Granulomatosis with polyangiitis: symptoms, diagnosis, treatment, and prognosis

Granulomatosis with polyangiitis is a rare systemic vasculitis in which inflammation predominantly affects small and medium-sized vessels. The disease is particularly characterized by necrotizing granulomatous inflammation of the airways and so-called pauci-immune glomerulonephritis, which is a severe inflammatory kidney disorder with minimal immune deposits in the tissue. [1] [2]

The disease belongs to a group of vasculitides associated with antineutrophil cytoplasmic antibodies. Most often, these patients are found to have antibodies to proteinase 3, and less commonly, antibodies to myeloperoxidase. In practice, this is important not only for understanding the disease mechanism, but also for prognosis, risk of relapse, and choice of maintenance therapy. [3] [4]

Granulomatosis with polyangiitis is classically associated with involvement of the upper respiratory tract, lungs, and kidneys, but the disease can affect almost any organ. Clinically, this means one patient may present with "persistent sinusitis," another with hemoptysis, a third with rapidly worsening kidney damage, and a fourth with damage to the eyes, skin, or peripheral nerves. [5] [6]

Modern treatment has significantly improved the prognosis, but the disease remains potentially life-threatening. Without timely diagnosis and immunosuppressive therapy, it can quickly lead to renal failure, alveolar hemorrhage, subglottic stenosis of the larynx, irreversible organ damage, and death. [7] [8]

Today, the main principle of managing this disease is to treat it as early as possible, but only after carefully ruling out infections, tumors, and other conditions that can mimic vasculitis. This is especially important because treatment for granulomatosis with polyangiitis suppresses the immune system, and a misdiagnosis can be very dangerous. [9] [10]

Key feature	What does this mean?
Type of disease	Systemic necrotizing vasculitis
Main group	Vasculitides associated with antineutrophil cytoplasmic antibodies
The most typical organs	Upper respiratory tract, lungs, kidneys
Frequent serology	Antibodies to proteinase 3
The main risk	Rapid irreversible damage to vital organs

Sources of the table. [11] [12]

Code according to ICD-10 and ICD-11

In the International Classification of Diseases, 10th revision, granulomatosis with polyangiitis is coded as M31.3. Historically, this category still retains the old name "Wegener's granulomatosis," but in fact, we are talking about the modern nosology of "granulomatosis with polyangiitis." [13]

In the International Classification of Diseases, 11th revision, the code 4A44.A1 is used for granulomatosis with polyangiitis. The disease is included in the section on vasculitis and the subgroup of vasculitides associated with antineutrophil cytoplasmic antibodies. [14] [15]

Classification	Code	Name
ICD-10	M31.3	Granulomatosis with polyangiitis
ICD-11	4A44.A1	Granulomatosis with polyangiitis

Sources of the table. [16] [17]

Epidemiology

Granulomatosis with polyangiitis is a rare disease. A recent meta-analysis of antineutrophil cytoplasmic antibody-associated vasculitides estimated the global incidence of granulomatosis with polyangiitis to be approximately 9.0 per million person-years, and the prevalence to be approximately 96.8 per million population. This makes the disease rare, but not uncommon. [18]

In European and North American populations, prevalence is often higher than the global average. Clinical reviews for these regions typically cite a target of approximately 120-140 per 1 million population, with the highest frequency reported in countries of the Northern Hemisphere. [19] [20]

In recent years, many registries have shown not so much a sharp increase in true incidence, but rather an increase in the detection and accumulation of living patients. Swedish data, reflected in modern reviews, show a stable incidence of new cases over many years, but an increase in prevalence due to better survival and better treatment. [21] [22]

Granulomatosis with polyangiitis is the most common form of this group of vasculitides. Epidemiological and genetic reviews emphasize that it accounts for a significant proportion of all cases of vasculitis associated with antineutrophil cytoplasmic antibodies and is most often associated with antibodies to proteinase 3. [23] [24]

The disease can also occur in children, although it is significantly less common. A modern review from 2024 indicates that the incidence in children is approximately 0.88-1.8 cases per 1 million people, and the onset of the disease in children and adolescents may have more pronounced lesions of the nasopharynx, kidneys, and subglottic region of the larynx. [25] [26]

