Oral Manifestations of Autoimmune Blistering Diseases 

Updated: Feb 11, 2019
Author: Nita Chainani-Wu, DMD, MS, MPH, PhD; Chief Editor: William D James, MD 

Overview

Background

Oral lesions are observed commonly in autoimmune blistering skin diseases. Oral lesions can be the predominant or minor clinical manifestation of a given disease. Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are the earliest recognized autoimmune blistering diseases, and, together, they account for about one half of the autoimmune blistering diseases. While most patients with pemphigus vulgaris have oral lesions, which usually are the first manifestation of this disease, only a few patients with bullous pemphigoid have oral lesions. Over the last few decades, many other autoimmune blistering diseases have been delineated, and some of these newly identified diseases have oral manifestations.

This article discusses the oral manifestations of several well-characterized autoimmune blistering diseases, including pemphigus vulgaris, bullous pemphigoid, linear immunoglobulin A (IgA) bullous dermatosis, and paraneoplastic pemphigus (PNP). A group of autoimmune blistering diseases affecting primarily the mucous membranes is termed mucous membrane pemphigoid (MMP) (also termed cicatricial pemphigoid). Because this topic is discussed in a separate article, it is not described in great detail in this article.

Animal models

Spontaneous animal homologues of human autoimmune blistering diseases have been identified in the last 2 decades.[1] Those diseases in which oral involvement occurs include pemphigus vulgaris (dogs, cats), paraneoplastic pemphigus (dog, cat),[2] bullous pemphigoid (dogs, cats, horses, pigs),[3, 4] mucous membrane pemphigoid (dogs, cats),[5] linear IgA bullous dermatosis (dogs), epidermolysis bullosa acquisita (dogs), and bullous systemic lupus erythematosus (1 dog). The histopathologic and immunopathologic findings usually are the same as that of human diseases and are not discussed here.

Pemphigus group

Pemphigus vulgaris is a very rare acantholytic skin disease. In most cases, oral involvement is severe, and the mouth sometimes can be the first site to exhibit lesions. Flaccid vesicles on the gums, tongue, and palate evolve rapidly into erosions and ulcerations with indistinct margins and peripheral sloughing of mucosal epithelium (Nikolsky sign). Pemphigus foliaceus, the most common form of pemphigus observed in animals, affects dogs and cats. It usually does not affect oral and other mucosal membranes.

Pemphigoid group

The pemphigoid group includes the following:

  • Bullous pemphigoid

  • Mucous membrane pemphigoid

  • Epidermolysis bullosa acquisita

  • Bullous systemic lupus erythematosus

Pathophysiology

As a group, autoimmune blistering skin diseases are recognized as autoantibody-mediated diseases. This group of diseases can be divided into two major subsets, the pemphigus subset and the pemphigoid subset. Whereas the pemphigus subset of diseases is mediated by autoantibodies that target the extracellular skin components that link one epidermal cell to another, the pemphigoid subset is mediated by autoantibodies that target the extracellular skin components that link the skin basement membrane components either to the lowermost layer of epidermal cells or to the dermal components. Accordingly, the pemphigus subset of diseases is termed intraepidermal blistering disease, while the pemphigoid subset of diseases is named subepidermal blistering disease. Passive transfer experiments have demonstrated that purified autoantibodies from patients with the pemphigus group of diseases can induce blister formation when delivered to newborn mice.

Passive transfer experiments using autoantibodies from human patients with two major forms of the pemphigoid group of diseases (ie, bullous pemphigoid, epidermolysis bullosa acquisita) failed to induce clinically observable blisters in newborn mice; however, rabbit antibodies raised against the recombinant proteins encoded by the gene of mouse bullous pemphigoid antigen 2 (BP180) are capable of inducing blisters in newborn mice in a complement-dependent manner. Furthermore, anti-BP180 autoantibodies from patients affected with BP are capable of inducing dermal-epidermal separation in cryosections of normal human skin, further supporting the pathogenic role of BP180.

