MRCP Revision Notes

Benign paroxysmal positional vertigo

2012-03-12T07:30:00.000Z

Benign paroxysmal positional vertigo (BPPV) describes a condition in which there is:

Rotational Vertigo
Provoked by turning head/change in position
Lasts around 10-30 seconds
Possibly with nausea

Most patients are over 40 years of age

Women > men (2:1)

Aetiology – believed to be due to free-floating endolymph particles in semi-circular canal.

Most cases (60-70%) are idiopathic.
Secondary BPPV may be due to

Head trauma (7-17% of all cases of BPPV)
Viral (up to 15% of all cases of BPPV)
Meniere’s disease (around 5% of cases of BPPV)
Migraines (less than 5% of all cases of BPPV)

Diagnosis: Dix-Hallpike manoeuvre – look for nystagmus

Treatment:Epley’s manoeuvre – series of head movements with the purpose of encouraging any foreign material out of the canal and into the utricle

References

Lempert, T., Gresty, M. and Bronstein, A. Benign positional vertigo: recognition and treatment. BMJ. 1995; 311(7003): 489-491.

Parnes, L., Agrawal, S. and Atlas, J. Diagnosis and management of benign paroxysmal positional vertigo. CMAJ. 2003; 169(7): 681-693.

Hypertrophic cardiomyopathy

2012-03-09T10:00:00.000Z

Hypertrophic cardiomyopathy is an autosomal dominant cardiac condition characterized by marked left ventricular hypertrophy with a non-dilated ventricular cavity, and in around 20% of patients left ventricular outflow obstruction.

It is the commonest genetic cardiac disease (incidence 1 in 500) and the commonest cause of sudden cardiac death in the young.

Presentation may be:

Sudden death
Syncope
Shortness of breath
Angina
Palpitations

Clinical findings may include:

Ejection systolic murmur

If obstruction is present this murmur may be increased by valsalva

Prominent A wave in JVP
Bifid pulse (obstructive only)
? MR
? split S2

Investigation

Echocardiography

Hypertrophied and non-dilated left ventricle

? LVH
? AF
? Q waves
? TWI

Prognosis include:

Sudden death (classically stated at 6% per year but now believed to be lower – around 1%)
Atrial fibrillation (20-25%)
Heart failure symptoms
No symptoms

Risk factors for sudden death

Family history of sudden death
Unexplained syncope
Massive LV hypertrophy (thickness >30mm)
Non-sustained VT on ambulatory ECG
Hypotensive on exercise

Management – depends on severity and symptoms

Medical

Beta blockers
Verapamil

Surgery
Percutaneous alcohol septal ablation
Dual chamber pacing
ICD
Avoid nitrates/ACE-i/digoxin in outflow tract obstruction

References

Maron, B. Hypertrophic cardiomyopathy: a systemic review. JAMA. 2002; 287(10): 1308-1320.

Maron, B. et al. American College of Cardiology/European Society of Cardiology Clinical expert consensus document on hypertrophic cardiomyopathy. European Heart Journal. 2003; 24: 1965-1991.Maron, B. Contemporary insights and strategies for risk stratification and prevention of sudden death in hypertrophic cardiomyopathy. Circulation. 2010; 121(3): 45-456.

Spirito, P. and Autore, C. Management of hypertrophic cardiomyopathy. BMJ. 2006; 332(7552): 1251-1255.

Wigle, E. et al. Hypertrophic cardiomyopathy. Clinical spectrum and treatment. Circulation. 1995; 92(7): 1680-1692.

Metabolic acidosis

2012-03-07T12:59:00.000Z

Definition of metabolic acidosis: low pH and low P_HCO3

Metabolic acidosis may be due to:

Accumulation of acids (= high anion gap) or
Loss of bicarbonate (= hyperchloraemic metabolic acidosis, normal anion gap)

Anion gap = (Na + K) - (Cl + HCO₃)

The normal anion gap is 14-16 mmol/l

Causes of a high anion gap metabolic acidosis: MUDPILES

Methanol (formic acid)
Uraemia
Diabetic ketoacidosis
Paraldehyde (acetic and chloroacetic acid)
Isoniazid
Iron
Inborn errors of metabolism

Glucose 6 phosphate deficiency

Lactic acid

Cyanide poisoning
Carbon monoxide poisoning
Short bowel syndrome
Excess inhaled beta agonists
Metformin
Seizures
Shock

Ethylene glycol (oxalic acid)
Salicylates

Also:
Toluene OD (an aromatic hydrocarbon used as a solvent in paints, glues etc)
Paracetamol OD – either due to lactic acidosis or pyroglutamic acidosis

Pyroglutamic acid (=intermediate in the gamma glutamyl cycle). Excess associated with ingestion of several medications, including flucloxacilin, vigabatrin and paracetamol.

Causes of a hyperchloraemic (=normal anion gap) metabolic acidosis

Gastrointestinal bicarbonate loss:

Diarrhoea
Intestinal fistula
Urinary tract diversion to intestine
Ileal conduit
Ureterosigmoidoscopy
Medications

Magnesium sulphate
Laxative abuse
Cholestyramine

Renal causes

Renal tubular acidosis
Renal failure
Drug-induced hyperkalaemia with renal insufficiency

spironolactone
ACE-i

Administration of fluid containing chloride

Small print gem: a major decrease in extra cellular fluid volume will raise the HCO₃, so the diagnosis of metabolic acidosis may be missed in the diabetic patient who has vomited lots and is severely dehydrated with concurrent DKA, or the cholera patient who has had massive diarrhoea

References

Dickson, R. and Luks, A. Toluene toxicity as a cause of elevated anion gap metabolic acidosis. Respir Care. 2009; 54(8): 1115-1117.

Green, T., Bijisma, J. and Sweet, D. Profound metabolic acidosis from pyroglutamic academia: an underappreciated cause of high anion gap metabolic acidosis. CJEM. 2010; 12(5): 449-452.

Halperin, M. and Kamel, K. Some observations on the clinical approach to metabolic acidosis. J Am Soc Nephrol. 2010; 21(6): 894-897.

Lim, S. Metabolic acidosis. Acta Med Indones. 2007; 39(3): 145-150.

Maccari, C. et al. The patient with a severe degree of metabolic acidosis: deductive analysis. QJM. 2006; 99(7): 475-485.

Glaucoma

2012-03-05T16:21:00.004Z

Glaucoma describes a range of disorders with a characteristic type of optic disc damage usually due to raised intraocular pressure.

Upper limit of normal intraocular pressure is 21mmHg.

2 main divisions of glaucoma are:

Open angle = chronic
Closed angle = acute

Open angle glaucoma

Primary open angle glaucoma occurs in 1-2% of over 40s and over 4% of over 80s

Patients are often asymptomatic – visual losses tend to occur late in the course of the disease and is often peripheral.

Fundoscopy may reveal optic disc cupping

Major risk factors

FH in a first degree relative
Myopia
Advanced age
Afro-caribean origin
Raised intra-occular pressure

Other risk factors

Diabetes
Hypertension
Hypothyroidism
Steroid use
Migraine
Sleep apnoea

Patients of afro-caribbean origin are at higher risk of progression to blindness

Management

Medical

Eye drops

First line: prostaglandin analogues (increase aqueous outflow from eye through the uveoscleral pathway) or beta blockers (reduce secretion of aqueous)
Second line: carbonic anhydrase inhibitors and alpha agonists

Oral medication: carbonic anhydrase inhibitors (reduce secretion of aqueous)

Surgical

Argon laser trabeculoplasty
Trabeculectomy

Closed angle glaucoma

Closed angle glaucoma is a sight-threatening ophthalmic emergency characterized by a rapid rise in intraocular pressure as a result of obstruction of aqueous humour drainage from the anterior chamber of the eye.

Presentation

Painful red eye
Semi-dilated, non-reactive pupil
Periocular headache
Halos around light
Loss of vision
Nausea and vomiting
Systemically unwell
Affected eye is tender and feels hard to the touch

Risk factors for closed angle glaucoma include:

Advanced age
Female gender
Far eastern origin
Hypermetropia
Medications (due to their pupil-dilating effects)

SSRIs
TCA
Anticholingergics

Treatment

Acetazolamide IV
Pilocarpine 4% eye drops
Laser iridotomy or iridoplasty
Iridectomy if laser treatment fails

Small print gem: carbonic anhydrase drugs are strucurally similar to sulfonamides so should be avoided if patients have an allergy to these

References

Adatia, F. and Damji, K. Chronic open-angle glaucoma. Review for primary care physicians. Can Fam Physician. 2005; 51: 1229-1237.

Gordon-Bennett, P. et al. Misdiagnosis of angle closure glaucoma. BMJ. 2006; 333(7579): 1157-1158.

Khaw, P., Shah, P. and Elkington, A. Glaucoma 1: diagnosis. BMJ. 2004; 328(7431): 97-99.

Khaw, P., Shah, P. and Elkington, A. Glaucoma 2: treatment. BMJ. 2004; 328(7432): 156-158.

Royal College of Ophthalmologists. Guidelines for the management of open angle glaucoma and ocular hypertension. 2004. Available at http://www.rcophth.ac.uk/page.asp?section=451§ionTitle=Clinical+Guidelines

Gout

2012-03-02T19:09:00.000Z

Gout is an inflammatory arthritis caused by monosodium urate crystals in and around joints.

The most commonly affected joint is the first metatarsophalangeal joint. When this is affected it is called a podagra.

Tophi may develop in chronic disease.

The most important risk factor for developing gout is hyperuricaemia.

Hyperuricaemia may be caused by:

Urate overproduction:

Psoriasis
Excessive dietary purine intake
Cytotoxics
B12
Alcohol

Urate underexecretion

Renal impairment
Diuretics
Low-dose aspirin (but not this should still be given for cardioprotection if indicated)
Hypothyroidism
Lead poisoning

Investigation

Microscopy of joint aspirate - monosodium urate crystals are fine, needlelike and negatively birefringent under polarized light.
Serum urate level – usually raised but may be normal during an acute attack
XR

Usually normal until chronic diseaseand then may show extra-articular erosions and widened joint space

Management

Acute gout

Rest joint
NSAIDs
Colchicine if NSAIDs contraindicated
Corticosteroids (orally or intraarticularly) if NSAIDs/colchicine not sufficient
Do not start allopurinol during an acute attack

Preventative options

Diet inclusive of soy beans, cherries and skimmed milk
Avoidance of liver, kidneys, shellfish and yeast extracts/purine rich foods
Restrict alcohol intake
Allopurinol

Works by inhibiting xanthine oxidase
Give if

Second attack or
Tophi or
Renal insufficiency or
Uric acid stones or
On diuretics

Start 1-2 weeks after inflammation has settled

Small print gem: a side effect of colchicine is diarrhoea

References

Dore, R. The gout diagnosis. Cleve Clin J Med. 2008; 75 Suppl 5: S17-S21.

Jordan, K. et al. British Society for Rheumatology and British Health Professionals in Rheumatology Guideline for the Management of Gout. Rheumatology (Oxford). 2007; 46(8): 1372-1374.

Perez-Ruiz, F. et al. Imaging of gout: findings and utility. Arthritis Res Ther.2009; 11(3):232.

Rider, T. and Jordan, K. The modern management of gout. Rheumatology (Oxford). 2010. 49(1): 5-14.

Roddy, E. and Doherty, M. Epidemiology of gout. Arthritis Res Ther. 2010; 12(6): 223.

Polycystic ovarian syndrome

2012-03-01T19:44:00.002Z

The definition for polycystic ovarian syndrome varies, but the one adopted by the RCOG is 2 of 3 of:

Polycystic ovaries (12 or more peripheral follicles or ovarian volume >10cm^3)
Oligo or anovulation
Clinical and/or biochemical signs of hyperandrogenism (hirsuitism, acne, alopecia)

Features associated with polycystic ovarian syndrome include:

Polycystic ovaries
Hirsuitism
Acne
Obesity (40-50% of patients)
Subfertility
Oligo/amenorrhoea
Hypertension
Acanthosis nigricans
Increased risk of

Type 2 diabetes
Obstructive sleep apnoea

Biochemically:

Raised LH (40% of women)
Raised testosterone
Low or normal FSH

Management

Lifestyle changes to encourage weight loss
OCP to block androgen effects
Topical eflornithine hydrochloride (an inhibitor of the enzyme ornithine decarboxylase) for hirsuitism
Metformin
Clomifene if fertility issues
?ovarian drilling

References

Badawy, A. and Einashar, A. Treatment options for polycystic ovary syndrome. Int J Womens Health. 2011; 3:25-35.

