Granulomatosis with polyangiitis or its mimic? A case report.

Differentiation between granulomatosis with polyangiitis (GPA) limited to the upper airways and cocaine-induced midline destructive lesion (CIMDL) may be particularly difficult because of their common histopathologic features and antineutrophil cytoplasmic antibody (ANCA) profiles. We herein present a case involving a young woman with an initial diagnosis of GPA based on upper and lower airway manifestations and constitutional symptoms, histopathologic evidence of granulomas, a positive cytoplasmic ANCA indirect immunofluorescent test result, and proteinase 3 positivity by enzyme-linked immunosorbent assay (ELISA). CIMDL was confirmed based on the appearance of a hard palate perforation, positivity for methylecgonine on urine toxicology, a positive perinuclear ANCA indirect immunofluorescent test result, and subsequent human neutrophil elastase (HNE) ANCA positivity by ELISA. Finally, based on the coexistence of CIMDL, constitutional symptoms, and lower airway manifestations, the diagnosis was modified to cocaine-induced GPA mimic. Urine toxicology for cocaine and HNE ELISA are indicated in young patients with GPA who develop limited airway disease to check for the presence of CIMDL and cocaine-/levamisole-induced ANCA-associated vasculitis. Continued abstinence from cocaine is the first-choice therapy for both CIMDL and cocaine-induced GPA mimic.

Significance of clinical-immunological patterns and diagnostic yield of biopsies in microscopic polyangiitis and granulomatosis with polyangiitis.

BACKGROUND: Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are the two major antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). OBJECTIVES: To characterize a homogenous AAV cohort and to assess the impact of clinicopathological profiles and ANCA serotypes on clinical presentation and prognosis. Clinical differences in GPA patients according to ANCA serotype and the diagnostic yield for vasculitis of biopsies in different territories were also investigated. RESULTS: This retrospective study (2000-2021) included 152 patients with AAV (77 MPA/75 GPA). MPA patients (96.1% myeloperoxidase [MPO]-ANCA and 2.6% proteinase 3 [PR3]-ANCA) presented more often with weight loss, myalgia, renal involvement, interstitial lung disease (ILD), cutaneous purpura, and peripheral nerve involvement. Patients with GPA (44% PR3-ANCA, 33.3% MPO, and 22.7% negative/atypical ANCA) presented more commonly with ear, nose, and throat and eye/orbital manifestations, more relapses, and higher survival than patients with MPA. GPA was the only independent risk factor for relapse. Poor survival predictors were older age at diagnosis and peripheral nerve involvement. ANCA serotypes differentiated clinical features in a lesser degree than clinical phenotypes. A mean of 1.5 biopsies were performed in 93.4% of patients in different territories. Overall, vasculitis was identified in 80.3% (97.3% in MPA and 61.8% in GPA) of patients. CONCLUSIONS: The identification of GPA presentations associated with MPO-ANCA and awareness of risk factors for relapse and mortality are important to guide proper therapeutic strategies in AAV patients. Biopsies of different affected territories should be pursued in difficult-to-diagnose patients based on their significant diagnostic yield.

Ocular manifestations of granulomatosis with polyangiitis: report from a tertiary eye care center.

PURPOSE: To report demographic characteristics and ophthalmological manifestations of patients with granulomatosis with polyangiitis (GPA) in a tertiary eye care center in Turkey. METHODS: Medical records of patients with GPA-related ocular manifestations evaluated between 2013 and 2023 were included. Demographic and clinical characteristics of the patients including nature of systemic involvement, ophthalmologic symptoms and signs, laboratory investigations and treatment modality were reviewed. RESULTS: Twelve eyes of 10 patients (5 female/5 male) were included. The mean age was 57.2 ± 12.2 (35-71) years. Five (50%) patients were already diagnosed with GPA. Ocular involvement was the first manifestation of GPA in 3 patients. The remaining 2 patients had simultaneous systemic and ocular symptoms at presentation. Conjunctival hyperemia (9 eyes) and pain (7 eyes) were the most frequent presenting symptoms followed by blurred vision (3 eyes). The frequencies of ocular manifestations were as follows:episcleritis (3 eyes), isolated peripheral ulcerative keratitis (PUK) (3 eyes), scleritis (3 eyes), simultaneous PUK and scleritis (2 eyes) and periorbital mass (1 eye). CONCLUSION: Ophthalmological manifestations can be the initial findings in GPA. Since GPA can affect different structures of the eye, it sometimes might be challenging for ophthalmologists. Therefore, it is crucial for ophthalmologists to be well-informed about GPA-related ocular findings and to have a high index of suspicion for GPA. Although PUK associated with scleritis is highly suggestive for GPA, isolated cases of PUK or scleritis can be seen in GPA. Therefore, it is important to adopt a multidisciplinary approach, consider GPA in differential diagnosis, and benefit from accurate diagnostic tests.

