Periarteritis nodosa

A rare pathology – periarteritis nodosa – is accompanied by damage to medium- and small-caliber arterial vessels. In the vascular walls, processes of connective tissue disorganization, inflammatory infiltration and sclerotic changes occur, resulting in the appearance of clearly defined aneurysms. [ 1 ]

Other names for the disease: polyarteritis, necrotic arteritis, panarteritis.

Epidemiology

Nodular periarteritis is a systemic pathology, necrotizing vasculitis, damaging medium and small arterial vessels of the muscular type. Most often, the disease spreads to the skin, kidneys, muscles, joints, peripheral nervous system, digestive tract, and other organs, less often - the lungs. The pathology usually manifests itself initially with general symptoms (fever, general deterioration in health), then more specific signs join.

The most common methods for diagnosing the disease are biopsy and arteriography.

The most acceptable medications for treatment are glucocorticoids and immunosuppressants.

The incidence of periarteritis nodosa is from two to thirty cases per 1 million patients.

The average age of those affected is 45-60 years. Men are more often affected (6:1). In women, the disease often occurs according to the asthmatic type, with the development of bronchial asthma and hypereosinophilia.

In approximately 20% of cases of diagnosed periarteritis nodosa, patients are found to have hepatitis (B or C). [ 2 ], [ 3 ]

Causes periarteritis nodosa

Scientists have not yet discovered a clear cause for the development of nodular periarteritis. However, the following main triggers for the disease are identified:

• reaction to taking medications;
• persistence of viral infection (hepatitis B).

Experts have compiled a fairly impressive list of drugs involved in the development of nodular periarteritis. Among these medications are:

• beta-lactam antibiotics;
• macrolide drugs;
• sulfonamide drugs;
• quinolones;
• antiviral agents;
• serums and vaccines;
• selective serotonin reuptake inhibitors (Fluoxetine);
• anticonvulsants (Phenytoin);
• Levodopa and Carbidopa;
• thiazides and loop diuretics;
• Hydralazine, Propylthiouracil, Minocycline, etc.

Every third or fourth patient with periarteritis nodosa had hepatitis B surface antigen (HBsAg) or immune complexes with it. Other hepatitis B antigens (HBeAg) and antibodies to the HBcAg antigen, formed during viral replication, were also detected. It is noteworthy that the incidence of periarteritis nodosa in France has significantly decreased in recent decades due to widespread vaccination against hepatitis B.

Also, approximately one in ten patients is found to have the hepatitis C virus, but the details of the relationship have not yet been proven by scientists. Other viral infections are also “under suspicion”: human immunodeficiency virus, cytomegalovirus, rubella and Epstein-Barr viruses, T-lymphotropic virus type I, parvovirus B-19, etc.

There is every reason to believe that vaccination against hepatitis B and influenza is involved in the development of periarteritis nodosa.

An additional suspected factor is genetic predisposition, which also requires evidence and further study. [ 4 ]

Risk factors

Nodular periarteritis is a poorly understood disease, but specialists already consider it polyetiological, since many causes and factors may be involved in its development. Often, a connection is found with focal infections: streptococcal, staphylococcal, mycobacterial, fungal, viral, etc. A significant role is played by human hypersensitivity to certain medications - for example, to antibiotics and sulfonamides. However, in many cases, even with careful diagnostics, the etiological factor cannot be identified.

Here are the risk factors that doctors know about today:

• age category over 45 years, as well as children from 0 to 7 years (genetic factor);
• sudden changes in temperature, hypothermia;
• excessive exposure to ultraviolet radiation, excessive tanning;
• excessive physical and mental stress;
• any damaging effects, including injuries or surgical interventions;
• hepatitis and other liver diseases;
• metabolic disorders, diabetes mellitus;
• hypertension;
• introduction of vaccines and persistence of HbsAg in blood serum.

Pathogenesis

The pathogenesis of the occurrence of nodular periarteritis consists of the formation of a hyperallergic response of the body to the influence of etiological factors, in the development of an autoimmune reaction of the antigen-antibody type (in particular, to the walls of blood vessels), in the formation of immune complexes.

Since endothelial cells are equipped with receptors for the Fc fragment of IgG with the first fraction of complement Clq, the mechanisms of interaction between immune complexes and vessel walls are facilitated. Deposition of immune complexes in the vessel walls is observed, which entails the development of an immune inflammatory process.

The formed immune complexes stimulate complement, which leads to damage to the walls and the formation of chemotactic components that attract neutrophils to the damaged area. [ 5 ]

Neutrophils perform a phagocytic function in relation to immune complexes, but at the same time, lysosomal proteolytic enzymes are released, which damage the walls of blood vessels. In addition, neutrophils "stick" to the endothelium and, in the presence of complement, release active oxygen radicals, which provoke vascular damage. At the same time, endothelial release of factors that favor increased blood clotting and thrombus formation in the affected vessels is potentiated.

