Table 2.
GPA - organ manifestations, differential diagnoses, and diagnostic techniques.
| Organ involved/main features | Clinical symptoms | Differential diagnoses | Diagnostic techniques |
|---|---|---|---|
| Lungs/pleura | |||
| Nodules and masses (with or without cavitation)Pulmonary infiltrates/opacities/alveolitis DAH ILD Pleuritis |
Cough (often with the sputum), hemoptysis, dyspnea, chest pain, fever Dyspnea until respiratory failure, hemoptysis (in part of cases), anemia Progressing dyspnea, dry cough, limited exercise tolerance Chest pain, dyspnoea |
Acute or chronic bacterial infections (e.g., TB or other Mycobacteria), fungal infection, as aspergillosis or cryptococcosis (others such as histoplasmosis, coccidiomycosis, blastomycosis should be considered in endemic areas), Nocardia, aspiration pneumonia, malignancy, NSG, RA, COP, lymphomatoid granulomatosis, BALT lymphoma, pulmonary infarct Primary (anti-GBM disease, MPA, cryoglobulinaemic vasculitis), and secondary vasculitides (APS, SLE, RA, MCTD, drug-induced), other non-immune mediated causes (infectious, CHF, coagulation disorders, acute respiratory failure syndrome, inhalation of toxic substances, hemosiderosis) CTD, drug-induced, smoking-related, chronic HP, IgG4-related disease, idiopathic Infection, pleural effusion secondary to heart or renal failure |
X-ray, CT, FOB with cytological and microbiological examinations, PFTs, lung biopsy X-ray, CT, FOB and BALF (determination of hemosiderin-laden macrophages), basic laboratory tests (including Cr, blood count), immunological examinations (e.g., ANA, anti-GBM and anti-phospholipids antibodies), cultures, ECHO, BNP, detailed medical interview Detailed medical interview, occupation, environmental exposure, drugs taking, immunological examinations (e.g., ANA, serum precipitins, anti-IgG-4 antibodies), PFT, FOB, BALF, lung biopsy USG, thoracocentesis with fluid examination and cultures, pleural biopsy |
| Trachea and bronchi | |||
| SGS Mucosal abnormalities, masses and polyps, TBISs, trachea- or bronchomalacia, bronchiectasis |
Dyspnea, stridor, hoarseness, cough, hemoptysis, recurrent infections | Polychondritis, inflammatory bowel disease, sarcoidosis, infection (especially fungal), asthma, allergy, neoplasm, amyloidosis, postintubation stenosis | CT, FOB, PFT, cultures, biopsy |
| ENT | |||
| Chronic rhinosinusitis, often purulent and with bone destruction, nasal septum perforation Otitis media unilateral or bilateral, with the obstruction of the eustachian tube, which may be complicated by facial nerve palsy and mastoiditis |
Nasal obstruction, sinus pain, nose deformity (collapse of the nasal bridge) Gradual or fluctuating hearing loss conductive (more common), sensorineural or mixed, otorrhea, earache |
Chronic infection (especially TB and fungal), sarcoidosis, cocaine abuse, lymphoma | Complete ENT assessment (with nasal endoscopy), sinus CT, or MR (of the ear), laryngoscopy, nasal swabs cultures, audiogram, biopsy |
| Kidney | |||
| GN (usually pauci-immune necrotizing, often crescentic) Interstitial nephritis |
Microscopic and dysmorphic hematuria, sub-nephrotic proteinuria, with or without rapid serum Cr increase, hypertension, with or without azotemia Sediment alterations with or without Cr increase (acute or subacute) |
Urinary tract infection, urolithiasis, CKD, CTD (e.g., SLE), hypertensive or diabetic nephropathy, bladder or renal malignancy, drug-induced kidney failure, anti-GBM disease | Urinalysis, 24-h proteinuria collection, blood urea, Cr, eGFR, anti-GBM, urine culture, USG, kidney biopsy |
| Heart/pericardium | |||
| Pericarditis (the most common) Cardiomyopathy/myocarditis, valvular disease, conduction disorder Artery disease (vasculitis) Rare: coronary artery aneurysms, coronary artery dissection, tumor of the heart, endocarditis |
Chest pain, dyspnea Chest pain, dyspnoea, palpitations, fever |
Infection, CTD, pericarditis secondary to malignancy (e.g., lung or breast cancer) or radiation Cardiomyopathy related to atherosclerosis or hypertension, infective myocarditis |
