Loa loa infection in a patient with thymoma

Pierre Landrya,*, Cecile Bassib, Brigitte Christenc

aLausanne University Medical Policlinic, Lausanne, SwitzerlandbHopital des Cadolles in Neuchatel, Neuchatel, SwitzerlandcInstitut Neuchatelois dAnatomie Pathologique, Neuchatel, Switzerland

Received 24 November 2003; received in revised form 16 February 2004; accepted 17 February 2004

Available online 20 April 2004

KEYWORDSLoa loa infection;

Thymoma

Summary An exceptional observation of a Loa loa infection occurring in a short termtraveller with a thymoma is described in details. We discuss the implications of theimmunodeficiency induced by a thymoma on a concomitant parasitic infection.q 2004 Elsevier Ltd. All rights reserved.

Case report

A 73-year-old Caucasian woman with no relevantprevious medical history spent 12 days in SouthernCameroon in May 2000 and five months laterdeveloped migrating oedema first of a calf andthen of wrists and forearms, painless and non-itching. No diagnosis was made and the lesionsdisappeared spontaneously. In March 2002, shecomplained of difficulties swallowing and oesopha-gal candidiasis diagnosed by gastroscopy wassuccessfully treated by seven days of fluconazole.

Three months later, following the appearance ofshortness of breath and 10 kg weight loss, sheconsulted again. A chest X-ray showed an extensiveright pleural effusion which was confirmed by CTscan, with the presence of an anterior mediastinalmass of 8 5 cm2, but no lymph node enlargementsuspect of malignancy (Fig. 1). Thoracentesis wasperformed and numerous sheathed microfilaria,diagnosed as Loa loa were found in the pleural

effusion, which contained 70% lymphocytes, 10%granulocytes, 10% macrophages and 10% mesothe-lial cells. There were no cancerous cells and noMycobacterium tuberculosis bacilli, neither ondirect smear nor after culture. Cultures for otherbacteria remained sterile too. The peripheral bloodeosinophilia was increased (910 cell/mm3 (13%))and the blood contained 2500 microfilaria/ml(midday blood sample). Serology for filaria waspositive but negative for strongyloidosis, schistoso-miasis, and HIV. Stool examination showedTrichuris trichiuria eggs. A needle biopsy of themediastinal mass revealed a T cell predominantinflammation tissue containing many microfilaria(Fig. 2), and excluded lymphoma.

A review of the literature on hypereosinophilia,pleural effusion and mediastinal mass led to thepossible diagnosis of a reactive tumor to filarialinfection. Therefore, immediate thoracotomy waspostponed and, after exclusion of oncocerciasis(negative skin snips), treatment with diethylcarba-mazine (DEC) was initiated under corticosteroidscover in hospital. The patient received in stepwisefashion up to 1 mg/kg of DEC for 21 days with noside effect. The eosinophil count returned tonormal value, and the microfilaria disappearedfrom blood one week after the start of DEC. Her

1477-8939/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.doi:10.1016/j.tmaid.2004.02.009

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*Corresponding author. Address: Place Pury 9, 2000Neuchatel, Switzerland. Tel.: 41-32-724-5533; fax: 41-32-724-5534.

E-mail address: pierrelandry@swissonline.ch

general health status improved, she regained 5 kgand resumed her normal activities.

Unfortunately 2 months later the pleural effusionincreased again and a new CT scan confirmed thestill present mediastinal mass. A sternotomy andresection of the tumor were performed. Histologyconfirmed a type B1 (or predominant cortical)invasive thymoma infiltrating the pericardium andthe right lung (CD3 reaction for T cells and CD99reaction for thymus T cells were strongly positive,whereas CD20 for B cells was scarcely positive).No parasite was found in the tumor and in theperipheral blood, but a few live microfilaria wereseen in the still present pleural effusion. A secondtreatment against Loa loa infection was initiated,

this time with albendazole 2 200 mg/day for 21days at the end of which the eosinophil countreached 660 cell/mm3. At that stage the patienthad lost some weight again, but was still active.Immunological analysis showed no hypogammaglo-bulinemia (gammaglobulins 8.8 g/l (6.013.0)), butmild lymphocytopenia (1105 cells/mm3) affectingT lymphocytes mainly (764 (69.1%) CD3 T cells/mm3

(13502350), 598 CD4 T cells/mm3 (8251575)and 168 CD8 T cells/mm3 (4751025), 341 (30.9%)B cells/mm3. The CD4/CD8 ratio was not invertedbut increased to 3.6.

At more than 14 months of follow-up, the patientis well, her CT scan shows no residual pleuraleffusion, and no sign of recurrence of the tumor.Her white blood cell count is normal, but the totallymphocyte count is gone down to 815 cells/mm3

(550 CD3 T cells/mm3, 436 CD4 cells/mm3 and 111CD8 cells/mm3), with immunoglobulins in thenormal range (IgA 1.45 g/l (0.74.0), IgG 9.00 g/l(7.016.0), IgM 0.9 g/l (0.4012.3).

Discussion

Thymoma are intrathoracic tumors of variableepithelial and lymphoid content. About 44% ofthem are linked to myasthenia gravis, 21% tovarious levels of cytopenia, 6% to hypogammaglo-bulinemia, and some cases to various autoimmunedisorders. A thymoma related immunodeficiencysyndrome (Good syndrome) has been describedcombining low or absent B cells in the peripheralblood, hypogammaglobulinemia and variablydemonstrable cell-mediated immunity defect,especially reduced CD4 T cells.1 On the otherhand, a common variable immunodeficiency syn-drome (CVID) combines variable antibodydeficiency and some cellular immune defects, butno reduced levels of B cells.1 Various infectionsrelated to the immunodepression associated withthymoma have been described, upper respiratoryinfections2 being the commonest, but also oeso-phagal candidiasis and a variety of viral (CMV,herpes) infections. But data on parasitic disease arescarce with a few cases of strongyloidosis,3 tox-oplasmosis4 and Pneumocystis carinii infections.1

Except for an accidental infection by dirofilaria, nocase of filarial infection has been published inpatients with immunodeficiency or Good syndrome.

