Pemphigus Vulgaris 

Updated: Jun 14, 2018
Author: Bassam Zeina, MD, PhD; Chief Editor: Dirk M Elston, MD 

Overview

Practice Essentials

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 (see the image below).

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

See Clues in the Oral Cavity: Are You Missing the Diagnosis?, a Critical Images slideshow, to help identify the causes of abnormalities of the oral cavity.

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,[2] esophagus (causes odynophagia and/or dysphagia),[3] labia, vagina, cervix, vulva,[4] penis, urethra, nasal mucosa, and anus.

Skin

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.[5, 6]

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 Clinical Presentation for more detail.

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

  • Direct immunofluorescence (DIF): On normal-appearing perilesional skin[7] ; demonstrates in vivo deposits of antibodies and other immunoreactants, such as complement[8]

  • Indirect immunofluorescence (IDIF): If DIF results are positive; circulating intercellular antibodies are detected using IDIF in 80-90% of patients with pemphigus vulgaris[9]

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:

  • Corticosteroids: Discourage the inflammatory process by inhibiting specific cytokine production

  • Immunosuppressants: Should be considered early in the course of disease as steroid-sparing agents

See Treatment and Medication for more detail.

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, pemphigus foliaceus, and paraneoplastic pemphigus.[10] Each type of pemphigus has distinct clinical and immunopathologic features. Pemphigus vulgaris accounts for approximately 70% of pemphigus cases.

Pathophysiology

Pemphigus vulgaris 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 pemphigus vulgaris are associated with the binding of 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 keratinocyte cell surface the 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 pemphigus vulgaris; however, the role of these antigens in the pathogenesis of pemphigus vulgaris is not known.

Antibodies

Patients with the mucocutaneous form of pemphigus vulgaris have pathogenic antidesmoglein 1 and antidesmoglein 3 autoantibodies. Patients with the mucosal form of pemphigus vulgaris have only antidesmoglein 3 autoantibodies. Patients with active disease have circulating and tissue-bound autoantibodies of both the immunoglobulin G1 (IgG1) and immunoglobulin G4 (IgG4) subclasses.[11, 12]

More than 80% of the patients with active disease produce autoantibodies to the desmosomal protein desmoglein. Disease activity correlates with antibody titers in most patients.[13] In patients with pemphigus vulgaris, the presence of antidesmoglein 1 autoantibodies, as determined by enzyme-linked immunosorbent assay (ELISA), is more closely correlated with the course of the disease compared with antidesmoglein 3 autoantibodies. Lack of in vivo antibody binding (reversion to a negative result on direct immunofluorescence) 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 2 is the main activator of T lymphocytes, and increased soluble receptors have been detected in patients with active pemphigus vulgaris.

Epidemiology

United States

Pemphigus vulgaris is uncommon, and the exact incidence and prevalence depends on the population studied.

International

Pemphigus vulgaris has been reported to occur worldwide. Pemphigus vulgaris incidence varies from 0.5-3.2 cases per 100,000 population. Pemphigus vulgaris incidence is increased 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.[14]

Race

Pemphigus vulgaris affects persons of all races. The prevalence of pemphigus vulgaris is high in regions where the Jewish population is predominant.[15] For example, in Jerusalem, the prevalence of pemphigus vulgaris is estimated at 1.6 cases per 100,000 population; in Connecticut, the prevalence has been reported as 0.42 cases per 100,000 population.[16] 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 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).[17] In Finland, where few people of Jewish or Mediterranean origin live, the prevalence is low, at 0.76 case per million population.[18]

Sex

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

Age

The 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.[19]

Mortality/Morbidity

Pemphigus vulgaris is a potentially life-threatening autoimmune mucocutaneous disease with a mortality rate of approximately 5-15%.[1] Mortality in patients with pemphigus vulgaris is 3 times higher than the general population. 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 pemphigus vulgaris and in older patients.

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. Additionally, Patients with pemphigus vulgaris typically heal without scarring unless the disease is complicated by severe secondary infection.

Reversion of direct immunofluorescence (DIF) to negative can be useful to predict sustained remission after withdrawal of medication. Plucked hairs are an alternative to skin biopsy to provide a specimen for immunofluorescence, as 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.[20, 21]

Prognosis

The severity and natural history of pemphigus vulgaris are variable, but before the advent of steroids, most patients with pemphigus vulgaris died. Treatment with systemic steroids has reduced the mortality rate dramatically.[22]

Untreated, pemphigus vulgaris is often fatal because of the susceptibility to infection and fluid and electrolyte disturbances.

Most deaths occur during the first few years of disease, and, if the patient survives 5 years, the prognosis is good. Early disease probably is easier to control than widespread disease, and mortality rates may be higher if therapy is delayed.

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.

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

Patient Education

Minimize trauma to the skin because the patient's skin is fragile both from the disease and from the use of topical and systemic steroids.

The patient's understanding of the disease and education about pemphigus vulgaris is important because of the chronic nature of this disorder.

Educate patients regarding their medications. They should know about dose, adverse effects, and symptoms of toxicity so they can report adverse effects to the physician.

