Sarcoidosis of the skin, lymph nodes, lungs, bone tissue and heart - methods of treatment. Sarcoidosis of the lungs (Besnier-Beck-Schaumann disease, Beck's sarcoidosis) Bone damage in sarcoidosis
The most complete answers to questions on the topic: "joint damage in sarcoidosis."
Sarcoidosis of bones, joints and muscles,
Joint damage in sarcoidosis, it is included in the symptom complex of Löfgren's syndrome. However, joint damage was not always typical. Joint damage in acute sarcoidosis reaches 88%. Most often, arthritis occurs in the knees and elbows, several joints are affected at once, which are moderately painful, mobile and often accompanied by erythema nodosum. Clinical manifestations disappear within a few weeks, chronic or erosive changes are extremely rare and always accompany systemic manifestations of sarcoidosis. For diagnosis, it is important to conduct a scintigram with gallium-67 citrate and measure the level of ACE in the blood. Synovial biopsy results are nonspecific and insensitive, and an open biopsy is often necessary. It should be remembered that spontaneous regressions are very frequent in sarcoidosis (Marvisi M., 1998).
In 1981, a case of chronic sarcoid arthritis without signs of damage to other organs and systems was described. The disease was very similar to rheumatoid arthritis and therefore sarcoidosis was diagnosed 20 years after the discovery of arthritis, when dry keratoconjunctivitis and fibrosis of the basal lung appeared (Feldman C., 1981).
Flexor synovitis in sarcoidosis without bone involvement or sarcoid dactylitis is rare. A patient was seen in Paris with arthralgia of the knees and ankles. The initial diagnosis - rheumatoid arthritis - turned out to be incorrect. A surgical synovectomy was performed to relieve the painful compression of the median nerve caused by synovitis. The correct diagnosis was made on the basis of histopathological examination, which revealed noncaseating epithelioid granulomas. This diagnosis was supported by a negative tuberculin test and an elevated serum ACE level. After excision of the synovial membrane and treatment with colchicine, there was no recurrence of synovitis, but arthralgia persisted (Bleton R. et al., 1991).
In Norway, in a 2-year prospective study of patients with evidence of probable reactive arthritis, acute sarcoid arthritis was diagnosed in 9% of cases. Every year in Oslo, an average of 2.9 cases of sarcoid arthritis were detected per 100 thousand of the population aged 18 to 60 years. Most often, this disease manifested itself in the spring. In all cases, joint damage was bilateral and was accompanied by bilateral adenopathy of the roots of the lungs, in 59% there was a triad, including erythema nodosum, arthritis, and lung damage. At a follow-up of 104 weeks (over 2 years), there was a complete remission of arthritis in all 17 cases observed. The duration of arthritis averaged 11 weeks (range 2 to 107). Erythema nodosum in all cases was moderate and insignificant. The authors noted that arthritis in sarcoidosis has a benign course. They also emphasized that the combination of bilateral ankle involvement, erythema nodosum, and bilateral lymphadenopathy on plain radiographs are pathognomonic of sarcoidosis (Glennas A. et al., 1995). Finnish researchers pointed to the fact that although acute sarcoid arthritis does not lead to joint destruction, musculoskeletal pain is quite typical for this disease, and arthritis is recurrent. Corticosteroids effectively control the symptoms of sarcoidosis, but relapses are much more common after their use than after spontaneous remission (Pettersson T., 1998).
Finnish authors described articular sarcoidosis in this way. The musculoskeletal manifestations of sarcoidosis include acute and chronic arthritis, and muscular and skeletal sarcoidosis. In some populations, acute sarcoidosis presents with systemic symptoms, polyarthritis, and erythema nodosum (Löfgren's syndrome). Erythema nodosum can often accompany other illnesses, including infections, drug reactions, and other conditions, along with joint symptoms. The diagnosis of sarcoidosis should be based on a tissue biopsy, but patients with typical Löfgren's syndrome may not require a biopsy. Non-steroidal anti-inflammatory drugs usually relieve symptoms of sarcoid arthritis and joint symptoms that accompany erythema nodosum. Corticosteroids may be required to control symptoms in severe acute and chronic arthritis (Pettersson T., 2000).
According to scientists from Kansas City (USA), the first census (registration) of children with sarcoidosis was conducted in 1991. In the next 5 years, 23 doctors from 14 countries registered another 53 patients. Nine patients had polyarthritis, 38 of 44 had persistent arthritis. Among patients with persistent polyarthritis, 16 out of 38 had arthritis at the onset of the disease (Lindsley C.B. et al., 2000).
Indian clinical immunologists conducted a retrospective analysis of cases of joint changes in patients with sarcoidosis in 1990-1999. – 29 patients (15 men and 14 women) aged 15 to 67 years (median 44 years) with articular syndrome (biopsy in 20 patients). 25 patients had arthritis. 15 patients had chronic arthritis (more than 6 months). Löfgren's syndrome was in 7% of cases. Acute arthritis was episodic (4 cases), more common in men (M/W=9/5), predominantly affected the joints of the lower extremities and was similar to reactive arthritis. Chronic arthritis was more common in women (M/W = 1:2) and manifested itself as a symmetrical lesion of the hand joints than resembled rheumatoid arthritis. Extra-articular manifestations such as neuropathy and general symptoms have been seen in acute arthritis. Skin patches, splenomegaly, and interstitial lung changes have been reported in chronic arthritis. At an average of 12 months, 10 out of 14 cases of acute arthritis and 5 out of 15 cases of chronic arthritis had a complete remission, while 2 and 9 cases, respectively, had only a partial remission of the articular syndrome. The authors noted articular syndrome as an early manifestation of sarcoidosis, resembling reactive or rheumatoid arthritis. They emphasized the need to combine steroids with immunosuppressive agents in chronic sarcoid arthritis (Govindarajan V. et al., 2001).
