the skin in systemic disease Flashcards
why is it important to look at the skin?
Rashes may be more than skin deep
Comprehensive assessment coupled with dermatological diagnostic skills can:
- Prevent or reduce internal organ damage by early diagnosis
- Allow detection of internal malignancy
in what ways can the skin play a role in systemic disease?
skin targeted -in diseases such as sarcoidosis
skin signs - may be present in internal disorders, such as flushing in carcinoid syndrome
tell-tale skin conditions - Skin conditions suggestive of underlying condition e.g. Pyoderma gangrenosum in inflammatory bowel disease
secondary skin involvement - Systemic disease secondary to skin disorder e.g. high output cardiac failure in erythroderma
what is a punch biopsy?
skin investigation taken under local anaesthetic
can be sent for histology - cells and inflammatory patterns and cellular abnormalities
checks for neoplasia or invasive cancer
can also be sent for immuno flourescencing, in which auto antibodies can be detected
they can also be sent for tissue culture
what is lupus erythematosus?
Two main groups:
Systemic Lupus Erythematosus
Cutaneous (Discoid) Lupus Erythematosus
- Overlap
what is the diagnostic criteria for systemic lupus erythematosus?
Cutaneous lupus - acute
Cutaneous lupus - chronic {Mucocutaneous}
Oral ulcers
Alopecia
Synovitis (joints)
Serositis (pleurisy or pericarditis)
Renal disorder
Neurological disorder
Haemolytic anaemia
Thrombocytopenia {Haematological}
Leukopenia
ANA
Anti-dsDNA
Anti-Sm
Antiphospholipid {Immunological}
Low Complement
Direct Coomb’s test
what are some symptoms (visible) of SLE?
Photodistributed rash (on areas exposed to the sun)
Cutaneous vasculitis
Chilblains
Alopecia
Livedo reticularis (nettle like erythema)
palpable purpura
Cutaneous vasculitis
Subacute cutaneous lupus (SCLE) (ring like/annular plaque) (also seen in cutaneous lupus erythemqtosus)
what are some symptoms of cutaneous lupus erythematosus?
in 95% of cases, no other organ involves - cutaneous only
distinct scarring (eg. on scalp and cheek)
also subacute cutaneous lupus (SCLE)
what is neonatal lupus?
one exception where you can make a spot diagnosis (dont need differential)
neonatal lupus (Ro positive)
Test ECG
– comes with arisk of heart block (50% risk)
shows up with annular/ring like plaques - subacute cutaneous lupus (SCLE)
what is dermatomyositis?
Autoimmune connective tissue disease
Proximal extensor inflammatory myopathy (muscle weakness)
Photo-distributed pink-violet rash favouring scalp, periocular regional and extensor surfaces
what are some distinct signs of dermatomyositis?
Photosensitive erythema - Photo-distributed pink-violet rash favouring scalp, periocular regional and extensor surfaces
Gottron’s papules - metacarpophylangeal joints and distal interphylangeal joints, vereacious plaques
Ragged cuticles - of nails
Shawl sign - redness on upper back/trunk
Heliotrope rash - erythema of the eyelids
muscle weakness
what are the subtypes of dermatomyositis?
Subtypes with clinical features that can be predicted by autoantibody profile
Anti Jo-1 – fever, myositis, gottron’s papules
Anti SRP – nectrotising myopathy
Anti Mi-2 – mild muscle disease
Anti-p155 – associated with malignancy (in adults)
Anti-p140 – juvenile, associated with calcinosis
Anti-SAE- +/- amyopathic
Anti- MDA5 – interstitial lung disease, digital ulcers / ischaemia
what investigations are done for dermatomyositis?
ANA (antinuclear antibodies) CK (creatine kinase) (muscles) Skin biopsy LFT (ALT often increased) EMG (electromyography) Screening for internal malignancy
what is IgA vasculitis?
vasculitis effecting the small blood vessels
Abdominal pain, bleeding, arthralgia, arthritis, IgA- associated, macula purpura (flat)
glomerulonephritis- may develop later
how does small vessel vasculitis present?
