Infections and Immunology

Question 1

Define Behcet’s disease

Answer 1

An autoimmune systemic vasculitis affecting all sized vessels, leading to recurrent oral and genital ulcers and uveitis. It can cause skin and mucosal lesions, uveitis, major arterial and venous vessel disease, and GI and neurological manifestations.

Question 2

Summarise the aetiology of Behcet’s disease

Answer 2

Underlying aetiology is unknown
Autoimmune or autoinflammatory
Associated with HLA-B51
Innate and active immune system involved

Risk factors:
Age 20-40 years
Family history of Behcet’s syndrome
Genetic predisposition.

Question 3

Summarise the epidemiology of Behcet’s disease

Answer 3

Most common in those 20-40 years old
More severe symptoms in men
Most common in Turkey, Mediterranean, Israel, East Asia

Question 4

What are the presenting symptoms and signs on physical examination of Behcet’s disease?

Answer 4

Recurrent oral and genital ulcers which are painful, slow healing and large
Anterior uveitis - painful, red eye with decreased vision and sterile pus
Posterior uveitis - painless eye with decreased vision and floaters
Skin lesions - erythema nodosum
Joint stiffness
Abdominal pain
Meningitis - headache, confusion, fever
Arthritis
Thrombophlebitis
Vasculitis
Myocarditis/pericarditis
CNS symptoms
Colitis

Question 5

What are appropriate investigations for Behcet’s disease?

Answer 5

Mostly a clinical diagnosis
Pathergy test - pin prick does not heal normally, becomes inflamed and forms ulcer or lesion (sterile pustule) at that site within 48 hours
Rheumatoid factor to rule out RA (negative)

Question 6

Define malaria

Answer 6

A parasitic infection caused by plasmodium species which is transmitted to humans through a bite from an infected female anopheles mosquito.

Question 7

Summarise the aetiology of malaria

Answer 7

There are 5 types of protozoa which can cause malaria in humans:
Plasmodium falciparum 
Plasmodium malariae
Plasmodium vivax
Plasmodium ovale
Plasmodium knowlesi

P. falciparum causes malaria most often and most severe malaria
Malaria is spread by the bite of an infected female Anopheles mosquito

Sickle cell disease, thalassemia and 6PD deficiency are protective against malaria

Question 8

Summarise the epidemiology of malaria

Answer 8

Endemic in the tropics

In endemic countries it is most common in children <5 years old and pregnant women

Question 9

What are the presenting symptoms of malaria?

Answer 9

Feverish traveller
Cyclic fevers
Headaches
Myalgia
Arthralgia
Fatigue
Rigors
Weakness
Anorexia
Flu-like symptoms
Sweating
Vomiting

Cerebral Malaria Symptoms: headache, disorientation, coma, confusion

Question 10

What are the signs on physical examination of malaria?

Answer 10

Pyrexia 
Anaemia (haemolytic) 
Hepatosplenomegaly 
Tachycardia 
Jaundice

Question 11

What are the appropriate investigations for malaria?

Answer 11

FBC - normocytic anaemia, thrombocytopenia

Giemsa-stained thick blood smear - identify the presence of parasite within RBC
Thin blood smear - identify the specific plasmodium
Rapid diagnostic tests
Serum LFTs: may show elevated BR/aminotransferases
Clotting profile - may have prolonged prothrombin time

Question 12

Define Sjogren’s syndrome

Answer 12

Autoimmune destruction and lymphocytic infiltration of exocrine glands, particularly the lacrimal and salivary glands, resulting in dry eye and dry mouth.

Question 13

Summarise the aetiology of Sjogren’s syndrome

Answer 13

Primary Sjogren’s syndrome - sicca syndrome when it occurs on its own
Secondary Sjogren’s syndrome - Sjogren’s occuring with another autoimmune disorder

Aetiology unknown
Associated with HLA-B8 and HLA-DR3
Associated with infection of exocrine glands

Can be associated with:
Rheumatoid arthritis
SLE
Scleroderma
Polymyositis
Organ-specific autoimmune diseases (e.g. PBC, autoimmune hepatitis, myasthenia gravis)

Question 14

Summarise the epidemiology of Sjogren’s syndrome

Answer 14

The most common of all systemic auto-immune rheumatic diseases
More common in women
Middle aged women - 50-60 years old
60% have the disease secondary to rheumatoid arthritis, SLE, or systemic sclerosis

Question 15

What are the presenting signs and symptoms of Sjogren’s syndrome?

