Legionella pneumonia

- Outbreak seen in previously fit individuals staying in hotels/institution where shower facilities/cooling systems are contaminated with the organism
- Flu-like symptoms, fever, malaise and myalgia typically precede a dry cough and dyspnea
- associated with hyponatraemia, lymphopenia and diarrhea
- diagnosis is by urinary Legionella antigen test, and four-fold increase in antibody titres
- treatment: Macrolide (Clarithromycin), ciprofloxacin and rifampicin
- mortality is 15-30% especially in elderly

Goodpasture syndrome

- occurs in people age more than 16 (male:female = 6:1)
- type II cytotoxic reaction (antibodies against basement membrane of both kidney and lungs)
- 80% HLA BR2 positive
- triad of glomerulonephritis, pulmonary hemorrhage and anti-GBM positive (against alpha-3 chain of type IV collagen) *alpha-5 in Alport's syndrome
- starts with URTI symptoms followed by cough, hemoptysis, tiredness and anemia.
- acute glomerulonephritis may presents with asymptomatic proteinuria or microscopic hematuria
- chest X-ray: bilateral diffuse infiltrates in lower zone, transient blotchy shadows (intrapulmonary hemorrhage)
- diffusion capacity for carbon monoxide is increased (pulmonary hemorrhage)
- diagnosis: renal biopsy (gold standard) - crescentic nephritis
- serial TLCO measurement can be used to monitor progresssion
- ANCA may be positive
- treatment: corticosteroid, cyclophosphamide, plasmapheresis

idiopathic pulmonary fibrosis

- a.k.a cryptogenic fibrosing alveolitis (CFA) / usual interstitial pneumonia (UIP)
- commonly seen in males age 50-60 years old
- features are progressive breathlessness in the absence of wheeze, non productive cough and cyanosis
- gross clubbing and fine bilateral end-inspiratory crackles
- acute form is known as Hamman-Rich syndrome
- Chest X-ray shows ground glass appearance, irregular reticulonodular shadowing and honeycomb lung

- lung function test : restrictive ventilatory defect
- bronchoalveolar lavage : increased number of neutrophils and macrophages
- treatment : prednisolone, add cyclophosphamide or azathioprine if no response, single lung transplant (best treatment option)

Behcet's disease

- Triad of aphthous (oral) ulcer + painless genital lesions + recurrent eye inflammation (iritis/uveitis)
- associated with HLA B5 (ocular disease) & HLA B12 (oral ulcer)
- other features: arthritis, erythema nodosum, abdominal pain (intestinal erosion or ulcer), diarrhea, cranial nerve palsies, aseptic meningitis, seizure
- it is the only vasculitic disease that involve both the arterial and venous system
- vascular thrombosis in 10%
- Pathergy test (small red bump/pustule at site of needle insertion in 48 hours)
- treatment : steroid, colchicine

Lateral medullary syndrome (Wallenburg) syndrome

Another favourite question in part 1....

- PICA (posterior inferior cerebellar artery) thrombosis

Signs of wallenburg syndrome
- Ipsilateral

• nystagmus (vestibular nuclei)
• cebebellar ataxia (inferior cerebellar peduncle)
• palatal / pharyngeal / vocal cord paralysis (IX, X nerve nuclei)
• facial numbness (nucleus V)
• Horner's syndrome (descending sympathetic fibers)
• loss of taste (tractus solitarius)

- Contralateral

• loss of pain and temperature (spinothalamic tract)

Notes:

- NO motor weakness

- crossed findings of loss of pain and temperature sensation on ipsilateral face and contralateral body

Polyarteritis nodosa (PAN)

- medium-size vessel vasculitis
- usually in middle aged men
- associated with hepatitis B antigenaemia (10-20%)
- pathology: fibrinoid necrosis of vessels walls with microaneurysm formation, thrombosis and infarction
- presents with fever, malaise, weight loss, myalgia, mononeuritis multiplex (arteritis of vasa nervorum), livedo reticularis, abdominal pain, hematuria/proteinuria, hypertension, myocardial infarction, subcutaneous hemorrhage/gangrene
- P-ANCA negative, rarely involved lungs (differentiate from Churg Strauss)
- investigations: raised ESR, elevated creatinine, anemia, leukocytosis, microaneurysm in angiography
- treatment: steroids, azathioprine

ACR Criteria for the Classification of Polyarteritis Nodosa (PAN)

American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa (PAN). Classified as PAN if at least three of the 10 criteria are present:

1. Weight loss > 4 kg: Loss of >4 kg body weight since illness began, not related to dieting or other factors.
2. Livedo reticularis: Mottled reticular pattern over the skin of portions of the extremities or torso.
3. Testicular pain/tenderness: Pain or tenderness of the testicles, not due to infection, trauma or other causes.
4. Myalgias, weakness or leg tenderness: Diffuse myalgias (excluding shoulder or hip girdle) or weakness of muscles or tenderness of leg muscles.
5. Mono- or polyneuropathy: Development of mononeuropathy,  multiple mononeuropathies orpolyneuropathy.
6. Diastolic BP >90 mmHg: Development of hypertension with the diastolic BP higher than 90 mmHg.
7. Elevated BUN or creatinine: Elevation of BUN >40 mg/dl or creatinine >1.5 mg/dl, not due to dehydration or obstruction.
8. Hepatitis B virus: Presence of hepatitis B surface antigen or antibody in serum.
9. Arteriographic abnormality: Arteriogram showing aneurysms or occlusions of the visceral arteries, not due to arteriosclerosis, fibromuscular dysplasia or other non-inflammatory causes.
10. Biopsy of small or medium-sized artery containing polymorphonuclear cells: Histologic changes showing the presence of granulocytes or granulocytes and mononuclear leucocytes in the artery wall.

These criteria have a reported sensitivity of 82.2% and a reported specificity of 86.6% for the classification of polyarteritis nodosa compared with other vasculitides.

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

- abnormal genes in chromosome 16 (PKD 1) - 85% and chromosome 4 (PKD 2)
   Note: there are 16 alphabates in polycystic kidney
- prevalence 1:400 - 1:1000 in Caucasian population
- presents with hypertension, painless hematuria, loin pain
- associated with Berry's aneurysm (80%) which can rupture leading to subarachnoid hemorrhage
- increased incidence of mitral valve prolapse and aortic/tricuspid incompetence associated with colonic diverticular disease with an increased rate of perforation
- ultrasound kidney (screening) best delayed to 3rd decade of life due to high false positive rate in young patients
- ACE inhibitors are first line treatment for hypertension
- by 70 years old, 30% sufferer requiring renal replacement therapy

Papillary necrosis

- chronic consumption of large amounts of analgesics (NSAIDs) leads to chronic tubulointerstitial nephritis and papillary necrosis

- diuretics may exacerbate any renal hypotension

- can cause pain and sterile pyuria

- urinary tract obstruction may occur owing to sloughing of renal papilla

- radiographic findings in papillary necrosis (always bilateral)

- IVU : clubbed calyces, ring sign (arrow) due to sloughed papilla

- causes of renal papillary necrosis may be recalled as 'POSTCARDS'

• pyelonephritis
• obstruction of renal tract
• shock
• TB
• cirrhosis of liver
• analgesic nephropathy
• renal transplant rejection
• diabetes
• sickle cell

Carcinoid tumor

- arise from enterochromaffin cells that are located predominantly in gastrointestinal mucosa
- carcinoid syndrome occurs in 5% of carcinoid tumor (with liver metastasis)
- associated with cardiac abnormality (TS/TR, PS/PR - accumulation of fibrous tissue in heart)
- presents with flushing, bronchospasm, diarrhea
- can present with acute appendicitis (obstruction of lumen by carcinoid)
- Pellagra syndrome is a complication (3Ds - dementia, diarrhea and  dermatitis). Because carcinoids utilise tryptophan, a nicotinamide precursor - causing nicotinic acid deficiency.
- Investigations: urinary 5-HIAA (100% specificity), plasma chromogranin A (100% sensitivity), ultrasound liver
  (Foods that can interfere the test includes bananas, eggplant, avocado and walnuts - avoid for 3 days   before the test)
- Treatment : octreotide, appendicectomy, hepatic artery ligation/embolization

Fabry's disease

- X-linked recessive lysosomal storage disorder
- deficiency of alpha-galactosidase A , causing accumulation of globotriaosylceramide
- myelin deposits in tubular epithelium and vascular endothelium resulting ischemic nephropathy
- presents with peripheral neuropathy (burning sensation of extremities evoked by vigorous exercise, hot weather or febrile illness) and cardiac conduction defect
- Absent of alpha-gal A in leukocytes confirm the diagnosis
- slit lamp examination revealed microscopic lipid deposits (corneal verticillata)
- skin lesion is known as angiokeratoma corporis diffusum (most prominent periumbilically)

Adynamic bone disease

- both bone formation and resorption are depressed
- associated with increased incidence of hip fracture
- features: hypercalcemia (bone loses its capacity to buffer calcium), low PTH levels, normal ALP
- can be caused by overtreatment with vitamin D

