• Primary oesophageal motility disorder characterised by the absence of oesophageal peristalsis and impairment of lower oesophageal sphincter relaxation.
  • Rare- affects 1 in 100000 per year
  • Infection with Trypansoma cruzi which causes Chagas' disease causes a syndrome clinically indistinguishable from achalasia


  • The lower oesophageal sphincter is regulated by excitatory (e.g. acetylcholine, substance P) and inhibitory (e.g. NO, vasoactive intestinal peptide) neurotransmitters
    • In achalasia, there seems to be a lack of nonadrenergic, noncholinergic, inhibitory ganglion cells (cholinergic activity is preserved), possibly as a result of an inflammatory process
    • the result is a chronically non-relaxing LOS


  • Most commonly- dysphagia
    • Affecting solid foods more than soft more than liquids
    • Develops gradually, commonly intermittent
    • Can be eased by drinking fluids, by standing up/moving about etc
  • Regurgitation and dyspepsia are also common.  Chest pain may occur due to oesophageal spasm, but heartburn is rare (LOS tone is increased so acid is unlikely to reflux)
  • Later in the disease, aspiration can be common (nocturnal pulmonary aspiration)


  • Barium swallow is usually performed before endoscopy (for risk of rupture)
    • Classic dilated oesophagus which is tapered distally (said to resemble a bird’s beak); only a small amount of contrast is able to pass through into the stomach
    • Acha
  • Manometry
    • Gold standard
    • Diagnostic features include high resting pressure of the LOS, incomplete relaxation on swallowing and absent peristalsis
    • Without any features on manometry, diagnosis is instead ‘pseudoachalasia’
      • Consider other causes e.g. malignancy, strictures
  • Endoscopy may be useful in evaluating causes of pseudoachalasia but is not necessarily required for true achalasia


  • Surgical myotomy is preferred if the patient is fit enough
    • requires fundoplication at the same time to avoid serious reflux disease post-operatively
    • PPIs are often prescribed post-operatively for this reason also
  • For older patients/patient not suitable for general anaesthetic etc, endoscopic pneumatic dilation may be used
  • Endoscopic botox injection is rarely used.  Other medical options include calcium channel blockers and nitrates but these are rarely successful
  • NB Endoscopic myotomy methods are now beginning to be used

Pharyngeal Pouch (Zenker’s diverticulum)

  • Rare- affects 1 in 100000 people, most commonly in middle-old age (>60) and in men (5:1)
  • Occurs most commonly as a result of in-coordination of swallowing within the pharynx, most likely due to upper oesophageal sphincter dysfunction
    • this leads to herniation of the oesophagus through the cricopharygeus muscle and formation of a pouch
  • Most patients are asymptomatic/minimally symptomatic
    • Dysphagia and regurgitation are the most common symptoms (95%)- patient often feels like food is getting lodged in the throat and food can be regurgitated, particularly on lying down
    • Halitosis is also common, as food can get trapped there
    • Chronic cough, aspiration pneumonia or unexplained weight loss can also feature
      • As such, cancer and strictures cannot be ruled out
  • Barium swallow is preferred over endoscopy as this may perforate the pouch
    • Nasopharyngoscopy may show salivary pooling in the piriform fossa
  • In patients with troublesome symptoms, surgical myotomy (diverticulotomy) +/- resection (diverticulectomy) can be performed
    • Endoscopic procedures may also be performed for small pouches where there is the clinical expertise

Gastro-oesophageal reflux disease (GORD)

Dyspepsia: upper abdominal discomfort/pain, often described as burning, heaviness or ache, often related to eating and may be accompanied by other symptoms such as nausea, fullness or belching.

GORD: reflux of gastric contents into the oesophagus, causing symptoms such as heartburn and acid regurgitation.


