Dermatology (Case-Based) Flashcards
State the two types of cutaneous adverse drug reactions (CADR)
- immunologic - type 1 or 4 hypersensitivity
- non-immunologic - not related to immune system
State the difference between type 1 and type 4 hypersensitivities. State examples, symptoms and duration.
TYPE 1 HS - IgE MEDIATED
- Eg: Urticaria/eczema
- Symptoms - swollen eyes, sausage lips
- Time - occurs within mintues to hours
TYPE 4 HS - T CELL MEDIATED
- Eg: Maculopapular exanthem
- Symptoms - Contact dermatitis, Tuberculin reaction, Autoimmune diseases
- Time - occurs within a few days
State some complications of CADRs
skin function compromised (skin failure) when large area of skin is loss
1. loss of barrier function against bacteria
2. volume dysregulation
3. thermodysregulation
4. pain
State whether type 1 or type 4 HS is acute/delayed
A - type 1 HS - acute
D - type 4 HS - delayed
Regarding EXANTHEM, state the
- latency
- pathogenesis
EXANTHEM
- Latency - 4 days-2 weeks
- Pathogenesis - Keratinocytes at basal layer of epidermis forms adducts with drugs –> body recognises it as foregin –> mounts immune response against the adducts –> basal vacuolar degeneration
Regarding EXANTHEM , state
- Morphology and Histo:
- Drugs indicated:
EXANTHEM
- Morpho + histo = Non-scaly erythematous maculopapular rash at trunk and limbs, basal vascuolar degeneration + epidermis otherwise healthy and viable
- Drugs = Antibiotics (beta lactams, sulfonamides), NSAIDs, Antiepileptics (carbamazepine, phenytoin), Allopurinol
Name the drugs indicated for exanthem
- NSAIDs
- Allopurinol - HLA 5801
- Antiepileptics (carbamazepine - HLA 1502, phenytoin)
- Antibiotics (beta lactams, sulfonamides)
State the presentation of exanthem
non-scaly erythematous maculopapular rash over trunk and limbs
- can spread to become patches and plaques
- BSA <30%
Regarding SJS/TEN, state
- latency
- pathogenesis
SJS/TEN
- latency - 1-4 weeks
- pathogenesis
Type 4 hypersensitivity reaction mediated by
1. drug-specific CD8+ lymphocytes
2. Fas-FasL pathway of apoptosis
3. Granule-mediated exoctyosis
4. TNF-a
resulting in intense T cell mediated damage to the keratinocytes –> full thickness epidermal necrosis
Regarding SJS/TEN , state
- Morphology and Histo:
- Drugs indicated:
SJS/TEN
- Morpho + Histo =
1. Scaly deeply erythematous/violaceous macules and patches
2. Erosions and ulcerations over genitalia, lips and back
3. Necrolytic plaques
4. Nikolsky’s sign - skin falls off with lateral pressure (basal layer of keratinocytes dead)
5. Oedema (resultant inflmmation under dead epidermis)
- Drugs - NSAIDs, allopurinol, antibiotics (beta-lactams, sulfonamides), antiepileptics (carbamazapine, phenytoin)
State the location of morphology of
- macolopapular exanthem
- SJS/TEN
maculopapular exanthem - non-scaly erythematous maculopapular rash on trunk and limbs + basal vacuolar degeneration
SJS/TEN - scaly deeply erythematous/violaceous macules and patches on genitalia, lips and back + necrolytic patches
State the difference percentages of BSA covered in
- SJS
- SJS-TEN
- TEN
SJS - <10% BSA
SJS-TEN - 10-30% BSA
TEN - >30% BSA
Recap
State the pathogensis of SJS/TEN
SJS/TEN
Type 4 hypersensitivity reaction mediated by
1. drug-specific CD8+ cytotoxic lymphocytes
2. Fas-FasL pathway of apoptosis
3. Granule-mediated apoptosis
4. TNF-a death receptor pathway
Intense T cell mediated damage to the keratinocytes → full thickness epidermal necrosis → forming blisters
State the morphology of SJS/TEN
- scaly deeply erythematous/violaceous macules and patches
- necrolytic patches
- erosions and ulcerations over genitalia, lips and back
- nikolsky’s sign
- oedema
Define AGEP
AGEP = acute generalised exanthematous pustulosis
- Acute exanthem with pustulation
Regarding AGEP, state
- latency
