Palmar xanthomas and tuberoeruptive xanthomas are found in type III hyperlipoproteinemia (dysbetalipoproteinemia,broad-beta disease, remnant removal disease)

Renal osteodystrophy is a metabolic bone disease often affecting long-term dialysis patients. The kidneys are no longer able to maintain the calcium levels in the blood, thus the PTH increases as the body attempts to raise blood calcium levels. Osteomalacia in these cases is most likely caused by the diminished activity of renal 1-a-hydroxylase that is important for hydroxylation of Calciferol to calcitriol (Vitamin D). This bioactive form of Vitamin D is responsible for increasing intestinal absorption of calcium.

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.

Gilles de la Tourette syndrome is the most severe and rare of the tic syndromes, consisting of multiple tics involving both motor actions and vocalisation. Onset is usually in childhood. Symptoms include utterance of obscenities (coprolalia); echolalia (repetition of another person’s spoken words) and palilalia (involuntary repetition of words, phrases, or sentences).
The underlying cause is unknown, with no particular imaging or standard histopathological abnormalities having been identified. The EEG shows non-specific abnormalities in about half of patients. However, more recent immunocytochemical studies have suggested altered dopamine uptake in the striatal system.
Risperidone is an effective therapeutic option without the effects associated with chlorpromazine and haloperidol.

ACE inhibitors are known to cause a dry cough and they should be stopped, to settle the cough. The next drug of choice is an angiotensin receptor blocker such as candesartan.

Café-au-lait spots is hyperpigmented lesions that vary in colour from light brown to dark brown, with borders that may be smooth or irregular. Causes include:
Neurofibromatosis type I
McCune–Albright syndrome
Legius syndrome
Tuberous sclerosis
Fanconi anaemia
Idiopathic
Ataxia-telangiectasia
Basal cell nevus syndrome
Benign congenital skin lesion
Bloom syndrome
Chediak-Higashi syndrome
Congenital nevus
Gaucher disease
Hunter syndrome
Maffucci syndrome
Multiple mucosal neuroma syndrome
Noonan syndrome
Pulmonary Stenosis
Silver–Russell syndrome
Watson syndrome
Wiskott–Aldrich syndrome

Normal pressure hydrocephalus is a form of communicating hydrocephalus characterised by enlarged ventricles with normal opening pressure on lumbar puncture. For diagnostic purposes, a triad of urinary incontinence, gait abnormality and dementia is necessary. It is necessary to diagnose the condition early because it is reversible by placing a ventriculoperitoneal shunt. It is most common in patients aged more than 60 years.

Of all the listed options, gastric cancer is least likely to be inherited.

The above mentioned tumours are ruled out as explained below:
1. Breast and Ovarian cancers: Between 5%–10% of all breast cancers are thought to be hereditary. Mutation in the BRCA1 and BRCA2 genes also increase the risk of ovarian cancer.

2. Colorectal and Endometrial cancers: About 5% of cases of colorectal cancer are caused by hereditary non-polyposis colorectal carcinoma (HNPCC) and 1% are due to familial adenomatous polyposis. Women who have HNPCC also have a markedly increased risk of developing endometrial cancer—around 5% of endometrial cancers occur in women with this risk factor.

CMV infection is usually asymptomatic in adults. However, if the mother is infected for the first time during pregnancy then there is high chances of this infection passing on to the foetus. CMV infection can cause blindness, deafness, learning difficulties, restricted growth etc. Hepatitis B, herpes simplex, syphilis and HIV do not present with these classical signs of CMV infection in new-borns. It is estimated that 10 stillbirths occur in England and Wales every year due to CMV infection. The foetus is most at risk in early pregnancy. There is no effective prevention.

Monoclonal gammopathy of undetermined significance (MGUS, also known as benign paraproteinemia and monoclonal gammopathy) is a pre-malignant condition not necessarily leading to its malignant form—multiple myeloma. Around 10% of patients eventually develop myeloma over 10 years, with 50% at 15 years. MGUS causes paraproteinemia and is usually asymptomatic. It is not associated with ostealgia or increased risk of infections. It is often mistaken for multiple myeloma, differing from the latter in, no immunosuppression, normal levels of beta-2 microglobulin, and stable lower levels of paraproteinemia.

People with polyarteritis nodosa often exhibit anaemia of chronic disease. Leucocytosis and eosinophilia may also be present. ANCA is only rarely positive. As polyarteritis nodosa affects the kidneys as well, the creatinine is elevated in most cases.