Answer 15

Keratoconjunctivitis:
Blurred vision
Red eye
Itchy eye
Dry eye
Burning eye

Xerosterma:
Dry mouth
Difficulty tasting and swallow
Cracks and fissures in mouth

Crusting and bleeding of nasal septum
Dry skin
Dry vagina - causes dyspareuria
Pain
Lymphadenopathy
Fever
Weight loss
Fatigue
Dry upper airways: leads to a dry cough and recurrent sinusitis 
Dry skin or hair
Dry upper airways: leads to a dry cough and recurrent sinusitis - Dry skin or hai
Dental caries
Myalgia

Question 16

What are the appropriate investigations for Sjogren’s syndrome?

Answer 16

ESR - elevated
Amylase - elevated if salivary gland involvement
Anti-SSA and anti-SSB - positive
Rheumatoid factor positive
ANA 

Schirmer’s Test:
A strip of filter paper is placed under the eyelid
Positive for Sjogren’s syndrome if < 10 mm of the strip is wet after 5 mins

Fluorescein/Rose Bengal Stains: May show punctate or filamentary keratitis

Reduced parotid salivary flow rate
Reduced uptake or clearance on isotope scan

Biopsy salivary or labial glands - shows lymphocytic infiltration

Sialometry - decreased saliva outflow

Question 17

Define systemic lupus erythematosus

Answer 17

A chronic multi-system autoimmune condition which mainly affects women of reproductive age and is characterised by the presence of anti-nuclear antibodies.

4 out of the 11 features must be present for diagnosis:
RASH OR PAIN

Rash - malar or discoid
Arhritis
Serositis - pleuritis, pericarditis
Haemological disorders - haemolytic anaemia, thrombocytopenia, leukopenia
Oral/nasopharyngeal ulcers
Renal disease - proteinuria, red cell casts
Photosensitivity
Anti-nuclear antibodies
Immunological disorder (anti-dsDNA, anti-smith, antiphospholipid)
Neurological disorder - seizures, coma

Question 18

Summarise the aetiology of systemic lupus erythematosus

Answer 18

Autoimmune disorder
Environmental risk factors cause cell apoptosis, leading to release of nuclear components
Genetic susceptibility increases likelihood of these nuclear components being recognised as non-self antigens and decreases clearance
Antigen-antibody complexes form and deposit

Question 19

Summarise the epidemiology of systemic lupus erythematosus

Answer 19

Most common in females of reproductive age
Most frequently 15-45 years old
More common and severe in those of Asian and African descent

Question 20

What are the presenting symptoms and signs on physical examination of systemic lupus erythematosus?

Answer 20

Fever, weight loss, malaise, lymphadenopathy, splenomegaly
Malar rash - gets worse after sun exposure
Discoid rash
Arthritis - pain in >2 joints
Raynaud’s phenomenon
Oral ulcers
Atypical rashes (e.g. photosensitivity, vasculitis, urticaria, purpura)

Systemic Involvement:
Musculoskeletal: arthritis, tendonitis, myopathy
Heart: pericarditis, myocarditis, arrhythmias, Libman-Sacks endocarditis
Lung: pleurisy, pleural effusion, basal atelectasis, restrictive lung defects
Neurological: headache, stroke, cranial nerve palsies, confusion, chorea
Psychiatric: depression, psychosis
Renal: glomerulonephritis, nephritic syndrome

Question 21

What are the appropriate investigations of systemic lupus erythematosus?

Answer 21

FBC - may have haemolytic anaemia, thrombocytopenia, leukopenia
U&Es - urea and creatinine elevated if renal involvement
ESR - elevated
Normal CRP

Anti nuclear antibodies
Anti-smith antibodies
Anti-dsDNA antibodies
Anti-phospholipid antibodies
Rheumatoid factor (30-50%) 
Anti-ENA 
Anti-RNP
Anti-SM
Anti-Ro
Anti-La 
Anti-histone 
Anti-cardiolipin

Urinalysis - red cell casts, proteinuria
Heart and Lungs: CXR, ECG, echocardiogram, CT
Kidneys: renal biopsy (if glomerulonephritis suspected)

Question 22

Define systemic sclerosis

Answer 22

An idiopathic, autoimmune condition characterised by functional and structural abnormalities of small blood vessels, fibrosis of skin and internal organs, and production of auto-antibodies.

