Oral Manifestations of Autoimmune Disorders

Pemphigus vulgaris


	Pemphigus vulgaris can affect the keratinized and nonkeratinized tissues of the oral cavity including the gingiva forming erosions often resembling desquamative gingivitis

Pemphigus disease is a rare and potentially life-threatening autoimmune blistering disease

The disease is most

commonly found in the Jewish population, particularly those of

Ashkenazi origin, and Eastern countries such as Malaysia, China,

and Japan, with a slight female predilection

This, combined with exogenous factors (medications,viral infection, diet, etc.) and/or endogenous factors (stress) initiate autoimmune mechanisms leading to tissue damage

Clinical features

Clinically, PV almost always begins with multiple mucosal site

involvement; frequently, those areas that are subjected to

frictional trauma such as the gingiva, palate, buccal mucosa,

and tongue .Oral involvement can precede skin

involvement by up to 1 year. Lesions begin as flaccid vesicles or

bullae that rupture quickly, leaving behind painful shallow ul-

cerations that heal without scarring.

Treatment considerations

Corticosteroids remain the most common treatment modality

for this condition. When there are only oral lesions present,

corticosteroids are applied topically in rinse or gel formulations.

PV is a potentially life-threatening disease and, therefore, re-

quires an early and more intensive therapeutic regimen than

other autoimmune blistering diseases; if skin lesions are present,

treatment consists of systemic steroids (pulse or continuous) and

may be combined with adjuvant immunomodulatory or immu-

nosuppressive medications, including azathioprine as first-line

therapy

Mucous membrane pemphigoid


	Mucous membrane pemphigoid frequently presents with bright erythema of the gingiva referred to as desquamative gingivitis note plaque accumulation because of pain on brushing

Pemphigoid disease is a blistering disorder affecting the skin or mucosa at the level of the subepithelia or

subepidermis. When the mucosal membranes are the primary

site of involvement it is known as mucous membrane pemphi-goid

Clinical features

Mucous membrane pemphigoid predominantly affects the mu-cous membranes of the oral cavity (85%);however, other

mucosal surfaces such as the ocular conjunctiva (65%) naso-

pharynx (20%e40%), anogenital (20%) ....and others can be affected

Oral involvement may precede skin involvement by up to 1 year.

Lesions will almost always begin with multiple intraoral mucosal site involvement, those areas that are subjected to

frictional trauma such as the buccal mucosa, labial mucosa,

palate, and gingiva frequently In contrast with PV,

vesicles or bullae may be more readily seen in the oral cavity

owing to the location of tissue separation, albeit rarely . It is not uncommon for ulceration to heal with scarring. Scarring of the conjunctiva could

lead to adhesions(symblepharons), eyelid inversions (entropion), and/or corneal abrasion from eyelashes (trichiasis). Laryngeal involvement

could potentially cause voice alterations and airway limitations

in severe cases

Treatment considerations

Topical treatments can effectively control mild to moderate disease of the oral cavity. Similar to PV, topical corticosteroids remain the most common treatment modality. If unsuccessful,

a treatment algorithm developed as part of a systematic

review then recommends systemic dapsone, tetracycline,

sulphamethoxypyridazine and sulphapyridine, azathioprine,

mycophenolate mofetil, and cyclophosphamide .a recent case report yielded success with topical tacro-limus solution as an oral rinse or, with localized lesions, a series

of repeated intralesional triamcinalone injections .With

systemic involvement, the primary outcome of therapy is reducing the possibility of irreversible scarring of the ocular,esophageal, genital, and laryngeal mucosa and preventing

blindness, strictures, or airway obstruction depending on the

areas of involvement. In severe cases intravenous immuno-

globulin and prednisolone/cyclophosphamide combination

Oral lichen planus


	Oral lichen planus most commonly present in the classic reticular form on the buccal mucosa, which is typically asymptomatic or as gingival erythema/erosion, also known as desquamative gingivitis

