Babesiosis

- tick-borne malaria-like illness caused by parasite of genus Babesia
- Babesia microti is the cause of babesiosis in northeastern United States
- intraerythrocytic Babesia destroy the red blood cells causing hemolytic anemia and hemoglobinuria
- mild illness presents with malaise, fatigue, weakness, fever, chills, sweat, headache, myalgia, anorexia, dry cough, arthralgia and nausea
- post-splenectomy, HIV, malignancy and immunosuppression are at risk of severe illness
- symptoms are greater with higher percentage of parasitism
- diagnosed by microscopic examination of Giemsa-stained thin blood smears - round or pear-shaped organism
- asymptomatic need not be treated
- mild illness: oral atovaquone + azithromycin for 7 - 10 days
- severe illness: IV clindamycin + oral quinine for 7 - 10 days

Stiff person syndrome

- spontaneous discharge of the motor neurons of the spinal cord cause involuntary muscle contractions mainly involving the axial (trunk) and proximal lower extremity muscles
- gait becomes more stiff and labored, with hyperlordosis of lumbar spine
- superimposed episodic muscle spasms are precipitated by sudden movements, unexpected noises and emotional upset
- serum antibodies against glutamic acid decarboxylase are present in approximately 2/3 of cases
- treatment is mostly palliative with muscle relaxant with potentiate GABA actions (such as benzodiazepines)

Calciphylaxis

- calcific uremic arteriolopathy seen almost exclusively in patients with advanced CKD
- heralded by livedo reticularis and advances to patches of ischemic necrosis especially on the legs, thighs, abdomen and breasts
- pathologically, there is vascular occlusion associated with extensive vascular (calcification of tunica media) and soft tissue calcification
- warfarin is a risk factor of calciphylaxis ( because warfarin decrease vitamin K dependent regeneration of matrix GLA protein which is important in preventing vascular calcification)
- optimal treatment is prevention, with rigorous and continuous control of phosphate and calcium balance
- no specific treatment

Allergic interstitial nephritis (AIN)

- classically presents with fever, rash, peripheral eosinophilia and oliguric renal failure after 7 - 10 days treatment with methicillin or another B-lactam antibiotics
- atypical reactions can occur with NSAIDs in which fever, rash and eosinophilia are rare but acute renal failure with heavy proteinuria is common
- urinalysis reveal pyuria with white blood cell casts and hematuria
- renal biopsy usually not required for diagnosis but reveals extensive interstitial and tubular infiltration of leukocytes, including eosinophils
- discontinuation of offending agent often leads to reversal of renal injury

Atrial fibrillation

- Should look for AF in patient who presents with dyspnea, palpitation, syncope/dizziness, chest discomfort, stroke/TIA
- In patient with permanent AF who need treatment for rate control, beta blocker or rate-limiting CCB should be preffer initial monotherapy, digoxin is considered in predominantly sedentary patient
- In patient with persistent AF considered for pharmacological cardioversion, Class Ic drug (flecainide or propafenone) should be drug of choice in the absence of structural heart disease and amiodarone in the presence of structural heart disease
- rate control strategy should be the preferred initial option in persistent AF patient with
  ~ age over 65
  ~ coronary heart disease
  ~ with contraindication to antiarrhythmic drug
  ~ unsuitable for cardioversion
  ~ without congestive heart failure
- rhythm control strategy should be the preferred initial option in persistent AF patient with
  ~ younger patient
  ~ symptomatic
  ~ presenting for first time with lone AF
  ~ those with AF secondary to a treated/corrected precipitant
  ~ with congestive heart failure
- patient should be maintained on therapeutic anticoagulation with warfarin to keep INR between 2.0-3.0 for minimum of 3 weeks before cardioversion and 4 weeks after cardioversion





Reference: NICE clinical guideline 36 Atrial fibrillation

Carotid sinus hypersensitivity (CSH)

- exaggerated response to carotid sinus stimulation
- diagnosis is made after ischemic heart disease and rhythm disturbance is excluded
- CSH may be predominantly cardioinhibitory (resulting in bradycardia), vasodepressor (resulting in hypotension) or mixture of both
- presents with recurrent dizziness, near syncope, syncope, unexplained falls (drop attacks), symptoms produced when wearing tight-fitting collar clothes or when taking carotid pulse
- cardioinhibitory CSH is managed with insertion of dual-chamber pacemaker and vasodilatory CSH is managed with support stocking, fludrocortisone and midodrine (alpha-1 agonist)

