The cause for bone marrow suppression in this patient is most probably mercaptopurine toxicity.
Azathioprine is metabolized to 6-mercaptopurine (6-MP), which itself is metabolized by xanthine oxidase.
Xanthine oxidase inhibition by allopurinol leads to the accumulation of 6-MP which then precipitates bone marrow failure.
This may be potentially fatal if unrecognized.
Clinical presentation:
Toxicity symptoms include gastrointestinal symptoms, bradycardia, hepatotoxicity, myelosuppression.

The patient’s underlying arthritis has most likely led to Renal tubular acidosis RTA type 1, which presents with the following symptoms consistent with the presentation of the patient: Normal anion gap metabolic acidosis/acidaemia, hypokalaemia and hyperchloremia. Comparatively, the other conditions are ruled out because Aspirin and diabetic ketoacidosis is associated with a raised anion gap, Conn’s syndrome explains hypokalaemia but not the metabolic acidosis, and RTA type 4 is associated with hyperkalaemia.

Friedreich’s ataxia is an autosomal recessive disorder that usually begins before the end of the teens. It has an estimated prevalence in Europe of 1 in 50,000 and life expectancy is around 40–50 years. Neurological features include a progressive ataxia, cerebellar dysarthria, lower limb areflexia, decreased vibratory sensation and proprioception, and pyramidal weakness. Pes cavus and scoliosis are also both seen. Cardiomyopathy occurs in over 70% of cases. Less common features include optic atrophic, diabetes mellitus, and deafness.

Before the initiation of trastuzumab, an echocardiography is a must to rule out any pre-existing cardiac abnormalities as trastuzumab is cardiotoxic.

Trastuzumab (Herceptin) is a monoclonal antibody directed against the HER2/neu receptor. It is used mainly in metastatic breast cancer although some patients with early disease are now also given trastuzumab.

Adverse effects include:
Flu-like symptoms and diarrhoea are common.
Cardiotoxicity:
– Risk increases when anthracyclines are used concomitantly.
– Trastuzumab-induced cardiac dysfunctions are regarded as less severe and largely reversible because primary cardiomyocyte do not show ultrastructure changes unlike those associated with anthracycline-induced cardiotoxicity.
– Primary myocyte injury does not occur in patients who were treated with trastuzumab.

Salbutamol stimulates beta-2 adrenergic receptors, which are the predominant receptors in bronchial smooth muscle (beta-2 receptors are also present in the heart in a concentration between 10% and 50%).

Stimulation of beta-2 receptors leads to the activation of enzyme adenyl cyclase that forms cyclic AMP (adenosine-mono-phosphate) from ATP (adenosine-tri-phosphate). This increase of cyclic AMP relaxes bronchial smooth muscle and decrease airway resistance by lowering intracellular ionic calcium concentrations. Salbutamol relaxes the smooth muscles of airways, from trachea to terminal bronchioles.

Increased cyclic AMP concentrations also inhibits the release of bronchoconstrictor mediators such as histamine and leukotriene from the mast cells in the airway.

The patient’s history and presentation and familial history, meets the diagnostic criteria for Neurofibromatosis type I, presenting with neurofibromas noted in this patient as hyperpigmented macules and freckles, musculoskeletal disorders like the scoliosis in this case, and a familial history. Neurofibromatosis type I is caused by a mutation on Chromosome 17.

Temporal arteritis is a chronic large- and medium-sized vessel vasculitis that typically involves the temporal arteries. Classical symptoms include temporal headaches, jaw claudication, amaurosis fugax. Physical exam shows scalp tenderness, palpation of the temporal area may demonstrate an absent pulse, knot-like swelling and vision loss. Lab results reveal an increased erythematous sedimentation rate and C-reactive protein. Temporal artery biopsy confirms the diagnosis. Management approach: high-dose systemic corticosteroids should be promptly administered even before the diagnosis is established. Temporal artery biopsy confirms the diagnosis. Inability to manage this or administer glucocorticoids might lead to development of blindness.

