Case 13: AID's, Syphilis and TB Flashcards
1
Q
Complications of HIV: CD4 count <50
A
- CMV retinitis
- Mycobacterium avium-intracellulare infection
2
Q
How to distinguish oral hairy leukoplakia and oral candidiasis
A
- oral hairy leukoplakia cannot be scraped away
- oral hairy leukoplakia is painless
- oral hairy leukoplakia is usually on the sides of the tongue
3
Q
Stages of HIV
A
- Stage 1: Asymptomatic, persistent generalised lymphadenopathy. CD4 >500
- Stage 2 (minor symptoms): folliculitis, shingles, herpes. CD4 350-500
- Stage 3 (moderate symptoms): oral candidiasis, TB, oral hairy Leukoplakia. CD4 200-350
- Stage 4 (AID’s defining illness): Kaposi sarcoma, Cryptococcus, Toxoplasmosis. CD4 <200
4
Q
Oral candidiasis
A
- Other causes: recent antibiotics, steroid inhaler use
- Treatment: oral fluconazole
- In advanced stages can cause dysphagia and be picked up on upper GI endoscopy (oesophageal candidiasis)
5
Q
AID’s defining illnesses
A
- pneumocystis pneumonia
- Kaposi’s sarcoma
- progressive multifocal leukoencephalopathy
- infections with non-tuberculosis mycobacteria e.g. avium complex
- retinitis or colitis due to reactivated CMV
- cerebral toxoplasmosis
- primary CNS lymphomas
- cryptococcal meningitis
- TB meningitis
- non-Hodgkin lymphoma
- cervical cancer
- persistent cryptosporidiosis diarrhoea
6
Q
Pneumocystis pneumonia (PCP)
A
- Causative agent: Pneumocystis jiroveci (fungus)
- Presents: exertional SOB, dry cough, fever, weight loss
- Treated with high dose co-trimoxazole and steroids. Prescribe HAART in 2 weeks
- Prophylaxis for PCP: Co-trimoxazole
7
Q
Investigations for PCP
A
- Bedside: measure oxygen sats whilst patient is exerting, if quickly desaturates suggests PCP
- Diagnosis: CXR, deep sputum sample (induced or bronchoalveolar lavage) for staining, PCR and fluoroscopic examination
- CXR: bilateral hilar interstitial infiltrates with bat wing distribution (no dense consolidation)
- BAL: PJP oocytes and PCP cysts
- Investigations: HIV test, ECG, ABG, D-dimer
8
Q
How does Kaposi sarcoma present
A
- Skin lesions: purple/ brown raised lesions, usually on lower limbs or head and neck. May affect mucosal surfaces in oropharynx causing small lesions on hard palate
- Visceral lesions: may involve bronchial walls causing dyspnoea and haemoptysis. may involve GI tract causing haematemesis, dysphagia, bowel obstruction and meleana
9
Q
Kaposi sarcoma: diagnosis and treatment
A
- Purple-brown lesions on lower limbs or head and neck
- Bronchial wall lesions: haemoptysis and dyspnoea
- GI tract: haematemesis, dysphagia, bowel obstruction and melaena
- Diagnosis: skin biopsies, investigate visceral lesions with OGD/colonoscopy
- Treatment: may regress with antiretroviral therapy. Visceral lesions or extensive skin disease may require chemotherapy
10
Q
Cerebral Toxoplasmosis: presentation and imaging
A
- Causative agent: Toxoplasma gondii (protozoan parasite)
- Cats are hosts can get it from a litter box or faecal-oral
- Imaging: causes space occupying lesions to form which are concentrated around the basal ganglia. Rim enhances with IV contrast
- Presents with focal neurology (weakness, jerking) and chronic headache. Can cause ‘glandular fever like picture.’ Causes CNS infection and space occupying lesion
11
Q
Cerebral Toxoplasmosis: diagnosis and treatment
A
- contrast enhanced CT head: ring enhancing lesion with surrounding oedema
- brain biopsy for definite diagnosis (high risk procedure so trial treatment first and see if this lesions decrease in size after two weeks)
- Treatment: Sulphadiazone, Pyrimethamine and folinic acid and started on antiretroviral treatment
12
Q
TB meningitis
A
- CSF protein is massively elevated
- Diagnosed: analysis of CSF including ZN stain
- IGRA: test for latent TB and TB exposure
13
Q
Cryptococcal meningitis
A
- Diagnosed: analysis of CSF including India ink stain (shows encapsulated yeast), PCR and culture
- CSF: protein slightly low and glucose slightly elevated but not as much as bacterial meningitis, its largely lymphocytic
- Presentation: headache is not always accompanied by fever or neurology