Symptoms periarteritis nodosa

Nodular periarteritis manifests itself through general non-specific symptoms: a person has a constantly elevated temperature, he progressively loses weight, and is bothered by pain in the muscles and joints.

An increase in temperature in the form of a persistent fever is typical for 98-100% of cases: the temperature curve is of an irregular type, there is no response to antibiotic therapy, but corticosteroid therapy is effective. The temperature may subsequently normalize, against the background of the development of multiple organ pathology.

The patients' emaciation is pathognomic. Some patients' weight decreases by 35-40 kg within a few months. The degree of emaciation exceeds that of oncopathologies.

Muscle and joint pain is especially characteristic of the initial stage of periarteritis nodosa. Pain most often affects large joints and calf muscles. [ 6 ]

Polyorgan pathologies are divided into several types, which determines the symptoms of the disease:

• When the renal vessels are affected (and this happens in most patients), there is an increase in blood pressure. Hypertension is persistent, stable, causing a severe degree of retinopathy. Loss of visual function is possible. Urine analysis reveals proteinuria (up to 3 g/day), micro or macrohematuria. In some cases, the vessel dilated by the aneurysm ruptures, forming a perirenal hemorrhage. Renal failure develops during the first three years of the disease.
• When vessels located in the abdominal cavity are damaged, symptoms appear already at an early stage of nodular periarteritis. The main symptoms are abdominal diffuse pain, persistent and progressive. Dyspeptic disorders are noted: diarrhea with blood up to ten times a day, weight loss, bouts of nausea and vomiting. If ulcerative perforation occurs, signs of acute peritonitis develop. There is a risk of developing gastrointestinal bleeding.
• Heart pain is not typical when coronary vessels are affected. Heart attacks occur, mostly of a small focal nature. Cardiosclerosis phenomena rapidly increase, which entails the appearance of arrhythmias and signs of cardiac insufficiency.
• When the respiratory system is affected, bronchospasms, hypereosinophilia, and eosinophilic infiltrates in the lungs are detected. The formation of vascular inflammation of the lungs is characteristic: the disease is accompanied by cough, scanty sputum secretions, less often - hemoptysis, increasing symptoms of insufficient respiratory function. The radiograph visualizes a sharply enhanced vascular pattern of the congestive lung type, infiltration of the lung tissue (mainly in the root region).
• When the peripheral nervous system is involved, asymmetric poly and mononeuritis are observed. The patient suffers from severe pain, numbness, and sometimes muscle weakness. Legs are most often affected, and arms are less often. Some patients develop polymyeloradiculoneuritis, paresis of the feet and hands. Peculiar nodules along the vascular trunks, ulcers, and necrotic foci on the skin are often found. Necrosis of soft tissues and the development of gangrenous complications are possible.

First signs

The initial clinical picture of periarteritis nodosa manifests itself as fever, a feeling of extreme fatigue, increased night sweating, loss of appetite and emaciation, muscle weakness (especially felt in the extremities). Many patients develop muscle pain, accompanied by focal ischemic myositis and joint pain. The affected muscles lose strength, and inflammatory processes in the joints may develop. [ 7 ]

The severity of the first signs varies, depending largely on which organ or organ system is affected:

• damage to the peripheral nervous system is manifested by motor and sensory disorders of the ulnar, median and peroneal nerves; the development of distal symmetrical polyneuropathy is also possible;
• the central nervous system responds to pathology with headaches; strokes (ischemic and hemorrhagic) are less common against the background of high blood pressure;
• kidney damage is manifested by arterial hypertension, a decrease in the daily amount of urine, uremia, general changes in urine sediment, the appearance of blood and protein in the urine in the absence of cellular casts, pain in the lower back, and in severe cases, signs of renal failure;
• the digestive tract makes itself known with pain in the liver and abdomen, nausea, vomiting, diarrhea, symptoms of malabsorption, intestinal perforation and peritonitis;
• there may be no pathological signs from the heart, or symptoms of heart failure may appear;
• on the skin there is a reticular livedo, reddened painful nodules, a rash in the form of bubbles or vesicles, areas of necrosis and ulcerative lesions;
• The genitals are affected by orchitis, the testicles become painful.

Kidney damage in periarteritis nodosa

The kidneys are affected in more than 60% of patients with periarteritis nodosa. In more than 40% of cases, the damage is renal failure.

