ANNALS OF CLINICAL AND LABORATORY SCIENCE, Vol. 7, No. 5Copyright © 1977, Institute for Clinical Science

Cutaneous Larva Migrans, an Occupational DiseaseIRENE E. ROECKEL, M.D. and EUGENE T. LYONS, Ph.D.

Central Kentucky Blood Center, Lexington, KY 40508

andCollege of Agriculture,

Department of Veterinary Science, University of Kentucky,

Lexington, KY 40506

ABSTRACT

Creeping skin eruption is known to follow exposure to canine and feline hookworm larvae found in contaminated soil encountered in humid, tropical and subtropical regions. A little known hazard of similar infections exists among veterinarians and laboratory workers exposed to Strongyloides larvae from horses located in temperate climates. The evolving clinical picture is described in detail. Continued exposure may lead to a state of hypersensitiv­ity to the parasitic protein resulting in severe hyperimmune reactions. The invasiveness of Strongyloides larvae through intact skin and the pathologic changes associated with infection were demonstrated in a rabbit.

Introduction

Creeping eruption or cutaneous larva migrans is a condition in man resulting from skin invasion by filariform larvae of a number of species of nematodes. Not much space is devoted in the literature to cases of cutaneous larva migrans, al­though this condition is prevalent in some regions with warm, humid, tropical or subtropical climates, including the south­ern United States and South, East and West Africa and Ceylon.7 In the United States, cases of creeping eruption are most

The investigations reported in this paper (No.77-4-106) are published with the approval of the D i­rector of the Kentucky Agricultural Experiment Sta­tion.

frequently reported following exposure to larvae of canine and feline hookworm, less commonly due to larvae of human and nonhuman species of Strongyloides.1

Experimentally, filariform larvae of Strongyloides myopotami from the nutria and Strongyloides procyonis of the rac­coon resulted in creeping eruption in a human volunteer.3 Accidental exposure, resulting in skin penetration of the hands of laboratory workers by larvae of Stron­gyloides ransomi of swine and Stron­gyloides papillosus from sheep, goats, and cattle and Strongyloides westeri from horses, has also been reported.6 Because cases are so infrequently seen, only a few physicians are familiar with the clinical picture and know the nematodes respon­

405

406 ROECKEL AND LYONS

sible for creeping eruption. Accidental exposure to free-living third-stage larvae of S. westeri was observed in three pa­tients and forms the basis for this report. The exposure resulted from the individu­als working with the parasites in the labo­ratory. In addition, free-living third-stage larvae of S. westeri were used to repro­duce skin lesions in a rabbit.

Aetiologic Agent

The adult parasite, S. westeri, is a tiny 8 to 9 mm long nematode found in the small intestines of young horses. The life cycle has been elucidated.4,5 Infection occurs predominantly from parasitic third-stage larvae passed through the milk of mares to their foals, and these stages mature in a minimum of about eight days. The adult worms lay eggs which pass in the embryonated state in the feces of foals. Larvae hatch from the eggs on the ground and develop, directly or indirectly, to free-living third-stage larvae, capable of skin penetration, that enter foals and mature or enter tissues of horses, possibly all ages, and become in­hibited as parasitic third stages. Shortly after parturition, the parasitic third-stage larvae begin passing in the milk of mares to foals where the parasite matures and the life cycle is completed.

Diagnosis

Diagnosis in the three reported cases were made after known accidental expo­sure to free-living third-stage larvae (fig­ure 1) of S. westeri resulting in the dif­ficult clinical pictures to be reported. All three subjects, while doing research, had previous contact for several years with free-living third-stage larvae of S. papil- losus from sheep and cattle and S. westeri from horses. The number of exposures prior to the illnesses reported in this paper remain unknown, but oppor­tunities to exposure were frequent. One

patient permitted skin biopsy of a lesion for diagnostic purposes. All three patients remain symptom free as long as there is no contact with the parasite.

