Chronic desquamative gingivitis in siblings: A report of two cases.

Desquamative gingivitis is a gingival response associated with a variety of clinical conditions and characterized by intense erythema, desquamation and ulceration of free and attached gingiva. A variety of diseases such as lichen planus, pemphigus, pemphigoid, dermatitis herpetiformis, linear IgA disease, lupus erythematosus, erythema multiformae manifest clinically as desquamative gingivitis. Of all the disease entities, Lichen Planus is a relatively common disorder affecting the skin and mucous membrane. Very often it has oral manifestations. These lesions of oral lichen planus (OLP) have myriad but distinct morphology. As they mimic other mucocutaneous disorders with regard to clinical appearance, many lesions of oral lichen planus go undiagnosed or are wrongly diagnosed. Reported here are two cases of desquamative gingivitis. One of these was diagnosed as erosive lichen planus based on the symptoms, clinical findings, histologic, and immunofluorescent examination. Further management was done in consultation with a dermatologist.

INTRODUCTION

Desquamative gingivitis is a peculiar condition characterized by intense erythema, desquamation and ulceration of free and attached gingiva. It is not a specific disease, but a gingival response manifested by a variety of clinical disease entities. Lichen planus, pemphigus, pemphigoid, erythema multiformae and lupus erythematosus are a few of the diseases which clinically manifest as desquamative gingivitis.[1]

Of these disease entities, lichen planus is a relatively common disorder affecting the skin and mucous membranes.[2] Very often it has oral manifestations. These lesions of oral lichen planus (OLP) have myriad but distinct morphology. Genetic or autoimmune factors, drugs and chemicals, infection and psychogenic influence/stress have all been suggested as predisposing factors.[3] Histopathologically, saw tooth rete pegs, hyperkeratosis, and a dense sub-epithelial lymphocytic infiltrate is seen. Immunofluorescence examination reveals antibodies deposited along the basement membrane.[1] Reported here are two cases of desquamative gingivitis. Due to poor compliance and financial constraints of the patient, one of the cases was only provisionally diagnosed based on the history and clinical examination. The other case was diagnosed as erosive lichen planus based on the symptoms and clinical findings and further supported by histologic and immunofluorescent examination.

CASE REPORTS

Case 1

A 42 year old female reported with the chief complaint of burning sensation in the gums in the anterior region of the upper jaw since the past 6 months. These symptoms exacerbated during times of increased psychological, emotional or physical stress, and on consumption of spicy food.

Past medical history revealed that the patient was suffering from vesiculobullous lesions on the lower extremities since the past 10-15 years. These lesions were present at the time of examination [Figure 1]. No active medication was undertaken for the same.

Figure 1

Extra oral manifestation of vesiculo bullous lesion (case 1)

The patients’ menstrual history revealed no major anomaly. With regard to the dental history, the patient had undergone extraction of molar teeth in upper and lower jaws 5-6 years back.

Brushing/teeth cleaning habits

A commercially available toothbrush with a fluoridated, commercially available dentifrice was used for teeth cleaning once a day. Horizontal method of tooth brushing was used. At the time of examination, no other means of oral hygiene measures were being practiced.

Examination of the gingiva

Erythema with areas of desquamation extending upto the attached gingiva was seen in relation to the gingiva in the maxillary anterior region [Figure 2]. Loss of stippling was also observed in the same region. Maxillary and mandibular anterior teeth exhibited gingival recession.

Figure 2

Intra oral examination denoting severe desquamation along the gingiva in relation to maxillary anterior teeth (case 1)

The intra oral findings were suggestive of desquamative gingivitis. Based on the symptoms, history given by the patient and clinical findings (intra oral as well as extra oral), a provisional diagnosis of desquamative gingivitis was arrived at. For reasons of poor compliance and financial constraints of the patient to carry out further investigations, further observations could not be made.

Case 2

A 35 year old female (sibling of the earlier mentioned patient) reported with the chief complaint of pain and burning sensation in the gums in the anterior region of the upper jaw since the past 7-8 months. These symptoms intensified during times of increased stress.

Past medical history revealed that the patient was under homeopathic medication for insomnia and gastritis. She had also experienced vesiculobullous lesions on the lower extremities a few years back. However, unlike the earlier case, the lesions were absent at the time of examination. The patients’ menstrual history did not reveal any correlation with the symptoms. With regard to the dental history, the patient had undergone uneventful extraction of molars 4-5 years back. Extra oral examination with regard to the temporo-mandibular joint, lymph nodes, and facial symmetry revealed no abnormality.

As a part of oral hygiene practice, the patient used a soft bristle, commercially available toothbrush along with a fluoridated, commercially available dentifrice once a day. However, tooth brushing was preceded by application of tobacco paste over the gums and the teeth. Horizontal method of tooth brushing was used. No other oral hygiene aids were being used by the patient at the time of examination.

