Prof. Jackson M.L. Costa. Dept° Patologia/FM /UFM A . Pavilhão Pedagógico. Pça Madre D eus 2,65025- 560 São Luis, MA. Fax (098) 222-5135. Recebido para publicação em 14/09/ 94.
patients w as cured w ith p rim aquine 30m g p er d ay fo r 2 m o nths, and did no t relap se o v er 14 mo nths. This case p ro bably sho w s that the rare case o f diffuse d isease w ith o nly o ne lesio n m ay self heal. A m p ho tericin B (lm g/ kg/ fo r abo ut 2 m o nths) w as used in 4 p atients. In Peru, p ento stam (20mg/ sbV/ day fo r 60 d ays) resulted in im p ro v em ent but no t cure7.
In Brazil, the drug o f cho ice fo r the treatm ent o f m uco cutaneo us and DCL is the p entav alent antimo nial (g lucantim e® )10 13. If relap se o ccurs, seco nd line therap y w ith am p ho tericin B o r p entam id ine are ind icated . Pentam id ine isethio nate is no t av ailable, being im po rted fro m England (p entacarinat® ). The Brazilian Ministry o f Health furnishes this drug fo r sp ecial cases such as DCL
Bry ceso n 19703 and Bo uchard and co ls 19821, rep o rted that p entam id ine may cause d iabetes mellitus. Recently, o ur team attend ed a p atient w ith DCL w ho d ev elo p ed d iabetes mellitus after p entam id ine isethio nate, that w e w o uld like to re p o rt.
CA SE R EPO R T
RNPS, 31 years old, man, land w o rker, fro m the state o f M aranhão , no rtheast o f Brazil, had DCL caused by Leishm ania am az o nensis, fo r at le ast n in e y ears. D u ring the last th ree y ears, he w as subm itted to v ario us therap y sched u les (g lu cantim e® , am p ho tericin B, g lu c a n tim e ® p lu s g a m m a - in te rf e ro n ) ,
R e lato d e C aso. C osta JM L, M ora e s M SC , S a ld an ha A C R , B a rra i A , B u ra ttin i M N . D iab e te s m ellitu s as s ociated w ith p e n ta m id in e is e thion ate in d iffus e cu ta n e ou s leis hmanias is . Rev ista d a Socie d ad e B ra s ile ira d e M e d icin a Tro p ica l 28:40 5- 40 7 , out- d ez, 1995.
sho w ing im p ro v em ent but w ith subsequent relapses.
Befo re the ad ministratio n o f p entam id ine ise th io n ate in Se p te m b e r 1991 a c lin ic al- labo rato rial ev aluatio n w as p erfo rm ed . At that o ccasio n the p atient had activ e lesio ns w ith small no d ules and erythem ato us tubercules asso ciated w ith scars o n his face, chest and abd o m en. A to tal o f 168 activ e lesio ns w ere fo und p laques and erythem ato us tubercules w ith ulceratio ns co v ered w ith crusts w ere o bserv ed o n his hand s and feet. Red and w hite blo o d cells co unts, urea, creatinine, alkaline p h o s p h a ta s e , A ST, A LA T w e re w ith o u t alte ratio n s. Th e b lo o d g lu c o se le v e l w as 77mg/ dl.
Pentam id ine isethio nate w as ad ministered in a d o se o f 4mg/ kg o n alternate days fo r 20 IM ap p licatio ns. W hen g lu co se alteratio n ap p eared (123mg/ d l), the drug w as d ismissed tempo rarily. A fter 3 mo nths, p entam id ine w as reintro d uced in the sam e d o se reg im en fo r 10 ap p licatio ns. At the end o f these series gluco se blo o d lev el w as lOOmg/ dl. A no ther regim en o f the drug w as d o ne three m o nths later, and the sam e ev o lutio n .o ccurred . The to tal d o se w as 8.4g o f p entam id ine isethio nate. In this perio d g luco se blo o d levels varied b etw een 80 to lOOmg/ dl in the last three regim ens. The p atient w as d ischarged w ith im pro vem ent, but still sho w ing crusts o n the lo w er limbs and scars thro ugho ut the bo d y. The M o ntenegro skin test rem ained negativ e.
He returned to the ho sp ital a m o nth after d ischarge (O cto b er 1992), w ith w eig ht lo ss of, 10kg , p o ly d y p sia, p o ly u ria, x ero sto m ia, w eakness and relap se o f the lesio ns o f the lo w er lim bs (u lceratio ns w ith crusts and seco nd ary infectio n). The g luco se blo o d level w as 420mg/ dl, g luco se and keto nic bo d ies w ere p resent o n the urinalysis. H e need ed insulin co ntro l fo r 22 days, w hen g luco se lev els b ecam e no rmal, p ersisting so m e activ e lesio ns o n his leg s. He later im pro ved after therap y w ith am ino sid ine.
D ISC U SSIO N
Bry ceso n2 3 treated 33 p atients w ith diffuse cutaneo us leishm aniasis (DCL) w ith a variety o f agents. Pentam id ine m esylate gave the best results, w ith initial im p ro v em ent in all patients and lo ng term cure in sev en. He co nclud ed that p en tam id ine g iv en w e e k ly o r b iw eekly
w as the b est av ailable therap y fo r this d isease altho ugh its to xic effects limited the d o sage and frequency o f injectio ns. The sid e effects includ ed co llap se (p resum ably d ue to the drug e n te rin g a v e in ) , p ro f o u n d w e a k n e s s , ano rexia, nausea, vo miting, abd o m inal pain, glyco suria, altered g luco se to lerance test and d iabetes.
A ltho ugh clinical exp erience ap p ears to be la c k in g , s e v e ra l au th o rs re c o m m e n d e d p en tam id in e fo r the treatm en t o f c ase s o f v isceral leishm aniasis and m u co cu taneo u s leishm aniasis that hav e b een unresp o nsiv e to antimo nial agents6 9. Jh a8 has rep o rted to hav e s u c e s s f u lly tre a te d 81 o f 82 c a s e s o f p entav alent antim o ny-resistant kalazar w ith p entam id ine m esylate in North Bihar, India.
T h e r e is a s u g g e s ti o n th a t th e d im e th an e su lfo n ate salt ( m e sy late ) o f p entam id ine m ay b e m o re d iabeto g enic than isethio nate2 4 6 8. The m echanism o f the
d ia b e to g e n ic e f f e c t o f p e n ta m id in e is co nsid ered to b e similar to that o f strep to zo cin, causing an early cito lytic release o f insulin and hyp o glicem ia, fo llo w ed by insulin d eprivatio n and d iabetes mellitus b ecau se o f a to xic effect o n the B-cells o f the p ancreas. A ppro xim ately 5% o f the treated patients w ill d ev elo p g luco se in to le ran c e o r in su lin -d e p e n d e n t d iab e te s during p entam id ine therapy, so m e having anteced ent hy p o glicem ia1 n.
O nly this p atient o ut o f fiv e cases o f DCL in M aran h ão tre a te d w ith is e th io n a te o f p entam id ine d ev elo p ed d iab etes m ellitus, being the first rep o rt o f DCL in Brazil, treated w ith th is d ru g th a t d e v e lo p e d d ia b e te s m ellitus, w itho ut p rev io us renal d am ag e. Fo rtunately insulin ind ep end ent, but co ntro l o f g luco se o n the blo o d , are being d o ne ev ery three m o nths.
RESU M O
0 5 a u tore s re la ta m o cas o d e u m p a cie n te p ro ce d e n te d e B a ca b a l, M A , p o rta d o r d e
leis hm a n ios e cu tâ n e a d ifu s a ( L C D ) hã 9 anos,
a pre s e n ta nd o u m tota l d e 168 lesões d is trib u íd a s
p e lo corpo, d e ca rá te r n ó d u lo tu m o ra l e a lgu m a s ulcerad as , te n d o s id o s u b m e tid o a tra ta m e n tos
a n te rio re s á base d e a n tim o n ia l p e n ta v a le n te ( g lu c a n t im e ® ) e a s s o c ia ç ã o in t e r f e r o m
g a m m a + g lu c a n tim e ® co m m e lh o ra e p o s te rio r re cid iv a d a s lesões. R e ce n te m e n te q u a n d o d a
u t iliz a ç ã o d o m e d ic a m e n to is o tia n a t o d e
R e lat o d e C aso. C osta JM L, M o r ae s M SC, S ald an h a A CR, B ar r ai A , B u r at t in i M N. D iabe t e s m e llitu s as s o c iat e d w ith p e n t am id in e is e t b io n at e in d iffu s e c u t an e o u s le is hm an ias is . R ev ista d a S o c ie d ad e B r as ile ir a d e M e d ic in a T r o p ic al 2 8 :4 0 5 - 4 0 7 , o u t - d e z; 1 9 9 5 .
p e n t a m id in a ( p e n t a c a r in a t ® ) n a d o s e d e
4mg/ kg/ peso/ dia, a plica d os 1M e m dias a lte rn a d os e m 3 séries d e 20, 10, 10 a plica çõe s co m interv alos e n tre as s é ries d e 3 meses. N a e v o lu çã o d o
tra ta m e n to de s e nv olv eu u m q u a d ro d e p e rd a de
pe s o 10kg, polid p s ia , p o liú ria , xe ros tom ia , lesões d e m e m b ro s in fe rio re s c o m s in a is d e a tiv id a d e .
G lic e m ia e m je ju m 420m g/ d l, p re s e n ça d e g lico s e e c o r p o s c e tô n ic o s n a u r i n a . I n s t i t u í d a
in s u lin o te ra p ia ho u v e m e lho ra d o q u a d ro e re to rn o
dos n ív e is g licê m ico s p e rm a n e ce n d o es tãv el a té o
pre s e n te m o m e n to . A le rta - s e os clín ico s q u e d e v id o a
d is p o n ib ilid a d e d a p e n ta m id in a co m o o p çã o
te rapêu tica, a m es m a dev e s e r us ada co m critérios , ob e d e ce n d o rigo ro s o co n tro le la b o ra to ria l in clu in d o
os nív e is g licê m ico s dos pacien tes .
Palav ras - cha v e s : Leis hm a n ios e cu tâ n e a difus a.
Is otio n a to d e p e n ta m id in a . D iab e te s m ellitus . Es tado d o M a ra n h ã o .
REFEREN C ES
1. Bo u ch ard P, Sai P, R each G, C am b arrere I, Fanavel
D , A s s an R. D i a b e te s m e l l i tu s f o l l o w i n g p entam id in e in d uced hy po g ly cem ia in hum an. D iab etes 3 1 : 4 0 - 4 5 ,1 9 8 2 .
2. B ry ce s o n A D . Pen tam id in e in d u ced d iab etes m ellitu s. East A frican M edical Jo u rn al 4 5 :1 1 0 - 1 1 7 , 1 9 6 8 .
3. B ry ceso n A D . D iffuse cu tan eo u s leishm aniasis in Ethiop ia. Il.T reatm en t T ransactio ns o f th e Royal S o ciety o f T ro p ical M ed icine and H ygiene 6 4 :3 6 9 - 3 7 9 , 1 9 7 0
4 . B ry ceso n A D , W o o d sto ck L.T h e cu m u lativ e eff ect o f p en tam id in e d im ethano su lfo nate o n th e b loo d sugar. East A frican M edical Jo u rn al 4 6 :1 7 0 - 1 7 3 , 1 9 6 9 .
5. C o n v it J, Pin ard i M E, R o n d o n A J. D iffuse cu tan eo u s leishm aniasis: a disease due to an
im m uno lo g ical d ef ect o n th e h o st.T ran sactio n s o f th e Royal S o ciety o f T ro p ical M ed icin e and H ygiene 6 6 :6 0 3 - 6 1 0 , 1 9 7 2 .
6 . C o sta JM L. O uso clín ico das p en tam id in as co m e s p e cial re f e rê n cia n as leish m an io ses. A cta
A m az ôn ica 2 3 :1 6 3 - 1 7 2 ,1 9 9 3 •
7. Frank EC , W ignall FS, C ruz M E, Rosales E, T ovar A A , Lucas CM , Llanos-C uentas EA , Berm an JD . Ef ficacy and to xicity o f sodium stib o g lu co n ate fo r m u co sal leishm aniasis. A nnals o f In ternal M ed icine 113: 9 3 4 - 9 4 0 ,1 9 9 0 .
8 . Jh a T K . Ev alu atio n o f d iam id in e co m p o u n d
(p en tam id in e iseth io n ate) in th e treatm en t o f resisten t cases o f K alazar o ccu rrin g in N o rth Bihar, India. T ransactio ns o f th e Royal S o ciety o f T ro p ical M ed icine and H ygiene 7 7 :1 6 7 - 1 7 0 ,1 9 8 3 .
9 . Jh aT K , Sharm aV W . Pentam idine in d u ced d iab etes m ellitus. T ransaction s o f th e Royal S ociety o f T ro p ical M edicine and H ygiene 7 8 :2 5 2 - 2 5 3 ,1 9 8 4 .
10. M arsd en PD . M ucosal leishm aniasis C 'Espundia" Esco m el, 1 9 1 1 ).T ransactio ns o f th e Royal So ciety o f T ro p ical M ed icin e and H y g ien e 8 0 :8 5 9
-8 7 6 ,1 9 -8 6 .
11. Sands M , K ron M A S, Bro w n RB. Pentam idine: A Review . Review s o f In fectio us D iseases 7 :6 2 5 - 6 3 4 ,1 9 8 5 .
12. Silva F. Fo rm a raríssim a d e leish m an io se teg um entar. Leish m an iose d érm ica não u lcerad a e m n ó d u l o s e e x te n s a s p l a c a s i n f i l tra d a s
e h i p e r p i g m e n t a d a s . II R e u n i ã o d e D erm ato ssif ilógraf icos Brasileiros, Rio d e Jan eiro 1 :9 7 - 1 0 3 ,1 9 4 5 .
1 3 - V ieira JB , Lacerd a M M , M arsden PD . N ational r e p o r t i n g o f l e i s h m a n i a s i s t h e B ra z i l i a n
e x p e r i e n c e . P a r a s i t o l o g y T o d a y 6 : 3 3 3 9
-3 -3 4 0 ,1 9 9 0 .