Educate patients about appropriate wound care.

 

Presentation

History

Mucous membranes

Pemphigus vulgaris presents with oral lesions in 50-70% of patients, 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 pruritic.

Drug-induced pemphigus vulgaris

Drugs reported most significantly in association with pemphigus vulgaris include penicillamine, captopril, cephalosporin, pyrazolones, nonsteroidal anti-inflammatory drugs (NSAIDs), and other thiol-containing compounds.[23] Rifampin, emotional stress, thermal burns, ultraviolet rays, and infections (eg, coxsackievirus, Herpesviridae family) have also been reported as triggers for pemphigus vulgaris.[24]

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.[34, 35]

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 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. Erosions 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 the cases.

Other mucosal surfaces may be involved, including the conjunctiva,[2] esophagus (causes odynophagia and/or dysphagia),[3] labia, vagina, cervix, vulva,[4] 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, as shown in the images below.

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

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 and is shown in the image below. Erosions often are large because of their tendency to extend peripherally with the shedding of the epithelium.

An erosion. 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.[5, 6] Patients with paronychial pemphigus usually also have oral involvement.

Pemphigus in pregnancy

Pemphigus vulgaris occurring 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.[36] 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.

Causes

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

Genetic factors

Predisposition to pemphigus is linked to genetic factors.[25] 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 pemphigus vulgaris.[26, 27, 28, 29, 30, 31]

Age

Peak age of onset is from 50-60 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 and thymoma.[32] A study of 110 patients with pemphigus found 4 patients with autoimmune thyroid disease and 3 patients with rheumatoid arthritis. In this study, however, autoimmune diseases were no more common in 969 first-degree relatives of patients with pemphigus than in the general population.[33]

 

DDx

 

Workup

Laboratory Studies

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

  • Histopathology from the edge of a blister

  • Direct immunofluorescence (DIF) on normal-appearing perilesional skin[7]

  • Indirect immunofluorescence (IDIF) using the patient's serum if DIF results are positive: The preferred substrate for IDIF is monkey esophagus or salt-split normal human skin substrate.

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. This pattern of immunoreactants is not specific for pemphigus vulgaris and may be seen in pemphigus vegetans, pemphigus foliaceus, and pemphigus erythematosus. 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. DIF results are shown in the image below.

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

Skin biopsy specimens placed in transport media may yield false-negative results; therefore, fresh tissue is the preferred substrate for DIF studies.

In the patient's serum, IDIF demonstrates the presence of circulating IgG autoantibodies that bind to epidermis. Circulating intercellular antibodies are detected using IDIF in 80-90% of patients with pemphigus vulgaris. The titer of circulating antibody correlates with disease course.[37]

Histologic Findings

Histopathology demonstrates an intradermal 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 foliaceous, 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.

 

Treatment

Medical Care

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. Note the images below. 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.[38]

Erosions and healing areas on the back. Erosions and healing areas on the back.
Healing areas on the chest and abdomen. Healing areas on the chest and abdomen.

Corticosteroids have improved overall mortality, but now much of the mortality and morbidity in these patients relates to the adverse effects of therapy. Whether massive doses of steroids have any advantage over doses of 1 mg/kg/d is unclear.[39]

Immunosuppressive drugs are steroid sparing and should be considered early in the course of the disease. Epidermal growth factor may speed healing of localized lesions.[40]  Many authorities now use rituximab, the anti-CD20 antibody, as first- or second-line therapy, with evidence from 2017 suggesting better outcomes when rituximab is used as a first-line agent.[41, 42, 43, 44, 45, 46, 47, 48, 49]  

Rituximab was approved by the US Food and Drug Administration (FDA) for treatment of pemphigus vulgaris in June 2018. Approval was based on a randomized trial that compared rituximab plus oral corticosteroid treatment with corticosteroid treatment alone as first-line therapy for patients with moderate-to-severe pemphigus vulgaris.[49] At month 24, 41 (89%) of 46 patients assigned to rituximab plus short-term prednisone were in complete remission off-therapy compared with 15 (34%) of 44 assigned to prednisone alone (P<.0001).

The antitumor necrosis factor drugs sulfasalazine and pentoxifylline have been reported as effective adjunctive treatments, reducing the serum level of tumor necrosis factor and resulting in rapid clinical improvement.[50] Methotrexate has also been used.[51, 52] Dapsone has been suggested as a steroid-sparing agent in the maintenance phase of pemphigus vulgaris treatment[53, 54] ; dapsone has also been suggested as a first-line agent.[55]

Intravenous immunoglobulin therapy has been suggested as efficacious in pemphigus vulgaris treatment.[56, 57, 58, 59] Amagai et al reported on the successful use of intravenous immunoglobulin in pemphigus patients who did not fully respond to systemic steroids,[60] and Asarch et al reported its use in pediatric patients.[61]

Infliximab has proven effective in some patients with refractory disease, and photodynamic therapy has been suggested as a possible adjunctive treatment for recalcitrant ulceration.[62] Mizoribine has been used for refractory ocular manifestations.[63]  

Plasmapheresis has been used in refractory cases, usually in conjunction with cytotoxic therapy.[64]

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 steroids.

