Pulmonary sarcoidosis is a disease belonging to the group of benign systemic granulomatoses, occurring with damage to the mesenchymal and lymphatic tissues of various organs, but mainly the respiratory system. Patients with sarcoidosis are concerned about increased weakness and fatigue, fever, chest pain, cough, arthralgia, skin lesions. In the diagnosis of sarcoidosis, chest x-ray and CT, bronchoscopy, biopsy, mediastinoscopy or diagnostic thoracoscopy are informative. With sarcoidosis, long-term treatment courses with glucocorticoids or immunosuppressants are indicated.
Pulmonary sarcoidosis (synonyms Beck’s sarcoidosis, Benier-Beck-Schaumann disease) is a polysystemic disease characterized by the formation of epithelioid granulomas in the lungs and other affected organs. Sarcoidosis is a disease mainly of young and middle-aged people (20-40 years old), more often female. The ethnic prevalence of sarcoidosis is higher among African Americans, Asians, Germans, Irish, Scandinavians and Puerto Ricans.
In 90% of cases, sarcoidosis of the respiratory system is detected with damage to the lungs, bronchopulmonary, tracheobronchial, intra-thoracic lymph nodes. Sarcoid lesions of the skin (48% – subcutaneous nodules, nodular erythema), eyes (27% – keratoconjunctivitis, iridocyclitis), liver (12%) and spleen (10%), nervous system (4-9%), parotid salivary glands (4-6%), joints and bones (3% – arthritis, multiple cysts of the finger phalanges of the feet and hands), heart (3%), kidneys (1% – nephrolithiasis, nephrocalcinosis) and other organs.
Causes of pulmonary sarcoidosis
Beck’s sarcoidosis is a disease with an unclear etiology. None of the theories put forward gives reliable knowledge about the nature of the origin of sarcoidosis. Followers of the infectious theory suggest that mycobacteria, fungi, spirochetes, histoplasm, protozoa and other microorganisms can serve as causative agents of sarcoidosis. There are research data based on observations of family cases of the disease and evidence in favor of the genetic nature of sarcoidosis. Some modern researchers associate the development of sarcoidosis with a violation of the body’s immune response to the effects of exogenous (bacteria, viruses, dust, chemicals) or endogenous factors (autoimmune reactions).
Thus, today there are grounds to consider sarcoidosis a disease of polyethological genesis associated with immune, morphological, biochemical disorders and genetic aspects. Sarcoidosis does not belong to contagious (i.e. contagious) diseases and is not transmitted from its carriers to healthy people. There is a definite trend in the incidence of sarcoidosis in representatives of some professions: workers of agriculture, chemical industries, healthcare, sailors, postal workers, millers, mechanics, firefighters due to increased toxic or infectious effects, as well as smokers.
As a rule, sarcoidosis is characterized by a multi-organ course. Pulmonary sarcoidosis begins with a lesion of the alveolar tissue and is accompanied by the development of interstitial pneumonitis or alveolitis, followed by the formation of sarcoid granulomas in the subpleural and peribronchial tissues, as well as in the interlobular furrows. In the future, the granuloma either resolves or undergoes fibrous changes, turning into a cell-free hyaline (vitreous) mass.
With the progression of pulmonary sarcoidosis, pronounced violations of the ventilation function develop, as a rule, according to the restrictive type. With compression of the bronchial walls by lymph nodes, obstructive disorders are possible, and sometimes the development of hypoventilation zones and atelectasis.
The morphological substrate of sarcoidosis is the formation of multiple granulomas from epitolioid and giant cells. Despite the external similarity with tuberculous granulomas, sarcoid nodules are not characterized by the development of caseous necrosis and the presence of mycobacterium tuberculosis in them. As sarcoid granulomas grow, they merge into multiple large and small foci. Foci of granulomatous accumulations in any organ disrupt its function and lead to the appearance of symptoms of sarcoidosis. The outcome of sarcoidosis is resorption of granulomas or fibrous changes in the affected organ.
Based on the X-ray data obtained during pulmonary sarcoidosis, three stages and their corresponding forms are distinguished.
