Research and development continue to produce advancements in hair and nail treatments. The recent U.S. Food and Drug Administration (FDA) approvals of Janus kinase (JAK) inhibitors, such as baricitinib and ritlecitinib, for patients with severe alopecia areata (AA) have marked significant milestones, showing promising results in hair regrowth. Recent studies also shed light on the off-label use of JAK and tumor necrosis factor (TNF) inhibitors for managing scarring alopecias such as lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA), providing hope for those facing these conditions. Low-dose minoxidil has also been shown to exhibit efficacy and safety in treating various forms of hair loss, as well as potential in addressing nail growth and brittleness. Staying abreast of these cutting-edge treatments is crucial for dermatologists aiming to optimize patient care and outcomes in 2024 and beyond.

Janus Kinase inhibitors

The FDA approval of the JAK inhibitor baricitinib for adults with severe AA in June 2022 marked a revolutionary milestone in AA treatment with regrowth of hair on the scalp, eyebrows, and eyelashes.^1,2 Ritlecitinib, a selective JAK-3 inhibitor, was the second JAK inhibitor approved by the FDA for treating AA patients, in June 2023, and the first to be approved in ages 12 and above at a 50-mg dose.3 Overall side effects commonly seen in more than 1% of patients on these medications include upper respiratory tract infections, nausea, diarrhea, headache, and acne. Although rare, severe adverse effects such as increased risks of infections, major adverse cardiac events, malignancy, and thromboembolism remain considerations in the overall risk-benefit assessment.4  

Treatment of Scarring Alopecias 

Scarring alopecias, such as LPP and FFA, are challenging for dermatologists. Many treatment options have been introduced, but there are still no true cures yet. 

Recent studies support the use of JAK inhibitors in managing scarring alopecia, particularly tofacitinib (10 mg or 15 mg) and baricitinib (4 mg).5 These medications are being used off-label in many specialized dermatology clinics and have been repurposed based on their immunomodulatory capabilities. Retrospective analyses of difficult cases of LPP and FFA show significant improvement in inflammation and fibrosis within a median time frame of 3 months and present minimal adverse effects. These results suggest JAK inhibitors can be used for patients struggling with controlling the progression of their hair loss.6 

TNF inhibitors have also shown potential in treating scarring alopecia disorders. Research shows that TNF inhibitors such as adalimumab were shown to be effective in managing cicatricial alopecia subtypes (LPP, FFA, and folliculitis decalvans) by curbing inflammation and, in some cases, inducing hair regrowth.7 The use of these inhibitors underscores the growing recognition of autoimmune mechanisms in scarring alopecia pathogenesis and their therapeutic targeting.

With recent studies demonstrating the efficacy of topical metformin in the treatment of central centrifugal cicatricial alopecia (CCCA), this raises the question of whether oral metformin would serve as a viable treatment modality. Currently, preclinical trials at Johns Hopkins University are exploring this as an option to manage symptoms.8 This treatment offers new hope through known anti-inflammatory and anti-fibrotic modulation properties, and, in some cases, has even shown regrowth, complementing traditional therapies such as intralesional corticosteroids and oral minoxidil.9

Answers on more invasive therapies such as hair transplantation and platelet-rich plasma (PRP) therapy are popular for treating a variety of scarring alopecias, though outcomes vary. Research shows that transplant success depends on the severity of the disease before the procedure, as it can either restore hair or exacerbate the condition.¹⁰ Therefore, patient selection, disease stabilization, and experienced transplant surgeons are crucial for successful outcomes. PRP therapy, meanwhile, may help control inflammation of the scalp and scarring.¹¹

Minoxidil 

Low-dose oral minoxidil (LDOM) is all the rage in the treatment of hair loss, attracting attention for its efficacy and low-side-effect profile. As a systemic medication, oral minoxidil is recognized not only for its potential as a primary treatment for various forms of alopecia but also for its distinctive pharmacological effects, which likely include vasodilation along with possible anti-inflammatory and antiandrogenic properties. The absorption of oral minoxidil is rapid, and its action involves the stimulation of potassium channels, which enhances nutrient delivery to the hair follicles. This may also reduce microinflammation and potentially impact hormonal factors critical to hair growth. Despite its promising benefits, the exact mechanisms through which oral minoxidil influences hair growth remain partially understood, necessitating further research to fully elucidate its therapeutic pathways.^12,13

