Ecology of Paracoccidioides brasiliensis, P. lutzii and related species: infection in armadillos, soil occurrence and mycological aspects.

Paracoccidioides brasiliensis and the related species P. americana, P. restrepiensis, P. venezuelensis, and P. lutzii (Ascomycota, Ajellomycetaceae) are the etiological agents of paracoccidoidoimycosis (PCM), one of the most important systemic mycoses in Latin America. They are dimorphic fungi, with a mycelial life cycle in soil and a yeast phase associated with tissues of mammalian hosts. This study aimed to detect Paracoccidioides spp. in armadillo tissues and associated soil samples in three well-defined geographic areas, including the Alta Floresta, an area not only endemic for PCM in the central region of Brazil but also of probable P. lutzii occurrence, whose ecology and geographic distribution are poorly elucidated. The isolates were genotyped by sequencing ITS-rDNA and the gp43-exon-2 region, and by PCR-RFLP of alpha tubulin (tub1) gene; mycological aspects such as yeast-to-mycelial transition, growth and conidial production in soil extract agar were also evaluated. We confirmed that while armadillos are highly infected by P. brasiliensis, including multiple infections by distinct genotypes or species (P. brasiliensis and P. americana) in the same animal, the same does not hold true for P. lutzii, which in turn seems to present less capacity for mycelial growth and conidial production, when developing in a soil-related condition.

Toxigenic profile of methicillin-sensitive and resistant Staphylococcus aureus isolated from special groups.

BACKGROUND: Staphylococcus aureus is characterized by its pathogenicity and high prevalence, causing disease in both healthy and immunocompromised individuals due to its easy dissemination. This fact is aggravated by the widespread dissemination of S. aureus carrying toxigenic genes. The objective of this study was to determine the toxigenic profile of methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in patients with purulent skin and/or soft tissue infections seen at the Dermatology Department of the University Hospital of the Botucatu Medical School, asymptomatic adults older than 60 years living in nursing homes, and prison inmates of the Avaré Detention Center. METHODS: PCR was used for the detection of the mecA gene, enterotoxin genes (sea, seb, and sec), exfoliative toxins A and B (eta and etb), toxic shock syndrome toxin 1 (tst), panton-valentine leukocidin (lukS-PV and lukF-PV), and alpha- and delta-hemolysins or cytotoxins (hla and hld). RESULTS: The results showed a significant prevalence of toxigenic genes among S. aureus isolates from asymptomatic individuals, with the observation of a higher prevalence of cytotoxin genes. However, the panton-valentine leukocidin gene was only detected in MSSA isolated from patients with skin infections and the tst gene was exclusively found in MSSA isolated from prison inmates. CONCLUSIONS: The present study demonstrated a significant prevalence of toxigenic genes in MSSA and MRSA strains isolated from asymptomatic S. aureus carriers. There was a higher prevalence of cytotoxin genes.

Paracoccidioidomycosis in patients with lymphoma and review of published literature.

This paper describes four new cases of lymphomas, two Hodgkin lymphomas and two non-Hodgkin lymphomas in patients with paracoccidioidomycosis. All had mycosis diagnosed before lymphomas with Paracoccidioides brasiliensis demonstrated in several lymph nodes, as seen in the disseminated form of the disease. When lymphoma was diagnosed, one patient was under regular paracoccidioidomycosis treatment and in clinic-serological remission for this disease, another was under regular treatment but with clinic-serological mycosis activity, one had abandoned paracoccidioidomycosis treatment 6 years earlier, and the other had not yet received any kind of antifungal drugs. Three patients received treatment for lymphomas with one remaining in remission until now, one achieving tumor remission which relapsed years later, and one having only residual lymphoma in bone marrow for a decade but clinically well. All three experienced paracoccidioidomycosis clinical remission, however, serology became negative just in one. Similar previously described cases were reviewed: five Hodgkin lymphomas, three non-Hodgkin lymphomas, and one described only as "lymphoma" without specifying type; a summary of their findings is presented. Finally, there is also a brief discussion on the possible pathophysiological mechanisms involved in the concomitance of these two disorders.

Clinical characterization, physical frailty, and depression in elderly patients with psoriasis from a reference center in Brazil: a cross-sectional study.

