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Chromoblastomycosis--a clinical and mycological study of 71 cases from Sri Lanka.

Chromoblastomycosis, a well-documented chronic fungal infection, represents a specific clinical entity with typical warty cutaneous nodules and a worldwide distribution. Although more prevalent in tropical and subtropical regions, only a few reports are available from Sri Lanka or from Asia. Five etiologic agents of chromoblastomycosis have been recognized worldwide. Of these the majority of infections have been caused by Fonsecaea pedrosoi. During the period from 1952 to 1962, only twelve culturally proven cases of this disease had been recorded from Sri Lanka. The fungus responsible was F. pedrosoi. The present report presents a study of the clinical and mycological features of 71 Sri Lankan patients with chromoblastomycosis for the 16-year period from 1978 to 1993. It documents three etiological agents. Culture identification was made in 69 cases. The three fungal species were Fonsecaea pedrosoi (64), Phialophora verrucosa (3) and a fungus compatible morphologically with F. compacta (2). The isolation of a fungus morphologically compatible with F. compacta is of significance since only 12 cases have been documented in the world's literature so far.

Adolescent↗

The cell-mediated immune reaction in the cutaneous lesion of chromoblastomycosis and their correlation with different clinical forms of the disease.

Chromoblastomycosis is a fungal infection caused by dematiaceous fungi inducing skin lesions of difficult treatment and of frequent recurrence. The objective of the present investigation was to characterize cell-mediated tissue reactions in the skin in cases of Chromoblastomycosis using histopathology and immunocytochemistry methods and to correlate them with different clinical forms of Chromoblastomycosis. Biopsies from 19 patients were stained with HE and Giemsa, and serial sections were immunohistochemically stained using CD45RO, CD20, CD4, CD8, CD68, CD1a, CD34, IL4, IL10, TNF-alpha and IFN-gamma antibodies. A quantitative and semiquantitative analysis of the cell subsets and cytokines in the inflammatory infiltrates was performed by counting ten high-power fields (400x). The cutaneous lesion presented as verrucous plaque (n = 15) or erythematous atrophic plaque (n = 4). We observed two types of tissue reaction: A) a granulomatous reaction with a suppurative granuloma with several fungi cells in the cutaneous lesion presenting as verrucous plaque; B) a granulomatous reaction with a tuberculoid granuloma with few fungi cells in the cutaneous lesion presenting as atrophic plaque. The data obtained suggest that patients with lesion presented as verrucous plaque have a type Th2 immunological response, while patients with lesion presented as erythematous atrophic plaque have a type Th1 response.

Adult↗

Chromoblastomycosis imported from Malta.

Chromoblastomycosis is a chronic fungal infection of the skin and subcutaneous tissues caused by pigmented fungi. It is primarily a disease of the tropics and subtropics. It is uncommon in the UK where it may occur as an imported disease. We describe a 42-year-old lady who developed chromoblastomycosis on her right forearm from Cladosporium, after visiting Malta. The lesion resolved after treatment with itraconazole for 6 months. To our knowledge there are no previous reports of chromoblastomycosis from Malta. We review the clinical course, diagnosis and management of this condition.

Adult↗

HLA-A29 and genetic susceptibility to chromoblastomycosis.

The distribution of 12 HLA-A, 14 HLA-B, seven HLA-C, seven HLA-DR and three HLA-DQ antigens was determined in 32 non-consanguineous white Brazilians suffering from chromoblastomycosis and 77 healthy controls, matched for ethnic background, sex and age and living in the same geographical area. A significant difference between the two groups was seen only in respect to one HLA-A antigen: A29 was present in 28% of patients as opposed to 4% of the controls (P corrected = 0.03). This finding indicates that susceptibility to chromoblastomycosis may be influenced by a gene located on chromosome 6, in the region of the major histocompatibility complex. The relative risk for an HLA-A29 carrier to develop chromoblastomycosis was estimated as 10.

Adult↗

Chromoblastomycosis caused by Exophiala spinifera.

We report the second case of chromoblastomycosis caused by Exophiala spinifera; this is the first known case in the United States. Examination of biopsied tissue showed thick-walled, internally septated, chestnut brown muriform cells (sclerotic bodies) within multinucleated giant cells present in the dermis that were characteristic of chromoblastomycosis. The individual cells within the muriform cells disarticulated from the outer wall of the parent cell and from each other to form endoconidia within the outer walls of the parent cells. After fracture of the outer walls, the endoconidia were released. This unique process of endoconidial formation in vivo for the propagation of muriform cells was observed for the first time. Initial treatment with itraconazole and 5-fluorocytosine followed by treatment with itraconazole and heat resulted in marked improvement in the patient's lesions. This infection reiterates the fact that the dematiaceous fungus E. spinifera, a well-known etiologic agent of phaeohyphomycosis, can cause more than one type of infection and supports earlier observations that chromoblastomycosis and phaeohyphomycosis represent extremes of a continuum of infections.

