DCNP - Immune-Mediated Vesiculobullous Disorders Flashcards
Positive Nikolsky sign
Pemphigus vulgaris (NOT bullous pemphigoid)* Staphylococcal scaled skin syndrome (SSS)* Steven Johnson’s syndrome/Toxic epidermal necrolysis (SJS/TEN)
DIF
direct immunofluorescence (DIF) is the gold standard for detecting the presenceand location of tissue-bound autoantibodies, complements and fibrin deposits inskin or mucous membrane
DIF should be taken from about <1cm away from the blister
DIF performed using “salt-split skin” allows further differentiation and identifiesantibodies either on the roof (epidermal side) or base (dermal side or basement.* You must have immunochemical test (DIF, IIF or ELISA) to diagnose a blisteringdisease.* You cannot diagnose a blistering disease with just a H&E.* Avoid DIF in lower extremities d/t higher risk for false negative
pemphigus
Pemphigus vulgaris* (PV)- most common
Pemphigus vegetans- variant of PV with verruciform and hypertrophic and plaquesthat form after the bullae rupture. Favors mucous membranes, intertriginous areasand extensor surfaces* Pemphigus foliaceous- crusted erosions favoring the seborrheic distribution* Paraneoplastic pemphigus*- rare and usually cause by underlying tumor ormalignancy. Patient rapidly deteriorates.
pemphigus vulgaris
PV high mortality (5-10%); >90% if untreated* High risk for infections, secondary to immunosuppression* Autoantibodies Desmoglein 1 and Desmoglein 3* Rare; M = F; 50-60 yrs* Jewish or Mediterranean descent 10-fold* Drug induced: Thiols (i.e. captopril & penicillamine, cephalosporine, penicillin), non-Thiols (i.e. NSAIDs, ACE, CCB), & phenols (rifampin, heroin, etc)* Correlation with dementia, Parkinson’s disease and epilepsy.
FLACCID vesicles/bullae, blisters (fragile),painful erosions, crusts* POSITIVE Nikolsky sign* POSTIVE Asboe-Hansen sign* Oral mucosa (>60%) but not obvious (erosions)* Any mucosal surface but usu oropharynx* Scalp, upper trunk, groin
1 year mortality rate 5%
Systemic glucocorticosteroids (1,.0- 1.5 mg/kg/day) and rituximabo Steroid sparing adjunctive agents: mycophenolate mofetil (MMF), azathioprineo No absolute guidelines but if there are no new blisters in 1 week, then beginSLOW taper of prednisone. Usually decrease by 0.5mg/kg/day no more frequentthan every 2 weeks
Taper SLOWLY w/negative ELISA & no new blisterso Topical steroids can provide minimal relief
RITUXIMAB* Alternative first-line treatment (new Gold standard)* Anti-CD20 antibody* PV and refractory pemphigus foliaceusIn RCT 90 patients:* IV rituximab 1000mg infusion on day 1 and 14, then 500mg at month 12 and18* PLUS oral prednisone 0.5 mg/kg moderate and 1.0 mg kg severe diseasetapered over 12 to 18 months* At 24 months (off tx) - 89% Ritux + prednisone patients in remission vs 34%prednisone only* Median delay to complete remission was 277 for Ritux + prednisone and 677days for prednisone only* Less frequent severe AEs for Retux + prednisone vs prednisone only* SEs- most common are infusion reactions and infections
paraneoplastic pemphigus
Very rare; 2:1 F to M; >60 yrs* Associated with malignancy (usu. lymphoproliferative), remission usually aftersurgeryClinical Presentation* Severe mucocutaneous erosions (PV like)* Dusky targetoid (EM like)* RAPIDLY progressing
subepidermal blistering diseases
Pemphigoid (BP)
Lupus (bullous SLE)
Epidermolysis Bullosa Aquisita
Linear IgA
Dermatitis herpetiformis
Golfers wearing PLAID pants will get blisters down there!
bullous pemphigoid
Disruption of adhesion at dermo-epidermal junction (cell-matrix)* Autoantibodies: hemidesmosomes: BP 230 (BPAg1) & BP 180 (BPAg2)* Different types target different areas of the BMZ
Most common AIBD; self-limiting, rarely fatal, relapsing* Age >60-80yrs; rare in children; M = F* Association w/some drug therapies incl. loop diuretics, NSAIDs, spironolactone,phenothiazines, gliptins, biologics, etc.* No ethnic/racial associations
Clinical Presentation* VARIABLE!* Early prodromal, non-bullous stage, verypruritic* Urticarial plaques, patches, erythema* Tense, large, bullae* Negative Nikolsky sign* Bilateral, symmetrical* Flexural surfaces extremities and trunk* Mucosa lesions not common, transient* Milia not scars
Management* Mildo Potent topical steroids* Moderate/Severeo Initially, intermediate doses prednisoneo Steroid sparing agents- dapsone,mycophenolate mofetil, azathioprine,methotrexate, tetracycline, niacinamideo Usu. azathioprine older pt w/severedisease (TPMT)o RITUXIMAB (off-label)* Pedso Tetracycline and nicotinamideMonitoring* Serial antibodies
mucous membrane pemphigoid
Previously called Cicatricial Pemphigoid* Chronic, progressive, USUALLY scarring
Painful mucosa erosions, usually oral (any structures)* Tense blisters w/urticarial base* Oral- Laryngeal- sore throat, hoarseness, dysphagia* Ocular-s/s conjunctivitis, photosensitivity, blepharitis* Possible anogenitalManagement* Oralo Topical dexamethasone or cyclosporine (wish/spit) +/- dapsone* Severe or ocular- SYSTEMIC THERAPIES!!o Prednisoneo Rituximab initial treatmento Consider azathioprine, dapsone, sulfapyridine, minocycline, IVIG, andcyclophosphamide.o Ophthalmologic treatment- pull eyelashes, freq. lubrication, surgicalintervention
