GPA and Sinusitis

Question 1

What is GPA?

Answer 1

Granulomatosis with polyangiitis (GPA) is a rare form of vasculitis.

Question 2

What is the pathophysiology of GPA?

Answer 2

It is thought to be an autoimmune inflammatory process affecting endothelial cells.

It is a multisystem disease which can affect many parts of the body, categorised by the ELK classification: it most commonly presents with lesions in the upper respiratory tract (E indicating ears/nose/throat, almost 100%), lungs (L most patients) and kidneys (K >75%).

Many other areas of the body may also be affected, with joint inflammation occurring in 25-50% of all cases. The sinuses, eyes and skin may also be affected

Question 3

What are the risk factors for GPA?

Answer 3

GPA has been linked to parvovirus and to chronic nasal carriage of Staphylococcus aureus.

Question 4

What are the symptoms of GPA?

Answer 4

As a multisystem disease, GPA often presents with nonspecific symptoms and can be difficult to recognise in primary care.

Symptoms may include:

• Fatigue, malaise, abdominal pain and joint pains
• Fever, night sweats
• Weakness, loss of appetite and weight loss
• Rhinorrhoea, sinusitis and hearing loss
• Facial pain
• Hoarseness, cough, dyspnoea, wheezing and chest pain

Question 5

What are the signs seen in GPA?

Answer 5

The signs found in GPA occur as a result of the inflammation of the small vessels and may affect any part of the body.

The most commonly seen signs relate to the upper and lower airways and the renal tract and may include:

• Ulcers, sores and crusting, in and around the nose, with destruction of nasal cartilage.
• Rhinorrhoea, often bloody.
• Haemoptysis.
• Haematuria.
• Subglottic stenosis (38% in one study) - causing hoarseness, stridor, dyspnoea, or cough.
• Rashes (up to 50%) - often small red/purple raised areas or blister-like lesions, ulcers or nodules
• Conjunctivitis, scleritis and episcleritis.
• Chronic ear infections.
• Mononeuritis multiplex.
• Peritonitis.

Question 6

What are the differentials of GPA?

Answer 6

Anti-GBM disease 
Legionella infection 
SLE 
Rheumatoid arthritis 
Churg-Strauss syndrome 
Renal vein thrombosis with PE

Question 7

What are the investigations done for GPA?

Answer 7

FBC, ESR.
Serum U&Es.
Blood test for ANCA, of two types: c-ANCA and p-ANCA - detectable in nearly all patients with active severe GPA. However, approximately 1 of 5 patients with active limited disease negative.
Urinalysis for protein, blood and casts.
Nasal endoscopy.
Lung function tests and flow volume loop looking for subglottic stenosis.
CXR looking for cavity formation and pulmonary infiltrates.
Chest CT imaging to exclude lung parenchymal involvement.
Sinus CT scan to exclude sinus disease.
Biopsy of affected tissue, which may include nasal mucosa, lung biopsy, renal biopsy, looking for presence of vasculitis and granulomas.

Question 8

What is the management of GPA?

Answer 8

Patients who are asymptomatic and have no organ damage may not need immunosuppressive treatment.

Such patients should initially be offered methotrexate to induce remission (with mycophenolate mofetil as an alternative for those intolerant of methotrexate).

Cyclophosphamide should be offered to promote remission in patients who have life-threatening and/or vital organ damage. Due to its serious adverse effects (e.g., renal, haematological and neurological toxicity), it is normally given as pulsed treatment intravenously every 2-4 weeks. Long-term toxicity is dependent on lifetime cumulative dose which should be ≤25 g.

Rituximab if cyclophosphamide is CI,

Prednisolone is given in addition to cyclophosphamide or rituximab, as it helps to increase patient survival and suppress local disease.

Once the patient is in remission, cyclophosphamide should be replaced by azathioprine or methotrexate.

Question 9

When is surgical treatment indicated for GPA?

Answer 9

Nasal deformity.
Subglottic stenosis.
Obstruction of lacrimal ducts.
Bronchial stenoses.
Eustachian dysfunction (insertion of grommets).
Acute kidney injury (renal transplant).

Question 10

What are the complications of GPA?

Answer 10

Acute kidney injury
Respiratory failure
Chronic conjunctivitis
Nasal septum perforation

Question 11

What are the paranasal sinuses?

Answer 11

The paranasal sinuses refer to the frontal, maxillary, sphenoidal and ethmoidal sinuses.

Question 12

What is sinusitis?

Answer 12

Sinusitis is an inflammation of the membranous lining of one or more of the sinuses.

Sinusitis is also referred to as rhinosinusitis because inflammation of the nasal mucosa generally accompanies sinusitis.

Question 13

What is the classification of sinusitis?

Answer 13

Acute: an infection lasting 7-30 days.
Subacute: the inflammation lasts 4-12 weeks.
Recurring: there are >3 significant acute episodes in a year lasting ≥10 days with no intervening symptoms.
Chronic: symptoms persist for >90 days (these may be caused by irreversible changes in the mucosal lining of the sinuses), with or without acute exacerbations.

Question 14

How can you differentiate between viral and bacterial sinusitis?

