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Granulomatosis with Polyangiitis

GPA

Granulomatosis with polyangiitis (GPA), formerly known as Wegener granulomatosis, is a form of granulomatous necrotizing vasculitis of small and medium-sized vessels. It can be restricted to the the respiratory tract, or may involve additional organs, primarily the kidneys, and it most commonly occurs in adults around 40 years of age, with slight male predilection. Diagnosis is achieved through biopsy, and treatment includes corticosteroids and immunosuppressants.

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Presentation

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].
Fever
  • Abstract A 77-year-old man visited our hospital with chief complaints of difficulty in hearing, nasal discharge and fever.[ncbi.nlm.nih.gov]
  • GPA should be considered when patients do not improve despite adequate treatment of otologic symptoms, when patients have unspecific symptoms suggesting systemic disease (e.g. fever, malaise), or when other organs are involved (kidney, lungs, etc.).[ncbi.nlm.nih.gov]
  • 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]
  • A 59-year-old man presented with a severe headache, ocular pain, blurred vision, shortness of breath, and mild fever. Clinical examination revealed conjunctival chemosis, corneal edema, and shallow anterior chambers.[ncbi.nlm.nih.gov]
  • Abstract A 33-year-old woman with a 7-month history of granulomatosis with polyangiitis F-FDG PET/CT scan due to low-grade intermittent fever and elevation of serum inflammatory markers, which revealed multiple hypermetabolic lesions in bilateral kidneys[ncbi.nlm.nih.gov]
Weight Loss
  • We present a case of a 65-year-old Caucasian man with a history of rheumatoid arthritis, off immunosuppression for 18 months, who presented with 2 years of chronic headaches, severe fatigue, saddle nose deformity and 20-kilogram unintentional weight loss[ncbi.nlm.nih.gov]
  • General signs (fever, arthralgia, myalgia, weight loss) are common.[orpha.net]
  • loss, runny nose, nosebleed, sinus pain, cough, shortness of breath, and skin sores.[merriam-webster.com]
  • The symptoms are weakness, malaise, progressive weight loss, purulent rhinitis, sinusitis, polyarthralgia, ulcerations of the nasal septum, signs of severe progressive renal disease, and fever. The disease commonly occurs in mid-adult life.[whonamedit.com]
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]
  • 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]
  • Without treatment, kidney failure and anemia often occur.[mayoclinic.org]
Rapidly Progressive Glomerulonephritis
  • OUTCOMES: 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]
  • We reported the case of a patient affected with upper airways-limited GPA who developed acute renal failure from rapidly progressive glomerulonephritis and then experienced colonic perforation due to CMV colitis a few weeks after immunosuppressive treatment[ncbi.nlm.nih.gov]
  • Rapidly progressive glomerulonephritis , which is life threatening, can develop. Venous system: Deep venous thrombosis can affect the lower extremities mostly when GPA is active.[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]
Malaise
  • GPA should be considered when patients do not improve despite adequate treatment of otologic symptoms, when patients have unspecific symptoms suggesting systemic disease (e.g. fever, malaise), or when other organs are involved (kidney, lungs, etc.).[ncbi.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]
  • The symptoms are weakness, malaise, progressive weight loss, purulent rhinitis, sinusitis, polyarthralgia, ulcerations of the nasal septum, signs of severe progressive renal disease, and fever. The disease commonly occurs in mid-adult life.[whonamedit.com]
  • The most common presenting symptoms are malaise and fever, sinusitis, epistaxis, and hematuria. Most patients have roentgenographic evidence of pulmonary and sinus disease and laboratory evidence of renal involvement on initial evaluation.[pediatrics.aappublications.org]
Cough
  • 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]
  • A 44 year old lady presented with acute onset of loss of vision in the right eye and cough with mucopurulent expectoration for two months. Ophthalmic examination revealed central retinal artery occlusion (CRAO).[ncbi.nlm.nih.gov]
  • A 39-year-old woman suffered from persistent cough, left back pain and appetite loss. At 21 years of age she was diagnosed with MCTD, but the persistent administration of prednisolone or immunosuppressants was not needed.[ncbi.nlm.nih.gov]
  • Symptoms include coughing, shortness of breath, wheezing or coughing up blood. Kidneys. Kidney damage affects most people with Granulomatosis with polyangiitis (Wegener's). But in many cases, this damage is mild and does not cause any symptoms.[drugs.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]
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]
  • We present a case of a 65-year-old Caucasian man with a history of rheumatoid arthritis, off immunosuppression for 18 months, who presented with 2 years of chronic headaches, severe fatigue, saddle nose deformity and 20-kilogram unintentional weight loss[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]
  • Typical signs and symptoms of nose or sinus involvement include crusting around the nose, stuffiness, nosebleeds, runny nose, and saddle-nose deformity due to a perforated septum.[en.wikipedia.org]
  • That's called saddle nose deformity. You may see other symptoms like chronic sinusitis. Constant inflammation in the sinuses causes this chronic pain and this blockage of sinuses due to swelling.[khanacademy.org]
Nasal Discharge
  • Abstract A 77-year-old man visited our hospital with chief complaints of difficulty in hearing, nasal discharge and fever.[ncbi.nlm.nih.gov]
  • discharge, and granulomatous inflammation on biopsy.[ncbi.nlm.nih.gov]
  • 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]
  • Symptoms may include: Persistent runny nose (also called rhinorrhea) or the formation of nasal crusts and sores Nasal or facial pain Nose bleeds or unusual nasal discharge, caused by inflammation of the nose or sinuses Cough that might include bloody[my.clevelandclinic.org]
  • Patients may present with upper and lower respiratory tract symptoms (eg, recurrent nasal discharge or epistaxis, cough), followed by hypertension and edema, or with symptoms reflecting multiorgan involvement. Diagnosis usually requires biopsy.[merckmanuals.com]
Hemoptysis
  • These criteria were the same as for the traditional format, but included hemoptysis. The classification tree was associated with a sensitivity of 87.1% and a specificity of 93.6%.[ncbi.nlm.nih.gov]
  • 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]
  • Possible S&S can include cough, hemoptysis, shortness of breath, and chest discomfort.[physio-pedia.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]
  • After that, dyspnea on exertion developed and chest X-ray examination indicated multiple infiltrative shadows.[ncbi.nlm.nih.gov]
  • 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]
  • 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]