Ganser syndrome

Features of Ganser syndrome
- approximate answer (vorbeiredin).Patient deliberately seems to give incorrect, yet approximate answers to questions that he would normally know answers to. For instance, when asked what his name is, he may state a name that isn't his or when asked what 2 + 2 is, he may say 5.
- pseudohallucination
- somatic conversion
- subsequent amnesia
- clouding of consciousness

Latex fruit syndrome

- 30-50% of individuals who are allergic to natural rubber latex (NRL) show an associated hypersensitivity to some plant-derived foods
- avocado, banana, chestnut, kiwi, peach, tomato, potato and bell pepper
- allergen cross-reactivity is due to IgE antibodies that recognize structurally similar epitopes on different proteins that are phylogenetically closely related or represent evolutionarily conserved structures
- Birch pollen induced oral allergy syndrome: stoned fruits (apple, potatoes, carrot)

Internuclear ophthalmoplegia (INO)

- In  INO, when the patient’s gaze is directed away from the side of the lesion, the ipsilateral (adducting) eye will not adduct and the contralateral (abducting) eye demonstrates horizontal nystagmus.
- Surprisingly, patients usually do not complain of diplopia
- lesion at medial longitudinal fasciculus (MLF)
- Causes:

• Multiple sclerosis —likely cause in adulthood/middle age; often bilateral. (bilateral INO is nearly pathognomonic of MS)
• Vascular brainstem lesion —likely cause in the elderly or people with vascular risk factors; often unilateral.
• Pontine glioma —more likely cause in children.
• Inflammatory encephalitis affecting the brainstem (e.g. autoimmune, infective)
• Myasthenia gravis (unusual)

- One and a half syndrome is internuclear ophthalmoplegia combined with a conjugate gaze paralysis in the other direction. One eye fails to adduct on attempted lateral gaze (‘the half’) and the other eye neither adducts nor abducts (‘the one’). The eye that can abduct may exhibit horizontal nystagmus when it does so. The responsible lesion is an extensive paramedian pontine lesion that involves the MLF and either the CN6 nucleus or the PPRF (parapontine reticular formation). Often ischemic.

Cardiac syndrome X

- triad of angina + positive (abnormal) cardiac stress test + normal coronary angiogram
- chest pain unpredictable and not relieved by GTN
- ECG: ST depression (not elevation)
- treatment : nitrates (isosorbide mononitrate), CCB (nifedipine, diltiazem)

Lyme disease

- tick-borne infection caused by spirochaete Borrelia burgdorferi
- transmitted by ixodid ticks
- ring like (bull's-eye) erythematous lesion (erythema chronicum migrans)
- presents with malaise, arthralgia, lymphadenopathy, radiculoneuritis (often involves cranial nerves,eg: Bell's palsy), lymphocytic meningitis (Bannwarth's syndrome) and carditis
- investigation: anti Borrelia burgdoferi titre
- treatment : oral doxycycline 100mg bd for 14-21 days, IV ceftriaxone for meningitis
- skin complication : acrodermatitis chronica atrophicans, borrelia lymphocytoma

Wolff Parkinson White (WPW) syndrome

- syndrome of pre-excitation of ventricles due to Bundle of Kent (accessory pathway)
- Type A WPW (posterior left atrial wall to left ventricle), negative delta wave in lead I and positive delta wave in leads V1-V6
- Type B WPW (lateral right atrial wall to right ventricle), positive delta wave in lead I and biphasic or negative delta wave in leads V1-V3
- common types of arrhythmias at presentation: reciprocating tachycardia (80%), atrial fibrillation(15%), atrial flutter (5%)
- associations : Hypertrophic cardiomyopathy (HCM), Ebstein's anomaly, mitral valve prolapse, thyrotoxicosis, Leber's hereditary optic neuropathy (LHON)
- ECG: delta wave
- can be associated with negative delta waves in II, III, aVF
- definite treatment : radiofrequency catheter ablation of accessory pathway
- Drugs to be avoided in WPW (ABCD)

• A - adenosine
• B - beta blocker
• C - calcium channel blocker
• D - digoxin

- treatment for WPW with AF : flecainide, sotalol, disopyramide, amiodarone
- Short PR interval without delta wave suggest Lown Ganong Levine (LGL) syndrome

Amiodarone

- Amiodarone has high iodine content (40% of its weight)
- can directly cause both sinus bradycardia and AV block due to its calcium channel blocking activity
- prolonged QT interval due to blockage of potassium channels

Side effects of Amiodarone : BITCH

• B - Bradycardia
• I  - Interstitial pulmonary fibrosis
• T - Thyroid disorder (hyper/hypo)
• C - Corneal microdeposits (visual haloes & photophobia)
• H - Hepatitis / Hypersensitive skin (slate grey)

