Granulomatosis with polyangiitis (GPA) is an idiopathic vasculitis of medium and small arteries, characterized by necrotizing granulomatous inflammation. GPA typically affects upper and lower respiratory tract with coexisting glomerulonephritis. This disease is generally characterized by antineutrophil cytoplasm antibodies (ANCA), nevertheless, there are rare cases with negative ANCA. GPA affects people at any age, with predominance of the sixth and seventh decade of life. In 80%-95% of the patients the first symptoms of GPA are otorhinolaryngological manifestations of head and neck including nose/sinuses, ears, eyes, larynx/trachea, oral cavity, and salivary glands. Diagnosis of GPA is based on Criteria of the American College of Rheumatology. In clinical practice diagnosis, the presence of distinctive ANCA antibodies and biopsy of affected organ are crucial. GPA must be differentiated from neoplastic, infectious or inflammatory ulcerative lesions of the head and neck. The standard treatment procedure is divided into two essential phases, induction and maintenance. The induction phase is based on combination of systemic corticosteroid and immunosuppressant therapy, whereas the maintenance phase comprises corticosteroids and azathioprine/methotrexate supplementation. Surgical treatment ought to be considered for patients who are not responding to pharmacotherapy.
Adrenal Cortex Hormones ; Antibodies ; Antibodies, Antineutrophil Cytoplasmic ; Arteries ; Biopsy ; Cytoplasm ; Diagnosis ; Drug Therapy ; Ear ; Glomerulonephritis ; Head ; Humans ; Inflammation ; Mouth ; Neck ; Otolaryngology ; Respiratory System ; Rheumatology ; Salivary Glands ; Ulcer ; Vasculitis ; Wegener Granulomatosis

PURPOSE: To report a case of nasolacrimal duct obstruction occurring in a patient with Wegener granulomatosis treated successfully with endoscopic dacryocystorhinostomy. CASE SUMMARY: A 36-year-old female diagnosed with Wegener's granulomatosis 3 years prior and treated with rituximab and currently taking azathioprine 100 mg presented with a 1-year history of left epiphora and mucus in the left eye. Her left tear meniscus was higher than the right and was a hard stop with lacrimal probe when a lacrimal probing test was performed. Mucus was regurgitated during lacrimal irrigation and middle turbinate was not observed due to granuloma in the nasal cavity. Dacryocystography showed proximal nasolacrimal duct obstruction and a well-defined dacryocystocele 6 x 5 x 6 mm in size was observed on the left lacrimal fossa on facial 3D computed tomography. After synechiolysis for a granuloma in the nasal cavity, endoscopic dacryocystorhinostomy was performed and silastic sheet sutured on the nasal septum to prevent resynechia. After 2 weeks and 4 months, the silastic sheet and silicon tube were removed, respectively. The patient was asymptomatic following surgery and there was no regurgitation during lacrimal irrigation test. The ostium was patent at 5 months after surgery using the endoscopic dye test. CONCLUSIONS: Nasolacrimal duct obstruction occurring in a patient with Wegener's granulomatosis can be treated effectively with endoscopic dacryocystorhinostomy even if the nasal cavity is narrow due to granuloma.
Adult ; Azathioprine ; Dacryocystorhinostomy* ; Female ; Granuloma ; Humans ; Lacrimal Apparatus Diseases ; Mucus ; Nasal Cavity ; Nasal Septum ; Nasolacrimal Duct* ; Silicones ; Tears ; Turbinates ; Wegener Granulomatosis* ; Rituximab

