ID / Haem / Immuno / Allergies / Genetics Flashcards

Question

CML - gene associated? Hx? Ix? Disease phases? Mx?

Answer 1

* Most assoc w/ **Philadelphia chromosome – BCR-ABL1 fusion gene** from **translocation of t(9;22)** --\> detected w/ _FISH_ * Hx/exam: * Age 35-55yrs * LUQ pain (from splenomegaly) * Asymptomatic if Dx in chr phase ± lethargy, fever, night sweats * Sx of acute leukaemia if in accelerate/blast phase (10%) * Investigations: * Bloods: **raised basophils** (specific), high WCC (neutrophilia), 50% thrombocytosis, low monocytes (high = CMML), unlikely sign anaemia (can be), precursor cells on blood differential (promyelocytes/myelocytes) * High WCC causes: * Acute bact inf (high **neutrophil**: lymphocyte ratio) * Acute viral inf (low neutrophil**: lymphocyte** ratio BUT COVID-19 --\> lymphopenia) * Fungal/parasitic (high eosinophils) * Monocytosis (in TB, endocarditis, inflame conditions) * Features: * **_Left shift_** – precursor cells present * High WCC, eosinophilia, basophilia * Hypo-lobated megakaryocytes – in BM * Disease phases: * Chr (90%) * Accelerated (increased blasts in BM, poor Tx-response, additional chromosomal abn) * Blast phase (\>20% blasts in BM, behaves like acute leukaemia) * Management: * Chronic phase --\> Tyrosine kinase inhibitors – 1^st gen = **Imatinib** (2^nd gen – Dasatinib/Nilotinib/Bosutinib, 3^rd gen – Ponatinib) * \>90% 10yr survival --\> small % need transplants * Blast phase – Tx similar to AML (allogenic SCT for young)

Answer 2

* Presentation: * Asymptomatic – routine bloods * \>50yrs (incidence increases w/ age), X2 M\>F * Possible LNs/splenomegaly * ITP (immune-mediated thrombocytopenic purpura)/haemolytic anaemia * Investigations: * Bloods: only anaemia if aggressive/haemolytic anaemia, high WCC (\>100, mature lymphocytes) * BF: **smear cells/smudge cells**, lymphocytosis * Dx: flow cytometry – Kappa/Lambda light chains * Mostly B cell CLL (but can be T cell) * Same pathology as _small lymphocytic lymphoma_ BUT different distribution (blood/BM Vs LNs) * B-cells **CD5** +ve (normal mature B-cells CD5 -ve), _CD38_ +ve = poor prognosis * Immunoglobin gene mutations: **IgH **_un_**mutated** = worse prognosis * FISH – **17p gene deletion** (TP53 – contains p53 tumour suppressor gene) gene deletion --\> worse prognosis * Management: * Staging: * A – no cytopenia, **\<3** areas lymphoid involvement --\> W&W * B – no cytopenia, **≥3** areas lymphoid involvement --\> consider Tx * C – **cytopenia** --\> TREAT * BCL-2 inhibitors (Venetoclax) – allows the normal apoptosis of B-cells * BCR-tyrosine kinase inhibitors (ibrutinib, idelalisib) * CAR T-cell therapy (for B cell cancers e.g., B-cell lymphoma) * NOTE: all very expensive * **Richters syndrome** – transformation of CLL --\> aggressive disease (ALL/high grade lymphoma)

Answer 3

Down's - trisomy 21 (most common trisomy) * Epicanthic folds, protruding tongue, hypotonia, congenital heart defects, learning disability Edwards - trisomy 18 (2nd most common trisomy, 80% female) * Rocker bottom feet, microcephaly, low-set malformed ears, cleft lip Patau's - trisomy 13 (3rd most common trisomy) * Most don't survive to term - 80% congenital heart defects, holoprosencephaly - brain doesn't divide into halves -> midline facial defects Klinefelter's - XXY * Tall, gynaecomastia, infertile, behavioural problems Turner's - X * Short, gonadal dysgenesis (prim/secondary amenorrhoea), lymphoedema Fragile X - mutated FMR1 on X-chr * Learning difficulties - delayed milestones * Facial asymmetry - high forehead, long face, large jaw, long ears * Large testes Williams - chr 7 deletion (rare AD) * 'Elfin' facial features, cardiac defects, learning disability