- Treatment: Amphotericin B and flucytosine followed by fluconazole
14
Q
Restarting HAART
A
- Antiretroviral therapy be commenced 5 weeks after cryptococcal meningitis
- ART should be started for most opportunistic infections within 2 weeks
- If ART is started too quickly in Cryptococcal meningitis there is a risk of IRIS (immune reconstitution inflammatory syndrome) which occurs as a failing immune system recovers and starts to mount more exaggerating inflammatory responses. Manage with NSAID’s
15
Q
HIV: Cryptosporadiun
A
- Diagnosis: stool culture
- Persistent Cryptosporidium infection is an AID’s defining illness
- Type of organism: Protozoan parasite
- Infection by drinking contaminated water
- Treatment: Antiretroviral therapy
16
Q
When to test for HIV
A
- Universal testing: TOP/ GUM/ ante-natal/ drug dependency/ TB/ hepatitis/ lymphoma services
- AIDS defining illness: TB, PCP, Cerebral Toxoplasmosis, Cryptococcal meningitis, PML, Kaposi sarcoma, NHL, Cervical cancer, CMV retinitis
17
Q
Syphilis
A
- A sexually transmitted disease caused by Treponema pallidum which is a Spirochaete
- Transmitted through minor abrasions at genital skin or mucous membranes: sexual contact (only in early syphilis), sharing of needles, vertical
18
Q
Syphilis: contact tracing/Partner notification
A
- done for all STI’s, is voluntary. Can be done by patient or clinic (provider referral).
- Syphilis: Primary (last 3 months), Secondary/Early latent (past 2 years or 3 months before last negative test)
- Management of syphilis contacts: test and empirical antibiotics or test now and at end of 12 week window period
Risk factors: MSM, HIV infection, IV drug use
19
Q
Syphilis stages
A
- Primary syphilis: chancre (ulcer), resolves after 3-6 weeks. Polymorphonuclear leukocytes infiltrate the lesion
- Secondary syphilis: due to haematogenous spread of bacteria causing endarteritis obliterans (inflammation of the tunica intima). Causes rash and systemic symptoms. 15-40% of untreated secondary syphilis progress to late. Resolves due to Macrophages
- Late syphilis: Neurosyphilis, Gummatous syphilis, cardiovascular syphilis
20
Q
Types of late syphilis
A
- Neurosyphilis: chronic inflammation of the meninges. Spinal cord involvement causes tabes dorsalis. Causes paraesthesia, personality change, loss of bladder control
- Gummatous syphilis: presence of granulomas, consistent with a cellular hypersensitivity reaction
- Cardiovascular syphilis: due to vasculitis of the vasa vasorum. Can cause necrosis of the tunica media leading to aortic aneurysms. Narrowing of the coronary ostia causes aortic regurgitation
- Progressive dementia (general paresis)
21
Q
Primary syphilis
A
- Painless chancre: highly infectious, hard anogenital ulcer with local lymphadenopathy, usually painless. Occurs at site of infection i.e. mouth, anus or vagina
- Develops 3 weeks post exposure and resolves within 3-6 weeks
22
Q
Secondary syphilis
A
- 6 weeks - 6 months post infection with systemic involvement.
- 2-6 weeks after primary infection
- Symmetrical maculopapular rash: on trunk, face, palms or soles, might be scaly not itchy
- Condylomata lata: moist, warty lesions near genitals
- Constitutional symptoms: fever, malaise, myalgia, fatigue and arthralgia
- Other symptoms: Lymphadenopathy, Tonsilitis, Splenomegaly, Hepatitis, alopecia
23
Q
Latent syphilis
A
- Asymptomatic infection following untreated primary or secondary syphilis
- Early latent syphilis: confirmed infection in the absence of any current clinical effects, <2 years of infection. Can transmit infection sexually and vertically. Can have recurrence of secondary syphilis. Can be treated with single dose on penicillin
- Late latent syphilis: >2 years of infection. Only vertical transmission. Requires longer treatment courses
24
Q
Ocular syphilis
A
- Uveitis: painful red eye
- visual disturbance (floaters/ flashing lights)
- may cause blindness
- Can occur at any stage
25
Q
Tertiary or late syphilis
A
- > 2 years post infection (typically 15-40)
- 15-30% of untreated patients will go on to develop the complications of tertiary syphilis.