- pathogenesis
AGEP (acute generalised exanthematous pustulosis)
- latency - days-weeks
- pathogenesis - type IV HS reaction with IL8 and CXCL8 as main players
symptoms - systemic symptoms (fever, joint pain, leukocytosis)
Regarding AGEP, state
- morpho + histo
- drugs indicated
AGEP
- morpho and histo: scaly erythematous plaques and patches + non-follicular sterile subcorneal pustules (filled with neutrophils and cellular debris)
- drugs - nsaids, antibiotics (beta-lactem, sulfonamide), anticonvulsants, antimalarial, calcium channels blockers
Recap
State the pathogenesis of AGEP
AGEP
- Type IV HS with IL8 and CXCL8 as key players
- symptoms - fever, leukocytosis and joint pain
- Acute erythematous oedema followed by formation of many small pustules
Recap
State the morphology of AGEP
AGEP
- scaly erythematous plaques and patches
- small non-follicular sterile sub-corneal pustules (filled with neutrophils and cellular debris)
State the drugs indicated in AGEP
nsaids
antibiotics (sulfonamides and beta-lactam)
anticonvulsants
antimalarial
calcium channel blockers
Regarding DHS, state
- latency
- pathogenesis
DHS = DRUG HYPERSENSITIVITY SYNDROME
- latency - 2-6 weeks (MUCH LONGER)
- pathogenesis - Type IV HS involving drug eruption that involves mutliple other organ systems (liver, LN, kidneys, heart, thyroid) –> systemic symptoms (high fever, creatinine rise in blood, borderline transamninitis)
Regarding DHS, state
- morpho + histo
- drugs indicated
DHS
- morpho + histo - (BSA >50%) non-scaly deeply erythematous/violaceous oedematous macules, papules and plaques over face and trunk + interface dermatitis
- drugs indicated - nsaids, antiepileptics (carbamazapine, phenytoin), antibiotics (sulfonamides, betalactams), allopurinol
State the pathogenesis of DHS
type IV HS involving drug eruption involving multiple systems (liver, LN, kidneys, heart, thyroid) –> systemic symptoms (fever, transamninitis, creatinine rise in blood)
State the common drugs indicated for DHS
- allopurinol
- nsaids
- antibiotics (sulfonamides, beta-lactams)
- antiepileptics (carbamazepine, phenytoin)
Regarding BULLOUS PEMPHIGOID, state
- latency
- pathogenesis
BULLOUS PEMPHIGOID
- latency - unknown
- pathogenesis - Type IV hypersensitivity reaction where autoantibodies target BP180 and BP230 –> blister formation
BP180 - integral protein of the hemidesmosomes (attaches keratinocytes to ECM)
Regarding BULLOUS PEMPHIGOID, state
- histo + morpho
- drugs indicated
Regarding BULLOUS PEMPHIGOID, state
- histo + morpho - scaly erythematous plaques, erosions, subepidermal blisters (separation between epidermis and dermis), bullae
- drugs indicated:
- DPP4 inhibitors - linagliptin
- immune checkpoint inhibitors - PD1, PDL1, CTLA4 inhibitors
- frusemide
- NSAIDs
State the risk factors of bullous pemphigoid
elderly
neurological diseases (stroke, dementia, parkinson’s)
movement problems
State the latency of
1. maculopapular exanthem
2. SJS/TEN
3. AGEP
4. DHS
5. BP
- maculopapular exanthem - 4 day - 2 weeks
- SJS/TEN - 1-4 weeks
- AGEP - days - weeks
- DHS - 2-6 weeks
- BP - unknown
State the pathogenesis of
1. maculopapular exanthem
2. SJS/TEN
3. AGEP
4. DHS
5. BP
(1) MACULOPAPULAR EXANTHEM
- keratinocytes at basal layer of epidermis form adducts with drugs –> body recognises as foreing and mounts immune response to adduct –> basal vacuolar degeneration (BSA < 30%)
(2) SJS/TEN
Type IV HS reaction mediated by
- drug-specific CD8+ Tc lymphocyte
- granulocyte-mediated exoctyosis
- TNF-a
- fas-fasL pathway of apoptosis
resuls in intense T cell mediated damge to keratinocytes –> full thickness epidermal necrosis –> blister formation
(3) AGEP
- type IV HS reaction involving IL8 and CXCL8 as key players
- systemic symptoms - fever, leukocytosis, joint pain