Bronchopneumonia presents as a patchy consolidation involving one or more lobes, usually the dependent lung zones, a pattern attributable to aspiration of oropharyngeal contents.

Symptoms of bronchopneumonia may be like other types of pneumonia. This condition often begins with flu-like symptoms that can become more severe over a few days. The symptoms include:
– fever
– a cough that brings up mucus
– shortness of breath
– chest pain
– rapid breathing
– sweating
– chills
– headaches
– muscle aches
– pleurisy, or chest pain that results from inflammation due to excessive coughing
– fatigue
– confusion or delirium, especially in older people

There are several factors that can increase your risk of developing bronchopneumonia. These include:
– Age: People who are 65 years of age or older, and children who are 2 years or younger, have a higher risk for developing bronchopneumonia and complications from the condition.
– Environmental: People who work in, or often visit, hospital or nursing home facilities have a higher risk for developing bronchopneumonia.
– Lifestyle: Smoking, poor nutrition, and a history of heavy alcohol use can increase your risk for bronchopneumonia.
– Medical conditions: Having certain medical conditions can increase your risk for developing this type of pneumonia. These include: chronic lung disease, such as asthma or chronic obstructive pulmonary disease (COPD), HIV/AIDS, having a weakened immune system due to chemotherapy or the use of immunosuppressive drugs.

The pattern of muscle involvement seen with quadriceps and long-finger flexors is characteristic of inclusion body myositis, an inflammatory myopathy. Polymyositis is likely to cause a predominantly proximal weakness, associated with muscle pain. The signs and symptoms are not consistent with upper cord compression, as there would likely be sensory signs, reflex changes, and possible urinary symptoms. Motor neuron disease cannot be ruled out, but there are no findings of upper motor neuron or bulbar features.

CADASIL is the most common form of hereditary stroke disorder. This case has a strong history of migraine with aura with stroke-like episodes, characteristic of CADASIL. Additionally, there is positive family history of migraine and early dementia but no other vascular risk factors like hypertension, diabetes, or hypercholesterolaemia, which all confirm the suspicion of CADASIL, an arteriopathy where there is thickening of the smooth muscle cells in the blood vessels.

Meconium ileus equivalent (MIE) can be defined as a clinical manifestation in cystic fibrosis (CF) patients caused by acute intestinal obstruction by putty-like faecal material in the cecum or terminal ileum. A broader definition includes a more chronic condition in CF patients with abdominal pain and a coecal mass which may eventually pass spontaneously. The condition occurs only in CF patients with exocrine pancreatic insufficiency (EPI). It has not been seen in other CF patients nor in non-CF patients with EPI. The frequency of these symptoms has been reported as 2.4%-25%.

The treatment should primarily be non-operative. Specific treatment with N-acetylcysteine, administrated orally and/or as an enema is recommended. Enemas with the water soluble contrast medium, meglucamine diatrizoate (Gastrografin), provide an alternative form for treatment and can also serve diagnostic purposes. It is important that the physician is familiar with this disease entity and the appropriate treatment with the above mentioned drugs. Non-operative treatment is often effective, and dangerous complications following surgery can thus be avoided.

Triamterene is a potassium-sparing diuretic that can cause hyperkalaemia, therefore, it was stopped in this patient. With all other lab results returning normal values and a normal ECG, management will simply require repeating the U & E after one week since the Triamterene has already be stopped.

Lewy body dementia is an increasingly recognised cause of dementia, accounting for up to 20% of cases. The characteristic pathological feature is alpha-synuclein cytoplasmic inclusions (Lewy bodies) in the substantia nigra, paralimbic and neocortical areas. Neuroleptics should be avoided in Lewy body dementia as patients are extremely sensitive and may develop irreversible parkinsonism. Questions may give a history of a patient who has deteriorated following the introduction of an antipsychotic agent.

This case presents with symptoms and lab results suggestive of uremic pericarditis, which is an indication for immediate haemodialysis. Uremic pericarditis is caused by inflammation of the membranes of the pericardial sac, which usually resolves after a period of intensive dialysis.

