Symptoms of GPA may appear abruptly, but an insidious onset is documented as well, and the full symptomatology usually takes years to develop. Several organs may be affected, but the most common symptoms are related to the upper and lower respiratory tract [11]. Sinusitis, often chronic in nature, epistaxis, nasal chondritis that is often accompanied by pain and swelling, and may lead to septal perforation. Secondary infections by Staphylococcus aureus are reported, and in severe inflammatory reactions, subglottic stenosis can occur, leading to symptoms such as hoarseness, dyspnea, stridor, wheezing and severe pain. Symptoms of lower respiratory tract occur as a result of inflammation of the bronchial tree, and include chest pain, dyspnea, development of pneumonia, and productive cough. In severe cases, potentially life-threatening alveolar hemorrhage may occur.

The kidneys are most commonly affected in addition to the respiratory tract, with the development of glomerulonephritis that may be rapidly progressive, and symptoms include hematuria, hypertension and edema.

Apart from the respiratory tract and the kidneys, other organs may be affected:

• Skin - Development of skin lesions, including subcutaneous papules, nodules, or livedo reticularis is observed. In more severe cases, pyoderma gangrenosum may occur.
• Ears - Hearing loss is not uncommon in patients with GPA, and additional findings include otitis, vertigo, and chondritis.
• Eyes - Inflammation and obstruction of the nasolacrimal duct, conjunctivitis, uveitis, retinal vasculitis, but also compression of the optic nerve may occur as a result of inflammatory changes in this disease, which may lead to blindness.
• Heart and the musculoskeletal system - Myalgias, arthralgias, and in rare cases, coronary heart disease can be encountered.
• Nervous system - Vasculitic changes in this disease can lead to ischemic neuropathy, primarily of the peripheral nerves, both changes in both peripheral and central nervous system have been documented [12].

• Axillary Lymphadenopathy

  The axillary lymphadenopathy worsened, and the lymph nodes further increased in size (Fig. 1B). [journals.lww.com]

• Fever

  Seven months later, he was hospitalized with symptoms of cough, high-grade fever, and loss of weight. [ncbi.nlm.nih.gov]

  […] is characterized chiefly by inflammation of small blood vessels and granuloma formation especially in the respiratory tract and kidneys and typically has an onset during the ages of 40 to 65 Note: Symptoms of Wegener's granulomatosis include fatigue, fever [merriam-webster.com]

  General signs (fever, arthralgia, myalgia, weight loss) are common. [orpha.net]

• Weight Loss

  loss, runny nose, nosebleed, sinus pain, cough, shortness of breath, and skin sores. [merriam-webster.com]

  General signs (fever, arthralgia, myalgia, weight loss) are common. [orpha.net]

  A previously healthy 21-year-old man presented with an 8-month history of weight loss, lethargy and dysuria unresponsive to empiric antibiotics and paraurethral drainage of a prostatic abscess. [ncbi.nlm.nih.gov]

• Fatigue

  […] cause that is characterized chiefly by inflammation of small blood vessels and granuloma formation especially in the respiratory tract and kidneys and typically has an onset during the ages of 40 to 65 Note: Symptoms of Wegener's granulomatosis include fatigue [merriam-webster.com]

  We present an interesting case of a 14-year-old female with eight-weeks of bilateral otalgia, unilateral facial nerve palsy, decreased appetite, and fatigue refractory to steroid, anti-viral, and antibiotic treatment ultimately diagnosed with GPA. [ncbi.nlm.nih.gov]

  Symptoms of granulomatosis with polyangiitis include: fatigue, weight loss, fevers, shortness of breath, bloody sputum, joint pains, and sinus inflammation. [rxlist.com]

  People with GPA may have: a constant runny nose ear infections sinusitis nosebleeds a cough joint pain shortness of breath skin sores fatigue (tiredness) loss of appetite fever Coughing up blood or blood in the urine also can be signs of GPA. [kidshealth.org]

• Anemia

  Based on emerging anemia and bilateral diffuse lung consolidation on computed tomography, we judged that diffuse alveolar hemorrhage (DAH) was complicated by GPA. The patient's DAH improved following additional mPSL pulse and IVCY. [ncbi.nlm.nih.gov]

  […] hemoglobinuria hemosiderinuria severe aplastic anemia Marchiafava-Micheli syndrome myelodysplastic syndrome acute leukemia Budd-Chiari syndrome mesenteric or portal vein thrombosis 증상 광범위 정맥 혈전증, 두통, 백혈구 및 혈소판 감소, 복통, 수면시 혈색소뇨증, 용혈빈혈, 허리통증, 헤모시데린뇨 관련 [raredisease.snuh.org]

  Here, we report a 59-year-old woman, with a medical history of GP, chronic anemia, and rapidly progressive glomerulonephritis, who presented with weakness, fatigue, dysuria, cough, and fever with chills for 2 weeks. [bloodjournal.org]

  A low red blood cell count is a sign of anemia, which is common in people with GPA whose kidneys are affected. Urine or blood creatinine. These tests measure levels of the waste product creatinine in your urine or blood. [healthline.com]

  References:[3][6][7] Diagnostics Laboratory analysis Blood ↑ Creatinine and ↑ BUN ↑↑ ESR and ↑ CRP Evidence of PR3-ANCA/c-ANCA (anti-proteinase 3): highly sensitive and positive in ∼ 90% of patients Normocytic normochromic anemia (in ∼ 50% of patients [amboss.com]

• Rapidly Progressive Glomerulonephritis

  Relapse occurred very early, despite immunosuppressive treatment, with a rare involvement of genital system (epididymitis) and rapidly progressive glomerulonephritis difficult to treat. [ncbi.nlm.nih.gov]