  •  More common in men than in women
  • Around 25% of adults experience heartburn and 5% have daily symptoms
    • Around a quarter of these patients will see a doctor.
  • More common in patients with asthma and more common in overweight individuals


  • Reduced lower oesophageal sphincter tone
  • Increase abdominal pressure
  • Smoking, alcohol, fatty foods, coffee
  • Pregnancy
  • Obesity
  • Tight clothes/big meals
  • Hiatus hernia; systemic sclerosis and post oesophageal surgery for achalasia


  • Heartburn/dyspepsia
    • Discomfort/pain may be epigastric, retrosternally or in the throat
    • Related to meals, and often made worse by lying down, stooping, straining etc
    • It may be relieved by certain drinks e.g. milk, or by antacids
  • Other symptoms include
    • “Acid brash”- acid reflux causing an acidic ‘taste’ in the back of the mouth
    • “Water brash”- essentially excess salivation (response of the salivary glands in response to acid in the gullet)
    • Odynophagia (painful swallowing) or dysphagia (feeling that the food is stuck in the gullet)
    • Food or acid reflux
  • Atypical features include
    • Chest pain- may be severe.  GORD can often mimic ACS, particularly in older patients
      • thought to perhaps be due to oesophageal spasm
    • Chronic hoarseness of the voice
    • recurrent chest infections
    • Chronic cough
    • Wheeze/shortness of breath
  • Examination is usually normal if symptoms are not present at the time.  They may or may not have a ‘tender’ epigastric area (palpation may worsen symptoms).

Differential Diagnosis

  • Peptic ulcer disease
  • Drugs e.g. NSAIDs
  • Infection (esp immunocompromised patients)
  • Oesophageal spasm
  • GI cancers


  • Bloods: FBC (?anaemia – peptic ulcer; leucopenia- infection
  • NB Many patients in whom there is a high clinical suspicion of GORD won’t require endoscopy, but for those with severe/problematic disease, or with red flag symptoms e.g. weight loss, dysphagia, anaemia, etc- further investigations may be used
  • Endoscopy is investigation of choice (NB can be normal)
    • NB This investigation may not show any abnormality (e.g. oesophagitis).  This DOES NOT exclude GORD as the diagnosis, it is mainly used for treatment planning (see below)
    • Patients should not have been taking any drugs that may contribute to symptoms for two weeks or more prior to endoscopy
  • You can also use pH measurements to check the acidity in the oesophagus/mouth
    • 24 hour pH monitoring- where the pH is <4 for >6-7% of the study time- suggestive of GORD
  • Urea breath test for H pylori infection can be used if a peptic ulcer is suspected
  • Finally, if there is suspicion of a motility disorder (e.g. if the patient is complaining more of dysphagia or odynophagia with reflux), consider imaging/manometry tests


  • If there are underlying causes and/or contributing factors, make sure to reverse these where possible e.g.
    • Drugs e.g. NSAIDs, calcium channel blockers, nitrates, theophyllines, bisphophonates, steroids
    • H pylori infection
    • Obesity
    • Diet (fatty food, spicy food, fizzy drinks etc) and eating before bed/large meals
    • Alcohol, smoking
  • Antacids/alginates e.g.
  • Proton pump inhibitors
    • trial for a minimum of 4 weeks at a reasonable dose then treat at the lowest therapeutic dose thereafter (if successful)
    • If the patient doesn’t have any relief, the dose can be doubled for a further month or an H2-receptor antagonist can tried
  • Other drugs that can be tried are prokinetics e.g. metoclopramide
  • Surgery may be used for patients with a hiatus hernia.  Occasionally, fundoplication can be performed in other patients with refractory symptoms.  However,


  • Barrett’s Oesophagus and Oesophageal adenocarcinoma
  • Oesophageal ulcers and/or haemorrhage
  • Oesophageal strictures
  • Aspiration pneumonia
  • Poor oral health (due to acid) e.g. caries/tooth decay, gingivitis, halitosis


Primary hyperthyroidism: excess of thyroid hormone due to an abnormality of the thyroid gland.

Secondary hyperthyroidism: excess of thyroid hormone due to abnormal stimulation of a normal thyroid gland.

Thyrotoxicosis (vs hyperthyroidism): thyrotoxicosis can be excess circulating hormone of any source; hyperthyroidism is a result of excess production of new thyroid hormone.