Balen, A. and Rutherford, A. Managing anovulatory infertility and polycystic ovary syndrome. BMJ. 2007. 335(7621): 663-666.

Conway, G. and Jacobs, H. Acanthosis nigricans in obese women with the polycystic ovary syndrome: disease spectrum not distinct entity. Postgrad Med J. 1990; 66(777): 536-538.

Royal College of Obstetricians and Gynaecologists (RCOG). Long-term consequences of polycystic ovary syndrome. 2007. Available at http://www.rcog.org.uk/womens-health/clinical-guidance/long-term-consequences-polycystic-ovary-syndrome-green-top-33

Cryoglobulins

2012-02-29T14:59:00.000Z

Cryoglobulins are immunoglobulins that precipitate at temperatures below 37 c and redissolve above 37 c. They are identified in the laboratory by storing clotted blood at 4 c for 7 days and looking for a precipitate.

There are 3 types of cryoglobulinaemia:

Type 1 cryoglobulinaemia

Monoclonal, usually IgM
Accounts for 10-15% of cases of cryoglobulinaemia
Associated with

Multiple myeloma
Waldenstroms macroglobulinaemia
CLL

Features of type 1 cryoglobulinaemia include

Raynaud’s
Acrocyanosis
Gangrene

Type 2 and Type 3 cryoglobulinaemia = mixed cryoglobulinaemias

Type 2 is mono and poly clonal while type 3 is polyclonal only
Type 2 is the commonest, accounting for 50-60% of all cases of cryoglobulinaemia
The IgM of mixed cryoglobulinaemia typically has rheumatoid factor activity
Features include

‘Classic triad’

Purpura
Arthralgia
Weakness

Widespread vasculitis
Ulcers
Peripheral neuropathy
Membranoproliferative glomerulonephritis

Associated with

Hepatitis C (most common association)
HIV
Sjogren’s syndrome

Mixed cryoglobulinaemia may be complicated by

B cell lymphoma
Hepatocellular carcinoma
Thyroid cancer

References

Ferri, C. Mixed cryoglobulinemia. Orphanet J Rare Dis. 2008; 3:25.

Josephensen, G. Images in clinical medicine. Mixed cryoglobulinemia. N Engl J Med. 2005; 352(25): 2627.

Morra, E. Cryoglobulinemia. Hematology Am Soc Hematol Educ Program. 2005; 368-372.
Sansonno, D. et al. Hepatitis C virus infection, cryoglobulinaemia, and beyond. Rheumatology (Oxford). 2007. 46(4): 572-578.

Liver abscesses

2012-02-27T13:59:00.004Z

Liver abscesses may be:

Pyogenic (80% of liver abscesses in the developed world)
Amoebic
Fungal

Presentation:

Fever
Abdominal pain/tenderness
Nausea/vomiting
Chest pain
Weight loss
Rarely: cough/hiccups from diaphragmatic irritation

Diagnosis:

US
CT
Bloods – raised ALP commonest finding on LFTs

Management

2-3 weeks broad-spectrum IV antibiotics followed by 2-4 weeks oral antibiotics
Percutaneous drainage if >3cm in size
Surgical drainage if multiple/loculated abscess

Small print gem: most abscesses (around 70%) are in the right lobe of the liver

References

Albenmousa, A. et al. Liver abscess presentation and management in Saudi Arabia and the United Kingdom. Ann Saudi Med. 2011; 31(5): 528-532.

Heneghan, H. et al. Modern management of pyogenic hepatic abscess: a case series and review of the literature. BMC Res Notes. 2011; 4:80.

Pang, T. et al. Pyogenic liver abscess: an audit of 10 years’ experience. World J Gastroenterol. 2011; 17(12): 1622-1630.

Narcolepsy

2012-02-24T19:19:00.003Z

Narcolepsy is excessive daytime sleepiness, possibly accompanied by features such as:

Cataplexy (=brief attacks of sudden loss of skeletal muscle tone and power, often in response to emotion)
Irresistible sleep attacks
Hyponagogic hallucinations
Sleep paralysis

It is believed that narcolepsy with cataplexy is due to loss of hypocretin-containing neurons in the hypothalamus.

Onset usually in teens/20s

Male predominance

Increased risk if a family member has the disorder

Associations with

HLA DQB1
Streptococcal infection
Heavy metal exposure
H1N1 vaccination or infection

Management

Narcolepsy

DVLA must be informed – usually able to continue driving cars (if controlled) but not bus/lorry
Good sleep hygiene
Medication

Amphetamine-like stimulants such as dexamphetamine
Modafinil
Sodium oxybate

Cataplexy

Antidepressant drugs such as clomipramine or SSRIs

References

Akintomide, G. and Rickards, H. Narcolepsy: a review. Neuropsychiatr Dis Treat. 2011; 7: 507-518.

Wise, M. et al. Treatment of narcolepsy and other hypersomnias of central origin. Sleep. 2007; 30(12): 1712-1727.

Zeman, A. et al. Narcolepsy and excessive daytime sleepiness. BMJ. 2004; 329(7468): 724-728.

Saddle nose deformity

2012-02-23T20:24:00.000Z

Causes of a ‘saddle nose’ deformity include:

Trauma
Wegener’s granulomatosis
Congenital syphilis
Relapsing polychondritis

References

Chauhan. S. and D’Cruz, S. Images in clinical medicine. Saddle nose deformity. N Engl J Med. 2007; 356(26): 2720.

Paddock, M., Lynch, C. and Paska, L. Wegener’s granulomatosis in primary care. JRSM Short Rep. 2010. 1(7): 59.

Riechelmann, H. and Rettinger, G. Three-step reconstruction of complex saddle nose deformities. Arch Otolaryngol Head Neck Surg. 2004; 130(3): 334-338.

Wegener’s granulomatosis

2012-02-22T18:54:00.003Z

Wegener’s granulomatosis is a small and medium vessel necrotizing granulomatous vasculitis which predominantly affects the upper airways, lungs and kidneys but can affect any organ system.

Possible features include:

Respiratory symptoms – 90%

Cough
Pleuritis
Haemoptysis
Rhinorrhoea
Epistaxis

Sinusitis
Subglottic stenosis -20%
Saddle-shaped nose
Perforation of the nasal septum
Glomerulonephritis – develops in 80% at some point

Investigations:

Biopsy

Necrotising granulomatous vasculitis with neutrophilic infiltrates

Bilateral nodular infiltrates
Alveolar haemorrhage

ANCA

c-ANCA – positive in 90%
p-ANCA – positive in 10%

Treatment: steroids and cyclophosphamide, with co-trimoxazole to decrease opportunitistic infections

5 year survival with treatment is around 76%

Small print gem: Long-term treatment with cyclophosphamide is associated with increased risk of bladder cancer and myelodysplasia

References

Langford, C. and Hoffman, G. Wegener’s granulomatosis Thorax. 1999; 54(7): 629-637.

Lapraik, C. et al. BSR and BHPR guidelines for the management of adults with ANCA positive vasculitis. Rheumatology (Oxford). 2007; 46(10): 1615-1616.

Paddock, M., Lynch, C. and Paska, L. Wegener’s granulomatosis in primary care. JRSM Short Rep. 2010. 1(7): 59.

Obstructive sleep apnoea/hypopnoea syndrome

2012-02-20T19:25:00.002Z

Obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is a condition in which a person experiences repeated episodes of apnoea/hypopnoea because of closing of the pharyngeal airway during sleep (NICE definition)

Symptoms

Excessive daytime sleepiness
Snoring
Morning headaches
Nocturia
Sexual dysfunction
Impaired cognition

Risk factors for OSA

Increasing age
Obesity
Male gender
Enlarged tongue or tonsils

Conditions associated with OSAHS

Marfans
Downs
Acromegaly
Hypothyroidism

Diagnosis

History
Sleep study

Severity graded on the apnoea/hypnoea index (AHI)

Mild: AHI 5-14
Moderate: AHI 15-30
Severe: AHI >30

Management

Lifestyle changes

Weight loss
Stop smoking
Decrease alcohol

Dental devices to keep upper airway open (mild to moderate OSA only)
CPAP
Surgery should only be as part of a clinical trial

OSAHS increases:

Depression
Hypertension
Increased motor accidents

References

Eishaug, A. et al. Upper airway surgery should not be first line treatment for obstructive sleep apnoea in adults. BMJ. 2008; 336(7634): 44-45.

NICE. Continuous positive airway pressure for the treatment of obstructive sleep apnoea/hypopnoea syndrome. 2008. Available at http://publications.nice.org.uk/continuous-positive-airway-pressure-for-the-treatment-of-obstructive-sleep-apnoeahypopnoea-ta139

Riha, R., Gislasson, T. and Diefenbach, K. The phenotype and genotype of adult obstructive sleep apnoea/hypopnoea syndrome. Eur Respir J. 2009; 33(3):646-655.

Hypothermia

2012-02-17T18:58:00.000Z

Mild hypothermia: core body temperature < 35C

Severe hypothermia: core body temperature < 28C

Signs associated with moderate hypothermia include:

Bradycardia, atrial arrhythmias
Hypotension
Hypoventilation
Dilated pupils
Hyporeflexia

Signs associated with severe hypothermia include:

Ventricular arrhythmias or asystole
Coma
Unreactive pupils
Pulmonary oedema

Investigations

J wave
arrhythmias

Metabolic acidosis

Bloods

FBC - ? thrombocytopenia due to hepatosplenic sequestration
Coagulation – hypothermia can cause coagulopathy

Treatment:

Mild to moderate hypothermia: passive rewarming
Severe hypothermia: active rewarming

Small print gem: neuroleptic drugs can predispose people to hypothermia as they disrupt hypothalamic functioning and hence thermoregulation.

References

Epstein, E. and Anna, K. Accidental hypothermia. BMJ. 2006; 332(7543): 706-709.

McCulough, L. and Arora, S. Diagnosis and treatment of hypothermia. Am Fam Physician. 2004; 70(12): 2325-2332.

Pseudomembranous colitis

2012-02-15T17:54:00.000Z

Pseudomembranous colitis is an acute infective colitis which occurs when changes in the bowel flora allows overgrowth of clostridium difficile and thus production of its toxins (especially toxin A and B)

Presentation

Watery diarrhoea – may be bloody
Fever
Abdominal pain
Raised WCC

Risk factors

Broad-spectrum antibiotic use, especially:

Clindamycin
Second and third generation cephalosporins
Fluoroquinolones
Carbapenem

Parenteral nutrition
Diabetes
Renal failure
Liver failure
Cystic fibrosis
Upper GI surgery
Malnutrition

Diagnosis

Cytotoxin assay
Stool culture
Endoscopy

Cream/green pseudomembrane

Mucosal thickening
‘thumbprinting’ (= wide transverse bands associated with haustral fold thickening)

CT abdomen

Wall thickening
‘accordion sign’
‘target sign’

Complications of pseudomembranous colitis

Hypokalaemia
Renal failure
Hypoproteinaemia
Peritonitis
Toxic megacolon

Management

Oral vancomycin (10 to 14 days) plus

? IV metronidazole
?? oral rifampicin
?? IV immunoglobulin

Colectomy in extreme cases

References

Brar, H. and Surawicz, C. Pseudomembranous colitis: an update. Can J Gastroenterol. 2000; 14(1): 51-56.

Chen, N. and Shih, S. Images in clinical medicine. Pseudomembranous colitis. N Engl J Med. 2011; 364(5): e8.

Department of Health and Health Protection Agency. Clostridium difficile infection: How to deal with the problem. 2009. Available at http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/ClostridiumDifficile/Guidelines/

Kawamoto, S., Horton, K. and Fishman, E. Pseudomembranous colitis: spectrum of imaging findings with clinical and pathologic correlation. Radiographics. 1999; 19(4): 887-897.

