Acute pyelonephritis is a bacterial infection of the kidney parenchyma that can cause organ damage and be life-threatening. It is associated with systemic symptoms and flank pain which are not usually present in lower urinary tract infections. Early recognition and aggressive management of sepsis is required to prevent serious complications. Patients should be urgently referred to the emergency department if they are unwell and showing signs of sepsis (hypotension, tachycardia, hypothermia or pyrexia, signs of systemic illness such as rigors). Patients at higher risk of severe disease (elderly comorbid patients or those in other risk groups) may also warrant urgent referral.

History and examination are sufficient to diagnose osteoarthritis (OA) in most cases. Joint pain and stiffness (lasting no longer than 30 minutes in the morning), which is worse with weight bearing or usage, in a patient aged 45 or over, is indicative of OA. Muscle strengthening and aerobic exercise remain core treatments and exercise should be tailored to the individual. Pharmacological therapy should be used ‘at the lowest effective dose for the shortest possible time’ in combination with non-pharmacological therapy. Referral for joint replacement should be based on severity of symptoms and failure of conservative treatment, and should not be influenced by factors such as age, gender or comorbidities.

Although classically asthma is characterised by variable airflow obstruction and inflammation, leading to symptoms of breathlessness, wheeze, chest tightness and cough, it can present with a broad spectrum of symptoms that have a wide differential diagnosis. Clinical examination is frequently entirely normal and clinical history alone is not sufficient to diagnose asthma. There is over-reliance on short-acting beta-agonists and a widespread underuse of inhaled corticosteroids. In mild to moderate disease, fluctuating symptoms can lead to an over-reliance on short-acting reliever treatment at the expense of preventative inhaled steroids. This risks the concealment of deteriorating symptoms and the potential build-up of critical airways inflammation.

Preterm birth is a key determinant of adverse infant outcomes. A previous preterm birth is the single most important risk factor; however, the majority of preterm births occur in first time mothers. Modifiable risk factors should be identified and addressed, both opportunistically during prepregnancy consultations and at the booking visit. Women at high and moderate risk of preterm birth should be identified at the booking visit and referred to the local or tertiary preterm birth prevention clinic by 12 weeks.

Autoimmune destruction of the pancreatic beta cells leads to onset of type 1 diabetes (T1D). Although T1D can occur at any age, 85% of patients are diagnosed under the age of 20. Patients usually present with typical features of thirst, polyuria, weight loss and hyperglycaemia, with or without ketosis. In adults, symptoms are similar to those in children but there is a wider differential diagnosis. The presence of certain other autoimmune diseases, in the patient or relatives, is highly suggestive of an autoimmune cause of diabetes.

Low back pain is a symptom with a range of possible causes. Most cases are either mechanical in origin or neurogenic. However, rarer secondary causes must also be considered to ensure serious pathology is not missed. A focused musculoskeletal and neurological examination should be carried out. If both red flag symptoms and radicular features are absent, the back pain is likely to be of mechanical origin and in many cases will resolve with simple management.

Pulmonary rehabilitation improves breathlessness and health status in a range of conditions. It is a multifaceted programme of exercise training, disease education and self-management. Many programmes also provide psychological support and advice about breathing control training and nutrition. All patients who complete a pulmonary rehabilitation programme should have a written programme for ongoing exercise, with or without a referral to a community exercise facility. Patients may need to repeat the programme after 1-2 years, as the benefits may diminish over that period.

Type 2 diabetes reduces life expectancy by up to 10 years and around half of all patients die from cardiovascular disease (CVD). NICE advises that in patients whose QRISK2 score is 10% or higher and those with established CVD, an SGLT2 inhibitor should be used early on. For those patients initially assessed as not having established CVD or a QRISK2 score of 10% or higher, at each assessment two factors should be considered: if the HbA_1c target has been achieved and whether their CVD risk has changed.

More than 50% of renal cell carcinoma (RCC) cases are detected incidentally on imaging, often at a late stage. Patients may present with mass-related localised symptoms, constitutional symptoms and symptoms of metastatic disease. Ultrasound is the optimal initial investigation to screen individuals with suspected RCC. NICE recommends that patients aged 45 and over with isolated haematuria, in the absence (or following treatment) of a urinary tract infection, are referred for investigation of a potential renal malignancy.