Background and Epidemiology

  • Overt (clinical) hyperthyroidism is thought to affect ~1.9% of women (0.8/1000/year) and 0.16% of men (0.14/1000/year)
    • Subclinical hyperthyroidism is likely to be higher


There are a wide range of symptoms and signs to possibly find in a patient with thyrotoxicosis:

  • Thyroid enlargement
    • Diffuse, unilateral, nodular
  • Dyspnoea, palpitations
    • sinus tachycardia, atrial fibrillation, heart failure, resting tachycardia, use-dependent oedema
  • Hyperactivity, emotional lability, insomnia, irritability, nervousness, anxiety, agitation
    • tremor
  • Exercise intolerance, fatigue, muscle (mainly proximal) weakness
    • Muscle wasting/weakness, proximal myopathy, hyperreflexia
  • Change in bowel habit (increased/diarrhoea)
  • Heat intolerance, increased sweating
    • Warm, moist skin (excess sweating- diaphoresis)
  • Increased appetite, weight change (loss or gain or stable despite intake change)
  • Infertility, oligomenorrhoea, amenorrhoea
  • Polyuria, thirst, generalised itch
    • Skin changes e.g. onycholysis, urticaria, diffuse pigmentation, diffuse non-scarring alopecia, palmar erythema,
  • Reduced libido; Gynaecomastia

NB There are also some symptoms/signs specific to different causes (see below)


  • FBC, U&Es, LFTs
  • TFTs
    • TSH normal- no hyperthyroidism
    • TSH increased- Check free T4
      • Normal/low- consider hypothyroidism
      • Free T4 high- secondary hyperthyroidism (rare)
        • MRI/CT head/pituitary- look for tumour or lesion that might be the cause
      • TSH Low- check free T4
        • Normal- measure free T3
          • Normal- likely transient cause e.g. acute illness
          • High- T3 toxicosis (occurs in 10-15%)- further investigation
    • If TSH is low and free T3/T4 is high, consider a thyroid uptake scan 
      • Low uptake
        • Single cold nodule – consider thyroid cancer
        • Diffusely low uptake- measure thyroglobulin
          • If this is high- possible thyroiditis (ectopic thyroid hormone production or excess iodine also possible)
          • If low, it is likely that exogenous hormone is the cause.
      • High uptake
        • Diffusely hot- Grave’s disease
        • Single hot nodule- Toxic thyroid adenoma
        • Multiple hot nodules- Toxic multinodular goitre
  • Thyroid Antibodies
    • thy


  • Grave’s disease
  • Toxic Thyroid adenoma
    • <5% of all cases of thyrotoxicosis
    • More common in women and >40 years old
    • Solitary adenoma which secretes thyroid hormone (predominantly T3 thyrotoxicosis- and usually mild thyrotoxicosis.)
      • Inhibits TSH secretion and therefore the rest of the thyroid gland shuts down (shrinks/atrophy)
    • Symptoms are usually mild.  The patient may have a palpable nodule or it may only be detected by thyroid scintigraphy (uptake scan)
    • Treatment is usually radioiodine (because the inactive ‘normal’ thyroid fails to take up any radioactive iodine)
      • Risk of post-treatment hypothyroidism is relatively low
      • Surgery is an alternative
  • Toxic Multinodular goitre
    • Accounts for about 30-40% of hyperthyroid cases.
    • Also most common in women >40 years.  May develop from a diffuse (and often euthyroid) goitre.
    • In a similar fashion with toxic nodules- multinodular goitre releases thyroid hormone and suppresses TSH secretion
    • Patients can be asymptomatic (free T3/T4 may be within normal levels as well but TSH will always be low)
    • There will usually be a goitre present with palpable nodules
    • Treatment is usually with radioiodine (even if asymptomatic it may be appropriate if TSH is chronically and markedly suppressed as this can be a risk factor for AF and osteoporosis)
      • Risk of post-treatment hypothyroidism is relatively low
      • Surgery is an option for large, problematic (e.g. tracheal compression) goitres
  • Thyroiditis
  • TSH-secreting tumour
    • Extremely rare
    • Consider if there are features of hyperthyroidism with raised TSH and raised thyroid hormone
    • There may also be clinical signs of tumour (~80% are macroadenomas) e.g. visual disturbance, headaches
    • MRI/CT imaging is the investigation of choice
    • Treatment can be with octreotide and antithyroid drugs (+/- beta-blocker) but the mainstay is surgical resection
  • Amiodarone
    • Often causes a thyroiditis type picture

