Arival Cardoso de Brito

HIV and lacaziosis, Brazil.

To the Editor: Jorge Lobo disease (lacaziosis) is a chronic deep mycosis for which prognosis is good in terms of survival but unclear in terms of regression of the lesions (1). No involvement of internal organs or mucous membranes is observed. The causative agent is Lacazia loboi (2), a fungus of uncertain phylogeny, which causes an inflammatory infiltrate accompanied by the formation of a granuloma in which giant cells phagocytose a larger number of fungi (3,4). Pecher and Funchs suggested that patients with lacaziosis have a cellular immunodeficiency (5). The disease is more frequent in men and persons 21–40 years of age. It is found exclusively in Latin America; only 1 case has been diagnosed in Europe, and that was due to accidental contamination with material from a dolphin (4). Trauma and injuries or sites of insect bites facilitate penetration of the fungus. Lesion progression is slow, with new lesions arising by contiguity with other lesions or through the lymphatic route (6,7). Clinically, lacaziosis manifests as keloidal lesions of solid consistency and variable size that contain small scales and crusts (6). The lesions are most frequently located in the auricle and on the upper and lower limbs. Cutaneous dissemination of the disease is observed in a relatively small number of cases. We describe a patient with Jorge Lobo disease. The patient was a 59-year-old man, a storeroom employee, who was seen at the Tropical Medical Center in Belem, Brazil, in April 2004. A papula had developed near his right knee in 1992 after a wood splinter had penetrated the skin. The lesion increased in size, and a histopathologic diagnosis of Jorge Lobo disease was made. The lesion was then surgically removed. Approximately 2 years later, the lesion recurred. The patient then went to a dermatology service and was treated with clofazimine, after which the lesion disappeared. However, the lesion reappeared 1 year later. HIV serologic analysis was performed in 2002, and the results were positive. The patient then began treatment for HIV infection. He is currently being monitored at the specialized referral unit in Belem. He does not have any opportunistic infections and is not taking any antiretroviral drugs. The patient came to the dermatology service of the Tropical Medical Center, where dermatologic and histopathologic examinations were conducted and CD cell counts and HIV viral load were measured. Dermatologic aspects of the lesion included an erythematous-infiltrated, hypertrophic plaque with a verrucous surface ≈4 cm long in the distal third of the medical aspect of the right thigh (Figure). A punch biopsy specimen of brown smooth skin 0.35 cm in diameter in an epidermal disk was fixed in formalin. Microscopy of skin sections containing epidermis showed compact keratinization, parakeratotic foci, and irregular hyperplasia with a pseudoepitheliomatous area. A highly dense, nodular, diffuse inflammatory infiltrate was observed at all levels of the dermis. It consisted of macrophages and numerous multinucleated cells, most of them of the foreign body type. Fibroplasia was also noted. Abundant, round parasitic elements surrounded by a double membrane and containing a basophilic nucleus were found in tissues, as well as other anucleated, intracellular, and free parasites that formed chains of >2 cells (Figure A1). Jorge Lobo disease was diagnosed. Laboratory results showed 146 CD4 cells/μL, 251 CD8 cells/μL, a CD4:CD8 ratio of 0.42, and 60,000 copies of HIV viral RNA/mL. Figure Erythematous-infiltrated, hypertrophic plaque with a verrucous surface ≈4 cm long in the distal third of the medical aspect of the right thigh of the patient. Since a cytotoxic response is observed in Jorge Lobo disease (7), HIV infection may increase the susceptibility to infection with L. loboi. Patients with AIDS show a predisposition to diverse fungal infections that classically affect different organs and systems. An association between Jorge Lobo disease and AIDS has not been reported. However, since Jorge Lobo disease is restricted to specific areas of the world and the number of AIDS cases is increasing, especially in Latin America, a possible correlation between HIV infection and Jorge Lobo disease should be considered because of the associated cellular immunodeficiency. The patient showed no signs of other opportunistic infections classically associated with AIDS, and he was not taking any antiretroviral drugs. His initial infection manifested as cutaneous lesions that occur in Jorge Lobo disease. Despite the cellular immunodeficiency, we did not observe atypical dissemination of the lesions. Further studies should be conducted to evaluate the relationship between the cellular immunosuppression of AIDS and secondary infection with L. loboi. In addition, epidemiologic studies are needed to determine the association of AIDS with Jorge Lobo disease.

CD1a and factor XIIIa immunohistochemistry in leprosy: a possible role of dendritic cells in the pathogenesis of Mycobacterium leprae infection.

Leprosy is a curable chronic granulomatous infectious disease caused by the bacillus Mycobacterium leprae. This organism has a high affinity for skin and peripheral nerve cells. In the evolution of infections, the immune status of patients determines the disease expression. Dendritic cells are antigen-presenting cells that phagocytose particles and microorganisms. In skin, dendritic cells are represented by epidermal Langerhans cells and dermal dendrocytes, which can be identified by expression of CD1a and factor XIIIa (FXIIIa). In the present study, 29 skin samples from patients with tuberculoid (13 biopsies) and lepromatous (16 biopsies) leprosy were analyzed by immunohistochemistry using antibodies to CD1a and FXIIIa. Quantitative analysis of labeling pattern showed a clear predominance of dendritic cells in tuberculoid leprosy. Difference between the number of positive cells of immunohistochemistry for the CD1a and FXIIIa staining observed in this study indicates a role for dendritic cells in the cutaneous response to leprosy. Dendritic cells may be a determinant of the course and clinical expression of the disease.

