Sarcoidosis is a chronic, multisystemic disease characterized by the formation of non-caseating, meaning non-necrotizing granulomas, which are nodules of chronically inflamed tissue in the lungs and lymph nodes. Less commonly, these granulomas can accumulate in the heart, kidneys, joints, eyes, liver, spleen, and skin.
Now, let’s quickly recap the physiology of the immune system. So, normally, the cells of the immune system are ready to spot and destroy any foreign pathogens that could harm the body. Some cells that help with this are called macrophages. When these cells come in contact with a pathogen, they latch onto it and then engulf or swallow it. The macrophage then breaks down the pathogen, presents a piece of it, called an antigen, to its surface, and carries it to a lymph node. That’s where macrophages find other immune cells called T-helper lymphocytes, which recognize and bind to the antigen, and start proliferating.
Proinflammatory cytokines, or signaling molecules, like tumor necrosis factor alpha, or TNF-ɑ for short, are then released by macrophages to help activate the helper T-cell and it begins to divide or proliferate. The new T-cells leave the lymph node and start secreting other cytokines that recruit more immune cells like additional T-cells and macrophages.
Okay, now, the exact cause behind sarcoidosis is still unknown, but there are several risk factors that can be grouped into modifiable and non-modifiable ones. Modifiable risk factors include exposure to mold, silica, or pesticides, whereas non-modifiable risk factors include age between 20 and 60 years, being assigned female at birth, and family history of pulmonary sarcoidosis. Clients who are of Black race or Northern European descent are also at a higher risk of developing pulmonary sarcoidosis.
Now, the pathology of pulmonary sarcoidosis starts with an antigen entering the body. This antigen gets picked up by macrophages, which secrete cytokines that attract other immune cells, in addition to activating T helper cells. As more and more immune cells gather at a particular spot, they form small nodules, called granulomas, that have T cells on the periphery and macrophages in the center.
Oftentimes, macrophages fuse together to form a single large multinucleated cell called a Langhans giant cell. The granulomas in sarcoidosis are noncaseating, which means the tissue at the center of the granuloma doesn’t necrose and turn into a yellow-greyish substance, unlike some other granulomatous diseases like tuberculosis. With time, these non-caseating granulomas accumulate in the lungs or other organs, damaging their structure and affecting their function. Granulomas often also form in the lymph nodes causing them to enlarge.
When granulomas form in the heart, it can lead to arrhythmias; in the kidneys, it can lead to kidney stones and reduced kidney function; in the joints, it can cause arthritis; and in the eyes, it can result in uveitis, or inflammation of the pigmented layer of the eye beneath the cornea and sclera. Sarcoid granulomas can also develop in the liver and spleen, causing them to enlarge, or it can develop in the skin, causing a variety of cutaneous lesions such as papules and nodules. Vitamin D dysregulation is common, which can result in hypercalcemia, ultimately leading to kidney stones or osteoporosis. Finally, the most serious complications of sarcoidosis include pulmonary fibrosis, leading to pulmonary hypertension, cor pulmonale, and right ventricular failure, as well as malignant cardiac arrhythmias and sudden cardiac death.
Other clinical manifestations of sarcoidosis depend on the involved organ and may include palpitations, syncope, flank pain, joint pain or swelling, vision changes such as photophobia, floaters, and blurry vision, as well as hepatomegaly, and splenomegaly. Finally, maculopapular lesions can be present on the neck, chin, nose, eyelids, and lips, as well as the torso or extensor surfaces of the arms. Clients can also develop painful nodules on the lower legs, along the tibias.
The diagnosis of sarcoidosis starts with the client's history and physical assessment, followed by a chest X-ray and CT scan, which typically show bilateral hilar lymph node enlargement. Pulmonary function tests can be also performed to look for decreased lung function. Additional diagnostic tests can be used to detect the involvement of other organs, and these tests include complete blood count, liver and kidney function tests, serum creatinine, serum and urinary calcium, as well as an ECG, which can show atrioventricular blocks, or atrial or ventricular arrhythmias. Finally, biopsies can be taken from lymph nodes, skin lesions, or the lacrimal glands.