Chronic sarcoid arthritis is rare and is usually not a destructive arthropathy of the mono, oligo, or polyarthritis type. The knees, ankles, shoulders, wrists, and small joints of the hands may be affected. At the same time, damage to the skin, eyes, exocrine glands (salivary and lacrimal), as well as other tissues, is possible. Italian scientists observed a 77-year-old woman with a history of nasopharyngitis and epistaxis and chronic laryngitis from youth, dry mouth and tongue, erythematous, infiltrative changes on the forehead, nape and neck, purple changes in the left eye and nose, degeneration of the skin of the hands in over the past 30 years. She underwent surgery for a broken hip with a blood transfusion 14 years ago. Then she developed polyarthritis of the small joints of her hands (II, III and IV of the right interphalangeal distal joints, I, III and V of the left interphalangeal distal joints; III and V on both sides of the proximal interphalangeal joints), knees, tarsal joints, joints of the fingers of the feet and left elbow. She had been diagnosed with chronic viral hepatitis C 6 years earlier. During the last 5 years she had a productive cough, dysphonia, dyspnea at rest, fever, mullet and asthenia. Laboratory tests revealed leukopenia, the presence of hepatitis C virus, elevated transaminase levels, and cryoglobulinemia. According to Italian scientists, the hepatitis C virus may be involved in the etiopathogenesis of rheumatic diseases, pulmonary fibrosis, and, moreover, may contribute to the onset and progression of sarcoidosis (Cossu A. et al., 2002).
Symptoms of early-onset sarcoidosis include skin rash, arthritis, and uveitis, which are similar to those of systemic juvenile rheumatoid arthritis. Japanese researchers observed 2 Japanese women who developed sarcoidosis at a young age and were initially diagnosed and treated as juvenile rheumatoid arthritis. Intermittent fever and synovial swelling may mask sarcoidosis in children younger than 4 years of age (Yotsumoto S. et al., 2000). The rheumatic manifestations of sarcoidosis include inflammatory arthritis, swelling of the soft tissues adjacent to the joint, tenosynovitis, dactylitis, bone involvement, and myopathy. There are 2 types of arthritis, differing in clinical course and prognosis. Acute sarcoid arthritis is self-limiting and resolves without sequelae. Chronic sarcoid arthritis, although less common, can progress and cause joint deformities. At the same time, proliferative and inflammatory changes in the synovium occur, and caseless granulomas occur in half of the patients. The pathogenesis of sarcoid arthritis is not fully understood, but genetic and environmental factors are considered important. Drug therapy for sarcoid arthritis with non-steroidal anti-inflammatory drugs, corticosteroids, colchicine, antimalarial drugs, and/or immunosuppressive drugs is based on open, uncontrolled studies. This review is focused on assessing current knowledge about the various features of sarcoid arthritis, including clinical manifestations, course, imaging, and pathology. A recently developed anti-TNF-alpha therapy is reviewed (Torralba K.D., Quismorio F.P.Jr., 2003).
A review of rheumatological signs and symptoms in the manifestations of sarcoidosis has shown that although sarcoidosis most often presents with lung involvement, musculoskeletal lesions are not only characteristic but may be the initial manifestation of this systemic inflammatory process, and may be similar to other arthritic and autoimmune diseases (Abril A. , Cohen M.D., 2004).
Artopathy refers to damage to the joints. This is a collective term for a dystrophic process that is caused by various factors. Arthropathy always manifests against the background of another underlying disease. There are several types of this pathology, depending on the factor causing it:
- neurological;
- metabolic;
- traumatic, etc.
Often it is caused by trauma, instability and degenerative changes (osteoarthritis, rheumatoid arthritis, etc.)
The cause may be autoimmune disorders, abscesses, sepsis, operations and injections, insect bites, etc. Sarcoidosis is one of the pathologies against which arthropathy develops.
Symptoms
This pathology can affect one or more joints;
- there is swelling and swelling;
- pain during movement and palpation;
- inflammation;
- dysfunction of the joint;
- instability, etc.
All manifestations directly depend on the disease that caused the lesion.
Arthropathy in sarcoidosis is characterized by the following specific manifestations:
- nodular redness of the skin;
- eye damage (conjunctivitis, lacrimal gland);
- fever
- mainly affects the knees and ankles
- enlarged lymph nodes in the chest on x-ray.
The combination of these symptoms is also called Lofgren's syndrome.
To understand the treatment and course of the disease, you need to learn more about what sarcoidosis is.
Sarcoidosis is a granulomatous disease that is multisystemic in nature and is manifested by an increase in mediastinal nodes on both sides, as well as the presence of infiltrates in the lung tissue. Significantly distinguish eye and skin symptoms.
In 25% of cases, osteoarticular syndrome is clearly distinguished.
They mostly affect young women and men (under 40).
The causes of the pathology are still not clearly defined. It is known that a certain infection plays a role, as well as immune disorders.
It begins in an acute form and has every chance of becoming chronic.
In the acute form, artopathic syndromes are clearly manifested. The joints become inflamed and ache on palpation, nonspecific synovitis is found. Leukopenia, anemia, an increase in ESR and other signs are also determined. This form is amenable to therapy and completely disappears within six months.
If left untreated, the disease can become chronic.
The chronic form gradually causes lung failure due to fibrotic changes. Lymph nodes also increase, it is likely that the spleen and liver will suffer.
