Pemphigus Vulgaris

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Practice Essentials

The term pemphigus (from Greek pemphix "bubble or blister") describes 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. Pemphigus was once considered to include most bullous eruptions of the skin, but diagnostic tests have improved, and bullous diseases have been reclassified accordingly.

The three primary subsets of pemphigus, each of which has its own distinct clinical and immunopathologic features, are as follows[1] :

Pemphigus vulgaris (see the image below) accounts for approximately 70% of pemphigus cases. It is a potentially life-threatening disease, with a mortality of approximately 5-15%.[2]



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Early, small blister filled with clear fluid arises on healthy skin.

Signs and symptoms

Mucous membranes

Mucous 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. Intact bullae are rare in the mouth. Erosions may be seen on any part of the oral cavity, and they may spread to involve the larynx, with subsequent hoarseness. In juvenile pemphigus vulgaris, stomatitis is the presenting complaint in more than 50% of cases.

Other mucosal surfaces may be involved, including the conjunctiva, esophagus (causing odynophagia and/or dysphagia), labia, vagina, cervix, vulva, penis, urethra, nasal mucosa, and anus.

Skin

The primary 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.

Vegetating pemphigus vulgaris

Lesions in skin folds readily form vegetating granulations. In some patients, erosions tend to develop excessive granulation tissue and crusting; these individuals display more vegetating lesions.

See Presentation for more detail.

Diagnosis

Laboratory studies include the following:

See Workup for more detail.

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:

See Treatment and Medication for more detail.

Pathophysiology

Pemphigus vulgaris is an autoimmune intraepithelial blistering disease that affects 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 indicated that the circulating autoantibodies are pathogenic. An immunogenetic predisposition has been well established.

Blisters in pemphigus vulgaris are associated with the binding of immunoglobulin G (IgG) autoantibodies to keratinocyte cell surface molecules. These intercellular or pemphigus vulgaris 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-to-cell adhesion, a process termed acantholysis. The antibody alone is capable of causing blistering without complement or inflammatory cells.

Pemphigus vulgaris antigen

Intercellular adhesion in the epidermis involves several keratinocyte cell surface molecules. Pemphigus antibody binds to the keratinocyte cell surface molecules desmoglein 1 (DSG1) and desmoglein 3 (DSG3). The binding of antibody to DSG may have a direct effect on desmosomal adherence 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 pemphigus vulgaris; however, the role of these antigens in the pathogenesis of pemphigus vulgaris has not been established.

Antibodies

Patients with the mucocutaneous form of pemphigus vulgaris have pathogenic anti-DSG1 and anti-DSG3 autoantibodies. Patients with the mucosal form of pemphigus vulgaris have only anti-DSG3 autoantibodies. Patients with active disease have circulating and tissue-bound autoantibodies of both IgG1 and IgG4 subclasses.

More than 80% of patients with active disease produce autoantibodies to DSG. Disease activity correlates with antibody titers in most patients. In patients with pemphigus vulgaris, the presence of anti-DSG1 autoantibodies, as determined by enzyme-linked immunosorbent assay (ELISA), is more closely correlated with the course of the disease than the presence of anti-DSG3 autoantibodies. Lack of in-vivo antibody binding (reversion to a negative result on direct immunofluorescence [DIF]) is the best indicator of remission and can help predict a lack of flaring when therapy is tapered.

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. T cells are clearly required for the production of the autoantibodies, but their role in the pathogenesis of pemphigus vulgaris remains poorly understood. Interleukin (IL)-2 is the main activator of T lymphocytes, and increased soluble receptors have been detected in patients with active pemphigus vulgaris.

Etiology

Although the cause of pemphigus vulgaris remains unknown, several potentially relevant factors have been identified, as follows.

Genetic factors

Predisposition to pemphigus is linked to genetic factors.[9]  Certain major histocompatibility complex (MHC) class II molecules—in particular, alleles of human leukocyte antigen (HLA) DR4 (DRB1*0402) and HLA DRw6 (DQB1*0503)—are common in patients with pemphigus vulgaris.[10, 11, 12, 13]

One study found that the genes FGA (fibrinogen alpha chain), VWF (von Willebrand factor), and ACTG1 (actin gamma 1) were dysregulated in patients with pemphigus vulgaris and suggested that such dysregulation may play a role in the pathogenesis of the disease.[14]

Age

Peak age of onset is between 50 and 60 years. Infants with neonatal pemphigus remit with clearance of maternal autoantibodies. The disease may develop in children or in older persons.

