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Granulomatosis with polyangiitis, usually shortened to GPA, is a rare condition in which the immune system inflames the walls of small blood vessels. It has a particular liking for three places: the nose and sinuses, the airways and lungs, and the kidneys. Because it starts in the nose and sinuses for many people, it is often mistaken at first for stubborn sinusitis or a chest infection that will not clear. GPA is treated with medicines that damp down the immune system, and modern treatment works well — most people get the disease into remission. What remains afterwards is often mechanical rather than inflammatory: a narrowed windpipe, scarred lung, weakened muscles after a long illness, or breathlessness that is out of proportion to the scans. That is the part physiotherapy is for. This page explains what GPA is, how it is treated, and where breathing and exercise work fit in.
Definition
GPA is one of a small family of conditions called the ANCA-associated vasculitides. Vasculitis means inflammation of blood vessel walls; ANCA refers to a particular type of antibody found in the blood of most people with the condition. In GPA the inflammation affects small vessels, and it is accompanied by granulomas — small clumps of immune cells that form in tissue and can destroy the structures around them.1
It was previously known as Wegener's granulomatosis. The name changed in 2011 to a description of what the disease does rather than who first described it, and both names still appear in older records and papers.1
GPA is rare, it is not contagious, and it is not caused by anything you did. It is not a cancer, although the scans early on can look worrying enough that cancer is one of the things doctors have to rule out.
Pathophysiology
The immune system produces antibodies that activate white blood cells inside small vessels. Those cells stick to the vessel lining and release enzymes that damage it. Two things follow from that, and they explain almost every symptom of the disease.
Vessels leak and block
Damaged small vessels leak blood into the tissue around them and can block off entirely, starving that tissue of its supply. In the lung that produces bleeding into the air sacs and areas of tissue death. In the kidney it damages the filtering units, which is why kidney function can fall quickly and why urine is checked at every review.
Granulomas destroy structures
Granulomas are the feature that separates GPA from its close relatives. They form in the nose, sinuses, airways and lungs, and as they grow they erode what is next to them. This is what causes the collapsed bridge of the nose that some people develop, the holes that can form in the nasal septum, and the scarred narrowing of the windpipe described further down this page.
Understanding the difference between these two processes matters, because they respond differently. Inflammation responds to immune-suppressing medicine. Scarring and structural damage do not — once tissue has been destroyed and replaced with scar, no drug returns it to normal, and the problem becomes a mechanical one to be managed rather than an inflammatory one to be treated.
Prevalence
Contemporary European studies put prevalence in the order of eight to sixteen people per hundred thousand, with new diagnoses running at roughly one person per hundred thousand per year. Older figures of two to three per hundred thousand derive from 1990s series and understate current ascertainment.3 It is diagnosed most often between the ages of 45 and 65, though it occurs in children and in much older adults. Men and women are affected in roughly equal numbers.
Because it is this rare, most GPs will see very few cases in a career, and delay between first symptom and diagnosis is common. That delay is not usually anyone's fault: the early symptoms are indistinguishable from far more common problems.
Symptoms
Nose, sinuses and ears
For many people this is where it starts, and it is why an ear, nose and throat surgeon is sometimes the first specialist involved. Persistent blocked nose, crusting inside the nostrils, bleeding, loss of smell, sinus pain that does not settle with antibiotics, and recurrent middle-ear problems with reduced hearing. Symptoms that would be unremarkable individually become significant when they persist for months and do not respond to the usual treatment.
Chest and airways
Cough, sometimes with blood, breathlessness, wheeze, chest pain, and a hoarse voice or noisy breathing if the larynx or windpipe is involved. Chest imaging often shows nodules, some of which have cavities in the middle. Coughing up any significant amount of blood is an emergency and is covered in the box below.
Kidneys
The kidneys frequently give no symptoms at all until function is already significantly reduced, which is exactly why they are monitored with urine and blood tests rather than by how you feel. When symptoms do appear they include blood in the urine, frothy urine, swollen ankles and rising blood pressure.