Adult onset Still disease

- rare form of inflammatory arthritis
- begins after the age of 16 years 
- diagnosis of exclusion
- serum ferritin is usually elevated
- RF and ANA are classically negative
- treatment: NSAIDs
- Yamaguchi's criteria

Echinococcosis

- infection caused by larval stage of Echinococcus granulosus complex (dog tapeworm), which produce unilocular cystic lesion
- slowly enlarging echinococcal cyst generally remain asymptomatic until their expanding size or their space occupying effect in an involved organ (commonly liver and lungs) elicits symptomss
- hydatid liver disease presents with right upper quadrant pain, palpable mass in right upper quadrant or bile duct compression resulting in jaundice
- calcification is often seen on abdominal X ray and ultrasound is excellent means of demonstrating the cyst
- the most pathognomonic finding if demonstrable is that of daughter cysts within the larger cyst
- diagnostic aspiration is not usually recommended because of risk of fluid leakage resulting in either dissemination or infection or anaphylactic reaction
- treatment: Albendazole or PAIR (percutaneous aspiration, infusion of scolicidal agent and reaspiration), or pericystectomy for complicated cyst

Yersiniosis

- zoonotic infection with an enteropathogenic Yersinia species (Yersinia enterocolitica or Yersinia pseudotuberculosis)
- presents with abdominal pain and diarrhea
- can present with pseudoappendicitis (mesenteric adenitis)
- initial replication in small intestine is followed by invasion of Peyer's patches of distal ileum via M cells with onward spread to mesenteric lymph nodes
- gold standard for diagnosis is serology
- most cases of diarrhea are self limiting
- fluoroquinolone therapy is effective for bacteremia in adults

Relapsing polychondritis

- characterised by inflammation of cartilage (ear, nose and laryngotracheobronchial tree)
- also manifested with scleritis, neurosensory hearing loss, polyarthritis, cardiac abnormalitis, skin lesion and glomerulonephritis
- most common in 5th decade
- systemic features such as fever, fatigue and weight loss precede the clinical signs by several weeks
- auricular chondritis is the most frequent presenting manifestation (40%), and eventually affecting 85% of patients
- typically involving pinna of ears and sparing earlobe because they do not contain cartilage
- treatment: prednisolone 40-60mg/day

Achalasia

- caused by loss of ganglion cells within the esophageal myenteric plexus
- incidence 1:100,000
- presents at age between 25 and 60 years
- defined as reduced or absence of peristalsis and failure of lower esophageal sphincter to relax when swallowing
- presents with dysphagia, regurgitation, chest pain (esophageal spasm) and weight loss
- patient with advanced achalasia are at risk for bronchitis, pneumonia or lung abscess from chronic regurgitation and aspiration
- differential diagnoses are diffuse esophageal spasm (DES), Chagas' disease and pseudoachalasia (tumor infiltration)
- diagnosed by barium swallow X ray (dilated esophagus with poor emptying and air fluid level, tapering at the LES giving a beak-like appearance) and esophageal manometry (impaired LES relaxation and absent peristalsis)
- treatment: endoscopic pneumatic dilatation of LES (efficacy 32-98%), intra-sphincteric injection of botulinum toxin or Heller's cardiomyotomy 
- increased risk of esophageal squamous cell cancer secondary to prolonged stasis esophagitis

