Efficacy of Fluocinonide\Bifonazole Cream for the Treatment of Trachyonychia: A Retrospective Case Series

Abstract

Background:

Trachyonychia is a benign nail condition, most commonly seen in children. Trachyonychia manifests as excessive longitudinal ridging, nail roughness, and nail brittleness. Treatment is sought mainly for esthetic reasons as well as functional reasons. A number of therapeutic approaches exist, mainly based on case reports or small non-comparative case series.

Aims:

To report treatment outcome among patients with trachyonychia.

Methods:

A retrospective case-series study was conducted among patients who were treated trachyonychia between years 2017 and 2020. Patients were prescribed fluocinonide 0.05% with bifonazole 1% cream, applied with or without occlusion, and methylprednisolone 1–2 mg/nail, injected into the involved nail matrix, or oral cyclosporine 3 mg/kg. Complete response (over 90% improvement) and partial response (over 50% improvement) were assessed.

Results:

A total of 43 patients with trachyonychia were included [mean age 10.0 years (±5.7), 69.8% males, mean disease duration 4.7 years (±3.0)]. In 90.7% of the cases, topical fluocinonide\bifonazole cream was prescribed. Under-occlusion topical application was found to be highly effective, achieving complete response in 35.3% and partial response in an additional 52.9% of the patients. Occluded application was also found to be significantly more effective than non-occluded application. Treatment efficacy was not affected by the severity of nail roughness, trachyonychia morphology, or whether trachyonychia was idiopathic or coexisted with other dermatological conditions.

Conclusion:

Occluded application of fluocinonide plus bifonazole cream is efficient for the treatment of trachyonychia and should be considered a first line of treatment.

Introduction

Trachyonychia is a benign nail condition arising because of proximal nail matrix inflammation. Trachyonychia develops mostly during the first and second decades of life, averaging 3–12 years of age but may develop later during adulthood.[1] The clinical characteristics are excessive longitudinal ridging, nail roughness and nail brittleness, and, often, hyperkeratotic cuticles. Two morphologic variants of trachyonychia have been described[2]: Opaque type, with a sandpaper-like appearance, and, less commonly, a shiny type, with shiny nails and numerous superficial pits. Classically trachyonychia was termed “twenty-nail dystrophy”; however, it is a misnomer since, in many cases, only some of the nails are affected.[1] Fingernails tend to be affected more commonly than toenails. Trachyonychia is mostly idiopathic but can also be associated with other skin conditions, mainly alopecia areata, atopic dermatitis, lichen planus, and psoriasis.[2] In addition, familial clusters of trachyonychia have been described.[3] Without treatment, trachyonychia tends to last for years, with spontaneous resolution thereafter. However, a previous study found that persistent changes of over 6 years and an onset in childhood were unlikely to disappear spontaneously.[4,5]

Treatment is mainly sought for aesthetic reasons as the condition is quite noticeable. In certain severe cases, treatment is desired because of interruption of manual activities.[1,2] For patients who seek treatment, there are several therapeutic options, such as topical steroids and emollients,[2,6,7] along with systemic treatments, including retinoids and immuno-suppressants.[8,9,10] However, treatment failure remains common. Recently, alitretinoin was reported beneficial in idiopathic recalcitrant trachyonychia.[11] Currently, treatment efficacy data are derived from non-comparative small case series and case reports.

Herein, we report our experience using various treatment options in a well-characterized retrospective cohort of 43 patients with trachyonychia. Furthermore, this study design allowed comparison between different topical steroid treatment regimes.

Materials and Methods

This retrospective study included patients with trachyonychia treated between the years 2017 and 2020. Patients were evaluated by a specialist dermatology out-patient nail clinic. Diagnosis was done clinically in all cases. Detailed baseline characteristics retrieved from their medical records included age, gender, disease duration, existence of other dermatological diseases, and a diagnosis of trachyonychia in family members. Additionally, at baseline, trachyonychia was clinically classified by the following parameters: Shiny- or opaque-variant trachyonychia; degree of nail roughness, mild, moderate, or severe; whether it was isolated dermatological finding or coexisted with other dermatological diseases. The number of nails involved was also recorded. Patients were prescribed one of the following treatments: A cream containing fluocinonide 0.05% with bifonazole 1% (Comagis™, Perrigo Pharmaceuticals LTD, Israel). The cream was applied with or without occlusion, applied topically over nails and surrounding nail folds, daily or every second day for 3–6 months or 7–12 months; methylprednisolone 1–2 mg/nail, injected into the involved nail matrix, every 3–4 weeks for 2–4 sessions; and cyclosporine 3 mg/kg, orally, once daily, for 6 months. A cream containing not only corticosteroids but also an anti-fungal agent was chosen to lower the risk of secondary fungal infection. Treatment response was clinically assessed based on a five-point global improvement scale (GIS): 0 = deteriorated or unchanged, 1 = mild (less than 25%) improvement, 2 = moderate (25–50%) improvement, 3 = marked improvement (50–90%), and 4 = complete or near-complete cure (above 90% improvement). Complete response was calculated by the proportion of patients achieving a complete or near-complete cure (GIS 4). Partial response rate was defined by the proportion of patients achieving GIS 3 (above 50% improvement).

