Periarteritis nodosa

A rare pathology - nodular periarteritis - is accompanied by the lesion of medium and small caliber arterial vessels. In the vascular walls there are processes of connective tissue disorganization, inflammatory infiltration and sclerotic changes, resulting in the appearance of well-defined aneurysms. [1]

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

Epidemiology

Periarteritis nodosa is a systemic pathology, a necrotizing vasculitis that damages 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, as well as other organs, less often - the lungs. Pathology is usually manifested first by general symptoms (fever, general deterioration of health), then more specific signs are added.

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

The most acceptable medications for treatment are glucocorticoid drugs and immunosuppressants.

The incidence of nodular periarteritis is between two and thirty cases per 1 million patients.

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

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

Causes of the periarteritis nodosa

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

• A reaction to taking medication;
• Persistence of viral infection (hepatitis B).

Specialists have compiled a rather impressive list of medications implicated in the development of periarteritis nodosa. Among these medications:

• Beta-lactam antibiotics;
• Macrolide drugs;
• Sulfonamide drugs;
• Quinolones;
• Antivirals;
• Serums and vaccines;
• Selective serotonin reuptake inhibitors (Fluoxetine);
• Anticonvulsants (Phenytoin);
• Levodopa and Carbidopa;
• Thiazides and loop diuretics;
• Hydralazine, Propylthiouracil, Minocycline, etc.

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

Also, about one in ten patients is detected hepatitis C virus, but the subtleties of the relationship scientists have not yet proven. Other viral infections are also "under suspicion": human immunodeficiency virus, cytomegalovirus, rubella and Epstein-Barr viruses, T-lymphotropic virus type I, parvovirus B-19 and others.

There is every reason to assume the involvement of hepatitis B and influenza vaccination in the development of periarteritis nodosa.

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

Risk factors

Periarteritis nodosa is a poorly understood disease, but experts already consider it polyetiologic, as many causes and factors may be involved in its development. It is often found to be related to focal infections: streptococcal, staphylococcal, mycobacterial, fungal, viral and others. An important role is played by hypersensitivity of a person to some medications - for example, to antibiotics and sulfonamides. However, in many cases, even with careful diagnosis, the etiologic factor cannot be identified.

These are the risk factors doctors know about today:

• Age group over 45 years old, and children from 0 to 7 years old (genetic factor);
• Sudden temperature changes, hypothermia;
• Excessive exposure to ultraviolet light, excessive sunbathing;
• Excessive physical and mental overload;
• Any damaging effects, including trauma or surgery;
• Hepatitis and other liver diseases;
• Metabolic disorders, diabetes mellitus;
• Hypertension;
• Vaccine administration and persistence of HbsAg in serum.

Pathogenesis

The pathogenesis of nodular periarteritis consists in the formation of a hyperallergic response of the body to the impact of etiologic factors, in the development of autoimmune reaction by antigen-antibody type (in particular, to the walls of blood vessels), in the formation of immunocomplexes.

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

The immunocomplexes formed stimulate complement, which leads to wall damage and the formation of chemotactic components that attract neutrophils to the area of damage. [5]

Neutrophils perform phagocytic function in relation to immunocomplexes, but at the same time they release lysosomal proteolytic enzymes that damage the vascular wall. In addition, neutrophils are "glued" to the endothelium and, in the presence of complement, release active oxygen radicals that provoke vascular damage. At the same time, endothelial release of factors favoring increased blood clotting and the formation of blood clots in the affected vessels is potentiated.

Symptoms of the periarteritis nodosa

Nodular periarteritis reveals itself by general nonspecific manifestations: a person has a constantly elevated temperature, he progressively thinner, bothers with pain in the muscles and joints.

Fever in the form of persistent fever is characteristic of 98-100% of cases: the temperature curve is irregular, there is no response to antibiotic therapy, but corticosteroid therapy is effective. Temperature may subsequently normalize, against the background of the development of multiorgan pathology.

Patients' weight loss is pathognomonic in nature. Some patients lose 35-40 kg of weight over several months. The degree of thinness is greater than in oncopathologies.