In addition, rabbit antibodies raised against type VII collagen (epidermolysis bullosa acquisita antigen) are also capable of inducing blisters in mice. So far, no truly active experimental animal models (in which healthy mice are induced to autoimmune disease de novo) are known to facilitate the studies on the induction phase of autoimmune blistering diseases. Nevertheless, autoantibodies can be induced by immunized healthy BALB/c mice with synthetic peptides of the mouse bullous pemphigoid antigen 2 NC16A domain.

In certain patient subsets, the development of the autoimmune disease has been proposed to have been triggered by an immune phenomenon, "epitope spreading," a concept stating that tissue injuries from an inflammatory event may expose the previously hidden autoantigen to autoreactive lymphocytes, leading to autoimmune disease.[6, 7] Possible clinical examples include mucous membrane pemphigoid and paraneoplastic pemphigus. For example, patients who developed ocular mucosal injury secondary to an inflammatory disease termed Stevens-Johnson syndrome are noted to subsequently develop ocular mucous membrane pemphigoid.[8]

Etiology

Autoimmune blistering diseases generally are caused by autoantibodies targeting the skin components of the epithelial cell surfaces or basement membrane zone. Certain human leukocyte antigen (HLA) alleles have been reported to be associated with autoimmune blistering diseases. For example, HLA-DQB1*0301 is associated strongly with bullous pemphigoid and mucous membrane pemphigoid.[9, 10]

Pemphigus group

Desmoglein-3 is the primary target antigen in pemphigus vulgaris, and desmoglein-1 is the exclusive target antigen in pemphigus foliaceus. In passive transfer experiments, these autoantibodies apparently induced (in newborn mice) blisters that have similar histology as the human diseases. These autoantibodies apparently are capable of inducing the blisters without the help of complement components; however, autoantibodies against desmoglein-1 are present in patients with pemphigus vulgaris and are capable of inducing blisters in newborn mice.

Paraneoplastic pemphigus

No true cause has been firmly established. Some patients have autoantibodies against desmoglein-3, and these autoantibodies can induce blisters in newborn mice.[11] The possible link between the underlying neoplasm and autoimmunity may be due to an immune dysregulation secondary to the presence of neoplasm. In addition to autoantibodies to desmoglein-3, most patients develop autoantibodies to many intracellular epithelial components, desmoplakins I and II, periplakin, envoplakin, BP230 (BPAg1), and a 170-kd membrane protein. Several other smaller proteins are involved.

Autoantibodies to these intracellular components probably develop as a secondary autoimmune response rather than a primary cause. Neoplasms are clearly associated with paraneoplastic pemphigus. The most common associated benign tumor is thymoma, followed by Castleman tumor, a rare and complex lymphoproliferative disease. The most common associated malignant tumor is non-Hodgkin lymphoma, followed by chronic lymphocytic leukemia.

Pemphigoid group

Autoantibodies to BP180 are the likely inducing autoantigen. Passive transfer experiments using rabbit antimouse BP180 antibodies induce blisters in newborn mice, and the blister induction apparently is complement dependent. The target antigen for linear IgA bullous dermatosis (childhood and adult) is a truncated BP180 protein. The target antigen for epidermolysis bullosa acquisita is type VII collagen, particularly the noncollagenous (NC1) domain.

Mucous membrane pemphigoid

Multiple target antigens have been identified, including BP180, laminin-5, laminin-6, type VII collagen, and beta-4 integrin, but no clinical hallmark distinguishes subsets of patients with regard to the target antigen. Rabbit antibodies generated against laminin-5 can induce blisters in newborn mice. Presently, the link between the autoantibodies and the scarring process that characterizes this group of diseases is missing.

Epidemiology

Frequency

United States

The prevalence at which autoimmune mucocutaneous blistering diseases occur in the United States is not known. Because of the rarity of these diseases and because of the wide clinical heterogeneity, epidemiologic study is difficult.

International

Likewise, the true prevalence of autoimmune mucocutaneous blistering diseases internationally is unknown. Nevertheless, it is now well recognized that this group of diseases does occur throughout Europe, Asia, the Americas, and Arabic countries.

