What is the major abnormality in Pyoderma gangrenosum?
Neutrophil dysfunction (respond to anti-neutrophil Tx such as dapsone)
Genetic, systemic inflammation
What are the clinical features of PG?
Appearnce of an inflammatory papule, pustule, vesicle, or nodule that subsequently expands and breaks down to form an erosion or ulcer. Lesion development is often rapid and the level of pain is often greater than expected based upon the appearance of the ulcer
lower extremities and trunk
The edge of the ulcer usually exhibits a bluish or violaceous color and demonstrates an undermined quality
The base of the ulcer is purulent and necrotic, and the depth of the ulcer often extends into subcutaneous fat and occasionally reaches the fascia
What are the association of PG?
IBD, IgA monoclonal gammopathy, Arthritis
What are the criteria for diagnosing PG?
Major criteria (must have both):Rapid progression of a painful, necrolytic cutaneous ulcer with an irregular, violaceous, and undermined border (1 to 2 cm per day or 50 percent increase in size within one month)Other causes of cutaneous ulceration have been excluded (usually necessitates skin biopsy and laboratory investigations)
Minor criteria (must have two):History suggestive of pathergy or clinical finding of cribriform scarring, Systemic disease associated with PG (inflammatory bowel disease, arthritis, IgA gammopathy, or malignancy), Histopathologic findings (sterile dermal neutrophilia, ± mixed inflammation, ± lymphocytic vasculitis), Treatment response (rapid response to systemic glucocorticoid treatment)
What is panniculitis?
Panniculitis is an inflammatory reaction in the subcutaneous adipose tissue that may preferentially affect (1) the connective tissue septa separating lobules of fat, or (2) the lobules of fat themselves. Panniculitis often involves the lower legs and usually has a subacute to chronic course.
What are the features of erythema nodosum?
Erythema nodosum is the most common form and usually has an acute presentation. Its occurrence is often associated with infections (β-hemolytic streptococcal infection, tuberculosis and, less commonly, coccidioidomycosis, histoplasmosis, and leprosy), drug administration (sulfonamides, oral contraceptives), sarcoidosis, inflammatory bowel disease
poorly defined, exquisitely tender, erythematous plaques and nodules that may be more readily palpated than seen
Over the course of weeks, lesions usually flatten and become bruiselike, leaving no residual clinical scars, while new lesions develop.
What are the features of Erythema induratum?
Uncommon type of panniculitis that affects primarily adolescents and menopausal women.
Primary vasculitis affecting deep vessels supplying lobules of the subcutis, with subsequent necrosis and inflammation within the fat.
Erythema induratum presents as an erythematous, slightly tender nodule that usually goes on to ulcerate.
What are the histopathological characteristics of EN and EI?
Erythema nodosum: In early lesions, widening of the connective tissue septa is due to edema, fibrin exudation, and neutrophilic infiltration. Later, infiltration by lymphocytes, histiocytes, multinucleated giant cells, and occasional eosinophils is associated with septal fibrosis. Vasculitis is not present.
In erythema induratum, granulomatous inflammation and zones of caseous necrosis involve the fat lobule. Early lesions show necrotizing vasculitis affecting small- to medium-sized arteries and veins in the deep dermis and subcutis.
What are the features of rosacea?
(1) flushing episodes (pre-rosacea), (2) persistent erythema and telangiectasia, (3) pustules and papules, and (4) rhinophyma—permanent thickening of the nasal skin by confluent erythemaous papules and follicular prominence.
What are the histological features of rosacea?
Rosacea is characterized by a nonspecific perifollicular infiltrate composed of lymphocytes surrounded by dermal edema and telangiectasia. In the pustular phase neutrophils may colonize the follicles, and follicular rupture may cause a granulomatous dermal response.
The development of rhinophyma is associated with hypertrophy of sebaceous glands and follicular plugging by keratotic debris.
What is the pathophysiology of rosacea?
Individuals with rosacea have high cutaneous levels of the endogenous antimicrobial peptide cathelicidin, an important mediator of the innate immune response
What are the major blister types?
A, In a subcorneal blister the stratum corneum forms the roof of the bulla (as in pemphigus foliaceus). B, In a suprabasal blister a portion of the epidermis, including the stratum corneum, forms the roof (as in pemphigus vulgaris). C, In a subepidermal blister the entire epidermis separates from the dermis (as in bullous pemphigoid).
What are the major types of antibodies in blister disease?
In pemphigus vulgaris, autoantibodies against Dsg1 and Dsg3 cause blisters in the deep suprabasal epidermis.
n pemphigus foliaceus, the autoantibodies are against Dsg1 alone, leading to superficial, subcorneal blisters.
In bullous phemphigoid, autoantibodies bind BPAG2, a component of the hemidesomes, leading to blister formation at the level of the lamina lucida of the basement membrane.
Dermatitis herpetiformis is caused by lgA autoantibodies to the fibrils that anchor hemidesmosomes to the dermis (reticulin)
What is the hallmark of pemphigus?
Pemphigus is a blistering disorder caused by autoantibodies that result in the dissolution of intercellular attachments within the epidermis and mucosal epithelium
What are the features of pemphigus vulgaris?
Mucosa and skin, especially on the scalp, face, axilla, groin, trunk, and points of pressure.
