Cutaneous Larva Migrans, an Occupational Disease

IRENE E. ROECKEL, M.D. and EUGENE T. LYONS, Ph.D.

Central Kentucky Blood Center, Lexington, KY 40508 and College 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 hypersensitiv ity 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 frequently reported following exposure to larvae of canine and feline hookworm, Creeping eruption or cutaneous larva less commonly due to larvae of human and migrans is a condition in man resulting nonhuman species of Strongyloides.1 from skin invasion by filariform larvae of a Experimentally, filariform larvae of number of species of nematodes. Not Strongyloides myopotami from the nutria much space is devoted in the literature to and Strongyloides procyonis of the rac cases of cutaneous larva migrans, al coon resulted in creeping eruption in a though this condition is prevalent in some human volunteer.3 Accidental exposure, regions with warm, humid, tropical or resulting in skin penetration of the hands subtropical climates, including the south of laboratory workers by larvae of Stron ern United States and South, East and gyloides ransomi of swine and Stron West Africa and Ceylon.7 In the United gyloides papillosus from sheep, goats, and States, cases of creeping eruption are most cattle and Strongyloides westeri from horses, has also been reported.6 Because The investigations reported in this paper (No. cases are so infrequently seen, only a few 77-4-106) are published with the approval of the D i rector of the Kentucky Agricultural Experiment Sta physicians are familiar with the clinical tion. picture and know the nematodes respon 4 0 5 4 0 6 ROECKEL AND LYONS

sible for creeping eruption. Accidental patient permitted skin biopsy of a lesion exposure to free-living third-stage larvae for diagnostic purposes. All three patients of S. westeri was observed in three pa remain symptom free as long as there is tients and forms the basis for this report. no contact with the parasite. The exposure resulted from the individu als working with the parasites in the labo Case Reports ratory. In addition, free-living third-stage larvae of S. westeri were used to repro Case 1. This 58-year-old white Caucasian male had about 17 years ofexperience working with fecal duce skin lesions in a rabbit. cultures containing free-living third-stage larvae of S. papillosus and S. westeri. He wore no gloves while working with the larvae. O n September 24, Aetiologic Agent 1966, a large, but undetermined number of S. wes teri larvae from a 30 ml syringe filled with water The adult parasite, S. westeri, is a tiny containing 2.25 m illion larvae, splashed on his 8 to 9 mm long nematode found in the forehead, leading to a striking edema with spon small intestines of young horses. The life taneous recovery after 360 hrs. The details are tabu lated in table I. He continued to work with fecal cycle has been elucidated.4,5 Infection cultures containing larvae of both species of Stron- occurs predominantly from parasitic gyloides for seven more years, wearing rubber third-stage larvae passed through the gloves, and remained free of symptoms. milk of mares to their foals, and these Case 2. This 29-year-old, red-haired individual stages mature in a minimum of about with light complexion had approximately 1 2 years experience with fecal cultures of larvae of both S. eight days. The adult worms lay eggs papillosus and S. westeri. This included cleaning which pass in the embryonated state in stalls as well as handling cultures. He wore no the feces of foals. Larvae hatch from the gloves while working. On October 6 , 1970, a mas sive accidental exposure on the right arm, wrist and eggs on the ground and develop, directly area of antecubital fossa, to probably several or indirectly, to free-living third-stage thousand free-living third-stage larvae of S. westeri, larvae, capable of skin penetration, that from a sample containing 6 .0 million larvae, led to the illness reported here. During the observation enter foals and mature or enter tissues of period, at least two additional exposures to the lar horses, possibly all ages, and become in vae occurred over a 60-day period. hibited as parasitic third stages. Shortly The patient became progressively sensitized and he experienced recurring edematous swelling of his after parturition, the parasitic third-stage hands and arms for several days after working with larvae begin passing in the milk of mares fecal cultures. Edema was pronounced on the right to foals where the parasite matures and hand and right forearm between 18 and 234 hrs, peaking between 42 and 138 hrs, after the initial the life cycle is completed. massive exposure. In addition, erythema was evi dent in two areas of known exposure, on the right wrist and in area of antecubital fossa, between 18 Diagnosis and 618 hrs (figure 4). At 234 and 1,362 hrs after the initial known exposure to the right arm, the left Diagnosis in the three reported cases hand was exposed to probably a small number of were made after known accidental expo free-living third-stage larvae. This resulted in sure to free-living third-stage larvae (fig edema of the left hand within 24 hours after each ure 1) of S. westeri resulting in the dif exposure, lasting for 384 and 48 hours, respectively. Two years following the first accidental massive ex ficult clinical pictures to be reported. All posure, he changed jobs and no longer experienced three subjects, while doing research, had reactions until when he one day milked a mare. As previously noted, mares’ milk may contain parasitic previous contact for several years with third-stage larvae ofS. westeri which could possibly free-living third-stage larvae of S. papil- cause recurrence of the allergic reaction. losus from sheep and cattle and S. westeri Case. 3. This 45-year-old white male had about from horses. The number of exposures 15 years of experience with larvae of S. papillosus prior to the illnesses reported in this and S. westeri, most contact being with the latter. The exposure was to parasitic third-stage larvae in paper remain unknown, but oppor milk and free-living third-stage larvae in fecal cul tunities to exposure were frequent. One tures. On September 3,1976, an accidental exposure, CUTANEOUS LARVA MIGRANS 407 probably on right middle finger, to free-living third- 24 hrs after exposure, spreading caudally as well as stage larvae of S. westeri led to the illness described laterally. Note a possible second exposure at 180 hrs in table II. A somewhat different clinical course was after the first one. seen than in the first two cases experienced. The Creeping eruptions occurred 324 hrs postexpo allergic reaction seen on the right hand (figure 5) and sure, moving mainly from right to left under the right detailed in table II consisted mostly of edema within pectoral muscle (figure 3), between both pectorals,