Recent studies have evaluated the safety of LDOM in treating hair loss, to go along with established effectiveness. One study involving 1,404 patients revealed that 80% experienced no major adverse effects while taking LDOM, with hypertrichosis as the most common side effect of the medication as seen in 15.1% of patients. Minor adverse effects such as light-headedness (1.7%) and fluid retention (1.3%) were generally manageable with dosage adjustments.¹⁴

For female pattern hair loss (FPHL) the recommended doses are between 0.25 mg and 2.5 mg daily of LDOM; for male pattern hair loss (MPHL), the recommended doses are 2.5 mg to 5.0 mg daily. For those worried about hypertrichosis, it is recommended to stay below 2.5 mg daily to minimize the undesirable effects of LDOM. 

Topical minoxidil is primarily used for androgenetic alopecia and is valued for its ease of application and minimal systemic impacts. However, recent studies suggest that when used in conjunction with oral minoxidil, there is no significant enhancement in overall efficacy.¹⁵ This could simplify treatment protocols, potentially eliminating the need for topical application if oral administration proves sufficient. Through ongoing research, further refinements in dosage and administration methods are likely to enhance the utility and acceptance of minoxidil as a vital treatment for hair loss across different patient demographics. 

Nails

Nail disorders comprise approximately 10% of all dermatological conditions and offer convenient insight into a patient’s overall health.¹⁶ Despite their prevalence, nails are often overlooked in dermatological practice, and treatment modalities for such conditions have remained limited.¹⁷ Recent studies have shown exciting new options for the improvement of nail growth and brittleness. 

Both topical and oral formulations of minoxidil, traditionally recognized for their efficacy in promoting hair growth, have demonstrated promising results in addressing nail concerns. The proposed mechanisms parallel those observed in hair growth, whereby minoxidil’s vasodilatory properties enhance oxygen and nutrient delivery to the nail matrix.¹⁸

In one study, applying 5% topical minoxidil solution twice daily to the proximal nail fold over 8 weeks led to a mean fingernail growth increase from 3.91 mm/month in untreated nails to 4.27 mm/month in treated nails.¹⁸ Similarly, oral minoxidil (0.625-1.25 mg) elicited faster fingernail growth in 53% of patients and strengthened fingernails in 37.9% of patients while on medication.¹⁹ Comparative analysis has shown the superiority of topical minoxidil 5% solution over oral biotin (2.5 mg), a popular hair and nail supplement, with 6% higher increases in nail growth after 28 days.²⁰ Interestingly, one study observed no significant differences in fingernail growth rates between the application of 2% and 5% topical minoxidil solution to the proximal nail fold after 4 weeks of treatment. However, by week 8, the 2% solution demonstrated greater mean growth rates.²¹ 

The effect of topical bimatoprost, a prostaglandin analog, on the nails has also been studied. Although its mechanism is incompletely understood, topical bimatoprost 0.01% solution exhibited purported improvements in nail growth (6.5% increase) and brittleness when applied twice daily to the proximal nail fold for 30 days.²²

Considering the relapsing and remitting nature of many nail disorders, patient education regarding treatment options and a shared understanding of treatment goals will ultimately yield improved outcomes. Further investigation is necessary to refine these treatment regimens, but a new era of nail therapeutics is on the horizon. 

The authors reported no relevant financial disclosures.

Sarah Choe and Abhinav Birda are medical students at the University of California, Irvine. Jesse Salas is a medical student at the University of California, Riverside. Natasha Atanaskova Mesinkovska, MD, PhD, is an associate professor of dermatology and vice chair for clinical research in dermatology at the University of California, Irvine.

1. King, B, al. Two phase 3 trials of baricitinib for alopecia areata. N Engl J Med. 2022;386(18):1687-1699. Doi:10.1056/NEJMoa2110343

2. Patient-reported outcomes for scalp, eyebrow and eyelash hair loss in patients with severe alopecia areata treated with baricitinib: 152-week results from two phase 3 clinical trials. Abstract #52709. Presented at: American Academy of Dermatology 2024 Annual Meeting, March 2024.