The likelihood of developing kidney disorders depends on the gender and age category of patients, the presence of pathologies of the skeletal muscles, the valvular system of the heart and the peripheral nervous system, the type of progression and phase of the disease, the presence of viral hepatitis antigen and cardiovascular values.

The rate of development of nephropathy is directly determined by the level of C-reactive protein and rheumatoid factor in the blood.

Renal disorders in periarteritis nodosa are caused by stenosis and the appearance of microaneurysms of the renal vessels. The degree of pathological changes is related to the severity of nervous system disorders. It is necessary to understand that kidney damage dramatically reduces the chances of patient survival. However, this issue of the influence of certain renal dysfunctions on the course of periarteritis nodosa has not been sufficiently studied.

The inflammatory process usually spreads to the interlobar arterial vessels and, less frequently, to the arterioles. Presumably, glomerulonephritis is not typical for nodular periarteritis and is observed mainly against the background of microscopic angiitis.

Rapid worsening of renal failure is caused by multiple infarctions in the kidneys. [ 8 ]

Heart failure

The picture of cardiovascular damage is observed in every second case out of ten. The pathology is manifested by hypertrophic changes in the left ventricle, increased heart rate, and cardiac arrhythmia. Inflammation of the coronary vessels in nodular periarteritis can provoke the appearance of angina pectoris and the development of myocardial infarction.

In macroscopic preparations, nodular thickenings of the rosary type are found in more than 10% of cases, from several millimeters to a couple of centimeters in diameter (up to 5.5 cm in case of damage to large vascular trunks). The section demonstrates an aneurysm, often with thrombotic filling. Histology plays the final diagnostic role. A typical feature of nodular periarteritis is polymorphic vascular damage. A combination of different types of connective tissue disorganization is noted: [ 9 ]

• mucoid swelling, fibrinoid changes with subsequent sclerosis;
• narrowing of the vascular lumen (up to obliteration), formation of blood clots, aneurysms, and in severe cases – rupture of blood vessels.

Vascular changes become a trigger mechanism in the development of necrosis, atrophic and sclerotic processes, hemorrhages. Some patients experience phlebitis.

In the heart, atrophy of the epicardial fat layer, brown myocardial dystrophy, and, in hypertension, left ventricular hypertrophy are detected. In coronary lesions, focal myocardial necrosis, dystrophy, and atrophy of muscle fibers develop. Myocardial infarctions are relatively rare, mainly due to the formation of collateral blood flow. Thrombovasculitis is detected in the coronary arterial trunks. [ 10 ]

Skin manifestations of periarteritis nodosa

Skin signs of the disease are observed in every second patient with nodular periarteritis. Often, the appearance of rashes is the first, or one of the first signs of the disorder. The following symptoms are typical:

• vesicular and bullous rash;
• vascular papulopetechial purpura;
• sometimes – the appearance of subcutaneous nodular elements.

In general, the skin manifestations of periarteritis nodosa are heterogeneous and varied. Common signs may include:

• the nature of the rash is inflammatory;
• the rash is symmetrical;
• there is a tendency towards swelling, necrotic changes and hemorrhages;
• at the initial stage, the rash is localized in the area of the lower extremities;
• evolutionary polymorphism is noted;
• a connection can be traced with previously existing infections, medication intake, temperature changes, allergic processes, autoimmune pathologies, and impaired venous circulation.

Skin lesions vary widely, from spots, nodules and purpura to necrosis, ulcers and erosions.

Periarteritis nodosa in children

Juvenile polyarteritis is a form of nodular polyarteritis, which is found mainly in pediatric patients. This variant of the disease is characterized by a hyperergic component, mostly peripheral vessels are damaged, there is a considerable risk of developing thromboangiotic complications in the form of dry tissue necrosis, gangrenous processes. Visceral disorders are relatively weak and do not affect the outcome of the pathology, but there is a tendency to a prolonged course with periodic relapses.

The classic form of juvenile polyarteritis has a severe course: kidney damage, high blood pressure, abdominal ischemia, cerebral vascular crises, inflammation of the coronary vessels, pulmonary vasculitis, and multiple mononeuritis are observed.

Among the causes of the disease, allergic and infectious factors are mainly considered. The classic form of nodular periarteritis is associated with the viral infection hepatitis B. Often, the onset of the disease is noted along with acute respiratory viral infections, otitis and tonsillitis, somewhat less often - with the introduction of vaccines or drug therapy. Genetic predisposition is also not excluded: often, rheumatological, allergic or vascular pathologies are found in direct relatives of a sick child.

The incidence of periarteritis nodosa in childhood is unknown: the disease is diagnosed very rarely.

