Innovative Combination of Tetracycline Rinse and CO Laser Ablation for Treating White Sponge Nevus in Adolescents: A Case Study

Introduction

White sponge nevus (WSN) is a rare genodermatosis affecting nonkeratinizing stratified epithelia, inherited as an autosomal dominant trait caused by mutation of keratin 4 (K4) and keratin 13 (K13) genes. This disorder is usually detected incidentally in early childhood and presents as asymptomatic, white coatings on mucous membranes that vary in intensity and thickness. White, spongy, corrugated, thickened plaques, particularly occur on the buccal mucosa, followed by labial and gingival mucosa and the floor of the mouth. Other mucosal sites of involvement include nasal, esophageal, and anogenital locations. Extra-oral lesions follow the development of oral lesions [1–3]. Lesions are non-scrapable and do not diminish after stretching.

White sponge nevus is considered a hereditary disorder, but there are many reports of WSN without familial involvement. Non-hereditary WSN localizes mostly only in the oral cavity, and lesions in oral mucosa are often solitary and mild. Biopsy is often necessary to confirm the diagnosis. Histological examination shows epithelial thickening, parakeratosis, vacuolization of the suprabasal keratinocytes, and characteristic perinuclear eosinophilic condensation, which is a unique feature for WSN [4].

Suprabasal keratinocytes of the oral cavity mucosa express keratin 4 (K4) and keratin 13 (K13) genes. The keratin cytoskeleton enables epithelial cells to resist traumatic damage, so genetic mutations in genes encoding these proteins may lead to conditions such as hypertrophy or epithelial fragility [5–8].

WSN often appears in early childhood with periods of remission and exacerbation. These abnormalities are usually asymptomatic and painless, although the literature mentions patients that suffered from pain and burning symptoms [9]. White lesions in the oral cavity are quite common and WSN can be easily mistaken with other conditions such as leukoplakia, lichen planus, candidiasis, or Darier disease [3]. Conditions similar to WSN are presented in Table 1. A proper diagnosis should be made to avoid unnecessary treatment.

Case Report

A 13-year-old girl, accompanied by her mother, presented to the Department of Pediatric Dentistry at Medical University of Warsaw with chronic white lesions of the oral mucosa that had been present since early childhood. Similar lesions elsewhere in the body were denied. The patient’s general health was reportedly good with no chronic diseases or allergies present. According to the interview, the lesions were first diagnosed as chronic oral candidiasis, then as leukoplakia. She had been treated with topical use of nystatin and systemic fluconazole, without success.

Clinical examination revealed the presence of bilateral, thick, furrowed coatings on the oral mucosa of the cheeks, vestibule of the oral cavity, and tongue, which did not cause any pain and could not be removed by scratching (Figures 1–3).

All permanent teeth were present, with no sign of caries. Oral hygiene was good and other oral structures were normal in appearance. Crowding of teeth was observed and the patient requested orthodontic treatment. Similar changes of much lesser severity were found in the patient’s mother (Figures 4, 5) and maternal uncle. Because of the severity of the lesions, the patient felt discomfort and had a sense of roughness of the mucosa and could not undergo orthodontic treatment since no orthodontist wanted to undertake treatment with fixed braces because of her condition.

A biopsy was taken from the lesion of the buccal mucosa. Histopathological examination revealed parakeratosis, acanthosis, and vacuolation of the stratum layer with peri- and paranuclear eosinophilic condensation (Figures 6, 7).

Based on the clinical and histological examination, the diagnosis of WSN was confirmed.

A solution with low-dose tetracycline (0.25%) was prepared for the patient to use twice a day (2×5 ml, 1 min). She rinsed her mouth with tetracycline solution from 04.2023 to 06.2023 and after 3 months of using the rinse, a slight reduction in lesions was noted (Figures 8–10).

Because we managed to obtain only slight improvement of the WSN lesions and the patient was still concerned about poor aesthetics and altered texture of the oral mucosa, it was decided to perform a laser CO2 ablation. CO2 laser has been recommended to treat benign oral lesions such as fibromas, gingival hyperplasia, and aphthous ulcers, as well as premalignant lesions such as oral leukoplakia, erythroplakia, papilloma, or lichen planus [10].

In August 2023, de-epithelialization of the left cheek mucosa was performed using a CO2 laser (Figure 11). It was assumed that production of new epithelium might reduce the hypertrophy of the spinous and squamous layer. At first, healing was promising, but a recurrence of the lesions was observed after about half a year later (Figure 12). Currently, the patient is under observation, and laser ablation was considered ineffective in treatment of white sponge nevus.

