Have you ever heard of sarcoidosis? Did you know that it is a disease of unknown cause? Sarcoidosis is a condition that occurs worldwide with highly variable statistics. It predominantly affects the lungs, but in general, it can involve any organ.
What Is Sarcoidosis?
Sarcoidosis is a multisystem disease (affecting multiple tissues) characterized by the development of granulomas (Spagnolo, 2018).
A granuloma is a small tumour or tissue collection of inflammatory nature usually composed of immune system cells such as macrophages, lymphocytes and Langhans giant cells (Yeldandi, 2016).
In sarcoidosis, these granulomas can be in any organ, but most frequently in the lungs, where they are in more than 90% of cases. The lymph nodes are also a target in sarcoidosis, but to a lesser extent than the lungs (James, 2018).
What Is Known So Far About The Cause(s) Of Sarcoidosis?
Researchers currently believe that sarcoidosis is caused by an inflammatory response to an environmental antigen (triggers) in a genetically susceptible person.
Let us recall the basic immunological principles. When a genetically susceptible individual has contact with an external agent for the first time, an immune activation arises without clinical reaction. Progressively, as there are more exposures, there will be more activation of the immune system until symptoms show. Something similar occurs in sarcoidosis.
An antigen is a substance that causes an unbalanced immune reaction that damages body tissues once several exposures. The antigen is the main trigger of the immune response.
Pulmonary sarcoidosis is a highly orchestrated immune response involving sequential antigen-driven CD4 T-cell activation, chemokine-driven recruitment of T cells to the lung, local accumulation of macrophages and, consequently, granuloma formation (Patterson, 2018).
One of the hypotheses about the genesis of sarcoidosis is the one that talks about autoimmunity (Patterson, 2018).
The autoimmunity hypothesis says that in patients with sarcoidosis, the reactivity of lymphocytes has been found against a protein called vimentin in the body.
Another hypothesis talks about the relationship between sarcoidosis and microorganisms. According to several studies, sarcoidosis may arise on the face of exposure to insecticides, mold, central home air conditioning, and birds, possibly representing contact with microbe-rich environments (Patterson, 2018).
Other proposed triggers include
- Propionibacterium acnes and mycobacteria (potentially Mycobacterium tuberculosis)
- Certain unidentified substances present in workplaces with musty odours
- Pesticides
Some studies also support the genetic hypothesis because it has been found that there is a higher rate of sarcoidosis in monozygotic twins than dizygotic twins, higher prevalence among first- or second-degree relatives, and a fivefold increase in the relative risk of developing it in siblings of patients who have sarcoidosis. However, the cause is still unknown, and investigations are ongoing.
Pulmonary Sarcoidosis
Sarcoidosis involves the lungs in 90% of cases, and the severity can range from only abnormal radiographic findings to chronic progressive disease that does not respond to treatment.
The disease is usually diagnosed through radiological tests and clinical symptoms. Something that increases the probability of diagnosis is the presence of non-caseating granulomas (Spagnolo, 2018)
Non-caseating granulomas are nodular formations (rounded) of inflammatory nature mainly formed by macrophages and lymphocytes (Butt, 2011). Only the biopsy can confirm its evidence to establish the diagnosis.
Bronchoscopy (and its ancillary sampling techniques) is the most efficient diagnostic method for sampling the lungs to see the granulomas -unless other more accessible sites (i.e., superficial lymph nodes, conjunctiva, or skin)-.
Diagnostic procedures at bronchoscopy include sampling the airways (endobronchial biopsy), lung parenchyma (transbronchial lung biopsy), or intrathoracic lymph nodes (Spagnolo, 2018).
This sampling can also be guided through ultrasound (endosonography), especially to have relevant and decisive information about the characteristics of the lymph nodes. However, a complication to be taken into account during this procedure is mediastinitis (infection of the sampled nodes) (Spagnolo, 2018).
