PV is an autoimmune, intraepithelial,blistering disease affecting the skin andmucous membranes. mediated by circulating autoantibodiesdirected against keratinocyte cell junctionproteins termed desmogleins.Definition
binding of IgG autoantibodies tokeratinocyte desmosomes results in aloss of cell-cell adhesion, a processtermed acantholysis. Spaces formed between cells are filledby transudate fluid causing a blister.
occurs worldwide. incidence varies from 0.5-3.2 cases per100,000. PV incidence is increased in patients ofAshkenazi Jewish descent and those ofMediterranean origin.Frequency
SexMale-to-female ratio is approximately equal.AgeMean age of onset is approximately 50-60years; however, the range is broad.
Mortality/Morbidity PV is a potentially life-threateningautoimmune mucocutaneous disease. mortality rate is approximately 5-15%. Prognosis is worse in patients withextensive disease and in older patients.
The cause of Pemphigus remains unknown;however, several potentially relevant factorshave been identified. Genetic factors: Predisposition to pemphigus islinked to Certain major histocompatibilitycomplex (MHC) class II molecules,Etiology
Antibodies develop to deep intraepidermalsuprabasal desmosomal proteins commonto both skin and mucosa, so the blister isdeeper in location. Mucosal lesions may precede cutaneouslesions by months. Patients with mucosal lesions may presentto dentists, oral surgeons, orgynecologists.Physical
patients have ill-defined, irregularlyshaped, gingival, buccal or palatineerosions, which are painful and slow toheal. The erosions extend peripherally withshedding of the epithelium.
Erosions may spread to involve the larynxwith subsequent hoarseness. The patient often is unable to eat or drinkadequately because the erosions are souncomfortable. Other mucosal surfaces may be involved,including the conjunctiva, esophagus, labia,vagina, cervix, penis, urethra, and anus.
The primary lesion of PV is a flaccid blister filledwith clear fluid that arises on normal skin or on anerythematous base. The blisters are fragile; therefore, intact blistersmay be sparse. The contents soon become turbid, or the blistersrupture producing painful erosions, which is themost common skin presentation. Erosions often are large because of their tendencyto extend peripherally with the shedding of theepithelium.Skin:
Nails: Acute paronychia, subungualhematomas, and nail dystrophies havebeen reported with PV.
Nikolsky sign: In patients with active blistering,firm sliding pressure with a finger separatesnormal-appearing epidermis, producing anerosion. This sign is not specific for PV and isfound in other active blistering diseases. Asboe-Hansen sign: Lateral pressure on theedge of a blister may spread the blister intoclinically unaffected skin.
In some patients, erosions tend to developexcessive granulation tissue and crusting, andthese patients display more vegetating lesions. This type of lesion tends to occur morefrequently in intertriginous areas and on thescalp or face. The vegetating type of response can be moreresistant to therapy and can remain in one placefor long periods of time.
IgG develops against a superficial epidermaldesmosomal Ag named DsG1. Acantholysis and separation occurssubcorneally. The patient presents with exfoliative skinlesions and very superficial erosions with mildcrusting. Usually no mucosal lesions.
Histopathology Pemphigus vulgaris shows detachment ofkeratinocytes from each other due to loss ofdesmosome integrity, causing acantholysisand intraepidermal bulla formation. The point of separation in pemphigus vulgarisis usually in the suprabasal epidermis.
Direct immunofluorescence showing intercellular immunoglobulin Gthroughout the epidermis of a patient with pemphigus vulgaris.
The aim of treatment in pemphigus vulgaris(PV) is to decrease blister formation, promote healing of blisters and erosions, and determine the minimal dose of medicationnecessary to control the disease process.Medical Care
Anti-inflammatory agents Inhibit the inflammatory process by inhibitingspecific cytokine production.Corticosteroids (Prednisone) 1-1.5 mg/kg/d PO initial every am or in divideddoses; taper as condition improves; singlemorning dose is safer for long-term use, butdivided doses have more anti-inflammatory effect SE : - osteoprosis -DM-hypertension hyperacidity
Immunosuppressive agents adjuvants in patients with PV unresponsive tosteroids and/or other anti-inflammatory agents orin patients unable to tolerate prednisone.Azathioprine(Imuran)1 mg/kg/dCyclophosphamidesIVIGRituximab (anti CD20 monoclonal antibodies)
other adjuvant therapies : -treatment of 2ry infection - fluids - proteins - diuretics
is an autoimmune blistering disorderassociated with a gluten-sensitiveenteropathy (GSE) cutaneous manifestation of celiac disease. Gluten is a protein present in barley, rye, andwheat. Rice and oats belong to different species andare generally well tolerated.
Pathophysiology genetic predisposition for gluten sensitivity, coupled with a diet high in gluten, leads to the formation of IgA antibodies to gluten-tissue transglutaminase (t-TG), which is found in thegut. cross-react with epidermal transglutaminase (e-TG) Deposition of IgA and epidermal TG complexes in thepapillary dermis which triggers an immunologic cascade, resulting inneutrophil recruitment and complement activation.
Clinicallycharacterized by waxing and waning, pruriticeruption formed of: grouped excoriations; erythematous, urticarial plaques; andpapules with vesicles that are often excoriated toerosions by the time of physical examination . on the extensor surfaces of the elbows,knees, buttocks, and back. exquisitely pruritic,
Prognosis Dermatitis herpetiformis is a lifelongdisease, although periods ofexacerbation and remission arecommon.
Diagnosis neutrophil accumulation at thedermoepidermal junction, frequently localizingto the papillary tips of the basementmembrane zone (dermal papillary neutrophilicmicroabscesses). direct immunofluorescence of a skin biopsyshow deposition of immunoglobulin A (IgA) ina granular pattern in the upper papillarydermis.
Treatment Strict gluten-free diet results in normalization ofthe small bowel mucosal changes and control of thecutaneous manifestations of dermatitis herpetiformisin most patients. Dapsone is the mainstay of treatment. dose : 2-4 tab/day (50 mg/tab) i.e. 100-200 mg/day -SE: hemolysis (so monitor RBCS) & liver insult (somonitor Serum bilirubin) colchicine, cyclosporine, azathioprine, andprednisone are second agents.
Complications : (1) 2ry infection (2) 2ry eczematization (3) psychological upset up to suicidalattempts dt severe itching ??? Increased incidence of nonHodgkinlymphoma is reported.
-mainly in newborns-infection with staph occurs through the umbilical stump-staph produces exotoxins which digest the desmosomalproteins causing bullous eruption of the skin-characteristically there is very large single bulla that involve theTrunk & may involve both lower and upper limbs, its ruptureCauses severe agonizing pain & scalding of the skin-bullae are filled with pus-very bad general condition, so need ICU careStaphylococcal scalded skinsyndrome (4S syndrome)
- treatment : in the ICU :-(1) Fluids to replace fluid loss by oozing-(2)antibiotics (anti-staph ) : Cloxacillin in large doses.
Similar to 4 S – SYNDROME , but:-occurs at any age- it is not dt infection , it is a hypersensitivity reaction to adrug : antibiotics (sulpha),NSAIDS, Anticonvulsants ,anxiolytics- large bullae which are filled with serum not pus- treatment :1. stop the offending drugsTOXIC EPIDERMAL NECROLYSIS(TEN)