Stage I (corresponds to the initial intra-thoracic lymphoid form of sarcoidosis) is a bilateral, often asymmetric increase in bronchopulmonary, rarely tracheobronchial, bifurcation and paratracheal lymph nodes.
Stage II (corresponds to the mediastinal-pulmonary form of sarcoidosis) – bilateral dissemination (miliary, focal), infiltration of lung tissue and damage to intra-thoracic lymph nodes.
Stage III (corresponds to the pulmonary form of sarcoidosis) – pronounced pneumosclerosis (fibrosis) of the lung tissue, there is no increase in intra-thoracic lymph nodes. As the process progresses, the formation of drain conglomerates occurs against the background of increasing pneumosclerosis and emphysema.
According to the clinical and radiological forms and localization, sarcoidosis is distinguished:
- Intra-thoracic lymph nodes (ITLN)
- of the Lungs and ITLN
- Lymph nodes
- Respiratory system, combined with damage to other organs
- Generalized with multiple organ lesions
During pulmonary sarcoidosis, an active phase (or an exacerbation phase), a stabilization phase and a phase of reverse development (regression, subsiding of the process) are distinguished. Reverse development can be characterized by resorption, compaction and, less often, calcification of sarcoid granulomas in lung tissue and lymph nodes.
According to the rate of increase of changes, abortive, delayed, progressive or chronic development of sarcoidosis may be observed. The consequences of the outcome of pulmonary sarcoidosis after stabilization of the process or cure may include: pneumosclerosis, diffuse or bullous emphysema, adhesive pleurisy, basal fibrosis with calcification or absence of calcification of intra-thoracic lymph nodes.
Pulmonary sarcoidosis symptoms
The development of pulmonary sarcoidosis may be accompanied by nonspecific symptoms: malaise, anxiety, weakness, fatigue, loss of appetite and weight, fever, night sweats, sleep disorders. With intra-thoracic lymphoid form, half of the patients have asymptomatic pulmonary sarcoidosis, the other half have clinical manifestations in the form of weakness, chest and joint pain, cough, fever, nodular erythema. With percussion, a bilateral increase in the roots of the lungs is determined.
The course of the mediastinal-pulmonary form of sarcoidosis is accompanied by cough, shortness of breath, chest pain. During auscultation, crepitation, scattered wet and dry wheezes are heard. Extrapulmonary manifestations of sarcoidosis are added: lesions of the skin, eyes, peripheral lymph nodes, parotid salivary glands (Herford syndrome), bones (Morozov-Jungling symptom). The pulmonary form of sarcoidosis is characterized by the presence of shortness of breath, cough with sputum, chest pain, arthralgia. The course of stage III sarcoidosis is burdened by clinical manifestations of cardiopulmonary insufficiency, pneumosclerosis and emphysema.
The most common complications of pulmonary sarcoidosis are emphysema, bronchopturation syndrome, respiratory failure, and pulmonary heart. Against the background of pulmonary sarcoidosis, tuberculosis, aspergillosis and nonspecific infections are sometimes noted. Fibrosis of sarcoid granulomas in 5-10% of patients leads to diffuse interstitial pneumosclerosis, up to the formation of a “cellular lung”. Serious consequences threaten the appearance of sarcoid granulomas of the parathyroid glands, causing a violation of calcium metabolism and a typical clinic of hyperparathyroidism up to a fatal outcome. Sarcoid lesion of the eyes with late diagnosis can lead to complete blindness.
The acute course of sarcoidosis is accompanied by changes in laboratory blood parameters indicating an inflammatory process: moderate or significant increase in ESR, leukocytosis, eosinophilia, lymphocytosis and monocytosis. The initial increase in the titers of α- and β-globulins as sarcoidosis develops is replaced by an increase in the content of γ-globulins.
Characteristic changes in sarcoidosis are detected during lung x-ray, during CT or MRI of the lungs – tumor-like enlargement of lymph nodes is determined, mainly at the root, a symptom of “backstage” (overlapping shadows of lymph nodes on each other); focal dissemination; fibrosis, emphysema, cirrhosis of the lung tissue. In more than half of patients with sarcaidosis, a positive reaction of the Quame is determined – the appearance of a purplish-red nodule after intradermal administration of 0.1—0.2 ml of a specific sarcoid antigen (a substrate of the patient’s sarcoid tissue).
