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Autoinflammatory Flashcards

1
Q

Epidemiology of Behcets

A
  • More common in Middle Eastern (Turkey), Japanese population
  • F>M
  • 20-35 age group
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2
Q

Pathogenesis of Behcets

A
  • Precipitating factors:
    • Infectious - HSV/HCV/Strep
    • Genes - HLA B51
  • Results in circulating immune complexes and neutrophils —> inflammatory cell infiltration
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3
Q

Clinical features of Behcets

A
  • Cutaneous - OSAGE
    • Oral apthosis
    • Superficial thrombophlebitis
    • Acral and facial pustules
    • Genital apthosis
    • Erythema nodosum
  • Systemic - CVJARGON
    • Cardiac
    • Vascular
    • Joints - 50% patients
    • Renal
    • GIT - abdominal pain, ulcers
    • Ocular - 90% - uveitis, conjunctivitis
    • Neuro - later onset, meningo-encephalitis
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4
Q

How do you diagnose Behcets?

A

Diagnosis

  • 1 major and 2 minor criteria
  • 1 major: oral aphtosis at least 3 in 12 months
  • Minor:
    • Genital
    • Pathergy
    • EN or papulopustular
    • Ocular
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5
Q

How do you treat Behcets?

A

Treatment

  • Topical steroids
  • Systemic steroids
  • Can try cyclosporin or azathioprine
  • If really severe - TNF alpha and MTX
  • If just mucocutaneous - dapsone and colchicine
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6
Q

What is the epidemiology of PAN?

A
  • 4-16 per 100 000
  • Male more than female
  • Cutaneous - 10% kids
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7
Q

What is the pathogenesis and associations of PAN?

A
  • Inflammation of medium sized blood vessels
  • Unknown exact cause
  • Associations:
    • Infectous
      • HBV 7%
      • HCV
      • Cutaneous only - P19
    • Medications
      • Minocycline
    • Malignancy
      • Hairy cell leukaemia
    • Autoimmune
      • IBD
      • Rheumatoid arthritis
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8
Q

What are the cutaneous features of PAN?

A
  • Livedo racemosa
  • Subcutaneous nodules
  • Retiform purpura
  • Ulcers
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9
Q

What are the extra-cutaneous features of PAN?

A
  • Lungs are spared
  • Kidneys
  • CNS - paraesthesias
  • Gastro - abdominal pain, mesenteric ischaemia
  • Rheum - arthralgia
  • Cardio - cardiac failure
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10
Q

What does cutaneous PAN look like?

A
  • 10% of cases
  • Painful S/C nodules, livedo, cutaneous necrosis, ulcers
  • Systemic: fevers, myalgia, arthralgia, peripheral neuropathy
  • When cutaneous resolves, leaves retiform hyperpigmentation
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11
Q

Investigations for PAN and findings?

A
  • Biopsy
    • Segmental necrosing vasculitis of the medium sized vessels
    • C3, fibrin and IgM positive
  • Leukocytosis
  • Elevated ESR and CRP
  • Elevated platelets
  • ANCA (rare)
  • Micro aneurysms on MRA
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12
Q

Treatment of PAN?

A
  • Classic - steroids 1 mg/kg, taper over 6 months, and cyclophosphamide if severe
  • Cutaneous
    • NSAIDs, topical/IL steroids
    • MTX/dapsone, IVIG
    • Colchicine, azathioprine
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13
Q

What are the types of lupus according to the depth of the skin?

A
  • Acute cutaneous lupus- involves epidermis and maybe upper dermis
  • SCLE- involves epidermis and upper-mid dermis
  • Discoid lupus- predominantly dermal, with epidermal changes, and particularly peri-adnexal
  • Tumid lupus- Superficial and deep dermal
  • Panniculitis lupus- subcutaneous involvement
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14
Q

Associated conditions of DLE

A
  • Thyomyoma
  • Myasthenia gravis
  • Pemphigus
  • PCT
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15
Q

Medications that can cause DLE

A

penicallamine, isoniazid, griseofulvin, dapsone

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16
Q

Cutaneous findings of DLE

A
  • Localised
    - Head and neck
    - Indurated, discoid lesions
    - Dyspigmentation
    - 1/3 have alopecia
    - 1/3 have prominent follicular openings in ears
    - Scarring (cribriform)
    - Usually to lateral cheeks, nasal bridge
    - 7.5% present with papulopustular - like rosacea
    • Disseminated
      • More recalcitrant to treatment
      • Torso and limbs
      • Multiple types: bullous, annular
      • Purple plaques on dorsums of hands
  • Rarely, at risk of SCC
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17
Q

Risk of DLE transformation to SLE

A

5-15%

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18
Q

SCLE clinical signs

A
  • Photo-distributed pattern
  • Annular, raised red border and central clearing
  • No induration
  • Borders may show vesícula tino and crusting and occasional bullae
  • Lesions resolves to leave grey-white hypopigmentation and telangiectases
  • Diffuse non-scarring alopecia
  • Photosensitivity- half of patients
  • Mouth ulceration
  • Peri-ungual telangiectasia
  • Reticular lívido
  • Complications
    • Urticaria vasculitis
    • Chronic interstitial pneumonitis
    • Hypokalaemia tetraparesis
    • Malignancy (rare): breast, meningioma, hepatocellcular, Hodgkin, lung, prostate, SCC
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19
Q

Medications associated with SCLE

A
  • Certain medications can cause: HCT, terbinafine, calcium channel blockers, NSAIDs, griseofulvin, histamines - TTCHANGE
    • Up to 65% are caused by drugs
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20
Q

Risk of SCLE turning into SLE

A

10-15%

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21
Q

ACLE clinical findings

A
  • Malar rash following sun exposure, resolve without scarring
  • Presence of telangiectasias, erosions, dyspigmentation and epidermal atrophy may assist with dx
  • May last from few hours to several week
  • If on hands, knuckles are spared
  • Rarely, develop reaction similar to TEN
  • Can have just localised, more commonly associated with active SLE
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22
Q

Lupus panniculitis clinical findings

A
  • Distributed to face, upper arms, upper trunk, breasts, buttocks and thighs
  • Occasionally have discoid lesions over the top
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23
Q

Lupus panniculitis risk of turning into SLE

A

35%

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24
Q

Chillblain lupus findings

A
  • Red or dusky purple papules and plaques on the toes, fingers and sometimes the nose, elbows, knees and lower legs
  • Worse in the cold
  • May be ordinary chilblains with LE
  • Associated with DLE
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25
Q

What causes neonatal lupus?