pemphigoid gestationis
Also called herpes gestationis* Usually resolves 6 months after delivery* Recurs w subsequent pregnancies, OCPs or menses (PEP is usually nulliparous/1st)* Low but risk of LBW or prematurity; <5% neonates w/blisters, some noted elevatedincidence of fetal demise reported; approx.. 1/3 patients have preterm labor* Incr. prevalence w/autoimmune disease (i.e. mom developing anti-thyroidantibodies/ Grave’s disease)
Goal to control pruritus and suppress blisters* Topical steroids and antihistamines* Oral steroids if severe (use lowest dose, non-fluorinated such as prednisone orprednisolone)* Only high risk systemics for severe &recalcitrant
dermatitis herpetiformis
Subepidermal blister at lamina lucida* Genetic predisposition for gluten sensitive enteropathy (GSE) (gliadin, the antigeniccomponent of gluten)* GSE causes IgA antibodies against tissue transglutaminase in GSE but cross reactswith epidermal transglutaminase in the skin
Onset 20-40 yrs old; M>F* 15-25% patients w/CD develop DH* Increased risk with other autoimmune dz (thyroid, DM, SLE, etc)* Higher incidence in northern European decent; lower in Asian and AA* Higher risk of intestinal lymphomas, B cell lymphoma at various sites, atrophic gastritis and achlorhydria, thyroid disease, IDDM, SLE, vitiligo, autoimmune
* INTENSELY pruritic (burning)
Chronic & remitting* MOSTLY excoriations, urticarial, papulovesicular.(usu smaller)* Clustered (herpetiform)* Extensor surfaces, symmetrical (Back/buttocks,arms/legs)* Prodrome burning/itching 8-12 hrs beforevesicles/bullae* VARIABLE course with flares* Subepidermal blister @ lamina lucida;neutrophilic microabscesses in dermal papillae,+/- fibrin deposition* DIF- Granular deposition of IgA on dermalpapillae; IIF- negative* Range of Pathology in DH is the Entire Range ofCeliac Disease* Virtually all patients some degree of celiac disease &are gluten sensitive but 80% noGI symptoms
IgA autoantibodies to epidermal transglutaminase(eTG) SKINo Most sensitive serology in treated/untreatedDHo 80-90% of DH patients on a regular dieto Responsible for the IgA deposition in skin ofDH* IgA autoantibodies to tissue transglutaminase (tTG) guto Hallmark of celiac disease and correlates with severity of intestinalinflammationo 30% DH are neg but have low grade CD & respond to gluten free diet
Life-long Gluten-free diet control of skin AND gut (↓ development of lymphoma)* Eliminating grains like wheat, barley, rye, spelt, kamut* Allowed: rice, oats & corn* Iodine & NSAIDS can induce eruptions
linear iga disease
Antibodies that target type VII collagen* IgA autoantibodies to BMZ targeting 97 kDa (a portion of the BPAg2 antigen) and +/-120 kDa antigen* Etiology but some h/o drug induced (vancomycin, NSAIDS, IFN-𝛼, etc.)
Adult- usually after 60 yrs old
Similar to BP and DH (no GI disease)* Symmetrical, favors extensor surfaces* Pruritic, annular or arcuate; “String ofbeads” or “cluster of jewels”* Secondary crusted excoriations* +/- mucous membrane (may appear likeocular MMF)* 30 to 60% of adults have spontaneousremission after couple years
First-line: Dapsone (responds quickly) off-labelo Start low and titrate up, adults start at 50mg – 150mg/dayo Topical corticosteroids or TIMs off-label for mild or localized lesions* Second-line:May add prednisone, or change to sulfapyridine, colchicine (especially if allergyof G6PD def., doxy + nicotinamide.o Severe disease and oral involvement may need more aggressive tx incl.prednisone +/or cyclophosphamideo Variable prognosis
epidermolysis bullosa acquisita
Autoantibody to Type VII collagen (acquired)* Middle age, rare in childhood* Assoc. w/ IBD, SLE, amyloidosis, RA, pulmonary fibrosis, thymoma, DM and CLL* NO family history of a bullous disorder
Rare autoantibody targeting Type VII collagen in DEJEpidemiology* Bimodal adult onset: 20-30s and 80-90s* Assoc. w/ Crohn’s & SLE. Patients should be screened* F>MClinical Presentation* 4 types with Classic most common(mechanobullous)* Trauma induced bullae (esp.hands/feet, fingers/toes & nails);fragility leading to poor QOL* Usually not involving mucousmembranes* Heal with milia/scarring
Topical steroids, dapsone or colchicine.o Moderate/severe▪ Prednisone (often high doses)▪ Recalcitrant- cyclosporine for control and then cyclophosphamide,azathioprine, IVIg, extracorporeal photopheresis, rituximab* Chronic and resistant, Childhood EBA better prognosis* Scarring, loss of hair/nails, strictures, contractures, miliaPatient Education* Avoid trauma/friction
epidermolysis bullosa
Inherited, usually presents soon after birth* Mechanobullous, skin and mucosa fragility* 4 types base on level of blister & mutation
Form shortly after birth with scarring or milia
Target management is supported!* Refer to EB Center w/experience dermatology specialists* NO targeted therapy* Individualize for age, type, severity,* Control of infection* Nutritional support* Prevention of complications* Handle newborns with extreme care* Genetic referral
