Cutaneous Paecilomycosis in a Cat

Case Report

A 5-year-old, 5-kg, neutered male domestic shorthair cat was referred to the Veterinary Teaching Hospital at Michigan State University’s College of Veterinary Medicine because of a recurrent, soft-tissue swelling over the left-lateral metacarpal region. The swelling was first noticed approximately 2 years previously over the fifth digit of the left front paw, at which time the soft-tissue swelling was surgically removed. The tissue was submitted for histopathological examination, which revealed a dermal nodular mycotic granuloma (a Microsporum species was suspected as the etiological agent). A fungal culture was not performed at this time, and no further treatment was done. The soft-tissue swelling recurred in the same region over a 4-month period, at which time the swelling and the affected fifth digit of the left front paw were amputated. Over a 4-month period, a soft-tissue swelling was noticed over the left-lateral metacarpal region, just proximal to the site of the digit amputation. The soft-tissue swelling was again surgically excised, and the cat was treated with griseofulvin^a (50 mg/kg body weight, per os [PO], q 24 hours) for 42 days. The soft-tissue swelling recurred over a 6-month period in the same left-lateral metacarpal region. The affected tissue was again surgically excised and submitted for histopathological examination, which revealed a dermal nodular mycotic granuloma. Postoperatively, the cat was treated empirically with fluconazole^b (5 mg/kg body weight, PO, q 24 hours) for 56 days. Four months later, the soft-tissue swelling rapidly redeveloped over the same lateral metacarpal region.

On physical examination at the time of referral, the cat was alert, responsive, and afebrile. The only abnormal finding was a 2 ×1-cm, soft mass palpable within the dermal and subcutaneous tissues over the left-lateral metacarpal region. The affected area was normally haired, and there was no evidence of ulceration. The owner indicated that there had not been any signs of systemic illness during the course of the recurrent disease process.

Radiography of the left carpal and metacarpal region revealed a soft-tissue density over the left-lateral metacarpal region without any evidence of bone involvement. The results of a complete blood count (CBC), serum biochemical profile, and urinalysis were within reference ranges, and enzyme-linked immunosorbant assays (ELISA) for feline leukemia virus (FeLV) antigen and feline immunodeficiency virus (FIV) antibody were negative.

The soft-tissue mass was again surgically excised, and the area around the mass was debrided, sparing the tendons and bone in the region. Half of the excised tissue was submitted for macerated tissue culture for aerobic and anaerobic bacteria and fungi, and the other half of the tissue was submitted for histopathological examination. The surgical site was not sutured closed, to allow for gradual closure by second-intention healing. The surgical site was covered with a wet povidone-iodine solution dressing, which was changed once daily for 5 days.

Bacterial culture results were negative, and fungal culture revealed the presence of the organism Paecilomyces lilacinus.^c Histopathological examination showed a dermal nodular mycotic granuloma. Further examination using the periodic acid-Schiff (PAS) stain, revealed the presence of numerous PAS-positive, septate pseudohyphae, and round to oval (occasionally budding) yeast forms measuring 5 to 8 μm in diameter [Figure 1], consistent with a Paecilomyces species.

Treatment with itraconazole^d (10 mg/kg body weight, PO, q 24 hours) was initiated 6 days postoperatively after obtaining the results of the fungal culture. Reexamination of the surgical site 7 days postoperatively showed evidence of a healthy granulation bed and reepithelialization. At 14 and 42 days of itraconazole therapy, a serum biochemical profile was submitted to monitor for any evidence of potential hepatotoxicity. Results were within reference ranges on both occasions. The surgical wound had reepithelialized within 14 days, and hair regrowth was covering the area after 42 days. Treatment with itraconazole was continued for a total of 60 days, and during this time there were no observable adverse side effects.