A

Occurs when maternal anti-Ro antibodies pass over to children

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26
Q

Clinical features of neonatal lupus

A
  • Experience annular lesions, typically the face
  • Resolve without scarring, however may have dyspigmentation and telangiectasias
  • Systemic things to watch out for: cardiac (heart block), liver, cytopenias
  • All children should have an: ECG, FBC, LFT
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27
Q

Medications that can cause SLE

A
  • Medications - ANTI-CHAPB
    • Anti-arrhythmics
      • Procainamide
      • Quinidine
    • Anti-hypertensives
      • Hydralazine
      • Methyldopa
      • Captopril
    • Anti-psychotics
      • CHlorpromazine
      • Lithium
    • Antibioitcs
      • Isoniazid
      • Minocycline
    • Anti- convulsants
      • Carbamazepine
      • Propylthiouracil
      • Penicillamine
      • Sulfasalazine
    • Others
      • PPI
      • Statins
      • Chemo
      • Biologics
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28
Q

Nail changes in SLE

A
  • Nails
    • Nail fold erythema
    • Splinter haemorrhages
    • Red lunulae
    • Nail fold hyperkeratosis
    • Nail ridging
    • Onycholysis
    • Onychomadesis
    • Punctate or striate leukonychia
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29
Q

Hair changes in SLE

A
  • Scarring or non-scarring
  • Telogen effluvium - >60% cases
  • Slow loss —> ‘lupus hair’
  • Alopecia areata
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30
Q

Cutaneous vascular reactions in SLE

A
  • Vasculitis
    • Retiform or stellate purpura
    • Gangrene
    • Periungual infarcts
    • Splinter haemorrhages
  • Vasculopathy
    • Rayanuds
    • Live do reticularis
    • Atrophied blanche
    • Cryoglobulinaemia
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31
Q

SLE diagnosis

A

SOAPBRAINMD —> need 4 or more

  • Serositis
  • Oral ulcers
  • Arthritis
  • Photosensitivity
  • Blood
  • Renal
  • ANA
  • Immunologic
  • Neurologic
  • Malar rash
  • Discoid rash
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32
Q

Lupus histology

A
  • Lichenoid: basal cell vacuolisation
  • Depending on subtype, dense lymphohistiocytic infiltration
  • Discoid: peri-adnexal inflammation, follicular plugging, scarring
  • Immunopath: granular deposition and the D-ED junction and around hair follicles, mostly IgG and/or IgM
  • If you do it of normal skin —> may show deposition inficating systemic involvement
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33
Q

Antibodies in lupus

A
  • Non-organ specific humor al autoantibodies are the hallmark of SLE
  • Disease specific: dsDNA and anti-Sm
  • More common: ANA and anti-Ro (latter SCLE)
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34
Q

Investigations of lupus

A
  • Biopsy
  • LBT
  • Leukopenia and lymphopenia
  • THrombocytopenia (correlates with increased morbidity and damage)
  • ESR elevated
  • Polyclonal gammopathy
  • Low albumin
  • Lupus anticoagulant, anti-cardiolipin
  • LE cell phenomenon: neutrophils that have engulfed nuclear material from degenerative white cells
  • ANA:
    • Homogenous most common
    • Peripheral: associated with poorer prognosis and higher risk of renal disease
    • Centromere: associated with CREST
  • Antibodies:
    • dsDNA
    • Anti-Sm 30%
    • Antihistone antibodies —> associated with drug induced
    • Anti-RNP 23-40% —> characteristic of mixed CT disease
    • Anti-Ro —> 30-40
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35
Q

Associations of PG

A
  • Unknown
  • Associated conditions in 15-25%
    • IBD - 20-30%
    • RA - 20%
    • Haematological malignancies - particularly AML, but also CML, monoclonal gammopathy (often IgA), hairy cell leukaemia
    • Neutrophilic dermatoses - Behcets, PAPA (pyogeneic sterile arthritis, PG and acne) (PTSP1P1 defect), Sweets
  • Implicated cytokines: IL-1 and IL-1B
  • Pathergy
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36
Q

Subtypes of PG

A
  • Superficial granulomatous
    • Favours trunk, following trauma
    • Less intense neutrophils on histo
    • Now thinking that perhaps it fits in more with wegeners? Not sure
  • Pyostoma vegetans
    • Vegetative plaques in bucal and oral mucosa
    • Associated with IBD
  • Pustular
    • Small, sterile pustules
    • Associated with IBD and BADAS
  • Vesiculobullous
    • Cross-over with sweets
    • Associated haematological malignancies: AML/CML, myelofibrosis, et
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37
Q

Diagnosis of PG

A
  • Major:
    • Clinical
    • Exclude other causes of ulcer
  • Minor
    • Pathergy
    • Responds to treatment
    • Histology
    • Associated condition identified
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38
Q

Management of PG

A
  • Underlying cause
  • Steroids - topical or systemic or Indra-lesional
  • Others with varying reports:
    • MIld - colchicine, dapsone, potassium iodide
    • Severe - thalidomide, cyclosporine, TNF-alphas (infliximab the most evidence), IL12/23, IL-2, methotrexate, azathioprine, MMF, IVIG, cyclosporine, chlorambucil
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39
Q

