last topic 1st sm Flashcards
explain Pemphigus vulgaris
-Thekeratinocytesare cemented together at unique sticky spots calleddesmosomes. In pemphigus vulgaris,immunoglobulintype G (IgG)autoantibodiesbind to aproteincalleddesmoglein3 (dsg3), which is found in desmosomes in the keratinocytes near the bottom of theepidermis. The result is the keratinocytes separate from each other, and are replaced by fluid (the blister). About 50% of patients with pemphigus vulgaris also have anti-dsg1antibodies.
-Most patients with pemphigus vulgaris first present withlesionson themucous membranessuch as the mouth. Blisters usuallydevelopon the skin after a few weeks or months,although in some cases,mucosallesions may be the onlymanifestationof the disease
-Skin lesions appear as thin-walledflaccidblisters filled with clear fluid that easily rupture causing itchy and painful erosions. They most often arise on the upper chest, back, scalp, and face. Erosions in the skin folds may develop into vegetative lesions which aregranularandcrusted(pemphigus vegetans). The skin around thenailsmay be painful, red, and swollen.
-In comparison to white skin, darker skin tones may differ in their presentation which can cause diagnostic delay. Diagnostic features in darker skin tones may include flaccid blister which lackerythemaandhyperpigmentedplaqueswith superficialerosionandhaemorrhagiccrusting. At later and more advanced stages, plaques with a pink base and surroundinghyperpigmentationare present
-The inside of the mouth is commonly involved in pemphigus vulgaris. Involvement of thepharynxandlarynxcause pain on swallowing and a hoarse voice. Nasal involvement causes congestion and bleeding. Theconjunctiva,oesophagus,labia,vagina,cervix, penis,urethraandanusmay also be affected.
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-Diagnosis of pemphigus vulgaris : generally requires abiopsyof a blister:Pemphigus is confirmed bydirectimmunofluorescencestaining ofperilesionalskin biopsy sections to reveal immunoglobulin (Ig)G antibodies orcomplementon the cell surfaces of keratinocytes.\
-In most cases, circulating antibodies can be detected by a blood test (indirect immunofluorescence test)
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-treatment :Theprimaryaim of treatment of pemphigus vulgaris is to decrease blister formation, prevent infections and promote healing of blisters and erosions [4.5].Systemiccorticosteroids>are the mainstay of medical treatment for controlling the disease, usually in the form of moderate to high doses oforal prednisone or prednisolone, or as pulsed intravenous methylprednisolone. Since their use, many deaths from pemphigus vulgaris have been prevented (themortalityrate dropped from 99% to 5–15%). Corticosteroids are not a cure for the disease but improve the patient’s quality of life by reducing disease activity. The doses of corticosteroids needed tocontrolpemphigus vulgaris and the length of time on treatment may result in serious side effects and risks.
-Topical therapy forcutaneouspemphigus vulgaris may includetopical steroidsandemollients.
Treatment of mucosal pemphigus vulgaris may include variousformulationsof atopical steroid,intralesional steroid, topicaltacrolimus, or topicalciclosporin.
explain Bullous pemphigoid
-Bullous pemphigoid often presents in people over 80 years of age, and mostly affects people over 50. It can occur in younger adults, butbullous pemphigoid in infants and childrenis rare.
-There is an association with humanleukocyteantigen(HLA) indicating ageneticpredispositionto the disease.
-A drug, an injury, or skininfectioncan trigger the onset of disease.
-Bullous pemphigoid is the result of an attack on thebasement membraneof theepidermisbyIgG+/-IgEimmunoglobulins(antibodies) and activatedTlymphocytes(white blood cells). The target is theproteinBP180 (also called Type XVIIcollagen), or less frequently BP230 (a plakin). Theseproteinsare within the NC16A domain of collagen XVII. They are associated with thehemidesmosomes, structures that ensure theepidermalkeratinocytecells stick to thedermisto make a waterproof seal, The binding of theautoantibodiesto the proteins and release ofcytokinesfrom theT cellslead tocomplementactivation, recruitment ofneutrophils(acuteinflammatorycells) and the release ofproteolyticenzymes. These destroy the hemidesmosomes and cause the formation of subepidermal blisters.