Muscle and joint pain is particularly characteristic of the initial stage of nodular periarteritis. The soreness particularly affects large joints and calf muscles. [6]

Polyorganic pathologies are subdivided into several types, which determines the symptomatology of the disease:

• When the renal vessels are affected (and this occurs in the majority of patients), there is an increase in blood pressure. Hypertension is persistent, persistent, causing a severe degree of retinopathy. Loss of visual function is possible. In urine analysis, proteinuria (up to 3 g/day), micro or macrohematuria is detected. In some cases, the vessel dilated by the aneurysm ruptures, perirenal hemorrhage is formed. Renal failure develops during the first three years of the disease.
• If the vessels in the abdominal cavity are damaged, symptomatology is already evident at an early stage of periarteritis nodosa. The main symptoms are abdominal pain, persistent and progressive. Dyspeptic disorders are noted: diarrhea with an admixture of blood up to ten times a day, emaciation, attacks of nausea and vomiting. If there is ulcer perforation, signs of acute peritonitis develop. There is a risk of gastrointestinal bleeding.
• In coronary lesions, heart pain is not characteristic. Infarcts occur, mainly of a small-focal nature. Rapidly increasing phenomena of cardiosclerosis, which entails the appearance of arrhythmias, signs of heart failure.
• When the respiratory system is affected, bronchospasms, hypereosinophilia, eosinophilic infiltrates in the lungs are detected. The formation of vascular inflammation of the lungs is characteristic: the disease is accompanied by coughing, scanty sputum discharge, less often - hemoptysis, increasing symptoms of insufficient respiratory function. X-ray visualizes sharply increased vascular pattern on the type of stagnant lung, infiltration of lung tissue (mainly in the root region).
• When the peripheral nervous system is involved, asymmetric poly and mononeuritis is noted. The patient is bothered by severe pain, numbness, and sometimes muscle weakness. Legs are more often affected, arms less often. Some patients form polymyeloradiculoneuritis, paresis of the feet and hands. Often found peculiar nodules along the trunks of vessels, ulcers and foci of necrosis of the skin. Soft tissue necrosis and the development of gangrenous complications are possible.

First signs

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

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

• Peripheral nervous system affection is manifested by motor and sensory disorders of the ulnar, median and peroneal nerves; distal symmetric polyneuropathy may also develop;
• The central nervous system responds to pathology with headaches, less often there are strokes (ischemic and hemorrhagic) 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 the urine sediment, the appearance of blood and protein in the urine in the absence of cellular cylinders, low back pain, and in severe cases - signs of renal failure;
• The digestive tract gives rise to liver and abdominal pain, nausea, vomiting, diarrhea, symptoms of malabsorption, intestinal perforation and peritonitis;
• On the part of the heart, there may be no pathologic signs, or symptoms of heart failure may appear;
• Reticulate livedo, reddening painful nodules, rash in the form of vesicles or vesicles, areas of necrosis and ulcerative lesions are noted on the skin;
• 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, renal failure occurs.

The probability of renal disorders depends on the sex and age category of patients, on the presence of pathologies of skeletal muscle, cardiac valve system and peripheral nervous system, on the type of course and phase of the disease, on the presence of viral hepatitis antigen and cardiovascular values.

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

Renal disorders in nodular periarteritis are caused by stenosis and the appearance of microaneurysms of renal vessels. The degree of pathologic changes correlates with the severity of nervous system disorders. It should be understood that renal lesions sharply reduce the chances of survival of patients. However, this question about the influence of certain renal function disorders on the course of periarteritis nodosa is not sufficiently studied.

The inflammatory process usually extends to the interlobular arterial vessels and less frequently to the arterioles. Presumably, glomerulonephritis is uncharacteristic for nodular periarteritis and is noted mainly on the background of microscopic angiitis.

The rapid worsening of renal failure is due to multiple infarcts in the kidneys. [8]

Heart damage

The picture of cardiovascular lesions is noted in every second case out of ten. Pathology is manifested by hypertrophic changes in the left ventricle, palpitations, heart rhythm disorders. Inflammation of the coronary vessels in nodular periarteritis can provoke the appearance of angina pectoris and the development of myocardial infarction.