MPA cutaneous clinical findings

A
  • Cutaneous
    • Palpable purpura
    • Livedo racemosa
    • Splinter haemorrhages
    • A real macules
    • Ulcers
    • Urticaria plaques
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40
Q

MPA extra-cutaneous findings

A
  • Extra-cutaneous
    • Renal —> 90% of cases, glomerulonephritis
    • Pulmonary
      • Capillarity —> pulmonary alveolar haemorrhage
    • Neurologic
      • Peripheral neuropathy
      • Mononeuritis multiples
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41
Q

MPA ANCA findings

A

MPO>PR3

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42
Q

Path of MPA

A
  • No granulomas

- Segmental necrotizing vasculitis of small blood vessels

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43
Q

Treatment of MPA

A
  • Induction fo remission
    • Pred 1 g/kg/day
    • Cyclophosphamide- 6 months, orally or IV pulses
    • Pred + ritux similar
  • Maintenance
    • MTX, alza, MMF, IVIG
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44
Q

Pathogenesis of GPA (Wegener’s)

A
  • 2 hallmarks:
    • Granulomas
    • Small to medium sized vasculitis
  • Factors:
    • Reduced alpha-1 antritrypsin deficiency
    • Environmental —> staph
    • ANCA - PR3
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45
Q

Diagnostic criteria for GPA (Wegener’s)

A

European criteria: 3 of 6

  1. Biopsy showing granulomatous
  2. CXR or CT findings
  3. Abnormal U/A
  4. URT inflammation
  5. Airway stenosis
  6. Bloods: anti-PR3, ANCA
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46
Q

Cutaneous findings of Wegener’s

A

Cutaneous

  • Palpable purpura
  • Oral ulcers
  • Strawberry gums - hyperplastic gingival tissue
  • S/C nodules and ulcers that look like PG
  • Papulonecrotic lesions
  • Acneiform and follicultiis like papules
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47
Q

Extra-cutaneous findings of Wegener’s

A

Extra-cutaneous

  • Pulmonary
    • Upper and lower RT - 90% cases
    • Nasal, sinus, ear, tracheal involvement
    • Epistaxis, mucosal ulceration, nasal septal perforation, saddle nose
    • Pulmonary: dispones, Haem Optus is, cough, pleuritis
  • Renal
    • 75% eventually develop
  • Ocular
    • Proptosis
    • Scleritis
  • Cardiac
  • Neurologic
  • GI
48
Q

Investigations for GPA

A
  • High ESR, CRP
  • Anaemia
  • Leukocytosis
  • ANCA - PR3
  • Renal
    • Urine sediments, Haem aturdía, proteinuria, red cell casts
  • Serum bio markers: MMP3, TIMP1, CXCL13
49
Q

Histopath for GPA

A
  • LCV or granulomas
  • Papulonecrotic - palisading neutrophil is dermatitis with areas of granulomatous inflammation that surround foco of basophilic necrobiosis
50
Q

Treatment of GPA

A
  • Pred + cyclophosphamide
  • Steroids + ritux equally effective now
  • ? Infliximab
  • If limited GPA —> just for trimethoprim
51
Q

Pathogenesis of EGPA

A
  • Triggers:
    • Quick steroid cessation
    • Omalizumab
    • Leukotrine inhibitors
    • Vaccination
    • Desensitation
  • T lymphocytes —> TH2 —> granulomas formation
  • Eosinophil de granulation —> tissue injury
  • ANCA —> vasculitis
52
Q

Phases of EGPA

A
  1. Phase 1:
    1. Years of allergic rhinitis, asthma, nasal polyps
  2. Phase 2:
    1. Peripheral eosinophilia
    2. Respiratory tract infections
    3. GI symptoms
  3. Phase 3:
    1. Systemic necrotizing vasculitis with granulomatous inflammation —> can occur several years to decade after initial symptoms
53
Q

Cutaneous findings of EGPA

A
  • Occur most commonly in the 3rd phase but can happen in any
  • Palpable purpura
  • Urticated plaques
  • Subcutaneous nodules
  • Livedo racemosa
  • Retiform pupura
  • Papulonecrotic lesions
54
Q

Extracutaneous findings of EGPA

A
  • Lung
    • Asthma
    • Capillarity —> haemorrhage
  • Neuro
    • Mononeuritis multiples
  • Cardio
    • Cardiomyopathy
    • Pericarditis
  • Renal
    • Necrotizing GN
  • MSK
  • GIT
  • Ocular
55
Q

EGPA findings

A
  • Peripheral eosinophilia
  • Elevated IgE
  • MPO> PR3
  • Some not ANCA positive
56
Q

EGPA pathology

A
  • Eosinophils
  • Extra-vascular granulomas
  • Necrotizing vasculitis
  • Papulonecrotic —> palisading dermatitis with eosinophil infiltration, granulomas formation, eosinophilia necrobiosis
57
Q

EGPA treatment

A
  • Steroids alone
  • Organ involvement/refractory —> step up
  • IL-5 mepolizumab —> being investigated
58
Q

Systemic sclerosis epidemiology

A
  • F>M 3-4:1
  • 1.5% of Systemic have one or more affected first degree relatives –> 10-15 fold higher risk
  • Systemic: 10 year survival of ~70%
59
Q

Prognostic factors for systemic sclerosis

A
  • Males
  • African-American
  • Older age at diagnosis
  • Internal organ involvement - especially pulmonary, at time of diagnosis
  • Skin fibrosis affecting the trunk
  • Elevated ESR
60
Q