- Tertiary latent syphilis: serological confirmation of infection in the absence of clinical features
- Gummatous, neurosyphilis
- Cardiovascular: Aortitis → Aneurysm, aortic regurgitation
26
Q
Syphilis Investigations
A
- Skin, genital, eye and neurological exam
- Referral to a GUM specialist for a full sexual health screen (including HIV)
- Primary syphilis (direct detection): Dark field microscopy (Spirochete), PCR
- Treponemal tests: show exposure to syphilis, positive for life so cant see response to treatment or re-infection. For example EIA, TPA, IgM
- Non-treponemal tests: Determine disease activity and show response to treatment. For example, RPR and VDRL
- Contact testing
27
Q
Syphilis Management
A
- Referral to GUM or other specialist sexual health services
- Avoid all sexual contact until successful treatment has been confirmed
- Benzathine benzylpenicillin IM
- Alternative: Doxycycline 14 days for early syphilis, 28 days for late syphilis
- In pregnancy: Erythromycin 500mg/6h PO
- Follow up: at 3, 6, and 12 months in specialist GUM clinic
- Monitoring efficacy: 4 fold decrease in non-treponemal test titre
28
Q
Duration of Syphilis treatment
A
- Early syphilis (primary, secondary, early latent)- single dose
- Lat syphilis (late latent, unknown, tertiary)- 3x weekly dose
- Ocular and neurosyphilis- daily for 10-14 days
29
Q
Jarsich-Herxheimer reaction
A
- Triggered by penicillin treatment: good sign as shows infection is being treated
- Acute onset fever, muscle ache, flushing, rash and palpitation
- Manage conservatively: steroids started prior to treatment for prevention in neurosyphilis
30
Q
How neurosyphilis will present (6%of untreated patients)
A
- Meningovascular: cranial nerve palsies e.g. decreased vision, stroke
- General paresis of insane: dementia, psychosis
- Tabes dorsalis: loss of proprioception, vibration sense, incontinence and ataxia
- Meningitis, altered behaviour, stroke secondary to vasculitits
- Asymptomatic: anormal CSF findings
- Can occur at any stage
31
Q
Congenital syphilis
A
- Adverse pregnancy outcomes: miscarriage, stillbirth, pre-maturity
- Early congenital syphilis: Hepatosplenomegaly, Lymphadenopathy, desquamating rash, severe anaemia, jaundice. Significant mortality
- Late congenital: Hutchinson’s triad (pegged teeth, keratitis, sensorineural deafness), saddle nose, bone and joint deformity, developmental delay
- All pregnant women have antenatal screening for syphilis
32
Q
Late syphilis Gummatous
A
Granulomas in skin, mucosa, bone, joints and viscera such as lung and testis. These are rubbery lesions with a necrotic centre and may gradually replace normal tissue.
33
Q
TB
A
- A disease caused by members of the Myobacterium tuberculosis complex.
- Typically affects the lungs and is transmitted via airborne droplets. Bacilli (rod like shape). Tends to spread in overcrowded living and prisons
- Organisms: M.tuberculosis (most common), M.bovis, M.africanum (central/west Africa)
- Called Acid Fast Bacilli (AFB)
34
Q
TB: facts and figures
A
- 10% develop the active infection. The remaining 90% contain the disease and will develop latent TB
- 20-30% of household contacts of infectious people become infected with TB
- Lifetime risk of reactivation of latent TB: 10% (higher if HIV, immunosuppressed or comorbidities)
35
Q
Ziehl Neelson stain: TB
A
- Special stain has to be used as TB cell wall contains mycolic acid (a high molecular weight lipid)
- Appears as a red colour against a light blue background
- Fluorescent staining: appear bright green against a dark background making it easy to spot
36
Q
Risk factors for TB
A
- Immunosuppression: HIV, Immunosuppressant drugs, TNFα inhibitors.
- Diabetes mellitus, end-stage renal disease.
- Previous lung disease (silicosis).
- Smoking.
- Drug abuse, alcoholism.
- Malnutrition, poverty.
- Certain living conditions (prisons, homeless shelters).
- Occupational (hospitals).
37
Q
Pathophysiology of TB
A
Inhalation of Mycobacterium tuberculosis via droplet → deposition in the lungs (alveoli) → engulfed by alveolar macrophages → proliferates in macrophages → release → immune response.