Antidotes

Agent	Indication
Activated charcoal with sorbital	used for many oral toxins
Adenosine	Theophylline antidote for adenosine poisoning
Atropine	organophosphate and carbamate insecticides,nerve agents, some mushrooms
Beta blocker	theophylline
Calcium chloride	calcium channel blockers, black widow spider bites
Calcium gluconate	hydrofluoric acid
Chelators such as EDTA, dimercaprol (BAL), penicillamine, and 2,3-dimercaptosuccinic acid (DMSA, succimer)	heavy metal poisoning
Cyanide antidote (amyl nitrite, sodium nitrite, or thiosulfate)	cyanide poisoning
Cyproheptadine	serotonin syndrome
Deferoxamine mesylate	Iron poisoning
Digoxin Immune Fab antibody (Digibind and Digifab)	digoxin poisoning
Diphenhydramine hydrochloride and benztropine mesylate	Extrapyramidal reactions associated withantipsychotic
Ethanol or fomepizole	ethylene glycol poisoning and methanol poisoning
Flumazenil	benzodiazepine poisoning
Glucagon	beta blocker poisoning and calcium channel blockerpoisoning
100% oxygen or hyperbaric oxygen therapy (HBOT)	carbon monoxide poisoning and cyanide poisoning
Insulin	beta blocker poisoning and calcium channel blockerpoisoning
Leucovorin	methotrexate and trimethoprim
Methylene blue	treatment of conditions that cause methemoglobinemia
Naloxone hydrochloride	opioid poisoning
N-acetylcysteine	Paracetamol (acetaminophen) poisoning
Octreotide	oral hypoglycemic agents
Pralidoxime chloride (2-PAM)	organophosphate insecticides, followed after atropine
Protamine sulfate	Heparin poisoning
Prussian blue	Thallium poisoning
Physostigmine sulfate	anticholinergic poisoning
Pyridoxine	Isoniazid poisoning, ethylene glycol
Phytomenadione (vitamin K) and fresh frozen plasma	warfarin poisoning and indanedione
Sodium bicarbonate	ASA, TCAs with a wide QRS

Water deprivation test

- Patients are deprived of fluid for 8 hours or until 5% of body weight is loss
- patient should be weighed hourly
- plasma osmolality is measured 4 hourly
- urine volume and osmolality 2 hourly
- then give 2microgram desmopressin IM and check urine volume & osmolality and plasma osmolality over next 4 hours
- Interpretation
 ~ if serum osmolality > 305 mOsmol/kg = diabetes insipidus
 ~ urine osmolality < 300 mOsmol/kg after fluid deprivation and rising to above 800mOsmol/kg after desmopressin = cranial diabetes insipidus
 ~ urine osmolality < 300 mOsmol/kg after fluid deprivation and remains < 300mOsmol/kg after desmopressin = nephrogenic diabetes insipidus
 ~ urine osmolality > 800 mOsmol/kg after fluid deprivation without desmopressin = primary polydipsia
 ~ urine osmolality between 300 and 800 mOsmol/kg = partial DI/polydipsia

Takayasu's arteritis

- an inflammatory and stenotic disease of medium and large-sized arteries characterized by strong predilection for the aortic arch and its branches
- a.k.a aortic arch syndrome
- 2-3 per million
- 80% are women and mean age of onset is 30 years
- panarteritis with inflammatory mononuclear cell infiltrates and occasionally giant cells
- presents with fever, night sweats, arthralgia, anorexia and weight loss
- pulses are commonly absent in the involved vessels, particularly subclavian artery
- hypertension occurs in 32-93% of patients and contribute to renal, cardiac and cerebral injury
- diagnosis is confirmed by the characteristic pattern on arteriography which includes irregular vessel walls, stenosis, post stenotic dilatation, aneurysm formation, occlusion and evidence of increased collateral circulation
- corticosteroid with the addition of steroid sparing agents such as methotrexate or azathioprine are mainstay of treatment

Paroxysmal cold hemoglobinuria

- rare form of AIHA occuring mostly in children
- usually triggered by a viral infection, usually self limited
- characterised by the involvement of Donath-Landsteiner antibody
- in vitro, this antibody has unique serologic feature: it has anti-P specificity and it binds to red cells only at low temperature (optimally at 4°C). When temperature is shifted to 37°C, lysis of red cells take place in the presence of complement
- consequently, in vivo there is intravascular hemolysis resulting in hemoglobinuria
- also presents with rigor and bone pain
- supportive treatment inlcuding blood transfusion is needed to control the anemia

Histoplasmosis

- caused by Histoplasma capsulatum, a thermal dimorphic soil fungus
- a.k.a Darling's disease (Histoplasma discovered in 1905 by Darling)
- infection follows inhalation of microconidia. Once they reach the alveolar space, microconidia are rapidly recognised and engulfed by alveolar macrophages
- clinical spectrum of histoplasmosis ranges from asymptomatic infection (immunocompetent individuals with low level of exposure) to life threatening illness (immunocompromised - progressive disseminated histoplasmosis)
- it causes TB-like illness
- fungal culture remains the gold standard diagnostic test for histoplasmosis (Groccott stain)
- treatment is indicated for progressive disseminated histoplasmosis, chronic pulmonary histoplasmosis or symptomatic patients with acute pulmonary histoplasmosis
- drug: liposomal amphotericin B or itraconazole