In macro preparations, more than 10% of cases reveal nodular thickenings like bangles, from a few millimeters to a couple of centimeters in diameter (up to 5.5 cm when large vascular trunks are affected). The incision demonstrates an aneurysm, often with thrombotic filling. The final diagnostic role is played by histology. A typical feature of nodular periarteritis is a polymorphous vascular lesion. A combination of different types of connective tissue disorganization is noted: [9]

• Mucoid swelling, fibrinoid changes with further sclerosis;
• Narrowing of the vascular lumen (up to obliteration), the formation of blood clots, aneurysms, in severe cases - rupture of blood vessels.

Vascular changes become a trigger mechanism in the development of necrosis, atrophic and sclerotic processes, hemorrhages. Phlebitis is noted in some patients.

The heart shows atrophy of the fatty layer of the epicardium, brown myocardial dystrophy, and in hypertension - left ventricular hypertrophy. 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 found in coronary arterial trunks. [10]

Cutaneous manifestations of periarteritis nodosa

Cutaneous signs of the disease are noted in every second patient with periarteritis nodosa. Often the appearance of rashes becomes the first, or one of the first signs of the disorder. Typical symptoms are:

• Vesicular and bullous rash;
• Vascular papulo-petechial purpura;
• Sometimes - the appearance of subcutaneous nodular elements.

In general, the cutaneous manifestations of nodular periarteritis are heterogeneous and varied. Common signs may be as follows:

• The rash is inflammatory;
• The rash is symmetrical;
• There is a tendency to swelling, necrotic changes and hemorrhages;
• At the initial stage, the rash is localized in the lower extremities;
• Evolutionary polymorphism is noted;
• Traceable connection with pre-existing infections, medications, temperature changes, allergic processes, autoimmune pathologies, impaired venous circulation.

Skin lesions are diverse, ranging from spots, nodules and purpura to necrosis, ulcers and erosions.

Periarteritis nodosa in children

Juvenile polyarteritis is a form of polyarteritis nodosa, which is found mainly in pediatric patients. This variant of the course of the disease is distinguished by a hyperergic component, most of the peripheral vessels are damaged, there is a significant risk of thrombangiitic complications in the form of dry tissue necrosis, gangrenous processes. Visceral disorders manifest themselves relatively weakly and do not affect the outcome of the pathology, but there is a tendency to a prolonged course with periodic relapses.

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

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

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

Pathogenesis is often due to immunocomplex processes with increased complement activity and leukocyte accumulation in the area of immunocomplex fixation. The inflammatory reaction occurs in the walls of small and medium-sized 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 disturbed, thrombosis and tissue ischemia are noted. Gradually, wall fibrosis is formed, aneurysms with a diameter size 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 intense generalization of vascular lesions. The course of the disease is severe from the moment of its onset. The patient has high fever of remitting fever type, profuse sweating, pronounced joint pain, myalgias, abdominal pain. When the peripheral circulation is affected, there is rapid formation of wide foci of skin necrosis, distal gangrenous process develops. When internal organs are affected, intense vascular-cerebral crises, myocardial infarction, polyneuritis, intestinal necrosis are noted. The acute period can be traced for 2-3 months or more, up to one year.
• The subacute stage begins gradually, mainly in patients with a predominant localization of the pathological process in the area of internal organs. For several months, patients have a subfebrile temperature, or periodically rises to high temperatures. There is a progressive deterioration, joint and headaches. Subsequently, there is an acute development of cerebro-vascular crisis, either abdominal syndrome or polyneuritis. The pathology remains active for up to three years.
• The chronic stage can be observed in both acute and subacute disease process. Patients begin to experience alternating periods of exacerbation and disappearance of symptoms. During the first few years, relapses are noted every six months, further remissions may become longer.

Acute course of periarteritis nodosa

The acute phase of nodular periarteritis is usually severe, as certain vital organs are affected. In addition to clinical manifestations, the assessment of the disease activity is also influenced by the indicators of laboratory changes, although they are not specific enough. There may be elevated COE, eosinophilia, leukocytosis, increased gamma-globulin and CIC count, decreased complement levels.

Nodular periarteritis is characterized by either a lightning course or periodic acute phases against the background of constant progression of pathology. Fatal outcome can occur almost at any moment with the development of renal or cardiovascular failure, damage to the digestive tract (especially vitally dangerous perforation infarction of the intestine). Disorders of the kidneys, heart, and central nervous system are often exacerbated by sustained arterial hypertension, leading to serious late complications that can also be fatal to the patient. In the absence of treatment, the five-year survival rate is estimated to be approximately 13%. [11]

Complications and consequences

The severity of the patients' condition and the probability of complications are caused by a steady increase in blood pressure, up to 220/110-240/170 mm Hg.

