JAK Inhibitors, Low-Dose Naltrexone Touted as New Options for Nail Lichen Planus
JAK inhibitors and low-dose naltrexone appear to be two game-changing options for treatment of nail lichen planus, Shari Lipner, MD, PhD, FAAD, said at the 2025 American Academy of Dermatology (AAD) Annual Meeting in Orlando, Florida.
Dr. Lipner noted the activity of the JAK pathway in lichen planus and the expression of interferon gamma, IL-21, CXCL9, and CXCL10 in tissues from lichen planus patients.
“We have data from patients with oral lichen planus and lichen planopilaris showing that JAK inhibitors can work well,” Dr. Lipner said. “Now, we don’t specifically have data on treatment of treatment of nail lichen planus in terms of trials, however, there are a number of case reports that have come out within the last few years that are very convincing for the treatment with JAK inhibitors being active in the nail lichen planus pathway.”
Dr. Lipner showed case reports featuring positive results in nail lichen planus with tofacitinib, baricitinib, and abrocitinib before also noting the potential of topical JAK inhibitors.
“JAK inhibitors seem to work well in these isolated case reports,” she said, “but, you know, if the patient just has nail involvement and maybe only a few nails involved, the physician or the patient may not be OK with the potential side effects, including thrombotic events. So, wouldn’t it be great to have a topical treatment for nail lichen planus? Generally, for nails, we have trouble with penetration of drugs, but Dr. [Matilde] Iorizzo recently published this paper about three cases of nail lichen planus, all biopsy proven, and she used a compounded cream consisting of 2% tofacitinib.1 These patients were treated for 12 weeks, and these patients did amazing—I would say as good as the patients who were given oral tofacitinib. So, JAK inhibitors definitely seem to be a good target for treatment of nail lichen planus, and I think it really revolutionizes the way we have thought about nail lichen planus.”
Another option is low-dose naltrexone, Dr. Lipner said, citing a recent case series.2
“What is the reason for using this? Well, low-dose naltrexone is increasingly being used in dermatology as well as for cutaneous lichen planus, and the theory is that naltrexone is an opioid receptor blocker, however at low doses there is only partial blocking and there is a paradoxical increase in endogenous opioids, which has an anti-inflammatory effect,” she said. “We also know from cutaneous lichen planus patients that naltrexone binds the toll-like receptor 4, decreasing synthesis of pro-inflammatory cytokines. … This is really something exciting. This is something that I’m doing for my patients now. And in terms of a side-effect profile, it’s actually a very safe treatment.”
With these options available, of course, maximizing their impact is critical.
“Nail lichen planus has a significant impact on quality of life. Diagnose and treat early to prevent irreversible nail loss,” Dr. Lipner said.
- Iorizzo M. Efficacy of topical tofacitinib 2% cream in the treatment of nail lichen planus. Indian J Dermatol Venereol Leprol. 2025:1-2. doi: 10.25259/IJDVL_1443_2024.
- Bray ER, Morrison BW. Low-Dose Naltrexone Use in Biopsy-Proven Lichen Planus of the Nails. JAMA Dermatol. 2024;160(12):1334-1337. doi: 10.1001/jamadermatol.2024.4098.