Pathogenesis is often caused by immune complex processes with increased complement activity and leukocyte accumulation in the area of immune complex fixation. Inflammatory reaction occurs in the walls of small- and medium-caliber arterial trunks. As a result, proliferative-destructive vasculitis develops, the vascular bed is deformed, blood circulation is inhibited, rheological and coagulation properties of blood are disrupted, thrombosis and tissue ischemia are observed. Mural fibrosis gradually develops, aneurysms with a diameter of up to 10 mm are formed.

Stages

Nodular periarteritis can occur in acute, subacute and chronic recurrent stages.

• The acute stage is characterized by a short initial period, with intensive generalization of vascular damage. The course of the disease is severe from the moment of its onset. The patient has a high temperature of the remittent fever type, profuse sweating, severe joint pain, myalgia, abdominal pain. When the peripheral circulation is affected, rapid formation of wide foci of skin necrosis occurs, and a distal gangrenous process develops. When internal organs are affected, intense vascular-cerebral crises, myocardial infarction, polyneuritis, intestinal necrosis are observed. The acute period can be observed for 2-3 months or more, up to one year.
• The subacute stage begins gradually, mainly in patients with predominant localization of the pathological process in the area of internal organs. For several months, patients have subfebrile temperature, or the temperature periodically rises to high values. Progressive emaciation, joint and headaches are observed. Subsequently, acute development of cerebrovascular crisis, or abdominal syndrome, or polyneuritis is noted. The pathology remains active for up to three years.
• The chronic stage can be observed both in acute and subacute disease processes. Patients begin to experience alternating periods of exacerbation and disappearance of symptoms. During the first few years, relapses are observed every six months, then remissions can become longer.

Acute course of periarteritis nodosa

The acute phase of periarteritis nodosa is usually severe, since certain vital organs are affected. In addition to clinical manifestations, laboratory changes also influence the assessment of disease activity, although they are not specific enough. Increased ESR, eosinophilia, leukocytosis, increased gamma globulins and the number of CICs, and decreased complement levels may be observed.

Periarteritis nodosa is characterized by either a fulminant course or periodic acute phases against the background of constant progression of the pathology. A fatal outcome can occur at almost any time with the development of renal or cardiovascular failure, damage to the digestive tract (perforation of the intestine is especially life-threatening). Disorders of the kidneys, heart and central nervous system are often aggravated by persistent arterial hypertension, which leads to serious late complications, which can also cause the death of the patient. In the absence of treatment, the five-year survival rate is estimated at approximately 13%. [ 11 ]

Complications and consequences

The severity of the patients' condition and the likelihood of complications are due to a persistent increase in blood pressure, up to 220/110-240/170 mm Hg.

The active stage of the disease often ends with cerebral circulation disorders. The progression of the pathology leads to hypertension becoming malignant, cerebral edema occurs, and some patients develop chronic renal failure, cerebral hemorrhage, and kidney rupture.

Often, renal syndrome develops, ischemia of the juxtaglomerular renal apparatus develops, and the mechanism of the renin-angiotensin-aldosterone system is disrupted.

On the part of the digestive tract, local and diffuse ulcers, foci of intestinal necrosis and gangrene, and appendicitis are observed. Patients experience intense abdominal pain syndrome, intestinal bleeding may develop, and signs of peritoneal irritation appear. Intraintestinal inflammatory disorders do not have histological signs of ulcerative colitis. Internal bleeding, pancreatitis with pancreatic necrosis, and infarction of the spleen and liver may occur.

Damage to the nervous system can be complicated by the development of a cerebral vascular crisis, which manifests itself abruptly, with headache and vomiting. Then the patient loses consciousness, clonic and tonic convulsions, sudden hypertension are noted. After the attack, lesions often appear in the brain, which is accompanied by paralysis of the gaze, diplopia, nystagmus, facial asymmetry, and visual impairment.

In general, periarteritis nodosa is a life-threatening pathology and requires the earliest possible diagnosis and aggressive ongoing treatment. Only under such conditions can stable remission be achieved and the development of severe dangerous consequences be avoided.

Outcome of periarteritis nodosa

More than 70% of patients with nodular periarteritis experience increased blood pressure and signs of increasing renal failure within the first 60 days of the onset of the disease. Damage to the nervous system is possible, with sensitivity preserved but motor activity limited.

The abdominal vessels may become inflamed, causing severe abdominal pain. Dangerous complications often include stomach and intestinal ulcers, gallbladder necrosis, perforation and peritonitis.

Coronary vessels are affected less frequently, but such an outcome is also possible: patients develop myocardial infarction. When cerebral vessels are damaged, strokes occur.

Without treatment, almost all patients die within the first few years from the onset of the pathology. The most common problems leading to death are: extensive arteritis, infectious processes, heart attack, stroke.

