Skin in Systemic Disease Flashcards
Why is the skin important in systemic disease?
Skin targeted - multi-organ systemic disease targeting skin, e.g. Sarcoidosis.
Skin signs - Sign of internal disorder, e.g. flushing in Carcinoid syndrome.
Tell-tale skin conditions - Skin conditions suggestive of underlying condition, e.g. Pyoderma gangrenosum in inflammatory bowel disease.
Secondary systemic involvement - Systemic disease secondary to skin disorder, e.g. high output cardiac failure in erythroderma.
What is an example of a test used to look at skin cells?
Punch biopsy
What are the 2 main groups of Lupus Erythematosus?
Systemic Lupus Erythematosus
Cutaneous (Discoid) Lupus Erythematosus
What are the Diagnostic criteria for Systemic Lupus Erythematosus?
Mucocutaneous - Cutaneous lupus - acute/chronic, Oral ulcers, Alopecia.
Synovitis, serostisis, renal disorder
Chilblains
Photodistributed erythematous rash
Neurological disorder
Haematological - Haemolytic anaemia, thrombocytopenia, leukopenia.
Immunological - ANA, Anti-dsDNA, Anti-Sm, Antiphospholipid, Low Complement, Direct Coomb’s test.
What are the presentations for Systemic Lupus Erythematosus?
Photodistributed rash Cutaneous vasculitis Chilblains Alopecia Livedo reticularis Cutaneous vasculitis Subacute cutaneous lupus (SCLE)
What are the presentations for Cutaneous (Discoid) Lupus Erythematosus?
Discoid lupus erythematosus
SCLE
Scarring
What is positive in Neonatal Lupus?
Ro positive antibody
What is the test that is essential for neonatal lupus?
ECG
50% have heart block
What is Dermatomyositis?
Autoimmune connective tissue disease
Proximal extensor inflammatory myopathy
Photo-distributed pink-violet rash favouring scalp, periocular regional and extensor surfaces
What are the signs of Dermatomyositis?
Gottron's papules Ragged cuticles Shawl's sign Heliotrope rash Photosensitive
What are some important antibodies associated with subtypes of Dermatomyositis?
Anti-p155 - associated with malignancy
Anti-MDA5 - interstitial lung disease, digital ulcers/ischaemia
What are the tests you should do if you suspect Dermatomyositis?
Anti-Nuclear Antibody - positive Creatine kinase Skin biopsy LFT (ALT often increased) EMG Screening for internal malignancy
What are the subclassifications of Cutaneous small vessel vasculitis?
Idiopathic
Infectious
Medication exposure
Inflammatory
What are the subclassifications of Small vessel vasculitis?
IgA vasculitis - Henoch Scholein
Urticarial vasculitis
Acute haemorrhagic oedema of infancy
Erythema elevatumdiutinum.
What are the subclassifications of small and medium vessel vasculitis?
Type 2 & 3 Cryogolulinemia ANCA- Associated; EGPA (Churg Strauss) Microscopic Polyangiitis GPA(Wegener)
What are the subclassifications of medium vessel vasculitis?
Polyarteritis Nodosa
Benign Cutaneous form
Systemic form
What are the Classifications of Large vessel vasculitis?
Temporal arteritis
Tayakasu
What are the manifestations of small vessel vasculitis?
Purpura (macular/palpable)
What are the manifestations of medium vessel vasculitis?
Digital necrosis
Retiform purpura ulcers
Subcutaneous nodules along blood vessels
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
Ulcerative
Scar sarcoid
Erythema nodosum
Histology–non-caseating epithelioid granulomas
Diagnosis of exclusion
Requires evaluation for internal organ involvement
How does Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) present?
Rash and systemic upset incorporating haematological and solid‐organ disturbances
What is 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 - body surface involvement
Cutaneous eruption suggestive of DRESS e.g. facial oedema
Biopsy suggestive of DRESS
What is the Internal organ involvement in DRESS?
Liver (hepatitis)- most frequent cause of death Kidneys (interstitial nephritis) Heart (myocarditis) Brain Thyroid (thyroiditis) Lungs (interstitial pneumonitis)
What is the Underlying mechanism in 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 triggers of DRESS?