Surawicz, C. and McFarland, L. Pseudomembranous colitis: causes and cures. Digestion. 1999; 60(2): 91-100.

Myocarditis

2012-02-13T17:14:00.000Z

Myocarditis is inflammation of the myocardium.

Presentation is highly variable and includes:

Prodrome of flu-like symptoms or gastroenteritis
Chest pain
Collapse
Heart failure

Causes of myocarditis include:

Viral

Adenovirus
Coxsackie
Parvovirus
HIV
HCV

Bacterial

Streptococcal
Mycoplasma pneumonia
Syphilis

Fungal
Drugs

Cocaine
TCA
Digoxin
Diuretics
Antibiotics – Cephalosporins, penicillin
Dobutamine

Other

Myocarditis may be classified by its cell type:

Lymphocytic (commonest; just over half of cases)
Granulomatous
Giant cell
Eosinophillic

Investigations

Bloods

Troponin/CKMB may be raised

ECG may show

Abnormal ST/T waves
Conduction disturbances

Echo findings may include

Transient wall thickening
Reduced wall motion
Pericardial effusion

Cardiac MRI
Cardiac catherisation with endomyocardial biopsy
Nuclear imaging

Management

Treat underlying cause
Support circulation as required

Complications

Dilated cardiomyopathy
Sudden cardiac death

References

JCS Joint Working Group. Guidelines for diagnosis and treatment of myocarditis (JCS 2009): digest version. Circ J. 2011;75(3):734-43.

Magnani J. and Dec, G. Myocarditis: current trends in diagnosis and treatment. Circulation. 2006;113(6):876-90.

Prader-Willi syndrome

2012-02-12T09:03:00.000Z

Prader-Willi syndrome is an inherited disorder characterized by:

Obesity
Hypotonia
Hypogonadism
Short stature
Mental retardation

Ironically, despite being characterized by obesity, babies with Prader-Willi have feeding problems and fail to thrive in infancy.

The classical phenotype of a patient with Prader-Willi Syndrome is:

Obese
Short stature
Almond-shaped eyes
Narrow bifrontal diameter
Downturned angles of the mouth
Small hands and feet
Straight ulnar border of hands

Prader-Willi Syndrome is caused by a deletion/disruption of gene(s) on chromosome 15.

Diagnosis is by genetic analysis.

Management

Strict control of food intake
Growth hormone replacement

References

Cataletto, M. et al. Prader-Willi syndrome: A primer for clinicians. Int J Pediatr Endocrinol. 2011; 1:12.

OMIM. Prader-Willi Syndrome. Available at http://omim.org/entry/176270

Wattendorf, D. and Muenke, M. Prader-Willi syndrome. Am Fam Phydician. 2005; 72(5): 827-830.

Acanthosis nigricans

2012-02-11T09:17:00.000Z

Acanthosis nigricans is characterized by velvety, brown-black plaques, typically located in the axilla and neck.

It is associated with:

Insulin-resistance:

Diabetes
Acromegaly
Cushing syndrome
Hypothyroidism
PCOS

Malignancy – especially gastric adenocarcinoma
Other

Primary biliary cirrhosis
Prader-Willi syndrome
Medications

Glucocorticoids
OCP
Niacin

Management

Treat underlying cause
? retinoids

References

Higgins, S., Freemark, M. and Prose, N. Acanthosis nigricans: a practical approach to evaluation and management. Dermatol Online j. 2008; 14(9): 2.

Talsania, N. et al. Paraneoplastic Acanthosis Nigricans: The importance of exhaustive and repeated malignancy screening. Dermatol Online J. 2010; 16(8):8.

Side effects of corticosteroid treatment

2012-02-10T08:38:00.000Z

Side effects of corticosteroid treatment include:

Musculoskeletal

Osteoporosis
Fractures – 12%
Avascular necrosis of femoral head (high doses)
Proximal myopathy

Gastrointestinal

Peptic ulceration
Acute pancreatitis

Endocrine

Weight gain
Diabetes
Adrenal suppression
Hypercholesterolaemia/hyperlipidaemia
Menstrual disturbances

Skin

Acne
Skin bruising/thinning
Hirsutism

Other

Sleep disturbance
Mood disturbance
Cataracts -15%
Glaucoma
Hypertension
Increased susceptibility to infection

Adrenal suppression may occur after just 5 days of high dose steroids, and can occur even at low doses after prolonged use.

Significance of adrenal suppression:

When stopping dose should be tapered rather than abruptly stopped
Increased dose is required during illness
Dose required during induction for surgery and increased dose afterwards

References

British National Formulary. 2011. Available at www.bnf.org

Curtis, J. et al. Population-based assessment of adverse events associated with long-term glucocorticoid use. Arthritis Rheum. 2006; 55(3): 420-426.

Peacey, S. et al. Corticosteroid therapy and intercurrent illness: the need for continuing patient education. Postgrad Med J. 1993; 69(810): 282-284.

Pisu, M. et al. The cost of glucocorticoid-associated adverse events in rheumatoid arthritis. Rheumatology (Oxford). 2005; 44(6): 781-788.

Polymyalgia rheumatica

2012-02-09T09:46:00.000Z

Polymyalgia rheumatica is an inflammatory rheumatic disease characterized by:

Bilateral shoulder and/or pelvic girdle aching
Morning stiffness >45 minutes duration
Raised ESR
Systemic symptoms

Low grade fever
Weight loss

Average age of onset is >70. It is very rare in those <50.

Females > males (3:1)

People of north European ancestery more likely to be affected.

There is evidence of a link to HLA DR4

Treatment

Oral prednisolone – 15mg OD – tends to improve condition dramatically within days. Taper dose to lowest level that works.
Limit risks of adverse effects of steroid treatment, e.g. with osteoporosis prophylaxis.
IM methylprednisolone may be used in milder cases and may reduce the risk of steroid-related complications.

Complications associated with PMR:

Carpel tunnel syndrome
Giant cell arteritis (30%)

References

Dasgupta, B. et al. BSR and BHPR guidelines for the management of polymyalgia rheumatica. Rheumatology (Oxford). 2010; 49(1): 186-190.

Michet, C. and Matteson, E. Polymyalgia rheumatic. BMJ. 2008; 336(7647): 765-769.

Van Hecke, O. Polymyalgia rheumatica – diagnosis and management. Aus Fam Physician. 2011; 40(5): 303-306.

Sickle Cell Disease

2012-02-08T08:30:00.000Z

Sickle cell disease is an autosomal recessive condition caused by an abnormal form of haemoglobin, HbS, which polymerises into long crystals when it deoxygenates, resulting in the sickling of red blood cells. This abnormality is caused by a glutamine to valine substitution on the beta globin chain.

Genotypes include:

HbSS = sickle cell anaemia = commonest form in UK and most severe
HbSC = SC disease = mild anaemia
HbS beta thalassaemia trait

Carriers are asymptomatic and have increased resistance to malaria.

Diagnosis of sickle cell disease is by electrophoresis.

Complications of sickle cell disease include:

Simple pain crisis
Sequestatration crisis

Acute chest syndrome

Breathlessness, chest/back pain, fever, cough
Possible causes include sequestatration, infection and pulmonary vascular occlusion

Splenic sequestration

Eventualy spleen becomes atrophic --> increased risk of infection

Aplastic crisis

Classically due to parvovirus

Haemolytic anaemia
Priapism – up to 8% of male patients
Avascular necrosis of the hip
Renal failure – up to 5%
Eye problems

Retinopathy
Retinal detachment

Infections
Splenomegaly
Gallstones
Stroke
Pulmonary hypertension
Iron overload (due to recurrent transfusions)

Precipitants of a sickle cell crisis:

Infection
Dehydration
Stress
Hypoxia

Management

Transfusion

Blood must be matched for minor blood group antigens Kell and Rh

Hydroxyurea

Increases production of HbF

Prophylactic antibiotics
Acute painmanagement: Oral/IV analgesia as per pain ladder; morphine/diamorphine/PCA may be needed

References

Brozovic, M. and Davies, S. Management of sickle cell disease. Postgrad Med J. 1987; 63(742): 605-609.

Claster, S. and Vichinsky E. Managing sickle cell disease. BMJ. 2003; 327(7424): 1151-1155.

Frenette, P. and Atweh, G. Sickle cell disease: old discoveries, new concepts, and future promise. J Clin Invest. 2007; 117(4): 850-858.

Piel, F. et al. Global distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis. Nat Commun. 2010; 1:104.

Taylor, C. et al. Clinical presentation of acute chest syndrome in sickle cell disease. Postgrad Med J. 2004; 80(944): 346-349.

Oesophageal carcinoma

2012-02-07T09:37:00.000Z

Oesophageal carcinoma has an incidence of 9.6/100 000 and a very poor prognosis – 5 year survival is less than 10%.

2/3rds of cases are in over 65s.

Presentation tends to be dysphagia.

In the UK the commonest type is adenocarcinoma.

Identified risk factors for oesophageal adenocarcinoma include:

Reflux/Barrett’s oesophagus
Hiatus hernia
Obesity
Diet lacking in fruit and vegetables
Fatty diet
Smoking
Male gender

Worldwide the commonest type of oesophageal cancer is squamous cell. It is especially common in China and Iran.

Identified risk factors for oesophageal squamous cell carcinoma include:

Diet lacking in fruit and vegetables
Fatty diet
Smoking
Male gender
Alcohol
Achalasia
Low socioeconomic status
Plummer-Vinson syndrome
Nutritional deficiencies – zinc, magnesium, riboflavin, nicotinic acid

Adenocarcinomas are usually located in the distal third of the oesophagus (94%) while squamous cell carcinomas are usually found in the middle and upper third.

Management is oesophagectomy + ?chemo/radiotherapy

References

Allum, W. et al. Guidelines for the management of oesophageal and gastric cancer. Gut. 2002; 50(Suppl 5): v1-23.

Bird-Lieberman, E. and Fitzgerald, R. Early diagnosis of oesophageal cancer. Br J Cancer. 2009; 101(1): 1-6.

Wolf, M. et al. Curative treatment of oesophageal carcinoma: current options and future developments. Radiat Oncol. 2011; 6:55.

Lymphadenopathy

2012-02-06T09:00:00.000Z

Causes of generalized lymphadenopathy

Neoplastic

Lymphoma
leukaemia

Infective

EBV
CMV
HIV
TB
Toxoplasmosis

Medications

Allopurinol
Atenolol
Penicillin
Phenytoin
Quinidine

Rheumatological

Storage diseases

Gaucher’s disease
Fabry’s disease

Causes of local lymphadenopathy

Local infection
Neoplasia

Small print gems:

Virchow's node - left supraclavicular node associated with intraabdominal cancer

Sister Mary Joseph node - umbilical node associated with intraabdominal cancer

References

Bazemore, A. and Smucker, D. Lymphadenopathy and malignancy. Am Fam Physician. 2002; 66(11): 2103-2110.

Ferrer, R. Lympadenopathy: differential diagnosis and evaluation. Am Fam Physician. 1998; 58(6): 1313-1320.

Karpf, M. Lymphadenopathy. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 149.

Familial adenomatous polyposis

2012-02-05T08:30:00.000Z

Familial adenomatous polyposis is a condition in which multiple polyps (up to tens of thousands) develop in the GI tract followed almost inevitably by the onset of colorectal cancer.

It is inherited in an autosomal dominant fashion but up to 30% of cases may be new mutations with no family history.

The mutation is in the tumour suppressor gene APC (adenomatous polyposis coli) on chromosome 5.

Management is with total colectomy and ileorectal anastomosis before cancer develops.

Patients still tend to have a lower life expectancy than the general population due to their propensity for duodenal and other upper GI cancers.

References

OMIM. Familial adenomatous polyposis. Available at http://omim.org/entry/175100

Wyman, A. and Shorthouse, A. Familial adenomatous polysis: an update. J R Soc Med. 1996; 89(4): 224P-228P.

