Vitiligo, Melasma, PIH, and Albinism: Clinical Update and Emerging Therapies

Pigmentary disorders, though rarely life-threatening, pose a significant therapeutic challenge. The impact on patient quality of life and emotional well-being—often intensified by social stigmatization—underscores the need for improved treatment strategies. This review examines emerging therapies and their challenges for common pigmentary conditions, encompassing topical therapies, systemic agents, light-based modalities, lasers, and more.

Clinical images courtesy of Bernard A.Cohen, MD

Vitiligo

Vitiligo, a chronic autoimmune disorder marked by depigmented skin patches, has historically lacked fully satisfactory treatments. However, recent advances have revolutionized the therapeutic landscape, offering new hope for patients. Traditional approaches such as topical corticosteroids, calcineurin inhibitors, oral corticosteroids, and narrow-band UVB (NB-UVB) phototherapy remain valuable, but each has limitations. A recent study highlighted the safety and efficacy of topical tacrolimus in infants, showing 100% repigmentation in infants younger than 2 years after 6 months of treatment, with no adverse effects or metabolite changes.¹ Oral corticosteroids, including oral mini-pulse (OMP) therapy, may be used for rapidly progressing vitiligo, but a recent review found inconclusive evidence regarding the efficacy of OMP monotherapy, necessitating further research.² NB-UVB phototherapy is highly effective, though time intensive. Emerging evidence suggests home-based phototherapy may offer comparable efficacy with greater convenience, though more studies are needed to confirm its safety and reliability.³

One of the most significant breakthroughs has been the identification of the Janus kinase (JAK)/signal transducer and activator of transcription pathway’s role in vitiligo pathogenesis. The JAK1/2 inhibitor ruxolitinib (Opzelura; Incyte) cream, the first FDA-approved treatment to repigment the skin of patients aged 12 years and older with nonsegmental vitiligo affecting 10% or less of their total body surface area, represents a monumental milestone for the vitiligo community. Clinical trial results show it is effective and well tolerated, though questions persist regarding optimal treatment duration and the durability of repigmentation post-treatment, with insights from the open-label extension of phase 3 trials (NCT04530344) expected soon.^4,5 Oral JAK inhibitors, including tofacitinib (Xeljanz; Pfizer, Inc) and baricitinib (Olumiant; Eli Lilly and Company, and Incyte), have shown promise in case reports, but repigmentation loss after discontinuation underscores the need for long-term studies.^6-8

Combination therapies enhance outcomes, particularly those integrating antioxidants such as vitamins C/E with phototherapy. A systematic review and meta-analysis revealed that combining antioxidants with phototherapy is more effective than phototherapy alone.⁹ Surgical options, including melanocyte-keratinocyte transplant procedures and mini-punch grafting, provide excellent results for stable vitiligo, with innovations such as transverse needling further boosting repigmentation rates.¹⁰ Platelet-rich plasma therapy has also shown potential, with a recent study reporting significant improvement after 1.5 sessions in refractory cases.¹¹ Afamelanotide, a synthetic α-melanocyte-stimulating hormone analogue used for other conditions, shows promise for vitiligo when combined with phototherapy, especially in darker skin types, with ongoing phase 2 and 3 trials further investigating its efficacy.¹²

Treatments for vitiligo should remain patient centered, balancing efficacy, tolerability, and lifestyle needs. Cosmetic camouflage continues to play a supportive role, improving self-esteem during prolonged treatment courses.¹³ Although no cure exists, these advancements, supported by robust clinical data, mark significant progress in managing vitiligo. Ongoing research will be critical in delivering truly transformative outcomes.

Melasma

Melasma is a chronic, acquired pigmentary condition characterized by hyperpigmented patches in photo-exposed areas. Current treatment options for melasma include sun protection, topical agents such as hydroquinone, retinoids, corticosteroids, azelaic acid, kojic acid, and tranexamic acid (TXA), as well as oral therapies such as TXA and antioxidant supplements, and procedural interventions, such as chemical peels and laser-based therapies. Recent advancements in the treatment of melasma include the use of visible light photoprotection, nonhydroquinone depigmenting agents, and new laser/energy-based therapies.

Broad-spectrum sun protection is a critical component of both the management and prevention of melasma. Recent studies have shown that sunscreens with iron oxide, which protects against both UV and visible light (VL), result in more effective pigment reduction than broad-spectrum UV alone.¹⁴ Furthermore, the use of UV-VL sun protection has also been shown to enhance the results of effective treatments such as hydroquinone.¹⁴

While topical hydroquinone and triple combination cream (TCC) therapy (comprising hydroquinone, a retinoid, and a mild steroid) have been gold standard treatments for targeting melanin production or melanosome transfer in melasma, newer therapies are emerging that may be safer alternatives. Thiamidol, a potent tyrosinase inhibitor, has shown equal or superior efficacy to hydroquinone with fewer adverse effects in trials.¹⁴ TXA, used orally, topically, or intradermally, also demonstrates comparable results with a better safety profile.¹⁴ Cysteamine, another depigmenting agent, has been trialed successfully and with few adverse effects, but shows less improvement than hydroquinone.¹⁴ Bakuchiol, an antimicrobial compound with anti-inflammatory and antioxidant properties, has been shown to have similar antiaging and lightening properties as retinoids and demonstrated improvement in melasma.¹⁵ Newer studies are recommending the consideration of thiamidol and TXA as first-line treatments over TCC or hydroquinone due to their superior safety profiles with comparable efficacy.¹⁶