Sulfonamides, anti-epileptics (carbamazepine, phenytoin, lamotrigine), allopurinol, Antibiotics (vancomycin, amoxicillin, minocycline, piperacillin-tazobactam), ibuprofen are common triggers
How does the Rash appear in DRESS?
Rash morphologies:
- Urticated papular exanthem - widespread papules - Maculopapular (morbilliform) eruption - Widespread erythema (Erythroderma) - Head / neck oedema - Erythema multiforme-like
What is the treatment for DRESS?
Withdrawal of culprit
Corticosteroids are first line treatment - may require months of treatment
Mortality 5-10%
How can you tell if a rash is caused by a drug or Graft versus Host Disease?
Face involvement
Acral involvement
Diarrhoea
all indicate that GvHD more likely
What is Graft versus Host disease?
Multiple-organ disease
Affects ~10-80% of allogenic haematopoetic stem cell transplants (HSCT
What is the Pathogenesis of Graft versus Host Disease?
Pathogenesis: donor-derived T-lymphocyte activity against antigens in an immunocompromised recipient
What does Graft versus Host Disease mostly affect?
- Skin
- Liver
- GI tract
What is Pruritis suggestive of?
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
What investigations should be done for Pruritis?
FBC, LDH Renal profile Liver function tests Ferritin XR Chest HIV / Hepatitis A / B /C
What does the patient develop if they are left scratching?
Nodular prurigo
What happens in Scurvy?
Vitamin C (ascorbic acid) deficiency
Spongy gingivae with bleeding and erosion
Petechiae, ecchymoses, follicular hyperkeratosis
Corkscrew hairs with perifollicular haemorrhage
What happens in Kwashiorkor?
Protein deficiency Systemic features: - Hepatomegaly - Bacterial / fungal infections - Diarrhoea - Loss of muscle mass - Oedema - Failure to thrive Skin signs: - Superficial dequamation 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
- 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 happens in Carcinoid syndrome?
Signifies metastases of a malignant carcinoid tumour 5-HT secretion Flushing in 25% of cases Other symptoms: - Diarrhoea - Bronchospasm - Hypotension
What is Stevens-Johnson syndrome/Toxic Epidermal Necrolysis(SGS/TEN)?
Derm emergency! (Rare)
Prodromal: flu-like sx
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
What classifies SGS/TEN?
10-30% BSA Detatchment
What happens in SGS/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
What can be a cause of SGS/TEN?
Antibiotics
Anti-Epileptics
NSAIDs
How do you determine severity in SGS/TEN?
SCORTEN – score used to help assess severity
Criteria: age >40, HR, initial % epidermal detachment, serum urea + glucose + bicarbonate, presence of malignancy
What are the complications in SGS/TEN?
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 Systemic manifestations reflect impairment in skin function: - Peripheral edema - Tachycardia - Loss of fluid and proteins - Disturbances in thermoregulation - Risk of sepsis Multiple etiologies: - Drug reactions - Cutaneous T-cell lymphoma – Sézary syndrome - Psoriasis - Atopic eczema - Idiopathic (25-30%)
What is 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 temperature.
Emollients to support skin barrier
+/- Topical steroids
+/- Antibiotics
What are the signs of Chronic Kidney disease?
Anaemia – mucosal pallor, hair thinning
Excoriations, prurigo
Calciphylaxis
Half and half nails
Signs related to primary disease
- ANCA-associated vasculitis - Systemic Lupus Erythematosus
Signs related to immunosuppression
- Viral warts - Skin cancer
What are the signs of Chronic Liver Disease?
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
What are some manifestations of Diabetes?
Terry's nails Granuloma annulare Neuropathic ulcers Acanthosis nigricans Xerosis Xanthelesma & Xanthomata Skin infections
What can be manifestations of HIV?
Severe seborrhoea dermatitis Extensive viral warts Norwegian scabies CMV Ulceration Kaposi sarcoma Eosinophilic folliculitis Bacillary angiomatosis
What are some other manifestations 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
What are dermal presentations of GI Disorders?
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 happens in Hidradentitis suppuritiva?
Inflamed nodes, sterile abscess, sinus tracts, fistulae and hypertrophic scars
Favours intertriginous zones: especially axillary, anogenital and inframammary area
What happens in Pyoderma Gangronesum?
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 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 is a sign of metastatic pancreatic carcinoma?
Haemorrhagic nodules