Epidemiological indicator	Modern assessment
Global incidence of new cases	About 9.0 per 1 million person-years
Global prevalence	About 96.8 per 1 million population
Prevalence in Europe and North America	Often around 120-140 per 1 million
Children's frequency	About 0.88-1.8 per 1 million
The trend of recent years	Prevalence is increasing due to improved survival rates

Sources of the table. [27] [28] [29]

Reasons

The exact cause of granulomatosis with polyangiitis remains unknown. Current reviews agree that it is an autoimmune disease with a multifactorial origin, where genetic predisposition is combined with external triggers and impaired immune tolerance to neutrophil proteins. [30] [31]

The most widely discussed immunological target is proteinase 3. In a significant proportion of patients, the immune system begins to recognize this protein as "foreign," resulting in the production of antibodies capable of activating neutrophils and triggering damage to the vascular wall. This is not the only disease pathway, but it is considered central to classic granulomatosis with polyangiitis. [32] [33]

The genetic contribution is also well documented. A review of epidemiology and genetics emphasizes the role of genes of the human leukocyte antigen system and a number of non-HLA loci associated with immune regulation. Therefore, the disease cannot be considered a random inflammation "without a prerequisite." [34]

Environmental triggers are considered to be triggers, not the sole cause. Among the most widely discussed factors are chronic nasal colonization with Staphylococcus aureus, silica exposure, smoking, mucosal inflammation, and certain drug exposures. These factors do not cause the disease in every individual, but they may contribute to the onset of the autoimmune process in predisposed individuals. [35] [36]

It is important to note that granulomatosis with polyangiitis is not an infection. It is not transmitted from person to person and is not caused by a single microbe, although infectious processes can mask its onset, complicate its course, and likely participate in the immune triggering of the disease. [37] [38]

Causality block	What is known today
The exact single cause	Not installed
The basis of the disease	Autoimmune inflammation
Key autoantigens	Most often proteinase 3, less often myeloperoxidase
Genetic contribution	Confirmed
External triggers	Possible, but do not explain all cases

Sources of the table. [39] [40]

Risk factors

Genetic predisposition is currently the most convincing risk factor. It doesn't necessarily mean a person will develop the disease, but it does create a background in which the immune system more easily loses tolerance to neutrophil proteins. This is particularly evident in studies of genes involved in the human leukocyte antigen system and immune regulators. [41]

Environmental factors primarily include exposure to inorganic dust, especially silica. This factor is not considered specific to granulomatosis with polyangiitis, but it has been repeatedly associated with vasculitis of this group and a higher likelihood of immune-mediated vascular inflammation. [42] [43]

The nasal mucosa is of particular interest. Chronic colonization with Staphylococcus aureus and persistent inflammation of the upper respiratory tract are considered possible triggers for exacerbations and, possibly, for the onset of the disease in some patients. This partially explains the long-standing interest in co-trimoxazole for certain types of nasal and sinus infections. [44] [45]

Smoking, chronic respiratory irritation, infections, and certain medications are also discussed as additional risk factors. However, they must be understood correctly: they do not replace the autoimmune nature of the disease, but may only contribute to its onset or recurrence. [46] [47]

The practically important conclusion is this: a person cannot completely "prevent" granulomatosis with polyangiitis, as, for example, infection can be prevented with a vaccine. However, reducing occupational exposure to dust, quitting smoking, and controlling chronic respiratory infections can theoretically reduce the inflammatory burden and the risk of exacerbations. [48] [49]

Risk factor	Comment
Genetic predisposition	One of the most convincing factors
Exposure to silica and dust	Possible environmental trigger
Chronic nasal colonization with Staphylococcus aureus	Possible trigger and recurrence factor
Smoking and chronic airway inflammation	Additional possible triggers
Certain medications and infections	Considered as potential triggers

Sources of the table. [50] [51] [52]

Pathogenesis

The pathogenesis is based on a combination of granulomatous inflammation and vascular damage. The immune system begins to produce antibodies against neutrophil components, primarily proteinase 3, after which neutrophils become hyperactive and begin to damage the vascular endothelium. [53] [54]