Subacute thyroiditis

- a.k.a De Quervain's /granulomatous / viral thyroiditis
- peak incidence 30-50 years, women affected 3 times more common than men
- during initial phase of follicular destrution, there is release of Tg and thyroid hormones, leading to increased circulating T4 and T3 and suppression of TSH (during this stage, radioactive iodine uptake is low or undetectable)
- after several weeks, the thyroid is depleted of stored thyroid hormone and a phase of hypothyroidism typically occurs
- finally thyroid hormone and TSH levels return to normal as disease subsides
- presents with painful and enlarged thyroid, sometimes fever
- malaise and URTI may precede the thyroid related features by several weeks
- patient typically complained of sore throat and pain is often radiated to jaw or ear
- ESR and CRP are markedly elevated
- treatment: NSAIDs (eg: aspirin 600mg QID), or prednisolone 40-60mg gradually tapered over 6-8 weeks
- thyroid function should be monitored every 2-4 weeks using TSH and unbound T4 levels

MRCP part 2 written

Tardive dyskinesia

- developed months to years after initiation of neuroleptic medications
- choreiform movements involving mouth, lips and tongue
- abnormal movement may develop after stopping the offending agent
- atypical antipsychotics has lower risk of TD
- treatment consists of stopping the offending agent
- TD remits within 3 months of stopping the drug and most patients gradually improve over the course of several years

Peripartum cardiomyopathy

- develops during the last trimester or within first 6 months after pregnancy
- between 1:3000 and 1:15,000 deliveries
- risk factors are increased maternal age, increased parity, twin pregnancy, malnutrition, tocolytics, and pre-eclampsia
- cause is unknown
- management is supportive with sodium restriction, digoxin, diuretics and vasodilators (eg:hydralazine)
- increased incidence of thrombosis and common to anticoagulate patient with heparin
- risk of recurrence in future pregnancy is 40%
- prognosis is reasonable with recovery of ventricular function in up to 50% patients

Loiasis

- filarial infection caused by Loa loa (African eye worm)
- transmitted by Chrysops fly
- adult parasites live in subcutaneous tissue
- microfilariae circulate in blood with a diurnal periodocity
- subconjunctival migration of an adult worm
- Calabar swelling (localised area of angioedema and erythema developing on extremities) is thought to result from a hypersensitivity reaction to adult worm antigens
- definitive diagnosis requires the detection of microfilariae in peripheral blood or isolation of adult worm from the eye or subcutaneous biopsy
- eosinophilia suggest the diagnosis
- diethylcarbamazine (DEC) for 3 weeks

Cholesterol embolism syndrome

- should be suspected in any patients who develop worsening renal function, hypertension, distal ischemia or acute multisystem dysfunction after an invasive arterial procedure (eg:CABG), anticoagulation or thrombolysis
- triad of livedo reticularis, eosinophilia and acute renal failure
- may presents with unexplained fever, weight loss, myalgia and anorexia initially
- risk of patient developing cholesterol embolism can be reduced by using brachial or axillary approach  in patient known to have severely ulcerated aortic plaque, using soft flexible catheter and avoiding high pressure jets of contrast materials
- trash foot
- low C3 level, raised ESR/CRP, pyuria/eosinophiluria
- tissue biopsy: demonstration of cholesterol crystal in occluded arterioles is the only definitive test for cholesterol embolism
- management is supportive

Neuroleptic malignant syndrome

- rare but life threatening, idiosyncratic reaction to a neuroleptic medication
- characterised by fever, muscular rigidity, dysautonomia (sweating, tachypnea, tachycardia and labile blood pressure) and altered mental status
- thought to be secondary to decreased dopamine activity in CNS either from blockade of dopamine D2 receptor or decrease availability of dopamine itself
- blockade of dopamine neurotransmission in nigrostriatum and hypothalamus results in muscular rigidity and altered thermoregulation
- most common cause are haloperidol, fluphenazine depot preparation and chlorpromazine
- high creatinine kinase and high white cell counts are seen
- complications include rhabdomyolysis and subsequent renal failure
- stop all neuroleptic, correct volume depletion and hypotension with IV fluid
- bromocriptine 5mg tds is the treatment of choice (dantrolene was formerly recommended as initial treatment of choice although recent studies suggest that it is associated with increased mortality when used without bromocriptine)