Race

No significant racial predilection for autoimmune blistering skin diseases exists other than an increase in frequency of pemphigus vulgaris in some Jewish populations.

Sex

No sexual predilection for autoimmune blistering skin diseases exists other than a slight predilection of females for mucous membrane pemphigoid.

Age

Autoimmune blistering diseases primarily affect elderly patients, although occasional cases of childhood onset have been reported. The noted exception is linear IgA bullous dermatosis; about one half of patients with this disease have onset during childhood.

Prognosis

The prognosis for patients with autoimmune blistering diseases generally is quite good. A small percentage of patients with pemphigus vulgaris do not respond well to treatment or may develop serious adverse effects from prednisone, which can lead to a fatal outcome. The prognosis for patients with paraneoplastic pemphigus is poor unless the associated primary neoplasm is found and eradicated.

Mortality/morbidity

The pemphigus vulgaris group of diseases is generally is more severe and has higher mortality than mucous membrane pemphigoid. Both pemphigus and pemphigoid are chronic inflammatory diseases and, therefore, carry significant morbidity from the diseases themselves and from the adverse effects of therapeutic medications.

Pemphigus group

Before the availability of corticosteroids, most patients with pemphigus vulgaris died. The extensively denuded skin surfaces from the broken blisters in these patients made them very susceptible for all kinds of infections, water loss, and electrolyte imbalance. Severe oral erosions interfered with patients' proper eating and drinking and significantly hindered their nutrient intake and the health of their immune functions, thus further reducing their ability to defend against infections. The long-term use of corticosteroids and immunosuppressives agents introduces significant adverse effects (eg, osteoporosis, diabetes, susceptibility to infections) after long-term use. Several cases of cutaneous squamous cell carcinomas and one case of primary brain lymphoma have been reported to develop in patients with pemphigus vulgaris who received long-term immunosuppressive treatments.[6]

Pemphigoid group

As a group, a much lower mortality exists for this group than for the pemphigus group of diseases; nevertheless, the chronicity of the diseases can bring significant morbidity to patients. Adverse effects from chronic use of corticosteroids and immunosuppressives also can contribute to morbidity.

Paraneoplastic pemphigus

This disease is the most resistant to conventional medical treatment. If the primary neoplasm associated with the pemphigus is found and removed completely, patients usually responded to the treatments relatively well and could recover completely; however, if the primary neoplasm is not found or cannot be eradicated completely, the disease will likely lead to a fatal outcome.

Patient Education

Educate patients with autoimmune diseases about the nature of the disease and the possible adverse effects of long-term use of immunosuppressives. In addition, patients should know about the benefits of taking calcium and vitamin D supplements while using systemic corticosteroids. Finally, educate patients to monitor signs and symptoms of infection in order to report possible complications to physicians in a timely manner.

 

Presentation

History

Autoimmune mucocutaneous blistering diseases generally have an insidious onset.

When oral lesions are present, they invariably are symptomatic, varying from mild to severe pain.[12]  Patients with mucous membrane pemphigoid often report spontaneous gum bleeding. Lesions start to surface in the oral cavity by approximately 6 months prior to the skin lesions in most patients with pemphigus vulgaris.

In some patients who have oral manifestations of autoimmune blistering diseases, the symptoms are so severe that they prevent them from proper dietary intake, resulting in severe malnutrition.

In patients who have rectal involvement, pain and bleeding could be early symptoms.

In patients with laryngeal involvement, hoarseness could be an early symptom.

Intractable hemorrhagic stomatitis is highly suggestive of paraneoplastic pemphigus.

