What are the recent advances in dermatology, including newer systemic biologic and small‑molecule therapies for inflammatory skin diseases, targeted treatments for skin cancers, procedural technologies, and emerging gene‑editing approaches?

Recent Advances in Dermatology

Biologic Therapies for Inflammatory Skin Diseases

The most transformative advance in dermatology has been the development of targeted biologic therapies that block specific molecular pathways in inflammatory skin diseases, fundamentally changing treatment paradigms for psoriasis, atopic dermatitis, and hidradenitis suppurativa. 1, 2

TNF Inhibitors

• TNF inhibitors (etanercept, infliximab, adalimumab) remain essential first-line agents for moderate-to-severe psoriasis, particularly when psoriatic arthritis or cardiovascular comorbidities are present. 1
• These agents demonstrate significant cardioprotective effects, reducing major adverse cardiovascular events with a hazard ratio of 0.50 (95% CI 0.32-0.79, P=.003) compared to other systemic therapies. 1
• Eligibility requires severe disease defined as PASI ≥10 (or BSA ≥10%) AND DLQI >10, plus failure, intolerance, or contraindication to standard systemic therapy. 1
• Adequate response is defined as either PASI 50 response AND 5-point or greater DLQI improvement, OR PASI 75 response, assessed at 14 weeks for infliximab, 12 weeks for etanercept, and 16 weeks for adalimumab. 1

IL-17 and IL-23 Inhibitors

• Newer biologics targeting IL-17 and IL-23 pathways have expanded the therapeutic armamentarium beyond TNF inhibitors, though TNF inhibitors remain critical first-line options. 1
• These agents provide targeted approaches through interaction with specific components of underlying immune and inflammatory disease processes. 3

Small Molecule Inhibitors

• Small molecule inhibitors represent a distinct class from biologics, targeting intracellular signaling cascades rather than extracellular cytokines. 2
• These agents offer oral administration advantages and different pharmacokinetic profiles compared to injectable biologics. 2

Targeted Therapies for Melanoma

Anti-PD-1 monotherapy (pembrolizumab or nivolumab) is the preferred first-line treatment for advanced melanoma regardless of BRAF mutation status, due to superior survival outcomes and lower toxicity. 4

Immune Checkpoint Inhibitors

• Pembrolizumab or nivolumab for 52 weeks is standard of care for completely resected Stage IIB-C melanoma, based on substantial recurrence-free survival benefits. 4
• Nivolumab plus ipilimumab combination shows superior progression-free survival (HR 0.51) and overall survival (HR 0.61) compared to ipilimumab alone, but reserve this for patients with symptomatic, bulky metastases or rapidly progressive disease where rapid response is critical. 4
• FDA-approved immune checkpoint inhibitors include anti-CTLA4 (ipilimumab), anti-PD-1 (pembrolizumab and nivolumab), and anti-PD-L1 (atezolizumab). 5

BRAF/MEK Inhibitor Combinations

• Dabrafenib 150 mg PO twice daily plus trametinib 2 mg PO once daily for 52 weeks is an equivalent adjuvant option for BRAF-mutant Stage III disease. 4
• Combined BRAF and MEK inhibitor therapy (dabrafenib/trametinib, encorafenib/binimetinib, or vemurafenib/cobimetinib) should be offered for unresectable/metastatic BRAF-mutant disease. 5
• BRAF mutation testing is mandatory for all Stage III-IV melanoma to determine eligibility for targeted therapy. 4

Dermatologic Toxicity Management

• Common dermatologic findings from immune checkpoint blockade include nonspecific morbilliform dermatitis with or without pruritus, vitiligo-like hypopigmentation, and lichenoid eruptions. 5
• Onset of vitiligo-like hypopigmentation may correlate with improved immune response, particularly for patients undergoing anti-PD-1 therapy. 5
• Combined BRAF and MEK inhibitor therapy causes rash and acneiform dermatitis in 24% and 12% of patients respectively, though usually less than grade 3 severity. 5
• Early recognition and control of dermatologic toxicities prevents unnecessary interruption of medication and improves patient quality of life, requiring interdisciplinary collaboration with oncology. 5

Emerging Diagnostic Technologies

Noninvasive imaging and molecular diagnostic tools are revolutionizing melanoma detection and diagnosis, though tissue biopsy remains the gold standard. 5

Imaging Technologies

• Reflectance confocal microscopy (RCM) provides real-time, noninvasive cellular-level imaging to improve diagnostic accuracy and guide optimal tissue sampling. 5
• Electrical impedance spectroscopy combined with digital dermoscopy, optical coherence tomography, cross-polarized light and fluorescence photography, and high-frequency ultrasound are FDA-approved adjunctive tools. 5
• Dermoscopy improves diagnostic accuracy and helps direct optimal tissue sampling in cosmetically or functionally sensitive areas. 5

Molecular Diagnostics

• Noninvasive genomic methods including adhesive patch "biopsy" are being investigated to classify melanocytic lesions as benign or malignant to guide biopsy decisions. 5
• Multigene somatic and germline mutational analysis provides prognostic information, though optimal clinical situations for testing require further study. 5

Procedural and Surgical Advances

Melanoma Surgery

• Excisional/complete biopsy is preferred for lesions clinically suggestive of melanoma, as partial biopsy may inaccurately stage disease and negatively affect treatment planning. 5
• Mohs micrographic surgery and other exhaustive margin control techniques for invasive and in situ melanoma require further study to establish optimal clinical indications. 5
• Sentinel lymph node biopsy remains standard for staging regional lymph nodes, with recommendations updated based on the 2017 eighth edition AJCC melanoma staging system. 5

Radiation Therapy

• Radiation therapy is now recognized for primary treatment of melanoma in situ, lentigo maligna type, and as adjuvant therapy for desmoplastic melanoma. 5

Critical Safety Considerations

Biologic Therapy Monitoring

• Tuberculosis testing is mandatory before starting TNF inhibitor therapy due to increased risk of TB reactivation. 1
• TNF inhibitors should not be used in patients with active infections or in first-degree relatives of patients with multiple sclerosis. 1
• Caution is warranted in patients with congestive heart failure due to reports of new onset and worsening CHF. 1

Melanoma Treatment Toxicities

• Immune-related adverse events require aggressive monitoring for colitis, hepatitis, pneumonitis, endocrinopathies, and dermatologic toxicities. 4
• Any systemic treatments for cutaneous reactions (e.g., oral corticosteroids) should be undertaken in partnership with medical oncology to avoid conflicts in therapeutic intent. 5