INTRODUCTION
Sporotrichosis, acquired by inoculation of the dimorphic fungus Sporothrix spp., is the main subcutaneous mycosis in Brazil. Clinically the typical presentation of sporotrichosis is a reddish lesion that appear near to the inoculation site and which tends to progress to erithematous nodules and ulcers with new similar lesions ascending in lymphatic vessels1,2.
Although ascending nodular lymphangitis is the commonest clinical presentation, the disease can manifest with distinct characteristics, which turns the diagnosis more difficult. Here we describe three atypical cases of sporotrichosis diagnosed in 2010 and 2011 at the University Hospital of Universidade Federal do Rio Grande (HU-FURG), Rio Grande, State of Rio Grande do Sul, Brazil. This study was approved by the Ethic Committee of the Institution (CEPAS-FURG 175/2011).
CASE REPORT
A male patient, 51-years-old, fisherman, was admitted with a complaint of pain and swelling on his right knee that had started one year before, since the occurrence of a local bruising trauma in a wood boat, but without skin penetration. Serology for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) were negative, but the patient suffered of diabetes, and was drinker and smoker in the past (two years and seven years before, respectively). Previous ultrasonography suggested septic arthritis, and patient was treated with surgical procedure and cefalotin without clinical resolution. In that occasion, laboratorial exams of the sinovial fluid showed no microorganism growth in bacterial and fungal culture. Clinical examination revealed pain with high intensity, difficulty walking, and flogistic signs on the affected joint (Figure 1). Ultrasound imaging showed an extensive suffusion with a viscous fluid and suprapatellar bursa distension. Suspecting of a septic arthritis reactivation an arthrocentesis was done. Cytology of synovial fluid revealed a count of 800 erythrocytes/mm3 and of 3,200 leukocytes/mm3 with 53% of lymphocytes and 47% of segmented neutrophil. Biochemical examination was not done due to the synovial thickening. At the microbiology lab, none bacterial growth was detected, but a great number of fungal colonies grew in Sabouraud agar. The characteristics of the colonies in Sabouraud agar at 25ºC and in Brain-Heart Infusion (BHI) agar at 37°C associated with its micromorphology allowed us to confirm the diagnosis of a Sporotrhix sp. articular infection. The patient was scheduled to treat his arthritis with itraconazole (200mg twice a day – BID) for one year. After six months of treatment, it was observed a significant improvement of his articular symptoms.
FIGURE 1 Black row showing swelling in the right knee of the patient with monoarthritis by Sporothrix sp. (Case 1).
Case 2
Male patient, 43 years-old, soldier, was admitted in the HU-FURG ambulatory showing ulcerated, papular and nodular lesions, with violaceous borders in both arms and distributed by the lymphatic pathway. The patient reported the practice of exercises crawling and rolling on the ground with vegetation. This professional practice occurred one week before the appearance of the first lesion on his left arm, which progressed following the lymphatic vessels and also appeared in the right arm. About ten lesions (1-3cm) in each arm were observed in the clinical examination, some with intact skin and others ulcerated with exudates (Figure 2). Regional lymphadenomegaly was also detected. According to the patient, the lesions had an evolution about three or four months without clinical resolution with previous antibacterial treatment. Clinical suspicion of bilateral lymphocutaneous sporotrichosis was done and patient was submitted to a skin biopsy. Histopathological evaluation showed mixed multifocal inflammatory process without any identifiable microorganism or malignity evidence. At mycology lab a great number of fungal colonies grew in Agar Sabouraud and were phenotipically identified as Sporothrix sp., confirming the initial clinical suspicion. Itraconazole was prescribed at 200mg/day for three months. Patient did not return to the evaluation of his clinical evolution.
Case 3
Female patient, 28 years-old, student, referred the appearance of a skin lesion about 15 days after a scratch of a cat with sporotrichosis. Physical examination revealed a 3cm pustular lesion with violaceous borders in the trauma region in her forearm, associated with a more recent 2cm lesion, nodular, erythematous and firm, following the lymphatic vessel. After eight days of the initial skin lesions at forearm, multiple painfull reddish nodules appeared in her both legs (Figure 3), featuring a typical case of erythema nodosum. Histopathology of the biopsy of the ulcerated lesion in forearm showed an inflammatory process with great number of multinucleated foreign body giant cells, and it cultive resulted in Sporothrix sp. growth, confirming the diagnosis of sporotrichosis. The immunological condition of the patient was investigated due to the probability of a fungal dissemination, but immunossupression was ruled out. Nonsteroidal antiinflammatory drugs resolved the eryhtema nodosum in a few weeks, and treatment with itraconazole 200mg/day for six months resulted in a clinical cure.
DISCUSSION
The clinical presentation of sporotrichosis described here, as septic arthritis, bilateral lymphatic lesions and hypersensitivity reaction to Sporothrix sp. infection, are rare with scarce reports in the literature.
