University of Alabama at Birmingham

Gorgas Case 2012-10

Universidad Peruana Cayetano Heredia

The Gorgas Courses in Clinical Tropical Medicine are given at the Tropical Medicine Institute at Cayetano Heredia University in Lima, Perú.  Each August we conduct one of our 2-week refresher courses for those with previous training in tropical medicine; currently in session is the Gorgas Expert Course.  For the past 12 years, we have been pleased to share interesting cases seen by the participants each week when our courses are in session; there will be one more case next week to complete the 2012 case series.  Each case includes a brief history and pertinent digital images, followed by a link to the actual diagnosis and a brief discussion.

David O. Freedman & Eduardo Gotuzzo
Course Directors

The following patient was seen by the Gorgas Expert Course participants in the outpatient department of the 450-bed Cayetano Heredia National Hospital.

120813History:  62-year-old female presents with a 16-day history of cutaneous lesions.  The problem began with a serpiginous-erythematous lesion of approximately 5 cm on the chest wall over the sternum that was intensely pruritic.  The lesion mostly disappeared within 2 days and a new nodular lesion appeared on the left breast.  Three days later the lesion migrated to the left arm and subsequently by the time of presentation to the face where it was associated with significant edema.  No other complaints.  No relevant past history.

Epidemiology:  From upper socio-economic class; of Japanese descent; born and lives in Lima.  Regularly consumes raw fish, including sushi and tiradito, but in good restaurants.  Last ingestion was approximately 2 weeks before symptoms started.  No recent rural travel; no contact with animals or feces.  Not on any medication.

Physical Examination:  Afebrile.  Indurated lesion on the left face with erythema and edema [Image A].  No lymphadenopathy or hepatosplenomegaly.  No other skin lesions.  Ocular and fundoscopic examination normal.  Chest clear.

Laboratory Results:  WBC 9700, 10% eos.  Normal liver and renal function.

Diagnosis:  Gnathostomiasis.
120813dDiscussion:  Gnathstomiasis is most often clinically diagnosed in endemic areas by obtaining a history of eating raw or partially cooked fish, intermittent subcutaneous or cutaneous migratory swelling, and eosinophilia.  Diagnosis may be made by direct visualization of the larvae in biopsy material [Image B; another Peruvian case courtesy of Dr. Francisco Bravo].  The findings are of an eosinophilic dermatitis/panniculitis.  The yield of biopsy is sub-optimal due to the ongoing movement of the migratory larvae (up to 1 cm/hour) and is usually unnecessary if the patient has a classical presentation.  When therapy is initiated dying larvae may migrate closer to the surface to a fixed position so newly dead larvae may be easier to isolate.  Our patient developed a new superficial lesion on the neck [Image C] two days after initiation of therapy with albendazole 400 mg bid, but she did not consent to biopsy.  Serology is not widely available.  An ELISA developed at Mahidol University in Bangkok is reported to have close to 100% sensitivity and specificity for G. spinigerum.  Many of our local cases have been confirmed in this way and serological confirmation of the present case is pending.  Mexican investigators have developed diagnostics based on the local G. binucleatum species [Am J Trop Med Hyg. 1998 Dec;59(6):908-15].

Gnathostomiasis is a disease that is most highly endemic Japan and Southeast Asia, particularly Thailand, but the disease is also endemic in Cambodia, Laos, Myanmar, Indonesia, Philippines, and Malaysia.  However, it is very much an emerging disease of local people and travelers in Latin America.  First reported in Mexico in 1970, there are now over 2,000 cases, mostly from the western part of the country from Nayarit State as well as the well-visited resort areas such as Acapulco.  Significant numbers of cases have now been reported from Ecuador, and in Perú we now have experience with several dozen cases in the past 12 years.  Cases have also been reported in China, Sri Lanka, India, Myanmar, Zambia, and, most recently, Botswana.  See Clin Microbiol Rev. 2009 Jul;22(3):484-92 for a comprehensive review of gnathostomiasis.

Human cases are predominantly caused by Gnathostoma spinigerum in Asia and G. binucleatum in Mexico.  At least 16 other zoonotic or veterinary species are recognized.  Definitive parasitic speciation and biology in Perú and Ecuador have not been established but is likely to be G. binucleatum.  Human infection is almost always acquired as a result of ingestion of immature larvae in undercooked freshwater fish.  The adult worms live in tumors in the stomachs of dogs and cats.  Eggs are passed via the feces and the resulting larvae are ingested by minute freshwater copepods, which are in turn ingested by an indiscriminate range of fish, frogs, as well as reptiles.  When accidently ingested by humans the immature larvae cannot become mature adults in the intestine but rather can migrate widely through subcutaneous as well as deeper tissues.  Third-stage larvae are large (2.5 to 12.5 mm long, 0.4 to 1.2 mm wide) and have a bulbous head, spinous cuticle, four cephalic ballonets (used in inflation of the head), and a prominent muscular esophagus [Image D].

Our patient demonstrates the most frequent clinical manifestation – that of inflammatory and sometimes mildly hemorrhagic necrosis along the track of the migrating larva.  Erythematous, edematous plaques are urticarial and pruritic.  The presentation is almost always of transient subcutaneous nodular lesions that appear in sequence along the track of the larvae.  The trunk is apparently more common than the limbs; face is relatively rare.  The larvae are long-lived and prolonged migration from 10 to 12 years may occur.  Less frequently in Gnathostoma infection, the larvae can migrate to vital organs, including the CNS (eosinophilic meningitis or subarachnoid hemorrhage), lungs, and eyes (with severe conjunctival edema), and the disease rarely can be fatal.  CNS involvement has yet to be reported from Latin America with G. binucleatum.  Peripheral eosinophilia is present in most patients, but its absence does not exclude the diagnosis.

The clinical pattern in gnathostomiasis is usually different from the typical well-demarcated and thin red linear serpentine lesions of creeping eruption (cutaneous larva migrans) due to Ancylostoma species of animals or the rare instances when Fasciola or Paragonimus larvae migrate subcutaneously [see Gorgas Case 2007-01].  In endemic areas of Africa the migratory Calabar swellings of Loa loa infection would be a consideration.  Subcutaneous dirofilariasis is emerging as a more frequent problem throughout Europe [Clin Microbiol Rev. 2012 Jul;25(3):507-44].  Subcutaneous nodules can be present with onchocerciasis, cysticercosis, or sparganosis but don’t present a migratory pattern.

In Latin America, ceviche is a fish dish where pieces of fish are marinated in lime juice and eaten with raw vegetables.  Tiradito is thinly sliced fish marinated in lime juice and olive oil or vinegar. Lime juice is ineffective in killing the larvae of Gnathostoma.  In Mexico, ceviche made from freshwater fish such as tilapia is common.  Our cases have typically been associated with ceviche ingestion although some have been related to sushi.  However, ceviche in Lima is never made with river fish.  No systematic study of local fish populations has been published yet in Perú.  Nevertheless, it is interesting to note that all our cases have been from the high socio-economic classes in Lima where ceviche made from corvina (sea bass) and lenguado (flounder) is most commonly ingested.  Corvina spends part of its life cycle near the mouth of freshwater estuaries.  In Guayaquil, Ecuador, Gnathostoma has been definitively isolated from local corvina.

Both albendazole 400-600 mg/day for 2-3 weeks and ivermectin 150-200 µg/kg/day for 1-3 days have been reported to have cure rates in the 95% range.  Patients that don’t respond to one agent often respond easily to the other or to a second course of the same agent.  Relapses do occur and usually respond well to re-treatment although most would use the other agent, if available, during a relapse.