Answer 4

AD condition (chr 19) - pigmented lesions on buccal mucosa + GI polyps --> increased risk of intestinal cancer * Normally Dx in early 20s with bowel obstruction from intussuception Gardner syndrome (familial colorectal polyposis, AD) - multiple polyps in colon + tumours outside colon Juvenile polyposis syndrome - multiple polyps in child GI tract - most benign but increased risk of adenocarcinoma Familial adenomatous polyposis (AD, chr 5 - APC gene) - large intestine benign polyps transforming into malignant if not Tx

Answer 5

CMV retinitis

Answer 6

oesophageal candidiasis

Answer 7

Pneumocystis jirovecii pneumonia

Answer 8

toxoplasmosis encephalitis

Answer 9

Kaposi sarcoma

Answer 10

Tx: * Neurosyphilis --\> IV aqueous benzylpenicillin 10-14 days * Latent syphilis --\> IM Benzathine benzylpenicillin STAT * Otherwise --\> IM Benzathine benzylpenicillin x3/2wks Jarisch-Herxheimer reaction - acute febrile illness in 1st 24hrs post-Tx * Acute headache, fever, myalgia Ix: * Lesion present - dark field microscopy (coiled spirochaete bacterium with corkscrew appearance with motility) * Otherwise - Treponema serological testing (+ve active & past)

Answer 11

Lymphogranuloma venereum (LGV)

Answer 12

Cause: plasmodium protozoa -> paroxysmal fever Def: * ≥10% RBCs infected * ≥1 sign of severe disease Ix: thick & thin blood film Mx: * Non-severe: oral artemisinin based combo therapy (ACT) * Severe: artemisinin derivative IV followed by oral ACT

Answer 13

salmonella typhi

Answer 14

Lyme disease

Answer 15

Lymphogranuloma venereum

Answer 16

* **Chlamydia** (Chlamydia trachomatis) – obligate intracellular G-ve (can’t be cultured on agar) * Classification: Serovars **A-C** = trachoma; **D-K** = genital, ophthalmia neonatorum, **L1-3** = Lympho-granuloma venereum (LGV) * Ix: genital swab/urine sample (FCU) --\> **NAAT** * Mx: **Azith 1g STAT**/Doxy 100mg BD 7 days * Complications: PID (infertility/ectopic/chr pain) * **Gonorrhoea** (Neisseria gonorrhoeae) – obligate intracellular G-ve diplococcus * Ix: swabs/urine sample --\> _culture_ * Mx: **ceftriaxone 250mg IM STAT** * **Syphilis** (Treponema pallidum) – obligate G-ve spirochaete * Ix: **dark-ground microscopy** (from primary lesions) * _Ab non-treponemal tests_ (non-specific antigens): VDRL, RPR (**false positives** common, declines with treatment) * _Ab treponemal tests_ (specific antigens): EIA/FTA/TPHA/TP-PA (confirmatory, +ve for years despite treatment) * Mx: **IM Ben Pen STAT** * Genital ulcers: * Painful = **herpes** \> chancroid * Painless = **syphilis** \> lymphogranuloma venereum (LGV) + granuloma inguinale

Answer 17

Anterior uveitis Hutchinson's sign: vesicles extending to the tip of the nose. This is strongly associated with ocular involvement in shingles Oral antivirals ± steroids * If eye involvement --\> urgent ophthalmological review * Eye lubricant if blink reflex affected to prevent damage to corneal epithelium

Answer 18

Miconazole Fluconazole if invasive oesophagitis (difficulty swallowing)

Answer 19

CMV retinitis (very common pre-ARTs) * Painless blurring, floaters * Fundoscopy: yellow-white exudates + haemorrhages on back of retina * Tx: valganciclovir HSV * Pain, rapid loss of vision in 1wk (acute retinal necrosis) * Fundoscopy: peripheral lesions Candida - oral lesions

Answer 20

DDx: * Toxoplasmosis - cat faeces, commonest CNS inf in HIV, flu-like illness, eye & basal ganglia involvement * Primary CNS lymphoma NOTE: PML - non-enhancing lesions in white matter (JC virus)