Oral lichen planus

Incidence, predilection, and genetics

Oral lichen planus (OLP) is a common mucosal inflammatory

disorder affecting up to 2% of the population. The true prev-

alence of OLP is not known; however; depending on the

particular population being examined, it has an estimated

prevalence of 1.27%. The typical age of presentation is in the

40s and affects women more so than men.13

The etiology of OLP is uncertain, but it is thought to be an

immune-related process triggered by an antigen(s) that alter

basal keratinocytes making them susceptible to cell mediated

immune response. CD4þ T and DC8þ T lymphocytes are acti-

vated and cytokines such as IL-2, interferon-gamma, and TNF

are produced. Other cells such as dendritic cells, mastocyte

cells, and macrophages may play a role in the pathologic pro-

cesses. The triggering antigen is unknown; however, several

reports have suggested a possible association between OLP and

viral infections (herpes simplex, Epstein-Barr, cytomegalo-

virus, herpes simplex-6, human papilloma virus, and hepatitis C

virus

Clinical features

Typically, patients present with complaints of pain and burning

in the mouth owing to the presence of erosions and shallow ul-

cerations, exacerbated by eating spicy or acidic foods. Forty

percent of patients may have both oral and cutaneous involve-

ment, cutaneous lesions alone in 35%, and mucosal lesions alone

in 25% of affected individuals.15 OLP has 4 distinct clinical pre-

sentations: reticular, erosive, plaque-like, and bullous. Each

can occur individually; however, patients frequently have a

combination of any of these patterns. Reticular OLP is the most

common and is usually asymptomatic. Lesions typically present

with bilateral buccal mucosa involvement followed by the

buccal vestibule, tongue, and gingiva

Treatment considerations

There is no cure for the condition, most likely because the

cause is unknown. Treatment goals are focused on alleviating

symptoms by hastening the healing of erosions and ulcerations

and, if possible, increasing the periods of disease remission. As

in the other blistering conditions discussed, topical cortico-

steroids are the first-line treatment modality. Topical macro-

lide immunosuppressants, including calcineurin inhibitors,

cyclosporine, rapamycin, and tetracycline, have used with

varying degrees of success. Systemic steroids as well as other

immunosuppressants are used in recalcitrant cases.

Behc‚et disease


	Shallow ulcers (arrows) of the soft palate in a patient with Behc‚et disease along with a superimposed candidal overgrowth on the tongue from topical oral steroid use.

BD is a rare systemic vasculitis characterized by recurrent oral,

ocular, and genital involvement. Cardiovascular, neurologic,and gastrointestinal involvement is associated with worsened

prognosis. Oral ulcerations are the earliest manifestation of

the disease and will affect almost all patients at some point

during the course of the disease. The pathophysiology is

characterized by hyperfunction of neutrophils in the absence

of infection with resultant increase in superoxide production,

enhanced chemotaxis, and excessive production of lysosomal

enzymes leading to tissue injury. The resultant autoimmune

response induces vascular injuries and superimposed hyper-

coagulation that may be due in part to activated endothelial

cells and activated platelets.

Clinical features

Recurrent, aphthous-like ulcerations (minor, major, or herpe-

tiform) are the earliest features of the disease and are the

main criteria for diagnosis (Fig. 7). Genital ulcers usually occur

on the scrotum and penis in men and on the vulva in women.

They are painful and morphologically similar to the oral ulcers,

but are usually larger, deeper, and heal with scarring. Ocular

lesions occur in the uvea and retina and symptoms include

blurred vision, eye pain, photophobia, lacrimation, floaters,

and periglobal hyperemia. Severe retinal disease can lead to

bilateral decrease in visual acuity. Erythema nodosum, pseu-

dofolliculitis, and acneiform nodules on the back, face, and

neck, especially along the hairline, are common cutaneous

manifestations. Joint involvement, including monoarthritis

or polyarthritis (knees, wrists, ankles, and elbows), develops

in about one-half of patients. Gastrointestinal involvement

causes abdominal pain, diarrhea, melena, and sometimes

perforation, but oral ulceration is usually considered sepa-

rately from the gastrointestinal involvement. Gastrointestinal

involvement may often be misdiagnosed as irritable bowel

disease, ulcerative colitis, or Crohn’s disease.17 Neurologic

involvement occurs infrequently but is associated with a poor

prognosis. Manifestations include headache syndromes,

meningoencephalitis, ophthalmoparesis, cranial neuropathy,

intracranial hypertension, and aneurysms. Cardiovascular

manifestations include thrombophlebitis, deep vein throm-

bosis, occlusions, aneurysms, pericarditis, myocarditis, and

endocarditis. Severe cardiovascular involvement in large ves-

sels resulting in sudden death by aneurysm rupture or throm-

bosis have been reported in up to 9.8% of patients

Treatment considerations

As in all of the conditions listed herein, treatment is gea-

red toward symptom relief of mucosal lesions with topical

corticosteroids. Another treatment strategy is decreasing sys-

temic inflammation, particularly important when other organ

systems are involved. For these, or if topical therapies are

ineffective, disease-modifying antirheumatic drugs are used

including colchicine and systemic steroids (see Table 2).

Because inflammatory mechanisms as well B-cell factors are

activated, biological drugs such as infliximab, adalimumab,

daclizumab, and tocilizumab are being used with increasing

frequency.

Oral Manifestations of Autoimmune Disorders