Vascular Flashcards
1
Q
Lymphocytic thrombophilic arteritis
A
Can mimic PAN - livedo racemosa and macular hyperpigmentation
Lymphocytic on histology
More mild
Have as a differential
2
Q
Adenosine deaminase 2 deficiency
A
Found in children with cutaneous PAN
Gene is CECR1
Leads to strokes and immunodeficiency
Prediliction for medium vessel vasculitis
3
Q
Infantile haemangioma epidemiology and risk factors
A
- most common first year of life
- 4-5% of infants experience
- F>M (2-5:1)
- risk factors: LBW, premature, placental insufficiency, advanced maternal age, Caucasian, family history, twins
4
Q
Infantile haemangioma pathogenesis
A
- proliferating endothelial cells
- Signalling + pathways:
- GLUT1 (glucose transporter protein 1) expressed in IHs and the placenta
- Vascular endothelial growth factor (VEGF) changes
- Genetics:
- Somatic mutations in genes that encode proteins involved in VEGF signaling
- Familial haemangiomas linked to Chromosome 5q
- Hypoxia
- Demonstrated by association with hypoxic states - placenta praevia, etc
- hypoxia increases GLUT1 and VEGF –> mobilising vascular engothelial cells
- Hypoxia + oestrogen results in synergistic effect on haemangiomas endothelial cell proliferation
- Other things
- Other cells may influence - monocytes, fibroblasts, pericytes, mesenchymal cells, adipocytes, etc
5
Q
Types of infantile haemangioma
A
- Superficial:superficial dermis, bright red –> most common ~50-60%
- Deep:deep dermis/subcutis, take longer to see, warm, ill-defined blue-purple masses with minimal or no overlying skin changes. When super deep mat gave arterial blood supply –> seen with USS –> least common ~15%
- Mixed:superficial and deep components, subsequently have both presentations
6
Q
Patterns of infantile haemangioma involvement
A
- Focal: arises from simple localised nidus
- Segmental:covering a broad area or developmental unit in a plaque like manner
- often begin as broad patches of confluent or reticulated erythema and/or telangiectasia
- more likely to be associated with regional extra-cutaneous manifestations: PHACES and LUMBAR
- 4 segments to face:
- S1 fronto-temporal
- S2 maxillary
- S3 mandibular
- S4 fronto-nasal
- Indeterminate: difficult to classify
Subset: infantile haemangioma with minimal or arrested growth- display little or no growth beyond patches of reticulated erythema. these are more on the lower body and may develop recalcitrant ulceration or be associated with syndromes.
7
Q
Phases of infantile haemangioma
A
‘Precursor lesion’: telangiectasias surrounded by vasoconstricted halo
- Early proliferation:rapid increase in size
- Mark out their territory early on
- as they proliferate become warmer and firmer in texture
- deep haemangiomas proliferate for a longer time
- 80% reach final size by end of this phase - mean age of 3 months
- Later proliferation:continued growth at a slower rate
- Plateau
- Involution
- Can occur as early as the first year of life
- 30% by 3 years, 70% by 7 years, 90% by 9 years
- when they involute, often no scar, occasionally atrophic, fibrofatty or telangiectatic residua
8
Q
Infantile haemangioma complications
A
- Ulceration
- ~10% of cases
- more likely in lip and ano-genital region
- more likely in large, mixed or segmental
- median age 4 months
- painful, incr risk of infection, rarely bleeding
- Disfigurement
- Interference with function
- Syndromes
- Rarely can result in congestive heart failure
- Classified by location:
- Peri-ocular:
- compresses the globe –> astigmatism
- obstructs visual axis –> visual abnormalities
- Orbital
- Proptosis
- Nasal tip
- Deformity: cryano-nose
- Columella
- Ulcerate and cause deformities with underlying cartilage
- Lip
- Ulceration –> feeding difficulties
- Distortion of vermillion border –> significant cosmetic residua
- Pinna
- Ulceration –> scarring –> conductive hearing loss
- Breast
- Breast asymmetry
- Peri-ocular:
9
Q
PHACES
A
- Posterior fossa
- Haemangioma
- Arterial anomalies of cardiac and cerebral vessels
- Cardiac defects
- Eye anomolies
- Sternal defects
10
Q
LUMBAR
A
- Lower body/lumbo-sacral haemangioma
- Urogenital abnormaltiies
- Myelopathy
- Bony deformities
- Anorectal and arterial anomalities
- Renal anomalies
11
Q
PELVIS
A
- Perineal Haemangioma
- External genital malformations
- Lipomyelomeningocele
- Imperforate anus
- Skin tags
12
Q
Infantile haemangiomas - locations with associations
A
large facial haemangiomas >5 cm often associated with syndrome
- Lower facial/beard:associated with airway involvement
