An example of vasculitis, Wegener's granulomatosis compromises the integrity of the affected blood vessels and affects the organs of the body supplied by these same blood vessels.
Initially, the disease affects the upper airways; subsequently, it extends to the lower ones and, in an even more advanced stage, reaches organs such as the kidneys, heart, ears and skin.
Without early diagnosis and prompt treatment, Wegener's granulomatosis seriously compromises the patient's health, leading to death within a few years.
Fortunately, today there are various therapies, mostly of a pharmacological type, which allow satisfactory control of the disease.
it is reduced and the organs of the body (directly connected to the vessels involved) are no longer properly supplied.
Usually, Wegener's granulomatosis affects the kidneys, lungs and upper and lower respiratory tract, but it is not excluded that it can have consequences elsewhere.
Without adequate therapeutic treatment or in case of late diagnosis, Wegener's granulomatosis can also have fatal outcomes, especially if the kidneys are involved.
What is Wegener's Granulomatosis: it is a Vasculitis
When we speak of vasculitis, we refer to an "inflammation of the blood vessels, arterial and / or venous.
Wegener's granulomatosis is to be considered a vasculitis, as it affects the arterial and venous vessels of medium and small caliber, as well as certain capillary systems.
Wegener's granulomatosis: why is it called that?
The term "granulomatosis" derives from the fact that the disease is characterized by the formation of granulomas.
Granulomas are proliferations of connective tissue, circumscribed and nodular in shape; their origin can vary from situation to situation: in the case of Wegener's granulomatosis, the presence of granulomas is certainly due to the inflammatory state characteristic of the disease.
The term "Wegener", on the other hand, is due to the first doctor who described the pathology: Friedrich Wegener.
Wegener's Granulomatosis or Granulomatosis with Polyangiitis
Wegener's granulomatosis is also known as granulomatosis with polyangiitis, where the term "polyangiitis" indicates an inflammatory process that involves multiple blood or lymphatic vascular structures.
Epidemiology Wegener's granulomatosis: how common is it?
In Europe, the annual incidence of Wegener's granulomatosis is around 10-20 cases per million people.
Wegener's granulomatosis has no gender preferences, while it appears to favor individuals of European (Caucasian) ancestry for a reason currently unknown.
The disease can arise at any age, but according to some epidemiological data it is more frequent among those aged between 40 and 60.
are those pathologies characterized by an exaggerated and improper response of the immune system: in individuals who are affected, in fact, the elements that should act exclusively as immune defenses of the organism recognize as foreign tissues and / or organs of the human body and attack them, damaging them.
Wegener's Granulomatosis: Genetics and Environmental Factors
According to some theories (but further studies are needed), the concomitant presence of certain genetic and environmental factors would be responsible for the improper immune reaction responsible for Wegener's granulomatosis.
In fact, scientific studies have shown that a large number of patients have:
- Abnormalities in genes such as CTLA-4, PTPN22, DPB1 and FCGR3B;
- Previous history of bacterial infections from Staphylococcus aureus.
Wegener's granulomatosis: pathophysiology
The hypothesis according to which Wegener's granulomatosis would be an autoimmune disease is essentially due to the finding of relevant amounts of ANCA (ie the Anti-Cytoplasmic Neutrophil Antibodies) in the blood of patients with the aforementioned pathology.
In subjects affected by Wegener's granulomatosis, ANCAs appear to react with the proteinase 3 present in neutrophil granulocytes; in vitro, the interaction between ANCA and proteinase 3 has been shown to favor the adhesion of neutrophil granulocytes to the vascular endothelium and their degranulation with consequent damage to the endothelium itself.
For further information: ANCA: What are they? Wegener's granulomatosis can appear suddenly or take several months to appear; each patient, therefore, represents a case in itself.
The first organs and parts of the body to pay for the vascular consequences of the disease are the upper airways (nose, mouth, sinuses and ears), the lower airways (larynx, trachea and bronchi) and the lungs.
Once in these sites, Wegener's granulomatosis can spread to other vascular networks and affect fundamental organs such as the kidneys.
