1
Q
what is azathioprine used for?
A
DMARD; used for Crohns
2
Q
what are the 3 MC types of skin cancer and how do they typically present?
A
- BCC
- MC type of skin cancer
- very slow growing
- almost always localised to the skin
- malignant tumour of the epidermal keratinocytes
- good chance of getting another BCC after having one
- earliest it is treated, the less destructive Tx is
- intermittently bleeding
- can be weepy - SCC
- second MC
- usually grow a little more quickly
- slightly more serious if left untreated
- locally invasive malignant tumour of the epidermal keratinocytes or its appendages, which has the potential to metastasise
- 2-10% risk of spread to other parts of the body, which could be fatal
- early Tx is less destructive and reduces the risk of spread
- red, sore
- increased risk in the immunosuppressed - melanoma
- 3rd MC
- most dangerous
- malignant tumour of the epidermal melanocytes, which has the potential to metastasise
- can be seen in younger individuals but if caught early the outlook is generally good
- develop from existing skin mole or appear as new mole-like marks on normal skin
3
Q
using the ABCDE approach, identify the red flag features of pigmented lesions
A
A - asymmetry**
B - border irregularity
C - colour: 2 or more OR chaotic appearance**
D - diameter>6mm… OR….dark or different (not like any other moles - ‘ugly-duckling’)
E - evolving, especially quickly over weeks to months
**major suspicious features
(nodular melanoma can sometimes present as a rapidly growing nodule which is not pigmented and instead pink, red or flesh coloured often raw or ulcerated)
4
Q
what is important in any skin lesion Hx and examination?
A
take a thorough history focussing on RFs and behaviour of skin lesion
examine the whole pt - allow comparison of index lesion to other naevi
5
Q
what technique is used to remove a mole to confirm diagnosis of a malignant melanoma? if diagnosis is confirmed what procedure follows?
A
elliptical excision under LA of the lesion with 2mm margins. defect repaired with direct, side-to-side closure
a wide local excision (probably with split-thickness skin grafting) is performed to reduce the risk of local recurrence of the melanoma. referral to plastics. sentinel lymph node biopsy, in view of the working stage of melanoma
6
Q
what are the possible risks of skin surgery which should be explained to the pt during consent process?
A
scarring infection bleeding pain incomplete excision delayed healing non-diagnostic biopsy
7
Q
as there is a risk of recurrence with malignant melanoma, including in local lymph nodes and other organs what time period of follow up is required for pt’s?
A
5 years
8
Q
what is Breslow thickness used for?
A
measurement of the depth of the melanoma from the surface of the skin through to the deepest point of the tumour. used for staging and prognosis
9
Q
what are the risk factors of skin cancer?
A
- fair skin that burns easily
- light coloured eyes
- naturally blonde or red hair
- numerous freckles
- outdoor occupation and/or had intense sun exposure without se of sunscreen
- frequent use of sun lamps and beds
- Hx of skin cancer
10
Q
how is DNA damaged?
A
constantly being damaged by…
- free radicals (associated with disease; Ca, atherosclerosis, Alzheimer D, Parkinsons D etc)
- radiation
- mutagenic chemicals
- errors in dan replication
11
Q
what is Werner’s syndrome?
A
- autosomal recessive syndrome
- average life expectancy of 48yrs. problem with DNA unwinding mechanism responsible for DNA repair and replication.
- results in premature ageing
12
Q
describe 3 dna repair mechanism and the type of damage
A
- dna mismatch repair - specifically recognises when base is mismatched e.g. c->t
- >damage = base mismatches, especially after DNA replication - base excision repair - responsible primarily for removing small, non-helix-distorting base lesions from the genome 🧬
- > damage = oxidation, deamination, alkylation, single strand dna breaks - non-homologous recombination re - repairing dna double strand breaks. relatively fast and slightly more error prone compared to homologous
- > damage = dna double strand breaks
13
Q
how does UV damage DNA?
