Bullous diseases * blistering diseases*
DefinitionBlister is well circumscribed ,elevated ,fuid filled lesion in the skin.
When its smaller than 0.5 cm its called vesicle and when larger than 0.5 cm its called bulla.
Classification
Bullous disease can be classified according to eitiology or to the level of lesion in the skin.
According to eitiology
1.autoimmune blistering diseases
Main diseases are pemphigus ,pemphigoid and dermatitis herpitiformis.
2.infecions
Like bullous impetigo , herpes simplex and herpes zoster.
3.inflammatory conditions
Like in sever acute dermatitis and bullous drug reaction
4.hereditery diseases
Like epidermolysis bullosa
According to the level of lesion
1.subcorneal blistering diseases, blister just beneath stratum corneumThe roof of these blisters is very lesion and blisters are ruptured very easily and early in the course of the disease
Like in bullous impetigo or pemphigus folaceus
2.intraepidermal blistering, blister within the prickle cell layer
The roof is thicker and rupture less easily
As in acute dermatitis , herpes siplex and pemphigus vulgaris
3.subepidermal blisters ,below epidermis
They have thick roof and dont rupture easily
As in bullous pemphigoid and burn bullae
Diagnosis and classification of autoimmune blistering diseases.
Blistering skin diseases are a group of autoimmune disorders that are characterized by autoantibodies against structural proteins of the epidermis or the dermal-epidermal junction and clinically by blisters and erosions on skin and/or mucous membranes. The differentiation between the various disorders became more important since prognosis as well as different treatment options are nowadays available for the various diseases.Pemphigus
There are many varients of this disease according to target antigens and level of blistering and clinical features . most commont and important type is pemphigus vulgaris.
Pemphigus vulgaris
Pemphigus vulgaris is an autoimmune, intraepithelial, blistering disease affecting the skin and mucous membranes. It is mediated by circulating autoantibodies directed against keratinocyte cell surfaces. A potentially life-threatening disease, it has a mortality rate of approximately 5-15%.[1]
The primary lesion of pemphigus vulgaris is a flaccid blister filled with clear fluid that arises on healthy skin or on an erythematous base .
The disease usually affect young and middle aged adults.
Signs and symptoms
Mucous membranesMucous membranes of the oral cavity are involved in almost all patients with pemphigus vulgaris
Patients may have ill-defined, irregularly shaped, gingival, buccal, or palatine erosions, which are painful and slow to heal
[2]
SkinPrimary lesion of pemphigus vulgaris is a flaccid blister filled with clear fluid that arises on healthy skin or on an erythematous base
Blisters are fragile and may rupture, producing painful erosions (the most common skin presentation)
Nails
Acute or chronic paronychia, subungual hematomas, and nail dystrophies affecting one or several fingers or toes have been reported with pemphigus vulgaris
Diagnosis
Laboratory studies include the following:
Histopathology: Demonstrates an intradermal blister; the earliest changes consist of intercellular edema with loss of intercellular attachments in the basal layer and then acantholysis .
Direct immunofluorescence (DIF): On normal-appearing perilesional skinHYPERLINK "javascript:showrefcontent('refrenceslayer');" [7] ; demonstrates in vivo deposits of antibodies and other immunoreactants, such as complement
Indirect immunofluorescence (IDIF): If DIF results are positive; circulating intercellular antibodies are detected using IDIF in 80-90% of patients with pemphigus vulgaris
Management
The aim of pharmacologic therapy for pemphigus vulgaris is to reduce inflammatory response and autoantibody production. Medications used in the disease’s treatment include the following:
Corticosteroids: Discourage the inflammatory process by inhibiting specific cytokine production
Immunosuppressants: Should be considered early in the course of disease as steroid-sparing agents
The aim of treatment in pemphigus vulgaris is the same as in other autoimmune bullous diseases, which is to decrease blister formation, promote healing of blisters and erosions, and determine the minimal dose of medication necessary to control the disease process. . Therapy must be tailored for each patient, taking into account preexisting and coexisting conditions. Patients may continue to experience mild disease activity while under optimal treatment.
Corticosteroids have improved overall mortality, but now much of the mortality and morbidity in these patients relates to the adverse effects of therapy.
Immunosuppressive drugs are steroid sparing and should be considered early in the course of the disease. most commonly used agents are azathioprine which is antimetabolite , dapson , antichemotactic , and biological therapy like rituximab.
Bullous pemphigoid
Bullous pemphigoid is a chronic, inflammatory, subepidermal, blistering disease. If untreated, it can persist for months or years, with periods of spontaneous remissions and exacerbations. The disease can be fatal, particularly in patients who are debilitated.Its usually a disease of middle aged and elderly persons
Signs and symptoms
Bullous pemphigoid may present with several distinct clinical presentations, as follows:
Generalized bullous form: The most common presentation; tense bullae arise on any part of the skin surface, with a predilection for the flexural areas of the skin
Vesicular form: Less common than the generalized bullous type; manifests as groups of small, tense blisters, often on an urticarial or erythematous base
Vegetative form: Very uncommon, with vegetating plaques in intertriginous areas of the skin, such as the axillae, neck, groin, and inframammary areas
Generalized erythroderma form: This rare presentation can resemble psoriasis, generalized atopic dermatitis, or other skin conditions characterized by an exfoliative erythroderma
Urticarial form: Some patients with bullous pemphigoid initially present with persistent urticarial lesions that subsequently convert to bullous eruptions; in some patients, urticarial lesions are the sole manifestations of the disease
Diagnosis
To establish a diagnosis of bullous pemphigoid, the following tests should be performed:
Histopathologic analysis: From the edge of a blister; the histopathologic examination demonstrates a subepidermal blister; the inflammatory infiltrate is typically polymorphous, with an eosinophil predominance; mast cells and basophils may be prominent early in the disease course
Direct immunofluorescence (DIF) studies: Performed on normal-appearing, perilesional skin direct immunofluorescence study performed on a perilesional skin biopsy specimen from a patient with bullous pemphigoid detects a linear band of immunoglobulin G deposit along the dermoepidermal junction.
