British lounial of Denmilobgn (1992) 126, Supplement i 9 . 51-55.
Treatment of cutaneous sporotrichosis with terbinafine P.R.HULL AND H.F.VISMER* Departnu-nt ol Dcrimilologii. Uuivcrsili/ of Pretoria. Preloriu. South Africa ' Resi-iirih Instiliite for I'.m'iwninental Diseases of the Mediiiil Hfseairh Coiiiuil. Pretoria. South Africa
Summary
Terbinafine. an ailylamine antifungal agent, has been shown to have excellent in-vltro activity against dermatophytes. Several other fungi of importance also show in-vitro sensitivity. Because terbinafine is fungicidal rather than fungistatic in action, its efficacy in treating such fungal infections requires evaluation. I'ive patients with cutaneous sporotrichosis were treated with 2 50 mg of terbinafine twice daily. All of the patients were cured. Overall, the clinical response was rapid. In three patients, negative culture was achieved within 8 weeks; In the other two. negative culture was obtained at 11 and 32 weeks, respectively. Terbinafine was well tolerated, although one patient developed erectile dysfunction while receiving treatment. This was completely resolved on stopping the treatment. The treatment of sporotrichosis is also reviewed in this article.
The clinical evaluation of terbinafine. a new oral antifungal agent of the allylamine class, has mainly focused on its use in a variety of dermatophyte Infections. This was because of its demonstrated excellent in-vifro activity against dermatophytes.'- Its effective in-vitro activity has been shown against several fungi of medical importance, including Sporotlirix schcnckii. Bhislonnici's (k'rnmtitidis, llislophisma capsuhitwn. Crtiptococ(iis neofornnms, and Asperyilhis. I-onscami. PhiaJophora
and \'hi(hircUii species/"' Also of importance is the fungicidal action of terbinaline against many of these tungi species, and it is of clinical relevance to establish its value across as wide a spectrum of fungal infections as possible. This is a report of several case studies as part of an open trial to assess the efficacy and tolerability of terbinafine in the treatment of cutaneous sporotrichosis.
Methods Fiitients
Five patients with culture: proven cutaneous sporotrichosis were recruited into the study. All patients were over 18 years of age, not pregnant or breast-feeding, and not known to have liver, renal or haematoiogical disease. Patients were seen at monthly intervals, at which time they were clinically assessed; cultures were repeated and the following special investigations monitored: complete Corrcspondoiiff: Ur I'.R.Hull. Division ol" Dermatulofiiy. [Jnivcrsity of Saskatchewan. S;isk;iU)on S7N 0X0. Saskatchewan. Canada.
blood count: potassium: creatinine: uric acid: serum glutamic-oxaloacetic transaminase (SCOT): serum glutamate pyruvate transaminase (StJPT): gamma glutamyltransferase; alkaline phosphatase: total bilirubin; lactate dehydrogenase; cholesterol: triglycerides: urinary protein and glucose. The treatment with terbinafine at a dose of 2 SO mg twice daily was continued for up to 12 weeks or, if the patient was responding within that period, until clinical and mycological cure was obtained.
Results Patients' details are given in Table 1. Case report I
A 75-year-old man with type II diabetes mellitus presented with a lymphatic form of sporotrichosis. The initial lesion was on the Index finger and had followed a minor gardening injury 13 weeks previously (Fig. 1). There WHS subsequent lymphatic spread to the back of the hand, forearm and arm. The primary lesion was crusted and granulomatous while the lesions on the hand were nodular. Numerous crusted, ulcerated and nodular lesions were present on both the flexor and extensor aspects of the forearm. The nodular lesions on the arm were deeply placed with little involvement ofthe overlying skin. His previous treatment had included several courses of antibiotics and his concurrent medication included metformin and chlorpropamide. Sporolhrix schcnckii was cultured from the primary lesion. After 4 weeks of treatment with terbinafine. the deeply placed nodules in the arm were barely palpable. Those
51
52
P.R.HLLL AND H.F.VISMER
on the forearm, although still either crusted or scaling, were flat, as were the lesions on the back of the hand. The primary lesion on the index finger remained crusted, but was less infiltrated and thickened. After 12 weeks, the lesions on the arm and forearm had completely healed. A single lesion on the hand was still palpable and the primary lesion still showed scaling (Fig. 2). At 20 weeks, it was still possible to culture S. schenckii from the index finger, which showed only minimal scaling. Cultures were negative after 32 weeks, but treatment was continued for a further 5 weeks. There has been no recurrence of disease.