A
if there is 2 thymine residues on the same strand of dna, they can become covalently bonded.
this distorts the helix and if it is not repaired can result in mutation when that strand is duplicated
-> important that our bodies can recognise and repair damage. or stop happening in the first place
14
Q
how does UV induce the expression of melanin?
A
melanocytes -> melanin that reside in the basal layer of the skin. following UV exposure, there is dramatic increase in the synthesis and they actively absorb the UVR and protect the skin from further damage
- in response to UV the melanocortin 1 receptor is activated to stimulate synthesis of eumelanin (Tyrosine —tyrosinase—> Dopa -> Dopaquinone -> Eu-melanin)
- in albinisms, there is a defect in tyrosinase which leads to production of pheo-melanin
- eumelanin is present in the skin and hair of dark-coloured persons and pheo-melanin is present in the skin and hair of light coloured persons
15
Q
repair systems recognise UVR damage and prevent it from becoming worse. what defect occurs if there is a defect in this repair pathway?
A
Xeroderma Pigmentosum
- genetic disorder in which there is a decreased ability to repair DNA damage caused by UV light
- mutation is in the nucleotide excision repair mechanism (involved in repairing larger single stranded lesions and more acutely distort shape of helix e.g. thymine dimers)
- symptoms include severe sunburn after only a few minutes in the sun, freckling in sun exposed areas, dry skin and changes in skin pigmentation
- increased risk of skin cancer
16
Q
Lynch syndrome is an inherited cancer syndrome: pt at high risk for colon cancer. what dna defect is it?
A
defect in the dna mismatch repair mechanism
autosomal dominant
tendency to develop tumours at an early age
17
Q
use breast Ca as another example to compare the consequences of inherited defects in a dna repair pathway
A
- some people (5-10% of breast Ca is familial/inherited) have developed defects to repair double strand break –> susceptible to breast and ovarian Ca
- two main gene defects identified: BRACA 1 and BRACA 2
BRACA 1:
- AD
- not got full penatrance
- therefore, increases lifetime risk to 50-80%
- lots of mutation found (via sequencing) distributed throughout gene. hard to disguise pathogenic and normal variant, but pathogenetic is usually truncated protein
- BRACA 1 usually involved in dna damage response.
BRACA2:
- again, lots of mutations found. most pathogenic result in truncated protein
- founder effect
- role in dna damage response
- > normally BRACA1 is involved in recognising the dna double strand break and initiating cutting back in order to reveal the single stranded section where BRACA 2 (+RAD51) can then bind and promote homologous recombination repair that BACA 1 and 2 are involved in
- > damage to these genes causes double strand breaks as homologous recombination is faulty.
18
Q
why does inherited defect of one copy predispose to Ca?
A
Nudson hypothesis ->in order for Ca to develop there needs to be mutations in both copies of tumour suppressor gene.
Concept is that in someone who develops a mutation in every cell of their body, if by chance there is a mutation in one copy of the other tumour suppressor gene that will leave them with no working gene and tendency to develop cancer
19
Q
describe how the relationship between different dna repair pathways can be exploited therapeutically
A
PARP:
- involved in recognising DNA damage in single dna breaks in base excision repair pathway
- > problem here is that if a single stranded break is not prepared, it will go on to cause a double stranded break, this is where we need BRACA1 and 2 pathway in older to resolve
- > the PARP and BRACA pathways are an example of synthetic lethality
- > potential PARP inhibitor drug that would kill mutated cells if BRACA2 -/-. sounds good, but cell lines become resistant over time
- > resistant cells lines can actually develop into reverse mutations and start working again
20
Q
describe the concept of synthetic lethality
A
where 2 genetic mutations, independently are compatible with life. But expression of both together –> mortality
21
Q
name 4 functions of the skin
A
- homeostasis - thermoregulation (vasodilation, sweating, hairs)
- sensation (pain, temp, touch, pressure, vibration)
- protection (UV, organisms, chemicals, water, mechanical)
22
Q
what embryonic layer are the layers of the skin derived from?