The active stage of the disease often ends with circulatory disorders of the brain. Progression of pathology leads to the fact that hypertension becomes malignant, cerebral edema occurs, some patients develop chronic renal failure, cerebral hemorrhage and kidney rupture.

Renal syndrome is often formed, juxtaglomerular renal ischemia develops, and the mechanism of the renin-angiotensin-aldosterone system is disturbed.

The development of local and diffuse ulcers, foci of necrosis and gangrene of the intestine, inflammation of the appendix is noted in the digestive tract. Patients have intense abdominal pain syndrome, intestinal bleeding may develop, there are signs of peritoneal irritation. Intraintestinal inflammatory disorders do not have histologic signs of ulcerative colitis. Internal bleeding, pancreatitis with pancreonecrosis, spleen and liver infarction may occur.

Nervous system damage can be complicated by the development of 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, there are often foci of lesions in the brain, which is accompanied by gaze paralysis, diplopia, nystagmus, facial asymmetry, visual dysfunction.

In general, periarteritis nodosa is a life-threatening pathology and requires the earliest possible diagnosis and aggressive and continuous treatment. Only under such conditions, it is possible to achieve a stable remission and avoid the development of severe dangerous consequences.

The outcome of periarteritis nodosa

More than 70% of patients with nodular periarteritis have elevated blood pressure and signs of increasing renal failure within the first 60 days of onset. The nervous system may be affected, with preserved sensitivity, but limited motor activity.

Abdominal vessels may become inflamed, resulting in severe abdominal pain. Dangerous complications often include gastric and intestinal ulcers, gallbladder necrosis, perforation and peritonitis.

Coronary vessels are less frequently affected, but the outcome is also possible: patients develop myocardial infarction. Strokes occur when cerebral vessels are damaged.

In the absence of treatment, almost all patients die within the first few years from the onset of pathology. The most frequent problems leading to fatal outcome: extensive arteritis, infectious processes, heart attack, stroke.

Diagnostics of the periarteritis nodosa

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

It is obligatory to conduct an external examination of the skin and joints, assess the location of rashes and areas of pain. The lesions are carefully palpated.

Laboratory tests are performed to assess the level of disease activity:

• General clinical gross blood count;
• General therapeutic biochemical blood work;
• Assessment of serum immunoglobulin levels in blood;
• Study of the level of complement with its fractions in the blood;
• Evaluation of the concentration content of C-reactive protein in plasma;
• Rheumatoid factor determination;
• General urinalysis.

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

Instrumental diagnostics is performed to clarify the diagnosis. In particular, skin and muscle biopsy is performed: biomaterial taken from the lower leg or anterior abdominal wall reveals inflammatory infiltrates and areas of necrosis in the vessel walls.

Nodular periarteritis is often accompanied by aneurysmal vascular changes seen on ocular fundus examination.

Ultrasound Doppler ultrasonography of renal vessels helps to determine their stenosis. Review chest radiography visualizes lung pattern enhancement and disruption of its configuration. Electrocardiogram and cardiac ultrasound can detect cardiopathies.

The micro specimen that can be used for study is the mesenteric artery in the exudative or proliferative stage of arteritis, subcutaneous tissue, calf nerve and musculature. Samples taken from the liver and kidney may give a false negative result provoked by a sampling error. In addition, such biopsies may cause bleeding from undiagnosed microaneurysms.

Macropreparation in the form of dissected pathologically changed tissue is fixed in ethanol, chlorhexidine, formalin solution for further histologic study.

Biopsy of tissue not affected by the pathology is inappropriate, as periarteritis nodosa has a focal character. Therefore, tissue whose lesion is confirmed by clinical examination is taken for biopsy.

If there is minimal or no clinical picture, electromyography and nerve conduction assessment procedures can identify the area of intended biopsy. For cutaneous lesions, biomaterial from deep layers or PJC is preferred, excluding superficial layers (demonstrating erroneous findings). Testicular biopsy is also often inappropriate.