The skin overlying these nodules was normal. Sporothrix schenckii was cultured from the lesion on the hand. Within 1 month of treatment with terbinaiine. the lymphatic nodules were no longer palpable and the primary lesion had become less Infiltrated: there was no crusting or scaling. Repeat cultures were negative. Treatment was continued for a further month and. at 8 weeks, there remained only scarring at the site of the primary lesion. Case report 3
A 44-year-old man. who had a 10-week history of a primary lesion on the medial aspett of his right hand, developed a series of deep lymphatic nodules, starting from below the right elbow and extending up the arm.
A 40-ycar-old man presented with a single granulomatous plague over the left shin. This plaque had been present for approximately 40 weeks and had been treated with a variety of steroid and antibiotic creams. Lymphatic nodules were not present. Sporolhrix schenckii was isolated from the lesion. After 4 weeks of treatment, the lesion had improved
Kigurc 1. Case report 1: Index- linger with cmstcii granulnnuilous pririiiiry icsion.
Hgurc 2. Case rcporl I: Afttir 2H weeks of trcatmoiU. tht-rc was only rcsiduiil minimal scaling.
Case report 2
TKRBINAFINH TRKATMENT OF SPOROTRICHOSIS
5?
;urf J. Ca.se reporl 4; Biy tiie with primary lesion on Ihe medial pt-'ci with regional spread.
Kigiire 4. Ci\sc report 4: Alter 1 2 weeks ol treatment, only skin disi'oloration marked the sites of the iesions.
slightly. It was still crusted and scaling, but the inflamination had decreased. After 8 weeks, a considerable improvement was observed, and only minimal scaling remained. Cultures were negative. Treatment was continued fora further month, following which only residual postinilammiitory hyperpigmentation marked the site.
lymphatic nodules had decreased in si/e and felt softer. After 8 weeks of treatment, these nodules were no longer palpable. The primary lesion also showed improvement while the papules on the toe had flattened. At 1 2 weeks, cultures were negative, and only skin discoloration marked the sites of the lesions (Fig. 4). The treatment was continued tor a further month.
Case report 4
A 42-year-old man had a verrucous granuloma on the medial aspect of his left big toe (Fig. 3) as the primary lesion. This lesion had heen present for 11 weeks. In addition, he had a number of papules on the dorsal aspect of bis big toe as well as several lymphatic nodules on the dorsal aspect of his foot extending to his ankle. His concomitant treatment included atenolol. nifedipine and , aspirin. After 4 weeks of treatment with terbinafine. the
Case report S
The inoculation site in a 20-year-old man was under the nail of his left middle finger. This primary lesion had been present for 8 weeks and had resulted in a small granuloma under the distal part of the nail with secondary onycholysis. Many deep lymphatic nodules were present, starting above the wrist and extending to the mid-upper arm. The skin overlying these nodules was normal.
54
P.R.HULL AND H.F.VISMHR
Following 1 month of treatment witb terbinafine. the lymphatic nodules were smaller and fewer. Cultures were also negative. After 8 weeks, the initial subungual lesion appeared to be healed and only two lymphatic nodules were present. After 12 weeks, the onycholysis had healed and only a single dermal nodule was palpable. This nodule persisted unchanged despite 19 weeks of treatment. At that stage, it was considered that this nodule was unrelated to the sporotrichosis and treatment was stopped. Nine months later, this dermal nodule was excised, and the histological diagnosis of an angiolipoma was made. There has not heen a recurrence oi the sporotrichosis.
Adverse reactions
Terhinafine was well tolerated by all five patients. One patient (case report 1) was convinced that there was an increased rate of hair growth on the affected arm. but this was not apparent to either the investigator or other observers. In addition, he alleged that his nails were growing more rapidly. Another patient (case report 3) complained that, during treatment, it took him longer to attain a penile erection which, furthermore, was of poor quality and consequently had adverse effects on his sexual performance. This began after 1 week of treatment and returned to normal on completion of the treatment. Orgasm and ejaculation were normal. No other adverse events were recorded, and the laboratory parameters measured remained within normal limits in all patients.
