The case was a female patient, 61 years old, with lesions in the right upper limb that began 8 months before her appointment in the medical service of Hospital das Clinicas, Faculdade de Medicina da Universidade de Sao Paulo, Brazil. She was born in Barros Mendes (Bahia, Brazil), but residing in Sao Paulo city (Sao Paulo State, Brazil) for the last 45 years, working as a teacher. She has three healthy cats that regularly visit vets; according to her report, the cats did not scratch her before the onset of cutaneous lesions. One year before the appearance of skin lesions, she traveled to the countryside of Sao Paulo state (Registro town), and although she had contact with the Atlantic forest, skin injury was not observed. Additionally, between travel and appointment at the Hospital das Clinicas, she had no skin injuries or contact with plants and soil. One month after the appearance of the lesion, she was admitted to the Dermatology Service of the Hospital das Clinicas. The lesions were ulcerated, and the borders showed erythema and were infiltrated; the lesions were also covered with yellowish and hematic crusts. Furthermore, some ascendant subcutaneous nodular lesions were detected that suggest lymphangitis in the right upper limb (Figure 1(a)). Mobile and painless lymphadenopathy was detected in the right axillary area. The patient complained of pain in the lesions, and discrete hyaline exudation was verified, and no other local and systemic symptoms were observed. Skin fragments were collected to identify the etiologic agent of the lesions, as the morphology of the lesions suggested lymphocutaneous sporotrichosis, skin tuberculosis, or leishmaniasis. The histopathological study showed chronic granulomatous dermatitis with focal necrosis and neutrophil exudation of neutrophils (Figures 1(b) and 1(c)).
Fite-Faraco and Grocott staining did not evidence the presence of alcohol-acid-resistant bacilli or fungi, respectively. The immunohistochemistry reaction was not positive for BCG. Bacterioscopy and direct fungi research as well as culture of aerobic and anaerobic bacteria were negative. Skin samples cultured in agar-dextrose Sabouraud medium supplemented with chloramphenicol at 25 C allowed the growth of a whitish membranous culture, with a blackened peripheral halo (Figure 2(a)). Microscopically septate hyaline hyphae present in the apex conidiophores and bouquet-like structures were observed, suggesting a fungus belonging to the genus Sporothrix (Figures 2(b) and 2(c)). At 37 C, a white/yellowish colony with a smooth aspect was observed; additionally, yeasts were visualized at this temperature. Techniques of molecular biology were not used to identify species.
Based on these findings, lymphocutaneous sporotrichosis was diagnosed, and potassium iodide was prescribed at 1 g/mL; it was started with three drops per day and gradually increased as the patient tolerated the metallic taste. After one month of treatment, and using 25 drops of potassium iodide per day, the patient reported lack of appetite, nausea, and vomiting. Potassium iodide was replaced by itraconazole, which was administered orally for 12 days at 100 mg/day; as the patient became tolerant, the dose of this antifungal drug was increased to 200 mg/day. The patient reported constant nausea and emetic events after seven days of treatment; however, levels of alanine and aspartate transaminases, alkaline phosphatase, and gamma-glutamyl transferase were normal. Fifty days after the beginning of itraconazole therapy, the patient reported severe gastrointestinal alterations, and the intravenous antiemetic drug metoclopramide was administered to the patient; constant hydration was recommended. Ten days after this event, no improvement of skin lesions was observed. Due to the side effects of both first-line drugs and the resistance of the patient to take oral medicines, such as terbinafine or fluconazole, she was admitted to the Hospital das Clinicas to initiate a treatment with systemic amphotericin B. Additionally, it is important to observe that all these side effects were associated with the therapy with potassium iodide or itraconazole since the patient had no underlying diseases. Electrolytes, renal, and hepatic biochemical tests as well as electrocardiogram were performed, before beginning treatment. Amphotericin B deoxycholate at 50 mg/day (diluted in 500 mL of sodium chloride 0.9% and glucose 5% solution for 6 hours) was given during three days due to the inaccessibility of the liposomal formulation. At the beginning of treatment, episodes of nausea and vomiting were reported, but antiemetic medicines controlled these side effects. Biochemical tests were performed and revealed an increase of serum potassium and creatinine. Correction of electrolyte disturbance was carried out; and to compensate the biochemical alterations, the treatment was suspended for three days. A second set of treatment was performed with liposomal amphotericin B seven days after the infusion with amphotericin B deoxycholate, and it was administered at 150 mg/day (diluted in 500 mL of sodium chloride 0.9% and glucose 5% solution for 6 hours) during 17 days. Clinical improvement of the lesions was observed during treatment (Figures 3(a) and 3(b)). A timeline containing the lesion appearance, diagnosis (Figure 4(a)), and treatment with iodide potassium, itraconazole (Figure 4(b)), or amphotericin B (Figure 4(c)) summarizes the whole treatment performed in this patient. The treatment with liposomal amphotericin B did not change the levels of blood biochemical parameters.
The patient was infused with a total dose of 2600 mg of liposomal amphotericin B and 150 mg of amphotericin B deoxycholate until complete clinical cure, with re-epithelization of the ulcerated lesion and involution of lymphadenopathy. The follow-up has been performed monthly, and relapses were not recorded.