Recent advances on mycotic keratitis caused by dematiaceous hyphomycetes.

Dematiaceous hyphomycetes (DH) are darkly pigmented fungi ubiquitously found all over the world as plant pathogens and saprophytes, and many of the members of this group have emerged as opportunistic pathogens. These fungi are responsible for a wide variety of infections including mycotic keratitis, which is considered as one of the major causes of corneal blindness, particularly in tropical and subtropical countries with an annual global burden of about 1 000 000 patients. The infection is more common in workers working in an outdoor environment. Moreover, trauma is found to be the most important predisposing cause of mycotic keratitis. Considerable delay in diagnosis and scarcity of effective pharmacological drugs are the major factors responsible for increased morbidity and visual impairment. Considering the crucial role of DH in mycotic keratitis, in the present review, we have focused on major DH with special emphasis on their pathogenicity, diagnosis and treatment strategies.

Trends in the molecular epidemiology and population genetics of emerging Sporothrix species.

Sporothrix (Ophiostomatales) comprises species that are pathogenic to humans and other mammals as well as environmental fungi. Developments in molecular phylogeny have changed our perceptions about the epidemiology, host-association, and virulence of Sporothrix. The classical agent of sporotrichosis, Sporothrix schenckii, now comprises several species nested in a clinical clade with S. brasiliensis, S. globosa, and S. luriei. To gain a more precise view of outbreaks dynamics, structure, and origin of genetic variation within and among populations of Sporothrix, we applied three sets of discriminatory AFLP markers (#3 EcoRI-GA/MseI-TT, #5 EcoRI-GA/MseI-AG, and #6 EcoRI-TA/MseI-AA) and mating-type analysis to a large collection of human, animal and environmental isolates spanning the major endemic areas. A total of 451 polymorphic loci were amplified in vitro from 188 samples, and revealed high polymorphism information content (PIC = 0.1765-0.2253), marker index (MI = 0.0001-0.0002), effective multiplex ratio (E = 15.1720-23.5591), resolving power (Rp = 26.1075-40.2795), discriminating power (D = 0.9766-0.9879), expected heterozygosity (H = 0.1957-0.2588), and mean heterozygosity (Havp  = 0.000007-0.000009), demonstrating the effectiveness of AFLP markers to speciate Sporothrix. Analysis using the program structure indicated three genetic clusters matching S. brasiliensis (population 1), S. schenckii (population 2), and S. globosa (population 3), with the presence of patterns of admixture amongst all populations. AMOVA revealed highly structured clusters (PhiPT = 0.458-0.484, P < 0.0001), with roughly equivalent genetic variability within (46-48 %) and between (52-54 %) populations. Heterothallism was the exclusive mating strategy, and the distributions of MAT1-1 or MAT1-2 idiomorphs were not significantly skewed (1:1 ratio) for S. schenckii (χ2 = 2.522; P = 0.1122), supporting random mating. In contrast, skewed distributions were found for S. globosa (χ2 = 9.529; P = 0.0020) with a predominance of MAT1-1 isolates, and regional differences were highlighted for S. brasiliensis with the overwhelming occurrence of MAT1-2 in Rio de Janeiro (χ2 = 14.222; P = 0.0002) and Pernambuco (χ2 = 7.364; P = 0.0067), in comparison to a higher prevalence of MAT1-1 in the Rio Grande do Sul (χ2 = 7.364; P = 0.0067). Epidemiological trends reveal the geographic expansion of cat-transmitted sporotrichosis due to S. brasiliensis via founder effect. These data support Rio de Janeiro as the centre of origin that has led to the spread of this disease to other regions in Brazil. Our ability to reconstruct the source, spread, and evolution of the ongoing outbreaks from molecular data provides high-quality information for decision-making aimed at mitigating the progression of the disease. Other uses include surveillance, rapid diagnosis, case connectivity, and guiding access to appropriate antifungal treatment.

Diagnostic implications of mycetoma derived from Madurella pseudomycetomatis isolates from Mexico.

