Oral manifestations caused by the linear IgA disease

EGUIA DEL VALLE A, AGUIRRE-URIZAR JM , MARTÍNEZ-SAHUQUILLO A . ORAL MANIFESTATIONS CAUSED BY LINEAR IGA DISEASE. MED ORAL 2004;9:39-44.

SUMMARY

The Linear IgA deposit related disease or Linear IgA disease (LAD) is a chronic, uncommon and autoimmunological mucocutaneous disease, characterised by linear IgA deposits along the basement membrane zone. In mainly cases, moreover cutaneous lesions, there are oral mucosal and other mucosal lesions. There are also, some cases published of Linear IgA disease limited to oral mucosa. The known of this disease is important for the establishment of a correct differential diagnosis in cases of blistering mucocutaneous diseases. In this paper, we analyze the most important features of this disease, attending specially to the oral manifestations.

Key words: Oral manifestations, linear IgA disease, mucocutaneous disease, autoantibodies.

INTRODUCTION

Linear IgA disease or Linear IgA dermatosis (LAD) in an autoimmunological mucocutaneous disease characterized by the presence of linear IgA deposits along the basal membrane zone (1).

Although LAD was first considered as a special kind of other diseases like bullous pemphygoid or herpetiform dermatitis, since the 70´s decade, LAD is considered an independent disease. Actually, some authors (1-3) believe that LAD could comprise different disorders, attending to the different patterns which can be observed using electronic microscopy.

LAD is one of the least common mucocutaneous diseases, although there are only few bibliographic references about its prevalence in different populations. Some cases previously diagnosed without immunofluorescence as pemphygoid or as other mucocutaneous diseases, probably are LAD cases in true.

This disease can develop at any age, but it seems to be more frequent in the 4th and 5th decades of the life. Some authors (1-5) differentiate between two clinical subtypes of LAD, the adult's subtype and the pediatric subtype, which affects mainly to children under 5 years old.

No gender predilection has been demonstrated when study groups have been wide enough (2-5).

ETIOPATHOGENESIS

LAD is idiopathic in mainly cases, but there are some cases in which drugs, virus infection, malignances or autoimmunological disorders seem to be the inducers (6-12).

LAD patients produce IgA autoantibodies against different components of the extracellular domain of the linking structures in the basal membrane. These linking structures (hemidesmosomes) joint the citoskeleton of basal keratinocytes of the epithelium to the dermis. BP-180 glycoprotein (XVII type collagen) is a component of the hemidesmosomes, which is targeted by IgA autoantibodies in LAD patients and in other diseases like bullous pemphygoid (13-19).

The reason why LAD patients produce these autoantibodies is still unknown. A hypothesis is that immunological system of LAD patients is sensitized against external antigens (e.g. virological antigens) similar to some domains in structural proteins. Some inducer factors are able to unchain the massive liberation of these antibodies and the development of the disease (13-19).

Bullae appear after IgA autoantibodies deposition and neutrophils and other defensive cells migration to the connective tissue next to the basal membrane. This connective tissue next to the basal membrane where IgA antibodies have been deposed becomes necrotic and the epithelium separates from the dermis developing the bullae. Finally these bullae are destroyed emptying its containing and leaving an ulcer (1,19,20).

CLINICAL FEATURES

In the skin, a vesiculobullous rash over a normal or erithematous skin and with a seric or sero-hemorragic contain characterizes LAD. This vesiculobullous rash usually appears in the lower trunk, extensor faces of arms and legs, buttocks and genital zone. Although it is less frequent, lesions may also be observed in face, scalp, feet dorsum or anus zone.

Lesions may or not be symmetric respect to the medial line of the body (1,3,21).

-Oral Manifestations:

Proximately in 80 % of patients mucosal lesions can be observed (oral, ocular, nasal or genital mucous). A 60 &endash; 70 % of LAD patients have oral mucosal lesions (22-24).

The most frequent oral lesions consist in painful erosive or ulcerative lesions caused by the rupture of bullae. These ulcerative or erosive lesions may appear anywhere in the oral mucous, including vestibular mucous, and the tongue (22-24). Occasionally, LAD can be manifested in the mouth as a chronic desquamative gingivitis, which cannot be clinically distinguished of the desquamative gingivitis produced by lichen planus, pemphygoid or other mucocutaneous diseases (22-24), (Fig1).

Although some case have been published, it is really uncommon the presence of oral lesion as the only manifestation of LAD, without extraoral findings. In such cases, LAD use to appear as a recalcitrant desquamative gingivitis (25-27).

DIAGNOSIS

The LAD diagnosis is initially clinical and should be confirmed by an immunofluorescence study.

A differential diagnosis must be established between this disease and other like pemphygoid, herpetiform dermatitis, lichen planus, pemphygus or bullous epidermolisis (1-3).

The definitive diagnosis must be realized according to the biopsy, histological study and immunofluorescence study results, because oral lesions are similar in all the diseases previously appointed.