Diagnostic criteria

The diagnosis of nodular periarteritis is based on the history, characteristic symptoms, and the results of laboratory diagnostics. It is worth noting that changes in laboratory parameters are nonspecific, since they reflect mainly the stage of activity of the pathology. Taking this into account, specialists distinguish such diagnostic criteria of the disease:

• Muscle pain (especially in the lower extremities), general weakness. Diffuse myalgia not affecting the lumbar and shoulder area.
• Pain syndrome in the testicular area, unrelated to infectious processes or traumatic injuries.
• Uneven lividity on the skin of the extremities and body in the type of reticulated livedo.
• A weight loss of more than 4 kg that is not due to dieting or other dietary changes.
• Polyneuropathy or mononeuritis with all neurologic signs.
• Increase in diastolic blood pressure above 90 mmHg.
• Increased blood urea (greater than 14.4 mmol/liter - 40 mg%) and creatinine (greater than 133 μmol/liter - 1.5 mg%), which is unrelated to dehydration or urinary tract obstruction.
• The presence of HBsAg or related antibodies in the blood (viral hepatitis B).
• Vascular changes on arteriogram in the form of aneurysms and occlusions of visceral arterial vessels, without association with atherosclerotic changes, fibromuscular dysplastic processes and other pathologies of non-inflammatory nature.
• Detection of granulocytic and mononuclear cell infiltration of vascular walls during morphological diagnosis of biomaterial taken from small and medium caliber arterial vessels.

Confirmation of at least three criteria makes the diagnosis of nodular periarteritis possible.

Classification

There is no generally accepted classification of nodular periarteritis. Specialists usually systematize the disease according to etiological and pathogenetic features, histological features, acute course, clinical picture. The vast majority of practitioners use morphological classification based on clinical tissue changes, on the depth of localization and caliber of damaged vessels.

A distinction is made between these clinical types of the disease:

• Classic variant (renal-visceral, renal-polyneuritic) - characterized by damage to the kidneys, central nervous system, periceric nervous system, heart and digestive tract.
• Monoorgan-nodular variant is a low-expressed type of pathology, manifested by visceropathies.
• Dermato-trombangitic variant is a slowly progressive form, which is accompanied by an increase in blood pressure, the development of neuritis and impaired peripheral blood flow due to the appearance of nodular formations along the vascular lumen.
• Pulmonary (asthmatic) variant - manifested by changes in the lungs, bronchial asthma.

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

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

According to the nature of the course of nodular periarteritis, such forms of pathology are divided:

• The lightning form is a malignant process in which the kidneys are affected, there is thrombosis of intestinal vessels, necrosis of intestinal loops. The prognosis is particularly negative, the patient dies within one year from the onset of the disease.
• The rapid form is not very rapid, but otherwise has much in common with the lightning-quick form. Survival is poor and patients often die of sudden rupture of the renal arterial vessel.
• The recurrent form is characterized by the suspension of the disease process as a result of treatment. However, the growth of 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 infectious-inflammatory process.
• The slow form is most often thrombangitic. It spreads to the peripheral nerves and vasculature. The disease can gradually increase its intensity over a dozen years and even more, provided that there are no serious complications. The patient becomes disabled and requires constant ongoing treatment.
• The benign form is considered the mildest variant of nodular periarteritis. The disease runs in isolation, the main manifestations are found only on the skin, there are long periods of remission. The survival rate of patients is relatively high - provided competent and regular therapy.

Clinical Guidelines

The diagnosis of periarteritis nodosa must be substantiated by appropriate clinical manifestations and laboratory findings. A positive biopsy is important to confirm the disease. Early diagnosis is necessary: emergency aggressive therapy should be started before the pathology spreads to vital organs.

The 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.

In patients with suspected nodular periarteritis, histology is recommended, revealing a typical picture of focal necrotizing arteritis with cellular infiltration of mixed type in the vessel wall. Biopsy of skeletal muscle is considered to be the most informative. During biopsy of internal organs, the risk of internal bleeding is significantly increased.

To determine the therapeutic tactics of patients with nodular periarteritis it is necessary to divide by the degree of severity of the pathology, as well as to distinguish the refractory type of the disease course, which is not characterized by reverse symptomatic development, or even strengthening of clinical activity in response to the conducted one and a half months of classical pathogenetic therapy.