Pathogenesis of systemic sclerosis

A
  1. Vascular dysregulation
    1. Impaired angiogenesis –> VEGF elevated in the dermis
    2. Smooth muscle cell altered responsiveness to vasoconstrictive and vasodilatory factors
    3. Intimal proliferation –> luminal occlusion –> hypoxia –> synthesis of fibroblast and collagen
  2. Immune dysregulation
    1. Anti-topoisomerase I (anti-Scl70), anti-RNA polymerase III and anti-centromere
    2. Lymphocytic infiltrates observed in skin and lungs –> demonstrate a Th2 predominant profile with increased IL-4 and IL-13
    3. Th17 and IL-17 have been implicated
    4. CXCL4 found to be significantly elevated, proposed as biomarker to monitor for development of lung disease in
  3. Extracellular matrix dysregulation
    1. Sclerosis: deposition of collagen, proteoglycans, fibronectin, fibrillins and adhesion molecules which sequester cytokines and growth factors
    2. accumulation fo collagen appears to be primary result of increased synthesis
61
Q

Clinical EUSCAR score for systemic sclerosis

A

START N UP

  • Sclerodactyly (2)
  • Thickening of both hands extending to proximal MCP (9)
  • Autoantibodies (3)
  • Raynaud’s (3)
  • Telangiectasias (2)
  • Nails - abnormal nail-fold capillaries
  • Finger ulcers or scars (2/3)
  • Puffy fingertips (2) + pulmonary involvement

EULAR criteria - socre >9 is definite.

62
Q

Limited sclerosis

A
  • Limited - associated with anti-centromere antibodies
    • Formerly called CREST - calcinosis, Raynauds, esophageal involvement, sclerodactyly, telangiectasias
    • Slower development
    • Later onset of internal organ involvement
    • Pulmonary hypertension more common
    • Can also have no cutaneous manifestations - systemis sclerosis sine scleroderma
63
Q

Systemic sclerosis

A
  • Sudden onset Raynauds (can develop early oedema too)
  • Associated with Scl-70
  • Rapidly progressive, more widespread cutaneous sclerosus
  • > 90% develop internal organ involvement within the first 5 days
  • Interstitial lung disease more than pulmonary arterial hypertension
  • Kidney disease
64
Q

Cutaneous findings of systemic sclerossi

A 
Digital pits
Fibrosis
Dyspigmentation
Raynaud's
Calcinosis cutis
Telangiectasias
Cutaneous ulcers
65
Q

Fibrotic changes in systemic sclerosis

A
  • Skin hardens - indurated phase, then thins - late atrophic phase
  • Fingers can develop flexion contractures and ulcers
  • Face: beaked nose, microstomia, youthful appearance
66
Q

Calcinosis cutis in systemic sclerosis

A
  • usually near joints and distal locations

- dry, hypohydrosis and pruritis, with diminished hair growth

67
Q

Raynaud’s Phenomenon

A
  • Episodic vasospasm of digital arteries resulting in white, blue and red discolouration
  • Primary develops in young females - 3-5% of the population
  • Secondary: uncommon, associated with an underlying medical problem
  • Primary have <5 attacks a day, onset udirng puberty, triggered by cold and emotional stress, with no autoantibodies where secondary onset is older, more attacks a day and mainly from cold, with abnormal capillaroscopy
  • Differential diagnosis of Raynauds:
    • Large/medium sized arterial issues - atherosclerosis, Takayasu arteritis
    • Small arteries/arterioles - SLE, sclerosis, cold injury, vibration disease, chemotherapies
    • Normal blood vessels - abnormal blood: cryoglobulinaemia, cryofibrinogenaemia, myeloproliferative
    • Abnormal vasomotion: primary Raynauds, drugs (eostrogen, cyclosporin, nicotine), carpal tunnel, carcinoid
68
Q

Extra-cutaneous features in systemic sclerosis

A
  • Lungs
    • Interstitial lung disease –> do PFT, HRCT
    • Pulmonary arterial hypertension –> TTE, BNP
  • Kidney
    • Renal crisis + hypertension –> BP, UEC, urinalysis
  • Heart
    • Cardiomyopathy, heart failure –> TTE/TOE
  • GIT
    • Oesophageal dysmotility and small bowel involvement –> barium swallow/endoscopy –> refer to GIT
69
Q

Autoantibodies in systemic sclerosis

A
  • Positive ANA –> speckled or nucleolar
  • Anti-centromere –> localised
  • Scl-70 –> systemic
  • Anti-RNA polymerase 3 antibodies –> more likely to have rapidly progressive, diffuse skin disease and renal involvement
70
Q

Histopathology of systemic sclerosis

A
  • Compact or hyalinized collagen, excessive collagen deposition
  • Loss of S/C fat
  • loss of glands
  • Sparse lymphocytic infiltrate in the dermis and subcutis
  • Adnexal structures - particularly eccrine - appear ‘trapped’
    DIF: usually negative
  • Ultrastructural level: endothelial damage
71
Q

Ddx of systemic sclerosis

A
  • Mucinoses –> scleredema, scleromyxoedema
  • Immunologic
    • Chronic scleroderma like GVHD
    • Eosinophilic fasciitis
    • Generalised morphoea
    • Fibroblastic rheumatism
    • Overlap syndromes
  • Paraneoplastic
    • POEMS
    • Amyloidosis
    • Carcinoid syndrome
    • Paraneoplastic scleroderma-like
  • Neoplastic - Carcinoma en cuirasse (sclerodermoid encasement by metastatic carcinoma)
  • Metabolic, Diabetic cheiroarthropathy, PCT
  • Neurologic -SPinal cord injury, Reflex sympathetic dystrophy
  • Toxin-mediated
    • Nephrogenic systemic fibrosis
    • Eosinophilia-myalgia syndrome
    • Silicosis
  • Drug induced- Bleomycin, Taxanes, Vinyl chloride
  • Venous insufficiency - Lipodermatosclerosis
  • Genetic
72
Q

Cutaneous sclerosis treatment

A
  • Cutaneous sclerosis
    • Topical therapies (same as morphoea - topical steroids, tacrolimus, IL steroid)
    • UV
    • Minocycline
    • MTX
    • MMF –> may be helpful
73
Q

