Loss or altered sense of smell

Smell loss is reduced (hyposmia) or absent (anosmia) ability to detect odours. Altered smell includes parosmia (distorted perception of an odour), phantosmia (smell without a source), and cacosmia (unpleasant smell). Most cases follow sinonasal disease or viral infection.

Anatomy and physiology. Odorants reach the olfactory cleft; receptor neurons in the olfactory epithelium project through the cribriform plate to the olfactory bulb, then to the piriform cortex. Taste complaints are often smell loss (retronasal olfaction), because true taste (sweet, sour, salt, bitter, umami) usually remains.

Classification. Conductive (blocked airflow: rhinosinusitis, polyps, septal deviation), sensorineural (neuroepithelium damage: post-viral, trauma, ageing, toxins, neurodegeneration), central (neurological and intracranial), and congenital (Kallmann syndrome).

Key distinctions. Sudden loss after a viral illness points to post-viral olfactory loss. Gradual loss in an older adult points to ageing or neurodegeneration. Loss with epistaxis, unilateral obstruction or neurological signs points to tumour. Loss after head injury points to shearing of olfactory filaments.

History. Onset (sudden or gradual), course, laterality, parosmia, phantosmia, associated nasal obstruction, discharge, facial pain, epistaxis, taste change, recent viral illness (COVID-19, influenza), head injury, surgery, exposure to toxins (solvents, heavy metals, cocaine), medication use, smoking, diabetes, thyroid disease, neurological symptoms (tremor, constipation, sleep behaviour, memory), puberty delay (Kallmann), and safety issues (gas leaks, spoiled food, smoke alarms).

Drug history. Intranasal zinc, ACE inhibitors, calcium channel blockers, statins, antibiotics (macrolides, tetracyclines, ciprofloxacin), antithyroid drugs, antiepileptics (carbamazepine, phenytoin), chemotherapy, topical decongestants, intranasal corticosteroids (rarely), and cocaine.

Examination. Nasal endoscopy (mucosa, discharge, polyps, olfactory cleft, mass), anterior rhinoscopy, face, eyes, cranial nerves (including visual fields and fundi: Foster Kennedy syndrome), neurological examination for parkinsonism, cognition, and thyroid.

Red flags

• Unilateral loss with blood stained discharge, mass or unilateral obstruction
• Headache, visual symptoms, papilloedema or other cranial nerve signs
• Head injury with CSF rhinorrhoea
• Cognitive decline or parkinsonism
• Sudden loss with neurological signs
• Absent puberty or hypogonadism (Kallmann syndrome)
• Persistent loss over 3 months without cause

Special groups. Children: congenital anosmia, Kallmann syndrome, adenoidal hypertrophy and rhinitis. Pregnancy: rhinitis of pregnancy and hyperosmia. Older adults: ageing, neurodegeneration, drug effects. Region specific: viral infection, occupational toxins and traditional nasal preparations.

Conductive (sinonasal)

• Allergic and non-allergic rhinitis, rhinitis medicamentosa
• Acute and chronic rhinosinusitis, nasal polyposis, allergic fungal sinusitis
• Septal deviation, turbinate hypertrophy, adenoidal hypertrophy
• Nasal and sinus tumours (inverted papilloma, carcinoma, olfactory neuroblastoma)
• Granulomatosis with polyangiitis, sarcoidosis, cystic fibrosis

Sensorineural

• Post-viral olfactory loss (COVID-19, influenza, other upper respiratory infections)
• Traumatic anosmia
• Ageing (presbyosmia)
• Toxins and drugs (cadmium, solvents, cocaine, topical zinc, medications)
• Radiotherapy and chemotherapy
• Diabetes, hypothyroidism, vitamin B12 and zinc deficiency, renal and hepatic failure
• Vitamin A deficiency, Cushing syndrome, and adrenal insufficiency

Central and neurological

• Parkinson disease, Alzheimer disease and dementia with Lewy bodies
• Anterior skull base and frontal lobe tumours (olfactory groove meningioma, glioma), temporal lobe epilepsy (phantosmia)
• Multiple sclerosis, stroke, hydrocephalus
• Congenital: Kallmann syndrome, congenital anosmia
• Migraine, depression, schizophrenia (phantosmia)

Reasoning. Separate conductive from sensorineural causes by endoscopy and history. Image any unilateral loss, neurological signs or failure to recover. Measure smell objectively when needed.

