Differential Diagnosis of Sarcoidosis by Bronchoscopy

Most people with sarcoidosis have pulmonary sarcoidosis, which may present with shortness of breath, night sweats and a dry cough. It may also be accompanied by fever, painful joints, rashes and clusters of red blood cells under the skin in the form of nodules, known as erythema nodosum.

After extensive blood and urine tests and X-rays, these symptoms narrow the range of possible diseases from several thousand to the most typical possibilities.

To confirm sarcoidosis with confidence and exclude lymphoma, tuberculosis and other diseases, so that appropriate treatment can be provided, it is necessary to examine fluid obtained by washing the airways with saline. Analysis of the washed fluid can confirm the diagnosis.

This sampling procedure is called bronchoalveolar lavage (BAL) and is performed during bronchoscopy.

BAL is essential for accurate diagnosis and successful treatment.

Although the procedure may appear invasive, experienced doctors can perform it safely and successfully. I relaxed and tried to move with the instrument. By offering as little resistance as possible, the examination became easier. It is important to think positively and recall pleasant memories.

The lavage sample is sent to a laboratory.

Results that support a diagnosis of sarcoidosis show a CD4/CD8 ratio greater than 3.5.

CD4 and CD8 are types of white blood cells, specifically T lymphocytes. CD4 cells (also called CD4+ T cells) are white blood cells that fight infections. Research suggests that they precede activation of CD8+ cells, which help destroy pathogen-infected cells.

CD8 cells release a cytotoxin into an infected cell, killing it; macrophages then break down the remains through a process called phagocytosis. This is why CD8 cells are called cytotoxic cells.

These cytotoxic T cells can kill any cell containing such pathogens by recognising foreign peptides presented on the cell surface bound to class I MHC molecules.

MHC molecules present antigens through macrophages or dendritic cells.

CD4+ cells perform multiple functions. They fight infection by activating cells of the innate immune system, B lymphocytes, cytotoxic CD8 cells and non-immune cells, and they play a key role in suppressing the immune response.

In more complex cases, when the differential diagnosis is unclear, a granuloma biopsy may be performed.

The procedure is called EBUS-TBNA (endobronchial ultrasound with real-time transbronchial needle aspiration).

The sample can show clusters of B lymphocytes, T lymphocytes, macrophages and other cells involved in the inflammatory process—the granuloma.

Unlike T lymphocytes, B lymphocytes do not kill infected cells through cytotoxic activity. They surround and immobilise the pathogen and present it to other immune cells, which then attack it.

Lymphocytes call other immune cells for help by producing cytokines. Cytokines are small glycoproteins secreted not only by lymphocytes but also by macrophages, fibroblasts and monocytes. Because they regulate the immune response, they can be thought of as messengers.

Because cytokines strongly influence tissue damage, they play an important role in autoimmune diseases.

In sarcoidosis, specific T lymphocytes, Th1 and Th17, are involved, with inflammatory signalling involving cytokines IL-23 and IL-12. Sarcoidosis also involves members of the IL-12, IL-23, IL-27 and IL-35 cytokine families.

Sarcoidosis is characterised by non-caseating granulomas, typically consisting of a core of Th1 cells and activated macrophages surrounded by B cells, fibroblasts, CD8 lymphocytes, Th17 cells and T-regulatory cells.

Granulomas develop through stages of initiation, accumulation, the effector phase, and resolution or development of fibrosis.

The increased number of Th17 cells in BAL fluid, blood and granulomatous tissue from people with sarcoidosis suggests that these cells contribute to the pathogenesis of sarcoidosis.

Dino-Josip Ključarić

27 May 2024