SERUM DISEASE — the allergic disease caused by administration of heterological or homologous serums or serumal drugs and which is characterized by preferential inflammatory damage of vessels and connecting fabric.
The term «serum disease» was offered in 1905. K. A tuberculine test and B. Shik at the description of treatment of scarlet fever and diphtheria immune serums. By domestic pediatricians N. F. Filatov, G. N. Speransky, A. A. Koltypin, etc. it was in detail described a wedge, a picture C. Its pathogeny in an experiment was studied by L. Johnes and Fleischer (M. S. Fleisher, 1934), and in clinic — E. N. Korovayev (1949). Interest in S., edges can serve as model of a number of the diseases caused by cell-bound immune complexes (see. Allergic diseases , Autoallergy ), everything increases.
S.'s emergence. depends on a look and a dose of the used proteinaceous drug, and also on extent of its cleaning and frequency of introduction. At the first introduction of S. develops less often, at repeated — is much more often. S. is the most frequent. developed at use of native anti-toxic serums (see). So, at treatment of diphtheria of S. about 85% of cases were noted, this figure at repeated administrations of serum reached 96 — 100%. At introduction to practice of the immune serums purified by methods of enzymic hydrolysis, electrodialysis, etc., the frequency of emergence of S. decreased to 1 — 10%. Allergic reactions to drugs immunoglobulins (see) note even less often. At babies of S. frequency meets seldom, with age, intensity and weight of its manifestations increase: children up to 5 years have a frequency of development of S. averages apprx. 12,4%, teenagers have 47%. Death at S. comes rather seldom, generally at development acute anaphylaxis (see).
The heterological proteinaceous drugs serving as an origin of S., anti-toxic serums against tetanus (see), diphtherias are (see), botulism (see), gas gangrene (see. Mephitic gangrene ), a staphylococcal infection (see), poison of snakes (see. Snake poison), anti-lymphocytic serum (see). Most often such serums are prepared from blood of giperimmunizirovanny horses. Proteins of these serums also represent the antigens (see) causing S.'s development. Allergenicity of originally used native horse serums was very high. After removal of ballast proteins as a result of use of various ways of purification of serums their allergenic properties decreased. In the USSR the way of cleaning and concoction of serum by the Diaferm-3 method was widely adopted (see. Antitoxins ). The ground mass of protein of serums after cleaning by this method is made by fraction of gamma-globulins. However and these serums are quite allergenic. Pork, bull serum would cause S. also often, as well as horse. Persons, sensibilized to horse serum, can react to the serums received from animal other types, in the presence in them the general group antigens. The expressed allergenicity of heterological serums served as the reason of replacement with their homologous proteinaceous drugs (an integral blood plasma of the person or its protein fractions — a seralbumin, at - globulins).
Allergenicity of homologous proteinaceous drugs, to-rye can also be an origin of S., is much lower, than heterological. The sensibilizing properties of gamma-globulins are connected with the fact that each their series is prepared from the blood taken not less than from 1000 persons and, therefore, each class of immunoglobulins represents a set of the molecules belonging to different allotypes; the drugs prepared from a placenta of rny blood are contaminated And - and the V-group-specific antigens of blood; it is tended to aggregation of molecules of immunoglobulins. Aggregation of molecules of protein can be the cause: complications and at introduction of a blood plasma or seralbumin. S.'s symptoms. can appear at administration of the nek-ry medicines which are peptides or proteins of animal origin or containing proteins of animal origin in the structure (insulin, AKTG, extracts from a liver, organopreparata, etc.).
The way of administration of immune serum would be of great importance for S.'s emergence. At intravenous administration of serum C. develops more often than at intramuscular, but S. can develop also at intranasal administration of immune serum. The spontaneous sensitization is possible (see) at the consumption of a horse-flesh, inhalation of horse dandruff or other components having an antigenic affinity with proteins of horse serum or at their hit in an organism in the enteral way.