It may present as oral ulcers that may persist for months before skin involvement appears.
Primary lesions are superficial vesicles and bullae that rupture easily, leaving shallow erosions covered with dried serum and crust
What are the features of pemphigus vegetans?
usually presents not with blisters but with large, moist, verrucous (wart-like), vegetating plaques studded with pustules on the groin, axillae, and flexural surfaces.
What are the clinical manifestations of pemphigus foliaceous?
Pemphigus foliaceus is a more benign form that is endemic in Brazil (where it is called fogo selvagem) and occurs sporadically in other geographic regions. Sites of predilection are the scalp, face, chest, and back.
No mucosal involvement
Bullae are so superficial that only zones of erythema and crusting, sites of previous blister rupture resulting in superficial erosions, are usually present on physical examination
What is the feature of Pemphigus erythematosus?
localized, less severe form of pemphigus foliaceus that may selectively involve the malar area of the face in a lupus erythematosus–like fashion
What is the strongest association in paraneoplastic pemphigus?
What is the histological hallmark of pemphigus?
What are the histopathological features of PV?
In pemphigus vulgaris and pemphigus vegetans, acantholysis selectively involves the cells immediately above the basal cell layer.
In the vegetans variant, there is also overlying epidermal hyperplasia.
The suprabasal acantholytic blister that forms is characteristic of pemphigus vulgaris
The single layer of intact basal cells that forms the blister base has been likened to a row of tombstones.
In pemphigus foliaceous blisters selectively involves ....................
the superficial epidermis at the level of the stratum granulosum
What is the IF features of pemphigus?
All forms of pemphigus are caused by IgG autoantibodies against desmogleins, and show linkage to specific HLA types. By direct immunofluorescence, lesional sites show a characteristic net-like pattern of intercellular IgG deposits.
IgG is usually seen at all levels of the epithelium in pemphigus vulgaris, but tends to be more superficial in pemphigus foliaceus
What is the mechanism of injury in pemphigus?
The antibodies seem to function primarily by directly disrupting the intercellular adhesive function of the desmosomes and may activate intercellular proteases as we
Why ab to only dsg3 does not cause skin manifestation but only mucosal manifestation?
Because on the skin dsg1 compensate for dsg3 loss
What are the clinical features of bullous pemphigoid?
tense bullae, filled with clear fluid, on normal or erythematous skin
The bullae do not rupture as easily as do the blisters seen in pemphigus and, if they are not secondarily infected, heal without scarring. Sites of involvement include the inner aspects of the thighs, flexor surfaces of the forearms, axillae, groin, and lower abdomen.
Oral lesions are present in 10% to 15% of affected individuals, usually appearing after the cutaneous lesions
Some patients have urticaria and pruritus
What is the histology of bullous pemphigoid?
The separation of bullous pemphigoid from pemphigus is based on the identification of subepidermal, nonacantholytic blisters.
Early lesions show a superficial and sometimes deep perivascular infiltrate of lymphocytes and variable numbers of eosinophils, occasional neutrophils, superficial dermal edema, and associated basal cell layer vacuolization.
Eosinophils showing degranulation are typically detected directly beneath the epidermal basal cell layer. The vacuolated basal cell layer eventually gives rise to a fluid-filled blister.
What is the IF of bullous pemphigoid?
linear deposition of immunoglobulin and complement in the basement membrane zone
Generation of auto-antibodies to this hemidesmosome component results in continuous and linear deposition of IgG along the basement membrane and the fixation of complement with subsequent tissue injury by means of locally recruited neutrophils and eosinophils.
Blister forms at lamina lucida of BM
What is the clinical feature of dermatitis herpetiformis?
urticaria and grouped vesicles
urticarial plaques and vesicles of dermatitis herpetiformis are extremely pruritic.
The lesions are bilateral, symmetric and grouped, involving preferentially the extensor surfaces, elbows, knees, upper back, and buttocks
What is the pathogenesis of DH?
Genetically predisposed individuals develop lgA antibodies to dietary gluten (derived from the wheat protein gliadin). The antibodies cross-react with reticulin, a component of the anchoring fibrils that tether the epidermal basement membrane to the superficial dermis
What are the histological features of DH?
As an early event, fibrin and neutrophils accumulate selectively at the tips of dermal papillae, forming small microabscesses
The basal cells overlying these microabscesses show vacuolization and focal dermoepidermal separation that ultimately coalesce to form a true subepidermal blister.
By direct immunofluorescence, dermatitis herpetiformis shows discontinuous, granular deposits of lgA selectively localized in the tips of dermal papillae
What is epidermolysis bullosa?
Epidermolysis bullosa constitutes a group of disorders caused by inherited defects in structural proteins that lend mechanical stability to the skin. The common feature is a proclivity to form blisters at sites of pressure, rubbing, or trauma, at or soon after birth
Simplex--> kerarin 5, 14
Junctional (lamina lucida)
Dystrophic-->Collagen VII beneath lamina densa
increased risk of SCC in chronic blisters
What are cutaneous features porphyria?
Cutaneous manifestations consist of urticaria and vesicles that heal with scarring and that are exacerbated by exposure to sunlight.
The primary alterations by light microscopy are a subepidermal vesicle with associated marked thickening of the walls of superficial dermal vessels.