RARE DISEASE
Granulomatosis with polyangiitis
Granulomatosis with polyangiitis
Granulomatosis with polyangiitis
Synonyms: GPA
Synonyms: GPA
Synonyms: GPA
Drug discovery
4
drugs
With orphan designations
Overview
Granulomatosis with polyangiitis (GPA) is a rare ANCA-associated vasculitis characterized by necrotizing inflammation of small-to-medium vessels, granuloma formation, and frequent involvement of the upper/lower respiratory tracts and kidneys [1][4][19]. Diagnosis relies on clinical presentation, ANCA serology (primarily PR3-ANCA), and histopathology [10][19]. Untreated mortality exceeds 80%, but modern regimens reduce this to ~10% [4][19].
Population
Incidence: 3-14.4 cases/million annually in Europe, 12.8/million in U.S. working-age adults [2][12][16]
Demographics: Peak onset 40-65 years; slight male predominance (1.2:1). More common in Caucasians (~90% of cases) [2][7][19]
Pediatric: Rare (1.8/million incidence), higher hematologic complications vs adults [12][19]
Burden
Morbidity: 35-44% relapse rate; chronic kidney disease in 20-25%, hearing loss in 22-42% [4][6][12]
Mortality: 10% at 5 years (vs 80% untreated), often from infections or cardiovascular events [4][19]
Economic: Annual costs ~$78,000/patient with relapses vs $27,000 in remission [9]. Pediatric patients incur 2-3× higher hospitalization rates [12].
Therapies
Induction: High-dose glucocorticoids + rituximab (preferred) or cyclophosphamide for severe disease [1][3][19]
Maintenance: Rituximab monotherapy or methotrexate/azathioprine for 12-24 months [1][19]
Emerging: Avacopan (complement C5a inhibitor) reduces steroid exposure [1], plasma exchange reserved for refractory cases [1][19]
Categories: rare circulatory system diseases, rare neurological diseases, rare renal diseases, rare respiratory diseases, rare systemic and rheumatological diseases, rare systemic or rheumatologic diseases of childhood, rare transplant-related disorders
Research Papers
2,011 drug discovery papers about Granulomatosis with polyangiitis, with 2 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2,011 drug discovery papers about Granulomatosis with polyangiitis, with 2 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-08 | A systematic review of abatacept and belatacept in immune-mediated diseases.
Abatacept (ABA) and belatacept (BEL) are immunomodulatory fusion proteins in which the extracellular domain of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is linked to the Fc fragment of human IgG1. Functionally, they bind to cell surface antigens CD80 and CD86 on antigen-presenting cells, thereby preventing CD28-mediated costimulatory signaling. This systematic review aims to evaluate the clinical efficacy of ABA and BEL in immune-mediated diseases, focusing on indications currently not approved by the United States Food and Drug Administration (FDA) or the European Medicines Agency (EMA). We searched PubMed and Web of Science for reports describing clinical efficacy of ABA or BEL in at least one patient with immune-mediated conditions outside FDA/EMA-approved indications. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist guided our data reporting. Of 5333 articles initially extracted, 2778 unique records were screened after de-duplication, and 96 matched our criteria and were included in this study. ABA was beneficial in patients diagnosed with Sjögren's syndrome (particularly secondary forms); autoimmunity in association with immunodeficiency; early, inflammatory and normal-like subtypes of systemic sclerosis; scleroderma; arthritis in systemic lupus erythematosus; inflammatory myopathies (polymyositis, immune-mediated necrotizing myositis, and antisynthetase syndrome); and giant-cell arteritis. Lower-level evidence studies reported positive results using ABA to treat granulomatosis with polyangiitis; relapsing polychondritis; sarcoidosis; and inflammatory eye diseases. Results of several studies highlighted the positive impact of ABA on arthritis in patients taking this drug for other indications. Likewise, several autoimmune diseases responded effectively to ABA when used to treat concomitant rheumatoid arthritis. Positive serological responses suggesting downstream modulation of B cell activation were reported in several randomized controlled trials. BEL was used after kidney transplantation in patients with proteinuric kidney disease or lupus nephritis, and in a few non-transplanted CTLA-4 haploinsufficiency carriers for immunodeficiency-associated autoimmunity. Our results provide a comprehensive summary of the efficacy of ABA and BEL across a broad spectrum of autoimmune diseases.
