ABSTRACT

Background
Owing to the increase of an immigrant population and of Italian citizens travelling for tourism or on business, it is nowadays possible to observe clinical pictures characteristic of tropical regions, often with indistinct symptoms. One of these pictures is Loa loa infestation, or loiasis, a form of filariasis caused by Loa loa and transmitted by Chrysops fly. We present the case of a male immigrant from Cameroon. Characteristic symptoms were intense xerosis, mostly of the third inferior part of the legs, intensely pruritic, with numerous lesions from scratching. No benefit was obtained by emollient topics, anti-acarus and systemic antihistamines.

Method
Serum samples and Giemsa, haematoxylin, haematoxylin+Giemsa concentration-on-membrane stained, have evidenced the presence of Loa loa microfilariae.

Results
A diagnosis for Loa loa (loiasis) infestation has been made.

Conclusions
At the beginning of migration phenomenon, particularly from Africa, Italian physicians, especially dermatologists, were eagerly looking for "tropical" diseases; this approach can defined as "Salgari's syndrome" from the name of the Italian novelist who, though never travelling out of Italy, had perfectly described environments and habits typical of far away countries. Now, conversely, we have to avoid the opposite approach of considering real tropical diseases as related to social or psychological difficult conditions.

Key words: Chrysops, loiasis, tropical dermatology

Received: 1 August 2001, accepted 11 December 2001

Introduction
Filarioses are helmintic infestations by nematode worms. They have been known since ancient times, and their first description was given by the famous Hindu physician Sparuta, while the clinical picture was described by Madhavakara (VII century BC) in the treatise "Madhava Nidhana"1.
The most common pathologies from human nematodes include onchocercosis (Oncocerca volvulus), streptocercosis (Mansonella streptocerca), lymphatic filarioses (Wuchereria bancrofti and Brugia malayi), loiasis (Loa loa), dracunculosis (Dracunculus medinensis), enterobiasis (Enterobius vermicularis), ancylostomiasis (Necator americanus and Ancylostoma duodenale) and strongyloidiasis (Strongyloides stercoralis).
Adult worms live in the lymphatic system and in the tissues (skin, connective, serosa) while larvae (microfilariae) produced by adult females (microfilariae) live in the circulatory system or in the skin1. There is a transmitting vector for each filaria type, namely an haematophagus dipteran belonging to various families of flies or mosquitos. Through a blood meal the vector ingests the microfilariae, which spend part of their life cycle inside the vector and are successively inoculated, through bite, to new human hosts2,3.
One of the most frequent filariases in Africa is loiasis, or loaiasis, responsible for a large number of nematode infestations on that continent, where it represents a major public health problem, together with O.volvulus and M. perstans infestation4.

Case report
A man from Cameroon, who had been in Italy for about 6 months, presented with intense itching, mostly localised in the inferior part of the legs and paraesthesiae, with a feeling of "parasites moving under the skin". He also reported transitory urticaria-type lesions, not detectable at the time of the medical visit and general symptoms such as general malaise, headache, arthralgia, widespread abdomen pain and sialorrhoea. Objective examination did not reveal any kind of lesions, except intense cutaneous xerosis particularly on the third inferior part of the legs, areas of lichenification and numerous lesions due to scratching (Fig. 1)
Given the poor psychological, social, and housing conditions of a large number of immigrants in Italy, symptoms were considered as essential pruritus and treated with emollient topics and antihistamines, without any benefit. Moreover, as the patient shared the house with other people, some of whom were suffering from scabies, an anti-acarus benzyl benzoate treatment was initiated, but no improvement of the pruritus symptoms was observed.
Allergometric tests of the patient were negative. Haematologic tests showed a 15% eosinophilia and marked IgE increase. For suspected parasite urticaria a parasitological test of the faeces was performed that did not show any anomaly. The dyspepsia was examined by gastroscopy, which revealed antrum hyperaemia with Helicobacter pylori. In Helicobacter pylori, urticaria treatment with pantoprazole and amoxicilline therapy was initiated that remarkably reduced gastralgic and dyspeptic symptoms, but there was no improvement in the pruritus, which, conversely, worsened.
Further anamnesis revealed that, before reaching Italy, the patient used to bathe in the River Sanaga, which is the main watercourse in Cameroon, and this allowed better identification of the urticarial lesions; at first these were only reported and not observed, but they turned out to be oedematous, characteristically transient and migrating, as the patient reported.
In the light of such findings, eosinophilia symptoms and cutaneous lesions were reinterpreted and haemoparasites research was performed.