- Midline lumbosacral:marker for occult spinal dysraphism
- Liver most common site of visercal haemangiomas in patients with multiple skin lesions
- can be focal, multi-focal or diffuse
- when diffuse, associated with hypothyroidism, high output cardiac failure due to AV and arterioportal shunts, abdominal compartment syndrome
- Screen these with serial ultrasounds, clinical assessments and laboratory evaluation for hypothyroidism
- When to look for extra-cutaneous:
- > 5 skin lesions
- Large segmental
13
Q
Thyroid changes with infantile haemangioma
A
- haemangiomas secrete type 3 iodothyronine deiodinase - this enzyme deactivates thyroid hormone, subsequently leading to hypothyroidism
- screen for this in hepatic haemangiomas or large cutaneous
14
Q
IH histology
A
- proliferating plump endothelial cells and pericytes
- small vascular lumens focally
- later in proliferation: lobules of endothelial massess separated by fibrous septae, larger feeding and draining vessels, some mitotic figures
- Involution: flattening of endothelium and reduced mitotic figures, fibrous and fatty tissue separating the vessels within and between lobules. fully involuted: fibrofatty tissues
- Special stains
- GLUT-1 positive
15
Q
DDx for IH
A
- Superficial
- pyogenic granulomas
- tufted angioma
- spindle cell haemangioma
- verrucous venous malformation
- Deep
- venous, lymphatic or combined malformation
- congential haemangioma
- kaposiform haemangiodenothelioma
- Kasabach-Merritt phenomenon - life threatening, thrombocytopaenic coagulopathy
- Congenital fibrosarcoma
16
Q
IH Management
A
- Active non-intervention
- close observation
- education
- discuss re bleeding and ulceration
- Ulceration
- Local wound care
- Infection treatment
- metronidazole gel in areas concerned of gram neg
- hydrocolloid dressings and foam dressings - i.e. Mepilex
- compression dressings for limbs
- Pain relief
- occlusive dressings
- oral panadol
- topical lidocaine ointment
- Beta-blockers
- Pulsed dye laser
- Systemic treatment
- indications:
- threatened vital functions - vision, airway
- potential for disfigurement - nose, columella, lip
- severe/recalcitrant
- high output cardiac failure
- indications:
17
Q
Topical beta blocker
A
- Timolol - non-selective beta-blocker for small lesions <1 mm thick and 2.5 cm in size
- 0.5 % gel or ointment, drop BD to area
- Dose be limited to <0.25 mg/kg/day
18
Q
Intralesional steroids for IH
A
- IL used for areas such as the lip
- Triamcimolone not be more than 3-5 mg/kg
19
Q
Propranolol in IH
A
- MOA: vasoconstriction via beta-2 adrenergic receptors on endothelial cells, disruption of VEGF signalling that drives vasculogenesis
- Target 2-3 mg/kg/day
- Continue for 6-12 months then tapered slowly to prevent rebound tachycardia
- ~25% then have recurrence after cessation
- A/E:
- hypotension, bradycardia
- hypoglycaemia –> give with food
- bronchospasm –> history of airway reactivity is an absolute contraindicatiojn
- More common:
- sleep disturbance
- cold extremities
- diarrhoea
- somnolence
- Atenolol may also work as well
20
Q
Laser for IH
A
- PDL
- 585-600 nm wavelength
- most beneficial for superficial
- generally well tolerated
- a/e: pigment alteration, ulceration, atrophic scarring
- Nd:YAG
- might be better for deeper lesions
21
Q
Vascular malformation definition
A
Localised defects of vascular morphogenesis - likely causes by dysfunction in pathways regulating the foramtion of vascular channels during embryonic development. Not truly proliferation.
22
Q
Haemangiomatosis
A
5 or more haemangiomas
Liver haemangioma acts as AVM and can have cardiac failure
Consumptive hypothyroidism
23
Q
CM-AVM SYNDROME
A
Autosomal dominant
Capillary malformations + AVM
Fast flow vascular anomalies
Skin mm bone brain and spine
Cx: heart failure, bleeding, neurological sequelae
Gene: RASA1 and EPHB4
Evidence to suggest that CMs and AVMs due to second hit phenomenon
24
Q
KS aetiology
A
- HHV-8: promotes cellular proliferation, angiogenesis and prevent apoptosis
- This is present in all Kaposi Sarcoma, though only a small percentage of those with HHV-8 get Kaposi sarcoma
- Argue as to whether is hyperplasia or neoplasia
25
Q
Subtypes of KS
A
- Classic
- M>F, 40-60s, Mediterranean and Ashkenazi Jews
- Clinically: pink macules and papules to unilateral limb that spreads bilaterally, coalesce to form nodules and polypoid tumours
- African endemic
- M>F in adults, however subtype in children
- 4 sub-types:
- Classic - as per classic
- Fulminant?
