High Altitude Cerebral Oedema (HACE) is a severe and potentially fatal manifestation of high altitude illness and is often characterized by ataxia, fatigue, and altered mental status. HACE is often thought of as an extreme form/end-stage of Acute Mountain Sickness (AMS). Although HACE represents the least common form of altitude illness, it may progress rapidly to coma and death as a result of brain herniation within 24 hours, if not promptly diagnosed and treated.

HACE generally occurs after 2 days above 4000m but can occur at lower elevations (2500m) and with faster onset. Some, but not all, individuals will suffer from symptoms of AMS such as headache, insomnia, anorexia, nausea prior to transitioning to HACE. Some may also have concomitant High Altitude Pulmonary Oedema (HAPE). HACE in isolation is rare, but the absence of concomitant HAPE or symptoms of AMS prior to deterioration does not rule-out the presence of HACE.

Most cases develop as a progression of AMS and will include a history of recent ascent to altitude and prior complaints/findings of AMS including a headache, fatigue, nausea, insomnia, and/or light-headedness. Some may also have signs/symptoms of HAPE. Transition to HACE is heralded by signs of encephalopathy including ataxia (usually the earliest clinical finding) and altered mentation which may range from mild to severe. Other symptoms may include a more severe headache, difficulty speaking, lassitude, a decline in the level of consciousness, and/or focal neurological deficits or seizures.

The mainstay of treatment is the immediate descent of at least 1000m or until symptoms improve. If descent is not an option, one may use a portable hyperbaric chamber and/or supplemental oxygen to temporize illness, but this should never replace or delay evaluation/descent when possible. If available, dexamethasone 8mg for one dose, followed by 4mg every 6 hours should be given to adults via PO, IM, or IV routes.
Acetazolamide has proven to be beneficial in only a single clinical study. The suggested dosing regimen for Acetazolamide is 250 mg PO, given twice daily. Though effective in alleviating or temporizing symptoms, none of the adjunct treatment modalities are definitive or a replacement for an immediate descent.

Mild cases are often not treated at all, or are simply covered up with normal cosmetics and avoiding sun exposure. Therapy for the treatment of rosacea is not curative, and is best measured in terms of reduction in the amount of facial redness and inflammatory lesions. The two primary modalities of rosacea treatment are topical and oral antibiotic agents (including metronidazole and tetracyclines). Laser therapy may be appropriate for patients with prominent telangiectasia.

Lymphedema is most commonly the result of removal or damage to lymph nodes.

A lucid interval, in which the patient portrays a temporary improvement in condition after a traumatic brain injury, is especially indicative of an epidural haematoma.

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.

Supravalvular aortic stenosis, is associated with a condition called William’s syndrome.
William’s syndrome is an inherited neurodevelopmental disorder caused by a microdeletion on chromosome 7. The most common symptoms of Williams syndrome are heart defects and unusual facial features. Other symptoms include failure to gain weight appropriately in infancy (failure to thrive) and low muscle tone. Individuals with Williams syndrome tend to have widely spaced teeth, a long philtrum, and a flattened nasal bridge.
Most individuals with Williams syndrome are highly verbal relative to their IQ, and are overly sociable, having what has been described as a cocktail party type personality.

The most sensitive test for detecting Hepatitis C infection (acute) is HCA RNA; it can be detected 1-2 weeks after infection. Anti-HCV antibodies take at least 6 weeks to develop and be positive.

Polymyalgia rheumatica, a syndrome characterized by proximal muscle pain and stiffness in older persons, generally is treated with prednisone. Dosages of 15 to 25 mg of prednisone per day can reduce inflammation considerably, although many patients relapse when therapy is tapered. Long-term (18 to 36 months) steroid treatment has been recommended by several studies, but this can result in multiple side effects, including osteoporosis, hypertension, cataracts, and hyperglycaemia. Methotrexate has been used to reduce inflammation in rheumatoid arthritis, systemic vasculitis, and giant cell arteritis, and in some studies has been combined with prednisone to treat polymyalgia rheumatica, decreasing the duration of treatment.

Minimal change glomerulonephritis usually presents as nephrotic syndrome wherein the patient (usually a young adult) will present with proteinuria, oedema, and impaired kidney function, which were evident in this patient.

Anorexia nervosa is an eating disorder characterized by an abnormally low body weight, an intense fear of gaining weight and a distorted perception of weight. People with anorexia place a high value on controlling their weight and shape, using extreme efforts that tend to significantly interfere with their lives.

