Anosmia

Complete loss of the sense of smell. Hyposmia is reduced smell and is considered separately, though the causes overlap almost entirely and differ mainly in severity.

Functional anatomy

Olfactory receptor neurons in the olfactory epithelium of the superior nasal cavity, olfactory cleft and superior septum project unmyelinated axons through the cribriform plate to synapse in the glomeruli of the olfactory bulb. Mitral and tufted cells project through the olfactory tract to the primary olfactory cortex, which includes the piriform cortex, amygdala and entorhinal cortex, without a thalamic relay. This direct limbic connection explains the strong emotional and memory associations of smell.

Olfactory receptor neurons are unique among neurons in regenerating from basal stem cells throughout life, with a turnover of weeks to months. This regenerative capacity is the basis for recovery after viral and traumatic injury and for olfactory training.

Aetiological categories, which determine treatment entirely

Conductive, that is obstruction of odorant access to the olfactory cleft, which is the most treatable group:

Chronic rhinosinusitis with nasal polyps, which is the commonest treatable cause.
Chronic rhinosinusitis without polyps.
Allergic and non allergic rhinitis with mucosal oedema.
Severe septal deviation obstructing the olfactory cleft.
Sinonasal tumour.

Sensorineural, that is damage to the epithelium, nerve or central pathways:

Post viral olfactory dysfunction, which is the commonest cause overall and which increased dramatically with SARS-CoV-2. In that infection the mechanism involves infection of sustentacular support cells expressing angiotensin converting enzyme 2 rather than the receptor neurons themselves, which explains why most patients recover.
Head trauma, through shearing of the olfactory filaments at the cribriform plate, contusion of the orbitofrontal cortex, or direct olfactory bulb injury. Occipital impact carries the highest risk through contrecoup. Loss is frequently permanent.
Neurodegenerative disease. Olfactory loss precedes the motor features of Parkinson disease by up to 10 years and precedes the cognitive features of Alzheimer disease, and is an early biomarker in both. Also occurs in Lewy body dementia, Huntington disease and multiple system atrophy, though it is preserved in progressive supranuclear palsy and essential tremor, which is a useful discriminator.
Ageing, with presbyosmia affecting a majority of those over 80.
Toxins: cadmium, chromium, nickel, formaldehyde, solvents, cigarette smoke, and intranasal zinc preparations.
Drugs: aminoglycosides, macrolides, methotrexate, antithyroid drugs, calcium channel blockers, angiotensin converting enzyme inhibitors, and intranasal zinc.
Iatrogenic: sinus, septal and skull base surgery, and cranial radiotherapy.
Tumours: olfactory groove meningioma, esthesioneuroblastoma, frontal lobe tumour, and pituitary lesions.
Endocrine and metabolic: diabetes, hypothyroidism, chronic kidney disease, liver failure, vitamin B12 and zinc deficiency.
Epilepsy, multiple sclerosis and stroke.

Congenital:

Kallmann syndrome, comprising congenital anosmia with hypogonadotrophic hypogonadism from failed migration of gonadotrophin releasing hormone neurons alongside the olfactory axons, with absent or hypoplastic olfactory bulbs on imaging.
Isolated congenital anosmia, in which patients frequently present in adolescence or adulthood having never realised they were different.

Loss of smell, which patients usually describe as loss of taste, since flavour is predominantly retronasal olfaction. Basic tastes of sweet, salt, sour, bitter and umami remain intact.
Reduced appetite, weight loss, or conversely weight gain from over seasoning and seeking texture and sweetness.
Inability to detect smoke, gas leaks and spoiled food, which is a genuine and underappreciated safety hazard.
Inability to detect personal body odour, with consequent anxiety about hygiene and social withdrawal.
Loss of pleasure in eating, which has a measurable effect on mood. Depression is significantly more common in patients with olfactory loss and should be asked about.
Parosmia and phantosmia, which are considered separately, and which frequently accompany recovering post viral and post traumatic loss.