Disease association

Pemphigus occurs in patients with other autoimmune diseases, particularly myasthenia gravis (MG) and thymoma. A study of 110 patients with pemphigus found four patients with autoimmune thyroid disease and three patients with rheumatoid arthritis (RA).[15] In this study, however, autoimmune diseases were no more common in 969 first-degree relatives of patients with pemphigus than in the general population.

Environmental factors

A case-control study suggested that the following may be associated with an increased risk of developing pemphigus vulgaris[16] :

Epidemiology

United States and international statistics

Pemphigus vulgaris is uncommon in the United States, and the exact incidence and prevalence depend on the population studied.

Pemphigus vulgaris has been reported to occur worldwide. The incidence of this condition has been reported to be in the range of 0.5-3.2 cases per 100,000 population. It is higher in patients of Ashkenazi Jewish descent and those of Mediterranean origin. Few familial cases have been reported. As with endemic pemphigus, there is some evidence to suggest clustering near industrial sites.[17]

Age-, sex-, and race-related demographics

Although most cases of pemphigus vulgaris occur between the ages of 50 and 60 years, the range is broad, and disease onset in older individuals and in children has been described. Patients are younger at presentation in India than they are in Western countries.[18]

The male-to-female ratio is approximately equal. In adolescence, girls are more likely to be affected than boys.

Pemphigus vulgaris affects persons of all races and ethnic groups. As noted, it is more prevalent in regions where the Jewish population is predominant[19]  and in Mediterranean regions. For example, in Jerusalem, the prevalence of pemphigus vulgaris has been estimated at 1.6 cases per 100,000 population, whereas in Connecticut, the prevalence has been reported as 0.42 cases per 100,000 population.[20]

The incidence in the United Kingdom is 0.68 case per 100,000 persons per year. The incidence of pemphigus vulgaris in Tunisia is estimated at 2.5 cases (women, 3.9; men, 1.2) per million population per year, whereas in France, the incidence is 1.3 cases per million population per year (no significant difference between men and women).[21] In Finland, where few people of Jewish or Mediterranean origin live, the prevalence is low, at 0.76 case per million population.[22]

Prognosis

The severity and natural history of pemphigus vulgaris are variable. Before the advent of steroids, most patients with pemphigus vulgaris died. Treatment with systemic steroids has reduced the mortality dramatically,[23] to approximately 5-15%.[2] If not properly treated, pemphigus vulgaris still is often fatal because of the susceptibility to infection and fluid and electrolyte disturbances.

Mortality in patients with pemphigus vulgaris is three times higher than that in the general population. Most deaths occur during the first few years of disease; if the patient survives 5 years, the prognosis is good. Early disease probably is easier to control than widespread disease, and mortality may be higher if therapy is delayed. Complications secondary to the use of high-dose corticosteroids contribute to mortality as well.

Morbidity and mortality are related to the extent of disease, the maximum dose of prednisolone required to induce remission, and the presence of other diseases. The outlook is worse in older patients and in patients with extensive disease. Prognosis is usually better in childhood than in adulthood.

Pemphigus vulgaris 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 may limit the patient's daily activities. Patients with pemphigus vulgaris typically heal without scarring unless the disease is complicated by severe secondary infection.

Reversion of DIF to negative can be useful for predicting sustained remission after withdrawal of medication. Plucked hairs are an alternative to skin biopsy in providing a specimen for immunofluorescence; the pilar sheath epithelium of the anagen hair typically demonstrates immunofluorescence comparable to skin. DIF on plucked hairs may be more acceptable to the patient than serial skin biopsies.[24, 25]

Relapses may occur in more than 50% of patients with pemphigus (including variants other than pemphigus vulgaris). In one study, the following were found to be risk factors for relapse[26] :

A few rare cases of pemphigus vulgaris transitioning to pemphigus foliaceus have been reported.

Patient Education

Because of the chronic nature of pemphigus vulgaris, it is important for patients to have a good understanding of the disease and to be educated regarding its management.

Patients should be advised to minimize skin trauma because their skin will be more fragile than usual as a result of both the disease itself and the use of topical and systemic steroids to treat it.

They should also be educated regarding their medications. If patients are informed about dosages, adverse effects, and symptoms of toxicity, they will be better able to report any adverse effects to the physician.

Finally, instructions regarding appropriate wound care should be provided.