Discussion

WSN is a rare disease, affecting about 1 in 200 000 people and lesions vary in size and severity [11]. It is also referred to as Cannon’s disease, familial white folded hypertrophy of the mucous membranes, hereditary leukokeratosis, white gingivostomatitis, and exfoliative leukoedema [12]. The diagnosis is based on clinical aspects confirmed by histopathological examination.

White sponge nevus is considered a benign condition and specific therapy is unnecessary [13]. Our patient required orthodontic treatment, but no orthodontist wanted to put on fixed braces due to patient’s condition and the fear that chronic irritation of the lesions with orthodontic brackets could lead to malignant transformation. However, there is only 1 report of malignant transformation of WSN. Downham and Plezia reported an occurrence of an oral squamous cell carcinoma within white sponge nevus lesions [14].

There is no standardized treatment method for patients with WSN. The literature mentions improvement after use of antibiotics such as tetracycline, azithromycin, and doxycycline [15–19].

Lamey et al found that systemic antibiotic therapy with tetracycline or amoxycillin can improve the condition of WSN lesions. The efficacy of these antibiotics may be related to their effect on epithelial maturation and possible bacterial infection that can exacerbate the condition [20]. Several authors stated that antibiotic treatment was successfully used to treat their patients. This seems to be possible in cases with less severe lesions. In patients with severe lesions, only partial improvement can be achieved.

Satriano et al reported a case of a young boy and his mother, both diagnosed with WSN. Their lesions were mild and affected only the buccal mucosa. They were prescribed chlorhexidine mouthwash 0.12% twice a day. The effects of therapy were promising but the lesions recurred after 1 month [17]. Marelli et al described 2 patients affected by WSN associated with an infection by Staphylococcus aureus. They were treated with chlorhexidine mouthwash twice a day, which decreased the number of Cotan bacteria present [9]. Our patient reported using rinses containing chlorhexidine in the past, but with no apparent effect.

Amores–Martin et al presented a case of a 46-year-old man with WSN who was treated with topical triamcinolone acetonide (0.1%) and retinoic acid (0.1%), with no clinical improvement, but treatment with oral doxycycline (100 mg/d) for 6 weeks partially improved the condition [19].

Akimori et al reported a case of a patient with mild lesions of WSN that was successfully treated by topical application of tetracycline ointment and intake of multivitamins containing B1, B2, B6, niacin, and pantothenic acid. B vitamins are associated with maintenance of mucosal function and their deficiency may lead to dermatitis and cheilitis [21]. In the past, our patient was also treated with multivitamins but with no apparent result.

Otobe et al presented 4 patients affected with WSN treated with aqueous tetracycline solution. Patients with familial involvement showed only partial improvement, but the treatment was highly effective for patients with non-hereditary white sponge nevus [22]. The possible effect of tetracycline in WSN treatment may be modulation of epithelial keratinization. According to previous studies, low doses of tetracycline show a cytotoxic effect on cells in the proliferative stage [22,23].

It has been mentioned in the literature that bacterial, viral or fungal infection may contribute to the expression of WSN lesions. That is the reason why using antimicrobial medications such as tetracycline, azithromycin or chlorhexidine had an effect in partial improvement of patient’s condition [24].

Akeel et al reported a case of a patient with milder white sponge nevus lesions and suggested that laser therapy may be beneficial in treatment of WSN [25].

Dufrasne et al performed a surgical resection in a 50-year-old man with a WSN lesion located on the tongue. No recurrences have been observed since [26]. This is interesting, since in most cases WSN occurs on mucous membranes, and rarely is seen only on the tongue.

Patients with non-hereditary WSN tend to have less severe lesions on the oral mucosa and respond better to the abovementioned therapeutic options compared to those with familial involvement. This case report of hereditary WSN broadens the known therapeutic measures for this condition. Laser ablation, mentioned in previous articles as a possible treatment for patients with white sponge nevus, appears to be ineffective. The recurrence of lesions after laser therapy is most likely related to the genetic background of the disease, while other benign lesions such as leukoplakia that are caused by environmental factors are successfully treated with laser ablation.

The clinical differential diagnosis should include other congenital or acquired oral white-colored conditions, as presented in Table 1 [1,27–32].

Conclusions

Dentists and pediatricians should know how to diagnose white sponge nevus because it can be easily misdiagnosed, causing unnecessary and ineffective treatment. It is also important to differentiate this condition from more serious, potentially premalignant lesions or lesions that are a manifestation of a systemic disease.

Because of the changed texture of the oral mucosa in WSN patients, there is a predilection to bacteria growth and accumulation on the surface layer of mucosa. Therefore, it is a better choice to use topically antimicrobial substances in the form of ointments or rinses. Frequent antibiotic administration should be avoided.

We consider laser ablation as an ineffective method of WSN treatment. Because therapeutic options recommended in the literature provide only partial improvement or are unsuccessful, further research is still needed to develop treatment methods for patients with WSN.