Whilst asthma and COPD are different diseases they cause similar symptoms, which can present a challenge in identifying which of the two diseases a patient is suffering from. COPD causes chronic symptoms and narrowed airways which do not respond to treatment to open them up. In the case of asthma the constriction of the airways through inflammation tends to come and go and treatment to reduce inflammation and to open up the airways usually works well.

COPD is more likely than asthma to cause a chronic cough with phlegm and is rare before the age of 35 whilst asthma is common in under-35s. Disturbed sleep caused by breathlessness and wheeze is more likely in cases of asthma, as is a history of allergies, eczema and hay fever. Differentiating between COPD and asthma requires a history of both symptoms and spirometry. The spirometry history should include post bronchodilator measurements, the degree of reversibility and, ideally, home monitoring which gives a history of diurnal variation.

Airflow Obstruction: Both asthma and COPD are characterised by airflow obstruction. Airflow obstruction is defined as a reduced FEV1 and a reduced FEV1/FVC ratio, such that FEV1 is less than 80% of that predicted, and FEV1/FVC is less than 0.7.

These episodes are usually associated with widespread, but variable, airflow obstruction within the lung that is often reversible either spontaneously or with treatment.

COPD: COPD is a chronic, slowly progressive disorder characterised by airflow obstruction (reduced FEV1 and FEV1/VC ratio) that does not change markedly over several months. The airflow obstruction is not fully reversible.

Spirometry COPD Asthma
VC Reduced Nearly normal
FEV1 Reduced Reduced in attack
FVC (or FEV6) Reduced Nearly normal
FEV1 Ratio
(of VC/FVC/FEV6) Reduced in attack

This man has a low FEV1 and FVC. His diffusions capacity is also low despite having a normal total lung capacity. These values confirm a diagnosis of COPD.

Felty syndrome is a severe subtype of seropositive Rheumatoid arthritis. Clinical triad consists of arthritis, splenomegaly, and neutropenia (leads to an increased risk of recurrent bacterial infections). Other symptoms include skin ulcers of the lower limbs (indicating vasculitis), hepatomegaly, fever, and chest pain (indicating pleuritis or pericarditis). It is associated with increased risk of developing non-Hodgkin lymphoma.

A study conducted showed that the average post smoking cessation weight gain was about 2 kg.
Withdrawal symptoms usually peak after 1–3 days and then decrease over a period of 3–4 weeks. After this time, the body has expelled most of the nicotine, and the withdrawal effects are mainly psychological.

Ramipril is an ACE inhibitor that blocks the conversion of angiotensin I to angiotensin II as well as preventing the breakdown of bradykinin, leading to blood vessel dilatation and decreased blood pressure. However, bradykinin also causes smooth muscles in the lungs to contract, so the build-up of bradykinin is thought to cause the dry cough that is a common side-effect in patients that are on ACE inhibitors.

The given clinical scenario is highly suggestive of a borderline personality disorder.

Borderline personality disorder is marked out by instability in moods, behaviour, and relationships. The diagnosis is confirmed by the presence of at least 5 of the following symptoms;
1) Extreme reactions including panic, depression, rage, or frantic actions to abandonment, whether real or perceived
2) A pattern of intense and stormy relationships with family, friends, and loved ones, often veering from extreme closeness and love to extreme dislike or anger
3) Distorted and unstable self-image or sense of self, which can result in sudden changes in feelings, opinions, values, or plans and goals for the future (such as school or career choices)
4) Impulsive and often dangerous behaviours, such as spending sprees, unsafe sex, substance abuse, reckless driving, and binge eating
5) Recurring suicidal behaviours or threats or self-harming behaviour, such as cutting, intense and highly changeable moods, with each episode lasting from a few hours to a few days
6) Chronic feelings of emptiness and/or boredom
7) Inappropriate, intense anger or problems controlling anger
8) Having stress-related paranoid thoughts or severe dissociative symptoms, such as feeling cut off from oneself, observing oneself from outside the body, or losing touch with reality.