Thyroiditis (Subacute/Transient) or De Quervain’s thyroiditis


  • Self-limiting condition which characteristically has three clinical phases
    1. Hyperthyroidism
    2. Hypothyroidism
    3. Euthyroidism
  • May be a cause of up to 15% of patients with thyrotoxicosis and up to 10% of patients with hypothyroidism.
  • There are also three different pathological types of subacute thyroiditis
    • Subacute granulomatous thyroiditis (de Quervain’s or subacute painful)
    • Subacute Lymphocytic thyroiditis (painless)
    • Subacute post-partum thyroiditis
  • As with other thyroid conditions, women are more at risk than men (3-5:1).  Average age of onset is 30-50 years old.

Aetiology/Risk factors

  • Subacute granulomatous
    • Most commonly follows an episode of viral illness
    • There are genetic factors that may predispose e.g. HLA-B35
  • Lymphocytic
    • Thought to be, at least in part, an autoimmune process, as antibodies (in particular antimicrosomal antibodies and antithyroid peroxidase antibodies) are often present in these patients
    • Can also occur in patients receiving or having received amiodarone or interferon-α treatment. (can present >2 years later)
  • Post-partum
    • Also thought to be autoimmune in nature
    • Much rarer in countries with iodine-rich diets
  • Other causes include radiotherapy and infective thyroiditis (rare- only really ever seen in immunodeficient patients)


  • The inflammatory process occurs.  This causes swelling/enlargement of the thyroid gland.  As the process continues, the thyroid follicles are broken down and thyroid hormone is inadvertently released.
  • Hyperthyroid phase occurs at this stage.  As the amount of T3/T4 is depleted, patient typically then become euthyroid and then hypothyroid, before recovering to a euthyroid state.
  • Histologically, there is a mixture of acute, subacute and chronic granulomatous, inflammatory change associated with follicle destruction.


  • Typically, patients present with a prodromal illness or infection
    • May complain of flu-like symptoms e.g. fever, malaise, myalgia, sore-throat, anorexia, fatigue etc
    • May have been diagnosed with infection e.g. pharyngitis, measles, mumps etc
    • NB constitutional symptoms may continue with the thyroiditis (even if symptoms of specific infection had resolved)
  • Often the thyroid enlarges (often firm enlargement and diffuse)
    • In painful (granulomatous) thyroiditis, the thyroid is usually acutely painful/tender (gradual/sudden)
      • this can start on one site and spread or begin bilaterally
    • Other local symptoms that can occur include
      • dysphagia
      • hoarseness
  • NB in post-partum thyroiditis, there is firm, painless enlargement of the thyroid which can occur up to 6 months after birth
  • Symptoms of hyperthyroidism and/or hypothyroidism


  • FBC
    • WCC may or may not be raised.  CRP can be slightly elevated
  • Thyroid function tests
    • NB cf toxic nodular disease, if there is hyperthyroidism- fT4 is usually disproportionately elevated compared to fT3
  • Radioiodine scan (decreased uptake can distinguish thyroiditis from Grave’s disease – which may otherwise be indistinguishable from painless thyroiditis)


  • Because thyroiditis is often self-limiting, no treatment is routinely required (important to diagnose correctly over Graves regarding unnecessary treatment)
  • If the patient remains chronically hypothyroid after the episode, replacement thyroxine can be considered.
  • If acute hyperthyroid symptoms are really troublesome, beta-blockers can be used for symptomatic relief

Grave’s Disease

An autoimmune disease characterised by hyperthyroidism due to thyroid-stimulating antibodies.