Physical Examination

Oral manifestations of autoimmune blistering diseases generally can affect any area of the oral cavity, including the gingiva, palate, buccal, tongue, floor of the mouth, and pharynx. Blisters are broken easily; therefore, they rarely are observed clinically. Instead, erosions and superficial ulcers more likely are observed. However, in pemphigoid, because the blisters are situated deeply, they are more likely to be observed intact clinically.[13, 14]

In pemphigus vulgaris, oral lesions occur in most patients. In most patients, the oral mucous membranes are affected within 6 months of disease onset. In some patients, it remains exclusively an oral disease for months or years before generalized skin disease develops. For pemphigus vulgaris, the oral lesions are usually first to surface and last to resolve in any given patient. Typically, small blisters rapidly evolve into erosions covered with white-yellow pseudomembranes. All areas of oral mucous membranes, gingiva, buccal, palate, tongue, and floor of the mouth can be affected (see the image below). A subgroup of patients with pemphigus vulgaris does not develop skin disease.

Oral manifestations, including blisters, hemorrhag Oral manifestations, including blisters, hemorrhagic erosions, and crusts, are shown on a patient with pemphigus vulgaris.

Pemphigus foliaceus is predominantly a skin disease. Oral or other mucous membrane involvements are very rare. In skin, desmoglein-3 is present predominantly in the lower layers of epithelial cells. By contrast, the layers of desmoglein-3 are present throughout the upper and lower layers of epithelium in the oral mucous membrane. Thus, the autoantibodies of patients with pemphigus foliaceus, which exclusively target desmoglein-1, are unable to break down the adherence of the upper layers of epithelium of oral mucosa, which is protected by the presence of desmoglein-3.

In paraneoplastic pemphigus, oral lesions, which are invariably present in this disease, can precede, follow, or appear at the same time of neoplasm discovery.[15] Severe mucositis with hemorrhagic blisters, erosion, or ulceration can be observed in various oral mucosae. Lesions at the vermilion border almost always are present, which often leads to misdiagnosis of paraneoplastic pemphigus as erythema multiforme. For paraneoplastic pemphigus, the intractable hemorrhagic stomatitis is extremely painful and could cause substantial morbidity for patients with this disease.

In patients with bullous pemphigoid, oral lesions rarely are observed. If present, they usually are mild and consist of small blisters or erosions. In one patient with bullous pemphigoid and hemophilia, extensive bullous lesions occurred in the mouth, along with substantial bleeding.[16]

With linear IgA bullous dermatosis (of adult and children), the oral lesions, rarely present, are similar to that of bullous pemphigoid or can mimic aphthaelike ulcers.[17]

Oral lesions in epidermolysis bullosa acquisita commonly are observed. The lesions are deep-seated blisters, erosions, and ulcers, sometimes hemorrhagic. Milia are clinically observed.

Regarding mucous membrane pemphigoid, the oral mucous membrane is the most frequently affected site in this heterogeneous group of diseases, followed by ocular, skin, nasal, genital, pharyngeal, esophageal, laryngeal, and anal mucous membranes.[18] Over 90% of patients with mucous membrane pemphigoid have oral mucosal lesions, as shown in the image below.[19]

Oral manifestations of mucous membrane pemphigoid Oral manifestations of mucous membrane pemphigoid (also known as cicatricial pemphigoid). Inflammatory gingival changes are characteristic of the disease.
 

DDx

 

Workup

Laboratory Studies

Direct immunofluorescence microscopy

Direct immunofluorescence microscopy (DIF) determines the types and locations of immune deposits within patients' epithelial tissues. DIF detects deposits at the epithelial cell surfaces and at the epithelial basement membrane zone of the perilesional skin biopsy specimens obtained from patients with the diseases of the pemphigus and pemphigoid groups, respectively. Note the images below.

Direct immunofluorescence microscopy performed on Direct immunofluorescence microscopy performed on epithelial biopsy specimen obtained from a patient with pemphigus vulgaris detects immunoglobulin G deposits at the epithelial cell surfaces.
Direct immunofluorescence microscopy performed on Direct immunofluorescence microscopy performed on biopsy specimen obtained from a patient with mucous membrane pemphigoid detects linear immunoglobulin G deposits at the epithelial basement membrane zone.

In paraneoplastic pemphigus, DIF usually reveals deposits at both the epithelial cell surfaces and the epithelial basement membrane zone.