Amiodarone-induced hyperthyrodism

- Type 1 : high iodine content cause release of thyroid hormones (Jod Basedow effect). Positive antithyroid antibodies,normal IL-6

- Type 2 : amiodarone cause destructive thyroiditis, raised IL-6
- colour flow doppler ultrasound can differentiate (increase in type 1 and reduced in type 2)

- treatment: antithyroid in type 1, steroid + antithyroid for type 2
                  consider stop amiodarone if possible

Amiodarone also can cause hypothyroidism by inhibiting the peripheral conversion of T4 to T3 (thus elevated T4, low T3 and raised TSH)

Lewy body dementia

- 25% of dementia (second most common neurodegenerative disease)
- abnormal aggregation of synaptic protein (alpha-synuclein)
- characterized by Parkinsonian features, fluctuating cognitive loss and visual hallucinations
- Avoid neuroleptics (eg:Haloperidol) due to risk of inducing irreversible parkinsonism
- treatment :Rivastigmine (acetylcholinesterase inhibitor), Donezepil

dermatitis herpetiformis

- intensely pruritic, blistering rash, typically causes tiny vesicles on extensor aspects of elbow, knee and buttocks
- skin biopsy: subepidermal blister with neutrophil microabscesses in dermal papillae, and positive for IgA
- associated with Coeliac disease
- treatment = Dapsone

Tropical sprue

- most common in Caribbean and far east
- severe malabsorption (2 or more substance) accompanied by diarrhea and malnutrition
- presents with diarrhea, anorexia, abdominal distension, weight loss and steatorrhea
- work up : detailed history (travel history), D-xylose absorption test, jejunal biopsy (blunting/atrophy of villi, with subepithelial lymphocytic infiltration)
- megaloblastic anemia in more than 50% of cases
- treatment : folic acid supplementation, IM vitamin B12, tetracycline for 6 months

Cystic fibrosis

- autosomal recessive

- carrier frequency in Caucasian (1:22)
- affects 1: 2500

- commonest abnormality is specific deletion at position 508 in amino acid sequence (chromosome 7, long arm)

- defect in CFTR (cystic fibrosis transmembrane conductance regulator)

- sweat test > 60mmol/L = diagnostic of CF (using pilocarpine iontophoresis)
- prolonged prothrombin time suggest both malabsorption of vitamin K and cirrhosis
- Burkholderia cepacia is seen in severe lung disease and associated with rapid deterioration.

- presenting signs (CF PANCREAS)

• Chronic cough and wheezing
• Failure to thrive
• Pancreatic insufficiency (symptoms of malabsorption like steatorrhea)
• Alkalosis and hypotonic dehydration
• Neonatal intestinal obstruction (meconium ileus)/ Nasal polyps
• Clubbing of fingers/ Chest radiograph with characteristic changes
• Rectal prolapse
• Electrolyte elevation in sweat, salty skin
• Absence or congenital atresia of vas deferens - males are almost always infertile
• Sputum with Staph or Pseudomonas (mucoid)

- human recombinant DNAase (dornase alfa 2.5mg daily) given as aerosol improve pulmonary function, decrease frequency of chest exacerbations

- Nebulised tobramycin may be given when airway pathogens are resistant to oral antibiotics


- Cystic fibrosis heterozygotes has an increased resistance to cholera


Causes of false positive sweat sodium test
- hypothyroidism
- familial hypoparathyroidism
- mucopolysaccharidoses
- alpha 1 antitrypsin deficiency
- Addison's disease

Multifocal motor neuropathy

- autoimmune neuropathy (absence of sensory features)
- distal weakness, asymmetrical
- progressive weakness affecting an isolated limb
- early on in the disease there is profound weakness disproportionate to the amount of wasting
- fasciculation can occur in the affected muscle
- it is localised to individual peripheral nerve, which in contrast to the pattern of MND that is myotomal
- important differential diagnosis of motor neurone disease (MND) because it is TREATABLE
- nerve conduction study : multifocal demyelination and motor conduction block (vs axonal degeneration in MND)
- positive anti-ganglioside GM1 antibodies
- treatment : IV immunoglobulins or cyclophosphamide. Avoid steroid because they exacerbate weakness

Hereditary spherocytosis

- autosomal dominant (thus family screening is important)
- commoner among northen europeans

- due to defect in red cell membrane

- most common defect is ANKYRIN (45%) - chromosome 8

- can present with jaundice, asymptomatic, anaemia, splenomegaly, leg ulcer, gallstones (pigment)

- Investigations : osmotic fragility test, full blood picture
- screening by AGLT (acidified glycerol lysis test)

- Treatment : splenectomy, folic acid supplementation