Results
Blood test at 1200 h revealed the presence of Loa loa microfilariae, well highlighted by Giemsa and haematoxylin staining (Fig. 2), besides techniques of concentration-on- membrane.
A diagnosis of loiasis was made and treatment with albendazole was started and doses were increased from 50 to 400 mg/d for 1 week and 600mg/d for the following 21 days, in combination with betamethasone 2 mg/d. Betamethasone was gradually decreased in the course of 10 days. Follow up showed a marked reduction of microfilaraemia, eosinophilia and itching.

Comment
A diagnosis of loiasis should always to be considered in patients from endemic areas who complaining of pruritus symptoms that do not relate to allergies, difficult social conditions or housing problems.
This disease is widespread in the rain forest covered areas in Central and West Africa, from the Guinea Gulf to the Great Lakes. It is particularly frequent in Cameroon and along Ogowe river4. The distribution includes the coasts and Zaire river for most of its course. Some cases have also been found in Sudan, Ethiopia and among immigrant communities in Australia, Zimbabwe and North America 5,6. Recently, some filariasis cases have been described in travellers coming back from the African continent7.
Loa loa is transmitted to humans from the bites of Chrysops2,3, a haematophagus gadfly, also called horse fly, or mangrove fly, of which there are a variety of species (C. siliacea and C. dimidiata in Western Africa, C. distinctipennis and C.longi-cornis in East Africa, C. zahrai and C. streptobalius in Ethiopia)3. About 10 days after assumption of microfilariae by the insect, these begin to mature in its thorax muscles and in its adipose tissue and migrate into its proboscis. Subsequently, they can transmit disease for about 1 week. Apparently, C. siliacea transmits infection particularly during the humid season (April-December) while C. dimidiata is absent during the rain season (June-October).
After reaching human host through the vector bite, microfilariae spread out in a circular way, showing a daytime periodicity, the cause of which is not yet clear. Oxygen and carbon dioxide daytime variation is considered insufficient to account for the phenomenon, while temperature could have a main role. Microfilariae seem to be extremely thermosensitive and, therefore, a slight rise in body temperature could increase their transmission1.
The adult worms migrate through the connective skin tissue and can often be observed in the trunk, fingers, fraenulum of the tongue, penis skin, eyelids, as well as in the conjunctiva and anterior chamber of the eye7. Such migration can cause intense itching, associated with a feeling of "parasites migrating under the skin"8,9 and hyperpigmentation10, or it can be asymptomatic1. Sometimes worms become evident under the skin layer and, when visible in the conjunctiva11, they cause a marked irritation with conjunctivitis, eyelid oedema, a sensation of extraneous matter 12, uveitis 13, choroidoretinitis and neuralgia.
Characteristic features of the disease, although not always present, are oedematous transient and migrating lesions, called Calabar oedemas (from the name of a Nigerian town)14,15, probably related to an inflammatory and allergic reaction of the body, as shown by the increase of IgE haematic level and other inflammation markers8.
Cases of worm calcification in the subcutaneous tissues15 have been also reported and granulomas from extraneous body16, arthralgic symptoms, lymphadenitis17, hydrocele17, meningoencephalitis, glomerulonephritis18,19,20. Another rare possibility is disseminated loiasis, which can even be fatatl20.
From the serological point of view, besides hypereosinophilia and increased IgE, there is also a detectable increase of other inflammation markers, particularly of C-reactive protein and high anti-Loa loa antibodies levels 21,22,23.
The most frequent typical symptom, however, is itching 8,15 which is sometimes the only symptom.
Therapy is based on dietilcarbamazine22, even if it does carry a possible risks of side-effects, which can also be serious due to the massive destruction of the microfilariae that can occasionally result in encephalitis23. This is why such treatment should be administered initially in a low dosage, and together with steroids, in order to prevent allergic reactions as may occur in onchocercosis.
Ivermectine has also been employed in variable dosages, from 100 to 400 µg/kg. It has a good microfilaricidal action,24,25 but also presents significant side-effects26.
In order to avoid the risks of dietilcarbamazine it is possible to employ albendazole,27 which proved efficacious on microfilaraemia and eosinophilia in some studies reported in literature28,29. Also reported in literature is the use of mebendazole30 with conflicting results: according to some authors29 it has no effects on microfilariae, while according to others30 it yields a marked reduction of microfilaraemia and clinical symptoms.
In case of intense microfilaraemia a plasmapheresis has been suggested31. Sometimes also surgical extraction of the worm can be performed from conjunctiva32 or from subcutaneous tissues.
Prophylaxis consists in the use of repellents such as dimetilphthalate33. The case is reported in order to point out the risk for the dermatologist of eagerly hunting down non-existent tropical diseases in immigrants. 33,37
Although a diagnosis of loiasis in a black immigrant from Africa is not surprising, the unusual clinical picture of our case could have suggested other dermatological diagnoses that are very frequent in immigrants.
Even if when diseases are observed that have very few symptoms, which also appear to be related to difficult social, housing, or food conditions, care should be made in the anamnesis and interpretation of the clinical and laboratory results, and the possibility of alternative aetiopathogenesis and diagnoses should be considered.