In a study of the sensitivity of DIF on oral mucosal tissues for oral diseases, it was found that positive DIF findings were detected in 100% of pemphigus vulgaris cases, 67% of cicatricial pemphigoid cases, and 56% of bullous pemphigoid cases. Interestingly, biopsy specimens taken from oral tissue location distant to the actual lesion provide essentially the same positive rate as those taken perilesionally. In addition, punch biopsies yielded significantly better positive rates than shave biopsies.[20]

Indirect immunofluorescence microscopy

Indirect immunofluorescence microscopy (IIF) determines the patterns of patients' circulating autoantibodies that bind the epithelial components.

IIF detects epithelial cell surface-binding and epithelial basement membrane zone-binding autoantibodies in patients with diseases of the pemphigus and pemphigoid groups, respectively. The titer of the circulating autoantibodies corresponds to the severity of disease in pemphigus.

In addition to binding to squamous epithelial cell surfaces (eg, skin, esophagus substrates), circulating autoantibodies from patients with paraneoplastic pemphigus also label transitional epithelium (eg, lumen of rat bladder).

Indirect immunofluorescence on salt-split substrate

Indirect immunofluorescence on salt-split substrate (ssIIF) uses epithelial substrates in which the lamina lucida of the basement membrane zone has been split at the middle, leaving the target antigens for the autoantibodies of bullous pemphigoid and epidermolysis bullosa acquisita to the roof and the base of the split substrate, respectively.

Using salt-split epithelial substrates, ssIIF detects the circulating autoantibodies from patients with bullous pemphigoid and epidermolysis bullosa acquisita binding respectively to the roof and the base of the substrates, thus distinguishing these two diseases.

In patients with mucous membrane pemphigoid, their circulating autoantibodies can bind to the roof, the base, or both, corresponding to the heterogeneity of the target antigens recognized by these autoantibodies.

Imaging Studies

No imaging studies generally are needed for establishing diagnoses for patients with oral manifestations of autoimmune blistering diseases; however, in patients with paraneoplastic pemphigus, a vigorous search for internal malignancies should be performed. Whenever patients' symptoms are suggestive, perform imaging studies (eg, CT scan, radiograph, bone scan, MRI, ultrasound).

Order dental periapical x-rays in patients with autoimmune blistering disease affecting the gingival mucosa to rule out periodontal disease.

Other Tests

Immunoelectron microscopy

Two methods of immunoelectron microscopy (IEM) can be used to delineate the ultrastructural location of the target antigens, direct method of IEM (DIEM) and indirect method of IEM (IIEM).[21] Whereas DIEM uses patients' epithelial tissues, IIEM uses patients' circulating autoantibodies (serum study). IEM tests are used primarily to study the various autoantigens in the epithelial basement membrane zone.

IEM detects the target antigens (BP180) for bullous pemphigoid, linear IgA bullous dermatosis, and a certain subset of mucous membrane pemphigoid at the upper lamina lucida/hemidesmosome areas[22] ; detects the target antigens laminin-5 and laminin-6 for a certain subset of mucous membrane pemphigoid at the lower lamina lucida; and detects the target antigen, type VII collagen, for epidermolysis bullosa acquisita at the lamina densa and sublaminar densa areas.

Immunoblotting

Immunoblotting (IB) test delineates the molecular sizes of the target antigens that are immunolabeled by patients' autoantibodies.[23, 24]

IB test is able to detect that the autoantibodies from patients with bullous pemphigoid and certain subsets of mucous membrane pemphigoid recognize a 230-kd (BPAg1) and/or a 180-kd (BPAg2) epithelial proteins; that the autoantibodies from patients with certain subset of mucous membrane pemphigoid recognize one or all of the 3 protein subunits, 200-kd/165-kd (alpha chain), 140-kd (beta chain), and 155-kd/105-kd (gamma chain) of laminin-5; and that the autoantibodies from patients with epidermolysis bullosa acquisita recognize the 290-kd type VII collagen.