Although there are a number of phenotypes of Alzheimer’s disease dementia, by far the most common is amnestic. Impairment of new learning, forgetting recent activities or conversations, is particularly prominent whereas memories of early life and knowledge are not affected until later. The posterior cortical atrophy variant is characterised by prominent visual disturbance not explained by other pathology; the logopenic primary progressive aphasia variant is dominated by language deficits. Visual and language symptoms can be present relatively early in the amnestic variant, but are not predominant.

Symptoms of deep vein thrombosis (DVT) typically consist of unilateral leg swelling, redness, pain and discomfort, and are usually of acute onset. However, symptoms are variable and can be minimal in up to 50% of patients. The symptoms and signs are non-specific, and only a third of patients with a clinical suspicion of DVT have the condition. A thorough history and careful examination will help rule out other causes. Patients with suspected DVT should have a Wells score performed in combination with a D-dimer assay. 

Postherpetic neuralgia (PHN) is defined as pain persisting for greater than three months following the onset or healing of herpes zoster. It may present as a continuation of pain following the acute pain of acute zoster reactivation, commonly referred to as shingles, or following a period of being pain free. Rarely PHN may develop without a classical herpetic rash (zoster sine herpete).

Basal cell carcinoma (BCC) is a slow growing, locally invasive malignant epidermal skin tumour. Metastases are very rare and morbidity results from the localised destruction of tissue particularly on the head and neck. Suspected high-risk BCCs on the central face (around the eyes, nose, lips and ears) should be referred for an urgent opinion. BCCs most commonly present on the head and neck and sun-exposed sites but may occur at any body site. Patients will often report a non-healing wound that recurrently bleeds, crusts and scabs but does not heal.

Exposure to intermittent intense sunlight and sunburn (especially in childhood) are the most common modifiable risk factors for melanoma. Individuals with lighter skin tones are at greatest risk (Fitzpatrick skin types I-II). A history of melanoma increases the risk of a further melanoma eight-fold. Approximately 5-10% of melanoma cases are estimated to be familial. The 7-point checklist is recommended by NICE to help determine when a referral is indicated. However, checklists should not be used in isolation as some melanomas will be missed. Amelanotic melanomas, estimated at 10% of all melanomas, remain a challenge. 

Nausea and vomiting in pregnancy is very common and affects up to 80% of women. It is usually mild and resolves during the first half of pregnancy. However, in a small proportion of women (0.3–3.6%), symptoms are so severe that they lead to dehydration, electrolyte imbalance and weight loss. This is known as hyperemesis gravidarum. Women who have persistent symptoms into the second trimester of pregnancy should have consultant-led antenatal care and serial fetal growth ultrasound.

Cutaneous squamous cell carcinoma (cSCC) can develop de novo or from pre-existing chronic actinic damage, although the probability and speed of transition from actinic keratosis to cSCC is highly variable. The occurrence of cSCC is related to chronic UV exposure, particularly occupational exposure. Risk factors include fairer skin, significant exposure to sunlight or PUVA. Incidence is also significantly increased in patients who are immunosuppressed. All patients with suspected cSCC should be referred via the two-week wait pathway to dermatology.

Primary hyperparathyroidism (PHPT) most commonly occurs sporadically, typically caused by a parathyroid adenoma. Such cases are more common in women and with increasing age. Other risk factors include neck irradiation and lithium use. Inherited cases can occur in relation to genetic conditions including MEN1. Parathyroid carcinoma is vanishingly rare. PHPT may present with symptoms of hypercalcaemia (such as thirst, excessive urination or constipation), or evidence of potential end organ effects. However, the most common presentation is an incidental finding of a raised albumin-adjusted serum calcium.

Anaphylaxis is a serious potentially life-threatening systemic hypersensitivity characterised by airway, breathing and/or circulation compromise. Where feasible, any trigger should be removed. Hypotensive patients should be placed in a supine position with or without leg elevation but those with airway or breathing compromise may prefer to sit up. A standard adrenaline dose of 500 micrograms (0.5 ml of 1:1,000 adrenaline) is recommended in adults, whereas dosage varies in children depending on age/weight. 

Many patients with chronic hepatitis C virus (HCV) infection remain unaware of their diagnosis until they present with decompensated chronic liver disease or hepatocellular carcinoma (HCC). Prolonged infection with HCV predicts increased risk of progression to cirrhosis and increased HCC risk. Consequently, all patients with a positive HCV RNA test should be considered for referral to specialist hepatology or infectious diseases services for prompt treatment and attempted cure.

