Arthus phenomenon is a kind of local hypersensitivity reaction, the peculiarity of which is the formation of immune complexes in the blood and damage to the microcirculatory bed of various tissues and organs. Most often there is a form of pathology that occurs after the administration of drugs. Its symptoms are sharp redness, pain, swelling at the injection site, further necrosis of the skin and underlying structures is possible. The diagnosis is made by examining the skin, collecting anamnesis of the patient’s life, determining which medications he has used recently. Treatment includes taking glucocorticoid and antihistamines, eliminating contact with the allergen.
T88.7 Pathological reaction to a drug or medications, unspecified
Arthus phenomenon is one of the variants of drug intolerance caused by immunological hypersensitivity to active or auxiliary substances in their composition. It was first described in 1903 by the French physician Maurice Arthus. It can occur at any age, usually manifests itself in response to parenteral (subcutaneous or intramuscular) administration of drugs. An increased incidence of the disease is observed among people with atopic conditions (bronchial asthma, dermatitis, pollinosis).
Despite the local nature of the condition, it poses a serious threat with its complications. Prolonged contact (exposure) with a provoking drug significantly aggravates the manifestations of the phenomenon. This is due to the late appearance of symptoms (after weeks or even months), when the pathology is detected after repeated administration of the allergen – for example, as part of a course of treatment.
The etiology of the disease is multifactorial, as in any other allergic condition. It is based on both individual internal characteristics of the body and the consequences of external influences (ecology, nutrition, past illnesses). The nature of the pathological process also depends on the nature of the allergen – only some groups of drugs are able to provoke the appearance of the phenomenon. Most often , the Arthus reaction occurs when using the following drugs:
- Immunological agents. These include serums, some vaccines, anatoxins and other drugs with high immunogenicity. They can directly interact with the immune system and sometimes provoke intolerance.
- Antibiotics. Certain groups of antibacterial agents can cause allergies with parenteral administration. Most often, such a reaction is potentiated by penicillins, tetracyclines, and extremely rarely by macrolides.
- Vitamin complexes. Vitamin solutions used in many maintenance treatment regimens may react with specific antibodies. As in the case of antibiotics, pathology is complicated by the course use of these drugs, which increases the amount of allergen in the body.
- Insulin. In a small proportion of patients with diabetes mellitus, the Arthus phenomenon occurs due to injections of insulin solutions. Hypersensitivity usually develops not to the hormone itself, but to impurities in the composition of the drug.
Such a reaction can also be detected when using other protein and polypeptide substances. Sometimes the phenomenon is registered after cosmetic procedures of an injectable nature (mesotherapy, biorevitalization, botulinum therapy). The main conditions are parenteral administration of the allergen, its solubility in biological fluids and certain immunogenicity.
The phenomenon of Arthus, which is a special form of allergy, at the same time has a slightly different nature of pathogenesis. Basically, the processes of the third (immunocomplex) type of hypersensitivity reaction are observed. At the first contact of the body with the provoking substance, sensitization occurs – the process of the immune response and recognition of the allergen is activated. The result is the release of antigen-specific immunoglobulins of classes G and M by plasmocytes .
Upon new admission, the compound binds with these antibodies to form immune complexes. At the same time, repeated stimulation of lymphocytes occurs with the synthesis of new portions of specific IgG and IgM. The resulting immune complexes, unlike antigens and antibodies, are insoluble, settle on the walls of the vessels of the microcirculatory bed. There they activate the complement system, damaging the endothelium and triggering the blood clotting process. The resulting microthrombs in combination with cytotoxic immune reactions lead to tissue necrosis.
The result of these processes is local damage to the skin, subcutaneous fat, muscle fibers in the area of the highest concentration of antigen – at the injection site. With a significant number of immune complexes, they are able to spread through the body with blood flow, leading to the clinical picture of chronic serum sickness (CSD).
Symptoms of Arthus phenomenon
In the presence of sensitization, a single injection of a drug containing an allergen in its composition is sufficient for the development of pathology. In the case of an intact organism, the occurrence of the phenomenon is possible only with repeated administration (course treatment) or repeated use of the drug after a while (for example, revaccination). The symptoms of the disease appear after 7-10 days from the moment of contact with the antigen, sometimes this period is up to several months. There is redness and swelling around the injection site, turning into a dense and tense infiltrate. Patients complain of severe itching, soreness in the area of the pathological process.
With a small amount of the injected allergen and low reactivity, the Arthus phenomenon is limited to infiltration, which spontaneously resolves over several weeks. In severe cases, skin necrosis develops with the formation of a long-term non-healing ulcer. With intramuscular administration of the drug, myositis may occur. Due to intoxication of the body with tissue necrosis products, the body temperature rises, a feeling of weakness, headache appears. Secondary bacterial infection is a particular threat, the inflammatory process acquires a purulent-necrotic character. The healing of the pathological focus occurs within 1-3 months with the formation of a noticeable scar.
