A, Mean (SD) single-hand Nail Psoriasis Severity Index (shNAPSI) score at baseline (week 0) (Lindioil group, 27.2 [7.8] and calcipotriol group, 27.4 [7.6]) and at week 24 (Lindioil group, 14.4 [8.9] and calcipotriol group, 20.4 [8.5]). B, Mean (SD) modified target NAPSI (mtNAPSI) score at baseline (week 0) (Lindioil group, 17.7 [6.2] and calcipotriol group, 16.9 [6.5]) and at week 24 (Lindioil group, 5.9 [4.1] and calcipotriol group, 9.5 [5.2]). Error bars indicate the standard error.aSignificance between the 2 groups within the same visit using the Bonferroni adjustment with a significance level of P = .007. (The comparison of the efficacy of the different treatments was conducted by a paired t test. The overall significance level of this study was P = .05; however, the Bonferroni method reduced the significance level. This was accomplished by dividing the numbers of multiple comparisons when comparing shNAPSI or mtNAPSI between the 2 hands over time [.05/7 visits].)
A, Fingers on the right hand at baseline (week 0), with a single-hand Nail Psoriasis Severity Index (shNAPSI) score of 26. B, Fingers on the left hand at baseline (week 0), with a shNAPSI score of 23. C, Fingers on the right hand after 24 weeks of treatment with Lindioil, with a shNAPSI score of 5. D, Fingers on the left hand after 24 weeks of treatment with calcipotriol, with a shNAPSI score of 16.
Trial Protocol Synopsis
eFigure 1. CONSORT Flow Diagram
Lin Y, Chang Y, Hui RC, See L, Chang C, Yang C, Huang Y. A Chinese Herb, Indigo Naturalis, Extracted in Oil (Lindioil) Used Topically to Treat Psoriatic NailsA Randomized Clinical Trial. JAMA Dermatol. 2015;151(6):672-674. doi:10.1001/jamadermatol.2014.5460
Indigo naturalis, a Chinese herb, has been used for decades.1 Olive oil was used to remove the blue component within indigo naturalis to yield a purple-red product to treat skin and nail psoriasis without obvious staining.2,3 This trial compared indigo naturalis extract in oil (Lindioil) with topical calcipotriol in treating psoriatic nails.
Lindioil was prepared by mixing indigo naturalis powder with olive oil.4 Calcipotriol solution (Daivonex scalp solution, 50 µg/mL) was purchased from LEO Pharmaceutical Products, Ltd. Both were distributed in 5-mL eyedropper bottles. This trial was approved by the Chang Gung Medical Foundation Institutional Review Board and was randomized by participant, rater blinded, and active controlled. All participants provided written consent prior to the study. Participants, who were recruited from January 2011 through May 2012, were aged 20 to 65 years and had symmetrically comparable nail disease severity on each hand. The full study protocol synopsis can be found in Supplement 1.
Participants applied 1 to 2 drops (0.05 mL/drop) of Lindioil to the fingernails of one hand and calcipotriol to the other hand twice daily for 24 weeks. Participants were followed up every 4 weeks for 24 weeks and photographs of their nails were taken at each follow-up visit. Psoriatic nail severity was assessed by 2 blinded dermatologists (Y.-C. C. and Y.-H. H.) using the single-hand Nail Psoriasis Severity Index (shNAPSI) and modified target NAPSI (mtNAPSI).4
Statistical analysis was performed with SAS statistical software, version 9.3 (SAS Institute Inc). The mixed-effect model and pairwise comparisons were used, with P < .05 considered significant.
Of the 33 enrolled and randomized participants (22 men, 11 women), 28 completed the study (eFigure 1 in Supplement 2). Mean (SD) age was 41.9 (9.4) years; duration of skin and nail psoriasis was 11.8 (10.9) and 5.8 (6.4) years, respectively. Mean Psoriasis Area Severity Index score was 8.9 (8.2) and NAPSI score was 54.3 (15.4). Eighteen participants used Lindioil on their right hand and 15 used Lindioil on their left hand.