BACKGROUND: At the dermatology service of the General Hospital of Mexico City, Mexico, two patients, father and son, with black-grain mycetoma were seen. The grains were isolated, and the cultured fungi were identified as Madurella mycetomatis based on morphology. Using the M. mycetomatis specific PCR, amplicons of a different size than that of the M. mycetomatis type strain were obtained. OBJECTIVE: To determine the causative agent of the two black-grain mycetoma cases and develop non-culture-based diagnostic tools to identify them to the species level. METHODS: The M. mycetomatis specific, the internal transcribed spacer (ITS) region, ß-tubulin (BT) and ribosomal binding protein 2 (RBP2) PCRs were used to confirm the identity of the isolates. Genetic variation was established by amplification fragment length polymorphisms. To determine the antifungal susceptibility profile, the Sensititre™ YeastOne™ assay was used. To develop a species-specific PCR primers were designed on the sequenced PCR amplicon from the M. mycetomatis specific PCR. RESULTS: By analyzing the ITS, BT and RBP2 regions the isolates were identified as Madurella pseudomycetomatis. The isolates from father and son were similar but not identical to M. pseudomycetomatis from Venezuela and one from an unknown origin. Madurella pseudomycetomatis isolates were inhibited by itraconazole, posaconazole and voriconazole but showed increased MIC values for amphotericin B and fluconazole. They were not inhibited by the echinocandins and five flucytosine. The two patients were treated with itraconazole resulting in cure for the father while the son was lost to follow-up. The species-specific PCR developed for M. pseudomyceotmatis was discriminative and specific. CONCLUSION: Madurella pseudomycetomatis is genetically diverse with same susceptibility profile as M. mycetomatis and causes eumycetoma in Latin America. The M. pseudomycetomatis specific PCR can be used to identify this causative agent to the species level; however, this needs to be validated in an endemic setting.

Actinomicetoma torácico con afección pulmonar. Tratamiento con carbapenémico y aminoglucósido / Thoracic actinomycetoma with lung compromise. Treatment with carbapenem and aminoglycoside

Resumen: El actinomicetoma, infección crónica, granulomatosa y progresiva de la piel y tejido celular subcutáneo que afecta más las extremidades inferiores y en especial los pies, se caracteriza por la tríada de trayectos fistulosos, aumento de volumen y granos. La afección en el tórax en México ocupa el segundo lugar en cuanto a frecuencia. Sin embargo, el daño pulmonar es muy raro, afecta menos de 1% de los casos, éste puede ocurrir por continuidad al afectar el tronco, lo que causa tratamientos antimicrobianos prolongados con falta de apego a los mismos, así como aumento de la mortalidad. El objetivo de este artículo es comunicar un caso clínico de actinomicetoma pulmonar, así como la respuesta al tratamiento prescrito a este paciente con base en carbapenémicos, aminoglucósidos y trimetoprim con sulfametoxazol.

Abstract: Actinomycetoma is a chronic, granulomatous and progressive infection of the skin and subcutaneous cellular tissue that affects the lower limbs and especially the feet, characterized by triad of localized swelling, draining sinuses and grains. The chest condition in Mexico ranks second in frequency. Nevertheless, pulmonary affectation is very rare with less than 1%, this can occur by continuity affecting the trunk leading to prolonged antimicrobial therapy and lack of attachment to it, as well as increased mortality. The aim of this paper is to report a case of pulmonary actinomycetoma as well as response to treatment with carbapenems, aminoglycoside and trimethoprim with sulfamethoxazole.

Paraneoplastic Pemphigus. A Life-Threatening Autoimmune Blistering Disease / Pénfigo paraneoplásico. Una enfermedad ampollosa autoinmune grave

Paraneoplastic pemphigus (PNP), a subset of pemphigus, is a unique autoimmune blistering condition that can affect multiple organs other than the skin. It is a life-threatening disease associated with an underlying malignancy, most commonly of lymphoproliferative origin. The clinical picture may resemble pemphigus, pemphigoid, erythema multiforme, graft-versus-host disease, or lichen planus. The earliest and most consistent finding is a painful, severe, chronic and often recalcitrant stomatitis. Treatment of PNP is difficult. Immunosuppressive agents are required to decrease blistering, and treating the underlying tumor may control autoantibody production. In this review, we included essential diagnostic aspects of PNP and the most useful treatment options in the dermatologist practice

El pénfigo paraneoplásico (PNP), una variedad de pénfigo, es una enfermedad ampollosa autoinmune que puede afectar a múltiples órganos distintos de la piel. Es una enfermedad grave asociada con una malignidad subyacente, comúnmente de origen linfoproliferativo. Las lesiones clínicas pueden parecerse al pénfigo, penfigoide, eritema multiforme, enfermedad de injerto contra huésped o liquen plano. El hallazgo más temprano y más consistente es una estomatitis dolorosa, grave, crónica y, a menudo, recalcitrante. El tratamiento del PNP es difícil. Se requieren agentes inmunosupresores para disminuir la formación de ampollas y el tratamiento del tumor subyacente puede controlar la producción de autoanticuerpos. En esta revisión se incluyeron los aspectos diagnósticos más esenciales del PNP y las opciones de tratamiento más útiles en la práctica dermatológica

Paraneoplastic Pemphigus. A Life-Threatening Autoimmune Blistering Disease.