The International Association for the Study of Pain has developed a new classification system for chronic pain. A fundamental distinction is made between chronic primary pain and chronic secondary pain. Chronic primary pain is defined as pain in one or more anatomical regions that persists for longer than three months, is associated with disability or emotional distress, not better accounted for by another diagnosis of chronic pain. Chronic primary pain is subdivided into five categories. Chronic secondary pain is pain secondary to an underlying disease.

Bronchiectasis increases in incidence and prevalence with age affecting > 1% of people aged 70 and older. It is associated with significant morbidity and mortality. Bronchiectasis can be congenital or acquired following a lung-damaging event such as severe infection, or have an immunological aetiology, but the cause is not always found. It can be associated with inflammatory bowel disease, rheumatoid arthritis and other connective tissue diseases. Most patients with bronchiectasis present with persistent cough and daily sputum production. Bronchiectasis is diagnosed using high resolution CT.

Psoriatic arthritis (PsA) is a seronegative systemic disease that belongs to the family of spondyloarthropathies. Its worldwide prevalence ranges from 0.05% to 1%, and it appears in 10-40% of patients with skin psoriasis; however, it is believed to be underdiagnosed. More than 80% of patients who are diagnosed with PsA already have skin disease, mainly in the form of plaque psoriasis. However, 15% of patients present with musculoskeletal involvement prior to psoriasis which makes the diagnosis of PsA challenging. It is important to do a thorough clinical assessment, take a family history and actively look for evidence of psoriasis: this includes examining nails, the scalp, intergluteal region and umbilicus.

In the UK, at least 100,000 people have an acute stroke each year. A first ever transient ischaemic attack (TIA) affects around 50 people per 100,000 per year and around 15% of people who have a first stroke have had a preceding TIA. Patients with a suspected TIA should be referred immediately for specialist assessment and investigation, to be seen within 24 hours of onset of symptoms. Patients with a suspected stroke should be admitted immediately to hospital, ideally to an acute stroke unit. Patients with a suspected TIA who have a bleeding disorder or are taking an anticoagulant should also be admitted to an acute stroke unit as haemorrhage must be excluded.

Multiple sclerosis (MS) is the leading cause of non-traumatic neurological disability in young adults. Between 1990 and 2016, the UK prevalence increased by 28%, due to earlier diagnosis and increased survival. The female to male ratio is 2:1, and patients have a minimally reduced life expectancy. Diagnostic criteria require that clinical, radiological and laboratory signs of MS are disseminated in both time and space. Diagnosis is based on a combination of features (relapses and clinical progression), MRI findings, and CSF analysis.

Diverticular disease is characterised by intermittent abdominal pain in the left lower quadrant of the abdomen associated with constipation or diarrhoea. It can be difficult to differentiate from other conditions such as colitis, irritable bowel syndrome and colorectal cancer. Acute diverticulitis typically presents with severe constant left lower quadrant pain associated with signs of systemic upset such as fever. The patient may also have a change in bowel habit or rectal bleeding. On examination there is tenderness in the left lower quadrant. Acute diverticulitis may be complicated by perforation, abscess, fistula formation, bleeding or a stricture.

In a large meta-analysis, the prevalence of depression was twice as common in adolescents (5.7%) than children (2.8%). The 2:1 female to male ratio of depression seen in adults becomes apparent from the age of 12 years. Three quarters of children aged 3-17 years with depression also have anxiety, and almost half have associated behaviour problems. Depression should be treated by child and adolescent mental health services unless the episode is mild and of < 2-3 months’ duration.

Hyperthyroidism affects up to 2% of women in the UK and the US and is ten times more common in women than men. In regions with normal levels of iodine, hyperthyroidism is caused by Graves’ disease in 60-80% of cases. In regions with iodine insufficiency toxic nodular disease (caused by toxic adenomas) accounts for 50% of cases of hyperthyroidism and this aetiology is more common in older people. Patients with hyperthyroidism should be referred. Overt hypothyroidism is present in 0.2-5% of the population and is more common in women and with advancing age. It is usually managed in primary care and rarely requires referral.

Peanut allergy currently affects around 2% of the population. It is the most common cause of fatal food related anaphylaxis. Most patients (80%) will have long-lived peanut allergy. Primary peanut allergy most commonly presents in the first 5 years of life after the first known exposure to peanut. Clinical features are those of an IgE-mediated reaction. All patients with a history suggestive of peanut allergy should be referred to an allergy clinic for comprehensive assessment and management.