History that localises the cause

Onset: sudden loss after a viral illness or head injury; gradual loss with sinonasal disease or neurodegeneration; fluctuating loss with rhinitis and rhinosinusitis.
Fluctuation with nasal obstruction, which strongly suggests a conductive cause.
Associated nasal symptoms: obstruction, discharge, facial pressure.
Head injury, including apparently minor injury.
Occupational and toxin exposure, medications, smoking.
Neurological symptoms: tremor, bradykinesia, memory impairment, personality change, visual disturbance, headache.
Onset at or before puberty with delayed or absent puberty, suggesting Kallmann syndrome.
Unilateral loss, which is rarely noticed by patients and which is detected only on separate nostril testing.

Examination

Nasal endoscopy in every patient, examining specifically the olfactory cleft between the superior septum and middle turbinate, which is not visualised on anterior rhinoscopy.
Assessment for polyps, mucosal oedema, discharge, crusting, septal deviation and masses.
Cranial nerve examination, including visual fields and fundoscopy. Optic atrophy on one side with papilloedema on the other, together with anosmia, constitutes Foster Kennedy syndrome and indicates a frontal or olfactory groove mass.
Neurological examination for parkinsonian features and cognitive assessment where indicated.
Examination for signs of hypogonadism and, in congenital cases, associated features such as synkinesia, cleft lip and palate, renal agenesis and dental agenesis.

Objective psychophysical testing in every patient, since self report correlates poorly with measured function and patients both over and underestimate their loss. Use a validated instrument: the University of Pennsylvania Smell Identification Test, the Sniffin Sticks battery which tests threshold, discrimination and identification, or a shortened validated screening test.
Test each nostril separately, since unilateral loss changes the differential toward a structural or neoplastic cause.
Distinguish taste from smell with formal gustatory testing where a true taste disorder is suspected, since true taste loss is uncommon and points to a different set of causes.
Nasal endoscopy, as above.
Computed tomography of the sinuses to assess the olfactory cleft, sinus disease, polyps and the anterior skull base.
Magnetic resonance imaging of the brain and olfactory apparatus with dedicated coronal T2 sequences through the olfactory bulbs and tracts. This is indicated for unilateral loss, post traumatic loss, loss with neurological signs, congenital anosmia to assess bulb and sulcus development, and any loss without an obvious sinonasal cause. Olfactory bulb volume correlates with function and with prognosis.
Blood tests directed by the history: glucose and HbA1c, thyroid function, full blood count, vitamin B12, zinc, renal and liver function.
Gonadotrophins, testosterone or oestradiol, and genetic testing where Kallmann syndrome is suspected, with endocrinology referral.
Neurology referral where parkinsonian or cognitive features are present.

Treat the conductive causes, which respond well, and use olfactory training for sensorineural loss, which is the only intervention with consistent evidence.

Conductive causes

Chronic rhinosinusitis with polyps: intranasal corticosteroid at high dose, steroid delivered by irrigation or in the head down forward position to reach the olfactory cleft, a course of oral prednisolone 0.5 mg/kg for 5 to 10 days, and escalation to surgery or biologic therapy. Smell recovery is one of the outcomes most improved by dupilumab, and its restoration is often the change patients value most.
Chronic rhinosinusitis without polyps: topical steroid, saline irrigation, and surgery where medical therapy fails.
Allergic rhinitis: intranasal corticosteroid and antihistamine, allergen avoidance, immunotherapy.
Septal deviation obstructing the olfactory cleft: septoplasty, with realistic counselling that smell improvement is not guaranteed.
A corticosteroid trial with oral prednisolone is both therapeutic and diagnostic: improvement indicates a substantial conductive or inflammatory component and predicts response to topical treatment and surgery.

Olfactory training

The mainstay for post viral and post traumatic loss, and the only intervention with robust supporting evidence.