  Cochrane Database of Systematic Reviews Background Renal vasculitis presents as rapidly progressive glomerulonephritis which comprises of a group of conditions characterised by acute kidney injury (AKI), haematuria and proteinuria. [doi.org]

  progressive glomerulonephritis has not been excluded) or alveolar hemorrhage. [merckmanuals.com]

  Here, we report a 59-year-old woman, with a medical history of GP, chronic anemia, and rapidly progressive glomerulonephritis, who presented with weakness, fatigue, dysuria, cough, and fever with chills for 2 weeks. [bloodjournal.org]

• Cough

  […] vessels and granuloma formation especially in the respiratory tract and kidneys and typically has an onset during the ages of 40 to 65 Note: Symptoms of Wegener's granulomatosis include fatigue, fever, weight loss, runny nose, nosebleed, sinus pain, cough [merriam-webster.com]

  You cough up blood. You have blood in your urine. You have other symptoms of this disorder. There is no known prevention. Formerly: Wegener's granulomatosis Falk RJ, Gross WL, Guillevin L, et al. [nlm.nih.gov]

  We report this case that presented with a productive cough, followed by arthralgia, DAH, and GIH. [ncbi.nlm.nih.gov]

  People may feel short of breath and cough, sometimes cough up blood. Difficulty breathing may result from bleeding in the lungs, which requires immediate medical attention. Joints: Joints and muscles often ache. Arthritis may develop. [msdmanuals.com]

• Saddle Nose

  Saddle nose reconstruction in GPA patients with minimal or no local disease is a safe procedure despite an increased rate of revision surgery. [ncbi.nlm.nih.gov]

  Ear, nose and throat symptoms are present in 50-95% (persistent nasal obstruction, destructive sinusitis, crusting and/or hemorrhagic rhinitis, nasal septum deformity, saddle nose deformity, and otitis media), bronchopulmonary symptoms in 60-80% (nodules [orpha.net]

  nose deformity) are the most common chief complaints! [amboss.com]

• Nasal Discharge

  A 77-year-old man visited our hospital with chief complaints of difficulty in hearing, nasal discharge and fever. [ncbi.nlm.nih.gov]

  Patients may present with constitutional symptoms, sinusitis associated with bloody nasal discharge, pulmonary symptomatology, and arthritis. [aao.org]

  discharge, oral/nasal ulcers, sinus pain haemoptysis pleuritic chest pain haematuria stridor (subglottic stenosis) myalgias arthalgia conjunctivitis corneal ulceration skin lesions at high risk of DVT EXAMINATION pleural effusions pulmonary infiltrates [lifeinthefastlane.com]

  Manifestations can affect various organ systems and may include upper and lower respiratory tract symptoms (eg, recurrent nasal discharge or epistaxis, cough), followed by hypertension and edema. [merckmanuals.com]

• Hemoptysis

  Soon after the initiation of intravenous methylprednisolone pulse therapy (mPSL pulse) and intravenous cyclophosphamide pulse therapy (IVCY), the patient experienced cough and hemoptysis. [ncbi.nlm.nih.gov]

  50%) Joints:migratory polyarthropathy (56%) Skin:inflammatory skin lesions (44%) Eyes and ears:proptosis and otitis media (29%) Heart and pericardium: myocardial infarction (28%) CNS: neuritis (22%) Symptoms Rhinorrhea Sinusitis Epistaxis Cough with hemoptysis [learningradiology.com]

  Cough and hemoptysis, proteinuria and hematuria as well as systemic symptoms such as anorexia, malaise and fever are also common 9. [radiopaedia.org]

  […] purulent discharge, sometimes containing blood Oral ulcers Chronic otitis Gingival hyperplasia (strawberry gingivitis) Lower respiratory tract (∼ 95% of cases): potentially life-threatening Treatment-resistant, pneumonia-like symptoms with cough, dyspnea, hemoptysis [amboss.com]

• Dyspnea

  CASE PRESENTATION: We report a case of eosinophilic granulomatosis with polyangiitis in a 50-year-old Caucasian woman who presented with chest pain, dyspnea at rest, fever, and periorbital swelling. [ncbi.nlm.nih.gov]

  Case Report A 29-year-old female patient presented to our department with symptoms of cough with expectoration, fever, dyspnea and occasional chest discomfort. [jacpjournal.org]

  After obtaining a biopsy from his tracheal lesions, dyspnea and hoarseness developed and progressed. In his second bronchoscopy, subglottic mixed type tracheal stenosis was detected and a stent was applied to the tracheal stenosis of the patient. [go.gale.com]

  Symptoms of lower respiratory tract occur as a result of inflammation of the bronchial tree, and include chest pain, dyspnea, development of pneumonia, and productive cough. [symptoma.com]

• Loss of Appetite

  Symptoms include nosebleeds, sinus pain, ear infections, a constantly runny nose, achy joints, skin sores, fever, weakness and loss of appetite. Treatment includes corticosteroids and immunosuppressive drugs, plus supplements such as folic acid. More [sharecare.com]

  People with GPA may have: a constant runny nose ear infections sinusitis nosebleeds a cough joint pain shortness of breath skin sores fatigue (tiredness) loss of appetite fever Coughing up blood or blood in the urine also can be signs of GPA. [kidshealth.org]

  Other common symptoms may include: Chronic ear infections Pain, and sores around the opening of the nose Cough with or without blood in the sputum Chest pain and shortness of breath as the disease progresses Loss of appetite and weight loss Skin changes [nlm.nih.gov]

  General signs of the disease may include: Loss of appetite Weight loss Fever Fatigue Most patients first notice symptoms in the respiratory tract. [my.clevelandclinic.org]