How Wegener's Granulomatosis manifests itself: the Symptoms
The patient with Wegener's granulomatosis typically experiences symptoms such as:
- Constant runny nose with presence of pus;
- Nosebleeds (epistaxis);
- Sinusitis;
- Anatomical modification of the nose (saddle nose);
- Ear infections
- Cough with or without bleeding (hemoptysis);
- Chest pain
- Shortness of breath;
- Generalized malaise;
- Weight loss for no reason
- Joint pain and swelling
- Blood in the urine (hematuria)
- Skin irritation;
- Redness, burning and pain in the eyes due to scleritis, episcleritis and / or conjunctivitis;
- Fever.
Wegener's granulomatosis: when to see a doctor?
Signs that must be taken into consideration and which could indicate the presence of Wegener's granulomatosis are:
- Persistence of a runny nose (even after several drug treatments);
- Epistaxis;
- Hemoptysis.
The presence of these three clinical manifestations should prompt one to contact the treating physician immediately.
Wegener's Granulomatosis: Complications
Wegener's granulomatosis results in complications when the inflammation it causes extends massively to organs such as the kidneys, eyes, ears, spinal cord, heart and / or skin.
In such circumstances, in fact, the disease can cause:
- Loss of hearing. When the inflammation reaches the blood vessels of the middle ear, there is a more or less consistent hearing loss.
- Cutaneous vasculitis and other marks on the skin. Cutaneous vasculitis is characterized by red spots on the skin; in addition, purpura and subcutaneous nodules may appear, usually at the elbow.
- Heart attack (myocardial infarction). It is a potential consequence of when inflammation reaches the coronary arteries, ie the vessels responsible for supplying the heart muscle (myocardium) with oxygenated blood.
Inflammation of the coronary vessels affects the blood supply to the myocardium; without the right supply of oxygen, the myocardium, at first, enters a state of suffering and, subsequently, undergoes necrosis; the necrosis of more or less extensive areas of myocardium compromises cardiac activity with a potentially fatal outcome for the patient.
Typical heart attack symptoms are chest pain, wheezing, profuse sweating and heartburn. - Kidney damage and subsequent kidney failure. Deprived of an adequate supply of oxygenated blood, the kidneys begin to suffer progressive damage and no longer function properly.
The alteration of renal function causes the accumulation of those toxic substances for the organism, which in normal conditions the renal system takes care of filtering and expelling.
The terminal stage of this slow and often asymptomatic early stage is renal failure, characterized by severe uremia (ie, high levels of nitrogenous substances in the blood).
Kidney failure is the leading cause of death for those suffering from Wegener's granulomatosis. - Anemia. It can develop over time; many patients with Wegener's granulomatosis are affected.
- Deep vein thrombosis and pulmonary embolism. They are potential consequences of when the disease reaches the lungs.
- Sensory neuropathy and multiple mononeuritis. They occur when the disease affects the nervous system.
Anamnesis and Physical Examination
Physical examination and anamnesis consist in the evaluation of the symptoms and in the critical study of the patient's state of health.
They are important for the purpose of differential diagnosis.
Symptoms and characteristic signs, assessed on physical examination:
- Runny nose and nosebleeds;
- Ear infection
- Sinusitis;
- Hemoptysis;
- Chest pain.
Blood tests
The blood tests useful for the detection of Wegener's granulomatosis are:
- Detection of anti-neutrophil cytoplasmic antibodies (ANCA). It is a test of limited reliability, as not all patients with Wegener's granulomatosis have ANCA in their blood.
- Erythrocyte sedimentation test. Evaluate the speed with which the red blood cells settle on the bottom of the tube that contains them; the faster the sedimentation, the more likely there is an "inflammation going on."
This test is not 100% reliable, as many other inflammatory diseases cause the same reactions. - C-reactive protein. It is an indicator of any ongoing inflammation; for the same reason as the erythrocyte sedimentation test, it is not sufficient to draw firm conclusions.
- Test for anemia. Not 100% reliable, because not all people with Wegener's granulomatosis are anemic.
