Wegener's granulomatosis is a rare autoimmune disease of a person, characterized by the damage of small and medium diameter vessels of granulomatous inflammatory character with subsequent necrotic changes. With Wegener's granulomatosis the organs of the respiratory system, as well as the vessels of the kidneys and eyes, are mainly affected. The disease has no sexual specificity. The most common are people aged 35-50 who are in working age. The incidence of the disease is approximately 1: 250,000 of the population.
The disease of Wegener's granulomatosis refers to the incurable diseases of man, but modern methods of treatment can significantly extend the life of patients.
Causes of Wegener's granulomatosis
Unfortunately, the cause of Wegener's granulomatosis is still unknown. There are several hypotheses of the development of the disease, which do not have reliable evidence, but also do not exclude each other. It is assumed that the mechanism of the disease is triggered by the development of a hyperergic reaction to the autoantigens of the organism and the golden staphylococcus present in all people. It is not excluded and the virus effect on the body.
The main role in the pathogenesis of the disease lies in the violation of humoral immunity. There is an active formation of antibodies (IgA, cytoplasmic antibodies, etc.) to certain human leukocytes - neutrophils. After the interaction of the antibody with the neutrophil, their adhesion to the wall of the vessel occurs with the release of active substances that cause localized inflammation of the vessel with its significant damage. At the site of inflammation, specific nodules are formed - granulomas containing giant cells. Most often, the respiratory organs are affected first, and then other organs and systems are involved. Growing in the vessels, the granulomas cause their traumatization and ruptures, leading to intense bleeding.
Symptoms and signs of Wegener's granulomatosis
Wegener's granulomatosis can be acute, subacute and chronic, and, according to the prevalence of the lesion, it can be localized or generalized. The first symptoms can also be general or local, characterized by problems in a particular organ or system. Usually the patients' well-being in the early days of Wegener's granulomatosis is very similar to the sensations that occur with a cold . Patients are concerned about general weakness, muscle and headaches, fever, loss of weight, weakness, thirst, anorexia, etc. The intensity of these symptoms may be different, and if they are weak, patients usually do not seek help. The duration of the first period of the disease does not exceed a month.
During the height of the disease, due to the variability of the vascular lesion, the symptoms may be different, but more often the Wegener's granulomatosis begins with a lesion of the respiratory system. Initially, patients are concerned about dryness and nasal congestion, most often one-sided, in the nasal cavity there are purulent-bloody crusts. Discharge from the nose may not be, or they are very meager, having a purulent-bloody character. Rarely can there be nosebleeds.
On the rhinoscopy the doctor discovers purulent-bloody crusts, on separation of which a thin, cyanotic-purplish surface of the nasal mucosa is exposed, sometimes necrotic. With further progression of Wegener's granulomatosis, the number of crusts increases, a fetid odor from the nose appears. At this stage, the patient may be suspected of developing atrophic rhinitis. The difference between atrophic rhinitis and Wegener's granulomatosis is that when the first disease the crusts have a greyish-green color, and at the second - brown-brown. Also, with atrophic rhinitis, both sides of the nose suffer, and with Wegener's granulomatosis, one-sided lesion is more common. Differential diagnosis is also carried out with tumors, t. sometimes a bulk granulation tissue is formed in the nasal cavity, often located in the upper part of the nasal septum and on the choana and bleeding on contact. In the anterior part of the septum, its ulceration is often noted. Initially, the defeat is of an erosive nature. Progressing, over time the defect of the mucosa becomes deeper and more extensive and, in the most severe cases, there is perforation of the nasal septum, along the edges of which there is also a granulation tissue. First, the cartilage tissue is damaged with its ulceration, and then the process passes to the bone tissue, destroying it. As a result of these processes, the root of the nose is deformed, and the nose itself takes a saddle shape characteristic of the disease. All the changes in bone tissue are confirmed on X-ray examination. In the case of local injury, Wegener's granulomatosis occurs without a general intoxication syndrome and is expressed only in changes from the respiratory system. The disease can occur in this form up to 2 to 3 years without involving other organs and systems in the process, but this form of Wegener's granulomatosis is extremely rare. Most often the disease is accompanied by periodic symptoms of intoxication, with fever, weakness, reactive arthritis, etc., and later the process is generalized.
When the nose is affected, the involvement of the paranasal sinuses often develops. More often the defeat is one-sided and it develops from the side of the nose involved in the pathological process. The maxillary sinus of the nose is most often affected. Inflammation and ulceration is exposed to the sinus wall, bordering the nasal cavity. Over time, the perforation of this wall occurs and the cavity of the maxillary sinus begins to border freely with the nasal cavity. In severe cases, the walls of the sinus are also lined with purulent-bloody, hard-to-remove crusts, and all of its mucosa is necrotic.
Bone tissue in Wegener's granulomatosis is destroyed in connection with the formation of granulomas in soft tissues immediately adjacent to the bone. In this case, the nutrition of the bone tissue is disturbed, its replacement by granulation, and then connective tissue, and eventually necrosis, demyelination and perforation of the wall. Bone tissue is not restored after treatment, which is associated with significant changes in blood supply and repair disorders.