Sniff four distinct odorants twice daily, morning and evening, for 20 to 30 seconds each, while consciously concentrating on the memory of that smell.
The classical set is rose, eucalyptus, lemon and clove, representing floral, resinous, fruity and spicy categories.
Continue for a minimum of 12 weeks, and preferably 6 to 12 months. Longer training produces better results.
Change the odorant set every 12 weeks, which improves outcomes over a fixed set.
It works through activity dependent regeneration and central reorganisation, and it is safe, inexpensive and available to all patients.
Adherence is the limiting factor. Explain the mechanism, set a routine linked to existing habits, and review to reinforce it.

Pharmacological treatment for sensorineural loss

Oral corticosteroid: prednisolone 0.5 mg/kg for 10 to 14 days may be trialled in post viral loss, though evidence of benefit in the absence of an inflammatory component is limited. Its main value is diagnostic.
Topical corticosteroid applied in the head down and forward position or as an irrigation, which reaches the olfactory cleft where a spray does not.
Omega 3 supplementation has some supporting evidence in post surgical and post viral loss.
Sodium citrate nasal spray, which chelates free calcium in the olfactory mucus and reduces feedback inhibition, has short lived benefit in some patients.
Intranasal vitamin A, theophylline, alpha lipoic acid, zinc and gingko biloba have inconsistent or weak evidence and should not be presented as established treatments.
Intranasal insulin and platelet rich plasma injection into the olfactory cleft are under investigation with early positive results in small studies, and are available in some centres.
Intranasal zinc preparations must be avoided entirely, since they cause anosmia.

Safety counselling, which is mandatory in every anosmic patient

Install and maintain smoke alarms, and check them regularly, since the patient cannot smell smoke.
Install a natural gas detector where gas is used, and consider changing to electric cooking.
Label food with dates and discard by date rather than by smell.
Take particular care with food storage and reheating.
Discuss occupational implications for chefs, sommeliers, firefighters, gas engineers, chemists and food industry workers, where anosmia may be career ending and where formal assessment and occupational health input are required.

Nutritional and psychological support

Dietitian input where weight loss or unhealthy compensatory eating occurs. Emphasise texture, temperature, and the trigeminal sensations of chilli, mint, and carbonation, which remain intact and can restore some pleasure in eating.
Screen for depression and treat it. Olfactory loss carries a substantial psychological burden that is routinely dismissed by clinicians, and acknowledging it is itself therapeutic.
Support groups and patient organisations are genuinely valuable in this condition.

Prognosis and follow up

Post viral loss: 60 to 80 percent show some recovery within 1 to 2 years, with the greatest improvement in the first 6 months. Younger age, female sex, milder initial loss and the presence of parosmia predict better recovery.
Post traumatic loss: recovery in only around 10 to 30 percent, and generally within the first year. Severity of loss and olfactory bulb volume on imaging predict outcome.
Conductive loss from polyps: excellent recovery with treatment, though relapse follows treatment cessation.
Congenital and neurodegenerative loss: no recovery.
Review with repeat objective testing at 6 and 12 months to document change, since patients cannot reliably self assess and objective improvement is often greater than perceived.

Clinical toolsCalculators

BMI GCS EDD Parkland Formula

Corrected Sodium Corrected Calcium Anion Gap Creatinine Clearance Insulin Calculations qSOFA Wells PE Wells DVT CHA₂DS₂-VASc HAS-BLED CURB-65 Centor/McIsaac

Recurrent Acute Rhinosinusitis

Four or more episodes of acute rhinosinusitis per year, each meeting the diagnostic criteria for acute disease, with complete resolution of symptoms and, critically, absence of inflammation on endoscopy and imaging between episodes. The interval normality is what distinguishes this entity from chronic rhinosinusitis with acute exacerbations, and the distinction matters because the two have different underlying causes and different treatment.

Why episodes recur

The task is to identify why an ordinary viral upper respiratory infection converts to bacterial sinusitis repeatedly in this individual when it does not in most people. The causes fall into three groups.

