Resolution of Eosinophilia after Treatment of …filariasis.md.chula.ac.th/acrobat/ortherpaper/resolution.pdfThe absolute eosinophil count (AEC) was higher than SOO/ut during infestation

Resolution of Eosinophilia after Treatment ofCutaneous Gnathostomiasis

Kanyarat Kraivichian MD*,Surang Nuchprayoon MD, PhD*, Padet Siriyasatien MD, PhD*,

Wilai Saksirisamphan MSc*, Issarang Nuchprayoon MD, PhD**

* Department of Parasitology, Faculty of Medicine, Chulalongkorn University** Department of Pediatrics, Faculty of Medicine, Chulalongkorn University

The present study was to investigate the dynamics of eosinophil in peripheral blood of patients with

cutaneous gnathostomiasis before and after worm removal. The total of28 proven cases of cutaneous gnathos-tomiasis treated by albendazole were included in the present study. The absolute eosinophil count (AEC) was

higher than SOO/utduring infestation in almost all the patients, the positive rate was 89%, and significantlydecreased to normal level after receiving albendazole and worm removal within 3 months in 96%. In conclu-sion, an increas of AEC is another important hallmarks of cutaneous gnathostomiasis and this parametercould be the earlier indicator for responsiveness to treatment.

Keywords: Gnathostomiasis, Eosinophilia, Albendazole

J MedAssoc Thai 2005; 88(Suppl 4): S163-6Fill! text. e-Jollr;tal: http://www.medassocthai.orgljournal

CutaneouS Gnathostomiasis is more CO!llmon

in Southeast Asia, especially in Japan, China andThailand (1-3).The most common skin manifestation is

characterized by intermittent migratory swelling. Therehave been reports of the worm migration to otherorgans (eye, lung, intestine and brain) that causesserious complications and death (4-7).To date, the defi-nitive diagnosis of cutaneous gnathostomiasis stillrequires the demonstration of the worm from the skin

lesion or biopsy material. The presumptive diagnosisis made by the history of consuming raw or under-cooked flesh of second intermediate orparatenic hostscontaining encysted L3 infective larvae, eosinophiliaand presence of antibodies against a specific 24-kDaantigen for Gnathostoma spinigerum by Western blotanalysis. One of the problems in disease treatment isthe monitoring of the patient during the follow-upperiod. Although the immunodiagnosis has been given100%sensitivity and 100% specificity for the disease,it could not differentiate between current and pastinfection (8),

Correspondence iO Kraivichian K, Department of Parasito-

logy, Faculrl' of Medicine. Chulalongkorn University. Bangkok10330, Thailand.

J MedAssoc Thai Vol. 88 Sllpp/.4 2005

In addition to the increase in the number of

circulating eosinophils in the patient with suspectedand proven cases of cutaneous gnathostomiasis, amassive eosinophil infiltration can be noted either atthe site of the parasite invasionor m:gcation, suggest-ing that eosinophil may play a pivotal role in the hostdefense during current infection with this parasite (9).Unfortunately,the correlationbetween clinical featuresof the disease and eosinophilia has not yet beenstudied. Absolute eosinophil count in the peripheralblood might be used as the indicator that relates toscreening, effect of treatment and follow-up in cuta-neous gnathostomiasis. The aim of the study was toinvestigate the dynamics of eosinophil before andafter treatment with albendazoleand wornl removal.

Materia! and Method

The study populations were recruited fromthe previous studies (10.11).All of the selected 28 patientswere diagnosed with cutaneous gnathostomiasis basedon 1)clinical manifestation, that is, a history of subcuta-neous migratory swelling; 2) stool examination resultsnegative for other parasites; 3) a history of eating rawfreshwater fish, crab, snake, bird or chicken and 4) wormdiscovery during the follow up period. The following

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information was extracted from each medical record:demographic information including gender and age,domicile and previous medical treatment. Clinicalassessmentand bloodexaminationfor absoluteeosino-

phil count were evaluated before and after treatmentand followingtreatmentonce a month for 12months oruntil AEC<500/ul. Eosinophilia (AEC>500/ul) wasclassified as mild eosinophilia (AEC between 500and1500/ul), moderate (AEC between1500 and 5000/ul), or severe (AEC>5000/ul). The date of worm dis-covery was also recorded. All patients were treatedwith 400-800 mg. of albendazoleper day for 21 days.Patients who had a history of allergic conditions wereexcluded from the present study.

Statistical analysisThe data were recorded and analyzed by

using SPSS 10.0. Numerical data were summarizedusing descriptive statistics. Time to resolution of eosi-nophilia was analysed by Kaplan-Meier analysis.