The generalized form of Wegener's granulomatosis is characterized by the defeat of several systems of the body. Most often, simultaneously with lesions in the respiratory system, eye damage occurs, which is due to their blood supply peculiarity. The first symptom of eye damage is keratitis, or inflammation of the cornea of the eye. It can be either a manifestation of toxic effects, or directly a granulomatous lesion. Granulomatous infiltrates can ulcerate, as a result of which a deep ulcer with raised margins forms on the cornea. Ulcers are marginal and are formed from infiltration of the marginal network of scleral vessels or conjunctival. The picture of the defeat of the cornea as a whole and depends on the fact which damage to the vessels leads to the formation of an infiltrate. Hyperemia, edema and subsequently ulceration are located at the site of the vessel, in severe cases, with both conjunctival and scleral blood supply, the ulcer affects the entire cornea. In severe cases, inflammation of the choroid of the gas - uveitis. The sclera of the eye can also be involved in the pathological process. There is a lesion of the upper layers of the sclera (episcleritis) or damage to the deep layers (sclerite). Complaints of patients depend on the degree of damage to the eyeball and can be quite extensive: photophobia, lacrimation, decreased visual acuity, edema of the eye, difficulty in opening the eyelids, etc.
The defeat of the visual system with Wegener's granulomatosis is also more often one-sided and develops on the side of the lesion of the nasal cavity and sinus. In advanced cases, deep ulceration of the eye can lead to the leakage of its contents. In case of eye damage, exophthalmos and enophthalmos may also be noted. Exophthalmos - the shift of the eye anteriorly, can develop in connection with the localization of granulomatous tissue in the orbit of the eye and is an earlier sign of the disease than enophthalmos (eyeball overgrowth). The cause of enophthalmos is the appearance of cicatricial changes that reduce the volume of tissues lying behind the eyeball and disturb the movement with the eye. When there are unilateral lesions of nasal cavities, sinuses of the nose and the eye, one should take into account the possibility of developing this disease.
The defeat of the pharynx and larynx is not such a frequent symptom of Wegener's granulomatosis, as the defeat of the two previous organs, but, nevertheless, and it has a place to be. Usually it is combined with a lesion of the larynx and manifests itself in the form of pain, discomfort, sensation of a foreign body in the throat , the appearance of abundant salivation. The patient is concerned about persistent sore throat, especially worse when swallowing. Weight loss in this case is not due to lack of appetite, but with fear of pain that appears when swallowing. Intoxication syndrome often accompanies this pathological process. Mucous on examination is hyperemic, tonsils are enlarged, on the posterior wall of the pharynx are formed tubercles. These tubercles tend to ulcerate, in place of ulcers, eventually, star-shaped scars form. Scar tissue tightens the edges and deforms the mucous membrane of the pharynx. When forming cicatricial processes in the soft palate, there is a nasal voice and a change in speech, there is a throwing of food into the nasopharynx, there is a choking when eating and drinking. Regional lymph nodes, however, as a rule, are not enlarged and painless.
The defeat of the hearing organs with Wegener's granulomatosis occurs in almost a third of the diseased. Patients complain of pain in the ear, a decrease in hearing acuity, a violation of sound perception. Affected by the inner and middle ear and they are also associated with the inflammation of the vessels that supply this area. The defeat is also one-sided. It is not only the one-sided nature of the lesion, combined with the damage to the nose and eyes, that should ward off the doctor, but also acute purulent otitis, which is not amenable to normal treatment.
Later, with the development of Wegener's granulomatosis, all large organs and systems are involved in the pathological process. The pathology of the lungs is quite common. In the lung tissue, granulation changes also occur with the formation of specific tubercles, which tend to break down. At the site of the destroyed tubercle a cavity is formed, in the cavities of which pus can accumulate and an abscess may form. Patients complain of a cough with hemoptysis, shortness of breath, chest pain. The radiological picture also confirms the presence of granulomas and cavities with a horizontal liquid level. In this situation it is necessary to conduct differential diagnostics with pulmonary tuberculosis .
Then, kidney damage is observed. With the active form of Wegener's granulomatosis, progressive renal dysfunction and nephrotic and nephritic syndrome development are noted. Subjectively, patients note the appearance of edema at the beginning of the upper part (face, eyelids, etc.), then edema and lower extremities join, pressure increases, urination disrupted, nocturia appears. In the general analysis of urine, the appearance of erythrocytes and an increase in protein content are noted. Specific diagnosis allows you to see a violation of the filtration capacity of the kidneys. The death of patients with Wegener's granulomatosis occurs usually in connection with renal insufficiency.
The defeat of the vessels of the skin leads to the appearance of purpura-specific purple-purple spots on the surface of the skin, usually in the region of the lower extremities.