Wegener's granulomatosis (WG) is highly correlated with cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA). Patients with rheumatoid arthritis (RA) rarely contract WG. Although several concurrent cases have been reported overseas, there are no known cases in Korea. Here we report a unique case of RA with atypical WG testing positive for perinuclear ANCA (p-ANCA) and negative for anti-myeloperoxidase (MPO) antibodies. The 62-yr-old female patient presented with multiple joint pain and showed typical blood test results for RA, i.e., an elevated erythrocyte sedimentation rate and C-reactive protein concentration, and positive for rheumatoid factor and anti-cyclic citrullinated peptide antibodies. RA was clear based on a total score of 10 when applying the classification criteria developed by the American College of Rheumatology/European League Against Rheumatism (2010). In an autoimmune target test, speckled and skeleton patterns were observed. In an ANCA test, p-ANCA was observed (titer, 1:2,560), and tests for anti-proteinase 3 (PR3) and anti-MPO antibodies were negative. After admission, multiple nodules were detected on a chest X-ray and a computed tomography scan. We suspected that she had rheumatic nodules or vasculitis and performed an open lung biopsy. We detected necrotic granulomatous vasculitis, classified as WG, thus leading to WG diagnosis. In conclusion, WG was diagnosed in an RA patient who was negative for c-ANCA (negative PR3) and positive for p-ANCA (negative anti-MPO), and this peculiar finding is likely to improve diagnosis in cases of RA with atypical WG.
Antibodies ; Antibodies, Antineutrophil Cytoplasmic ; Arthralgia ; Arthritis, Rheumatoid* ; Biopsy ; Blood Sedimentation ; C-Reactive Protein ; Classification ; Cytoplasm ; Diagnosis ; Female ; Hematologic Tests ; Humans ; Korea ; Lung ; Rheumatic Diseases ; Rheumatic Nodule ; Rheumatoid Factor ; Skeleton ; Thorax ; Vasculitis ; Wegener Granulomatosis*

OBJECTIVE: Granulomatosis with polyangiitis (GPA), formally known as Wegener's granulomatosis, is a systemic vasculitis with necrotizing granulomatous inflammation. As treatment directed against tumor necrosis factor (TNF)-alpha failed in GPA, we investigated whether "TNF-alpha signature" (i.e. gene expression profile of TNF-alpha activation) was present in peripheral blood mononuclear cells (PBMCs) of patients with GPA. METHODS: Gene expression profiling was performed using total RNA from PBMCs of 41 patients with GPA and 23 healthy control subjects using the Illumina microarray technique. Gene set enrichment analysis (GSEA) was performed to detect the presence of TNF-alpha signature using the curated list C2-V3.0 by the Broad Institute. False discovery rate<0.05 was considered statistically significant. RESULTS: GSEA did not show significant enrichment of any TNF-alpha associated gene sets in GPA. Expression levels of genes up-regulated by TNF-alpha did not differ between healthy control subjects, patients in remission (Birmingham Vasculitis Activity Score [BVAS]=0), and those with active disease (BVAS> or =1). In addition, an unsupervised hierarchical clustering of those genes failed to cluster the samples into healthy control subjects and GPA in remission or with active disease. B cell activation signature was enriched in GPA patients. CONCLUSION: Absence of a TNF-alpha signature in PBMCs may suggest that TNF-alpha plays a less important role in the pathogenesis of GPA than previously accepted.
Gene Expression ; Gene Expression Profiling ; Humans ; Inflammation ; RNA ; Systemic Vasculitis ; Transcriptome ; Tumor Necrosis Factor-alpha* ; Vasculitis ; Wegener Granulomatosis

No abstract available.
Wegener Granulomatosis*

Wegener's granulomatosis (WG) classically consists of necrotizing granulomatous inflammation of the upper and/or lower respiratory tract, necrotizing glomerulonephritis, and an autoimmune necrotizing systemic vasculitis affecting predominantly small vessels. We report a case of WG with central nervous system (CNS) involvement. WG is being diagnosed through pulmonary nodule biopsy. A small nodular lesion in the left posterior basal ganglia of brain being highly suspicious for granulomatosis was detected by MRI. After IV pulse cyclophosphamide and oral corticosteroid treatment for over 4 months, clinical manifestations and CNS lesions in brain MRI is improved. WG might have multiple granulomatous lesions which could be misdiagnosed due to malignancy. CNS involvement in WG is rare but careful evaluation is necessary when there are suspicious symptoms or lesions in CNS.
Basal Ganglia ; Biopsy ; Brain ; Central Nervous System ; Cyclophosphamide ; Glomerulonephritis ; Inflammation ; Lung ; Lung Neoplasms ; Neoplasm Metastasis ; Respiratory System ; Systemic Vasculitis ; Wegener Granulomatosis

Wegener's granulomatosis (WG) is defined as a granulomatous inflammation of the upper and lower respiratory tract due to a systemic vasculitis. Facial nerve palsy may occur during the course of any granulomatous or vasculitis disease. But very few cases have been reported in which facial nerve palsy is the presenting feature of WG. We recently experienced an interesting case of WG presenting as acute middle ear infection and subsequent bilateral facial palsy.
Ear, Middle ; Earache ; Facial Nerve ; Facial Paralysis ; Inflammation ; Paralysis ; Respiratory System ; Systemic Vasculitis ; Vasculitis ; Wegener Granulomatosis

