1B the skin in systemic disease Flashcards
What are the two main categories of lupus erythematosus?
- Systemic lupus erythematosus
- Cutaneous (discoid) lupus erythematosus
What are the 3 types of diagnostic criteria for systemic lupus erythematosus?
- Mucocutaneous
- Haematological
- Immunological
Give examples of mucocutaneous systemic lupus erythematosus
- Cutaneous lupus- acute- e.g. chillblains and photodistributed (Sun-exposed areas) erythematosus rash
- Cutaneous lupus- chronic
- Oral ulcers
- Alopecia
Give examples of haematological systemic lupus erythematosus
- Haemolytic anaemia
- Thrombocytopenia
- Leukopenia
Give examples of immunological systemic lupus erythematosus
- ANA
- Anti-dsDNA
- Anti-Smith
- Antiphospholipid
- Low Complement
- Direct Coomb’s test
Aside from mucocutaneous, immunological and haematological criteria, what other diagnostic criteria are there for SLE?
- Synovitis
- Serositis (pleurisy or pericarditis)
- Renal disorder
- Neurological disorder
- Livedo reticularis
- Palpable purpura
- Subacute cutaneous lupus (SCLE)
What is livedo reticularis?
Net-like erythema
What is palpable purpura?
Small vessel cutaneous vasculitis
What is SCLE?
Ring-like (annular) plaques
What are the diagnostic criteria for cutaneous (discoid) lupus erythematosus?
- Discoid lupus erythematosus
- SCLE
What is dermatomyositis?
Autoimmune connective tissue disease
What is dermatomyositis characterised by?
- Proximal extensor inflammatory myopathy
- Photodistributed pink-violet rash favouring scalp, periocular regional and extensor surfaces
What are the distinct features of dermatomyositis?
- Gottron’s papules
- Ragged cuticles
- Shawl sign
- Heliotrope rash
- Photosensitive erythema
What are Gottron’s papules?
Violaceous plaques at the MCP and DIP joints
What is Shawl sign?
Redness of upper trunk
What is heliotrope rash?
Erythema of the eyelids
What different subtypes of dermatomyositis are there?
- Anti Jo-1
- Anti SRP
- Anti Mi-2
- Anti p155
- Anti p140
- Anti SAE
- Anti MDA5
What clinical features are associated with Anti Jo-1 dermatomyositis?
- Fever
- Myositis
- Gottron’s papules
What clinical features are associated with Anti SRP dermatomyositis?
Necrotising myopathy
What clinical features are associated with Anti Mi-2 dermatomyositis?
Mild muscle disease
What clinical features are associated with Anti p155 dermatomyositis?
Associated with malignancy in adults
What clinical features are associated with Anti p140 dermatomyositis?
Juvenile, associated with calcinosis
What clinical features are associated with Anti SAE dermatomyositis?
With or without amyopathy (no problems in muscle weakness)
What clinical features are associated with Anti MDA5 dermatomyositis?
- Interstitial lung disease
- Digital ulcers/ischaemia
What diagnostic tests do we do for dermatomyositis?
-
ANA
- positive in most cases
-
LFT
- ALT often increased which helps in diagnosis
-
CK and EMG
- Look at muscles
- Skin biopsy
-
Screening for internal malignancy
- Imaging and tumour markers
- Patients are at increased risk, esp with p155 antibody
An 86 year old man admitted with GI bleed, recently diagnosed with lung cancer and lower leg rash noted macular purpura comes in with a biopsy consistent with small vessel vasculitis.
The biopsy for direct immunofluorescence showing perivascular autoantibodies IgA- what is this?
IgA vasculitis (Henoch-Schonlein purpura)
What symptoms does Henoch-Schonlein purpura cause?
- Abdominal pain
- GI bleeding
- Arthralgia (joint stiffness)
- Arthritis
- IgA-associated glomerulonephritis (may develop later)
What types of small vasculitis are there?
- Small vessel vasculitis
- Cutaneous small vessel (leukocytoclastic) vasculitis
What small and medium types of vasculitis are there ?