• Hypertension

  Risks were also increased for hypertension (HR = 2.45, 95% CI: 1.84, 3.26), type 2 diabetes (HR = 2.13, 95% CI: 1.36, 3.32), dyslipidaemia (HR = 1.98, 95% CI: 1.29, 3.04) and depression (HR = 1.77, 95% CI: 1.10, 2.86) among GPA patients during the first [ncbi.nlm.nih.gov]

  Manifestations can affect various organ systems and may include upper and lower respiratory tract symptoms (eg, recurrent nasal discharge or epistaxis, cough), followed by hypertension and edema. [merckmanuals.com]

  Manifestations can affect various organ systems and often include upper and lower respiratory tract symptoms (eg, recurrent nasal discharge or epistaxis, cough), followed by hypertension and edema (due to kidney involvement). [msdmanuals.com]

• Chest Pain

  CASE PRESENTATION: We report a case of eosinophilic granulomatosis with polyangiitis in a 50-year-old Caucasian woman who presented with chest pain, dyspnea at rest, fever, and periorbital swelling. [ncbi.nlm.nih.gov]

  Other common symptoms may include: Chronic ear infections Pain, and sores around the opening of the nose Cough with or without blood in the sputum Chest pain and shortness of breath as the disease progresses Loss of appetite and weight loss Skin changes [nlm.nih.gov]

  […] haemoptysis pleuritic chest pain haematuria stridor (subglottic stenosis) myalgias arthalgia conjunctivitis corneal ulceration skin lesions at high risk of DVT EXAMINATION pleural effusions pulmonary infiltrates skin vasculitis lesions INVESTIGATIONS [lifeinthefastlane.com]

• Tachycardia

  The event was associated with multiple episodes of sustained ventricular tachycardia without any structural heart changes or electrolyte disturbances. [ncbi.nlm.nih.gov]

  Upon presentation to the emergency department, she developed a wide complex tachycardia consistent with monomorphic ventricular tachycardia (see Figure 1). [hindawi.com]

• Otalgia

  We present an interesting case of a 14-year-old female with eight-weeks of bilateral otalgia, unilateral facial nerve palsy, decreased appetite, and fatigue refractory to steroid, anti-viral, and antibiotic treatment ultimately diagnosed with GPA. [ncbi.nlm.nih.gov]

  Patient: We present the case of a 57-year-old white male patient who was admitted to our ENT Hospital with a six weeks' history of otalgia and incomplete ipsilateral facial palsy since the day before admission. [thieme-connect.com]

  Associated conditions rapidly progressive glomerulonephritis Prognosis glucocorticoids can lead to remission at 6 months in > 90% of patients Presentation Symptom/physical exam upper respiratory symptoms sinusitis (most common) recurrent otitis media otalgia [medbullets.com]

  Otitis, otalgia, and both sensorineural and conductive hearing loss have all been reported in GPA. [clinicaladvisor.com]

  CASE 2 A 27 year old woman had had a previous normal pregnancy three years previously when she complained, in April 1993, of a one month history of nasal obstruction, otalgias, arthralgias, and haemoptysis. [ard.bmj.com]

• Hearing Impairment

  We present a case study of severe hearing impairment in an attempt to raise awareness of ear involvement as an early feature of this unusual condition. 2016 BMJ Publishing Group Ltd. [ncbi.nlm.nih.gov]

• Diplopia

  A 54-year-old gentleman noticed binocular vertical diplopia 4 months prior to presentation. The patient felt his symptoms were progressively worsening. [webeye.ophth.uiowa.edu]

  A 77-year-old Japanese woman presented to an ophthalmologist with an erythematous swollen upper eyelid and diplopia which was initially diagnosed to be idiopathic dacryoadenitis on the basis of a histological evaluation of an orbital mass that was in [ncbi.nlm.nih.gov]

  Ophthalmological examination showed dislocation of the left eyeball, diplopia, myopia and secondary glaucoma. Hertel exophtalmometry was used to examine the ocular protrusion. [austinpublishinggroup.com]

• Eye Pain

  Five days later, she presented to the eye clinic with eye pain, redness and blurred vision. She was diagnosed with iritis, conjunctivitis and keratitis. [ncbi.nlm.nih.gov]

  Other common symptoms include: Lungs - breathlessness, wheeze, dry cough or coughing up blood Skin - rashes, ulcers, and necrosis (death of tissue) Eyes - red (blood shot) eyes, painful, dry or gritty eyes, visual loss or other changes in vision Nerves [vasculitis.org.uk]

  The most common problems are: Proptosis (bulging of the eye) Pain (which may be very severe) Loss of vision. Skin disease The skin may be affected in 40–50% of patients with granulomatosis with polyangiitis. [dermnetnz.org]

  pain burning sensation in the eyes eye redness vision problems fever weakness, often due to anemia unintended weight loss blood in the urine It can lead to a rapidly progressive glomerulonephritis, a syndrome of the kidney that, if left untreated, rapidly [medicalnewstoday.com]

  […] symptoms, such as: Eye pain Redness A burning sensation Weakened vision or double vision (this is rare) Skin symptoms, including: Red or purple patches Small blisters Ulcers Small nodules Swollen joints (due to arthritis) Swollen limbs (due to blood [drugs.com]

• Arthritis

  Arthritis Rheum. 2011 Feb 17. [Medline]. Heijl C, Harper L, Flossmann O, et al. [emedicine.medscape.com]

  Semin Arthritis Rheum. 2006 ; 35(5) : 284 –292. [aao.org]

  Arthritis: Pain or swelling (60%), often initially diagnosed as rheumatoid arthritis Skin: subcutaneous nodules (granulomas) on the elbow, purpura, various others (see cutaneous vasculitis) Nervous system: occasionally sensory neuropathy (10%) and rarely [en.wikipedia.org]