ECG, ECHO, serum troponin and BNP, 24-h ECG, cardiac MR (optionally FDG-PET/CT), rare cardiac biopsy CT or MR angiography, TEE, blood cultures, rare conventional angiography |
| Digestive tract | |||
| Any organ may be affected Intestine, stomach Liver Spleen Pancreas Gallbladder |
Abdominal pain and bloody diarrhea, nausea, vomiting, hematochezia or melena, dysphagia, perforation, may be subclinical course with positive occult blood in the feces Elevated liver enzymes, organ enlargement, rare vasculitis on the portal spaces and centrolobular territories Segmental infarction, rather asymptomatic Recurrent pancreatitis, pseudotumoral masses Cholecystitis, infarction |
Infection, inflammatory bowel disease (e.g., CD, UC), peptic ulcer disease, malignancy, diverticulitis, neoplasm Pancreatitis of the other cause (alcohol, drugs, cholelithiasis), malignancy Cholelithiasis, infection, dietary mistake, other causes of acute abdominal pain (gastritis, appendicitis, biliary colic, peptic ulcer disease), neoplasm |
Fecal occult blood tests (3x), liver enzymes (cholestatic and hepatocellular pattern), lipase, amylase, abdominal USG, CT/MR, endoscopy, biopsy Screening for HBV and HCV infection is recommended at the beginning of GPA diagnosis in all patients |
| Nervous system | |||
| Peripheral | |||
| Distal symmetrical sensory neuropathy, mononeuritis multiplex, peroneal, tibial, ulnar, and median nerves are commonly involved Cranial neuropathies (II-VIII) |
Pain, burning sensation, numbness, limb weakness, foot or wrist drop and other sensory and/or motor deficits Often secondary to the external compression from ENT and/or orbit mass |
Paraneoplastic, AIDS, DM, chronic liver disease, infection (Guillain-Barre syndrome), vit B6 or B12 deficiency, drugs, other type of vasculitis Tumor, stroke |
Clinical evaluation, EMG, nerve biopsy, laboratory and serological tests MR |
| Central | |||
| Brain parenchyma (symptoms related to vasculitis) Posterior reversible encephalopathy syndrome (PRES) (rare) Isolated parenchymal mass lesions (very rare) Cognitive impairment |
Ischemic or hemorrhagic events Headache, seizures, altered mental status and visual loss Variable symptoms due to CNS compression, seizures are the most common Mostly subclinical or mild, affecting mainly abstract reasoning, attention and non-verbal memory |
Vascular atherosclerotic disease, acute disseminated encephalomyelitis Primary and secondary degenerative diseases, age-related dementia, brain tumor, infection (AIDS) Primary (i.e., glioma) or secondary (metastases) brain tumors, infection (e.g., in the course of AIDS) Degenerative diseases (e.g., Alzheimer disease), age-related – dementia, infection |
MR/MR angiography, cerebrospinal fluid examination and cultures, biopsy (rare) |
| Meninges | |||
| Hypertrophic pachymeningitis of the brain Spinal pachymeningitis |
Headache, dizziness, seizures, cranial neuropathy, e.g., paresis of the ocular motor nerves Paraplegia, truncal sensory abnormality, neck and back pain |
Infection, neoplasms (e.g., lymphomas), sarcoidosis | |
| Skin/mucosa | |||
| Skin | |||
| Purpura, ulcers, nodules, pyoderma, gangrenosum - like lesions, other (e.g., livedo reticularis) Mucous membranes Strawberry gingivitis, oral or nasal ulcers, genital ulceration |
Pain, necrosis Pain, bleeding, nasal crusting, purulent or blooding nasal discharge |
Infection, allergic vasculitis, cutaneous vasculitis in CTD, Henoch – Schonlein purpura, HCV - induced vasculitis, cryoglobulinemic vasculitis, vasculitis associated with vasculopathic disorders (e.g., factor V Leiden mutation), immunodeficiency (e.g., AIDS), classic pyoderma gangrenosum, lymphoproliferative disorders, ulcerative colitis, pseudovasculitis | Clinical and serological evaluation, biopsy |
| Ocular | |||
| Orbit | |||
| Orbital or retro-orbital mass, usually unilateral, often coexists with sinus disease with bone destruction |