Primary biliary cirrhosis

2012-02-04T19:13:00.001Z

Primary biliary cirrhosis is an autoimmune cholestatic liver disease which is diagnosed when 2 of the following 3 criteria are met:

At least 6 months biochemical evidence of cholestatic liver disease
Anti-mitochondrial antibody (AMA) positive
Characteristic histological features on liver biopsy

Loss of biliary epithelial cells
Portal infiltration of T cells, B cells, NK cells, macrophages and eosinophils

Females > males, 10:1Onset usually around 5th decade of life

Blood tests

LFTs show

Raised ALP and gammaGT
ALT, AST and bilirubin may be raised

Raised PT only in advanced disease
AMA – 90% sensitive, 95% specific
ANA – non-specific, present in 30%

Complications

Cirrhosis

If cirrhosis present increased risk of hepatocellular carcinoma

Portal hypertension
Osteoporosis (1/3)

Treatment

ursodeoxycholic acid
liver transplant
osteoporosis prophylaxis

References

European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of cholestatic liver disease. Journal of Hepatology. 2009; 51: 237-267.

Jones, D. Pathogenesis of primary biliary cirrhosis. Gut. 2007; 56(11): 1615-1624.

Nguyen, D., Juran, B. and Lazaridis, K. Primary biliary cirrhosis. Best Pract Res Clin Gastroenterol. 2010; 24(5): 647-654.

Thrombocytopenia

2012-02-03T16:56:00.002Z

Normal platelet count is 150x10^9 to 400x10^9.

Presentation of thrombocytopenia may include epistaxis, bruising or menorrhagia.

Causes of thrombocytopenia

Decreased production

Congenital

Fanconi’s anaemia
Wiskott-Aldrich syndrome

Acquired

Aplastic anaemia
Leukaemia
Marrow infiltration
Radiotherapy
Drugs

Penicillamine
Chemotherapy

Viral infection
Malaria
Alcohol
B12/folate deficiency

Increased destruction

Idiopathic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura
Disseminated intravascular coagulation
Splenomegaly
Infection
Drugs

Heparin
Quinine
Sulphates
Penicillin

Post-transfusion purpura

Treatment depends on the cause.

Small print gem: platelets have a life span of 7 to 10 days

References

Laub, D. Isoniazid causing drug-induced thrombocytopenia. Eplasty. 2011; 11:ic10.

Liesner, R. and Machin, S. ABC of clinical haematology. Platelet disorders. BMJ. 1997; 314(7083): 809-812.

Polycystic kidney disease

2012-01-26T19:51:00.001Z

Autosomal dominant polycystic kidney disease

Incidence 1 in 1000

2 types exist:

Type 1

mutation in PKD1 on chromosome 16
85% of cases
more severe disease – earlier end stage renal failure

Type 2

mutation in PKD2 on chromosome 4

Presentation:

Flank/back pain
Haematuria
UTI
Abdominal mass
Hypertension (75%)

Note that autosomal dominant polycystic kidney disease is a systemic disease:

Cysts may also be found in:

Liver (75% of patients)
Pancreas
Ovaries
Choroid plexus

Other associated complications include

Aortic aneurysm
Mitral valve prolapse and MR
Aortic regurgitation
Subarachnoid haemorrhage

Autosomal recessive polycystic kidney disease

Incidence 1 in 6000 - 40000
Inherited on chromosome 6
Up to 30% die by the neotnatal period
End stage renal failure occurs in a third in childhood
Associated with congenital hepatic fibrosis

Other genetic diseases causing renal cysts include:

Von Hippel-Lindau
Tuberous sclerosis
Zellweger syndrome

References

Harris, P. and Torres, V. Polycystic kidney disease. Annu Rev Med. 2009; 60: 321-337.

Igarasfi, P. and Somio, S. Genetics and pathogenesis of polycystic kidney disease. J Am Soc Nephrol. 2002; 13(9): 2384-2398.

Leptospirosis

2012-01-25T20:52:00.002Z

Leptospirosis is the infection caused by the spirochaete leptospira.

Transmission is classically by exposure of skin/mucous membranes to contaminated rats urine, for example swimming in rivers/ falling out of boats. This is known as Weil’s disease.

Transmission may also be from cattle to humans – this is the Hardjo form of leptospirosis.

Incubation period is 2 to 20 days.

Presentation

Fever
Headache
Myalgia
Arthralgia
Nausea/vomiting
Jaundice
Photophobia

Complications of leptospirosis, which usually occur 5 to 10 days after infection, include:

Renal failure
Hepatic failure
Aseptic meningitis
Pulmonary haemorrhage

Diagnosis may be by culture, PCR or serology.

Treatment is with doxycycline, ceftriaxone, amoxicillin, erythromycin or benzylpenicillin.

References

Philipp, R., King, C. and Hughes, A. Understanding of Weil’s disease among canoeists. Br J Sports Med. 1992; 26(4): 223-227.

Slack, A. Leptospirosis. Aust Fam Physician. 2010; 39(6): 495-498.

WHO. Human leptospirosis: Guidance for diagnosis, surveillance and control. 2003. Available at www.who.int/csr/don/en/WHO_CDS_CSR_EPH_2002.23.pdf

Giant cell arteritis

2012-01-24T21:37:00.002Z

Giant cell arteritis (=temporal arteritis) is a systemic medium and large vessel vasculitis with a predilection for the extracranial branches of the carotid arteries.

Presentation may include

Headache (around 70%)
Jaw claudication (around 40%)
Fever (around 30%)
Amarosis fugax (around 25%)

Roughly 50% of people with giant cell arteritis also have polymyalgia rheumatica

Almost all patients are >50 years old

There is an association with HLA-DR4

Diagnosis

ESR – usually raised
Abnormal temporal arteries on examination
Temporal artery biopsy

Mononuclear infiltrates or granulomas
Normal biopsy does not exclude diagnosis as there are ‘skip lesions’

Treatment is oral steroids.

Complications

Irreversible blindness (up to 10%)
Aortic aneurysms
Aortic regurgitation
Ischaemic strokes

References

Calvo-Romero, J. Giant cell arteritis. Postgrad Med J. 2003; 69(935): 511-515.

Swannell, A. Polymyalgia rheumatic and temporal arteritis: diagnosis and management. BMJ. 1997; 314(7090): 1329-1332.

Ankylosing spondylitis

2012-01-23T20:59:00.000Z

Ankylosing spondylitis is a chronic inflammatory disease that primarily affects the axial skeleton, with sacroilitis being the main feature. It is one of the spondyloarthropathies.

It affects more males than females (5:1)

There is a strong association with HLA B27 (around 95% of patients)

Classic presentation:

Low back pain

Worse in morning
Worse after rest
Improves with activity

Examination

Restricted flexion and extension of lumbar spine

Schober’s test: 2 marks on patient’s back 10cm apart, with lower mark at level of posterior superior iliac spinenormal flexion results in an increase of 5cm or more

Loss of lumbar lordosis
Increased thoracic kyphosis
Decreased chest expansion

Investigation

Spinal XR

Squaring of vertebral bodies
Ossification of spinal ligaments
Fusion of vertebral column - ‘bamboo spine’

Extra-articular associations:

Psoriasis
Uveitis
Inflammatory bowel disease
Increased risk of cardiovascular disease
Increased risk of osteoporosis
Aortic regurgitation
Pulmonary fibrosis
Cardiac conduction problems

Treatment

Regular exercise
NSAIDs
Anti-TNF therapy
No evidence for DMARDs in axial disease, but sulfasalazine may be considered for peripheral arthritis

References

Braun, J. et al. 2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis. 2011; 70(6): 896-904.

McVeigh, C and Cairns, A. Diagnosis and management of ankylosing spondylitis. BMJ. 2006. 333(7568): 581-585.

Siper, J. et al. Ankylosing spondylitis: an overview. Ann Rheum Dis. 2002. 61(Suppl 3): iii8-iii18.
Ward, M. and Kuzis, S. Ceiling effects and the Schober test. J Rheumatol. 2003; 30(12): 2732-2733.

Pyoderma gangrenosum

2012-01-22T18:42:00.001Z

Pyoderma gangrenosum is an ulcerating skin disease.

Presentation:

A deep violet-blue ulcer with a well-defined, undermined edge

Can occur anywhere but is most common on the legs
Usually painful

Systemic symptoms – fever, arthralgia, malaise

It is a neutrophillic dermatoses, like Sweet’s syndrome

Around half of cases of pyoderma gangrenosum are idiopathic.

The other half may be associated with:

Inflammatory bowel disease – commonest association

Overall 2% of patients with IBD will have pyoderma gangrenosum

Arthritis
Haematological malignancies

Myeloid > lymphoid, AML most commonly
myeloproliferative disorders
myeloma

Sarcoidosis
Wegeners granuomatosis
Diabetes mellitus
Behcet’s disease

Diagnosis

Pyoderma gangrenosum is a clinical diagnosis
Biopsy may be undertaken to exclude other diagnoses, such as malignancy or vasculitis

Treatment

Currently a lack of definitive evidence but in general systemic steroids or ciclosporin are used.

References

Brooklyn, T., Dunnill, G. and Probert, C. Diagnosis and treatment of pyoderma gangrenosum. BMJ. 2006; 333(7560): 181-184.

Lear, J., Atherton, M. and Byrne, J. Neutrophilic dermatoses: pyoderma gangrenosum and Sweet's syndrome. Postgrad Med J. 1997; 73(856):65-68.

Von Willebrand disease

2012-01-21T19:33:00.001Z

Von Willebrand disease is defined as impaired Von Willebrand Factor (VWF) function resulting in impaired haemostasis.It is the commonest of the inherited bleeding disorders.

Von Willebrand’s factor is a glycoprotein made in epithelial cells and megakaryocytes which:

Acts as a bridging molecule between platelets and the sub-endothelium
Helps platelets bind to each other
Is a carrier of factor VIII, helping to prevent its breakdown in the circulation

Types of Von Willebrand’s disease:

Type 1

Decreased quantity of VWF
Mild to moderate bleeding

Type 2 (several subtypes exist)

Qualitative defect - abnormal types of VWF

Type 3

Trace of VWF
Autosomal recessive
Severe bleeding disorder

Presentation includes

Prolonged bleeding after injury
Easy bruising
Prolonged epistaxis
Menorrhagia
Oral bleeding (eg after tooth extraction)

Investigation

VWF antigen level

At least 2 occasions
Will be low or normal in Von Willebrand’s disease
Note it is elevated by exercise and hyperthyroidism
It is decreased by hypothyroidism

Von Willebrand factor ristocetin cofactor activity
PT, platelet count and fibrinogen levels are usually normal

Treatment

Desmopressin (DDAVP)

Increases factor VIII and VWF
Useful in type 1, variably useful in type 2, not useful in type 3

Tranexamic acid

An antifibrinolytic agent
Useful in management of epistaxis and menorrhagia
Avoid in patients with history of thromboembolic disease or current upper urinary tract bleeding

VWF/factor VIII concentrate

Acquired von Willebrand syndrome is associated with

Myeloproliferative disorders
Autoimmune diseases
Neoplasia
Lymphoproliferative disorders
Structural cardiac defects

Small print gem: VWF is an acute phase protein and so may be raised in infection, malignancy and inflammatory conditions.

References

Crownover, B. et al. Sle Diagnosing von Willebrand disease. Am Fam Physician. 2010; 81(12):1415-1418.

Federici, A. The von Willebrand factor from basic mechanisms to clinical practice. Blood Transfus. 2011; 9 Suppl 2:s1-2.

Laffan, M. et al. The diagnosis of von Willebrand disease: a guideline from the UK Haemophilia Centre Doctors Organization. Haemophilia (2004), 10, 199–217

Pasi, K. et al. Management of von Willebrand disease: a guideline from the UK Haemophilia Centre Doctors’ Organization. Haemophilia (2004), 10, 218–231

Rodeghiero, F., Castaman, G. and Tosetto, A. How I treat von Willebrand disease. Blood. 2009; 114(6):1158-1165.

Barrett’s oesophagus

2012-01-20T07:30:00.000Z

Barrett’s oesophagus is a change in the lining of the oesophagus from normal multilayered squamous mucosa to single layered metaplastic columnar mucosa.

It occurs in 2% of the population

Causes of Barrett’s oesophagus:

Gastrooesophageal reflux disease – main cause - Barrett’s develops in 5% of patients with GORD
Chemotherapy
NSAID use
Viral oesophagitis
Congenital retardation syndromes

Diagnosis is by endoscopy with biopsy

The main complication associated with Barrett’s oesophagus is conversion to oesophageal adenocarcinoma. This occurs in 5% men and 3% women with Barrett’s oesophagus.