Indirect immunofluorescence (IDIF) studies: Performed on the patient’s serum, if the DIF result is positive Indirect immunofluorescence study performed on salt-split normal human skin substrate with the serum from a patient with bullous pemphigoid detects immunoglobulin G class circulating autoantibodies that bind to the epidermal (roof) side of the skin basement membrane.
.mangement
As in other autoimmune bullous diseases, the goal of therapy in bullous pemphigoid is as follows:
Decrease blister formation
Promote healing of blisters and erosions
Determine the minimal dose of medication necessary to control the disease process
The most commonly used medications for bullous pemphigoid are anti-inflammatory agents (eg, corticosteroids, tetracyclines, dapsone) and immunosuppressants (eg, azathioprine, methotrexate, mycophenolate mofetil )
Most patients affected with bullous pemphigoid require therapy for 6-60 months, after which many patients experience long-term remission of the disease. However, some patients have long-standing disease requiring treatment for years.
Most mortality associated with bullous pemphigoid occurs secondary to the effects of medications used in treatment. For example, the population at risk for bullous pemphigoid is at an increased risk for comorbid conditions, such as hypertension, diabetes mellitus, and heart disease, which treatment may exacerbate.
Dermatitis herpitiformis
Clinical aspects
Dermatitis herpetiformis (DH) is an autoimmune blistering disorder associated with a HYPERLINK "http://emedicine.medscape.com/article/171805-overview" \t "_self" gluten-sensitive enteropathy (GSE). Dermatitis herpetiformis is characterized by grouped excoriations; erythematous, urticarial plaques; and papules with vesicles. The classic location for dermatitis herpetiformis lesions is on the extensor surfaces of the elbows, knees, buttocks, and back. Dermatitis herpetiformis is exquisitely pruritic, and the vesicles are often excoriated to erosions by the time of physical examination .
Patients typically present with a waxing and waning, pruritic eruption on the extensor surfaces of the arms, knees, and buttocks. It may become generalized. Small vesicles may have been noted but have often been excoriated by the time of presentation to the physician. They may have associated worsening of disease with dietary intake of gluten. Many do not report any GI symptoms, even when prompted.
The diagnosis is suspected based on the distribution of the eruption.
Dermatitis herpetiformis rarely occurs on the posterior (nuchal) scalp and face. Lesions occur infrequently on the oral mucosa, but males are more likely than females to have involvement of the oral and genital membranes.HYPERLINK "javascript:showrefcontent('refrenceslayer');" [19] Palms and soles are spared.
The eruption is intensely pruritic; patients often present with erosions and crusts in the absence of vesicles, which have ruptured due to excoriation.
Dermatitis herpetiformis is a lifelong disease, although periods of exacerbation and remission are common.
.
The gluten-sensitive enteropathy does not cause symptoms in most dermatitis herpetiformis patients. Less than 10% exhibit symptoms of bloating, diarrhea, or malabsorption. However, greater than 90% show abnormalities upon endoscopic examination. Two thirds have villous atrophy detected on intestinal biopsy specimens.
The critical role of associated gluten-sensitive enteropathy in the pathogenesis of dermatitis herpetiformis is confirmed by the fact that resumption of a gluten-containing diet in patients with dermatitis herpetiformis results in a return of the characteristic skin disease.
Main characteristic histopathological feature is neutrophilic infiltrate in aggregates in the dermal papillae.
treatment
Treatment of dermatitis herpetiformis (DH) include avoidance of gluten by consuming a gluten-free diet and pharmacotherapy.
Dapsone (diaminodiphenyl sulfone) and sulfapyridine are the primary medications used to treat dermatitis herpetiformis. The exact mechanism of action is unknown but is thought to be related to inhibition of neutrophil migration and function. Patients report a symptomatic improvement within hours after initiation of dapsone therapy. Patients should be monitored for the adverse effects of dapsone, primarily hemolytic anemia, methemoglobinemia, agranulocytosis, and neuropathy. For patients unable to tolerate dapsone, particularly those who develop hemolysis, sulfapyridine may be substituted. New lesion formation is suppressed for up to 2 days after a dose of dapsone; however, dapsone does not improve GI mucosal pathology.
Hereditary blistering disease
Epidermolysis bullousa
It’s a heterogenous group of heridetety disease characterized by development of blisters at differen levels in the skin after minimal trauma due to genetic abnormalities in some of structural components of the skin.Main types include
1.simple type AD , due to loss of some keratins in the epidermis and the level of blistering is above the basal layer..so ,lesions heal rapidly without scarring.
Lesions usually occur aroud hands and feet early in childhood as these sites are subjected to friction and trauma. And best management is protection.
2.junctional type AR, the defect is in anchoring filaments in the basement membrane. Its sever type ..sever blistering and erosions occur early at birth and usually fatal.
3.dystrophic type AD and AR ,the abnormality in anchoring fibrils that attach the basement membrane to the underlying dermis. The separation and blistering is subepidermally.
The lesions occur at site of trauma and heals with sever scarring