Granulomatosis With Polyangiitis of Spinal Dura Presenting With "Bottle Brush Sign" on 18 F-FDG PET/CT.

ABSTRACT: A 72-year-old man with fever and weakness in both lower limbs underwent thoracolumbar MRI and 18 F-FDG PET/CT. The PET/CT scan revealed diffused FDG uptake along the spinal dura mater from T7 to S2 level like a "bottle brush." Pathologic examination after biopsy of spinal canal lesions manifested granulomatous inflammation. The blood test showed cytoplasmic antineutrophil cytoplasmic antibody (ANCA) and myeloperoxidase-ANCAs were positive, whereas the perinuclear ANCA was negative. Eventually, he was diagnosed with granulomatosis with polyangiitis.

Audiological Manifestations in Patients with Granulomatosis with Polyangiitis.

Background and Objectives: Granulomatosis with Polyangiitis (GPA) is a rare, autoimmune, multisystemic disease characterized by vasculitis and necrotizing granuloma that commonly affects the upper and lower respiratory tract and kidneys. Audiovestibular dysfunction in GPA diseases may have different clinical presentations. The aim of the present study was to evaluate hearing function in patients with GPA and to compare the results with a healthy control group. Materials and Methods: A total of 34 individuals participated in the study. The GPA group consisted of 14 participants, and the control group was composed of 20 healthy participants with no signs or symptoms of ear disease. The ages ranged from 18 to 65 years old, with a mean age of 43.8 years. The participants underwent a complete audiological evaluation using otoscopy, impedance audiometry, pure tone audiometry, speech audiometry-evaluation of speech thresholds, and speech recognition in quiet. Both ears were tested. All of the participants of the study were native Lithuanian speakers. Data were statistically analyzed using the Statistical Analysis System software SAS® Studio 3.8. A p value < 0.05 was regarded as statistically significant. Results: 92.85% of patients from the GPA group reported hearing-related symptoms: hearing loss, tinnitus, and fullness in the ears. The arithmetic means of all hearing thresholds at frequencies from 125 Hz to 8000 Hz were significantly higher in the GPA group. The results revealed statistically significant differences between the two groups in the Speech Detection Threshold, Speech Recognition Threshold, Speech Discomfort level, and Word Recognition Scores. Conclusions: The frequency of hearing loss, the average hearing thresholds, and speech thresholds were higher in GPA patients than in healthy individuals. The most common type of hearing loss was sensorineural. Audiological assessments should be considered during the routine evaluation of patients with GPA disease to prevent hearing-related disabilities.

Granulomatosis with polyangiitis presenting headache: A case report and review of literature.

RATIONALE: Central nervous system involvement is a rare manifestation of active-phaselocalized Granulomatosis with polyangiitis (GPA). In hypertrophic dura meningitis, GPA with headache is typical. In this case, cerebral magnetic resonance (MR) enhancement revealed no meningeal thickening, to our knowledge, this manifestation had not been found previously. PATIENT CONCERNS: The patient presented to the Rheumatology and Immunology Clinic with severe headache and hearing loss, and central nervous system granulomatosis with polyangiitis was confirmed after a series of examinations. The patient had no significant effect after treatment with cyclophosphamide (CTX), but after the use of rituximab, the headache and hearing loss were significantly improved, and laboratory indicators returned to normal levels. DIAGNOSIS: We comprehensively screened for craniocerebral infection and malignant tumors, diagnosed central nervous system granulomatosis with polyangiitis. INTERVENTIONS: We gave sequential treatment of rituximab. OUTCOMES: All indicators are mostly back to normal when the patient was monitored at the outpatient clinic. LESSONS: GPA and severe headache are more prevalent in hypertrophic dura meningitis, but the patient early headache could not be explained by hypertrophic dura meningitis or localized granulomatous lesions that invaded the central nervous system. Patients with severe headaches likely have vascular inflammation and local bone destruction at the base of the skull.