The joints are not affected immediately, but months or years after the onset of the primary disease. Prior to this, the symptoms are similar to outbreaks of polyarthritis. It appears symmetrically, touches the small joints of the hands. In the synovium, specific granulomas can be identified.
How to be treated?
Treatment consists of an integrated approach to eliminate all symptoms. Sarcoidosis in the early stages is treatable with salicylates. In more advanced cases, use
Sarcoidosis is a systemic inflammatory disease characterized by granulomatous, noncaseating inflammation of the affected organs. The etiology of the disease remains unknown, the clinical manifestations are diverse, and the diagnosis is often made by excluding other diseases. Distinguishing sarcoidosis from other systemic diseases is aided by the clinical presentation, medical history, biopsy findings, and appropriate response to treatment. Although the lungs are more commonly affected, theoretically any organ can be affected, so the presence and dynamics of characteristic extrapulmonary manifestations support the diagnosis.
Prevalence
The prevalence of the disease is from 1 to 10 cases per 100,000 population in various countries (Denmark, Belgium, Japan). In Sweden, for unclear reasons, the incidence is 60-80 cases per 100,000, in the USA - 10-40 per 100,000 population. Studies with chest radiography as a screening method have identified a large number of patients with asymptomatic sarcoidosis. Other methods of detection, such as autopsy, show an even higher incidence of the disease. Sarcoidosis is more often found in young patients (20-40 years old), the second peak occurs in Caucasian women over 50 years old. In the US, the highest incidence of sarcoidosis is among young African American women.
pathological anatomy
Sarcoidosis presents with well-formed epithelial granulomas in the absence of other causes of the granulomatous process, such as infectious disease and malignancy. Granulomas, as a rule, do not contain foci of caseous necrosis. Sometimes fibrinoid necrosis is found in them. In the lungs, granulomas are localized along bronchovascular structures.
Cause
The cause of sarcoidosis remains unclear. Active granulomatous inflammation is accompanied by a predominance of cytokine expression by T-helper (Th) type 1 (IFNy, IL-12, IL-18) and tumor necrosis factor (TNF). Oligoclonal growth of T cells in the presence of an unchanged number of T-cell receptors in the lungs, skin, and other organs supports the hypothesis that sarcoidosis is an antigen-dependent reaction. The most striking support for this theory is the abundance of T cells carrying the V-alpha subunits of T cell type 2 and 3 receptors in Scandinavian patients.
According to one theory, the starting point in the development of sarcoidosis is an external influence, for example, microbial. Recent laboratory studies suggest that sarcoidosis is associated with a history of exposure to certain micro-organisms, but the disease itself is not an active infectious process. A large multicenter study of the etiology of sarcoidosis ACCESS did not confirm the association of the influence of environmental factors and occupational hazards with an increased risk of sarcoidosis.
Thus, sarcoidosis differs from many rheumatic diseases in its reduced reactivity and the absence of periodic relapses and remissions. An exception to this rule is neurosarcoidosis with optic neuritis and cranial neuropathies, which can recur several years after stable remission.
In most cases, remission occurs within 2 years of diagnosis. Acute sarcoidosis (Löfgren's syndrome) is characterized by a high remission rate (over 70%). Chronic active sarcoidosis is accompanied by a higher incidence of lung (stage 3 or 4), sinus and upper respiratory tract involvement, lupus pernio, neurosarcoidosis, and cardiac involvement, characterized by an insidious course. To identify the nature of the course of the disease, long-term observation (more than 2-3 years) is necessary. Long-term follow-up is also necessary to confirm that a patient with active chronic sarcoidosis is receiving adequate treatment to minimize the progression of organ damage against a background of chronic inflammation.
Although sarcoidosis is a systemic disease, the prevalence of organ involvement is determined primarily at the time of diagnosis. The ACCESS study showed that new lesions appear in less than 25% of cases within 2 years of follow-up.
Genetic factors and family history
The availability of data on families with several cases of sarcoidosis suggests the role of genetic factors in the development of the disease. The recently completed US multicenter sarcoidosis etiology study (ACCESS) found that the relative risk of sarcoidosis is about 5 among first-degree relatives of patients with sarcoidosis. Despite a higher incidence of sarcoidosis among African Americans (35.5 per 100,000) compared with Caucasians (10.9 per 100,000), the relative risk of sarcoidosis among first-degree relatives of Caucasian patients is significantly higher than among relatives of African American patients. the same degree of relationship.
Many genetic associations link sarcoidosis to genes at the major histocompatibility complex (MHC) locus. Recently, in a cohort of Caucasian patients, a genome analysis found an association of the BTNL2 gene (butyrophilin-like) with the development of sarcoidosis. This fact was confirmed by a separate analysis in groups of patients of African American origin in the Sarcoidosis Genetic Analysis (SAGA) consortium.
Symptoms
Sarcoidosis affects several organs. Clinical manifestations (frequency of organ damage)
- Light 70-90%
- Skin 20-30%
- Paranasal sinuses and upper respiratory tract 5-10%
- Eyes 20-30%
- Musculoskeletal system 10-20%
- Abdominal organs 10-20%
- Blood system 20-30%
- Salivary glands (parotid) 5-10%
- Cardiovascular system 5-10%
- Nervous system 5-10%
Acute sarcoidosis
There are two forms.
The first is Löfgren's syndrome (symmetrical polyarthritis and uveitis, erythema nodosum, fever, bilateral hilar lymphadenopathy). More often diagnosed in Scandinavians. In most patients, it disappears after a few weeks, without specific treatment. Sometimes you need to prescribe NSAIDs, low doses of glucocorticoids. Relapses - 30%.