Purpura (macular / palpable)
macular is flat, papular is raised
how does medium vessel vasculitis present?
Digital necrosis
Subcutaneous nodules along blood vessels
Retiform purpura Ulcers
what is ANCA associated vasculitis?
small and medium vessel
can get nose saddle deformities
cough, dyspnoea, chest pain
ulcerative rash
stuffy nose and nosebleeds
what is sarcoidosis?
Systemic granulomatous disorder of unknown origin
Can affect multiple organs: most commonly lungs
Cutaneous manifestations in ~33%
- Highly variable – ‘the great mimicker’
- Red-brown to violaceous papules and face, lips, upper back, neck, and extremities
Lupus pernio – NB (nothing to do with lupus, redness on face) (often on nose ears and lips, often shiny, blue-red)
Ulcerative
Scar sarcoid
Erythema nodosum (lower legs, fat inflammation)
Histology – non-caseating epithelioid granulomas (no necrosis)
Diagnosis of exclusion
Requires evaluation for internal organ involvement
what is DRESS?
Drug Reaction with Eosinophilia and Systemic Symptoms
Rash and systemic upset incorporating haematological and solid‐organ disturbances
Underlying mechanism not known
Starts 2-6 weeks after drug exposure
Liver most common internal organ involved – majority of deaths associated with this
Sulfonamides, anti-epileptics (carbamazepine, phenytoin, lamotrigine), allopurinol, Antibiotics (vancomycin, amoxicillin, minocycline, piperacillin-tazobactam), ibuprofen are common triggers
what are the diagnostic criteria for DRESS?
Diagnosis is based on scoring criteria including:
Fever ≥ 38.5°C
Lymphadenopathy ⩾ 2 sites, > 1cm
Circulating atypical lymphocytes
Peripheral hypereosinophilia >0.7 × 109
Internal organs involved - (liver, kidneys, cardiac
Negative ANA, Hepatitis / mycoplasma, chlamydia
Skin involvement:
>50% BSA
Cutaneous eruption suggestive of DRESS e.g. facial oedema
Biopsy suggestive of DRESS
what internal organ involvement is present in DRESS?
Liver (hepatitis)- most frequent cause of death Kidneys (interstitial nephritis) Heart (myocarditis) Brain Thyroid (thyroiditis) Lungs (interstitial pneumonitis)
what are the rash morphologies associated with DRESS?
- Urticated papular exanthem - widespread papules
- Maculopapular (morbilliform) eruption
- Widespread erythema (Erythroderma)
- Head / neck oedema
- Erythema multiforme-like (target like lesions)
how is DRESS treated?
Withdrawal of culprit
Corticosteroids are first line treatment - may require months of treatment
Mortality 5-10%
what is graft versus host disease?
Multiple-organ disease
Affects ~10-80% of allogenic haematopoetic stem cell transplants (HSCT)
Pathogenesis: donor-derived T-lymphocyte activity against antigens in an immunocompromised recipient
Mainly affects:
- Skin - Liver - GI tract
how can you tell if as rash is caused by DRESS or graft versus host disease?
Face involvement
Acral (didtal limbs) involvement
Diarrhoea
all indicate that GvHD more likely
what is pruritus?
Itching without rash suggestive of internal cause: Haematological causes: lymphoma, polycythemia Uraemia Cholestasis Iron deficiency or iron overload HIV / Hepatitis A / B / C Cancer Drugs (NB opiates / opioids) Psychogenic Pruritus of old age
may cause Nodular prurigo
a defence mechanism, thickening of the skin
what investigations are done if someone has pruritus?
FBC, LDH Renal profile Liver function tests Ferritin XR Chest HIV / Hepatitis A / B /C
what is scurvy?
Vitamin C (ascorbic acid) deficiency
symptoms:
Spongy gingivae with bleeding and erosion
Petechiae, ecchymoses, follicular hyperkeratosis
Corkscrew hairs with perifollicular haemorrhage
what is kwashiorkor?