Though a common community pathogen, Staphylococcus Aureas is found twice as frequently in pneumonias in hospitalized patients. It often attacks the elderly and patients with CF and arises as a co-infection with influenza viral pneumonia. The clinical course is characterized by high fevers, chills, a cough with purulent bloody sputum, and rapidly progressing dyspnoea. The gross pathology commonly reveals an acute bronchopneumonia pattern that may evolve into a necrotizing cavity with congested lungs and airways that contain a bloody fluid and thick mucoid secretions.

Measles and chickenpox are spread by droplets. Thus, patients should be isolated.
Rheumatic fever and post-streptococcal glomerulonephritis are immune mediated diseases that don’t require isolation.
Herpetic gingivostomatitis spreads by direct transmission of infected secretions to the stratified squamous epithelium.
HSP is not an infectious disease.

This man has a small-cell lung cancer (SCLC) and associated Lambert-Eaton myasthenic syndrome – a well-recognized paraneoplastic manifestation of SCLC. This classically affects the proximal muscles, especially in the legs, causing difficulty in standing from a seated position and climbing stairs. In contrast to myasthenia gravis, eye involvement is uncommon. Treatment with steroids is often helpful, which explains his transient symptomatic improvement during treatment for his COPD exacerbation. Steroid myopathy does not fit as the symptoms started well before his course of prednisolone. Although the patient is mildly hypercalcaemic, this would not be sufficient to produce his presenting symptoms, although it does reinforce the suspicion of lung malignancy. Motor neurone disease would be unlikely in this context and would not improve with steroids. Myasthenia gravis could produce these symptoms, but in the context of a new lung mass is a less viable diagnosis.

Uhthoff’s phenomenon is worsening of vision following a rise in body temperature.
Lhermitte’s sign describes paraesthesia in the limbs on neck flexion.
Oppenheim’s sign is seen when scratching of the inner side of leg leads to extension of the toes. It is a sign of cerebral irritation and is not related to multiple sclerosis.
Werdnig-Hoffman’s disease is also known as spinal muscular atrophy.

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.

Several dipeptidyl peptidase-4 (DPP-4) inhibitors are in clinical development; these are orally active and increase levels of active glucagon-like peptide-1 (GLP-1), which in turn increases insulin secretion and reduces glucagon secretion, thereby lowering glucose levels.
Sitagliptin and vildagliptin both have a long duration of action, allowing once-daily administration. Both sitagliptin and vildagliptin are safe and tolerable with a low risk of hypoglycaemia. In drug-naïve subjects with type 2 diabetes, both sitagliptin and vildagliptin reduce A1C levels by ,1% as monotherapy.

Vestibular damage is a neurological side effect of streptomycin.

Streptomycin is an aminoglycoside bactericidal antibiotic. It is used in the treatment of tularaemia and resistant mycobacterial infections.
The most common neurological side-effect is vestibular damage leading to vertigo and vomiting.
Cochlear damage is less frequent and results in deafness.
Other side-effects include rashes, angioneurotic oedema, and nephrotoxicity.

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.

The NICE 2017 guidelines state that in patients who are uncontrolled with a SABA (Salbutamol) and ICS (Inhaled corticosteroid e.g. Beclomethasone), a leukotriene receptor antagonist (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.

This recommendation is also stated in NICE 2019 guidelines.

During pregnancy, profound changes in thyroid physiology occur to provide sufficient thyroid hormone (TH) to both the mother and foetus. This is particularly important during early pregnancy because the fetal thyroid starts to produce considerable amounts of TH only from approximately 20 weeks of gestation, until which time the foetus heavily depends on the maternal supply of TH. This supply of TH to the foetus, as well as increased concentrations of TH binding proteins (thyroxine-binding globulin) and degradation of TH by placental type 3 iodothyronine deiodinase, necessitate an increased production of maternal TH. This requires an intact thyroid gland and adequate availability of dietary iodine and is in part mediated by the pregnancy hormone human chorionic gonadotropin, which is a weak agonist of the thyroid-stimulating hormone (TSH) receptor. As a consequence, serum-free thyroxine (FT4) concentrations increase and TSH concentrations decrease from approximately the eighth week throughout the first half of pregnancy, resulting in different reference intervals for TSH and FT4 compared to the non-pregnant state.

