Pulmonary dirofilariasis

Pulmonary dirofilariasis Two cases of dirofilariasis are presented, the first to be reported from Philadelphia. The diagnosis of dirofilariasis must be made by pathological examination of the lesion, as the roentgenographic characteristics are of little aid in differential diagnosis. It may be necessary to examine multiple sections of the lesion microscopically to discover the parasite. It is suggested that dirofilariasis is found more frequently than reports in the literature indicate and that it can be found in the eastern Atlantic states.

Willis S. Hoch, M.D., * Martin E. Wershba, M.D., ** and Arthur S. Patchefsky, M.D., *** Philadelphia, Pa.

Dirofilaria is a nematode parasite which commonly infects cats, dogs, and other canines and has a world-wide distribution. In the United States, Dirofilaria immitis, the common heartworm of dogs, is the most frequent species. Dirofilariasis is rare in man; subcutaneous infection is the most common, followed by pulmonary involvement.' Since Dashiell' published the first case of pulmonary dirofilariasis in 1961, a total of 29 cases have been recorded in the English Iiterature.» 3, 10, 12-14,22, 26, 44 The rarity of the disease and its apparently increasing incidence in the United States suggest the desirability of heightened clinical familiarity. The clinical, radiologic, and pathological findings of the first 2 cases recorded from the Philadelphia are the subject of this report. Case reports CASE 1. J. H. (TJUH No. X578872), a 56-yearold male streetcar operator, was admitted to Thomas Jefferson University Hospital on March 21, 1967, because of nonproductive cough of 3 months' duration. A chest x-ray film taken on Oct. 7, 1966, during an earlier admission for urinary retention secondary to benign prostatic hypertro-

From the Thomas Jefferson University Hospital, Philadelphia, Pa. Received for publication June 18, 1973. Address for reprints: Willis S. Hoch, M.D., Thomas Jefferson University Hospital, 11th and Walnut Streets, Philadelphia, Pa. 19107. 'Assistant Professor of Pathology. "Resident in Radiology. '" Associate Professor of Pathology.

phy, was reported as unremarkable. He smoked cigarettes occasionally but denied dyspnea, chest pain, or hemoptysis. Aside from frequent visits to mosquito-infested New Jersey shore regions, he did not travel extensively and was a life-long resident of Philadelphia. He had no pets. Physical and laboratory examinations, including a hemogram, were unremarkable. Chest x-ray films showed a homogeneous density measuring 1.5 em. in diameter in the lingular segment of the left upper lobe. Tomograms revealed ill-defined margins and no calcification. A thoracotomy was performed on April 10, 1967. The resected specimen measured 2.0 by 1.5 by 1.0 crn., was pink gray, and was partially walled off from adjacent parenchymal tissue by a fibrous capsule. Microscopic examination revealed a circumscribed infarcted lesion with a well-developed fibrous capsule and a granulomatous, necrotizing inflammatory reaction in the adjacent tissue. A degenerated round worm was seen in a branch of the pulmonary artery, adjacent to the lesion. The worm had a thick, laminated cuticle, large muscle cells, broad lateral cords, and an absence of longitudinal ridges on the cuticle (Fig. 1). Its morphology and location in a pulmonary artery confirmed the diagnosis of Dirofilaria immitis (Fig. 2). Because of marked necrosis, it was impossible to identify the sex. Postoperative recovery was uneventful. CASE 2. J. S. (TJUH No. X789842), a 60-yearold white male high school teacher, was admitted to TJUH on March 6, 1971, because of transient left chest pain, productive cough, and fever of 4 weeks' duration. Treatment with analgesic and antibiotic drugs was ineffective. Chest x-ray examination revealed a solitary coin lesion in the left upper lobe (Fig. 3, A and B, and Fig. 4). Results of the annual chest roentgenograms and tuberculin tests given at his place of employment had previously been negative. He

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Fig. 1. Case 1. Cross section of worm showing alimentary tube, large muscle cells, and broad lateral cords . (Hematoxylin and eosin; original magnification x200.)