- Cryoglobulinemia
- ANCA-associated
What medium types of vasculitis are there ?
Polyarteritis nodosa (PAN)
What large types of vasculitis are there ?
- Temporal arteritis
- Tayakasu
What subclassifications of small vessel vasculitis are there?
- IgA vasculitis (Henoch-Scholein)
- Urticarial vasculitis
- Acute haemorrhagic oedema of infancy
- Erythema elevatum diutinum
What are the subclassifications of cutaneous small vessel (leukocytoclastic) vasculitis?
- Idiopathic
- Infectious
- Medication exposure
- Inflammatory (CTD)
What are the subclassifications of cryoglobulinemia?
Type 2 or 3
What are the subclassifications of ANCA-associated vasculitis?
- GPA (Wegener)
- EGPA (Churg-Strauss)
- Microscopic polyangiitis
What are the subclassifications of polyarteritis nodosa (PAN)?
- Benign cutaneous form
- Systemic form
What are the small vessel manifestations of Vasculitis?
Purpura (macular/palpable)
What are the medium vessel manifestations of vasculitis?
- Digital necrosis
- Retiform ‘net-like’ purpura ulcers
- Subcutaneous nodules along blood vessels
What does this show?
Digital necrosis
What does this show?
Retiform ‘net-like’ purpura ulcers
What does this show?
Subcutaneous nodules along blood vessels
What is sarcoidosis?
Systemic granulomatous disorder of unknown origin
Where can sarcoidosis affect?
It can affect multiple organs, most commonly lungs
What are the cutaneous manifestations of sarcoidosis?
- Highly variable- ‘the great mimicker’
- Red-brown violaceous papules on face, lips, upper back, neck and extremities
- Involvement of face: lupus pernio (nothing to do with lupus erythematosus)
- Ulcers
- Scar sarcoid
- Erythema nodosum (swollen fat under skin of legs)
What does histology show in sarcoidosis?
Non-caseating (means no necrosis) epithelioid granulomas
What kind of a diagnosis is done for sarcoidosis?
Diagnosis of exclusion- you need to exclude an infection e.g. by doing TB culture/PCR
Internal organ involvement also requires evaluation, e.g. CXR for lung involvement
What is DRESS?
Drug Reaction with Eosinophilia and Systemic Symptoms
Rash and systemic upset involving haematological and solid-organ disturbances
What are the scoring criteria for DRESS? (patients don’t have to have all of them, just score up to a certain amount of them)
- Fever ≥38.5°C
- Lymphadenopathy ≥2 sites, 1cm
- Circulating atypical lymphocytes
- Peripheral hypereosinophilia >0.7 x 10^9
- Internal organ involvement:
- Liver (hepatitis): most frequent cause of death
- Kidneys (interstitial nephritis)
- Heart (myocarditis)
- Thyroid (thyroiditis)
- Lungs (interstitial pneumonitis)
- Brain
- Negative ANA, hepatitis/mycoplasma, chlamydia
- Skin involvement
- > 50% BSA
- Cutaneous eruption suggestive of DRESS e.g. facial oedema
- Biopsy suggestive of DRESS
What do we know about the mechanism of DRESS?
- Underlying mechanism not known
- Starts 2-6 weeks after drug exposure
- Liver most common internal organ involved (majority of deaths associated with this)
What are some common drug triggers of DRESS?
- Sulfonamides
- Allopurinol
- Anti-epileptics (lamotrigine, carbamazepine, phenytoin)
- antibiotics (vancomycin, amoxicillin, minocycline, piperacillin-tazobactam)
- Ibuprofen
What different ways can the rash in DRESS look like?
- Urticated papular exanthem- widespread papules e.g. bottom right pic
- Maculopapular (morbilliform) eruption
- Widespread erythema (erythroderma)
- Head/neck oedema
- Erythema multiforme-like (with targetoid lesions) e.g. top right pic
What is the treatment of DRESS?
- Withdrawal of culprit
- Corticosteroids are first line treatment- may require months of treatment
- 5-10% mortality
What is Graft vs Host disease (GvHD)?