Pain, proptosis, diplopia, eyelid swelling, periorbital cellulitis, ocular movement impairment, visual loss | Infection, lymphoma, sarcoidosis, cellulitis, cavernous hemangioma, venolymphatic malformation | MR, optic tomography, fluoroangiography, slit lamp examination, USG (in some cases), biopsy (rare) |
|
Eye Conjunctivitis, scleritis, episcleritis, keratitis, retinal involvement |
Red eye, tearing, corneal ulceration, blurred vision | Infection, CTD, sarcoidosis, IgG4-related disease, inflammatory bowel disease | |
| General/ Musculoskeletal | |||
| Fever, weakness, weight loss, malaise, myalgia, arthralgia, arthritis usually not-deformative | Infection (including TB), malignancy, CTD, polymyalgia rheumatica, hormonal disorders (e.g., hyperthyroidism) | Clinical evaluation, laboratory and immunological tests, hormone examinations, articular USG, cancer screening | |
| Other rare involvements | |||
| Urogenital | |||
| Prostatitis, renal pseudotumor, orchitis, epididymitis, ureteral stenosis, penis ulceration | Pain, swelling, fever, difficulty urinating | Infection, neoplasm, benign prostatic hyperplasia | CT or MR, cystoscopy, biopsy |
| Endocrine | |||
| Salivary glands Lacrimal glands Pituitary Thyroid Adrenal glands |
Swelling, pain, necrosis, dry mouth Pain, tearing, reddening Cranial diabetes insipidus, hypogonadism, secondary hypothyroidism, hyperprolactinemia, growth hormone deficiency, polyuria, polydipsia, decreased libido, muscular atrophy, asthenia, amenorrhea, compressive symptoms (headache, vomiting, visual field loss) Hypothyroidism Adrenal insufficiency |
Infection, Sjogren syndrome Infection, allergy Adenoma, lymphoma, metastasis, radiation, LCH, post-traumatic damage, stroke, sarcoidosis Hashimoto disease, cancer, subacute thyroiditis, drug-induced CS treatment, infection (TB), autoimmune adrenal inflammation, stroke of the hypothalamic–pituitary region, neoplasm |
Clinical evaluation, USG, MR, biopsy Clinical evaluation MR, hormone examinations USG, hormone and serology examinations, scintigraphy, biopsy USG, MR, hormone examinations, biopsy (rare) |
| Breast | |||
| Breast | More common in women, pain, ulceration | Breast cancer | Biopsy is decisive |
| Vertebral | |||
| Paravertebral masses, usually not associated with bone erosion or compression of vessels | Often asymptomatic, sometimes back pain | Cancer, lymphoma | MR |
| Large and medium-sized vessels | |||
| Thoracic and abdominal aorta (periaortitis the most common), carotid and subclavian artery, pulmonary arteries, renal arteries | Stenosis, occlusion, aneurysms, periaortic mass, thoracic or abdominal pain, fainting, stealing syndrome, low cardiac output syndrome, decrease of blood pressure, may be asymptomatic | Isolated large vessel vasculitis, atherosclerosis, thrombosis, congenital | CT/MR angiography, optionally FDG-PET/CT, conventional angiography (rare) |
GPA, granulomatosis with polyangiitis; CT, computed tomography; FOB, fiberoptic flexible bronchoscopy; PFTs, pulmonary function tests; RA, rheumatoid arthritis; COP; cryptogenic organizing pneumonia; BALT, bronchus-associated lymphoid tissue; DAH, diffuse alveolar hemorrhage; anti-GBM, anti-glomerular basement membrane antibodies; MPA, microscopic polyangiitis; BALF, bronchoalveolar lavage fluid; APS, antiphospholipid syndrome; SLE, systemic lupus erythematosus; CTD, connective tissue disease; MCTD, mixed connective tissue disease; HP, hypersensitive pneumonia; ANA, anti-nuclear antibodies; Cr, creatinine; ECG, electrocardiography; ECHO, echocardiography; BNP, brain natriuretic peptide; USG, ultrasonography; ENT, ear, nose, throat; MR, magnetic resonance; FDG-PET/CT, F-18 fluorodeoxyglucose - positron emission tomography; TEE, transesophageal echocardiography; HBV, hepatitis B virus; HCV, hepatitis C virus; AIDS, acquired immune deficiency syndrome; DM, diabetes mellitus, CNS, central nervous system, TB, tuberculosis; AIH, autoimmune hepatitis; PSC, primary sclerosing cholangitis; PBC, primary biliary cholangitis; CD, Crohn’s disease; UC, ulcerative colitis.