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

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

F i g u r e 4. Erythema on right wrist and in F i g u r e 5. Edema of right hand; left hand area of antecubital fossa (Case No. 2). normal (Case No. 3). 40 8 ROECKEL AND LYONS

TABLE I

Clinical Picture in Case 1 Following Accidental Exposure to Forehead of Several Thousand F ree-living Third-stage Larvae o f S. westeri on September 24, 1966

Time ______Edema______Erythema Postexposure ______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 injected through 16-gauge needle into rear hip mus the right shoulder and on the lower right shoulder, as cles. On May 14, 1971, 0.5 milliliter of the same detailed in table II. mixture was injected into hip muscles, prior to appli Blood eosinophiles rose from 6 percent at 96 hrs to cation o f600,000 live larvae on the shaved abdomi a peak of 18 percent at 504 hrs postexposure. The 6 nal area. The area at the site of the application be percent level returned by 912 hours after exposure. came red. On May 21, 1971, 0.5 milliliter of frozen One site of the allergic dermatitis, on the right larvae with Freund’s adjuvant was injected again just forearm, was biopsied, showing areas of epidermal prior to application of 300,000 live larvae on shaved thickening overlying the most intense inflammatory abdomen. process in the dermis. O n serial section, an area of Under local anesthesia, the following biopsies intradermal necrosis, thought to be the site of a were taken within one to two min after larval expo nematode penetration, was demonstrated. The der sure: (1 ) skin from area where larvae were placed, (2 ) mal inflammatory infiltrate consisted of lymphocytes shaved area away from where larvae were placed and and many eosinophiles. One vascular channel (3) area of skin exposed to larvae five min following suggested areas ofnecrosis ofthe vessel wall. Parasi exposure. Grossly, the skin within three to four min tic remnants or parasites could not be demonstrated had a reddish, thickened appearance but no in any of the sections. The patient has had no further generalized edematous reaction. contact with the parasite and has remained free of Histologic examination of biopsies: Larvae could symptoms. be seen penetrating the epidermis. In the dermis, an intense inflammatory reaction was present, com posed of a mixture of lymphocytes and eosinophiles. Animal Experiment Scattered throughout in the deeper dermal tissues . One rabbit, six weeks old, was used in an effort to were multi-nucleated giant cells with foreign mate study the clinical picture of experimentally pro rial within their cytoplasm. However, the material duced skin eruptions after exposure to free-living could not definitely be identified as nematodes. third-stage larvae ofS. westeri infection. On October 16, 1970, 50,000 live larvae were placed on the back of a shaved area two inches in diameter. Following Discussion 60 min observation and complete drying of the area with an air hose, the animal was placed back in the Significant clinical illness can be ex cage. On April 1, 1971, freshly shaved abdominal pected in veterinarians and laboratory skin was exposed to 500,000 live larvae; the rabbit was immobilized for 60 min. Two weeks later, workers exposed to filariform larvae of 300,000 live larvae were applied to shaved abdomi several species of Strongyloides. The nal skin for ten min. Simultaneously, 50,000 live cases reported here were characterized larvae were injected subcutaneously in areas of the shaved skin. On May 5,1971, one milliliter of frozen by a clinical picture of hypersensitivity larvae was mixed with Freund’s complete adjuvant reaction in addition to the mechanical CUTANEOUS LARVA MIGRANS 40 9 damage caused by the larvae invading the hypersensitivity reaction, it may the skin. In two cases, however, the travel great distances from the site of the hypersensitivity reaction overshadowed penetration of the skin, causing the red the lesion caused by the migration of the streaky channels, a result of the migration parasite in the dermis. In the hyper by the parasite in the dermis, as seen in sensitive individual, edema and ery Case 3, and described as “creeping erup thema are the presenting clinical features tion.” in the area invaded by the parasite. If the Both the allergic manifestations and parasite is not arrested in its migration by the skin migration of larval nematodes