The most serious complication of the Arthus phenomenon is the development of serum sickness – a systemic immunocomplex reaction. Symptoms include severe fever, papular or erythematous rash throughout the body, swelling of the joints, disorders of the heart and kidneys. Usually, CSB occurs 1-3 weeks after the administration of a drug containing provoking compounds. Often, an infiltrate or a focus of skin necrosis is affected by a bacterial infection, the severity of symptoms depends on the nature of the microflora. In extremely rare cases, the phenomenon is combined with reactions such as urticaria or angioedema. This is considered an alarming sign because it indicates the risk of anaphylactic shock.
The diagnosis is made based on the results of an examination by an allergist-immunologist and a number of laboratory tests. A dermatologist’s consultation is often required to exclude other skin pathologies, as well as the opinion of the specialist who prescribed the injection of the drug. Some diagnostic techniques are aimed at detecting early signs of complications – bacterial infection or CSB. The definition of the Arthus phenomenon is performed according to the following algorithm:
- Survey and anamnesis collection. During the conversation with the patient, it turns out exactly when the symptoms of pathology appeared, whether parenteral administration of drugs was performed before that. The medical history is studied (if any), the type and dosage of drugs are determined.
- Inspection. A visual examination of the area of the pathological process is carried out – most often the phenomenon manifests itself on the lateral surface of the shoulder, in the scapular region or on the buttocks. The presence of localized infiltration or limited necrosis of the skin indicates an allergic condition.
- Laboratory tests. In uncomplicated forms, the picture of the general blood test changes slightly – ESR increases, a small leukocytosis is recorded. When a secondary infection is attached, the number of neutrophils increases. Changes in the biochemical analysis of blood (increased concentration of C-reactive protein, AsAT, AlAT) indicate the beginning of the development of CSB.
- Immunological tests. An enzyme-linked immunoassay (ELISA) to determine circulating immune complexes is necessary for early diagnosis of CSB. With mild variants of the Arthus phenomenon, the results are usually negative. Also, antibodies to antibiotics or other drugs that were administered to the patient are detected.
Differential diagnosis is carried out with pustular and inflammatory skin lesions (streptoderma, staphyloderma) and other dermatological conditions. To confirm CSB, an ECG, a biochemical blood test, and a general urinalysis may be required.
Treatment of Arthus phenomenon
The main goals of therapy are to weaken the immunological reaction, eliminate the allergen present in the body and prevent further contact with it. To do this, a number of therapeutic measures are used in immunology, their specific plan depends on many factors – the severity of the phenomenon, the duration of exposure to the antigen, its nature and amount in the body. Attention should also be paid to local treatment aimed at easing symptoms, accelerating healing processes and preventing infection. Therapy of the Arthus phenomenon includes the use of the following drugs and techniques:
- Glucocorticosteroids. Prednisolone and other compounds of this group contribute to the effective weakening of allergic reactions, slow down both the formation of immune complexes and cytotoxic processes in tissues. With early detection of the disease and the appointment of corticosteroids, it is almost always possible to avoid the development of necrosis and other complications.
- Infusion therapy. It is aimed at accelerating the elimination of the allergen from the body, it is produced by taking a large amount of fluid, intravenous infusions. Sometimes it is adjusted depending on the nature of the provoking antigen – for example, by taking certain diuretics, changing the pH of urine to better dissolve the provoking substance.
- Antihistamines. Effective in most cases of the Arthus phenomenon, significantly reduce the risk of necrosis and further spread of the pathological process. They are used in combination with steroid products.
- Local events. For the prevention of infectious complications, careful aseptic treatment of the affected area is necessary. To reduce itching and weaken the inflammatory process, ointments and gels containing steroids (hydrocortisone) are used. When the skin ulcerates, wound-healing agents are applied.
At the first detection of signs of the Arthus phenomenon, the administration of any medications is canceled, with the exception of vital ones before the allergen is determined. In the future, any use of a provoking substance and compounds similar to it in chemical structure is prohibited – for example, if penicillin is intolerant, all antibiotics of this series are contraindicated. If the cause of the pathology was an insulin drug, the drug is replaced with a hormone from another manufacturer, after which regular monitoring by an allergist-immunologist is required. The control lasts 3-6 months, this is necessary to ensure that there is no reaction to the new drug.
Prognosis and prevention
In the vast majority of cases, the Arthus phenomenon has a favorable prognosis. With proper treatment, pathology does not pose a threat to human life, skin disorders disappear without a trace. With the development of necrosis, a noticeable scar remains after healing. The main danger is complications, especially CSB, which can lead to systemic vasculitis with damage to many organs. There is also a potential risk of hypersensitivity to certain medications – this often requires expensive treatment of infectious and other diseases.
Prevention consists in the use of better drugs – it has been established that a high degree of purification of active substances reduces the likelihood of adverse reactions. If there is a confirmed intolerance to certain drugs, their use should be avoided – in particular, when contacting a doctor, always inform a specialist about it.