Risk factors for conversion:

Male gender
White ethnicity
Length affected >8cm
Smoking
Obesity
Diet low in fruit and veg but high in fats

Management:

Endoscopy with biopsy every 2 years
Acid suppression therapy (usually PPIs)
?Nissen fundiplication

References

Jankowski, J. Diagnosis and management of Barrett's oesophagus. BMJ. 2010; 341:c4551

Working Party of the British Society of Gastroenterology. Guidelines for the diagnosis and management of Barrett's columnar-lined oesophagus. 2005. Available at http://www.bsg.org.uk/clinical-guidelines/oesophageal/guidelines-for-the-diagnosis-and-management-of-barrett-s-columnar-lined-oesophagus.html

Mesothelioma

2012-01-19T08:00:00.000Z

Most cases of mesothelioma are caused by asbestos fibres. Amphibole asbestos fibre has a higher risk of mesothelioma than amphibole fibre.

The median latency between exposure to asbestos and death from mesothelioma is 32 years

Presentation:

Chest pain – may be dull, heavy, aching or pleuritic
Dyspnoea
Less commonly:

Cough
Abdominal pain
Pneumothorax

Metastatic symptoms are uncommon

Diagnosis

History – look for occupational asbestos exposure
Examination

Pleural effusion
Finger clubbing – 30%

Investigations

CXR – may show

Pleural thickening
Pleural effusion

CT chest
Pleural tap
If doubt about diagnosis - biopsy

Management

Early pleurodesis for symptomatic relief
Palliative radiotherapy
Possible chemotherapy
Make patients aware of medicolegal aspects
Radical surgery only indicated as part of a clinical trial

Prognosis

Median survival once diagnosed is 8 to 14 months

Small print gem: mesothelioma may also be peritoneal but this is rarer – there are 12 cases of pleural mesothelioma for each case of peritoneal mesothelioma

References

British Thoracic Society Standards of Care Committee. BTS statement on malignant mesothelioma in the UK, 2007. Thorax. 2007; 62: ii1-ii19.

Moore, A., Parker, R. and Wiggins, J. Malignant mesothelioma. Orphanet J Rare Dis. 2008; 3:34.

Dumping syndrome

2012-01-18T08:00:00.000Z

Dumping syndrome develops after gastric surgery in up to 50% of cases, with up to 10% having significant symptoms.

Dumping syndrome can be divided into early and late:

Early dumping syndrome

Occurs 10 to 30 minutes after eating
Symptoms

Vasomotor symptoms

Palpitations
Sweating
Weakness

Gastrointestinal symptoms

Bloating
Cramping
Diarrhoea

Thought to be due to rapid emptying of hypermosmolar stomach contents into the small bowel, causing fluid shift from extravascular space into the intestinal lumen
accounts for 75% of dumping syndrome

Late dumping syndrome

Occurs 2 to 4 hours after eating
Symptoms

Sweating
Palpitations
Confusion
Occasionally syncope

Thought to be due to reactive hypoglycaemia
Diagnosis may be confirm by frequent blood samples after an oral glucose challenge

Management

Reduction of carbohydrate intake
? octreotide in severe cases

References

Kreckler, S., Dowson, H. and Willson, P. Dumping syndrome as a complication of laparoscopic Nissen fundoplication in an adult. JSLS. 2006; 10(1):94-96.

Li-Ling, J. and Irving, M. Therapeutic value of octreotide for patients with severe dumping syndrome--a review of randomised controlled trials. Postgrad Med J. 2001; 77(909): 441-442.

Mitral stenosis

2012-01-17T08:30:00.000Z

The normal area of the mitral valve is 4-6cm ^2

Mild mitral stenosis: area 1.6-2cm^2 with a mean pressure drop of <5mmHg

Severe mitral stenosis: area <1cm^2 with a mean pressure drop of >10mmHg

Aetiology

Most commonly rheumatic fever
Rarely:

Carcinoid syndrome
Weight loss medications

Presentation

Exertional dyspnoea
Orthopnoea
Paroxysmal nocturnal dyspnoea
Haemoptysis – due to pulmonary hypertension causing rupture of anastomoses of bronchial veins
Rarely –horseness due to compression of left recurrent laryngeal nerve

On examination

Mitral facies
AF – 40%
Loud S1 (or absent S1 in severe disease)
Opening snap
Rumbling mid-diastolic murmur
Occasionally – high-pitched blowing murmur at cardiac base = Graham Steell murmur
If pulmonary hypertension has developed:

Hepatomegaly
Ascites
Oedema

Diagnosis is usually by echocardiography

Management

Medications

Diuretics/long-acting nitrates to improve dyspnoea
Beta-blockers/calcium channel blockers may improve exercise tolerance
Anticoagulate if AF

Percutaneous mitral commissurotomy (=balloon dilation)

Indicated if valve area <1.5cm^2 AND

symptomatic OR
asymptomatic but at high risk of embolism OR
haemodynamic decompensation

Risks:

Mortality 0.5-4%
Haemopericardium 0.5-10%
Embolism 0.5-5%
Severe MR 2-10%

Surgery

References

Carabello, B. Modern management of mitral stenosis. Circulation. 2005;112(3):432-437.

Masani, N. et al. Echocardiography: Guidelines for valve quantification. Available at: http://www.bhf.org.uk/publications/view-publication.aspx?ps=1001602

Vahanian, A. et al. Guidelines on the management of valvular heart disease. European Heart Journal. 2007; 28: 230–268.

Pleural effusion

2012-01-16T08:00:00.000Z

Pleural effusions can be divided into transudates and exudates. Light’s criteria is used to distinguish between them.

Light’s criteria:

Pleural fluid is an exudate if one or more of the following criteria are met:

Pleural fluid protein divided by serum protein is >0.5
Pleural fluid LDH divided by serum LDH is >0.6
Pleural fluid LDH is >2/3 the upper limits of laboratory normal value for LDH

Diagnostic pleural taps should ideally be done under US guidance and the fluid sent for:

All cases:

Protein
LDH
Gram stain
Cytology and cell count
Microbiological culture

Specific cases:

pH – if pleural infection suspected
Amylase – only if oesophageal rupture or pancreatic-associated effusion suspected
Glucose – useful in diagnosis of rheumatoid effusion
Triglycerides and cholesterol – if effusion milky and chylothorax suspected
Haematocrit – if haemothorax suspected

Causes of exudative pleural effusions:

Common

Malignancy
Parapneumonic
TB

Less common

PE
RA
Benign asbestos effusion
Pancreatitis
Post MI
Post CABG

Rare

Yellow nail syndrome
Drugs

Methotrexate
Amiodarone
Phenytoin
Nitrofurantoin
Beta blockers
Penicillamine
Cyclophosphamide

Fungal infections

Causes of transudative pleural effusions

Very common

LVF
Liver cirrhosis

Less common

Hypoalbuminaemia
Peritoneal dialysis
Hypothyroidism
Nephrotic syndrome
Mitral stenosis

Rare causes

Constrictive pericarditis
Meigs’ syndrome
Superior vena cava obstruction

Causes of lymphocytic pleural effusion:

Very high (>80%) lymphocytes

Less high (>50%):

Any long-standing pleural effusion
Malignancy –mesothelioma, metastatic adenocarcinoma
Cardiac failure
Yellow nail syndrome
Uraemia

pH <7.2 indicates the need for drainage
pH <7.3

malignant effusions
pleural infection
connective tissue diseases
TB
Oesophageal rupture

Glucose

Low (<3.4mmol/l)

Parapneumonic
RA
TB
Malignancy
Oesophageal rupture

Very low (<1.6mmol/l)

RA
Empyema

When PE's cause effusions, the dyspneoa is often disproportionate to the size of the effusion.

Post CABG effusions: left >right

Management

If clinically a transudate is suspected, treat cause
If cause unclear, perform a diagnostic tap and then treat cause as appropriate
If pleural aspiration (thoracocentesis) is indicated:

Stop when patient develops chest discomfort or cough or when 1.5l has been drained

Malignant pleural effusion (symptomatic)

Unless very short life expectancy, chest drain as high probability of recurrence if theraupetic aspiration alone
Consider pleurodesis once effusion drained and lung re-expanded

Drain large effusions in a controlled fashion to decrease risk of re-expansion pulmonary oedema

Small print gem: there needs to be around 200mls of fluid for it to be detectable on a PA CXR.

References

Hooper, C. et al. Investigation of a unilateral pleural effusion in adults: British Thoracic Society pleural disease  guideline 2010. Thorax. 2010; 65(Suppl 2): ii4-ii17.

Medford, A. and Maskell, N. Pleural effusion. Postgrad Med J. 2005; 81(961):702-10.

Roberts, M. et al. Management of a malignant pleural effusion: British Thoracic Society pleural disease guideline 2010. Thorax. 2010; 65(Suppl 2): ii32-ii40.

Silicosis

2012-01-15T07:30:00.000Z

Silicosis is a condition caused by inhalation of silica dust resulting in lung fibrosis.

Silica is found in sand, rock and mineral ore. Occupational exposure may occur through mining, drilling, sandblasting or quarrying.

Crystalline/free silica (such as quartz) is a carcinogen and linked to lung cancer.

Radiographs may show small nodules or more widespread fibrotic changes.

Spirometry shows a restrictive pattern

References

Akgun, M. et al. An epidemic of silicosis among former denim sandblasters. Eur Respir J. 2008; 32(5):1295-1303.

Peretz, A. et al. Silica, silicosis, and lung cancer. Isr Med Assoc J. 2006; 8(2):114-118.

Thomas, C. and Kelley, T. A brief review of silicosis in the United States. Environ Health Insights. 2010; 4:21-26.

Courvoisier’s sign

2012-01-14T18:00:00.000Z

Courvoisier’s sign/law is that a palpable gallbladder in a patient with obstructive jaundice is unlikely to be due to gallstones.

Courvoisier observed that if a stone was causing the obstruction the gallbladder was likely to be fibrotic from chronic inflammation and would therefore not dilate, whereas if the obstruction was due to a cause other than a stone the gallbladder would not have been subjected to chronic inflammation so would be able to dilate and thus be palpable on examination.

Courvoisier’s sign suggests pancreatic cancer or cholangiocarcinoma.

References

Anonymous. Ludwig Courvoisier (1843–1918): Courvoisier’s sign. JAMA 1968; 204:627

Parmar, M. Courvoisier’s Law. CMAJ. 2003; 168(7)): 876-877.

Pancreatic cancer

2012-01-14T07:30:00.000Z

Pancreatic cancer has a poor prognosis - 5 year survival is <5%

Commonest pathology is ductal adenocarcinoma (>90%) and commonest location is head of pancreas.

Presentation

Weight loss
Pain

Persistent back pain suggests retroperitoneal infiltration

Jaundice
Adult-onset diabetes in past 2 years (5% of cases)
Abdominal mass
Ascites
Courvoisier’s sign
Migratory thrombophlebitis

Risk factors for pancreatic cancer

Smoking
Alcohol
Family history
Peutz-Jeghers syndrome
HNPCC
Chronic pancreatitis
Hereditary pancreatitis
Diabetes mellitus

Investigation

Most useful initial investigation: abdominal US
CT/MR/MRCP

Management

Surgical resection if appropriate
Stenting if required to relieve jaundice
?Chemo

References

Johnson, C. et al. Guidelines for the management of patients with pancreatic cancer periampullary and ampullary carcinomas. Gut. 2005; 54:v1-v16.

Zavoral, M. et al. Molecular biology of pancreatic cancer. World J Gastroenterol. 2011;17(24):2897-908.

Dermatitis herpetiformis

2012-01-13T08:30:00.000Z

Dermatitis herpetiformis is an autoimmune skin condition characterized by pruritic vesicles and papules most commonly on the extensor surfaces of elbows and proximal forearms.

It is strongly associated with coeliac disease.

Diagnosis is by biopsy showing IgA deposits.

Treatment

Gluten-free diet – but this alone would take around 2 years to decrease the rash
Dapsone or sulphonamides

Dapsone must be avoided in those with G6PD deficiency as it will cause haemolytic anaemia.

