What two antigens can be targets for bullous pemphigoid?
BP1(BP230) and BP2 (BP180)
*Note: these are both components of hemidesmosomes.
What is the most common region on BP180 that's targeted by autoantibodies in bullous pemphigoid?
NC16A domain (non-collagenous 16A domain), which is located extracellularly but close to the transmembrane domain
*Note: additional antigenic sites exist within both the extracellular and intracellular domains of BP180.
Other than bullous pemphigoid, list five other autoimmune blistering disorders that produce subepidermal blisters.
Linear IgA bullous dermatosis
Epidermolysis bullosa acquisita
Bullous systemic lupus erythematosus
Can bullous pemphigoid occur in children?
Yes, but only rarely
True or false: in about half of patients with bullous pemphigoid, a peripheral blood eosinophilia is noted.
True or false: systemic medications can lead to the development of bullous pemphigoid.
*Note: the list of implicated drugs is long.
True or false: in patients with bullous pemphigoid, circulating antibasement membrane antibodies will be present.
True; in 60-80% of patients circulating antibasement membrane antibodies can be detected (in addition to the antibodies deposited in the skin)
Where should a biopsy for DIF be taken if you suspect bullous pemphigoid?
Perilesional (i.e. unaffected) skin
What concentration of NaCl should be used to perform a salt split-skin test?
1 M NaCl
Can mucous membranes be affected in epidermolysis bullosa acquisita (EBA)?
Yes, just like in bullous pemphigoid (although it's not super common)
True or false: epidermolysis bullosa acquisita (EBA) has a classic "non-inflammatory" form and an "inflammatory" form.
True; the "inflammatory" form closely resembles bullous pemphigoid
Which finding on DIF is associated with bullous pemphigoid: an "n-serrated" or "u-serrated" pattern?
"n-serrated" pattern (also associated with LABD)
What type of pattern on DIF is associated with epidermolysis bullosa acquisita?
What enzyme should you test for before starting azithioprine?
What enzyme should you test for before starting dapsone?
True or false: potent topical steroids appear to be as effective as oral steroids for the treatment of bullous pemphigoid.
Can cicatricial pemphigoid lead to blindness?
What two mucosal sites are most commonly affected by cicatricial pemphoid?
Oral and conjunctival mucosae
Symblepharon can occur in cicatricial pemphigoid. What's symblepharon?
Fibrous tracts between the bulbar and palpebral conjunctival surfaces
Trichiasis can occur in cicatricial pemphigoid. What's trichiasis?
Eyelashes that grow back towards the eye, causing irritation to the cornea or conjunctiva
True or false: BP usually heals with scars.
False; cicatricial pemphigoid heals with scars (hence the name) but bullous pemphigoid does not
True or false: patients with cicatricial pemphigoid have disease limited to the mucosal surfaces.
False; most of the time lesions are limited to the mucosal surfaces, but in 25-30% of cases, skin lesions also occur
*Note: these present as erythematous plaques, which become sites for blister formation and erosions, with subsequent atrophic scarring.
What's Brunsting-Perry pemphigoid?
A variant of cicatricial pemphigoid where mucosal involvement is absent or minimal, and there's skin lesions limited to the head and neck. On the scalp, scarring results in cicatricial alopecia.
True or false: the histologic features of cicatricial pemphigoid and bullous pemphigoid are very similar.
True; both show subepithelial blister formation and linear IgG/C3 on DIF
Loss of vision is the most important complication of cicatricial pemphigoid, and life-threatening complications are rare. List one possible life-threatening complication.
Involvement of the larynx, trachea, or esophagus, leading to respiratory failure or inability to eat
Systemic steroids are generally inadequate for treating cicatricial pemphigoid. What is the systemic treatment of choice for rapidly progressive or severe ocular disease?
True or false: dapsone is a first-line therapy for controlling the oral and cutaneous lesions of cicatricial pemphigoid, however it is only appropriate for the treatment of mild ocular disease.
True; cyclophosphamide should be used to treat rapidly progressive or severe ocular disease
What is the autoimmune target in epidermolysis bullosa acquisita?
Do mucous membrane lesions occur in epidermolysis bullosa acquisita?
Yes, they can, although involvement is variable
The two clinical presentations of EBA are the inflammatory and non-inflammatory forms. Which diseases are mimicked in these two different presentations of the disease?