  Arthritis Rheum. 64, 3472–3477 (2012). 20. Faurschou, M. et al. Reply. Arthritis Rheum. 65, 844 (2013). 21. Langford, C. A. & Hoffman, G. S. [doi.org]

• Arthralgia

  We report this case that presented with a productive cough, followed by arthralgia, DAH, and GIH. [ncbi.nlm.nih.gov]

  General signs (fever, arthralgia, myalgia, weight loss) are common. [orpha.net]

  To the Editor: A 52-year-old woman with a history of arthralgia, rhinitis, sinusitis, and episodic epistaxis was admitted to the hospital with multiple nonhealing severe leg ulcerations. [mdedge.com]

• Myalgia

  General signs (fever, arthralgia, myalgia, weight loss) are common. [orpha.net]

  […] necrotizing vasculitis predominantly affecting small to medium vessels involvement of respiratory tract HISTORY rhinorrhea, bloody nasal discharge, oral/nasal ulcers, sinus pain haemoptysis pleuritic chest pain haematuria stridor (subglottic stenosis) myalgias [lifeinthefastlane.com]

  Vision changes can include swelling, redness of the eyes or cases of conjunctivitis Intestinal involvement is rare, but can include vasculitis, ischemia, inflammation and ulceration of the large and/or small bowel [9] Musculoskeletal issues such as myalgia [physio-pedia.com]

• Migratory Polyarthritis

  polyarthritis, granulomatous skin lesions, proptosis, ocular manifestations with nasolacrimal duct obstruction, episcleritis, chondritis of ear, acute MI from vasculitis, aseptic meningitis and nonhealing granulomas of CNS may occur; upper respiratory [medical-dictionary.thefreedictionary.com]

• Night Sweats

  Etiology Idiopathic References:[4][5] Pathophysiology Clinical features Constitutional symptoms: fever;, night sweats, weight loss, arthralgias ENT involvement(∼ 90% of cases): often the first clinical manifestation Chronic rhinitis/sinusitis: nasopharyngeal [amboss.com]

  Other early symptoms include a fever that has no clear cause, night sweats, fatigue, and a general ill feeling ( malaise ). [nlm.nih.gov]

  Other early symptoms include fever, night sweats, fatigue and a general ill feeling (malaise). For some people, the disease is limited to the respiratory system and doesn't involve the kidneys. [arthritis.org]

  sweats Complications Ongoing Granulomatosis with Polyangiitis can result in: Collapse of cartilage in the nose Infections of sinuses and ears Hearing loss Kidney damage Kidney failure Death When to call a doctor Call your doctor if you are experiencing [stlouischildrens.org]

• Skin Ulcer

  Ulcerations with undermined, raised erythematous-violaceous border resembling pyoderma gangrenosum (PG) have rarely been reported as skin involvement in GPA. [ncbi.nlm.nih.gov]

  The diagnosis of GPA had been made by symptoms of multiple lung nodule, otitis media, sinusitis, skin ulcer, and periocular granuloma 20 years ago. [surgicalcasereports.springeropen.com]

  […] lumps skin ulcers (localised areas of tissue loss) joint pain. [betterhealth.vic.gov.au]

  […] symptoms with formation of skin ulcers, skin rash and skin nodules which are often painful Presence of blood and protein in urine on urine analysis Nerve symptoms causing tingling and weakness affecting either a single nerve (mono neuropathy) or multiple [dovemed.com]

  Other organs frequently affected by Granulomatosis with Polyangiitis granulomatosis include the eye (proptosis and double-vision from retro-orbital pseudotumor, scleritis), skin (ulcers, purpura). or peripheral nerve (mononeuritis multiplex). [hopkinsvasculitis.org]

• Skin Rash

  Other common symptoms include: Lungs - breathlessness, wheeze, dry cough or coughing up blood Skin - rashes, ulcers, and necrosis (death of tissue) Eyes - red (blood shot) eyes, painful, dry or gritty eyes, visual loss or other changes in vision Nerves [vasculitis.org.uk]

  Other early symptoms can include joint pain, decreased hearing, skin rashes, eye redness and/or vision changes, fatigue, fever, appetite and weight loss, night sweats, and numbness or loss of movement in the fingers, toes, or limbs. [rheumatology.org]

  Depending on which systems are involved, additional symptoms can include skin rashes, inner ear pain, swollen and painful joints, and numbness or tingling in the limbs. GPA is most common in middle-aged adults, although it can occur at any age. [ghr.nlm.nih.gov]

  […] symptoms with formation of skin ulcers, skin rash and skin nodules which are often painful Presence of blood and protein in urine on urine analysis Nerve symptoms causing tingling and weakness affecting either a single nerve (mono neuropathy) or multiple [dovemed.com]

  Skin Granulomatosis with Polyangiitis can cause many kinds of skin rashes. The most common rash occurs in the form of small purple or red dots on the lower extremities (known as “palpable purpura”). [hopkinsvasculitis.org]

• Erythema

  It concerns a 37 year-old female undergoing treatment for pulmonary TB, who presented with left ocular proptosis, eyelid and conjunctival edema and erythema. Orbital biopsy revealed GP. C-Anti-neutrophil cytoplasmic antibodies were elevated. [ncbi.nlm.nih.gov]

  Occasional patients with erythema nodosum, pyoderma gangrenosum and Sweet syndrome may also have ANCA-positive disease 6. [slideshare.net]

  Here, we describe a case of GPA complicated by tuberculous lymphadenitis, in which several etiologies may be considered to explain this complication. 2 Case report A 50-year-old Filipino woman presented with nodular erythema on the arms, legs, and face [journals.lww.com]