The cat was reexamined 4 months after discontinuation of the itraconazole therapy, because a nodular lesion developed on the left upper lip, which was first noticed 1 month previously. At that time, the cat had a cough that resolved spontaneously in 10 days and was no longer present at the time of reevaluation. On physical examination, the cat was alert, responsive, and afebrile. The only abnormal finding was a nonulcerated, 6 mm in diameter, cutaneous mass on the left upper lip. It was considered a possibility that this lesion may have developed as a result of the direct transfer of the Paecilomyces organism from the licking and grooming over the previously affected left metacarpus. Other than the history of coughing, there had not been any other signs of systemic illness during the past 4 months. The results of a CBC, serum biochemical profile, and chest radiographs were within reference ranges. The left upper lip soft-tissue mass was removed by performing a full-thickness resection, followed by a cosmetic closure of the remaining healthy lip tissue using an absorbable suture material. Half of the excised tissue was submitted for macerated tissue culture for aerobic and anaerobic bacteria and fungi, and the other half of the tissue was submitted for histopathological examination. Bacterial culture results were negative, and fungal culture again revealed the presence of the organism Paecilomyces lilacinus.^c Histopathological examination showed a dermal nodular mycotic granuloma with the presence of numerous PAS-positive, septate pseudohyphae, and round to oval (occasionally budding) yeast forms consistent with a Paecilomyces species. Treatment with itraconazole^d (10 mg/kg body weight, PO, q 24 hours) was reinstituted 5 days postoperatively after obtaining the results of the fungal culture. Reexamination of the surgical site 14 days postoperatively showed evidence of normal healing.

Treatment with itraconazole was continued for the next 2 months, at which time a nonulcerated, 1 cm in diameter, cutaneous mass was noticed over the left-lateral metacarpal region. The results of a serum biochemical profile were within reference ranges, and the soft-tissue mass was again surgically excised, with the site being sutured closed. The excised tissue was submitted for histopathological examination and revealed a dermal, nodular, mycotic granuloma with the presence of numerous PAS-positive, septate pseudohyphae and round to oval (occasionally budding) yeast, consistent with a Paecilomyces species. The treatment with itraconazole was continued; however, the dosage was increased (20 mg/kg body weight, PO, q 24 hours). Reexamination of the surgical site 14 days postoperatively showed evidence of normal healing, and the skin sutures were removed.

Treatment with itraconazole (20 mg/kg body weight, PO, q 24 hours) was continued for the next 2 months, at which time an ulcerated, 1 cm in diameter, cutaneous mass was noticed over the left-lateral metacarpal region. The results of a serum biochemical profile were within reference ranges, and the soft-tissue mass was again surgically excised, with the site being sutured closed. Half of the excised tissue was submitted for macerated tissue culture for aerobic and anaerobic bacteria and fungi, and the other half of the tissue was submitted for histopathological examination. Bacterial and fungal culture results were negative. Histopathological examination showed an ulcerative, granulating, lymphonodular to lymphocytic dermatitis and cellulitis. Special stains failed to reveal the presence of any infectious organisms. It was suggested that this could represent a reaction to some of the previously buried absorbable suture material. The itraconazole was continued (20 mg/kg body weight, PO, q 24 hours). Reexamination of the surgical site 14 days postoperatively showed evidence of normal healing, and the skin sutures were removed. The cat was kept on itraconazole for 1 more month, at which time the drug was discontinued. On physical examination, the surgical site was completely healed, and the results of a serum biochemical profile were within reference ranges. In addition, there had not been any observable side effects regarding the use of itraconazole during the entire treatment time period. At the time of this writing, there had not been a recurrence of the soft-tissue swellings for the past 3 years, and the cat has remained clinically healthy.

Discussion

This case presents a challenging example of a chronic and recurrent, nodular skin disease in a cat. The differential diagnosis for such a presentation should initially include neoplastic diseases and infectious diseases. Many infectious skin diseases need to be considered and will vary in frequency and occurrence depending on geographic location. However, some of the more important infectious diseases are bacterial infections (aerobic and anaerobic bacteria including actinomycosis, nocardiosis, and mycobacteria) and fungal infections (including sporotrichosis, cryptococcosis, coccidioidomycosis, blastomycosis, histoplasmosis, pythiosis, and hyalohyphomycosis). The early recognition of the presence of a progressively enlarging nodular skin lesion is critical, and such nodules should be completely excised whenever possible. This diagnostic and potential treatment modality alone may be curative in many cases of neoplastic disease and some deep fungal infections. Once a neoplastic process has been excluded and the histopathological examination indicates the presence of a granulomatous to pyogranulomatous reaction, the biopsy sections should be reexamined with special stains for bacteria (including acid-fast bacteria) and fungi. In addition, a portion of the excised nodule should be submitted to a microbiology laboratory for macerated tissue culture to include isolation techniques for aerobic and anaerobic bacteria, as well as fungi.