Differential diagnosis

Nodular periarteritis is primarily differentiated with other known systemic pathologies involving connective tissue.

• Microscopic polyarteritis is a form of necrotizing vasculitis in which capillary vessels, as well as venules and arterioles are affected with the formation of antineutrophil antibodies. The disease is typified by the appearance of glomerulonephritis, 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, lung tissue disintegrates. Often anti-neutrophil antibodies are detected.
• Rheumatoid vasculitis is characterized by the appearance of trophic ulcerative lesions on the legs, the development of polyneuropathy. In the course of diagnosis, the degree of joint syndrome is necessarily assessed (presence of erosive polyarthritis with a violation of the configuration of the joints), rheumatoid factor is detected.

In addition, skin manifestations similar to periarteritis nodosa occur in septic embolism, left atrial myxoma. It is important to exclude septic conditions before using immunosuppressants for the treatment of periarteritis nodosa.

A cluster of symptoms such as polyneuropathy, fever, and polyarthritis is found in patients with Lyme disease (another name for borreliosis). To rule out the disease, it is necessary to trace the epidemiologic history. Moments that allow to suspect borreliosis are as follows:

• Tick bites;
• Visiting natural focal areas during the period of special tick activity (late spring - early fall).

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

Treatment of the periarteritis nodosa

Treatment should be as early and prolonged as possible, with the prescription of an individualized therapeutic regimen depending on the severity of clinical symptoms and the stage of nodular periarteritis.

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

The treatment approach is always comprehensive, with the recommended addition of Cyclophosphamide (2 mg/kg orally per day), which is beneficial for accelerating the onset of remission and reducing 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 attenuated by early administration of Prednisolone at least 60 mg/day orally. In pediatric patients, normal immunoglobulin for intravenous administration is appropriate.

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

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 form of venous insufficiency, etc.

External treatment for erosions and ulcers involves the use of 1-2% solutions of aniline dyes, epithelializing ointments (Solcoseryl), hormonal ointments, enzyme agents (Iruscol, Chymopsin), applicator application of Dimexide. Dry heat is applied to the nodes.

Medications

Drugs that have shown efficacy in the treatment of periarteritis nodosa:

• Glucocorticoids: Prednisolone 1 mg/kg twice daily orally for 2 months, with further dosage reduction to 5-10 mg/day in the morning (day after day) until the disappearance of clinical symptoms. Possible side effects: exacerbation or development of gastric and 12-perintestinal ulcers, weakening of immunity, edema, osteoporosis, impaired secretion of sex hormones, cataract, glaucoma.
• Immunosuppressants (if glucocorticoids are ineffective), cytostatics (Azathioprine in the active stage of pathology at 2-4 mg/kg per day for a month, with further transition to a maintenance dosage of 50-100 mg / day for a year and a half or two years), Cyclophosphamide orally at 1-2 mg / kg per day for 2 weeks with further gradual reduction of dosage. In case of intensive growth of the pathological process, 4 mg/kg per day for three days, then - 2 mg/kg per day for a week, with a gradual decrease in dosage for three months. The total duration of therapy - at least one year. Possible side effects: suppression of 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, Cyclophosphamide at a dosage of 10-15 mg/kg per day is administered on the first day.

A combined treatment regimen with glucocorticoids and cytostatics is warranted:

• Efferent treatment in the form of plasmapheresis, lymphocytopheresis, immunosorption;
• Anticoagulant therapy (Heparin 5 thousand units 4 times a day, Enoxiparin 20 mg daily subcutaneously, Nadroparin 0.3 mg daily subcutaneously;
• Antiaggregant therapy (Pentoxifylline 200-600 mg daily orally, or 200-300 mg daily intravenously; Dipyridamole 150-200 mg daily; Reopolyglukin 400 mg intravenous 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 daily with food, Nimesulide or Nimesil 100 mg twice daily, Celecoxib or Celebrex 200 mg daily);
• Aminocholine agents (Hydroxychloroquine 0.2 g per day);
• Angioprotectors (Pamidin 0.25-0.75 mg three times a day, Xanthinol nicotinate 0.15 g three times a day, for a month);
• Enzyme preparations (Wobenzyme 5 tablets three times a day for 21 days, further - 3 tablets three times a day for a long time);
• Antiviral and antibacterial drugs;
• Symptomatic drugs (medications to normalize blood pressure, to normalize cardiac activity, etc.);
• Vasodilators and calcium channel blockers (e.g., Corinthar).

