Background
Pemphigus is derived from the Greek word pemphix meaning bubble or blister. Pemphigus describes a group of chronic bullous diseases, originally named by Wichman in 1791. The term pemphigus once included most bullous eruptions of the skin, but diagnostic tests have improved, and bullous diseases have been reclassified.
The term pemphigus refers to a group of autoimmune blistering diseases of the skin and mucous membranes characterized histologically by intraepidermal blister and immunopathologically by the finding of in vivo bound and circulating immunoglobulin G (IgG) antibody directed against the cell surface of keratinocytes. The 3 primary subsets of pemphigus include pemphigus vulgaris (PV), pemphigus foliaceus, and paraneoplastic pemphigus. Each type of pemphigus has distinct clinical and immunopathologic features. PV accounts for approximately 70% of pemphigus cases.
Pathophysiology
PV is an autoimmune, intraepithelial, blistering disease affecting the skin and mucous membranes and is mediated by circulating autoantibodies directed against keratinocyte cell surfaces. In 1964, autoantibodies against keratinocyte surfaces were described in patients with pemphigus. Clinical and experimental observations indicate that the circulating autoantibodies are pathogenic. An immunogenetic predisposition is well established.
Blisters in PV are associated with the binding of IgG autoantibodies to keratinocyte cell surface molecules. These intercellular or PV antibodies bind to keratinocyte desmosomes and to desmosome-free areas of the keratinocyte cell membrane. The binding of autoantibodies results in a loss of cell-cell adhesion, a process termed acantholysis. The antibody alone is capable of causing blistering without complement or inflammatory cells.
PV antigen: Intercellular adhesion in the epidermis involves several keratinocyte cell surface molecules. Pemphigus antibody binds to keratinocyte cell surface molecules desmoglein 1 and desmoglein 3. The binding of antibody to desmoglein may have a direct effect on desmosomal adherens or may trigger a cellular process that results in acantholysis. Antibodies specific for nondesmosomal antigens also have been described in the sera of patients with PV; however, the role of these antigens in the pathogenesis of disease is not known.
Antibodies: Patients with active disease have circulating and tissue-bound autoantibodies of both the immunoglobulin G1 (IgG1) and immunoglobulin G4 (IgG4) subclasses.1 Disease activity correlates with antibody titer in most patients.2
Complement: Pemphigus antibody fixes components of complement to the surface of epidermal cells. Antibody binding may activate complement with the release of inflammatory mediators and recruitment of activated T cells.
Frequency
United States
PV is uncommon, and the exact incidence and prevalence depends on the population studied.
International
PV has been reported to occur worldwide. PV 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.
Mortality/Morbidity
PV is a potentially life-threatening autoimmune mucocutaneous disease with a mortality rate of approximately 5-15%. Complications secondary to the use of high-dose corticosteroids contribute to the mortality rate. Morbidity and mortality are related to the extent of disease, the maximum dose of systemic steroids required to induce remission, and the presence of other diseases. Prognosis is worse in patients with extensive disease and in older patients.
PV involves mucosa in 50-70% of patients. This may limit oral intake secondary to dysphagia. Blistering and erosions secondary to the rupture of blisters may be painful and limit the patient's daily activities.
Patients with PV typically heal without scarring unless the disease is complicated by severe secondary infection.
Race
PV affects all races. The prevalence of PV is high in regions where the Jewish population is predominant.3 For example, in Jerusalem, the prevalence of PV was estimated at 1.6 cases per 100,000 population; in Connecticut, the prevalence was 0.42 cases per 100,000 population.4 Incidence of PV in Tunisia is estimated at 2.5 cases per million population per year (3.9 in women, 1.2 in men), while in France, the incidence is 1.3 cases per million population per year (no significant difference between men and women).5 In Finland, where few people of Jewish or Mediterranean origin live, the prevalence is low, at 0.76 cases per million population.6
Sex
Male-to-female ratio is approximately equal. In adolescence, girls are more likely to be affected than boys.
Age
Mean age of onset is approximately 50-60 years; however, the range is broad, and disease onset in older individuals and in children has been described. Patients are younger at presentation in India than in Western countries.7
Clinical
History
Mucous membranes: PV presents with oral lesions in 50-70% of patients, and almost all patients have mucosal lesions. Mucosal lesions may be the sole sign for an average of 5 months before skin lesions develop, or they may be the sole manifestation of the disease.
Skin: Most patients develop cutaneous lesions. The primary lesion of PV is a flaccid blister, which usually arises on normal-appearing skin but may be found on erythematous skin. New blisters usually are flaccid or become flaccid quickly. Affected skin often is painful but rarely pruritic.
Drug-induced PV: Drugs reported most significantly in association with PV include penicillamine, captopril, and other thiol-containing compounds. Rifampin and emotional stress have recently been reported as triggers for PV.8
Physical
Mucous membranes typically are affected first in PV. Mucosal lesions may precede cutaneous lesions by months. Patients with mucosal lesions may present to dentists, oral surgeons, or gynecologists.
Mucous membranes
Intact bullae are rare in the mouth. More commonly, 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.
The mucous membranes most often affected are those of the oral cavity, which is involved in almost all patients with PV and sometimes is the only area involved. Erosions may be seen on any part of the oral cavity. Erosions can be scattered and often extensive. 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,9 esophagus,10 labia, vagina, cervix, penis, urethra, and anus.
Skin: 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.
Early, small blister filled with clear fluid arises on healthy skin.
[ CLOSE WINDOW ]
Early, small blister filled with clear fluid arises on healthy skin.
Flaccid blister filled with clear fluid arises on healthy skin.
[ CLOSE WINDOW ]
Flaccid blister filled with clear fluid arises on healthy skin.
Vegetating PV: Ordinary PV erosions may develop vegetation. Lesions in skin folds readily form vegetating granulations. 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.
An erosion.
[ CLOSE WINDOW ]
An erosion.
Nails: Acute paronychia, subungual hematomas, and nail dystrophies have been reported with PV.11,12
Pemphigus in pregnancy: Occurrence in pregnancy is rare. When present, maternal autoantibodies may cross the placenta, resulting in neonatal pemphigus. Neonatal pemphigus is transient and improves with clearance of maternal autoantibodies.13
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.
Causes
The cause of PV remains unknown; however, several potentially relevant factors have been identified.
Genetic factors: Predisposition to pemphigus is linked to genetic factors.14 Certain major histocompatibility complex (MHC) class II molecules, in particular alleles of human leukocyte antigen DR4 (DRB1*0402) and human leukocyte antigen DRw6 (DQB1*0503), are common in patients with PV.15,16,17,18
Age: Peak age of onset is from 50-60 years. Infants with neonatal pemphigus remit with clearance of maternal autoantibodies. The disease may present in childhood or in older persons.
Disease association: Pemphigus occurs in patients with other autoimmune diseases, particularly myasthenia gravis and thymoma.19
Pemphigus is derived from the Greek word pemphix meaning bubble or blister. Pemphigus describes a group of chronic bullous diseases, originally named by Wichman in 1791. The term pemphigus once included most bullous eruptions of the skin, but diagnostic tests have improved, and bullous diseases have been reclassified.
The term pemphigus refers to a group of autoimmune blistering diseases of the skin and mucous membranes characterized histologically by intraepidermal blister and immunopathologically by the finding of in vivo bound and circulating immunoglobulin G (IgG) antibody directed against the cell surface of keratinocytes. The 3 primary subsets of pemphigus include pemphigus vulgaris (PV), pemphigus foliaceus, and paraneoplastic pemphigus. Each type of pemphigus has distinct clinical and immunopathologic features. PV accounts for approximately 70% of pemphigus cases.
Pathophysiology
PV is an autoimmune, intraepithelial, blistering disease affecting the skin and mucous membranes and is mediated by circulating autoantibodies directed against keratinocyte cell surfaces. In 1964, autoantibodies against keratinocyte surfaces were described in patients with pemphigus. Clinical and experimental observations indicate that the circulating autoantibodies are pathogenic. An immunogenetic predisposition is well established.
Blisters in PV are associated with the binding of IgG autoantibodies to keratinocyte cell surface molecules. These intercellular or PV antibodies bind to keratinocyte desmosomes and to desmosome-free areas of the keratinocyte cell membrane. The binding of autoantibodies results in a loss of cell-cell adhesion, a process termed acantholysis. The antibody alone is capable of causing blistering without complement or inflammatory cells.
PV antigen: Intercellular adhesion in the epidermis involves several keratinocyte cell surface molecules. Pemphigus antibody binds to keratinocyte cell surface molecules desmoglein 1 and desmoglein 3. The binding of antibody to desmoglein may have a direct effect on desmosomal adherens or may trigger a cellular process that results in acantholysis. Antibodies specific for nondesmosomal antigens also have been described in the sera of patients with PV; however, the role of these antigens in the pathogenesis of disease is not known.
Antibodies: Patients with active disease have circulating and tissue-bound autoantibodies of both the immunoglobulin G1 (IgG1) and immunoglobulin G4 (IgG4) subclasses.1 Disease activity correlates with antibody titer in most patients.2
Complement: Pemphigus antibody fixes components of complement to the surface of epidermal cells. Antibody binding may activate complement with the release of inflammatory mediators and recruitment of activated T cells.