  Local site reactions included injection site bruising, erythema, pain and reaction. The analysis was performed on Safety Population which comprised of all participants who receive at least one dose of study treatment. [clinicaltrials.gov]

• Epistaxis

  CASE REPORT A 67-year-old woman was referred for evaluation of episodes of epistaxis and recurrent severe sinusitis. Her physical examination showed nasal congestion and purpuric rash on the lower extremities. [ncbi.nlm.nih.gov]

  Manifestations can affect various organ systems and may include upper and lower respiratory tract symptoms (eg, recurrent nasal discharge or epistaxis, cough), followed by hypertension and edema. [merckmanuals.com]

  To the Editor: A 52-year-old woman with a history of arthralgia, rhinitis, sinusitis, and episodic epistaxis was admitted to the hospital with multiple nonhealing severe leg ulcerations. [mdedge.com]

  […] glomerulonephritis (50%) Joints:migratory polyarthropathy (56%) Skin:inflammatory skin lesions (44%) Eyes and ears:proptosis and otitis media (29%) Heart and pericardium: myocardial infarction (28%) CNS: neuritis (22%) Symptoms Rhinorrhea Sinusitis Epistaxis [learningradiology.com]

  He was treated with cautery for the epistaxis, and ultimately, a polypectomy/anstrostomy was performed. [webeye.ophth.uiowa.edu]

• Hematuria

  She had sinusitis and hematuria; she was diagnosed with granulomatosis with polyangiitis. Hypertrophic pachymeningitis (HPM) was considered to have interrupted the venous flow and caused vasogenic edema. [ncbi.nlm.nih.gov]

  Renal involvement Focal lesions can give proteinuria and hematuria while diffuse lesions can give acute renal failure. [radiopaedia.org]

  Wegener's granulomatosis is a systemic disease characterized by a clinical triad of paranasal sinus and nasal mucosa involvement, pulmonary infiltration and cavitation, and renal disease with hematuria. [pediatrics.aappublications.org]

• Kidney Failure

  People with GPA develop tissue damage in the lungs, airways, and the kidneys. Kidney involvement may result in blood in the urine and kidney failure. Kidney disease can quickly get worse. [nlm.nih.gov]

  When GPA is fatal, this is normally because of kidney failure. [medicalnewstoday.com]

  Kidneys: The kidneys are often affected. Kidney function may be slightly or severely impaired. Severe kidney damage causes high blood pressure and swelling due to fluid retention (edema). Life-threatening kidney failure may occur. [msdmanuals.com]

  Some individuals may experience kidney failure, a serious complication that requires dialysis and/or a kidney transplant. Finally, an option for those with very serious GPA affecting the kidneys or lungs is “plasmapheresis.” [vasculitisfoundation.org]

• Peripheral Neuropathy

  Skin lesions (purpura and cutaneous nodules) are observed in 10-50%, peripheral neuropathy (multineuritis) in 25%, central nervous system manifestations (headaches, sensorimotor deficit, hemiplegia and epilepsy) in 10%, and ocular anomalies (scleritis [orpha.net]

  neuropathy 名前の由来 Friedrich Wegener 典拠管理 Q1161568 Reasonator Scholia 統計学 下位カテゴリ このカテゴリに属する 3 個のサブカテゴリのうち、 3 個を表示しています。 [commons.wikimedia.org]

  Nervous system involvement may be seen in approximately one-third of patients with peripheral neuropathies, the most common being mononeuritis multiplex; less frequently observed are cranial neuropathies, seizures, stroke syndromes, and cerebral vasculitis [aao.org]

• Headache

  © 2016 American Headache Society. [ncbi.nlm.nih.gov]

  Skin lesions (purpura and cutaneous nodules) are observed in 10-50%, peripheral neuropathy (multineuritis) in 25%, central nervous system manifestations (headaches, sensorimotor deficit, hemiplegia and epilepsy) in 10%, and ocular anomalies (scleritis [orpha.net]

• Vertigo

  Eight months prior to current presentation, she developed vertigo and decreased hearing in her left ear which she felt was “full of air” all the time. She was found to have sensorineural deafness in her left ear. [hindawi.com]

  Ears: Otitis, sensorineural hearing loss, vertigo, and chondritis may occur. The middle ear, inner ear, and mastoids are often affected. Eyes: Eyes may appear red and swollen. [merckmanuals.com]

  Ears - Hearing loss is not uncommon in patients with Wegener granulomatosis, and additional findings include otitis, vertigo, and chondritis. [symptoma.com]

• Dizziness

  Your doctor may alter the dose of particular medications, usually over a period of time to reduce the risk of withdrawal symptoms, such as low blood pressure and dizziness. [betterhealth.vic.gov.au]

  Signs and symptoms of a sinus infection include: Facial swelling Sore throat Bad breath Tooth pain Sensitive teeth Dizziness Pain or pressure around the eyes or cheeks From Reviewed on 10/12/2018 Sources: Patient Comments & Reviews Wegener's Granulomatosis [emedicinehealth.com]

  […] assisted him in performing self-care whenever needed Gradually increased activities and exercise; assisted him in doing passive to active and full range of motions Monitored his vital signs before and after activities to prevent falls and injuries from dizziness [ijcne.org]

The diagnosis of GPA comprises a full workup, including laboratory tests, imaging studies, and often tissue biopsy to confirm the diagnosis.

Laboratory tests should include a complete blood count (CBC), and findings may include eosinophilia, thrombocytosis and anemia may be present. Serum albumin and total protein content are decreased, while creatinine values are increased, as a result of poor kidney function. Urinalysis may reveal proteinuria, as well as dysmorphic RBCs. Inflammatory markers, such as ESR and CRP are elevated.