Anatomical obstruction of the osteomeatal complex:

Concha bullosa, an aerated middle turbinate, particularly when large or infected.
Paradoxical middle turbinate.
Marked septal deviation with contact against the lateral wall.
Haller or infraorbital ethmoid cells narrowing the maxillary infundibulum.
Agger nasi and frontal recess cells obstructing frontal drainage.
Uncinate process variations, including medialisation or lateral attachment to the lamina papyracea.
Post traumatic and post surgical scarring.

Host defence impairment:

Common variable immunodeficiency, immunoglobulin A deficiency, immunoglobulin G subclass deficiency, and specific polysaccharide antibody deficiency, which is the commonest immune abnormality found in this group and is detected only by measuring vaccine responses.
HIV infection.
Diabetes mellitus.
Immunosuppressive therapy and haematological malignancy.
Primary ciliary dyskinesia and cystic fibrosis, which typically produce chronic rather than recurrent acute disease but should be considered.

Local and environmental drivers:

Allergic rhinitis, which produces mucosal oedema at the osteomeatal complex with every allergen exposure.
Odontogenic disease, which produces repeated unilateral maxillary infection until the tooth is treated.
Gastro oesophageal and laryngopharyngeal reflux.
Smoking, both active and passive.
Occupational irritant exposure.
Nasal foreign body in children.
High exposure settings, such as young children in day care and teachers.

Discrete, well demarcated episodes with the full symptom complex of acute rhinosinusitis: obstruction, purulent discharge, facial pain and reduced smell.
Complete or near complete symptom freedom between episodes, which the patient can usually date precisely.
Frequent antibiotic courses with prompt response and then recurrence weeks later.
Consistent unilaterality of episodes, which points strongly to a local anatomical or dental cause.
Clustering in winter, or with allergen season, which points to viral or allergic triggers respectively.
Impact on work, school and quality of life, and cumulative antibiotic exposure with its consequences.

Features that indicate a different diagnosis

Persistent symptoms between episodes, which means chronic rhinosinusitis with exacerbations, not recurrent acute disease.
Facial pain as the sole recurrent symptom with no obstruction, discharge or objective findings, which is usually migraine or midfacial segment pain. This group is commonly and wrongly operated on.
Unilateral bloody discharge, facial numbness or orbital signs, requiring exclusion of neoplasm.
Recurrent infections at other sites, chronic wet cough, bronchiectasis, otitis media and skin infections, indicating immunodeficiency.

The essential principle is to investigate between episodes, not during them, since imaging and endoscopy during an acute episode cannot demonstrate the interval normality that defines the condition.

Confirm the episodes objectively where possible. Documented episodes with recorded endoscopic findings or purulent discharge carry far more weight than patient report, since a substantial proportion of self reported recurrent sinusitis is recurrent viral illness or migraine.
Nasal endoscopy between episodes, which should show a normal or near normal middle meatus. Persistent oedema or discharge redirects the diagnosis to chronic disease.
Non contrast computed tomography of the sinuses performed between episodes, ideally at least 4 to 6 weeks after the last one. This is the key investigation. A normal scan between episodes confirms recurrent acute disease and simultaneously defines the anatomical variants that may be responsible.
Endoscopically guided middle meatal culture during an episode, to document the organisms and guide targeted therapy.
Allergy assessment with skin prick testing or specific immunoglobulin E.
Immunological workup, which should be performed in essentially all adults with genuine recurrent acute rhinosinusitis: full blood count with differential, immunoglobulin G, A, M and E, immunoglobulin G subclasses, HIV testing, and specific antibody titres to pneumococcal polysaccharide and tetanus before and 4 weeks after booster immunisation. A failure to mount a fourfold rise or to achieve protective titres to the majority of pneumococcal serotypes indicates specific antibody deficiency.
Dental assessment with panoramic radiography or cone beam computed tomography where episodes are unilateral and maxillary.
Sweat chloride testing, cystic fibrosis genetics, nasal nitric oxide and ciliary studies where the history suggests these.
Glucose and HbA1c.