Neutrophil priming plays a major role. Inflammatory cytokines and complement component C5a create targets for autoantibodies on their surface, after which antineutrophil cytoplasmic antibodies trigger the release of enzymes, reactive oxygen species, and damage to the vascular wall. [55] [56]

Granulomatous inflammation develops in parallel, particularly in the respiratory tract. This explains the destruction of the nasal septum, chronic sinusitis, orbital inflammatory pseudotumors, and subglottic stenosis. This means the disease damages not only the vessels but also the surrounding tissues. [57] [58]

The kidneys are affected by a different, predominant mechanism—poorly immune necrotizing glomerulonephritis. The danger here is that glomerular inflammation can progress rapidly, and clinically initially manifest only as microhematuria and increasing creatinine, without severe pain or other "obvious" symptoms. [59] [60]

It is the involvement of the complement system that explains the interest in avacapan, a C5a receptor blocker. This is one of the most notable modern advances in therapy, because it allows for a reduction in steroid load without sacrificing inflammation control. [61] [62]

Pathogenetic link	What's happening
Loss of immune tolerance	Autoantibodies to neutrophil proteins appear
Neutrophil activation	Vascular endothelial damage
Complement activation	Strengthening the inflammatory cascade
Granulomatous inflammation	Destruction of respiratory tissue
Pauci-immune glomerulonephritis	Rapid damage to the glomeruli of the kidneys

Sources of the table. [63] [64] [65]

Symptoms

The most common onset of the disease is associated with the upper respiratory tract. Patients are treated for months for "sinusitis," "rhinitis," or "otitis," until it becomes clear that this is not a simple infection. Typical symptoms include nasal congestion, crusting, nosebleeds, sinus pain, hearing loss, chronic otitis media, and a saddle-shaped nasal deformity. [66] [67]

Lung damage varies greatly. Cough, shortness of breath, chest pain, hemoptysis, infiltrates, and pulmonary nodules, sometimes with disintegration, are possible. With diffuse alveolar hemorrhage, symptoms can progress very rapidly and become life-threatening, although not everyone experiences hemoptysis. [68] [69]

Kidney damage is often cryptic. Initially, a person may feel nothing but weakness, but red blood cells and protein may already appear in a urine test. Later, edema, high blood pressure, and a rapid decline in kidney function develop. This is why a complete urine analysis is always mandatory for patients suspected of having vasculitis. [70] [71]

Ocular symptoms are less common but are very important because they can threaten vision. The disease can cause scleritis, episcleritis, orbital inflammation, double vision, and even exophthalmos. Cutaneous manifestations usually include purpura, ulcers, nodules, or necrotic changes. Neurological manifestations most often include peripheral neuropathy. [72] [73]

Subglottic stenosis is especially important to consider. This is one of the most dangerous and insidious manifestations, as it can occur even against the background of an apparently "silent" systemic disease and lead to stridor, shortness of breath, and life-threatening narrowing of the airways. [74] [75]

Organ or area	Typical manifestations
Nose and sinuses	Crusting, bleeding, chronic sinusitis, saddle nose
Ear	Otitis, hearing loss
Lungs	Cough, nodules, infiltrates, hemoptysis, alveolar hemorrhage
Kidneys	Microhematuria, proteinuria, increased creatinine
Eyes	Scleritis, orbital inflammation
Respiratory tract	Subglottic stenosis, stridor

Sources of the table. [76] [77]

Classification, forms and stages

From a clinical perspective, granulomatosis with polyangiitis is conveniently divided into localized and systemic forms. In the localized form, the upper respiratory tract, ears, eyes, or lungs are predominantly affected, with no apparent severe renal component. In the systemic form, the disease affects vital organs and carries a high risk of organ failure. [78] [79]

Current treatment guidelines make another important distinction: between non-threatening and organ- or life-threatening disease. This is not simply an academic classification, but the basis for choosing therapy: methotrexate can be considered for some non-threatening forms, while severe kidney damage, pulmonary hemorrhage, or significant ocular or nerve damage require more potent remission-induction regimens. [80] [81]