Other options:
There are no features consistent with endogenous depression, such as early morning wakening or loss of appetite.
There are also no features consistent with hypomania such as pressure of speech, a flight of ideas, or over-exuberant behaviour.
The lack of history of drug abuse rules out drug-induced psychosis.
An anti-social personality disorder is characterized by a failure to conform to social norms and repeated lawbreaking. There is consistent irresponsibility, impulsivity, and disregard for both their safety and that of others. This is not the case in the given scenario.

Methotrexate lung disease (pneumonitis and fibrosis) is the specific etiological type of drug-induced lung disease. It can occur due to the administration of methotrexate which is an antimetabolite, which is given as disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis. The typical clinical symptoms include progressive shortness of breath and cough, often associated with fever. Hypoxemia and tachypnoea are always present and crackles are frequently audible. Symptoms typically manifest within months of starting therapy. Methotrexate withdrawal is indicated in such cases.

Illness anxiety disorder (IAD) is a recent term for what used to be diagnosed as hypochondriasis, or hypochondrial disorder. People diagnosed with IAD strongly believe they have a serious or life-threatening illness despite having no, or only mild, symptoms.

Symptoms of IAD may include:
-Excessive worry over having or getting a serious illness.
-Physical symptoms are not present or if present, only mild. If another illness is present, or there is a high risk for developing an illness, the person’s concern is out of proportion.
-High level of anxiety and alarm over personal health status.
-Excessive health-related behaviours (e.g., repeatedly checking body for signs of illness) or shows abnormal avoidance (e.g., avoiding doctors’ appointments and hospitals).
-Fear of illness is present for at least six months (but the specific disease that is feared may change over that time).
-Fear of illness is not due to another mental disorder.

Desmopressin test (done to differentiate nephrogenic diabetes insipidus from central diabetes insipidus), and serum lithium levels can together confirm a diagnosis of lithium-induced nephrogenic diabetes insipidus.

Bipolar disease is most often managed with mood stabilizers like lithium. This patient develops gastrointestinal symptoms followed by an acute confusional state associated with polyuria and polydipsia. These symptoms are suggestive of diabetes insipidus.

In a case where these symptoms occur in a bipolar patient under treatment, lithium-induced nephrogenic diabetes insipidus should be considered as the most probable cause.

Lithium intoxication can present with symptoms of nausea, vomiting, mental dullness, action tremor, weakness, ataxia, slurred speech, blurred vision, dizziness, especially vertical nystagmus and stupor or coma. Diffuse myoclonic twitching and nephrogenic diabetes insipidus can also occur. Such a clinical syndrome occurs above the serum level of lithium of 1.5–2.0 mEq/L.

Management:
– Correcting electrolyte abnormalities in patients with acute disease is critical and often life-saving.
– Treatment should be initiated with parenteral fluids to replete hypovolemia (normal saline at 200-250 mL/h), followed by administration of hypotonic fluid (0.5% normal saline).
– On the restoration of the volume status of the patient forced diuresis should be initiated by the administration of parenteral furosemide or bumetanide accompanied by continued intravenous hypotonic fluid administration to maintain volume status.
– Polyuria is managed with hydrochlorothiazide combined with amiloride, acetazolamide.

Pseudogout is a paroxysmal joint inflammation due to calcium pyrophosphate crystal deposition (calcium pyrophosphate dihydrate). Arthrocentesis should be performed, especially in acute cases.
Polarized light microscopy: detection of rhomboid-shaped, positively birefringent CPPD crystals.
Synovial fluid findings: 10,000-50,000 WBCs/μL with > 90% neutrophils.
X-ray findings: cartilage calcification of the affected joint (chondrocalcinosis).
Fibrocartilage (meniscus, annulus fibrosus of intervertebral disc) and hyaline cartilage (joint cartilage) may be affected.

The principal mechanism by which strontium inhibits osteoclast activity is by enhancing the secretion of osteoprotegerin (OPG) and by reducing the expression of the receptor activator of nuclear factor κB ligand (RANKL) in osteoblasts.

Osteoporosis is defined as low bone mineral density caused by altered bone microstructure ultimately predisposing patients to low-impact, fragility fractures.