Answer 14

Viral disease is said to last less than 10 days, whereas worsening symptoms after 5 days, or symptoms extending beyond 10 days, suggest bacterial infection.

Question 15

What are the risk factors for sinusitis?

Answer 15

Upper respiratory tract infection.
Allergies and asthma.
Smoking and hormonal status (e.g., pregnancy).
Nasal dryness and DM
Presence of a foreign body and inhalation of irritants (e.g., cocaine).
Iatrogenic (e.g., nasogastric tubes, mechanical ventilation).
Dental problems (e.g., trauma, infection).
Some sporting activities (e.g., swimming, diving, high-altitude climbing).
Mechanical obstruction (e.g., normal anatomical variations, nasal polyps).
Previous history of trauma (nose, cheeks).
Immunocompromise.

Question 16

What are the rare causes of sinusitis?

Answer 16

Rare causes include cystic fibrosis, neoplasia, as a part of Samter’s triad, sarcoidosis, granulomatosis with polyangiitis (GPA) and immotile cilia syndrome. Sinus surgery can also predispose individuals.

Question 17

What is the Samter’s triad?

Answer 17

(aspirin sensitivity, rhinitis, asthma)

Question 18

How do you assess for sinusitis?

Answer 18

In general practice, the most helpful examination technique is simple palpation, as this is quick and easy to perform. Percussion and transillumination are also described, although these are not reliable and diagnosis should not rely on these alone.

Examination of the sinuses should be complemented by assessment of the nose (external and speculum examination) to assess for evidence of related pathology. Thereafter, investigations are guided by clinical suspicion.

Question 19

What is acute sinusitis?

Answer 19

This is defined as a bacterial or viral infection of the sinuses lasting fewer than four weeks and resolving completely with the appropriate management.

It tends to arise as a result of a viral infection and a diagnosis of acute sinusitis is made if there is sinus drainage obstruction and subsequent secondary bacterial infection.

Question 20

Are there specific symptoms for acute sinusitis?

Answer 20

No specific clinical symptom or sign is sensitive or specific for acute sinusitis, so the overall clinical impression should be used to guide management.

Question 21

What is the aetiology of acute sinusitis?

Answer 21

It is commonly caused by Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis.

The latter is more common in children. In adult patients with suspected acute maxillary sinusitis following a viral upper respiratory infection, about one half have been found to have pus or mucopus in the sinus aspirate, and one third had bacterial pathogens growing in culture

Question 22

What are the symptoms of sinusitis?

Answer 22

Non-resolving cold (>1 week or worsening symptoms over 4-5 days) with a biphasic character: initial viral infection which begins to settle is followed by further malaise related to the sinusitis.
Pain over the affected sinusitis
Pyrexia
Purulent nasal discharge with or without anosmia

Question 23

How do you diagnose acute sinusitis?

Answer 23

Acute sinusitis is diagnosed if there is:

• Facial discomfort (eg, a feeling of congestion or fullness, often unilateral and worse when bending forwards) or pain.
• Nasal obstruction or (purulent) nasal discharge or postnasal drip.
• Decreased or absent sense of smell.

This may be accompanied by:
-Headache, halitosis, fatigue, dental pain, cough and a feeling of pressure or fullness in the ears.

In children, symptoms of rhinitis predominate ± the additional feature of ear discomfort due to the blockage of the Eustachian tube.

Question 24

What are the investigations done for acute sinusitis?

Answer 24

Not generally require and investigations usually not helpful.

Possibilities in case of real diagnostic uncertainty include ESR, CRP (although they lack sensitivity), plain X-ray films, ultrasonography, nasendoscopy, CT imaging, MRI scan and sinus puncture.

Question 25

What are the differentials for sinusitis?

Answer 25

Allergic rhinitis
Common cold
Adenoiditis

Question 26

What is the management of acute sinusitis?

Answer 26

Most patients can be reassured that this is generally a viral infection similar to a cold but which takes a little longer to resolve (about 2.5 weeks).

People presenting with symptoms for around 10 days or fewer should not be offered an antibiotic prescription

When the person has been unwell for around 10 days or more, with no improvement, the clinician can consider prescribing a high-dose nasal corticosteroid for 14 days for adults and for children aged 12 years and over.

Question 27

What are helpful measures to relieve symptoms of sinusitis?

Answer 27

Paracetamol/ibuprofen for pain/fever.

Intranasal decongestant (oral is not recommended for sinusitis) for a maximum of a week.

Nasal irrigation with warm saline solution.

Warm face packs, which may provide localised pain relief.

Adequate fluids and rest.

Question 28

When should you refer a patient with sinusitis?

Answer 28

Refer if there is severe systemic infection or complications of sinusitis such as meningitis, orbital cellulitis.

Question 29

What is the antibiotics used in the treatment of acute sinusitis?

Answer 29

If a decision is made to use antibiotics, there are several guidelines available to follow. NICE CKS suggests:

First-line: phenoxymethylpenicillin (500 mg qds for five days) or co-amoxiclav if more systemically unwell. Alternatives for those who are allergic to penicillin are doxycycline (200 mg stat then 100 mg od for seven days - not in children aged <12 or pregnant women) or clarithromycin (250 mg-500 mg bd for seven days), or erythromycin.