2026-08-08 | Eosinophilic granulomatosis with polyangiitis complicated by pulmonary aspergillosis and misdiagnosed as allergic bronchopulmonary aspergillosis: a case report.
To enhance the diagnostic and therapeutic awareness of eosinophilic granulomatosis with polyangiitis (EGPA) complicated by pulmonary aspergillosis. We report a case of EGPA initially misdiagnosed as allergic bronchopulmonary aspergillosis (ABPA) in a 52-year-old female patient. The patient presented with intermittent wheezing for more than six months and had a history of sinusitis. An outside hospital diagnosed ABPA based on pulmonary opacities, bronchiectasis, and evidence of Aspergillus infection, but standard therapy proved ineffective. Upon admission, laboratory findings revealed a markedly elevated absolute peripheral blood eosinophil count (5.29 × 109/L) and positivity for MPO-ANCA and p-ANCA. Serum total IgE was 8.85 IU/mL, and specific IgE to Aspergillus fumigatus was <0.10 IU/mL, both of which were inconsistent with ABPA. Chest CT showed multiple bilateral patchy and nodular opacities with bronchiectasis. Bronchoalveolar lavage fluid targeted next-generation sequencing (tNGS) detected Aspergillus at the genus level (23 sequence reads, relative abundance 33.39%). The diagnosis was revised to EGPA complicated by pulmonary aspergillosis. The patient was treated with glucocorticoids combined with mepolizumab, supplemented with voriconazole. Following treatment, the patient's symptoms resolved, with near normalization of imaging findings and pulmonary function. After 10 months of follow-up, methylprednisolone was completely discontinued in December 2025, and at the last follow-up in May 2026, the patient had been off glucocorticoids for 5 months, with sustained remission and successful extension of the mepolizumab dosing interval to 8 weeks. For patients presenting with refractory asthma accompanied by eosinophilia and pulmonary opacities, EGPA should be highly suspected. Glucocorticoids combined with mepolizumab is effective. In patients achieving sustained remission, extending the mepolizumab dosing interval to 8 weeks may be a safe and effective long-term maintenance strategy in carefully selected patients, though this observation requires further validation in prospective studies.
2026-08-07 | Hepatic granulomas as a manifestation of ANCA-associated vasculitis:a systematic review.
ANCA-associated vasculitides (AAV) - granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA) - are rare small-vessel autoimmune diseases. Liver involvement in AAV is uncommon and generally manifests as biochemical hepatitis; true hepatic granulomatosis is exceedingly rare and diagnostically challenging. We conducted a systematic scoping review following PRISMA-ScR guidelines and the Arksey & O'Malley framework, searching PubMed, Google Scholar, ScienceDirect, and Scopus without date restriction (through March 2026). A total of 7, 033 records were initially retrieved; after deduplication, title/abstract screening, and full-text review, five articles meeting strict inclusion criteria were included for qualitative synthesis. Five published cases of hepatic granulomas in AAV patients with no confirmed confounding etiology were identified. All were GPA or EGPA; no case of pure MPA was documented. Three patients were female and two were male, with a mean age of 57.6 years. Liver histology revealed non-necrotizing epithelioid granulomas (n = 2), granulomatous inflammation with necrosis (n = 1), incomplete septal cirrhosis with vasculopathic changes (n = 1), and incidental calcified granulomas (n = 1). Immunosuppressive therapy with corticosteroids and/or cyclophosphamide achieved clinical and biochemical improvement in all treated patients. Hepatic granulomatosis is a rare but genuine extra-respiratory manifestation of AAV, most frequently reported in GPA. It may antedate the canonical ENT-pulmonary-renal triad, presenting as incidental hepatomegaly or unexplained liver function test elevation. Systematic exclusion of competing etiologies (sarcoidosis, tuberculosis, primary biliary cholangitis, drug-induced hepatitis) is mandatory before attributing granulomas to AAV. Liver biopsy remains pivotal in confirming the diagnosis. Immunosuppression is the therapeutic cornerstone, with generally favourable outcomes.