Cases of osteoarticular sporotrichosis are frequently characterized as chronic monoarthritis, mainly affecting the knee3-5, as described in our patient 1. Although less common, the involvement of elbows, ankles and wrists can also occur5. The two hypotheses about the source of infection in our case 1 are: fungal inoculation by the initial traumatic lesion occurred in a wooden boat as reported by the patient; or articular contamination during the surgical procedures performed to diagnostic evidences6. In fact, a case of sporotrichosis after the onset of infusion drug for the treatment of arthritis has been described in the literature as a result of non-sterile handling of the lesion6. However, the non-regression of the lesion in our patient, even with the use of antibiotics, anti-inflammatory and surgical procedures, suggests the fungal involvement since the beginning, probably acquired by the trauma reported. Similar monoarthritis case as the only evidence of sporotrichosis without the presence of a skin lesion has been previously reported in the literature4, and authors also did not found a specific source of infection.
Arthritis due to Sporothrix sp. is often associated with immunosuppressed patients, especially those with acquired immunodeficiency syndrome (AIDS). In our case 1, patient despite being negative for HIV, had a history of chronic alcoholism and diabetes, factors also cited as a predisposition to the onset of extra-cutaneous sporotrichosis1,5. Differential diagnosis of monoarthritis include other infectious causes, and noninfectious, as hypothyroidism, amyloidosis, multiple myeloma, paraneoplastic syndrome, among others4.
According to the majority of reported cases of bilateral sporotrichosis, this presentation may occur by self-inoculation, multiple inoculations or re-infection7. The crawling exercise in soil with decaying vegetation, performed by our patient 2 prior to the onset of the bilateral lymphocutaneous lesions, suggests that there has been simultaneous multiple inoculations of the fungus into the dermis through microtrauma by plant material, since this is the natural habitat of Sporothrix sp., similar to that reported by other authors7,8. The bilateral presentation of sporotrichosis is described as atypical and rare, although it have already been reported in children by zoonotic transmission9 or by trauma with plants in adults7,8. Differential diagnosis of this clinical presentation of sporotrichosis include cutaneous tuberculosis, atypical mycobacterial infection, prurigo, nocardiosis, and cutaneous leishmaniasis in its sporothrichosis-like clinical form1,7.
Hypersensitivity reactions to infection by Sporothrix sp. as occurred in our case 3 may present themselves as different clinical manifestations. Case of a reactional episode of polyarthritis was described in an immunocompetent patient with lymphocutaneous sporotrichosis that showed the involvement of ankles and elbows10. Three cases of erythema multiforme (EM) associated with Sporothrix sp. infection had been described in adult patients that developed a skin rash after 7-30 of the primary infectious cutaneous11. And, similar to our case 3, hypersensitivity fungal triggering erythema nodosum (EN) associated with sporotrichosis was first described in 2002, in three patients in Rio de Janeiro12. According to our case reported, the lesions of EN described in the literature may arise after 7 to 40 days of the initial injury12.
Although few cases of hypersensitivity to Sporothrix sp. infection are reported in the literature, as in our case 3, all of them10-12 occurred through zoonotic transmission from sick cats. A hypothesis that could explain this association is the constant and intense stimulation of the immune system of patients when they are in touch with cats with sporotrichosis11,12. This could occur due to the fact that this species tends to have a great amount of fungal propagules in their lesions, triggering an intense exposure of humans to fungus antigens and even culminating with subclinical infection and reinfection, causing hypersensitivity2,11,12.
We must remark that the gold standard for diagnosis of sporotrichosis in any clinical presentation is mycological culture for fungi isolation and identification1, as occurred in the three cases reported here. The fungal culture is required because the sporotrichosis lesions in humans tend to have few yeast cells which provide a difficulty in observe them either in cytological or histopathological examination1,4.
However, the difficulty of diagnosis of atypical sporotrichosis described in this study are also frequently reported in the literature, either in bilateral case of sporotrichosis7,9 or in the osteoarticular involvement3,4, especially given the numerous other causes more commonly associated with, which are raised as the main diagnostic hypotheses2,4. In this scenario, it is common the occurrence of a late diagnosis, and, especially in relation to osteoarticular involvement, the delay in identifying the etiology of the injury can lead to unfavorable prognosis and may result in loss of function of the affected area4,5, similar to that observed in our patient that showed signs of muscle atrophy by disuse as a consequence of chronic difficulty in walking.
In conclusion, the three reported cases of atypical sporotrichosis described here emphasize the disease importance in the region, and highlight the need to include it as differential diagnosis even in cases of non-classic lesions of the disease. Thus, fungal culture will be conducted leading in the diagnosis confirmation and favoring the prognosis through an early and correct treatment.