Antifungal Agents↗

Itraconazole in the treatment of chromoblastomycosis due to Fonsecaea pedrosoi.

The efficacy and tolerability of itraconazole in chromoblastomycosis due to Fonsecaea pedrosoi were evaluated in a non-comparative open clinical trial in 19 Brazilian patients with histopathologically and mycologically proven active chromoblastomycosis. Patients were classified in terms of severity and received itraconazole at the dosage of 200 to 400 mg per day until previously described criteria of cure have been reached. Clinical, mycologic, histopathologic, and laboratory evaluations were performed before, during, and after therapy. The plasma levels of itraconazole and the in vitro susceptibility of the isolates were determined in 15 cases. Clinical and biologic cure were achieved by eight patients (42%) having mild to moderate disease, after a mean duration of therapy of 7.2 months (3.2-29.6 months). Sterile scarred lesions were observed in a post-therapy follow-up lasting on average 9.6 months that was carried out in this subgroup. Clinical cure alone occurred after a mean period of 25.1 months of treatment (16-30.5 months) in seven patients (36%) with moderate to severe disease. Finally, clinical improvement was obtained in four patients (21%) with severe lesions after a mean treatment time of 17.6 months (10.7-22.5 months). All patients responded favorably to itraconazole therapy. No significant side effects nor biochemical alteration during this trial were important enough to interrupt the treatment. Our results support those of previous trials, suggesting that itraconazole is an effective compound against chromoblastomycosis due to Fonsecaea pedrosoi.

Adult↗

Chromoblastomycosis simulating rhinosporidiosis in a patient from Ceylon.

A case of chromoblastomycosis confined to the mucous membrane of one side of the nasal septum is reported. The organism was not cultivated, but its characteristics in histological preparations were typical of those of the organisms in sections of cutaneous lesions known to be caused by Phialophora pedrosoi and related fungi. The diagnosis is considered to have been justified in spite of the great rarity of mucosal involvement in chromoblastomycosis and of the complete absence of lesions in the skin. The patient was a Sinhalese student working in London. He had first noticed the lesion before he left Ceylon, but the symptoms of nasal obstruction and bleeding were not sufficient to make him seek medical advice until two years later. If it is correct to assume that he contracted the infection in Ceylon his case is only the second on record in which there has been reason to suggest that Ceylon has been the geographical source of chromoblastomycosis. The lesion was excised and its site cauterized. There has been no sign of recurrence of the infection during the two years that have passed since the operation.

Chromoblastomycosis↗

Cerebral chromoblastomycosis complicated by meningitis and multiple fungal aneurysms after resection of a granuloma. Case report.

Cerebral chromoblastomycosis is a rare intracranial lesion. This lesion was found in a 23-year-old man, who presented with right proptosis and fainting attacks. Computerized tomography revealed a moderately enhanced irregular mass in the right frontal region. Angiography disclosed that the mass was avascular. At surgery, a hard elastic avascular tumor was totally removed piecemeal. Histological diagnosis was a granuloma of fungal origin. Characteristic brown pigments in the hyphae of fungus in the granuloma strongly suggested that the fungus was chromoblastomycosis. The postoperative course was complicated by meningitis and rupture of fungal aneurysms. The patient remained vegetative and died 2 1/2 years later. The literature on such fungal aneurysms is briefly reviewed; no previous case of fungal aneurysms associated with cerebral chromoblastomycosis could be found.

Adult↗

Development of a chronic chromoblastomycosis model in immunocompetent mice.

An experimental model to study chromoblastomycosis caused by Fonsecaea pedrosoi was developed in immunocompetent BALB/c mice. Unlike previous models of chromoblastomycosis, in this model a chronic, progressive infection mimicking the infection in humans was developed. This model may be suitable for use in experimental studies of chromoblastomycosis.

Animals↗

Chromoblastomycosis.

Chromoblastomycosis, together with phaeohyphomycosis and mycetoma, makes up the disease entities caused by the dematiaceous fungi. Most cases of chromoblastomycosis are caused by five genera of fungi: Fonsecaea compactum, Fonsecaea pedrosoi, Phialophora verrucosa, Cladosporium carrionii, and Rhino-cladiella aquaspersa. The disease has a cosmopolitan distribution but predominates in rural, agricultural settings. Clinically, chromoblastomycosis is hallmarked by verrucous nodules at the site of fungal implantation. Treatment involves surgical excision of the affected area, antimycotic agents, physical modalities such as temperature manipulation, or a combination of these.

Adult↗

A Samoan case of chromoblastomycosis caused by Cladophialophora ajelloi.