2026-08-05 | Anterior ischaemic optic neuropathy as an initial manifestation of eosinophilic granulomatosis with polyangiitis: The importance of early and appropriate immunosuppressive treatment for visual recovery.
Eosinophilic granulomatosis with polyangiitis (EGPA) is an antineutrophil cytoplasmic antibody-associated vasculitis, affecting various organs. Although ocular involvement occurred in 6.8-11.1% of patients, anterior ischaemic optic neuropathy (AION) is rare. We present the case of a 57-year-old woman with an 11-year history of asthma who developed sudden, painless visual loss in her left eye. On admission (3 days after symptom onset), visual acuity was counting fingers in the left eye and 20/20 in the right eye. Funduscopy showed left optic disc oedema. Magnetic resonance imaging revealed intravitreal protrusion of the left optic nerve head with restricted diffusion and local contrast enhancement of the left intraorbital and retrobulbar fat. Given also peripheral eosinophilia, myeloperoxidase-antineutrophil cytoplasmic antibody positivity, mononeuritis multiplex, nasal polyps, sinusitis, and pulmonary involvement, EGPA with AION was diagnosed. Intravenous methylprednisolone pulse was urgently administered, followed by mepolizumab 2 weeks later. Although eosinophilic inflammation and imaging findings improved, visual acuity remained unchanged over 1 year. A literature review identified 14 cases of EGPA-associated AION. Including our case, 11 cases with available data (14 eyes) were analysed. Overall, visual recovery was observed in 29%. Among 12 eyes with severe visual impairment before treatment, visual recovery occurred only in those treated earlier or with cyclophosphamide except for one, whereas no recovery occurred in those with delayed treatment or without cyclophosphamide. This case highlights the potential of AION as an initial manifestation of EGPA. Both earlier initiation and adequate intensity of immunosuppressive therapy, particularly including cyclophosphamide when clinically appropriate, may be important for visual recovery in EGPA-associated severe AION.
2026-08-05 | Antineutrophil cytoplasmic antibody-positive giant cell arteritis: Small-vessel vasculitis mimicking large-vessel vasculitis.
Giant cell arteritis is the most common vasculitis in those over 50 years old with a peak incidence between 70 and 80. Symptoms include a new-onset headache, scalp tenderness, jaw/tongue claudication, and visual symptoms, which can be sight-threatening. We report a case of an 82-year-old lady who presented with typical symptoms of giant cell arteritis and bilateral halo sign on an ultrasound scan. Despite initial steroid treatment she deteriorated and developed neurological symptoms including mononeuritis multiplex. Following further investigations, it was found that she was suffering from granulomatosis with polyangiitis and treatment was adjusted accordingly with additional immunomodulating treatment preventing further progression of symptoms. This case highlights how granulomatosis with polyangiitis can mimic giant cell arteritis and should be considered in refractory cases.
2026-08-08 | A systematic review of abatacept and belatacept in immune-mediated diseases.
Abatacept (ABA) and belatacept (BEL) are immunomodulatory fusion proteins in which the extracellular domain of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is linked to the Fc fragment of human IgG1. Functionally, they bind to cell surface antigens CD80 and CD86 on antigen-presenting cells, thereby preventing CD28-mediated costimulatory signaling. This systematic review aims to evaluate the clinical efficacy of ABA and BEL in immune-mediated diseases, focusing on indications currently not approved by the United States Food and Drug Administration (FDA) or the European Medicines Agency (EMA). We searched PubMed and Web of Science for reports describing clinical efficacy of ABA or BEL in at least one patient with immune-mediated conditions outside FDA/EMA-approved indications. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist guided our data reporting. Of 5333 articles initially extracted, 2778 unique records were screened after de-duplication, and 96 matched our criteria and were included in this study. ABA was beneficial in patients diagnosed with Sjögren's syndrome (particularly secondary forms); autoimmunity in association with immunodeficiency; early, inflammatory and normal-like subtypes of systemic sclerosis; scleroderma; arthritis in systemic lupus erythematosus; inflammatory myopathies (polymyositis, immune-mediated necrotizing myositis, and antisynthetase syndrome); and giant-cell arteritis. Lower-level evidence studies reported positive results using ABA to treat granulomatosis with polyangiitis; relapsing polychondritis; sarcoidosis; and inflammatory eye diseases. Results of several studies highlighted the positive impact of ABA on arthritis in patients taking this drug for other indications. Likewise, several autoimmune diseases responded effectively to ABA when used to treat concomitant rheumatoid arthritis. Positive serological responses suggesting downstream modulation of B cell activation were reported in several randomized controlled trials. BEL was used after kidney transplantation in patients with proteinuric kidney disease or lupus nephritis, and in a few non-transplanted CTLA-4 haploinsufficiency carriers for immunodeficiency-associated autoimmunity. Our results provide a comprehensive summary of the efficacy of ABA and BEL across a broad spectrum of autoimmune diseases.