Scabies

- caused by Sarcoptes scabei, an arachnid
- transmitted by prolonged skin to skin contac with someone who has it
- fertilised female has to be transferred for infestation to take place, she will then find a place to lay eggs (burrow), 4-6 weeks later hypersensitivity rash occurs
- papular rash (on abdomen and medial thigh)
- itchy at night
- diagnosis is confirmed by one or more burrows (in digital web spaces and flexor wrist skin)
- treatment: 5% permethrin cream over whole body including scalp, face, neck and ears. Wash after 8-12 hours
- bedding, clothing and close contacts should be decontaminated (washing in hot water and drying in hot dryer)

Leptospirosis

- zoonotic disease caused by spirochetes of genus Leptospira
- most important source of transmission to humans are rats, dogs, cattle and pigs
- flooding is a major risk for epidemic severe disease. Military training, outdoor athletic activities and adventure travel have led to recognised outbreaks and spradic cases of leptospirosis
- Leptospires infect humans through the mucosa or macerated, punctured or abraded skin
- incubation period averages 5-14 days
- leptospirosis is classically described as biphasic
 ~ leptospiremic phase: acute fever lasts for 3-10 days (blood culture postive up to day 4 of illness)
 ~ immune phase : fever not responsive to antibiotic but leptospires can be isolated from urine
- conjunctival suffusion, pharyngeal edema without exudate, muscle tenderness (esp calves), rash, jaundice or signs of meningism
- Weil's disease is characterised by jaundice, acute renal failure, hypotension and hemorrhage (usually pulmonary), aseptic meningitis, cholecystitis, acute abdomen and pancreatitis
- diagnosis is by serologic assay
- treatment: oral doxycycline 100mg bd for mild infection, IV penicillin G 1.5 mega unit QID for severe infection
- chemoprophylaxis: oral doxycycline 200mg once a week

acquired hemophilia

- FVIII is the most common target of antibody formation against specific clotting factor
- occurs predominantly in older adults (median age of 60)
- 50% idiopathic, others are associated with autoimmune disease, malignancy and pregnancy
- bleeding episodes occur commonly in soft tissues, GI or urinary tracts, haemarthrosis is rare
- prolonged APTT with normal PT
- Bethesda assay using FVIII deficient plasma as performed for inhibitor detection will confirm the diagnosis
- treatment with factor VIII is ineffective as the inhibitor has rapid activity
- bleeding is treated with recombinant activated factor VII or FEIBA(factor eight bypassing agent)

Non alcoholic fatty liver disease (NAFLD)

- prevalence range from 14-20%
- should always be considered in obese individuals with abnormal liver function test (raised ALT or AST) without evidence of alcohol excess
- often asymptomatic but hepatic enlargement due to lipid deposition within hepatocyte (making them appear bright on ultrasound) can lead to RUQ pain
- abnormal ferritin values are seen in 50% of patients with NASH, and may be a marker of insulin resistance in NASH
- liver biopsy: macrovesicular steatosis with occasional microvesicular fat
- rapid weight loss has been shown to increase fat deposition in liver and precipitate NASH
- weight loss of 1kg/week and exercise with an initial target loss of 10% bodyweight has been shown to be effective at restoring normal liver function

Asbestosis

- caused by inhalation of asbestos fibres
- asbestos used in building trade for fire proofing, pipe lagging, electrical wire insulation and roofing felt
- chrysotile (white asbestos) - least fibrogenic
- amosite (brown asbestos) - intermediate fibrogenicity, least common
- crocicolite (blue asbestos) - most fibrogenic
- presents with progressive dyspnea, clubbing and fine end inspiratory crackles
- causes pleural plaques
- increased risk of bronchial adenocarcinoma and mesothelioma
- mesothelioma can be diagnosed by thoracoscopy and biopsy