Management:
Vitamin D and calcium supplementation should be offered to all women unless the clinician is confident they have adequate calcium intake and are vitamin D replete
Alendronate is the first-line treatment. Around 25% of patients cannot tolerate alendronate, usually due to upper gastrointestinal problems. These patients should be offered risedronate or etidronate.
Strontium ranelate and raloxifene are recommended if patients cannot tolerate bisphosphonates.
Other medications that are useful in the treatment of osteoporosis are denosumab, teriparatide, raloxifene, etc.

Acute angle closure glaucoma can manifests itself with severe headache, nausea or vomiting, very blurry or hazy vision, seeing rainbows or halos around lights and redness in the white part of the affected eye. It is caused by a rapid or sudden increase in pressure inside the eye – intraocular pressure (IOP). In order to establish the diagnosis and start treatment immediately, IOP should first be measured.

Botulinum toxin is a neurotoxic protein from Clostridium botulinum that causes flaccid paralysis as it acts by preventing the release of Ach at the neuromuscular joint. It is the first-line treatment for cervical dystonia (torticollis) because the condition is a neurological disorder characterised by unusual muscle contractions of the neck. With the use of Botulinum toxin, the contractions would be released.

The differential diagnosis of bilateral exercise-induced pain would include metabolic muscle disease, lumbar canal stenosis and intermittent claudication. The patient’s age, history and lack of other risk factors make the latter two options unlikely.

The syndrome described is in fact McArdle’s disease (myophosphorylase deficiency). This is a disorder of carbohydrate metabolism. Clinical features of pain and fatigue are precipitated in early exercise, as carbohydrates cannot be mobilized to provide an energy substrate to the muscle. With prolonged exercise, fatty acid metabolism provides energy, and symptoms lessen. The dark urine described is likely to represent myoglobinuria following rhabdomyolysis. Definitive diagnosis of most metabolic muscle diseases relies on muscle biopsy and enzyme analysis.

TNF-alpha inhibitors are known to ameliorate the symptoms and disease activity of Arthritis mutilans (a rare and severe form of psoriatic arthritis), by disabling the cytokines that are involved in inflammation and joint destruction. From the mentioned choices, this would be the most effective option. Methotrexate is the most commonly used DMARD, followed by sulfasalazine used in mild to moderate forms of psoriatic arthritis but has not shown much efficacy in arthritis mutilans. Phototherapy, narrowband UVB light therapy can be very effective in clearing skin lesions.

A lesion on the cavernous sinus would explain the palsy observed on the III and VI cranial nerves because the cranial nerves III, IV, V, and VI pass through the cavernous sinus. Pain in the eye is due to the nearby ophthalmic veins that feeds the cavernous sinus. Additionally, the lesions in the other structures would have presented with pupil abnormalities and less localized pain and symptoms.

Cystinuria is strongly suspected because of the recurrent passing of cystine stones and otherwise non-remarkable medical history of this young adult patient. Like Cystinuria, all the conditions listed are also inherited disorders, however, the other differentials usually present in the early years of childhood, usually with failure to thrive.

The given history suggests a small fibre painful peripheral sensory neuropathy, the most common cause of which is diabetes. Joint position sense and vibratory sensation are carried through large fibres, and therefore are not currently affected. Sensory nerves are affected more often than motor, so reflexes usually remain in tact.

Vitamin B12 deficiency causes impairment of joint position and vibratory sensation.

Chronic inflammatory demyelinating polyneuropathy (CIPD) causes a large fibre peripheral neuropathy with areflexia.

In syringomyelia there is impaired pain and temperature noted in the upper limbs.

Finally, with alcoholic polyneuropathy, all fibre types are affected (sensory and motor loss). It is usually gradual with long term alcohol abuse and may be accompanied by a nutritional deficiency. In addition, pain is a more dominant feature.

Beckwith-Wiedemann syndrome is a inherited condition associated with organomegaly, macroglossia, abdominal wall defects, Wilm’s tumour and neonatal hypoglycaemia. Wilm’s tumour is a kidney cancer that usually occurs in children. The causes are unknown, however, risk factors include race and family history. Of note, Wilm’s tumour can occur as part of the following syndromes: WAGR syndrome, Denys-Drash syndrome, and Beckwith-Wiedmann syndrome and not the other listed options in this question.