Background and Epidemiology

  • Most common cause of primary hyperthyroidism (60-90%)
  • Can be associated with other autoimmune disorders (as part of polyglandular autoimmune syndromes) e.g. pernicious anaemia, type I diabetes, vitiligo, autoimmune adrenal insufficiency, systemic sclerosis, myaesthenia gravis, Sjogren’s syndrome, rheumatoid arthritis and SLE
  • More common in women (7.5:1), commonly aged 30-50 but general incidence is around 0.8-2/1000 per year


  • There is a strong genetic/hereditary component
    • Polymorphisms in MHC (HLA-DRB1 and HLA-DQB1); CTLA4, PTPN22, TSHR1 and FCRL3
  • It is hypothesised that susceptible individuals may begin produce autoantibodies after an infection (possible that some bacteria e.g. E coli and Yersinia, may have TSHR-like proteins on their cell wall; antibodies produced to fight off this infection may cross react with TSHRs
  • Autoantibodies against the TSH-receptor (TRABs) are produced and stimulate the thyroid gland to produce and release thyroid hormone
    • Not subject to negative feedback
  • The goitre seen in Grave’s is caused not just by the action of TRABs but also due to inflammation/lymphocytic infiltration.  Likewise, the ophthalmopathy of thyroid eye disease is due to retro-orbital swelling from lymphocyte and macrophage infiltration (secondary to autoantibody-mediated inflammatory process: orbital fibroblasts are known to express TSHR so this can bind to TRABs)
  • NB Smoking is not directly associated with the risk of Grave’s BUT if the patient does have graves, symptoms (particularly eye disease) is worse
    • due to increased inflammatory changes


  • In addition to symptoms/signs of hyperthyroidism (see here), Graves’ disease also causes a number of other features specific to this diagnosis
    • Diffusely enlarged thyroid gland
      • there may also be a thyroid bruit (vascular bruit)
      • usually soft and symmetrical
    • Ophthalmopathy (thyroid eye disease)
      • Early thyroid eye disease can be misdiagnosed as conjunctivitis
      • Patients may have
        • Tearing, gritty sensation, photophobia, eye pain (particularly on movement but also retro-orbital pain), exophthalmos, diplopia, visual loss, impaired eye movements
    • Thyroid dermopathy
      • inflammatory reaction in the skin can cause non-pitting, pink/purple plaques
      • most commonly over the pretibial region (pretibial myxoedema) and over sites of previous trauma
      • oedema can also present in the eyelid and cause further eyelid retraction and lid lag.
    • Thyroid acropachy
      • Again, inflammatory process of the fingertips/nails (indistinguishable from finger clubbing) 


  • TRAb antibody test positive and clinical features of hyperthyroidism
    • Including low TSH and high free T3/T4
  • Thyroid uptake scan
    • Diffuse high-uptake


  • In general, younger patients (<40) are prescribed anti-thyroid drugs:
      • Carbimazole
      • Side effects of CARMBIMAZOLE include nausea and GI upset (common).  Rash/Pruritus- allergy is relatively common (change to PTU).  AGRANULOCYTOSIS is a rare but serious side effect.  If the patient develops a severe sore throat, check FBC and stop immediately
      • Propylthiouracil
    • NB Usually start with high doses and titrate down to an appropriate maintenance dose
      • A beta-blocker may help to control symptoms of palpitations and tachycardia in the mean time.
  • Older patients with Grave’s tend to have radio-iodine treatment
    • May worsen eye disease
  • Occasionally, Grave’s can be treated with surgery, although this isn’t common
  • Advise to stop smoking
  • Glucocorticoids may improve opthalmopathy symptoms
    • Rarely, radiotherapy can be used to aid opthalmopathy (surgery is last resort)


  • The majority of patients who receive surgery/radioiodine will end up with a permanent reduction in thyroid function and so may require thyroid hormone supplementation