2026-08-08 | Eosinophilic granulomatosis with polyangiitis complicated by pulmonary aspergillosis and misdiagnosed as allergic bronchopulmonary aspergillosis: a case report.
To enhance the diagnostic and therapeutic awareness of eosinophilic granulomatosis with polyangiitis (EGPA) complicated by pulmonary aspergillosis. We report a case of EGPA initially misdiagnosed as allergic bronchopulmonary aspergillosis (ABPA) in a 52-year-old female patient. The patient presented with intermittent wheezing for more than six months and had a history of sinusitis. An outside hospital diagnosed ABPA based on pulmonary opacities, bronchiectasis, and evidence of Aspergillus infection, but standard therapy proved ineffective. Upon admission, laboratory findings revealed a markedly elevated absolute peripheral blood eosinophil count (5.29 × 109/L) and positivity for MPO-ANCA and p-ANCA. Serum total IgE was 8.85 IU/mL, and specific IgE to Aspergillus fumigatus was <0.10 IU/mL, both of which were inconsistent with ABPA. Chest CT showed multiple bilateral patchy and nodular opacities with bronchiectasis. Bronchoalveolar lavage fluid targeted next-generation sequencing (tNGS) detected Aspergillus at the genus level (23 sequence reads, relative abundance 33.39%). The diagnosis was revised to EGPA complicated by pulmonary aspergillosis. The patient was treated with glucocorticoids combined with mepolizumab, supplemented with voriconazole. Following treatment, the patient's symptoms resolved, with near normalization of imaging findings and pulmonary function. After 10 months of follow-up, methylprednisolone was completely discontinued in December 2025, and at the last follow-up in May 2026, the patient had been off glucocorticoids for 5 months, with sustained remission and successful extension of the mepolizumab dosing interval to 8 weeks. For patients presenting with refractory asthma accompanied by eosinophilia and pulmonary opacities, EGPA should be highly suspected. Glucocorticoids combined with mepolizumab is effective. In patients achieving sustained remission, extending the mepolizumab dosing interval to 8 weeks may be a safe and effective long-term maintenance strategy in carefully selected patients, though this observation requires further validation in prospective studies.
2026-08-07 | Hepatic granulomas as a manifestation of ANCA-associated vasculitis:a systematic review.
ANCA-associated vasculitides (AAV) - granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA) - are rare small-vessel autoimmune diseases. Liver involvement in AAV is uncommon and generally manifests as biochemical hepatitis; true hepatic granulomatosis is exceedingly rare and diagnostically challenging. We conducted a systematic scoping review following PRISMA-ScR guidelines and the Arksey & O'Malley framework, searching PubMed, Google Scholar, ScienceDirect, and Scopus without date restriction (through March 2026). A total of 7, 033 records were initially retrieved; after deduplication, title/abstract screening, and full-text review, five articles meeting strict inclusion criteria were included for qualitative synthesis. Five published cases of hepatic granulomas in AAV patients with no confirmed confounding etiology were identified. All were GPA or EGPA; no case of pure MPA was documented. Three patients were female and two were male, with a mean age of 57.6 years. Liver histology revealed non-necrotizing epithelioid granulomas (n = 2), granulomatous inflammation with necrosis (n = 1), incomplete septal cirrhosis with vasculopathic changes (n = 1), and incidental calcified granulomas (n = 1). Immunosuppressive therapy with corticosteroids and/or cyclophosphamide achieved clinical and biochemical improvement in all treated patients. Hepatic granulomatosis is a rare but genuine extra-respiratory manifestation of AAV, most frequently reported in GPA. It may antedate the canonical ENT-pulmonary-renal triad, presenting as incidental hepatomegaly or unexplained liver function test elevation. Systematic exclusion of competing etiologies (sarcoidosis, tuberculosis, primary biliary cholangitis, drug-induced hepatitis) is mandatory before attributing granulomas to AAV. Liver biopsy remains pivotal in confirming the diagnosis. Immunosuppression is the therapeutic cornerstone, with generally favourable outcomes.