- Infiltrative - erodes down to S/C fat, mm and bone
- Lymphadenopathic: in children and fatal
- HIV
- CD4 count <500
- Generalised, widespread
- Iatrogenic immunosuppressed
- M>F, transplant patients
26
Q
KS Histology
A
- All look the same regardless of sub-type
- Patch:
- Pauci-inflammatory
- Slit like vessel network??
- Nodule
- Sieve-like pattern of vascular spaces
- Mitotic figures and pleomorphism
- Degenerated erythrocytes
- Special stain: LANA-1
27
Q
KS treatment
A
- If solitary and classic - monitor, nothing
- Topicals:
- Steroids
- IL-steroids
- IL-chemo
- Cryotherapy
- Radiation
- Systemic (if severe)
- Chemotherapy - taxanes
- Interferon
28
Q
ISSVA Classification 2018
A
- Vascular tumours
- Benign
- Locally aggressive/borderline
- Malignant
- Vascular malformations
- Simple - capillary, lymphatic, venous, AV malformation, AV fistula
- Combined - CVM, CLM, LVM, CLVM, CAVM, CLAVM
- Of Major named vessels
- Associated with other anomalies
29
Q
Most common vascular malformations
A
CMs, then VMs
30
Q
Vascular malformation pathogenesis
A
- Embryology:
- Vasculogenesis - primitive vascular plexus
- Then angiogenesis: secondary sprouting of mesoderm-derived endothelial cells, forms new vessels from existing ones. Generates blood and lymphatic vessels
- Endothelial differentiation: recruits smooth muscle cell precursors to ensheathe endothelial cells and build vessel walls
- Change in channel size
- Somatic mutations –> found often in lesional tissue, but not elsewhere
- Germline mutations –> more systemic
31
Q
Naevus simplex
A
- Represents remains of the foetal circulation
- Pink-red macules and patches in a ‘V’ shape (angel kiss), become more prominent with crying, can have preferential eczema
- Locations: eyelids, philtrum, occiput, nape (‘stork bite’) and lumbosacral
- If persistent midfacial naevus, associated with Beckwith-Wiedemann (overgrowth syndrome) and megalencephaly-CM
- Fades spontaneously between 1-3 years of age, extra-facial more persistent
32
Q
Persistent mid-facial naevus simplex associated syndromes
A
Beckwith-Wiedemann (overgrowth syndrome)
Megalencaphaly -CM
33
Q
PWS genetic mutation
A
- GNAQ somatic activating mutation –> in affected skin and regional extra-cutaneous tissue
- A mutation in this stimulates MAPK signalling, resulting in increased cell proliferation and decreased apoptosis
34
Q
Port Wine Stain clinical
A
- well-demarcated bright/deep red macules and patches
- Distribution of facial PWS thought to reflect the prominences that form during embryonic craniofacial development and their associated vascular. Divided into branches of trigeminal nerve - V1, V2 and V3.
- Over time thicken, nodular, may develop superimposed pyogenic granulomas
- Extra-cutaneous: overgrowth of soft tissues and facial bones can occur, so get open bite, gums, lips enlargening –> gingival bleeding, macrocheilia, lip incompetence
35
Q
Types of PWS and variants
A
PWS Naevus roseus Reticulated CM - Distribution: - Localised - Segmental - Multi-focal - widespread
36
Q
Sturge Weber genetics
A
Again, GNAQ somatic activating mutation - mosaic
37
Q
Definition of forehead area in Sturge Weber
A
line from outer canthus to top of ear.