Paecilomyces spp. are considered ubiquitous soil saprophytic fungi, which have also been isolated from sheep wool,¹ the fur of dogs,² and Ixodes ricinus ticks.³ Paecilomyces spp. have the potential of being pathogenic organisms under certain conditions. In humans, disease caused by this organism is most frequently observed as a postoperative nosocomial infection, with or without the concurrent use of prosthetic implants, or in association with immunosuppression.^4–8 Paecilomycosis is considered a rare cutaneous or systemic fungal disease, which has also been reported in the dog,^9–16 cat,¹⁷ horse,¹⁰ goat,¹⁸ rhesus monkey,¹⁹ crocodile,²⁰ tortoise,²¹ armadillo,²² and green sea turtle.²³

As in previously published reports of paecilomycosis in the dog and cat,^9–17 there was no evidence of immunosuppression or association with surgery or use of prosthetic implants in this case. In naturally occurring disease, the opportunistic organism has been assumed to gain access to the body via direct inoculation into subcutaneous or submucosal tissues from the environment, with the soil serving as the potential reservoir for infection. Dissemination from the primary site of inoculation to various tissues (e.g., peripheral, sublumbar, mediastinal, and hilar lymph nodes, liver, spleen, kidney, myocardium, lungs, and retina) is common. In this case, there was no known history of an injury or wound over the left-lateral digit prior to the development of the soft-tissue swelling. However, it is quite possible that the owners were simply unaware of such an injury in an indoor/outdoor cat. The recent isolation of Paecilomyces spp. from Ixodes ricinus ticks suggests that this parasite may also serve as a vector and could be a possible source of infection.³ All previous reports of paecilomycosis in dogs and cats have developed into disseminated or systemic forms of the disease. However, paecilomycosis localized to the skin has been reported in humans,⁶ as observed in this cat. The single prior case report in a cat also began as a solitary soft-tissue swelling over a digit on the left front paw.¹⁷ However, 2 months after the initial surgical excision, the cat presented for dissemination of the disease. The cat was nonresponsive to a second surgical debridement and postoperative treatment with ketoconazole and was subsequently euthanized due to progression of the disease.

Paecilomyces lilacinus has been shown to be resistant to griseofulvin, amphotericin B, and 5-fluorocytosine but sensitive to the imidazoles.⁵ Itraconazole was chosen as the postoperative drug because of its successful use in the treatment of paecilomycosis in humans.⁵⁶²⁴²⁵ Surgical excision and postoperative treatment with griseofulvin on one occasion and fluconazole on a subsequent occasion had been unsuccessful in resolving the recurrent nature of the disease in this cat. It has also been reported that many Paecilomyces spp. have been shown to be resistant to fluconazole on in vitro susceptibility testing.²⁶ Ketoconazole was not chosen as a potential imidazole for the treatment of this patient, as this drug can be hepatotoxic in cats, and the one previously reported case of paecilomycosis in the cat was nonresponsive to ketoconazole. Also, the recent limited use of itraconazole in cats indicates that this drug is better tolerated than ketoconazole, in that it appears to be less hepatotoxic, with only the side effects of anorexia and vomiting reported.²⁷²⁸ Therefore, when cats are treated with itraconazole, they should be closely observed for any evidence of side effects and monitored periodically for evidence of hepatotoxicity.

Previous attempts to treat paecilomycosis in the dog and cat have been unsuccessful.^9–17 Multiple surgical excisions of the affected soft tissues, debridement of the surrounding area, and postoperative treatment with itraconazole (10 to 20 mg/kg body weight, PO, q 24 hours) proved to be an effective treatment in this cat. It is difficult to state which of these treatments effected the ultimate cure in this case, as it may have been due to the numerous surgical excisions and debridements, the use of the itraconazole, or a combination of both of these treatments. For this reason, it is hard to make a specific recommendation regarding treatment. As previously stated, the early recognition of the presence of a progressively enlarging nodular skin lesion is critical, and such nodules should be completely excised whenever possible. When considering the use of an adjunct antifungal treatment agent for such infections, one may need to consider that the initial duration of therapy should be at least 4 months. To the author’s knowledge, this is the first case report of the successful treatment of cutaneous paecilomycosis in a mammalian species other than humans.