Scand J Infect Dis 25: 543-545, 1993

CASE REPORT

Ketoconazole Treatment of a Family with Zoonotic Sporotrochosis

SHEHLA H. NAQVI', PAUL BECHERER' and SUHASINI GUDIPATI' From the 'Section of infectious Diseases, Department of Pediatrics, Brookdate Hospital Medical Center, Brooklyn, New York and the 'Division of Infectious Diseases, Department of Internal Medicine, St. Louis University, St. Louis, Missouri, USA

All 3 members of a family developed lymphocutaneous and cutaneous sporotrichosis after exposure to an infected cat. The lesions resembled acute bacterial lymphadenitis and lymphan- gitis and responded within 2 weeks to ketoconazole treatment with complete healing and no recurrence over the next 6 months. Immunologically normal children and adults with lym- phocutaneous or cutaneous sporotrichosis may respond well to ketoconazole therapy.

S . H . Nuqvi, MD, Brookdale Hospital Medical Center, Rm. 801, Linden Blvd. at Brookdale Plaza, Brooklyn, NY 11212, USA

INTRODUCTION

Sporotrichosis is a chronic granulomatous infection caused by Sporothrix schenckii, a dimorphic fungus found in soil in temperate and tropical areas of high humidity. The infection affects both animals and humans and generally remains limited to skin, sub- cutaneous tissue and lymphatics. Infection occurs after a break in the skin, e.g. with a contaminated thorn, splinter or rock; often as an occupational hazard of farmers, miners, gardeners and florists. Rare cases of human to human (1) and animal to human (2) transmissions have been described. However, most familial clusters are caused by exposure to the same environmental soursce (3).

We report a cluster of sporotrichosis in all 3 members of a family exposed to a cat with an injured foot pad and multiple draining skin lesion for over a month. The cat had been diagnosed by a veterinarian as having sporotrichosis.

CASE REPORTS A Y-year-old girl from a small town in southern Illinois was bitten on the terminal phalanx of the right niiddlc finger by the sick cat. Over the next 2 weeks the distal phalanx became red and swollen. Purulent drainage occurred by pressure on the nail. She was treated with cephalexin for 10 days but the lesion did not resolve. A month after the bite, her oral temperature was 37.4"C and she had a partly avulsed nail

Table I . Susceptibility to antifungal agents ofthe Sporothrix schenckii by macro broth dilution using an inoculum of I X 10,000 blastoconidialml

Drug MIC ( P d m MLC (pg/ml)

24 h 48 h 24 h 48 ti

Aniphotericin B Ketoconazole Fluconazole Ttraconazole

0.2Y 0.58 0.2 0.4

> 80 -

50.018 0.15

0.58 >18.47 1.6 12.8

0.6 10 - -

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544 S. H . Naqvi et al. Scand J Infect Dis 25

Fig. 1. Lesions 3 weeks after ini- tial presentation, before antifun- gal therapy.

on the right middle finger. There was minimal swelling and erythema; no drainage was seen. Pain-free, full flexion of the finger was possible. A 2 x 2 cm erythematous, warm, non-tender and non-fluctuant lymph nodc was noted along the brachial artery.

The rest of the physical examination was unremarkable. Resolving cat scratch disease was diagnosed and no antibiotics were prescribed. Three weeks later the lymph node had diminished (1 X 1.5 cm), was non-erythematous and firmer, but the finger had still not healed.

Three weeks after the injury the girl’s 11-year-old brother developed pustules on both hands and painful lumps on both arms. There were no systemic complaints. He was seen a week after the onset of his symptoms, with an oral temperature of 37.4”C; there were pustules on the right index finger and left thumb. These pustules were 1 cm in diameter on erythematous bases and were filled with yellow purulent material (Fig. 1). A red lymphangitic streak was apparent on the ventral aspect of the right foream. There were multiple healing screatch marks on his hands.

Two weeks after the onset of the boy’s illness his mother complained of generalized malaise and low-grade fever. She had had a non-healing, 1 cm painless shallow ulcer with minimal serous drainage on her left knee for 1 month. In addition, during the past 2 weeks she had noted erythematous papules on her nose and right proximal lateral thigh. No lymphangitis or lymphadenopathy was seen. The mother had held the cat in her lap but did not remember any scratches or bites.

Gram stain and bacterial culture of material collected from the boy and mother’s skin lesions failed to reveal any organisms. Drainage from the skin lesions of the mother and son yielded Sporothrix schenckii on fungal culture. In vitro, the minimum inhibitory concentration of antifungal agents after 24 h of incubation are shown in Table I. The isolate was resistant to fluconazole. The infected cat was destroyed after the mother became symptomatic. Because of the mother’s multifocal cutaneous lesions, especially those on her face, hematogenous dissemination was suspected but blood cultures for fungus showed no growth. She was treated with 400 mg ketoconazole daily for 6 weeks. The 11-year-old boy was treated with 200 mg ketoconazole, while the 9-year-old girl received 100 mg per day. After 2 weeks, marked improvement was noted in all 3. The girl’s finger lesion recurred when the ketoconazole was discontinued after 2 weeks, but healed completely with an additional 6-week therapy. Six months after the completion of therapy, there have been no relapses.

