Huyenlan Dinh, DO; Stephen M. Purcell, DO; Catherine Chung, MD; Andrea L. Zaenglein, MD
Abstract
Lichen sclerosus is an uncommon, inflammatory disease of the skin and mucosa that can cause significant pruritus, pain, and scarring. There are two peaks of incidence: one in adult females, and the other in young girls. Early recognition and prompt management of the disorder is crucial in preventing long-lasting complications. This article reviews lichen sclerosus in children and provides evidence-based guidance for treatment in the pediatric population. J Clin Aesthet Dermatol. 2016;9(9):49–54
Background
Lichen sclerosus (LS) is a chronic inflammatory disease of the skin and mucosa. It commonly develops in the anogenital region, but can affect any area. LS presents more frequently in females with two peak ages of presentation: prepubertal girls and postmenopausal women. A study of 327 patients with LS showed a mean age of onset of disease at 5.4 years in girls and 55.1 years in women.[1] The prevalence rate ranges between 1:70 to 1:1000 in women and 1:900 in children.[2],[3] Delayed diagnosis is not uncommon in girls with LS, with an average duration until diagnosis of 1 to 1.6 years.[4–6]
The pathogenesis of LS is unknown. Autoimmune factors have been investigated and autoantibodies to extracellular matrix protein 1 titers were found in 80 percent of affected patients.[7] Association with other autoimmune diseases has been reported. In a study of 350 women with LS, 21.5 percent had one or more autoimmune-related diseases, most commonly, autoimmune thyroiditis, vitiligo, alopecia areata, and pernicious anemia.[8]
Celiac disease has also been associated with LS.[9] In 30 prepubertal girls with anogenital LS, 6.6 percent had associated autoimmune diseases, such as vitiligo and alopecia areata.[10] Genetic, hormonal, environmental, and infectious factors have also been implicated as possible causes of this disease.[11–15]
Clinical Features
Presenting symptoms in girls include pain, pruritus, and a burning sensation along the perineal region. Dysuria and local spotty bleeding can result due to fissuring of the skin along the affected areas. A classic “figure 8” pattern is described, involving the labia minora, clitoral hood, and perianal region (Figure 1). Lesions initially are white, flat-topped papules, thin plaques, or commonly atrophic patches. Purpura is a hallmark feature of vulvar LS. Hyperpigmentation, erosions, and ulceration can result. Secondary constipation is also a common complication, occurring in 67 percent of girls with anogenital LS.[4] Young girls will withhold stooling due to the pain; subsequent management can be quite difficult, with habits and symptoms persisting even after effective treatment of the LS. Due to the nature of the symptoms, suspicion for child abuse can arise and may warrant further investigation when dealing with the pediatric population.[3]
In males, LS on the penis is called balanitis xerotica obliterans. The incidence has varied with some reporting 0.07 to up to 0.3 percent occurring in children as young as two years old and in adults, with the highest prevalence at ages 61 or older.[16],[17] Atrophic, shiny white, thin plaques usually involve the glans penis and can extend onto the shaft. Boys commonly present with associated phimosis. In a study of 1,178 boys with acquired phimosis, 40 percent were found to have LS on circumcision pathology.[18]
Extragenital LS can occur anywhere on the body, but typically involves the back, chest, and breasts (Figure 2). Oral mucosal involvement has also been reported and can mimic vitiligo early on.[19] Clinically, extragenital LS presents as white flat papules that coalesce into plaques. The color often has a shiny porcelain look and may be surrounded by an erythematous or violaceous halo (Figure 2). Scarring is common. Blaschkoid, segmental, and bullous types have been reported as well as overlap with cutaneous morphea. The lesions are mostly asymptomatic and can occur with or without genital involvement.[20]
Diagnosis
Since the diagnosis of LS is usually clinical, biopsy is reserved for cases if there is a doubt in diagnosis, a suspicion for neoplastic change, resistance to adequate treatment, or atypical extragenital presentations. Histopathologically, well-developed lesions of LS show an atrophic epidermis, hyperkeratosis, edema in the papillary dermis with collagen homogenization, and an underlying lymphocytic infiltrate. This pattern is often referred to as “red, white, and blue” on low-power hematoxylin and eosin evaluation due to the eosinophilic hyperkeratosis (red), pale-staining papillary dermis (white), and basophilic lymphocytic infiltrate (blue). Follicular plugging is also a common feature (Figure 3 and Figure 4).[21]