Diagnostics periarteritis nodosa

Diagnostic measures begin with collecting complaints from the patient. Particular attention is paid to the presence of rashes, the formation of necrotic foci and ulcerative skin lesions, pain in the area of the rash, in the joints, body, limbs, muscles, as well as general weakness.

An external examination of the skin and joints is mandatory, the location of the rash and the painful areas are assessed. The lesions are carefully palpated.

To assess the level of disease activity, laboratory tests are performed:

• general clinical blood test;
• general therapeutic biochemical blood test;
• assessment of the level of serum immunoglobulins in the blood;
• study of the level of complement with its fractions in the blood;
• assessment of the concentration content of C-reactive protein in blood plasma;
• determination of rheumatoid factor;
• General examination of urine fluid.

In nodular periarteritis, hematuria, cylindruria and proteinuria are detected in the urine. Blood analysis reveals neutrophilic leukocytosis, anemia, thrombocytosis. The biochemical picture is represented by an increase in the fractions of γ and α2-globulins, fibrin, sialic acids, seromucoid, C-reactive protein.

Instrumental diagnostics are performed to clarify the diagnosis. In particular, a skin-muscle biopsy is performed: in the biomaterial taken from the shin or anterior abdominal wall, inflammatory infiltrates and necrotic zones in the vessel walls are detected.

Nodular periarteritis is often accompanied by aneurysmatic vascular changes visible during examination of the fundus.

Ultrasound Dopplerography of the renal vessels helps to determine their stenosis. Survey chest X-ray visualizes the increase in the lung pattern and the disruption of its configuration. Electrocardiogram and ultrasound examination of the heart help to identify cardiopathies.

The microscopic specimen that can be used for the study is the mesenteric artery in the exudative or proliferative stage of arteritis, subcutaneous tissue, sural nerve and muscles. Samples taken from the liver and kidneys may give a false negative result caused by an error in selection. In addition, such a biopsy may cause bleeding from undiagnosed microaneurysms.

A macroscopic specimen in the form of excised pathologically altered tissue is fixed in a solution of ethanol, chlorhexidine, and formalin for further histological examination.

A biopsy of tissue not affected by pathology is inappropriate, since nodular periarteritis has a focal nature. Therefore, tissue is taken for biopsy, the damage of which is confirmed by clinical examination.

If the clinical picture is minimal or absent, then electromyography and nerve conduction testing can identify the area of the proposed biopsy. In case of skin lesions, it is preferable to remove biomaterial from the deep layers or subcutaneous fat, excluding the superficial layers (they show erroneous indicators). Testicular biopsy is also often inappropriate.

Diagnostic criteria

The diagnosis of nodular periarteritis is made based on anamnesis data, characteristic symptoms, and laboratory diagnostic results. It is worth noting that changes in laboratory parameters are non-specific, since they mainly reflect the stage of pathology activity. Taking this into account, specialists distinguish the following diagnostic criteria for the disease:

• Muscle pain (especially in the lower limbs), general weakness. Diffuse myalgia, not affecting the lumbar region and shoulders.
• Pain syndrome in the testicles that is not related to infectious processes or traumatic injuries.
• Uneven cyanosis on the skin of the limbs and body, similar to livedo reticularis.
• Weight loss of more than 4 kg, which is not associated with diets and other changes in nutrition.
• Polyneuropathy or mononeuritis with all neurological signs.
• An increase in diastolic blood pressure above 90 mm Hg.
• Increased blood urea (more than 14.4 mmol/liter – 40 mg%) and creatinine (more than 133 μmol/liter – 1.5 mg%), which is not related to dehydration or urinary tract obstruction.
• The presence of HBsAg or corresponding antibodies in the blood (viral hepatitis B).
• Vascular changes on the arteriogram in the form of aneurysms and occlusions of visceral arterial vessels, without connection with atherosclerotic changes, fibromuscular dysplastic processes and other non-inflammatory pathologies.
• Detection of granulocytic and mononuclear cell infiltration of vascular walls during morphological diagnostics of biomaterial taken from small and medium-sized arterial vessels.

Confirmation of at least three criteria makes it possible to make a diagnosis of periarteritis nodosa.

Classification

There is no generally accepted classification of periarteritis nodosa. Specialists usually systematize the disease by etiological and pathogenetic signs, histological features, severity of the course, clinical picture. The overwhelming majority of practicing doctors use a morphological classification based on clinical changes in tissues, the depth of localization and the caliber of damaged vessels.

