Brief overview
- Description: rare inflammatory vascular disease that can affect the whole body and is accompanied by the formation of small tissue nodules (granulomas). It mainly affects adults.
- Symptoms: Initially mostly symptoms in the ear, nose and throat area (e.g. runny nose, nosebleeds, sinusitis, middle ear infection) as well as general complaints (fever, night sweats, tiredness, etc.). Later, further symptoms such as joint and muscle pain, inflammation of the eyes, lungs and kidneys, numbness, etc.
- Therapy: immunosuppressive medication (cortisone, methotrexate, azathioprine, cyclophosphamide, etc.), other active substances (e.g. rituximab). In severe cases, plasmapheresis (a type of blood washing), kidney transplantation if necessary.
- Causes: Autoimmune disease, the exact cause of which is unknown. Genetic factors and infectious agents may play a role.
- Diagnosis: Medical history, blood and urine tests, imaging procedures, analysis of tissue samples (biopsy)
Granulomatosis with polyangiitis (Wegener’s disease): Definition
Granulomatosis with polyangiitis (formerly: Wegener’s disease) is a rare inflammation of the blood vessels (vasculitis), accompanied by the formation of small tissue nodules (granulomas). These develop partly near blood vessels and partly far from them.
The term “granulomatosis” refers to the tissue nodules (= granulomas) that form. “Polyangiitis” means inflammation of many vessels.
It becomes dangerous as soon as the lungs or kidneys are affected. In extreme cases, this can lead to acute pulmonary hemorrhage or acute kidney failure. Both complications can be fatal.
New name
Granulomatosis with polyangiitis was known as Wegener’s disease (also known as Wegener’s granulomatosis or Wegener’s granulomatosis) until 2011. The name change recommended by American and European rheumatism associations is based on the controversial role of the former namesake Friedrich Wegener during the National Socialist era.
ANCA-associated vasculitis
This group of diseases also includes microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis (EGPA, formerly known as Churg-Strauss syndrome).
Frequency
Granulomatosis with polyangiitis is rare. Every year, eight to ten out of a million people develop the disease (incidence). This is based on data from Europe, the USA and Australia. The total number of people affected (prevalence) varies from country to country. It lies between around 24 and 160 per million inhabitants.
The disease can occur at any age. However, adults are most frequently affected: The average age at the time of diagnosis is between 50 and 60. Men and women are affected in roughly equal numbers.
Granulomatosis with polyangiitis can affect various organ systems. Which organs are affected and to what extent varies from patient to patient.
In addition, the symptoms of Wegener’s disease usually change as the disease progresses: the ear, nose and throat area is generally affected in the initial stages before the disease spreads further and sometimes spreads to vital organs.
Symptoms in the early stages
At the beginning of the disease, the ear, nose and throat region is usually affected. Common symptoms in the nasal area are
- (bloody) rhinitis with a constantly runny or chronically blocked nose
- nosebleeds
- Brownish crusts in the nose
Starting from the nose, granulomatosis with polyangiitis (Wegener’s disease) can spread further into the paranasal sinuses and cause inflammation there (sinusitis). Pain in the jaw or forehead area that is difficult to localize may indicate this.
If the disease spreads further, an inflammation of the middle ear (otitis media) can develop. This is primarily characterized by severe ear pain, sometimes combined with dizziness. In extreme cases, granulomatosis with polyangiitis can even lead to hearing loss (deafness).
Ulcers often form in the mouth and nose. Throat infections also occur more frequently.
Symptoms as the disease progresses
As the disease progresses, the inflammatory symptoms can spread further and further throughout the body. Most affected are
- lower respiratory tract: In the trachea, a narrowing below the vocal fold (subglottic stenosis) and acute shortness of breath can develop. There is often a (severe) affection of the lungs, for example in the form of inflammation of the smallest blood vessels (pulmonary capillaritis) with bleeding into the lungs (alveolar hemorrhage) as well as bloody sputum and shortness of breath.
- Kidneys: In many granulomatosis patients, the renal corpuscles become inflamed (glomerulonephritis). Classic signs of this are blood and protein in the urine, high blood pressure (hypertension) and water retention in the tissue (edema). In severe cases, kidney failure develops.
- Eyes:In the course of granulomatosis with polyangiitis (Wegener’s disease), inflamed, painful eyes and visual disturbances (visual loss) may occur. Bleeding into the eye and protrusion of the eyeball (exophthalmos) due to granulomas behind the eye are sometimes visible from the outside.
- Skin:Punctiform hemorrhages may appear on the skin. Extensive discoloration and ulcers are also possible. If medium-sized blood vessels are involved, tissue may die locally (necrosis), especially on fingers and toes (gangrene).
More rarely, the heart (e.g. with myocarditis) and/or the gastrointestinal tract (with ulcers, bleeding, etc.) are affected.
Granulomatosis with polyangiitis: therapy
As with many other diseases, the earlier granulomatosis with polyangiitis is recognized, the greater the chance of successful treatment.
Acute therapy
The aim of acute therapy is to eliminate the symptoms and achieve remission of the disease. The severity of the disease plays a major role in determining the type of acute therapy for Wegener’s disease: The decisive factor is whether vital organs (such as the kidneys) are affected and/or there is an acute danger to life or not.