BACKGROUND: There are few studies dedicated to the characterization of the geriatric population with psoriasis, which has particularities in terms of clinical manifestations and therapeutic limitations. As psoriasis is a chronic disease, presenting a higher prevalence with age, the increase in life expectancy in Brazil demands knowledge about the behavior of the disease among the elderly. OBJECTIVES: To characterize elderly people with psoriasis from a tertiary service, from the clinical-epidemiological point of view, presence of comorbidities, physical frailty, and affective impact, and to compare these aspects with adults with psoriasis and elderly people without the disease. METHODS: Cross-sectional study of 64 elderly patients with psoriasis, 64 adults with psoriasis, and 64 elderly patients without the disease. Clinical-demographic aspects, the Beck depression scale, and Skindex-16 were evaluated. Indicators of physical frailty were evaluated in elderly patients: handgrip, sit-to-stand test, fatigue, and weight loss >5%. RESULTS: In the elderly, the mean age (SD) of psoriasis onset was 44 (10) years, men represented 47% of the sample, the prevalence of arthritis was 22%, and ungual involvement occurred in 72%. Topical corticosteroids were used more often among elderly people with psoriasis (100%) than among adults with the disease (86%), with no difference among other systemic treatments. Diabetes mellitus occurred in 30% of the elderly. Hypertension (59%), dyslipidemia (52%), depression (34%), and fatigue (59%) were more prevalent among the elderly with psoriasis than among the healthy controls. STUDY LIMITATIONS: The study was carried out in a public reference service for patients with psoriasis, all of which were undergoing treatment. CONCLUSIONS: Elderly people with psoriasis from a tertiary service showed greater affective impairment, metabolic comorbidities, and physical frailty than elderly controls.

Infections in the era of immunobiologicals.

Immunobiologicals represent an innovative therapeutic option in dermatology. They are indicated in severe and refractory cases of different diseases when there is contraindication, intolerance, or failure of conventional systemic therapy and in cases with significant impairment of patient quality of life. The main immunobiologicals used in dermatology basically include inhibitors of tumor necrosis factor-alpha (anti-TNF), inhibitors of interleukin-12 and -23 (anti-IL12/23), inhibitors of interleukin-17 and its receptor (anti-IL17), inhibitors of interleukin-23 (anti-IL23), rituximab (anti-CD20 antibody), dupilumab (anti-IL4/IL13) and intravenous immunoglobulin. Their immunomodulatory action may be associated with an increase in the risk of infections in the short and long term, and each case must be assessed individually, according to the risk inherent to the drug, the patient general condition, and the need for precautions. This article will discuss the main risks of infection associated with the use of immunobiologicals, addressing the risk in immunocompetent and immunosuppressed patients, vaccination, fungal infections, tuberculosis, leprosy, and viral hepatitis, and how to manage the patient in the most diverse scenarios.

Intestinal microbiome characterization of adult Brazilian men with psoriasis compared to omnivore and vegetarian controls.

BACKGROUND: Psoriasis is a chronic inflammatory disease associated with systemic inflammation and comorbidities. Changes in the composition of the intestinal microbiome are involved in the pathogenesis of inflammatory diseases and metabolic syndrome. Characterizing the intestinal microbiome of patients with psoriasis may be relevant for the understanding of its clinical course and comorbidity prevention. OBJECTIVE: To characterize the intestinal microbiome of men with psoriasis compared to omnivore and vegetarian controls (without psoriasis). METHOD: Cross-sectional study of 42 adult males: 21 omnivores with psoriasis; and controls: 14 omnivores and 7 vegetarian individuals. The characterization of the intestinal microbiome was performed by metagenomic analysis. Serum levels of lipopolysaccharide-binding protein (LPB) and C-reactive protein (CRP) were evaluated. RESULTS: The groups differed from each other regarding nutritional aspects and microbiome; individuals with psoriasis had a higher consumption of protein and lower consumption of fibers. Levels of LPB, CRP, and the Firmicutes/Bacteroidetes ratio were higher in the group with psoriasis than in the vegetarian group (p<0.05). The genera Prevotella, Mogibacterium, Dorea, Bifidobacterium and Coprococcus, differed in the group with psoriasis compared to vegetarians; the genera Mogibacterium, Collinsella and Desulfovibrio differed from omnivores. A microbiome pattern linked to psoriasis (plsPSO) was identified, which was associated with higher LPB levels (rho=0.39; p=0.02), and lower dietary fiber intake (rho=-0.71; p<0.01). STUDY LIMITATIONS: Only adult men were evaluated. CONCLUSION: A difference was identified in the intestinal microbiome of adult men with psoriasis when compared to healthy omnivores and vegetarian controls. The identified microbiome pattern was correlated with dietary fiber intake and serum levels of LPB.

Paracoccidioidomycosis in a dog: case report of generalized lymphadenomegaly.