Authors confirm that the ethical policies of the journal, as noted on the journal's author guidelines page, have been adhered to and the appropriate ethical review committee approval was attained. Ethical approval for this study was obtained from the Research Ethics Committee of Laniado Hospital (LND-0104-09).

Statistical analysis

Values are presented as mean (± standard deviation) or number (percentage). Categorical variables were compared using the Chi-squared test, and continuous variables were tested using the independent samples T-test. All statistical tests were two-sided, and P value <0.05 was considered statistically significant. SPSS (IBM Corp. Released 2015. IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp.) was used for all analyses.

Results

Baseline characteristics and clinical features

A total of 43 patients with trachyonychia were included in this retrospective cohort. Baseline demographic and clinical characteristics of the study participants are shown in Tables 1 and 2. The mean age was 10.0 years (±5.7), with 69.8% males. The disease lasted averagely 4.7 years (±3.0). Existence of other dermatological conditions was reported in 39.5% (17/43) of the cases: 25.6% had atopic dermatitis, 11.1% had alopecia areata, 7.0% had psoriasis, and 2.3% had lichen planus. The family history of trachyonychia was reported in 16.3% of the cases.

Table 1.

Baseline characteristics of the study population

Characteristic	Study population (n=43)
Age, mean (SD), years	10.0 (5.7)
Male gender (%)	69.8%
Co-morbid skin disease (%)
Alopecia areata	11.1%
Atopic dermatitis	25.6%
Lichen planus	2.3%
Psoriasis	7.0%
None	61.5%
Relatives with trachyonychia (%)	16.3%

Table 2.

Clinical features of the study population

Clinical feature	Study population (n=43)
Duration of trachyonychia, mean (SD), years	4.7 (3)
Number of affected nails, mean (SD)
Total	14.0 (3.9)
Toes	5.4 (3.3)
Fingers	8.6 (1.5)
Nail roughness (%)
Mild	14.0%
Moderate	72.1%
Severe	14.0%
Trachyonychia type (%)
Shiny	14.0%
Opaque	86.0%

The average number of nails affected by trachyonychia was 14.0 (±3.9) per patient [mean involvement of 8.6 (±1.5) fingernails and 5.4 (±3.3) toenails]. Twenty-nail dystrophy was seen in only 5 patients (11.6%). Opaque trachyonychia was significantly more common than shiny trachyonychia (86.0% vs 14.0%, respectively). Roughness of nails affected with trachyonychia was graded as severe in 14.0% of cases and moderate in 72.1% of cases, whereas the rest (14.0%) had a mild condition.

Treatment outcomes

Topical fluocinonide\bifonazole cream was administered to the vast majority of patients [occluded (n = 17) or non-occluded (n = 22)]. Most of the patients (64.7% and 68.2%; occluded and non-occluded, respectively) applied the cream for 7–12 months, whereas the rest applied it for a shorter term of 3–6 months. A minority (3 patients) of the study cohort received nail matrix injections of methylprednisolone (2–4 treatment sessions) or oral cyclosporine (1 patient). All the patients, except one patient who was prescribed cyclosporine, were treatment-naïve. A comparative statistical analysis could only be calculated between topical steroid treatment regimens. Gender, existence of a dermatological co-morbidity, trachyonychia severity, trachyonychia type, and the length of treatment course were similar among the two topical steroid treatment groups. An older age (11.5 vs 8.0 years, P < 0.05) and a longer disease duration (4.9 vs 3.0 years, P < 0.01) were reported among those treated with topical steroids under occlusion versus without occlusion.

Treatment efficacy is summarized in Table 3. Overall, improvement of nail condition was achieved in all treated cases, whereas the degree of improvement differed between treatment regimens. For topical steroid treatment, the complete response and mean GIS were significantly higher for under-occlusion application compared to non-occluded application (35.3% vs 0%; mean GIS 3.2 vs 1.6; P < 0.01, <0.001, respectively). Partial response (above 50% improvement) was achieved in an additional 52.9% and 0% of patients treated with topical steroids applied under occlusion versus non-occluded, respectively (p < 0.001). Only a mild to moderate improvement (of less than 50%) was seen with the application of non-occluded topical steroids. Daily and alternate day topical steroid application had similar effects. Injected steroid and oral cyclosporine were also found to be highly effective, causing a complete response in 67% and 100% and a mean GIS of 3.7 and 4.0, respectively. Isolated trachyonychia and trachyonychia coexisted with other dermatological diseases responded similarly to treatment. Furthermore, neither nail roughness severity nor trachyonychia morphology affected the treatment outcome.