Anxiety disorders are common, highly treatable conditions, with a strong evidence base for cognitive behaviour therapy. In a recent population sample of the under 12s, only 65% of those who met criteria for a diagnosis of an anxiety disorder had sought professional help and only 3.4% had received an evidence-based treatment. Assessment should include an exploration of neurodevelopmental conditions, drug and alcohol misuse, and speech and language problems.

Dermoscopy as a clinical tool was developed primarily to evaluate pigmented lesions, particularly suspected melanoma. It is also useful in many other clinical situations, including the evaluation of a variety of benign and malignant skin tumours, inflammatory conditions, hair disorders, connective tissue diseases, and common infections and infestations. Images can be archived or exported for a second opinion and can also be shown to, and discussed with, the patient.

NICE stipulates that two of the following are required for the diagnosis of hypertension: clinic blood pressure (BP) 140/90 mmHg or higher and ambulatory BP monitoring daytime average or home BP monitoring average 135/85 mmHg or higher. Evaluation of newly diagnosed hypertension includes an assessment of underlying cardiovascular disease (CVD) risk and target organ damage. Treatment threshold varies with underlying risk. For those at lower risk (< 10% risk of a CVD event over 10 years), drug treatment is not recommended below 160/100 mmHg.

After a potentially traumatic event (PTE), many individuals experience either no distress or only transient distress, while others suffer considerable morbidity and may develop post-traumatic stress disorder (PTSD). Around one-third of people experiencing a PTE will develop PTSD, though this varies depending on the type of traumatic event and rates of PTSD are higher with type 2 trauma. Type 2 trauma involves repeated traumatic experiences over extended periods. Although PTSD symptoms can be present acutely, the diagnosis requires the persistence of symptoms for at least one month and the symptoms should cause functional impairment.

Pulmonary hypertension (PH) is a haemodynamic state where the mean pulmonary artery pressure measured at cardiac catheterisation is 25 mmHg or more. Precapillary PH arises from increased resistance to blood flow in the pulmonary arterioles and postcapillary PH from elevated left atrial pressure. In postcapillary PH the cause is left heart disease whereas precapillary PH may be caused by any other form of PH. Patients develop symptoms only when the disease is advanced. Symptoms at presentation are non specific. Adults almost always present with breathlessness and may also complain of exercise-induced dizziness or syncope and angina. An echocardiogram is the best investigation to ascertain the probability of PH.

NICE recommends urgent referral via a suspected cancer referral pathway to the two week wait service if: chest X-ray findings suggest lung cancer or if patients aged 40 and over have unexplained haemoptysis. However, studies have indicated that around 20-25% of patients with confirmed lung cancer may have a chest X-ray reported as normal and this figure may be higher for early stage lung cancers. Therefore, the National Optimal Lung Cancer Pathway recommends that where there is a high suspicion of underlying malignancy (but the chest X-ray is normal), GPs should refer patients directly for a CT scan.

Epidermolysis bullosa (EB) arises from mutations within genes encoding for different proteins which contribute to the structural integrity of the epidermis and basement membrane zone. There are four major EB types: EB simplex (EBS), dystrophic EB (DEB), junctional EB (JEB) and Kindler syndrome. The main cutaneous features of inherited EB are mechanical fragility of the skin and formation of blisters and erosions with minimal trauma. The initial diagnosis of EB is based on the patient’s personal and family history and examination. Skin biopsies are taken from newly induced blisters to identify the level of skin cleavage which helps to determine the subtype.

In patients with suspected dementia, the history should cover cognitive, behavioural and psychological symptoms, and the impact symptoms have on daily life. A physical examination is necessary to look for any focal neurological signs and to exclude any visual or auditory problems. Baseline blood tests should be carried out. A medication review should be undertaken as many commonly prescribed drugs have anticholinergic effects which can exacerbate cognitive impairment. A brief cognitive screening test should be performed before referral to a memory clinic.

Hidradenitis suppurativa is a chronic inflammatory skin disease which can develop from puberty onwards, with painful, deep-seated inflamed lesions at characteristic sites. It is much more common in smokers. There is also a clear link with obesity. Patients complain of recurring painful boils in one or more of the typical areas. In women the most common areas affected are under the arms, under the breasts, in the groin, medial thighs, or suprapubic area and in men the armpits, buttocks and perianal area. Hidradenitis suppurativa is diagnosed on history and clinical appearance.

Hypertension is the most common medical complication of pregnancy, affecting 8-10% of pregnancies in the UK. It is associated with risks to both the woman and the fetus, with increased risks of pre-eclampsia, preterm delivery, fetal growth restriction, placental abruption and perinatal death. Any new onset of hypertension after 20 weeks or symptoms or signs suspicious of pre-eclampsia should be referred for same day assessment at a secondary care antenatal assessment unit.