The phrenic nerve provides the primary motor supply to the diaphragm, the major respiratory muscle.
Phrenic nerve paralysis is a rare cause of exertional dyspnoea that should be included in the differential diagnosis. Fluoroscopy is considered the most reliable way to document diaphragmatic paralysis. During fluoroscopy a patient is asked to sniff and there is a paradoxical rise of the paralysed hemidiaphragm. This is to confirm that the cause is due to paralysis rather than unilateral weakness.

Postmenopausal oestrogen therapy and hormone therapy are associated with an increased risk of thromboembolism. The relative risk seems to be even greater if the treated population has pre-existing risk factors for thromboembolism, such as obesity, immobilization, and fracture. Cor pulmonale can occur secondary to small recurrent pulmonary embolisms. Pneumonias and bronchiectasis usually present with purulent sputum, and in case of carcinoma there may be other associated symptoms like weight loss, etc.

Osteoarthritis (OA) is a disabling joint disease characterized by a noninflammatory degeneration of the joint complex (articular cartilage, subchondral bone, and synovium) that occurs with old age or from overuse. It mainly affects the weight-bearing and high-use joints, such as the hip, knee, hands, and vertebrae. Despite the widespread view that OA is a condition caused exclusively by degenerative “wear and tear” of the joints, newer research indicates a significant heterogeneity of causation, including pre-existing peculiarities of joint anatomy, genetics, local inflammation, mechanical forces, and biochemical processes that are affected by proinflammatory mediators and proteases. Major risk factors include advanced age, obesity, previous injuries, and asymmetrically stressed joints. In early-stage osteoarthritis, patients may complain of reduced range of motion, joint-stiffness, and pain that is aggravated with heavy use. As the disease advances, nagging pain may also occur during the night or at rest. Diagnosis is predominantly based on clinical and radiological findings. Classic radiographic features of OA do not necessarily correlate with clinical symptoms and appearance. RA involves proximal interphalangeal joints not distal. Gout occurs as a result of overproduction or underexcretion of uric acid and frequently involves first toe. Fibromyalgia is a disorder characterized by widespread musculoskeletal pain accompanied by fatigue, sleep, memory and mood issues.

Citalopram is an antidepressant medication that works in the brain. It is approved for the treatment of major depressive disorder (MDD). Stopping citalopram abruptly may result in one or more of the following withdrawal symptoms: irritability, nausea, feeling dizzy, vomiting, nightmares, headache, and/or paraesthesia (prickling, tingling sensation on the skin).

When discontinuing antidepressant treatment that has lasted for >3 weeks, gradually taper the dose (e.g., over 2 to 4 weeks) to minimize withdrawal symptoms and detect re-emerging symptoms. Reasons for a slower titration (e.g., over 4 weeks) include use of a drug with a half-life <24 hours (e.g., paroxetine, venlafaxine), prior history of antidepressant withdrawal symptoms, or high doses of antidepressants.

Ankylosing spondylitis (spondylarthritis) is a chronic inflammatory disease of the axial skeleton that leads to partial or even complete fusion and rigidity of the spine. Males are disproportionately affected and upwards of 90% of patients are positive for the HLA-B27 genotype, which predisposes to the disease. The most characteristic early finding is pain and stiffness in the neck and lower back, caused by inflammation of the vertebral column and the sacroiliac joints. The pain typically improves with activity and is especially prominent at night. Other articular findings include tenderness to percussion and displacement of the sacroiliac joints (Mennell’s sign), as well as limited spine mobility, which can progress to restrictive pulmonary disease.
The most common extra-articular manifestation is acute, unilateral anterior uveitis. Diagnosis is primarily based on symptoms and x-ray of the sacroiliac joints, with HLA-B27 testing and MRI reserved for inconclusive cases. There is no curative treatment, but regular physiotherapy can slow progression of the disease. Additionally, NSAIDs and/or tumour necrosis factor-α inhibitors may improve symptoms. In severe cases, surgery may be considered to improve quality of life. The spine adopts a bamboo shape, not lordosis. The pain usually improves as the day progresses. leg raise test causes pain in cases of meningitis etc not in this case.