Pathogeny Page. turns on several immune mechanisms, from to-rykh conducting — the damaging action of the circulating cell-bound immune complexes. General mechanism of development of S. it is possible to present as follows. In response to introduction to an organism of antigen there is antibody formation, relating, obviously, to different classes of immunoglobulins. It would also define a possibility of inclusion in S.'s pathogeny, different immune mechanisms. One types of antibodies (which are preferential belonging to the class IgG) are precipitant antibodies and form the circulating cell-bound immune complexes (see Antigen antibody reaction), to-rye promote bystry removal of antigen from a blood-groove due to phagocytosis (see) these complexes mononuklear-ny phagocytes (see System of mononuclear phagocytes) that represents the usual immune response of an organism on antigen playing a protective role. In order that this reaction led to development of the damaging effect and by that to S.'s development., a number of conditions is necessary: a certain size of a complex antigen — an antibody (according to experimental data, the constant of its sedimentation shall make apprx. 19 S), a certain structure of a complex antigen — an antibody (small excess of antigen is necessary), participation of some mechanisms increasing permeability of a vascular wall. In these conditions the cell-bound immune complex gains ability to be postponed in a vascular wall in the place of its hyperpermeability, to activate a complement (see) and to cause damage of those fabrics, in vessels to-rykh this complex it is postponed. Increase in permeability of a vascular wall can be caused by various reasons. One of them is participation in process of antibodies of other look — the reagins relating hl. obr. to IgE. Such antibodies are tsitotropny and can be fixed on a surface of nek-ry cells, including and on basophiles. Activation of this immune response leads to release by basophiles of blood of a platelet activating factor (see Mediators of allergic reactions), to-ry causes aggregation of thrombocytes and release of a histamine from them (see) and serotonin (see), leading to change of permeability of a vascular wall. The cell-bound immune complex activates a complement. The SZ and S5 components of the activated complement are factors of a chemotaxis for neutrophils and stimulate phagocytosis. In the course of phagocytosis of cell-bound immune complexes neutrophils emit the enzymes causing destruction of connective tissue structures (elastic and collagenic fibers, basal membranes, etc.) * At the same time same components of a complement cause emission of a histamine by mast cells (see) that, in turn, leads to increase in permeability of a vascular wall. In 3 — 7 days after emergence of antibodies in a blood-groove cell-bound immune complexes are removed, antigen eliminirutsya from an organism and the patient recovers. In blood free antibodies continue to circulate (see), the caption to-rykh gradually decreases. Antibodies have no the damaging effect on fabrics.
Usually after the first administration of serum and the more so gamma-globulins conditions for S.'s development would not always be created. They arise, as a rule, at repeated administrations of serum.
Page. can develop also without immune response of an organism on the entered protein. It happens when administer the drugs of gamma-globulins or serums, in to-rykh there was a formation of complexes due to polymerization of molecules of gamma-globulins, especially, if these drugs are administered intravenously. Such drugs, possessing not only antigenic properties, but also expressed biol. activity, can activate a complement and cause so-called allergic reactions of not immune nature. Nonspecific biol. activity of drugs of gamma-globulins is caused by presence in them of vitamins, enzymes, hormones. Nek-rye from them, despite very low concentrations, can participate in pseudo-allergic reactions as catalysts of biochemical processes. In these cases at once there is complement activation, release of a histamine to all following behind it changes and bystry development of anaphylactoid reactions (see).
S.'s pathogeny. the hl was studied. obr. on experimental animals. Most often for S.'s reproduction. to rabbits intravenously enter protein, napr, a bull seralbumin at the rate of 250 mg/kg or horse serum at the rate of 10 ml/kg. S.'s symptoms. develop in 6 — 8 days after administration of protein with emergence in a blood-groove of antibodies in the corresponding quantities and formation of cell-bound immune complexes. The last are postponed in balls of kidneys that leads to development glomerulonephritis (see). At height of development it is defeat it is characterized by swelling and proliferation of endotheliocytes and mesangiocytes with narrowing or an obliteration of a gleam of glomerular circulatory capillaries. At people at S. damage of kidneys meets much less often. Chronic S. experimentally reproduce on animals by long daily administration of protein in small doses.
At the persons who died of S. of the B. t shown in the form of shock are established morfol. changes, / characteristic of an acute anaphylaxis (see). In other cases find the defeat of small vessels of internals (heart, pochekt a pancreas, etc.) reminding defeat of these bodies at a nodular periarteritis (see the Periarteritis nodular): type of a fibrinoid necrosis with hyalinization and infiltration by leukocytes, and also disturbances of microcirculation (see) — staz, fibrinferments, hemorrhages. Frequent manifestation of S. myocarditis (see) with diffusion intersticial eosinophilic infiltration, an endocarditis (see) with the centers of a fibrinoid necrosis in aortal valves is. The hyperplasia likhmf is characteristic. nodes, a spleen where accumulations of «foamy» macrophages around arterioles (so-called granulematozny defeat) are observed.