Enzyme-linked immunosorbent assay

Enzyme-linked immunosorbent assay (ELISA) test detects the target antigens of circulating autoantibodies from patients using the known recombinant proteins.[25] ELISA test detects autoantibodies that recognize their autoantigens in nondenatured form; therefore, it is a more sensitive detection method than IB test. ELISA test also can be a quantitative method.

Immunoprecipitation

Immunoprecipitation (IP) test detects the target antigens of circulating autoantibodies from patients. IP test detects autoantibodies that recognize their autoantigens in native form; therefore, it is a more sensitive detection method than IB test but is more difficult to perform.

Procedures

No diagnostic procedures for cancer detection above those age-related tests generally are needed for oral manifestations of autoimmune blistering diseases; however, when encountering patients with paraneoplastic pemphigus, a vigorous search for internal malignancies should be performed. Besides a thorough history and physical examination, when patients' symptoms are suggestive, proper use of diagnostic procedures (eg, colonoscopy, upper GI endoscopy) may be needed.[26]

Histologic Findings

Histology determines the levels in which the blisters occur and the types of inflammatory infiltrates, both of which help determine the final diagnosis. Histopathology delineates the blisters occurring within the epithelium and below the epithelium for the diseases of the pemphigus and pemphigoid groups, respectively. In addition to blisters occurring at the epithelium level, histology of paraneoplastic pemphigus reveals a lichenoid pattern of inflammatory cell infiltration and necrotic epithelial cells.

 

Treatment

Medical Care

Patients with oral manifestations of autoimmune blistering diseases should be treated conjointly with an oral medicine specialist. Furthermore, patients should have an oral prophylaxis performed by a dental hygienist or dentist prior to initiation of systemic or topical therapy. During the course of therapy, patients should have oral prophylaxis (oral hygiene) performed every 3-4 months. Additionally, they should be monitored for oral candidiasis, especially once on immunosuppressive therapy.

For patients who are treated with systemic corticosteroids, calcium and vitamin D blood levels should be monitored and supplements given if needed to reduce steroid-induced osteoporosis. Furthermore, and especially in patients with pemphigus vulgaris, a baseline bone density test should be performed.

For patients with severe disease who are treated with systemic corticosteroids, steroid-induced osteoporosis should be prevented or reduced by taking an osteoclast-mediated bone resorption inhibitor-bisphosphonate (eg, Fosamax).[27, 28]

For pemphigus vulgaris patients who do not respond to more conventional therapies, intravenous infusion of humanized monoclonal antibodies to B cells (anti-CD20, rituximab) should be discussed with the patient's primary physician, after the precaution to assess for serious infections is taken into account.[29, 30, 31, 32, 33, 34, 35]

Elderly patients who have other significant health problems (eg, diabetes mellitus, hypertension, heart diseases) may require treatment with a more conservative approach (eg, topical corticosteroids, tetracycline[36] ). The goal of treatment is to achieve disease control with low doses of medications and minimal adverse effects.

Inpatient care frequently is required for patients with the pemphigus group of diseases, particularly for those with pemphigus vulgaris and paraneoplastic pemphigus.

Transferring patients with extremely severe disease with most of the skin denuded to a burn unit for close skin care may be indicated.

Surgical Care

Surgical care usually is not needed in treating the oral manifestations of patients with autoimmune blistering diseases.

Consultations

Examination by pulmonary specialists is recommended for patients with severe oral lesions, especially those patients with paraneoplastic pemphigus if the patients have symptoms or signs suggestive of respiratory difficulty. Respiratory failure and death have been reported in these patients.[37, 38]

Examination by gastroenterologists is recommended for some patients with severe oral lesions to detect possible involvement of the esophagus. Dysphagia can be an associated symptom.

Examination by ophthalmologists experienced in external eye diseases is recommended for those patients with oral lesions and symptoms or signs of ocular inflammation.

Thorough examination by consulting physicians experienced in mucous membrane pemphigoid (cicatricial pemphigoid) is recommended for some patients with oral lesions that also can have genital mucosal involvement.