Revisiting the Clinical and Histopathological Aspects of Patients with Chromoblastomycosis from the Brazilian Amazon Region

BACKGROUND AND AIMS Chromoblastomycosis is a chronic fungal infection caused by species of the family Dematiaceae. Fonsecaea pedrosoi is the most common etiological agent. The objective of this study was to describe the epidemiological and mycological profile of patients with chromoblastomycosis from the Amazon region of Brazil and to correlate the clinical forms with the histopathological findings and severity criteria. METHODS Sixty-five patients were submitted to mycological (direct, culture, and microculture) and histopathological (hematoxylin-eosin staining) examination. Severity of the disease was classified according to the criteria proposed by Carrión in 1950. RESULTS Most patients were males (93.8%) and laborers (89.2%). There was a predominance of verrucous lesions (55.4%), which were mainly found on the lower limbs (81.5%). Two major types of tissue reaction were observed: a granulomatous reaction characterized by the formation of suppurative granulomas rich in fungal cells, which were almost always seen in verrucous lesions, and a reaction characterized by the formation of tuberculoid granulomas with few parasites, which were mainly found in well-delimited erythematous plaque-like and cicatricial lesions (p = 0.0001). A peculiar type of organized mycotic granuloma was observed in 20 subjects. Suppurative granulomas were more frequently detected in severe lesions (p = 0.0189) and in lesions with a duration of >10 years (p = 0.0408). CONCLUSIONS These results suggest that verrucous lesions present a less competent inflammatory tissue response than patients who develop a well-formed tuberculoid reaction. The latter is associated with a more effective immune response as observed in the limited clinical forms of chromoblastomycosis.

Clinical, epidemiological and mycological report on 65 patients from the Eastern Amazon region with chromoblastomycosis

BACKGROUND Chromoblastomycosis is a chronic fungal infection caused by fungi from the Dematiaceae family. According to several studies, Fonsecaea pedrosoi is the most common of these fungi. The infection is more common in tropical countries, with the Brazilian state of Pará having one of the largest infected populations worldwide. The disease is difficult to treat and recurrences are common. OBJECTIVES To describe the epidemiological and mycological aspects of cases of chromoblastomycosis and its clinical forms in the state of Pará, Brazil. METHODS Mycological exams (direct mycological examinations, culture and microculture) were performed and a clinical/epidemiological evaluation was made of 65 patients receiving care at the Dermatology Department of the Federal University of Pará between 2000 and 2007. The clinical classification proposed by Carrión in 1950 was used in this study. RESULTS The majority of the patients were male (93.8%), agricultural workers (89.2%) of 45 to 55 years of age, and the majority of lesions (55.4%) were of the verrucous type, located principally on the lower limbs (81.5%). In the majority of the cases investigated (61.5%), the infection had been present for a long time, with a mean duration of 11 years. Direct mycological examination was performed in 86.2% of the patients (n=56). Of these, 96.4% (n=54) tested positive. Culture and microculture were performed in vitro in 47 cases of those that tested positive at direct microscopy, results showing Fonsecaea pedrosoi to be the only agent present in this sample. CONCLUSION This study highlighted the extent to which chromoblastomycosis still affects the quality of life of the local population, principally individuals working in agriculture. This is a chronic disease for which there is no effective treatment. The importance of continuing to investigate this disease should be emphasized, as further studies may lead to new clinical or epidemiological findings.

Transepidermal elimination of parasites in Jorge Lobo's disease

BACKGROUND Few studies have focussed on the transepidermal elimination of parasites in Jorge Lobos disease (lobomycosis). OBJECTIVE To identify the morphological features of the transepidermal elimination of parasites in lobomycosis. METHODS Sections were obtained from paraffin-embedded biopsy specimens of patients with lobomycosis and stained with hematoxylin-eosin for microscopic examination. Only the presence of parasites in epidermal structures was considered to constitute transepidermal elimination. RESULTS Forty biopsies from 37 patients were included in the study (31 males and 6 females). The mean age of patients was 51.03 years (range 29-80 years). Biopsies performed over a period of 37 years (1967-2003) were used, from which 511 sections were obtained (a mean of 12.77 sections per case; range 2-39 sections per case). Transepidermal elimination of parasites was found in 110/511 (21.52%) and was absent in 401/511 sections (78.48%) (p<0.0001). Features consistent with the phenomenon were found in 15/37 patients (40.5%) and were absent in 22/37 (59.5%) (p>0.05). Parasites in the epidermis were detected within hyperplastic infundibula, either connected in chains or as isolated units, associated or not with inflammatory cells. CONCLUSION Features consistent with transepidermal elimination of parasites were found in a statistically nonsignificant number of patients in the sample (p>0.05), suggesting that in Jorge Lobos disease, this phenomenon invariably occurs through the infundibular epithelium. Future studies are required to evaluate the significance of this finding in the epidemiology of mycosis.