Ezetimibe is a cholesterol-lowering agent that acts to prevent cholesterol absorption by directly inhibiting cholesterol receptors on enterocytes.
It does not affect the absorption of drugs (e.g. digoxin, thyroxine) or fat-soluble vitamins (A, D and K) as the anion-exchange resins do. It does not affect the cytochrome P450 enzyme system.
The increased risk of myositis associated with the statins is not seen with ezetimibe.
The most common adverse effects include headache, runny nose, and sore throat.
Less common reactions include body aches, back pain, chest pain, diarrhoea, joint pain, fatigue, and weakness.

The NICE 2019 guidelines states that in patients who are uncontrolled with a SABA (Salbutamol) and ICS (Beclomethasone), LTRA should be added.
If asthma is uncontrolled in adults (aged 17 and over) on a low dose of ICS as maintenance therapy, offer a leukotriene receptor antagonist (LTRA) in addition to the ICS and review the response to treatment in 4 to 8 weeks.

In such a clinical scenario, NICE guidelines support initiating treatment with bisphosphonates without waiting for a DEXA scan.

Osteoporosis is defined as low bone mineral density caused by altered bone microstructure ultimately predisposing patients to low-impact, fragility fractures.

Management:
Vitamin D and calcium supplementation should be offered to all women unless the clinician is confident they have adequate calcium intake and are vitamin D replete
Alendronate is the first-line treatment. Around 25% of patients cannot tolerate alendronate, usually due to upper gastrointestinal problems. These patients should be offered risedronate or etidronate.
Strontium ranelate and raloxifene are recommended if patients cannot tolerate bisphosphonates.
Other medications that are useful in the treatment of osteoporosis are denosumab, teriparatide, raloxifene, etc.

Ataxic telangiectasia is an inherited combined immunodeficiency disorder that is characterised by cerebellar ataxia and telangiectasia as seen in this child, as well as frequent infections as noted in this child’s history. The other differentials would not present with this clinical picture:

Friedreich’s ataxia and Infantile-onset spinocerebellar ataxia do not present with immune problems, whereas Cerebral palsy and Di-George Syndrome do not present with ataxia.

The most common causes of a sudden painless loss of vision are:
– ischaemic optic neuropathy
– occlusion of central retinal vein or artery
– vitreous haemorrhage
– retinal detachment.
Central retinal artery occlusion is due to thromboembolism (from atherosclerosis) or arteritis (e.g. temporal arteritis). Features include afferent pupillary defects, and a ‘cherry red’ spot on a pale retina.

The Stages of COPD:
Mild COPD or Stage 1—Mild COPD with a FEV1 about 80 percent or more of normal.
Moderate COPD or Stage 2—Moderate COPD with a FEV1 between 50 and 80 percent of normal.
Severe COPD or Stage 3—Severe emphysema with a FEV1 between 30 and 50 percent of normal.
Very Severe COPD or Stage 4—Very severe or End-Stage COPD with a lower FEV1 than Stage 3, or people with low blood oxygen levels and a Stage 3 FEV1.

This patient has a FEV1 percent of 37 which falls within the stage 3 or severe COPD.
During stage 3 COPD, you will likely experience significant lung function impairment. Many patients will experience an increase in COPD flare-ups or exacerbations. For some people, the increase in flare-ups means they could need to be hospitalized at times as well.

Inhaled corticosteroid (ICS) use in combination with long-acting β2-agonists (LABAs) was shown to provide improved reductions in exacerbations, lung function, and health status. ICS-LABA combination therapy is currently recommended for patients with a history of exacerbations despite treatment with long-acting bronchodilators alone. The presence of eosinophilic bronchial inflammation, detected by high blood eosinophil levels or a history of asthma or asthma–COPD overlap, may define a population of patients in whom ICSs may be of particular benefit.