Ileal perforation involvement in Wegener granulomatosis comorbid with COVID-19 infection: A case report and review of the literature.

RATIONALE: Granulomatosis with polyangiitis (GPA) is a systematic autoimmune disease. The typical clinical involvement of GPA entails the upper and lower respiratory tracts, and the kidneys. Gastrointestinal (GI) involvement is uncommon and unless detected and treated promptly, may lead to life-threatening complications such as perforation. We aim to review all available publications since the first description in 1982 dealing with GI perforation in patients with Wegener granulomatosis and draw attention to this serious situation. PATIENT CONCERNS: We present a 54-year-old man diagnosed with GPA who presented initially with nasal symptoms and suffered ileal perforation following Corona Virus Disease 2019 infection. We also review previously reported patients with Wegener granulomatosis who had GI perforation to investigate the perforation site and period, pathology, diagnosis, and treatment methods. DIAGNOSES AND INTERVENTIONS: The case of a GPA-diagnosed patient who presented initially with nasal symptoms and suffered ileal perforation following Corona Virus Disease 2019 infection. We recommended a renal puncture biopsy, steroids, and immunosuppressants to improve the patient condition. The patient and his family refused these treatment recommendations. OUTCOMES: Our patient exhibited continued progressive vascular inflammatory changes and eventual irreversible systemic damage. These sequelae were attributed to the patient declining prednisolone and immunosuppressant therapy. LESSONS: GI perforation is rare in GPA but severe complication. Consequently, we recommend that early diagnosis and treatment with steroid hormones and immunosuppressants for GPA patients with GI perforation.

Clinical characteristics of hypertrophic cranial pachymeningitis in granulomatosis with polyangiitis: a retrospective single-center study in China.

BACKGROUND: Hypertrophic cranial pachymeningitis (HCP) is uncommon but a poorly understood complication of granulomatosis with polyangiitis (GPA). OBJECTIVES: We conducted this retrospective study to elucidate the clinical characteristics and factors independently associated with granulomatosis with polyangiitis (GPA) complicated by hypertrophic cranial pachymeningitis (HCP) in China. METHODS: We collected the medical records of 78 patients diagnosed with GPA who were admitted to the inpatient department of Peking Union Medical College Hospital between January 2003 and September 2021. Clinical features, laboratory and radiological findings, and Birmingham Vasculitis Activity Scores (excluding meningitis score) were recorded. A binary logistic regression analysis was performed to analyze factors independently associated with GPA-related HCP. RESULTS: Headache (100%) and cranial nerve palsy (61.5%) were common manifestations of HCP. Compared to 52 GPA patients without HCP, 26 patients with HCP required more time from initial symptoms to diagnosis, with a lower ratio of pulmonary and renal involvement, a higher ratio of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) positivity, conductive or sensorineural hearing loss, mastoiditis, and decreased vision or sudden visual loss. Binary logistic regression analysis indicated that proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) negativity (OR 10.698, p = 0.001), conductive or sensorineural hearing loss (OR 10.855, p = 0.005), and decreased vision or sudden visual loss (OR 8.647, p = 0.015) were significantly associated with GPA-related HCP. Of the 26 patients, 18 received methylprednisolone pulse treatment, and 18 received intrathecal injections of dexamethasone and methotrexate. CONCLUSIONS: HCP was a severe manifestation of GPA in our study. Independent factors associated with the occurrence of HCP in patients with GPA included PR3-ANCA negativity, conductive or sensorineural hearing loss, and decreased vision or sudden visual loss. Furthermore, GPA-related HCP was associated with higher disease activity, requiring more intensive treatments.