Raynauds treatment

A
  • 1: cold avoidance, warm hands, cease smoking
  • 2: calcium channel blockers - nifedipine SR 30 mg daily, amlodipine
  • 3: phosphodiesterase type 5 inhibitors: sildenafil, alpha-adrenergic blockers (prazosin), ARB, endothelin receptor antagnosit (bosentan)
  • 4: SSRI - fluoxetine
74
Q

Cutaneous ulcer in systemic sclerosis treatment

A

avoid excessive debridement, moist, non-adherent dressings, low-dose aspirin or clopidogrel, IV prostanoid

75
Q

Calcinosis cutis treatment

A

low dose warfarin, calcium channel blockers, sodium thiosulfate

76
Q

Dermatomyositis epi

A
  • Females 2-3 times more

- Malignancy most associated with adult onset clinically amyopathic dermatomyositis

77
Q

Dermatomyositis pathogenesis

A
  • trigger –> immune mediated process in genetically predisposed people
  • Genetics:
    • HLADR3 and B8 - Juvenile
    • HLADR52 - anti-Jo
    • DR7 and DRw53 - Mi-2
    • B14 and B40 - overlap
    • DRB1*15021 - Japanese with juvenile dermatomyositis
  • Cellular immunity
  • Humoral immunity
    • Associated with other autoimmune conditions - thyroid, diabetes, dermatitis herpetiformis, etc
    • upregulation of interferon pathway and complement activation
    • Anti-synthetase antibodies are directed against cytoplasmic antigens, therefore the ANA test may be negative
  • Infectious
    • Seasonal variation
    • E coli, echovirus, coxsackie
  • Drugs
  • Malignancy
    • TIF-1 gamma antibodies and NXP-2 antibodies
78
Q

Dermatomyositis drug causes

A
  • 2C HOT PANTS Z
  • Cyclophosphamide, checkpoint inhibitors
  • Hydroxyurea
  • Omeprazole
  • TNF-alpha blockers
  • Phenytoin
  • A
  • NSAIDs
  • Terbinafine
  • Statins
  • Zoledronic acid
79
Q

Dermatomyositis clinical - cutaneous

A
  • Head:
    • Heliotrope
    • Eyelid oedema
    • Facial erythema
    • scalp erythema and scale
    • Non-scarring alopecia
  • Trunk
    • Photodistributed poikiloderma: Shawl signV sign, poikiloderma - pink-violet colour
    • Holster sign
    • Centripetal flagellate erythema
  • Limbs
    • Gottron’s sign - papules on elbows and/or knees
    • Gottron papules - pink papules on knucles
    • Raynaud’s
    • Calcinosis cutis - more common in juvenile, associated with delay in diagnosis and treatment. Can occur in deep fascia and intramuscular CT. Hard, irregular papules or nodules that occasionally drain a chalky material. Favours sites of trauma such as the elbows and knees
    • Pustular eruptions of elbows and knees
  • Nails and hands
    • nail fold changes - telangiectasias: dilated capillary loops alternate with capillary dropout, cuticular hypertrophy
    • mechanics hands + ragged cuticles
    • Tender palmar papules or hyperkeratotic palmar papules
  • Mouth
    • Ovoid palatal patch
    • Gingival telangiectasias
  • Other
    • cutaneous erosions or ulcerations
    • exfoliative erythroderma
    • wong variant: PRP
    • psoriasiform lesions
    • vesiculobullous
    • Panniculitis
    • Lipoatrophy (juvenile)
    • Small vessel vasculitis (juvenile)

Cutaneous - further

  • more accenutated on extensor surfaces
  • poikiloderma can occur in photoprotected places as well, and is often misdiagnosed as psoriasis. can be pink-red in 1-2, but more violaceous/purple in darker
  • Can be ++ pruritic - which can help distinguish dermatomyositis from LE
  • Can get erosions adn ulcerations
  • Wong-type: more common in Asians, looks like PRP
  • Also look for other signs of autoimmune connective tissue diseases
80
Q

Dermatomyositis clinical - systemic

A
  • Symmetric inflammatory myopathy
    • triceps and quadriceps usually affected first and may be tender
    • proximal muscle groups, especially the extensors
    • advanced - all muscle groups
  • Interstitial lung disease
    • 15-30% of patients
    • diffuse interstitial fibrosis
    • dry cough, progressive breathlessness
    • anti-MDA5 - high risk of rapidly progressive lung disease and poor prognosis despite lack of muscle disease
    • particular feature of antisynthetase syndrome –> if Jo present there is 70% likelihood will have pulmonary disease
  • GIT: dysphagia, GORD, in kids vasculopathy of GIT
    • Dysphagia –> investigate for overlap with systemic sclerosis
  • Cardiac: arrhythmia
  • Inflammatory polyarthritis
81
Q

Dermatomyositis investigations

A
  • Skin biopsy
  • Muscle: CK, serum aldolase, urine creatinine, EMG, muscle biopsy, MRI or USS
  • Lung: PFT, if abnormal high res CT
  • Cardiac: ECG
  • Eosophageal: barium swallow if indicated or manometry
  • FBC, UEC, LFT, CMP, fasting glucose and lipids, autoantibodies
  • Malignancy: UA, stool, PSA, CA125, CA19-9, CT CAP, scopes, Pap smear, etc
82
Q

Dermatomyositis histology

A
  • can be subtle
  • epidermal atrophy
  • interface dermatitis with vacuolar alteration of basal keratinocytes and pigment incontinence
  • dermal: interstitial mucin deposition and sparse lymphocytic infiltrate
  • Colloidal iron: mucin
  • Ddx: lupus
  • Gottron papules: interface dermatitis with acanthosis and hyperkeratosis
  • Muscle bioopsy: type 2 muscle fibre atrophy, etc –> biopsy the triceps
83
Q

Dermatomyositis ddx

A
  • Other causes of polymyositis
  • SLE
  • Psoriasis
  • Airborne and allergic contact dermatitis
  • Photodrug eruption
  • CTCL
  • Atopic dermatitis
  • Systemic sclerosis
  • Trichomoniasis
  • Photodistributed form of multicentric reticulohistiocytosis
84
Q