Intra oral examination

Intra oral examination revealed lesions on the buccal mucosa and labial mucosa. Interlacing, white striations with melanin pigmentation were present on the buccal mucosa opposite mandibular molars bilaterally [Figures 3 and 4]. A white linear lesion was also observed in the labial mucosa opposing maxillary anterior teeth.

Figure 3

Bilateral interlacing, striated lesions with melanin pigmentation in buccal mucosa opposite mandibular molars

Figure 4

Bilateral interlacing, striated lesions with melanin pigmentation in buccal mucosa opposite mandibular molars

Examination of gingiva

Gingiva in the maxillary anterior region was erythematous with areas of desquamation extending upto the attached gingiva [Figure 5]. Loss of stippling was also observed in the same region. Gingiva in other areas of oral cavity was normal with respect to its color, contour, consistency, size, position, and texture.

Figure 5

Erythematous gingiva with areas of desquamation in the maxillary anterior region

Following intra oral examination, a provisional diagnosis of chronic desquamative gingivitis was arrived at. Since the patient had a history of vesiculobullous lesions on the lower extremity, a dermatologist's referral was sought. After consultation with the dermatologist, a diagnosis of erosive lichen planus was made subject to confirmation by biopsy and immunofluorescence.

Biopsy and immunofluorescence

After consultation with the Department of Oral Pathology, the site of biopsy was chosen as lower left buccal mucosa. A 1 × 1 × 1 cm3 specimen was collected via incisional biopsy. The tissue was then divided into two parts: one subjected to immunofluorescent examination and the other subjected to histopathologic examination under hematoxylin and eosin stain. The tissue to be observed under immunofluorescence was placed in Mitchell's medium and carried to the laboratory for further investigations. Direct immunofluorescence was carried out and antibodies against complement factor 3 (C3), fibrinogen, immunoglobins (IgG, IgA, IgM) were checked for. Of these, the tissue was positive for anti-fibrinogen antibodies [Figure 6]. This feature was suggestive of OLP.

Figure 6

Immunofluorescence examination reveals a linear deposition of antibodies to fibrinogen along the basement membrane at ×40 magnification. Inset: immunofluorescence examination at ×10 magnification

Hematoxylin and eosin and toludine blue stained sections showed parakeratotic stratified squamous epithelium with saw tooth reteridges. Sub-epithelial region showed a band of inflammatory infiltrate. Deeper areas had fibrous and adipous tissue [Figure 7]. Clefts were also observed at the epithelium-connective tissue interface indicating basement membrane damage [Figure 8].

Figure 7

Hematoxylin and Eosin stained tissue specimen (under ×10 magnification) reveals hyperkeratosis and a dense sub epithelial infiltrate

Figure 8

Hematoxylin and Eosin stained tissue specimen (under ×10 magnification) reveals clefts at the epithelium-connective tissue specimen

Further management

Following the confirmatory tests, the patient was referred back to the dermatologist for further treatment. A conservative line of treatment was chosen based on the dermatologists’ advice. The patient was counseled for stress reduction and prescribed clobetasol propionate gel to be used twice daily over the affected areas. The patient was recalled at 1, 3, and 6 months [Figure 9]. At each recall visit, the patient experienced significant regression of symptoms.

Figure 9

3 month recall reveals regression of the gingival lesion

DISCUSSION

Chronic desquamative gingivitis is a peculiar clinical condition characterized by intense erythema, desquamation, and ulceration of the free and attached gingiva. It is not a diagnosis per se but a gingival response associated with a variety of clinical conditions. Women in the fourth to fifth decade of life are most commonly affected with the complaints of burning sensation or intense pain. Some cases may be asymptomatic. Upto 75% cases also have a dermatologic basis. Lichen planus and cicatricial pemphigoid account for more than 95% of these dermatologic cases.[1]

About 50% of patients who have OLP also have skin lesions.[4] The condition was initially described by Wilson in 1869. Prevalence in the general population is between 0.5 and 2% while it is 1.5% in Indians. The relative risk is highest for those individuals who smoke and chew tobacco.[5] Clinically, the oral lesions are seen as bilateral white striations, papules or plaques on buccal mucosa, tongue and gingiva with erythema, erosions or blisters.[6]

With regard to its etiology, lichen planus is believed to be a T-cell mediated auto immune disorder. The CD8 + T cells or the cytotoxic T cells trigger apoptosis of the oral epithelium by recognizing class I major histocompatibility complex (MHC) antigen on oral keratinocytes.[5] Unmasking of the antigen could be induced by drugs as NSAID's, sulfonylureas, anti-malarials, β blockers, and ACE inhibitors. Alternately, it could also be induced by contact allergens in dental restorative materials or toothpastes.[78] The lesions of lichen planus exacerbate during stress followed by periods of remission.[3]

Clinically, oral erosive lichen planus is manifested by the presence of vesicles, bullae or ulcers of the oral mucosa. Lesions of erosive lichen planus are sometimes surrounded by fine white radiating striations. These lesions usually persist for weeks to months.[9]

In the current cases, two female siblings reported with similar chief complaints albeit different in severity. Similar intra oral sites viz. maxillary marginal and attached gingiva in the anterior areas were affected. Both patients were middle aged with stress as the common precipitating factor in the pathogenesis. They also had a history of extra oral vesiculo bullous lesions on the lower extremities. Of the two cases, one was subsequently confirmed as erosive lichen planus.