Therapy with Cyclophosphamide is performed only when there are strong indications and when glucocorticosteroid agents are ineffective. Possible side effects from taking the drug: myelotoxic and hepatotoxic effects, anemia, sterile hemorrhagic cystitis, severe nausea and vomiting, secondary infection.

Therapy with immunosuppressants should be accompanied by monthly monitoring of blood parameters (general blood count, platelet count, activity of serum hepatic transaminases, alkaline phosphatase and bilirubin).

Systemic glucocorticosteroids are taken (administered) predominantly in the morning, with a mandatory gradual reduction in dosage and increasing the interval of intake (administration).

Physiotherapeutic treatment

Physical therapy is contraindicated in nodular periarteritis.

Herbal treatment

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

In the early stage of nodular periarteritis, the use of herbal remedies may be warranted.

• Pass through a meat grinder three medium lemons, 5 tbsp. Cloves, mix with 500 ml of honey and pour 0.5 liters of vodka. Everything is well mixed, poured into a jar, close the lid and send to the refrigerator for 14 days. Then the tincture is filtered and begin to take 1 tbsp. Three times a day, half an hour before meals.
• Prepare a herbal equivalent mixture of faggot, immortelle and elecampane rhizome. Take 1 tbsp. Of the mixture, pour a glass of boiling water, insist for half an hour. Take 50 ml of the infusion three times a day before meals.
• Prepare an equivalent mixture of dried violet flowers, leaves of succession and dried cowberries. Pour 2 tbsp. Of the mixture 0.5 liters of boiling water, insist 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, insist for two hours. Then the infusion is filtered and taken three times a day for 100 ml.

A simple and effective way to strengthen the vascular walls in 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 lure or ginseng, which will help to get rid of unwanted manifestations of the disease. Such tinctures can be bought in any pharmacy.

Surgical treatment

Surgical treatment is not the main treatment for periarteritis nodosa. Surgery may be indicated only in critical stenotic conditions clinically caused by regional ischemia or in occlusion of the main arterial trunks (Takayasu's arteritis). Other indications for surgery include:

• Obliterative thrombangiitis;
• Peripheral gangrene and other irreversible tissue changes;
• Subpharyngeal stenosis in Wegener's granulomatosis (mechanical tracheal dilation in combination with local use of glucocorticosteroids).

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

Prevention

There is no clear concept of prevention of nodular periarteritis, since the true causes of the disease are not known in detail. 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.

If the first suspicious signs of the disease appear, it is necessary 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 are increased.

Prevention of exacerbations of the disease in patients with remission of nodular periarteritis is reduced to regular dispensary observation, systematic supportive and strengthening treatment, elimination of allergens, avoid self-medication and uncontrolled medication. Patients with vasculitis or nodular periarteritis should not be administered any serum, vaccination.

Forecast

If nodular periarteritis is untreated, 95 out of a hundred patients will die within five years. At the same time, the vast majority of patient deaths occur in the first 90 days of the disease. This can happen if the pathology is incorrectly or untimely diagnosed.

The main causes of lethal outcomes in nodular periarteritis are extensive vascular inflammation, accession of infectious pathologies, heart attack, stroke. [12]

Timely administration of glucocorticoids increases the five-year survival rate by more than half. The combination of glucocorticosteroids with cytostatics has an even better effect. If complete disappearance of the symptoms of the disease is achieved, the probability of its exacerbation is estimated at about 56-58%. An unfavorable factor for the prognosis is considered to be the lesion of spinal structures and the brain. [13]

Genetically determined nodular periarteritis in childhood is completely cured in about every second case. In 30% of children, the disease is marked by a persistent disappearance of symptoms against the background of constant drug support. Lethality at an early age is 4%: death is due to damage to brain structures, cranial nerves. [14]

Even with a favorable outcome, nodular periarteritis requires regular rheumatologic control. [15] To avoid relapses, the patient should beware of infectious diseases, sudden temperature changes, any variants of self-medication. In some cases, relapses can be provoked by pregnancy or abortion.