Protein deficiency Systemic features: - Hepatomegaly - Bacterial / fungal infections - Diarrhoea - Loss of muscle mass - Oedema - Failure to thrive Skin signs: - Superficial desquamation large areas of erosion - Sparse, dry hair - Soft, thin nails - Cheilitis
what happens in zinc deficiency?
Important role in 200 enzymes – regulation of lipid, protein, nucleic acid synthesis
Roles in wound healing, antioxidant
Deficiency: genetic (SLC39A4) or acquired (dietary)
- Triad of Dermatitis | Diarrhoea | Depression
Perioral, acral and perineal skin in particular is affected with scaly erosive erythema
what happens in vitamin B3 deficiency?
Required for most cellular processes
Deficiency:
- Dermatitis | Diarrhoea | Dementia | Death
Cutaneous manifestations:
- Photodistributed erythema
- ‘Casal’s necklace’
- Painful fissures of the palms and soles
- Peri-anal, genital and perioral inflammation and erosions
what is carcinoid syndrome?
Signifies metastases of a malignant carcinoid tumour
5-HT secretion (serotonin) (only happens when the tumour has metastasised)
Flushing in 25% of cases Other symptoms: - Diarrhoea - Bronchospasm - Hypotension
(flushing, with wheezing, light headedness and diarrhoea is strongly suggestive)
what is stevens-johnson syndrome (aka toxic epidermal necrolysis)?
Derm emergency! (Rare)
Prodromal: flu-like symptoms
Abrupt onset of lesions on trunk > face/limbs
Macules, blisters, erythema – atypical targetoid
Blisters merge – sheets of skin detachment ‘like wet wallpaper’
Extensive full thickness mucocutaneous (epidermal) necrosis <2-3 days
Complications
Death - Overall mortality 30%
Blindness, dehydration, hypothermia/hyperthermia, renal tubular necrosis, eroded GI tract, interstitial pneumonitis, neutropaenia, liver and heart failure
what is the pathway from stevens johnson syndrome to toxic epidermal necrolysis?
BSA Detachment (%):
SJS- <10
SJS/TEN- 10-30
TEN- >30
Mortality (%) -SCORTEN -ABCD-10: SJS- ≤10 TEN- ≥30
what causes SJS/TEN?
Cell-mediated cytotoxic reaction against epidermal cells
Drugs cause >80% of cases
May be started up to 3 weeks prior to onset of rash
DDx: Staphylococcal scalded skin syndrome (SSSS) Thermal burns Cutaneous graft versus host disease erythema multiforme
causes: antibiotics (Beta-lactams Sulphonamides), antiepileptics (Phenytoin Carbamazepine
Lamotrigine), allopurinol, NSAIDs
how is the severity and prognosis of SJS/TEN determined?
SCORTEN – score used to help assess severity
Criteria: age >40, HR, initial % epidermal detachment, serum urea + glucose + bicarbonate, presence of malignancy
Complications
Death - Overall mortality 30%
Blindness, dehydration, hypothermia/hyperthermia, renal tubular necrosis, eroded GI tract, interstitial pneumonitis, neutropaenia, liver and heart failure
what is erythroderma?
Generalized erythema affecting >90% BSA (body surface area)
Systemic manifestations reflect impairment in skin function:
- Peripheral edema - Tachycardia - Loss of fluid and proteins - Disturbances in thermoregulation - Risk of sepsis
what may cause erythroderma?
Multiple etiologies:
- Drug reactions - Cutaneous T-cell lymphoma – Sézary syndrome - Psoriasis - Atopic eczema - Idiopathic (25-30%)
how is erythroderma managed?
support the skin function
Underlying cause (e.g. treat psoriasis, withdraw drug if drug cause, etc)
Hospitalisation if systemically unwell
Restore fluid and electrolyte balance, circulatory status and manage body temperature.