Fig. 2. Case 1. Two cross sections of Dirofilaria immitis in a branch of the pulmonary artery. (Hematoxylin and eosin; original magnification x50.)

had smoked one pack of cigarettes per day intermittently for 50 years. The patient had no previous history of hospitalization or any serious illnesses. He had had a pet dog until approximately 1 year prior to admission. His summer months were spent at Cape May, New Jersey, which is heavily infested with mosquitoes. Admission physical examination was unremarkable. The results of an intermediate purified protein derivative test were negative, as were sputum cultures and smears for acid-fast bacilli. A complete blood count, sequential multiple analyzer 12-60, electrocardiogram, upper gastrointestinal series, intravenous pyelogram, and liver scan yielded normal findings. Barium enema revealed a probable adenomatous sigmoid polyp and sigmoid diverticulosis. On March 16, 1971, a left thoracotomy was performed and a nodular lesion was found in the lingula. Centrally located in the subpleural region was a spherical nodule measuring 2.0 em. in greatest diameter. The mass was soft, encapsulated, red gray, and well demarcated from adjacent lung tissue. A single firm, white, 5.0 mm. satellite nodule was peripheral to the primary lesion. Frozen-section diagnosis was reported as lung infarct. Histologic examination revealed a coagulative infarction (Fig. 5), surrounded by granulomatous reaction, and a fibrous capsule. Because of the inflammatory vasculitis (Fig. 6), granulomatous reaction, and a coagula-

tive necrosis of the lung, the lesion was originally interpreted as a limited form of Wegener's granulomatosis. The remaining tissue was examined, and the satellite lesion proved to be a pulmonary artery containing a necrotic round worm surrounded by granulomatous vasculitis . The morphology and location of the worm were consistent with Dirofilaria immitis. Serologic antibody studies for Dirofilaria performed at the Communicable Disease Center in Atlanta, Georgia, were negative. The patient made an uneventful recovery. Results of a subsequent dextrocardiogram were normal.

Discussion

Faust," in 1957, reviewed the previous literature from 1887 and cited 37 cases of dirofilariasis in man, mostly from Mediterranean countries, southern Europe, and South America. All but 3 cases involved subcutaneous infestations. In 1941, he" reported a case from New Orleans with involvement of the inferior vena cava. Twentyone cases of dirofilarial infection in the United States were cited by Orihel and Beaver" in 1965. Three of these cases were of the pulmonary type. While mostly distributed in the southeastern states, several

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Fig. 3. Case 2. Posteroanterior (A) and lateral (B) roentgenograms demonstrate a solitary nodule in the lingula segment of the left upper lobe.

of the northern states were included (Massachusetts, Washington, Wisconsin, Michigan, and New York). One case has been reported from Japan" and one from Australia." Our 2 cases are the first reported from Philadelphia. The principal host of Dirofilaria immitis is the dog, although cats, foxes, and other carnivores may be infected . Several common insect vectors have been implicated, including Culex, Aedes, and Anopheles mosquitoes and possibly fleas, ticks, and lice. 11, 19 , 22 The mosquito acquires microfilariae from infected animals. Partial maturation occurs as the microfilariae migrate through the gut to the mouth parts, where they become infective (third stage larva). At the mosquito's next meal, these infected larvae are deposited into subcutaneous tissues of new host where they undergo further moult ing stages. Maturation continues after the final moult (fifth stage adolescent worm), as the larvae migrate into peripheral veins and are carried to the right side of the heart. Sexual maturation usually is reached before full adult size is attained. After primary infection of the host, it takes approximately 190 days until the stage of microfilaremia is reached. I" A detailed morphologic study is given by Orihel and Beaver." Man appears to be an unsuitable host for the parasite, and the full cycle cannot be completed.' Although 2 cases of subcutaneous infection with sexually mature worms have been reported , microfilaremia has not been recorded

Fig. 4. Case 2. Tomogram demonstrates fairly discrete margins and lack of calcium.