Case Reports

Case 1. This 58-year-old white Caucasian male had about 17 years ofexperience working with fecal cultures containing free-living third-stage larvae ofS. papillosus and S. westeri. He wore no gloves while working with the larvae. On September 24,1966, a large, but undetermined number of S. wes­teri larvae from a 30 ml syringe filled with water containing 2.25 m illion larvae, splashed on his forehead, leading to a striking edema with spon­taneous recovery after 360 hrs. The details are tabu­lated in table I. He continued to work with fecal cultures containing larvae of both species of Stron- gyloides for seven more years, wearing rubber gloves, and remained free of symptoms.

Case 2. This 29-year-old, red-haired individual with light complexion had approximately 1 2 years experience with fecal cultures of larvae of both S. papillosus and S. westeri. This included cleaning stalls as well as handling cultures. He wore no gloves while working. On October 6 , 1970, a mas­sive accidental exposure on the right arm, wrist and area of antecubital fossa, to probably several thousand free-living third-stage larvae of S. westeri, from a sample containing 6 .0 million larvae, led to the illness reported here. During the observation period, at least two additional exposures to the lar­vae occurred over a 60-day period.

The patient became progressively sensitized and he experienced recurring edematous swelling of his hands and arms for several days after working with fecal cultures. Edema was pronounced on the right hand and right forearm between 18 and 234 hrs, peaking between 42 and 138 hrs, after the initial massive exposure. In addition, erythema was evi­dent in two areas of known exposure, on the right wrist and in area of antecubital fossa, between 18 and 618 hrs (figure 4). At 234 and 1,362 hrs after the initial known exposure to the right arm, the left hand was exposed to probably a small number of free-living third-stage larvae. This resulted in edema of the left hand within 24 hours after each exposure, lasting for 384 and 48 hours, respectively. Two years following the first accidental massive ex­posure, he changed jobs and no longer experienced reactions until when he one day milked a mare. As previously noted, mares’ milk may contain parasitic third-stage larvae ofS. westeri which could possibly cause recurrence of the allergic reaction.

Case. 3. This 45-year-old white male had about 15 years of experience with larvae of S. papillosus and S. westeri, most contact being with the latter. The exposure was to parasitic third-stage larvae in milk and free-living third-stage larvae in fecal cul­tures. On September 3,1976, an accidental exposure,

CUTANEOUS LARVA MIGRANS 407

probably on right middle finger, to free-living third- stage larvae of S. westeri led to the illness described in table II. A somewhat different clinical course was seen than in the first two cases experienced. The allergic reaction seen on the right hand (figure 5) and detailed in table II consisted mostly of edema within

24 hrs after exposure, spreading caudally as well as laterally. Note a possible second exposure at 180 hrs after the first one.

Creeping eruptions occurred 324 hrs postexpo­sure, moving mainly from right to left under the right pectoral muscle (figure 3), between both pectorals,

FIGURE 1. Free-living third-stage larva of Strongyloides westeri (Total length is about 500 fx).

F ig u r e 2. Creeping eruption on right side F ig u r e 3. Creeping eruption under rightof neck (Case No. 3). pectoral area (Case No. 3).

F ig u r e 4. Erythema on right wrist and in F ig u r e 5. Edema of right hand; left handarea of antecubital fossa (Case No. 2). normal (Case No. 3).

408 ROECKEL AND LYONS

TABLE I

C lin ic a l P icture in Case 1 Following Accidental Exposure to Forehead of Several Thousand Free-living Third-stage Larvae o f S. westeri on September 24, 1966

Time ________Edema_____ _______________________________ ErythemaPostexposure ____________Top of Head___________

(Hours) Right Orbit Nose Forehead Anterior Middle Posterior Rear of Head

0 0 0 - - - - -

24 0 0 - - - - -

48 2 0 + - - - -

72 3 3 + + + - -

96 4 3 + + + + -

120 4 4 + + + + +144 3 3 + + + + +168 2 2 + + + + +

192 to 288 1 1 + + + + +312 0 0 - - - - -

360 1 0 - - - - -

364 0 0 - - - - -

Edema graded from 0 to 4. Erythema marked - = absent; + = present.

on the right side of the neck (figure 2 ), over the top of the right shoulder and on the lower right shoulder, as detailed in table II.

Blood eosinophiles rose from 6 percent at 96 hrs to a peak of 18 percent at 504 hrs postexposure. The 6 percent level returned by 912 hours after exposure.