Emollients to support skin barrier
+/- Topical steroids
+/- Antibiotics
what are some cutaneous signs of systemic disease?
excoriation/prurigo
xerosis (dry skin)
half and half nails
calciphylaxis (big black crustyness)
muehrckes lines (white stripes on nails)
jaundice
spider telalngiectasia (spider veins)
terrys nails
palmar erythema
Porphyria cutaneous tarda
clubbing
how does chronic kidney disease effect the skin?
Anaemia – mucosal pallor, hair thinning
Excoriations, prurigo
Calciphylaxis
Half and half nails
Signs related to primary disease that caused the kidney disease
- ANCA-associated vasculitis - Systemic Lupus Erythematosus
Signs related to immunosuppression
- Viral warts - Skin cancer
how does chronic liver disease effect the skin?
Excoriations, prurigo Jaundice Muehrcke’s lines of nails Terry’s nails Palmar erythema Spider telangiectasia Clubbing
what is necrobiosis lipoidica?
20-65% of cases occur in setting of Diabetes Mellitus
Plaques with red-brown raised edge with yellow-brown atrophic centre
Treatment: topical / intralesional steroids
how might diabetes mellitus effect the skin?
Terry’s nails
Granuloma annulare
Neuropathic ulcers
Acanthosis nigricans
Xerosis
Xanthelesma & xanthomata
Skin infections
what are some ways in which endocrine diseases can effect the skin?
Pre-tibial myxoedema (Grave’s disease)
Hyperpigmentation (Addison’s disease)
Acne (Acromegaly , cushing’s syndrome, polycystic ovarian syndrome
Cutis gyrata verticis (Acromegaly) (weird head wrinkles)
how might HIV effect the skin in general?
may cause sever forms of common conditions
such as severe: Severe seborrhoeic dermatitis Extensive viral warts Norwegian scabies Severe psoriasis CMV ulceration Eosinophilic folliculitis Kaposi sarcoma Bacillary angiomatosis
what are the effects of HIV?
Seroconversion – variable nonspecific manifestations:
- Morbilliform rash - Urticaria - Erythema multiforme - Oral / genital ulceration - NB Low threshold for testing
Persistent or atypical manifestations or common infections
Opportunistic infections
Severe manifestations of common dermatoses (e.g. psoriasis, seborrheic dermatitis)
Itch
Suggestive dermatoses e.g. eosinophilic folliculitis
how do GI disorders effect the skin?
Cutaneous diseases associated with inflammatory bowel disease:
– Pyoderma gangrenosum
- Orofacial granulomatosis
- Panniculitis (erythema nodosum)
- Aphthous ulceration
- Association with psoriasis, pemphigoid
Cutaneous manifestation of celiac disease
- Dermatitis herpetiformis
what is hidradenitis suppuritiva
Inflamed nodes, sterile abscess, sinus tracts, fistulae and hypertrophic scars
Favours intertriginous zones: especially axillary, anogenital and inframammary area
devastating condition
seen in people with high BMA
what is Pyoderma gangrenosum?
Pustule on an erythematous base –ulcerates and extends with necrotic undermined border
Painful
Associated with inflammatory bowel disease, leukemia, seronegative arthritis in 50-70% of cases
what are the cutaneous signs of internal malignancy?
Cutaneous metastases
Malignancy reflecting internal malignancy
- Extramammary Paget’s disease
Genetic condition predisposing to internal cancer and skin lesions
- Hereditary leiomyomatosis and renal cell cancer - Peutz–Jeghers syndrome
Skin disease associated with malignancy
- Dermatomyositis - Erythema gyratum repens - Pyoderma gangrenosum - Paraneoplastic pemphigus
Non-specific skin disease
- Pruritus - Vasculitis - Urticaria
what are some specific skin conditions in different cancers?
Peau d’orange – breast carcinoma
Groin metastases (prostatic carcinoma
Metastatic bronchial carcinoma (skin on shoulders)
Metastatic oesophageal carcinoma (skin on fingers)
Leukemia cutis (blackening of arms)
Haemorrhagic nodules (metastatic pancreatic carcinoma
Extramammary Paget’s disease (groin)
Paget’s disease of the nipple
Acanthosis nigricans