Care provided by oral medicine specialists or physicians experienced in the field of oral medicine is recommended for patients with severe oral disease.

Diet

Advise patients with oral mucosal manifestations of autoimmune blistering diseases to eat a balanced diet and to avoid rough or spicy foods. Patients generally have no dietary restrictions once the disease is under control.

During periods of flare-up, soft and bland diets are preferred since it will cause less trauma to the injured tissue. Foods with strong acidity and spicy foods should be avoided. Patients with epidermolysis bullosa acquisita should avoid foods with a hard-to-chew quality since this disease tends to be exacerbated by minor trauma.

Activity

Generally, no activity restrictions are recommended for patients with oral manifestations of autoimmune blistering diseases; however, strenuous physical activities may not be advisable for patients with epidermolysis bullosa acquisita since this disease is exacerbated by trauma.

Complications

Monitoring treatment complications (eg, infection, osteoporosis, adrenal suppression) for patients receiving long-term immunosuppressive treatments is needed. If observed, treat complications properly.

Prevention

Institute a combined supplement of calcium and vitamin D for patients treated with systemic corticosteroid for longer than 1 month to prevent osteoporosis. The guideline for dosage and frequency of this supplement is stated in the 1996 recommendations established by the American College of Rheumatology Task Force.[39]

Institute a combined regimen of a non-alcohol–based mouthwash (Biotene mouthwash) and a weekly dose of systemic antifungal medication for patients at risk for oral candidiasis.

Long-Term Monitoring

Regular follow-up care for patients with oral and skin involvement by their dermatologist and oral medicine specialist is recommended when the disease is active and during the tapering of medication when the disease is in remission.

Patients with oral disease alone should receive follow-up care from an oral medicine specialist, otherwise poor oral hygiene will interfere with treatment outcome. Furthermore, complications from poor oral care could lead to periodontal disease and early teeth loss.

During the active disease stage, patient follow-up care every 4-6 weeks is recommended. Patients should be monitored for oral yeast infection. During the clinical remission stage, patient follow-up care every 6 months is recommended.

 

Medication

Medication Summary

The treatment strategy for oral manifestations of autoimmune blistering diseases generally is the same as the treatment for the autoimmune blistering diseases themselves; therefore, please see Pemphigus Vulgaris, Bullous Pemphigoid, and Linear IgA Dermatosis for treatment options for those patients with these diseases who have oral involvement.

For mucous membrane pemphigoid in which mucous membranes primarily are affected, the treatment strategy is discussed in detail in a separate article; therefore, the treatment for mucous membrane pemphigoid is not discussed herein. Adjunct treatments particularly relevant to oral lesions as a result of these autoimmune diseases are outlined below.[18]

Anti-inflammatory agents are used to treat oral lesions.[40, 41, 42]

Anti-inflammatory agents

Class Summary

These agents are used to treat oral lesions.

Clobetasol (Temovate)

Clobetasol suppresses mitosis and increases the synthesis of proteins that decrease inflammation and cause vasoconstriction. It is a class I superpotent topical steroid useful in treating oral lesions. Topical corticosteroids commonly are used intraorally for oral manifestations of autoimmune blistering skin diseases. Since these diseases are chronic and inflammatory in nature, topical corticosteroids are very useful as an adjunct treatment. Patients with disease confined to the gingiva should see a dentist for a custom-made soft tray to carry the medication.

Dapsone (Avlosulfon)

The mechanism of action is similar to that of sulfonamides, in which competitive antagonists of PABA prevent the formation of folic acid, inhibiting bacterial growth. Its anti-inflammatory mechanism of action remains unknown but probably relates to the suppression of neutrophil function. Dapsone is used alone or in conjunction with other anti-inflammatory medications or immunosuppressives for oral lesions.

Tetracycline (Sumycin)

The mechanism of action probably is by its anti-inflammatory properties, although it is an antibiotic by nature. Tetracycline can be used alone or in conjunction with niacinamide.

Niacin (Vitamin B-3)

This is the source of niacin used in tissue respiration, lipid metabolism, and glycogenolysis.