Clinical picture C. differs in variety of symptoms. Page. proceeds differently at persons, not sensibilized and sensibilized to serum proteins. At primary administration of heterological serum to not sensibilized persons C. develops after the incubation interval proceeding 7 — 12 days. The disease (at 33 — 73,1% of patients) usually begins with fervescence from subfebrile temperature to high figures. At the same time or a bit later there is enanthesis (in 85 — 98% of cases) having an appearance of a small tortoiseshell, erythematic, bark - and scarlatinal, papulovezikulezny, seldom hemorrhagic rashes. Rash arises most often in an injection site of serum, extending then is (often symmetric) on all body. Emergence of rash is followed by a severe itch, frustration of a hemodynamics, frequent hypostases (22 — 33% of cases), a hyperplasia limf, nodes (regional, and &zatm and remote), morbidity and swelling of joints (at 4.6 — 21,6% of patients, at repeated administration of serum at 50 — 60% of patients). Quite often note increase in a spleen. In patol. process is involved heart (quite often state myocardites, sometimes acute ischemia of a myocardium from an attack of stenocardia up to a heart attack), kidneys (a focal or diffusion glomerulonephritis), lungs (emphysema, a pulmonary eosinophilia, an acute fluid lungs, etc.), the alimentary and nervous system, a liver, mucous membranes is more rare. In blood — a leukopenia with a relative lymphocytosis at height of a disease, low sizes ROE at the beginning of a disease about a nek-eye its increase later. Sometimes note a thrombopenia, a hypoglycemia. Depending on severity of S. (easy, average, heavy) the occurred changes can last 5 — 6 days and have reversible character. A recurrence of process, in such cases of S. is characteristic. several months can proceed. Hron. S.'s current. it is caused or continuous intake of antigen in an organism, or inclusion in a pathogeny of autoallorgichesky mechanisms.
Picture C. at repeated administrations of heterological serum depends on the term which passed after its first introduction that, obviously, is connected with a type of the antibodies formed in response to the first administration of serum and their credits. At an interval between administrations of serum of 2 — 4 weeks reaction, as local, in the form of hypostasis and an inflammation as Artus-sa (see. Artyusa phenomenon ), and system (fever, rash, arthralgias, sometimes an acute anaphylaxis) develops almost immediately and quite violently. With increase in an interval between administrations of serum of an organism intensity of direct reaction decreases up to total disappearance and usual development of S. would be observed., but in terms shorter, than after the first administration of serum. Complications at S. observe seldom. Polyneurites, synovites, diffusion defeat of connecting fabric, a necrosis of skin and a hypodermic fatty tissue, hepatitises are described.
the Diagnosis in the presence of the characteristic anamnesis and complaints (an itch, a fever, a headache, perspiration, the alternating joint pains), and also an objective picture (skin rash with primary rashes in a zone of an injection, swelling limf, nodes, fervescence, tachycardia, hypotonia, a leukopenia with a lymphocytosis) does not represent work. As auxiliary diagnostic tests use a labor. methods of detection of precipitant antibodies, cell-bound immune complexes.
Differential diagnosis at polymorphic skin rashes is carried out with scarlet fever (see), to a bark (see), a clumsy rubella (see), an infectious mononucleosis, rashes of a medicamentous or alimentary origin. Severe form of S. sometimes it is necessary to differentiate with sepsis (see), damages of joints at S. — with acute joint rheumatism (see), acute arthritises (see).
Treatment depends on a form of a disease. At heavy immediate allergic reactions, as well as at an acute anaphylaxis (see. The acute anaphylaxis, treatment), is required acute management. At heavy S.'s development. with damage of joints and a nervous system carry out short (7 — 14 days) courses of therapy by steroid hormones; at S. moderately severe appoint injections of adrenaline, ephedrine, antihistaminic drugs (Suprastinum, Pipolphenum, etc.), drugs of calcium; at the expressed hypostases — diuretics (furosemide, Acidum etacrynicum); at joint defeats — non-steroidal anti-inflammatory drugs (acetylsalicylic acid, analginum, Brufenum); at fibrinferment of vessels — anticoagulants. In other cases a symptomatic treatment. At an easy current of S. happens purposes of antihistaminic drugs inside and topical administration of antipruritic means enough. At widespread to a small tortoiseshell (see) and a sharp itch apply rubdowns of 1 — 5% spirit solution of menthol, heat baths.
The forecast and Prevention
the Forecast in uncomplicated cases favorable. At complications — depends on their nature, adequacy and timeliness of treatment.
S.'s prevention. consists in improvement of quality of heterological serums generally by improvement of ways of their cleaning and improvement of quality of drugs of human gamma-globulins at the expense of the prevention of aggregation of their molecules. It is necessary to enter medical serums only according to strict indications and to replace them where only it is possible, with homologous gamma-globulins. Preliminary testing of patients for predisposition to S.
would be necessary. — careful collecting the allergological anamnesis, skin tests (see), Scarifying tests carry out by drawing a drop of water solution of serum in cultivation 1:100, then 1:10. At negative scarifying test carry out an intracutaneous test from 0,02 ml of serum in cultivation 1:100. At persons with the burdened allergological anamnesis concerning ispytuyemy serum the dose is reduced to 0,005 ml in cultivation 1:1000.
Medical doses of serum enter or is fractional (across Bezredka), or with preliminary administration of divorced serums (see. Bezredki methods ). At an allergy to dandruff of a horse, horse serum and in need of administration of antitetanic serum introduction human at - the globulin prepared from blood serum of people, immunizirovanny by tetanic anatoxin is more preferable.
In order to avoid cross-reactions to the persons who transferred S., do not recommend to eat horse meat, koumiss, to contact to those animal species, blood to-rykh is usually used for preparation of serums (horses, cattle).
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