No danger to life or involvement of vital organs
Danger to life or involvement of vital organs
If organs such as the lungs or kidneys are already affected by the disease or there is a risk to life, aggressive immunosuppressive combination therapy is indicated: Doctors prescribe glucocorticoids (“cortisone”) in combination with cyclophosphamide or the artificially produced antibody rituximab.
Since 2022, a new active substance has been approved in the EU and Switzerland for the treatment of granulomatosis with polyangiitis: Avacopan. It blocks the docking sites (receptors) of an inflammation-promoting complement factor (protein of the immune system). Avacopan is considered in severe cases of the disease, in combination with cortisone and rituximab or cyclophosphamide.
In this complex procedure, blood is removed from the patient’s body via an infusion tube and fed into the plasmapheresis device. Using a centrifuge, this separates the liquid component of the blood (blood plasma or plasma for short) with the substances dissolved in it from the solid components (red blood cells etc.) and replaces it with a substitute fluid – a mixture of electrolytes and hydrogen carbonate. The blood is then returned to the patient’s body.
The purpose of it all: Plasmapheresis also removes the antibodies in the plasma that are involved in the inflammatory processes in granulomatosis with polyangiitis (Wegener’s disease).
Maintenance therapy (maintenance of remission)
If the acute treatment has brought the disease to a standstill (remission), this is followed by at least 24 months of maintenance therapy. The aim is to maintain the freedom from symptoms achieved by the acute treatment in the long term.
Low-dose cortisone is used in combination with azathioprine, rituximab, methotrexate or mycophenolate mofetil. If there is an intolerance to such active substances, leflunomide can be given as an alternative. Like azathiprine and methotrexate, it is an immunosuppressant.
Maintenance therapy can be supplemented with cotrimoxazole. This combination of two antibiotics (trimethoprim and sulfamethoxazole) can reduce the risk of relapse and reduce the dose of immunosuppressants.
Repeated treatment
It is important to note that all treatment measures can only alleviate the symptoms. There is no cure for Wegener’s disease.
In addition, relapses often occur. Repeated treatment is then necessary. Experts often recommend a change of active ingredient from the previous therapy (e.g. cyclophosphamide instead of rituximab).
Granulomatosis with polyangiitis: prognosis
With timely and appropriate treatment, the spread of inflammation in granulomatosis with polyangiitis can be counteracted. In around two thirds of those affected, the symptoms disappear completely.
However, the disease often breaks out again over time. Such relapses require immunosuppressive combination therapy each time.
Mortality
The introduction of immunosuppressive therapy has steadily improved the prognosis for granulomatosis with polyangiitis. According to long-term studies, the mortality rate of those affected is only slightly higher than in the normal population or even the same.
However, mortality in the first year (early mortality) is quite high (approx. 11 percent). Those affected die more frequently from infections (which are favored by the intensive immunosuppressive therapy) than from the disease itself.
Granulomatosis with polyangiitis: causes
This malfunction is probably due to genetic factors that occur in combination with other factors. Experts consider an infection of the nasal mucosa with bacteria such as Staphylococcus aureus to be a triggering factor. Parts of the bacteria can activate certain immune cells, which then trigger an excessive immune reaction against the body’s own cells.
Granulomatosis with polyangiitis (Wegener’s disease): Diagnosis
If Wegener’s disease is suspected, it should be clarified as quickly and carefully as possible. This enables rapid treatment if granulomatosis with polyangiitis is indeed present.
Medical history
First, the doctor will take your medical history (anamnesis). This gives you the opportunity to describe your symptoms in detail. You should feel free to mention anything you have noticed. Even small details that may seem unimportant or trivial to you can help the doctor to find out the cause of your symptoms. The doctor may also ask questions such as
- When did you first notice the changes (e.g. tissue nodules)?
- Have you noticed any other symptoms?
- Have you noticed blood in your urine?
- Do you have pain when coughing or when breathing is increased, for example during sport?
Blood test
As a rule, a blood test is carried out first to clarify the suspected diagnosis.
Granulomatosis patients very often have elevated inflammation levels in the blood: ESR (blood sedimentation rate), CRP (C-reactive protein) and leukocytes (white blood cells).
Other common abnormalities are, for example, reduced erythrocyte (red blood cell) values, increased platelet (thrombocyte) values and increased kidney values.
Urinalysis
Urine tests can also provide indications of kidney involvement, for example if protein can be detected in the urine. An elevated creatinine level in the urine indicates kidney weakness (renal insufficiency).
Imaging procedures
The pathological changes in lung infestation can be visualized on X-ray images (chest X-ray) or using computer tomography. However, such abnormalities can also have causes other than Wegener’s disease. A tissue sample (biopsy) then provides certainty.
The condition of the kidneys can be assessed in more detail using ultrasound.
Tissue samples
Tissue samples (biopsies) from affected areas, such as the nasal mucosa, skin, lungs or kidneys, are very informative. If the typical pathological changes (granulomatous inflammation with tissue loss in the walls of arteries or around vessels) are found, this confirms the diagnosis of granulomatosis with polyangiitis (Wegener’s disease).