in man." These two infections were with Dirofilaria tenuis , which commonly occurs in raccoons." Dipetalonema reconditum.t" a filarial worm resembling Dirofilarium, is found in subcutaneous tissues of dogs and is capable of infecting man via the flea as the intermediate host.' This parasite appears capable only of subcutaneous infection in man. In the human lung, the parasite lodges in a branch of the pulmonary artery producing an ischemic infarct which undergoes or-

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Fig. 6. Case 2. Granulomatous vasculitis in pulmonary artery near site of Dirofilaria immitis. (Hematoxylin and eosin; original magnification x50.) Fig. 5. Case 2. Normal lung with artery involvement. Granulomatous reaction in left upper corner and infarct in right lower corner. (Hematoxylin and eosin; original magnification xlO.)

ganization by proliferation of histiocytes, Langhans giant cells, and the production of a fibrous capsule. The worm is usually seen in cross section and has the following characteristics: a thick laminated cuticle, large muscle cells, broad lateral cords, and absence of longitudinal ridges on the cuticle. Surrounding the zone of fibrosis, there may be an inflammatory infiltrate of eosinophils, plasma cells, and lymphoid nodules. Occasionally one sees ad inflammatory vasculitis in this region. One of us (A. S. P . ~) previously reported 12 cases of a limited form of Wegener's granulomatosis which had, as two of its pathological features, inflammatory vasculitis and pulmonary parenchymal infarcts. Because of these similarities, we reviewed our cases of limited forms of Wegener's granulomatosis but found no evidence of dirofilariasis.

Roentgenologically, pulmonary dirofilariasis presents as a well-circumscribed coin lesion," under 6 em. in diameter. The contour is usually smooth and spherical. In no case has calcification or cavitation been described. There is no lobar predilection . The lesions are usually solitary, although I patient had coin lesions in the left and right upper Iobes-' and 2 patients had two separate lesions in the same lobe. t:l-14 The disease has not been reported in children. Roentgenographic differentiation from malignant tumors may be difficult. Steele> reported that, in patients over the age of 50 years, 50 per cent of pulmonary coin lesions are malignant. Although most neoplasms have indistinct margins, 12 per cent of those in his group had sharply demarcated borders. The uniform lack of calcification tends to exclude such benign lesions as granulomas or hamartomas. The clinical history may be of some importance in suggesting this rare disease. Many of the reported patients had pleuritic

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pain several weeks prior to discovery of the lesion. Our second patient had fever and cough a few weeks prior to diagnosis. Dirofilariasis is important not only in human pathology but also in history; it was involved in the experimental development of extracorporeal systems for hemodialysis and cardiopulmonary bypass. During experimental studies in which cardiopulmonary bypass procedures were employed in dogs, a syndrome consisting of dyspnea, bradycardia, hypotension, urticaria, and eventual cardiovascular collapse suggesting anaphylaxis occurred with unexplained frequency." The mortality rate in affected animals ranged from 30 to 100 per cent. In 1962, Ota and colleagues!" discovered the cause of the reaction was the presence of two varieties of microfilaria in the donor canine blood. After this discovery, careful screening of animals allowed for the rapid development of cardiopulmonary bypass procedures in dogs and subsequently in man. We would like to acknowledge the secretarial assistance of Miss Geraldine Moore. REFERENCES

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Beaver, P. c., and Orihel, T. C.: Human Infection With Filariae of Animals in the United States, Am. J. Trop. Med. Hyg. 14: 1010, 1965. Beskin, C. A., Calvin, S. H., and Beaver, P. C.: Pulmonary Dirofilariasis: Cause of Pulmonary Nodular Disease, J. A M. A 198: 665, 1966. Brine, 1. A., Finlay-Jones, L. R., and Charters, A. D.: Pulmonary Dirofilariasis: A Case in Western Australia, Med. J. Aust. 2: 1238, 1971. Dashiell, G. F.: A Case of Dirofilariasis Involving the Lung, Am. J. Trop. Med. Hyg. 10: 37, 1961. Faust, E. C., Thomas, E. P., and Jones, J.: Discovery of Human Heartworm Infection in New Orleans, 27: 115, 1941. Faust, E. C.: Human Infection With Species of Dirofilaria, Z. Tropenmed. Parasitol. 8: 59, 1957. Harrison, E. G., and Thompson, J .H.: Dirofilarosis of Human Lung, Am. J. Clin. Pathol. 43: 224, 1965. Israel, H. L., and Patchefsky, A S.: Wegener's Granulomatosis of Lung: Diagnosis and Treatment. Experience With 12 Cases. Ann. Intern. Med. 74: 881,1971. Jung, R. C; and Espenan, P. H.: A Case of Infection in Man With Dirofilaria, Am. J. Trop. Med. Hyg. 16: 172, 1967.

