History and exam

Key diagnostic factors

common

upper and lower respiratory tract involvement

More than 90% of patients present with signs and/or symptoms involving the upper or lower respiratory tract.[10]

In the upper respiratory tract, these can include otorrhoea, pain or a muffled sensation in the ears, sinus pain, nasal discharge and crusting, epistaxis, hoarseness, stridor, oral and nasal ulcers, mucosal bleeding and inflammation, nasal septal perforation, saddle nose deformity, sinus tenderness, and tympanic perforation.

In the lower respiratory tract, these can include shortness of breath, cough, haemoptysis, chest pain, dyspnoea, focal dullness to percussion, crackles, rhonchi, focal reduction of air entry on auscultation.[1][2][3][21][22]

renal involvement

Microscopic haematuria is a frequent finding. Urinalysis should be performed in all patients with suspected granulomatosis with polyangiitis (GPA) (formerly known as Wegener's granulomatosis).[22]

Patients typically only have renal symptoms once involvement has progressed sufficiently to cause significant renal impairment. In these cases, oedema and hypertension can occur.

Macroscopic haematuria and mass lesions occur rarely in people with GPA.

constitutional features

Patients typically have non-specific symptoms for 2 to 3 months before presentation. Common constitutional effects include fatigue, malaise, fever, night sweats, anorexia, and weight loss.

Other diagnostic factors

common

ocular manifestations

Involvement of the eyes can result in redness, pain, tearing, proptosis, diplopia, visual blurring, visual loss, and retinal exudates/haemorrhages.[1][2][3][21][22]

cutaneous manifestations

Skin features that may be noted included palpable purpura or petechial, nodular, vesicular, haemorrhagic, and ulcerative lesions.[1][2][3][21][22]

musculoskeletal manifestations

Myalgia, arthralgia (typically migratory), joint swelling, or muscle weakness may all be present. Joint deformities are normally absent.[1][2][3][21][22]

neurological manifestations

Features can include numbness, dysaesthesias, localised muscle weakness, headache, seizures, and cognitive deficits.[1][2][3][21][22]

Findings are usually consistent with mononeuritis multiplex (i.e., preservation of reflexes and sensorimotor function generally, except in the regions served by the specific nerves affected), peripheral sensorimotor polyneuropathy, or cranial neuropathy. Less commonly they may appear as focal central nervous system deficits (e.g., hemiparesis).

signs or symptoms of thromboembolism

Particularly associated with periods of active disease.[4][5]

Characteristic features include limb swelling, pain, tenderness, and erythema. However, it is often asymptomatic and consequently overlooked. More than one limb may be affected.

Embolisation to the lung typically causes dyspnoea, tachycardia, and hypotension.

uncommon

gastrointestinal involvement

Typical conditions that may occur with granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) include colitis, enteritis, and bowel perforation, which may present with signs and symptoms such as abdominal pain, nausea, vomiting, diarrhoea, blood or mucus in the stool, abdominal distension, peritonitis, fever, urgency, fatigue, or weight loss.[1][2][3][21][22]

Rarely, the disease may manifest as cholecystitis (right upper abdominal pain, nausea, fever, jaundice, pale stools, ileus), unexplained ascites, non-healing perianal ulcers, recurrent acute pancreatitis (upper abdominal pain radiating to back, abdominal tenderness, nausea, vomiting), or as a pancreatic mass.

cardiac involvement

May cause a wide range of cardiac conditions including pericarditis, myocarditis, congestive heart failure, conduction system abnormalities, coronary vasculitis, myocardial ischaemia, and valvulitis.[1][2][3][21]​​[22]​​

The range of signs and symptoms that may be noted include typical or atypical chest pain, orthopnoea, fatigue, cough, wheeze, pulmonary oedema, peripheral oedema, arrhythmias, and syncope.

breast mass

This is an unusual and rare finding. It may present as a single or multiple breast mass(es). Histological analysis allows correct identification.[35]

lower genitourinary tract involvement

May cause dysuria and/or testicular, genital or pelvic pain, associated with a range of urological conditions including necrotising urethritis, orchitis, epididymitis, prostatitis, cystitis, penile necrosis, or mass lesions affecting the ureter, testes, ovary, or uterus.

endocrine involvement

Involvement of the pituitary can result in central diabetes insipidus, with characteristic findings of polydipsia, polyuria, weight loss, fever, diarrhoea, and vomiting.

It may also present as a thyroid mass.

isolated mass lesions/focal granuloma

Can cause mass lesions/focal granulomas anywhere in the body; involvement of the salivary glands, liver, and spleen have all been reported.[25][26][27] These lesions are frequently asymptomatic.

Risk factors

weak

genetic predisposition

Low prevalence in first-degree relatives, but a genome-wide association study has demonstrated an association between antiproteinase 3 anti-neutrophil cytoplasmic antibody (ANCA) and HLA-DP, alpha-1-antitrypsin, and proteinase 3.[14][15]

infection

No role established in disease initiation.

Staphylococcus aureus nasal carriage has been associated with relapse in established disease.[17]

environmental exposures

Silica and other occupational exposures have been proposed as triggers, but this has not yet been proven.[16]

white ethnicity

GPA is most commonly seen in white people, but may occur in any racial and ethnic group.[7][9][10]

Use of this content is subject to our disclaimer