Dermatomyositis treatment principles

A
  • Many can become muscle disease-free off treatment after a period of 24-48 months, with a slow steroid wean
  • There is a discordance between skin and and muscle response
  • If minimal mm involvement, comes under control pretty rapidly
  • In terms of follow-up, juvenile requires twice yearly and monitoring of trigs and insulin
  • For cutaneous management:
    • Topical steroids, tacrolimus
    • antimalarials, low dose methotrexate, MMF, IVIG, dapsone, tofacitinib, thalidomie
    • increased risk of cutaneous reaction to plaquenil in patients with DM - still frequently used as a first line therapy, but pre-treatment warning is recommended
    • Calcinosis cutis: diltizem, excision, warfarin, bisphosphonates, probenecid, colchicine, TNF inhibitors
  • Systemic: common therapeutic approach: antimalarials, then MTX, MMF, IVIG
  • Studies:
    • Rituximab failed to reach its primary and secondary endpoints
    • no benefit with plasmapheresis
  • Physical therapy
85
Q

Dermatomyositis treatment options

A
  • Systemic:
    • Prednisone - 1mg/kg tapered to 50% over 6 months and to zero over 2-3 years
    • MTX 5-25 mg weekly
    • Azathioprine: 2-3 mg/kg
  • Other systemic:
    • IVIG, MMF, cyclophosphamide, chlorambucil, cyclosporin, rituximab, tacrolimus, sirolimus, TNF alpha inhibitors, flarabine, plasmapharesis, stem cell
  • Cutaneous
    • Photoprotection
    • Topical steroids, tacrolimus
    • Plaquenil or chloroquine
    • MTX
    • MMF
    • Retinoids
    • Dapsone
    • Thalidomide
    • Leflunomide
    • Anti-oestrogenes
    • TNF alpha blockers
    • Rituximab
    • Tacrolimus
    • Tofacitinib
86
Q

Dermatomyositis malignancy

A
  • likely 15-25% risk
  • malignancy associated with adults, not juvenile
  • Associated: genitourinary (ovarian and colon), nasopharyngeal cancer, breast, lung, gastric, pancreatic, lymphomas
  • Risk of malignancy may return to relative baseline after 3 years
  • Approach: ongoing vigilance
    • physical exams
    • lab screening
    • CT chest, abdomen and pelvis and pelvic USS in women
  • Tif antibody particularly associated with malignancy
87
Q

Anti-Jo DM

A
  • Anti-synthetase: autoantibodies, fever, erosive polyarthritis, mechanic’s hands, Raynaud, interstitial lung disease
  • about 20%
  • targets intracytoplasmic protein synthesis
88
Q

Anti-SRP DM

A
  • acute onset necrotizing myopathy - severe weakness, high CK, may be refractory to treatment
  • 5%
89
Q

Anti-Mi2 DM

A
  • Adult DM and juvenile DM
  • Cutaneous disease, milder muscle disease with good response to treatment
  • 15%
90
Q

Tif-1 gamma DM

A
  • targets cell proliferation, apoptosis, innate immunity
  • cancer associated myositis: extensive cutaneous disease in adult DM and juvenile DM
  • palmar hyperkeratotic papules, psoriasiform lesions, red on white telangiectatic patches, ovoid palatal patch
  • 80% antibody frequency
91
Q

NXP2 DM

A
  • cancer associated in adult DM

- DM with calcinosis, peripheral oedema, myalgia, dysphagia, mild skin disease

92
Q

SAE DM

A

adult DM, may present with clinically amyopathic

93
Q

MDA5 DM

A
  • cutaneous ulcerations - periunual region and overlying Gottron papules and/or Gottron sign, oral ulcerations, prominent alopecia, arthritis
  • clinically amyopathic DM, interstitial lung disease including a rapidly progressive form
94
Q

Eosinophilic Fasciitis clinical

A
  • history of strenuous physical activity precedes in 30% of patients
  • initially: oedema and pain of the involved extremities –> fibrosis and dimpled/pseudo-cellulite
  • symmetric, spares hands, feet and face
  • Groove sign: linear depressions where veins appear to be sunken within the indurated skin
95
Q

Eosinophilic Fasciitis investigations

A
  • Bloods: elevated ESR, hypergammaglobulinaemia, peripheral eosinophilia
    • Association with pancytopaenia, myeloproliferative disorders, monoclonal gammopathy
    • some argue if have EF plus unexplained anaemia that they should have BM biopsy
  • Histology:
    • thickening of the deep fascia
    • within fascia and subfascial muscle, a patchy infiltrate composed of lymphocytes and plasma cells is seen
    • +/- eosinophils and mast cells, and dermal fibrosis
  • MRI
96
Q

Eosinophilic Fasciitis treatment

A
  • prompt treatment to preserve mobility and function and prevent joint contractures
  • Rx: oral steroids, tapered over 6-24 months
  • Response within first few weeks, clinical improvement may be seen over several months
  • Other medications trialled: plaquenil, CsA, dapsone, MTX, PUVA, infliximab, UVA +/- retinoid
  • ?Consider haematologic malignancy
97
Q

Nephrogenic Systemic Fibrosis epi and path

A
  • Middle-aged adults
  • No gender prediliction
  • Now that it has been associated with renal dysfunction and exposure to gadolinium-based contrast, then the number has reduced
  • mechanism by which fibrosis develops is still not known
  • may involve circulating fibrocyte
98
Q

Nephrogenic Systemic Fibrosis clinical

A
  • thick, indurated plaques distributed symmetrically on the extremities and trunk
  • plaques are erythematous - hyperpigmented, can have irregular advancing edge with an ameboid appearance
  • confluent involvement on the extremities can result in joint contractures
  • pain, loss of mobility
  • Extracutaneous:
    • yellow scleral plaques
    • systemic fibrosis affecting the heart, lungs and skeletal muscle
99
Q