Results

Therewere28patients includedin the presentstudy; 7males and 21 females,with a mean age 000.1:1::9.8years (range 15-57years). The skin involvementsite and the severityof eosinophiliaat the time of diag-nosis are shown in Table I.Among all the 28 patientswith gnathostomiasis, the AEC ranged from 255 to12,800/ul, with a geometricmean of989 /ul. Eosino-philia (AEC>500/ul) was present in 25 of28 patientsthus the positive rate of eosinophilia in cutaneousgnathostomiasis was89%.21 ofthe 28 patients (75%)had mild eosinophiliaand only one patient had severeeosinophilia. After treatment with albendazole, theworm migrated superficiallytoward the epid~rmisandcould be manuallyor surgicallyextracted and removedfromall thepatients.Theparasiticwormswere removed

Table 1. The skin involvement site and the severity ofeosinophilia at the time of diagnosis

Total PatientsSite of skin Involvement

Head and neck

Upper extremitiesTrunkLower extremities

Blood eosinophilia: No. (range)Normal

Mild eosinophiliaModerate eosinophiliaSevere eosinophilia

28

5 (17.8%)15 (53.4%)2 (7.1%)6 (21.2%)

3 (255-380/ul)21 (525-1430/ul)3 (1910-2424/ul)I (I2,800/ul)

S164

between 4 and 45 days (average 14.0:1::9.9 days, median10.5 days) after treatment. Around 2 weeks after para-site removal, 3 of 25 patients had a transient rise ineosinophil count, from 525-1910/ul to 634-2050/ulfollowed later by resolution of eosinophilia. Of 25patients with eosinophilia, 15 patients (60%) hadreso-lution of eosinophilia (AEC<500/ul) by day 32, and 7patients (28%) resolved between day 32 - day 53,2patients (8%) resolved between day 54-day 95 and onlyone patient had persistent eosinophiJia for more than6months before resolution after worm removal. Of all28patients who had serial blood counts for 6-9 monthsafter initial treatment, it was observed that the AECbecame <200/ul in 23 patients, and below 100/ul in 18patients. Around half of the patients had normal eosi-nophil count (AEC<200/ul) by 3 months (day 83), andAEC <1O0/ul by 6 months (day 193) after parasiteremoval. Most (75 %) had normal AEC «200/ut) around6 months (between day 180 and 194, Fig. 1) after para-site removal. Among all 3 patients who had normalrange of AEC before initial treatment, after the wormswere removed, the AEC reached a minimal level (rangefrom 46.5-87/ul), which was approximately an 80%c'~crease within 3 months.

Discussion

Eosinophilia is commonly associated withgnathostomiasis (12.13).The authors found that the posi-tive rate of eosinophilia in a proven case of cutaneousgnathostomiasis was 89%. Treatment with albendazolemay immediately kill the parasite and is likely to inducethe migration toward the upper epidermis. at present,there are 3 parameters for practical use to evaluate the

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28 168 196 224 252 28056 84 112 140

Days after worm removal to resolution of eosinophilia

Fig.! Resolution of eosinophilia after albendazoleand worm removal

J Med Assoc Thai VoL88 Supp/.4 2005

responseto treatment, Firstly, the disappearance ofcutaneousswelling, it may occur as the worm migratesdeeper into the human tissue; or when the worm iskilledand destroyed. Thus, absence of skin lesionsdoesnotessentiallyimplythat the worm has been eradi-catedor the patient cured. Secondly, Gnathostoma-specificantibody titer measured by ELISA (14.15),thedecreasingof titer can predict the result of treatmentbut this parameter is not appropriate for short-termfollow-upas test results take over 6 months (10.11.16).Finally,disappearanceof eosinophilia, from the presentstudy,the decreasing AEC <500/ul could be obtainedina timelier manner and is a highly appropriate indi-cator for responsiveness to treatment in cutaneousgnathostomiasis.After the worm removal, 24 from 25patients(96%) had resolution of eosinophilia within 3months.The eosinophilia persisted for more than 3monthsin only one patient; possibly due to the resi-dualsof the worm inside the body that still inducedtheproduction of eosinophil. The resolution of eosi-nophillevelsafter treatmentwas gradual, ranging fromseveralweeks to months after initial treatment. TheAEC>500/ulhas been customarily defined as eosino-philia,and is useful for clinical diagnosis. The truebaseline AEC in uninfected patient is very Iow.BecauseAEC<200 /ul, but not <IOO/ul,is achieved inmostsubjects in this study, we used AEC <200/ul as acut-offlevel for 'normal' eosinophil count. In case ofpatientswith normalAEC, after treatment, the level ofAEC should decrease to lower than 80% from the

baselineof each patient. Our study suggests that thedynamics of AEC in the proven case of cutaneousgnathostomiasis before and after treatment shouldbe useful as follow-up guidelines in patients thatparasiteswere never recovered. The AEC would be apracticalparameter diagnosis and follow-up patientswithgnathostomiasis,especially in remote areas whereWesternblot analysis or ELISA to detect specific anti-bodiesarenot widely available. In conclusion, eosino-philiais an important hallmark of cutaneous gnathos-tomiasisand its resolution could be the earlier indica-tor for responsiveness to treatment.

AcknowledgmentsThe authors wish to thank Associate Professor

PhisaiKraivichian, Mr. Paisai Yingyourd, Miss SavitreeChandraprasert and Mr. Poonpat Lohachitranont fortheir kind advice and revising the manuscript.

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