- acute oedematous erythema followed by formation of sterile pustules
(4) DHS
- type IV HS reaction involving drug eruption involving multiple organ systems (liver, LN, heart, kidneys, thyroid)
- systemic symptoms - fever, creatinine rise in blood, borderline transamninitis
(5) BP
- type IV HS where autoAb targets BP180 and BP230
- BP180 is an integral protein of hemosiderines which anchor epidermis to the dermis –> subepidermal blister formation
- risk factors - elderly, neurological diseases, movement disorders
State the morphology of
1. maculopapular exanthem
2. SJS/TEN
3. AGEP
4. DHS
5. BP
(1) Maculopapular exanthem
- non-scaly erythematous maculopapular rash on trunk and limbs
- BSA involves < 30%
(2) SJS/TEN
- scaly deeply erythematous/violaceous macules and patches
- erosions and ulcerations over lips, genitalia and back
- necrolytic patches
- nikolsky’s sign - sloughing of the dead epidermal layer (basal layer of keratinocytes dead)
- oedema (inflammation under dead epidermis)
(3) AGEP
- scaly erythematous patches and plaques
- small non-follicular sterile subcorneal pustules
(4) DHS
- non-scaly deeply erythematous/violaceous macules, papules and plaques over face and trunk
- marked interface dermatitis
- BSA involves > 50%
(5) BP
- scaly erythematous plaques
- erosions
- subepidermal blsiters (separation of dermis and epidermis
State some causes of blisters
- SJS/TEN
- BP
- Disseminated zoster
Explain how blisters form in disseminated zoster
DISSEMINATED ZOSTER
- viral cytopathic changes –> undergo balloon degeneration
- epidermal cells die but not because of T cells attacking them but because of virus directly attacks them
State the risk factors of acne vulgaris
- family history
- cushing’s syndrome
- cosmetic usage
- high glycemic index foods
- low oestrogen
- hyperandrogenism
State the treatment for acne vulgaris
DO NOT ADMINISTER CORTICOSTEROIDS
- topical steroids (retinoids)
- oral antibiotics
State the morpholgoical differences between
- non-inflammatory acne
- inflammatory acne
NON-INFLAMMATORY ACNE
- closed comedones (whiteheads) - skin covered papules with obvious follicular opening
- open comedones (blackheads) - filled with keratin plug
INFLAMMATORY ACNE
- erythematous papules and pustules
- nodules and cysts with pus or serosanguinous fluid (can coalesce and form sinus tracts)
State the pathogenesis of acne vulgaris
- hyperkeratinisation –> comedones
- increased sebum production (seborrhoea) from elevated androgen levels
- acute and chronic inflammation
- cutibacterium acnes
State the retinoids that are contraindicated in pregnant women
pregnancy category c - tretinoin and adapalene
pregnancy category x - tazarotene
Name the preferred choice of systemic oral antibiotics
**tetracycline class of antibiotics **(doxycyline, minocycline) - 1st line therapy in moderate to severe acne
- MOA = inhibits protein synthesis by binding the 30S subunit of bacterial ribosome
- anti-inflammaotry effect - inhibits chemotaxis, inhibits metalloproteinase activity
NEUROFIBROMA
- ____ peripheral nerve tumour
- Cell of origin =
- ____ patients
- ____ solitary and not associated with ____
NEUROFIBROMA
- BENIGN peripheral nerve tumour
- Cell of origin = SCHWANN CELLS
- YOUNG patients
- 90% solitary and not associated with NEUROFIBROMATOSIS 1
NEUROFIBROMATOSIS 1
- Benign/Malignant
- Autosomal ____ mutation of ____ gene (____)
- Presentation
- Increased risking of developing ____
NEUROFIBROMATOSIS 1
- Benign
- Autosomal DOMINANT mutation of NF-1 gene (NEUROFIBROMIN)
- Presentation =
1. F - fibrosis
2. I - iris hamartoma (lisch nodules)
3. B - bone lesions (sphenoid dysplasia)
4. R - relatives
5. O - optic glioma
6. M - macules (cafe au lait macules)
7. A - axillary freckling
8. N - neurologic abnormalities
- Increased risking of developing PHEOCHROMOCYTOMA