Serologic detection of ANCA antibodies should be performed in all patients with clinical criteria, and in addition to ANCA, anti-PR3 antibodies should be evaluated as well. Positive ANCAs are usually highly suggestive of GPA, but patients with bacterial endocarditis, tuberculosis, as well as other inflammatory conditions, may have positive ANCAs. For these reasons, imaging studies, and eventual tissue biopsy is necessary to confirm the disease.

A plain chest X-ray usually reveals multiple pulmonary nodules that may be cavitating, as well as parenchymal infiltration that may be bilateral. X-ray of the sinuses may also reveal chronic inflammation. CT scan may provide a more specific view of the lungs and sinuses, and is preferred in establishing the lesions [13].

Tissue biopsy should be performed in patients with clear diagnostic criteria, and biopsy should be performed on affected organs, which are the lungs and the kidneys in the majority of cases. In addition to biopsy and microscopic examination, culture of the material should be obtained, to exclude possible infections (such as tuberculosis).

• Pulmonary Infiltrate

  Treatment with high-dose steroids, followed by rituximab resulted in normalisation of inflammatory markers with subsequent resolution of joint pains, rash and pulmonary infiltrates and improvement of neuropathic symptoms. [ncbi.nlm.nih.gov]

  […] granulomas renal biopsy: segmental necrotizing glomerulonephritis, crescents Urine casts proteinuria CXR pulmonary infiltrates nodules alveolar or pleural opacities hilar adenopathy MANAGEMENT Induction proportional to severity (localised, early systemic [lifeinthefastlane.com]

  Churg-Strauss syndrome is a rare systemic necrotizing vasculitis that is characterized by asthma, peripheral eosinophilia, non-fixed pulmonary infiltrates, neuropathy and histopathologic features of extravascular eosinophilic infiltration and granuloma [dbpia.co.kr]

  Wegener's granulomatosis is a systemic disease characterized by a clinical triad of paranasal sinus and nasal mucosa involvement, pulmonary infiltration and cavitation, and renal disease with hematuria. [pediatrics.aappublications.org]

• Cavitary Lesion

  CT of the chest showed two right-sided cavitary lesions. CT of the abdomen and pelvis demonstrated a prostatic abscess. A prostate biopsy demonstrated necrotising granulomatous prostatitis. [ncbi.nlm.nih.gov]

  Tissue biopsy establishes the histologic diagnosis; chest x-ray may disclose nodular, diffuse, or cavitary lesions; and laboratory evaluation may note proteinuria or hematuria, elevated ESR, and the presence of C-reactive protein and ANCAs. [aao.org]

  He was referred to our hospital for diagnosis and treatment of the bilateral located cavitary lesions in his chest X-ray. [go.gale.com]

  Chest CT without contrast is nearly always necessary because the chest x-ray may miss nodules, masses, and/or cavitary lesions caused by granulomatosis with polyangiitis. [merckmanuals.com]

  Examination included a chest X-ray with findings of multiple nodules, cavitary lesions, and infiltrates. [ajnr.org]

• Atelectasis

  (A) Chest radiograph at admission shows left side pleural effusion, and suspicious atelectasis in left lower lung field. (B) Chest CT scan shows left pleural effusion with passive atelectasis with no evidence of focal leision in lung parenchyma. [docsplayer.org]

  Inflammation of the major bronchi and branches can cause localized wheezing, postobstructive pneumonia, and atelectasis. [merckmanuals.com]

• Thrombocytosis

  The thrombocytosis was severe in its magnitude but not unexpected and previously observed in the literature. The resolution of this thrombocytosis with appropriate treatment for vasculitis helps confirm this clinical impression. [hindawi.com]

  […] pleuritic chest pain haematuria stridor (subglottic stenosis) myalgias arthalgia conjunctivitis corneal ulceration skin lesions at high risk of DVT EXAMINATION pleural effusions pulmonary infiltrates skin vasculitis lesions INVESTIGATIONS leucocytosis thrombocytosis [lifeinthefastlane.com]

  Blood count abnormalities in granulomatosis with polyangiitis may include: Raised white cell count (leucocytosis) Reduced haemoglobin (normocytic normochromic anaemia ) Raised platelet count (thrombocytosis) Raised erythrocyte sedimentation rate ( ESR [dermnetnz.org]

  Paraclinical tests were requested to clarify the causes of her symptomatology: ocular ultrasound with mild vitritis, negative C-reactive protein, hemogram with leukocytosis, without neutrophilia, thrombocytosis, elevated erythrocyte sedimentation rate [elsevier.es]

  In most patients with active disease, ESR and C-reactive protein are elevated, and serum albumin and total protein are decreased; anemia, thrombocytosis, and mild-to-moderate eosinophilia are detected. [merckmanuals.com]

• Abnormal Renal Function

  GPA can also affect the eyes, skin, joints and nervous system.37 Renal involvement is characterised by abnormal renal function with red cell casts in urinalysis, and glomerulonephritis on renal biopsy.38 The most common features of nasal disease activity [ncbi.nlm.nih.gov]

• Granulomatous Tissue

  The first patient also had T1 hyperintensity within the anterior lobe, presumably due to hemorrhagic elements within granulomatous tissue. [ajnr.org]

  Granulomatous inflammatory tissue around the skull base resulted in cavernous sinus syndrome, facial nerve palsy, palsies of cranial nerves IX-XII (Collet-Sicard syndrome), and the rare complication of cranial diabetes insipidus due to pituitary infiltration [bmcneurol.biomedcentral.com]

