Granulomatosis With Polyangitis

History

Presenting Complaint:

• Main symptoms prompting the patient to seek medical attention

History of Presenting Illness:

• Onset, duration, and progression of symptoms

• Associated symptoms, such as fever, malaise, and weight loss

• Any interventions and their response, including medications, procedures, or previous hospitalisations

Past Medical History:

• Previous diagnoses of vasculitis, autoimmune diseases, or related conditions

• Any history of asthma or other respiratory illnesses

• Previous surgeries or procedures

• Medications, including immunosuppressive agents, corticosteroids, or antibiotics

Allergies:

• Drug allergies, including reactions to medications used in GPA treatment, such as penicillin or sulfa drugs

Family History:

• Family members with autoimmune diseases, vasculitis, or other related conditions

Social History

• Occupation and the impact of the disease on the patient's daily life and activities

Personal History

• Smoking and alcohol use, as these may have an impact on disease progression and treatment response

Travel History

• Recent travel, which may be relevant if the patient has been exposed to infections

Review of Systems:

• Respiratory: sinusitis, rhinitis, nasal congestion, epistaxis, cough, hemoptysis, dyspnea

• Cardiovascular: chest pain, palpitations, peripheral oedema

• Gastrointestinal: abdominal pain, nausea, vomiting, diarrhoea, hematochezia, melena

• Genitourinary: hematuria, dysuria, changes in urine output

• Musculoskeletal: joint pain, swelling, muscle weakness, or tenderness

• Dermatological: rashes, nodules, ulcers, purpura, digital gangrene

• Neurological: headache, visual disturbances, focal neurological deficits, sensory abnormalities, reduced reflexes

• Ocular: conjunctivitis, episcleritis, uveitis, retinal vasculitis, vision changes

• Ears: Hearing impairment

Physical Examination

General Examination:

• Appearance and overall demeanour

• Vital signs: temperature, blood pressure, pulse, respiratory rate, oxygen saturation

Head and Neck Examination:

• Nasal and oral findings: crusting, ulcers, septal perforation, saddle-nose deformity

• Lymphadenopathy: cervical, supraclavicular, axillary, inguinal

Respiratory Examination:

• Inspection: chest deformity, use of accessory muscles, respiratory pattern

• Palpation: chest expansion, tracheal deviation, tactile fremitus

• Percussion: resonance, dullness

• Auscultation: breath sounds, crackles, wheezing, pleural rub

Cardiovascular Examination:

• Inspection: jugular venous distention, peripheral oedema

• Palpation: carotid pulse, apical impulse, peripheral pulses, oedema

• Auscultation: heart sounds, murmurs, pericardial rub

Abdominal Examination:

• Inspection: distension, scars, visible masses or pulsations

• Auscultation: bowel sounds, bruits

• Palpation: tenderness, masses, organomegaly (liver, spleen), renal angle tenderness

• Percussion: tympany, dullness, shifting dullness

Musculoskeletal Examination:

• Inspection: deformities, swelling, erythema, skin lesions

• Palpation: joint tenderness, warmth, effusion, crepitus

• Range of motion: active and passive movements, restrictions

Neurological Examination:

• Mental status: level of consciousness, orientation, memory, speech

• Cranial nerves: visual acuity, visual fields, extraocular movements, facial symmetry, hearing, gag reflex, shoulder shrug, tongue movement

• Motor examination: muscle bulk, tone, strength, involuntary movements

• Sensory examination: light touch, pinprick, vibration, proprioception

• Reflexes: deep tendon reflexes, plantar reflexes

• Coordination: finger-nose-finger test, heel-shin test, rapid alternating movements

• Gait: stability, stride, heel-toe walking

Dermatological Examination:

• Inspection: rashes, nodules, ulcers, purpura, digital gangrene

• Palpation: texture, warmth, tenderness, induration

Ophthalmologic Examination:

• Visual acuity, colour vision, pupillary reflexes

• External eye: conjunctival injection, scleral or conjunctival nodules

• Fundoscopy: retinal haemorrhages, exudates, vasculitis

Investigations

Blood Tests:

• Complete blood count: anaemia, leukocytosis, thrombocytosis

• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP): markers of inflammation

• Renal function tests: urea, creatinine, estimated glomerular filtration rate (eGFR)