S1 and bilateral higher risk of issues
38
Q
Sturge Weber Extra-cutaneous
A
- Ocular: enlarged venous vessels affecting the conjunctiva, retina, episclera, choroid. Glaucoma in 30-60% of patients
- Neurologic: hypoperfusion of ipsilateral brain due to CVM within the pia mater, can have absence of superficial cortical veins and dilated deep draining veins. Seizures in first 2 years of life, may also have stroke-like episodes, developmental delay, emotional and behavioural problems, ADD, migraines
- Endocrine: central hypothyroidism and growth hormone deficiency
39
Q
Sturge Weber investigations
A
- You must investigate any child with a facial PWS involving the forehead:
- MRI with gadolinium contrast or MR susceptibility weighted image
- Wait until >1 year of age as before that can be insensitive
- FLAIR or MRV may improve detection of leptomeningeal disease
40
Q
Capillary malformations with overgrowth - genetics
A
mosaicism for mutations that result in activation of the PI3K/AKT pathway have been found to underly many of these conditions
41
Q
Diffuse capillary malformation with overgrowth
A
- GNA11 in some patients
- presents at birth, not progressive
- Clinically:
- digits: syndactyly, sandal-gap, macrodactyly
- CM: reticulated, confluent areas, widespread and block-like
- Venous: variable prominent veins
- Normocephalic
42
Q
Megalencephaly-capillary malformation
A
- Gene: mosaic PIK3CA
- Present at birth, progressive
- Clinically:
- Digits - syndactyly
- Macrocephaly: hemimegalencephaly, dolichocephaly
- CM: reticulated, widespread, block-like, persistent naevus simplex
- Venous: variable prominent veins
- Other: hyperelastic, soft, doughy skin
- Tumours: rarely Wilms tumour
- MRI: cerebellar tonsillar ectopia + herniation, polymicrogyria, cerebral asymmetry
43
Q
Klippel Trenaunay genetics
A
PIK3CA mosaic
44
Q
Klippel Trenaunay clinical
A
- Defined by triad of:
- PWS
- Vascular malformation
- Progressive overgrowth of affected extremity
- Present at birth, progressive, correlates with sites of vascular malformation
- Is either a CVM or CLVM
- Clinically:
- Geographic CM - well demarcated, dark red to purple stain with irregular borders, favours the lateral aspect of the thigh, usually associated with a lymphatic component. Can have superimposed purple papules or haemorrhagic vesicles. Associated with more complications
- Other children might not have a geographic CM and might just be pink-red blotchy
- Progressive limb growth:
- Leg length discrepancy
- Lymphoedema
- Sometimes can affect the anogenital area, bladder, pelvis, retroperitoneum, and GIT
- VM: can be associated with intravascular coagulopathy with high D dimer and low fibrinogen, risk of developing clots –> consider prophylactic anticoagulation particularly when have other risk factors
45
Q
How to investigate Klippel Trenaunay
A
MRI
46
Q
CLOVES
A
Congenital lipomatous overgrowth, vascular anomalies, epidermal naevi, scoliosis/skeletal abnormalities
47
Q
CLOVES genetics and clinical
A
- Is a possible CVLM
- At birth, progressive, correlates with sites of vascular malformation
- Clinically:
- Digits: Broad hands/feet, macrodactyly, sandal gap
- Macrocephaly: 30%
- CM: geographic, well-demarcated, on trunk overlying lipomatous mass
- VM: of superficial, deep thoracic and often major central veins
- LM: truncal within lipomatous mass, overlying vesicles
- AVM: variable spinal/paraspinal
- Rarely: Wilms tumour
- High risk of pulmonary embolism
48
Q
Proteus genetics
A
AKT1, mosaic
49
Q
Proteus clinical
A
- Not present at birth, but progressively develops at 6-18 months
- Asymmetric, disproportionate overgrowth
- CM: well demarcated, variable VM and LM
- Cerebriform connective tissue naevi of palms and soles, epidermal naevi, lipomatous overgrowth, regional lipohypoplasia, regional absence of fat
- Bullous pulmonary degeneration
- Tumours: parotid monomorphic adenoma, ovarian cystadenoma
- DVT results in premature death in up to 20% of patients
50
Q
CLAPO
A
CM of the lower lip and LM of the tongue and neck, with Asymmetry and Partial Overgrowth of the face (CLAPO
51
Q
Cutis marmorata telangiectatica congenita
A
- Dark purple-red purple, broad reticulated vascular pattern intermingled with telangiectasias
- commonly affects one or more limbs with the corresponding trunk quadrants
- To differentiate with physiologic: persists upon warming
- Atrophic depression evident within net-like pattern, particularly over joints –> result in ulceration and scarring
- lightens within first year of life
- 50% –> hypoplasia (girth>length) + other vascular malformations
- Can have skeletal, ocular and neurologic defects
- Adams Oliver syndrome - CMTC or reticulated CM with distal transverse limb defects, cardiac malformations and scalp/skull defects
- Occasionally neonatal lupus can have cutis marmorata like features
52
Q
How to differentiate cutis mamorata physiologic and pathologic
A
To differentiate with physiologic: persists upon warming
53
Q
Adams Oliver syndrome
A
cutis marmorata or reticulated CM with distal transverse limb defects, cardiac malformations and scalp/skull defects
54
Q
Angioma serpiginosum
A
clusters of tiny punctate telangiectasias in serpiginous patterns
55
Q
Unilateral naevoid telangiectasia
A
segmental configuration favouring the face, neck, chest and arms
56
Q
Hereditary haemorrhagic telangiectasia genetics
A
Autosomal dominant –> heterozygous mutation in ENG, ACVRL1, SMAD4