Common mental health disorders affect around one in five women during pregnancy and the first year following childbirth. Depression and anxiety disorders are the most prevalent mental health disorders during this period as they are at other times of life. It is important to distinguish postnatal depression from baby blues, which is common and requires no treatment, although it is a potential risk factor for postnatal depression. Postpartum psychosis affects 1 in 1,000 women and can develop very quickly in the first two weeks postpartum, often requiring urgent admission to a specialised mother and baby unit. One in six women with bipolar disorder will develop postpartum psychosis. 

A detailed patient history is key to the assessment of patients with urinary incontinence and to guiding initial investigation and management. Clinical examination should include abdominal palpation to assess for masses, including an enlarged bladder. Visual inspection of the perineum and vagina helps determine whether the patient may be hypo-oestrogenic and can confirm the presence and grading of pelvic organ prolapse. Digital vaginal examination enables detection of masses, and an assessment of pelvic floor muscle strength. Urinalysis should also be carried out. Most patients will have either stress, urgency, or mixed urinary incontinence.

For obese women the risks of adverse outcomes during pregnancy, for both the mother and her child, are significantly higher than for the general population. In 2016, 21% of all women attending antenatal services in the UK were reported to have a BMI of 30 kg/m² or higher. In 2003-2005, 27% of all maternal deaths occurred in women with a BMI of 30 kg/m² or higher. Obesity increases the risk of venous thromboembolism, gestational diabetes, pre-eclampsia and hypertension. There is an increased likelihood of induction of labour, instrumental delivery and postpartum haemorrhage. The greatest effect on risk reduction is weight loss prior to conception.

COPD should be suspected in an older adult (at least 35 years old but typically more than 45 years old) who presents with symptoms such as breathlessness, wheeze, cough and sputum production and has one or more risk factors, typically current, or a past history of, cigarette smoking. A diagnosis should also be suspected when an individual with a risk factor develops a lower respiratory tract infection requiring treatment. COPD is far more common in smokers of heroin and crack cocaine, in whom it occurs at a younger age.

Although patients can present with non-specific symptoms and minimal clinical signs, generally, in the community, patients with heart failure present with symptoms of dyspnoea or fluid retention. In order to confirm (or refute) the diagnosis, NICE recommends natriuretic peptide testing (ideally N-terminal pro B-type natriuretic peptide; NT-proBNP) in all patients with suspected heart failure. An NT-proBNP level > 2,000 ng/L is highly suggestive of heart failure and NICE recommends echocardiography and specialist review within 2 weeks. Conversely, an NT-proBNP level < 400 ng/L suggests that a diagnosis of heart failure is unlikely. Patients with an NT-proBNP of 400-2,000 ng/L should have echocardiography and specialist assessment within 6 weeks.

Rates of erectile dysfunction (ED) increase with age, with an estimated 70% of men aged 70 affected to some extent. ED is a significant predictor of underlying cardiovascular disease. In addition to the onset and duration of symptoms, important points in the history to clarify are: how the patient defines their ED, whether they have ever had erectile function, whether morning erections are preserved, the context of ED and recent sexual history. Men should be asked about symptoms of hypogonadism such as loss of libido or low energy levels. Cardiovascular risk should be evaluated.

Kidney transplantation is the optimum form of renal replacement therapy for suitable patients with end-stage renal disease. A successful transplant represents a much closer approximation to true renal replacement with excretion of waste products, regulation of electrolytes and other substances, than dialysis. The longer a recipient has been dialysis dependent before transplantation the poorer the outcome. Living donor transplantation is associated with better graft and patient survival than transplantation from a deceased donor. A genetic relationship with the recipient is not a prerequisite to becoming a living donor. Having a living donor offers the opportunity of pre-emptive transplant (i.e. avoidance of dialysis altogether).

Early recognition, prompt referral to secondary care and close monitoring for complications is important in improving outcomes in acute pancreatitis. The diagnosis of acute pancreatitis should be considered in any patient presenting with abdominal pain. The most common pattern of pain is severe epigastric pain that radiates to the back, is exacerbated by movement, and is alleviated by sitting forwards.

Juvenile idiopathic arthritis (JIA) affects approximately 1-4 per 1,000 children under the age of 16. Girls are more commonly affected than boys. It is a heterogeneous condition, even within JIA categories, ranging from insidious arthritis affecting one to two joints to florid and life-threatening systemic arthritis. All patients with suspected JIA should be referred urgently to a specialist paediatric rheumatology team. Coordinated, multidisciplinary care within a specialist team is required to achieve optimal outcomes.