Paraneoplastic pemphigus (PNP), a subset of pemphigus, is a unique autoimmune blistering condition that can affect multiple organs other than the skin. It is a life-threatening disease associated with an underlying malignancy, most commonly of lymphoproliferative origin. The clinical picture may resemble pemphigus, pemphigoid, erythema multiforme, graft-versus-host disease, or lichen planus. The earliest and most consistent finding is a painful, severe, chronic and often recalcitrant stomatitis. Treatment of PNP is difficult. Immunosuppressive agents are required to decrease blistering, and treating the underlying tumor may control autoantibody production. In this review, we included essential diagnostic aspects of PNP and the most useful treatment options in the dermatologist practice.

Multicenter, International Study of MIC/MEC Distributions for Definition of Epidemiological Cutoff Values for Sporothrix Species Identified by Molecular Methods.

Clinical and Laboratory Standards Institute (CLSI) conditions for testing the susceptibilities of pathogenic Sporothrix species to antifungal agents are based on a collaborative study that evaluated five clinically relevant isolates of Sporothrixschenckii sensu lato and some antifungal agents. With the advent of molecular identification, there are two basic needs: to confirm the suitability of these testing conditions for all agents and Sporothrix species and to establish species-specific epidemiologic cutoff values (ECVs) or breakpoints (BPs) for the species. We collected available CLSI MICs/minimal effective concentrations (MECs) of amphotericin B, five triazoles, terbinafine, flucytosine, and caspofungin for 301 Sporothrix schenckii sensu stricto, 486 S. brasiliensis, 75 S. globosa, and 13 S. mexicana molecularly identified isolates. Data were obtained in 17 independent laboratories (Australia, Europe, India, South Africa, and South and North America) using conidial inoculum suspensions and 48 to 72 h of incubation at 35°C. Sufficient and suitable data (modal MICs within 2-fold concentrations) allowed the proposal of the following ECVs for S. schenckii and S. brasiliensis, respectively: amphotericin B, 4 and 4 µg/ml; itraconazole, 2 and 2 µg/ml; posaconazole, 2 and 2 µg/ml; and voriconazole, 64 and 32 µg/ml. Ketoconazole and terbinafine ECVs for S. brasiliensis were 2 and 0.12 µg/ml, respectively. Insufficient or unsuitable data precluded the calculation of ketoconazole and terbinafine (or any other antifungal agent) ECVs for S. schenckii, as well as ECVs for S. globosa and S. mexicana These ECVs could aid the clinician in identifying potentially resistant isolates (non-wild type) less likely to respond to therapy.

Actinomicetoma en el embarazo. Reporte de un caso: ¿Qué hacer y cómo tratarlo? / Actinomycetoma in pregnancy. Case report: what to do, how to handle?

Resumen ANTECEDENTES: El micetoma es una infección causada por hongos y actinomicetos aeróbicos. Es un padecimiento frecuente en México, con mayor afectación en hombres que en mujeres (3:1). Se caracteriza por aumento de volumen, deformidad del sistio de lesión y formación de fístulas. OBJETIVO: Reportar un caso de actinomicetoma durante el embarazo y analizar el protocolo de tratamiento. CASO CLINICO: Paciente de 29 años de edad, en su cuarto embarazo, con 29 semanas de gestación. El padecimiento se inició 13 años atrás, con dermatosis localizada en la extremidad inferior izquierda, constituida por un nódulo indoloro, que permaneció sin cambios hasta el inicio de la gestación actual, cuando le aparecieron múltiples lesiones nodulares y fístulas. En el examen directo de la secreción se observaron granos y en el cultivo se identificó Nocardia brasiliensis. Después del embarazo a término y con recién nacido sano, si indicó lactancia durante 4 meses y se interrumpió para prescribir bromocriptina. La dermatosis se extendió al doble, sin afectación ósea; se indicó tratamiento con sulfametoxazol-trimetoprima y dapsona. El tiempo total de tratamiento fue de 15 meses y seguimiento sin medicación durante un año. Se obtuvo curación clínica y microbiológica. CONCLUSIONES: El micetoma en mujeres embarazadas es excepcional. La mayor parte de los portocolos de tratamiento deben contraindicarse durante el embarazo. Cuando el micetoma se localiza en una zona que no afecta otros órganos ni se extiende, se sugiere continuar el embarazo y la lactancia sin prescripción de medicamentos pero iniciarla posterior al nacimiento.