2026-08-05 | Anterior ischaemic optic neuropathy as an initial manifestation of eosinophilic granulomatosis with polyangiitis: The importance of early and appropriate immunosuppressive treatment for visual recovery.
Eosinophilic granulomatosis with polyangiitis (EGPA) is an antineutrophil cytoplasmic antibody-associated vasculitis, affecting various organs. Although ocular involvement occurred in 6.8-11.1% of patients, anterior ischaemic optic neuropathy (AION) is rare. We present the case of a 57-year-old woman with an 11-year history of asthma who developed sudden, painless visual loss in her left eye. On admission (3 days after symptom onset), visual acuity was counting fingers in the left eye and 20/20 in the right eye. Funduscopy showed left optic disc oedema. Magnetic resonance imaging revealed intravitreal protrusion of the left optic nerve head with restricted diffusion and local contrast enhancement of the left intraorbital and retrobulbar fat. Given also peripheral eosinophilia, myeloperoxidase-antineutrophil cytoplasmic antibody positivity, mononeuritis multiplex, nasal polyps, sinusitis, and pulmonary involvement, EGPA with AION was diagnosed. Intravenous methylprednisolone pulse was urgently administered, followed by mepolizumab 2 weeks later. Although eosinophilic inflammation and imaging findings improved, visual acuity remained unchanged over 1 year. A literature review identified 14 cases of EGPA-associated AION. Including our case, 11 cases with available data (14 eyes) were analysed. Overall, visual recovery was observed in 29%. Among 12 eyes with severe visual impairment before treatment, visual recovery occurred only in those treated earlier or with cyclophosphamide except for one, whereas no recovery occurred in those with delayed treatment or without cyclophosphamide. This case highlights the potential of AION as an initial manifestation of EGPA. Both earlier initiation and adequate intensity of immunosuppressive therapy, particularly including cyclophosphamide when clinically appropriate, may be important for visual recovery in EGPA-associated severe AION.
2026-08-05 | Antineutrophil cytoplasmic antibody-positive giant cell arteritis: Small-vessel vasculitis mimicking large-vessel vasculitis.
Giant cell arteritis is the most common vasculitis in those over 50 years old with a peak incidence between 70 and 80. Symptoms include a new-onset headache, scalp tenderness, jaw/tongue claudication, and visual symptoms, which can be sight-threatening. We report a case of an 82-year-old lady who presented with typical symptoms of giant cell arteritis and bilateral halo sign on an ultrasound scan. Despite initial steroid treatment she deteriorated and developed neurological symptoms including mononeuritis multiplex. Following further investigations, it was found that she was suffering from granulomatosis with polyangiitis and treatment was adjusted accordingly with additional immunomodulating treatment preventing further progression of symptoms. This case highlights how granulomatosis with polyangiitis can mimic giant cell arteritis and should be considered in refractory cases.
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Drug Discovery Landscape
4 orphan drug designations for Granulomatosis with polyangiitis, including 1 approved therapy.
4 orphan drug designations for Granulomatosis with polyangiitis, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
(2R,3S)-2-(4-cyclopentylaminophenyl)-1-(2-fluoro-6-methylbenzoyl)piperidine-3-carboxylic acid(4-methyl-3-trifluoromethylphenyl)amide | small molecules | EMA | 2014-11-19 | 2022-01-19 | Vifor Fresenius Medical Care Renal Pharma France |
gusperimus trihydrochloride | small molecules | FDA | 2011-06-29 | — | Nordic Group B.V. |
Gusperimus trihydrochloride | small molecules | EMA | 2001-03-29 | — | Nordic Group B.V. |
Etanercept | proteins | FDA | 1999-04-06 | — | Immunex Corporation |
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