The following clinical types of the disease are distinguished:

• The classic variant (renal-visceral, renal-polyneuritic) is characterized by damage to the kidneys, central nervous system, peripheral nervous system, heart and digestive tract.
• The monoorgan-nodular variant is a mild type of pathology, manifested by visceropathies.
• The dermato-thrombangic variant is a slowly progressive form, which is accompanied by an increase in blood pressure, the development of neuritis and a disruption of peripheral blood flow caused by the appearance of nodular formations along the vascular lumen.
• Pulmonary (asthmatic) variant – manifests itself as changes in the lungs, bronchial asthma.

According to the international classification ICD-10, nodular vascular inflammation occupies class M30 with the following distribution:

• M30.1 – allergic type with lung damage.
• M30.2 – juvenile type.
• M30.3 – changes in the mucous tissues and kidneys (Kawasaki syndrome).
• M30.8 – other conditions.

According to the nature of the course of nodular periarteritis, the following forms of pathology are distinguished:

• The fulminant form is a malignant process in which the kidneys are affected, thrombosis of intestinal vessels, and necrosis of intestinal loops occur. The prognosis is especially negative, the patient dies within one year from the onset of the disease.
• The rapid form does not progress very rapidly, but otherwise has much in common with the fulminant form. Survival is poor, and patients often die from a sudden rupture of the renal arterial vessel.
• The recurrent form is characterized by the suspension of the disease process as a result of the treatment. However, the growth of the pathology resumes when the dosage of drugs is reduced, or under the influence of other provoking factors - for example, against the background of the development of an infectious and inflammatory process.
• The slow form is most often thromboangitic. It spreads to the peripheral nerves and vascular network. The disease can gradually increase its intensity over a period of ten years or even more, provided there are no serious complications. The patient becomes disabled and requires constant, uninterrupted treatment.
• The benign form is considered the mildest variant of nodular periarteritis. The disease occurs in isolation, the main manifestations are found only on the skin, long periods of remission are noted. The survival rate of patients is relatively high - subject to competent and regular therapy.

Clinical guidelines

The diagnosis of periarteritis nodosa should be based on the relevant clinical manifestations and laboratory diagnostic data. Positive biopsy results are of great importance for confirming the disease. The earliest possible diagnosis is necessary: emergency-aggressive therapy should be started before the pathology spreads to vital organs.

Clinical symptoms of nodular periarteritis are characterized by pronounced polymorphism. Signs of the disease with and without the presence of HBV are similar. The most acute development is typical for pathology of drug genesis.

Patients with suspected periarteritis nodosa are recommended to undergo histology, which reveals a typical picture of focal necrotizing arteritis with mixed-type cellular infiltration in the vessel wall. The most informative is considered to be a biopsy of skeletal muscles. During the biopsy of internal organs, the risk of internal bleeding increases significantly.

To determine the treatment tactics, patients with nodular periarteritis must be divided according to the severity of the pathology, and also to identify the refractory type of the disease, which is not characterized by reverse symptomatic development, or even an increase in clinical activity in response to a one-and-a-half-month classical pathogenetic therapy.

Differential diagnosis

Nodular periarteritis is primarily differentiated from other known systemic pathologies affecting connective tissue.

• Microscopic polyarteritis is a form of necrotizing vasculitis that affects capillary vessels, as well as venules and arterioles, with the formation of antineutrophil antibodies. The disease is characterized by the appearance of glomerulonephritis, a later gradual increase in blood pressure, rapidly increasing renal failure, the development of necrotizing alveolitis and pulmonary hemorrhage.
• Wegener's granulomatosis is accompanied by the development of tissue destructive changes. Ulcers appear on the mucous tissue of the nasal cavity, the nasal septum is perforated, and lung tissue disintegrates. Antineutrophil antibodies are often detected.
• Rheumatoid vasculitis is characterized by the appearance of trophic ulcerative lesions on the legs, the development of polyneuropathy. During the diagnosis, the degree of joint syndrome (the presence of erosive polyarthritis with a violation of the configuration of the joints) is necessarily assessed, and the rheumatoid factor is detected.

In addition, skin manifestations similar to nodular periarteritis appear against the background of septic embolism, left atrial myxoma. It is important to exclude septic conditions even before using immunosuppressants to treat nodular periarteritis.

A combination of symptoms such as polyneuropathy, fever, polyarthritis is found in patients with Lyme disease (another name is borreliosis). To exclude the disease, it is necessary to trace the epidemiological anamnesis. The moments that allow one to suspect borreliosis are the following:

• tick bites;
• visiting natural focal zones during periods of particular tick activity (late spring – early autumn).

To make a diagnosis, a blood test is performed to detect the presence of antibodies to Borrelia.

Treatment periarteritis nodosa

Treatment should be as early and long-term as possible, with the appointment of an individual therapeutic regimen depending on the severity of clinical symptoms and the stage of periarteritis nodosa.