Thyroid Physiology and Thyroid Function tests

Thyroid Anatomy

  • Two lobes in the anterior neck on either side of the trachea inferior to the thyroid cartilage. About 25-30g.  About 5cm long
    • Joint by the isthmus and may have an additional ‘pyramidal lobe’ (remnant of the hypoglossal tract)
  • Lies deep to the sternothyroid and sternohyoid muscles; parathyroid glands usually lie between the posterior border of the thyroid glands and its sheath; internal jugular vein and common carotids lie postero-laterally; the recurrent laryngeal nerve lies between the trachea and the thyroid
  • Highly vascular- supplied by the
    • superior thyroid artery
      • first branch of ECA
    • inferior thyroid arterie
      • branch of the thyrocervical trunk of the subclavian
  • Venous drainage from the superior, middle (both into the internal jugular) and inferior (drains into the brachio-cephalic veins) thyroid veins


  • Thyroid tissue is subdivided by capsular septa into lobules containing follicles
    • spherical structures filled with colloid of mostly iodinated thyroglobulin
    • surrounded by follicular cells (produce hormone and Tg), between which are parafollicular cells (including C cells- produce calcitonin)
    • Follicles are the functional unit of the thyroid.  Production of thyroglobulin and thyroid hormone occurs.
      • Involves active transportation of iodine into the cells (stimulated by TSH), oxidation of iodine to I- (by thyroid peroxidase), iodination of tyrosine residues on Tg molecule

Thyroid Physiology

  • The thyroid produces and secretes 2 metabolic hormones
    • Thyroxin (T4) and triiodothyronine (T3)
      • Act on many different cellular processes- main effect is an increase in metabolism
        • Effects can be split into two groups
          • Those that take minutes to hours after receptor binding (i.e. do not require protein synthesis)
            • e.g. activation of the membrane bound Na/K/ATPase and mitochondrial oxygen consumption
          • Those that take hours and require new protein synthesis.
            • e.g. effects on growth, proliferation, maturation etc
        • In general, in normal, low concentrations, the effect is anabolic i.e. stimulates growth.  In abnormally high concentrations, the effect is catabolic i.e. increased energy expenditure and protein breakdown.
  • Under homeostatic control via a negative feedback loop involving the hypothalamic-pituitary-thyroid axis:
    • Thyroid releasing hormone is produced by the hypothalamus
      • Release is pulsatile and circadian
        • Downregulated by free T3 levels
      • Stimulates TSH formation and release
    • Thyroid stimulating hormone is produced by the anterior pituitary by thyrothroph cells
      • Release is
        • upregulated by TRH
        • downregulated by T4 and T3
      • Stimulates thyroid hormone production and release (possibly indirectly via stimulation of iodine uptake, colloid pino/endocytosis and growth of the thyroid gland)
  • A note about thyroid hormone in the plasma and action
    • More than 99% of T3 and T4 is bound to plasma carrier proteins (they are both highly water soluble and would otherwise be delivered straight into the tissues)
      • Majority bound to thyroxine binding globulin (TBG) (~75%)
        • Others include thyroxine binding pre-albumin and albumin, as well as HDLs
    • Only unbound (free) hormone has metabolic activity and physiological effects
      • ~0.03% of T4 and 0.3% of T3
      • NB T3 is 3-7 times more potent than T4
    • T4 is the primary secretory product of the thyroid gland (~70-90μg/day).
    • T3 is derived from 2 sources
      • About 20% directly secreted from the thyroid
      • About 80% (of 15-30μg total) is produced via deiodination of T4 in the periphery (mainly liver)
        • NB In the liver, about 40% is converted to T3, another 40% to reverse T3 (metabolically inactive) and 20% is excreted via bile
    • It is important to measure TBG, total bound thyroxine and free thyroxine in order to judge abnormalities of thyroid function (as TBG can be affected by a number of things e.g. drugs (OCP, clofibrate, heroin/methodone, tamoxifen etc) and conditions e.g. liver disease