One site of the allergic dermatitis, on the right forearm, was biopsied, showing areas of epidermal thickening overlying the most intense inflammatory process in the dermis. On serial section, an area of intradermal necrosis, thought to be the site of a nematode penetration, was demonstrated. The der­mal inflammatory infiltrate consisted of lymphocytes and many eosinophiles. One vascular channel suggested areas ofnecrosis ofthe vessel wall. Parasi­tic remnants or parasites could not be demonstrated in any of the sections. The patient has had no further contact with the parasite and has remained free of symptoms.

Animal Experiment

. One rabbit, six weeks old, was used in an effort to study the clinical picture of experimentally pro­duced skin eruptions after exposure to free-living third-stage larvae ofS. westeri infection. On October16, 1970, 50,000 live larvae were placed on the back of a shaved area two inches in diameter. Following 60 min observation and complete drying of the area with an air hose, the animal was placed back in the cage. On April 1, 1971, freshly shaved abdominal skin was exposed to 500,000 live larvae; the rabbit was immobilized for 60 min. Two weeks later, 300,000 live larvae were applied to shaved abdomi­nal skin for ten min. Simultaneously, 50,000 live larvae were injected subcutaneously in areas of the shaved skin. On May 5,1971, one milliliter of frozen larvae was mixed with Freund’s complete adjuvant

injected through 16-gauge needle into rear hip mus­cles. On May 14, 1971, 0.5 milliliter of the same mixture was injected into hip muscles, prior to appli­cation o f600,000 live larvae on the shaved abdomi­nal area. The area at the site of the application be­came red. On May 21, 1971, 0.5 milliliter of frozen larvae with Freund’s adjuvant was injected again just prior to application of 300,000 live larvae on shaved abdomen.

Under local anesthesia, the following biopsies were taken within one to two min after larval expo­sure: (1 ) skin from area where larvae were placed, (2 ) shaved area away from where larvae were placed and (3) area of skin exposed to larvae five min following exposure. Grossly, the skin within three to four min had a reddish, thickened appearance but no generalized edematous reaction.

Histologic examination of biopsies: Larvae could be seen penetrating the epidermis. In the dermis, an intense inflammatory reaction was present, com­posed of a mixture of lymphocytes and eosinophiles. Scattered throughout in the deeper dermal tissues were multi-nucleated giant cells with foreign mate­rial within their cytoplasm. However, the material could not definitely be identified as nematodes.

Discussion

Significant clinical illness can be ex­pected in veterinarians and laboratory workers exposed to filariform larvae of several species of Strongyloides. The cases reported here were characterized by a clinical picture of hypersensitivity reaction in addition to the mechanical

CUTANEOUS LARVA MIGRANS 409

damage caused by the larvae invading the skin. In two cases, however, the hypersensitivity reaction overshadowed the lesion caused by the migration of the parasite in the dermis. In the hyper­sensitive individual, edema and ery­thema are the presenting clinical features in the area invaded by the parasite. If the parasite is not arrested in its migration by

the hypersensitivity reaction, it may travel great distances from the site of the penetration of the skin, causing the red streaky channels, a result of the migration by the parasite in the dermis, as seen in Case 3, and described as “creeping erup­tion.”

Both the allergic manifestations and the skin migration of larval nematodes

TABLE I I

C lin ic a l Picture in Case 3 Following Accidental Exposure, Probably to Right Middle Finger, o f Low Undertermined Number of Free-living Third-stage Larvae o f S. westeri on September 3, 1976

___________________ Edema________________________ _______ ________________ Erythema______________Time .__________Right Hand_______________ Right Hand and Arm

Postexposure Right Forearm _______________ Fingers________________ Meta- Meta- Forearm- Upper Arm-(Hours) Proximal Thumb Index Middle Ring Little carpus carpus Distal Distal

