Tofacitinib in Overlapping Autoimmune and Autoinflammatory Disorders: A Case Report of a Dual Graham-Little-Piccardi-Lasseur Syndrome and Hidradenitis Suppurativa

Abstract

Introduction

Graham-Little-Piccardi-Lassueur Syndrome (GLPLS) is an autoimmune disorder characterized by a triad of cicatricial alopecia of the scalp, non-cicatricial alopecia, and follicular eruptions in the axillae and groin. Immune system dysregulation can contribute to associations with other inflammatory diseases.

Case Presentation

Here, we present a female patient with a history of scalp hair loss and follicular purulent lesions on the trunk. Biopsies from three sample sites on the scalp and trunk confirmed the diagnosis of both GLPLS and hidradenitis suppurativa (HS). Due to a limited response to previous treatments, including immunosuppressants and antibiotics, the patient was considered for tofacitinib 5 mg twice daily. After 6 months of treatment, improvement in hair loss and resolution of trunk lesions were observed. Additionally, no recurrence or adverse events were noted during a 2-year follow-up.

Conclusion

This case report underscores the likelihood of co-occurrence of two hard-to-treat disorders, both with autoimmune and autoinflammatory basis, and significant improvement of both diseases with a Janus kinase inhibitor.

Introduction

Graham-Little-Piccardi-Lassueur Syndrome (GLPLS) is a T-cell-mediated autoimmune disorder characterized by a triad of clinical signs: cicatricial alopecia of the scalp, non-scarring alopecia affecting the axillae and/or groin, and follicular eruptions on the body or scalp [1]. The follicular inflammation of the hair follicles leads to permanent destruction and a reduced likelihood of hair regrowth, resulting in significant cosmetic concerns, anxiety, and psychological distress [2]. Hidradenitis suppurativa (HS) is an inflammatory dermatosis characterized by recurrent, painful lesions filled with pus in areas rich in apocrine glands. The dysregulation of the immune system in this condition leads to perifollicular lymphocytic infiltration and the destruction of sebaceous glands [3].

Current treatment options for GLPLS are limited and often associated with adverse effects. This case report presents a patient diagnosed with both GLPLS and HS, both of which exhibited a remarkable response to tofacitinib, a Janus kinase (JAK) inhibitor primarily used for rheumatoid arthritis. The successful treatment with tofacitinib in this case highlights its potential as a promising therapeutic option for patients with Graham-Little syndrome, offering hope for a more effective and well-tolerated treatment approach.

Case Presentation

A 36-year-old female presented to our clinic with a 6-month history of hair loss and a 4-month history of multiple purulent nodular and follicular lesions on the trunk and in the axillary regions. She denied any additional symptoms.

Physical examination revealed cicatricial alopecia on the scalp and non-cicatricial hair loss involving the eyebrows, axillae, groin, and trunk. The trunk showed follicular keratotic papules, pustules, and lesions resembling keratosis pilaris alongside purulent nodular and follicular lesions in the trunk and axillary regions, consistent with features of follicular HS.

Three sample biopsies were obtained: one from the scalp and two from the trunk lesions. The scalp biopsy showed perifollicular lymphocytic inflammation targeting the hair follicles’ infundibulum and isthmus, along with interface dermatitis characterized by vacuolar degeneration of the basal layer and Civatte bodies. Additionally, perifollicular fibrosis and epidermal atrophy were observed, consistent with lichen planopilaris (LPP) (Fig. 1). The trunk biopsy, taken from keratotic lesions, exhibited acanthosis, spongiosis, and hyperkeratosis of the epidermis. There was evidence of fibrosis and infiltration of mixed inflammatory cells in the dermis. Furthermore, perifollicular lymphocytic inflammation and interface dermatitis characterized by vacuolar degeneration of the basal layer were present (Fig. 2).

Fig. 1.

Scalp biopsy. Skin tissue with low hair density with a few atrophic follicles surrounded by fibromucinous degeneration and lichenoid infiltration. The overlying epidermis shows a lichenoid pattern with no evidence of deep infiltration. ×10.

Fig. 2.

Trunk biopsy (keratotic lesions). Acanthosis, spongiosis, and hyperkeratosis of the epidermis. Perifollicular lymphocytic inflammation and interface dermatitis are characterized by vacuolar degeneration of the basal layer. ×10.

The third sample was obtained from the purulent lesions suspected of being HS. The histopathology revealed follicular hyperkeratosis and dilated follicular infundibulum with marked hyperplasia. Perifollicular inflammatory infiltration and fibrosis were also observed, with sinus tract connected to skin surface (Fig. 3). Based on these histopathological findings and the patient’s clinical presentation and history, a diagnosis of GLPLS combined with follicular HS was confirmed.

Fig. 3.

Trunk biopsy (purulent lesions). Follicular hyperkeratosis and dilated follicular infundibulum with marked hyperplasia of its epithelium is noted. Prefollicular inflammatory infiltration and fibrosis is evident. ×40 (a). Plasma cell-rich inflammatory infiltration is seen. ×100 (b).

The patient had previously tried various treatments for her scalp hair loss with the diagnosis of LPP, including intralesional and systemic corticosteroids, azathioprine, mycophenolate mofetil, hydroxychloroquine, and antibiotics (doxycycline, ciprofloxacin, azithromycin, and cephalexin) for the purulent nodular and follicular lesions of her trunk. These therapies led to some improvement in halting the activity of the scalp disease but did not significantly affect the body lesions.

Given the limited response to prior treatments, necessary workups, including complete blood count (CBC), liver function tests (LFTs), lipid profile, along with infection tests (HIV, HCV, and HBV) were conducted to ensure the patient was a suitable candidate for JAK inhibitors. Subsequently, tofacitinib 5 mg twice daily was initiated.