Discussion Sporotrichosis presents most frequently as either a single localized granulomatous skin lesion, sometimes referred to as the 'fixed cutaneous form", or as proximal lymphatic spread in addition to the primary cutaneous granuloma at the inoculation site. This may manifest with deeply placed dermal nodules arising at intervals along the course of the draining lymphatics without overlying skin involvement, or there may be extension from such lymphatic nodules into the overlying skin, producing secondary granulomatous plaques or ulcers. Occasionally, sporotrichosis may primarily involve bone, joints, or the lungs. Disseminated sporotrichosis is rare, but will probably he seen more frequently in patients with acquired immunodeficiency syndrome (AIDS) and in the immune-suppressed."' From the beginning of this century, potassium iodide
has been the treatment of choice for cutaneous sporotrichosis.'' This treatment is both effective and inexpensive, an important factor in those underdeveloped countries where sporotrichosis is endemic. Despite the relative antiquity of this treatment, its mechanism of action is not well understood.' Although serious side-effects are rare, previous hypersensitivity reactions occasionally preclude its use in sporotrichosis. Less serious adverse reactions occur more frequently and include gastrointestinal upsets, rhinorrhoea and cold-like symptoms, headache, lacrlmation. swelling of the salivary glands, fever, acneforme rashes and iododermas. Potassium iodide is not as effective for the arthritic and disseminated forms of sporotrichosis: in these cases, amphotericin B is currently the recommended therapy. Ketoconazole has been used in cutaneous and disseminated sporotrichosis. but the results have been disappointing.^ Itraconazole. however, is very effective in cutaneous sporotrichosis and. in our own experience. 60 patients with cutaneous sporotrichosis have been successfully treated (unpublished results). Similar success has also been reported by others.'* Furthermore, itraconazole has been used sticcessfully in cases of disseminated sporotrichosis"* and. although clinical experience is limited, itraconazole is recommended in cases where amphotericin B treatment fails or is contraindicated. Fluconazole is also effective in cutaneotis sporotrichosis. We have successfully treated two patients, and MonteroCiei and colleagues have also reported on its efficacy." Terbinafine has been shown to have good in-vitro activity against S. schemkii (MIC range. 0-l-()-4 g/ml)^ yet. despite this, it was not efficacious in the treatment of experimental murine systemic sporotrichosis.'Our study is the first reported use of terbinafine in cutaneous sporotrichosis. All five patients treated were cured. The clinical response was rapid in all cases. In two patients, culture was negative after 4 weeks of treatment: in a further patient, this occurred after H weeks and. in the remaining two patients, hy 1 2 and 32 weeks (case report 11. respectively. It has been our experience that, with both potassium iodide and itraconazole. while scaling and crusting are present. S, scheiickii may be cultured with relative ease. The scaling may be minimal and apparently not worth the bother of scraping, as in case report 1. In this patient, despite his other lesions being healed, there was persistent minimal scaling over his original lesion which regularly yielded ftmgus. In the past, we have seen relapses if medication was prematurely stopped: this has led us to continue treatment for 1 month beyond conversion to negative culture, as was the policy
TERBINAFINE TREATMENT OF SPOROTRICHOSIS
Tiiblf I. Ilemoi^riiphic patient data and resuil.s ol treatment
Patient
1
Age (yearsi ('ii'iider Duration nf disease (weeks) Type
1
J
4
55
S
7J
44
4*J
42
20
Male
.Male
.Male
Male
Male
13
10
40
II
8
[,ymph
Lymph
I.OC
[,ymph
Lymph
Duration of treatment (weeks)
i7
S
12
14
19
Time lo negative eultiire iweeks)
M
4
S
12
4
Lymph = lyniphatie; Loc = localized.
followed in these patients. However, all previous treatments of sporotrichosis have heen fungistatic. so it is possible that this extension of treatment heyond myeologieal cure is unnecessary with terbinaline. hut this has yet to be established. Terhinatine was well tolerated by all these patients, except for one patient who experienced difficulty in achieving an erection during treatment. This returned to normal when the treatment was concluded. To our knowledge, this is the first report of erectile dysfunction with terhinaiine. In conclusion, our results indicate that terbinafine is efficacious in the treatment of hoth the fixed eutaneous and lymphatic forms of sporotrichosis.
