Management of a granulomatous lesion in a patient with Kindler's Syndrome.

Kindler's syndrome is a rare vesiculobullous dermatological disorder sometimes involving multiple organs. First described by Kindler. The differential diagnosis includes Rothmund-Thomson syndrome and epidermolysis bullosa. Fisher's criteria have simplified the diagnosis with major and minor criteria. Oral manifestation of this syndrome includes multiple painful oral ulcers in the mucosa, periodontal attachment loss, gingival bleeding, and fragile mucosa. These manifestations may impair proper nutrition intake, may cause growth and development problems. This case report deals with the management of oral and gingival manifestations in a 12-year-old female child patient diagnosed with Kindler's syndrome.

INTRODUCTION

Kindler's syndrome (KS) is a rare vesiculobullous dermatological disorder characterized by acral bullae in infancy and early childhood, generalized progressive poikiloderma, and diffuse cutaneous atrophy.[1] It was first described by Kindler in 1954 and by Forman et al., in 1989. A number of oral features have been described in dermatology journals, such as gingival swelling and bleeding, mucosal white patches, atrophy, erosions, and pigmentation of the lips.[2] Although there is an overlap of the clinical features between KS and epidermolysis bullosa, the genetic mutation responsible for KS is yet to be determined.[1] Dental and oral findings in relation to KS have been described in literature that include oral lesions, atrophy of buccal mucosa, limited oral opening, malocclusion, caries, dystrophic teeth, ankyloglossia, bleeding gingiva, lip erosions, leukokeratosis, geographic tongue, gingival atrophy, erosion of hard palate, gingival swelling, and desquamative gingivitis.[12]

Genetic studies have explained the association of oral ulceration in KS to KIND1 gene mutation. KIND1 gene also known as FERMT1 encodes the protein INDLIN1 expressed at the basal layer of keratinocytes. KINDLIN1 is said to be involved in the interaction between bundles of actin filaments and the extracellular matrix. Mutant KINDLIN1 protein can reduce adherence between epithelium and the underlying connective tissue, making this tissue more prone to ulceration.[3]

This article emphasizes on the need for frequent examination and management of oral manifestations in a 12-year-old female child patient diagnosed with KS.

CASE REPORT

A 12-year-old female child patient reported to the Department of Periodontology and Implantology with the chief complaint of gum swelling in the upper right quadrant of oral cavity. The patient also complained of gum bleeding on provocation and difficulty in mastication owing to multiple oral ulcers in the vestibular region. The swelling had been present for approximately 6 months and was gradually increasing in size to attain the present dimension [Figure 1].

Figure 1

Gingival overgrowth in relation the maxillary right quadrant

On enquiry, medical history reports revealed the patient to be a case of KS. Treatment procedures carried out to treat it included vaginoplasty, urethroplasty, esophageal dilatation, and transfusion for immune thrombocytopenic purpura. Family history revealed a consanguineous descent.

General physical examination revealed the patient to be small stature and underweight for her age. Therefore, height and weight were recorded which showed 100 cm and 25 kg, respectively. The patient presented with multiple hyper- and hypo-pigmented macules distributed all over the body including face with prominent poikilodermatous changes, xerosis, atrophy of the skin, sparse, and thin hair [Figure 2a]. Sclera appeared icteric [Figure 2b]. The dorsum of the hands and feet revealed cigarette paper-like wrinkling [Figure 3a]. The patient appeared mentally sound.

Figure 2

(a) Poikilodermatous changes on the face; (b) Sclera appeared icteric

Figure 3

(a)The dorsum of the hands revealed marked cigarette paper-like wrinkling (b) Intra oral view showing ulceration on buccal mucosa

Dental history revealed excision of a similar type of overgrowth in mandibular posterior region 2 years back. Details were not presented.

Extraoral examination revealed facial asymmetry with diffuse swelling extending superoinferiorly from zygomatic arch to lower border of mandible and anteroposteriorly from right commissure of the lip to tragus of the right ear. Bilateral angular cheilitis was discernible.

Intraoral hard tissue examination revealed the presence of all permanent teeth except third molars in maxillary arch; mandibular arch revealed retained deciduous first and second molars bilaterally. Slight mobility was noted on all teeth in maxillary right quadrant. Proclination of anterior teeth were noted. Oral hygiene status appeared poor. A 2 × 2” ovoid pedunculated, lobulated, tender reddish pink gingival overgrowth was noted in the buccal and palatal aspect of maxillary right quadrant. The surface appeared smooth with ulceration. Its extension beyond the occlusal plane gave an appearance of open mouth. The gingiva appeared erythematous with an increased tendency to bleed. The differential diagnosis included was pyogenic granuloma, peripheral giant cell granuloma, and ulcerative fibroma.

Radiographic surveillance with orthopantomogram and intraoral periapical of maxillary posterior area revealed normal anatomic structures and presence of mixed dentition. Maxillary arch revealed developing tooth buds of 18 and 28. Mandibular arch showed erupting tooth bud of 34, 35, 44, and 45. An erupting 34 was appreciated at the level of the alveolar ridge. Periapical aspect of 75 revealed presence of tooth bud of 35 and the mesial root resorption of 85 [Figure 4a and b].

Figure 4

(a) Orthopantomogram revealing mixed dentition period (b) Intraoral periapical radiograph of the affected region

Hematological screening reports revealed no abnormality. A medical consent was obtained from physician to perform minor surgical procedure under local anesthesia. Two weeks after phase I therapy, the overgrowth was excised by electrosurgical unit after scaling. Antibiotics, analgesics, and nutritional supplements were prescribed for 5 days. Oral hygiene instructions included the use of a soft toothbrush, nonfoaming toothpaste, chlorhexidine mouthwash, and 20% benzocaine ointment for application on mucosal ulcers [Figure 3b]. She was advised to consume bland food with lots of fluid intake and refrain from eating hot and spicy food, acidic beverage which could lead to soreness.

Histopathological examination of the excised specimen at ×50, ×200, and ×400 revealed epidermis layer with ulcerated stratified squamous epithelium and mild hyperkeratosis in stratum corneum. Epithelial zone showed polymorphonuclear leukocytes and lymphocytes with focal areas showing mild reactive atypia and dysplasia in the lower one third involving stratum basale and spinosum. Aggregates of plasma cells and proliferation of the vascular channels in the superficial region of dermis layer were seen. Collagenized stroma with deeper areas showed predominantly plasma cells aggregates around the dilated blood vessels; thus, overall features suggested a diagnosis of “granulomatous lesion with plasma cell infiltrate” [Figure 5a–c].

Figure 5

(a) Histopathological image revealing hyperkeratosis and mild reactive atypia in the basal cells scanner; (b) Histopathological image revealing proliferation of vascular channels with perivascular area showing inflammatory infiltrate mainly showing plasma cells and lymphocytes with few polymorphonuclear leukocytes (×200); (c) Histopathological image revealing plasma cells (flame-shaped cells) (×400 high power)

On follow-up visit, after 10 days, uneventful healing was appreciated. The patient was relieved as she could occlude and masticate properly. The patient was followed up for 1, 2, and 3 months [Figure 6]. Although periodontal therapy proved to be beneficial to have food and proper nutrition, owing to restored masticatory activity, persistent, and recurrent oral ulcers were seen in buccal mucosa which compromised her oral hygiene activity. The patient underwent oral prophylaxis once again with reinforcement for proper oral hygiene maintenance. She is put on recall therapy with shorter periodic intervals of 4 weeks.

Figure 6

Postoperative view at the end of 3 months

DISCUSSION

Many case reports and few original articles were retrieved through literature search regarding KS, which revealed it be a rare syndrome. Other syndromes with similar overlapping features include Rothmund Thomson syndrome and Weary syndrome.[3] KS presents with clinical features similar to epidermolysis bullosa. In KS, there is spontaneous regression and appearance of reticular pigmentation, which is not seen in epidermolysis bullosa. Urethral stenosis and esophageal strictures are also recognized in KS,[2] which were present in our case, and the patient had undergone treatment for the same.

Although the etiology of KS revolves around consanguineous decent as in our case, there have also been sporadic cases reported.

The typical clinical features of KS are multiple with trauma-induced skin blisters that heal spontaneously, are present since childhood, and increase in frequency with age. Other symptoms present include diffuse skin atrophy followed by progressive poikiloderma, different levels of photosensitivity, dystrophic or absent nails, skin and gingival fragility, and severe esophageal stenosis.[36] These features were evident in our case.

In an attempt to make diagnosis simpler and more conclusive, Fischer et al., in 2005 established groups of minor and major criteria.[4] The major criteria are acral blistering in infancy and childhood, progressive poikiloderma, skin atrophy, photosensitivity, and gingival fragility, and/or swelling. The minor criteria proposed were syndactyly and involvement of other mucosal sites. The additional features included were nail dystrophy, ectropion, palmoplantar keratoderma, leukokeratosis of lips, squamous cell carcinoma, anhidrosis, skeletal abnormalities, and dental problems. According to the proposed criteria, the presence of four major criteria makes the diagnosis certain, the presence of three major and two minor criteria makes the diagnosis probable, and diagnosis is considered to be likely if two major and two minor/additional features are present.[5] According to these criteria, our patient had definitive diagnosis of KS as it fulfilled both major and minor criteria.

The case described here showed oral characteristics similar to those reported by other authors[25] such as ulcers in the oral mucosa, red and swollen marginal gingival, which appeared fragile, keratosis of the lips, angular cheilitis, and premature loss of teeth due to periodontal disease, over retained deciduous teeth, spontaneous bleeding on provocation and halitosis. These were managed by oral prophylaxis and reinforcement of oral hygiene instructions. It is also said that the oral mucosa and gingiva continue to be fragile with episodes of sloughing and inflammation despite treatment. Similar findings were appreciated in our case at the end of 3 months. The patient was weighed once again which showed 25 kg revealing increase in weight due to the proper nutritional intake.

Host susceptibility factors under genetic influence may play an important role in periodontitis.[3] Whether these patients suffer from periodontitis is still exactly unknown, although cases have been reported showing progressive periodontitis and early loss of teeth. In the present case, maxillary teeth showed the same degree of mobility with progressive attachment loss, as was present before, even at the end of 3 months. Similar findings were noticed by Wiebe et al.[7]

In the present case, generalized ulceration of the mucosa with poor oral hygiene and inability to maintain the same lead to the progressive proliferation of inflammatory enlargement. In this regard, oral health-care providers should be capable of recognizing such oral manifestations of this condition and adequately handle them, thus playing a key role in the multidisciplinary team that will deal with these types of patients.[25]

As recommended for the dermatologic visits, frequent dental visits should also be held to adequately manage the oral cavity. It is said that nonsurgical periodontal treatment consisting of scaling and root planing, followed by oral hygiene instructions, should be considered and may improve treatment, even though teeth with a doubtful prognosis may continue to lose bone support.[57] Therefore, patients diagnosed with KS should ideally be included in a rigorous preventive maintenance program so as to continuously improve their overall clinical status and symptoms.

CONCLUSION

KS patients need a multidisciplinary approach with proper medical and dental care. Awareness about such cases, their management can lead to a better understanding of the course of the disease, thus helping the affected patients to take extra care of their oral and overall general well-being. Recall periodontal examination at frequent intervals can help these patients maintain their oral hygiene and allay the symptoms for a longer duration of time.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initial will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.