N acetyl cysteine for Lichen Planopilaris:

Is N-acetyl cysteine an option for treating LPP?

N-acetylcysteine (NAC) and Pentoxifylline (PTX) are two agents with immunomodulatory, anti-inflammatory, anti-oxidative and anti-fibrotic properties.

PTX has anti-inflammatory effects by decreasing the activity of natural killer cells and lymphocytes and reducing the production of inflammatory cytokines. It’s also anti-fibrotic and this appears to be due to its role in increasing collagenase in fibroblasts and decreasing the production of collagen

NAC has anti-inflammatory, anti-oxidant and anti-fibrotic properties in some studies.

Kahjoogh et al. 2022

Authors of a new study from Iran set out to evaluate the effectiveness, safety and tolerability of N-acetylcysteine (NAC) and Pentoxifylline (PTX) in the treatment of lichen planopilaris.

They conducted a blinded randomized controlled trial. 10 patients received clobetasol lotion alone, 10 patients received clobetasol and oral PTX (oral PTX 400 mg twice daily) and 10 patients received clobetasol and NAC (NAC 600 mg twice daily). Patients could not be on any other medication to be enrolled in the study. The authors assessed the degree of disease activity at the beginning of therapy and then again at 2 and 4 months

Key Results

a) Two month data

After two months of therapy, no statistically meaningful differences were noted between the patients concerning LPPAI or the severity of pruritus, burning, pain, scalp erythema, perifollicular erythema and scale. “Disease spreading” seemed to be more significantly halted with either of the combination therapies compared to those receiving only topical corticosteroids. (P=0.02 for PTX and 0.01 for NAC)

b) Four month data

After four months, four patients (44%) in the clobetasol-only group continued to have a positive pull test as opposed to zero patients in the clobetasol + PTX or clobetasol + NAC groups. (P=0.009). Disease spreading seemed to be more significantly halted with either of the combination therapies compared to those receiving only topical corticosteroids.

It also appeared that there were other features that were improved in the combination groups than the clobetasol only groups at 4 months including pruritus (P=0.01), scalp erythema (P=0.005), perifollicular erythema (P=0.001) and perifollicular scale (P=0.03).

Changes in LPPAI

The Lichen planopilaris activity index (LPPAI) is a measure of disease activity in LPP. In this study, a decline in the LPPAI was seen in all groups. The reduction was higher in the clobetasol + NAC group than in the clobetasol-only group (81.9 % versus 47.2 %, P=0.03). There was no statistically significant difference between the clobetasol only group and the PTX group.+ PTX (75.1 % versus 47.2%, P=0.08)

Satisfaction and Side Effects

Satisfaction was slightly higher in the control (clobetasol only) group than intervention groups. This will need more exploration. About 80% of those receiving clobetasol only rated satisfaction as “moderate to high to excellent” whereas just 56 % of those receiving NAC rated satisfaction as “moderate to high to excellent.”

Two patients, one in the NAC group and one in the control group, experienced disease aggravation resulting in the discontinuation of the medication and their exclusion from the study. One patient using PTX had transient nausea and one had hypotension and withdrew from the study. In the end, there were 8 patients in the PTX group and 9 in the control group and 9 in the NAC group.

Summary

All in all, this is an interesting but very small study with relatively short follow up. It appears that there is a hint of evidence that NAC could be a helpful add on to traditional therapies. It appears to be well tolerated and could help reduce the disease activity by the LPPAI. It seems that NAC helped a greater proportion of patients achieve a negative pull test and helped a greater proportion of patients halt spread of the disease.

REFERENCE

Kahjoogh et al. Efficacy, safety, tolerability and satisfaction of N-acetylcysteine and pentoxifylline in lichen planopilaris patients under treatment with topical clobetasol: a triple arm blinded randomized controlled trial. Dermatol Ther. 2022 Jun 15;e15639. doi: 10.1111/dth.15639. Online ahead of print.