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]
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]
  • Abstract We describe the case of a 45-year-old woman presenting with troponin positive cardiac-sounding chest pain. An initial emergency angiogram demonstrated two vessel coronary disease, including a distal right coronary artery occlusion.[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]
  • pain and shortness of breath.[mountsinai.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 3 years[ncbi.nlm.nih.gov]
  • Following treatment, the patient was asymptomatic for 6 weeks until he developed acute renal failure, generalised arthralgia, acute hypertensive anterior uveitis, and dacryoadenitis.[ncbi.nlm.nih.gov]
  • Edema and hypertension may result. Rapidly progressive glomerulonephritis , which is life threatening, can develop. Venous system: Deep venous thrombosis can affect the lower extremities mostly when GPA is active.[merckmanuals.com]
  • Delivery Models Health Care Economics, Insurance, Payment Health Care Policy Health Care Quality Health Care Reform Health Care Safety Health Care Workforce Health Disparities Health Informatics Health Policy Hematology History of Medicine Humanities Hypertension[doi.org]
Tachycardia
  • The event was associated with multiple episodes of sustained ventricular tachycardia without any structural heart changes or electrolyte disturbances.[ncbi.nlm.nih.gov]
Diplopia
  • Abstract 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[ncbi.nlm.nih.gov]
  • CNS manifestations included the following: sensor/sensorimotor symptomatology (33.3%), severe headache and hearing loss (33.3%), delirium/seizures (22.2%), diplopia (11.1%), and cerebellar symptoms (11.1%).[ncbi.nlm.nih.gov]
  • 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]
  • .  Eyes :conjunctivitis, corneal ulceration, episcleritis/scleritis, optic neuropathy, nasolacrimal duct obstruction, proptosis, diplopia, retinal vasculitis, and uveitis  Nervous system mononeuritis multiplex, cranial nerve abnormalities, central nervous[slideshare.net]
  • Extension into the extraocular muscles leads to diplopia. If serious eye symptoms develop, evaluation and treatment are required immediately to prevent permanent vision loss. Lower respiratory tract: Respiratory manifestations are common.[merckmanuals.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 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 clots) Symptoms caused[drugs.com]
  • pain, watering of eyes, vision problems Skin 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[dovemed.com]
Red Eye
  • Symptoms such as orbital pain, decreased vision, double vision, red eye, scleritis, orbital wall destruction, primary gaze strabismus, and ocular motility restriction were significantly more common in the 1st group.[ncbi.nlm.nih.gov]
  • Scene 4: Red Eyes Redux We return now to the patient going to the CCU in 2003 for congestive heart failure.[hopkinsarthritis.org]
Night Sweats
  • 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]
  • 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]
Skin Ulcer
  • ulcers (localised areas of tissue loss) joint pain.[betterhealth.vic.gov.au]
  • 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 nerves (poly neuropathy).[dovemed.com]
  • Cutaneous involvement can lead to palpable purpura or skin ulcers. [1] Necrotic, purpuric, and blistering plaque on the wrist in a patient with granulomatosis with polyangiitis.[emedicine.medscape.com]
  • ulcers (45%) [1] ; ulcerations may resemble pyoderma gangrenosum Petechiae, vesicles, pustules, hemorrhagic bullae, livedo reticularis, digital necrosis, subungual splinter hemorrhages, and genital ulcers resembling squamous cell carcinoma have been[emedicine.com]
Arthritis
Arthralgia
  • Following treatment, the patient was asymptomatic for 6 weeks until he developed acute renal failure, generalised arthralgia, acute hypertensive anterior uveitis, and dacryoadenitis.[ncbi.nlm.nih.gov]
  • General signs (fever, arthralgia, myalgia, weight loss) are common.[orpha.net]
  • We report this case that presented with a productive cough, followed by arthralgia, DAH, and GIH.[ncbi.nlm.nih.gov]
  • Upon discussion with the cardiopulmonary section and having seen two patients on a clinical rotation, it seems that the current practice is focused primarily on cardiovascular endurance, treatment of pulmonary disfunction, and pain management from arthralgia[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]
Epistaxis
  • Upper respiratory tract: Sinus pain, serosanguineous or purulent discharge, and epistaxis may occur. The mucosa appears granular (like cobblestones) and is friable; ulcers, thick dark crusts, and septal perforation are common.[merckmanuals.com]
  • The most common presenting symptoms are malaise and fever, sinusitis, epistaxis, and hematuria. Most patients have roentgenographic evidence of pulmonary and sinus disease and laboratory evidence of renal involvement on initial evaluation.[pediatrics.aappublications.org]
  • […] 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]
  • Sinusitis, often chronic in nature, epistaxis, nasal chondritis that is often accompanied by pain and swelling, and may lead to septal perforation.[symptoma.com]
Peripheral Neuropathy
  • 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]
  • 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]
  • Neurologic involvement has been reported in 30-55% of patients. 37-39 Most common is peripheral neuropathy, followed by cranial neuropathy, ophthalmoplegia, stroke, and seizures.[epilepsy.com]
  • 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
  • CASE PRESENTATION: We report here the case of a 63-year old man who presented with severe positional headache.[ncbi.nlm.nih.gov]
  • A 59-year-old man presented with a severe headache, ocular pain, blurred vision, shortness of breath, and mild fever. Clinical examination revealed conjunctival chemosis, corneal edema, and shallow anterior chambers.[ncbi.nlm.nih.gov]
  • We describe the case of a 50-year-old woman with a history of a limited form of GPA with chronic pachymeningitis who presented with acute-onset headache accompanied by nausea and vomiting, and who developed consciousness impairment.[ncbi.nlm.nih.gov]
  • We present a case of a 65-year-old Caucasian man with a history of rheumatoid arthritis, off immunosuppression for 18 months, who presented with 2 years of chronic headaches, severe fatigue, saddle nose deformity and 20-kilogram unintentional weight loss[ncbi.nlm.nih.gov]
  • CNS manifestations included the following: sensor/sensorimotor symptomatology (33.3%), severe headache and hearing loss (33.3%), delirium/seizures (22.2%), diplopia (11.1%), and cerebellar symptoms (11.1%).[ncbi.nlm.nih.gov]
Vertigo
  • Ears - Hearing loss is not uncommon in patients with Wegener granulomatosis, and additional findings include otitis, vertigo, and chondritis.[symptoma.com]
  • Ears - Hearing loss is not uncommon in patients with GPA, and additional findings include otitis, vertigo, and chondritis.[symptoma.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]
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]