History

Mucous membranes

Pemphigus vulgaris presents with oral lesions in 50-70% of cases, and almost all patients have mucosal lesions at some point in the course of their disease. 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. The diagnosis of pemphigus vulgaris should be considered in any patient with persistent oral erosive lesions.

Skin

Most patients with pemphigus vulgaris develop cutaneous lesions. The primary lesion of pemphigus vulgaris is a flaccid blister, which usually arises on healthy-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 is pruritic.

Drug-induced pemphigus vulgaris

Drugs reported most frequently in association with pemphigus vulgaris include penicillamine, captopril, cephalosporin, pyrazolones, nonsteroidal anti-inflammatory drugs (NSAIDs), and other thiol-containing compounds.[27] Rifampin, emotional stress, thermal burns, ultraviolet (UV) light, and infections (eg, coxsackievirus, Herpesviridae family) have also been reported as triggers for pemphigus vulgaris.[28]

Physical Examination

Mucous membranes typically are affected first in pemphigus vulgaris. Mucosal lesions may precede cutaneous lesions by weeks or months. Patients with mucosal lesions may present to dentists, oral surgeons, or gynecologists.[29, 30]

Mucous membranes

Intact bullae are rare in the mouth. More commonly, patients have ill-defined and 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 in pemphigus vulgaris are those of the oral cavity, which is involved in almost all patients with pemphigus vulgaris and sometimes is the only area involved. Erosions may be seen on any part of the oral cavity. They can be scattered and often are 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.

In juvenile pemphigus vulgaris, stomatitis is the presenting complaint in more than 50% of cases.

Other mucosal surfaces may be involved, including the conjunctiva, esophagus (causes odynophagia and/or dysphagia), labia, vagina, cervix, vulva, penis, urethra, nasal mucosa, and anus.

Skin

The primary lesion of pemphigus vulgaris is a flaccid blister filled with clear fluid that arises on healthy skin or on an erythematous base (see the images below).



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Early, small blister filled with clear fluid arises on healthy skin.



View Image

Flaccid blister filled with clear fluid arises on healthy skin.

Because the blisters are fragile, relatively few of them may remain intact. The contents soon become turbid, or the blisters rupture, producing painful erosions, which is the most common skin presentation (see the image below). Erosions often are large because of their tendency to extend peripherally with the shedding of the epithelium.



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An erosion.

Vegetating pemphigus vulgaris

Ordinary pemphigus vulgaris 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.

Nails

Acute or chronic paronychia, subungual hematomas, and nail dystrophies affecting one or several fingers or toes have been reported with pemphigus vulgaris.[31, 32] Patients with paronychial pemphigus usually also have oral involvement.

Pemphigus in pregnancy

Pemphigus vulgaris occurring in pregnancy is rare. When it is present, maternal autoantibodies may cross the placenta, resulting in neonatal pemphigus. Neonatal pemphigus is transient and improves with clearance of maternal autoantibodies.[33] Treatment of pemphigus vulgaris in pregnancy is with oral corticosteroids; however, prednisone and its metabolites cross the placenta and have been associated with low birth weight, prematurity, infection, and adrenal insufficiency.

Signs

For the 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 pemphigus vulgaris and is found in other active blistering diseases.

For the Asboe-Hansen sign, lateral pressure on the edge of a blister may spread the blister into clinically unaffected skin.

Laboratory Studies

To establish a diagnosis of pemphigus vulgaris, the following tests are performed:

The best location for DIF testing is on normal perilesional skin. When DIF testing is performed on lesional skin, false-positive results can be observed. Skin biopsy specimens placed in transport media may yield false-negative results; therefore, fresh tissue is the preferred substrate for DIF studies.

DIF demonstrates in vivo deposits of antibodies and other immunoreactants, such as complement. DIF usually shows immunoglobulin G (IgG) deposited on the surface of the keratinocytes in and around lesions; IgG1 and IgG4 are the most common subclasses. Complement components such as C3 and immunoglobulin M are present less frequently than IgG. DIF shows intercellular deposition throughout the epidermis (see the image below). This pattern of immunoreactants is not specific for pemphigus vulgaris and may be seen in pemphigus vegetans, pemphigus foliaceus, and pemphigus erythematosus. 



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

In the patient's serum, IDIF demonstrates the presence of circulating IgG autoantibodies that bind to epidermis. Circulating intercellular antibodies are detected by means of IDIF in 80-90% of patients with pemphigus vulgaris. The titer of circulating antibody correlates with disease course.

