R e v i s t a d a S o c i e d a d e B r a s i le i r a d e M e d ic in a T r o p ic a l 2 5 ( 4 ) : 2 5 7 - 2 5 9 , o u t- d e z , 1 9 9 2
RELA TO D E CASO
REDUCTIO N OF SPLEEN SIZE IN A CHILD W ITH HYPERREACTIVE M ALARIOUS
SPLENOM EGALY (HM S) TREATED O UTSIDE THE BRAZILIAN ENDEM IC AREA OF M ALARIA W ITH ONLY
O NE COURSE OF Q UININE
M aria Im aculada M uniz-Junqueira, M ário A. P. M oraes and Philip Davis Marsden
W e r e p o r t th e c lin ic a l p ic t u r e , tr e a tm e n t a n d e v o lu tio n o f a c h ild w ith h y p e r r e a c tiv e m a la r io u s s p le n o m e g a ly tr e a te d o u ts id e th e e n d e m ic a r e a o f m a la r ia . T h e p a t i e n t p r e s e n t e d g r o s s s p le n o m e g a ly , p r o c e e d e d f r o m a n a r e a w h e r e m a la r ia is e n d e m ic , s h o w e d i n c r e a s e d im m u n o g lo b u lin s le v e ls , h ig h a n tim a la r ia l a n tib o d y titr e s a n d h e p a tic s i n u s o id a l ly m p h o c y to s is . T h e c h il d d i d n o t r e tu r n to a n a r e a w h e r e m a la r ia is e n d e m ic a n d s h o w e d a f a v o r a b l e r e s p o n s e to o n ly o n e c o u r s e o f q u in in e . T h e r e s p o n s e o f th is p a ti e n t to lim ite d a n tim a la r ia l th e r a p y s u g g e s ts th e im p o r ta n c e o f r e in fe c tio n w ith m a la r ia in th e d e v e l o p m e n t a n d m a in te n a n c e o f th is s y n d r o m e .
K e y - w o r d s : H y p e r r e a c tiv e m a la r io u s s p le n o m e g a ly (H M S ). C h r o n ic m a la r ia . S h o r t a n tim a la r ia l th e r a p y .
Hyperreactive malarious splenomegaly (HMS) has been described from malarious areas throughout the tropics123 45 u 14, and js usually characterised by m ark e d h e p a to sp le n o m e g a ly , ra ise d immunoglobulins, a high titre o f antimalarial antibodies and hepatic sinusoidal lymphocytosis7 8 9 10_
The pathogenesis of this syndrome is not clarified6, but there is strong evidence that malaria play an important role3 6 7 9. Genetic factors governing a disregulation of the immune response has been suggested as an explanation of this syndrome3 1.
In areas o f high malaria transmission successful therapy o f this syndrome implies that antimalarials must be used regularly and for a prolonged time. The syndrome may recur if the patient stops this treatment in such areas6 7 9 13.
We describe here the clinical picture, treatment and evolution of a child with this syndrome treated in the University Hospital of Brasilia. This child
Departamento de Pediatria, de Patologia e de Clínica Médica, da Faculdade de Ciências da Saúde da Universidade de Brasília, Brasília, DF, Brasil.
Address fo r correspondence '. Dra. Maria Imaculada Muniz- Junqueira, Depto de Pediatria, Faculdade de Ciências da Saúde/UnB, 70910-900, Brasilia, DF, Brasil.
Recebido para publicação em 09/04/92.
did not return to an area where malaria is endemic and responded to limited antimalarial therapy.
CASE REPORT
The patient was an eleven year old, white girl who arrived from state o f Pará, Brazil, with a palpable spleen 8cm from the left costal margin reaching the umbilicus (Hackett grade 4).
T he h aem o g lo b in w as 10.8g% and the reticulocyte was 1.3% .The white blood cell count was 7000/mm3, with a normal differencial count. The platelet count was 190500/mm3, and the ery trocy te sedimentation rate 16mm in the first hour. H a em o g lo b in e le c tro p h o re s e sh o w ed o nly haemoglobin A l. Hepatic and renal function were normal. The total serum protein was 7.0g% , with 3.0g% of total globulin (alpha l= 0 .1 5 g % ; alpha 2= 0.50g% ; beta=0.55g% and gam m a=1.8g% ). The diameter o f the portal vein was normal when evaluated by abdominal ecography. Oesophageal varices were not detected on barium swallow. The serum gammaglobulin estimation showed 2650mg/ dl of IgG, 271mg/dl o f IgM and 144mg/dl o f IgA. Malaria parasites were not identified in multiple p e rip h e ra l b lo o d film s. T h e in d ire c t immunofluorescent antibody test using P la s m o d iu m
R e l a t o d e C a s o . M u n iz - J u n q u e ir a M l , M o r a e s M A P , M a r s d e n P D . R e d u c tio n o f s p l e e n s i z e in a c h il d w ith h y p e r r e a c t i v e m a l a r i o u s s p l e n o m e g a l y (H M S ) t r e a t e d o u ts id e th e b r a z ili a n e n d e m ic a r e a o f m a l a r i a w ith o n ly o n e c o u r s e o f q u in in e . R e v i s t a d a S o c i e d a d e B r a s i l e i r a d e M e d i c in a T r o p ic a l 2 5 : 2 5 7 - 2 5 9 , o u t- d e z , 1 9 9 2 .
f a l c i p a r u m antigen showed a titre o f 320 for IgG and 80 for IgM. Histophatological examination of the liver obtained by percutaneous biopsy identified lymphocytosis in dilated sinusoids (grade II)8. The portal tracts also showed lymphocyte infiltration without portal fibrosis (Figurel).