References

Bickle K, Roark TR, Hsu S. Autoimmune bullous dermatoses: a review. Am Fam Physician. 2002;65(9):1861-70.

Fry L. Dermatitis herpetiformis: problems, progress and prospects. Eur J Dermatol. 2002;12(6):523-31.

Coeliac disease

2012-01-12T08:00:00.000Z

Coeliac disease is an autoimmune condition in which there is increased immunological responsiveness to ingested gluten resulting in villous atrophy and malabsorption.

Gluten is found in wheat, barley and rye.

Signs and symptoms of coeliac disease:

Abdominal pain
Weight loss
Diarrhoea
Steatorrhoea
Bloating
Nausea and vomiting
Fatigue
Unexplained iron deficiency or other anaemia

Conditions associated with coeliac disease include:

Dermatitis herpetiformis (up to 90% of patients with dermatitis herpetiformis will have coeliac disease)
IBS
Type 1 diabetes
Multiple autoimmune conditions, including autoimmune thyroid disease and autoimmune liver disease

Genetics

There is 75% concordance in monozygotic twins.
HLA DQ2 is associated with most cases of coeliac disease.
HLA DQ8 is present in a minority of cases

Diagnosis

Serology

Need to have a gluten-containing diet for 6 weeks prior to testing
IgA tissue transglutaminase (tTGA) is the first choice test (sensitivity 95%)
IgA endomysial antibodies (EMA) is recommended if tTGA result is equivocal
If tTGA is negative, test for IgA deficiency (which is associated with coeliac disease) and if present do IgG tTGA
If a positive serology result is obtained, or it is negative but there is an ongoing clinical suspicion of coeliac disease, an intestinal biopsy should be performed

Intestinal biopsy

Small bowel villous atrophy
Crypt hyperplasia
Thickening of basement membrane
Decreased numbers of goblet cells
Increased intraepithelial lymphocytes

NB IgA or IgG anti-gliadin antibody tests are NOT recommended by NICE

Complications of coeliac disease

Small bowel lymphoma (50x more common, but low absolute risk)
Osteoporosis
Reduced fertility
Functional hyposplenism

Management

Gluten-free diet

Small print gem: false positive tTGA results may occur in chronic liver disease, type 1 diabetes, myeloma and monoclonal gamopathy.

References

Dickson BC, Streutker CJ, Chetty R. Coeliac disease: an update for pathologists. J Clin Pathol. 2006; 59(10):1008-16.

Hopper AD, Hadjivassiliou M, Butt S, Sanders DS. Adult coeliac disease. BMJ. 2007; 335(7619):558-62.

NICE. Coeliac disease: quick reference guide. 2009. Available at http://guidance.nice.org.uk/CG86/QuickRefGuide/pdf/English.

Schistosomiasis

2012-01-11T07:30:00.000Z

Schistosomiasis (=bilharzia) is an intravascular infection caused by the parasitic trematode worms schistosoma. It is carried by freshwater snails which release cercariae (=parasitic larvae). Human infection occurs after contact with water containing cercariae, for example after swimming.

Schistosomiasis is common in Asia/Africa/South America.

Presentation:

Early:

Maculopapular rash – lasts up to 2 weeks
“swimmer’s itch”

Acute disease (=Katayama syndrome) – occurs 16 to 90 days after infection:

Fever
Fatigue
Myalgia
Diarrhoea
RUQ pain
Cough

Chronic disease (granuloma formation):

Splenomegaly
Hepatomegaly
Gastrointestinal inflammation, possibly causing haematochezia
Liver fibrosis (S. mansoni, S. japonicum)
Inflammation/obstruction of urinary tract with haematuria (S. haematobium)

Increased risk of squamous cell carcinoma of bladder

Acute transverse myelitis/subacute myeloradiculopathy (S mansoni and S haematobium)

Diagnosis:

Examination

FBC – look for eosinophilia
Microscopy of urine/stools

Characteristic eggs – they have a lateral or terminal spine so look a little like a cartoon “speech bubble”
Wait 2 months since last freshwater contact as it takes this length of time for eggs to become apparent

Treatment: oral praziquantel

References

Gray DJ, Ross AG, Li YS, McManus DP. Diagnosis and management of schistosomiasis.BMJ. 2011; 342: 2651.

Lambertucci JR. Acute schistosomiasis mansoni: revisited and reconsidered. Mem Inst Oswaldo Cruz. 2010;105(4):422-435.

Venous sinus thrombosis

2012-01-10T08:00:00.000Z

Venous sinus thrombosis can occur in any of the venous sinuses, but occur most commonly in the superior sagittal and lateral sinuses (70% of cases). The other famous location for venous sinus thrombosis is the cavernous sinus.

Aetiology may be aseptic or septic.

Aseptic venous sinus thrombosis is associated with

Haematological causes

polycythaemia rubra vera
inherited prothrombotic disorders
Factor V Leiden
Protein S/C deficiency
Antithrombin III deficiency

Post surgical causes
Drugs

OCP
Androgens
Ecstasy

Pregnancy - most commonly postpartum
Inflammatory conditions

Behcet's disease
Sarcoidosis
Inflammatory bowel disease

Malignancies

Septic venous sinus thrombosis is associated with

Facial infections
Dental infections
Sinusitis
Otitis media
Bacterial meningitis
Orbital infections

Presentation of venous sinus thrombosis include

headache
focal seizures
paresis
papilloedema
impairment of consciousness

Features suggestive of cavernous sinus thrombosis include

Headache
Ophthalmoplegia
Proptosis
Eyelid swelling
Decreased visual acuity
Chemosis

Investigations

MRI/CT - classically look for empty delta sign - but this is only present in 20%
LP – raised opening pressure, raised protein, pleocytosis

Treatment is to treat cause and heparin

Complications include PE and in the case of cavernous sinus thrombosis hypopituitarism.

The diagram below is a brief reminder of the anatomy of the cavernous sinus:

References

Agayev, A. and Yilmaz, S. Images in clinical medicine. Cavernous sinus thrombosis. N Engl J Med. 2008; 359(21):2266.
Allroggen, H. and Abbott R. Cerebral venous sinus thrombosis. Postgrad Med J. 2000;76(891):12-15.

Clifford-Jones, R. et al. Cavernous sinus thrombosis. J Neurol Neurosurg Psychiatry. 1982; 45(12): 1092-1097.
Cohen, J., Boitsova, S. and Itshayek, E. Cerebral venous sinus thrombosis. Isr Med Assoc J. 2009; 11(11):685-8.
Kimber, J. Cerebral venous sinus thrombosis. QJM. 2002; 95(3): 137-142.

Lai, P. and Cusimano, M. The spectrum of cavernous sinus and orbital venous thrombosis: a case and a review. Skull Base Surg. 1996; 6(1): 53-59.

Lee JH, et al. Cavernous sinus syndrome: clinical features and differential diagnosis with MR imaging. AJR Am J Roentgenol. 2003; 181(2):583-90.

Zahller, M. et al. Cavernous sinus thrombosis. West J Med. 1980;133(1):44-48.

Felty’s syndrome

2012-01-09T07:30:00.000Z

Felty’s syndrome is a rare complication of rheumatoid arthritis. It is characterized by splenomegaly and leucopenia.

It affects <1% of patients with RA.

Treatment is usually with systemic immunosuppression, e.g. methotrexate.

References

Ghavami, A. et al. Etanercept in treatment of Felty's syndrome. Ann Rheum Dis. 2005; 64(7):1090-1091.

Wassenberg S, Herborn G, Rau R. Methotrexate treatment in Felty's syndrome. Br J Rheumatol. 1998; 37(8):908-911.

Polycythaemia/erythrocytosis

2012-01-08T08:00:00.000Z

The term polycythaemia has traditionally been used to described disorders in which there is an increase in the number of red cells resulting in a persistently raised haematocrit. However, since usually only red cells are involved erythrocytosis is a more accurate term, and polycythaemia should really be reserved for polycythaemia vera which involves 3 cell lineages.

Erythrocytosis is defined as a raised haematocrit >0.52 in men or >0.48 in women for >2 months

It may be subdivided into

primary polycythaemia (=polycythaemia rubra vera)
secondary erythrocytosis
apparent erythrocytosis

The initial investigations on a finding of erythrocytosis should be

History and examination
FBC and blood film
JAK2 mutation
Serum ferritin
U&Es and LFTs

If the JAK2 is negative and there is no obvious secondary cause the next line of investigations should be:

Red cell mass
Arterial oxygen saturation
Abdominal ultrasound
Serum erythropoietin level
Bone marrow aspirate and trephine
Cytogenetic analysis
BFU-E culture

Primary polycythaemia

Presentation

Thrombosis
Pruritus after baths
Burning pain in distal extremities
Splenomegaly
Weight loss
Sweating
Plethora
Haemorrhagic events
Gout

Diagnostic criteria are:

If JAK2 positive (= around 95%)

High haematocrit (>0.52 in men, >0.48 in women) OR raised red cell mass (>25% above predicted)

If JAK2 negative

Raised haematocrit >0.60 in men or 0.56 in women OR raised red cell mass >25% above predicted AND
No cause of secondary erythrocytosis
Then either

Palpable splenomegaly OR
presence of an acquired genetic abnormality (excluding BCR-ABL) in the haematopoietic cellsOR
2 of

Thrombocytosis (platelet count >450x10^9/l)
Neutrophil leukocytosis (neutrophil count > 10 x10^9/l in non-smokers or 12.5x10^9/l in smokers
Radiological evidence of splenomegaly
Endogenous erythroid colonies or low serum erythropoietin

Management

Venesection – maintain haematocrit at less than 0.45
Aspirin 75mg od unless contraindicated
Cytoreduction (interferon or hydroxycarbamide = hydroxyurea) should be considered if

Venesection isn’t tolerated
Symptomatic or progressive splenomegaly
Thrombocytosis
Evidence of disease progression, eg weight loss, night sweats

Secondary erythrocytosis

Causes

Hypoxia

COPD
High altitude
Cyanotic congenital heart disease

Renal pathology

Polycystic kidneys
Hydronephrosis
Renal artery stenosis

Erythropoietin-secreting tumours

Hepatoma
Fibroids
Cerebellar
Hypernephroma
Phaeochromocytoma

Apparent erythrocytosis

Apparent erythrocytosis is defined as raised haematocrit but normal red cell mass.

Possible causes for apparent erythrocytosis include:

Physiological variant
Obesity
Smoking
Alcohol
Renal disease
Hypertension
Diuretics

If the apparent erythrocytosis is due to decreased plasma volume (ie dehydration) it is called relative erythrocytosis.

Management

Reduction of risk factors
Consider venesection if

Recent history of thrombosis or risk factors for thrombosis
Haematocrit >0.54

References

McMullin, M. et al. Guidelines for the diagnosis, investigation and management of polycythaemia/erythrocytosis. British Journal of Haematology. 2005; 130: 174-195.

McMullin, M. et al. Amendment to the guideline for the diagnosis, investigation and management of polycythaemia/erythrocytosis. British Journal of Haematology. 2007; 138:812-813.

Pearson TC, Messinezy M. Investigation of patients with polycythaemia. Postgrad Med J. 1996;72(851):519-24.

Stuart BJ, Viera AJ. Polycythemia vera. Am Fam Physician. 2004; 69(9):2139-2144.

Cavernous Sinus Syndrome

2012-01-07T08:00:00.000Z

Cavernous sinus syndrome is a syndrome characterized by neuropathies of the cranial nerves passing through the cavernous sinus.

The nerves passing through the cavernous sinus are:

Occulomotor (III)
Trochlear (IV)
Ophthalmic (V1)
Maxillary (V2)
Abducens (VI)

The optic nerve (II) runs just above the cavernous sinus.

A diagram illustrating the anatomy of the cavernous sinus is shown below:

Presentation of cavernous sinus syndrome is with palsies of whichever cranial nerve is affected, such as impairment of eye movement or Horner’s syndrome.