High dose produces quicker improvement but there is an increased risk of diarrhoea.

Offer review in seven days for patients not treated with antibiotics and whose symptoms worsen within 72 hours, or do not resolve after 72 hours for those treated with antibiotics.

Question 30

What are the complications of acute sinusitis?

Answer 30

Rare and commonly occur in children. This includes orbital cellulitis, meningitis, brain abscess, osteomyelitis and cavernous sinus thrombosis.

Symptoms are likely to be relatively slow to resolve (2-3 weeks, regardless of whether antibiotics are taken or not) but over two thirds of patients experience improvement or resolution of symptoms without antibiotic treatment.

Question 31

What is the cause of chronic sinusitis?

Answer 31

Aetiologies such as allergic rhinitis (dust mites, molds), exposures (airborne irritants, cigarette smoke or other toxins), structural causes (nasal polyps, deviated nasal septum), ciliary dysfunction, immunodeficiencies, and fungal infections should be considered

When infection does occur, it is most frequently caused by anaerobes, Gram-negative bacteria, S. aureus, and coagulase-negative staphylococci. Patients with chronic sinusitis are more likely to have a chronic underlying problem

Question 32

What are the symptoms of chronic sinusitis?

Answer 32

Same as acute sinusitis but not as florid and a dull ache on palpation.

Question 33

How do you diagnose chronic sinusitis?

Answer 33

The diagnostic criteria are as for acute sinusitis but the symptoms last for more than 12 weeks.

It is worth noting that, compared with acute sinusitis, loss of smell is more commonly described and facial pain is less common.

Question 34

What are the investigations done for chronic sinusitis?

Answer 34

Not usually needed

Evidence for predisposing factors should be sought: 
Allergic rhinitis 
Asthma 
Immunosuppression 
Chronic dental infection 
Presence of a foreign body (especially in children) 
Aspirin sensitivity 
GPA 
Churg-Strauss syndrome

Question 35

What are the differentials for chronic sinusitis?

Answer 35

Rhinitis 
Nasal polyps 
Cystic fibrosis 
Turbinate dysfunction 
Fungal sinusitis 
Juvenile nasopharyngeal angiofibroma

Question 36

What is the management of chronic sinusitis?

Answer 36

Attention to good dental hygiene and stopping smoking (including avoiding passive smoking where possible) are helpful.

When nasal steroids are used, treatment should last at least eight to 12 weeks with proper usage.

Antihistamines should only be used if an allergic component is suspected.

Antibiotics can be given for an extended period of three weeks. However, there is no consensus on their routine use in chronic sinusitis, nor is there consensus on antibiotic selection.

Empiric antifungal treatment should not be given.

Chronic sinusitis with polyps should be treated with topical nasal steroids. If severe or unresponsive to therapy after 12 weeks, a short course of oral steroids can be considered.

Functional endoscopic sinus surgery can be considered for patients who fail medical management. In more complicated cases, it can serve as an adjunct to medical management.

Question 37

What is the role of endoscopic sinus surgery in chronic sinusitis?

Answer 37

The goal of this surgery is to relieve obstructions, to restore drainage and mucociliary clearance, and to ventilate the sinuses

Question 38

What are the complications of chronic sinusitis?

Answer 38

Exacerbations 
Meningitis 
Osteomyelitis 
Orbital cellulitis 
Laryngitis and adenoiditis in children 
Mucocele formation 
Scuba divers are more likely to develop chronic sinusitis due to barotrauma

Question 39

In which patients is fungal sinusitis seen?

Answer 39

Seen in immunocompromised patients.

The most common culprits are the Aspergillus and Mucor species

Question 40

What is the classification of fungal sinusitis?

Answer 40

Non-invasive has a chronic sinusitis picture before the correct diagnosis is made.

Invasive has an acute, fulminant character and it is associated with a high mortality rate

Question 41

What is the management of fungal sinusitis?

Answer 41

Diagnosis is made after referral to the ENT department. Microbiology and histology provide final diagnosis.

The mainstay of treatment is surgical, the aim being to debride the infected tissue. Antifungal treatment is used when there is invasive infection.

Question 42

When does barosinusitis occur?

Answer 42

Barotrauma of the paranasal sinuses is a risk factor for anyone exposed to ambient pressure changes.

These pressure changes most often result from travel through mountainous regions, flying or diving. The problem arises as a result of the small size of the ostia of the sinuses so limiting the exchange of gases and mucus. This may lead to accumulation of secretions and an acute or chronic sinusitis.

Question 43

What is the presentation of barosinusitis?

Answer 43

Mild inflammation may give rise to pain (particularly on returning to starting conditions - eg, back to sea level), congestion and occasional epistaxis.

More severe inflammation is characterised by severe, sharp pain and a pressure sensation which is typically in the forehead, in the mid-face or retro-orbital. Epistaxis is common. Clinical examination and findings are similar to those in acute sinusitis.

Question 44

What is the management of barosinusitis?

Answer 44

Same as for acute sinusitis