Pleural tuberculosis and endocarditis as complications of multifactorial origin in granulomatosis with polyangiitis: Clinical case report.

We present the case of a 36-year-old woman with a history of granulomatosis with polyangiitis; chronic kidney disease; systemic arterial hypertension. Debut with dyspnea, weakness, and hemoptysis, she was suspected in atypical pneumonia, discarded, persisting with tachypnea, tachycardia, chest pain. The protocol for pulmonary tuberculosis was started with negative sputum samples, positive blood culture for S. haemolyticus, chest tomography with left pneumothorax and ipsilateral pleural effusion, exudate-type pleural fluid was obtained, acid-fast staining, negative PCR for M. tuberculosis; A follow-up echocardiogram was performed due to a new murmur, reporting valvular vegetation, concluding a diagnosis of pleural tuberculosis and endocarditis as complications of multifactorial origin associated with immunosuppression in granulomatosis with polyangiitis.

Intrathecal injection of methotrexate and dexamethasone for vasculitis granuloma of the fourth ventricle: a case report and literature review.

Granulomatosis with polyangiitis (GPA) is a pauci-immune small vessel vasculitis characterised by neutrophil-mediated vasculitis and granuloma. The presence of intracranial parenchymal space-occupying lesions is rarely seen in GPA patients. In this manuscript, we report a case of GPA with granuloma of the fourth ventricle accompanied by obstructive hydrocephalus. Treatment with glucocorticoids (GCs) and multiple immunosuppressants cyclophosphamide (CYC), mycophenolate mofetil (MMF), and rituximab (RTX) showed poor efficacy in this case. After removal of the granuloma by craniotomy, GPA relapsed within 3 months. Under the premise of GC and MMF treatment combined with intrathecal injection of dexamethasone (DXM) and methotrexate (MTX), the intracranial granuloma gradually shrank, and the patient's general condition was alleviated, showing that this is an effective treatment method. Key Points • To date, there are few reports of granulomatous vasculitis combined with granuloma of the fourth ventricle, and our case is the second. • In this case, multiple immunosuppressants and rituximab were ineffective treatments, and the intracranial granuloma was effectively controlled by intrathecal injection of dexamethasone (DXM) and methotrexate (MTX). • Based on this report, it can be suggested that intrathecal injection is effective in treating patients with GPA and central nervous system involvement, but large-scale sample studies are needed.

Data quality and patient characteristics in European ANCA-associated vasculitis registries: data retrieval by federated querying.

OBJECTIVES: This study aims to describe the data structure and harmonisation process, explore data quality and define characteristics, treatment, and outcomes of patients across six federated antineutrophil cytoplasmic antibody-associated vasculitis (AAV) registries. METHODS: Through creation of the vasculitis-specific Findable, Accessible, Interoperable, Reusable, VASCulitis ontology, we harmonised the registries and enabled semantic interoperability. We assessed data quality across the domains of uniqueness, consistency, completeness and correctness. Aggregated data were retrieved using the semantic query language SPARQL Protocol and Resource Description Framework Query Language (SPARQL) and outcome rates were assessed through random effects meta-analysis. RESULTS: A total of 5282 cases of AAV were identified. Uniqueness and data-type consistency were 100% across all assessed variables. Completeness and correctness varied from 49%-100% to 60%-100%, respectively. There were 2754 (52.1%) cases classified as granulomatosis with polyangiitis (GPA), 1580 (29.9%) as microscopic polyangiitis and 937 (17.7%) as eosinophilic GPA. The pattern of organ involvement included: lung in 3281 (65.1%), ear-nose-throat in 2860 (56.7%) and kidney in 2534 (50.2%). Intravenous cyclophosphamide was used as remission induction therapy in 982 (50.7%), rituximab in 505 (17.7%) and pulsed intravenous glucocorticoid use was highly variable (11%-91%). Overall mortality and incidence rates of end-stage kidney disease were 28.8 (95% CI 19.7 to 42.2) and 24.8 (95% CI 19.7 to 31.1) per 1000 patient-years, respectively. CONCLUSIONS: In the largest reported AAV cohort-study, we federated patient registries using semantic web technologies and highlighted concerns about data quality. The comparison of patient characteristics, treatment and outcomes was hampered by heterogeneous recruitment settings.