The blood investigations in this patient reveal hyponatremia as well as hypokalaemia. Among the options provided, Bendroflumethiazide therapy can cause the above presentation with the electrolyte disturbances.
Note:
– Spironolactone is a potassium-sparing diuretic that is associated with hyperkalaemia.
– Enalapril therapy can cause side effects of dizziness, hypotension, cough, and rarely a rash.
– Felodipine therapy can cause side effects of dizziness, headache, cough, and palpitations.

Aortic dissection is defined as separation of the layers within the aortic wall. Tears in the intimal layer result in the propagation of dissection (proximally or distally) secondary to blood entering the intima-media space. This can be caused as a result of both congenital or acquired factors like chronic uncontrolled hypertension. This patient shows no sign of hypertension but his physical examination hints towards Marfan Syndrome. Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder affecting the microfibrils and elastin in connective tissue throughout the body. MFS is associated with pathological manifestations in the cardiovascular system (e.g., mitral valve prolapse, aortic aneurysm, and dissection), the musculoskeletal system (e.g., tall stature with disproportionately long extremities, joint hypermobility), and the eyes (e.g., subluxation of the lens of the eye). Decreased collagen production occurs in ageing, hydroxylation defects are present in vitamin C deficiency, copper deficiency affecting lysyl oxidase enzyme occurs in Menke’s disease.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare presynaptic disorder of neuromuscular transmission in which release of acetylcholine (ACh) is impaired, causing a unique set of clinical characteristics, which include proximal muscle weakness, depressed tendon reflexes, post-tetanic potentiation, and autonomic changes.

In 40% of patients with LEMS, cancer is present when the weakness begins or is found later. This is usually a small cell lung cancer (SCLC). However, LEMS has also been associated with non-SCLC, lymphosarcoma, malignant thymoma, or carcinoma of the breast, stomach, colon, prostate, bladder, kidney, or gallbladder.

In patients with acute renal tubular necrosis, infection in the form of gram-negative septicaemia is the most common cause of death, especially while the patient is awaiting spontaneous recovery of their renal function.

The presentation of the patient is typical of chronic lithium toxicity (due to the presence of mainly neurological manifestations). Additional to the blood investigations mentioned, urine analysis, electrolyte levels, and renal function should also be performed. A low urine Anion gap and a low urine specific gravity are highly suggestive of lithium toxicity.
ECG obtained in this patient is likely to show: nonspecific, diffuse ST segment depression with T wave inversion.
Acute lithium toxicity presents with more GI manifestations while, the clinical features of chronic lithium toxicity are mainly neurological and can include:
Coarse tremors (fine tremors are seen in therapeutic levels), hyperreflexia, acute confusion, seizures, and coma.
The management of lithium toxicity is as follows:
Immediate GI decontamination with gastric lavage (in case of acute intoxication)
Saline Administrations: the goal of saline administration is to restore GFR, normalize urine output and enhance lithium clearance.
Haemodialysis remains the mainstay treatment for lithium toxicity as lithium is readily dialyzed because of water solubility, low volume of distribution, and lack of protein binding.
The Extracorporeal Treatments in Poisoning Workgroup (EXTRIP Workgroup) recommendations for dialysis (extracorporeal treatment) in lithium toxicity include:
• Impaired kidney function and lithium levels > 4.0 mEq/L
• Decreased consciousness, seizures, or life-threatening dysrhythmias, regardless of lithium levels
• Levels are > 5.0 mEq/L, significant confusion is noted, or the expected time to reduce levels to < 1.0 mEq/L is more than 36 hours
As post-dialysis rebound elevations in lithium levels have been documented, continuous veno-venous hemofiltration (CVVH) has been advocated.

Normal cerebrospinal fluid (CSF) glucose together with lymphocytosis, an increased opening pressure and raised CSF protein are typical of a viral meningitis.