The patient had most o f the criteria defined for the diagnosis o f the HMS. She presented with a gross splenomegaly, proceeded from an area where m a la ria is e n d e m ic , sh o w ed in c re a se d immunoglobulins levels, high antimalarial antibody titres and hepatic sinusoidal lym phocytosis. Curiously hepatomegaly was not detected and the IgM level was normal.
As the child was living in Brasilia for 3 months and Would not return to area where malaria is endemic it was decided to treat the child with a curative dose of ten days oral quinine sulphate, 30 mg/kg/day.
S eventy days a fte r th e tre a tm e n t, the splenomegaly had reduced to 3cm from the left costal margin and the indirect immunofluorescent antibody test to P . f a l c i p a r u m showed a titre of 160 to IgG and 40 to IgM . Unfortunately the patient was lost to further following and repeat liver biopsy was not possible.
DISCUSSION
For established HMS short term therapy with antimalarial had been attempted with disappointing
results9. Watson Williams and Allan in 1968 reported for the first time success with prolonged treatment with antimalarials for patients with this syndrome15. HMS usually occurs in endemic areas where malarial transmission is intense and children may be exposed to about 2 or 3 bites from infected mosquitoes per week6. Therefore it is clear that treatment must be regular and prolonged7 9. In patients living in malarial endemic areas and submitted to this treatment it has needed 6 months to one year of co n tin u o u s th erap y to have a m easu rab le improvement in spleen size and antibody titre 91213.
The case reported here presented the peculiarity that she was emigrating from the endemic area, and this provided the opportunity to evaluate therapy with only one course o f quinine in a situation where repeated malarial infection could not occur. Quinine was used because chloroquine resistance is so frequent in Brazilian falciparum infections. We observed after 70 days an important reduction in spleen size and the serum levels o f antimalarial antibodies tended to decrease. Unfortunately full follow up proved impossible.
The favourable response o f this patient to only one course of quinine suggests the importance of reinfection with malaria in the development and maintenance of this syndrome and attributes an important role to an alteration in immunereactivity to P la s m o d iu m in such patients.
RESUMO
R e la ta m o s o c a s o c lín ic o , tr a ta m e n to e e v o lu ç ã o d e u m a c r i a n ç a c o m a s í n d r o m e d a e s p l e n o m e g a l i a h ip e r r e a tiv a d a m a lá r ia t r a ta d a f o r a d a á r e a e n d ê m ic a p a r a a m a lá r ia . A c r ia n ç a a p r e s e n ta v a im p o r ta n te e s p le n o m e g a lia , e r a p r o c e d e n t e d e á r e a e n d ê m ic a p a r a m a lá r ia , o s n ív e is d e im u n o g lo b u lin a s e d e a n tic o r p o s a n tim a lá r ic o s e s ta v a m e l e v a d o s e o b s e r v o u - s e lin fo c ito s e s i n u s o id a l h e p á tic a . A c r ia n ç a n ã o v o lt a r i a m a is p a r a a á r e a e n d ê m ic a d e m a lá r ia , p e l o q u e f o i t r a ta d a c o m a p e n a s u m c u r s o d e q u in in o a p r e s e n ta n d o r e s p o s ta c lín ic a f a v o r á v e l . E s ta r e s p o s ta a u m ú n ic o c u r s o d e te r a p ia c u r a tiv a a n tim a lá r ic a s u g e r e a im p o r tâ n c ia d a r e in fe c ç ã o c o m o p a r a s i t a d a m a lá r ia n o d e s e n v o lv im e n to e n a m a n u te n ç ã o d e s t a s ín d r o m e .
P a la v r a s - c h a v e s : E s p le n o m e g a lia h ip e r r e a ti v a d a m a l á r i a . M a l á r i a c r ô n i c a . T r a t a m e n t o c u r a t i v o a n tim a lá r ic o .
R e l a t o d e C a s o . M u n iz - J u n q u e ir a M l , M o r a e s M A P , M a r s d e n P D . R e d u c tio n o f s p l e e n s i z e in a c h il d w ith h y p e r r e a c t i v e m a l a r i o u s s p l e n o m e g a l y (H M S ) tr e a t e d o u ts id e th e b r a z ili a n e n d e m ic a r e a o f m a l a r i a w ith o n ly o n e c o u r s e o f q u in in e . R e v i s t a d a S o c ie d a d e B r a s i le i r a d e M e d i c in a T r o p ic a l 2 5 : 2 5 7 - 2 5 9 , o u t- d e z , 1 9 9 2 .
ACKNOWLEDGMENTS
The authors thank Dr. Carlos Eduardo Tosta and M rs. R ozeneide M . Alves for indirect immunofluorescent test using P . f a lc ip a r u m antigen and Mr. Paulo Hipólito Bezerra Leite for illustration.
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