Pemphigus - Clinicals, Diagnosis, and Management

Dermatology

Clinicals - History

Fact Explanation
Skin lesions Pemphigus is an autoimmune blistering disease. Desmosomes are cell–to-cell adhesion junctions mainly in the epithelia that functions to mediate cell adhesion and anchorage for intermediate filaments via their cytoplasmic plaque. Desmosomes are made up of desmogleins (Dsg)1 and desmocollins (Dsc). Pathogenesis of the condition is related to the autoantibodies acting against desmoglein 3 (Dsg3) causing loss of cell–to-cell adhesion of keratinocytes in the basal and immediate suprabasal layers of stratified squamous epithelia. Proteases release from keratinocytes, may also contributing to the disease formation. Pemphigus is manifesting as a life-threatening, blistering disease of the skin and mucous membranes. Skin lesions
Pemphigus is an autoimmune blistering disease. Desmosomes are cell–to-cell adhesion junctions mainly in the epithelia that functions to mediate cell adhesion and anchorage for intermediate filaments via their cytoplasmic plaque. Desmosomes are made up of desmogleins (Dsg)1 and desmocollins (Dsc). Pathogenesis of the condition is related to the autoantibodies acting against desmoglein 3 (Dsg3) causing loss of cell–to-cell adhesion of keratinocytes in the basal and immediate suprabasal layers of stratified squamous epithelia. Proteases release from keratinocytes, may also contributing to the disease formation. Pemphigus is manifesting as a life-threatening, blistering disease of the skin and mucous membranes.
Blisters and bullae There may be flaccid blister, sorrounding skin may be reddish in colour at times. Flaccid, thin-walled bullae, may arise on normal-appearing or erythematous skin. Clear fluid within the blister amy become hemorrhagic, turbid, or even seropurulent. Postinflammatory hyperpigmentation may be seen and scaring is infrequent. Occasionally they can appear as multiple pustules in the body. Blisters and bullae
There may be flaccid blister, sorrounding skin may be reddish in colour at times. Flaccid, thin-walled bullae, may arise on normal-appearing or erythematous skin. Clear fluid within the blister amy become hemorrhagic, turbid, or even seropurulent. Postinflammatory hyperpigmentation may be seen and scaring is infrequent. Occasionally they can appear as multiple pustules in the body.
Involvement of mucous membrane Mucosal involvement is common in pephigus and oral lesions occur in majority of patients. They appear as painful erosions. Intact blisters are rare. Involvement of mucous membrane
Mucosal involvement is common in pephigus and oral lesions occur in majority of patients. They appear as painful erosions. Intact blisters are rare.
Associated features There may be associated pain, and sometimes itching around the lesions. Associated features
There may be associated pain, and sometimes itching around the lesions.
Thirst, reduced urine output These may be the features of dehydration. Both loss of fluid through skin lesions and avoidance of food and fluids due to the mucous membrane lesions leads to dehydration. Thirst, reduced urine output
These may be the features of dehydration. Both loss of fluid through skin lesions and avoidance of food and fluids due to the mucous membrane lesions leads to dehydration.
Delayed wound healing Proteins are an essential component in wound healing. Loss of proteins via the skin lesions may cause deficit of body proteins. Delayed wound healing
Proteins are an essential component in wound healing. Loss of proteins via the skin lesions may cause deficit of body proteins.
Risk to the life This is a life threatening condition without timely treatment. Large areas of erosion in the skin and mucous membranes leads to massive fluid and electrolyte loss, which can be exaggerated by the reduced fluid intake. Skin lesions are also prone to infections, which contribute to mortality. Risk to the life
This is a life threatening condition without timely treatment. Large areas of erosion in the skin and mucous membranes leads to massive fluid and electrolyte loss, which can be exaggerated by the reduced fluid intake. Skin lesions are also prone to infections, which contribute to mortality.
Neonatal pemphigus Mothers with active lesions who deliver a baby might transfer the disease to the infant. Passively transferred maternal IgG is gradually catabolized, causing the the recovery of the infant. Neonatal pemphigus
Mothers with active lesions who deliver a baby might transfer the disease to the infant. Passively transferred maternal IgG is gradually catabolized, causing the the recovery of the infant.
History of drug use Drug-induced pemphigus vulgaris has been documented with drugs such as penicillamine, captopril, cephalosporin, pyrazolones, nonsteroidal anti-inflammatory drugs (NSAIDs). History of drug use
Drug-induced pemphigus vulgaris has been documented with drugs such as penicillamine, captopril, cephalosporin, pyrazolones, nonsteroidal anti-inflammatory drugs (NSAIDs).
History of infections, neoplasms, and radiation These factors are known to cause remissions. History of infections, neoplasms, and radiation
These factors are known to cause remissions.
Pathological fractures, bone pain, visual problems and recurrent infectoions Osteoporosis, avascular necrosis, HPA-axis suppression, cataract, cushingoid features, myopathy, mood changes, and immunosuppression may be the complications of long term immunosupressive treatment. Pathological fractures, bone pain, visual problems and recurrent infectoions
Osteoporosis, avascular necrosis, HPA-axis suppression, cataract, cushingoid features, myopathy, mood changes, and immunosuppression may be the complications of long term immunosupressive treatment.