Everything else
Fatigue that is out of proportion to activity, fever, weight loss, joint and muscle aches, skin rashes, red painful eyes, and numbness or weakness in a hand or foot from involvement of the nerves. The general symptoms are often the ones people remember as the first sign that something was properly wrong.
Some features of GPA are emergencies, and knowing them is part of living with the diagnosis:
- Coughing up blood — more than streaks, or any amount that is new for you. Bleeding into the lungs can develop over hours.
- Breathlessness that is worsening quickly, or noisy breathing in at rest.
- Passing much less urine than usual, or new swelling of the legs and face.
- New numbness, weakness, or loss of vision.
If you are on immune-suppressing treatment, fever is also urgent — not because it means the vasculitis is back, but because your ability to fight infection is reduced and infection is a greater risk to you than it was before.
Diagnosis
There is no single test. Diagnosis comes from putting the pattern together, and usually includes:2
- Blood tests — inflammatory markers, kidney function, full blood count, and ANCA antibody testing. Most people with GPA have antibodies directed against proteinase 3, though a proportion do not, and a negative result does not by itself exclude the disease.
- Urine testing — for blood and protein, which is the most sensitive early sign of kidney involvement.
- Imaging — CT of the sinuses and chest, which shows the nodules, cavities and sinus changes.
- Biopsy — a small tissue sample, most often from the nose, lung or kidney. Biopsy is the closest thing to a definitive test and is usually sought where treatment decisions depend on it.
- Airway assessment — nasendoscopy or bronchoscopy where the voice box or windpipe may be involved, and lung function testing with flow-volume loops.
Management
Medical treatment is led by a rheumatologist, often with a respiratory physician and a kidney specialist involved. It runs in two phases, and the distinction is worth understanding because the second phase lasts years.
Getting the disease under control
The first phase uses strong immune-suppressing treatment to stop active inflammation. This usually combines glucocorticoids with either rituximab or cyclophosphamide,4,5 and for severe disease affecting the kidneys or causing lung bleeding it is started urgently in hospital. Steroid doses are higher at the start and reduced over the following months.
Keeping it under control
Once the disease is quiet, treatment continues at lower intensity to prevent relapse, typically for at least a couple of years and sometimes much longer. Relapse is common enough in GPA that ongoing monitoring is standard even when you feel entirely well.5
What the treatment costs you
Immune suppression raises infection risk, so vaccination, prompt attention to fevers and sometimes preventative antibiotics all become part of routine care. Steroids taken over months affect bone density, blood sugar, weight, mood and muscle strength — and the muscle effect is one of the reasons people finish treatment in remission but nowhere near their previous fitness.
Narrowing of the windpipe
A proportion of people with GPA develop subglottic stenosis — scarred narrowing of the airway just below the voice box. It deserves its own section because it behaves unlike the rest of the disease and is frequently misread.6,7
The symptoms are noisy breathing in, breathlessness on effort that arrives abruptly at a particular level of exertion, a hoarse or weak voice, and a cough that sounds different from before. Because it can appear when blood tests are entirely normal, it is often assumed to be asthma and treated with inhalers that make no difference. A flow-volume loop and direct visualisation of the airway are what settle it.
It is important because it is mechanical, not inflammatory. Increasing immune-suppressing medication does not open a scarred airway. Treatment is procedural — dilatation, and sometimes injection or surgery — and it often needs repeating.7 Between procedures, breathing pattern work makes a genuine difference to how manageable the narrowing feels, because people naturally respond to a restricted airway by breathing faster and higher in the chest, which increases turbulence and makes the obstruction feel worse than it is.
Living with GPA
Most people reach remission, and many return to work and to the activities that matter to them. What tends to persist is not usually active disease:
- Fatigue, which is frequently the last symptom to improve and the one people find hardest to explain to others.