Abstract BACKGROUND: Mycetoma is an infection caused by fungi and aerobic actinomycetes. It is a frequent condition in Mexico; it presents less in women than men (1:3). It is characterized by increased volume deformity of the region and sinuses. OBJECTIVE: We present a case of actinomycetoma in a pregnant patient and to analyze the behavior in its therapeutic management CLINICAL CASE: We present female, 29 years old, attending her fourth pregnancy at 29 weeks of gestation. It began 13 years ago with a localized dermatosis of the lower left limb, constituted by a painless nodule, remained unchanged until the beginning of the current gestation, developed multiple nodules and sinuses. A direct examination of the secretion was performed, observing grains, Nocardia brasiliensis was identified. After product birth, lactation was allowed for 4 months and discontinued with bromocriptine. The dermatosis extended to double without bone affection, treatment with sulfamethoxazole/trimethoprim + dapsone was given. Total time was 15 months and follow-up without medication for one year. Clinical and microbiological cure was achieved. CONCLUSIONS: The development of mycetoma in pregnant women is rare, it is important to know the etiology, in eumycetoma all the antimycotics are teratogenic and in actinomycetoma most antibiotics cannot be used in pregnancy with some exceptions. If mycetoma is located in an area that does not compromise other organs or does not spread it is best to leave the course of pregnancy and lactation and then start treatment.

Afectación cutánea en las micosis profundas: una revisión de la literatura. Parte 1: micosis subcutáneas / Cutaneous involvement in the deep mycoses: a literature review. Part I-subcutaneous mycoses

Las micosis profundas son infecciones poco frecuentes en nuestro medio. Se presentan principalmente en pacientes inmunodeprimidos o en regiones de climas tropicales, que abarcan las micosis subcutáneas y las micosis sistémicas. Las micosis subcutáneas o por implantación siempre producen signos de afectación cutánea. En la primera parte de esta revisión se realizará una revisión de las principales micosis subcutáneas: esporotricosis, cromoblastomicosis, micetomas, feohifomicosis, hialohifomicosis y lacaziosis. Reconocer y tratar estas micosis subcutáneas de forma precoz es importante, ya que a menudo están asociadas a una alta morbilidad

The deep mycoses are uncommon in our setting. These fungal infections occur mainly in immunosuppressed patients or in tropical climates, and include subcutaneous infections and systemic infections. The skin is always involved in the former. In the first part of this review, we describe the main subcutaneous mycoses: sporotrichosis, chromoblastomycosis, mycetoma, phaeohyphomycosis, hyalohyphomycosis, and lacaziosis. Early recognition and treatment is important, as these infections are frequently associated with high morbidity

Afectación cutánea en las micosis profundas: una revisión de la literatura. Parte 2. Micosis sistémicas / Cutaneous involvement in the deep mycoses: a review. Part II -Systemic mycoses

En la segunda parte de este artículo se revisan las principales micosis sistémicas y sus manifestaciones cutáneas: paracoccidioidomicosis, coccidioidomicosis, histoplasmosis, mucormicosis y criptococosis. Las micosis sistémicas presentan lesiones en la piel solo en algunas ocasiones, ya sea por afectación directa de ella como puerta de entrada o tras la diseminación de la infección a partir de un foco profundo. Muchas veces estos signos cutáneos serán la única pista para el diagnóstico certero de patologías potencialmente fatales. Por lo mismo, y con mucho mayor énfasis que las micosis tratadas en la primera parte, es importante saber reconocer y tratar las micosis sistémicas

In the second part of this review on the deep mycoses, we describe the main systemic mycoses-paracoccidioidomycosis, coccidioidomycosis, histoplasmosis, mucormycosis, and cryptococcosis-and their cutaneous manifestations. Skin lesions are only occasionally seen in deep systemic mycoses either directly, when the skin is the route of entry for the fungus, or indirectly, when the infection has spread from a deeper focus. These cutaneous signs are often the only clue to the presence of a potentially fatal infection. As with the subcutaneous mycoses, early diagnosis and treatment is important, but in this case, even more so

Cutaneous involvement in the deep mycoses: A review. Part II -Systemic mycoses. / Afectación cutánea en las micosis profundas: una revisión de la literatura. Parte 2. Micosis sistémicas.