The Towards a Revolution in COPD Health (TORCH) trial was a pivotal, double-blind, placebo-controlled, randomized study comparing salmeterol plus fluticasone propionate (50 and 500 µg, respectively, taken twice daily) with each component alone and placebo over 3 years.26 Patients with COPD were enrolled if they had at least a 10-pack-year smoking history, FEV1 <60% predicted, and an FEV1:FVC ratio ≤0.70.26 Among 6,184 randomized patients, the risk of death was reduced by 17.5% with the ICS-LABA combination vs placebo (P=0.052). ICS-LABA significantly reduced the rate of exacerbations by 25% compared with placebo (P<0.001) and improved health status and FEV1 compared with either component alone or placebo.

Bronchiectasis is a long-term condition where the airways of the lungs become abnormally widened, leading to a build-up of excess mucus that can make the lungs more vulnerable to infection. The most common symptoms of bronchiectasis include:
– a persistent productive cough
– breathlessness.

The 3 most common causes in the UK are:
– a lung infection in the past, such as pneumonia or whooping cough, that damages the bronchi
– underlying problems with the immune system (the body’s defence against infection) that make the bronchi more vulnerable to damage from an infection
– allergic bronchopulmonary aspergillosis (ABPA) – an allergy to a certain type of fungi that can cause the bronchi to become inflamed if spores from the fungi are inhaled

In acute angle closure glaucoma (AACG) there is a rise in IOP secondary to an impairment of aqueous outflow. Management options include reducing aqueous secretions with acetazolamide and inducing pupillary constriction with topical pilocarpine.

Early morning waking is a highly suggestive feature of depression in this patient.

NICE use the DSM-IV criteria to grade depression:
1. Depressed mood most of the day, nearly every day
2. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day
3. Significant weight loss or weight gain when not dieting or decrease or increase in appetite nearly every day
4. Insomnia or hypersomnia nearly every day
5. Psychomotor agitation or retardation nearly every day
6. Fatigue or loss of energy nearly every day
7. Feelings of worthlessness or excessive or inappropriate guilt nearly every day
8. Diminished ability to think or concentrate, or indecisiveness nearly every day
9. Recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide

Subthreshold depressive symptoms: Fewer than 5 symptoms
Mild depression: Few, if any, symptoms over the 5 required to make the diagnosis, and symptoms result in only minor functional impairment
Moderate depression: Symptoms or functional impairment are between ‘mild’ and ‘severe’
Severe depression: Most symptoms and the symptoms markedly interfere with functioning. Can occur with or without psychotic symptoms.

Treatment of depression:
Psychotherapy (in the form of cognitive behavioural therapy or interpersonal therapy) alone or in combination with medications such as:
– Selective serotonin reuptake inhibitors (SSRIs)
– Serotonin/norepinephrine reuptake inhibitors (SNRIs)
– Atypical antidepressants
– Serotonin-Dopamine Activity Modulators (SDAMs)
– Tricyclic antidepressants (TCAs)

There is also empirical support for the ability of CBT to prevent relapse.

Electroconvulsive therapy is a useful treatment option for patients with severe depression refractory to medication or those with psychotic symptoms. The only absolute contraindications is raised intracranial pressure.

Side-effects:
Headache
Nausea
Short term memory impairment
Memory loss of events before ECT
Cardiac arrhythmia
Long-term side-effects: Impaired memory

The likely diagnosis in this case is Haemolytic Uremic Syndrome (HUS), which is generally seen in young children presenting with a triad of symptoms, namely: acute renal failure, microangiopathic haemolytic anaemia, and thrombocytopenia. The typical cause of HUS is ingestion of a strain of Escherichia coli.

Severe acute respiratory syndrome (SARS) is a viral respiratory illness caused by a coronavirus called SARS-associated coronavirus (SARS-CoV). SARS was first reported in Asia in February 2003.
In general, SARS begins with a high fever (temperature greater than 38.0°C). Other symptoms may include headache, an overall feeling of discomfort, and body aches. Some people also have mild respiratory symptoms at the outset. About 10 to 20 percent of patients have diarrhoea. After 2 to 7 days, SARS patients may develop a dry cough. Most patients develop pneumonia. 

Because of the patient’s history of chronic analgesic use of daily paracetamol intake, the most likely diagnosis of this case is Analgesic misuse headache. In these cases, the headache is only temporarily relieved by analgesics. Treatment involves gradual withdrawal of analgesics.