In the acute period, bed rest is mandatory, which is especially important if the pathological foci of periarteritis nodosa are located on the lower extremities.

The approach to treatment is always comprehensive, with the recommended addition of Cyclophosphamide (orally 2 mg/kg per day), which helps to accelerate the onset of remission and reduce the frequency of exacerbations. To avoid infectious complications, Cyclophosphamide is used only if Prednisolone is ineffective.

In general, treatment is often ineffective. The intensity of the clinical picture can be reduced by early administration of Prednisolone in an amount of at least 60 mg/day orally. In pediatric patients, it is appropriate to prescribe normal immunoglobulin for intravenous administration.

The quality of treatment is assessed in the presence of positive dynamics in the clinical course, stabilization of laboratory and immunological values and a decrease in the activity of the inflammatory reaction.

Correction or radical elimination of concomitant pathologies that can negatively affect the course of nodular periarteritis is recommended. Such pathologies include foci of chronic inflammation, diabetes mellitus, uterine fibroids, chronic venous insufficiency, etc.

External treatment for erosions and ulcers involves the use of 1-2% solutions of aniline dyes, epithelializing ointment preparations (Solcoseryl), hormonal ointments, enzymatic agents (Iruskol, Himopsin), and applicator application of Dimexide. Dry heat is used for nodes.

Medicines

Medicines that are effective in the treatment of periarteritis nodosa:

• Glucocorticoids: Prednisolone 1 mg/kg twice daily orally for 2 months, with further reduction of the dosage to 5-10 mg/day in the morning (every other day) until the clinical symptoms disappear. Possible side effects: exacerbation or development of gastric ulcer and duodenal ulcer, weakened immunity, edema, osteoporosis, impaired secretion of sex hormones, cataract, glaucoma.
• Immunosuppressants (if glucocorticoids are ineffective), cytostatics (Azathioprine in the active stage of the pathology at 2-4 mg / kg per day for a month, with a further transition to a maintenance dosage of 50-100 mg / day for one and a half to two years), Cyclophosphamide orally at 1-2 mg / kg per day for 2 weeks with a further gradual reduction in dosage. With an intensive increase in the pathological process, 4 mg / kg per day is prescribed for three days, then 2 mg / kg per day for a week, with a gradual reduction in dosage over three months. The total duration of therapy is at least one year. Possible side effects: suppression of the hematopoietic system, decreased resistance to infections.
• Pulse therapy in the form of Methylprednisolone 1000 mg or Dexamethasone 2 mg/kg per day intravenously for three days. At the same time, on the first day, Cyclophosphamide is administered at a dosage of 10-15 mg/kg per day.

A combined treatment regimen using glucocorticoids and cytostatics is justified:

• efferent treatment in the form of plasmapheresis, lymphocytapheresis, immunosorption;
• anticoagulant therapy (Heparin 5 thousand units 4 times a day, Enoxaparin 20 mg daily subcutaneously, Nadroparin 0.3 mg daily subcutaneously;
• antiplatelet therapy (Pentoxifylline 200-600 mg per day orally, or 200-300 mg per day intravenously; Dipyridamole 150-200 mg per day; Rheopolyglucin 400 mg intravenously by drip, every other day, in the amount of 10 infusions; Clopidogrel 75 mg daily);
• non-steroidal anti-inflammatory drugs - non-selective COX inhibitors (Diclofenac 50-150 mg per day, Ibuprofen 800-1200 mg per day);
• selective COX-2 inhibitors (Meloxicam or Movalis 7.5-15 mg per day daily with food, Nimesulide or Nimesil 100 mg twice a day, Celecoxib or Celebrex 200 mg per day);
• aminocholine agents (Hydroxychloroquine 0.2 g per day);
• angioprotectors (Pamidine 0.25-0.75 mg three times a day, Xanthinol nicotinate 0.15 g three times a day, for a month);
• enzyme preparations (Wobenzym, 5 tablets three times a day for 21 days, then 3 tablets three times a day for a long time);
• antiviral and antibacterial drugs;
• symptomatic drugs (medicines for normalizing blood pressure, for normalizing cardiac activity, etc.);
• vasodilators and calcium channel blockers (eg, Corinfar).

Cyclophosphamide therapy is carried out only if there are compelling indications and if glucocorticosteroids are ineffective. Possible side effects from taking the drug: myelotoxic and hepatotoxic effects, anemia, sterile hemorrhagic cystitis, severe nausea and vomiting, secondary infection.

Immunosuppressant therapy should be accompanied by monthly monitoring of blood parameters (complete blood count, platelet count, serum liver transaminase, alkaline phosphatase and bilirubin activity).