Lateral epicondylitis (tennis elbow) is an overuse injury of the hand and finger extensor tendons that originate in the lateral humeral epicondyle that occurs following repeated or excessive pronation/supination and extension of the wrist (e.g., in racquet sports). Clinical features include pain and tenderness over the lateral epicondyle and along extensor muscles and thickening of the tendons. The examiner holds the patient’s hand with the thumb placed over the lateral epicondyle – The patient makes a fist, supinates the forearm, deviates radially, and extends the fist against the examiner’s resistance which will result in pain over the lateral epicondyle. Conservative treatment includes rest, physiotherapy and orthotic braces. If this fails corticosteroids and lidocaine injections are employed. Surgery is indicated in patients with persistent symptoms despite 6 months of conservative treatment. Excision of abnormal tendon tissue; longitudinal incisions (tenotomies) in scarred and fibrotic areas to promote healing.

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.

Dilation of systemic veins is a beneficial effect of nitro-glycerine.

Administration of nitro-glycerine results in the dilation of systemic veins and decrease of myocardial wall tension and oxygen demand. Dilatation of systemic veins can cause reduced systemic vascular resistance leading to reduced cardiac workload thus reducing anginal symptoms secondary to demand ischemia.

This is accompanied by vasodilation of large and medium-sized coronary arteries with increased coronary blood flow to the sub endocardium.

Churg-Strauss disease (CSD) is one of three important fibrinoid, necrotizing, inflammatory leukocytoclastic systemic small-vessel vasculitides that are associated with antineutrophil cytoplasm antibodies (ANCAs).
The first (prodromal) phase of Churg-Strauss disease (CSD) consists of asthma usually in association with other typical allergic features, which may include eosinophilia. During the second phase, the eosinophilia is characteristic (see below) and ANCAs with perinuclear staining pattern (pANCAs) are detected. The treatment would therefore be different from asthma. For most patients, especially those patients with evidence of active vasculitis, treatment with corticosteroids and immunosuppressive agents (cyclophosphamide) is considered first-line therapy

Extrinsic allergic alveolitis (EAA) refers to a group of lung diseases that can develop after exposure to certain substances. The name describes the origin and the nature of these diseases:

‘extrinsic’ – caused by something originating outside the body
‘allergic’ – an abnormally increased (hypersensitive) body reaction to a common substance
‘alveolitis’ – inflammation in the small air sacs of the lungs (alveoli)

Symptoms can include: fever, cough, worsening breathlessness and weight loss. The diagnosis of the disease is based on a history of symptoms after exposure to the allergen and a range of clinical tests which usually includes: X-rays or CT scans, lung function and blood tests.

EAA is not a ‘new’ occupational respiratory disease and occupational causes include bacteria, fungi, animal proteins, plants and chemicals.

Examples of EAA include:

Bird fancier’s lung (BFL) is a type of hypersensitivity pneumonitis (HP). It is triggered by exposure to avian proteins present in the dry dust of the droppings and sometimes in the feathers of a variety of birds. The lungs become inflamed, with granuloma formation. Birds such as pigeons, parakeets, cockatiels, shell parakeets (budgerigars), parrots, turtle doves, turkeys and chickens have been implicated.

People who work with birds or own many birds are at risk. Bird hobbyists and pet store workers may also be at risk. This disease is an inflammation of the alveoli in the lungs caused by an immune response to inhaled allergens from birds. Initial symptoms include shortness of breath (dyspnoea), especially after sudden exertion or when exposed to temperature change, which can resemble asthma, hyperventilation syndrome or pulmonary embolism. Chills, fever, non-productive cough and chest discomfort may also occur.

A definitive diagnosis can be difficult without invasive testing, but extensive exposure to birds combined with reduced diffusing capacity are strongly suggestive of this disease. X-ray or CT scans will show physical changes to the lung structure (a ground glass appearance) as the disease progresses. Precise distribution and types of tissue damage differ among similar diseases, as does response to treatment with Prednisone.