Based on serological variant, the disease is often divided into a form with antibodies to proteinase 3, a form with antibodies to myeloperoxidase, and a seronegative variant. This is important for practice, because the form with antibodies to proteinase 3 is more often associated with granulomatosis with polyangiitis and has a higher risk of relapse. [82] [83]

The 2022 classification criteria of the American College of Rheumatology and the European Alliance of Rheumatology Associations deserve special mention. They use weighted features and a 5-point threshold, but are intended specifically for classification in studies after the physician has already established the presence of vasculitis and ruled out facial expressions. They are not a "quick self-diagnosis test" or a substitute for clinical judgment. [84]

The disease does not have stages in the traditional oncological sense, but in practice, we can speak of onset, the phase of active organ damage, remission, and relapse. It is precisely the tendency to relapse that makes long-term monitoring so important, even when the patient is feeling well and laboratory parameters have improved. [85] [86]

Approach to classification	Options
By prevalence	Localized and systemic form
By severity	Non-threatening and organ- or life-threatening form
By serology	Antibodies to proteinase 3, antibodies to myeloperoxidase, seronegative form
With the flow	Onset, active disease, remission, relapse

Sources of the table. [87] [88]

Complications and consequences

The most severe complication is rapidly progressing kidney damage leading to terminal renal failure. If glomerulonephritis is not recognized promptly, some nephrons are irreversibly lost, and even with subsequent monitoring of vasculitis, renal function may never fully recover. [89] [90]

Diffuse alveolar hemorrhage is no less dangerous. It can lead to severe hypoxemia, the need for mechanical ventilation, and death. However, blood is not always present in the sputum, so the absence of obvious hemoptysis does not rule out a critical pulmonary complication. [91] [92]

Subglottic and tracheobronchial stenosis are complications that can significantly impair quality of life and sometimes be life-threatening, even with relative control of systemic inflammation. For some patients, respiratory cicatricial complications become the most long-term and challenging problem, requiring repeated endoscopic procedures. [93] [94]

Long-term sequelae include saddle-nose deformity, permanent hearing loss, chronic kidney disease, decreased lung function, eye damage, and complications of the treatment itself, including infections, hypogammaglobulinemia, osteoporosis, cyclophosphamide-induced infertility, and cardiovascular risk. Therefore, successful treatment involves not only suppressing disease activity but also minimizing cumulative damage.[95][96]

Complication	Why is it dangerous?
Rapidly progressive glomerulonephritis	May result in terminal renal failure.
Diffuse alveolar hemorrhage	Life-threatening and requires immediate treatment.
Subglottic stenosis	May cause critical narrowing of the airways
Deformation of the nose and ear	Causes permanent structural damage
Infectious complications of treatment	One of the leading causes of hospitalizations and adverse outcomes

Sources of the table. [97] [98] [99]

When to see a doctor

You should consult a doctor not when the disease has become completely obvious, but when persistent symptoms from the nose, ears, or sinuses are combined with systemic malaise. Signs of concern include crusting and bleeding in the nose, sinusitis that doesn't resolve with standard treatment, persistent ear infections, hoarseness, cough, unexplained weakness, weight loss, and low-grade fever. [100] [101]

Urgent consultation is required if blood is present in the sputum, shortness of breath is increasing, hearing loss is acute, eye pain and redness are present, blood or protein is present in the urine, swelling is present, blood pressure is elevated, and a rapid deterioration in health occurs. In these situations, systemic vasculitis with the risk of kidney, lung, or eye damage should be considered. [102] [103]

Emergency care is needed if signs of alveolar hemorrhage, severe respiratory failure, sudden vision loss, severe chest pain, a sharp decrease in urine output, or stridor occur. For granulomatosis with polyangiitis, these symptoms do not indicate a "temporary flare-up," but rather potential damage to vital organs. [104] [105]

Situation	How urgent is it to act?
Chronic "unusual" sinusitis, crusts, nosebleeds	A planned but quick assessment is needed
Blood in urine, protein in urine, increased blood pressure	Urgent consultation
Hemoptysis, dyspnea, stridor	Urgent Care
Pain and redness of the eyes, deterioration of vision	Urgent consultation