The mixed-effect model revealed significant interactions between treatments and time for shNAPSI scores (P < .001) and mtNAPSI scores (P < .001) (Figure 1). At baseline, there was no statistically significant difference in shNAPSI scores (P = .45) or in mtNAPSI scores (P = .03) between the use of Lindioil and the use of calcipotriol. At week 24, use of Lindioil showed significant improvements compared with calcipotriol for shNAPSI and mtNAPSI scores (P < .001 for both).
The percentage reduction in shNAPSI scores between baseline and week 24 for the use of Lindioil (51.3%; 95% CI, 40.6%-62.0%) was greater than that with the use of calcipotriol (27.1%; 95% CI, 16.2%-38.0%) (P < .001). Fourteen participants (50%) had shNAPSI scores that improved 50% or greater with the use of Lindioil and 7 participants (25%) had shNAPSI scores that improved 50% or greater with the use of calcipotriol (Figure 2). More participants preferred Lindioil (82.1%) compared with calcipotriol to treat their psoriatic nails (17.9%).
Onycholysis and subungual hyperkeratosis had the most improvement among the 8 nail features for both treatments. Although results are not shown, Lindioil was statistically superior for onycholysis.
Two participants (6.1%) experienced irritation with the use of Lindioil and 10 participants (30.3%) experienced irritation with the use of calcipotriol, but no participants experienced serious adverse effects.
This study comparing a Chinese herb, indigo naturalis, with a current topical medication, calcipotriol solution, showed that Lindioil is a safe and effective alternative therapy for psoriatic nails. Psoriasis is a refractory disease; therefore, owing to the long-term nature of the treatment, efficacy and safety are very important. Lindioil had the greatest effects on onycholysis and subungual hyperkeratosis, which arise from hyperproliferation, hyperkeratosis, and parakeratosis of the nail bed. Our studies indicated that indigo naturalis regulates proliferation and differentiation of epidermal keratinocytes, restores the epidermal barrier function, and inhibits inflammatory reactions.5,6 Lindioil may improve psoriasis of the nails via these mechanisms; however, further investigation is necessary.
Accepted for Publication: December 11, 2014.
Corresponding Author: Yu-Huei Huang, MD, Department of Dermatology, Chang Gung Memorial Hospital, 199, Tung-Hwa North Rd, Taipei, Taiwan (email@example.com).
Published Online: March 4, 2015. doi:10.1001/jamadermatol.2014.5460.
Author Contributions: Dr Lin had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Lin.
Acquisition of data: Lin.
Analysis, and interpretation of data: Lin, Huang.
Drafting of the manuscript: Lin, Huang.
Critical revision of the manuscript for important intellectual content: Lin, Hui, See, Yang.
Statistical analysis: See, C.-J. Chang.
Obtained funding: Lin.
Administrative, technical, or material support: Lin, Y.-C. Chang, Hui, Yang.
Study supervision: Lin.
Conflict of Interest Disclosures: None reported.
Funding/Support: This study was supported by grant CMRPG2A0191-2 from Chang Gung Memorial Hospital at Keelung, Taiwan (Dr Lin).
Role of the Funder/Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Trial Registration: Clinicaltrials.gov Identifier: NCT01445886.
Additional Contributions: We thank Shu-Tuan Chiang, MSc, Chuang Song-Zong Pharmaceutical Co, Ltd, for the preparation of the study medication and Hsiao-Jung Tseng, MS, Biostatistical Center for Clinical Research (supported by grant CLRPG340599 from Chang Gung Memorial Hospital at Linkou) and Louis Tuan, MBA, Contract Research Organization Service Division, Formosa Biomedical Technology Corp, for statistical analysis of the clinical data. Chuang Song-Zong Pharmaceutical Co, Ltd, was compensated for producing the drugs used in the study. Ms Tseng and Mr Tuan were not compensated for their contributions.