Histologic Findings

Histopathologic evaluation demonstrates an intraepidermal blister. The earliest changes consist of intercellular edema with loss of intercellular attachments in the basal layer. Suprabasal epidermal cells separate from the basal cells to form clefts and blisters. Basal cells are separated from one another and stand like a row of tombstones on the floor of the blister, but they remain attached to the basement membrane. Blister cells contain some acantholytic cells. Histopathology can help differentiate pemphigus vulgaris from pemphigus foliaceus, which demonstrates a more superficial epidermal cleavage.

Tzanck preparation is a smear taken from the base of a blister or an oral erosion that contains acantholytic cells. Blistering is preceded by eosinophilic spongiosis in some patients. The superficial dermis has a mild, superficial, mixed inflammatory infiltrate, which includes some eosinophils.

Medical Care

The aims of treatment are the same in pemphigus vulgaris as in other autoimmune bullous diseases—namely, to decrease blister formation, to promote healing of blisters and erosions (see the images below), and to 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.[34, 35, 36, 37]  Target-specific therapy is not available, and nontargeted treatments are used. Corticosteroids have been the most commonly used medications.



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Erosions and healing areas on the back.



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Healing areas on the chest and abdomen.

Treatment with corticosteroids has improved the overall mortality, but significant morbidity remains. Much of the mortality and morbidity in patients with pemphigus vulgaris is now related to the adverse effects of such therapy. Whether massive doses of steroids have any advantage over a dosage of 1 mg/kg/day is unclear.[38]

Immunosuppressive drugs are steroid-sparing and should be considered early in the course of the disease. Mycophenolate mofetil[39] and azathioprine[40] have been the agents usually considered as initial choices. Some suggest measuring levels of thiopurine methyltransferase (TPMT), a key enzyme in azathioprine metabolism, before starting patients on azathioprine.[41, 42] One placebo-controlled blinded study of mycophenolate demonstrated more rapid improvement in the short run but no significant steroid-sparing effects in the long term.[43]

A retrospective chart review suggested a therapeutic ladder for patients with pemphigus vulgaris, in which a combination of mycophenolate mofetil and prednisone was given initially, followed by rituximab if this initial regimen was unsuccessful.[44]

Rituximab is approved by the US Food and Drug Administration (FDA) for moderate-to-severe pemphigus vulgaris. It has been employed as first- or second-line therapy. Evidence suggests that outcomes are better when rituximab is given as a first-line agent,[45, 46, 47, 48, 49, 50, 51, 52]  and it is increasingly being used in this way.[7, 8] It is commonly used in combination with corticosteroids.[53]

Targeted B-cell depletion is promising.[54]

The anti–tumor necrosis factor (TNF) drugs sulfasalazine and pentoxifylline have been reported to be effective adjunctive treatments, reducing the serum level of TNF and yielding rapid clinical improvement.[55] Methotrexate has also been used.[56] Dapsone has been suggested as a steroid-sparing agent in the maintenance phase of pemphigus vulgaris treatment[57, 58] ; it has also been suggested as a first-line agent.[59]

Intravenous immunoglobulin (IVIG) therapy has been suggested as efficacious in pemphigus vulgaris treatment.[60, 61, 62, 63] Amagai et al reported on the successful use of IVIG in pemphigus patients who did not fully respond to systemic steroids,[64] and Asarch et al reported its use in pediatric patients.[65]  IVIG has been used together with rituximab to treat refractory pemphigus vulgaris.[66]  A small case-control trial showed improved laboratory and clinical outcomes in patients with pemphigus vulgaris treated with a combination of cytotoxic agents plus IVIG as compared with patients treated with IVIG alone.[67]

Cyclophosphamide is used for refractory disease.[68]

Infliximab has proved effective in some patients with refractory disease, and photodynamic therapy has been suggested as a possible adjunctive treatment for recalcitrant ulceration.[69] Mizoribine has been used for refractory ocular manifestations.[70]  

Each of these agents should be prescribed and monitored by physicians familiar with them.

Plasmapheresis has been used in refractory cases, usually in conjunction with cytotoxic therapy.[71, 72]

Wound care for erosions includes daily gentle cleaning, application of topical agents to promote wound healing, and use of nonadhesive dressings. The goal of wound care is to promote healing, minimize trauma to the surrounding skin, and diminish scarring. Epidermal growth factor (EGF) may speed healing of localized lesions.[73]  

Complications

Secondary infection, which may be either localized to the skin or systemic, may occur because of the use of immunosuppressants and the presence of multiple erosions. Cutaneous infection delays wound healing and increases the risk of scarring. The impaired immune responsiveness caused by immunosuppressive drugs may result in the rapid spread of infection. Corticosteroids suppress clinical signs of infection and may allow conditions such as bloodstream infection or tuberculosis to reach an advanced stage before being diagnosed.

Long-term immunosuppressant therapy may result in infections and secondary malignancies (eg, Kaposi sarcoma), owing to impaired immune surveillance.

Growth retardation has been reported in children taking systemic corticosteroids and immunosuppressants.

Bone marrow suppression has been reported in patients receiving immunosuppressants. An increased incidence of leukemia and lymphoma is reported in patients receiving prolonged immunosuppression.

Osteoporosis may occur following the use of systemic corticosteroids.

Adrenal insufficiency has been reported following prolonged use of glucocorticoids.

Diet

No dietary restrictions are needed, but patients with oral disease may benefit from avoiding certain foods that may be chemical irritants (eg, spicy foods, tomatoes, and orange juice), as well as hard foods that may traumatize the oral epithelium mechanically (eg, nuts, chips, and hard vegetables and fruit).

Activity

Patients should be advised to minimize activities that traumatize the skin and that may precipitate blistering, such as contact sports. Nontraumatic exercises, such as swimming, may be helpful. Additionally, dental plates, dental bridges, or contact lenses may precipitate or exacerbate mucosal disease.

Consultations

Management of patients with pemphigus vulgaris requires coordination of care between the dermatologist and the patient's primary care physician.

An ophthalmologist should evaluate patients with suspected ocular involvement and those requiring prolonged high-dose steroid therapy.

Patients with oral disease may require a dentist, an otolaryngologist, or both for evaluation and care.

Patients on systemic steroids should maintain adequate vitamin D and calcium intake through diet and supplements. Patients with a history of renal calculi should not receive calcium carbonate.

Patients receiving long-term systemic corticosteroid therapy should be evaluated by a rheumatologist within the first 30 days of treatment for osteoporosis risk assessment and consideration of a bisphosphonate for prophylaxis against osteoporosis.

Prednisone (Deltasone, Prednisone Intensol, Rayos)

Clinical Context: 

Azathioprine (Azasan, Imuran)

Clinical Context: 

Mycophenolate (CellCept, MMF, Myfortic)

Clinical Context: 

Infliximab (Avsola, Inflectra, Infliximab-abda)

Clinical Context: 

Methotrexate (Jylamvo, Otrexup, Rasuvo)

Clinical Context: 

Rituximab (Riabni, Rituxan, Rituximab-abbs)

Clinical Context: 

Immune globulin IV (IGIV)

Clinical Context: 

Dapsone

Clinical Context: 

Cyclophosphamide (Cytoxan)

Clinical Context: 

Sulfasalazine (Azulfidine, Azulfidine EN)

Clinical Context: 

Pentoxifylline (Pentoxifylline SR, Pentoxil, Trental)

Clinical Context: 