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10 Lewis, J. F., Williams, R. W., and Tinsley, E. A: Pulmonary "Coin" Lesion Due to Dirofilaria immitis, Arch. Surg. 98: 388, 1969. 11 Ludlam, K. W., Jackowski, L. A, and Otto, G. F.: Potential Vectors of Dirofilaria immitis, J. Am. Vet. Med. Assoc. 157: 1354, 1970. 12 Maher, F. T., Watkins, L. C., Broadduct, J. C., and Bollman, J. L.: Significance of Homologous Donor Blood to the Toxic Reaction in Dogs Undergoing Extracorporeal Hemodialysis, Circ. Res. 6: 47, 1958. 13 Navarrete, R. A., and Noon, G.: Pulmonary Dirofilariasis Manifested as a Coin Lesion: Report of a Case and Review of the Literature, Arch. Pathol. 85: 266, 1968. 14 Navarrete, R. A: Pulmonary Dirofilariasis, Chest 61: 51, 1972. 15 Neafie, R. C., and Piggot, J.: Human Pulmonary Dirofilariasis, Arch. Pathol. 92: 342, 1971. 16 Newton, W. L., and Wright, W. H.: The Occurrence of a Dog Filariid Other Than Dirofilaria immitis in the United States, J. Parasitol. 42: 246, 1956. 17 Orihel, T. C., and Beaver, P. C.: Morphology and Relationship of Dirofilaria tenuis and D. conjunctivae, Am. J. Trop. Med. Hyg. 14: 1030, 1965. 18 Ota, Y., Camishion, R. C., and Gibbon, J. G., Jr.: Dirofilaria immitis (Heartworms) and Dipetalonema Species as Causes of "Transfusion Reaction" in Dogs, Surgery 51: 518, 1962. 19 Otto, G. F.: Geographical Distribution, Vectors, and Life Cycle of Dirofilaria immitis, J. Am. Vet. Med. Assoc. 154: 370, 1969. 20 Pacheco, G., and Schofield, H. L., Jr.: Dirofilaria tenuis Containing Microfilariae in Man, Am. J. Trop. Med. Hyg. 17: 180, 1968. 21 Schlotthauer, J. c.. Host Parasite Relationship of Dirofilaria immitis in the Dog, Thesis of University of Minnesota, 1965. 22 Schlotthauer, 1. C., Harrison, E. G., and Thompson, J. H.: Dirofilariasis: An Emerging Zoonosis, Arch. Environ. Health 19: 887, 1969. 23 Spear, H. C., Steele, J., Daughtry, D. C., Chesney, J. G., et al.: Solitary Pulmonary Lesion Due to Dirofilaria, N. Engl. J. Med. 278: 832, 1968. 24 Steele, 1.: The Solitary Pulmonary Nodule, Springfield, Ill., 1964, Charles C Thomas, Publisher. 25 Tannehill, A W., and Hatch, H. B.: Coin Lesions of the Lung Due to Dirofilar.ia immitis, Chest 53: 369, 1968. 26 Tauzon, R. A., Firestone, F., and Blaustein, A. V.: Human Pulmonary Dirofilariasis Manifesting as a "Coin" Lesion, J. A. M. A 199: 103, 1967. 27 Yoshimura, H., and Yokogawa, M.: Dirofilaria Causing Infarct in Human Lung, Am. I. Trop. Med. Hyg. 19: 63, 1970.