Eosinophilia-myalgia syndrome is a rare condition caused by taking certain drugs containing the amino acid tryptophan and characterized by pronounced systemic lesions (lungs, muscular system, joints and fascia). Symptoms include cough, shortness of breath, increased fatigue, muscle pain, neurological disorders and joint inflammation. Diagnosis is carried out through laboratory tests (general blood test), X-ray techniques and the study of the patient’s anamnesis. Treatment consists in canceling the administration of the provoking medication and conducting symptomatic therapy.
General information
Eosinophilia-myalgia syndrome was first diagnosed and isolated as a separate nosological unit in the mid-80s of the XX century. In those years, an outbreak of this pathology arose due to the widespread use of a tryptophan-based drug produced by one of the Japanese pharmaceutical companies. Currently, funds containing such an amino acid are practically not produced in the world, but cases of the disease still occur. It is usually caused by the use of falsifications of certain products (rapeseed oil) and medicines containing harmful impurities in their composition. The syndrome is equally likely to affect both men and women, and poses a potential danger to life.
Causes
An investigation conducted shortly after the discovery of eosinophilia-myalgia syndrome showed that its cause was not tryptophan itself (a vital amino acid), but some impurities in the drug. They got into the drug during the chemical synthesis of the main components and were considered conditionally safe because of the negligible concentration. Presumably, these impurities triggered unusual allergic processes leading to lung damage, a sharp increase in the number of eosinophils in the blood, muscle soreness and other disorders. The development of the syndrome was the main reason for the prohibition of such drugs.
There is also an assumption that the main cause of the pathology was the metabolites of tryptophan – compounds under the conditional names EBT and MTSA. Several other substances are suspected of participating in the pathogenesis of the syndrome. However, studies conducted with pure variants of these compounds have had mixed results, so their role in the etiology of the disease is disputed by some scientists. In addition to them, more than 60 impurities were found in those batches of medicines, the use of which is associated with a pathological condition. A number of researchers believe that the occurrence of violations is due to the combined action of multiple substances at once.
There is an opinion that L-tryptophan itself, when ingested in elevated doses, could provoke the development of eosinophilia, myalgia and other disorders. It has been established that this amino acid in its pure form is able to slow down the degradation of histamine-like compounds involved in many inflammatory and allergic reactions. Only in some patients taking tryptophan, the development of the syndrome is explained by the presence of reactivity features or other predisposition mechanisms. At the same time, this point of view does not explain why pathology occurs when using other products or medicines (for example, toxic oil syndrome has similar symptoms).
Pathogenesis
The pathogenetic processes in eosinophilia-myalgia syndrome have been studied even worse than its etiology, since the compound provoking the disease has not been reliably determined. Based on clinical data, it can be assumed that a certain factor provokes an increase in the formation or slowing down the breakdown of inflammatory stimulants – histamine, some interleukins and prostaglandins. This causes an immune inflammatory reaction in the lungs, muscle fascia, joints and nerves. The affected tissues are infiltrated by macrophages and lymphocytes, which further aggravates the pathological process. The development of eosinophilia, according to this hypothesis, is associated with an increase in the concentration of histamine – eosinophils play a central role in the processes of its decay.
According to another theory of the pathogenesis of the disease, the root cause, on the contrary, is precisely the activation of eosinophils, which begin to penetrate into tissues and contribute to the accumulation of toxic products in them. This, in turn, provokes the occurrence of inflammation involving other immunocompetent cells and the development of lymphocytic infiltration. But, as in the previous hypothesis, the triggering factor of the disease remains unknown. Histochemical data can be interpreted as evidence of both the first and second assumptions, so the study of the syndrome continues.
Symptoms
Manifestations of the syndrome occur after the use of medicines or other products containing tryptophan and its metabolites. The timing of the development of the disease can vary greatly – from a few days to 3-5 months after the start of admission. Initially, there is increased fatigue and fatigue, which is replaced by severe pain in the muscles, which increases with movements. At the same time, there are complaints about the weakness of the muscular system – the patient becomes unable to withstand the usual loads for him. Myalgia can be combined with unpleasant sensations in the heart area, which indicates involvement in the pathological process of the myocardium.
More than half of the patients have lesions of the respiratory system, manifested by coughing, wheezing when breathing, shortness of breath. The course of pathology is sometimes complicated by the symptoms of pleurisy – chest pain when breathing, increased dry cough. Respiratory disorders can persist for several weeks or even months. Edema of subcutaneous fat on the hands or feet is often determined. In especially severe cases, there is an accumulation of fluid in the body cavities – abdominal, pleural, pericardial. A number of patients with eosinophilia-myalgia have neurological symptoms in the form of sensitivity disorders of fingers, hands, feet.