A case of chromoblastomycosis from American Samoa was studied. Histopathological examination of the biopsy material from the lesion revealed the presence of thick-walled, dematiaceous, muriform cells characteristic of chromoblastomycosis. Detailed mycological study of the dematiaceous mould isolated from the biopsy material disclosed that the fungus not only produced long, branched chains of holoblastic conidia similar to those of Cladosporium carrionii, but that many of the terminal and intercalary catenulate, holoblastic conidia had been converted into flask-shaped phialides with flaring collarettes that produced ovate to fusiform phialoconidia. These phialides were morphologically similar to those formed by members of the genus Phialorphora. The Samoan case is the second known case of chromoblastomycosis caused by Cladophialophora ajelloi Borelli.

Adult↗

Corneal chromoblastomycosis.

PURPOSE: We sought to illustrate the difficulty in managing uncommon, pigmented mold-related corneal ulceration and to highlight the role of itraconazole in treating these patients. METHOD: We describe the management and clinical course of a patient with a recurring corneal infection caused by Fonsecaea pedrosoi and discuss this experience in the light of existing literature on management of cutaneous chromoblastomycosis. RESULTS: A corneal ulcer caused by this organism healed initially on treatment with topical and systemic antifungal medication, but infection recurred in the deep stroma 4 months after cessation of therapy. After failure to respond to a further period of medical therapy, a small therapeutic penetrating keratoplasty was performed. Culture of a fibrinous membrane from the anterior iris surface demonstrated intraocular fungal infection, and postoperatively, an episode of marked fibrinous uveitis developed, suggesting the presence of viable intraocular fungal elements. A large penetrating keratoplasty was therefore performed with excision of involved iris in combination with extracapsular cataract extraction. F. pedrosoi was again cultured from the fibrinous membrane adherent to the iris and from the anterior lens capsule. Postoperatively the patient received a 5-month course of systemic itraconazole, and no further recurrences have been encountered after a further 2 months. CONCLUSION: F. pedrosoi is the organism most commonly isolated from the chronic cutaneous mycosis, chromoblastomycosis, and is relatively resistant to medical therapy. As has been reported for cutaneous disease, surgery in combination with systemic itraconazole may provide the best chance of cure in corneal chromoblastomycosis.

Antifungal Agents↗

Relationship between tissue reactions and morphological changes of the fungi in chromoblastomycosis: morphometry and electron microscopy.

To investigate the histological distribution and the morphology of the fungi and the tissue reactions in chromoblastomycosis, especially in the process of transepidermal elimination, cutaneous lesions of two patients with this disease were studied morphometrically and ultrastructurally. In the dermis, most of the fungal elements appeared as sclerotic cells and their cell wall showed an irregular, worm-eaten leaf-like appearance; they seemed to be continuously attacked by polymorphonuclear neutrophils. The epidermis eliminated 10-20% of all the organisms in the skin lesions, and the hypha-forming activity tended to be higher in the epidermis than in the dermis. Ultrastructurally, basal keratinocytes facing the dermal abscess containing fungal elements frequently appeared as dark cells, suggesting an increased proliferation activity. Spinous keratinocytes facing intraepidermal microabscesses containing fungal elements showed an abnormal accumulation of tonofilaments and further early keratinization in the spinous cell layer. All of the morphological changes of the dermis and epidermis are regarded as defence reactions against the fungi existing in the skin lesions. There is a close relationship between tissue reactions and morphological changes of fungi in chromoblastomycosis.

Aged↗

Chromoblastomycosis. A morphological investigation of the host-parasite interaction.

Chromoblastomycosis is a distinct cutaneous mycotic infection. Histologically it is characterized by the presence of fungus invariably in the yeast phase and by macrophages in large numbers. The morphology of fungus in both yeast and hyphal phases and its interaction with mononuclear phagocytes were examined using ultrastructural techniques. The major structural difference between the fungus in cutaneous tissue and that from a culture medium was a striking increase in cell wall thickness in the former. In the skin, the organisms were phagocytised by macrophages and enclosed in large membrane limited intracytoplasmic vacuoles. The thick, stratified, electron-dense fungal cell wall was observed in stages of alteration of varying severity. Most common was a granular modification of the outermost layers of the cell wall in contact with the vacuolar content. Fragmentation, splitting and rupture of this and deeper layers was also seen. Several ultrastructural features suggested that cell wall damage resulted from an active host cell digestion. The cell wall changes were in sharp contrast with the usual normal fungal cytoplasmic appearance. Only rare intracellular debris which we supposed to represent dead yeast cells were found. These findings suggested that the yeast responsible for chromoblastomycosis resisted fungicidal activities of cutaneous macrophages which possessed the ultrastructural features of stimulated phagocytes.

Chromoblastomycosis↗

Partial suppression of cell mediated immunity in chromoblastomycosis.

