Successful treatment of lichen sclerosus and morphea on the hand with JAK inhibitor upadacitinib

Dear Editor,

Lichen sclerosus (LS), an inflammatory sclerosing skin disorder, is characterised by the presence of atrophic hypopigmented patches predominantly affecting the genital area, with only 15% of cases occurring outside this region. It does overlap with morphea in 5.7% of cases thus complicating treatment approaches.^1,2 Here, we report a 53-year-old woman with coexisting LS and morphea resistant to conventional treatments, who improved significantly with upadacitinib.

A 53-year-old woman presented with painful papules and plaques on her right thumb since 3 months. On examination, multiple linearly arranged, pale and yellowish, waxy, firm papules and plaques were observed on the right thumb and wrist [Figure 1]. Histopathological examination showed a thin epidermis, hyperkeratosis, subepidermal blisters, arranged dense collagen bundles [Figure 2]. This was consistent with LS-morphoea overlap. She did not respond to 6 weeks of topical clobetasol propionate 0.05% ointment. Janus kinase (JAK) inhibitors are known to inhibit the mechanism of cellular activation, proliferation, and collagen overproduction. Therefore a trial of upadacitinib (15 mg/d) was given. Within three weeks, the lesions softened and pain improved. At three months, there was significant improvement, and at six months, near resolution of lesions [Figure 3]. No adverse effects were observed during treatment.

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Figure 1:

Clinical photographs before and after treatment with upadacitinib. Multiple pale and yellowish waxy firm papules and plaques on the right thumb before upadacitinib treatment.

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Figure 2:

Thinned epidermis, hyperkeratosis, subepidermal blisters, and oedematous homogenisation of the collagen (Haematoxylin-eosin, 200×).

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Figure 3:

Clinical photographs before and after treatment with upadacitinib. After six months of upadacitinib treatment, the papules and plaques have almost disappeared.

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LS is a chronic inflammatory sclerosing disease, and its coexistence with morphoea, although reported in a study of 472 histopathologically confirmed cases, remains controversial.¹ Traditionally viewed as two distinct entities, cases with overlapping clinical and histopathologic features have sparked debate about a possible common underlying pathology. Treating such cases is particularly challenging.

The aetiology of LS with morphoea is unknown, with proposed factors including genetic factors, autoimmune factors, infection, drugs, trauma, and hormonal.¹ Histopathologically, the condition is characterised by hyperkeratosis, involvement of reticular dermis, swollen collagen fibres, perivascular infiltrate, and papillary dermal homogenisation. Extra-genital involvement is uncommon, with most cases occurring on the proximal extremities, and involvement of palms and soles being uncommon.^1,2 Although LS exhibits a low malignant potential, the literature has recorded two cases.³

Treatment remains challenging with potent topical corticosteroids often used as first line treatment. Other options include antimalarial agents, colchicine, methotrexate and phototherapy, each exhibiting differential levels of efficacy.³ JAK inhibitors, like tofacitinib and baricitinib, have shown promise in treating morphoea.^4,5 Previous studies showed that interleukin (IL)-4 and transforming growth factor (TGF)-β drive morphoea by stimulating collagen overproduction.⁶ JAK inhibition, which blocks IL-4 signalling and is crucial in TGF-β-induced fibrosis in animal models, has also shown to improve the symptoms of sclerodermatous cutaneous graft-versus-host disease.⁷ These observations prompted us to successfully try a JAK inhibitor, upadacitinib for our patient. Although upadacitinib carries risks of infections, gastrointestinal effects, and increased cardiovascular risks, our patient experienced no such effects, although long-term monitoring remains essential. To our knowledge, there is no report in the literature on the use of the JAK inhibitor upadacitinib to treat LS -morphea overlap on the palms.

In summary, our case suggests that upadacitinib could be a viable therapeutic alternative for LS and morphea patients who are resistant to conventional treatments.