- Deconditioning after weeks or months of illness, hospital admission and steroid treatment. Muscle is lost quickly and does not return on its own.
- Breathlessness out of proportion to the scans, often driven by breathing pattern, reduced fitness and anxiety about symptoms returning, rather than by ongoing inflammation.
- Scarred lung or airway, which is permanent and managed rather than cured.
- Sinus and nasal symptoms, which commonly continue after the disease is otherwise quiet and need their own ongoing care.
Exercise is safe in remission and is one of the few things that reliably helps fatigue and deconditioning.8 The caution is not about intensity but about interpretation: you should know which symptoms are your normal and which mean a call to your specialist team.
Role of the physiotherapist
Physiotherapy does not treat the vasculitis — that is what the immune-suppressing medicine is for. What physiotherapy addresses is what is left behind, which is often what determines how you actually live. We work alongside your rheumatologist, respiratory physician and GP rather than in place of them.
Assessment first, always. Breathlessness after GPA can be scarred lung, a narrowed airway, lost fitness, an altered breathing pattern, anaemia, or several of those at once, and they need different treatment. The point of the first appointment is to work out which.
- Physiotherapy Assessment — measure breathing pattern, exercise tolerance and strength, and identify which cause is driving your breathlessness
- Cardiorespiratory Rehabilitation — supervised, monitored exercise to rebuild what illness and steroids took — the treatment for deconditioning
- Airway Clearance Therapy — for those left with bronchiectasis or scarred, sputum-retaining airways after the disease is quiet
- Functional Capacity Assessments — objective documentation of what you can do, where a plan, an employer or an insurer needs it in writing
Part 1 · References
- Jennette JC, Falk RJ, Bacon PA, et al. 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 2013;65(1):1–11.
- Robson JC, Grayson PC, Ponte C, et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for granulomatosis with polyangiitis. Ann Rheum Dis 2022;81(3):315–320.
- Watts RA, Mahr A, Mohammad AJ, Gatenby P, Basu N, Flores-Suárez LF. Classification, epidemiology and clinical subgrouping of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Nephrol Dial Transplant 2015;30 Suppl 1:i14–22.
- Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 2010;363(3):221–232.
- Hellmich B, Sanchez-Alamo B, Schirmer JH, et al. EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update. Ann Rheum Dis 2024;83(1):30–47.
- Martinez Del Pero M, Jayne D, Chaudhry A, Sivasothy P, Jani P. Long-term outcome of airway stenosis in granulomatosis with polyangiitis. JAMA Otolaryngol Head Neck Surg 2014;140(11):1038–1044.
- Quinn KA, Gelbard A, Sibley C, et al. Subglottic stenosis and endobronchial disease in granulomatosis with polyangiitis. Rheumatology 2019;58(12):2203–2211.
- Tuin J, Sanders JSF, Buhl C, van Beek AP, Stegeman CA. Fatigue in ANCA-associated vasculitis: determinants and effects of exercise. Clin Exp Rheumatol 2019;37 Suppl 117:143–149.
Clinical evidence
Part 1 covers the same condition without the technical detail. What follows is the evidence base behind it, written for clinicians — the literature, the reasoning and the gaps.
For clinicians: this summary supports clinical reasoning and is not a protocol. Check current guidelines and local policy before applying it, and read it alongside the key references and guidelines directory.
Framing. Granulomatosis with polyangiitis is a necrotising, granulomatous, ANCA-associated small-vessel vasculitis, defined within the 2012 Revised Chapel Hill Consensus nomenclature and classified for research purposes by the 2022 ACR/EULAR criteria.1,2 It is predominantly PR3-ANCA positive, with MPO-ANCA and ANCA-negative disease both recognised; ANCA serotype now carries more prognostic and therapeutic weight than the clinical syndrome label in much of the literature.3 Reported prevalence in contemporary northern European cohorts is approximately 8–16 per 100,000 with annual incidence near 1 per 100,000 (1990s series reported 2–3 per 100,000), with geographical variation that is only partly explained by ascertainment.4
Pathogenesis relevant to rehabilitation
- ANCA-mediated neutrophil activation drives endothelial injury, while granuloma formation produces the destructive upper-airway and pulmonary lesions characteristic of GPA.
