Infections and Immunology Flashcards
Define Behcet’s disease
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.
Summarise the aetiology of Behcet’s disease
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.
Summarise the epidemiology of Behcet’s disease
Most common in those 20-40 years old
More severe symptoms in men
Most common in Turkey, Mediterranean, Israel, East Asia
What are the presenting symptoms and signs on physical examination of Behcet’s disease?
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
What are appropriate investigations for Behcet’s disease?
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)
Define malaria
A parasitic infection caused by plasmodium species which is transmitted to humans through a bite from an infected female anopheles mosquito.
Summarise the aetiology of malaria
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
Summarise the epidemiology of malaria
Endemic in the tropics
In endemic countries it is most common in children <5 years old and pregnant women
What are the presenting symptoms of malaria?
Feverish traveller Cyclic fevers Headaches Myalgia Arthralgia Fatigue Rigors Weakness Anorexia Flu-like symptoms Sweating Vomiting
Cerebral Malaria Symptoms: headache, disorientation, coma, confusion
What are the signs on physical examination of malaria?
Pyrexia Anaemia (haemolytic) Hepatosplenomegaly Tachycardia Jaundice
What are the appropriate investigations for malaria?
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
Define Sjogren’s syndrome
Autoimmune destruction and lymphocytic infiltration of exocrine glands, particularly the lacrimal and salivary glands, resulting in dry eye and dry mouth.
Summarise the aetiology of Sjogren’s syndrome
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)
Summarise the epidemiology of Sjogren’s syndrome
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
What are the presenting signs and symptoms of Sjogren’s syndrome?
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
What are the appropriate investigations for Sjogren’s syndrome?
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
Define systemic lupus erythematosus
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
Summarise the aetiology of systemic lupus erythematosus
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
Summarise the epidemiology of systemic lupus erythematosus
Most common in females of reproductive age
Most frequently 15-45 years old
More common and severe in those of Asian and African descent
What are the presenting symptoms and signs on physical examination of systemic lupus erythematosus?
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
What are the appropriate investigations of systemic lupus erythematosus?
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)
Define systemic sclerosis
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
Describe the aetiology of systemic sclerosis
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
Summarise the epidemiology of systemic sclerosis
Women three times more commonly affected than men
Onset 30-60 years old
What are the presenting symptoms and signs on physical examination of systemic sclerosis?
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
What are the appropriate investigations for systemic scleroderma?
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)
Define vasculitides
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
Summarise the aetiology of vasculitides
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
Summarise the epidemiology of vasaculitides
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
What are the presenting symptoms and signs on physical examination of vasculitides?
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
What are the appropriate investigations of vasculitides?
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
Define abscess
A painful collection of pus (dead cells and tissue, pathogens and immune cells) in a walled off area usually caused by bacterial infection.
Summarise the aetiology of abscess
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.
Summarise the epidemiology of abscess
Skin abscesses are relatively common
IV drug use is a major risk factor for skin abscesses
Internal abscesses are less common
What are the presenting symptoms of abscess
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
What are the signs on physical examination of abscess?
Swollen, pus-filled lump under the surface of the skin which comes to a head
Fever
What are the appropriate investigations for abscess?
Mainly clinical diagnosis and examination - will be fluctuant
USS visualisation of abscess
Pus analysis
What is the management of abscesses
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
What are the possible complications of abscesses?
Recurrence Sepsis Spread of the infection to brain or spinal cord Endocarditis Gangrene Osteomyelitis
Define HIV
Infection by the Human Immunodeficiency Virus which targets immune cells, leading to a decreased immune system strength
Summarise the aetiology of HIV
Transmitted by: Sexual intercourse Mother-to-child - intrauterine, breastfeeding, childbirth Blood transfusion IVDU Needlestick Organ transplant
Summarise the epidemiology of HIV
Increasing incidence in Asia and Africa
What are the presenting symptoms and signs on physical examination of HIV?
There are THREE phases of HIV:
- Seroconversion: Self-limiting, fever, night sweats, generalised lymphadenopathy, sore throat, oral ulcers, rash, myalgia, headache, encephalitis, diarrhoea
- Early/Asymptomatic: Apparently well but some may have persistent lymphadenopathy. Progressive minor symptoms (e.g. rash, oral thrush, weight loss)
- 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
What are the appropriate investigations of HIV?
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