The first case was diagnosed provisionally due to limitations in carrying out histo-pathologic examination. Clinical conditions such as lichen planus, chronic ulcerative stomatitis, lichenoid reaction, pemphigus, cicatricial pemphigoid, and erythema multiformae were considered as differential diagnosis. The presence of chronic infections and endocrine imbalances were ruled out. Of the disease entities, pemphigus manifests intra-orally as a vesiculo bullous lesion mainly involving the soft palate. In case of erythema multiformae, the intra-oral lesions are also vesiculo bullous but the onset is more acute and gingiva is not commonly involved. Oral lesions of erythema multiformae mainly involve the lips and recur with short duration. The erosive form of lichen planus is associated with severe erythema, burning sensation and sensitivity to heat, acid or spicy foods.[1] The patient's medical history and clinical examination were suggestive of lichen planus. Further confirmatory investigations in this regard were not carried out.

In view of the current cases, there may be a possible association in the occurrence of desquamative gingivitis in siblings subject to confirmation by genetic tests. Most diseases included under desquamative gingivitis are auto immune bullous diseases. It has been hypothesized that there is a genetically transmitted susceptibility to these disorders. However, the presence of environmental factors is required for the disease to actually manifest itself.[10] Different forms of desquamative gingivitis such as pemphigoid, lupus erythematosus, linear IgA disease, pemphigus vulgaris have been shown to exhibit a genetic susceptibility.[1112]

With regard to the genetic aspect of lichen planus, literature suggests that a possible association exists between inheritance of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-a) gene polymorphism and its occurrence.[13] This observation was further strengthened by Huang et al.,[14] who inferred that hereditary factors play a role in the pathogenesis of familial forms of lichen planus.

In a recent study, Wang et al.,[15] conducted a genetic linkage analysis in Chinese family members afflicted with severe form of erosive and reticular OLP. They found that chromosome 3p14-3q13 was the candidate gene region for OLP. This finding could pave the way for further studies investigating this genetic link.

Histopathological features

Under routine hematoxylin and eosin stain, hyperparakeratosis or hyperorthokeratosis, saw tooth configuration of the rete pegs, and a dense band-like inflammatory cell infiltrate in the upper lamina propia are seen in a lesion of OLP. The inflammatory cells were shown to be macrophages and T lymphocytes. The degenerating basal keratinocytes and disruption of anchoring elements of epithelial basement weaken the epithelium-connective tissue interface. As a result, histologic clefts called Max Joseph clefts are seen. It has also been suggested that separation of basal lamina and basal cell layer is an early manifestation of lichen planus.[4] Our findings from the histologic examination are in agreement with the above mentioned features.

The degenerating basal keratinocytes are present as colloid/-cytoid/-civatte bodies. These contain fibrin, IgM, C3, C4 and keratin. Additionally, it has been suggested that laminin and fibronectin which are important constituents of basement membrane are absent. This suggests basement membrane damage.[5]

Immunofluorescence

Two types of immunofluorescence methods are usually used:-direct and indirect. Direct immunofluorescence employs monoclonal and polyclonal antibodies conjugated to a fluorescein marker that binds with the bacterial antigen to form a fluorescein immune complex. This complex can be detected under the microscope. On the other hand, indirect immunofluorescence employs a secondary fluorescein conjugated antibody that reacts with primary antigen antibody complex.

For OLP, direct immunofluorescence is positive. Under light microscope examination of the immunofluoresced tissue, fibrinogen, and fibrin are seen to be deposited in a linear pattern along the basement membrane. Indirect immunofluorescence is usually negative.

Treatment

Before instituting treatment, drug therapy and underlying disease should be ruled out. The treatment of choice for erosive form of lichen planus is topical corticosteroids. Intra lesional steroids can be used for indolent lesions, and for severe exacerbation, systemic steroids may be considered for short periods of time. For patients with severe erosions resistant to topical steroids, cyclosporine rinses may be advised.[16] Tacrolimus has recently been used in a topical form and has been reported to be useful. Systemic etretinate, dapsone, or photochemotherapy have also been reported to be effective in severe resistant cases.[1718]

CONCLUSION

A significant number of cases of erosive lichen planus present with a picture of desquamative gingivitis. However, it is essential to remember that desquamative gingivitis is not a diagnosis per se. It also includes other disorders such as pemphigus, pemphigoid, linear IgA disease, and erythema multiformae. Consequently, many lesions of OLP go undiagnosed or are wrongly diagnosed. The erosive or bullous forms of lichen planus are particularly painful. Hence, it is of paramount importance to correctly diagnose and treat a case of lichen planus for optimum patient care.