Diffuse cutaneous systemic scleroderma:
Sclerodactyl
Skin thickening
Pulmonary fibrosis
Raynaud’s phenomenon followed by skin changes with truncal involvement
Tendon friction, joint contracture, heart, GI and renal disease

Limited cutaneous systemic scleroderma/CREST syndrome:
5 main symptoms - calcinosis cutis, raynaud’s phenomenon, eosophageal dysfunction, sclerodactyly, telangiectasis

Scleroderma sine scleroderma: internal organ disease with no skin involvement

Question 23

Describe the aetiology of systemic sclerosis

Answer 23

Aetiology unknown
Genetic predisposition with environmental triggers - EBV, parvovirus B19, cocaine
Autoimmune

Diffuse associated with anti-Scl70 and anti-RNA polymerase III antibodies
Localised associated with anti-centromere antibodies

Question 24

Summarise the epidemiology of systemic sclerosis

Answer 24

Women three times more commonly affected than men

Onset 30-60 years old

Question 25

What are the presenting symptoms and signs on physical examination of systemic sclerosis?

Answer 25

Raynaud's phenomenon - in cold, fingers turn white, then blue, then red due to vasospasm Sclerodactyly - initially hands swollen and puffy, develop to tight, thick, shiny skin with no markings Changes in pigmentation of hands Digital ulcers Calcified deposits in fingers Oesophageal dysmotility - dyshpagia, GORD Telangiectasia on skin and face Microstomia (puckering of the skin around the mouth) Pulmonary fibrosis - cough, restrictive lung pattern Pulmonary hypertension Heart: pericarditis or pericardial effusion, myocardial fibrosis, heart failure, arrhythmias Kidneys: hypertensive renal crisis, chronic renal failure Neuromuscular: trigeminal neuralgia, muscular wasting, weakness Beaked nose Joints - pain, stiffness, restricted movement Diffuse: symptoms rapidly developing, across whole body, organ involvement early on Limited: slower development, no organ development, restricted to face and distal limbs

Question 26

What are the appropriate investigations for systemic scleroderma?

Answer 26

Autoantibodies: Anti-centromere - limited Anti-RNA polymerase III - diffuse Anti-topoisomerase II/Anti-Scl70 - 30% of diffuse Pulmonary function tests - show restrictive pattern in diffuse Lungs: CXR (check for fibrosis), CT scan Heart: ECG, echocardiography (look for R ventricular hypertrophy secondary to pulmonary fibrosis) GI: endoscopy, barium studies to check for oesophageal dysfunction Kidneys: U&Es, creatinine clearance Neuromuscular: electromyography, biopsy Joints: radiography Skin: biopsy (rarely needed)

Question 27

Define vasculitides

Answer 27

Group of inflammatory diseases affecting large, medium and small vessels, caused by immunological processes and triggered by infection. Classified based on the vessels size: Large artery vasculitis - giant cell arteritis, Takayasu's arteritis Medium artery vasculitis - polyarteritis nodosa Small artery vasculitis - granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis

Question 28

Summarise the aetiology of vasculitides

Answer 28

Unknown Potentially autoimmune condition Immune complex deposition in the walls of blood vessels leads to inflammation Risk factors: Hepatitis B - Polyarteritis nodosa Age >50 - GCA Asian female <40 - Takayasu c-ANCA - granulomatosis with polyangiitis p-ANCA - microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis

Question 29

Summarise the epidemiology of vasaculitides

Answer 29

RARE Takayasu's arteritis is most common in JAPANESE FEMALES <40 years old Giant cell arteritis - females >50y/o Polyarteritis nodosa - middle aged men, hep B infection

Question 30

What are the presenting symptoms and signs on physical examination of vasculitides?