• Pleural Effusion

  effusion (25%) Alveolar infiltrate occasionally Other Organs Urinary tract:focal glomerulonephritis (50%) Joints:migratory polyarthropathy (56%) Skin:inflammatory skin lesions (44%) Eyes and ears:proptosis and otitis media (29%) Heart and pericardium [learningradiology.com]

  effusions pulmonary infiltrates skin vasculitis lesions INVESTIGATIONS leucocytosis thrombocytosis elevated ESR and CRP normochromic, normocytic anaemia Antineutrophil cytopasmic antibiodies (ANCA) PR3-ANCA = GPA MPO-ANCA (myeloperoxidase) = MPA Tissue [lifeinthefastlane.com]

  Pleural effusions and mediastinal nodal enlargement are also encountered. Renal involvement Focal lesions can give proteinuria and hematuria while diffuse lesions can give acute renal failure. [radiopaedia.org]

  (A) Chest radiograph at admission shows left side pleural effusion, and suspicious atelectasis in left lower lung field. (B) Chest CT scan shows left pleural effusion with passive atelectasis with no evidence of focal leision in lung parenchyma. [docsplayer.org]

  The chest radiograph showed a normal cardiac silhouette, clear lungs, and a small left pleural effusion. The ECG performed on admission showed sinus rhythm, normal PR interval, and diffuse flattened T waves. [circ.ahajournals.org]

• Leukocytosis

  A normocytic anemia, leukocytosis, elevated erythrocyte sedimentation rate, positive rheumatoid factor and ANCA (specifically PR3-ANCA) are often shown on serology. [jacpjournal.org]

  ANCA negative patients typically presented concomitant leukocytosis, neutrophilia and lymphopenia. Laboratory findings are presented in Table II. [ncbi.nlm.nih.gov]

  Paraclinical tests were requested to clarify the causes of her symptomatology: ocular ultrasound with mild vitritis, negative C-reactive protein, hemogram with leukocytosis, without neutrophilia, thrombocytosis, elevated erythrocyte sedimentation rate [elsevier.es]

  Anemia, mild leukocytosis, and elevated Erythrocyte sedimentation rate (ESR) are nonspecific laboratory findings. [hopkinsvasculitis.org]

The choice of treatment depends on the severity of the disease at the time of diagnosis, and organ-specific involvement.

The recommended regimen for patients with severe, and possibly life-threatening manifestations, such as rapidly progressive glomerulonephritis and alveolar hemorrhage, is the administration of high-dose corticosteroids together with immunosuppressive therapy, such as cyclophosphamide. Corticosteroid therapy usually lasts for several months, until patients reach remission, and in the next few years, the goal of therapy is to gradually eliminate the use of corticosteroids, as well as the use of less potent immunosuppressants. Treatment options include methylprednisolone 15mg/kg or 1g q24h in the first few days, together with oral prednisone 1mg/kg q24h for several weeks. Then, the dose is slowly tapered, usually by 10mg per week until the patients reach the dose of 40mg q24h. Then the dose is reduced by 5mg every 14 days until it reached 10mg q24h, and eventually reducing the dose by 1mg each month until the cessation of therapy is indicated. However, changes in therapy may occur in the case of relapses, or if patients develop complications. Cyclophosphamide is a potent immunosuppressant, and is used as a first-line therapy together with corticosteroids in severe cases of GPA, in doses of 2mg/kg q24h per os, for at least 3 months, or more, until remission is reached. Because this drug may cause severe leukopenia, WBC counts must be monitored, while Pneumocystis jirovecii pneumonia may also be a potentially adverse effect, which is why patients are often given trimethoprim-sulfamethoxazole in prophylactic regimens. Rituximab, which is a form of monoclonal antibody targeted against B cell activity, has shown good results in patients with relapsing disease [14].

In milder cases, corticosteroid therapy is used together with methotrexate or azathioprine, which are less potent immunosuppressants, and they are used to maintain remission [15]. Careful monitoring of WBC count should be monitored in these patients as well.

In most severe cases, when kidney function cannot be maintained with therapy and even dialysis, kidney transplantation is indicated, and the risk of relapse is significantly reduced, due to concomitant use of potent immunosuppressive drugs.

Supportive therapy may include muciprocin nasal ointment, and irrigation of sinuses with saline, to reduce the chances of secondary infections.

Prognosis of patients with GPA depends on the time of diagnosis, and the magnitude of the disease (organ involvement and damage). Renal involvement has shown to be a valid indicator of outcome, as 5-year survival rates are 100% for patients without renal disease, compared to 70% for patients with glomerulonephritis [9].

The outcome is quite good if this disorder is treated promptly, with the majority of patients going into long-term remission. Renal function may be significantly improved with intensive immunosuppressive therapy, and more than half of patients may be dialysis-independent [10]. However, relapses are common in patients with GPA, and more than 50% of patients develop relapses within the first several years of treatment.

Overall 10-year survival rates range between 75-88%, and poor outcomes are related to older age, multiorgan involvement, and delayed therapy.

The cause of GPA is not completely understood, but genetic, immune, as well as infectious factors have been proposed in the pathogenesis of this disorder [2].

The genetic basis of the disease is supported by findings that associate major histocompatibility complex (MHC) abnormalities, notably HLA-DP, and genes encoding anti-PR3 antibodies, alpha-1 antitrypsin, and ANCA antibodies [3]. Cell-mediated hypersensitivity, supported by the presence of granulomas and rapid remission of symptoms and the disease to immunosuppressive therapy, has been hypothesized as a factor in the development of this disorder as well. Infectious agents have been implied in the pathogenesis of this disorder, including chronic nasal carriage of Staphylococcus aureus [4], but without solid conclusions.

The rates of GPA vary across the globe, and prevalence rates in the United States are estimated to be 3 per 100,000 individuals, although rates may be higher [5]. Prevalence rates in Nordic countries include 160 per million [6], but in general, this disease develops in approximately 1 in 25,000 individuals.

