Cryosurgery as an adjuvant treatment in sporotrichosis : a three-case report

Sporotrichosis is a disease caused by the dimorphic fungus Sporothrix spp. The number of cases has been increasing, notedly in the city of Rio de Janeiro, Brazil, where it is now considered a public health problem. The recommended treatment employs antifungals, however in case of persistence of the lesions or when there is contraindication, cryosurgery is an option, since the fungus is sensitive to extreme temperatures. The authors report 3 cases of sporotrichosis treated for longer than 6 months with itraconazole and/or potassium iodide, all yielding incomplete response and where cryosurgery was successfully used as an adjuvant treatment.


INTRODUCTION
Sporotrichosis is a disease caused by the inoculation of the dimorphic fungus Sporothrix spp. on the skin, usually as a result of handling contaminated soil and vegetables. 1,2.2 The main tests for diagnosis are the mycological (mainly culture), the histologic and molecular biology. 1 Different drugs have been used in the treatment of sporotrichosis.The choice of the medicament depends on the clinical form, patient's morbidity, side effects and drug interactions.The objective of the present study is to describe 3 cases of sporotrichosis, confirmed by mycological test and treated with itraconazole and / or saturated solution of potassium iodide (KI) for longer than 6 months, in which cryosurgery with liquid nitrogen (LN) was used as an adjuvant treatment.

CASE REPORT
Case 1: A 53-year old male patient residing in the Brazilian city of Rio de Janeiro presented a nodular lesion with 1cm in diameter on the dorsum of the left hand, and a rounded erythematous plaque on the left elbow.After 10.5 months of treatment with 200 mg/day itraconazole, the lesions had little regression (Figures 1A and 1B), with cryosurgery having been indicated.The device used was the Cry-Ac ® (Brymill, Ellington, USA), with the intermittent spray technique, tip A, central solid pattern, with a 0.5 cm margin, two cycles of freezing and thawing observing a 4-minute interval between them (Figure 1C).After 2 weeks, the lesion showed healing (Figure 1D).The patient completed 13 months of use of itraconazole and moved to another city, with the follow up having been lost.
Case 2: A 15-year old male patient, student, residing in the Brazilian city of Rio de Janeiro, area of Belford Roxo described the reappearance of nodules with crusts on the third, fourth and fifth fingers and dorsum of the left hand over cicatricial lesions of sporotrichosis (Figure 2A) one month after the completion of treatment with KI, followed by 200 mg/day itraconazole for six months.Itraconazole was reintroduced and 3 sessions of cryosurgery with LN carried out observing intervals of one month, using the Cry-Ac ® deice, intermittent spray technique, nozzle B, central solid pattern with 2 cycles of freezing and thawing, with 4-minute intervals between the cycles (Figure 2B).Also, the use of itraconazole was recommended for an additional month, making for a total of 10 months.Two months after the procedure, the patient presented scars (Figure 2C).The patient remains free of active lesions of the disease during 3 years of follow-up.
Case 3: Cryosurgery was indicated for a 59-year old female patient, maid by occupation, residing in the Brazilian city of Rio de Janeiro.The indication ensued the use of itraconazole for one year and seven months (100 mg/day for 7 months, and 200 mg/day during the remaining of the period) for the treatment of a resistant ulcerated lesion, without signs of healing (Figure 3A).One session of cryosurgery was carried out with the Nitrospray ® device (Criotécnica, Campinas (SP, Brazil), contact probe with 2 cm in diameter, two cycles of freezing and thawing observing a 4-minute interval between the cycles, after total thawing (Figure 3B).The lesion receded (Figure 4A) and after 3 months showed a scar (Figure 4B).

