Introduction:
A granuloma is a group, lump, or cluster of white blood cells and tissues. It is a focal aggregate of immune cells formed in response to inflammation. The granulomas are found in the skin and lungs. The granuloma starts with inflammation, such as a foreign body or infectious pathogen. Granulomas are chronically inflamed areas characterized by a collection of macrophages.
What Are Granulomas?
Granulomas are non-cancerous conditions (benign). They are frequently found in the lungs, skin, head, and other body parts. Granulomas act as a defensive mechanism against the antigens that trigger the body. Common causes are inflammatory conditions like sarcoidosis, histoplasmosis, tuberculosis, and irritants foreign to the body.
What Is the Pathophysiology of Granulomas?
Granulomas are the local formation of macrophages and lymphocytes due to a chronic inflammatory reaction against an infection.In response to inflammation, the monocytes are converted into macrophages.
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Macrophages are advanced when compared to neutrophils. Macrophages deal the bacterial antigens differently compared to neutrophils. The macrophages have the advanced capacity to kill or bring the bacteria out of the bacterial structure and process the antigens. They engulf bacteria The activated macrophages transform into an epitheloid appearance with a flattened cell shape and ovoid nuclei. Many macrophages fuse to produce multinucleated giant cells (Langerhans cells). Tubercular granulomas frequently become necrotic.
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The macrophages that move under the skin are called Langerhans cells. The macrophages undergo multiple changes in the granuloma. When the granulomas mature, the cells become necrotized. The necrotic area has a cheese-like macroscopic appearance.
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The granuloma appears in response to a foreign body or infectious pathogen. Additionally, macrophages move to the inflammatory site, and chronic inflammation develops. The macrophages develop a tight aggregate surrounding the inflammatory stimulus and are surrounded by a cuff of lymphocytes.
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The inflammatory focus is called a granuloma. The infectious stimuli are parasites, Mycobacteria, schistosomiasis, and fungi.
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The non-infectious causes are neoplasia (cancer), an autoimmune condition, and foreign bodies. The granulomas are made up of macrophages and epithelioid cells.
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The epitheloid cells are derived from activated macrophages in the granuloma's center. CD4+ T-lymphocytes in the center form it, and its peripheral area is populated with CD8+ T-lymphocytes. Different cytokines form granulomas such as interleukin 2, interferon-gamma, TNF alpha, and interleukin1.
What Are the Causes of Granulomas?
Granulomas are caused due to infections. Infections form caseating granulomas. It is found in fungal infections and tuberculosis. Noncaseating granulomas are formed by inflammatory conditions such as Crohn's disease and sarcoidosis. Certain diseases cause granulomas. Granulomatous disease is an inherited genetic mutation that reduces the ability of the white cells to kill certain bacteria and fungi such as Aspergillus and Staphylococcus aureus. Chronic granulomatous disease leads to granuloma development throughout the body.
How Do Granulomas Form?
Granulomas are formed when the immune system reacts to infection and foreign objects. The macrophages take up the antigen produced by the pathogen (bacteria or fungi). The macrophages present the antigen on the major histocompatibility complex class II to the CD4+ helper T cells.
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It produces cytokines that result in the conversion of CD4+ helper T-cells to the TH1 subtype. The T-helper cells 1 secrete cytokine. The interleukin 2 and interferon-gamma release activates the macrophages.
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Tumor necrosis factor is released by the macrophages and T lymphocytes that stimulate the macrophages leading to the accumulation of inflammatory cells. During this process, the macrophages begin to resemble epithelial cells called epithelioid cells. Multiple macrophages fuse to form multi-nucleated cells. These giant cells (multinucleated cells) pack together to form granuloma.
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The tuberculosis granuloma is formed by the host’s immune response to the Mycobacterium tuberculosis infection. The innate and adaptive immune cells are formed in response to infected macrophages.
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The infected macrophages trigger the migration of uninfected macrophages to the site of infection to contain the bacteria (Mycobacterium tuberculosis). The caseous granulomas are formed by epitheloid macrophages surrounding the necrotic central portion with a rim of T and B lymphocytes.
What Are the Types of Granulomas?
There are two types of granulomas called caseating and non-caseating granulomas. The central region of granuloma appears ‘cheese-like’ and is called the caseating granuloma. The caseating granulomas form in the lungs in tuberculosis and fungal infections. The non-caseating granulomas do not have necrosis in the center area. They occur more commonly in response to foreign material. It is found in conditions such as sarcoidosis and Crohn’s disease. Sarcoidosis is a non-infectious disease that causes multiple granulomas in different body parts. Crohn's disease is an inflammatory bowel disease. The different types of granulomas are:
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Foreign Body Granulomas - When a foreign body penetrates the skin or other body parts, it leads to foreign body granuloma. The causes of foreign body granulomas are spider bites, bee stings, irritating substances like silica or tattoo links, and stitches.
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Skin Granulomas - Granuloma annulare is a skin condition. It forms bumps beneath the skin. The bumps are pink or flesh-colored. They occur in fingers, feet, hands, elbows, and legs. It is called localized granuloma annulare.
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Subcutaneous Granuloma Annulare - It is a single lump present beneath the skin. It is present mostly in children than adults. They appear on the scalp, legs, and arms.
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Linear Granuloma - The lumps develop in the line of the fingers.
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Perforating Granuloma Annulare- It causes lumps with yellow centers and contains clear liquid leaking from the lumps before they crust. The perforating granuloma annulare creates a scar.
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Internal Granulomas - They occur inside the body. They affect the gut, lungs, and blood vessels. Autoimmune conditions such as sarcoidosis and Crohn’s disease cause internal granulomas.
How Can Granulomas Be Diagnosed?
The diagnosis depends on the location of the granulomas. The tests include blood and imaging tests such as X-rays and CT scans. Genetic tests and needle biopsies are done. The scan will show images of minute granulomas in organs such as the lungs. The doctor might do a physical examination in the case of skin granulomas.
What Is the Treatment for Granulomas?
Granulomas are treated with medications that target the underlying inflammation. The individual is tested for tuberculosis before initiating the treatment. Because the TB bacteria stored within the granuloma can be released when treated with anti-TNF medications. So if the patient is tested for tuberculosis, anti-tubercular drugs such as Rifampin, Isoniazid, Ethambutol, and Pyrazinamide are given. Anti-inflammatory sarcoidosis is treated with anti-inflammatory corticosteroids.
Conclusion:
Granulomas are small, round nodules that form when immune cells cluster together in response to an infection, inflammation, or foreign substance that the body is unable to eliminate. These nodules are typically composed of macrophages, which are a type of white blood cell that engulfs and digests foreign substances, as well as other immune cells such as lymphocytes and plasma cells. So the granulomas can develop anywhere in the body and are non-cancerous. Generally, the underlying condition is treated to cure the granulomas. They are part of the body’s natural defense mechanism. They go away on their own if there are no underlying conditions.