The second is the defeat of the lacrimal glands and salivary glands, dry keratoconjunctivitis, known as Heerforzt's syndrome (uveoparotitis fever). The syndrome consists of granulomatous inflammation of the lacrimal glands and parotid salivary glands, uveitis, fever, bilateral hilar lymphadenopathy, and cranial neuropathies.
Sarcoidosis of the lungs
It is detected in 90% of cases with x-rays. The most common symptoms are shortness of breath and cough. An objective examination does not reveal specific symptoms.
In a small proportion of patients, an atypical chest is possible, which cannot be stopped with glucocorticoids. The cause of pain, which can appear both during exercise and at rest, is likely to be severe mediastinal lymphadenopathy. However, most patients with mediastinal lymphadenopathy do not complain of pain. Of particular importance is the exclusion of cardiac, gastroesophageal and musculoskeletal causes of pain.
A rare complication of pulmonary sarcoidosis is pulmonary hypertension (less than 5% of cases), usually detected with progressive lung disease (stage 3 or 4). Pulmonary hypertension is associated with high mortality. As with atypical pain, other causes of pulmonary hypertension must be ruled out, such as sleep apnea and thromboembolic disease.
Sarcodosis of the skin
Approximately one third of patients with sarcoidosis present with various skin lesions. The most common are hyperpigmented nodules, purple plaques, hypopigmented macules, and subcutaneous nodules. The elements are usually located on the extensor surfaces of the arms and legs, heal with scarring and skin tightening. Lupus pernio ("lupus pernio" is not quite the correct term, since the condition has nothing to do with systemic lupus erythematosus) is a specific manifestation of sarcoidosis in the form of purple plaques on the nose, nose wings, cheekbones, eyelids, hairline and hairy parts of the head. These elements heal slowly and are often difficult to treat.
Sarcoidosis of the paranasal sinuses and upper respiratory tract
The upper respiratory tract is often affected in sarcoidosis. Symptoms of the lesion include persistent nasal congestion and pain in the paranasal sinuses. When hoarseness and stridor appear, a consultation is necessary to confirm the involvement of the larynx. In the chronic course of the disease or as a result of repeated surgical interventions, a saddle deformity may appear on the nose. Mucocutaneous lesions are associated with other manifestations such as lupus pernio.
Sarcoidosis of the eye
The eyes in sarcoidosis are often affected. Nodules can appear in almost all parts of the eye. Common changes sometimes available for biopsy are granulomatous conjunctivitis and conjunctival nodules. Intraocular sarcoidosis develops more often in the anterior region and may be accompanied by the appearance of nodules along the edge of the pupils, on the surface of the iris and trabecular meshwork. Granulomatous anterior uveitis may result in posterior corneal precipitates that appear as “sheep fat droplets” on slit lamp examination.
Intermediate uveitis causes the formation of a deposit in the form of "snowballs". Posterior uveitis is accompanied by superficial waxy exudates. Both types of damage to the posterior segment can lead to a sudden sharp decrease in vision. Occasionally, ocular manifestations include involvement of the lacrimal glands, lacrimal organs (dacryocystitis), orbits (usually on one side), cornea, and sclera (scleritis). The variety and often insidious onset of ocular symptoms in sarcoidosis necessitate regular ophthalmological examination.
Damage to the musculoskeletal system and joints
joints
As stated above, severe arthritis develops in acute sarcoidosis (Löfgren's syndrome). Arthralgias are more common in patients with chronic active sarcoidosis. Chronic sarcoid arthritis is a rare manifestation of the disease (less than 1% of cases), can cause joint deformity, and is associated with other chronic manifestations such as cutaneous sarcoidosis. During arthrocentesis, a slight increase in the number of leukocytes (250-5000 per 1 ml) with a predominance of mononuclear cells is detected in the joint fluid. Synovial biopsy specimens show noncaseating granulomatous inflammation. True tendovaginitis and periarticular inflammation are less common than arthralgias or arthritis, while periarthritis (inflammation of the periarticular structures that is often difficult to distinguish from synovitis) is well documented in sarcoidosis. Other articular manifestations of sarcoidosis include dactylitis characterized by purple 2 or 3 fingers, sacroiliitis, and heel pain.
Sarcoidosis of the bones
Cystic perforated and reticular masses are usually detected by radiography and other imaging modalities. Such changes, as a rule, are located in the bones of the hands and feet, the skull, and also in the vertebrae. When the pelvic bones are affected, the pain may resemble sacroiliitis. In sarcoidosis of the bones, a bone biopsy is indicated to exclude infections and oncological pathologies accompanied by similar bone changes.
Myositis
Random muscle biopsy reveals granulomas in 70% of cases, but muscle damage has no clinical manifestations. Muscle inflammation is also occasionally detected incidentally during gallium x-ray or MRI. In patients with sudden muscle weakness after initiation of glucocorticoid treatment, glucocorticoid-induced myopathy should be suspected.
Abdominal sarcoidosis
Granulomatous inflammation in liver biopsies is found in every second patient with sarcoidosis, but the clinical picture of liver damage is present in only 10% of cases. High activity of liver enzymes usually decreases spontaneously or against the background of the appointment of glucocorticoids. Chronic granulomatous hepatitis, if severe and untreated, can progress to cirrhosis of the liver. The combination of hepatosplenomegaly, abdominal lymphadenopathy, and hypercalcemia (and often bone marrow involvement) is collectively referred to as abdominal sarcoidosis.
The gastrointestinal tract is rarely affected. Involvement of the gastrointestinal tract presents with pain and dysmotility. It does not respond to glucocorticoid therapy. In patients with sarcoidosis, in whom the gastrointestinal tract is the only or main manifestation, it is necessary to exclude,.
