Pemphigus Tiffany Hsu 529 Joanne Kim 140 Jonathan

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Pemphigus Tiffany Hsu #529 Joanne Kim #140 Jonathan Miller #149 Hamid Shafizadeh #174

Pemphigus Tiffany Hsu #529 Joanne Kim #140 Jonathan Miller #149 Hamid Shafizadeh #174

Pemphigus Pathogenesis §Intraepithelial blister formation results from breakdown of intercellular adhesion, thus producing epithelial

Pemphigus Pathogenesis §Intraepithelial blister formation results from breakdown of intercellular adhesion, thus producing epithelial cell separation known as acantholysis §Caused by antibody-mediated autoimmune reaction to desmogleins (Dsg), desmosomal transmembrane glycoproteins, leading to acantholysis § Classified into pemphigus vulgaris (PV), with suprabasal acantholysis, and pemphigus foliaceus (PF), with acantholysis in the more superficial epidermis §Pemphigus vulgaris is characterized by Ig. G autoantibodies against desmoglein 3 (Dsg 3), whereas the target of PF is Dsg 1, although about 50% of PV patients also have Dsg 1 autoantibodies; desmoplakin is another target

Pathogenesis § Circulating autoantibodies are responsible for disruption of intercellular junctions and loss of

Pathogenesis § Circulating autoantibodies are responsible for disruption of intercellular junctions and loss of cell-to -cell adhesion. § Extent of epithelial cell separation are directly proportional to the titer of circulating pemphigus antibody. § It is believed pemphigus antibody, once bound to the target antigen (desmoglein 1, desmoglein 3, desmoplakin), activates an epithelial intracellular proteolytic enzyme that acts at the desmosometonofilament complex.

Clinical Presentation § Three major types of pemphigus: n n n Pemphigus vulgaris Pemphigus

Clinical Presentation § Three major types of pemphigus: n n n Pemphigus vulgaris Pemphigus folaceus Paraneoplastic pemphigus Pemphigus vulgaris is by far the most common of the three types.

Clinical Presentation § Pemphigus presents with vesicles and/or bulla on skin and mucous membranes.

Clinical Presentation § Pemphigus presents with vesicles and/or bulla on skin and mucous membranes. § These vary in size from 1 -3 cm in diameter. § These rupture quickly and more often appear as ulcerations. § The mucous membranes of the mouth are the most common site for pemphigus lesions § Other common sites: n n n Face and scalp Chest and armpits groin

Pemphigus vulgaris

Pemphigus vulgaris

Pemphigus vulgaris

Pemphigus vulgaris

Clinical Presentation § Most common age group initially diagnosed with pemphigus is 40 -60

Clinical Presentation § Most common age group initially diagnosed with pemphigus is 40 -60 years old. § Children are very rarely affected. § People of Jewish or Mediterranean descent are most commonly diagnosed.

Diagnostic tests for Pemphigus § Positive Nikolsky sign § Indirect fluorescent antibody (IFA) -the

Diagnostic tests for Pemphigus § Positive Nikolsky sign § Indirect fluorescent antibody (IFA) -the qualitative and semi-quantitative detection of antibodies associated with pemphigus § The direct immunofluorescence test (DIF) -detects the antibody deposition in the tissues -very reliable diagnostic test for pemphigus -can remain positive for several years after regression of the disease

Pemphigus Immunofluorescence

Pemphigus Immunofluorescence

Histology of Pemphigus §Pemphigus typically displays acantholysis with some dyscanthosis near the granular layer.

Histology of Pemphigus §Pemphigus typically displays acantholysis with some dyscanthosis near the granular layer. The acantholytic, rounded cells are termed Tzanck cells, which are pathognomonic to Pemphigus Vulgaris §Within the papillary dermis there is a sparse perivascular lymphocytic infiltrate with scattered eosinophils.

Treatment Goals § Reduce inflammatory response -decrease blister formation -promote healing of blisters and

Treatment Goals § Reduce inflammatory response -decrease blister formation -promote healing of blisters and erosions § Reduce autoantibody production § Use minimal dose of medication needed to control the disease

Conventional Therapy § Systemic corticosteroids -1 mg/kg prednisone initially used with gradual tapering -severe

Conventional Therapy § Systemic corticosteroids -1 mg/kg prednisone initially used with gradual tapering -severe adverse side effects: HTN, osteoporosis, atherosclerosis, peptic ulcer disease, aseptic necrosis, diabetes, susceptibility to infections, septicemia, others § Immunosuppressive and anti-inflammatory agents -Used in combo with corticosteroids to provide a potential corticosteroid-sparing effect (minimize steroid use) -adverse side effects

Other Therapies § § Dapsone Methotrexate Mycophenolate mofetil Dexamethasone-Cyclophosphamide Pulse Therapy § Plasmapheresis §

Other Therapies § § Dapsone Methotrexate Mycophenolate mofetil Dexamethasone-Cyclophosphamide Pulse Therapy § Plasmapheresis § Rituximab + Intravenous Immune Globulin

Other Therapies § Dapsone (anti-inflammatory) -clinical response usually seen after 1 st week of

Other Therapies § Dapsone (anti-inflammatory) -clinical response usually seen after 1 st week of treatment -most common adverse effect: hemolytic anemia § Methotrexate (immunosuppressant) -risk of megaloblastic anemia, bone marrow suppression, liver and renal toxicity § Mycophenolate Mofetil (chemotherapeutic) -inhibits lymphocyte proliferation -more studies with long-term follow up are needed to determine efficacy and proper dosing § Dexamethasone-Cyclophosphamide Pulse Therapy (Anti-inflammatory + chemotherapeutic agent) -studies have shown remission of PV, but patients suffered multiple infections due to receiving high doses of immunosuppressants § Plasmapheresis -reduces the autoantibody in the plasma through a filtration mechanism -for severe refractory PV -few studies done; no established protocol

Other Therapies § Rituximab (monoclonal antibody) + Intravenous Immune Globulin (IVIg) -study published October

Other Therapies § Rituximab (monoclonal antibody) + Intravenous Immune Globulin (IVIg) -study published October 2006: study on 11 patients who had inadequate responses to conventional therapy -Initially 2 cycles of rituximab given once weekly for 3 weeks and IVIg given in the 4 th week; followed by monthly infusion of rituximab and IVIg for 4 consecutive months -Of 11 patients, 9 had complete and rapid resolution of lesions and a clinical remission lasting an average of 31 months. All immunosuppressive therapy, including prednisone, could be discontinued before ending rituximab treatment in all patients. Side effects that have been associated with rituximab were not observed, nor were infections. -recommended for refractory PV -larger, controlled study needed

1. Pemphigus is characterized by Ig. G autoantibodies against which proteins: A. Desmogleins B.

1. Pemphigus is characterized by Ig. G autoantibodies against which proteins: A. Desmogleins B. Epiligrin C. Collagen D. Bullous pemphigoid antigen-2 Answer: A 2. What is the most common type of pemphigus? A. Pemphigus foliaceus B. Pemphigus vulgaris C. Paraneoplastic pemphigus D. None of the above Answer: B