References 1 Cloiidard M, IJtiffarcl Y. Ferrari H. Regli 1*. Spectre d'actiun in vitro d'un nouvel anlilonfiique derive de \a nartiHne: la terbinatine (SF S(i-J27l. l'at}\oi Hiai l9S(r S4: 680-3. 2 Pelriinyi (1, Meingassner |G. Mieth H. Antifungal aetivity of the allylamine derivative terhinafine in vitro. Antimiiroh Agents Chemother 1987; 51: I UiS-8. J Shadomy S, Kspinel-lngroft'A. Obhart K|. In-vitro studies with SF
8li- 327. a new orally aetivr allyinmine derivative. / Med Vet 1985:23: 125-J2. 4 Clayton YM. In-vitro activity of terbinaline. Clin Exp Di-rnuitol 1989; 14: 101-3. 5 Shaw ]C. Levinson VV, Montanaro A. Sporotrichosis in the acquired iniriKinodeticiency syndrome. / Am Acad Denmitol 1989; 21: 1145-7. fi IX' Beurniann L. Ramond I.. Abces sousculanes multiples d'origine mycosique. Ami Dermatol Siiphiligr 1903: 4: (J78. 7 Kex ]ll. Bennett |F. Administration of potassium iodide to normal volunteers docs not increase killing o\'Sporothrix seiieiukii by their neutrophils or nionocyies. / Med Vet .Mtjcoi 1990; 28: iSS-9. H I'luss jL. Opal SM. I'ulmonary sporotrichosis; Review of treatmeni and oulcome. jVWii(lie 198b; 65: 143-53. 9 Reslrepo A. Kohlcdo |. (.Sonien 1 et al. Itraeona/ole iherapy in lymphatic and cutaneous sporotrichosis. Anh Deriniito! 1986: 122:413-7. 10 Baker JH. Goodpasture HC. Kuhns HR, Riniiidi MCi. Fungemia caused by an amphoteriein B-resistant isolate of Sporothrix schenikii. Successful treatmeni witb itracoiiazole. Arch I'uthol Lab Med 1989; 11: 1279-81. 11 Montero-(lei h". Syevens DA. Siles L. Melendez M. I'lueonazole therapy in culaneousaud lympharigitic sporotrichosis. (Abstract). Thirtieth liHersdeme Conferenrc on Antimicrobial Aifents and Cheinot/icr((/»/. Atlanta. Georgia. 1990; 182. 12 Kan VL, Bennett \li. Hfheaeies of four antifungal agents in experimental murine sporotrichosis. Antimicroh AiienlH Chemother 19S8; 32: 1619-2 J.
Treatment of cutaneous sporotrichosis with terbinafine P.R.HULL AND H.F.VISMER* Departnu-nt ol Dcrimilologii. Uuivcrsili/ of Pretoria. Preloriu. South Africa ' Resi-iirih Instiliite for I'.m'iwninental Diseases of the Mediiiil Hfseairh Coiiiuil. Pretoria. South Africa
Summary
Terbinafine. an ailylamine antifungal agent, has been shown to have excellent in-vltro activity against dermatophytes. Several other fungi of importance also show in-vitro sensitivity. Because terbinafine is fungicidal rather than fungistatic in action, its efficacy in treating such fungal infections requires evaluation. I'ive patients with cutaneous sporotrichosis were treated with 2 50 mg of terbinafine twice daily. All of the patients were cured. Overall, the clinical response was rapid. In three patients, negative culture was achieved within 8 weeks; In the other two. negative culture was obtained at 11 and 32 weeks, respectively. Terbinafine was well tolerated, although one patient developed erectile dysfunction while receiving treatment. This was completely resolved on stopping the treatment. The treatment of sporotrichosis is also reviewed in this article.
The clinical evaluation of terbinafine. a new oral antifungal agent of the allylamine class, has mainly focused on its use in a variety of dermatophyte Infections. This was because of its demonstrated excellent in-vifro activity against dermatophytes.'- Its effective in-vitro activity has been shown against several fungi of medical importance, including Sporotlirix schcnckii. Bhislonnici's (k'rnmtitidis, llislophisma capsuhitwn. Crtiptococ(iis neofornnms, and Asperyilhis. I-onscami. PhiaJophora
and \'hi(hircUii species/"' Also of importance is the fungicidal action of terbinaline against many of these tungi species, and it is of clinical relevance to establish its value across as wide a spectrum of fungal infections as possible. This is a report of several case studies as part of an open trial to assess the efficacy and tolerability of terbinafine in the treatment of cutaneous sporotrichosis.