Other important manifestations
Approximately one third of patients with sarcoidosis have various hematological disorders. Peripheral lymphadenopathy usually appears at the onset of the disease, with severe lymphadenopathy persisting in 10% of cases. Splenomegaly is present in 5% of cases, lymphopenia and leukopenia - in 30-50% of cases, thrombocytopenia occurs less frequently. Polyclonal gammopathy is also commonly found in active sarcoidosis (approximately 25%). Variable unclassified immunodeficiency should be suspected in the presence of a deficiency of serum protein fractions or the occurrence of frequent infectious diseases (which is not typical for sarcoidosis).
Sarcoidosis of the heart- a rare dangerous manifestation that can cause heart block, persistent arrhythmias and cardiomyopathy. According to autopsy, the frequency of cardiac sarcoidosis is about 25%, while the clinical diagnosis is made only in 10% of cases. Endomyocardial biopsy reveals granulomatous inflammation in less than 25% of patients. Diagnosis is often suggested by confirmed sarcoidosis in other organs and by the results of appropriate myocardial imaging such as exercise radioisotope, gadolinium MRI of the heart, or positron emission tomography.
Manifestations neurosarcoidosis can be divided into three main groups.
- The most common form is neuropathy of the 2nd (optic nerve), 5th, 7th, 9th, or 12th pair of cranial nerves. Cranial neuropathies are often associated with aseptic basilar meningitis and tend to recur.
- The second manifestation of neurosarcoidosis is encephalopathy or myelopathy in combination with the appearance of a volumetric formation or an increase in the signal from the affected area during MRI. In such cases, the appointment of long-term immunosuppression is effective.
- The third manifestation of neurosarcoidosis is peripheral neuropathy. This complication is potentially insidious and often does not respond to glucocorticoid treatment. Recently, an association has been found between small fiber neuropathy and chronic pain and fatigue in sarcoidosis.
radiographic features
Chest x-ray reveals changes in approximately 90% of cases. Changes on the radiograph usually characterize the category (stage) of sarcoidosis (according to Scudding): 0 - normal; 1 - bilateral hilar lymphadenopathy (DPL); 2 - DPL, interstitial infiltrates; 3 - only interstitial infiltrates; 4 - fibrocystic lung disease. Chest CT also reveals lung infiltrates that are nodular and tend to be located along bronchovascular structures.
Gadolinium MRI or positron emission tomography can detect signs of inflammation characteristic of sarcoidosis in the brain, cranial nerves, spinal cord, heart, and other organs. Cardiac sarcoidosis can also be detected on a thallium equilibrium scan. The classic signs of sarcoidosis on gallium scans include isotope uptake by the parotid salivary glands and lacrimal glands ("panda sign"), and bilateral isotope uptake by the hilar and right paratracheal lymph nodes ("lambda sign"). Although these features are specific to sarcoidosis, a biopsy is necessary to confirm the diagnosis.
Laboratory signs
Screening tests for extrapulmonary sarcoidosis include routine blood tests: metabolic profiling and (to assess kidney, liver function, detect lymphopenia, hypercalcemia, hypergammaglobulinemia). There are no biological markers that allow assessing the prognosis and adjusting treatment in sarcoidosis. In some cases, with active sarcoidosis, an increase in the blood serum of ACE and the active form of vitamin D (1,25-dihydroxycholecalciferol) is noted, however, these indicators have low specificity and do not play a fundamental role in the diagnosis and treatment.
Treatment
The first principle of choice of treatment is the exclusion of life-threatening manifestations of the disease. In cases of only a limited cutaneous form of the disease or Löfgren's syndrome, NSAIDs are sufficient to control symptoms. Local injections of glucocorticoids are also prescribed for isolated skin lesions. Patients with damage to the heart, central nervous system should receive high doses of glucocorticoids. In all cases, therapy should be adjusted based on specific parameters (pulmonary function tests, chest radiographs, blood tests, MRI), and not on subjective symptoms (malaise, cough, local pain). Although sarcoidosis is considered a restrictive pulmonary disease (decreased forced VC or total lung capacity), in some cases of lung involvement, clinical deterioration is preceded by changes in airway patency (FEVh) and/or changes in lung diffusing capacity for carbon monoxide.
If systemic therapy is required against the background of active inflammation, glucocorticoids remain the drugs of choice. Their local application (inhalation, in the form of ointments) is ineffective (except in some cases of eye damage). In general, initial therapy should last 8-12 months, only after this time one can try to cancel glucocorticoids (gradually reduce the dose). With Löfgren's syndrome, the prognosis is usually favorable, and therefore an earlier cancellation of these drugs is possible. Patients with chronic active sarcoidosis should receive maintenance treatment with low doses of glucocorticoids rather than repeated courses of high doses. Final changes (scarring) are not subject to treatment. In most cases, the minimum effective dose of prednisone is sufficient (further reduction will lead to relapses), initially higher doses of glucocorticoids (20-40 mg / day) are needed to control the active form, which after the first month of treatment can be reduced by 5 mg every 2 weeks to 20 mg / day, then the dose is reduced more slowly - by 2.5 mg in a month. If symptoms reappear or lung function is impaired when the dose is reduced, the dose should be increased to a previously effective dose and a drug should be prescribed to reduce the dose of glucocorticoids. The average maintenance dose for sarcoidosis is 5-15 mg/day. At. Neurosarcoidosis and cardiac sarcoidosis improve with higher doses of glucocorticoids in combination with immunosuppressants to reduce the dose of hormones.