Sources of the table. [106] [107]

Diagnostics

The diagnosis of granulomatosis with polyangiitis is always complex. No single test alone confirms the disease. The physician must compare the patient's complaints, physical examination, laboratory signs of inflammation, urinalysis, renal function, imaging data, and, if possible, a biopsy of the affected tissue. [108] [109]

Antineutrophil cytoplasmic antibody testing is very important, but it is not definitive. Most patients with systemic disease test positive, most often for antibodies to proteinase 3. However, in limited forms, and especially with localized involvement of the upper respiratory tract, it may be negative. Therefore, a negative test does not automatically rule out the diagnosis. [110] [111]

Biopsy remains the gold standard for confirmation. The most informative tissues are the kidney, lung, and sometimes the nasal mucosa or other affected tissues. However, even biopsy does not always provide a perfect picture, especially in superficial and limited forms. Therefore, treatment is sometimes initiated even before the final histological response if the clinical risk is high. [112] [113]

Of the basic tests, the most important are a complete urinalysis, creatinine, glomerular filtration rate, complete blood count, C-reactive protein, and hemoglobin. It is urine and kidney function that allow us to detect "silent" kidney damage, which may be subjectively barely noticeable. [114] [115]

The most commonly needed instruments are a chest CT scan and an ear, nose, and throat examination. A chest X-ray may be the initial test, but CT is better at showing nodules, cavities, infiltrates, and signs of alveolar hemorrhage. In the localized form, nasal and laryngeal endoscopy is important. [116] [117]

It is very important to properly understand the role of the 2022 classification criteria. They are useful for standardization and scientific research, have high sensitivity and specificity at a threshold of 5 points, but they cannot be used as a substitute for a full diagnosis in a person in whom infection, tumor, or other mimics of vasculitis have not yet been ruled out. [118]

Diagnostic step	What really needs to be done
Clinical suspicion	Assess the nose, lungs, kidneys, eyes, skin, nerves
Laboratory	Urinalysis, creatinine, blood, inflammatory markers, antineutrophil cytoplasmic antibodies
Visualization	Chest X-ray or CT scan, ear, nose and throat examination
Confirmation	Biopsy of the affected organ if possible
Exclusion of mimics	Infections, tumors, other vasculitides and systemic diseases

Sources of the table. [119] [120] [121]

Differential diagnosis

Infections are at the forefront of the differential diagnosis. Chronic bacterial sinusitis, tuberculosis, fungal infections, infective endocarditis, and severe pneumonia can closely resemble granulomatosis with polyangiitis in terms of symptoms, CT scans, and even inflammatory blood tests. Therefore, ruling out infection is a mandatory step before initiating severe immunosuppression. [122] [123]

The second major block is other vasculitides, especially microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis. They can overlap in kidney and lung involvement and antineutrophil cytoplasmic antibodies, so the clinical picture, histology and nature of the respiratory tract involvement are crucial. [124] [125]

One must also be aware of diseases that mimic granulomatous inflammation: lung and nasopharyngeal tumors, lymphoma, sarcoidosis, cocaine-induced nasal septal lesions, IgG4-associated disease, and antiglomerular basement membrane disease. For this reason, a biopsy sometimes changes the entire diagnosis and the entire therapeutic strategy. [126] [127]

Limited forms pose a particular challenge for otolaryngologists and pulmonologists. Patients may be treated for years as "chronic sinusitis" or "atypical pneumonia" until signs of renal damage appear or a meaningful biopsy is performed. Contemporary reviews clearly point to diagnostic delays as a significant problem with the disease. [128] [129]

What needs to be distinguished	Why is this important?
Infections	Immunosuppression can be dangerous if done incorrectly.
Microscopic polyangiitis	Similar in renal and vascular components
Eosinophilic granulomatosis with polyangiitis	Similar to the vasculitis group, but differs in phenotype
Tumors and lymphoma	They can mimic granulomas and infiltrates.
Sarcoidosis and other inflammatory diseases	Sometimes a similar picture is seen in the lungs and nasopharynx.