Methods Fiitients
Five patients with culture: proven cutaneous sporotrichosis were recruited into the study. All patients were over 18 years of age, not pregnant or breast-feeding, and not known to have liver, renal or haematoiogical disease. Patients were seen at monthly intervals, at which time they were clinically assessed; cultures were repeated and the following special investigations monitored: complete Corrcspondoiiff: Ur I'.R.Hull. Division ol" Dermatulofiiy. [Jnivcrsity of Saskatchewan. S;isk;iU)on S7N 0X0. Saskatchewan. Canada.
blood count: potassium: creatinine: uric acid: serum glutamic-oxaloacetic transaminase (SCOT): serum glutamate pyruvate transaminase (StJPT): gamma glutamyltransferase; alkaline phosphatase: total bilirubin; lactate dehydrogenase; cholesterol: triglycerides: urinary protein and glucose. The treatment with terbinafine at a dose of 2 SO mg twice daily was continued for up to 12 weeks or, if the patient was responding within that period, until clinical and mycological cure was obtained.
Results Patients' details are given in Table 1. Case report I
A 75-year-old man with type II diabetes mellitus presented with a lymphatic form of sporotrichosis. The initial lesion was on the Index finger and had followed a minor gardening injury 13 weeks previously (Fig. 1). There WHS subsequent lymphatic spread to the back of the hand, forearm and arm. The primary lesion was crusted and granulomatous while the lesions on the hand were nodular. Numerous crusted, ulcerated and nodular lesions were present on both the flexor and extensor aspects of the forearm. The nodular lesions on the arm were deeply placed with little involvement ofthe overlying skin. His previous treatment had included several courses of antibiotics and his concurrent medication included metformin and chlorpropamide. Sporolhrix schcnckii was cultured from the primary lesion. After 4 weeks of treatment with terbinafine. the deeply placed nodules in the arm were barely palpable. Those
51
52
P.R.HLLL AND H.F.VISMER
on the forearm, although still either crusted or scaling, were flat, as were the lesions on the back of the hand. The primary lesion on the index finger remained crusted, but was less infiltrated and thickened. After 12 weeks, the lesions on the arm and forearm had completely healed. A single lesion on the hand was still palpable and the primary lesion still showed scaling (Fig. 2). At 20 weeks, it was still possible to culture S. schenckii from the index finger, which showed only minimal scaling. Cultures were negative after 32 weeks, but treatment was continued for a further 5 weeks. There has been no recurrence of disease.
The skin overlying these nodules was normal. Sporothrix schenckii was cultured from the lesion on the hand. Within 1 month of treatment with terbinaiine. the lymphatic nodules were no longer palpable and the primary lesion had become less Infiltrated: there was no crusting or scaling. Repeat cultures were negative. Treatment was continued for a further month and. at 8 weeks, there remained only scarring at the site of the primary lesion. Case report 3
A 44-year-old man. who had a 10-week history of a primary lesion on the medial aspett of his right hand, developed a series of deep lymphatic nodules, starting from below the right elbow and extending up the arm.
A 40-ycar-old man presented with a single granulomatous plague over the left shin. This plaque had been present for approximately 40 weeks and had been treated with a variety of steroid and antibiotic creams. Lymphatic nodules were not present. Sporolhrix schenckii was isolated from the lesion. After 4 weeks of treatment, the lesion had improved
Kigurc 1. Case report 1: Index- linger with cmstcii granulnnuilous pririiiiry icsion.
Hgurc 2. Case rcporl I: Afttir 2H weeks of trcatmoiU. tht-rc was only rcsiduiil minimal scaling.
Case report 2
TKRBINAFINH TRKATMENT OF SPOROTRICHOSIS
5?
;urf J. Ca.se reporl 4; Biy tiie with primary lesion on Ihe medial pt-'ci with regional spread.
Kigiire 4. Ci\sc report 4: Alter 1 2 weeks ol treatment, only skin disi'oloration marked the sites of the iesions.
slightly. It was still crusted and scaling, but the inflamination had decreased. After 8 weeks, a considerable improvement was observed, and only minimal scaling remained. Cultures were negative. Treatment was continued fora further month, following which only residual postinilammiitory hyperpigmentation marked the site.
lymphatic nodules had decreased in si/e and felt softer. After 8 weeks of treatment, these nodules were no longer palpable. The primary lesion also showed improvement while the papules on the toe had flattened. At 1 2 weeks, cultures were negative, and only skin discoloration marked the sites of the lesions (Fig. 4). The treatment was continued tor a further month.