-symptoms :Bullous pemphigoid causes severe itch and (usually) large, tensebullae(fluid-filled blisters), which rupture formingcrustederosions.
-sites :Bullous pemphigoid typically involves theflexoraspects of the limbs. It may belocalisedto one area, orwidespreadon the trunk andproximallimbs.
Frequently it affects the skin around skin folds.
Blisters inside the mouthand ingenitalsites are uncommon.
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–treatment :
-If the pemphigoid is very widespread, hospital admission may be arranged to dress blisters and erosions.
—Medical treatment involves:
-Ultrapotenttopical steroidsto treat limited disease < 10% of body surface (eg, clobetasol propionatecream)
-Moderate potencytopical steroidsandemollientsto relieve itch and dryness
-Systemicsteroids(eg, prednisone)
-Tetracyclineantibiotics, usually doxycycline 200 mg/day; doxycycline has fewer adverse effects than oralcorticosteroidsand is effective on its own for mild disease
-Other steroid-sparing medications on their own or in combination with steroids
-Antibioticsfor secondarybacterial infection
-Pain relief.
-NB! Nikolsky’s sign has been a very useful diagnostic tool in cases of skin disorders like pemphigus, toxic epidermal necrolysis, etc., The sign is demonstrated when lateral pressure is applied on the border of an intact blister, which results in the dislodgment of the normal epidermis and extension of the blister.
explain Duhring-Brocq disease
-Dermatitis herpetiformis (DH) is aninflammatoryimmunobullousdisease of the skin and acutaneousmanifestationof coeliac (celiac) disease, agluten-sensitive enteropathy.
The name herpetiformis is derived from the tendency for blisters to appear in clusters, resemblingherpessimplex. However,DH is not due to viralinfection.
DHis also known as Duhring-Brocq disease.
-Who gets dermatitis herpetiformis?
1-age at diagnosis is 40–50 years.
2-There is a male predominance of 2:1.
3-More females <20 years are affected than males; males tend to present at a later age.
4-There is ageneticpredispositionwith an association with humanleukocyteantigens(HLA) DQ2 and DQ8. ~90% of patients with coeliac disease carry HLA-DQ2, leaving only a small proportion of patients with lower risk heterodimers (such as HLA-DQ8).10–15% of individuals with DH have an affectedfirst degree relative.
–pathogenesis :Dermatitis herpetiformis (DH) and coeliac disease are due to intolerance to the gliadinfractionof gluten found in wheat, rye, and barley.
Gluten triggers production ofIgAantibodiesand an autoimmune process that targets the skin and gut.
In coeliac disease, gluten causes intestinalinflammationresulting in diarrhoea, tiredness, weight loss, abdominal discomfort, and metabolic consequences of malabsorption.
The majority (>90%) of patients withDH also havegluten-sensitive enteropathy. Gastrointestinal symptoms are usually mild; some patients remainsymptom-free.
-symptoms :DH presents as intense itch and asymmetricalblisteringrash.Vesicles(often 3–5 mm in diameter) or blistersdeveloponerythematousskin but are often eroded andcrusteddue to scratching.
-How does dermatitis herpetiformis differ in skin of colour?
While uncommon, clinical features are similar, although postinflammatorypigmentationis more prominent
-diagnosis :
1-Skinbiopsyis usually necessary to confirm DH.
2-Perilesional skin biopsy usingdirectimmunofluorescenceis the gold standard test for diagnosis of DH (90–95% sensitivity; 95–100% specificity).
–treatment :
–life style : Gluten-free diet
A gluten-free diet for life is strongly recommended in patients with DH, as it:
Reduces the requirement for medication tocontrolDH
Improves associatedgluten-sensitive enteropathy
Enhances nutrition and bone density
May reduce the risk ofdevelopingother autoimmune conditions
May reduce the risk of intestinallymphoma.
It may take up to 2 years for a gluten-free diet to reach itsmaximaleffect.
-medication :Dapsoneis the treatment of choice for DH, as it usually reduces itch within 3 days.