DISCUSSION
Sporotrichosis is a subcutaneous mycosis with universal distribution and increasing number of cases. 1 Since 1997, the State of Rio de Janeiro is going through an zoonotic epidemic / endemic with more than 5,000 human cases having been di-    Itraconazole is the treatment of choice for sporotrichosis, however other substances can also be used: saturated KI solution, terbinafine, fluconazole, ketoconazole and amphotericin B. 1.3 The average duration of treatment is 3 months, and the criterion for cure is clinical, corresponding to the healing of the lesions and the disappearance of erythema and crusts. 3Sporothrix spp. is sensitive to temperature, both to excessive heat and cold.As a result, cryosurgery with LN can be used as an adjuvant to traditional treatment.
Cryosurgery is effective in the treatment of various benign, pre-malignant and malignant cutaneous diseases.5][6] This form of treatment is based on the selective destruction of cells or tissues through freezing, which depends on the minimum temperature reached during cryogenic injury.In order to obtain a severe injury, the freezing process is maintained for a longer period, reaching -20ºC to -30ºC, resulting in necrosis..6 The following techniques can be used in sporotrichosis: intermittent spraying with central solid pattern and tips A or B (Cry-Ac ® ) and tips 8, 9 and 10 (Nitrospray ® ); confined spraying using open cones for deepening the freezing process without causing lateral damage to the round lesions; and the solid contact technique, which uses previously frozen solid tips (probes) of varying diameters, in flat areas and ulcerated lesions.The lateral margin ranges from 3mm to 4mm, and the freezing time varies depending on the size of the lesion.Two cycles of freezing and thawing (in the minimum duration ratio of 1:3) are recommended, with a 4-minute interval between the cycles, and sessions every 30 days or with healed lesions.
Ferreira et al. described 9 patients with lymphocutaneous and localized sporotrichosis treated with LN (two cycles of 15 seconds and an average of 2.2 sessions at monthly intervals) after having undergone prior treatment with KI, itraconazole (isolated or combined with terbinafine) (Table 1). 7Moraes et al. cited a case of resistance to the use of KI and itraconazole that experienced regression of signs of the disease activity and good development of healing after cryosurgery (Table 1). 4 Bargman also reported 3 cases of the fixed form that experienced cure (Table 1). 8The present article describes 3 patients who had active sporotrichosis lesions for over 6 months after previous treatment with KI and / or itraconazole, experiencing therapeutic success after undergoing cryosurgery (Table 1).
The combination of cryosurgery with itraconazole for the treatment of feline sporotrichosis lends effectiveness and swiftness to the therapy.Souza et al. found clinical cure in 84.6% of cats treated with the combination therapy for an average duration of 32 weeks, decreasing the cost and side effects of antifungals. 9t is worth noting that the accessories used in cryosurgery, such as probes and open tips, must be sterilized in autoclave or ethylene oxide.
Furthermore, the fact that sporotrichosis is a zoonosis with a larger number of cases caused by infected animals, implies that the disease should be diagnosed and treated early with a view to stop the epidemiological chain.

Figure 1 :
Figure 1: A: Erythematous plaque of 1.5 cm in diameter with a central crust, located on the left elbow.B: Presence of lymphatic cord from the dorsum of the left hand up until the lesion in the left elbow.C: Cryosurgery with the device Cry-Ac ® / Brymill -USA, spraying technique, tip A. D: Ulcerated crusted lesion 2 weeks after cryosurgery

Figure 2 :
Figure 2: A: Nodules with crusts on the third, fourth and fifth fingers and dorsum of the left hand, over cicatricial lesions of sporotrichosis.B: Exulcerated lesions and erythematous plaque on left hand 15 days after cryosurgery.C: Cicatricial lesions two months after cryosurgery

Figure 3 :
Figure 3: A: Ulcer with clean and erythematosus background, and 2.5cm in diameter, on the back of the right hand B: Cryosurgery with the device Nitrospray® (Criotécnica, Campinas (SP), Brazil), contact probe, two cycles of freezing and thawing, 4mm margin

Figure 4 :
Figure 4: A: Healing ulcerated lesion with granulation tissue two months after cryosurgery.B: Scar three months after cryosurgery