Oral Tofacitinib for Refractory Lichen Planus Pigmentosus Coexisting with Frontal Fibrosing Alopecia

Dear Editor, Lichen Planus Pigmentosus (LPPigm) is a long-standing variant of lichen planus presenting with hyperpigmented macules distributed on the sun-exposed areas and the flexures. A low-grade type IV hypersensitivity reaction to an unknown antigen is believed to incite interface dermatitis, causing keratinocyte destruction and pigment incontinence, resulting in dermal pigmentation. This inflammation is largely driven by interferon-γ (IFN-γ) signaling, with IFN-γ-induced chemokines (CXCL9, CXCL10, CXCL11) playing a major role.[1] Frontal fibrosing alopecia (FFA) is a progressive cicatricial alopecia presenting as a band-like recession of the hairline, mostly in postmenopausal females. Strong Th1 skewing has been demonstrated in FFA with significant upregulation of IFN-γ, CXCL9, CXCL10, and signal transducer and activator of transcription-1 (STAT1). FFA has been described in patients with pre-existing LPPigm.[2,3] Since the IFN-γ/CXCL-10 axis signaling occurs through the Janus kinase – signal transducer and activator of transcription (JAK-STAT) pathway, JAK inhibitors represent promising treatment options and have been successfully tried in various lichen planus (LP) variants. We present the use of oral tofacitinib in a patient with refractory LPPigm and coexistent FFA, who exhibited near-complete resolution of the hyperpigmentation and cessation of progression of FFA. A 48-year-old homemaker presented with hyperpigmentation on the forehead for the past 2 years, which was insidious in onset and refractory to topical hydroquinone-based triple combinations, glycolic acid creams, and oral isotretinoin. One year after the onset of hyperpigmentation, the patient noticed progressive recession of her hairline [Figure 1a]. The patient was postmenopausal, and no other significant medical history was disclosed. On examination, diffuse confluent brownish hyperpigmentation was seen on the forehead extending up to the temples laterally. A frontotemporal symmetrical band of alopecia was also present, and a few isolated hair strands were visible. Eyebrows and other body hair appeared normal. Polarized dermoscopy of the forehead with the ILLUCO IDS 1100 dermatoscope showed a brownish background with linearly arranged dark-brown dots and globules, relatively sparing the skin creases, interspersed with few white dots (normal eccrine openings), suggestive of LPPigm [Figure 2]. Dermoscopy of the hairline showed absence of vellus and intermediate hairs along the receded hairline, loss of follicular ostia and single-hair follicular units, “lonely hair sign”, and the distinctive “transparent proximal hair” emergence, typical of FFA [Figure 3]. A skin biopsy from the forehead revealed interface dermatitis with pigment incontinence, while the biopsy from the hairline showed perifollicular fibrosis and lymphocytic infiltrate. Thus, the patient was diagnosed as a case of LPPigm with FFA.Figure 1: Clinical improvement of lichen planus pigmentosus and frontal fibrosing alopecia during treatment with oral tofacitinib. (a) Clinical photographs of skin lesions at initial presentation with brownish confluent hyperpigmented macules on the forehead extending till the temples and band-like hairline recession; (b) Decrease in hyperpigmentation visible at 6 months; (c) Substantial reduction in hyperpigmentation and no progression of hairline recession at 12 months; (d) Near-complete clearance of the hyperpigmentation and complete cessation of hairline recession at 18 monthsFigure 2: Polarized dermoscopy of the forehead showing a brownish background with numerous linearly arranged dark-brown dots and globules, relatively sparing the skin creases, interspersed with few white dots (normal eccrine openings), suggestive of lichen planus pigmentosus (ILLUCO IDS 1100 dermatoscope, 10×)Figure 3: Dermoscopy of the hairline showing the absence of vellus and intermediate hairs along the receded hairline, loss of follicular ostia and single-hair follicular units, subtle follicular hyperkeratosis, the “lonely hair sign” (black circle), and the distinctive “transparent proximal hair” emergence (purple circle), typical findings of frontal fibrosing alopecia (ILLUCO IDS 1100 dermatoscope, 10×)Routine laboratory investigations showed normal complete blood count, liver enzymes, and lipid profile. The patient reported no response with modified Kligman’s formulation, six sessions of chemical peeling with 35%–50% glycolic acid, and with oral hydroxychloroquine for 6 months. She was then prescribed oral tofacitinib 5 mg twice daily along with strict sun protection. Six months later, she reported that the hyperpigmentation and hairline recession were no longer progressing [Figure 1b]. Clinical follow-up and laboratory monitoring were performed at 3-monthly intervals. She demonstrated a substantial reduction in the hyperpigmentation at 12 months [Figure 1c] and near-complete clearance of the hyperpigmentation with cessation of hairline recession at 18 months [Figure 1d]. No adverse effects were reported, and the laboratory parameters remained within normal limits. Tofacitinib was stopped after 18 months, while sun protection was continued. One year after treatment cessation, the patient continues to be in remission. Both LPPigm and FFA are notoriously difficult conditions to treat and often show minimal or incomplete response.[2,3] Rao et al.[3] reported marginal improvement with modified Kligman’s formulation/kojic acid and intralesional corticosteroids, while Mulinari-Brenner et al.[2] noted minimal improvement on hydroxychloroquine 400 mg/day, oral finasteride 5 mg/day, and 5% minoxidil with 0.05% clobetasol in their respective patients of LPPigm with FFA.The ability of tofacitinib to arrest disease progression has been reported in LP variants, albeit mostly in the form of case reports. Cornman et al.[4] recently reported the successful use of topical ruxolitinib in recalcitrant LPPigm, while Dunn et al.[5] detailed the use of topical ruxolitinib along with oral baricitinib in 3 patients with FFA, one of whom had comorbid LPPigm. Although further prospective and larger studies would shed more light on the efficacy and safety of oral tofacitinib in LPPigm and FFA, it does hold promise as an effective therapy for these recalcitrant conditions. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. Use of artificial intelligence (AI) The preparation of this manuscript was carried out entirely by the authors without the use of artificial intelligence technologies.