A
epidermis = ectoderm
dermis and hypodermis = mesoderm
melanocytes = neural crest cells
*the appendages of the epidermis are derived from ectoderm but extend downwards into the dermis
23
Q
list the 4(5) layers of the epidermis deep to superficial
A
- stratum basale - 1 cell thick, active, epidermal stem cells with melanin
- stratum spinous - spikes of processes linking cell to cell
- stratum granulosum - cells containing deeply staining keratohyalin granules
**4. stratum lucidum - only in ‘thick’ skin
- stratum corneum - surface laters of flat, keratinised cells, stuck together, but no longer having nuclei; water barrier
24
Q
list 4 cells of the epidermis
A
- keratinocytes - continuous migration from basal to corneum
- melanocytes - cell bodies in basal layer; processes extending into spinous layer. secrete melanin
- Langerhan’s cells - dendritic cells scattered in the epidermis; part of the macrophage system. protection, but also involved in delayed hypersensitivity reactions like contact dermatitis
- Merkel’s cells - sense organ. with afferent n. fibres immediately below, they form Merkel’s Capsules, a mechanoreceptor
25
the dermis is CT with n. endings, blood vessels and epidermal appendages. what are the 2 main layers of the dermis?
1. papillary layer
| 2. reticular layer (deep). Langer's lines are in this layer
26
list the sense organs of the skin
1. free nerve endings - fine touch, temp, pain
2. merkels cells - steady pressure
3. pacinian corpuscle - pressure and vibration
4. Krause end bulbs - touch and pressure
5. meissners corpuscle - light touch i.e lips, palms, soles
6. Ruffini corpuscle - skin stretch and torque, sustained pressure
27
list epidermal appendages and their function
- hair follicles and hair - thermoregulation
- sweat glands (eccrine and apocrine) - thermoregulation and pheromones
- sebaceous glands - sebum protection
- nails
* reservoir of epidermal cells for skin repair
28
classify burn depth
1st degree, superficial - epidermis (painful)
2nd degree, superficial partial thickness - papillary layer (very painful)
2nd degree, deep partial thickness - reticular later (pressure and discomfort)
3rd degree, full thickness - through entires dermis (painless)
4th degree, through entire skin and underlying tissue, fat, muscle and bone (painless): amputation
*depth affects the healing. 1st and superficial 2nd can re-epithelialize. deep 2nd is borderline. 3rd and 4th require skin graft
29
what causes hairs to stand up
erector pili muscle. it is smooth muscle, stimulated by SNS
- contraction also aids sebaceous gland secretion - their ducts open into infundibulum of the follicle
- sebum is a holocrine secretion. protects the hair and augments the water barrier of the stratum corneum
30
list 3 normal skin microbiota
1. staphylococcus epidermidis and aureus (Gram +ve)
2. streptococcus pyrogens (G+ve)
3. propionibacterium acnes (G+ve)
31
provide an example of infections that occur at different sites/layer of skin
keratinised epithelium -> ringworm
epidermis -> impetigo
hair follicles -> folliculitis
dermis -> erysipelas (superficial cellulitis)
subcutaneous layers -> cellulitis
multi-layer -> necrotising fasciitis
muscle -> gangrene
32
how can bacteria, virus' and fungi cause infection?