Allergy to milk and egg are the two most prevalent food allergies in children. They are typically diagnosed in infancy and carry a good prognosis with the majority of cases resolving before the child reaches school age. Other allergies may present later in childhood and are more likely to persist. There is evidence of a causal link between early onset severe and widespread eczema that is unresponsive to moderate topical steroids and development of IgE mediated food allergy, in particular peanut allergy. The EAT study showed that infants who were weaned early and exposed to egg and peanut had a significant reduction in allergy to both foods.

The prevalence of hypertension increases with age and older people are likely to benefit more from BP reduction because of their high baseline cardiovascular risk. However, older people are a very heterogeneous group and a single BP target will not be appropriate for all. Current evidence is based on ambulatory or healthy older populations as patients with significant complex conditions were not represented in randomised clinical trials. 

The Landmark study, from 15 countries, reported that 94% of patients attending a GP with episodic disabling headache had migraine. Generally, an untreated migraine headache is moderate to severe and lasts for more than four hours. It is often pulsating, but patients may describe a feeling of ‘expanding pressure’ within the head. Most sufferers experience nausea although fewer patients actually vomit. Acute treatment should be taken as soon as a migraine headache starts to develop as later in the attack central sensitisation occurs and treatments become less effective.

Pelvic inflammatory disease (PID) is caused by infection ascending from the cervix. It can affect the uterus, fallopian tubes, ovaries, and peritoneum. Important sequelae include infertility, ectopic pregnancy and tubo-ovarian abscess. PID is associated with sexually transmitted infections. These are more prevalent in younger women. A diagnosis of PID should be considered in any sexually active woman with recent onset pelvic pain associated with tenderness on bimanual examination where other differentials have been excluded. Delay in commencing treatment for PID has been shown to increase the risk of long-term complications.

Itch is a common symptom of many dermatological conditions (e.g. eczema, urticaria and lichen planus) but can also be a manifestation of underlying systemic, neurological and psychological disorders, or an adverse reaction to medication. The assessment of patients with generalised itch but no rash requires a detailed history and examination to narrow the spectrum of potential causes. Examination should include inspection of the entire skin. Physical examination should include palpation for lymphadenopathy and organomegaly.

Oesophageal cancer commonly presents with dysphagia or odynophagia and can be associated with weight loss and vomiting. Referral for urgent endoscopy should always be considered in the presence of dysphagia regardless of previous history or medication. NICE recommends urgent referral (within 2 weeks) for direct access for upper GI endoscopy in patients with dysphagia and those aged 55 years or over with weight loss and any of the following: upper abdominal pain, reflux, or dyspepsia.

The clinical features of sepsis are: fever; tachycardia, with no other explanation; tachypnoea, with no other explanation; leukocytosis or leucopenia. To meet the International Pediatric Sepsis Consensus Conference definition, a patient should have two of these features, one of which should be fever or abnormal white cell count, in the presence of infection. Every time a child who has symptoms or signs suggestive of infection is assessed, it is important to consider whether this could be sepsis. This may seem obvious in a child presenting with fever, but not all children with sepsis present with high fever or focal signs.

While the three cardinal motor symptoms of Parkinson’s disease (PD), bradykinesia, rigidity and tremor, are key to the diagnosis of the condition, there is evidence that non-motor symptoms start long before motor features arise. Two of these in particular, REM sleep behaviour disorder and olfactory dysfunction, have been strongly associated with the development of PD. Non-motor symptoms are increasingly recognised as main features of PD with a high impact on quality of life. Their progression has been shown to be independent of motor deterioration. Sleep, GI and attention/memory problems become more prevalent over time, whereas psychiatric and cardiovascular problems become less prevalent.

Alopecia affects up to 50% of men and women at some time in their lives. In primary care the first step is to establish whether hair loss is focal or diffuse and if focal whether it is scarring or non scarring. It is usually possible to establish the pattern of hair loss from a combination of the history and clinical examination. Dermatoscopic examination and pull testing can be useful in confirming the diagnosis. If hair loss is accompanied by scaling or significant inflammation it is important to exclude infective causes.