Immunohistochemical study of Langerhans cells in cutaneous lesions of the Jorge Lobo's disease.

Jorge Lobos disease is a chronic infection caused by the fungus Lacazia loboi endemic in South America. The infection is characterized by the appearance of parakeloidal, ulcerated or verrucous nodular or plaque-like cutaneous lesions. The histopathological aspect is characterized by poorly organized granulomas with histiocytes and multinucleated giant cells. Little is known about local immune response in lobomycosis skin lesions. Thirty-three skin biopsies from patients with Jorge Lobos disease were selected from Ambulatory of Dermatology, UFPA. The control group was constituted by ten biopsies from normal skin. Langerhans cells were identified by immunohistochemistry using anti-CD1a antibody (Serotec). The number of positive cells was statistically analyzed. Langerhans cells were visualized along the epidermis in biopsies from Jorge Lobos disease and the morphology and the number of Langerhans cells did not differ from normal skin (p>0.05). In Jorge Lobos disease, this cell population probably presents some escape mechanism of the local immune system to evade the antigen presentation by those cells.

Stewart-Treves Syndrome of the Lower Extremity

Stewart-Treves syndrome is a rare cutaneous angiosarcoma that develops in long-standing chronic lymphedema. Though most commonly this angiosarcoma is a result of post mastectomy lymphoedema, it also develops in Milroy disease, idiopathic, congenital, traumatic and filarial lymphoedema. Despite the rarity of this syndrome and its poor prognosis, early diagnosis associated with radical surgery can provide improved survival. We report a case of angiosarcoma in the lower limb in a patient with chronic lymphedema associated with history of repeated erysipela episodes.

Líquen escleroso e atrófico acral: relato de caso

O liquen escleroso e atrofico e uma doenca cronica da pele e mucosas, que, usualmente, afeta a area genital de mulheres. Poucos casos de liquen escleroso e atrofico, confinados nos pes e/ou maos, tem sido relatados. Relatamos um caso de liquen escleroso e atrofico envolvendo as extremidades e,posteriormente, a area perigenital

Comparison between histopathologic features of leprosy in reaction lesions in HIV coinfected and non-coinfected patients*

BACKGROUND Leprosy and HIV are diseases that have a major impact on public health in Brazil. Patients coinfected with both diseases, appear to be at higher risk to develop leprosy reactions. OBJECTIVE The aim of this study is to describe the histopathological aspects of cutaneous lesions during reactional states in a group of patients with HIV-leprosy coinfection, compared to patients with leprosy, without coinfection. METHODS Two groups were established: group 1 comprised of 40 patients coinfected with HIV-leprosy; group 2, comprised of 107 patients with leprosy only. Patients presenting reactional states of leprosy had their lesions biopsied and comparatively evaluated. RESULTS Reversal reaction was the most frequent feature in both groups, with dermis edema as the most common histopathological finding. Giant cells were seen in all group 1 histopathological examinations. Dermis edema was the most common finding in patients with erythema nodosum leprosum. CONCLUSION Few histopathological differences were found in both groups, with reversal reaction as the most significant one, although this fact should be analyzed considering the predominant BT clinical form in the coinfected group and BB form in the group without HIV. Larger prospective studies in patients with HIV-leprosy coinfection are needed to confirm and broaden these results.

Plasmacytoid dendritic cells in cutaneous lesions of patients with chromoblastomycosis, lacaziosis, and paracoccidioidomycosis: a comparative analysis

Plasmacytoid dendritic cells (pDCs) are characterized by expression of CD123 and BDCA-2 (Blood Dendritic Cell Antigen 2) (CD303) molecules, which are important in innate and adaptive immunity. Chromoblastomycosis (CBM), lacaziosis or Jorge Lobos disease (JLD), and paracoccidioidomycosis (PCM), are noteworthy in Latin America due to the large number of reported cases. The severity of lesions is mainly determined by the hosts immune status and in situ responses. The dendritic cells studied in these fungal diseases are of myeloid origin, such as Langerhans cells and dermal dendrocytes; to our knowledge, there are no data for pDCs. Forty-three biopsies from patients with CBM, 42 from those with JLD and 46 diagnosed with PCM, were evaluated by immunohistochemistry. Plasmacytoid cells immunostained with anti-CD123 and anti-CD303 were detected in 16 cases of CBM; in those stained with anti-CD123, 24 specimens were obtained from PCM. We did not detect the presence of pDCs in any specimen using either antibody in JLD. We believe that, albeit a secondary immune response in PCM and CBM, pDCs could act as a secondary source of important cytokines. The BDCA-2 (CD303) is a c-type lectin receptor involved in cell adhesion, capture, and processing of antigens. Through the expression of the c-lectin receptor, there could be an interaction with fungi, similar to other receptors of this type, namely, CD207 in PCM and CD205 and CD209 in other fungal infections. In JLD, the absence of expression of CD123 and CD303 seems to indicate that pDCs are not involved in the immune response.