Drugs to reduce the dose of glucocorticoids
To reduce the maintenance dose of glucocorticoids (ideally to 15 mg/day), a variety of immunosuppressants and immunomodulators are recommended to do this. However, most of these agents have not been studied in randomized clinical trials. Unlike glucocorticoids. with the use of which the response is observed within days or weeks, with the appointment of agents that allow to reduce the dose of glucocorticoids, 2 to 6 months of treatment are necessary to achieve clinical improvement.
Antimalarials (hydroxychloroquine, chloroquine) and synthetic tetracyclines (minocycline, doxycycline), which have several severe side effects, are prescribed for the mucocutaneous form of the disease. Pentoxifylline and thalidomide are sometimes effective, but their side effects are more pronounced. Other immunosuppressive agents (methotrexate, MMF, azathioprine, cyclophosphamide) are prescribed in combination with glucocorticoids in severe sarcoidosis and in the absence of the effect of treatment with lower doses of glucocorticoids or in case of intolerance to glucocorticoids. A recently completed phase 2 study showed that infliximab (an anti-TNF monoclonal antibody) has a modest improvement in lung function. Etanercept (a soluble TNF inhibitor) was not effective in a randomized clinical trial. Further studies are needed to evaluate the effectiveness of TNF inhibitors in sarcoidosis, such as infliximab (and its analog, adalimumab).
The article was prepared and edited by: surgeonRelevance. Every neurologist should know about sarcaidosis no less than, for example, about acute cerebrovascular accidents. This is due, firstly, to a rather high incidence of sarcoidosis and the prevalence of sarcoidosis in Russia ( ! sarcoidosis has ceased to be a rarity), secondly, the high frequency of cases of damage to the nervous system in patients with sarcoidosis, and, thirdly, the possibility of damage to any parts of the central and peripheral nervous system in sarcoidosis, individually or in various combinations.
Sarcoidosis. The following definition can be considered the most capacious: sarcoidosis (Besnier-Beck-Schaumann disease) is a multisystem disease of unknown etiology, characterized by the formation of sarcoid granulomas (epithelioid-cell non-caseating granulomas [in the center of the granuloma there is no caseous necrosis - in contrast to tuberculous granuloma *]) with the most frequent lesions of the intrathoracic lymph nodes and lungs (occurs in more than 90% of cases), skin, eyes and liver, and has a predominantly chronic undulating course [* - with sarcoidosis, central necrosis may develop, however, it is usually punctate, poorly visualized ].
Sarcoidosis is a multifactorial disease, the development of which is dominated by an autoimmune mechanism in response to an unidentified antigen, leading to the formation of sarcoid granulomas.
It is believed that sarcoidosis, like other variants of granulomatous inflammation similar to it, is formed mainly in initially predisposed individuals. The role of infections (tuberculosis, brucellosis, tularemia, chlamydia, histoplasmosis, coccidioidomycosis, etc.; certain types of viruses: hepatitis C virus, herpes virus, JC virus), as well as occupational factors (berylliosis, pneumoconiosis) are discussed. Inhalation of metal dust or smoke can cause granulomatous changes in the lungs, similar to sarcoidosis. Dust of aluminum, barium, beryllium, cobalt, copper, gold, rare earth metals (lanthanides), titanium and zirconium have antigenic properties, the ability to stimulate the formation of granulomas. Also of interest are granulomatous reactions, which are secondary, for example, in tumors (in this case, clinical manifestations of a sarcoid-like reaction can occur regardless of the stage of the tumor lesion). A combination of sarcoid granulomatosis with autoimmune disorders is possible: there are descriptions of intrathoracic lymphadenopathy and changes in the lungs in rheumatoid arthritis, systemic lupus erythematosus. Genetic factors play an undoubted role in the development of the disease, as evidenced by familial cases of sarcoidosis and the results of HLA typing. The relationship of sarcoidosis with HLA-A1, B8-, DR5- and DR17 loci has been repeatedly studied.
Pathologically, sarcoid granuloma is represented by various subpopulations of activated macrophages, multinucleated giant cells, lymphocytes, central CD4+ and peripheral CD8+ cells. Granuloma has well-defined central and peripheral zones (parts). The central part of the granuloma is made mainly by macrophages, and along the periphery there are epithelioid cells, giant multinucleated cells. Domestic authors distinguish three stages of granuloma formation: proliferative, granulomatous and fibrous-hyalinous.
What is a granuloma? Regardless of the etiology, all granulomas, including infectious ones, are built according to a common histogenetic plan. The main cell of each granuloma is not local cells, but macrophages, mononuclear cells, phagocytes, descendants of the monocytic cell line arising from the bone marrow stem cell. In the latter, the cells of this line develop from a monoblast to a promonocyte and a monocyte. From the bone marrow, monocytes enter the general circulation and capillaries of tissues and organs, and then migrate into the tissues through the wall of the venular knee of the microvasculature. Here, monocytes are converted and fixed resident macrophages, which acquire some special qualities and new names. During the formation of granulomas, monocytogenic (hematogenous origin) macrophages accumulate in the lesion. In the immune granuloma, macrophages gradually transform into epithelioid cells. The latter are considered as markers of the presence of an immune mechanism in granuloma formation. This is well shown in granulomas caused by Mycobacterium tuberculosis, BCG vaccine, Mycobacterium leprosy and schistosome egg antigen, as well as in sarcoid, beryllium and other immune granulomas resulting from the development of a delayed-type hypersensitivity reaction. When macrophages or epithelioid cells merge, giant cells of the original type of giant cells of foreign bodies with a disordered arrangement of nuclei are formed, and later - cells of the Pirogov-Langhans type with an ordered peripheral arrangement of nuclei in the form of a crown. Below is a schematic representation of the structure of a granuloma using the example of a tuberculous granuloma:
General information about the clinical picture . Sarcoidosis is a multi-organ pathology, so patients can turn to various specialists. The clinical picture depends on ethnicity, the duration of the process, the location and extent of the lesion, and the activity of the granulomatous process. Nonspecific symptoms: fever, weakness, malaise, weight loss - can occur in about a third of patients (in other cases, a gradual asymptomatic or asymptomatic development of the disease is possible). Most often, the fever is low, but there are cases of a rise in temperature up to 39 - 40 ° C. Weight loss is usually limited to 2 - 6 kg for 10 - 12 weeks prior to diagnosis. Fatigue is not always detected, ranging from barely noticeable to very pronounced. Sometimes there is night sweats. Patients with sarcoidosis are often diagnosed with fever of unknown origin, tuberculosis, rheumatism, pneumonia, lymphogranulomatosis, cancer. With sarcoidosis, the lymph nodes of the root of the lung and mediastinum, the lungs are most often affected, less often the skin, eyes, joints, kidneys, liver and spleen, heart, nervous system, and other organs.