Thyroid Function tests

  • Remember to always base test requests/interpretation of results on the clinical history and examination
  • Hyperthyroidism
    • Low TSH and High T3/T4
      • Common causes
        • Primary hyperthyroidism e.g. Graves’; multinodular goitre; toxic nodule
      • Other common causes with low-radio-iodine uptake
        • transient thyroiditis (post-partum, post-viral, DeQuervain’s)
      • Rare
        • Over medication with thyroxine
        • Iodine induced
        • Amiodarone tx
        • Ectopic thyroid tissue
  • ‘Normal’ (Investigation for other symptom e.g. AF) or hypothyroidism
    • Low TSH and normal T3/T4
      • Subclinical hyperthyroidism or medication (thyroxine) for hyperthyroidism
      • Rarer causes include steroids, dopamine/dobutamine infusions
      • Acute illness can also cause this picture
    • Low TSH and low T3/T4
      • Treatment for hyperthyroidism or acute illness are most common causes
      • Rarely, pituitary disease or congenital TSH/TRH deficiencies
  • Hypothyroidism
    • Raised TSH, Low T3/T4
      • Common
        • Chronic autoimmun thyroiditis
        • Post radio-iodine/thyroidectomy
        • Transient thyroiditis (hypothyroid phase)
      • Other
        • Post radiotherapy
        • Drugs e.g. amiodarone, lithium
        • Iodine deficiency
        • Congenital causes
    • Raised TSH, normal T3/4
      • Subclinical autoimmune hypothyroidism
      • Drugs e.g. amiodarone, sertraline
      • Recovery post acute-illness
    • Raised TSH, raised T3/4
      • Unusual- causes include amiodarone, TSH-secreting tumours (pituitary), interfering antibodies (test picks up mimics of TSH/T3/T4)

Bowen’s disease (SCC in situ)

Background and Epidemiology

  • Although commonly called SCC in situ, Bowen’s disease differs slightly in its aetiology and pathophysiology.  (AK is a truer representation of SCC in situ).
  • It is estimated to have an incidence of around 15/100000 per year but can be higher.
  • Unlike actinic keratosis, it is much more common in women


  • Similar to that of SCC and AK but (in contrast to AK) there is full thickness epidermal involvement (atypical keratinocytes) and mitotic figures can be present.
    • Bowen’s disease is also thought to have an inflammatory (as well as genetic) component
      • Quite often, there is accompanying inflammatory, mostly lymphocytic, infiltrate in the superficial dermis

Risk factors/Aetiology

  • Age
  • UV exposure
  • Other irradiation damage e.g. radiotherapy, photochemotherapy
  • Carcinogens e.g. arsenic (could be used as an ingredient in old ointments for psoriasis/asthma
  • There is a significant associated with the HPV virus (typically HPV-16)
  • Immunosuppression
  • Chronic skin injury/conditions e.g. seborrhoeic keratosis


  • Slowly growing, usually solitary, patch/plaque with clearly defined borders, scaling/hyperkeratosis, and an erythematous (pink/red) surface.
    • Usually several centimetres in size.
    • Usually otherwise asymptomatic
    • Most commonly found on the lower limbs (shins are common).  Otherwise, the head/neck and upper limbs can be sites.
      • Occasionally, bowen’s disease may be found in areas not exposed to the sun e.g. sub-/peri-ungual, genital (on the penis this is known as Queyrat’s erythroplasia) or perianal
  • Under the dermatoscope:
    • Characterised by scaly surface and glomerularly arranged vessels (clustering throughout the lesion)


  • Skin biopsy should be taken for the definitive diagnosis


  • In contract to SCC and AK, topical therapy e.g. topical 5-fluorouracil (first line) or imiquimod treatments are preferred.
  • Cryotherapy may be used as an alternative, particularly in smaller lesions
  • Other managements e.g. surgery/curettage and PDT can also be used (the latter particularly for immunosuppressed patients; the former may be suitable for small lesions)
  • Radiotherapy can be used if the area is unsuitable for other treatment options

Actinic (or Solar) Keratosis

Pre-neoplastic lesion of sun-damaged skin.