38
Q
TB: stages of disease
A
- When infected an immune response occurs and the Primary complex forms. You then get clinical symptoms or containment
- Primary disease: active disease 1-2 years after infection
- Latent infection: Can either get resolution, persistent latent infection or reactivation with Post-primary tuberculosis
- If you have resolution and re-infection that will be Post primary TB
- Reactivation: occurs when the immune system is suppressed
- Miliary tuberculosis: disseminated and severe disease
39
Q
TB transmissibility facts
A
- Only 20-30% of household contacts are infected
- Immunosuppression i.e. HIV increases risk
- Primary TB: (only 5-10% of people): more likely in infancy, adolescence or old age
40
Q
Symptoms or primary or re-activated TB
A
- Constitutional: Fever (gradual and low grade), Night sweats, Weight loss, anorexia and malaise
- Pulmonary tuberculosis: most common: cough (dry then productive- yellow +/- blood)
- Pleural TB: pleurisy
- Weeks to months for symptoms to occur
- Extrapulmonary tuberculosis: less common
41
Q
Pulmonary TB
A
- Dyspnoea,cough (+/-haemoptysis), chest pain.
- Cough: over 2 to 3 weeks; initially dry, later productive. (yellow sputum)
- Chest examination: crackles, bronchial breath sounds, or maybe normal.
42
Q
Clinical signs of TB O/E
A
- often normal but there may be
- effusion
- crackles
- lymphadenopathy
- clubbing (rare)
- hepatomegaly
- CNS signs in TB meningitis
- abdo masses
- skin manifestations (erythema nodosum)
43
Q
Extrapulmonary TB
A
- Pleura, bones/joints, lymphatic system, liver, central nervous system, urogenital tract, gastrointestinal tract, and the skin.
- Symptoms based on the organ-involvement (enlarged lymph node, pleuritic chest pain, skeletal pain, urinary symptoms, abdominal swelling, abdominal pain, headache).
- Spinal pain in spinal tuberculosis (Pott’s disease of the skin)
- CNS i.e. TB meningitis
- Miliary TB: where TB ruptures and spreads
44
Q
Latent TB
A
- Lifetime risk of reactivating TB is about 10% and is highest in first two years
- TH1 response forms caseating granulomas which causes containment.
- Risk factors: immunosuppression, age and frailty and co-morbidities
45
Q
Latent TB investigations
A
- Tuberculin skin test (TST) or interferon-gamma release assays (IGRAs): for latent TB
- IGRA is preferred with history of BCG vaccine. For example, Quantiferon test
- Dont use tests alone to exclude diagnosis
- TST: tuberculin is injected into arm measure diameter after 48-72hr. (Mantoux test)
- IGRA: blood test to measure levels on interferon-y
46
Q
TB investigations- active pulmonary infection
A
- Chest x-ray, threesputum samples obtained for microscopy, culture, sensitivity and NAAT.
- If unable to produce sputum spontaneously induce with nebulised saline (airway irritant) or bronchoalveolar lavage
- Acid-fast stain (Ziehl-Neelsen stain) identifies the bacilli: AFB smear +
- Sputum culture (gold standard): takes 4-8 weeks
- Sputum: NAAT: Can detect drug resistance and allows rapid diagnosis
- CT and bronchoalveolar lavage (BAL): if CXR shows nothing
47
Q
MoA of TB drugs
A
- Ethambutol: does not kill bacterial but prevents drug resistance and replication
- Isoniazid: kills rapidly dividing organisms
- Rifampicin: kills rapidly dividing organisms and persisters
- Pyrazinamide: kills intracellular organisms taken over by macrophages and lymphocytes
48
Q
Non diagnostic tests for TB
A
- Aspirate or biopsy lymph nodes, pleural fluid, ascites, organs, pus, urine or CSF for microscopy, culture and sensitivities. Especially if unable to produce sputum
- Lumbar puncture: for TB meningitis
- Pleural fluid: lymphocytes predominant on cytology, exudate on lights criteria
- Pleural biopsy or lung biopsy: if other testing is not diagnostic
- Whole genome sequencing: to see if sensitive to TB drugs
- Endobronchial US and fine needle aspiration/biopsy of lymph node
- Routine bloods, HIV screen
49
Q
Stains and cultures for TB diagnosis
A
- Solid or liquid culture: to confirm species. Medium for TB solid culture- Lowenstein Jenson (LJ)
- TB identification: whole genome sequencing (can identify outbreaks in community- by matching genomic profiles) and PCR (quicker can identify resistance). Identifies the bacteria and tests for antibiotic susceptibility
50
Q
TB: CXR
A
- Primary: hilarlymphadenopathy effusion, pulmonary infiltrates, calcification.
- Reactivation: upper lobe cavitary lesion with mediastinal adenopathy
- thick walled cavities/ cavitating consolidation
- nodular tree in bud pattern
- Necrotic adenopathy
- Disseminatedmiliary tuberculosisgives an appearance ofmillet seedsuniformly distributed across the lung fields.
