Dr. Ted Rosen on JAK Inhibitors for Refractory Granulomatous and Autoimmune Dermatoses

The role of JAK inhibitors in diseases characterized by chronic macrophage–T-cell interactions continues to grow, Theodore Rosen, MD, said at the DEF Essential Resource Meeting 2025 (DERM2025). The discussion focused on granuloma annulare (GA), sarcoidosis, lichen planus (LP), and lupus erythematosus—conditions for which standard treatments frequently fail. With interferon-γ acting as a critical signal in these diseases, JAK-STAT pathway inhibition may interrupt the pathogenic loop.

All four conditions share a pathogenic axis involving T cells and macrophages engaging in reciprocal activation via cytokines, particularly interferon-γ. By targeting JAK-STAT signaling, JAK inhibitors can downregulate inflammatory mediators, decrease granuloma formation, and modulate autoimmune responses.

Dr. Rosen reviewed clinical evidence for JAK inhibitors to treat several diseases:

Granuloma Annulare (GA)

• Tofacitinib: Eight reported cases of generalized GA showed near-complete or complete resolution after failure of steroids, methotrexate, and antimalarials.
• Baricitinib: Three patients with recalcitrant GA achieved clearance at 4 mg daily.
• Abrocitinib: Two cases with significant response at intermediate dosing.
• Ruxolitinib 1.5% cream: Demonstrated complete facial GA clearance within 12 weeks in multiple cases. Dr. Rosen reported sustained remissions after drug discontinuation.

Cutaneous Sarcoidosis

• Conventional therapies (steroids, methotrexate, anti-TNF agents) often fail.
• A case series and a small trial with tofacitinib (10–15 mg daily) showed marked cutaneous improvement, supported by gene expression profiling indicating suppression of interferon-driven pathways.
• Imaging studies confirmed granuloma resolution in responders.

Lichen Planus (LP)

• Systemic JAK inhibitors (tofacitinib, abrocitinib, baricitinib) have achieved high rates of partial or complete resolution, including relief from pruritus.
• Topical options: Ruxolitinib and other agents demonstrated efficacy in oral, hypertrophic, and nail LP, preventing disease progression even when scarring was established.
• Dr. Rosen noted: “If it starts with the word ‘lichen,’ it probably responds to a JAK inhibitor.”

Lupus Erythematosus

• TYK2 inhibitors such as deucravacitinib target interferon signaling—critical in lupus pathogenesis.
• Phase 2 data (n=363) demonstrated dose-dependent improvements in cutaneous lupus erythematosus and discoid lupus, without the black box warnings associated with traditional JAK inhibitors.

Most JAK inhibitors carry black box warnings (infection, malignancy, cardiovascular risk), based on rheumatoid arthritis cohorts >50 years with comorbidities, Dr. Rosen noted, but dermatology-focused reviews suggest lower observed risks in younger, otherwise healthy patients.

Practical challenges include the high cost and the lack of FDA approval for these indications necessitating prior authorization and advocacy. Off-label use, he noted, requires careful documentation and patient counseling.

Still, JAK inhibitors provide promising therapeutic options for refractory granulomatous and autoimmune dermatoses. Although off-label, accumulating case reports and small trials support their use in select, treatment-resistant patients.