Most researchers distinguish two variants of the course of this disease: acute and chronic. The acute course is characterized by a sudden onset, high activity of the inflammatory process and, in most cases, its spontaneous regression within a few months. It includes Löfgren's syndrome, which includes a combination of erythema nodosum, hyperthermia, arthritis and intrathoracic lymphadenopathy, as well as Heerfordt's syndrome (uveoparotid fever). The chronic course of sarcoidosis is understood to mean asymptomatic or asymptomatic and, as a rule, its long-term existence. The use of positron emission tomography and scintigraphy in sarcoidosis showed that the inflammatory process in the lymph nodes, lung tissue and other organs can proceed without clinical, laboratory and radiological symptoms of the disease. Approximately 2/3 of all patients suffering from sarcoidosis recover spontaneously at different times, although the process of regression of the disease can be delayed for several years, and in 15% of patients with a progressive course of pulmonary sarcoidosis, signs of pulmonary fibrosis of varying severity develop over time.
To confirm the diagnosis of sarcoidosis, a histological examination of the lymph nodes, skin, and muscle lesions is mandatory. Laboratory tests are also used: Kveim's skin reaction, an increase in the activity of angiotensin-converting enzyme (ACE) and lysozyme in the blood serum and cerebrospinal fluid, in 30% of patients the calcium content in the blood and urine is increased. Changes in the cerebrospinal fluid are nonspecific: a slight lymphocytic pleocytosis is determined, a moderate increase in protein, in 10% - a decrease in glucose.
Read more about sarcaidosis:
in the article "Sarcoidosis" E.I. Shmelev (magazine "Pulmonology and Allergology" No. 2 - 2004) [read];
in the article "Sarcoidosis and problems of its classification" by S.A. Terpigorev, B.A. El-Zein, V.M. Vereshchagin, N.R. Paleev (magazine "Bulletin of the Russian Academy of Medical Sciences" No. 5 - 2012) [read];
in the Federal Consensus Clinical Guidelines for Diagnosis and Treatment of Sarcoidosis (2014) [read];
in the teaching aid for students of postgraduate and additional professional education "Sarcoidosis"; under the general editorship of the chief therapist of the Ministry of Health and Social Development of the Russian Federation, Academician of the Russian Academy of Medical Sciences, Professor A.G. Chuchalin; Kazan, 2010 [read].
Neurosarcoidosis(NS). The defeat of the nervous system in sarcoidosis (neurosarcaidosis) occurs in 5 - 31% of cases (according to most authors - in 5 - 7% of patients). In this case, the cranial nerves, hypothalamus and pituitary gland are most often affected, but involvement of the brain parenchyma, meningeal membranes, brain stem, subependymal plate of the ventricles, choroid plexuses, as well as vessels supplying blood to various parts of the nervous system is possible. Symptoms of neurosarcoidosis can be either acute or chronic. Irritation of the meningeal membranes may be accompanied by headache, stiff neck muscles; damage to the cranial nerves - Horner's syndrome, Bell's palsy; with hypothalamic-pituitary disorders, there is diabetes insipidus, obesity, panhypopituitarism, galactorrhea-amenorrhea syndrome (diabetes insipidus and hyperprolactinemia are, according to the literature, the two most common neuroendocrine manifestations of NS), sleep disturbance and thermoregulation. Manifestations of NS can also be episyndrome (convulsive seizures), paresis and paralysis, speech disorders, and in addition - amnesia, dementia and drowsiness due to intracranial hypertension and hydrocephalus. With NS, mental disorders can be observed in the form of paranoid psychoses, amnestic syndromes, schizophrenia-like states, hypochondriacal syndromes, and depression. In 1% of cases, there is an expansive growth of granulomas with a typical clinic of a volumetric brain process. Sarcoid angiitis (in the substance of the brain) is manifested by transient ischemic attacks, cerebral infarctions or intracerebral hemorrhages. These disorders lead to variable focal symptoms, the development of epileptic seizures.
Especially difficult for diagnosis is isolated NS, in which there are no clinical and paraclinical signs of damage to other organs and systems. Isolated NS occurs, according to various sources, in 11-17% of cases. The disease is more common among women. The onset of the disease occurs between the ages of 20 and 40. Comparison of patients with isolated NS and patients with systemic sarcoidosis in general showed similar demographics and neurological manifestations. It can be noted that in isolated NS, headache is more common (associated with both the involvement of the meninges and intracranial hypertension), damage to the cranial nerves (in acute intracranial hypertension, damage to the II, III, VII, VIII pairs of cranial nerves is also possible). ), hemiparesis, involvement of the meningeal membranes according to MRI, cell-protein dissociation in the study of cerebro-spinal fluid (CSF) and a more favorable prognosis is noted.