TABLE I I

Clinical Picture in Case 3 Following Accidental Exposure, Probably to Right Middle Finger, of Low Undertermined Number of Free-living Third-stage Larvae of 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 Right Pectoral 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. 4 1 0 ROECKEL AND LYONS are a self-limiting process, and these to the foreign protein of penetrating live conditions do not recur as long as the in Strongyloides larvae, it is recommended dividual is not exposed to the parasite.1 If that veterinarians and laboratory workers accidental exposure of the skin to infec carefully protect their exposed skin from tive larvae occurs, immediate application those parasites that are capable of penet of tincture of iodine has been found effec rating the epidermis, resulting in sensiti tive to relieve the itching as well as the zation and eventually a disabling hyper swelling.6 Thiabendazole administered immune state. orally or topically and freezing the skin with ethyl chloride or carbon dioxide References may be helpful in arresting the larvae.2 1. Be a v e r , P. C.: Cutaneous larva migrans. Ind. The allergic manifestations in the cases Med. Surg. 33:319-321, 1964. reported were ameliorated by systemic 2. B r o w n , H. W.: Basic Clinical Parasitology, 4th ed. Appleton-Century-Crofts, New York, p. administration of antihistaminics (benad- 355, 1975. ryl and pyribenzamine). 3. L it t l e , M. D.: Dermatitis in a human volun Experimentally, it was possible to teer infected with Strongyloides of nutria and raccoon. Amer. J. Trop. Med. Hyg. 24:1007- create the hypersensitivity reaction in a 1009, 1965. rabbit by administering free-living 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. third-stage larvae of S. westeri in con- C.: Parasites from mare’s milk. The Blood- junction with Freund’s adjuvant demon Horse 95:2270-2271, 1969. 5. L y o n s , E. T., D r u d g e , J. H., and T o l l i v e r , S. strating that in the hypersensitive indi C.: On the life cycle of Strongyloides westeri vidual the larvae do penetrate the in the equine. J. Parasitol. 59:780-787, 1973. 6 . MALYGIN, S. A.: A case of cutaneous form of epidermis but are stopped from further strongyloidiasis caused by larvae of S. ransomi, migrating by the intense inflammatory S. westeri and S. papillosus. Med. Parazitol. i. reaction in the dermis and epidermis. Parasitar. Bolezni 27:446-447, 1958. 7. WlLCOCKS, C. and MANSON-BAHR, P. E. C.: In view of the marked hypersensitivity Manson’s Tropical Diseases, 17th ed. Williams that may be acquired following exposure and Wilkins, Baltimore, p. 1164, 1972.