Coexistence of IgG4-related disease and ANCA-associated vasculitis: case report and review of the literature.

IgG4-related disease (IgG4-RD) is a fibroinflammatory condition that is characterized by storiform fibrosis, infiltration of IgG4-positive lymphocytes, obliterative phlebitis, and high IgG4 levels. Since IgG4-RD affects a wide variety of organs, a differential diagnosis must include multiple conditions. IgG4-RD is also believed to coexist with certain diseases. In recent years, case reports and case series describing the co-occurrence of IgG4-RD and ANCA-associated vasculitis (AAV) have been published. We intended to evaluate patients with IgG4-RD and AAV overlap in the literature using a case similar to one that was diagnosed and monitored in our department. We searched the databases of Web of Science, Scopus, and Google Scholar as well as PubMed with the keywords ANCA, IgG4, IgG4-RD, granulomatosis with polyangiitis, Wegener's granulomatosis, microscopic polyangiitis, Eosinophilic granulomatosis with polyangiitis, and Churg-Strauss syndrome. Cases and Case series addressing the coexistence of IgG4-RD and AAV have been selected. Comprehensive diagnostic criteria are used to diagnose IgG4-RD. The Chapel Hill Consensus Conference nomenclature criteria were used for the inclusion of AAV. Out of a total of 910 publications, 20 articles, including 65 cases, were found to be eligible. Forty-seven cases with IgG4-RD were evaluated as definitive (71.2%), 10 cases as probable (15.1%), and 9 cases as possible IgG4-RD (13.6%). 26 patients were diagnosed with GPA, 1 patient with localized GPA, 23 patients with MPA, and 4 patients with EGPA. The aorta, lacrimal tissue, pancreas, and retroperitoneum are the sites of IgG4-RD rather than AAV. AAV and IgG4-RD might coexist in the same patient. IgG4-RD is mainly associated with GPA.

Intracranial granuloma in a patient with granulomatosis with polyangiitis under rituximab maintenance: A case report.

BACKGROUND: Rituximab (RTX) is being used for both induction and maintenance of anti-neutrophil cytoplasmic antibody (ANCA) -associated vasculitis. However, the efficacy of RTX for the granulomatous findings of granulomatosis with polyangiitis (GPA) has not been demonstrated as clearly as its vasculitic manifestations. CASE SUMMARY: A 46-year-old man was diagnosed in 2019 with GPA with constitutional symptoms, bilateral mastoiditis, prostatic necrosis, nodules in both lungs, pauci-immune necrotizing glomerulonephritis and high level of PR3-ANCA. He reached clinical remission after induction with high-dose corticosteroids and intravenous cyclophosphamide pulses at the 3rd month. Two months following the second cycle of RTX as maintenance, he developed multiple cranial mass lesions, and excisional biopsy revealed necrotizing vasculitis with granuloma formation. Remission was achieved with long-term high-dose corticosteroid therapy after surgical excision. CONCLUSION: We observed a relapse of GPA with intracranial granulomatous lesions in a patient under RTX maintenance. Limited efficacy of RTX should be considered for mainly granulomatous manifestations in patients with GPA.

Uncommon presentation of granulomatosis with polyangiitis: Prostate involvement.

Granulomatosis with polyangiitis (GPA) is an autoimmune granulomatous disease of unknown etiology; frequently associated with anti-proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA). Although any organ can be involved, prostatic involvement in GPA is very rare. We present a male patient with GPA, 26 years old, with pulmonary manifestations and prostatic involvement who underwent exhaustive evaluation. The patient's laboratory tests and imaging scans showed evidence of lesions in multiple areas, including the prostate. Histopathological testing confirmed that the lesions were consistent with granulomatosis with polyangiitis. The patient was treated with oral steroids and rituximab and showed significant improvement. He was later maintained on azathioprine without any relapse.