Paracoccidioidomycosis (PCM) is a severe systemic mycosis, endemic in Latin America and highly prevalent in Brazil, where it ranks eighth as a mortality cause among infectious and parasitic diseases in humans. The disease in animals has been little explored. It is observed that armadillos can harbor the fungus at high frequencies, although the active disease has not been well documented in this wild mammal. Dogs are susceptible to experimental infection, and the naturally acquired PCM-disease was reported only recently in a dog from Brazil. The present work reports the second case of naturally acquired PCM in a 6-year-old female dog that presented emaciation, lymphadenomegaly, and hepatosplenomegaly. Biochemical and pulmonary radiographic evaluation did not reveal any abnormalities. PCM was diagnosed by clinical findings, culturing, immunohistochemistry, and histopathology of popliteal lymph node. The fungus was recovered from popliteal lymph node, and the molecular analysis showed respective sequencing similarities of 99 and 100% for 803 nucleotides of the Gp43 gene and 592 nucleotides from the ITS-5.8S region of Paracoccidioides brasiliensis. Immunohistochemistry revealed severe lymphadenitis and presented numerous yeasts, which reacted against the gp43 antibody. Histopathology revealed a severe granulomatous lymphadenitis associated with numerous single or multiple budding yeasts. After diagnosis, the dog was successfully treated with itraconazol for 2 years. Veterinarians should be aware of the importance of considering PCM for differential diagnosis, especially in dogs from PCM-endemic areas, whose monophagocytic system involvement is evident.

Blastoid mantle cell lymphoma: cutaneous infiltration.

Mantle cell lymphoma is an aggressive B-cell, non-Hodgkin's lymphoma, with lymph node or extranodal origin, and a mean survival of three to five years. Skin involvement is rare, secondary and indicates neoplasia dissemination. The authors report a case of a female patient, 69 years old, diagnosed previously, after lymph node and bone marrow biopsy. She was undergoing the second chemotherapy regimen when she showed infiltrated plaque-like lesions, nodules and tumors on the trunk and thigh root. Histopathology and immunohistochemistry demonstrated cutaneous infiltration of the blastoid lymphoma.

Disseminated paracoccidioidomycosis in a liver transplant patient.

Paracoccidioidomycosis is an endemic systemic mycosis caused by Paracoccidioides brasiliensis complex and P. lutzii. It is a rare disease in non-HIV-induced immunosuppressed individuals. In organ transplant recipients, it is more frequently associated with immunosuppression after kidney transplantation. In a liver transplant patient, only one case has been published in the literature to date. The present report comprises the case of a 47-year-old female patient with disseminated skin lesions associated with signs and symptoms of systemic involvement of paracoccidioidomycosis that manifested one year after liver transplantation and under an immunosuppression regimen with tacrolimus and mycophenolate mofetil.

Paracoccidioidomycosis: an unusual presentation in a young girl disclosing an unnoted HIV-infection.

The association of paracoccidioidomycosis with AIDS is apparently less frequent than expected. The authors present an unusual case of paracoccidioidomycosis in a 13-year-old female student which was later found to be the first opportunistic infection in the course of the patient's HIV-infection. The clinical presentation followed an accidental incised wound on the palmar region initially described as a 'sporotrichotic-chancre'. After good response under sulfamethoxazole-trimethoprin, the patient relapsed and presented an associated oral candidiasis. HIV-infection was documented and additional investigation showed CD4(+) T-cells=22/mm(3), CD8(+)=280 cell/mm(3) and viral load=4,043 log. This case report presents an uncommon dermatological-clinical picture in the youngest patient in which such association has been reported to date.

Fungal infections of the mucous membrane.

A clinical review of three potentially severe fungal diseases, which are characterized in many cases by mucosal involvement, is presented. They are paracoccidioidomycosis, histoplasmosis, and mucormycosis. Mucosal involvement for paracoccidioidomycosis and rhinocerebral mucormycosis is frequent. Thus, oral involvement may provide early clue for diagnosis. In paracoccidioidomycosis, the mucosal lesion classically shows superficial ulcers with granular appearance and hemorrhagic points, usually on lips, palate, and jugal mucosa. In mucormycosis, necrosis of the palate followed for purulent discharge is a hallmark of rhinocerebral disease. Treatment with amphotericin B desoxycholate or the new second-generation triazoles is highly efficacious.

Severe bacterial skin infections.

The severe bacterial diseases discussed herein are those that present dermatological lesions as their initial manifestations, for which the dermatologist is often called upon to give an opinion or is even the first to examine the patient. This review focuses on those that evolve with skin necrosis during their natural history, that is, necrotizing fasciitis, Fournier gangrene, and ecthyma gangrenosum. Notice that the more descriptive terminology was adopted; each disease was individualized, rather than being referred by the generic term "necrotizing soft tissue infections". Due to their relevance and increasing frequency, infections by methicillin-resistant Staphylococcus aureus (MRSA) were also included, more specifically abscesses, furuncle, and carbuncle, and their potential etiologies by MRSA. This article focuses on the epidemiology, clinical dermatological manifestations, methods of diagnosis, and treatment of each of the diseases mentioned.

Paracoccidioidomycosis: an uncommon clinical presentation.