The onset of GPA most commonly occurs around age 40, and it is seen in all ethnic groups, although Caucasians comprise the majority of cases. This disorder affects males more commonly than females, for unknown reasons.

The hallmark of GPA is granulomatous inflammation of both tissues and blood vessels. Typically, granulomas form with epitheloid and giant cells, while the presence of various leukocytes, including neutrophils, lymphocytes, and eosinophils, has been observed. Granulomatous inflammation is accompanied by tissue and vessel necrosis, which can result in the formation of ulcerative lesions in the nasopharynx and nose, while severe patterns of necrosis may result in the development of cavitary lesions in the lungs.

Anti-neutrophilic cytoplasmic antibodies (ANCA) are present in the vast majority of patients with GPA [7], and their involvement implicated activation of the immune system in the pathogenesis of the disorder. The role of B cells in the development of this diseases, including antibody and cytokine production, as well as antigen presentation, has been reported [8]. On the other hand, T-cell involvement is the presumable mechanism of granuloma formation, and autoreactive PR3-specific cells have been described.

Kidney damage occurs due to focal glomerular necrosis as a result of intense inflammation, while more severe lesions lead to crescentic glomerulonephritis, in which diffuse necrosis and proliferation of parietal cells occur. These events may progressively lead to kidney failure if not treated early with immunosuppressive therapy.

Prevention of GPA is currently not achieved, but recognizing the disease in its early stages may provide a significantly better outcome for patients, which is why a timely diagnosis and prompt treatment is essential for patients suffering from this disease.

GPA is a form of necrotizing vasculitis, usually consisting of three principal components: necrotizing granulomatous inflammation (most commonly in the upper or lower respiratory tract), granulomatous vasculitis of small and medium-sized vessels, including arteries, arterioles, capillaries and venules; and kidney disease (focal glomerulonephritis, often with necrosis and crescent formation) [1]. The cause and pathogenesis of this disorder presumably include autoimmune mechanisms that lead to formation of granulomas consisting of lymphocytes, plasma cells, neutrophils, and eosinophils, and inflammation targets both tissues and vessels. Prevalence rates vary across the world, but averages about 1 in 30,000 individuals, with males being affected more commonly than women. The onset of disease is most commonly around 40 years of age, and Caucasian race is affected in the majority of cases. Clinical presentation depends on the site of disease, but the principal target is the upper respiratory tract including the sinuses and nasopharynx. Chronic sinusitis, epistaxis, and secondary infections due to Staphylococcus aureus, are commonly encountered signs and symptoms, while hoarseness, dyspnea, and wheezing may occur in severe forms of disease in which subglottic stenosis develops. In addition to both upper and lower respiratory tract, the ears, eyes, heart, kidneys, musculoskeletal and nervous system can be affected, depending on the severity of the disease. The course of disease may be abrupt or it may take a prolonged period of time to develop, up to several years, but in more severe forms with multiorgan involvement the onset is acute, and may pose significant morbidity, which is why prompt identification and treatment must be conducted. The diagnosis of GPA is achieved through laboratory tests, such as evaluation of inflammatory markers (sedimentation rate, C-reactive protein), proteins, albumin, and urinalysis, while anti-neutrophil cytoplasmic antibodies (c-ANCA), together with anti-proteinase-3 (PR-3) antibodies and clinical findings are highly suggestive of GPA. A definite diagnosis is achieved by obtaining a biopsy of the affected tissue, and is most commonly performed on the lungs and kidneys. If patients are timely treated, the majority will enter complete remission, but relapses are not uncommon, particularly in patients who stopped treatment. Treatment principles include immediate treatment with corticosteroids, together with cyclophosphamide (in severe forms) or methotrexate (for milder forms), and in most severe cases, dialysis and kidney transplantation is indicated. If left untreated, the disease is fatal in the majority of patients.

Granulomatosis with polyangiitis (GPA) is a disease which results in inflammation of small blood vessels and tissues. The exact cause of this disorder is not known, but it presumably involves autoimmune mechanisms, which lead to inflammation and formation of granulomas, which are masses containing blood cells, inflammatory cells, and can cause significant damage in organs in which they develop. The onset of this disease is most commonly around 40 years of age, and occurs in males more commonly than females, for unknown reasons. The principal organs that are targeted in this disease are the lungs and the upper respiratory tract, with symptoms such as nose bleeding, pain and recurrent secondary infection of the sinuses, cough, and difficulty breathing are commonly reported. In addition to the lungs, the kidneys are also affected in a substantial number of patients, and manifests as the presence of blood in urine (hematuria) and increased blood pressure. Many other organs may be affected, most notably the nervous system and the eyes, but the heart, musculoskeletal system, and the skin may be affected in patients suffering from GPA. The diagnosis is achieved by performing blood tests that confirm the presence of inflammation in the body, evaluation of kidney function, while a vast majority of patients test positive for anti-neutrophil cytoplasmic antibodies (ANCAs), which are one of the main features of this disease. Chest and sinus X-rays, as well as computed tomography (CT scan) can be helpful in assessing the damage caused by inflammatory events, while a definite diagnosis is obtained by performing a biopsy, which includes obtaining a sample of the affected organ. In most cases, either the lungs or the kidneys are favorable sites for obtaining biopsy material. Because the prognosis is not good in patients with untreated disease, prompt diagnosis and treatment is necessary, as the majority of patients enter remission with good treatment strategies. Treatment includes the use of drugs that suppress inflammation, including corticosteroids and drugs such as methotrexate and cyclophosphamide, although they should be used with caution, as they can have significant adverse effects. Overall, survival rates are very high with proper therapy, but relapses of the disease may occur.

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