The sarcoidosis (from ancient Greek σαρκωειδής sarkoeidés "meaty, fleshy"), also called sarcoidosis ( BUK ), Boecksche disease or Crohn Schaumann Besnier called, is a systemic disease of the connective tissue with granuloma formation, mostly between the 20th and 40th Year of life occurs. The exact cause of the disease is still unknown.
A distinction is made between an initially acute form of sarcoid, the so-called Löfgren syndrome , from the creeping and low-symptom onset chronic form. In Germany, sarcoid occurs in 20 to 30 cases per 100,000 inhabitants.
It was first described as a skin disease by Ernest Besnier and Cæsar Peter Møller Boeck in 1889 and 1899 . In 1924 Jörgen Nilsen Schaumann recognized that this was a systemic disease of various organs. In 1953, the Swede Sven Halvar Löfgren described the acute form that is named after him .
Sarcoid is a global disease that affects men slightly more often than women, with numbers reversing with age. There is a significant accumulation between the ages of 20 and 30, although this accumulation is even more pronounced in men than in women. The number of cases decreases again significantly after the age of thirty. Children under ten years of age are practically not affected, and neither are people over 70. In the USA and (Western) Europe, the proportion of people affected, the so-called prevalence , is between 1 and 40 per 100,000 inhabitants, depending on the assessment basis. An above-average accumulation can be found among Northern Europeans and the Afro-American population in the USA. The highest proportion of new cases ( incidence ) is found in Sweden and Iceland with over 60 cases per 100,000 inhabitants per year. In Germany the incidence is 10–12 per 100,000 inhabitants per year. The epidemiology suggests a genetic contributory cause. Sarcoidosis is more common in some families; close relatives of a sarcoid patient are about twenty times more likely to get the same disease, but spouses are not more likely.
An increased inflammatory activity and an increased cellular immune response with the development of non-melting granulomas form the pathogenesis . These granulomas show differentiated epithelial and giant cells . The inflammatory reaction described is based on a disruption of the T lymphocyte function and, at the same time, increased B lymphocyte activity. This leads to local immunological overactivity with the granuloma formation described above, particularly in the lung tissue and the lymphatic system. Lymph nodes (90% of cases, lymph node sarcoid ) and the lungs (90%, pulmonary sarcoid ) are particularly affected . But also other organs like liver (60–90%, liver sarcoidosis ), eyes (25%, eye sarcoidosis ), heart (5%, cardiac sarcoidosis ), skeleton (25–50%, skeletal sarcoidosis ), spleen (50–60%, splenic sarcoidosis ) or skin (25–50%, cutaneous sarcoid ) and bone marrow (15–40%) can be affected. If the nerve tissue is affected, one speaks of neurosarcoidosis . Since the disease can occur in families, a genetic predisposition is suspected. In February 2005, the first genetic mutation was found that correlated with an outbreak of the disease . The mutation of a single base pair in the BTNL2 gene on chromosome 6 is sufficient to increase the probability of the disease by 60%. A change in the gene copies on both chromosomes increases the risk three-fold. BTNL2 affects an inflammatory response that activates certain white blood cells .
Mostly the lungs are affected, but since other organs can be affected in around 30%, the symptoms are variable. The disease usually manifests itself through a feeling of pressure in the upper body with increasing coughing up to shortness of breath as well as swelling of the lymph nodes, most often in the mediastinum . Patients often experience tiredness ( fatigue ) and joint pain. In the common Löfgren syndrome , fever , joint pain, swelling of the liver and spleen as well as acute inflammation of the subcutaneous fatty tissue with "lump formation" ( erythema nodosum ) are the symptoms most frequently mentioned, usually on the lower legs and ankles. If skin is involved, skin nodules can also appear in different distribution patterns. The changes visible on the skin are often the first noticeable symptom to indicate the diagnosis. A characteristic chronic course of the skin is known as lupus pernio and is characterized by a bluish swelling with erosions of the cheeks, nose, lips and hands.
If the heart is affected, cardiac arrhythmias or cardiac muscle weakness can occur. A pleural effusion is also rarely found . If the eye is involved, one often finds uveitis (inflammation of the middle skin of the eye), which, if the tear duct is involved, can develop into keratoconjunctivitis sicca . A disturbed calcium metabolism , which can be associated with nephrocalcinosis (kidney calcification ), is seldom found with kidney involvement . The cystic transformation of the finger bones ( youth syndrome ) is an expression of bone involvement.