- Creatinine levels. It is used to evaluate kidney function. If the disease has invaded the kidneys, it is a valid test; otherwise, it could lead to incorrect conclusions.
Urine Tests
Urine tests provide information about the health of the kidneys.
In individuals with Wegener's granulomatosis, where the disease has spread to the kidneys, urine tests show hematuria (blood in the urine) and proteinuria (protein in the urine), two findings indicative of kidney damage.
Diagnostic for Images
Imaging exams include classic x-rays, CT scans, and / or MRIs.
The subject of these investigations are the organs in which suspected Wegener's granulomatosis may have spread (also based on blood and urine tests).
Diagnostic imaging is very important, because, in addition to helping in the diagnosis, it also allows us to understand the severity of the present condition.
Among the various diagnostic imaging procedures, the chest X-ray is particularly noteworthy for its relevance in the identification of pulmonary anomalies.
Biopsy
Biopsy is the most reliable investigation for diagnostic confirmation.
Performed under local anesthesia, it involves taking a cell sample from the organs that have shown abnormalities in previous tests and its subsequent analysis in the laboratory.
If the laboratory analyzes show the presence of granulomas and / or signs of vasculitis, the diagnosis of Wegener's granulomatosis is unequivocal.
Origin of tissues for biopsy:
- Nasal and paranasal cavities;
- Upper and lower airways;
- Lungs;
- Skin;
- Kidneys.
Corticosteroids for Wegener's Granulomatosis
Indicated at the beginning of the therapeutic process to control the acute phase of the disease, corticosteroids are powerful anti-inflammatories, capable of reducing inflammation.
These drugs can cause numerous side effects, which explains why they are administered at the lowest effective dose.
In patients with Wegener's granulomatosis, the most commonly used corticosteroid is prednisone.
Immunosuppressants for Wegener's Granulomatosis
Indicated in a secondary phase of the therapeutic process to keep the condition under control, immunosuppressants reduce inflammation by acting on the immune defenses, which, in the patient with Wegener's granulomatosis, act improperly and cause serious damage to the organism.
Among the immunosuppressants used in the presence of Wegener's granulomatosis, the following are reported: cyclophosphamide, azathioprine and methotrexate.
Taking immunosuppressants exposes the patient to a greater risk of contracting infections.
Rituximab for Wegener's granulomatosis
Rituximab is a monoclonal antibody that reduces B lymphocytes, immune system cells involved in inflammation.
Approved by the FDA as a drug for the treatment of Wegener's granulomatosis, rituximab can be used in the acute phase of the disease, in combination with corticosteroids.
Wegener's Granulomatosis Drugs: What to Do Against Side Effects?
The drugs listed above have several side effects, especially when taken for long periods of time (as is the case in patients with Wegener's granulomatosis).
To control such side effects, the doctor generally indicates:
- Sulfamethoxazole associated with trimethoprim, to prevent infections affecting the lungs.
- Bisphosphonate drugs, calcium and vitamin D supplements, to reduce or prevent osteoporosis.
- Folic acid, to prevent the effects of methotrexate treatment.
Wegener's granulomatosis: other therapies
Certain circumstances, such as late diagnosis of the disease or neglect of treatment, may require plasmapheresis and surgery.
Plasma exchange for Wegener's granulomatosis
Plasmapheresis is a rather complicated procedure, which is carried out on the patient's blood.
This therapy is practiced not only in the case of Wegener's granulomatosis, but also in the occurrence of autoimmune diseases, such as systemic lupus erythematosus.
Surgery for Wegener's Granulomatosis
Surgery, on the other hand, can include kidney transplantation, when the kidneys are irreparably damaged, or interventions for the resolution of complications in the airways or problems in the middle ear.
Wegener's Granulomatosis: Periodic Checks
The patient with Wegener's granulomatosis must undergo periodic checks by the treating physician both during treatment and at the end of the treatment: during treatment, to clarify whether the therapies are working and when to stop them; at the end of the therapeutic course, to promptly identify any relapses.