Diseases of the gastrointestinal tract are rare. Symptoms at the same time resemble the picture of enterocolitis and colitis, gastric and intestinal ulcer. There is localization of pain in all areas of the abdomen, stool disorders, more often diarrhea, feces include mucus and blood.
Diagnosis of Wegener's granulomatosis
Diagnosis of Wegener's granulomatosis begins with a general examination of the patient. Attention should be paid to: one-sidedness of the process, ulceration of mucous membranes, their hyperemia, duration of the process, absence of positive dynamics for usual treatment. Then proceed to collect general analyzes. In the general analysis of blood there is a sharp increase in ESR up to 80 mm / h, leukocytosis , anemia , thrombocytosis . In the biochemical analysis of the blood, the appearance of a rheumatoid factor, hypergammaglobulinemia and an increase in the content of fibrinogen are noted. In the general analysis of urine - microalbuminuria and hematuria.
Instrumental research methods allow to see the destruction of bone tissue, formed cavities, the presence of granulomas, etc. For this, ultrasound, x-ray, computer and magnetic resonance imaging are used. After the carried out researches proceed to specific methods of diagnostics. Important for determining the disease have tests for the definition of antibodies, as well as a histology of Wegener's granulomatosis.
Wegener's granulomatosis is confirmed by the detection of specific antibodies to protease-3, but it should be noted that a number of oncological diseases can have a false positive result. Therefore, the most important is the histology of Wegener's granulomatosis. The most sensitive are the lung biopaths, then the biopaths of the nasal cavity. A positive sign enabling this diagnosis is the presence in the biopath of vasculitis , combined with granulomatous formations. A kidney biopsy confirms the presence of glomerulonephritis.
With a typical picture of the disease, the diagnosis of Wegener's granulomatosis does not cause difficulties, but it is by no means always the case. In the case of an unusual course of the disease, all the symptoms should be compared and the expected diagnosis confirmed by specific analyzes. There are certain classification criteria for the disease, in the presence of two of which and more the diagnosis is confirmed in almost 100 percent of cases:
- ulcerative and necrotic changes in the nasal cavity and mouth;
- X-ray revealed characteristic changes in the lungs;
- hematuria and microalbuminuria in urinalysis;
- granulomatous inflammation of the vascular wall and perivascular space in the biopath.
In addition, to confirm the diagnosis use the definition in the blood of classical antineutrophil cytoplasmic antibodies.
If the diagnosis is confirmed, the prediction of Wegener's granulomatosis is disappointing.
Treatment of Wegener's granulomatosis
Virtually all autoimmune diseases, including the disease of Wegener's granulomatosis, belong to incurable diseases, but in recent years scientists and doctors have managed to significantly improve the quality of life of people with this problem. If earlier the life expectancy of patients was not more than a year, now, in some cases, a person can live up to 10 years. The basis of treatment is the appointment of cytostatics with glucocorticosteroids. Monotherapy with glucocorticosteroids slightly improves the condition of patients, although it has little effect on the prediction of Wegener's granulomatosis.
Modern therapy of Wegener's granulomatosis includes treatment with cyclophosphamide and Prednisolone in tableted form. At the same time, blood leukocytes are monitored. When remission is achieved, the medications are continued for a year, and then gradually reduced by 25 mg every three months, while monitoring the patient's general condition. Also, the positive effect is provided by the infusion pulse therapy with cyclophosphamide. In the case of intolerance to cyclophosphamide, it is replaced with methotrexate. The positive effect of a combination of Methotrexate and Prednisolon is quite high in the morbidity structure. Also, Methotrexate is used as a deterrent when remission is achieved with cyclophosphamide. With rational remission therapy, about 90% of patients achieve.
It should be remembered that the establishment of remission does not exclude repeated possible exacerbations of Wegener's granulomatosis, and the use of these highly toxic preparations is characterized by the development of significant complications leading to disability of patients. Cyclophosphamide is safer than Methotrexate, which is why it is usually the drug of choice. Currently, work is underway related to the possibility of replacing Cyclophosphamide with other less toxic drugs. Positively, Azathioprine and Chlorbutin proved to be successful. There are also intensive studies on anticytokine therapy, which are highly expected.
In addition to the direct cytotoxic treatment of Wegener's granulomatosis, we use drugs aimed at reducing the risk of purulent complications. As a rule, these drugs are ineffective, but still have a positive effect. Applied local applications and ointments of antibacterial and astringent substances, use physiotherapy treatment. Plasmapheresis and hemosorption did not have a significant positive effect in the treatment of many patients. Since the greatest mortality in this disease occurs as a result of the development of renal failure, there is a kidney transplant.
Unfortunately, despite comprehensive treatment, it is impossible to achieve absence of complications and reverse development of the disease. Deafness, decreased visual acuity, impairment of respiratory function, as well as visual changes in the appearance of the patient significantly worsen its quality of life, even if remission is formed. For the patient, the prediction of Wegener's granulomatosis directly depends not only on the form of the disease, but also on the beginning of treatment and the development of complications. The earlier treatment is started, and the less neglected the disease, the better the prognosis.