Heerfordt's syndrome is a special form , in which granulomatous inflammation of the parotid glands can lead to compression of the facial muscle nerves and thus to partial or complete paralysis of the halves of the face on one or both sides ( facial paralysis ). Involvement of the meninges ( meninges ) and the paranasal sinuses with possible subsequent destruction of the cartilage is also described (occurrence in 2 to 18% of patients). Infestation of the hypothalamus - pituitary control circuit with the resultant diabetes insipidus is very rare .
Since any organ can potentially be affected by the disease, the diagnosis is based on the respective symptoms. Due to the swelling of the lymph nodes, which are often symptom-free, sarcoid is often discovered by chance on a chest x-ray . Depending on the pattern of involvement and drawing in the X-ray image or in computed tomography can pulmonary sarcoidosis in the following stages (after Scadding, 1967) are divided, this division often does not reflect the severity and prognosis of the disease:
- Stage 0: normal lung findings when another organ is involved
- Stage I: symmetrical lymph node enlargement without visible involvement of the lung tissue
- Stage II: enlargement of the lymph nodes on both sides with perilymphatic formation of granulomas in the lung tissue
- Stage III: lung involvement with missing lymph node enlargement
- Stage IV: fibrotic remodeling of the lung tissue with loss of function of the lungs.
The older classification according to Wurm (1958) with stages I to III was used even earlier.
In the laboratory, the acute form often shows an increase in the erythrocyte sedimentation rate (ESR) and an increased proportion of blood cells in the blood count of younger age (the so-called left shift ). Raised antibody and immunoglobulin G levels in more than half of the patients are signs of increased B-cell activity . At the same time, there is a disorder of the T cells , which can be expressed clinically in a negative tuberculin test .
The angiotensin conversion enzyme (ACE) and the soluble interleukin-2 receptor (s-IL-2R) can also be increased in over 60% of patients, but this also occurs in other diseases, so that they are predominantly process parameters or activity parameters. If the kidneys are involved, increased calcium levels in the urine and blood and an increased calcitriol level are measured. An elevated neopterin level usually correlates with the inflammatory activity of the macrophages .
A lung function test , usually also an X-ray of the lungs and a computer tomography, are carried out in order to assess the need for therapy. A bronchoalveolar lavage (BAL) with cytology can often be useful for the diagnosis. It typically shows lymphocytic alveolitis with an increase in the CD4 / CD8 ratio due to an increase in the number of T helper cells . The quotient is approx. 2 in healthy individuals and> 5 in acute sarcoid. A transbronchial lung biopsy or endobronchial ultrasound (EBUS) targeted transbronchial biopsy of the enlarged mediastinal lymph nodes can histopathologically help to confirm the diagnosis. In particular, non- caseating , epithelial cell granulomas with Langhans giant cells and a marginal wall of lymphocytes , monocytes and fibroblasts are observed in the preparations . However, the histological picture is not specific to sarcoid. The previously recognized 67 Ga - scintigraphy was replaced by the FDG-PET / CT examination. On the one hand, it serves to control the effectiveness of the therapy carried out; on the other hand, an examination can provide an overview of the number of organ systems affected.
The diagnosis is made as a diagnosis of exclusion. The suspicion of sarcoid must be differentiated from pulmonary tuberculosis , tumor seeding of the lungs ( lymphangiosis carcinomatosa ) or lymphoma . Other fibrosing lung diseases such as Langerhans cell histiocytosis , exogenous allergic alveolitis and pneumoconiosis such as silicosis , berylliosis , mixed dust silicosis or asbestosis are also possible. In the presence of erythema nodosum , borreliosis , Yersinia , various bacteria, cystic fibrosis , Crohn's disease , lupus erythematosus and other diseases that are associated with the same symptoms must be considered.
Course and prognosis
Depending on the stage, the course of the sarcoid must be assessed. In stage I, the sarcoid almost always heals in an acute form without the need for further therapy, just as a high spontaneous healing rate is observed in stage II. Overall, around 60% of patients experience spontaneous remission in the first 3 years. In other cases, the disease is chronic, mostly relapsing, with a relatively favorable prognosis. Only a few cases develop into a chronically progressive form. Rarer, severe forms of the disease can progress to pulmonary hypertension (with cardiac involvement referred to as cor pulmonale ) and respiratory insufficiency ( shortness of breath ).