Paracetamol poisoning

- 150mg/kg or 12gm in adult may be fatal
- PCM overdose causes hepatic injury through its reactive metabolit (NAPQI), which is normally rapidly detoxified by glutathione in liver cells. In PCM overdose, NAPQI production exceeds glutathione capacity and the metabolite reacts directly with the hepatic macromolecules causing liver injury
- treatment includes oral activated charcoal within 3-4 hours of ingestion
- antidote: N-acetylcysteine or methionine if allergic to NAC
- criteria for transfer to liver unit
 ~ encephalopathy or raised ICP
 ~ INR >2.0 at <48hours or INR>3.5 at <72hours (so measure INR every 12hours)
 ~ renal impairment (creainine > 200 μmol/L)
 ~ blood pH < 7.3 (lactic acidosis)
 ~ systolic BP < 80mmHg
- liver markers are poor indicator of hepatocyte death
- King's college criteria for liver transplantation
~ arterial pH < 7.3 or lactate >3.0 after adequate fluid resuscitation
~ or if all three of the following occurs in first 24 hours
   i) creatinine > 300
   ii) PT > 100 or INR > 6.5
   iii) grade III/IV encephalopathy

Parkinson's disease

- degeneration of dopaminergic neurons in the substantia nigra pars compacta associated with Lewy bodies, causes reduced striatal dopamine levels
- 3 cardinal signs : resting tremor, rigidity and bradykinesia
- 2 of 3 including bradykinesia are required to make a clinical diagnosis
- medical therapy of PD
 ~ Levodopa 
    - for older patient
    - risk risk of disease acceleration and motor fluctuations & dyskinesia
 ~ Dopamine agonist (ropinirole, pramipexole)
    - for younger patients
    - used as monotherapy to delay starting L-dopa in early stage of PD
    - lower risk of dyskinesia
 ~ COMT inhibitor (entacapone)
 ~ MAO-B inhibitor (selegiline)
 ~ anticholinergic (benzhexol) - improve tremor and sialorrhea
 ~ apomorphine
- DaT (dopamine transporter) scan helps to differentiate PD from essential tremor
- deep brain stimulation or pallidotomy when medical therapy fails

Chronic lymphocytic leukemia (CLL)

- accumulation of mature B cells that have escaped apoptosis and undergone cell cycle arrest in the G0/G1 phase
- commonest leukemia
- often asymptomatic, incidentally diagnoses on routine FBC
- may be anemia, infection prone, weight loss, night sweats and anorexia
- blood smear : smudge cells
- complications includes AIHA, frequent infections (hypogammaglobulinemia) and marrow failure
- death is often due to infections (pneumococcus, haemophilus, meningococcus, candida or aspergillosis) or transformation to aggressive lymphoma (Richter's syndrome)
- if asymptomatic - periodic follow up
- indications for chemotherapy (Fludarabine) * to give with co-trimoxazole for PCP prophylaxis
   ~ night sweats, fever, rapid weight loss, progressive marrow failure, symptomatic splenomegaly
- supportive care (transfusion or IVIG if recurrent infections), steroids for AIHA
- positivity to ZAP (zeta associated protein) 70 is associated with poorer prognosis

Organophosphate poisoning

- organophosphorus insecticides include malathion, parathion, dichlorvos and diazinon
- organophosphate irreversibly inhibit acetylcholinesterase and nicotinic synapses
- poisoning characterised by muscarinic and nicotinic effects
- muscarinic effect : nausea, vomiting, miosis, abdominal cramp, urinary and fecal incontinence, bronchorrhea, diaphoresis, salivation, lacrimation, bradycardia, conduction block, pulmonary edema
- nicotinic effect: twitching, fasciculation, weakness, cramp, hypoventilation with respiratory failure
- cholinesterase activity in plasma and red blood cells is reduced to less than 50% normal
- remove contaminated clothing and wash skin and mucous membrane with copious amount of water
- Atropine (muscarinic receptor antagonist) 0.5-2mg given IV every 5-10minutes until atropinization is adequate (drying of tracheobronchial secretion, dry mouth, flushing, dilated pupils, HR>120)
- Pralidoxime (oxime that reactivates phosphorylated cholinesterase) counteracts weakness (nicotinic effects)
- pralidoxime is contraindicated in carbamate poisoning.