Sources of the table. [130] [131]

Treatment

Treatment is divided into two major phases: remission induction and remission maintenance. Induction is needed to stop active inflammation as quickly as possible and save organs, while maintenance therapy is needed to maintain control and reduce the risk of relapse. This two-phase logic underlies all modern recommendations. [132] [133]

In severe, organ- or life-threatening cases, current guidelines consider rituximab and cyclophosphamide as the primary agents for remission induction. The 2021 American guidelines conditionally favor rituximab over cyclophosphamide in patients with severe granulomatosis with polyangiitis or microscopic polyangiitis, while the 2025 British guidelines consider both candidates acceptable and specifically allow for a combination of both drugs in some patients with very severe cases. [134] [135]

Glucocorticoids remain an important part of initial therapy, but their role is now being reconsidered, with a focus on reducing the total dose. American guidelines recommend a reduced steroid regimen for severe disease compared to the old standard approach, and recent studies have confirmed that a lower steroid load can reduce toxicity without significant loss of efficacy when properly combined with basic immunosuppression. [136] [137]

Avacapane has become one of the leading new drugs for remission induction. It is a C5a receptor blocker that helps reduce glucocorticoid exposure. In the ADVOCATE study, it was found to be non-inferior to the standard prednisolone regimen in achieving remission by week 26 and superior in sustained remission by week 52, and current European and renal guidelines allow its use as part of a steroid-reduction strategy. [138] [139] [140]

In benign cases, when there is no severe kidney damage, pulmonary hemorrhage, or other critical organ threat, treatment may be more lenient. American guidelines for some such patients with granulomatosis with polyangiitis suggest methotrexate as an initial treatment option instead of more toxic regimens. However, it is important not to underestimate the disease: if organ damage progresses rapidly, the strategy should be reconsidered immediately. [141]

Plasmapheresis is no longer considered routine treatment for all severe cases. Both US and renal guidelines after PEXIVAS have moved away from the old policy of widespread use. Plasmapheresis is now generally not recommended for everyone, but may be considered in patients with a very high risk of renal failure, rapidly rising creatinine, those already requiring dialysis, hypoxemic diffuse alveolar hemorrhage, and glomerular basement membrane antibody overlap syndrome. [142] [143] [144]

Once remission is achieved, maintenance therapy begins. Here, current recommendations are significantly more consistent: rituximab is now considered the preferred option for maintaining remission in most patients with severe disease, as it reduces the risk of relapse compared with azathioprine. The 2025 UK guidelines recommend rituximab as the preferred maintenance drug, administered at 500-1000 mg every 4-6 months, with the duration of maintenance therapy typically being 24-48 months. [145] [146]

If rituximab is unavailable, contraindicated, or poorly tolerated, azathioprine and methotrexate remain alternatives. The 2024 renal guidelines recommend maintenance therapy with either rituximab or azathioprine in combination with low-dose glucocorticoids, and if azathioprine is intolerant, mycophenolate mofetil or methotrexate are acceptable, although the risk of relapse is generally assessed as less favorable for mycophenolate.[147] [148] [149]

Co-trimoxazole is no longer considered a full-fledged, stand-alone maintenance therapy in place of basic immunosuppressants. American guidelines explicitly prefer methotrexate or azathioprine over co-trimoxazole for maintaining remission. However, it still has two important roles: prevention of Pneumocystis carinii pneumonia during immunosuppression and treatment of some patients with infection-associated sinonasal disease activity. [150] [151] [152]

Prevention of infections and complications of therapy is crucial. Low-dose co-trimoxazole is often recommended for the prevention of Pneumocystis pneumonia in patients receiving rituximab, cyclophosphamide, and high doses of glucocorticoids, usually during induction and for at least several months after the last dose of rituximab or cyclophosphamide. Immunoglobulins, vaccinations, osteoporosis risk, glycemia, and blood pressure are monitored simultaneously. [153] [154] [155]