skin - pores, hair follicles
wounds - scratches, cuts, burns
bites - insects, animals
33
compare non-bulbous and bulls impetigo (highly contagious bacterial skin infection of the superficial layers, caused by staph pyogenes or aureus, that mainly affects children)
non-bulbous:
- AKA crusted impetigo
- thin walled vesicles or pustules that rupture quickly. associated with golden exudate
- crust separates leaving mild erythema which fades spontaneously without scarring within 2-3weeks
- found anywhere on body
- usually asymptomatic, mild itchy
- Rx = antiseptic cream 1st line -> topical fusidic acid (localised lesions) or oral flucloxacillian if widespread
bullous:
- flaccid fluid filled vesicles and blisters that can persist for 2-3days then rupture leaving yellow/brown crust
- common on the flexures; face, trunk and limbs
- systemic features may occur if large area are affected and include fever, lymphadenopathy, diarrhoea and weakness
- healing within 2-3weeks without scaring
- oral or IV flucloxacillian
Mx:
- advise hygiene measures, help to aid healing and stop infection spreading
34
describe staphylococcal scalded skin syndrome
- serious bacterial (staph aureus) infection. bacterium produces an exfoliative toxin that causes the outer layers of the skin to blister and peal (looks like a second degree burn)
- can be a complication of severe and widespread bullies impetigo
- fever and irritability
- +ve Nikolsky sign - gentle stroking of the skin causes it to separate at the epidermis
- same day contact with on call dermatologist
- parental ABs e.g. flucloxacillin
- supportive treatment if evidence of shock
- mortality rate = low in children. high in adults
35
discuss cellulitis
- deeper infection of the dermis and SC tissue. characterised by erythema, oedema, tenderness
- staph aureus or strep pyogens
- foreign travel or salt water exposure could be other organism
- describe and delineate the infection by drawing a line
- symptoms indicate severity
- classification:
Class 1 – no systemic toxicity or comorbidity
Class 2 – systemic toxicity or comorbidity that might complicate or delay resolution of the infection (e.g. PAD)
Class 3 – significant systemic toxicity or significant comorbidity
Class 4 – sepsis or life threatening (NF)
- Tx. high-dose oral ABs (Flucloxacillin)! may require hospital admission for IV ABs if class 3/4 or immunosuppressed. Give pain relief and elevation.
36
discuss erysipelas
- s.pyogenes infection usually face, shin, dorsum of foot
- superficial form of cellulitis
- very hot, aching throbbing and tenderness
- clear boundary with normal skin
- moderate fever and rise WBC
- Dx is clinical
- Tx same as cellulits
37
discuss necrotising faciitis
- very high mortality rate. results in death of parts of the body soft tissues
- 2 types of infection: 1. mon-infection by strep-pyrogens and 2. mixed infection (whole range of organisms)
- early symx (<24hrs) = intense and extreme pn that may seem out of proportion to any external signs of infection. small but painful cut or scratch. fever and other flu-like symptoms
- advanced symx (3-4days) = swelling, rash, D+V, large dark blotches, that will turn into blisters.
- critical symx = severe hypotension. shock, unconsciousness as the body weakens
-Mx = admitted. IV ABs, surgery
debridement, amptation, Iv abs e.g. benzyslpenacillin and clindamycin
38
provide examples of fungal infections of the skin
eg. dermatophytes (tinea pedis, tinea corporis, tinea cruris) or yeasts
- ringworm
- athletes foot
39
Provide examples of viral infections of the skin
HPV - warts
herpes simplex 1 - cold sores
herpes simplex 2 - genital warts
varicella zoster virus - chicken pox, shingles
coxsackie A virus - hand, foot and mouth
40
provide examples of parasites of the skin
sarcoptes scabei (mite)
- causes scabies
- burrows into skin
- female lays eggs
- infection is asymptomatic
- hypersensitivity may occur
- may lead to superinfection
41
Define the terms therapeutic drug monitoring
TDM:
- measuring the plasma concentration (Cp) of a drug in order to determine if target levels are met, or if therapeutic or toxicity suspected
- aims to individualise dosage of certain drugs in certain pt;s to achieve desired therapeutic effect and minimise adverse effects
42
list indications for therapeutic drug monitoring
- high risk drug with narrow therapeutic index
- if there is wide inter-pt variation from a given dose
- individualising therapy at beginning of therapy or when doses adjusted
- diagnosing under treatment
- avoiding toxicity
- monitoring any potential drug interactions