Workup

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
  • Sixteen patients showed pulmonary infiltrates on chest X-ray. C-ANCA was positive in all of the patients compared with 21.6% p-ANCA positivity. A total of 13 biopsies were done. The median Birmingham Vasculitis Activity Score was 12.[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]
  • 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]
  • infiltrates and nodules is relatively specific Diagnosis: biopsy of affected upper airway or skin showing inflammatory change is helpful Limited granulomatosis with polyangiitis : confined to lungs, no glomerulonephritis (or occurs many years later),[pathologyoutlines.com]
  • When fever persists in a patient with a significantly high ESR value, and radiographic and CT findings reveal sinusitis or a large pulmonary infiltrate with a central cavitation, Wegener’s granulomatosis must be considered. 1 Differential diagnosis of[aafp.org]
Cavitary Lesion
  • 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]
  • lesions, pulmonary haemorrhage causing haemoptysis, and rarely bronchial stenosis.[en.wikipedia.org]
  • Granulomatous inflammation is accompanied by tissue and vessel necrosis, which can result in formation of ulcerative lesions in the nasopharynx and nose, while severe patterns of necrosis may result in development of cavitary lesions in the lungs.[symptoma.com]
  • 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[symptoma.com]
  • Examination included a chest X-ray with findings of multiple nodules, cavitary lesions, and infiltrates.[ajnr.org]
Thrombocytosis
  • […] 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]
  • Laboratory tests should include a complete blood count (CBC), and findings may include eosinophilia, thrombocytosis and anemia may be present.[symptoma.com]
  • 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]
Granulomatous Tissue
  • The first patient also had T1 hyperintensity within the anterior lobe, presumably due to hemorrhagic elements within granulomatous tissue.[ajnr.org]
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]
  • 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]
  • 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]
  • 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 biopsy[lifeinthefastlane.com]
  • effusion Tracheobronchial disease - May manifest as hoarseness, cough, dyspnea, stridor, and wheezing Subglottic or tracheal stenosis – May also manifest as stridor; stenosis may prove fatal if untreated Hemoptysis - may result from cavitated pulmonary[emedicine.medscape.com]

Treatment

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

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.

Etiology

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.

Epidemiology

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.

Sex distribution
Age distribution

Pathophysiology

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

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.

Summary

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.

Patient Information

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.

References

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Last updated: 2018-09-24 07:01