The minimum level of severity is based, for adults, on current body mass index (BMI) (see below) or for
children and adolescents, on BMI percentile. The ranges below are derived from World Health
Organization categories for thinness in adults; for children and adolescents, corresponding BMI percentiles
should be used. The level of severity may be increased to reflect clinical symptoms, the degree of
functional disability, and the need for supervision.
Mild: BMI > 17 kg/m2
Moderate: BMI 16-16.99 kg/m2
Severe: BMI 15-15.99 kg/m2
Extreme: BMI < 15 kg/m2 Anorexia nervosa is more common in women than in men, with a female-to-male ratio of 10-20:1 in developed countries. The prognosis of anorexia nervosa is guarded. Morbidity rates range from 10-20%, with only 50% of patients making a complete recovery. Of the remaining 50%, 20% remain emaciated and 25% remain thin. The main change in the diagnosis of Anorexia Nervosa was to remove the criterion of amenorrhea (loss of menstrual cycle). Removing this criterion means that boys and men with Anorexia will finally be able to receive an appropriate diagnosis.
Similarly, girls and women who continue to have their period despite other symptoms associated with Anorexia, such as weight loss and food restriction, will now be eligible for a diagnosis of Anorexia.

Favus is a fungal infection of the scalp, resulting in the formation of a yellowish crusted plaque over the scalp and leads to scar formation with alopecia. Tinea capitus is a fungal infection of the scalp resulting in scaling and non scarring hair loss. Folliculitis presents with multiple perifollicular papules which can be caused by both bacteria and fungi. Cradle cap usually affects infants where the whole scalp is involved. It can lead to hair loss and responds to topical antifungals and keratolytics.

In hyperkalaemia the ECG will show tall, tented T waves as well as small P waves and widened QRS complexes. 

Live virus vaccines include: Vaccinia (smallpox), Measles, Mumps, Rubella (MMR combined vaccine), Varicella (chickenpox), Influenza (nasal spray), Rotavirus, Zoster (shingles) and Yellow fever. Inactivated vaccines are Polio (IPV), Hepatitis A and Rabies.

The patient is asymptomatic but matches the diagnostic criteria for multiple myeloma (MM). Therefore, the underlying diagnosis of this condition is smouldering multiple myeloma (SMM). SMM is an early precursor to MM. Its treatment is typically to watch and wait.

MM is a neoplasm of the bone marrow plasma cells. Peak incidence is in patients aged 60–70 years.

Clinical features of MM include:
1. Ostealgia, osteoporosis, pathological fractures (typically vertebral), and osteolytic lesions
2. Lethargy
3. Infections
4. Hypercalcaemia
5. Renal failure
6. Other features: amyloidosis e.g. macroglossia, carpal tunnel syndrome; neuropathy; hyperviscosity

Diagnosis of MM is based on the confirmation of (a) one major criterion and one minor criterion or (b) three minor criteria in an individual who has signs or symptoms of multiple myeloma.

Major criteria:
1. >30% plasma cells on bone marrow biopsy
2. Monoclonal band of paraprotein on electrophoresis: >35g/L for IgG, 20g/L for IgA, or >1g of light chains excreted in the urine per day

Minor criteria:
1. 10–30% plasma cells on bone marrow biopsy
2. Abnormal monoclonal band but levels less than listed above
3. Lytic bone lesions observed radiographically
4. Immunosuppression

Tiotropium is a specific long-acting antimuscarinic agent indicated as maintenance therapy for patients with COPD (chronic obstructive pulmonary disease).
It should be used cautiously in patients with narrow-angle glaucoma, prostatic hyperplasia or bladder neck obstruction.
The most frequently encountered adverse effects of tiotropium include pharyngitis, bronchitis, sinusitis, dry mouth, cough, and headaches. Paradoxical bronchospasm may also occur as a rare side-effect.
Dry mouth occurs in up to 14% of patients taking tiotropium, in keeping with its anticholinergic profile.
Rarer side-effects include tachycardia, blurred vision, urinary retention, and constipation.

Pulmonary metastasis is seen in 20-54% of extrathoracic malignancies. The lungs are the second most frequent site of metastases from extrathoracic malignancies. Twenty percent of metastatic disease is isolated to the lungs. The development of pulmonary metastases in patients with known malignancies indicates disseminated disease and places the patient in stage IV in TNM (tumour, node, metastasis) staging systems.
Chest radiography (CXR) is the initial imaging modality used in the detection of suspected pulmonary metastasis in patients with known malignancies. Chest CT scanning without contrast is more sensitive than CXR.
Breast, colorectal, lung, kidney, head and neck, and uterus cancers are the most common primary tumours with lung metastasis at autopsy. Choriocarcinoma, osteosarcoma, testicular tumours, malignant melanoma, Ewing sarcoma, and thyroid cancer frequently metastasize to lung, but the frequency of these tumours is low.

