Remission of chronic actinic dermatitis on baricitinib: A case report

Abstract Chronic actinic dermatitis (CAD) is an immune‐mediated photodermatosis characterised by eczematous, pruritic changes to sun‐exposed skin. The pathophysiology of CAD is poorly understood, with current explanations including a hypersensitivity reaction and cross‐reactivity to contact allergens. The disease is often refractory to immunosuppressive treatment and has a marked impact on patient quality of life. Janus kinase inhibitors (JAKi) are a novel class of small molecules licenced for the management of certain inflammatory conditions, including atopic dermatitis We present the case of a 69‐year‐old gentleman with a history of severe CAD, unresponsive to standard therapies, who was prescribed baricitinib, a janus kinase (JAK) inhibitor as a single agent treatment for his disease. The patient experienced a dramatic clinical improvement with this therapy. In addition, normalisation of photo test and improvement of patch test results following treatment were observed. There is one previous case report in the literature describing the clinical response of patients with CAD to JAK inhibitor therapy, but no comment on pre or post treatment photo testing, patch testing or photo‐patch testing results was made. In this case report, we discuss our understanding of the role of JAK inhibitors in CAD and highlight a potential new therapeutic avenue for this disabling disease.

A 69-year-old gentleman was referred to the specialist photobiology centre in 2005 with a 5-year history of a photo-distributed rash.The patient first noticed erythema and pruritus of the palms and dorsal aspect of the forearms after commencing work with Royal Mail.His rash spread to affect predominantly sun-exposed sites, later spreading to covered sites.His symptoms worsened in summer after a few minutes in the sun.He had no prior dermatological history.He was otherwise fit and well, with no history of atopy or notable family history.
Monochromator and solar simulator testing in 2010 showed abnormal responses consistent with chronic actinic dermatitis.Patch testing in 2013 showed allergic reactions to cobalt, thiuram and epoxy resins.In 2014, reactions were also noted to methylisothiazolinone, colophony and clobetasol.In 2017, photo-patch tests were positive to colophony, epoxy resin, evernia furfuracea and linalool.Despite stringent allergen avoidance, symptoms persisted.
Initial treatment comprised potent topical corticosteroids and multiple weaning courses of systemic steroid.Systemic therapy was commenced in 2012 with azathioprine 50 mg daily but stopped after nine days due to intolerable gastrointestinal side effects.Over the following 9 years, multiple other systemic agents were trialled including mycophenolate mofetil, methotrexate, acitretin and alitretinoin.Each demonstrated limited therapeutic effect, requiring adjuvant therapy with further courses of topical and systemic steroid.The patient's quality of life deteriorated, remaining indoors during summer and winter months.In June 2021, baricitinib 2 mg orally once daily was commenced as single-agent treatment for CAD.Baseline disease severity scores were markedly raised, with DLQI 25, PHQ9 22, GAD7 14 and POEM 28.
At week seven of treatment the patient developed blistering on the tips of his fingers.This resolved with flucloxacillin and empiric valaciclovir.Baricitinib was restarted at week 9 at an increased dose of 4 mg daily.At 9 months, the patient reported improvement, with an EASI score of 0.5 and DLQI 2 (a 90% improvement in his scores).At 16 months, he had clear skin and could go gardening on sunny days without sun protection.By November 2022 repeat photo testing was normal.Repeat patch testing showed persistent allergy to colophony, epoxy resin and clobetasol.Photo-patch testing showed a new reaction to diclofenac, notably only apparent on the patch exposed to UVA at 5 J/cm2 , higher than the patient 's previous exposure, given his disease severity.

| DISCUSSION
To our knowledge, this is the first case of CAD reported in the literature to respond to JAK inhibitor therapy as single-agent treatment (as illustrated in Figures 1-3), with induction of complete clinical remission, and normalisation of photo-testing.CAD was first described by Ian Magnus in 1969 in a case series of 10 patients at the St John's Institute of Dermatology with persistent photo-sensitive dermatitis. 5Consistent with our case, CAD is characterised by eczematous, pruritic, and often lichenified changes to sun-exposed skin.The face, scalp, neck, upper chest, and dorsal aspect of hands and forearms are the worst affected sites. 6atients of all ages and ethnicities can be affected. 7mportant investigations include photo testing, patch testing and photo-patch testing.Photosensitivity to UV wavelengths, particularly UVB but also UVA, and sometimes visible wavelengths, is described. 6Lupus serology is usually negative. 8Treatment includes strict sun avoidance, use of sunscreens, emollients, and F I G U R E 1 Frontal view of patient depicting improvement in skin post commencement of baricitinib.topical corticosteroids.Standard systemic immunosuppression is considered if CAD is not controlled with skin-directed measures.The pathophysiology of CAD is poorly understood.However, given its clinical and histopathological appearances and the presence of CD8 positive T cells in the dermis, a hypersensitivity reaction akin to persistent allergic contact dermatitis is broadly accepted to be the mechanism 8 ; causative allergens are endogenous and photo-induced.Most cases exhibit pre-existing allergic contact dermatitis. 3It has been suggested that UV-damaged DNA may trigger an allergic contact response which, sometimes, is due to contact-dermatitis-enhanced immune reactivity. 8AKi are a novel class of oral immunosuppressant medications licenced for the management of atopic dermatitis, psoriatic, and rheumatoid arthritis and alopecia areata.By inhibiting the action of four key tyrosine kinases, JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2), they affect various cell lineages including CD8 positive T cells, and suppress interferon gamma and interleukin pathways.Baricitinib is a JAK 1,2 inhibitor, used to treat atopic eczema.Given current evidence suggesting CAD as a cytotoxic T cell mediated disease, one could infer a therapeutic role for JAK pathway inhibition.Our patient's dramatic response to treatment with baricitinib supports this hypothesis.
Spontaneous remission of CAD has been described by Dawe et al.One in five patient's abnormal photosensitivity resolves 10 years after diagnosis. 3However, the presence of multiple contact allergens in two or more patch test series, as in our patient's case, is usually a predictor of poor prognosis for spontaneous resolution of disease. 3As shown in Figure 4, normalisation of monochromator testing in the presence of multiple contact allergens suggests that the improvement in our case may be attributed to baricitinib, rather than spontaneous resolution.We propose that treatment be paused following one clear summer period, with regular follow up to monitor for recurrence of skin disease.

| CONCLUSION
Our patient with treatment refractory CAD has achieved full clinical remission of disease and normalisation of photo test results with baricitinib treatment.We propose that JAK pathway inhibition represents a potential new therapeutic avenue for this disabling disease and that consideration be given to baricitinib earlier in the treatment pathway.

F I G U R E 2
Profile view of patient depicting improvement in skin post commencement of baricitinib.F I G U R E 3 View of right dorsal forearm and hand depicting improvement in skin post commencement of baricitinib.