DISCUSSION

Although sporotrichosis occasionally involves lungs, blood, meninges, and joints, more than 80% of cases of sporotrichosis in the United States of America are of the lymphocutaneous form. This localized form involves skin and draining lymphatics. The initial skin lesion is a non-tender papule or pustule at the site of inoculation which enlarges and ulcerates.

The regional lymph nodes become involved in an ascending pattern, with development of nodules which ulcerate or undergo abscess formation. This linear pattern of spread is not seen when the face is involved, due to the distribution of lymphatic drainage. The ulcers may heal with scarring. The lymphatics become cord-like as the disease progresses. Patients generally remain free of systemic signs and symptoms. However, without proper treatment the infection can persist for years.

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Scand J Infect Dis 25 Ketoconazole in sporotrochosis 545

A fixed cutaneous form of sporotrichosis also occurs in which a chronic ulcer develops without lymph node involvement. This presentation is seen more often in hot climates, probably in association with high immunity (4).

These children had lymphocutaneous sporotrichosis without evidence of simultaneous bacterial infection. Contrary to the description in the literature, one had acute lymphangitis and both had acutely inflamed and tender lymphadenitis. The acute inflammation subsided over 3 4 weeks, though not in response to antibiotic therapy.

Sporotrichosis should be considered in the differential diagnosis of pustules and acute lymphadenitis. This acute presentation resembles cat scratch disease, staphylococcal skin infection, tularemia and anthrax. The diagnosis should be confirmed by fungal culture which generally takes more than 1 week. Histopathology of a biopsy specimen or smear is often unrevealing because of the small number of fungal elements in the tissues (4). Antibody to S. schenckii becomes detectable 4 weeks after onset of infection. A history of possible exposure to cat scratch disease, tularemia, tuberculosis. atypical mycobacteria (e.g. Mycobacterium marinum), primary syphilis, herpes simplex virus, leishmania and anthrax should be ob- tained and appropriate tests performed as indicated.

Sporotrichosis rarely resolves spontaneously (4) and may lead to scarring and mutilation. Oral iodides have been the mainstay of therapy for the lymphocutaneous and cutaneous forms for the last 70 years. However, the response may take many months and relapses are common (5 ) . The efficacy of oral iodides is limited in extracutaneous sporotrichosis (6) and side effects are common (5) . Amphotericin B is efficacious in extracutaneous sporotrichiosis and a favorable outcome has been noted with itraconazole (7); fluconazole has not proved beneficial (8).

Ketoconazole inhibits S. schenckii in vitro (9). It has been effective in the treatment of lymphocutaneous sporotrichosis in adults ( 2 ) . Prolonged therapy with ketoconazole along with surgical debridement are reported to have cured 6/10 patients with deep S. schenckii infecton (10). However, ketoconazole has not been successful in the therapy of sporotricho- sis in individuals infected with human immunodeficiency virus (9).

Our experience indicates that in otherwise healthy children and adults, lymphocutaneous and cutaneous sporotrichosis may respond adequately to ketoconazole therapy.

ACKNOWLEDGEMENT Antifungal susceptibility testing was performed by Michael G. Rinaldi, Ph.D. V.A. Mocology Refer- encc Laboratory, Audie L. Murphy Memorial Veterans’ Hospital, San Antonio, Texas.

REFERENCES 1. Xue-Zhu Jin, Huo-Da Hang. Hiruma M, Yamamoto I. Mother-and-child cases of sporotrichosis

2. Samorodin CS. Sina B. Ketokonazole-treated sporotrichosis in a veterinarian. Cutis 33: 487488,

3. Yoshitaka Yamada, et al. A familial occurrence of Sporotrichosis. J Dermatol 17: 255-259, 1990. 4. Bclknap BS. Sporotrichosis. Dermatol Clin 7: 193-202, 1989. 5. Urabe H and Honbo S. Sporotrichosis. Int J Dermatol25: 255-257, 1986. 6. Friedman SJ, Doyle JA. Extracutaneous sporotrichosis. Int J Dermatol 1983; 22: 171-176. 7. Restrepo A, Robledo J , Gomez I. et al. Itraconazole therapy in lymphangitic and cutaneous

8. Winn RE. Sporotrichosis. Infect Dis Clin North Am 2: 899-911, 1988. 9. Calhoun DL, Waskin H, White MP, et al. Treatment of systemic sporotrichosis with ketoconazole.

Rev Infect Dis 13: 47-51, 19Y1. 10. Shadomy S, White SC, Yu HP, Dismukes WE. The NIAID Mycoses Study Group. Treatment of

systemic mycoses with ketoconazole in vitro susceptibilities of clinical isolates of systemic and pathogenic fungi to ketoconazole. J Infect Dis 152: 1249-1256, 1985.

infection. Mycoses 33: 33-36, 1990.

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sporotrichosis. Arch Dermatol 122: 413417, 1986.

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