The patient’s skin is usually pale or cyanotic, which indicates insufficient blood oxygenation and impaired pulmonary function. Sometimes there is a lesion of the joints, accompanied by pain during movement, swelling, redness of the articulation area. But more often, arthralgia becomes the only sign of joint involvement in the disease process. Systemic disorders (fever, fever, headaches, vomiting) occur only in some patients with this syndrome.
Complications
Eosinophilia-myalgia, according to medical statistics, leads to death in about 4-5% of cases. The cause of death is severe respiratory failure or cardiac dysfunction caused by myocarditis and fluid accumulation in the pericardial cavity (hydropericardium). With a prolonged course of the disease, there is a decrease in the respiratory volume of the lungs due to fibrosis, which reduces the quality of life and the ability to work of the patient. Cases have been described when rheumatoid polyarthritis occurred after the development of the syndrome. This indicates the possibility of immunological disorders due to the disease, but a reliable relationship between these two pathologies has not yet been found.
Diagnostics
To determine the eosinophilia-myalgia syndrome, many diagnostic techniques are used – a patient’s survey, X-ray examinations, general laboratory tests. If difficulties arise, microscopic examination of sputum, histological studies of affected tissues can be additionally performed. An unambiguous sign of pathology is the patient’s use of drugs or products containing synthesized free tryptophan. The diagnosis of the condition is carried out in stages as follows:
- Survey and anamnesis collection. When communicating with a patient, it is important for an allergist-immunologist to find out whether he has used any medications, oil products, some types of sports nutrition in recent days and weeks. With this in mind, it is possible to determine whether the patient has been in contact with tryptophan and its toxic metabolites. Among the complaints, shortness of breath, pain in different muscle groups, weakness are most often noted.
- X-ray examinations. On the chest X-ray, it is possible to detect signs of compaction of the lung tissue in the form of a mesh-nodular or mesh lesion. There are also signs of pleurisy and changes in the contours of the heart with hydropericardium. Radiography is not the main diagnostic method, since pathological changes are detected only in 20% of cases of the syndrome.
- Laboratory tests. In the general blood test, pronounced eosinophilia is determined – up to 1000 / ml. Signs of an inflammatory reaction are often recorded – an increase in ESR, leukocytosis.
- Histological examination. For the diagnosis of pathology, biopsies of the lungs (for respiratory disorders), muscles and fascia (for myalgia) and other tissues can be performed, depending on the clinical picture. Histological examination of the tissues of the affected organs reveals infiltration of small-caliber blood vessels by monocytes, eosinophils, lymphocytes.
Differential diagnosis is carried out with infectious and inflammatory lung lesions (bronchitis, pneumonia), heart diseases and systemic autoimmune conditions – some forms of rheumatism and polyarthritis. The main signs of the syndrome are the presence in the anamnesis of taking medications or products with tryptophan, the absence of signs of infection by blood tests.
Treatment of eosinophilia-myalgia syndrome
The main condition for the successful treatment of the disease is the exclusion of a tryptophan-containing drug or product that caused the pathological process. Therefore, during the diagnosis, it is important to determine where the patient receives the provoking substances. To reduce symptoms, corticosteroids are prescribed, which have a pronounced anti-inflammatory effect. The scheme and duration of their use depends on the specific clinical situation. In about half of the patients, the symptoms of pathology disappear a few days after the start of treatment, while in others they persist for 2-3 weeks.
Symptomatic measures are rarely required, with a strong cough, medications that reduce the activity of the cough center can be used. Edema is eliminated through the use of diuretic drugs. Antihistamines are not used because of their ambiguous and weak effect in this pathology. Sometimes supportive treatment is prescribed using multivitamin preparations.
Prognosis and prevention
The prognosis of eosinophilia-myalgia syndrome is conditionally favorable with early detection and timely referral to a specialist. After the exclusion of the provoking substance and corticosteroid therapy, the symptoms disappear without consequences. In the case of a prolonged flow in the lungs, sclerotic processes may develop, reducing the vital capacity and the surface of gas exchange. This leads to shortness of breath with moderate physical exertion, cyanotic skin and other disorders. Prevention of the syndrome consists in refusing to use drugs containing tryptophan, especially of questionable origin. It is necessary to cancel the use of such drugs as soon as possible if muscle soreness, cough, shortness of breath occurs against the background of their use.