Causes of cavernous sinus syndrome include:

Infection

Bacterial – staph, strep, tuberculosis
Fungal
Viral

Vascular

Aneurysm of internal carotid artery
Thrombosis

Inflammation

Sarcoidosis
Toloso-Hunt syndrome
SLE

Neoplasia

Pituitary adenoma
meningioma
mets – especially nasopharangeal carcinoma, lymphoma, meningioma, lung and breast metastases

Treatment depends on the cause.

References

Lee JH, et al. Cavernous sinus syndrome: clinical features and differential diagnosis with MR imaging. AJR Am J Roentgenol. 2003; 181(2):583-90.

Sharkawi E, Tumuluri K, Olver JM. Metastastic choriocarcinoma causing cavernous sinus syndrome. Br J Ophthalmol. 2006; 90(5): 654-5.

Zarei M, Anderson JR, Higgins JN, Manford MR. Cavernous sinus syndrome as the only manifestation of sarcoidosis. J Postgrad Med 2002;48:119

Basophilic stippling

2012-01-06T08:30:00.000Z

Basophilic stippling of erythrocytes (as illustrated diagrammatically below) is a non-specific finding which an American study suggests occurs in around 25% of medical inpatients.

The classical conditions associated with basophilic however are

Lead poisoning
Sideroblastic anaemia
Thalassemia

References

Cheson, B., Rom, W. and Webber, R. Basophilic stippling of red blood cells: a nonspecific finding of multiple etiology. Am J Ind Med. 1984; 5(4): 327-334. (abstract only)

Lynch, E. Peripheral blood smear. In:Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 155.

Splenomegaly

2012-01-05T08:30:00.000Z

The spleen normally lies along the long axis of the 10th rib. Its lower pole extends forward as far as the midaxillary line.

Causes of splenomegaly include:

Haematological

Lymphoma
Polycythaemia vera
Leukaemias, especially CML
Myelofibrosis
Haemolytic conditions

Thalassemia
Haemoglobinopathies
Hereditary spherocytosis

Infection

Tuberculosis
Malaria
Leishmaniasis
Schistosomiasis
Mycobacterium avium complex
Endocarditis
Infectious mononucleosis

Autoimmune

Splenomegaly of portal hypertension

Liver cirrhosis
Hepatic and splenic vein obstructions

Other

Gaucher’s disease
Sarcoidosis
Congestive cardiac failure

Diseases in which splenomegaly if present is most likely to be massive are:

However, the commonest cause of massive splenomegaly in a large study in America was chronic liver disease.

References

Howells, L. The differential diagnosis in splenomegaly. Postgrad Med J. 1937. 13(141): 241-246.

O’Reilly, R. Splenomegaly in 2,505 patients at a large university medical center from 1913 ro 1995. 1963 to 1995: 449 patients. West J Med. 1998; 169(2): 88-97.

Yang, J., Rickman, L. and Bosser, S. The clinical diagnosis of splenomegaly. West J Med. 1991; 155(1): 47-52.

Howell-Jolly bodies

2012-01-04T09:23:00.000Z

Howell-Jolly bodies are remnants of DNA in the cytoplasm of erythrocytes which are normally removed by the spleen.

They are round, usually about 0.5 micrometer in diameter, and purple-staining using Wright’s stain. Typically there is only one in a cell although there may be multiple.

Below is a diagrammatic representation of the appearance of Howell-Jolly bodies:

The presence of Howell-Jolly bodies suggests:

Splenectomy
Hyposplenism
Rarely megaloblastic anaemia

Differentials for inclusions within the cytoplasm of an erythrocyte include:

Basophilic stippling
Pappenheimer bodies
Malaria parasites

References

Hutchison, H. and Ferguson-Smith, M. The significance of Howell-Jolly bodies in red cell precursors. J Clin Pathol. 1959; 12(5): 451-453.

Lynch, E. Peripheral blood smear. In:Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 155.

Pituitary apoplexy

2012-01-03T07:00:00.000Z

Pituitary apoplexy is a life-threatening medical condition in which there is sudden haemorrhage and/or infarction of the pituitary gland.

It is characterized by

Sudden onset of headache – usually retro-orbital
Vomiting
Visual impairment – bitemporal hemianopia
Decreased consciousness

The most common cranial nerve palsy associated with pituitary apoplexy is the third.

The fourth and sixth nerves are also vunerable.

Pituitary apoplexy usually occurs in patients with pre-existing pituitary adenomas.

Precipitating factors include:

Hypertension
Major surgery, especially CABG
Dynamic pituitary function tests with GnRH, TRH and CRH
Pregnancy
Head trauma
Anticoagulation therapy

Investigations

Bloods – U&Es, LFTs, FBC, clotting, random cortisol, prolactin, free T4, TSH, IGF-1, GH, LH and FSH
MRI

Management

IV hydrocortisone 100-200mg (acute secondary adrenal insufficiency occurs in 2/3rds of patients)
Urgent endocrinological and neurosurgical input

References

Rajasekaran, S. et al. UK guidelines for the management of pituitary apoplexy. Clinical Endocrinology. 2011; 74: 9-20.

Ranabir, S. and Baruah, M. Pituitary apoplexy. Indian J Endocrinol Metab. 2011; 15(Suppl 3): 188-196.

Sheehan syndrome

2012-01-02T08:00:00.000Z

Sheehan syndrome is a rare complication of postpartum haemorrahage in which there is necrosis of the pituitary gland resulting in hypopituitarism.

The degree of hypopituitarism varies, with the anterior pituitary more susceptible to damage than the posterior.

Signs and symptoms are those of hypopituitarism.

References

Prabhaker, V. and Shalet, S. Aetiology, diagnosis and management of hypopituitarism in adult life. Postgrad Med J. 2006; 82(966): 259-266.

Schrager, S. and Sabo, L. Sheehan syndrome: a rare complication of postpartum hemorrhage. J Am Board Fam Parct. 2001; 14(5): 389-391.

Hypopituitarism

2012-01-01T16:30:00.000Z

Hypopituitarism describes either a partial or complete deficiency of pituitary hormones.

Causes:

Pituitary adenoma

Macroadenomas (>1cm) cause a hormone deficit in 30% of cases
Microadenomas (<1cm) rarely affect pituitary function but those producing prolactin may cause hypogonadism due to its suppressive effects on FSH and LH secretion

Radiotherapy
Surgery
Peri-pituitary lesions

Craniopharyngioma
Meningioma
Optic nerve glioma

Metastatic lesions
Infiltrative conditions

Infections

Head injury
SAH
Sheehan’s syndrome
Pituitary apoplexy

Signs and symptoms of pituitary insufficiency depend on the hormones affected:

Lack of growth hormone

Decreased energy
Muscle weakness

Lack of ACTH (= secondary adrenal insufficiency)

Fatigue
Weakness
Anorexia
Weight loss
Nausea and vomiting
Abdominal pain
Hypoglcaemia
Decreased bone mineral density
Loss of axillary and pubic hair

Lack of Gonadotrophins

Erectile dysfunction
Reduced muscle mass
Oligo/amenorrhoea

Lack of TSH (= secondary hypothyroidism)

Fatigue
Dry skin
Cold intolerance
Constipation
Weight gain

Lack of antidiuretic hormone (= cranial diabetes inspidus)

Polyuria
Polydipsia

Management

Treat cause
Replace hormones as needed

References

Prabhaker, V. and Shalet, S. Aetiology, diagnosis and management of hypopituitarism in adult life. Postgrad Med j. 2006; 82(966): 259-266.

The Pituitary Foundation. GP factsheet. Available at http://www.pituitary.org.uk/content/view/482/249/

Turner syndrome

2011-12-31T08:02:00.000Z

Turner syndrome affects females and is due to the partial or total absence of one X chromosome.

Incidence is around 1 in 3000 live female births

Features include:

Congenital heart defects – occur in 1/3; most commonly

Biscuspid aortic valve
Coarctation of the aorta

Short stature
Widely-spaced nipples
Webbed neck
Prominent ears
Short fourth metacarpals
Cubitus vulgaris
Lack of spontaneous puberty
Congenital lymphoedema

Complications associated with Turner syndrome include

Osteoporosis
Sensorineural hearing loss
Aortic root dilation

Diagnosis is by karyotyping

References

Davenport, M. Approach to the patient with Turner syndrome. J Clin Endocrinol Metab. 2010; 95(4): 1487-1495.

Morgan, T. Turner syndrome: diagnosis and management. Am Fam Physician. 2007; 76(3): 405-410.

Porphyria

2011-12-30T07:24:00.003Z

Porphyrias are inherited disorders of haem synthesis resulting in the accumulation of porphyrin and porphyrin precursors.

There are 7 main types of porphyria; only 3 are considered here.

Acute intermittent porphyria

Caused by a defect of porphobilinogen deaminase
Most common in those around the age of 30
Females > males 5:1
Autosomal dominant inheritance, although only 10 to 20% of carriers become symptomatic
Signs/symptoms may include

Abdominal pain
Tachycardia
Muscle weakness
Sensory changes in a ‘bathing suit’ distribution
Constipation
Nausea and vomiting
Postural hypotension
Hypertension
Low sodium
Seizures
Paralysis
Psychosis

Precipitants

Medications – sulphonamides, methyldopa, danazol, diazepam, phenytoin, carbamazepine, sulphonylureas, chloramphenicol, tetracyclines, some anthistamines
Alcohol
Illicit drugs – cocaine, amphetamines, ecstasy, marijuana
Fasting
Stress
Infections
Smoking
Pregnancy
Pre-menstrual hormone variation

Diagnosis

Urine dark on standing due to polymerisation of porphobilinogen to porphyrins
Urinalysis of urine protected from light looking for raised aminolaevulinic acid and porphobilinogen

Management of acute attacks

Pain relief – opiates if required
Convulsions managed with gabapentin or vigabatrin
Monitor sodium – if low, fluid restrict
Glucose
Haem arginate - slow IV infusion

Variegate porphyria

Causesd by a mutation in the gene for protoporphyrinogen oxidase
Most common in South Africans
Features

Cutaneous manifestations

Photosensitive blistering
Hyperpigmentation

Abdominal pain
Dark urine
Neuropsychiatric symptoms

Porphyria Cutanea Tarda

This is the commonest of all the porphyrias
2 forms – sporadic (around 90%) and familial (10%)
It is caused by a mutation in the gene encoding uroporphyrinogen decarboxylase
Features

Light-sensitive dermatitis – blisters
Hypertrichosis
Often iron overload
Urine glows pink under Wood’s lamp due to raised uroporphyrinogen

Precipitants of attacks include

Alcohol
Iron
Oestrogens

Associations

Hepatitis C
Haemochromatosis

Treatment:Chloroquine

References

Chan, C. and Lin, S. Images in clinical medicine: porphyria cutanea tarda. N Engl J Med. 2011; 365(12): 1128.

OMIM: Porphyria, acute intermittent. Available at http://omim.org/entry/176000

OMIM: Porphyria cutanea tarda. Available at http://omim.org/entry/176100

OMIM: Porphyria Variegata. Available at http://omim.org/entry/176200

Thadani, H., Deacon, A. and Peters, T. Diagnosis and management of porphyria. BMJ. 2000; 320(7250): 1647-1651.

Lesch-Nyhan Syndrome

2011-12-29T09:00:00.000Z

Lesch-Nyhan Syndrome is a recessive x-linked disorder caused by a mutation in the HPRT gene encoding hypoxanthine guanine phosphoribosyltransferase, which results in increased levels of uric acid.

Features include:

Mental retardation
Self-mutilation – biting fingers and lips
Orange crystals in nappies
Gout
Megaloblastic anaemia

Management: allopurinol

Prognosis: death in 20s/30s

References

OMIM: Lesch-Nyhan Syndrome. Available at http://omim.org/entry/300322?search=LESCH%20NYHAN&highlight=lesch%20nyhan

Torres, R. and Puig, J. Hypoxanthine-guanine phosophoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome. Orphanet J Rare Dis. 2007; 2:48.

COPD

2011-12-28T08:30:00.000Z

Chronic Obstructive Pulmonary Disease (COPD) is characterised by airflow obstruction that is not fully reversible, with a reduced FEV1/FVC ratio of less than 0.7.