Nephrogenic Systemic Fibrosis histo

A
  • need a deep biopsy specimen
  • disease process extends along fibrous septa into the subcutis
  • Haphazard arrangement of thickened collagen bundles and increased dermal fibroblast-like cells
  • Spindle cells
  • Stains positively for CD34 and procollagen I
  • Vascular proliferation
  • Mucin deposition
  • Increased number of dendritic cells
  • No loss of elastic fibres
  • Osseus metaplasia (osteoid bodies)
100
Q

Nephrogenic Systemic Fibrosis treatment

A
  • quite recalcitrant
  • steroids and immunosuppressives not that good
  • anecdotal: imatinib, rapamycin, UVA1, phototherapy, ECP, PDT, plasmapheresis, high dose IVIG, stopping erythropoieitin
  • Improvement in renal function after renal transplant noted
101
Q

Stiff skin syndrome pathogenesis

A
  • Gene mutation in FBN1 which encodes fibrillin-1

- disturbance in organization of collagen and glycosaminoglycans within the ECM results in giant collagen fibrils

102
Q

Stiff skin syndrome clinical

A
  • rock hard induration and thickening of skin and subcutaneous tissues –> more pronounced on buttocks and thighs
  • spares inguinal folds
  • hands and feet not involved
  • mild hypertrichosis
  • restricted joint mobility –> characteristic posture of hip and knee flexion, and lumbar lordosis
  • short stature
  • stable or slowly progressive
  • internal organs not involved
  • unilateral involvement –> can have scleredema, deep morphoea, linear melorheostotic scleroderma
103
Q

Stiff skin syndrome histology

A
  • thick, hyalinised fascia without any inflammatory infiltrate
  • thickened collagen bundles and mucin deposition may or may not be present in the overlying dermis
104
Q

Stiff skin syndrome treatment

A
  • nothing works

- physical therapy

105
Q

Sclerodermoid Syndromes Induced by Exogenous Substances

A
  • Toxic oil syndrome: ingestion of aniline-degraded and reprocessed rapeseed oil –> morbilliform eruption and flu like symptoms, headache, fever, peripheral eosinophilia./ Lichen planus like, progresses to a morphoeaform or sclerodermoid picture
  • Eosinophilia-myalgia: L-tryptophan contamination –> severe myalgias, fever, dyspnoea, oedema, macular exanthem, peripheral eosinophilia
  • Drugs: bleomycin, taxanes –> can induce cutaneous sclerosis and pulmonary fibrosis, mimicking Ssc.
    • Other chhemotherapy agents
    • Alkaloids
    • Carbidopa
    • Cocaine
    • Appetite suppressants
  • Chemicals: vinylchloride, organic solvents (trichloroethylene), pesticides or epoxy resins induces a slowly progressive process of sclerosis. Get insidious acrosclerosis and Raynauds phenomenon. Can also get morpheaform plaques and fibrotic nodules. Can get acral osteolysis, hepatic toxicity, pulmonary involvement. Autoantibodies are negative, and it reverses once you remove the exposure.
  • Silicosis
    • Miners and foundry workers
    • Mean duration of exposure was 14 years
    • Quartz absorbed via inhalation and percutaneously, and silicosis is caused by particles with a diameter less than 5 microns.
    • once absorbed, silica cannot be removed from the body
    • Silica. has been associated with Ssc (pulmonary), AI-CTD, Sjogren, SLE, RA
106
Q

Morphoea epidemiology

A
  • prevalence increases with age
  • F>M 2.6:1
  • linear morphoea has no gender preference
  • rarely life threatening
  • 11% –> substantial disability, particularly for linear morphoea
107
Q

Morphoea pathogenesis

A
  • Autoantibodies generally same as population except for the following 2:
      1. anti-ssDNA-topoisomerase 2a, phospholipid, fibrillin-1 and histone bodies (AHA)
      1. High ANA in juvenile linear morphoea and individuals with generalised morphoea
  • Those with linear morphoea: ssDNA antibodies or AHA associated with increased risk of functional impairment
  • Sclerosis involves three major components:
    • Vascular Damage
      • Microvascular injury results in hypoxia
      • Reduction in number of capillaries and increase in endothelial cell activation signallers are elevated (VEGF, PDGF, TGF-beta)
      • Initial changes: expression of adhesion molecules, endothelial swelling, BM thickening and intimal hyperplasia
    • Activated T cells and Altered connective tissue production by fibroblasts
      • TH2 –> IL-4, IL-13 and TGF-beta –> collagen and ECM production
      • TH1 –> interferons –> suppressed ECM proteins
      • Th1-> STAT4->IL-12. STAT4 polymorphisms in Ssc has been reported
      • Susceptible immune related genes: CD247, IRF5 and HLA + promoter region of gene that encodes for connective tissue growth factor
      • When elevated chemokine ligand CXCL4 –> higher lung fibrosis and faster progression of skin fibrosis
  • Genetics: fibrillin-1 gene (implicated in stiff skin syndrome)
  • Triggering events
    • Morphoea could be localised trigger, whilst SSc is systemic insult
108
Q

Morphoea subtypes (8)