First line. Nasal endoscopy, neurological screen, and bedside smell test (University of Pennsylvania Smell Identification Test, Sniffin' Sticks, or familiar odours tested in each nostril).

Targeted tests. CT sinuses without contrast for chronic rhinosinusitis. MRI of the olfactory bulbs and brain with contrast for unilateral loss, neurological signs, trauma or loss persisting over 3 months (bulb volume and sulcus depth are reduced in post-viral and congenital loss).

Blood tests: glucose or HbA1c, thyroid stimulating hormone, vitamin B12, zinc, urea, creatinine, liver function, full blood count, and ANCA or angiotensin converting enzyme for granulomatous disease. Hormonal tests (luteinising hormone, follicle stimulating hormone, testosterone or oestradiol) and genetic testing for suspected Kallmann syndrome. CSF beta-2 transferrin for suspected leak. COVID-19 and influenza testing early in the illness.

Limitations. Subjective reports correlate poorly with objective smell tests. A normal MRI does not exclude post-viral or traumatic loss.

Safety advice. Smoke and gas alarms, checking food dates and storage, labelling, and care with cleaning agents.

Conductive causes.

• Rhinitis and rhinosinusitis: intranasal corticosteroid (mometasone 50 micrograms, 2 sprays to each nostril once daily, maximum 200 micrograms daily), saline irrigation, and treatment of allergy.
• Nasal polyps: prednisolone 30 mg orally daily for 7 to 14 days (check glucose, blood pressure and mood), then topical steroid irrigation or drops, with ENT referral for surgery when medical treatment fails over 3 months. Biologic therapy (dupilumab, omalizumab, mepolizumab) by specialists for refractory polyps.
• Rhinitis medicamentosa: stop decongestant.
• Structural disease and tumours: ENT surgical referral and biopsy.

Post-viral olfactory loss.

• Olfactory training: sniff four distinct odours (rose, lemon, clove, eucalyptus) twice daily, 20 seconds each, for at least 3 to 6 months. Evidence supports improvement and recovery rates are higher with training, and many patients recover over months.
• Short course oral prednisolone (30 to 40 mg orally daily for 7 to 10 days) may be tried in the early phase; evidence is limited and risks include hyperglycaemia and mood change.
• Intranasal corticosteroid when sinonasal inflammation is present. Platelet rich plasma injections and other treatments are experimental.
• Vitamin A, zinc and other supplements have no proven benefit unless a deficiency exists.

Traumatic loss. Olfactory training, and treat sinonasal contribution. Recovery is limited, and CSF leak needs neurosurgical repair.

Drug induced loss. Stop or substitute the offending drug when possible.

Deficiency states and systemic disease. Treat diabetes, hypothyroidism (levothyroxine 1.6 micrograms/kg orally daily; start at 25 to 50 micrograms in older adults and heart disease), vitamin B12 deficiency (hydroxocobalamin 1 mg IM on alternate days until no further improvement, up to 3 weeks, then 1 mg every 2 months) and zinc deficiency (zinc sulphate 220 mg orally once daily with food).

Neurodegenerative disease. Neurology referral. No treatment restores smell.

Kallmann syndrome. Endocrine referral for hormone replacement (testosterone in males, oestrogen and progestogen in females, gonadotropin therapy for fertility).

Counselling. Explain the course, expected partial recovery in many post-viral cases, nutritional and safety implications, and screening for depression, which is common.

Monitoring. Review at 3 months with repeat smell testing, and at 6 to 12 months for persistent loss. MRI for loss persisting over 3 months without cause.

Referral and escalation. ENT within 2 weeks for unilateral loss, mass or blood stained discharge. Neurology for neurological features or cognitive change. Endocrinology for Kallmann syndrome. Neurosurgery for CSF leak or skull base lesion.

Admission criteria. CSF leak with meningitis, intracranial tumour with deficits, or severe head injury.

Discharge and safety netting. Return for new headache, visual change, nosebleeds, one sided obstruction, clear fluid from the nose after injury, cognitive change or worsening mood.