Case report 4
A 42-year-old man had a verrucous granuloma on the medial aspect of his left big toe (Fig. 3) as the primary lesion. This lesion had heen present for 11 weeks. In addition, he had a number of papules on the dorsal aspect of bis big toe as well as several lymphatic nodules on the dorsal aspect of his foot extending to his ankle. His concomitant treatment included atenolol. nifedipine and , aspirin. After 4 weeks of treatment with terbinafine. the
Case report S
The inoculation site in a 20-year-old man was under the nail of his left middle finger. This primary lesion had been present for 8 weeks and had resulted in a small granuloma under the distal part of the nail with secondary onycholysis. Many deep lymphatic nodules were present, starting above the wrist and extending to the mid-upper arm. The skin overlying these nodules was normal.
54
P.R.HULL AND H.F.VISMHR
Following 1 month of treatment witb terbinafine. the lymphatic nodules were smaller and fewer. Cultures were also negative. After 8 weeks, the initial subungual lesion appeared to be healed and only two lymphatic nodules were present. After 12 weeks, the onycholysis had healed and only a single dermal nodule was palpable. This nodule persisted unchanged despite 19 weeks of treatment. At that stage, it was considered that this nodule was unrelated to the sporotrichosis and treatment was stopped. Nine months later, this dermal nodule was excised, and the histological diagnosis of an angiolipoma was made. There has not heen a recurrence oi the sporotrichosis.
Adverse reactions
Terhinafine was well tolerated by all five patients. One patient (case report 1) was convinced that there was an increased rate of hair growth on the affected arm. but this was not apparent to either the investigator or other observers. In addition, he alleged that his nails were growing more rapidly. Another patient (case report 3) complained that, during treatment, it took him longer to attain a penile erection which, furthermore, was of poor quality and consequently had adverse effects on his sexual performance. This began after 1 week of treatment and returned to normal on completion of the treatment. Orgasm and ejaculation were normal. No other adverse events were recorded, and the laboratory parameters measured remained within normal limits in all patients.
Discussion Sporotrichosis presents most frequently as either a single localized granulomatous skin lesion, sometimes referred to as the 'fixed cutaneous form", or as proximal lymphatic spread in addition to the primary cutaneous granuloma at the inoculation site. This may manifest with deeply placed dermal nodules arising at intervals along the course of the draining lymphatics without overlying skin involvement, or there may be extension from such lymphatic nodules into the overlying skin, producing secondary granulomatous plaques or ulcers. Occasionally, sporotrichosis may primarily involve bone, joints, or the lungs. Disseminated sporotrichosis is rare, but will probably he seen more frequently in patients with acquired immunodeficiency syndrome (AIDS) and in the immune-suppressed."' From the beginning of this century, potassium iodide
has been the treatment of choice for cutaneous sporotrichosis.'' This treatment is both effective and inexpensive, an important factor in those underdeveloped countries where sporotrichosis is endemic. Despite the relative antiquity of this treatment, its mechanism of action is not well understood.' Although serious side-effects are rare, previous hypersensitivity reactions occasionally preclude its use in sporotrichosis. Less serious adverse reactions occur more frequently and include gastrointestinal upsets, rhinorrhoea and cold-like symptoms, headache, lacrlmation. swelling of the salivary glands, fever, acneforme rashes and iododermas. Potassium iodide is not as effective for the arthritic and disseminated forms of sporotrichosis: in these cases, amphotericin B is currently the recommended therapy. Ketoconazole has been used in cutaneous and disseminated sporotrichosis. but the results have been disappointing.^ Itraconazole. however, is very effective in cutaneous sporotrichosis and. in our own experience. 60 patients with cutaneous sporotrichosis have been successfully treated (unpublished results). Similar success has also been reported by others.'* Furthermore, itraconazole has been used sticcessfully in cases of disseminated sporotrichosis"* and. although clinical experience is limited, itraconazole is recommended in cases where amphotericin B treatment fails or is contraindicated. Fluconazole is also effective in cutaneotis sporotrichosis. We have successfully treated two patients, and MonteroCiei and colleagues have also reported on its efficacy." Terbinafine has been shown to have good in-vitro activity against S. schemkii (MIC range. 0-l-()-4 g/ml)^ yet. despite this, it was not efficacious in the treatment of experimental murine systemic sporotrichosis.'Our study is the first reported use of terbinafine in cutaneous sporotrichosis. All five patients treated were cured. The clinical response was rapid in all cases. In two patients, culture was negative after 4 weeks of treatment: in a further patient, this occurred after H weeks and. in the remaining two patients, hy 1 2 and 32 weeks (case report 11. respectively. It has been our experience that, with both potassium iodide and itraconazole. while scaling and crusting are present. S, scheiickii may be cultured with relative ease. The scaling may be minimal and apparently not worth the bother of scraping, as in case report 1. In this patient, despite his other lesions being healed, there was persistent minimal scaling over his original lesion which regularly yielded ftmgus. In the past, we have seen relapses if medication was prematurely stopped: this has led us to continue treatment for 1 month beyond conversion to negative culture, as was the policy
TERBINAFINE TREATMENT OF SPOROTRICHOSIS
Tiiblf I. Ilemoi^riiphic patient data and resuil.s ol treatment
Patient
1
Age (yearsi ('ii'iider Duration nf disease (weeks) Type
1
J
4
55
S
7J
44
4*J
42
20
Male
.Male
.Male
Male
Male
13
10
40
II
8
[,ymph
Lymph
I.OC
[,ymph
Lymph
Duration of treatment (weeks)
i7
S
12
14
19
Time lo negative eultiire iweeks)
M
4
S
12
4
Lymph = lyniphatie; Loc = localized.