Treatment of ear, throat, and nose lesions and airway stenosis requires a separate approach. The 2025 British guidelines specifically address these conditions because systemic remission does not always automatically resolve the local problem. Subglottic stenosis may require local glucocorticoid injections, dilation, laser, and surgical procedures, while chronic infectious and inflammatory changes in the nose require local irrigation, rotating antibacterial regimens, and joint management by a rheumatologist and otolaryngologist. [156] [157]

Treatment stage	Modern approach
Induction of remission in severe disease	Rituximab or cyclophosphamide plus glucocorticoids
Steroid-sparing strategy	Avakapan possible
Non-threatening form	Methotrexate may be used in some patients
Plasmapheresis	Not routinely, only in certain difficult situations
Maintenance of remission	Rituximab is preferred
Alternatives	Azathioprine, methotrexate, less commonly mycophenolate mofetil
Prevention of infections	Co-trimoxazole is often used for Pneumocystis pneumonia.
Local complications of the respiratory tract	Certain local and sometimes surgical interventions are required.

Sources of the table. [158] [159] [160] [161] [162]

Prevention

There is currently no primary prophylaxis that can reliably prevent the development of granulomatosis with polyangiitis. Because the exact cause of the disease is unknown, no specific vaccine, diet, or screening can be recommended that would reliably protect against the onset of the disease. [163] [164]

Real prevention in modern practice is primarily secondary and tertiary. This includes early recognition of the disease, prompt initiation of treatment before irreversible damage to the kidneys and respiratory tract occurs, and careful long-term monitoring to prevent relapses and accumulation of organ damage. [165] [166]

Prevention of infectious complications of therapy is of great importance. When using rituximab, cyclophosphamide, and glucocorticoids, vaccination is necessary, if possible, before starting immunosuppression, monitoring immunoglobulins, preventing Pneumocystis pneumonia in high-risk patients, and careful attention to chronic upper respiratory tract infections. [167] [168]

Control of the nasal cavity and sinonasal infection remains part of the prevention of relapses. For some patients with frequent ear, throat, and nose infections, local measures are important, and in some cases, co-trimoxazole is used as a treatment specifically for infection-associated sinonasal activity, but not as a substitute for basic maintenance immunosuppression. [169] [170]

Preventive purpose	What do they actually do?
Prevention of disease onset	There is no reliable method
Prevention of organ damage	Early recognition and prompt treatment
Prevention of relapse	Supportive therapy and regular monitoring
Prevention of infections	Vaccination, co-trimoxazole in some patients, immune monitoring
Prevention of local complications	Observation by a rheumatologist and otolaryngologist

Sources of the table. [171] [172] [173]

Forecast

Before the advent of modern immunosuppressive therapy, the prognosis was extremely grave. Now the situation is fundamentally different: most patients achieve remission, and survival and organ function have improved significantly. However, the disease remains chronic, recurrent, and potentially dangerous, especially when it involves the kidneys and lungs. [174] [175]

The prognosis is most strongly influenced by renal function at diagnosis, the presence of diffuse alveolar hemorrhage, the time of initiation of therapy, and the type of serologic variant. Patients with antibodies to proteinase 3 typically have a higher risk of relapse, so they often require longer and more carefully considered maintenance therapy. [176] [177]

Relapse remains a major long-term problem. Even after a good response to remission induction, the disease can return, sometimes locally—for example, in the nose, ears, or subglottic region of the larynx—and sometimes systemically. Therefore, the absence of symptoms today does not mean that monitoring can be stopped forever. [178] [179]

A separate layer of prognosis is related not to the disease itself, but to treatment. Infections, cardiovascular events, hypogammaglobulinemia, bone damage, infertility after cyclophosphamide, and cumulative drug toxicity remain significant causes of adverse outcomes. Therefore, the physician's task is not only to "quench vasculitis" but also to do so as safely as possible to ensure the patient's long-term survival. [180] [181]

What influences the prognosis the most?	Why is this important?
Early initiation of treatment	Reduces irreversible organ damage
Kidney damage at the start	One of the main factors for an unfavorable outcome
Alveolar hemorrhage	Associated with a high risk of life-threatening complications
Relapsing course	Requires longer term maintenance therapy
Infectious complications of treatment	Significantly impact long-term survival

