bullous diseases(group a)

Blistering diseases

ByCarmen I Farid . MD

Definition :

They are skin diseases presenting mainly by blistering lesions

Classification :

A. congenital : Epidermolysis bullosa B. immunological : 1. pemphigus 2. dermatitis herpitiform C. OTHERS : 1. 4 S-syndrome 2. toxic epidermal necrolysis

Autoimmune Blistering Diseases

PEMPHIGUS

PV is an autoimmune, intraepithelial, blistering disease affecting the skin and mucous membranes.

mediated by circulating autoantibodies directed against keratinocyte cell junction proteins termed desmogleins.

Definition

binding of IgG autoantibodies to keratinocyte desmosomes results in a loss of cell-cell adhesion, a process termed acantholysis.

Spaces formed between cells are filled by transudate fluid causing a blister.

occurs worldwide. incidence varies from 0.5-3.2 cases

per 100,000. PV incidence is increased in patients

of Ashkenazi Jewish descent and those of Mediterranean origin.

Frequency

SexMale-to-female ratio is approximately

equal.AgeMean age of onset is approximately

50-60 years; however, the range is broad.

Mortality/Morbidity

PV is a potentially life-threatening autoimmune mucocutaneous disease.

mortality rate is approximately 5-15%.

Prognosis is worse in patients with extensive disease and in older patients.

The cause of Pemphigus remains unknown; however, several potentially relevant factors have been identified.

Genetic factors: Predisposition to pemphigus is linked to Certain major histocompatibility complex (MHC) class II molecules,

Etiology

PEMPHIGUS should encourage the physician to consider pesticides (PE), malignancy (M), pharmaceuticals (P), hormones (H), infectious agents (I), gastronomy (G), ultraviolet light (U), and stress (S).

Clinical types

Deep type: 100% mucosal affection Pemphigus vulgaris (Anti DsG3 Abs) Pemphigus vegetans (Anti DsG3 Abs)

Superficial type. No or rare mucosal affection. Pemphigus foliaceous (Anti DsG1 Abs) Pemphigus erythematosus (Anti DsG1

Abs)

Pemphigus vulgaris

Antibodies develop to deep intraepidermal suprabasal desmosomal proteins common to both skin and mucosa, so the blister is deeper in location.

Mucosal lesions may precede cutaneous lesions by months.

Patients with mucosal lesions may present to dentists, oral surgeons, or gynecologists.

Physical

patients have ill-defined, irregularly shaped, gingival, buccal or palatine erosions, which are painful and slow to heal.

The erosions extend peripherally with shedding of the epithelium.

Erosions may spread to involve the larynx with subsequent hoarseness.

The patient often is unable to eat or drink adequately because the erosions are so uncomfortable.

Other mucosal surfaces may be involved, including the conjunctiva, esophagus, labia, vagina, cervix, penis, urethra, and anus.

Pemphigus vulgaris

Pemphigus vulgaris

Pemphigus vulgaris

Pemphigus vulgaris

Pemphigus vulgaris

Pemphigus vulgaris

The primary lesion of PV is a flaccid blister filled with clear fluid that arises on normal skin or on an erythematous base.

The blisters are fragile; therefore, intact blisters may be sparse.

The contents soon become turbid, or the blisters rupture producing painful erosions, which is the most common skin presentation.

Erosions often are large because of their tendency to extend peripherally with the shedding of the epithelium.

Skin:

Nails: Acute paronychia, subungual hematomas, and nail dystrophies have been reported with PV.

Nikolsky sign: In patients with active blistering, firm sliding pressure with a finger separates normal-appearing epidermis, producing an erosion. This sign is not specific for PV and is found in other active blistering diseases.

Asboe-Hansen sign: Lateral pressure on the edge of a blister may spread the blister into clinically unaffected skin.

Bulla spreading testBulla spreading test

Vegetating Pemphigus

In some patients, erosions tend to develop excessive granulation tissue and crusting, and these patients display more vegetating lesions.

