Explore the vast range of titles available.

Chromoblastomycosis (CBM) is a neglected human disease, caused by different species of pigmented dematiaceous fungi that cause subcutaneous infections. This disease has been considered an occupational disease, occurring among people working in the field of agriculture, particularly in low-income countries. In 1914, the first case of CBM was described in Brazil, and although efforts have been made, few scientific and technological advances have been made in this area. In the field of fungi and host cell relationship, a very reduced number of antigens were characterized, but available data suggest that ectoantigens bind to the cell membrane of host cells and modulate the phagocytic, immunological, and microbicidal responses of immune cells. Furthermore, antigens cleave extracellular proteins in tissues, allowing fungi to spread. On the contrary, if phagocytic cells are able to present antigens in MHC molecules to T lymphocytes in the presence of costimulation and IL-12, a Th1 immune response will develop and a relative control of the disease will be observed. Despite knowledge of the resistance and susceptibility in CBM, up to now, no effective vaccines have been developed. In the field of chemotherapy, most patients are treated with conventional antifungal drugs, such as itraconazole and terbinafine, but these drugs exhibit limitations, considering that not all patients heal cutaneous lesions. Few advances in treatment have been made so far, but one of the most promising ones is based on the use of immunomodulators, such as imiquimod. Data about a standard treatment are missing in the medical literature; part of it is caused by the existence of a diversity of etiologic agents and clinical forms. The present review summarizes the advances made in the field of CBM related to the diversity of pathogenic species, fungi and host cell relationship, antigens, innate and acquired immunity, clinical forms of CBM, chemotherapy, and diagnosis.

Dermatophytosis is a cutaneous mycosis caused by a plethora of keratinophilic fungi, but Trichophyton rubrum is the most common etiological agent. Despite its high prevalence worldwide, little is known about the host defense mechanisms in this infection, particularly the in situ immune response. Using an immunohistochemistry approach, we investigated the density of CD1a+, factor XIIIa+ and CD68+ cells in the skin of dermatophytosis patients. Langerhans cells (CD1a+ cells) were significantly decreased in the epidermis of patients, both in affected and unaffected areas. In the dermis, however, no differences in the density of macrophages (CD68+ cells) and dermal dendrocytes (factor XIIIa+ cells) were observed. These results suggest that the decreased number of Langerhans cells may be a risk factor for development of dermatophytosis.

Dermatophytes are known as a common cause of superficial mycosis, but atypical presentations in immunosuppressed patients make the diagnosis more challenging. Here, we report a case of a 39-year-old patient, a renal transplant recipient from a living donor, who presented with atypical cutaneous lesions of lower extremities caused by Arthroderma gypseum (Nannizzia gypsea), four months after receiving a renal transplant. It is important to highlight the importance of the early detection of fungal infections in immunosuppressed patients. Clinicians should have a high degree of suspicion for the early detection and treatment of the cases.

The pathogenesis of chromoblastomycosis (CBM) is associated with Th2 and/or T regulatory immune responses, while resistance is associated with a Th1 response. However, even in the presence of IFN-γ, fungi persist in the lesions, and the reason for this persistence is unknown. To clarify the factors associated with pathogenesis, this study aimed to determine the polarization of the cellular immune response and the densities of cells that express markers of exhaustion in the skin of CBM patients. In the skin of patients with CBM, a moderate inflammatory infiltrate was observed, characterized primarily by the occurrence of histiocytes. Analysis of fungal density allowed us to divide patients into groups that exhibited low and high fungal densities; however, the intensity of the inflammatory response was not related to mycotic loads. Furthermore, patients with CBM exhibited a significant increase in the number of CD4+ and CD8+ cells associated with a high density of IL-10-, IL-17-, and IFN-γ-producing cells, indicating the presence of a chronic and mixed cellular immune response, which was also independent of fungal load. A significant increase in the number of PD-1+ and PD-L1+ cells was observed, which may be associated with the maintenance of the fungus in the skin and the progression of the disease.

Chromoblastomycosis (CBM) is a neglected human disease, caused by different species of pigmented dematiaceous fungi that cause granulomatous and suppurative dermatosis. This infection is difficult to treat and there are limited therapeutic options, including terbinafine, itraconazole, and tioconazole. Classic treatment is administered for a long period of time, but some patients do not respond properly, and therefore, such therapeutic approaches possess low cure rates. Therefore, it is vital to develop new strategies for the treatment of CBM. In this regard, it has been observed that the association of immunomodulatory molecules such as glucan with therapy carried out with antifungal drugs improves cutaneous lesions in comparison to treatment with antifungal drugs alone, suggesting that drug association may be an interesting and significant approach to incorporate into CBM therapy. Thus, the aim of this work was to associate classical antifungal therapy with the adjuvants imiquimod and acitretin. In the present case, we reported a patient with extensive CBM caused by Fonsaecae pedrosoi, that affected an extensive area of the right leg, that was left without treatment for 11 years. He was treated with a classical combination of itraconazole and terbinafine via the oral route plus topical imiquimod and oral acitretin, as an adjuvant therapy. After five months of treatment, a significant regression of verrucous plaques was observed, suggesting that the use of these adjuvants combined with the classical antifungal drugs, intraconazole plus terbinafine, can reduce treatment time and rapidly improve the patient’s quality of life. This result confirms that the use of coadjuvant drugs may be effective in the treatment of this infectious disease.