The incidence of sepsis in the UK is estimated at 200,000 cases a year. Around 70% of cases of sepsis originate in the community. Most infections are self-limiting and can be managed outside hospital. However, patients with sepsis will deteriorate rapidly and each hour of delay to antibiotic administration is linked to decreased survival by 7.6%. Infants (< 1 year) and the elderly (> 75 years) seem to be far more likely to progress to sepsis than others. The assessment of sepsis in primary care should be standardised and include measurement of temperature, heart rate, respiratory rate, blood pressure, level of consciousness and oxygen saturation in young people and adults.

Atopic eczema is the most common endogenous type of eczema in infants and children and affects around 15-20% of school-age children in the UK. Its prevalence is highest in children under the age of two and subsequently diminishes with age. It has a chronic, relapsing course. An emergency referral to a dermatologist or paediatrician should be made via telephone when there is a suspicion of eczema herpeticum or eczema coxsackium. Other indications for referral include diagnostic uncertainty, recurrent secondary infection, when control remains poor despite topical treatments, and for patients with emotional distress or significant sleep disturbance.

Heart failure is a common, complex clinical syndrome resulting from the impaired ability of the heart to cope with the metabolic needs of the body, leading to breathlessness, fatigue and fluid retention. It is a progressive disease characterised by high levels of morbidity and mortality. Measuring plasma levels of natriuretic peptides is recommended for ruling out heart failure, as patients with normal levels are unlikely to have heart failure. An echocardiogram is indicated if the natriuretic peptides are elevated, or natriuretic peptide testing is not available.

Fibromyalgia is a chronic condition characterised by regional pain at multiple sites, non-restorative sleep and fatigue. In the UK, it is a common cause of musculoskeletal pain and significant disability, affecting around 2% of the population. It has a female preponderance with a female to male ratio of 7:1. Self-help strategies are important. There is strong evidence of benefit from a slow graded increase in daily aerobic exercise which can increase delta sleep and restore descending pain inhibition mechanisms. Sleep hygiene should also be considered to promote delta sleep.

Rheumatoid arthritis is a common, chronic systemic inflammatory disease of unclear aetiology leading to synovial hypertrophy and joint inflammation. It typically presents with symmetrical polyarthritis of small joints of the hands or feet, but can also involve larger joints, and have associated extra-articular manifestations. Diagnosis is based on duration of symptoms, joint distribution, level of inflammatory markers and autoantibodies. The presence of synovitis or effusion is essential for diagnosis. Early referral of patients with suspected synovitis results in significant improvements in long-term outcomes.

Diabetic neuropathy is thought to affect 1.9% of the world’s population and 50% of patients with a diagnosis of diabetes mellitus which would equate to 2.25 million people in the UK. The term diabetic neuropathy includes multiple distinct clinical entities that have been classified under the broad headings of focal and multifocal neuropathies and symmetrical neuropathies. Peripheral diabetic neuropathy, a chronic distal symmetrical predominantly sensory neuropathy, is the most common form of diabetic neuropathy. The common presentation is of painful symptoms originating in the feet, that then spread to the knees before involving the distal portion of the upper limbs in a ‘glove and stocking’ distribution.

More than 200 hereditary cancer susceptibility syndromes have been described, and it is thought that they account for 5-10% of all cancers. Many have dermatological manifestations (usually lesions, occasionally rashes) which frequently precede other systemic pathology. Dermatological signs are usually non-specific and often trivial in appearance, making their significance easy to overlook and a clinical diagnosis challenging.

Morbidity and mortality associated with cirrhosis are on the increase. Cirrhosis generally results from chronic liver damage over many years. Common causes include: alcohol misuse, hepatitis B (± delta) and hepatitis C and non-alcoholic fatty liver disease. Patients with confirmed cirrhosis should be assessed for potential complications (ascites, encephalopathy, oesophageal varices or hepatocellular carcinoma). Reviewing cirrhotic patients regularly in primary care provides a valuable opportunity to ensure hepatocellular carcinoma and variceal surveillance is being undertaken and to give advice on losing weight or reducing alcohol intake.

Actinic, or solar, keratosis is caused by chronic ultraviolet-induced damage to the epidermis. In the UK, 15-23% of individuals have actinic keratosis lesions. Dermatoscopy can be helpful in excluding signs of basal cell carcinoma when actinic keratosis is non-keratotic. It is always important to consider the possibility of squamous cell carcinoma. The principal indication for referral to secondary care is the possibility of cutaneous malignancy. However, widespread and severe actinic damage in immunosuppressed patients also warrants referral.