Patients with oral disease may require a dentist and/or an otolaryngologist 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 corticosteroids 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.

Diet

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

Activity

Advise patients 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.

Complications

Secondary infection, which may be either systemic or localized to the skin, 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.

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.

Impaired immune responsiveness caused by corticosteroids and other immunosuppressive drugs may result in the rapid spread of infection. Corticosteroids suppress clinical signs of infection and may allow diseases such as septicemia or tuberculosis to reach an advanced stage before diagnosis.

Osteoporosis may occur following the use of systemic corticosteroids.

Adrenal insufficiency has been reported following prolonged use of glucocorticoids.

 

Medication

Medication Summary

The aim of treatment is to reduce the inflammatory response and autoantibody production. While target-specific therapy is not available, non–target-specific treatments currently are used. The most commonly used medications are corticosteroids.

The introduction of corticosteroids has reduced mortality greatly, but significant morbidity remains. Immunosuppressants should be considered early in the course of disease, as steroid-sparing agents. Mycophenolate mofetil and azathioprine are the usual agents considered as initial choices.[65, 66] Some suggest measuring levels of thiopurine methyltransferase (TPMT), a key enzyme in azathioprine metabolism, before starting patients on azathioprine.[67, 68, 69] Only one placebo-controlled blinded study of mycophenolate has demonstrated more rapid improvement in the short run but no significant steroid-sparing effects in the long term.[70] A retrospective chart review has suggested a therapeutic ladder for patients with pemphigus vulgaris, but these authors' approach has not been validated.[71] Rituximab and intravenous immunoglobulin have also proven useful alone or in combination, and some authorities are now using rituximab as first-line therapy for severe disease.[72] Rituximab was approved by the FDA for the treatment of pemphigus vulgaris in June 2018.[75]

A small case control trial showed improved laboratory and clinical outcomes in patients with pemphigus vulgaris treated with a combination of cytotoxic agents plus intravenous immunoglobulin (IVIG)compared with those treated with just IVIG.[73]

Cyclophosphamide is used for refractory disease.[74] The role of biologic agents is being investigated. Each of these agents should be prescribed and monitored by physicians familiar with them. 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.

Anti-CD20 Monoclonal Antibodies

Class Summary

Monoclonal antibodies target the CD20 antigen expressed on the surface of pre-B and mature B-lymphocytes. B cells may be acting at multiple sites in the autoimmune/inflammatory process, including T-cell activation and/or proinflammatory cytokine production.

Rituximab (Rituxan)

Rituximab is an anti-CD20 monoclonal antibody indicated for adults with pemphigus vulgaris in combination with short-term corticosteroid therapy.

Anti-inflammatory agents

Class Summary

Anti-inflammatory agents inhibit the inflammatory process by inhibiting specific cytokine production.

Prednisone (Deltasone, Meticorten, Orasone, Sterapred)

Prednisone may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. It stabilizes lysosomal membranes and suppresses lymphocytes and antibody production. For treating pemphigus vulgaris, administer it orally and use alone or in combination with topical or intralesional steroids or in conjunction with other immunosuppressives.

In pediatric patients, disease management with this medication in consultation with the patient's pediatrician is advised.

Immunosuppressive agents

Class Summary

Immunosuppressive agents are useful adjuvants in patients with pemphigus vulgaris with generalized disease unresponsive to steroids and/or other anti-inflammatory agents or in patients unable to tolerate prednisone. Some suggest measuring levels of thiopurine methyltransferase (TPMT), a key enzyme in azathioprine metabolism, before starting patients on azathioprine.

Azathioprine (Imuran)

Azathioprine antagonizes purine metabolism and inhibits the synthesis of DNA, RNA, and proteins. It may decrease the proliferation of immune cells, which results in lower autoimmune activity. In conjunction with prednisone, it is more effective than prednisone alone. OFf-label use of azathioprine may be an effective monotherapy in mild cases, although therapeutic effects are delayed 3-5 weeks. Consider withdrawal if no improvement is seen within 3 months.

 

Questions & Answers

Overview

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 mortality rate of pemphigus vulgaris?

What is an alternative to serial skin biopsies for obtaining immunofluorescence specimens of pemphigus vulgaris?

What is the prognosis of pemphigus vulgaris?

What is included in patient education about pemphigus vulgaris?

Presentation

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?

DDX

What are the differential diagnoses for Pemphigus Vulgaris?

Workup

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?

Treatment

What are the goals of treatment for pemphigus vulgaris?

Which drugs are used in the treatment of pemphigus vulgaris?

Which specialist consultations may be needed for the treatment 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?

What are potential complications of pemphigus vulgaris?

Medications

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 Immunosuppressive agents are used in the treatment of Pemphigus Vulgaris?

Which medications in the drug class Anti-inflammatory agents are used in the treatment of Pemphigus Vulgaris?

Which medications in the drug class Anti-CD20 Monoclonal Antibodies are used in the treatment of Pemphigus Vulgaris?