In the second part of this review on the deep mycoses, we describe the main systemic mycoses-paracoccidioidomycosis, coccidioidomycosis, histoplasmosis, mucormycosis, and cryptococcosis-and their cutaneous manifestations. Skin lesions are only occasionally seen in deep systemic mycoses either directly, when the skin is the route of entry for the fungus, or indirectly, when the infection has spread from a deeper focus. These cutaneous signs are often the only clue to the presence of a potentially fatal infection. As with the subcutaneous mycoses, early diagnosis and treatment is important, but in this case, even more so.

Cutaneous Involvement in the Deep Mycoses: A Literature Review. Part I-Subcutaneous Mycoses. / Afectación cutánea en las micosis profundas: una revisión de la literatura. Parte 1: micosis subcutáneas.

The deep mycoses are uncommon in our setting. These fungal infections occur mainly in immunosuppressed patients or in tropical climates, and include subcutaneous infections and systemic infections. The skin is always involved in the former. In the first part of this review, we describe the main subcutaneous mycoses: sporotrichosis, chromoblastomycosis, mycetoma, phaeohyphomycosis, hyalohyphomycosis, and lacaziosis. Early recognition and treatment is important, as these infections are frequently associated with high morbidity.

Sporotrichosis: an update.

Sporotrichosis is the most frequent and worldwide distributed subcutaneous mycoses. The aim of this article is to review the most recent aspects of sporotrichosis about its epidemiology, etiologic agents, mycologic characteristics, clinical features, diagnosis and treatment. The causative agents of sporotrichosis belong to five well defined species of dimorphic fungi of the called Sporothrix schenckii complex. Sporotrichosis and its etiologic agents have specific endemic areas, but it is possible to find epidemics of the disease in practically every continent, the entrance via is cutaneous due to the inoculation of the fungi into the skin after a traumatism and less frequent due to respiratory way. Clinical manifestations are widely variable, with important involvement of the skin and the superficial lymphatic system, but also with affection of the mucosa and some organs like lungs, bones and joints. Nowadays sporotrichosis is considered a true zoonosis with important changes related to the endemic areas and the ecologic features of the causative pathogens. The therapy of choice is the potassium iodide (KI), but other alternatives are itraconazole, terbinafine, thermotherapy and in severe cases amphotericin B. The importance of the recognition of the clinical manifestations of the disease in some non-endemic areas helps to challenge the diagnosis and give an accurate therapy.

Rhinocladiella aquaspersa, proven agent of verrucous skin infection and a novel type of chromoblastomycosis.

We report a case of chromoblastomycosis which resembled sporotrichosis due to the presence of warty nodules and lymphatic distribution on the forearm in a 56-year-old male. Mycological and histopathological investigation of exudates and biopsy tissue samples revealed a granulomatous lesion with muriform cells, the hallmark of chromoblastomycosis. The infection showed only localized expansion with verrucous plaques suggesting a new clinical type of the disease. The causative agent was identified as Rhinocladiella aquaspersa. This case prompted a study of the clinical spectrum of R. aquaspersa, through which we identified a second case caused by this fungus in a 62-year-old Brazilian female. The case was unusual in that R. aquaspersa exhibited hyphae rather than muriform cells in tissue. Given the difficulties treating chromoblastomycosis and other infections caused by melanized fungi, we evaluated the in vitro activities of extended-spectrum triazoles, amphotericin B, and echinocandins against these clinical isolates of R. aquaspersa. Itraconazole (MIC; 0.063 mg/l) and posaconazole (MIC; 0.125 mg/l) had the highest in vitro activities, while voriconazole and isavuconazole had somewhat lower activities (MICs; 2 mg/l) against the isolates. Amphotericin B and anidulafungin each had an MIC of 1 mg/l, whereas the MIC of caspofungin was 8 mg/l.