Among the cranial nerves, the facial nerve is most often (in 50% of cases) affected (less common is the defeat of other cranial nerves - optic, vestibulocochlear and glossopharyngeal). Neuropathy of the facial nerve in NS can be unilateral or bilateral. With isolated neuropathy of the facial nerve, the composition of the CSF may be normal. Quite common is the defeat of several cranial nerves. The literature also describes a number of syndromes of unilateral cranial nerve injury, depending on the location of the granulomas at the base of the skull. Often (in 35% of cases) there is damage to the optic nerve. Sometimes, optic nerve damage may be the only manifestation of isolated NS. The clinical picture of optic neuritis includes: decreased visual acuity, visual field defects, atrophy of the optic disc, damage to the optic chiasm. In this case, the optic nerves can be affected on one or both sides. Retrobulbar pain, pupillary reaction disturbances to light are described. The literature also suggests a possible spread of sarcoidosis to the brain via the optic nerves. There are indications that patients with damage to the optic nerves have a worse prognosis of the disease.
Forms of NS leptomeninges (a combination of arachnoid and pia mater) are represented by: accumulation of granulomas in the form of solitary nodular formations; diffuse spread of granulomas; mixed form. The clinical picture of the NS of the meninges includes: headaches, meningeal symptoms (significantly vary in intensity), damage to the cranial nerves. Meningeal syndrome in NS usually occurs without fever with signs of impaired CSF production and resorption and changes in CSF. A case of NS debut with acute hydrocephalus is described. Mechanisms for the development of hydrocephalus in NS can be as followsb: violation of CSF resorption with the spread of granulomas in the leptomeninge and subarachnoid space of the lower surface of the brain, which leads to the formation of aresorptive communicating hydrocephalus; obliteration of the aperture of the IV ventricle with the spread of granulomas and the formation of internal occlusive hydrocephalus.
Damage to the peripheral nervous system (PNS) in NS occurs in 6–23% of cases and can be represented by several options: in the form of chronic sensory-motor polyneuropathy, multiple mononeuropathy (the ulnar and peroneal nerves are more often affected), Guillain-Barré syndrome, sensory polyneuropathy with involvement of thin fibers, carpal tunnel syndrome. An EMG study reveals the axonal nature of the lesion. Sometimes there may be damage to the autonomic nerve fibers. Various mechanisms of neuropathy are described: compression, immune mechanisms, ischemic mechanisms of axonal degeneration due to vasculitis. However, often the mechanisms of damage to the PNS remain unclear. Diagnosis is based on peripheral nerve biopsy, which shows characteristic epi- or perineurally localized granulomas.
In NS, damage to the spinal cord can occur, with sarcoid granulomas accumulating both in the substance and in the meninges of the spinal cord or spinal roots. Symptoms of radiculo-myelopathy develop gradually, starting with radicular pain, then radicular prolapse symptoms (paresis, anesthesia, amyotrophy) may join. With the progression of the disease, conduction disorders appear, including Brown-Sekara syndrome, funicular myelosis syndrome. A pseudotumorous course is possible and rarely - compression of the spinal cord by collapsing vertebrae (with vertebral sarcoidosis) or impaired spinal circulation. Some authors suggest considering spinal cord injury in NS as an alternative diagnosis in all patients with subacute and chronic myelopathy.
Myopathic syndrome in NS occurs in 26-80% of cases and can often be asymptomatic. With a symptomatic course, the myopathic syndrome is characterized by proximal muscle weakness (muscle damage can occur in the form of acute sarcoid proximal myopathy, polymyositis).
Differential diagnosis of NS is carried out with multiple sclerosis, diffuse connective tissue diseases, neurosyphilis, neuroborreliosis, neuroAIDS, vasculitis, toxoplasmosis, brucellosis, lymphomas, tumors. An important, albeit nonspecific, diagnostic criterion for neurosarcoidosis is a decrease in symptoms during treatment with corticosteroids (in the absence of positive dynamics against the background of adequate therapy, the diagnosis of neurosarcoidosis should be questioned).
There are no specific laboratory parameters for diagnosing NS. MRI of the brain is the most sensitive method for diagnosing NS. Neuroradiological features of NS include involvement of the periventricular substance of the brain, involvement of the hypothalamus and pituitary gland, involvement of the cranial nerves (eg, thickening of the optic nerves), and involvement of the meninges with contrast accumulation and hydrocephalus. At the same time, there is no clear correlation between damage to the brain and its membranes and clinical symptoms, since many lesions detected on MRI remain “silent”. In case of damage to the spinal cord, MRI reveals focal or diffuse changes (of the spinal cord) in the form of its thickening or atrophy, thickening of the roots of the cauda equina.
To date, the generally accepted diagnostic criteria for NS are:
■ possible NS: clinical manifestations characteristic of NS, exclusion of alternative diagnoses;
■ probable NS: clinical manifestations characteristic of NS, laboratory confirmation of the inflammatory process of the CNS (increased protein level or pleocytosis in the CSF, the presence of oligoclonal antibodies), MRI data characteristic of NS, exclusion of alternative diagnoses, confirmation of systemic sarcoidosis morphologically or laboratory (with radioisotope scinting - accumulation of gallium in foci, computed tomography of the chest organs, an increase in ACE in the blood serum);
■ significant NS: clinical manifestations characteristic of NS, exclusion of alternative diagnoses (multiple sclerosis, mass lesions, infectious lesions of the nervous system), positive results of the morphological study of the nervous system, positive dynamics against the background of immunosuppressive therapy during 1 year of observation.
Read more about neurosarcaidosis:
