This is an investigator-initiated, proof of concept, open study to assess efficacy of a topical Ruxolitinib in subjects with Chronic Hand Dermatitis (CHD). The study will be conducted at the University of Rochester Medical center, Dermatology Department - Rochester, NY. Qualified and enrolled subjects (see Inclusion/Exclusion criteria) will be required to come to URMC Dermatology Clinic for at least five visits.

This is a single-center study anticipating to enroll 15 participants with chronic hand dermatitis. Eligible participants will receive Ruxolitinib to apply twice daily for 12 weeks. Participants will be required to be seen every 4 weeks until week 16.

Inclusion Criteria:

• Diagnosis of chronic hand eczema defined as hand eczema, which has persisted for more than 3 months or returned twice or more within the last 12 months.
• Disease severity graded as moderate to severe according to IGA (i.e., IGA ≥2).
• Recent history (within 1 year before the screening visit) of inadequate response to topical corticosteroid and/or calcineurin inhibitors treatment or topical corticosteroid treatment being medically inadvisable.

Exclusion Criteria:

• Active atopic dermatitis in regions other than the hands requiring medical treatment.
• Active psoriasis in regions other than the hands requiring medical treatment.
• Clinically significant infection (e.g., impetiginized hand eczema or tinea manum) on the hands.
• Patients with excessive contact of hands with water (longer than 2 hours at day; or > 20 hands washing at day) that is believed to be a predominant cause of the hand dermatitis.
• Subjects with known antigen sensitization based on Patch test (with 3 years) that are unable to reduce contact with the specific antigen(s).
• Subjects chronically and consistently exposed to known-irritant or other substance known to impact skin barrier will be excluded based on PI judgement
• Systemic treatment with immunosuppressive drugs, immunomodulating drugs, retinoids, or corticosteroids within 4 weeks prior to baseline.
• Systemic treatment with antibiotics within 4 weeks prior to baseline
• Phototherapy on the hands within 4 weeks prior to baseline.
• Use of topical immunomodulators (e.g., phosphodiesterase-4 (PDE-4) inhibitors, pimecrolimus, tacrolimus) or topical corticosteroids on the hands within 2 weeks prior to baseline.
• Use of topical antibiotics on the hands within 2 weeks prior to baseline.
• Change in systemic antihistamine therapy within 2 weeks prior to baseline i.e., subjects must not start antihistamine treatment or change the current dosage regime within 2 weeks prior to baseline.
• Other topicals applied therapy on the hands (except for the use of subject's own emollients) within 1 week prior to baseline.
• Receipt of any marketed or investigational biologic agents within 6 months or 5 half-lives prior to baseline
• Any disorder which is not stable and in the investigator's opinion could affect the safety of the subject, influence the findings of the trial, or impede the subject's ability to complete the trial.
• Participants with clinically significant cytopenia at screening
• Participants with severely impaired liver or kidney function and unstable.
• Participants who have previously received JAK inhibitor therapy, systemic or topical.
• History of any known primary immunodeficiency disorder including a positive human immunodeficiency virus (HIV), or the subject taking antiretroviral medications.
• Females who are breastfeeding, pregnant, or anticipate becoming pregnant during the study time frame
• History of skin cancer on hands within 5 years.
• History of recalcitrant warts on hands within 1 year

12 weeks