Answer 21

**Viral** * **Measles** * Maculopapular rash over hairline/forehead/behind ears, spreading downwards. * _Koplik spots_ - white papules on buccal mucosa * **Rubella** * Erythematous maculopapular rash on face --\> spreads to extremities * _Tender lymphadenopathy_ * **Infectious mononucleosis (EBV)** * Morbilliform rash, pharyngitis, fatigue, myalgia * _Hepatosplenomegaly_, lymphadenopathy Bacterial * **Meningococcal disease** * Meningism + _non-blanching rash_ * **Scarlet fever** * Group A beta-haemolytic strep * Erythema of axilla/neck/chest --\> progress to pink papules on erythematous background --\> _7-10 days later = hand/foots desquamation_ * Pastia’s lines (linear petechial streaks in body folds), red _strawberry tongue_ * Ix: clinical +/- Anti-streptolysin O titre * Mx: penicillin

Answer 22

Type 4 See table for more types

Answer 23

Tetanus-prone wound (req surgical intervention delayed >6hrs, sig devitalised tissue/puncture wound contaminated soil, foreign body, compound fracture, sepsis) Tx: Immediate reinforcing dose of vaccine and 1 dose human tetanus Ig at different site

Answer 24

X-linked -> haemolytic crisis after oxidant stress (viral/bacterial illness, sulfa/quinines, fava beans) * Hb denaturated -> Heinz bodies

Answer 25

Encapsulated bacteria - SHiN KiS * Strep pneumo & GBS * Haemophilus influenzae type B (HiB) * Neisseria meningitides * Kleb pneumo * Salmonella typhi Vaccines 2wks post-surgery (pneumococcal, HiB, meningococcal, influenza) Preventative abx in some - oral phenoxymethylpenicillin OD

Answer 26

Single gene defects block metabolic pathway * Neonatal screening best way of detecting with heel prick test - day 5-8 (PKU, CF, congen hypothy, SCD, medium-chain acyl-CoA dehydrogenase def (MCADD), maple syrup urine disease (MSUD), homocystinuria, glutaric acidaemia T1 (GA1), isovaleric acidaemia) Defects in amino-acid metabolism (AR) * Phenylketonuria - learning disability, **very fair + blue eyes** * MSUD - encephalopathy/prog neurodegen + **'sweet' urine/sweat smell** * Homocystinuria - CNS/MSK/CVS disorder in childhood * GA1 - movement disorder by 2yrs -> Tx w/ diet * Isovaleric acidaemia - toxic to CNS - some present in first days of life/others during childhood by inf/protein-rich food with vom/seizures = **sweaty feet smell** * Hartnup disease - mostly asymptomatic but **episodic neuro/derm Sx assoc w/ trigger** (sunlight, fever, poor nutrition, exercise, sulfonamides) Defects in lipid metabolism * MCADD - inability to generate energy during high-demand (can cause hypoglyaemia/hepatic encephalopathy/death) -> preventative Tx * Others Galactosaemia - can't breakdown galactose into glucose -> cataracts, hepatosplenomegaly, interlectual-disability - presents in milk-fed infants shortly after birth Lesch-Nyhan syndrome - X-linked def - causes self-mutilation = **lip/finger biting** Porphyrias - def enzymes in haem synth e.g. acute intermittent porphyria (AD) - attacks of abdo pain, GI dysfunct, neuro disturbance

Answer 27

X-linked mutation in haematopoetic stem cells - def in GPI protein (anchor protein moieties to erythrocyte surface) - responsible for CD55/59 deactivation -> chr complement-mediated haemolysis of PNH cells (worsened if stress e.g. surgery, trauma, inflam) Presentation: * Haemolytic anaemia (haemoglobinuria) - dark brown first thing in morning, urine dip = bl+ (not RBC on microscopy) * Thrombosis - hepatic/abdominal/cerebral/subdermal veins (VTE most common cause of death) * Deficient haematopoiesis - SoB on exertion, fatigue. Neutropenia/thrombocytopenia can cause infection/purpura NOTE: also Sx assoc w/ smooth-muscle dysfunction e.g. oesophageal dysfunction - resolve over day. Can have errectile dysfunction. Ix: flow cytometry - blood CD55/59 Mx: * Blood transfusion as required * Meningococcal vaccine * Eculizumab - prevents activation of C5 * Anticoag (reduce risk of thrombosis if not on eculizumab) * Pred (reduces haemolysis) * Bone marrow transplant currative (Tx-related toxicity is an issue)

Answer 28

1. BCG, MMR, Varicella, Rotavirus, Nasal flu, Yellow fever, oral typhoid 2. MMR (can still give if allegic under supervision), Influenza, Yellow fever

ID / Haem / Immuno / Allergies / Genetics Flashcards

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