Management has two arms: correcting the underlying cause, and managing each episode appropriately while reducing unnecessary antibiotic exposure.

Treat the identified cause

Allergic rhinitis: continuous intranasal corticosteroid such as mometasone furoate 100 micrograms per nostril once daily, an oral antihistamine such as cetirizine 10 mg daily during exposure, allergen avoidance, and allergen immunotherapy for confirmed single or dominant allergen sensitivity where symptoms persist despite pharmacotherapy. Immunotherapy is the only treatment that modifies the underlying allergic disease and can reduce recurrence substantially.
Odontogenic source: dental extraction, endodontic treatment, or removal of a displaced root, implant or filling material. The sinus disease will recur indefinitely until this is done.
Immunodeficiency: refer to immunology. Immunoglobulin replacement therapy for common variable immunodeficiency and for severe specific antibody deficiency with recurrent infection, and pneumococcal conjugate vaccination for specific antibody deficiency, which frequently produces a response where the polysaccharide vaccine did not.
Smoking cessation and removal of occupational irritant exposure.
Optimise glycaemic control.
Treat reflux where present with a proton pump inhibitor such as omeprazole 20 mg twice daily for 8 to 12 weeks with lifestyle modification.

Managing the acute episodes

Treat each episode as acute rhinosinusitis, using intranasal corticosteroid, saline irrigation and analgesia as the foundation.
Reserve antibiotics for episodes meeting bacterial criteria, and use culture directed therapy where a previous culture is available.
Given repeated antibiotic exposure, use co amoxiclav 625 mg three times daily for 7 days rather than plain amoxicillin, or a culture directed alternative.
Avoid the pattern of a telephone prescription for every episode without assessment, which perpetuates unnecessary antibiotic use and delays diagnosis of the underlying cause.

Preventive medical therapy

Continuous intranasal corticosteroid, which reduces episode frequency in patients with an allergic or inflammatory component.
Daily saline irrigation year round.
Influenza and pneumococcal vaccination.
Prophylactic antibiotics are generally not recommended for recurrent acute rhinosinusitis given resistance and adverse effects. Where they are used in exceptional cases, such as during a winter season while awaiting surgery in a patient with very frequent episodes, this should be a specialist decision with a defined review point.

Surgery

Indications: documented recurrent acute rhinosinusitis, generally four or more objectively confirmed episodes per year, with a demonstrated anatomical abnormality obstructing the osteomeatal complex, after correction of medical and allergic factors, and with a normal interval scan confirming the diagnosis.

Functional endoscopic sinus surgery targeted at the obstruction rather than a routine full clearance. This may consist of uncinectomy with maxillary antrostomy, resection of the lateral lamella of a concha bullosa, removal of a Haller cell, or anterior ethmoidectomy, tailored to the scan findings.
Septoplasty where a deviation obstructs the middle meatus or prevents access.
Balloon sinus dilation is an option in selected patients with limited disease and no polyps, dilating the maxillary, frontal or sphenoid ostium without tissue removal, and can be performed under local anaesthesia. Evidence for durable benefit in recurrent acute disease is less robust than for endoscopic surgery, and it does not address ethmoid disease.
Outcomes are good in appropriately selected patients, with meaningful reductions in episode frequency and antibiotic use. Outcomes are poor in patients selected on symptoms alone with a normal interval scan, which is the most important selection principle in this condition.

Counselling and follow up

Explain that surgery reduces but does not abolish episodes, and that it does nothing for an immune deficiency or an untreated allergy.
Do not offer surgery to patients whose recurrent facial pain has no objective correlate. They will not improve, and pain frequently worsens.
Review at 6 weeks and 3 months postoperatively with endoscopy, then annually, tracking episode frequency and antibiotic use as the outcome measures.
Continue preventive medical therapy indefinitely after surgery.

Anosmia

Overview

Clinical Features

Diagnosis

Management

Overview

Clinical Features

Diagnosis

Management