After 6 months of treatment, the patient experienced marked improvements: her scalp lesions became inactive, generalized hair loss improved, nodular and follicular lesions and keratotic papules resolved, and even her keratosis pilaris showed unexpected improvement (Fig. 4–6). During the 2-year follow-up period, the patient has experienced no lesion recurrence and remains free of any adverse events.

Fig. 4.

Right armpit and breast. a Before treatment. b 6 months after starting tofacitinib.

Fig. 5.

Scalp. a Before treatment. b 6 months after starting tofacitinib.

Fig. 6.

Trunk. a Before treatment. b 6 months after starting tofacitinib.

Discussion

GLPLS is a type of LPP that primarily affects adults between the ages of 30 and 70. This syndrome is reported to occur four times more frequently in females compared to males. LPP can be classified into three clinical variants: classical LPP, frontal fibrosing alopecia, and GLPLS. In GLPLS, there is scarring scalp alopecia along with some additional features, such as non-scarring alopecia of the axilla and groin, and follicular papules on the trunk [4]. HS is a chronic inflammatory disorder of the hair follicle characterized by recurrent nodules, abscesses, and pus-discharging sinus tracts in the flexural regions [5].

GLPLS and HS may share overlapping pathophysiological features, particularly in follicular occlusion and inflammatory processes. While they are distinct entities, some potential relationships can be hypothesized, like shared features of follicular occlusion and inflammatory pathways and immune dysregulation. The follicular occlusion in both diseases could suggest a shared pathway of follicular hyperkeratosis and inflammation [1, 6, 7].

Previous studies have demonstrated that both diseases respond effectively to anti-TNF treatment [8]. Additionally, Th1 and IFN-γ, which are crucially involved in the pathogenesis of GLPLs, are highly expressed in HS lesions [9, 10].

Despite the rarity of the co-occurrence of GLPLS and HS, some studies have documented this association. For instance, one study reported a man with GLPLS, HS, and HCV infection, for whom these conditions were diagnosed based on clinical, histopathological, and trichoscopy findings [11]. In another case report, a 67-year-old woman with similar characteristics was also diagnosed with concomitant GLPLS and HS. The proposed shared mechanism for both diseases was the IL-17 pathway [12].

While no established therapeutic guidelines are specific to GLPLS, LPP treatments are used for GLPLS because the classic LPP is far more prevalent than GLPLS, and there is a lack of data for GLPLS treatment. The first-line approach for LPP often includes topical or intralesional corticosteroids; various treatment options have been used for patients with LPP and GLPLS, though with limited success. These include systemic corticosteroids, retinoids, psoralen plus ultraviolet light A (PUVA) therapy, antimalarial medications, and tetracycline antibiotics. Recently, there have been some reports about the effectiveness of JAK inhibitors in LPP [13–15]. Previous studies have also documented the effectiveness of tofacitinib in HS patients. In a case report by Savage et al. [16], 2 severe HS patients with a long HS history who have used several treatments including antibiotics, biologics, and immunosuppressants, demonstrated a significant improvements after treatment with tofacitinib. No adverse events were reported in both patients. Sadeghzadeh Bazargan et al. [17] also reported on 2 cases of HS treated with tofacitinib, both showing successful results. However, disease recurrence was noted in 1 case. LFT rise was observed in another patient, which resolved after dose reduction.

Tofacitinib, a JAK inhibitor, likely exerts its therapeutic effects in GLPLS and HS by targeting shared immune-mediated pathways involved in their pathogenesis. Tofacitinib inhibits JAK1 and JAK3, thereby disrupting the signaling of multiple cytokines that rely on the JAK-STAT pathway. JAK1, JAK3, and STAT1 upregulation has been observed in both diseases. IFNγ and TNFα are key cytokines in their pathogenesis, and JAK-STAT pathway inhibition also targets the overexpression of shared pro-inflammatory cytokines, including IL-17, IL-22, and IL-23. Suppressing the intracellular cytokine pathway through JAK inhibition reduces abscess formation in HS and prevents keratinocyte apoptosis and hair follicle destruction in GLPLS [18–21].

Emerging evidence suggests a role for innate immune dysregulation in HS and autoimmunity in GLPLS, both involving the activation of the JAK-STAT pathway. Tofacitinib’s ability to suppress T-cell activation and reduce dendritic cell-mediated cytokine release may restore immune homeostasis in these overlapping conditions [19, 21, 22]. The drug’s broad immunomodulatory effects thus provide a plausible explanation for its efficacy in this patient, highlighting its potential as a targeted therapy for diseases with shared inflammatory pathophysiology.

In conclusion, we present a rare case of GLPLS that concurrently manifested with follicular HS demonstrating a remarkable response to treatment with tofacitinib. This treatment significantly improved the resolution of scalp lesions, keratotic and purulent papules, pustules, and nodules on the trunk and axillae. The patient has been monitored continuously, and no signs of new lesions or recurrence have been observed.

The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000552170).

Statement of Ethics

This study protocol was reviewed and the need for approval was waived by the Ethics Committee of Razi Hospital and Tehran University of Medical Sciences. Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study was not supported by any sponsor or funder.

Author Contributions

Supervision and conceptualization: K.B.; investigation: K.K.H. and N.N.E.; writing – original draft: S.H. and S.B.; writing – review and editing: K.B., S.H., and N.N.E.

Funding Statement

This study was not supported by any sponsor or funder.

Data Availability Statement

The data that support the findings of this study are not publicly available due to patient confidentiality but are available from the corresponding author upon reasonable request.