Blurring of vision and dry mouth are antimuscarinic side-effects that are more common with imipramine than other types of tricyclic antidepressants.

Tricyclic antidepressants (TCAs) are used less commonly now for depression due to their side-effects and toxicity in overdose. They are however used widely in the treatment of neuropathic pain, where smaller doses are typically required.

Mechanism of action: Tricyclic antidepressants impose their therapeutic effects by inhibiting presynaptic reuptake of norepinephrine and serotonin in the central nervous system (this, may give rise to seizures).

Common side-effects:
Drowsiness
Dry mouth
Blurred vision
Constipation
Urinary retention

Low-dose amitriptyline is commonly used in the management of neuropathic pain and the prophylaxis of headaches (both tension and migraine).
Lofepramine has a lower incidence of toxicity in overdose
Amitriptyline and dosulepin (dothiepin) are considered the most dangerous in overdose.

Many drugs are responsible for causing drug induced lupus. However, it is most commonly associated with hydralazine, procainamide and quinidine.

The carotid body consists of chemosensitive cells at the bifurcation of the common carotid artery that respond to changes in oxygen tension and, to a lesser extent, pH. In contrast to central chemoreceptors (which primarily respond to PaCO2) and the aortic bodies (which primarily have circulatory effects: bradycardia, hypertension, adrenal stimulation, and also bronchoconstriction), carotid bodies are most sensitive to PaO2. At a PaO2 of approximately 55-60 mmHg, they send their impulses via CN IX to the medulla, increasing ventilatory drive (increased respiratory rate, tidal volume, and minute ventilation). Thus, patients who rely on hypoxic respiratory drive will typically have a resting PaO2 around 60 mm Hg.

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.

The walls of the ascending limb of the loop of Henle are not permeable to water. The tubular fluid thus becomes increasingly dilute as it ascends toward the cortex, whereas the interstitial fluid around the loops of Henle in the medulla becomes increasingly more concentrated.

The ascending limb actively reabsorbs NaCl but has an extremely low transepithelial osmotic water permeability, even in the presence of vasopressin. This combination of NaCl reabsorption without water reabsorption serves two vital functions: it provides NaCl to increase the osmolality of the medullary interstitium, tubules, vasculature, and collecting ducts; and it dilutes the luminal fluid within the thick ascending limb.

The a wave indicates atrial contraction. The c wave indicates ventricular contraction and resulting bulging of the tricuspid valve into the right atrium during isovolumetric systole. The v wave indicates venous filling. The x descent indicates the atrium relaxation and the movement of tricuspid valve downward. The y descent indicates the filling of the ventricle after the opening of the tricuspid valve.

Cerebral venous sinus thrombosis (CVST) is associated with headache (>90% of cases), seizures, focal weakness (40%) and papilledema (40%), all seen in this patient.
Risk factors for CVST include genetic or acquired prothrombotic disorders, pregnancy, the oral contraceptive pill, vasculitis, malignancy, dehydration and infection. However, there are multiple other associated factors.
Diagnosis is normally confirmed with magnetic resonance venography (MRV). Treatment is with anticoagulation, initially with heparin and subsequently with warfarin.

The history is suggestive of leptospirosis. This is a zoonotic infection caused by a spirochete. As the patient is in shock, resuscitation with IV fluids is the first step in the management. IV antibiotics should be started (Doxycycline or Penicillin) as soon as possible. Other investigations mentioned are important during the management to rule out other possible diagnoses.

Extended-spectrum beta-lactamases (ESBL) are enzymes that confer resistance to most beta-lactam antibiotics, including penicillins, cephalosporins, and the monobactam aztreonam. Extended spectrum beta-lactamase (ESBL) production is the main reason for multi-drug resistance among E.coli. Commonly used medications to treat ESBL-involved infections include carbapenems (imipenem, meropenem, and doripenem), cephamycins (cefoxitin and cefotetan), Fosfomycin, nitrofurantoin, beta-lactamase inhibitors (clavulanic acid, tazobactam, or sulbactam), non-beta-lactamases and colistin (if all other medications have failed.)

Sun burn reactions usually occur after individuals with a light skin tone have prolonged exposure to the sun. The usual symptoms are redness and itching of the skin. The best treatment plan would be further avoidance of sun exposure and the topical application of emollients. These are Ist degree burns and aggressive therapy is not required in such cases.

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.

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.

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.

Narrow complex tachycardia with hypotension is a medical emergency. Immediate synchronized cardioversion is the ideal management.