Frequency
United States
PV is uncommon, and the exact incidence and prevalence depends on the population studied.
International
PV has been reported to occur worldwide. PV 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.
Mortality/Morbidity
PV is a potentially life-threatening autoimmune mucocutaneous disease with a mortality rate of approximately 5-15%. Complications secondary to the use of high-dose corticosteroids contribute to the mortality rate. Morbidity and mortality are related to the extent of disease, the maximum dose of systemic steroids required to induce remission, and the presence of other diseases. Prognosis is worse in patients with extensive disease and in older patients.
PV involves mucosa in 50-70% of patients. This may limit oral intake secondary to dysphagia. Blistering and erosions secondary to the rupture of blisters may be painful and limit the patient's daily activities.
Patients with PV typically heal without scarring unless the disease is complicated by severe secondary infection.
Race
PV affects all races. The prevalence of PV is high in regions where the Jewish population is predominant.3 For example, in Jerusalem, the prevalence of PV was estimated at 1.6 cases per 100,000 population; in Connecticut, the prevalence was 0.42 cases per 100,000 population.4 Incidence of PV in Tunisia is estimated at 2.5 cases per million population per year (3.9 in women, 1.2 in men), while in France, the incidence is 1.3 cases per million population per year (no significant difference between men and women).5 In Finland, where few people of Jewish or Mediterranean origin live, the prevalence is low, at 0.76 cases per million population.6
Sex
Male-to-female ratio is approximately equal. In adolescence, girls are more likely to be affected than boys.
Age
Mean age of onset is approximately 50-60 years; however, the range is broad, and disease onset in older individuals and in children has been described. Patients are younger at presentation in India than in Western countries.7
Clinical
History
Mucous membranes: PV presents with oral lesions in 50-70% of patients, and almost all patients have mucosal lesions. Mucosal lesions may be the sole sign for an average of 5 months before skin lesions develop, or they may be the sole manifestation of the disease.
Skin: Most patients develop cutaneous lesions. The primary lesion of PV is a flaccid blister, which usually arises on normal-appearing skin but may be found on erythematous skin. New blisters usually are flaccid or become flaccid quickly. Affected skin often is painful but rarely pruritic.
Drug-induced PV: Drugs reported most significantly in association with PV include penicillamine, captopril, and other thiol-containing compounds. Rifampin and emotional stress have recently been reported as triggers for PV.8
Physical
Mucous membranes typically are affected first in PV. Mucosal lesions may precede cutaneous lesions by months. Patients with mucosal lesions may present to dentists, oral surgeons, or gynecologists.
Mucous membranes
Intact bullae are rare in the mouth. More commonly, 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.
The mucous membranes most often affected are those of the oral cavity, which is involved in almost all patients with PV and sometimes is the only area involved. Erosions may be seen on any part of the oral cavity. Erosions can be scattered and often extensive. 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,9 esophagus,10 labia, vagina, cervix, penis, urethra, and anus.
Skin: 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.
Early, small blister filled with clear fluid arises on healthy skin.
[ CLOSE WINDOW ]
Early, small blister filled with clear fluid arises on healthy skin.
Flaccid blister filled with clear fluid arises on healthy skin.
[ CLOSE WINDOW ]
Flaccid blister filled with clear fluid arises on healthy skin.
Vegetating PV: Ordinary PV erosions may develop vegetation. Lesions in skin folds readily form vegetating granulations. 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.
An erosion.
[ CLOSE WINDOW ]
An erosion.
Nails: Acute paronychia, subungual hematomas, and nail dystrophies have been reported with PV.11,12
Pemphigus in pregnancy: Occurrence in pregnancy is rare. When present, maternal autoantibodies may cross the placenta, resulting in neonatal pemphigus. Neonatal pemphigus is transient and improves with clearance of maternal autoantibodies.13
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.
Causes
The cause of PV remains unknown; however, several potentially relevant factors have been identified.
Genetic factors: Predisposition to pemphigus is linked to genetic factors.14 Certain major histocompatibility complex (MHC) class II molecules, in particular alleles of human leukocyte antigen DR4 (DRB1*0402) and human leukocyte antigen DRw6 (DQB1*0503), are common in patients with PV.15,16,17,18
Age: Peak age of onset is from 50-60 years. Infants with neonatal pemphigus remit with clearance of maternal autoantibodies. The disease may present in childhood or in older persons.
Disease association: Pemphigus occurs in patients with other autoimmune diseases, particularly myasthenia gravis and thymoma.19
I am regularly gotten some information about Pemphigus Natural Treatment in any case; really, the wording of this request makes me somewhat uncomfortable.
ReplyDelete