What is pemphigus vulgaris?What are the signs and symptoms of pemphigus vulgaris in the oral cavity?What are the signs and symptoms of pemphigus vulgaris on the skin?What are the signs and symptoms of pemphigus vulgaris on nails?What are the signs and symptoms of vegetating pemphigus vulgaris?Which lab studies are performed in the workup of pemphigus vulgaris?What is the role of pharmacologic therapy for pemphigus vulgaris?What is pemphigus vulgaris?What is the pathophysiology of pemphigus vulgaris?What is the role of antigens in the pathogenesis of pemphigus vulgaris?What is the role of antibodies in the pathogenesis of pemphigus vulgaris?What is the role of complements in the pathogenesis of pemphigus vulgaris?What is the prevalence of pemphigus vulgaris in the US?What is the global incidence of pemphigus vulgaris?What are the racial predilections of pemphigus vulgaris?How does the incidence of pemphigus vulgaris vary by sex?How does the incidence of pemphigus vulgaris vary by age?What is the prognosis of pemphigus vulgaris?What is included in patient education about pemphigus vulgaris?What is the mortality rate of pemphigus vulgaris?What is an alternative to serial skin biopsies for obtaining immunofluorescence specimens of pemphigus vulgaris?What is the prevalence of oral lesions in pemphigus vulgaris?How are skin lesions characterized in pemphigus vulgaris?Which drugs may induce pemphigus vulgaris?What is the initial physical finding of pemphigus vulgaris?What are the characteristic mucosal findings of pemphigus vulgaris?What are the cutaneous findings of pemphigus vulgaris?What are the physical findings characteristic of vegetating pemphigus vulgaris?What are the physical findings on nails characteristic of pemphigus vulgaris?What are the physical findings characteristic of pemphigus vulgaris during pregnancy?What are the Nikolsky sign and Asboe-Hansen sign in pemphigus vulgaris?What causes pemphigus vulgaris?What is the role of genetics in the etiology of pemphigus vulgaris?Which age groups are at highest risk for pemphigus vulgaris?What disorders are associated with pemphigus vulgaris?What are the differential diagnoses for Pemphigus Vulgaris?What is the role of indirect immunofluorescence (IDIF) in the workup of pemphigus vulgaris?What is the role of lab testing in the diagnosis of pemphigus vulgaris?What is the role of direct immunofluorescence (DIF) in the workup of pemphigus vulgaris?What are the histologic features of pemphigus vulgaris?What are the goals of treatment for pemphigus vulgaris?Which drugs are used in the treatment of pemphigus vulgaris?What are potential complications of pemphigus vulgaris?Which dietary modifications are used in the treatment of pemphigus vulgaris?Which activity modifications are used in the treatment of pemphigus vulgaris?Which specialist consultations may be needed for the treatment of pemphigus vulgaris?What are the goals of treatment for pemphigus vulgaris?What is the efficacy of drug treatment for pemphigus vulgaris?What is the role of cyclophosphamide in the treatment of pemphigus vulgaris?Which medications in the drug class Antineoplastics, Anti-CD20 Monoclonal Antibodies are used in the treatment of Pemphigus Vulgaris?Which medications in the drug class Immunosuppressants are used in the treatment of Pemphigus Vulgaris?Which medications in the drug class Corticosteroids are used in the treatment of Pemphigus Vulgaris?

Author

Bassam Zeina, MD, PhD, Consulting Staff, Department of Dermatology, Milton Keynes Hospital, UK

Disclosure: Nothing to disclose.

Coauthor(s)

Nicole Sakka, MBBS, Foundation Year 2, Royal Liverpool and Broadgreen University Hospital, Liverpool, UK

Disclosure: Nothing to disclose.

Sohail Mansoor, MBBS, MSc, Dermatologist and Lead Physician in Dermatologic Surgery, Department of Dermatology, Barnet Hospital, UK

Disclosure: Nothing to disclose.

Specialty Editors

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Disclosure: Nothing to disclose.

Jeffrey P Callen, MD, Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine

Disclosure: Received income in an amount equal to or greater than $250 from: Biogen US (Adjudicator for study entry cutaneous lupus erythematosus); Priovant (Adjudicator for entry into a dermatomyositis study); IQVIA (Serono - adjudicator for a study of cutaneous LE) <br/>Received honoraria from UpToDate for author/editor; Received royalty from Elsevier for book author/editor; Received dividends from trust accounts, but I do not control these accounts, and have directed our managers to divest pharmaceutical stocks as is fiscally prudent from Stock holdings in various trust accounts include some pharmaceutical companies and device makers for these trust accounts for: Stocks held in various trust accounts: Allergen; Amgen; Pfizer; 3M; Johnson and Johnson; Merck; Abbott Laboratories; AbbVie; Procter and Gamble;; Celgene; Gilead; CVS; Walgreens; Bristol-Myers Squibb.

Chief Editor

Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Abby S Van Voorhees, MD, Assistant Professor, Director of Psoriasis Services and Phototherapy Units, Department of Dermatology, University of Pennsylvania School of Medicine, Hospital of the University of Pennsylvania

Disclosure: Received honoraria from Amgen for consulting; Received honoraria from Abbott for consulting; Partner received salary from Merck for management position; Received honoraria from Abbott for speaking and teaching; Received honoraria from Amgen for review panel membership; Received honoraria from Centocor for consulting; Received honoraria from Leo for consulting; Received none from Merck for other.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Mohsin Ali, MBBS, FRCP, MRCP, to the development and writing of this article.

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Early, small blister filled with clear fluid arises on healthy skin.

Early, small blister filled with clear fluid arises on healthy skin.

Flaccid blister filled with clear fluid arises on healthy skin.

An erosion.

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

Erosions and healing areas on the back.

Healing areas on the chest and abdomen.

Early, small blister filled with clear fluid arises on healthy skin.

Flaccid blister filled with clear fluid arises on healthy skin.

An erosion.

Erosions and healing areas on the back.

Healing areas on the chest and abdomen.

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