Systemic glucocorticosteroids are taken (administered) mainly in the morning, with a mandatory gradual reduction in dosage and an increase in the interval of administration (administration).

Physiotherapy treatment

Physiotherapy is contraindicated for periarteritis nodosa.

Herbal treatment

Despite the fact that nodular periarteritis is a fairly rare pathology, there are still folk methods of treating this disorder. However, the possibility of herbal treatment must be discussed in advance with the attending physician, since it is necessary to take into account the severity of the disease and the likelihood of developing unwanted side effects.

In the early stages of periarteritis nodosa, the use of herbal preparations may be justified.

• Three medium lemons, 5 tbsp. of cloves are put through a meat grinder, mixed with 500 ml of honey and poured with 0.5 l of vodka. Mix everything well, pour into a jar, close the lid and put in the refrigerator for 14 days. Then filter the tincture and start taking 1 tbsp. three times a day, half an hour before meals.
• Prepare a herbal equivalent mixture of tansy, immortelle and elecampane rhizome. Take 1 tbsp of the mixture, pour a glass of boiling water, and leave for half an hour. Take 50 ml of the infusion three times a day before meals.
• Prepare an equal mixture of dried violet flowers, celandine leaves and dried lingonberries. Pour 2 tbsp of the mixture into 0.5 l of boiling water and leave until cool. Take 50 ml 4 times a day, between meals.
• Mix 1 tbsp. of immortelle, wormwood and elecampane, pour 1 liter of boiling water, leave for two hours. Then filter the infusion and take 100 ml three times a day.

A simple and effective way to strengthen the vascular walls in case of nodular periarteritis is regular consumption of green tea. You should drink 3 cups of the drink every day. Additionally, you can take alcohol tinctures of zamaniha or ginseng, which will help to get rid of unwanted manifestations of the disease faster. Such tinctures can be bought at any pharmacy.

Surgical treatment

Surgical treatment is not the main treatment for periarteritis nodosa. Surgery may be indicated only in the case of a critical stenotic condition, clinically caused by regional ischemia, or in the case of occlusion of the main arterial trunks (Takayasu's arteritis). Other indications for surgical care are:

• thromboangiitis obliterans;
• peripheral gangrene and other irreversible changes in tissues;
• subpharyngeal stenosis in Wegener's granulomatosis (mechanical dilation of the trachea in combination with local use of glucocorticosteroids).

Emergency surgery is prescribed for abdominal complications: intestinal perforations, peritonitis, intestinal infarction, etc.

Prevention

There is no clear concept of prevention of nodular periarteritis, since the true causes of the disease are not completely known. It is definitely necessary to avoid exposure to factors that can provoke the development of pathology: avoid hypothermia, physical and psycho-emotional overstrain, lead a healthy lifestyle, eat right, protect yourself from bacterial and viral infections.

When the first suspicious signs of the disease appear, you need to visit a doctor as soon as possible: in this case, the chances of diagnosing and treating nodular periarteritis at the initial stage of its development increase.

Prevention of exacerbations of the disease in patients with remission of nodular periarteritis comes down to regular dispensary observation, systematic maintenance and strengthening treatment, elimination of allergens, prevention of self-medication and uncontrolled intake of drugs. Patients with vasculitis or nodular periarteritis should not be administered any serums or vaccinated.

Forecast

Without treatment of nodular periarteritis, death occurs within five years in 95 patients out of a hundred. Moreover, the overwhelming majority of deaths occur in the first 90 days of the disease. This can happen if the pathology is diagnosed incorrectly or untimely.

The main causes of death in periarteritis nodosa are extensive vascular inflammation, the addition of infectious pathologies, heart attack, and stroke. [ 12 ]

Timely use of glucocorticoid drugs increases the percentage of five-year survival by more than half. An even more optimal effect can be achieved by combining glucocorticosteroids with cytostatics. If it is possible to achieve complete disappearance of the symptoms of the disease, then the probability of its exacerbation is estimated at approximately 56-58%. An unfavorable factor for the prognosis is considered to be damage to the spinal cord structures and the brain. [ 13 ]

Genetically determined nodular periarteritis in childhood is completely cured in approximately every second case. In 30% of children, the disease shows persistent disappearance of symptoms against the background of constant drug support. Mortality in early childhood is 4%: death is caused by damage to brain structures, cranial nerves. [ 14 ]

Even with a favorable outcome, periarteritis nodosa requires regular rheumatological monitoring. [ 15 ] To avoid relapses, the patient should avoid infectious diseases, sudden temperature changes, and any self-medication. In some cases, relapses can be provoked by pregnancy or abortion.