From the Guidelines
A granulomatous disease is a condition characterized by the formation of nonnecrotizing granulomatous inflammation in one or more tissue samples, as noted in the diagnosis of sarcoidosis 1. Granulomatous diseases can affect multiple organ systems and are often caused by persistent pathogens, autoimmune reactions, or unknown factors. Common examples include sarcoidosis, tuberculosis, and Crohn's disease. In granulomatous diseases, the immune system attempts to wall off substances it perceives as foreign but cannot eliminate, leading to the formation of granulomas, which can interfere with normal organ function if they become numerous or large enough. The specific symptoms and treatment of granulomatous diseases vary depending on the underlying cause and affected organs, but they often involve long-term management to control inflammation and prevent tissue damage, as seen in the diagnosis and detection of sarcoidosis 1. Key features of granulomatous diseases include the presence of well-formed, concentrically arranged layers of immune cells, most prominent being the central core of macrophage aggregates and multinucleated giant cells, as well as an outer layer of loosely organized lymphocytes, mostly T cells. The differential diagnosis of granulomatous diseases is broad and includes conditions such as berylliosis (chronic beryllium disease), which can present with similar histological features. Therefore, the diagnosis of a granulomatous disease requires a combination of clinical presentation, histological evaluation of tissue granulomas, and exclusion of alternative causes of granulomatous disease 1. Some of the key points to consider when diagnosing granulomatous diseases include:
- The presence of nonnecrotizing granulomatous inflammation in one or more tissue samples
- The exclusion of alternative causes of granulomatous disease
- The clinical presentation and symptoms of the disease
- The histological features of the granulomas, including the presence of well-formed, concentrically arranged layers of immune cells. Overall, granulomatous diseases are complex conditions that require careful diagnosis and management to control inflammation and prevent tissue damage 1.
From the Research
Definition of Granulomatous Disease
A granulomatous disease is characterized by the formation of granulomas, which are clusters of immune cells that can be formed in reaction to infection or other stimuli [ 2 ]. These structures can display signs of necrosis, such as in tuberculosis, or can be non-caseating, as seen in several immune disorders like sarcoidosis, Crohn's disease, and common variable immunodeficiency [ 2 ].
Characteristics of Granulomas
Granulomas are organized aggregates of macrophages, often with characteristic morphological changes, and other immune cells [ 3 ]. They form in response to persistent particulate stimuli, which can be infectious or non-infectious, that individual macrophages cannot eradicate [ 3 ]. The granulomatous response unfolds in a stepwise program characterized by a series of macrophage activations and transformations that recruit additional cells and produce structural changes [ 3 ].
Types of Granulomatous Diseases
Granulomatous diseases can be classified into infectious and non-infectious types [ 4 ]. Infectious granulomas usually reveal necrosis and abscess, while non-infectious ones occasionally also reveal necrosis [ 4 ]. Examples of granulomatous diseases include:
- Sarcoidosis [ 2 , 4 , 5 ]
- Crohn's disease [ 2 ]
- Common variable immunodeficiency [ 2 ]
- Farmer's lung [ 4 ]
- Hot tub lung [ 4 ]
- Granuloma annulare [ 5 ]
Pathogenesis of Granulomatous Diseases
The pathogenesis of granulomatous diseases is still poorly understood, but it is thought to involve a complex interplay between immune cells, cytokines, and other factors [ 2 , 3 , 6 ]. Different cytokines, such as IL2, interferon gamma, TNF alpha, 1,25(OH)2D3, and IL1, have been identified as mediators involved in the formation and maintenance of granulomas [ 6 ].