Clinicals - Examination

Fact Explanation
Blisters in the skin and mucous membranes Earliest change is the detachment of the epithelium just above the basal cells. There are flaccid, thin-walled bullae, and blisters which arises on an erythematous base on healthy skin or filled with clear fluid. Blisters can be either intact or ruptured. There can be large erosions with the shedding of the epithelium. Blisters in the skin and mucous membranes
Earliest change is the detachment of the epithelium just above the basal cells. There are flaccid, thin-walled bullae, and blisters which arises on an erythematous base on healthy skin or filled with clear fluid. Blisters can be either intact or ruptured. There can be large erosions with the shedding of the epithelium.
Oral lesions There will be large, flaccid, superficial bullae/erosions in the mouth, involving tongue. There can be shallow erosions on oral mucosa and desquamative gingivitis. Oral lesions
There will be large, flaccid, superficial bullae/erosions in the mouth, involving tongue. There can be shallow erosions on oral mucosa and desquamative gingivitis.
Nikolsky sign Nikolsky's sign is elicited by applying lateral pressure on the blister it self or perilesional skin or normal appearing skin that result in removal of upper layer of epidermis. There are two types of Nikolsky's sign, wet Nikolsky's sign in base of skin is moist, glistening, and exudative, and dry Nikolsky's if the base of eroded skin is relatively dry after removal of the epidermis. Active disease is manifested by wet Nikolsky's sign, and re-epithialization is manifested by a dry Nikolsky's sign. Nikolsky sign
Nikolsky's sign is elicited by applying lateral pressure on the blister it self or perilesional skin or normal appearing skin that result in removal of upper layer of epidermis. There are two types of Nikolsky's sign, wet Nikolsky's sign in base of skin is moist, glistening, and exudative, and dry Nikolsky's if the base of eroded skin is relatively dry after removal of the epidermis. Active disease is manifested by wet Nikolsky's sign, and re-epithialization is manifested by a dry Nikolsky's sign.
Asboe-Hansen sign Asboe-Hansen sign is elicited by applying gentle pressure on an intact bulla that forces the fluid to spread under the skin away from the site of pressure. Asboe-Hansen sign
Asboe-Hansen sign is elicited by applying gentle pressure on an intact bulla that forces the fluid to spread under the skin away from the site of pressure.
Hyperpigmentation There can be postinflammatory associated occasionally with true scarring. Hyperpigmentation
There can be postinflammatory associated occasionally with true scarring.
Secondary bacterial infections Lesions are more prone to colonization with microbes causing secondary bacterial infections. Secondary bacterial infections
Lesions are more prone to colonization with microbes causing secondary bacterial infections.
Features of dehydration : sunken eyes, reduced skin turgor, dry skin and mucous membranes Loss of fluid through the skin lesions and avoidance of food and fluids due to the mucous membrane lesions causes dehydration. Features of dehydration : sunken eyes, reduced skin turgor, dry skin and mucous membranes
Loss of fluid through the skin lesions and avoidance of food and fluids due to the mucous membrane lesions causes dehydration.
Cataract, cushingoid features, myopathy, mood changes These features are due to the drugs used for the treatment, such as steroids. These adverse effects are particularly seen when using over a long period of time. Cataract, cushingoid features, myopathy, mood changes
These features are due to the drugs used for the treatment, such as steroids. These adverse effects are particularly seen when using over a long period of time.

