A 52-year-old woman is evaluated due to 2 weeks of fever, fatigue, nonproductive cough, and dyspnea, which began shortly after visiting her family in Ohio. She also lost 1.5 kg (3.3 lb) over the same period. The patient has a history of rheumatoid arthritis and has been taking adalimumab for the past 6 months. She had negative tuberculosis skin testing prior to beginning the drug. Temperature is 38 C (100.4 F), blood pressure is 130/70 mm Hg, pulse is 92/min, and respirations are 18/min. Physical examination reveals bilateral lung crackles, mild generalized lymphadenopathy, and hepatosplenomegaly. Chest x-ray shows bilateral nodular densities and hilar lymphadenopathy. Urine testing is positive for a fungal antigen. Which of the following pathogenic processes is most important during the development of this patient's infection?

Question

A 52-year-old woman is evaluated due to 2 weeks of fever, fatigue, nonproductive cough, and dyspnea, which began shortly after visiting her family in Ohio.  She also lost 1.5 kg (3.3 lb) over the same period.  The patient has a history of rheumatoid arthritis and has been taking adalimumab for the past 6 months.  She had negative tuberculosis skin testing prior to beginning the drug.  Temperature is 38 C (100.4 F), blood pressure is 130/70 mm Hg, pulse is 92/min, and respirations are 18/min.  Physical examination reveals bilateral lung crackles, mild generalized lymphadenopathy, and hepatosplenomegaly.  Chest x-ray shows bilateral nodular densities and hilar lymphadenopathy.  Urine testing is positive for a fungal antigen.  Which of the following pathogenic processes is most important during the development of this patient's infection?

Quizplus · Accepted Answer

11ec160b_3870_f1f9_9249_87cc685c605a_MD0001_00 This patient's rheumatoid arthritis is being treated with adalimumab, a tumor necrosis factor (TNF)-alpha inhibitor. TNF-alpha is a crucial cytokine of the cell-mediated immune response that aids in macrophage activation, phagolysosome function, and the formation and maintenance of granulomas. Blockade of TNF-alpha increases the risk of infection with pathogens controlled by the cell-mediated immune response such as intracellular bacteria (eg, Mycobacterium tuberculosis), viruses, and granulomatous fungi. This patient's pulmonary and reticuloendothelial (eg, lymphadenopathy, splenomegaly) findings and positive urine fungal antigen test raise strong suspicion for infection with Histoplasma capsulatum, a dimorphic fungus endemic to the Ohio and Mississippi River Valleys. H capsulatum is a mold that is inhaled from contaminated soil and converts to a yeast form in the lungs. Phagocytosis by alveolar macrophages does not result in destruction of the organism due to microbial virulence factors that prevent phagolysosome acidification. Therefore, for the first several weeks of infection, H capsulatum is able to proliferate within macrophages in an unchecked fashion. Eventually, the cell-mediated immune response controls the infection in most healthy patients. However, those with impaired immunity (as in this case) are at high risk for life-threatening disseminated disease. The lungs, reticuloendothelial system, and mouth (oral ulcers) are most commonly affected. Urine Histoplasma antigen testing is often used to quickly confirm the diagnosis. (Choice B) Aspergillus fumigatus is a monomorphic mold that can cause invasive disease in those who are immunocompromised. This organism is inhaled into the lungs and can invade the vascular endothelial lining, leading to dissemination through the bloodstream. However, patients usually have fever, chest pain, and hemoptysis. (Choice C) Candida species are part of the endogenous human flora, but overgrowth can occur in those with immunocompromisation and lead to mucocutaneous (eg, thrush) or invasive (pneumonia, fungemia) disease. Invasive Candida infections are generally diagnosed by blood culture or biopsy with histopathology, not urine antigen testing. (Choice D) Cryptococcus neoformans is a yeast with a thick, antiphagocytic, polysaccharide capsule that primarily causes infections in those who are immunocompromised (particularly patients with advanced AIDS). Although pulmonary infection can occur, disseminated disease is usually marked by meningoencephalitis (eg, headache, confusion, altered mental state). (Choice E) Malassezia is a dimorphic fungus that is part of normal skin flora. Conversion from yeast form to the pathogenic mycelial form results in tinea versicolor, which is associated with the characteristic spaghetti and meatballs appearance on microscopy (ie, both hyphae and yeasts seen). Educational objective: Tumor necrosis factor-alpha inhibitors are associated with impairments to the cell-mediated immune response and increase the risk of infection with intracellular bacteria and granulomatous fungi (eg, Histoplasma capsulatum). Histoplasma replicates within the intracellular space of macrophages and can spread from the lungs to the lymph nodes and the reticuloendothelial system (liver, spleen, bone marrow). __________ References: The calcified lung nodule: what does it mean? (http://www.ncbi.nlm.nih.gov/pubmed/20582171)

A 52-Year-Old Woman Is Evaluated Due to 2 Weeks of Fever