Subepidermal bullae containing neutrophils or eosinophils may be observed in the histological exam. This may also be observed in pemphygoid or herpetiform dermatitis (1-3). Thus, it is absolutely necessary to realize an immunological examination for a proper diagnosis. This examination reveals subepithelial IgA deposits, which is the patognomonic fact of LAD (Fig2).

In some cases, IgM deposits may also be observed accompanying to IgA deposits (1,13-17). Some authors consider that such cases as a special kind of LAD that should be denominated IgA/IgM bullous dermatosis (28).

THERAPEUTIC FEATURES

LAD treatment is difficult and unfortunately the disease cannot be controlled in all cases.

The usage of different immunomodulating agents alone or in combination is effective in mainly cases. However, such agents must be administrated with caution because of their serious secondary effects. It is absolutely necessary to maintain patients monitorized and under safety controls during the treatment.

LAD is a chronic disease with exacerbation and remission periods. In next to a half of cases a total remission can be obtained with a proper treatment (29-33).

Oral lesions are especially recalcitrant and do not respond as well as skin lesions to the treatment (1-3, 22-24).

Some of the drug that have been used with effectiveness are:

* Dapsone or diaminodiphenilsulfona. It is a bacteriostatic, antinflammatory and immunomodulating agent sensitized in the first years of the last century. It has been classically used in the treatment of the leprae and the malaria. Because of its toxicity, theratogenic and secondary effects dapsone applications are limited.

In doses from 50 to 500 mg/day is effective for the treatment of LAD lesions. However, dapsone can produce secondary effects like lethargy, cephalea, fever, sickness, vomits, agranulocitopenya, and cutaneous lesions as urticaria, toxic erythema, multiform erythema or epidermic necrolisis.

Previously to the dapsone treatment, the presence of hematological alterations must be discarded using the proper complementary exams. Renal, hearth, lung or hepatic alterations, glucose-6-phosphate-dehidrogenase (G6PDH) or Folic acid deficit and pregnancy must be also discarded.

During the treatment patients must be monitorized and blood and urine counts must be realized weekly during the first month and monthly after first month (25,29,30). The usage of dapsone is forbidden during pregnancy and lactation.

* Corticoids. High doses of prednisone (>40 mg/day) are effectives for treating LAD (25,27). The prednisone administration in combination to dapsone (100-500 mg/day) is one most efficacious treatment for LAD, but secondary effects are very frequent using this combination (25,27).

The administration of corticoids during long periods can develop renal, cardiovascular, neurological or ocular alterations and immunosuppression. Because of this immunosupression is frequent the apparition of opportunist infections (candidosis) that should be quickly detected and treated (25,27,29).

Patients under treatment with corticoids must be monitorized and periodic urine and blood counts must be realized. A good hydratation and a diet with a high proportion of potassium and without salt should be established. Dosage protocols must de strictly performed to minimize adrenocortical insufficiency due to corticoids usage.

* Topical corticoids are only effectives as coadjuvant of other treatments (23,27). Topical corticoids have been used in oral rinses and applied in soft mouthguards for treating oral lesions. Fluocinolone (0.05 %), triamcinolone (0.05 %), betametasone (0.1 %) and clobetasol (0.05 %) are the corticoids most used for LAD therapy. The long-term usage of such drugs may propitiate the development of opportunist infections because of their immunodepressant effects.

* Sulphapiridyne and other sulphonamydes. These are secondary election drugs for LAD treatment, used when dapsone and corticoids are not effectives or may not be used. Sulphapiridyne is employed in doses from 0.5 to 3 gr. a day. This drug is theratogenic and produces severe secondary effects like sickness, vomits, pruritic rash, urticaria, megaloblastic anemia, neutropenya, leucopenya, trombocitopenya or severe cutaneous reactions (25,27,31).

The usage of sulphonamydes is contraindicated in case of hematological, renal, hepatic or cardiovascular alterations, asthma, severe allergic disorders, glucose-6-phosphate-dehidrogenase (G6PDH) deficit, Folic acid deficit, antidiuretic or anticoagulant therapy and during pregnancy or lactation period (27,31).

Patients under treatment with these drugs must be monitorized and periodic blood and urine counts should be done, weekly along the first month, and monthly after first month.

* Colchicine. This antimitotic agent has an unknown action in the treatment of LAD. It has been used as a secondary drug in doses from 0.5 to 2 mg. a day with different dosage protocols (32-35). It is an effective treatment for LAD, but it has a high toxicity and it could produce neurological, gastric, intestinal, hematological or renal disorders. Because of this toxicity, its utility is reduced.

The usage of colchicine is absolutely forbidden in pregnancy, lactation period and in case of hepatic or renal insufficiency (32-35).

As for the previous mentioned drugs, patients must be monitorized during the treatment and blood and urine counts must be done, weekly during the first month and monthly after first month.

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