Chromoblastomycosis (CMB) is a cutaneous fungal infection caused by dematiaceous fungi. According to the World Health Organization CMB has been elected as a tropical disease, and it is prevalent in tropical and subtropical regions. The lower extremities are the most affected areas, and the lesions progress with erythema, papules, nodules, verrucose plates and/or ulcerations. So far, few works have demonstrated neoplastic transformation in chronic CMB lesions, and it may be a consequence of prolonged inflammatory response. In the present case report, we described a neoplastic transformation from CMB lesion of a 55- year-old man, presenting lesions only in the left leg for 35 years. After treatment, a verrucous white plate with thick and irregular borders emerged in the ankle, which was identified as a sarcomatoid squamous cell carcinoma. The present case report highlights the importance of an early diagnosis and treatment.

Sporotrichosis is a fungal infection endemic in Latin America and has been attributed to the thermodimorphic fungus of the genus Sporothrix. Transmission to humans occurs during a traumatic injury with soil or organic material; additionally, lesions caused by infected cats play an important role in the epidemiology of the disease. The classic treatment of sporotrichosis is performed with itraconazole or potassium iodide; second-line medications, such as amphotericin B and terbinafine, can alternatively be used in cases of first-line drug failure. In the present study, a patient with lymphocutaneous sporotrichosis in the right upper limb exhibited intolerance to itraconazole and potassium iodide, additionally during the period of use; these drugs did not control skin lesions. In this patient, amphotericin B deoxycholate and its liposomal version were used in this patient; and complete recovery of the lesions was observed.

There are few studies on the role of innate immune response in dermatophytosis. An investigation was conducted to define the involvement of Toll-Like Receptors (TLRs) 2 and 4 in localized (LD) and disseminated (DD) dermatophytosis due to T. rubrum. Fifteen newly diagnosed patients, eight patients with LD and seven with DD, defined by involvement of at least three body segments were used in this study. Controls comprised twenty skin samples from healthy individuals undergoing plastic surgery. TLR2 and TLR4 were quantified in skin lesions by immunohistochemistry. A reduced expression of TLR4 in the lower and upper epidermis of both LD and DD patients was found compared to controls; TLR2 expression was preserved in the upper and lower epidermis of all three groups. As TLR4 signaling induces the production of inflammatory cytokines and neutrophils recruitment, its reduced expression likely contributed to the lack of resolution of the infection and the consequent chronic nature of the dermatophytosis. As TLR2 expression acts to limit the inflammatory process and preserves the epidermal structure, its preserved expression may also contribute to the persistent infection and limited inflammation that are characteristic of dermatophytic infections. A literatura sobre o papel da resposta imune inata em dermatofitose é escassa. Este estudo se propôs a investigar a participação dos receptores do tipo Toll 2 e 4 (TLRs) 2 e 4 em pacientes com dermatofitose localizada (LD) e disseminada (DD, definida como lesões em pelo menos três segmentos corpóreos distintos), causadas por Trichophyton rubrum. Foram analisados cortes histológicos de 15 pacientes recém-diagnosticados, oito com LD e sete com DD. O grupo controle foi composto por 20 amostras de pele de indivíduos saudáveis submetidos a cirurgia plástica. TLR-2 e TLR-4 foram quantificados em lesões cutâneas por imunohistoquímica. Encontramos uma expressão reduzida de TLR-4 na epiderme superior e inferior nos dois grupos, LD e DD, quando comparados com o grupo controle; a expressão de TLR-2 foi preservada na epiderme superior e inferior de todos os três grupos. Como a sinalização por TLR-4 induz produção de citocinas inflamatórias e recrutamento de neutrófilos, a menor expressão desta molécula provavelmente contribui para a não resolução da infecção e conseqüente natureza persistente da dermatofitose. Como a sinalização via TLR-2 tem sido descrita como fator de regulação do processo inflamatório e de preservação da estrutura epidérmica, a sua expressão inalterada nas lesões dos pacientes com DD e DL pode contribuir também para a persistência da infecção e do reduzido processo inflamatório que são característicos das infecções por dermatófitos.

Chromoblastomycosis is a subcutaneous mycosis that remains a therapeutic challenge, with no standard treatment and high rates of relapse. On the basis of our recent discoveries in mouse models, we tested the efficacy of topial applications of imiquimod to treat patients afflicted with this chronic fungal infection. We report results of treatment for the first 4 recipients of topical imiquimod, all of whom displayed a marked improvement of their lesions, both with and without concurrent oral antifungal therapy.

According to the spread of 'Cryptococcus' sp., fungal infections can be classified as primary or secondary. In primary cutaneous cryptococcosis, the fungi are restricted to the skin of the patients, without systemic involvement. The incidence of primary cutaneous cryptococcosis is high in patients with immunosuppression, and this type of infection is rarely observed in patients who are immunocompetent. In the present case report, a patient who is immunocompetent and has systemic comorbidity reported that, after skin trauma, ulcerovegetative lesions appeared in the right upper arm; the etiologic agent was identified as 'Cryptococcus gatti', serotype B. The cutaneous lesions healed completely after 5 months of fluconazole treatment.