Wegener's granulomatosis (WG) is a systemic vasculitis affecting small and medium-sized vessels with granulomatous formation. Though it is known for respiratory tract and kidney involvement, neurologic manifestation has been also reported. Herein we report a patient who suffered pansinusitis with multiple lower cranial nerve palsies but reached remission by immunosuppressant after the diagnosis of WG. A 54-yr-old female visited with headache, hearing difficulty, and progressive bulbar symptoms. She experienced endoscopic sinus surgeries due to refractory sinusitis. Neurologic examination revealed multiple lower cranial nerve palsies. Vasculitic markers showed no abnormality. Nasal biopsy revealed granulomatous inflammation and vasculitis involving small vessels. Given cyclophosphamide and prednisolone, her symptoms were prominently improved. WG should be considered in the patient with multiple cranial nerve palsies, especially those with paranasal sinus disease. Because WG can be lethal if delayed in treatment, prompt immunosuppressant is warranted after the diagnostic tissue biopsy.
Anti-Inflammatory Agents/therapeutic use ; Antibodies, Antineutrophil Cytoplasmic ; Antineoplastic Agents, Alkylating/therapeutic use ; Cranial Nerve Diseases/*diagnosis/drug therapy/radionuclide imaging ; Cyclophosphamide/therapeutic use ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Prednisolone/therapeutic use ; Sinusitis/surgery ; Vasculitis ; Wegener Granulomatosis/*diagnosis/drug therapy/radionuclide imaging

Wegener's granulomatosis is a very rare systemic vasculitis characterized by necrotizing granulomatosis. The detection of antineutrophil cytoplasm antibody (ANCA) is a valuable finding in diagnosing Wegener's granulomatosis because ANCA is positive in approximately 90 percent of patients with active, generalized Wegener's granulomatosis. But ANCA is not necessarily positive to make a diagnosis. A 59-year-old man was transferred to our hospital. He was diagnosed with lung abscess and treated with antibiotics at previous hospital. Initially, the ANCA was negative in immunofluorescence assay but we suspected Wegener's granulomatosis because of systemic inflammatory symptoms. Clinical symptoms deteriorated rapidly so we did bronchoscopic biopsy early. Wegener's granulomatosis was diagnosed according to pathologic finding that reported necrotizing granulomatous inflammation associated with vasculitis. Thus we treated with steroid then clinical symptoms and laboratory findings were improved.
Anti-Bacterial Agents ; Antibodies, Antineutrophil Cytoplasmic ; Biopsy ; Cytoplasm ; Fluorescent Antibody Technique ; Humans ; Inflammation ; Lung Abscess ; Systemic Vasculitis ; Vasculitis ; Wegener Granulomatosis

Wegener's granulomatosis (WG) is a systemic disease characterized by necrotizing granulomas and vasculitis involving the upper and lower respiratory tract as well as the kidneys. Limited form of WG usually involves the head and neck, lacks renal involvement, and may not progress to generalized disease. We report the case of limited form of WG who presented not systemic symptom but several times relapsed multiple ulcerating lesions on the face, uveitis and keratoconjunctivitis. A 23 year-old female initially presented with ulcerative skin lesions on the left cheek and nose. The skin lesion had commenced as an ulcerative and nodulopapular lesion on her right cheek initially, 8 months ago. Subsequently, there was progression of the disease to her left cheek and nose. The patient was treated with oral prednisolone and oral cyclophosphamide. Two weeks later, skin lesion had started to heal, oral prednisolone tapered to 15 mg. Eight weeks later, all of skin lesions were healed well. With silicone gel sheets and Laser therapies, we gained excellent cosmetic results. In the aesthetic aspect, early recognition of rare variants of limited form of WG, facial chronic ulcerative wounds that are nonresponsive to conservative treatment, is very important as appropriate therapy can prevent facial mutilation.
Cheek ; Cosmetics ; Cyclophosphamide ; Female ; Granuloma ; Head ; Humans ; Keratoconjunctivitis ; Kidney ; Laser Therapy ; Neck ; Nose ; Prednisolone ; Respiratory System ; Silicone Gels ; Skin ; Ulcer ; Uveitis ; Vasculitis ; Wegener Granulomatosis