Due to the chronicity of inflammation, progression of LS can obliterate the normal anatomic structures due to scarring. The disease can relapse and become a lifelong condition. A prospective case series followed 12 girls with prepubertal LS for 10 years until adolescence. The results showed that 25 percent had complete remission, whereas 75 percent remained symptomatic with clinical signs of the disease as adolescents.[22] Even though they were diagnosed early and received treatment, childhood onset LS can still be complicated by distortion of vulvar architecture. Other complications include a five percent lifetime risk of developing squamous cell carcinoma; however, this is usually seen in older adult patients who had longer duration of LS.[23] Vulvar melanoma has also been reported in a child with LS.[24]
Treatment
The use of ultrapotent topical corticosteroids (UPTCS) has been the mainstay of treatment of LS in all age groups. Studies have shown that application of UPTCS led to improvement of symptoms in almost all patients.[1],[25] In pediatric LS, a case series showed successful treatment in childhood vulvar LS with topical corticosteroids (betamethasone dipropionate 0.05% ointment, diflorasone diacetate 0.05% ointment, or clobetasol propionate 0.05% ointment) twice daily for 6 to 8 weeks with minimal side effects observed.[26] Another study of 74 girls treated with potent or UPTCS demonstrated marked improvement, with 72 percent becoming symptom free after at least three months of topical treatment.1 Long-term follow up (4.7 years) in a retrospective review of 15 young girls showed that early aggressive treatment led to a better therapeutic response.[27] While mid-potency topical corticosteroids (TCS), such as triamcinolone acetonide or mometasone furoate, have been found to be effective in LS,[28],[29] most current recommendations do not support their use for first-line treatment.
Topical calcineurin inhibitors (TCIs), tacrolimus and pimecrolimus, are also used as adjunctive therapy for LS, but have not been shown as effective in initial treatment for LS both clinically and histologically.[30],[31] Several studies have shown the efficacy of using TCIs daily or twice daily in children and adults with partial to complete remission ranging from 6 weeks to 10 months of treatment.[32–36] After using TCIs after 16 weeks, complete remission was seen in only 43 percent of patients and partial remission was seen in 34 percent of patients.[36] Side effects of TCIs included stinging and burning. Concern for the use of TCIs stems from the intrinsic malignant potential that TCIs may increase the risk of SCC development in patients with LS especially with long-term use.[37],[38] Combining therapy with TCS and TCIs has been studied. Several authors reported remission in pediatric cases with LS after alternating clobetasol 0.05% ointment with tacrolimus ointment.[39] Clobetasol 0.05% ointment was used first and then tacrolimus ointment was bridged into the therapy regimen. As patients cleared, clobetasol ointment was discontinued all together and maintenance was achieved with tacrolimus ointment on weekends only. Clearance ranged from 4 to 156 weeks with an average time of 43.1 weeks.
Recent data emphasizes the importance of maintenance therapy for anogenital LS in both women and children to prevent long-term sequelae.[6],[40] These studies used low-to-mid potent TCS for maintenance. In a study involving 46 girls with prepubertal onset vulvar LS, patients were treated early with UPTCS daily and then decreased to a low-to-mid potency TCS for maintenance.[6] With this regimen, the patients were followed for a mean duration of 32.8 months. Of the 46 patients, 71.3 percent were adherent to the long-term treatment and 93.3 percent of those achieved complete disease suppression. None of the patients who stayed on the maintenance therapy with the low potency TCS experienced progression of scarring. The authors concluded that long-term maintenance with low- or mid-potency TCS was recommended until at least puberty.