- guiding withdrawal therapy
43
give examples of drugs where therapeutic drug monitoring is commonly used in practice to guide drug treatment
- > phenytoin:
- inter-pt variation. it has non-linear kinetics and minor changes in dose may push phenytoin level into toxic range
- diagnosing under treatment in prophylaxis from presenting fits after neurosurgery or trauma
-> Lithium for bipolar disorder:
diagnosing undertreatment
- > ciclosporin:
- diagnosing under treatment in preventing organ transplant rejection
- > Gentamicin and Vancomycin:
- broad spec IV ABs used for severe infections; requires individualised dosing based on pt's renal function to maximise therapeutic effects and minimise toxicity
- > Digoxin:
- cardiac glycoside for AF. TDM justified if toxicity suspected or inadequate digitalisation despite good dosing regime
44
understand the prescribers role and responsibility in therapeutic drug monitoring processes
- understand which drugs may require TDM to maximise efficacy and reduce toxicity
- individualise dosing based on pt's age, size, organ function and clinical state
- to adjust doses logically based on Cp
- be aware of drug interactions or other physiological variables which might be affecting response e.g. digoxin with concurrent hypokalaemia will raise risk of digoxin toxicity eve if Cp is within target range
- if unsure about what blood sampling tube to use, correct sampling times, target levels and how to interpret then seek advice from the pharmacy team and biochemistry lab
- know that it is not always about the levels! observe and monitor pt response/ signs of toxicity e.g. BP, pulse, ECG, temp, RR, biochem (urea, creatinine, eGFR and electrolytes, LFTs and FBC)
45
define high risk medicines
HRMs:
- medicines that have a high risk of causing injury or harm if they are misused or used in error
- all meds may be considered to have a high risk for the pt depending on the circumstances
- when problems occur, consequences can be more significant
- several adverse incidents involving high-risk medicines may have been prevented if there had been greater awareness of the risks associated with the med
46
describe the processes involved in ensuring the safe and effective use of high risk medicines
BNF -> interaction checker
stop high risk med and potential interaction meds
discuss with labs treatment options
monitor bloods
discuss with speciality teams about specific meds/ when they can be stopped/restarted
shared care protocol
pt education (e.g. sick day rules)
healthcare professional education
electronic alerts on prescribing software to highlight pt on high risk med
effective monitoring
accurate
47
what are the main risks with 'high risk' medicines
- narrow therapeutic index means little difference between sub-therapeutic, therapeutic and toxic doses
- risk of worsening renal or liver function
- drug interactions can be more pertinent --> significant harm
48
give examples of HRMs
- methotrexate: serious signs of MTX toxicity are blood dyscrasias and renal impairment (drop in eGFR). interacts with trimethoprim (risk of severe bone marrow depression), ibuprofen (reduces MTC secretion)
- Lithium
- anticoagulants
- any med if situations change. e.g. pt is dehydrated or polypharmacy
49
understand the clinicians role and responsibility in the use of high risk meds
- identify and review pt's on HRM
- ensure accurate medicine reconciliation across the interfaces of care
- ensure drug prescribed safely
- ensure appropriate monitoring and reliable recall systems in operation
- be aware of increased significance/risk of drug-drug/ drug/disease interactions
- ascertain pt knowledge on that drug and improve
50
list the clinical features of Stevens-Johnson syndrome and toxic epidermal necrolysis
SJS is less severe than TEN
- abrupt onset fever
- systemic toxicity
- usually 7-21 days after commencement of offending medicine
- epidermal apoptosis causes generalised erythematous rash with atypical target lesions and blister
- skin is friable with epidermal loss and significant pain
- positive Nikolsky sign
- mucosa (eyes, mouth, genital tract, GIT, Resp.T) can also be affected --> GI haemorrhage +bronchial obstruction
51
list 3 drugs associated with SJS and TEN
1. ABS (sulphonamides (esp. trimethoprim), beta-lactams, tetracycline, quinolone (esp. ciprofloxacin))
2. aromatic anticonvulsants (phenytoin, phenobarbitone, carbamazepine)
3. NSAIDS
52
outline a scoring tool that can be used to assess disease severity in SJS/TEN
SCORTEN - score within 1st 24hr of presentation and repeat on day 3.
