Pemphigus complex Flashcards
Prevention of auto-immunity by auto-reactive T cells (and B cells):
- Clonal deletion (central tolerance)
- Peripheral deletion (T cells, perhaps B cells): recognition of self-antigen → Fas-FasL interaction → apoptosis
- Immunological ignorance (T cells): hidden antigens
- Anergy (T cells, B cells): antigen presentation without co-stimulatory signals
- Suppression (T cells): Treg
Factors involved
- Genetics: genes for MHC, cytokines, Treg, IgA deficiency
- Infections: production of INF-γ (MHC-II up-regulation), superantigens, molecular mimicry
- IgA deficiency: exposure to mucosal microbes → cross-reactivity
- Vaccination
- Environmental: UV
- Hormonal: female predisposition in humans and rodents; not in D, C
Auto-immune- definition
adaptive immune response to autoantigens
Which part of the body have normal Ig deposition
nasal planum and footpads
Demonstration of serum auto-antibodies: indirect IF
-wich tissues are the best for PF,PV, PNP, AISBD
Canine PF: substrate of choice is neonatal mouse skin; in C feline footpad and oral mucosa
Canine PV: substrate of choice is canine gingival mucosa
Canine PNP: bladder epithelium
AISBD: substrate of choice is canine lip (especially intact and salt-split)
Phases of treatment:
- Induction: days to weeks
- Transition: gradual tapering until recurrence or discontinuation
- Maintenance: if recurrence during tapering; usually x 8-12 months
- Determination of cures: at transition or after maintenance phase
MOA of tetracyclines
a) inhibition of lymphocyte blastogenesis, Ab production;
b) inhibition of WBC chemotaxis;
c) inhibition of C3;
d) inhibition of PG, lipases and MMPs (collageneases);
e) downregulation of cytokines;
f) inhibition of angiogenesis,
g) inhibition of apoptosis
MOA of niacinamide
a) inhibition of mast cell degranulation;
b) inhibition of PDE;
c) inhibition of enzymes (proteases);
d) photoprotectant;
e) AcR agonist (cholinomimetic)
MOa of hydroxychloroquine
Increase pH → interference with MHC and antigen complex formation → blocks stimulation of Th cells; reduced presentation of auto-antigens (but not of foreign antigens)
Block TLR7 and TLR9 activation of DCs → inhibition of inflammatory cytokines
Protection from UV-induced cell damage and inflammation
Indications for hydroxychloroquine
generalized DLE (D), ECLE (D)
MOA of methotrexate
antimetabolite (cell cycle specific; folic acid antagonist) → alteration of DNA and RNA synthesis
Causes of Pemphigus
- Genetic factors
- UV light
- Drugs:
1) sulfydril (penicillamine),
2) amide (captopril, penicillins-also in H, cephalosporins),
3) thiol
Th of Pemphigus
- Glucocorticoids
- azathioprine
- mycophenolate mofetil
- chlorambucil,
- chrysotherapy;
In selected cases: 1) dapsone, 2) tetracycline-niacinamide, 3) vitamin E, 4) ω3/ω6 fatty acids, 5) PTX; 6) rituximab: monoclonal anti-CD20 antibody; 7) IV human immunoglobulin; 8) plasmapheresis and imunoabsorption
In refractory cases: restricted diet trial
+ Sun avoidance
Drug induced PF - def
-self-cure
-due to pharmacologic acantholysis,
drug-triggered PF- def
=continues
-due to auto-antibody production
Concurrent autoimmune diseases (19%) in PF
- immune-mediated polyarthritis,
- KCS,
- immune-mediated thrombocytopenia
Clinical peculiarities in H with PF
Urticaria may be a prodromal sign
Oedema of limbs and ventral abdomen: vasculitis, hypoalbuminemia
IHC - immunofluoresecnce of PF
- Direct: IgG (IgG2, IgG4) > C3 > IgM, IgA;
- Indirect: IgG1, IgG4;
polysulfated glycosaminoglycan- in wich disease we use
PF
Adequan 4.4 mg/kg IM or SC every 4 days (or less or more frequently as needed) as adjunctive treatment in refractory cases
wich drugs we add to PF in horses
1) fatty acids,
2) PTX,
3) sun avoidance,
4) polysulfated glycosaminoglycan (Adequan)
Causes of PV
- Idiopathic
- Drug-induced: thiabendazole (D), procainamide (D), phenytoin (D), sulfasalazine (D), polymyxin B (D)
Targeted Ag in PV
- Dsg III : H, D (60%),
- Dsg I (150 kDa): D (40%), possible in H
Antigens vs clinical subtype in PV
- Mucosal-dominant: dsg III
- Mucocutaneous: dsg III (mucosal lesions) + dsg I (skin lesions)
- Cutaneous: dsg I + dsg III (but the latter Abs are pathogenetically weak)
What is c-Myc and in wich disease is important
-pro-oncogen
-up-regulation in lesional and perilesional skin and mucosae → prolonged basal cell proliferation → delayed strengthening of desmosomes
PV
Specific clinical forms of PV
- Follicular PV: only hair follicles are affected; no mucosal or mucocutaneous lesions; truncal alopecia
- Nasal PV: only nasal planum (Dx from DLE, MMP and epitheliotropic lymphoma)
Ag in PNP
1) Desmoplakin I/II,
2) Envoplakin,
3) Periplakin,
4) Dsg III,
5) BPAG-1
Wich tumors are connected with PNP
- lymphoma,
- thymoma (also in C, H),
- sarcoma (spleen),
- mammary carcinoma,
- Sertoli cell tumour
Clinical forms in humans P Veg
- Hallopeau type: pustules → proliferative wart-like lesions, plaques, oral lesions; benign course
- Neumann type: pustules, vesicles, bullae → widespread erosions, oral lesions; refractory to treatment
P Veg is correlated with autoimmune
It represents panepidermal pustular pemphigus (some clinical differences; PPV does not have mucosal lesions
It is a more benign or abortive form of pemphigus vulgaris
Targeted Ag in P veg
Dsg I (D)
Clinical manifestations of P veg
- Vesicles, pustules
- Vegetations-papillomatous proliferations with pustules
- Mucosal lesions
IHC- immunofluorescence of Pemphigus erythematosus
Direct: IgG > C3; epidermis and basement membrane (D, C)
Indirect: negative (D, C)
ANA: low titres in 50% (D); a positive test is necessary for the diagnosis