As a rule of thumb, the younger the patient, the more acute the course, the better the prognosis.
Therapy status 2018
There is no causal therapy for sarcoid. Therapy makes sense if there are symptoms or complications. Since up to 60% of sarcoidoses have a spontaneous remission , one can first observe closely and try to alleviate the various symptoms symptomatically . On the other hand, in the case of symptomatic organ involvement, cortisone therapy is carried out, for example in the case of functional limitations of the lungs, especially stage III or hypercalcaemia (including bone marrow involvement). The dosage is often 20–80 mg / day prednisolone , after a while an attempt can be made to reduce it and then taper it off . Steroid-related side effects should be kept as low as possible. In some cases, methotrexate is also used , usually at a dose of 10–15 mg / week, to reduce the dose of cortisone. Immunosuppressants such as azathioprine and chloroquine can also be used in long-term therapy . All therapies must be closely monitored by a doctor.
In Löfgren's syndrome and in acute attacks, acetylsalicylic acid , ibuprofen or diclofenac , and possibly additional painkillers, are used instead of (or in addition to) corticoids . If the skin symptoms are in the foreground in sarcoid (cutaneous sarcoid), therapy with tetracyclines or allopurinol can be tried. The mechanism of action of allopurinol is unclear.
The timing of the start of therapy with corticosteroids in sarcoidosis is not without controversy, since this therapy only suppresses the symptoms and could cause them to reappear when the therapy is ended. A study on cortisone therapy came to the conclusion that treatment with cortisone significantly increased the relapse rate . On the one hand, the cortisone treatment itself is mentioned as a possible cause, alternatively it could simply be due to the fact that predominantly more severe disease courses were treated with cortisone. Small studies give indications of the effect of the TNF-α blocker infliximab as well as in other diseases from the rheumatic group. It may, however, increase mortality.
An accompanying psychotherapeutic treatment can have a positive effect on the course of the disease.
Possible contributory causes
The places of manifestation lungs, skin and eyes suggest an exogenous agent, for example inorganic dust components. For example, firefighters from Ground Zero were more often affected by granulomas. Organic substances such as bacterial DNA have also been found in granulomas.
Certain similarities between sarcoid and tuberculosis led to the suspicion that sarcoid could also have bacterial causes. Attempts to treat sarcoid with anti-tuberculosis drugs have been largely unsuccessful. A meta-study summarized all work between 1980 and 2006 that attempted to find mycobacteria in sarcoid with the help of PCR . There was a clear association of some types of sarcoid with the presence of the pathogen. Other pathogens as a cause cannot be excluded.
As describer of sarcoidosis (more synonyms: lymphogranuloma (tosis) benigna, Boeck-Besnier-Schaumannsche disease Lungentuberkuloid, benign Miliarlupoid, multiple benign sarcoid, epithelioid reticuloendotheliosis ) can Jonathan Hutchinson are considered (1828-1913). In 1863 he presented a patient suffering from gout who also had skin changes and died four years later of kidney failure . However, Hutchinson attributed this to gout - today it is believed that the change in calcium metabolism due to sarcoidosis was the actual cause. The French dermatologist Ernest Henri Besnier (1831-1909) described in 1889 a symmetrical skin change on the extremities. His Norwegian colleague Cæsar Peter Møller Boeck (1845–1917) mentioned the histological skin changes in the scientific article multiple benign sarcoid of the skin in 1899 and even then suspected a systemic disease. The skin changes have since been known as Boeck's sarcoid .
The Danish ophthalmologist Christian Frederick Heerfordt (1871-1953) described a febrile inflammation of the conjunctiva with nerve involvement in 1909 and assigned this to mumps based on laboratory values . In 1924, the Swedish dermatologist Jörgen Nilsen Schaumann (1879–1953) confirmed Boeck's discoveries that this is a systemic disease of various organs, and called sarcoid disease Lymphogranulomatosis benigna in order to differentiate it from Hodgkin's lymphoma .
In 1941, the Norwegian doctor Morten A. Kveim (1892–1966) described the Kveim test for diagnosing sarcoid, but it went out of use in the 1990s.
The Swede Sven Halvar Löfgren (1910–1978) described the acute form in 1953 using the symptom triad erythema nodosum , arthritis and biliary lymphadenopathy (bilateral involvement of the lymph nodes in the lungs). This clinical picture, which is often found in young people, is known as Löfgren's syndrome.
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