- Inflammatory and structural sequelae diverge, and this is the clinically important corollary for physiotherapy: the former is immunosuppression-responsive, the latter is not.
- Findings that do not track with serological or radiological activity should raise structural, deconditioning or behavioural mechanisms rather than prompting escalation of immunosuppression.
Induction and maintenance
- RAVE established rituximab as non-inferior to cyclophosphamide for induction in severe ANCA-associated vasculitis, and superior in relapsing disease; RITUXVAS reported comparable findings in renal disease.5,6
- MAINRITSAN demonstrated superiority of rituximab over azathioprine for maintenance.7
- PEXIVAS found no benefit of plasma exchange on death or end-stage kidney disease, and showed a reduced-dose glucocorticoid regimen to be non-inferior for that outcome while reducing serious infection — a finding that has materially lowered cumulative steroid exposure.8
- ADVOCATE supported avacopan as a glucocorticoid-sparing agent.9
- Current EULAR recommendations consolidate these.10
Why steroid-sparing matters to a physiotherapist
- Glucocorticoid myopathy preferentially affects type II fibres and proximal musculature, is dose- and duration-dependent, and is compounded by disuse during acute illness.
- Reduced-dose regimens do not remove the problem: a patient in serological remission may still present with substantial proximal weakness, reduced exercise tolerance and impaired bone density.
- Progressive resistance training has the clearest rationale here, and should be prescribed against measured strength rather than symptom report.
Subglottic stenosis
- It occurs in a meaningful minority of GPA, disproportionately in younger patients and in PR3-ANCA disease, and characteristically follows a course independent of systemic activity — it may progress while systemic disease is quiescent.11,12
- It is commonly misdiagnosed as asthma. Spirometry may be interpreted as obstruction without inspection of the flow-volume loop, where inspiratory limitation and a flattened inspiratory limb are the discriminating features.
- Management is interventional, not pharmacological — endoscopic dilatation with or without intralesional corticosteroid, occasionally open reconstruction — and recurrence requiring repeat dilatation is usual.13
- It is a differential for, and can coexist with, inducible laryngeal obstruction, and the behavioural component is amenable to breathing pattern retraining even where the fixed narrowing is not.
Exercise and pulmonary rehabilitation evidence
- There is no adequately powered randomised trial of exercise training specific to ANCA-associated vasculitis, and this should be stated plainly rather than obscured.
- The available evidence is small-cohort and observational, reporting that supervised exercise is feasible and well tolerated in stable disease with improvements in exercise capacity, fatigue and quality of life.14
- Practice is extrapolated from rehabilitation in interstitial lung disease, bronchiectasis and post-critical-illness populations, where the evidence for supervised, progressive, individually prescribed exercise is strong.15,16
- Extrapolation is defensible because the limiting impairments are mechanistically shared — deconditioning, myopathy, restrictive or obstructive defect, fatigue — but it is not a substitute for disease-specific trials, which remain a genuine gap.
Assessment set that changes management
- Full lung function with flow-volume loops, the inspiratory limb inspected explicitly rather than merely reported.
- Field walking test with continuous oximetry, since desaturation may be exertional only.
- Objective proximal strength testing, given steroid exposure.
- Breathing pattern assessment at rest and during recovery from effort.
- Screening for anaemia, which is common and independently limits exercise capacity.
- Direct visualisation where subglottic disease is suspected — request or confirm it. Physiotherapy should not be the terminus of an undiagnosed fixed upper-airway obstruction.
Relapse literacy as a rehabilitation outcome
- Relapse rates in GPA are substantial, and higher in PR3-ANCA disease.