Sarcoidosis Clinical Outcomes
The forms in which sarcoidosis arises are very varied and can even occur in different syndromes; Löfgren syndrome, Heerfordt syndrome, and Blau syndrome.
Löfgren’s syndrome manifests as a triad of acute polyarthritis, erythema nodosum and hilar adenopathy. It often causes fever, malaise and uveitis and sometimes parotitis.
Heerfordt syndrome exhibits inflammation of the parotid gland, uveitis, and chronic fever and, less frequently, facial nerve palsy. Both Löfgren’s syndrome and Heerfordt’s syndrome may disappear spontaneously.
Blau syndrome is usually confusing because it is unclear whether it is caused by sarcoidosis or related to adult sarcoidosis. It affects children and also disappears spontaneously.
In addition to these syndromes, sarcoidosis may have nonspecific symptoms or even no symptoms at all (asymptomatic).
Nonspecific symptoms may include shortness of breath (dyspnea), cough, chest discomfort and crackles. Fatigue, malaise, weakness, anorexia, weight loss and low-grade fever are also common. However, not all of these symptoms need to arise simultaneously to speak of sarcoidosis; only fever may be present in some cases.
Severe Pulmonary Sarcoidosis
When progressive inflammation attacks the lungs, normal lung function may be expected in the early stages of the disease. However, once the disease progresses, there is a significant restriction in carbon monoxide flow, airflow obstruction, and injury in the lining of the lungs (mucous membranes).
Gradually, pulmonary function decreases with increased work of breathing expressed as breathing problems with effort desaturation on pulse oximetry.
Disease Monitoring and Prediction of Prognosis
Follow-up of pulmonary sarcoidosis is an evaluation that requires assessment of serial changes in symptoms, pulmonary function, and imaging, although the optimal means of quantifying these changes is unclear.
Progressive worsening of exceptional dyspnea and exercise tolerance, for example, could be due to extra pulmonary disease, especially when imaging and lung function shows no substantial change. In contrast, slowly progressive lung disease may not be followed by symptomatic worsening, especially in patients with relatively preserved lung function.
Imaging, specifically baseline chest computed tomography (CT), plays a crucial part in predicting the prognosis in patients with pulmonary sarcoidosis. Changes in lung function correlated more closely with morphologic changes defined by serial high-resolution chest CT than with the extent of disease evident on radiographs (Spagnolo, 2018). To date, sarcoidosis etiology remains an enigma, but researchers are getting closer. With a clear etiology, physicians can target therapeutic approaches precisely and with a higher probability of success.
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LITERATURE CITED:
Butt, S., Alzebdeh, R., Kable, T. D., & Soubani, A. O. (2011). Non-caseating granulomas in patients after the diagnosis of cancer: clinical characteristics and outcome. Sarcoidosis, Vasculitis, and Diffuse Lung Diseases, 28(1), 44–49.
Iannuzzi, M. C. (2019, February). Sarcoidosis. Retrieved June 16, 2021, from MSD Manuals website: https://www.msdmanuals.com/professional/pulmonary-disorders/sarcoidosis/sarcoidosis
James, W. E., Koutroumpakis, E., Saha, B., Nathani, A., Saavedra, L., Yucel, R. M., & Judson, M. A. (2018). Clinical features of extrapulmonary sarcoidosis without lung involvement. Chest, 154(2), 349–356.
Patterson, K. C., & Chen, E. S. (2018). The pathogenesis of pulmonary sarcoidosis and implications for treatment. Chest, 153(6), 1432–1442.
Spagnolo, P., Rossi, G., Trisolini, R., Sverzellati, N., Baughman, R. P., & Wells, A. U. (2018). Pulmonary sarcoidosis. The Lancet. Respiratory Medicine, 6(5), 389–402.
Yeldandi, A. V. (2016, January 28). Pathology of Pulmonary Infectious Granulomas. Retrieved June 16, 2021, from Medscape website: https:/https://emedicine.medscape.com/article/2078678-overview