  • Caused by abnormal skin development due to UV radiation.
  • Considered a precancerous form of SCC
    • Most common precancerous skin lesion
    • It is thought that around 65% of primary SCC and 35% of primary BCC arise from lesions of actinic keratosis.
    • The number of patients that progress from AK to SCC is not fully known but estimated between 1-10% (most do not progress)
  • More common in men than women


  • UV-radiation induced gene mutations in e.g. p53 or p16 tumour regulating genes
  • In many ways the histopathology of AK is the same as that of SCC, only milder
    • Atypical, pleaomorphic keratinocytes at the basal layer that can extend into the more superficial layers.  The epidermis is abnormal (acanthosis, parakeratosis and dyskeratosis)- but by definition this is not full thickness abnormality.  Mitotic figures may be present.

Risk factors/Aetiology

  • Type I skin type
  • Age
  • UV exposure (including proximity to the equator)
    • Consider lifestyle e.g. occupation, holidays, tanning booths etc
  • Immunosuppression


  • Multiple flat or thickened, scaly/warty, skin-coloured/erythematous lesion
    • Most <1cm wide
  • Commonly on areas of sun exposure e.g. bald scalp, ear, face, nose, back of hands, upper limbs
  • Under the dermatoscope actinic keratosis can have the following features
    • Facial
      • erythema, with a marked pink-red ‘pseudonetwork’ surrounding hair follicles
        • fine, linear-wavy vessels surround the hair follicles too
        • the hair-follicle opening itself can be surrounded by a white-yellow halo (keratotic plug)
      • white-yellow surface scale
      • => often described as a ‘strawberry’ appearance
      • NB lesions can also be pigmented and misdiagnosed- presence of the pseudonetwork is often helpful
    • Non-facial
      • dense surface scale with some dot vessels

Differential Diagnosis

  • lentigo maligna
  • seborrhoeic keratosis
  • Basal cell carcinoma
  • Bowen’s disease
    • tends to be a large plaque with a sharp outline, most commonly found on the lower limbs


  • Skin biopsy is only really required if this is suspicious of malignancy.
  • Treatment isn’t necessarily required, but options are
    • topical treatment
      • 5-fluorouracil
      • Imiquimod
      • Diclofenac
    • Others
      • Cryosurgery
      • Photodynamic therapy
      • Excision
  • Advise the patient about UV protection.

Squamous cell skin cancer


  • Tumour originating from the keratinocytes in the skin
  • Second most common skin cancer after BCC (accounts for ~20% of non-melanomatous skin cancer)
  • Incidence is rising.  Currently around 17 per 100,000 people per year (around 10,000 cases per year)

Risk Factors

  • UV exposure
  • Immunosuppression
  • Exposure to radiation or carcinogens
  • HPV infection (warts)
  • Fair (type I) skin
  • Chronic inflammation
  • Development from pre-malignant disease e.g. Bowen’s disease, actinic keratosis


  • Loss of function mutations in p53 (e.g. caused by UV-light)
  • Other genetic neoplastic changes e.g. mutations in BCL2, RAS and eGFR
  • Typical histological features include
    • nuclear atypia, frequent mitotic figures, cellular pleomorphism, hyper- and parakeratosis (retaining the nuclei in the stratum corneum), a disorganised progression of cells from basal to apical layers of the epidermis
    • SCC can be graded based on histology as
      • Well differentiated (normal looking nuclei with abundant cytoplasm and extracellular keratin)
      • Moderately differentiated
      • Poorly differentiated (many atypical nuclei and mitotic figures; >nuclear:cytoplasmic ratio; less keratinisation)


  • Usually on sun-exposed areas e.g. bald scalp, ears, face and hands
  • Variable presentation
    • from rapid development of a painful keratotic nodule
      • may be over an area of pre-existing dysplasia
    • to new, erythematous, infiltrated, warty nodule/plaque that can ulcerate
    • Usually, a slowly-growing, tender, scaly/crusted lump


  • Excisional biopsy is the management of choice for most patients
    • As with BCC, Mohs surgery can be considered for tumours that are high risk or those in difficult areas
    • Radiotherapy may be required in unresectable tumours
    • Cryotherapy is an option for small, well-defined and low risk tumours