Successful treatment of refractory primary follicular mucinosis with Tofacitinib

Dear Editor,

Follicular Mucinosis (FM), a rare cutaneous mucinosis, is characterized by erythematous infiltrated plaques with follicular prominence. There is no consensus on the treatment of FM. Current therapeutic options include mild-to-moderate potency topical corticosteroids, topical and oral antibiotics, retinoids, dapsone, sulfacetamide, imiquimod, pentoxifylline, pimecrolimus, Psoralen Plus Ultraviolet A (PUVA), and nitrogen mustard.¹ Emerging evidence suggests that tofacitinib may be effective for cuta-neous mucinoses, with reported efficacy in both pretibial myxedema and refractory papulonodular mucinosis.²,³ Here, we report a patient with refractory FM who was successfully treated with tofacitinib.

A 55-year-old female patient presented to the dermatol-ogy clinic with a 4-month history of a left facial plaque. She denied any topical application, drug intake, or photosensi-tivity. Her systemic and family history was unremarkable. Physical examination demonstrated a poorly demarcated, edematous, erythematous plaque on the left cheek. (Fig. 1A) No other cutaneous involvement was observed. According to clinical and histopathological features, the patient was diagnosed with Primary Follicular Mucinosis (PFM). Initial treatment with hydroxychloroquine (200 mg twice daily) and high-potency topical corticosteroids (clobetasol propionate 0.05% ointment) resulted in no clinical improvement after 8-weeks of therapy. Monotherapy with tofacitinib 5 mg twice daily was started. After 3-months of treatment, significant clinical improvement was observed, manifested by com-plete resolution of skin lesions (Fig. 1B). No recurrence was observed during the three-month follow-up period following treatment discontinuation. Histopathological examination revealed the accumulation of mucin in pilosebaceous fol-licles and sebaceous glands, with perifollicular infiltrates of lymphocytes and eosinophils observed (Fig. 2A). Alcian blue staining confirmed mucin deposition within the fol-licular epithelium (Fig. 2B). Immunohistochemical analysis demonstrated that lymphocytes were positive for Leuko-cyte Common Antigen (LCA), Ki-67 (20% positivity rate), CD8, CD20, CD7, CD79a, CD4, and CD3, with a balanced CD4⁺/CD8⁺ ratio. (Figs. 2C-D) The result of the T-cell Recep-tor (TCR) gene rearrangement was negative.

Figure 1
(A) A poorly demarcated edematous erythematous plaque was observed on the right cheek. (B) Complete clinical resolution was achieved after 3-months of tofacitinib monotherapy.

Figure 2
(A) Massive mucin deposition in the follicular epithelium (Hematoxylin & eosin, ×40). (B) Deposition of mucin confirmed by Alcian blue staining (×200). Immunohistochemical analysis demonstrated that lymphocytes were positive for CD4 (C) and CD8 (D) with a balanced CD4⁺/CD8⁺ ratio (×100).

Follicular mucinosis is characterized by the extensive deposition of mucin at the external root sheath and seba-ceous glands. FM can be categorized as Primary Follicular Mucinosis (PFM) and Secondary Follicular Mucinosis (SFM). The most common clinical symptom of PFM is a solitary lesion in the head or neck region in young patients. As for the histopathological findings, the presence of extensive mucin deposition in cystic spaces, minimal perivascu-lar and periadnexal polyclonal infiltration of non-atypical lymphocytes, the absence of epidermotropism, and an equivalent CD4⁺/CD8⁺ cell rate pointed towards a diag-nosis of PFM. Secondary Follicular Mucinosis (SFM) may be associated with certain medications, benign conditions, and malignancies (most commonly lymphomas). Lymphoma-associated FM typically presents with multiple extracranial lesions in elderly patients. Histopathological examination reveals a dense band-like infiltrate with atypical lympho-cytes, epidermotropism, a prominent CD4⁺ immunophe-notype, and monoclonal gene rearrangement of the infiltrate.¹

The pathogenesis of Follicular Mucinosis (FM) remains incompletely understood. Current evidence suggests that follicular keratinocytes may be the source of mucin depo-sition, a process activated by T-cell-mediated immune mechanisms and cytokines. T-lymphocytes secrete IL-4, IL-2, and IL-26, inducing phosphorylation of Signal Transducer and Activator of Transcription (STAT), thereby affecting keratinocyte function.⁴ Tofacitinib, as a pan-JAK1/JAK3 inhibitor, can interrupt pathological signaling by blocking STAT phosphorylation.⁵ Studies have also demonstrated a significant correlation between the quantity of mucin within hair follicles and the severity of perifollicular inflammatory infiltration. Mediators released by T-lymphocytes, including IFN-γ, IL-5, TGF-(3, and IL-4, trigger and amplify inflam-matory cascades.⁴ The JAK-STAT pathway plays a vital role in immune regulation, cell differentiation, apoptosis, and proliferation.⁵ By inhibiting JAK1/JAK3, tofacitinib effec-tively reduces the production of proinflammatory cytokines in T-lymphocytes. Tofacitinib, in our case, was selected pri-marily due to its comparatively lower cost relative to other highly selective JAK inhibitors. Furthermore, published literature has indicated its promising efficacy in the treatment of mucinous dermatosis.²,³

There are currently no established treatment guide-lines for follicular mucinosis, and management remains individualized. Available therapeutic options have demon-strated limited efficacy in clinical practice. This pioneering case demonstrates the first successful therapeutic appli-cation of JAK inhibitors in follicular mucinosis. While these findings are promising, the inherent limitations of this single-case study underscore the need for validation through large-scale randomized controlled trials. Addition-ally, further mechanistic investigations are essential to elucidate the precise therapeutic pathways of tofacitinib in FM.

• Financial support
  None declared.

Acknowledgment

The patient in this manuscript has given written informed consent to publication of his case details.

Research data availability

Does not apply.

References

• ¹ Khalil J, Kurban M, Abbas O. Follicular mucinosis: a review. Int J Dermatol. 2020;60:159-65.
• ² Luo SY, Fang S. Refractory papulonodular mucinosis successfully treated with tofacitinib. Clin Exp Dermatol. 2025;50:448-50.
• ³ Wang S, Chen X, Bai J, Sun Q, Fang H, Qiao J. Tofacitinib treat-ment for pretibial myxedema. JAMA Dermatol. 2024;160:578-80.
• ⁴ Akdis M, Aab A, Altunbulakli C, Azkur K, Costa RA, Crameri R, et al. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor(3, and TNF-α: receptors, functions, and roles in diseases. J Allergy Clin Immunol. 2016;138:984-1010.
• ⁵ Xue C, Yao Q, Gu X, Shi Q, Yuan X, Chu Q, et al. Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer. Signal Transduct Target Ther. 2023;8:204.

Edited by

• Editor Luciana P. Fernandes Abbade. E-mail:[e-mail] (S. Fang).

Publication Dates

• Publication in this collection
  07 Aug 2026
• Date of issue
  2026

History

• Received
  20 June 2025
• Accepted
  13 Sept 2025
• Published
  23 Apr 2026