The cellular immune response of 8 patients from the Brazilian Amazon region with chromoblastomycosis was analyzed. Primary immunological responses of patients were tested by contact sensitization to 2,4-dinitro-chlorobenzene (DNCB), or rejection of first set skin allografts. 2 of 8 patients were reactive to DNCB after sensitization, and skin allograft rejection occurred in an average of 14 days. Capacity of patients to mount recall immunological responses was measured by skin testing with two fungal antigens and three bacterial antigens. Delayed skin reaction to trichophytin and candida antigens was negative in the majority of the patients. However, reactivity to mycobacterial (tuberculin), and bacterial (staphylococcal, streptococcal) antigen was high, or only slightly diminished respectively. The data suggest that patients with chromoblastomycosis have suppressed nonspecific, cell mediated immunity for some antigens (skin allografts, DNCB, fungal antigens), while reactivity to bacterial and mycobacterial antigens is not impaired.

Aged↗

Evaluation of skin test for chromoblastomycosis using antigens prepared from culture filtrates of Fonsecaea pedrosoi, Phialophora verrucosa, Wangiella dermatitidis and Exophiala jeanselmei.

Antigenic substances were prepared from culture filtrates of Fonsecaea pedrosoi, Phialophora verrucosa, Wangiella dermatitidis and Exophiala jeanselmei. These antigenic substances were evaluated for detecting cutaneous delayed hypersensitivity in rats experimentally-infected with F. pedrosoi, P. verrucosa. W. dermatitidis, E. jeanselmei, Cladosporium carrionii and Fonsecaea compactum and in patients with chromoblastomycosis caused by F. pedrosoi. The F. pedrosoi antigen elicited positive reactions in all of the animals infected with F. pedrosoi and in 5 of 6 patients. The P. verrucosa, W. dermatitidis and E. jeanselmei antigens elicited positive reactions in all of the animals infected with the homologous species. These antigens displayed cross-reactivity in some of the animals and patients, whereas more than half of them exhibited positive reactions only to the antigens prepared from the homologous species. These results suggest that a delayed-type skin test using the antigens prepared by the authors may be useful not only for the diagnosis of chromoblastomycosis but also for the identification of species of the causative agent.

Animals↗

[Diagnosis, clinical aspects and therapy of early chromoblastomycosis in a case example].

Despite the availability of modern antimycotics, which produce high cure rates in early infections, the therapy of advanced chromoblastomycosis is still unsatisfactory. An initial chromoblastomycosis caused by a hitherto unidentified species of the genus Phialophora was diagnosed in a 46-year-old teacher. The organism was isolated twice at an interval of 6 weeks from a partly psoriasiform, partly verrucous lesion on the 4th toe. The infection was apparently acquired 4 years ago during a holiday at Cape Verde. Treatment with itraconazole (Sempera). 200 mg/day, and amphotericin B (Ampho-Moronal) cream for 6 weeks initially resulted in rapid regression. However, 4 weeks after cessation of therapy, the Phialophora species was cultured again from skin scrapings. Complete healing was achieved after re-treatment with itraconazole for 20 weeks at the same dosage in combination with topical amorolfine and local hyperthermia. Until now, no relapse has occurred. The present case demonstrates that this rare disease, which mainly occurs as a traumatic mycosis in the rural population of tropical regions, must be included in the differential diagnosis of psoriasiform or verrucous skin lesions and also included in the list of diseases which may be acquired while on vacation in exotic locations.

Administration, Topical↗

Inhibition of nitric oxide production by macrophages in chromoblastomycosis: a role for Fonsecaea pedrosoi melanin.

Chromoblastomycosis is a chronic and progressive deep mycosis that is usually found in tropical and subtropical areas. Fonsecaea pedrosoi is considered its most frequent etiologic agent and causes a typical granulomatous inflammatory response, whose degree reflects the immune status of the host. Since macrophages play a fundamental role in the control of the infection, this study aimed at investigating the production of oxygen reactive specimens, the phagocytic capacity and the production of nitric oxide (NO) by macrophages employing in vitro assays and an in vivo model of chromoblastomycosis. Our results demonstrated that, during the infection, peritoneal macrophages show an increased phagocytic capacity and H2O2 production, but also a reduced ability to produce NO. Moreover, F. pedrosoi stimulated H2O2 production in vitro but not the synthesis of NO. The incubation of IFNgamma and LPS-stimulated macrophages with melanin, obtained from the fungus, inhibited NO production. Examination of the liver and spleen of infected animals, at day 30 or 60 following inoculation, showed a progressive increase in the number and size of granulomas, indicating that macrophages are properly mobilized and activated. Our data suggest that the inability of the host to clear F. pedrosoi, leading to a chronic disease, is due, at least in part, to the inhibition of NO synthesis by macrophages by fungus-produced melanin.

Animals↗