1pnt for:
- age>40
- pulse >120
- pt has Ca or haematological malignancy
- epidermal detachment >10% on day 1
- serum urea >10mmol/l
- serum glucose >14mmol/l
- serum bicarbonate <20 mEg/l
53
briefly describe the acute management of SJS/TEN
assess severity (SCORTEN). institute initial Ix and management. stop culprit drug
contact dermatology team if during working hours
if out of hours and <10% epidermal detachment -->manage in MHDU. supportive management as per guideline and contact dermatology asap. pt should have daily senior medical review ad level of care escalated as appropriate
if out of hours and >10% epidermal detachment --> supportive management as per guidelines. discuss with ITU +/- on-call plastic surgeon
supportive care including nutritional care, antiseptics, analgesics and ophthalmology input. treat with steroids, immunoglobulins and immunosuppressants
54
define erythodermal and outline CFs, assessment and acute Mx
- 'red skin'. exfoliative dermatitis (generalised erythema and oedema) affecting 90% or more of the skin surface
- causes: previous skin disease (eczema, psoriasis), lymphoma, drugs/ cutaneous ADRs (sulphonamides, gold, sulphonylureas, penicillin, allopurinol) and idiopathic
- CFs: widespread skin erythema. skins appears inflamed, oedematous and scaly. systemically unwell with lymphadenopathy and malaise
- A: same as acutely unwell pt. thorough look at fluid balance. explore potential causes. exam skin for evidence of secondary infection. baseline FBC , U+Es, LFTs, albumin, bone profile and CRP
-M
> strict bed rest, monitor temp and fluids, IV fluids if fluid balance or U+Es suggest necessary
> discontinue unnecessary meds and treat underlying cause
> copious heavy weight emollients (paraffin ointments) and wet wraps to maintain skin moisture
> steroids may help inflammation
> ABS if secondary infection
55
describe the CFs, assessment and acute management of severe cutaneous drug reactions
CFs: - rash appears 4-21 days after drug started
- maculopapular rash usually beginning in the trunk and upper limbs and progressively become more confluent
- NO involvement of mucous membranes
- generally well
- lab Ix usually unremarkable
A: - examine the skin closely, signs of secondary infection
- Nikolsky's sign and check mucous surfaces
- examiner lymphadenopathy and organomegaly
- baseline IX = FBC, U+Es, LFTs, bone profile and CRP
- exclude DRESS (delayed type IV hypersensitivity reaction thought to be mediated by antiviral Tcells. severe multi system reaction to a drug, characterised by fever rash, lymphadenopathy, haematological abnormalities and internal organs involvement)
M = identify culprit drug
- oral fluid intake
- emollients and topical steroids will lesson itch and probably speed clearance of rash
- sedating anti-histamine at night
- oral prednisolone rarely
56
describe the rule of 9s
quick way to determine the percentage of burn and is used to help guide treatment
57
name 3 subtypes of BCC
1. nodulocystic
2. infiltrative
3. superficial
58
what therapies are available to treat BCC?
- surgical incl Mohs micrographic surgery
- cryotherapy
- imiquimod (cream)
- photodynamic therapy
- vismodegib (systemic Tx for metastatic or inoperable BCC)
59
list 3 DDx of BCC
1. fibrous papule of the nose
2. sebaceous hyperplasia - small bumps resulting from overproduction of sebum and blocking glands
2, haemangioma - benign tumour of blood vessels
60
some SCC are derived from what other skin condition?