State the neurologic abnormalities in neurofibromatosis 1
NEUROFIBROMATOSIS 1
1. cognitive deficits and learning difficulties
2. headaches
3. seizures
4. gross and fine motor developmental delays
5. macrocephaly
EPIDERMAL CYST
- Most common skin cyst
- ____ lesion made up of a ____ filled with ____
- Common sites =
- Can be ____, ____, ____, ____, ____
- Treatment =
EPIDERMAL CYST
- Most common skin cyst
- ROUND lesion made up of a CAPSULE filled with KERATIN
- Common sites = FACE + UPPER TRUNK
- Can be INFLAMED, RED, SWOLLEN, PAINFUL, OOZE A WHITE CHEESY SMELLY MATERIAL
- Treatment = Observation + Surgery
IMPETIGO
- Causative agent =
- Common demographic =
- Compare primary and secondary impetigo
- Manifestations (3)
IMPETIGO
- Causative agent = STAPH AUREUS
- Common demographic = Children 2-5 years old
- Primary impetigo = direct bacterial invasion into previously normal skin
- Secondary impetigo = infections at skin of minor skin trauma
- Manifestations (3)
- non-bullous impetigo - golden crust appearnace, papules that progress to vesicles surrounded by erythema
- bullous impetigo - young children, vesicles form flaccid bullae with clear yellow fluid –> rupture to leave thin brown crust
- ecthyma - punched out ulcers covered with yellow crust surrounded by violaceous margins, lesions extend through epidermis deep into dermis
State the treatment of impetigo
limited impetigo
- topcial therapy - mupirocin, fusidic acid x5 days
extension impetigo
- systemic antibiotics - cloxacillin + cephalexin x7 days
INFANTILE HEMANGIOMA
- Proliferative ____ of ____ endothelium
- Common sites =
- Latency =
- Morphology =
INFANTILE HEMANGIOMA
- Proliferative HAMARTOMAS of VASCULAR endothelium
- Common sites = HEAD AND NECK
- Latency = Appears in first few weeks of life
- Morphology = Raised plaque
Regarding ATOPIC DERMATITIS,
(1) ACUTE PHASE OF ATOPIC DERMATITIS
- ____ driven
- Cytokines produced by ____ =
(2) CHRONIC PHASE OF ATOPIC DERMATITIS
- ____ driven
Regarding ATOPIC DERMATITIS,
(1) ACUTE PHASE OF ATOPIC DERMATITIS
- Th2 driven
- Cytokines produced by Th2 = IL-4, IL-5, IL-13, IL-31
(2) CHRONIC PHASE OF ATOPIC DERMATITIS
- Th1 driven
State the histological features of SPONGIOTIC DERMATITIS
SPONGIOTIC DERMATITIS = eczematous dermatitis
- slightly thickened epidermis
- intercellular oedema
gross
- Little vesicles forming on skin of palm and sole for acute dermatitis
State the distribution of eczema in infants, children and adults
infants
- face, scalp, neck
- extremities - knees, elbows (extensor surfaces)
children and adults
- face and neck
- extremities and flexor surfaces
State the presentation of chronic plaque psoriasis
- Psoriatic plaque around the umbilicus,
- Affecting hairline, nape of the neck - a lot of plaques and scales, flaking away
- Nail changes common
State the risk factors of psoriasis
GENETIC
- HLACW6 - early onset psoriasis
- HLAB27 - psoriasis and psoriatic arthritis
- Genes encoding TNFa and IL23
ENVIRONMENT
- Metabolic syndrome (DM, osteoporosis. HTN, non-alcoholic fatty liver, hyperlipidemia)
- Smoking
- Obesity
- Alcohol use
- Drugs - lithium blockers, beta-blockers, anti-malarials, non-steroidal anti-inflammatory drugs, immune-checkpoint inhibitors
- Infections - bacterial and viral
- Stress
State the histological features of PSORIASIS
- Parakeratosis
- Aggregates of neutrophils - munroabscesses
- Predominantly lymphocytes and eosinophils
State the treatment of psoriasis
- Topical medications
- Glucocorticoids and corticosteroids
- Calcineurin inhibitors
- PDE-4 inhibitros
- Vitamin D analogues - Phototherapy
- Systemic retinoid
- Systemic immunosuppression
- Methotrexate
- Cyclosporine - Biologics
- TNFa inhibitors - infliximab, adalimumab
- IL-17 inhibitors
- IL-12 inhibitors
- IL-23 inhibitors