3. Hordinsky M, et al. Efficacy and safety of ritlecitinib in adolescents with alopecia areata: Results from the ALLEGRO phase 2b/3 randomized, double-blind, placebo-controlled trial. Pediatr Dermatol. 2023;40(6):1003-1009. Doi: 10.1111/pde.15378

4. Choe S, et al. Characteristics and outcomes of patients on tofacitinib for alopecia areata or rheumatoid arthritis: A retrospective cohort study. Pharmacoepidemiol. 2024;3:51-56. Doi:10.3390/pharma301000

5. Plante J, et al. Tofacitinib in the treatment of lichen planopilaris: A retrospective review. J Am Academ Dermatol. 2020;83(5):1487-1489. Doi:10.1016/j.jaad.2020.05.104. 

6. Moussa A, et al. Treatment of lichen planopilaris with baricitinib: A retrospective study. J Am Academ Dermatol. 2022 Sep;87(3):663-666. Doi:10.1016/j.jaad.2022.02.027. Epub 2022 Feb 22. PMID: 35202778.

7. Hajizadeh N, et al. Tumor necrosis factor inhibitors and janus kinase inhibitors in the treatment of cicatricial alopecia: A systematic review. PLOS ONE. 2024;19(2):e0293433. Doi:10.1371/journal.pone.0293433

8. Johns Hopkins Applied Physics Laboratory. Orally administered metformin to treat hair loss in central centrifugal cicatricial alopecia. 2024. URL: jhu.technologypublisher.com/technology/54193. Accessed May 1, 2024.  

9. Araoye E, et al. “Hair regrowth in 2 patients with recalcitrant central centrifugal cicatricial alopecia after use of topical metformin.” JAAD case reports vol. 2020;6(2):106-108. Doi:10.1016/j.jdcr.2019.12.008

10. Lee JA, et al. Hair transplantation in frontal fibrosing alopecia and lichen planopilaris: A systematic review. Laryngoscope. 2021;131(1):59-66. Doi:10.1002/lary.28551. 

11. Jha AK. Platelet-rich plasma for the treatment of lichen planopilaris. J Am Acad Dermatol. 2018;79(5):e95-e96. Doi:10.1016/j.jaad.2018.05.029. 

12. Randolph M, Tosti, A. Oral minoxidil treatment for hair loss: A review of efficacy and safety. J Am Academ Dermatol. 2021;84(3):737–746. Doi:10.1016/j.jaad.2020.06.1008

13. Pekmezci E, Türkoğlu M. Minoxidil acts as an antiandrogen: A study of 5α-reductase type 2 gene expression in a human keratinocyte cell line. Acta Dermatovenerol Croat. 2017;25(4):271-275. PMID:30064598.

14. Vañó-Galván S, et al. Safety of low-dose oral minoxidil for hair loss: A multicenter study of 1404 patients. J Am Acad Dermatol. 2021;84(6):1644-1651. Doi:10.1016/j.jaad.2021.02.054. 

15. Klein EJ, et al. Comparing combination low-dose oral minoxidil and topical minoxidil with oral minoxidil alone for the treatment of non-scarring alopecia: A retrospective chart review. J Cosmet Dermatol. 2022;21(11):6473-6475. Doi:10.1111/jocd.15138.

16. David A, et al. Nail abnormalities associated with various dermatoses in a tertiary care center in North India: A cross-sectional study. J Dermatol Dermatol Surg. 2021;25(2):119-123. Doi:10.4103/jdds.jdds_22_21

17. Arasu A, et al. Evaluation and management of nail diseases. Medicine Today. 2023;24(3):31-37. URL: https://medicinetoday.com.au/mt/2023/march/feature-article/evaluation-and-management-nail-diseases

18. Aiempanakit K, et al. The use of topical minoxidil to accelerate nail growth: a pilot study. Int J Dermatol. 2017;56(7):788-791. Doi:10.1111/ijd.1362

19. Alsalhi W, et al. Effects of oral minoxidil on nails: a cross-sectional analysis. International journal of dermatology. 2023;62(9):e489-e490. Doi:10.1111/ijd.16608

20. Garbers L, et al. Efficacy of 2.5 mg oral biotin versus 5% topical minoxidil in increasing nail growth rate. Experiment Dermatol. 2021;30(9):1322-1323. Doi:10.1111/exd.14316

21. Nitayavardhana S, et al. Comparison of the efficacy and safety of topical 2% minoxidil and 5% minoxidil solution in fingernail growth rate. Asia Med J Alt Med. 2023;23(3):18–23.

22. Palmer D, et al. The effect of cutaneous prostaglandin application on nail growth, nail brittleness, and intraocular pressure. J Cosmet Dermatol. 2018;17(2):263-267. Doi:10.1111/jocd.12372