Actinic keratosis
| rough, scaly patch on your skin that develops from years of exposure to the sun
61
why should we treat AK?
aim is to reduce the number of AK lesion at any one time. the fewer the lesions, the less risk they have for developing SCC
```
2 option:
1. lesion directed therapy
OR
2. field-directed therapy
OR
both
```
(topical therapy's, cryotherapy)
62
what name is given to the thread-like blood vessels commonly seen in BCC and AK, indicating sun damage
telangiectasia
63
what is the management of malignant melanomas?
wide local excision and sentinel lymph node biopsy
sun protection advice
long term follow up for 5 years
64
list 4 subtypes of melanoma
1. superficial spreading malignant melanoma
2. lentigo malignant melanoma
3. nodular/amelanotic malignant melanoma (*important not to miss as can be aggressive)
4 aural lentiginous malignant melanoma
65
when should you consider a sentinel LN biopsy?
- pt's with a breslow thickness of 1mm or more
- if +ve, consider proceeding to clearance of lymph node basin
- significant morbidity
66
what drug therapies are there for advanced melanoma?
- melanoma not very chemosensitive
- specimen tested for presence of BRAF gene mutation
- targeted therapies showing promise (if pt has BRAF mutant they are eligible for 2 drugs; vemurafenib that delays the growth of advanced melanoma (oral) and Ipilimumab that triggers immune system to attack cancer cells (IV). if pt doesn't have mutant then only eligible for BRAF wild-type Ipilimumab)
67
what skin Ca's are an urgent referral?
SCC and melanomas
BCC not urgent
68
how is the skin linked to systemic disease?
- when the systemic disease has classical skin findings
- when a specific dermatological diagnosis can involve other organs e.g. vasculitis
- when skin signs may be initial presentation of an internal malignancy
69
define vasculitis
inflammation of blood vessels (causes changes in blood vessel wall; thickening, weakening, scarring, narrowing)
*Tx = steroids
- these changes can restrict blood flow to other organs
- can get small, medium and large vessel vasculitis
- general symx = fever, headache, fatigue, weight loss, aches and pains, night sweats, rash
- a purpuric rash (purple and non-blanching painful papules) is small vessel vasculitis
70
how do we screen for vasculitis?
- clinical exam/Hx
- Blood pressure (high)
- FBC
- CRP/ESR (inflammatory markers)
- U+E, LFT
- autoantibodies:
1. antinuclear antibody ANA (most often elevated in pts with SLE and other types of AI disorders)
2. antineutrophil cytoplasmic antibody ANCA (commonly elevated in certain forms of vasculitis, but impossible to establish vasculitis Dx based on ANCA alone)
3. extractable nuclear antigen ENA (elevated can mean nothing to SLE)
- urinalysis and urine albumin creatinine ratio (look for blood in protein or losing more protein)
- skin biopsy (histology e.g. leukocytoclastic vasculitis) ± immunofluorescence
- IgA deposits in kidney, purpuric rash, arthritis, abdo pain suggest HSP
71
list causes of vasculitis
infections
connective tissue disease:
- SLE, RA
- systemic sclerosis
- dermatomyositis
malignancy:
- haematologic
drugs
- antibiotics, antihypertensives
idiopathic:
-HSP
72
differentiate small, medium and large vessel vasculitis
small:
- arterioles, venues and capillaries
- palpable purpura and plaques
- e.g. IGA vasculitis (HSP)
medium:
- more often associated with systemic vasculitis
- e.g. PAN (polyarteritis nodasa)
large:
- affecting large aa.