followed in these patients. However, all previous treatments of sporotrichosis have heen fungistatic. so it is possible that this extension of treatment heyond myeologieal cure is unnecessary with terbinaline. hut this has yet to be established. Terhinatine was well tolerated by all these patients, except for one patient who experienced difficulty in achieving an erection during treatment. This returned to normal when the treatment was concluded. To our knowledge, this is the first report of erectile dysfunction with terhinaiine. In conclusion, our results indicate that terbinafine is efficacious in the treatment of hoth the fixed eutaneous and lymphatic forms of sporotrichosis.
References 1 Cloiidard M, IJtiffarcl Y. Ferrari H. Regli 1*. Spectre d'actiun in vitro d'un nouvel anlilonfiique derive de \a nartiHne: la terbinatine (SF S(i-J27l. l'at}\oi Hiai l9S(r S4: 680-3. 2 Pelriinyi (1, Meingassner |G. Mieth H. Antifungal aetivity of the allylamine derivative terhinafine in vitro. Antimiiroh Agents Chemother 1987; 51: I UiS-8. J Shadomy S, Kspinel-lngroft'A. Obhart K|. In-vitro studies with SF
8li- 327. a new orally aetivr allyinmine derivative. / Med Vet 1985:23: 125-J2. 4 Clayton YM. In-vitro activity of terbinaline. Clin Exp Di-rnuitol 1989; 14: 101-3. 5 Shaw ]C. Levinson VV, Montanaro A. Sporotrichosis in the acquired iniriKinodeticiency syndrome. / Am Acad Denmitol 1989; 21: 1145-7. fi IX' Beurniann L. Ramond I.. Abces sousculanes multiples d'origine mycosique. Ami Dermatol Siiphiligr 1903: 4: (J78. 7 Kex ]ll. Bennett |F. Administration of potassium iodide to normal volunteers docs not increase killing o\'Sporothrix seiieiukii by their neutrophils or nionocyies. / Med Vet .Mtjcoi 1990; 28: iSS-9. H I'luss jL. Opal SM. I'ulmonary sporotrichosis; Review of treatmeni and oulcome. jVWii(lie 198b; 65: 143-53. 9 Reslrepo A. Kohlcdo |. (.Sonien 1 et al. Itraeona/ole iherapy in lymphatic and cutaneous sporotrichosis. Anh Deriniito! 1986: 122:413-7. 10 Baker JH. Goodpasture HC. Kuhns HR, Riniiidi MCi. Fungemia caused by an amphoteriein B-resistant isolate of Sporothrix schenikii. Successful treatmeni witb itracoiiazole. Arch I'uthol Lab Med 1989; 11: 1279-81. 11 Montero-(lei h". Syevens DA. Siles L. Melendez M. I'lueonazole therapy in culaneousaud lympharigitic sporotrichosis. (Abstract). Thirtieth liHersdeme Conferenrc on Antimicrobial Aifents and Cheinot/icr((/»/. Atlanta. Georgia. 1990; 182. 12 Kan VL, Bennett \li. Hfheaeies of four antifungal agents in experimental murine sporotrichosis. Antimicroh AiienlH Chemother 19S8; 32: 1619-2 J.