Investigations - Diagnosis

Fact Explanation
Histopathology Detachment of the epithelium just above the basal cells, with no, or minimal, inflammation in an early lesion. “Row of tombstones” patternis seen due to the detached basal cells from one another while while preserving the attachment to the basement membrane. Histopathology ia helpful in differentiating pemphigus vulgaris from pemphigus foliaceous, as latter will demonstrates a more superficial epidermal cleavage. Histopathology
Detachment of the epithelium just above the basal cells, with no, or minimal, inflammation in an early lesion. “Row of tombstones” patternis seen due to the detached basal cells from one another while while preserving the attachment to the basement membrane. Histopathology ia helpful in differentiating pemphigus vulgaris from pemphigus foliaceous, as latter will demonstrates a more superficial epidermal cleavage.
Direct immunofluorescence IgG autoantibodies to the cell surface of keratinocytes of stratified squamous epithelia are found in the skin and sera of these patients. A sample from the normal-appearing perilesional skin can be used to direct immunofluorescence. It will demonstrate the deposits of antibodies and other complement. Immunoglobulin G (IgG) is deposited on the keratinocytes surface in and around lesions. Direct immunofluorescence
IgG autoantibodies to the cell surface of keratinocytes of stratified squamous epithelia are found in the skin and sera of these patients. A sample from the normal-appearing perilesional skin can be used to direct immunofluorescence. It will demonstrate the deposits of antibodies and other complement. Immunoglobulin G (IgG) is deposited on the keratinocytes surface in and around lesions.
Indirect immunofluorescence Indirect immunofluorescence is alsl able to detect thje pathogenic IgG autoantobodies. Indirect immunofluorescence
Indirect immunofluorescence is alsl able to detect thje pathogenic IgG autoantobodies.

Investigations - Management

Fact Explanation
IgG antibody titre Serum antibody titers can be used to monitor disease activity. Higher the level may indicate the more severe disease. IgG antibody titre
Serum antibody titers can be used to monitor disease activity. Higher the level may indicate the more severe disease.
Serum electrlytes Large areas of erosions on mucous membranes and skin due to the rapid loss of the superficial epithelia causes prevent protein and electrolyte loss from the body. Serum electrlytes
Large areas of erosions on mucous membranes and skin due to the rapid loss of the superficial epithelia causes prevent protein and electrolyte loss from the body.
Full blood count These patients are vulnerable for the secondary bacterial infections, and evaluation of the leucocytosis in the bacterial infections and lymphocytosis in the viral infections may be needful. Full blood count
These patients are vulnerable for the secondary bacterial infections, and evaluation of the leucocytosis in the bacterial infections and lymphocytosis in the viral infections may be needful.
Indirect immunofluorescence Indirect immunofluorescence, will detect the autoantibody titer, that correlates well with the disease activity. Higher antibody titer, is associated with more severe disease. Paraneoplastic pemphigus can be diagnosed by demonstration of immunoglobulin G autoantibodies to desmoglein 3 and plakins on immunofluorescence. Indirect immunofluorescence
Indirect immunofluorescence, will detect the autoantibody titer, that correlates well with the disease activity. Higher antibody titer, is associated with more severe disease. Paraneoplastic pemphigus can be diagnosed by demonstration of immunoglobulin G autoantibodies to desmoglein 3 and plakins on immunofluorescence.

Management - Supportive

Fact Explanation
Patient education Patient should be informed about the nature of the disease, potential complications particularly secondary infections, inability to take food, dehydration and involvement of the oral cavity. Psychological support is also important as they might be depressed, anxious and irritable with the disease. Patient education
Patient should be informed about the nature of the disease, potential complications particularly secondary infections, inability to take food, dehydration and involvement of the oral cavity. Psychological support is also important as they might be depressed, anxious and irritable with the disease.
Skin care Secondary infections with bacteria, can occur and lesion may progress to ulcers. Therefore appropriate skin care is important in the healing of lesions and avoidance of complications. Gentle cleansing of the erosions, liberal application of antibiotic ointments or petroleum jelly, and avoidance of trauma are some measures to prevent the complications. Skin care
Secondary infections with bacteria, can occur and lesion may progress to ulcers. Therefore appropriate skin care is important in the healing of lesions and avoidance of complications. Gentle cleansing of the erosions, liberal application of antibiotic ointments or petroleum jelly, and avoidance of trauma are some measures to prevent the complications.
Diet and nutrition Usually there are no dietary restrictions. But the disease may involve mucous membrane of the oral cavity causing difficulty in food and water intake. Certain foods like spicy foods, tomatoes, orange juice and hard food cause more discomfort. Nutritional support is important as there is loss of proteins from the lesions. Diet and nutrition
Usually there are no dietary restrictions. But the disease may involve mucous membrane of the oral cavity causing difficulty in food and water intake. Certain foods like spicy foods, tomatoes, orange juice and hard food cause more discomfort. Nutritional support is important as there is loss of proteins from the lesions.
Follow up Osteoporosis risk assessment and if needed bisphosphonate for prophylaxis against osteoporosis may be valueble. Opthalmological review, blood pressure check up may be needed in patients receiving steroids. Follow up
Osteoporosis risk assessment and if needed bisphosphonate for prophylaxis against osteoporosis may be valueble. Opthalmological review, blood pressure check up may be needed in patients receiving steroids.
Managing the complications Complications may be either due to disease or therapy. Patients receiving long-term systemic corticosteroids are suseptible to get complications like osteoporosis, avascular necrosis, HPA-axis suppression, cataract, cushingoid features, myopathy, mood changes, and immunosuppression. Secondary bacterial infections are common and need appropriate wound and skin care. Managing the complications
Complications may be either due to disease or therapy. Patients receiving long-term systemic corticosteroids are suseptible to get complications like osteoporosis, avascular necrosis, HPA-axis suppression, cataract, cushingoid features, myopathy, mood changes, and immunosuppression. Secondary bacterial infections are common and need appropriate wound and skin care.