In type 2 diabetes regular physical activity totalling 30 minutes most days of the week improves muscle insulin sensitivity, lipid profile and blood pressure although a total of 60-75 minutes a day is required for weight reduction and better metabolic profiles. NICE guidelines acknowledge the need for individualised treatment targets. Lowering HbA_1c is beneficial in reducing microvascular complications and may have macrovascular benefits in the long term. However, intensive glycaemic control in the elderly with more advanced disease may not have similar benefits and poses a risk due to hypoglycaemia.

Bacterial meningitis and meningococcal sepsis are rare in adults. Any diagnostic delays with subsequent delay to treatment can have disastrous consequences. The classic triad of neck stiffness, fever and altered consciousness is present in < 50% of cases of bacterial meningitis. Patients with viral meningitis also present with signs of meningism (headache, neck stiffness and photophobia) possibly with additional non-specific symptoms such as diarrhoea or sore throat. Suspected cases of meningitis or meningococcal sepsis must be referred for further assessment and consideration of a lumbar puncture.

Type 2 or complex trauma results from multiple or repeated traumatic events occurring over extended periods. Complex trauma is often associated with other adversity and stressors such as neglect, loss or deprivation. For many individuals these traumas occur at a developmentally vulnerable time with the perpetrator often in a caregiving role. Patients who have experienced complex trauma should be assessed for the core symptoms of PTSD. In addition, patients should be assessed for disturbances in the three domains of emotional dysregulation, negative self-concept and interpersonal disturbances.

Erectile dysfunction (ED) has been shown to share risk factors with cardiovascular disease including age, diabetes mellitus, smoking, hypertension and hypercholesterolaemia, suggesting an underlying vascular pathology. Evidence reveals that there is a potential link between ED and subsequent development of coronary artery disease. ED itself may also increase cardiovascular risk. As ED often predates the development of coronary artery disease this provides GPs with a valuable window of opportunity for risk assessment, subsequent primary prevention and early referral to a cardiologist.

The most common cause of adolescent heel pain is calcaneal apophysitis also known as Sever’s disease. Sever’s disease, Osgood Schlatter’s disease (tibial tuberosity) and Sinding-Larsen Johansson syndrome (distal patella) are all overuse syndromes brought about by repetitive submaximal loading and microtrauma. They are, however, entirely self-limiting and resolve at skeletal maturity or earlier. Careful assessment is required to differentiate them from other rare pathologies.

Hidradenitis suppurativa affects the apocrine-bearing areas of the skin. The onset is variable but usually occurs in the second and third decades of life, coinciding with development of the apocrine glands. The condition is characterised by painful, inflammatory papules and nodules which frequently progress to form abscesses, sinus tracts and hypertrophic scars.The most important non-genetic factors implicated in hidradenitis suppurativa are obesity and smoking.

Thunderclap headache is a severe and acute headache that reaches maximum intensity in under one minute and lasts for more than five minutes. Thunderclap headaches may be associated with symptoms such as photophobia, nausea, vomiting, neck pain, focal neurological symptoms or loss of consciousness. Subarachnoid haemorrhage (SAH) accounts for 10-25% of all thunderclap headaches and, despite advances in medical technology, has a 90-day mortality of 30%. Up to a quarter of cases of SAH are misdiagnosed, often through failure to follow guidance.

There are two main types of oesophageal cancer, oesophageal squamous cell carcinoma and oesophageal adenocarcinoma. They present in the same manner and both carry a five-year survival of only 16%. Oesophageal cancer commonly presents with dysphagia or odynophagia. This can be associated with weight loss and vomiting. All patients with recent onset dysphagia should be referred for rapid access endoscopy. Referral for urgent endoscopy should still be considered in the presence of dysphagia regardless of previous history or medication. Dysphagia is not always present so all patients with alarm symptoms should be considered for endoscopy.

There is no standard definition regarding the severity of psoriasis, and a number of factors should be considered, including the extent and stability of skin disease, involvement of joints, response to treatment, and impact on quality of life. Erythrodermic psoriasis and pustular psoriasis are severe conditions and the patient may be systemically unwell and febrile.

Type 1 diabetes affects around 370,000 adults in the UK, about 10% of all those diagnosed with diabetes. In type 1 diabetes there is a lack of beta cell insulin secretion as a result of autoimmune destruction of the beta cells. However, patients are not affected by insulin resistance, and so do not routinely experience the features of metabolic syndrome that occur in type 2 diabetes. It is therefore important to classify the type of diabetes correctly and to recognise that type 1 diabetes is a condition with its own management requirements. Structured education is the cornerstone of care providing tools to allow effective self-management.