Systemic therapy can be considered in refractory LS, or in generalized LS. Oral corticosteroids, methotrexate, acitretin, isotretinoin, cyclosporine, hydroxyurea, ceftriaxone, penicillin G, sulphasalazine, and vitamin A combined with vitamin E or D may be used for treatment-resistant LS.[41] However, the level of evidence and grade of the recommendations is very low due to limited numbers of patients and lack of clinical trials. Pulsed corticosteroids (methylprednisolone 1gm IV daily for three consecutive days monthly for 3 months) combined with low-dose methotrexate (15mg/wk), similar to morphea management, has been used in refractory extragenital LS.[42] Patients showed improvement after three months of treatment and they were treated for at least six months. Systemic retinoids did show some efficacy in the treatment of genital LS and can be considered if standard therapy for LS has failed. Acitretin dosed at 20 to 30mg/day for 16 weeks did show symptomatic improvement in patients.[43] Cyclosporine was used in patients with refractory vulvar LS with symptomatic improvement and decrease in erythema and erosions after one month of therapy.[44]
Recommendations for Management
Based on the data listed above, several groups created recommendations for topical treatment of LS. In 2010, the British Association of Dermatologists recommended that patients with LS should be managed with UPTCS as first-line treatment in newly diagnosed LS with an alternating schedule every four weeks; however, no long-term maintenance regimen was included.37 In 2015, Ellis and Fischer6 recommended both short-term treatment and long-term maintenance therapy for prepubertal patients with LS. They endorsed starting with daily use of a superpotent or potent TCS, depending on the initial severity. Patients should be evaluated at 4 weeks and continue monotherapy until all symptoms and signs resolve. Every six weeks, patients should be monitored for remission and side effects. If symptoms resolve, TCS potency can be gradually reduced and maintenance therapy started. A combination therapy that included hydrocortisone 1% ointment and methylprednisolone aceponate 0.1% ointment was recommended. Hydrocortisone 1% ointment was used daily and methylprednisolone aceponate 0.1% ointment used on the weekends. Patients were re-evaluated three months after, then every six months after while on maintenance therapy. If the disease was controlled for two years without side effects, it was recommended that patients be monitored yearly. Maintenance therapy is to be continued at least until patients reach puberty. It should be noted that the authors in this study did not incorporate TCIs into their regimen.
The European Academy of Dermatology and Venerology recommended incorporating TCS and TCIs.41 They recommended initiating treatment with clobetasol propionate 0.05% ointment or cream once or twice daily for three months with possible reduction in application frequency after one month. Depending on the patient, TCS may only need to be used once or twice a month, up to two to three times a week. Mometasone furoate 0.1% ointment was the recommended TCS for proactive maintenance therapy with twice-weekly application. The first follow-up should be at three months and if the diseases remain uncomplicated, follow-up visits can be done at six months. Moisturizers and silk underwear were also recommended, as decreasing friction was associated with fewer symptoms. The authors did not provide a specific guideline or recommendation for TCIs, but they did note that TCIs may be an effective alternative to strong TCS and could be used as maintenance therapy.
Taking into account the available data and various recommendations, the authors suggest a management plan for pediatric LS with combination therapy (Table 1 ).
Conclusion
Pediatric treatment of LS can be complex and should be individualized based on the patient’s degree of symptoms. Using UPTCS initially can halt or slow the degree of inflammation. Maintenance should be obtained with the use of TCIs or low potency TCS. Regular follow up is needed to assess the degree of inflammation and symptoms. Pediatric LS should be treated promptly to reduce symptoms and decrease the risk of vulvar scarring and distortion. Long-term follow up is needed as recurrences are not uncommon.
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