Paracoccidoiomycosis is a systemic mycosis with a higher incidence in males with history of exposure to the rural environment; its classic clinical manifestation is an oro-pulmonary lesion. The authors report a case of a female, urban, 76-year-old patient with atypical clinical-dermatological presentation and diagnostic conclusion after histopathological examination. The clinical response was quick and complete after treatment with itraconazole 400mg/day in the first month, decreased to 200mg/day until the sixth month of treatment.

Disseminated tuberculosis associated with reactive arthritis of Poncet in an immunocompetent patient.

Cutaneous tuberculosis is a rare extrapulmonary manifestation of tuberculosis which, like disseminated tuberculosis, commonly occurs in immunocompromised patients. Poncet reactive arthritis is a seronegative arthritis affecting patients with extrapulmonary tuberculosis, which is uncommon even in endemic countries. We report a previously healthy 23-year-old male patient with watery diarrhea associated with erythematous ulcers on the lower limbs and oligoarthritis of the hands. Histopathological examination of the skin showed epithelioid granulomatous process with palisade granulomas and central caseous necrosis. AFB screening by Ziehl-Neelsen staining showed intact bacilli, the culture was positive for Mycobacterium tuberculosis, and colonoscopy revealed multiple shallow ulcers. Disseminated tuberculosis associated with reactive Poncet arthritis was diagnosed, with an improvement of the clinical and skin condition after appropriate treatment.

American tegumentary leishmaniasis: severe side effects of pentavalent antimonial in a patient with chronic renal failure.

Pentavalent antimonials are the first-line drug treatment for American tegumentary leishmaniasis. We report on a patient with chronic renal failure on hemodialysis who presented with cutaneous lesions of leishmaniasis for four months. The patient was treated with intravenous meglumine under strict nephrological surveillance, but cardiotoxicity, acute pancreatitis, pancytopenia, and cardiogenic shock developed rapidly. Deficient renal clearance of meglumine antimoniate can result in severe toxicity, as observed in this case. These side effects are related to cumulative plasma levels of the drug. Therefore, second-line drugs like amphotericin B are a better choice for patients on dialysis.

Clinical characterization, physical frailty, and depression in elderly patients with psoriasis from a reference center in Brazil: a cross-sectional study

Abstract Background: There are few studies dedicated to the characterization of the geriatric population with psoriasis, which has particularities in terms of clinical manifestations and therapeutic limitations. As psoriasis is a chronic disease, presenting a higher prevalence with age, the increase in life expectancy in Brazil demands knowledge about the behavior of the disease among the elderly. Objectives: To characterize elderly people with psoriasis from a tertiary service, from the clinical-epidemiological point of view, presence of comorbidities, physical frailty, and affective impact, and to compare these aspects with adults with psoriasis and elderly people without the disease. Methods: Cross-sectional study of 64 elderly patients with psoriasis, 64 adults with psoriasis, and 64 elderly patients without the disease. Clinical-demographic aspects, the Beck depression scale, and Skindex-16 were evaluated. Indicators of physical frailty were evaluated in elderly patients: handgrip, sit-to-stand test, fatigue, and weight loss >5%. Results: In the elderly, the mean age (SD) of psoriasis onset was 44 (10) years, men represented 47% of the sample, the prevalence of arthritis was 22%, and ungual involvement occurred in 72%. Topical corticosteroids were used more often among elderly people with psoriasis (100%) than among adults with the disease (86%), with no difference among other systemic treatments. Diabetes mellitus occurred in 30% of the elderly. Hypertension (59%), dyslipidemia (52%), depression (34%), and fatigue (59%) were more prevalent among the elderly with psoriasis than among the healthy controls.

Infections in the era of immunobiologicals

Abstract Immunobiologicals represent an innovative therapeutic option in dermatology. They are indicated in severe and refractory cases of different diseases when there is contraindication, intolerance, or failure of conventional systemic therapy and in cases with significant impairment of patient quality of life. The main immunobiologicals used in dermatology basically include inhibitors of tumor necrosis factor-alpha (anti-TNF), inhibitors of interleukin-12 and -23 (anti-IL12/23), inhibitors of interleukin-17 and its receptor (anti-IL17), inhibitors of interleukin-23 (anti-IL23), rituximab (anti-CD20 antibody), dupilumab (anti-IL4/IL13) and intravenous immunoglobulin. Their immunomodulatory action may be associated with an increase in the risk of infections in the short and long term, and each case must be assessed individually, according to the risk inherent to the drug, the patient general condition, and the need for precautions. This article will discuss the main risks of infection associated with the use of immunobiologicals, addressing the risk in immunocompetent and immunosuppressed patients, vaccination, fungal infections, tuberculosis, leprosy, and viral hepatitis, and how to manage the patient in the most diverse scenarios.