• Liver function tests: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin, albumin

• Electrolytes: sodium, potassium, calcium, magnesium, phosphate

• Coagulation profile: prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalised ratio (INR)

• Autoantibodies: antineutrophil cytoplasmic antibodies (ANCA), specifically proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA)

Imaging Studies:

• Chest X-ray: infiltrates, nodules, cavities, pleural effusions

• Sinus X-ray or computed tomography (CT) scan: sinusitis, sinus opacification, bony erosions

• Abdominal ultrasound or CT scan: organomegaly, masses, fluid collections

• CT or magnetic resonance imaging (MRI) of the brain: if neurological involvement is suspected

Pulmonary Function Tests:

• Spirometry: to assess for restrictive or obstructive patterns, if respiratory symptoms are present

• Diffusing capacity of the lung for carbon monoxide (DLCO): to evaluate gas exchange

• Renal Investigations:

• Urinalysis: hematuria, proteinuria, red and white blood cell casts

• Urine protein-to-creatinine ratio or 24-hour urine protein: to quantify proteinuria

• Renal biopsy: to confirm renal involvement and assess disease severity

Tissue Biopsy:

• Biopsy of the affected organ(s), such as nasal mucosa, skin, or lung: to confirm the diagnosis and assess disease activity

• Histopathology: necrotising granulomatous inflammation and vasculitis

Management

Induction Therapy:

• Glucocorticoids: oral or intravenous prednisolone or methylprednisolone, tapered over time

• Cyclophosphamide: oral or intravenous, for severe or life-threatening GPA

• Rituximab: as an alternative to cyclophosphamide, particularly in patients with relapsing disease or contraindications to cyclophosphamide

Maintenance Therapy:

• Azathioprine: after remission induction, to maintain remission and reduce relapse risk

• Methotrexate: an alternative to azathioprine, particularly in patients with mild to moderate disease and no significant renal involvement

• Mycophenolate mofetil: another option for maintenance therapy, especially in patients intolerant or unresponsive to azathioprine or methotrexate

• Rituximab: for maintenance therapy, particularly in patients with a history of relapse or who initially responded to rituximab

Supportive Care:

• Prophylaxis against Pneumocystis jirovecii pneumonia (PCP): trimethoprim-sulfamethoxazole or alternative prophylaxis, particularly during induction therapy

• Osteoporosis prevention: calcium, vitamin D, and bisphosphonates if indicated, particularly in patients on long-term glucocorticoids

• Vaccinations: ensure patients are up-to-date with age-appropriate vaccinations, avoiding live vaccines during immunosuppressive therapy

• Blood pressure control: management of hypertension, if present

• Management of hyperlipidemia, diabetes, and other comorbidities: as needed, depending on the patient's clinical condition

Monitoring:

• Regular follow-up appointments to assess disease activity, treatment response, and side effects

Where can you take a biopsy in GPA patients? How do you decide about that?

The best site to take a biopsy in patients with granulomatosis with polyangiitis (GPA) depends on the clinical manifestations and the organs involved. The goal is to select a site that is easily accessible, has a high likelihood of diagnostic yield, and poses minimal risk to the patient. Some of the most common biopsy sites for GPA include:

1. Nasal mucosa or sinus tissue: In patients with sinus involvement or nasal lesions, biopsying the nasal mucosa or sinus tissue may be informative. However, the sensitivity for diagnosing GPA in these sites may be lower than in the other sites.

2. Lung: In patients with pulmonary involvement, such as nodules, infiltrates, or cavities, a lung biopsy can provide valuable diagnostic information. This can be done through bronchoscopy with transbronchial biopsy, CT-guided percutaneous biopsy, or video-assisted thoracoscopic surgery (VATS), depending on the patient's condition and the location of the lesion.

3. Kidney: Renal biopsy is the gold standard for diagnosing renal involvement in GPA, especially in patients with rapidly progressive glomerulonephritis. It can help determine the severity of renal disease and guide treatment decisions. Kidney biopsies are typically performed percutaneously under ultrasound or CT guidance.

4. Skin: In patients with cutaneous lesions, such as nodules, ulcers, or purpura, a skin biopsy can help confirm the diagnosis of GPA. Skin biopsies are relatively safe and easy to perform.