0 0 0 0 0 0 0 0 _ -

24 0 0 0 4 0 0 0 - - _

36 0 0 0 4 1 1 0 _ - _

48 0 0 0 4 1 1 1 - _ _

60 0 0 0 4 3 3 2 _ -

72 to 84 0 1 1 4 3 3 3 _ _ _

96 to 144 0 1 1 4 3 3 4 _ _

156 to 180* 0 1 1 1 1 1 3 _ - _

186 0 1 1 1 1 1 3 - + _

192 0 1 1 1 1 1 3 _ _ _

204 0 1 4 1 1 1 3 + + _

228 0 1 4 1 1 1 3 _ _ +240 0 1 3 1 1 1 3 _ _ _

252 0 1 3 1 1 1 3 _ +264 0 1 1 1 1 1 1 - - -

276 0 0 0 0 0 0 0 _ _ _

288 to 312 0 0 0 0 0 0 0 - - -

__________________________________Cutaneous Larva M i g r a n s _____________________________________________Primary Trails_______________________________ Secondary Trails__________

Right Both Neck Right Shouldert Left Right Upper RightPectoral Pectorals Right Top upper Middle Lower Shoulder Shoulder Middle Forearm-Under -Between Side Back Proxii}

324 0 +336 0 + - - - _ _ _ _ _ _341 0 + + - _ _ _ _ _ _ _ _348 1 + + - - - - _ - _ _ _350 1 + + + - - _ _ _ _ _ _

360 to 364 2 + + + - - _ - _ _ _ +367 2 + + + + - - _ _ _ +369 2 + + + + + - - - - - +

372 to 389 2 + + + + + + - - - - +394 to 398 3 + + + + + + - + + - -406 to 416 3 + + + + + + + + + + -418 to 430 2 - - + + + + + + + + -

436 1 - - - + + + + + + + -440 to 454 0 - - - - - + + - - + -465 to present 0 - - - - - - - - - - -

*Second exposure on September 10, 1976.tTrail, almost straight line, diagonal, from right side of neck to right axilla.Edema graded from 0 to 4. Erythema and larval migration marked - = absent; + = present.

410 ROECKEL AND LYONS

are a self-limiting process, and these conditions do not recur as long as the in­dividual is not exposed to the parasite.1 If accidental exposure of the skin to infec­tive larvae occurs, immediate application of tincture of iodine has been found effec­tive to relieve the itching as well as the swelling.6 Thiabendazole administered orally or topically and freezing the skin with ethyl chloride or carbon dioxide may be helpful in arresting the larvae.2 The allergic manifestations in the cases reported were ameliorated by systemic administration of antihistaminics (benad- ryl and pyribenzamine).

Experimentally, it was possible to create the hypersensitivity reaction in a rabbit by administering free-living third-stage larvae of S. westeri in con- junction with Freund’s adjuvant demon­strating that in the hypersensitive indi­vidual the larvae do penetrate the epidermis but are stopped from further migrating by the intense inflammatory reaction in the dermis and epidermis.

In view of the marked hypersensitivity that may be acquired following exposure

to the foreign protein of penetrating live Strongyloides larvae, it is recommended that veterinarians and laboratory workers carefully protect their exposed skin from those parasites that are capable of penet­rating the epidermis, resulting in sensiti­zation and eventually a disabling hyper­immune state.

References1. Be a v e r , P. C.: Cutaneous larva migrans. Ind.

Med. Surg. 33:319-321, 1964.2. Br o w n , H. W.: Basic Clinical Parasitology, 4th

ed. Appleton-Century-Crofts, New York, p. 355, 1975.

3. L it t l e , M. D.: Dermatitis in a human volun­teer infected with Strongyloides of nutria and raccoon. Amer. J. Trop. Med. Hyg. 24:1007- 1009, 1965.

4. L y o n s , E. T., D r u d g e , J. H., and T o l l iv e r , S. C.: Parasites from mare’s milk. The Blood- Horse 95:2270-2271, 1969.

5. L y o n s , E. T., D r u d g e , J. H., and To l l iv e r , S.C.: On the life cycle of Strongyloides westeri in the equine. J. Parasitol. 59:780-787, 1973.

6 . MALYGIN, S. A.: A case of cutaneous form of strongyloidiasis caused by larvae of S. ransomi,S. westeri and S. papillosus. Med. Parazitol. i. Parasitar. Bolezni 27:446-447, 1958.

7. WlLCOCKS, C. and MANSON-BAHR, P. E. C.: Manson’s Tropical Diseases, 17th ed. Williams and Wilkins, Baltimore, p. 1164, 1972.