A
  1. Plaque type
    - Asymptomatic, insidious onset of slightly elevated erythematous or violaceous plaques –> centrifugal expansion
    - Central shiny white colour that becomes sclerotic/scar like, and peripheral violaceous or lilac ring
    - Lilac ring is the sign of activity, when lesion progression halts then that lilac ring is lost
    - PIH in mature lesions, can have residual atrophy and dyspigmentation
    - Loss of skin structures - loss of hair and sweat glands
  2. Guttate - multiple, superficial nummular plaques that can become really deep
  3. Atrophoderma of Pasini and Pierini - superficial variant of plaque-type. Hyperpigmented patches on the posterior trunk following Blaschkoid pattern.
  4. Deep - deep demis, S/C fat, and underlying structures. Can calcify and become dystrophic calcinosis cutis, can mimic eosinophilic fasciitis.
  5. Nodular or keloidal
  6. Bullous - diffuse, rapidly progressive oedema, lymphoceles from lymphatic fluid stasis. Seen more in generalized morphoea and sclerodermoid or morpheaform GVHD
  7. Linear Morphoea
    - Starts as linear, erythematous streak that extends longitudinally and becomes scar like
    - Function: can affect underlying limb - fascia, muscle, tendons
    - Can be quiescent for ages then flare
    - Good ddx: linear melorheostosis - underlying candlewax like linear hyperostosis
    1. En coup de sabre: forehead and scalp, unilateral (often paramedian), atrophic or sclerotic. Hair is lost, can involve underlying muscles and osseous structures, rarely can progress into the meninges and brain.
    2. Parry-Romberg: hemi-facial atrophy, very severe variant of linear morphoea. Progressive loss of fat, but little to no sclerosis. Can involve Trigeminal nerve.
  8. Generalized
    - Starts on trump as plaque morpheoa, then rapidly coalesces and can affect nearly the entire trunk, sparing the nipples
    - Puffy oedema of the hands
    - Can cause dyspnoea due to intercostal muscle involvement
    - Recalcitrant and aggressive
109
Q

Morphoea in childhood

A
  • Makes up 20% of cases
  • F>M
  • 2/3 with linear, the disease onset is prior to 18 years
  • Growth retardation of affected limb, permanent limb asymmetry from unilateral hypoplasia
  • Disabling pansclerotic morphoea of children: starts before 14, like generalized morphoea. Persistent atrophy of the underlying muscles and contractures. Periodontal atrophy may occur. Might be hard to tell from Ssc
110
Q

Morphoea lab findings

A
  • Unremarkable usually except for generalized and linear
  • ESR and serum protein usually normal, but eosinophilia may be present in early active phases of the disease
  • High titres of ANA or antibodies to ssDNA and histones in 40-80% in linear and generalized
  • 40% of <18 year olds have elevated ANA titres
111
Q

Morphoea histo

A
  • histology of morphoea depends on 2 factors:
    • stage and area of the lesion sampled
    • depth to which the disease extends
  • most changes best seen between the dermis and the subcutaneous fat
  • specimen definitely needs S/C fat
  • Inflammatory border:
    • vascular changes: vessel walls have endothelial swelling and oedema
    • capillaries and aterioles are surrounded by an infiltrate that has CD4 T cells, eos, plasma and mast cells
  • Later stages:
    • inflammatory infiltrate gone
    • rete ridges diminished, flattened DEJ
    • no oedema in the dermis and upper subcutis
    • collagen bundles with decreased space between the bundles
    • collagen in reticular dermis - densely packed
    • eccrine glands are atrophic and trapped
  • Deep morphoea: deep S/C tissue, involvement of underlying fascia
112
Q

Morphoeaform and Sclerodermoid Inflammatory Syndromes

A
  • variety of inflammatory diseases can result in sclerosis, some are associated with eosinophilia
  • eosinophils may be from an immune reaction to a defined toxic insult or antigenic stimulus (L-tryptophan syndrome or GVHD)
  • only some people develop sclerosis to exogenous agents so obviously there are only some people who are susceptible
  • Things to consider:
    • Lipodermatosclerosis
    • Vitamin K1 injection –> localized eosinophilic fasciitis
    • Vaccination associated morphoea
    • Paraffin and silicone injections or implants
    • Porphyrias –> morphoea like sclerosis in UV exposed sites
    • Radiation induced
      • 1/500 patients
      • primarily seen in breast caancer treatment
      • can present several years after therapy
      • marked sclerosis, erythema and pigmentary changes
    • Nephrogenic systemic fibrosis
    • Chronic GVHD
    • Mucinoses –> scleredema: diffuse woody induration to upper back and neck
    • Insulin dependent diabetics –> tightness and induration of acral skin
113
Q

Risk of all the different types of lupus turning into SLE

A
  1. Localized DLE have a 5% risk of developing SLE
  2. Generalized DLE have a 20% risk of developing
  3. Lupus panniculitis has a 35% risk of developing, and makes up to 2-3% of all SLE
  4. Rarely get SLE transformation with LE tumidus
  5. Chillblain lupus: 20% go on to develop SLE –> can ulcerate, hyperkeratotic keratodermous skin, mutations in TREX1 have been described
  6. SCLE 15-25%
114
Q

Meds that cause pemphigus erythematosus

A

penicillamine, propranolol, captopril, pyritinolol, thiopronine

115
Q

SLE in pregnancy

A
  • fertility fine if renal function good
  • worsening during pregnancy is uncommon
  • clinical remission or minimal lupus activity in 6 months before conception lowers the chances of a significant flare
  • renal disease predicts risk of pre-eclampsia, 1/3 will have preterm delivery, another third will have a c-section
  • APLS: foetal loss increases –> rx with LMWH and low dose aspirin
  • Prednisone recommended as <10% dose will cross the MF membrane
  • No evidence fo azathioprine to be discontinued, same for plaquenil
  • Screen patients for APLS before putting on oestrogen contraceptive
116
Q

Lupus IF

A

Granular deposits at DEJ & around Hair follicles  IgG/IgM (+/- C3 & IgA) at DE junction

117
Q

Antibody positivities in SLE

A
  • dsDNA - SLE specific
  • Anti-Sm 30% - SLE specific
  • ribosomal P - SLE specific - lupus psychosis more common
  • Antihistone antibodies —> associated with drug induced, but limited value in dx apparently now
  • Anti-RNP 23-40% of SLE—> characteristic of mixed CT disease
  • Anti-Ro —> 30-40% in SLE< 60-90% in SCLE, and ANA negative SLE patients
  • Anti-La: 10-15% –> increased risk of neonatal lupus (along with Ro)

Derm (57 decks)

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