Lichen planus (LP) is often mischaracterized as a mere dermatologic condition.

In reality, it represents a chronic, immune-mediated mucocutaneous disorder that can manifest in various anatomical regions including the skin, mucosa, genitalia, nails, and scalp.

First described in the 19th century, its true clinical complexity is only now being fully appreciated through recent immunopathological studies. LP is not contagious, nor is it malignant by default, but the chronicity, symptom burden, and potential for malignant transformation in mucosal variants make it a condition of significant clinical importance.

Pathophysiology: T-Cell-Mediated Damage Beyond the Surface

The underlying mechanism of LP involves a cytotoxic T-cell-driven response against basal keratinocytes, which are falsely targeted as antigen-presenting cells. A 2023 review in Nature Reviews Immunology emphasized the role of CD8+ T cells, IFN-γ, and cytoplasmic granule proteins like granzyme B in this immune dysregulation.

According to Dr. Steven D. Feldman, a dermatology expert at Wake Forest School of Medicine, "The activation of resident memory T cells appears to sustain inflammation long after the initial trigger has resolved, highlighting LP as a disorder of immune memory." Environmental triggers such as hepatitis C infection, certain medications (e.g., antihypertensives, NSAIDs), and dental amalgams have also been implicated in precipitating or exacerbating LP in genetically susceptible individuals.

Clinical Variants: Not Just Cutaneous

Although cutaneous LP presents with characteristic polygonal, pruritic, purple papules often on the wrists, ankles, or lumbar region, several other variants carry more significant clinical implications:

Genital LP: Frequently co-occurs with disease, particularly in women, and may result in scarring or atrophy if left untreated.

Lichen Planopilaris (LPP): A follicular variant that leads to scarring alopecia, often resistant to conventional therapies.

Nail LP: May cause longitudinal ridging, fissuring, or even pterygium formation, potentially leading to permanent nail loss.

Diagnosis: The Role of Histopathology and Direct Immunofluorescence

A definitive diagnosis requires clinical examination supported by histopathology. Classic features include saw-tooth lymphocytic infiltrate at the dermoepidermal junction, Civatte bodies (apoptotic keratinocytes), and hypergranulosis.

When mucosal lesions are present or the diagnosis is uncertain, direct immunofluorescence (DIF) aids in differentiation from mimickers such as mucous membrane pemphigoid or chronic ulcerative stomatitis. DIF typically reveals shaggy fibrinogen deposition along the basement membrane zone. Additionally, biopsy remains essential in erosive OLP, given its association with squamous cell carcinoma.

Therapeutic Strategies: Targeted, Long-Term, and Multi-Disciplinary

Topical Corticosteroids as First-Line

For localized skin and lesions, high-potency corticosteroids (e.g., clobetasol propionate) remain the mainstay. Intraoral lesions may require compounded preparations in orabase for mucosal adherence.

Systemic Therapy for Extensive or Refractory Disease

In moderate to severe cases, systemic treatments are considered. Corticosteroids, methotrexate, mycophenolate mofetil, or hydroxychloroquine have shown efficacy, particularly in lichen planopilaris. Recent studies, including a 2024 clinical trial in The Lancet Dermatology, have demonstrated that JAK inhibitors (e.g., baricitinib) significantly reduce inflammation in erosive LP by blocking IFN-γ signaling.

Phototherapy and Immunosuppressives

Narrowband UVB phototherapy offers benefit in generalized cutaneous LP, particularly in patients intolerant to systemic drugs. In resistant and genital LP, topical calcineurin inhibitors like tacrolimus may offer relief, though with caution due to the risk of malignancy with long-term use.

Psychosocial Implications and Surveillance Needs

The chronic pain, visible lesions, and potential for malignancy—especially in genital LP—warrant psychological support and long-term surveillance. Routine follow-up is crucial to detect dysplastic changes, especially in patients with erosive disease. A multidisciplinary approach involving dermatologists, medicine specialists, gynecologists, and psychologists is often required to provide holistic management and improve patient outcomes.

Future Perspectives: Immunobiologics and Precision Medicine

With deeper understanding of LP's immunological underpinnings, targeted biologic therapies are emerging. Monoclonal antibodies against IL-17 and IL-23, already used in psoriasis, are under early-phase trials for LP. Likewise, PD-1 inhibitors, paradoxically known to induce LP-like reactions in cancer therapy, are now being studied for their dual-modulatory potential. The application of single-cell RNA sequencing and T-cell receptor clonotyping may soon personalize LP management by identifying pathogenic clones and immune signatures unique to each patient.

Lichen planus is far more than a cosmetic dermatologic issue. It is a systemic, immune-mediated, and clinically heterogeneous condition with real implications for patient morbidity. Timely diagnosis, individualized treatment, and multidisciplinary care remain the cornerstones of effective management. As precision immunology advances, new therapeutic horizons are emerging—transforming how clinicians approach and treat this underestimated disease.