Table 3.

Treatment outcomes of trachyonychia with occluded versus non-occluded fluocinonide/bifonazole cream and with methylprednisolone injection and cyclosporine

	Fluocinonide/Bifonazole cream		Methyl-prednisolone injection	Cyclosporine
	without occlusion	under occlusion
No. of patients	22	17	3	1
GIS, mean (SD)	1.6 (0.5)	3.2 (0.6) *	3.7 (0.5)	4 (0)
Complete response (%)a	0%	35.3% **	66.7%	100%
Partial response (%)b	0%	52.9% **	33.3%	0%
Less than 50% improvement	100%	11.8% **	0%	0%

GIS=global improvement scale. ^aComplete response=above 90% improvement; ^bPartial response=50–90% improvement. *P<0.01, **P<0.001

Discussion

This retrospective study assessed demographic and clinical characteristics as well as treatment outcomes among patients with trachyonychia. Because most of our cohorts were treated topically, we were able to compare various topical treatment regimens. Application of fluocinonide/bifonazole cream under occlusion was found to be highly efficient, achieving complete response in 35% of the cases and partial response in an additional 52.9% of cases. This treatment regimen was shown to be effective for isolated trachyonychia as well as trachyonychia coexisting with other dermatological diseases. Furthermore, application of fluocinonide/bifonazole cream under occlusion demonstrated a statistically significant superiority over non-occluded application. Interestingly, we found that disease severity, assessed by nail roughness and trachyonychia morphology, did not affect treatment outcome. Thus, topical treatment might be suitable even for patients with a severe condition.

As previously reported,[2,6] most of our cohorts comprised children, with opaque trachyonychia being the most common morphology. In line with previous studies,[1,2,6] isolated trachyonychia was mainly seen, whereas in the rest of the cases, atopic dermatitis and alopecia areata were common.

Few studies have assessed treatment outcomes among patients with trachyonychia. Regarding topical treatments, various treatments have been suggested,[2,6,12] including corticosteroids, tazarotene, 5-fluorouracil, urea-containing ointments, emollients, and retinoids. However, these were not thoroughly studied; thus, efficacy data could not be withdrawn. Of the topical treatments, only a single study, held by Park et al.,[7] reported treatment outcome in a relatively large cohort. In that study, comprising 39 patients with trachyonychia, calcipotriol/betamethasone ointment was reported to improve the condition of 98.6% of the nails with trachyonychia and to achieve 4.2% total clearance after 6 months of treatment. Similar to our study, the studied medication was composed of corticosteroids and the disease lasted on average nearly 5 years. Conversely, their patients were older than our study group (36 vs 10 years of age, respectively), which could potentially affect the treatment outcome. Furthermore, in their study, the ointment was applied without occlusion, which was found in our study to be less effective than occluded application. This could explain the better outcome reported in our study for the occluded application treatment group. Occluded application improves percutaneous absorption by increasing stratum corneum hydration, increasing the local skin temperature, and preventing accidental wiping of the product.[13] For nail plate and nail fold topical application, occlusion might be crucial as drug absorption through the nail plate is lower than that through any other skin region.[14]

Sparse data have also been collected regarding nail matrix injections and systemic treatments. Of them, most established efficacy data were collected regarding nail matrix triamcinolone injections and cyclosporine. Grover et al.[9] reported over 75% improvement after a 6-month course of triamcinolone injection among 59% of patients. Oh et al.[8] reported oral cyclosporine (daily dose of 3–5 mg\kg; average treatment duration: 66 weeks) to achieve some improvement in all treated cases (n = 38) and a complete response in only 13.2% of cases. Similarly, our study also found steroid injections and cyclosporine to be highly effective; however, only few were treated with those regimens. In addition, oral alitretinoin was found beneficial in treating isolated recalcitrant trachyonychia, achieving complete treatment response in 50% (6 of 12 patients) within 6 months of treatment.[11]

Based on our study and previous studies,[2,6,7,8,9,11,12] we suggest the following treatment ladder: For patients who desire treatment, topical steroids applied under occlusion should be considered as the first line of treatment. Nail matrix steroid injections or oral treatment, either cyclosporine or allitretinoin, should be considered as the second line of treatment.

Our investigation has strengths and limitations. The main strengths of the study are its relatively large retrospective cohort and the well-documented demographic and clinical characteristics. The study design allowed comparing the efficacy of various topical treatment regimens. Regarding limitations, mostly children were recruited, thus assessing treatment efficacy for adults could only be extrapolated. Furthermore, efficacy assessment of oral cyclosporine and steroid injections was limited to only a few cases.

The current study demonstrates that the use of fluocinonide/bifonazole cream under occlusion is an effective treatment for trachyonychia. Clinical improvement was achieved in most of the cases, including severe cases. Thus, this treatment regimen could potentially be used as first-line treatment for patients who seek treatment.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.