Fatal miliary Coccidioidomycosis in a patient receiving infliximab therapy: a case report

A 78-year-old white male from Iowa in the United States of America receiving the anti- tumor necrois factor (TNF) agent infliximab therapy for rheumatoid arthritis developed a cheek ulcer which failed to respond to empiric antibiotic therapy. He subsequently presented with progressive respiratory failure from miliary coccidioidomycosis which proved fatal. The patient vacationed in Arizona 6 months previously and likely contracted the organism there as Iowa is not an endemic area for coccidioidomycosis. Respiratory failure from miliary infiltration is an uncommon presentation of coccidioidomycosis. Physicians should be aware of the importance of travel history and potential for life-threatening coccidioidomycosis in patients receiving tumor necrosis factor inhibitors

Manifestações cutâneo-mucosas da coccidioidomicose: estudo de trinta casos procedentes dos estados do Piauí e Maranhão Skin and mucous membrane manifestations of coccidioidomycosis: a study of thirty cases in the Brazilian states of Piauí and Maranhão

FUNDAMENTOS: A coccidioidomicose é micose sistêmica usualmente manifesta como infecção benigna de resolução espontânea; porém, uma pequena proporção dos infectados desenvolve quadros progressivos potencialmente fatais, podendo atingir a pele com lesões pleomórficas disseminadas. OBJETIVOS: Identificar e descrever as manifestações cutâneo-mucosas da coccidioidomicose, as ocupações de risco relacionadas à doença e o quadro clínico associado. MÉTODOS: Estudo realizado entre os anos 2003 e 2006 em 30 pacientes portadores de coccidioidomicose provenientes dos estados do Piauí e Maranhão e diagnosticados por exame microscópico direto, cultivo do escarro ou sorologia de triagem de imunodifusão dupla em gel de ágar, aliados à anamnese e exame físico. RESULTADOS: Identificaram-se lesões extrapulmonares em 13 casos (43,3%), com predomínio de manifestações dermatológicas de hipersensibilidade: eritema nodoso (26,6%), exantema com lesões eritemato-escamosas (26,6%) e eritema multiforme (23,3%), além de úlceras de língua (13,3%) e lábio (6,6%) e abscesso subcutâneo (3,3%). Tais manifestações foram observadas na fase aguda da doença. CONCLUSÕES: As manifestações cutâneas associadas à infecção respiratória aguda fortalecem a hipótese diagnóstica desta doença, especialmente, em caçadores de tatus ou pessoas expostas à escavação do solo.<br>BACKGROUND: Coccidioidomycosis is a systemic mycosis that usually presents as a benign infection. Patients generally recover spontaneously; however, a small proportion of infected individuals develop progressive complications that may affect the skin in the form of disseminated pleomorphic lesions and may become fatal. OBJECTIVES: To identify and describe skin and mucous membrane manifestations of coccidioidomycosis, to identify occupational hazards associated with the disease and to determine its associated clinical presentation. METHODS: A study conducted between 2003 and 2006 involving 30 patients from the Brazilian states of Piauí and Maranhão with coccidioidomycosis diagnosed by direct microscopy, sputum culture or screening serology using agar gel double immunodiffusion, in association with anamnesis and physical examination. RESULTS: Extrapulmonary lesions were found in 13 cases (43.3%), consisting predominantly of dermatological manifestations of hypersensitivity: erythema nodosum (26.6%), exanthema with erythematosquamous lesions (26.6%) and erythema multiforme (23.3%), as well as ulcerations of the tongue (13.3%), lip ulcers (6.6%) and subcutaneous abscess (3.3%). These manifestations were seen during the acute phase of the disease. CONCLUSIONS: Skin manifestations associated with an acute respiratory infection reinforce the hypothesis of a diagnosis of coccidioidomycosis, particularly in individuals who hunt armadillos or in those exposed to soil excavation

The Guanine Nucleotide Exchange Factor RIC8 Regulates Conidial Germination through Gα Proteins in Neurospora crassa

Heterotrimeric G protein signaling is essential for normal hyphal growth in the filamentous fungus Neurospora crassa. We have previously demonstrated that the non-receptor guanine nucleotide exchange factor RIC8 acts upstream of the Gα proteins GNA-1 and GNA-3 to regulate hyphal extension. Here we demonstrate that regulation of hyphal extension results at least in part, from an important role in control of asexual spore (conidia) germination. Loss of GNA-3 leads to a drastic reduction in conidial germination, which is exacerbated in the absence of GNA-1. Mutation of RIC8 leads to a reduction in germination similar to that in the Δgna-1, Δgna-3 double mutant, suggesting that RIC8 regulates conidial germination through both GNA-1 and GNA-3. Support for a more significant role for GNA-3 is indicated by the observation that expression of a GTPase-deficient, constitutively active gna-3 allele in the Δric8 mutant leads to a significant increase in conidial germination. Localization of the three Gα proteins during conidial germination was probed through analysis of cells expressing fluorescently tagged proteins. Functional TagRFP fusions of each of the three Gα subunits were constructed through insertion of TagRFP in a conserved loop region of the Gα subunits. The results demonstrated that GNA-1 localizes to the plasma membrane and vacuoles, and also to septa throughout conidial germination. GNA-2 and GNA-3 localize to both the plasma membrane and vacuoles during early germination, but are then found in intracellular vacuoles later during hyphal outgrowth