NICE recommends that a diagnosis of COPD is considered in patients older than 35 with a risk factor (generally smoking) who present with one or more of the following:

exertional breathlessness
chronic cough
regular sputum production
frequent winter ‘bronchitis’
wheeze

Investigations

Spirometry - obstructive pattern

Severity

Mild – FEV1 ≥ 80% predicted
Moderate – FEV1 50 – 79% predicted
Severe – FEV1 30 – 49% predicted
Very severe – FEV1 <30% predicted or < 50% predicted with respiratory failure

CXR
FBC
BMI calculation

Management

General management

Stop smoking

Offer NRT, varenicline or bupropion

Inhaled therapy

Short-acting beta 2 agonists (SABA) for symptomatic relief
Preventative therapy:

FEV1 ≥ 50% predicted: long-acting beta 2 agonist (LABA) or long-acting muscarinic antagonist (LAMA)
FEV1< 50% predicted: either LABA with inhaled corticosteroid or LAMA

Oral theophylline

Plasma levels must be monitored
Dose must be reduced if macrolide or fluroquinolone antibiotics prescribed

Mucolytic drugs
Long term oxygen therapy

Indications

PaO2 less than 7.3kPa in stable COPD
PaO2 less than 8kPa if stable and one of:

Secondary polycythaemia
Nocturnal hypoxaemia (= sats <90% for more than 30% of the time)
Peripheral oedema
Pulmonary hypertension

Need at least 2 ABGs done at least 3 weeks apart
Need 15 hours per day, greatest benefits if used for 20 hours per day

Lung surgery

IfSingle large bulla on CT and FEV1 <50% predicted or
Breathless and marked restriction in daily living and all of the following criteria met:

FEV1 more than 20% predicted
PaCO2 less than 7.3 kPa
upper lobe predominant emphysema
TLCO more than 20% predicted

Management of an exacerbation

Oral corticosteroids – prednisolone 30mg od for 7 to 14 days
Nebulised salbutamol and ipratropium bromide
If infective, antibiotics – empirically a macrolide or tetracycline
IV theophylline if inadequate response to nebulisers
NIV for persistent hypercapnic ventilatory failure

Consider if ongoing acidosis after one hour of standard medical treatment
If pH <7.26 higher risk of NIV failure so should be managed in high dependency setting
Initial IPAP 10cm H20, titrated in increments of around 5cm H20 each 10 minutes to usual target IPAP of 20cm H20
EPAP 4-5cms H2O
ABGs at 1 hour, 4 hours and 12 hours as a minimum

Small print gem: spacers should not be cleaned more than monthly and should be allowed to air dry. Frequent cleaning or towel-drying decreases their effectiveness due to a build-up of static

References:

NICE guideline. Chronic obstructive pulmonary disease. 2010. Available at http://www.nice.org.uk/guidance/CG101/NICEGuidance

British Thoracic Society. The Use of Non-Invasive Ventilation in the management of patients with chronic obstructive pulmonary disease admitted to hospital with acute type II respiratory failure. 2008. Available at http://www.brit-thoracic.org.uk/guidelines/nippv-%E2%80%93-niv-in-acute-respiratory-failure-guideline.aspx

Warfarin

2011-12-23T16:12:00.000Z

Warfarin is an anticoagulant that works by inhibiting vitamin K epoxide reductase, which prevents vitamin K being recycled. As vitamin K is essential for the activation of factors II, VII, IX and X this decreases coagulation.

However, vitamin K is also a cofactor for protein C and protein S, both of which are inhibitors within the clotting cascade. They also have shorter half-lives than factors II, VII, IX and X. Therefore, warfarin is initially a procoagulant.

Indications for warfarin therapy include:

Venous thromboembolism (DVT/PE)

Target INR 2.5 (unless recurrent VTE whilst on anticoagulant, in which case target INR = 3.5)
Start with heparin cover which should be continued for at least 5 days and until INR ≥ 2 for at least 24 hours, whichever is longer
Duration of treatment with warfarin

Proximal DVT (= popliteal vein or above) or PE: 3 months
Isolated calf vein DVT: 6 weeks

Cancer-associated VTE: 6 months with therapeutic LMWH rather than warfarin

Atrial fibrillation

Warfarin is not required for all AF patients
If it is, target INR = 2.5

Prosthetic heart valves

Mechanical valves

Target INR depends on valve and risk factors
Risk factors:

valve in mitral, tricuspid or pulmonary position
AF
Left atrium diameter >50mm
Mitral stenosis
LVEF <35%

Examples of valve types and INR

St Jude Medical – INR 2.5 if no risk factors, INR 3.0 if risk factors
Starr-Edwards – INR 3.5

Bioprosthetic valves

Some require initial anticoagulation with warfarin

Elective cardioversion

Anticoagulate for 3 weeks prior to procedure and 4 weeks post
Target INR 2.5

Mitral stenosis or regurgitation

If warfarin indicated, target INR 2.5

Warfarin is metabolised by cytochrome P450.

Interactions with warfarin which may result in a raised INR include:

Medications

Antibiotics

Metronidazole
Erythromycin
Clarithromycin
Ciprofloxacin
Tetracyclines

Allopurinol
Amiodarone
SSRIs
Fluconazole
Cimetidine
Omeprazole

Drinks

Cranberry juice
Alcohol

Hyperthyroidism

Interactions with warfarin which may result in a lower INR include

Rifampacin
St Johns Wort
Carbamazepine
phenyotin

Management of high INR

Major bleeding

Prothrombin complex concentrate
5mg IV vitamin K
FFP is suboptimal and should only be used if prothrombin complex is not available

Non-major bleeding

1-3mg IV vitamin K

Non-bleedingINR > 8.0

1-5mg oral vitamin K

Non-bleeding INR >5.0

Withhold 1-2 doses of warfarin
Reduce subsequent dose

Warfarin is contraindicated in pregnancy as it is teratogenic

Side effects/complications of warfarin include:

Haemorrhage – around 2%
Alopecia
Skin necrosis
Purple toe syndrome

Small print gem: warfarin possibly enhances the hypoglycaemic effect of sulphonylureas

References

British Committee for Standards in Haematology. Guidelines on oral anticoagulation with warfarin – 4th edition. 2011. Available at http://www.bcshguidelines.com/4_HAEMATOLOGY_GUIDELINES.html

British National Formulary. Available at http://bnf.org/

Suvarna, R., Pirmohamed, M. and Henderson, L. Possible interaction between warfarin and cranberry juice. BMJ. 2003; 327(7429): 1454.

Tadros, R. and Shakib, S. Warfarin – indications, risks and drug interactions. Aust Fam Physician. 2010; 39(6): 476-479.

Kearns-Sayre Syndrome

2011-12-22T12:01:00.000Z

Kearns-Sayre Syndrome is a rare disorder caused by mitochondrial DNA mutations which can result in:

Ptosis
Progressive external opthalmoplegia
Atypical retinal pigmentation
Heart block
Muscle weakness
Ataxia

Diagnosis is by demonstrating ragged-red fibres on muscle biopsy

References

OMIM: Kearns-Sayre Syndrome. Available at http://omim.org/entry/530000?search=kearns-sayre&highlight=kearnssayre

Park, S. et al. Kearns-Sayre syndrome -3 case reports and review of clinical feature. Yonsei Med J. 2004; 45(4): 727-735.

Tetralogy of Fallot

2011-12-21T11:40:00.002Z

Tetralogy of Fallot is the commonest cyanotic congenital heart disease, occurring in 1 in 3600 live births.

The four features of Tetralogy of Fallot are:

Pulmonary stenosis
Ventricular septal defects
Right ventricular hypertrophy
Overriding of the aorta

Treatment is surgical repair.

Prognosis:

40 year survival rate at least 90%
Complications in adulthood include

pulmonary regurgitation (low-pitched, diastolic murmur)
right heart failure
arrhythmias (6% risk of sudden cardiac death)

References

Fox, D. et al. When 'blue babies' grow up: What you need to know about tetralogy of Fallot. Cleve Clin J Med. 2010; 77(11): 821-828.

Shinebourne, E., Babu-Narayan, S. and Carvalho, J. Tetralogy of Fallot: from fetus to adult. Heart. 2006; 92(9): 1353-1359.

Vitamin C and scurvy

2011-12-21T07:30:00.000Z

Vitamin C, also known as ascorbic acid, is a vitamin found in many fruits and vegetables which plays a vital role in the formation of collagen.

A deficiency of vitamin C causes scurvy, features of which include:

Bruising
Fatigue
Gingival hyperplasia
Bleeding
Anaemia
Bone pain
Myalgia
Corkscrew hairs

Reasons for deficiency include

Poor diet

Alcoholism
Food faddism
Psychiatric illness

Haemodialysis (as vitamin C is not reabsorbed by the kidneys)

Treatment is to increase vitamin C intake.

Small print gem: clinical manifestations of scurvy can be seen within 8 to 12 weeks of inadequate intake.

References

Dolberg, O., Elis, A. and Lishner, M. Scurvy in the 21st century. Isr Med Assoc J. 2010; 12(3): 183-184.

Leger, D. Scurvy: reemergence of nutiritional deficiencies. Can Fam Physician. 2008; 54(10): 1403-1406.

Gingival hyperplasia

2011-12-20T08:30:00.000Z

Causes of gingival hyperplasia include:

Drug-induced

Phenytoin
Cyclosprin
Calcium channel blockers (nifedipine, verapamil, nimodipine)
Bleomycin

Hormonal surges

Puberty
Pregnancy
Menopause

Vitamin C deficiency
Leukaemia
Bacterial infection
Hypothyroidism

References

Fisekcioglu, E., Dolekoglu, S. and Llguy, D. Idiopathic gingival hyperplasia: clinical features and differential diagnosis. J Can Dent Assoc. 2011; 77:b148.

Hassell, T. and Hefti, A. Drug-induced gingival overgrowth: old problem, new problem. Crit Rev Oral Biol Med. 1991; 2(1): 103-137.

Hyposplenism

2011-12-19T10:30:00.000Z

Hyposplenism may be:

Absence of spleen

Trauma
Congenital asplenia
Iatrogenic - for example in treatment of Gaucher's disease or autoimmune haemolytic anaemia

Functional – associated with

GI causes

Coeliac disease
Inflammatory bowel disease
Whipples disease
Liver cirrhosis

Haematological causes

Autoimmune

SLE
Rheumatoid arthritis
Graves’ disease

Other

Amyloidosis
Sarcoidosis
Acute alcoholism

Blood film in hyposplenism may show

Howell-Jolly bodies
Acanthocytes
Target cells

Hyposplenism results in an increased risk of life-threatening infection, particularly by:

Encapsulated organisms such as

Pneumococci
Haemophilus influenzae
Meningococci

Intraerythrocytic parasites

Plasmodia falciparum
Babesia microti

Management of hyposplenism/asplenism:

Vaccination

Pneumococcal vaccine, Hib vaccine and meningococcal B and C vaccines
Yearly influenza vaccination

Lifelong prophylactic antibiotics should be considered with either penicillin or macrolides

Small print gem: after splenectomy, the risk of overwhelming infection is greatest in the first 2 years.

References:

Brigden, M. Detection, education and management of the asplenic or hyposplenic patient. Am Fam Physician. 2001; 63(3): 499-506.

Davies, J. et al. Review of guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen: Prepared on behalf of the British Committee for Standards in Haematology by a Working Party of the Haemato-Oncology Task Force. British Journal of Haematolofy. 155(3): 308-317.

Muller, A. and Toghill, P. Hyposplenism in gastrointestinal disease. Gut. 1995; 36(2): 165-167.

Thrombocytosis

2011-12-18T09:42:00.003Z

Thrombocytosis is a raised number of platelets, usually defined as ≥ 450 x 10^9

Thrombocytosis may be divided into :

Spurious

Caused by non-platelet structures in the blood which are counted as platelets by modern automated counters
Examples include

Cryoglobulin crystals
Microspherocytes (eg from severe burns)
Schistocytes
Pappenheimer bodies
Bacteria

Primary thrombocytosis

Increase in platelets caused by alterations targeting the haematopoietic cells
Causes are

Essential thrombocytheameia

Megakaryocyte proliferation
Not meeting WHO criteria for CML, PV, PMF or MDS
Presence of JAK 2 or other clonal marker and no evidence of reactive thrombocytosis
Increases risk of both thrombosis and bleeding
Treatment: