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RELATO DE CASO/CASE REPORT
Lues maligna in an HIV-infected patient
Lues maligna em um paciente com infecção pelo HIV
Luiz Fernando Cabral Passoni
1, Jacqueline Anita de Menezes
1, Sayonara Rocha Ribeiro
1and Érica Coutinho O. Sampaio
1ABSTRACT
We re p o rt su c h a c a se o f m a li gn a n t syp h i li s i n a 4 2 - ye a r- o ld HIV- i n f e c te d m a n , c o - i n f e c te d wi th h e p a ti ti s B vi ru s, wh o p re se n te d n e u ro lu e s a n d th e c la ssi c a l sk i n le si o n s o f lu e s m a li gn a . Th e se ru m VDRL ti te r, wh i c h wa s 1 :6 4 a t p re se n ta ti o n , i n c re a se d to 1 :2 ,0 4 8 th re e m o n th s a f te r su c c e ssf u l th e ra p y wi th p e n i c i lli n , d e c re a si n g 1 5 m o n th s la te r to 1 :8 .
Ke y-words: Ma li gn a n t syp h i li s. Lu e s m a li gn a . Ne u ro lu e s. HIV i n f e c ti o n .
RESUMO
De sc re ve m o s u m c a so d e sí f i li s m a li gn a e m u m p a c i e n te d e 4 2 a n o s c o m i n f e c ç ã o p e lo HIV e p e lo ví ru s d a h e p a ti te B. O p a c i e n te , c o m le sõ e s c u tâ n e a s c lá ssi c a s d e lu e s m a li gn a e VDRL p o si ti vo n o so ro e n o lí q u o r, te ve u m a re sp o sta e x c e le n te a o tra ta m e n to c o m p e n i c i li n a c ri sta li n a . O VDRL sé ri c o , q u e n o d i a gn ó sti c o e ra d e 1 :6 4 , a u m e n to u trê s m e se s d e p o i s p a ra 1 :2 .0 4 8 e d i m i n u i u p a ra 1 :8 a p ó s 1 5 m e se s.
Pal avr as-chave s: Sí f i li s m a li gn a . Lu e s m a li gn a . Ne u ro lu e s. In f e c ç ã o HIV.
1 . Se r viç o de Do e nç as Infe c c io sas e Par asitár ias do Ho spital do s Se r vido r e s do Estado , Rio de J ane ir o , RJ , B r asil.
Addr e ss to: Dr. Luiz Fe r nando Cab r al Passo ni. R. Mal Masc ar e nhas de Mo r ais 1 9 1 /1 0 0 7 , Co pac ab ana, 2 2 0 3 0 - 0 4 0 Rio de J ane ir o , RJ , B r asil. Te l: 5 5 2 1 2 5 1 8 - 1 5 9 4
e - mail: lfpasso ni@ ig. c o m. b r
Re c e b ido par a pub lic aç ão e m 2 1 /5 /2 0 0 3 Ac e ito e m 1 9 /1 1 /2 0 0 4
Lues maligna is a rare ulc erative form of sec ondary syphilis
c harac terized by papulopustular skin lesions that rapidly enlarge
and evolve into round or oval ulc ers with sharp borders, c entrally
c overed by a dark, sometimes rupioid c rust6. Lesions in various
stages of development c onfer a pleomorphic pic ture. Muc ous
me mb r ane s o f the mo uth and no se may b e invo lve d, and
prodromes of fever, headac he, and myalgia are c ommon6 1 4.
Although its inc idenc e had been dec reasing sinc e the beginning of the 2 0th Century, the number of reported c ases has inc reased
after 1 9 8 8 , most oc c urring in patients with HIV infec tion. We
desc ribe a c ase of malignant syphilis in an HIV-infec ted patient, the third diagnosed at the Infec tious Diseases Department of the
Ho sp i ta l d o s Se rvi d o re s d o Esta d o, Rio de Jane ir o , B r azil,
fr o m 1 9 8 6 -2 0 0 2 . Previously, in April 1 9 8 9 and January 1 9 9 3 ,
r espec tively, a 4 3 -year-o ld b isexual man and a 4 4 -year-o ld
ho mo sexual man presented with lues maligna as their first
manifestation of HIV-infec tion1 2.