Inflammatory: mimics bullous pemphigoid or cicatricial pemphigoid
Non-inflammatory form: mimics dystrophic epidermolysis bullosa
Will EBA have a "n-serrated" or "u-serrated" pattern on DIF of salt-split skin?
True or false: EBA tends to respond rapidly to systemic steroids.
False; EBA tends to be chronic and refractory, and reponds only occasionally to systemic steroids and systemic immunosuppressants
What 2 self-Ag are directed against in BP?
BPAG2 (aka BP180, type XVII collagen) and BPAG1 (BP230); they are components of hemidesmosomes
In Caucasians, which HLA class II alleles are associated with BP?
DQB1*0301. In Japanese patients, alleles are DRB1*04, *1101 and DQB1*0302
Which domain of BPAG1 is bound by autoAb in BP?
NC16A domain (non-collagenous 16A domain)
What is one of the major isotypes of anti-BPAG2 autoAb?
IgG4 subclass, which is regulated by Th2 cytokines, which themselves are produced by T lymphocytes
When do you perform cancer screening in BP patients?
Systemic manifestations, atypical presentations, middle aged
Which drugs have been implicated in drug-induced BP? Name 3 classes
Diuretics (furosemide), analgesics, D-penicillamine antibiotics
Other than DIF, what other tests can be done for BP?
H&E, indirect DF, immunoelectron microscopy using gold, immunoblot, immunoprecipitation, ELISA
What are the 4 clinical criteria that STRONGLY indicate BP?
1) no skin atropy, 2) no mucosal involvement, 3) no H&N involvement, 4) >70yo
What is the treatment for BP?
Systemic corticosteroids (prednisone 0.5-1mg/kg/d, controls disease in 1-2wks, tapered over 6-9mths), superpotent topical steroids, +/- immunosuppressive drugs (MMF 1.5-3g/d, cyclosporine 1-5mg/kg/d, azathioprine, MTX, chlorambucil, cyclophosphamide). Remember to minimize complications (osteoporosis prophylaxis, gastric protection, assess cardiovascular function, infection)
What is the pathogenesis of CP? Hint: there are 4 subgroups of autoAb
Tissue-bound (less often circulating) autoAb against components of the BMZ in stratified epithelia of mucosa and skin. 1) anti-laminin 5, 2) anti-beta4 of alpha6beta4 integrin (ocular CP), 3) anti-BPAG2 (anti-BP Ag mucosal pemphigoid, mucosa and skin), 4) ?auto-Ab mediated (variable mucosa involvement, no skin involvement)
What are some complications of CP?
Blindness, periodontal ligament damage, teeth loss, adhesions, scarring (affecting conjunctiva, nasopharynx, esophagus, but rarely genitals/anus)
What is the skin variant of CP?
Brunsting-Perry pemphigoid (skin lesions on H&N, minimal mucosal involvement)
What is the treatment for CP?
Potent topical corticosteroids (mouthwash, gel, sprays, inhalers), tetracycline mouthwashes, good hygiene, intralesional steroids,
When is systemic treatment required for CP?
Severe ocular, laryngeal, esophageal involvement, unresponsive to topical tx. Dapsone 50-150mg/d, cyclphosphamide 1-2mg/kg/d, azathioprine 2mg/kg/d (note: adjust as per thiopurine methyltransferase), +/- surgery
What is the Ag targeted in epidermal bullosa acquisita?
Type VII collagen
What are the "classical" clinical features of EBA?
Non-inflammatory, mechanobullous disease, acral blisters that heal with atrophic scarring/milia/hyper/hypopigmentation
What are some complications of EBA?
Mitten deformity, syndactyly, nail dystrophy, nail loss, scarring alopecia
What distinguishes EBA from inherited dystrophic epidermolysis bullosa?
Lack FHx, late onset, positive DIF findings
What is the treatment for EBA?
Colchicine, systemic corticosteroids, azathioprine, MTX, cyclophosphamide, dapsone, gold, IGIv, syclosporine, extracorporeal photochemotherapy
What are the different clinical variants in BP? Hint: there are 11 varients
Classical, pretibial pemphigoid, dyshidrosiform pemphigoid, vesicular pemphigoid, pemphigoid nodularis, erythrodermic BP, lichen planus pemphigoides, gestiational pemphigoid, childhood BP, vulvar childhood BP, drug-induced BP
What are the predeominant IgG subclasses in BP?