The burning sensation described is typical of a neuropathy affecting the small unmyelinated and thinly myelinated nerve fibres. General neurological examination and reflexes are usually normal in this type of neuropathy unless there is coexisting large (myelinated) fibre involvement. Neuropathy affecting the large myelinated sensory fibres generally causes glove and stocking sensory loss and loss of reflexes.

Computed tomographic pulmonary angiography (CTPA) is the standard investigative tool, used for diagnosing a pulmonary embolism. Pulmonary angiography is indicated if CTPA is not available.

This patient is having vaso-occlusive event/crisis (thrombotic crisis) which is a type of sickle cell crisis. It may be associated with ostealgia.

There is no evidence of an aplastic crisis in this case as the haemoglobin level is reasonable with a good reticulocyte count. Conversely, the haemoglobin is not low enough and reticulocyte count and bilirubin are not high enough for a haemolytic crisis.

Sickle cell anaemia is characterised by periods of good health with intervening crises. The four main types of sickle cell crises are thrombotic crisis (painful or vaso-occlusive crisis), sequestration crisis, aplastic crisis, and haemolytic crisis.

Thrombotic crisis is precipitated by infection, dehydration, alcohol, change in temperature, and deoxygenation. Sequestration crisis is characterised by acute chest syndrome (i.e. fever, dyspnoea, chest/rib pain, low pO2, and pulmonary infiltrates). Aplastic crisis is characterised by a sudden fall in haemoglobin without marked reticulocytosis. It usually occurs secondary to parvovirus infection. In haemolytic crisis, a fall in haemoglobin occurs secondary to haemolysis. It is a rare type of sickle cell crisis.

Good prognosis of chronic lymphocytic leukaemia (CLL) is associated with deletion of the long arm of chromosome 13 (del 13q). This is the most common abnormality, seen in around 50% of all CLL patients. Poor prognosis of the disease is related to deletion of part of the short arm of chromosome 17 (del 17p). This is seen in around 5-10% of the patients suffering from CLL.

Poor prognostic factors of CLL include:
1. Male sex
2. Age >70 years
3. Lymphocyte count >50
4. Prolymphocytes comprising more than 10% of blood lymphocytes
5. Lymphocyte doubling time <12 months
6. Raised LDH
7. CD38 expression positive

Pregnant patient in a third world country with hepatitis: The answer is most likely Hepatitis E. The mortality for Hepatitis E in pregnant women is very high. It is transmitted faecal-orally. There is no hepatitis G. Hepatitis C, B, A are less likely to be the correct answer than E given it’s classic association with pregnancy and poor living conditions.

First and foremost, the patient should be put on ECG monitoring to identify the cardiac state, and because of the markedly raised serum potassium, a calcium gluconate bolus will have the immediate effect of moderating the nerve and muscle performance.

Androgen insensitivity syndrome (AIS), previously referred to as testicular feminization, is an X-linked disorder in which the patients are genotypically male (possessing and X and Y chromosome) and phenotypically female. This disorder is rare, with reported incidences from 1 in 20,000 to 1 in 60,000 live male births, and is the result of a missing gene on the X chromosome that is responsible for the cytoplasmic or nuclear testosterone receptor. In its absence, the gonad, which is a testis, produces normal amounts of testosterone; however, the end tissues are unable to respond due to the deficient receptors leading to the external genitalia developing in a female fashion. Anti-mullerian hormone, which is produced by the testis, is normal in these patients, leading to regression of the Mullerian duct. Wolffian duct development, which depends on testosterone, does not occur as the ducts lack the receptors.
The cumulative effect is a genotypic male with normal external female genitalia (without pubic or axillary hair), no menses, normal breast development, short or absent vagina, no internal sex organs, and the presence of testis. Frequently, these patients have bilateral inguinal hernias in childhood, and their presence should arouse suspicion of the diagnosis.

Heterochromia (difference in iris colour) is seen in congenital Horner’s syndrome, as well as anhidrosis. Other features of non-congenital Horner’s include miosis, ptosis and enophthalmos.

This is most likely describing irritable bowel syndrome (IBS). Symptoms are either diarrhoea, constipation, or both, abdominal pain, bloating, with various durations. It is a functional, not organic, problem, as far as research shows at this point. It is essentially a diagnosis of exclusion. Treatment is a high fibre diet with fluids. Caffeine should be avoided as this can worsen symptoms. Full colonoscopy is not warranted at this time, neither is a barium enema. A wheat-free diet is not likely to help as there is no evidence they have an allergy to this.