Multi-organ disease
Who does GvHD affect?
10-80% of allogenic haematopoietic stem cell transplants (HSCT)
How do we know if a rash is caused by a drug or GvHD?
GvHD associated with:
- Face involvement
- Acral (distal limb) involvement
- Diarrhoea
What body parts does GvHD mainly affect?
- Skin
- Liver
- GI tract
What is the pathogenesis of GvHD?
Donor-derived T-lymphocyte activity against antigens in an immunocompromised recipient
What things need to be considered when there is itching without a rash?
Internal cause:
- Haematological causes (lymphoma, polycythaemia)
- Uraemia
- Cholestasis
- Iron deficiency or iron overload
- HIV/hepatitis ABC
- Cancer
- Drugs (esp opiates/opioids)
- Psychogenic
- Pruritus of old age
What tests do pruritus patients need?
- FBC, LDH
- Renal profile
- Liver function test
- Ferritin
- CXR
- HIV/hep ABC test
What do patients develop if they keep itching?
Nodular prurigo- skin thickening as a defence mechanism from the scratch
What is carcinoid syndrome?
When a malignant carcinoid tumour metastasises and secretes 5-HT into system
What symptoms happens in 25% of cases of carcinoid syndrome?
Flushing
What are symptoms of carcinoid syndrome?
- Diarrhoea
- Bronchospasm
- Hypotension
What is SJS/TEN?
Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis
What is the sequence of development of symptoms of SJS/TEN?
1) Prodrome of flu-like symptoms
2) Abrupt onset of lesions on trunk then face/limbs
3) Macules, blisters, erythema- atypical targetoid
4) Blisters then merge and sheets of skin detach ‘like wet wallpaper’
5) This represents extensive full thickness mucocutaneous (epidermal) necrosis in 2-3 days
This is a derm emergency (rare)
When is the disease called SJS and when TEN?
- When <10% of BSA detachment → SJS
- When 10-30% of BSA detachment → SJS/TEN
- When >30% of BSA detachment → TEN
What is the pathophysiology of SJS/TEN?
Cell-mediated cytotoxic reaction against epidermal cells
What is SJS/TEN mostly caused by?
Drugs cause it in >80% of cases
May be started up to 3 weeks prior to onset of rash
What types of drugs most commonly cause SJS/TEN?
- Antibiotics e.g. beta-lactams, sulphonamides
- Allopurinol
- Anti-epileptic drugs e.g. phenytoin, carbamazepine, lamotrigine
- NSAIDs
What are differential diagnoses for SJS/TEN?
- Staphylococcal scalded skin syndrome (SSSS)
- Thermal burns
- Cutaneous GvHD
How is the severity of SJS/TEN determined?
SCORTEN score calculated with criteria:
- Age >40
- Initial % epidermal detachment
- Serum urea + glucose + bicarbonate
- Presence of malignancy
What complications are there for SJS/TEN?
- Death- overall mortality is 30%
- Blindness
- Dehydration
- Hypothermia/hyperthermia
- Renal tubular necrosis
- Eroded GI tract
- Interstitial pneumonitis
- Neutropenia
- Liver and heart failure
What is erythroderma?
Generalised erythema affective >90% BSA
What can erythroderma manifest as systemically?
- Peripheral oedema
- Tachycardia
- Loss of fluid and proteins
- Disturbances in thermoregulation
- Risk of sepsis
What can cause erythroderma?
- Drug reaactions
- Cutaneous T-cell lymphoma called Sezary syndrome
- Sudden flare up of psoriasis
- Atopic eczema
- Idiopathic (25-30%)
Describe the management for erythroderma
- 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 temp
- Emollients to support skin barrier
- Maybe topical steroids
- Maybe antibiotics
What are different cutaneous signs of systemic disease?
- Excoriations/prurigo
- Xerosis
- Half and half nails
- Muehrcke’s lines
- Terry’s nails
- Clubbing
- Calciphylaxis
- Jaundice
- Palmar erythema
- Spider telangiectasia
- Porphyria cutaneous tarda