Answer 30

``` Non-specific symptoms: Fever Myalgia Weight loss Fatigue Arthritis Night sweats ``` Giant cell arteritis - unilateral headache, jaw claudication, pain on brushing hair, visual disturbance, visual inflammed temporal artery Takayasu arteritis - carotid bruit, weak or no upper extremity pulses, visual disturbances, neurological signs, difference in blood pressure between two arms Polyarteritis nodosa - microaneurysms, thrombosis, infarctions, hypertension, testicular pain Granulomatosis with polyangiitis - haemoptysis, saddle nose deformity, dyspnoea, haematuria, granulomatous vasculitis of upper and lower respiratory tract, nasal discharge, ulceration and deformity, sinusitis, glomerulonephritis Eosinophilic granulomatosis with polyangiitis - adult onset asthma

Question 31

What are the appropriate investigations of vasculitides?

Answer 31

Bloods: FBC - normocytic anaemia, high platelets, high neutrophils ESR/CRP - elevated Autoantibodies: cANCA - granulomatosis with polyangiitis pANCA - microscopic polyangiiitis, eosinophilic granulomatosis with polyangiitis Urinalysis: haematuria, proteinuria, red cell casts (if glomerulonephritis) CXR: diffuse, nodular or flitting shadows (granulomatosis with polyangiitis, microscopic polyangiitis) Biopsy: renal, lung, temporal artery (in GCA) Angiography: to identify aneurysms - string of beads sign in polyarteritis nodosa

Question 32

Define abscess

Answer 32

A painful collection of pus (dead cells and tissue, pathogens and immune cells) in a walled off area usually caused by bacterial infection.

Question 33

Summarise the aetiology of abscess

Answer 33

They can develop anywhere in the body There are TWO main types of abscess: skin abscess and internal abscess Skin abscess often caused by staphylococcus aureus Bacterial infection leads to activation of an immune response and recruitment of neutrophils. As the white cells attack the bacteria, surrounding tissue is damaged creating a cavity which fills with pus to form an abscess.

Question 34

Summarise the epidemiology of abscess

Answer 34

Skin abscesses are relatively common IV drug use is a major risk factor for skin abscesses Internal abscesses are less common

Question 35

What are the presenting symptoms of abscess

Answer 35

``` Swollen pus-filled lump under the surface of the skin Pain Redness Warmth Swelling Inflammed skin ``` If weakened immune system and unable to wall off abscess: Fever Vomiting Nausea ``` Internal abscesses: Not visible Pain in the affected area (or referred pain) Swinging fevers Malaise ```

Question 36

What are the signs on physical examination of abscess?

Answer 36

Swollen, pus-filled lump under the surface of the skin which comes to a head Fever

Question 37

What are the appropriate investigations for abscess?

Answer 37

Mainly clinical diagnosis and examination - will be fluctuant USS visualisation of abscess Pus analysis

Question 38

What is the management of abscesses

Answer 38

Small abscesses may heal by themselves Incision and drainage (surgical or using long needle if deep abscess) If large abscess, to prevent reinfection of empty cavity, fill with gauze Antibiotics if needed

Question 39

What are the possible complications of abscesses?

Answer 39

``` Recurrence Sepsis Spread of the infection to brain or spinal cord Endocarditis Gangrene Osteomyelitis ```

Question 40

Define HIV

Answer 40

Infection by the Human Immunodeficiency Virus which targets immune cells, leading to a decreased immune system strength

Question 41

Summarise the aetiology of HIV

Answer 41

``` Transmitted by: Sexual intercourse Mother-to-child - intrauterine, breastfeeding, childbirth Blood transfusion IVDU Needlestick Organ transplant ```

Question 42

Summarise the epidemiology of HIV

Answer 42

Increasing incidence in Asia and Africa

Question 43

What are the presenting symptoms and signs on physical examination of HIV?

Answer 43

There are THREE phases of HIV: 1. Seroconversion: Self-limiting, fever, night sweats, generalised lymphadenopathy, sore throat, oral ulcers, rash, myalgia, headache, encephalitis, diarrhoea 2. Early/Asymptomatic: Apparently well but some may have persistent lymphadenopathy. Progressive minor symptoms (e.g. rash, oral thrush, weight loss) 3. AIDS: Syndrome of secondary diseases resulting from immunodeficiency Direct Effects of HIV Infection: Neurological: polyneuropathy, dementia Lung: lymphocytic interstitial pneumonitis Heart: cardiomyopathy, myocarditis Haematological: anaemia, thrombocytopaenia GI: anorexia, wasting Eyes: cotton wool spots Secondary effects resulting from immunodeficiency: Bacterial Infection: TB, skin infections, pneumococcal infections Viral: CMV, HSV, VZV, HPV, EBV Fungal: pneumocystic jirovecii pneumonia, Cryptococcus, candidiasis, invasive aspergillosis Protozoal: toxoplasmosis, cryptosporidia Tumours: Kaposi sarcoma, SCC, non-Hogkin's lymphoma, Hodgkin's lymphoma

Question 44

What are the appropriate investigations of HIV?

Answer 44

HIV antibodies PCR for viral RNA CD4 count Viral load ``` Pneumocystic pneumonia - CXR Cryptococcal meningitis - brain CT or MRI, LP CMV (colitis) - colonoscopy and biopsy Toxoplasmosis - brain CT or MRI Cryptosporidia - stool microscopy ```