CASE REPORT
In June 1 9 9 9 , a 4 2 -ye ar-o ld ho mo se xual male pr e se nte d
with a two -we e k histo r y o f multiple e r ythe mato us papule s o n
his fac e , tr unk and e xtr e mitie s, whic h pr o gr e sse d to pustule s
and c r uste d ulc e r s. All le sio ns we r e painle ss and he de nie d having any syste mic sympto ms.
He was advised that he was HIV-positive in June 1 9 9 5 , when he was seen for evaluation of spleen enlargement and anemia. At
that time, laboratory investigations revealed a positive serology for both HIV ( ELISA and Western-Blot) and HTLV I/II infec tion.
Serology for hepatitis B showed the presenc e of HB sAg and HBc Ab, whereas serology for hepatitis C was negative. A liver biopsy was refused and he was lost to follow-up until June 1 9 9 6 ,
wh e n h e s o ugh t m e dic a l a s s is ta n c e pr e s e n tin g c lin ic a l fe atur e s o f live r failur e and hype r sple nism . Six m o nths late r his CD4+ c ell c ount was 2 4 2 /mm3 ( 2 0 % ) , but he refused to use
antiretroviral drugs, whic h were begun only in May 1 9 9 8 . At that time, his CD4+ c ell c ount was 4 0 4 /mm3 ( 3 4 % ) and his HIV viral
load 5 ,8 0 0 copies/ml ( nucleic acid sequence based amplification, NASBA) . Six weeks after starting stavudine and lamivudine, CD4+
c ount inc reased to 4 9 4 /mm3 ( 5 9 % ) and viral load dropped to
undetec table levels ( < 4 0 0 c opies/ml) . He had been taking the medic ines regularly until two months before the appearanc e of
the skin lesions, when he disc ontinued the antivirals.
On examination the patient appeared underweight. He was
1 8 2
C
Pa sso ni LFC e t alFi gu r e 1 - Mu l ti pl e ski n l e si on s of l u e s m al i gn a i n an HIV-i n f e cte d patie n t: A) papu lopu stu lar le sion s an d n e cr otic u lce r s ove r the face ;
B a nd C) tr u n k; D a nd E) e x tr e m i ti e s.
A
D
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plaques and nodules, some with a nec rotic c enter, and ulc ers
c overed by a dark brown c rust, present in his fac e, trunk, and extremities, inc luding palms and soles ( Figure 1 ) . A large fetid
rupioid c rusted ulc er was observed on his jaw. No muc osal
l e s i o n s we r e s e e n . He h a d c e r vi c a l l ym p h a de n o p a th y,
splenomegaly, and gynec omastia. The remainder of the physic al examination was normal, inc luding the neurologic system.
La bo r a to r y inve s tiga tio ns r e ve a le d. He m o glo b in, 1 0 .1 g/dL; leukoc ytes, 3 ,0 0 0 /mm3 ( 5 8 % granuloc ytes and 3 2 %
lymphoc ytes) ; platelets, 6 3 ,0 0 0 /mm3; erythroc yte sedimentation
rate, 1 0 3 mm/hr. Levels of serum AST, ALT, bilirubin, and alkaline phosphatase were normal. Syphilis serology showed a VDRL titer
of 1 :6 4 and a positive Tre po ne m a pa llidum hemagglutination
( TPHA) . Chest x-ray film was normal. The c erebrospinal fluid
examination showed: 2 c ells/mm3; protein 4 5 mg/dl; gluc ose
5 0 mg/dl; VDRL 1 :1 ; and TPHA positive.
Treatment was started with intravenous aqueous c rystalline
pe nic illin G 1 8 MU pe r day, pr e c e de d b y a single do se o f
prednisone 6 0 mg. On the sixth day of treatment he had fever
with rigo rs that defervesc ed o ver the next 3 6 ho urs. B lo o d c ultures were negative. It was assumed to be a late Jarisc
h-Herxheimer reac tion. The response to penic illin was exc ellent
and he was disc harged from hospital after 1 4 days of treatment.
Thr e e mo nths afte r c o mple tio n o f the r apy, he had gaine d
3 k g, and was tak ing the antir e tr o vir als r e gular ly. All sk in le sio ns we r e he ale d, tho ugh so me with r e sidual sc ar s. His
CD4+ c e ll c o unt was 2 9 7 /mm3 ( 4 1 % ) and HIV vir al lo ad was
6 7 0 c o pie s/ml ( 2 .8 lo g) . VDRL te st sho we d a tite r o f 1 :2 ,0 4 8 .
The patie nt de nie d maintaining se xual r e latio nships sinc e ho spital disc har ge . No spe c ific tr e atme nt was pr o vide d. At
1 5 and 3 5 mo nths late r, the VDRL was 1 :8 .
DISCUSSION
Lues maligna was first desc ribed by Bazin ( 1 8 5 9 ) and Dubuc ( 1 8 6 4 ) , who applied this term based on the bizarre c linic al
features and progressive course of this variant of syphilis1 4. During
some dec ades, there was c ontroversy about whether lues maligna
wa s a s e ve r e va r ia n t o f s e c o n da r y s yph ilis o r a n e a r ly
manifestation of tertiary syphilis; a question c larified by Haslund and Neisser in 1 8 9 6 -1 9 9 71 4. In c ontrast to tertiary syphilis, the
lesio ns o f lues maligna ar e multiple, have a r o und o r o val
c onfiguration, with no tendenc y to c entral healing, and exhibit a lamellated, brown-blac k rupioid c rust. Moreover, the early onset
o f nec r o tic ulc er s in the disease is in c o ntr ast to the later oc c urring gummas of tertiary syphilis6. The c riteria for diagnosis
of lues maligna listed by Fisher e t a l6 inc lude strongly positive
serologic al test results, a severe Herxheimer reac tion, and an exc ellent response to antibiotic therapy. In the past, serologic al
anergia was one of the c harac teristic features of the disease, a c onc ept no longer supported1 0 2 2. Even taking into ac c ount the
extensive c linic al differential diagnosis of lues maligna, whic h in c lude s pyo de r m a ga n gr e n o s um , va s c ulitis , lym ph o m a , le ishmaniasis, le pr o sy, yaws, and myc o b ac te r ial o r fungal
infec tions, no other disease proc ess c ould explain both the
m o r pho lo gy o f the le sio ns and the r apid invo lutio n with treatment6.
Our case showed the classical clinical picture of lues maligna,
and had an excellent response to penicillin. A Jarisch-Herxheimer
reac tion oc c urred late in the c ourse of therapy, probably due to
the use of prednisone prec eding the first penic illin dose2 1. The
patient had a serologic response not previously desc ribed in
malignant syphilis oc c urring in HIV-infec ted patients, or that is,
the VDRL titer, whic h was 1 :6 4 at presentation, inc reased to
1 :2 ,0 4 8 three months after suc c essful treatment. Gregori e t a l 7
reported an HIV-infec ted patient with lues maligna – desc ribed
as tertiary syphilis with lesions of early and advanc ed sec ondary
syphilis – in whom the rapid plasma reagin ( RPR) titer was 1 :2 5 6
at pr e se ntatio n, r aise d to 1 : 8 , 1 9 2 o ne we e k late r ( b e fo r e therapy) , and dec reased to 1 :3 2 eight weeks after suc c essful
treatment. Sinc e a polyc lonal antibody response is doc umented
in some HIV-infec ted individuals, patients c o-infec ted with HIV
and T. pa llidum may have a serologic al response with very high
titers, which is common, or present persistently high titers despite
antibiotic therapy2 0. Thus, high serologic al titers after treatment
sho uld no t b e viewed as ther apy failur e, b ut as a po ssib le
phenomenon. Even c onsidering that falsely rising titers oc c ur in individuals with pr e vio usly tr e ate d syphilis, r e infe c tio n with
T. pa llidum should not be disc arded.
The first c ases of lues maligna in HIV-infec ted individuals
were reported in 1 9 8 7 by Rosenheim e t a l1 3, and in 1 9 8 8 by
Armignac c o e t a l1, Sc hröter e t a l1 7, and Shulkin e t a l1 8. Sinc e
then, the number of c ase reports has inc reased, whic h might be
related to better rec ognition or reporting1 5. However, it seems to
represent an ac tual inc rease in the oc c urrenc e of this type of
syphilis4 5. In a German multicenter retrospective survey of 1 1 ,3 6 8
HIV-infec ted patients, ac tive syphilis was reported in 1 5 1 ( 1 .3 % )
patients, 1 1 ( 7 .3 %) of whom presented with malignant syphilis1 6.
In Chandigarh, India, lues maligna was reported in 2 /5 5 patients
with syphilis diagnosed from 1 9 9 0 to 1 9 9 9 : one of three
HIV-infec ted patients presented with lues maligna8. In Rio de Janeiro,
at the Infe c tio us Dise ase s De par tme nt o f the Ho sp i ta l d o s
Se rvido re s do Esta do, lues maligna was diagnosed in three
HIV-infec ted individuals from 1 9 8 6 to 2 0 0 2 , a finding that c ontrasts with a previous report of lues maligna oc c urring in 3 /3 ,2 5 3
patients with ac quired syphilis diagnosed at the Dermatology and
Venereology Department of our Institution between 1 9 4 8 and
1 9 7 21 4. All tho se repo rts reinfo rc e the hypo thesis that
HIV-infec ted individuals are at risk for developing malignant syphilis.
It is still unc lear why only a few T. pa llidum-infec ted patients
develop lues maligna. The progressive and destruc tive c ourse of this type of syphilis might be due to an immunoc ompromised status of the host, a more virulent strain of T. pa llidum, or even an exc essive immune response2. However, it appears unlikely
that there are T. pa llidum strains of different virulenc e1 0, and an
immune complex mediated mechanism is apparently not involved in the disease proc ess9. Cell-mediated immunity seems to play
an important role in the pathogenesis of syphilis, but the CD4+
1 8 4
1 ,2 0 0 CD4+ c ells/mm34. Qualitative or func tional defec ts of both
c ell-mediated and humoral immunity are probably involved in the pathogenesis of malignant syphilis: the pathogenic interac tion
between HIV and Tre po n e m a pa lli du m b o th leading to an
immunodefic ienc y state may reduc e the immunologic response
to treponemal infec tion through a dec rease in c ell-mediated im m un ity, m a c r o ph a ge fun c tio n a l de fe c ts , a n d po s s ib ly
immunomodulation of the humoral immunity response1 9. The
loc al immune response to T. pa llidum may be c ritic al to the
development of c linic al manifestations as well as to the c learanc e of spiroc hetes from infec ted tissues. However, relatively little is
known about the loc al immune responses to T. pa llidum in skin
and other body sites, and virtually nothing is known about the
subpopulations of immune c ells in the lesions of patients with syphilis c o-infec ted with HIV1 1.
Although the c linic al manifestations and the c ourse of syphilis
may be altered in the presence of HIV infection, most HIV-infected
patients with syphilis have typic al disease manifestations. Clinic al
features of syphilis are protean, and the diagnosis of lues maligna sho uld b e c o nside r e d in all HIV- infe c te d individuals with
ulc e r o no dular sk in le sio ns3 2 2. This appr o ac h might avo id
unnec essary efforts or more c omplex investigations of other
diseases oc c urring in these patients. As Witkowsky and Parish2 2
emphasized, a simple serologic test for syphilis c an bring a c ase
to a speedier and less c ostly c onc lusion.
ACKNOWLEDGMENTS
We gr a te fully tha nk Dr. Eliza b e th Ma c ha do , Dr. Le o n
Claude Sidi and Dr. Fe r nando Luiz Lo pe s Car do so , c o lle ague s
at the Infec tio us Disease Depar tment, Ho spital do s Ser vido r es do Estado , fo r the ir c o mme nts.
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