This type of lesion tends to occur more frequently in intertriginous areas and on the scalp or face.

The vegetating type of response can be more resistant to therapy and can remain in one place for long periods of time.

P vegetans

Pemphigus Foliaceus

IgG develops against a superficial epidermal desmosomal Ag named DsG1.

Acantholysis and separation occurs subcorneally.

The patient presents with exfoliative skin lesions and very superficial erosions with mild crusting.

Usually no mucosal lesions.

P foliaceous

Pemphigus erythematosus

(also known as "Senear–Usher syndrome") is simply a localized form of pemphigus foliaceus together with LE or seborrheic dermatitis like manifestations on photo-exposed areas.

P erythematosus

Histopathology Pemphigus vulgaris shows detachment

of keratinocytes from each other due to loss of desmosome integrity, causing acantholysis and intraepidermal bulla formation.

The point of separation in pemphigus vulgaris is usually in the suprabasal epidermis.  

Direct immunofluorescence showing intercellular immunoglobulin G throughout the epidermis of a patient with pemphigus vulgaris.

Treatment

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 medication

necessary to control the disease process.

Medical Care

Anti-inflammatory agents Inhibit the inflammatory process by inhibiting

specific cytokine production.

Corticosteroids (Prednisone) 1-1.5 mg/kg/d PO initial every am or in

divided doses; taper as condition improves; single morning dose is safer for long-term use, but divided doses have more anti-inflammatory effect

SE : - osteoprosis -DM

-hypertension hyperacidity

Immunosuppressive agents adjuvants in patients with PV unresponsive to

steroids and/or other anti-inflammatory agents or in 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

-management of S.E of drugs e.g DM, HTN

Dermatitis herpetiformis (DH)

is an autoimmune blistering disorder associated with a gluten-sensitive enteropathy (GSE)

cutaneous manifestation of celiac disease.

Gluten is a protein present in barley, rye, and wheat.

Rice and oats belong to different species and are 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 the gut.

cross-react with epidermal transglutaminase (e-TG)

Deposition of IgA and epidermal TG complexes in the papillary dermis

which triggers an immunologic cascade, resulting in neutrophil recruitment and complement activation.

Clinically

characterized by waxing and waning, pruritic eruption formed of:

grouped excoriations; erythematous, urticarial plaques; and

papules with vesicles that are often excoriated to

erosions by the time of physical examination .

on the extensor surfaces of the elbows, knees, buttocks, and back.

exquisitely pruritic,

Prognosis

Dermatitis herpetiformis is a lifelong disease, although periods of exacerbation and remission are common.

Diagnosis neutrophil accumulation at the

dermoepidermal junction, frequently localizing to the papillary tips of the basement membrane zone (dermal papillary neutrophilic microabscesses).

direct immunofluorescence of a skin biopsy show deposition of immunoglobulin A (IgA) in a granular pattern in the upper papillary dermis.

Treatment Strict gluten-free diet results in

normalization of the small bowel mucosal changes and control of the cutaneous manifestations of dermatitis herpetiformis in 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

(so monitor Serum bilirubin) colchicine, cyclosporine, azathioprine, and

prednisone are second agents.

Complications :

(1) 2ry infection

(2) 2ry eczematization

(3) psychological upset up to suicidal attempts dt severe itching

??? Increased incidence of nonHodgkin lymphoma is reported.

-mainly in newborns

-infection with staph occurs through the umbilical stump

-staph produces exotoxins which digest the desmosomal proteins causing bullous eruption of the skin

-characteristically there is very large single bulla that involve the

Trunk & may involve both lower and upper limbs, its rupture

Causes severe agonizing pain & scalding of the skin

-bullae are filled with pus

-very bad general condition, so need ICU care

Staphylococcal scalded skin syndrome (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 a drug : antibiotics (sulpha),NSAIDS, Anticonvulsants , anxiolytics

- large bullae which are filled with serum not pus

- treatment :

1. stop the offending drugs

2 .corticosteroids

TOXIC EPIDERMAL NECROLYSIS (TEN)

TEN