- e.g. Takayasu arteritis (affecting aorta and its branches) and temporal (giant cell) arteritis
73
give examples of other systemic conditions that may present on the skin
Sarcoidosis:
- may present with non-specific symptoms e.g. dry cough
- pink slightly scaly small plaques
- multisystem granulomatous disorder normally affecting the lungs, skin and eyes
- Tx with topical corticosteroids for cutaneous disease. oral steroids for more severs. immunosuppression such as hydroxychloroquine
erythema nodosum:
- acute reactive inflammation of subcutaneous tissue
- hot tender nodules
- fever, arthralgia and malaise
- generally self-limiting/ supportive Tx
hypothyroidism:
- pretibial myxoedema
- dry skin
- pruritis
- brittle hair
- loss of lateral 1/3 of eyebrow
- Tx =L-thyroxine
dermatitis herpetiformis:
- pruritic vesicular eruption on elbows/buttocks
- associated with coeliac disease
- may pr-date bowel symptoms
- Tx = gluten free diet ± Dapsone
Addinsons disease:
- gingival (+skin) pigmentation
- lethargy, generally unwell, weight loss and nausea
- short synacthen test
74
give 2 examples of skin signs that may be initial presentation of systemic malignancy?
erythema gyratum repens:
- rash may pre-date malignancy
- pruitus
- rapid spreading of lesions - wood grain pattern
- lung Ca is most common
sweet's syndrome:
- association with haematological malignanct
- acute neutrophilic dermatosis (red tumid patches/plaques on the skin)
- fever and neutrophilia
75
give 3 causes of generalised pruritus
1. haematological:
- iron def anaemia
- myeloproliferative disorders
- myeloma and lymphoma
2. renal disorders:
- uraemia
3. liver disorders:
- cholestasis
4. endocrine:
- hypo/hyperthyroidism
76
Ix and Tx of pruritus
exam: thorough clinical exam. exclude scabies, excess and other primary skin disorders
Ix: FBC, U+Es, TFT, iron studies, electrophoresis, glucose, CXR
Tx: if no cause, menthol in aqueous cream, sedating anti-histamines at night, low dose Doxepin
77
give 2 examples of syndromes with genetic predisosition to malignancy
Birt-Hogg-Dube syndrome:
- AD. mutation on chromosome 17
- risk of colon and renal Ca
- benign tumours on head, face and upper body
- skin biopsy, renal USS, CT abdomen, CXR, ?colonoscopy
- regular screening
Gardner syndrome:
- subtype of familial adenomatous polyposis
- polyps, multiple osteomas, skin and soft tissue tumours
- polyps from at puberty - progression to malignancy
- AD. mutations on APC gene (TS gene)
- need bone XR (+mandible), eye exams, colonoscopy every 1-2yrs
78
discuss DRESS syndrome
- type IV hypersensitivity reaction to a drug
- eosinophilic
- severe multi system reaction characterised by fever, skin rash (maculopapular), lymphadenopathy, haematological abnormalities and internal organ involvement (e.g. hepatitis, renal dysfunction)
- later onset or 2-6weeks after starting drug
- RegiSCAR diagnostic criteria
- Mx = stop culprit, push oral fluids, emollients and topical steroids, contact dermatologist
79
what is acute generalised exanthematous pustulosis (AGEP) and what is pustular psoriasis?
AGEP:
- acute, often febrile, neutrophilic drug eruption
- <4days
- rapid appearance of pin-head sized sterile pustules on oedematous erythema
Pustular psoriasis:
- clinically similar to AGEP but pt is more systemically unwell (fever/chills, headache, anorexia, nausea and muscle weakness)
- usually starts with areas of dry, fiery red and tender skin before development of crops of tiny, superficial, sterile pustules which go on to coalesce and form lakes of pus
- usually a Hx of plaque psoriasis (not always) and no obvious drug culprit
- triggers like withdrawal from corticosteroids, infection, pregnancy, drugs
80
what is eczema herpeticum?
- widespread eruption - serious complication of atopic eczema
- cause = herpes simplex virus
- extensive crusted papule, blisters and erosions
- systemically unwell with fever and malaise
- Mx = antivirals (acyclovir) and ABs if secondary infection
- complications = herpes hepatitis, encephalitis, DIC
week 38: a mole
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