Laser-based therapies are often reserved for severe or refractory cases and include Q-switched neodymium-doped yttrium aluminum garnet (QS Nd:YAG), intense pulsed light, radiofrequency, and combinations with other treatments. Studies have suggested that combination therapy often leads to the highest efficacy and most sustained results, but this often comes with an increased risk of adverse effects.¹⁴ Picosecond lasers are a newer option that recent trials have suggested offer similar efficacy when compared with QS Nd:YAG lasers but with significantly reduced pain and acneiform eruptions.¹⁴

Despite these advancements, challenges remain. Melasma frequently relapses, necessitating maintenance therapy, and treatments often cause adverse effects such as irritation or postinflammatory hyperpigmentation.¹⁴ Additionally, responses vary across different skin types and ethnic groups, requiring tailored approaches. A lack of universal guidelines and issues with patient adherence to long-term regimens further complicate management. While progress is evident, addressing recurrence and improving treatment personalization are key areas for future focus.

Postinflammatory Hyperpigmentation

Postinflammatory hyperpigmentation (PIH) arises from excess melanin production following skin inflammation or injury, appearing as darkened skin patches. Common triggers include acne, eczema, trauma, and cosmetic procedures. Treatments for PIH align with those for melasma, incorporating broad-spectrum UV-VL sun protection, topical agents (eg, hydroquinone, retinoids, azelaic acid, kojic acid, and TXA), chemical peels (eg, glycolic and salicylic acid), laser therapies (eg, fractional and low-fluence Q-switch lasers), and oral medications such as TXA.¹⁶

Management is complicated by the risk of exacerbating inflammation or hyperpigmentation with certain treatments, such as chemical peels or laser therapies, particularly in darker skin types.¹⁷ Although these procedures may carry a heightened post-treatment PIH risk, microneedling combined with topical treatments has been shown to be efficacious in the treatment of pigmentary disorders without worsening PIH, providing a potentially safer alternative to patients with darker skin.¹⁶ As with melasma, newer therapies, including thiamidol, cysteamine, bakuchiol, and topical TXA, have shown efficacy in PIH treatment with limited adverse effects.¹⁶ Oral TXA also demonstrates effectiveness for both management and prevention, but recurrence rates remain high upon discontinuation.¹⁶ Among retinoids, trifarotene is emerging as a promising option for PIH due to its rapid efficacy and tolerability in recent trials.¹⁸

Novel treatment pathways are also being explored for the treatment of PIH. A 2024 study highlighted the potential of the NF-κB inhibitor Bay 11-7082 to suppress both inflammation and melanogenesis, offering promise as a topical therapy for PIH.¹⁷ Additionally, carnosic acid recently demonstrated effectiveness in reducing melanin deposition and ameliorating hyperpigmentation after wound healing in animal models, suggesting its potential as a safe and effective drug for PIH management.¹⁹

Although PIH remains a challenging condition to treat due to risk of exacerbation and high recurrence rates, advancements in both traditional and emerging therapies provide hope for improved outcomes. Tailored approaches, patient adherence, and continued research into safer, more targeted therapies are essential for optimizing PIH management and addressing its complexities.

Albinism

Oculocutaneous albinism (OCA) comprises rare, inherited disorders of reduced melanin biosynthesis, manifesting in hypopigmentation of skin, eyes, and hair, and ocular issues such as decreased visual acuity and nystagmus. Currently, albinism is incurable, and treatment aims either surgically or pharmacologically to optimize vision and protect the skin. Although emerging therapies that aim to directly address the underlying molecular defects, such as l-dihydroxyphenylalanine and nitisinone, are being developed and have entered human trials, clinical success has been limited. A 1-year pilot study on nitisinone in OCA-1B patients showed potential increases in hair and skin pigmentation, though iris melanin content remained unchanged.²⁰ Importantly, the significantly elevated skin cancer risk in OCA requires vigilant dermatologic care. Early pediatric dermatology referral, parental education on skin protection and cancer prevention, and a low threshold for biopsy of suspicious lesions are crucial for early detection and improved patient outcomes.

Looking Ahead

The continually evolving landscape of pigmentary disorders presents dermatology clinicians with an expanding range of therapeutic options. Future research will define optimal combinations of topical, systemic, and light-based therapies for each disorder. For vitiligo, the availability of topical JAK inhibitors and refined combination therapies offers significantly improved treatment outcomes. In melasma, a shift toward thiamidol and TXA as first-line agents may be warranted based on their enhanced safety and efficacy profiles. These treatments along with the retinoid trifarotene and oral TXA also show promise for improved PIH management. Despite their impact on quality of life, many pigmentary disorders are still considered cosmetic by payers, limiting patients’ access to treatments. Although treatments are improving, limited payer support, recurrence rates, and the need for long-term data remain challenges. Only through continued research, advocacy, and the integration of new therapies into clinical practice can we achieve optimal outcomes for patients with pigmentary disorders.

Rebecca Urbonas is a rising fourth-year medical student at Florida Atlantic University, where she developed an interest in pediatric dermatology. Currently, she serves as a research fellow at Johns Hopkins University, where she leads patient-oriented investigations into chronic skin diseases in children.

Sumrah Jilani is a rising fourth-year medical student at Johns Hopkins University School of Medicine, where she is currently serving as a research fellow in the Division of Pediatric Dermatology.

Bernard A. Cohen, MD, is a professor of pediatrics and dermatology at Johns Hopkins University School of Medicine in Baltimore, Maryland.

References

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