During bronchoscopy with biopsy, indirect and direct signs of sarcoidosis may be detected: vasodilation in the mouths of the lobular bronchi, signs of enlarged lymph nodes in the bifurcation zone, deforming or atrophic bronchitis, sarcoid lesions of the bronchial mucosa in the form of plaques, tubercles and warty growths. The most informative method of diagnosis of sarcoidosis is a histological examination of a biopsy obtained by bronchoscopy, mediastinoscopy, precalescent biopsy, transthoracic puncture, open lung biopsy. Morphologically, elements of epithelioid granuloma are determined in the biopsy without necrosis and signs of perifocal inflammation.
Pulmonary sarcoidosis treatment
Taking into account the fact that a significant part of cases of newly diagnosed sarcoidosis is accompanied by spontaneous remission, patients are dynamically monitored for 6-8 months to determine the prognosis and the need for specific treatment. Indications for therapeutic intervention are severe, active, progressive course of sarcoidosis, combined and generalized forms, damage to the intra-thoracic lymph nodes, pronounced dissemination in the lung tissue.
Treatment of sarcoidosis is carried out by prescribing long courses (up to 6-8 months) of steroid (prednisolone), anti-inflammatory (indomethacin, acetylsalicylic acid) drugs, immunosuppressants (chloroquine, azathioprine, etc.), antioxidants (retinol, tocopherol acetate, etc.). Prednisolone therapy begins with a shock dose, then gradually reduces the dosage. With poor tolerance of prednisone, the presence of undesirable side effects, exacerbation of concomitant pathology, sarcoidosis therapy is carried out according to an intermittent regimen of glucocorticoids after 1-2 days. During hormonal treatment, a protein diet with a restriction of table salt, taking potassium preparations and anabolic steroids is recommended.
When prescribing a combined therapy regimen for sarcoidosis, a 4-6-month course of prednisolone, triamcinolone or dexamethasone is alternated with nonsteroidal anti-inflammatory therapy with indomethacin or diclofenac. Treatment and dispensary supervision of patients with sarcoidosis is carried out by phthisiologists. Patients with sarcoidosis are divided into 2 dispensary groups:
- I – patients with active sarcoidosis:
- IA – diagnosis is established for the first time;
- IB – patients with relapses and exacerbations after the course of the main treatment.
- II – patients with inactive sarcoidosis (residual changes after clinical and radiological treatment or stabilization of the sarcoid process).
Dispensary registration with a favorable development of sarcoidosis is 2 years, in more severe cases – from 3 to 5 years. After the cure, patients are removed from the dispensary register.
Prognosis and prevention
Pulmonary sarcoidosis is characterized by a relatively benign course. In a significant number of individuals, sarcoidosis may not give clinical manifestations; in 30%, it may go into spontaneous remission. The chronic form of sarcoidosis with the outcome of fibrosis occurs in 10-30% of patients, sometimes causing severe respiratory failure. Sarcoid lesion of the eyes can lead to blindness. In rare cases of generalized untreated sarcoidosis, a fatal outcome is possible. Specific measures for the prevention of sarcoidosis have not been developed due to unclear causes of the disease. Non-specific prevention consists in reducing the impact on the body of occupational hazards in persons at risk, increasing the immune reactivity of the body.
- Clinical aspects and immune reactions in sarcoidosis. Grunewald J. Clin Respir J. 2007 Dec;1(2):64-73. link
- Fatal outcome of a multisystemic sarcoidosis in a 54-year-old patient. Bauer H. Pneumologie. 2001 Jul;55(7):343-6. link
- Infliximab treatment for chronic sarcoidosis–a case series. Jounieaux F, Chapelon C, Valeyre D, Israel Biet D, Cottin V; Groupe sarcoïdose francophone de la SPLF. Rev Mal Respir. 2010 Sep;27(7):685-92. link
- Sarcoidosis. Nunes H, Bouvry D, Soler P, Valeyre D. Orphanet J Rare Dis. 2007 Nov 19;2:46. link
- Drug therapy reviews: treatment of sarcoidosis. Fanburg BL. Am J Hosp Pharm. 1979 Mar;36(3):351-4. link