Management - Specific

Fact Explanation
Corticosteroids Prednisone and methylprednisolone may be used. Starting dose of prednisone is 1mg/kg/day divided into two or three doses and clinical remission will occur within 4–12 weeks. Dose is maintained for further 6–10 weeks to prevent relapses. Dose is then gradually decreased and if there is no recurrence, maintenance dose of 5 mg daily for several years is used to prevent recurrences. When the patient is having severe disease or not responding adequately to the standard dose of prednisone, either increment in dose upto 1.5 or 2 mg/kg/day until remission. or pulse-steroid therapy (intravenous methylprednisolone 1 g daily given for three consecutive days) are used. Topical steroid gel (clobetasol propionate) can be used for the mucosa. Corticosteroids
Prednisone and methylprednisolone may be used. Starting dose of prednisone is 1mg/kg/day divided into two or three doses and clinical remission will occur within 4–12 weeks. Dose is maintained for further 6–10 weeks to prevent relapses. Dose is then gradually decreased and if there is no recurrence, maintenance dose of 5 mg daily for several years is used to prevent recurrences. When the patient is having severe disease or not responding adequately to the standard dose of prednisone, either increment in dose upto 1.5 or 2 mg/kg/day until remission. or pulse-steroid therapy (intravenous methylprednisolone 1 g daily given for three consecutive days) are used. Topical steroid gel (clobetasol propionate) can be used for the mucosa.
Immunosuppressive drugs There are steroid-sparing immunosuppressive agents such as azathioprine, mycophenolate mofetil (MMF), and cyclophosphamide that are used for the treatment of pemphigus.
Azathioprine is the most commonly using drug. Gastrointestinal intolerance, mild hepatotoxicity, and bone marrow suppression may be the side effects of treatment and it shoud not be used for pregnant mothers. Mycofenate mofetil causes adverse effects such as gastrointestinal side effects, mild dose-related bone marrow suppression. Cyclophosphamide is an alkylating cytotoxic steroid sparing agent given as pulse therapy (1 g intravenously every four weeks). Acute myelosuppressio, mucosal ulcers, alopecia, nephrotoxicity, urotoxicity (hemorrhagic cystitis), cardiotoxicity, hepatotoxicity, interstitial lung fibrosis, and toxicity in reproductive systems resulting in amenorrhea are the side effects of cyclophosphomide therapy.
Immunosuppressive drugs
There are steroid-sparing immunosuppressive agents such as azathioprine, mycophenolate mofetil (MMF), and cyclophosphamide that are used for the treatment of pemphigus.
Azathioprine is the most commonly using drug. Gastrointestinal intolerance, mild hepatotoxicity, and bone marrow suppression may be the side effects of treatment and it shoud not be used for pregnant mothers. Mycofenate mofetil causes adverse effects such as gastrointestinal side effects, mild dose-related bone marrow suppression. Cyclophosphamide is an alkylating cytotoxic steroid sparing agent given as pulse therapy (1 g intravenously every four weeks). Acute myelosuppressio, mucosal ulcers, alopecia, nephrotoxicity, urotoxicity (hemorrhagic cystitis), cardiotoxicity, hepatotoxicity, interstitial lung fibrosis, and toxicity in reproductive systems resulting in amenorrhea are the side effects of cyclophosphomide therapy.
Intravenous immunoglobulin therapy Intravenous immunoglobulin is useful in pemphigus patients who are not fully responingd to systemic steroids. It is given as an infusion of a total of 2 g/kg body weight over four or five days and that gives a rapid clinical improvement. Intravenous immunoglobulin therapy
Intravenous immunoglobulin is useful in pemphigus patients who are not fully responingd to systemic steroids. It is given as an infusion of a total of 2 g/kg body weight over four or five days and that gives a rapid clinical improvement.
Plasmapheresis Plasmapheresis is the withdrawal of the patient’s blood, using a filter and is effective in combination with cyclophosphamide for patients with severe disease who are unresponsive to conventional therapy. Plasmapheresis
Plasmapheresis is the withdrawal of the patient’s blood, using a filter and is effective in combination with cyclophosphamide for patients with severe disease who are unresponsive to conventional therapy.

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