References

ZUIN R., Le filariasi, CLUEP, Padova, 1979: 60-69.

HARMAN R., Loiasis, In: CANIZARES O., HARMAN R.R.M. (ed.), Clinical tropical dermatology, Boston, Blackwell Scientific Publications, 1992: 342-344.

BRYCESON ADM, HAY RJ., Parasitic worms and protozoa, in: ROOK/WILKINSON/EBLING, Textbook of Dermatology, Oxford, Blackwell Sciences, 1998: 1387-1388.

THOMSON M.C., OBSOMER V., DUNNE M. et al. Satellite mapping of Loa loa prevalence in relation to ivermectin use in west and central Africa, Lancet, 2000; 356: 1077-1078.

HUBLER WR, GREGORY JF, KNOX JM., Loiasis, Arch Dermatol, 1973; 108: 835-836.

MARRIOTT WR, Loiasis in a young child in Oregon, Int J Dermatol, 1986; 25: 252-254.

DAZA R.M., GUTIERREZ J., BURKHART P., PIEDROLA G., Lesiòn cutànea edematosa y pruriginosa en antebrazo izquierdo tras un viaje a Guinea Equatorial, Medicina Clinica, 2000; 114, (20): 39-40.

PRUFER L., Juckende Hautödeme - Allergie oder Parasitose?, Munch Med Wschr, 1983; 125, (16): 105.

NOIREAU F., APEMBET J.D., NZOULANI A., CARME B., Clinical manifestation of loiasis in an endemic area in the Congo, Trop Med Parasitol, 1990; 41: 37-39.

CUADROS J.A., MARTINEZ R., LIZASOAIN M., ALOS J.I., Generalized pruritus and eosinophilia in an African woman, Enferm Infecc Microbiol Clin, 1992; 10: 169-170.

PISELLA P.J., ASSARAF E., ROSSAZA C. et al. Conjunctivitis and ocular parasitic diseases. J Fr Ophtalmol 1999; 22(5): 585-588.

WIESINGER E.C., WINKLER S., EGGER S. et al. Afrikanischer Augenwurm als Erstmanifestation einer Loiasis, Dtsch Med Wochen, 1995; 120: 1156-1160.

GARIN J.P., ROUGIER J., MOJON M., Loase et uveite posterieure. A propos d’une observation, Acta Tropica, 1975 ; 32: 384-388.

GRASA-JORDAN P., MARRON GASCA J., GOMEZ LUS R. et al. Filariasis por Loa loa (loaiasis), Actas Dermo-Sifil, 1979; 70: 467-474.

CARME B., MAMBOUENI J.P., COPIN N., NOIREAU F., Clinical and biological study of Loa loa filariasis in Congolese, Am J Trop Med Hyg, 1989; 42, (65): 331-337.

LE GUYADEC T., WOLKENSTEIN P., ORTOLI J.C. et al. Granulome à corps étrangers sur filaire Loa loa calcifiée, Ann Derm Venereol, 1992 ; 119: 127-130.

SACHS H.G., HEEP M., GABEL V.P., Surgical worm extraction in Loa loa ophthalmia. Klin Monatsbl Augenheilkd 1998; 213, (6): 367-369.

