We present the case of a 70-year-old woman with a history of seronegative arthritis, recurrent pleural effusion and weight loss. A prior lung biopsy had revealed non-caseating epithelioid cell granulomas without evidence for microbial organisms on special stains. Intestinal biopsy findings where suspicious for Whipple’s disease, which was confirmed by PCR testing, both on the intestinal and retrospectively on the lung tissue. Treatment with ceftriaxone resulted in clinical deterioration with fever, arthritis and recurrent pleuritis consistent with immune reconstitution inflammatory syndrome. Dose increase of glucocorticoids and therapy rotation to doxycycline and hydroxychloroquine resulted in rapid clinical improvement.
Mycobacterium tuberculosis (Mtb) causes chronic granulomatous lung disease in humans. Recently, novel strategies such as host-directed therapeutics and adjunctive therapies that enhance the effect of existing antibiotics have emerged to better control Mtb infection. Recent advances in understanding the metabolic interplay between host immune cells and pathogens have provided new insights into how their interactions ultimately influence disease outcomes and antibiotic-treatment efficacy. In this review, we describe how metabolic cascades in immune environments and relevant metabolites produced from immune cells during Mtb infection play critical roles in the progression of diseases and induction of anti-Mtb protective immunity. In addition, we introduce how metabolic alterations in Mtb itself can lead to the development of persister cells that are resistant to host immunity and can eventually evade antibiotic attacks. Further understanding of the metabolic link between host cells and Mtb may contribute to not only the prevention of Mtb persister development but also the optimization of host anti-Mtb immunity together with enhanced efficacy of existing antibiotics. Overall, this review highlights novel approaches to improve and develop host-mediated therapeutic strategies against Mtb infection by restoring and switching pathogen-favoring metabolic conditions with host-favoring conditions.
Crohn’s disease is a chronic inflammatory bowel disease that can affect any part of the GI tract, which is frequently associated with extra-intestinal manifestations. Pulmonary parenchymal disease is very uncommon and usually considered to be debilitating and harder to diagnose. Pulmonary granulomas are rarely described in the literature as a complication of Crohn’s disease. Here, we present a patient with Crohn’s disease exacerbation who developed granulomatous lung disease under treatment with vedolizumab. Our case may add evidence to the emerging theory that gut-selective biologic agents could lead to upregulation of some pro-inflammatory factors leading to the evolution of pulmonary disease.
A 19-year-old boy presented with signs of a granulomatous lung disease. Sputum testing for tuberculosis was negative. After a year, he returned with generalised lymphadenopathy. Though a clinical diagnosis of tuberculosis was then made and treatment was commenced, a lymph node biopsy revealed Langerhans cell histiocytosis. We are not aware of any other such case described in the Pacific.
Understanding Metabolic Regulation Between Host and Pathogens: New Opportunities for the Development of Improved Therapeutic Strategies Against Mycobacterium tuberculosis Infection