Sources of the table. [182] [183] [184]

FAQ

Can a diagnosis be made based solely on a positive antineutrophil cytoplasmic antibody test?
No. A positive test supports the diagnosis but does not replace a clinical evaluation, organ examination, urinalysis, and, if possible, a biopsy. Furthermore, in the limited form, the test may be negative.[185][186]

Does granulomatosis with polyangiitis always affect the kidneys?
No, especially at the onset. However, renal involvement is common and can be almost asymptomatic at first, so urinalysis and creatinine are checked even when complaints are primarily nasal or pulmonary. [187] [188]

Is rituximab better than cyclophosphamide for everyone?
No. Many current guidelines prefer rituximab for severe granulomatosis with polyangiitis, but cyclophosphamide remains an important and fully relevant drug, especially in certain severe or organizationally challenging clinical situations. [189] [190]

Is plasmapheresis necessary for all patients with severe disease?
No. It is no longer routinely recommended for everyone. It is now considered only in specific situations, such as very severe kidney disease, hypoxemic alveolar hemorrhage, or glomerular basement membrane antibody overlap syndrome. [191] [192]

Is it possible to achieve a permanent cure?
Most patients can achieve remission, sometimes long-term, but the disease is considered chronic and prone to relapse. Therefore, even if you feel well, routine checkups, tests, and monitoring of maintenance therapy are necessary. [193] [194]

Why is cotrimoxazole needed if it is not the primary treatment for vasculitis?
Its role today is primarily related to the prophylaxis of Pneumocystis pneumonia during immunosuppression and for some infection-associated sinonasal manifestations. It is not generally considered a full-fledged maintenance replacement for basic immunosuppression. [195] [196] [197]

Key points from experts

Bernhard Hellmich, MD, professor, is one of the leading authors of the European Alliance of Rheumatology guidelines on vasculitis. The main thesis of his school in 2024 is that granulomatosis with polyangiitis should be treated with maximum activity control, but with minimization of total steroid damage. This is precisely why interest in avacapane and more gentle steroid regimens has increased. [198] [199]

Sharon A. Chang, MD, MS, is a co-author of the 2021 American College of Rheumatology and Vasculitis Foundation guidelines. Her key practice message for granulomatosis with polyangiitis is that rituximab should be considered as the preferred option for remission induction in severe, active patients, and that it often outperforms conventional agents in terms of relapse risk for maintenance of remission. [200] [201]

David Jain, MD, professor, was a key researcher on avacapane and modern vasculitis treatment strategies. His work shifted modern therapy toward targeted blockade of the C5a pathway and reduction of glucocorticoid load. This did not eliminate basic immunosuppression, but it significantly changed the understanding of how severe vasculitis can be treated with lower steroid costs. [202] [203]

Richard A. Watts, MD, professor, is a leading expert on the epidemiology and classification of systemic vasculitides. His thesis is particularly important for diagnosis: correct classification of the disease is necessary, but criteria should not replace clinical diagnosis, and granulomatosis with polyangiitis must always be distinguished from infections and other vasculitides with overlapping patterns. [204] [205]

Conclusion

Granulomatosis with polyangiitis is a rare but highly significant systemic vasculitis that most commonly attacks the upper respiratory tract, lungs, and kidneys. Its danger lies not only in the severity of its onset but also in its tendency to relapse, organ damage, and treatment complications. [206] [207]

Modern medicine has learned to treat this disease much better than before. Rituximab, cyclophosphamide, more rational steroid regimens, avacapane, and thoughtful supportive therapy have significantly improved inflammation control and prognosis, but success still depends on early diagnosis and the correct selection of strategies. [208] [209] [210]

The most practical conclusion is this: if a person has a combination of persistent nasal or sinus lesions, pulmonary symptoms, and changes in urine or renal function, granulomatosis with polyangiitis should be considered early. Early suspicion, confirmation of the diagnosis, and timely initiation of treatment best protect the patient from irreversible loss of kidney, lung, hearing, and vision function. [211] [212]