Loasis is a parasitic disease acquired in CentralWest Africa only, usually in people with a normalimmune status. Following the bite of a tabanid fly ofthe genus Chrisops, the infective larvae burrow inthe skin where they develop into adults moving

Figure 1 Thoracic CT scan showing a mediastinal mass.A: aorta; H: heart; PA: pulmonary atelectasia; PE: pleuraleffusion; T: thymoma.

Figure 2 Loa microfilaria in the biopsy of the mass.

P. Landry et al.86

in the connective tissues and producing numerousmicrofilaria found in the blood. Clinical featuresare migrating subcutaneous swellings (Calabaroedema) most commonly on the wrists and ankles,lasting from a few hours to a few days, sometimeswith pruritus and arthralgia. The adult filarial canoccasionally be seen passing under the skin or theconjunctiva, rarely resulting in serious compli-cations when invading the central nervous system,or other organs. In expatriates hypereosinophilia iscommon.

In this case, the initial presentation, e.g. apleural effusion with loasis and an intrathoracicmass suggested a reactive tumor due to the possiblepresence of an adult parasite in the thorax. Twocases of filarial infection causing a mediastinal masshave been reported, one over 50 years ago, with Loaloa5 and a more recently one due to Wucherariabancrofti.6 Both resolved after antiparasitictherapy. Some cases of pleural effusion or pulmon-ary infiltrates with high contents in eosinophils havebeen associated to loasis.7 In the case we describeeosinophil counts in the pleural effusion and in thebiopsy of the mediastinal mass were not increased.At the time of surgical removal of the type B1thymoma, the Loa loa infection was still present,although less intense, despite a three weeks courseof DEC. It is known that T Helper cells responsive-ness play an important role in the clearanceof parasites.8,9 Thus this relative failure of treat-ment could be related to some degree ofimmunodeficiency.

There was no immunoglobulin deficiency and nohypogammaglobulinemia, but T lymphocytopenia,affecting both the CD4 and CD8 subsets, whichremained after removal of the tumor. Theseabnormalities do not qualify for CVID or for Goodsyndrome, but the patient clearly has immunode-ficiency. The decrease in T lymphocytes a year or soafter the tumorectomy, although without symp-toms, is consistent with published data of thepersistence of immunological abnormalities evenafter removal of the tumor.1 Looking for opportu-nistic infections as in Good syndrome or CVID ismandatory. Noteworthy is a published case ofsevere strongyloidosis and thymoma with no

hypogammaglobulinemia either.3 Organ involve-ment of loasis is well known, especially in kidney,heart, brain and lungs, but of interest, we found noreference to unusual manifestations of loasisrelated to HIV infection, although both diseasesare frequent in Central Africa. Rare studies haveanalyzed the effect of steroids in the clinical aspectof this infection.10

In summary, thymoma are tumors which aresometimes related to some degree of immunodefi-ciency, leading to complicated infections includingparasitic ones. We described the possible first caseof thymoma and loasis, in a short-term traveler.

References

1. Tarr PE, Sneller MC, Mechanic LJ, et al. Infections in patientswith immunodeficiency with thymoma (Good syndrome).Report of 5 cases and review of the literature. Medicine2001;80:123133.

2. Granel B, Gayet S, Christides C, et al. Thymoma andhypogammaglobulinemia. Goods syndrome: a propos of acase and review of the literature. Rev Med Interne 1999;20:347349.

3. Godoy P, Camargos Campos ChM, Costa G, et al. Associationof thymoma and severe intestinal strongyloidiasis. Rev SocBras Med Trop 1998;31(5):481485.

4. Shaikh BS, Schwab IR, Morse LS. Association of oculartoxoplasmosis and thymoma. Retina 1997;17(4):354356.

5. Madell SH, Spingam CL. Unusual thoracic manifestations infilariasis due to Loa loa. Am J Med 1953;15:272280.

6. Gilbert H, Hartman BJ. Short report: a case of fibrosingmediastinitis caused by Wucheraria bancrofti. Am J TropMed Hyg 1996;54(6):596599.

7. Boornazian JS, Fagan MJ. Tropical pulmonary eosinophiliaassociated with pleural effusions. Am J Trop Med Hyg 1985;34(3):473475.

8. Baize S, Wahl G, Soboslay PT, et al. T helper responsivenessin human Loa loa infection; defective specific proliferationand cytokine production by CD4 T cells from microfilar-aemic subjects compared with amicrofilaraemic. Clin ExpImmunol 1997;108:272278.

9. Ungeheuer M, Elissa N, Morelli A, et al. Celullar responses toLoa loa experimental infection in mandrills (Mandrillussphinx) vaccinated with irradiated infective larvae. ParasiteImmunol 2000;22:173183.

10. Wanji S, Tendongfor N, Vuong PN, et al. The migration andlocalization of Loa loa infective and fourth stage larvae innormal and immunosuppressed rodents. Ann Trop MedParasitol 2002;96:823830.

Loa loa infection in a patient with thymoma 87

Loa loa infection in a patient with thymomaCase reportDiscussionReferences