NEGESSE Y., LANOIE L.O., NEAGIE R.C., CONNOR D.H., Loiasis: "Calabar" swellings and involvement of deep organs. Am J Trop Med Hyg, 1985; 34: 537-546.

PAKASA N.M., NSEKA N.M., NYIMI L.M., Secondary collapsing glomerulopathy associated with Loa loa filariasis. Am J Kidney Dis 1997; 30 (6): 836-839.

PILLAY VKG, KIRCH E., KURTZMAN NA, Glomerulopathy associated with filarial loiasis, JAMA, 1973; 225:179-181.

AKUE J.P., HOMMEL M., DEVANEY E., Markers of Loa loa infection in permanent residents of a loiasis endemic area of Gabon, Trans Royal Soc Trop Med Hyg, 1996; 90: 115-118.

KLION A.D., OTTESEN E.A., NUTMAN T.B., Effectiveness of diethylcarbamazine in treating loiasis acquired by expatriate visitors to endemic regions: long-term follow-up, J Infect Dis 1994; 169 (3): 604-610.

CARME B., BOULESTEIX J., BOUTES H., PURUHENCE M.F., Five cases of encephalitis during treatment of loiasis with diethylcarbamazine, Am J Trop Med Hyg1991; 44 (6): 684-690.

YARA S., HIGA F., ARAKAKI N. et al. A case of loiasis, Kansenshogaku Zasshi 2001; 75, (2): 151-154.

MARTIN-PREVEL Y., COSNEFROY H.Y., TSHIPAMBA P. et al. Tolerance and efficacy of single high-dose ivermectin for the treatment of loiasis, Am J Trop Med Hyg, 1993; 48: 186-192.

DUCORPS M., GARDON-WENDEL N., RANQUE S. et al., Secondary effects of the treatment of hypermicrofilaremic loiasis using ivermectin, Am J Trop Med Hyg, 1988; 39: 480-483.

KLION A.D., MASSOUGBODJI A., HORTON J. et al. Albendazole in human loiasis: results of a double-blind, placebo-controlled trial. J Infect Dis, 1993 ; 168, 202-206.

PALEOLOGO F.P., NEAFIE R.C., CONNOR D.H., Lymphadenitis caused by Loa loa, Am J Trop Med Hyg. 1984; 33, (3): 395-402.

KLION A.D., HORTON J., NUTMAN T.B., Albendazole therapy for loiasis refractory to diethylcarbamazine treatment., Clin Infect Dis. 1999; 29, (3): 680-682.

BURCHARD G.D., KERN P., Failure of high dose mebendazole as a microfilaricide in patients with loiasis., Trans R Soc Trop Med Hyg 1987; 81, (3): 420.

VAN HOEGAERDEN M., IVANOFF B., FLOCARD F. et al. The use of mebendazole in the treatment of filariases due to Loa loa and Mansonella perstans, Ann Trop Med Parasitol, 1987; 81: 275-82.

WHITE G.B., Man-biting species of Chrysops meigen, Culicoides latreille and Simulium latreille in Ethiopia, with discussion of their vector potentialities. Trans R Soc Trop Med Hyg, 1977 ; 71: 161-175.

VAN HOEGAERDEN M., FLOCARD F., Treatment of recurrent filarial, Calabar-type oedema with mebendazole. Trop Geogr Med. 1986; 38, (3): 296-298.

MORRONE A.: Tropical dermatology, 10th Congress EADV Munich 2001 JEADV November 2001; 15 (Suppl. 2): S12-S16.

MORRONE A., MUSCARDIN L.M., BARTOLI F. et al. Imported dermatose in Italy, 7th Congress EADV Nice J Eur Acad Dermatol Venereol 1998; 11 (Suppl. 2): 306.

SHENOY R.K., JOHN A., BABU B.S. et al. Two-year follow-up of the microfilaraemia of asymptomatic brugian filariasis, after treatment with two, annual, single doses of ivermectin, diethylcarbamazine and albendazole, in various combinations, Ann Trop Med Parasitol. 2000; 94, (6): 607-614.

GARRAUD O., NKENFOU C., BRADLEY J.E. et al. Identification of recombinant filarial proteins capable of inducing polyclonal and antigen-specific IgE and IgG4 antibodies. J Immunol 1995; 155, (3): 1316-1325.

J Eur Acad Dermatol Venereol 2002 May; 16 (3):280-283