- Patients undertaking exercise need an explicit framework distinguishing expected training responses from features warranting urgent specialist contact — haemoptysis, rapidly progressive dyspnoea, reduced urine output, new neurological deficit, or fever on immunosuppression.
- Building that discrimination is a legitimate rehabilitation objective, and its absence is a safety problem rather than an educational nicety.
Evidence gaps
- No trial evidence establishes the optimal timing of exercise initiation after induction therapy.
- No evidence shows that inspiratory muscle training modifies fixed subglottic stenosis, and it should not be offered on that basis — though it has a rationale where inspiratory muscle weakness is measured.
- The durability of rehabilitation gains across relapse-remission cycles has not been characterised.
- Each of these is a reasonable clinical judgement, not a supported recommendation, and should be presented to patients as such.
References for the clinical evidence summary
- Jennette JC, Falk RJ, Bacon PA, et al. 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 2013;65(1):1–11.
- Robson JC, Grayson PC, Ponte C, et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for granulomatosis with polyangiitis. Ann Rheum Dis 2022;81(3):315–320.
- Lyons PA, Rayner TF, Trivedi S, et al. Genetically distinct subsets within ANCA-associated vasculitis. N Engl J Med 2012;367(3):214–223.
- Watts RA, Mahr A, Mohammad AJ, Gatenby P, Basu N, Flores-Suárez LF. Classification, epidemiology and clinical subgrouping of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Nephrol Dial Transplant 2015;30 Suppl 1:i14–22.
- Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 2010;363(3):221–232.
- Jones RB, Tervaert JWC, Hauser T, et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med 2010;363(3):211–220.
- Guillevin L, Pagnoux C, Karras A, et al. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med 2014;371(19):1771–1780.
- Walsh M, Merkel PA, Peh CA, et al. Plasma exchange and glucocorticoids in severe ANCA-associated vasculitis. N Engl J Med 2020;382(7):622–631.
- Jayne DRW, Merkel PA, Schall TJ, Bekker P; ADVOCATE Study Group. Avacopan for the treatment of ANCA-associated vasculitis. N Engl J Med 2021;384(7):599–609.
- Hellmich B, Sanchez-Alamo B, Schirmer JH, et al. EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update. Ann Rheum Dis 2024;83(1):30–47.
- Gluth MB, Shinners PA, Kasperbauer JL. Subglottic stenosis associated with Wegener’s granulomatosis. Laryngoscope 2003;113(8):1304–1307.
- Martinez Del Pero M, Jayne D, Chaudhry A, Sivasothy P, Jani P. Long-term outcome of airway stenosis in granulomatosis with polyangiitis. JAMA Otolaryngol Head Neck Surg 2014;140(11):1038–1044.
- Quinn KA, Gelbard A, Sibley C, et al. Subglottic stenosis and endobronchial disease in granulomatosis with polyangiitis. Rheumatology 2019;58(12):2203–2211.
- Tuin J, Sanders JSF, Buhl C, van Beek AP, Stegeman CA. Fatigue in ANCA-associated vasculitis: determinants and effects of exercise. Clin Exp Rheumatol 2019;37 Suppl 117:143–149.
- Dowman L, Hill CJ, May A, Holland AE. Pulmonary rehabilitation for interstitial lung disease. Cochrane Database Syst Rev 2021;2:CD006322.
- Spruit MA, Singh SJ, Garvey C, et al. An official ATS/ERS statement: key concepts and advances in pulmonary rehabilitation. Am J Respir Crit Care Med 2013;188(8):e13–64.
Physiotherapy does not treat the vasculitis — that is what the immune-suppressing medicine is for. It addresses what is left behind, which is often what decides how you feel day to day. Assessment comes first: breathlessness after GPA can be scarred lung, a narrowed airway, lost fitness or an altered breathing pattern, and those need different treatment.
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