Autoinflammatory Flashcards

Question

What causes neonatal lupus?

Answer 1

Occurs when maternal anti-Ro antibodies pass over to children

Answer 2

- 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

Answer 3

- 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

Answer 4

- Nails - Nail fold erythema - Splinter haemorrhages - Red lunulae - Nail fold hyperkeratosis - Nail ridging - Onycholysis - Onychomadesis - Punctate or striate leukonychia

Answer 5

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

Answer 6

- Vasculitis - Retiform or stellate purpura - Gangrene - Periungual infarcts - Splinter haemorrhages - Vasculopathy - Rayanuds - Live do reticularis - Atrophied blanche - Cryoglobulinaemia

Answer 7

SOAPBRAINMD —> need 4 or more - Serositis - Oral ulcers - Arthritis - Photosensitivity - Blood - Renal - ANA - Immunologic - Neurologic - Malar rash - Discoid rash

Answer 8

- 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

Answer 9

- 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)

Answer 10

- 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

Answer 11

- 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

Answer 12

- 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

Answer 13

- Major: - Clinical - Exclude other causes of ulcer - Minor - Pathergy - Responds to treatment - Histology - Associated condition identified

Answer 14

- 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

Answer 15

- Cutaneous - Palpable purpura - Livedo racemosa - Splinter haemorrhages - A real macules - Ulcers - Urticaria plaques

Answer 16

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

Answer 17

- No granulomas | - Segmental necrotizing vasculitis of small blood vessels

Answer 18

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

Answer 19

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

Answer 20

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

Answer 21

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

Answer 22

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

Answer 23

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

Answer 24

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

Answer 25

- Pred + cyclophosphamide - Steroids + ritux equally effective now - ? Infliximab - If limited GPA —> just for trimethoprim

Answer 26

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

Answer 27

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

Answer 28

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

Answer 29

- Lung - Asthma - Capillarity —> haemorrhage - Neuro - Mononeuritis multiples - Cardio - Cardiomyopathy - Pericarditis - Renal - Necrotizing GN - MSK - GIT - Ocular

Answer 30

- Peripheral eosinophilia - Elevated IgE - MPO> PR3 - Some not ANCA positive

Answer 31

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

Answer 32

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

Answer 33

- 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%

Answer 34

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

Answer 35

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

Answer 36

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.

Answer 37

- 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

Answer 38

- 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

Answer 39

``` Digital pits Fibrosis Dyspigmentation Raynaud's Calcinosis cutis Telangiectasias Cutaneous ulcers ```

Answer 40

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

Answer 41

- usually near joints and distal locations | - dry, hypohydrosis and pruritis, with diminished hair growth

Answer 42

- 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

Answer 43

- 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

Answer 44

- 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

Answer 45

- 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

Answer 46

- 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

Answer 47

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

Answer 48

- 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

Answer 49

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

Answer 50

low dose warfarin, calcium channel blockers, sodium thiosulfate

Answer 51

- Females 2-3 times more | - Malignancy most associated with adult onset clinically amyopathic dermatomyositis

Answer 52

- 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

Answer 53

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

Answer 54

- 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

Answer 55

- 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

Answer 56

- 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

Answer 57

- 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

Answer 58

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

Answer 59

- 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

Answer 60

- 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

Answer 61

- 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

Answer 62

- Anti-synthetase: autoantibodies, fever, erosive polyarthritis, mechanic's hands, Raynaud, interstitial lung disease - about 20% - targets intracytoplasmic protein synthesis

Answer 63

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

Answer 64

- Adult DM and juvenile DM - Cutaneous disease, milder muscle disease with good response to treatment - 15%

Answer 65

- 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

Answer 66

- cancer associated in adult DM | - DM with calcinosis, peripheral oedema, myalgia, dysphagia, mild skin disease

Answer 67

adult DM, may present with clinically amyopathic

Answer 68

- 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

Answer 69

- 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

Answer 70

- 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

Answer 71

- 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

Answer 72

- 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

Answer 73

- 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

Answer 74

- 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)

Answer 75

- 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

Answer 76

- Gene mutation in FBN1 which encodes fibrillin-1 | - disturbance in organization of collagen and glycosaminoglycans within the ECM results in giant collagen fibrils

Answer 77

- 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

Answer 78

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

Answer 79

- nothing works | - physical therapy

Answer 80

- 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

Answer 81

- 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

Answer 82

- Autoantibodies generally same as population except for the following 2: - 1. anti-ssDNA-topoisomerase 2a, phospholipid, fibrillin-1 and histone bodies (AHA) - 2. 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

Answer 83

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

Answer 84

- 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

Answer 85

- 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

Answer 86

- 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

Answer 87

- 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

Answer 88

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%

Answer 89

penicillamine, propranolol, captopril, pyritinolol, thiopronine

Answer 90

- 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

Answer 91

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

Answer 92

- 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)