Lichen planopilaris induced by infliximab: A case report

Case report

A 31-year-old Caucasian female presented to the dermatology outpatient clinic for evaluation and management of a widespread itchy rash and progressive hair loss. Prior to presenting to dermatology, the patient was started on intravenous infliximab for her IBD (ulcerative colitis) in January 2018. She first became symptomatic a couple of days after her initial infliximab infusion, with the development of widespread pruritus. The patient received a second loading dose and developed severe pruritus and a rash, which was more pronounced over her abdomen. It took until September 2018 for the rash to completely clear. In January 2019, the patient had a flare of her ulcerative colitis, which prompted the re-initiation of infliximab. Two weeks after her infliximab infusion, the patient developed a pruritic rash, which involved almost all of her integument, as well as marked alopecia involving 60% of her scalp and eyebrows. Her rash and severe pruritus failed to improve with conventional therapy, including 35 mg of oral prednisone daily and topical betamethasone valerate 0.1% ointment twice daily.

Upon presentation to dermatology in March 2019, the patient had a rash of grouped and confluent, flat-topped, erythemato-violaceous papules disseminated in a symmetric fashion over her trunk and extremities. Her palms and soles showed macular erythema (Figure 1). Her oral cavity did not show signs of a lichenoid rash, but some white film suggestive of oral thrush. On the scalp, the patient had mottled alopecia with intact hair follicles and perifollicular erythema (Figure 2). Dermoscopy of the scalp showed yellow dots.

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Figure 1.

Macular erythema of the palmar aspect of the hand and flat-topped, erythemato-violaceous papules on the distal aspect of the volar forearm.

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Figure 2.

Mottled alopecia of the scalp and eyebrows.

Two skin punch biopsies were taken, one from the scalp and one from the dorsum of the right foot. The biopsy from the scalp showed mild perivascular and heavy lichenoid lymphocytic infiltrate of the hair follicles that focally obscured the junction between follicular epithelium and dermis, and extended into the basal follicular epithelium (Figure 3). Scattered eosinophils were also identified, in keeping with the drug-induced LPP. The biopsy from the right foot also displayed moderately intense lichenoid lymphocytic infiltrate at the dermoepidermal junction, with mild perivascular lymphocytic inflammation. Also apparent were patches of spongiosis associated with prominent lymphocytic exocytosis. Parakeratosis and individual apoptotic keratinocytes were identified.

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Figure 3.

(a) Lichenoid interface dermatitis involving the hair follicles with hematoxylin phloxine saffron (HPS) stain and 50× magnification; (b) lichenoid inflammatory infiltrate around the hair bulb (star) composed of predominantly lymphocytes with scattered eosinophils (arrows) with HPS stain and 100× magnification.

Although the patient’s IBD responded well to infliximab, the medication was discontinued due to poor tolerance. The patient continued with her regime of 35 mg of prednisone daily supplemented by topical betamethasone 0.1% valerate cream twice daily to cutaneous lesions, which resulted in partial improvement.

Discussion

Lichenoid drug eruptions are much less common than morbilliform drug exanthema or urticaria. They are often caused by certain drugs or drug classes, such as gold, antimalarial drugs, and beta-blockers. ⁸ Most reports of cutaneous eruptions from TNF-α inhibitors have described the paradoxical development of psoriasis and psoriasiform drug reaction; however, lichenoid reactions represent an emerging adverse effect of novel drugs such as anti-TNF-α therapy. We describe a case of patient who developed lichenoid dermatitis and LPP while on the TNF-α inhibitor, infliximab, for the treatment of her IBD.

Four patterns of lichenoid reactions have been described in the literature based on their unique clinical features and common lichenoid histology: lichen planus, maculopapular lichenoid reaction, psoriasis-like with lichen planus histology, and LPP. ⁹ A recent review of the literature revealed 21 reported cases of lichenoid reactions to various TNF-α inhibitors. ¹⁰ These cases have been reviewed and summarized elsewhere.^2,9,10

LPP is the most recent cutaneous lichenoid adverse reaction to anti-TNF-α therapy, with the first case reported by Garcovich et al. ¹¹ in 2008 from etanercept. LPP is a lymphocytic inflammatory disorder that selectively involves the hair follicles, leading to a scarring alopecia that presents with perifollicular erythema, hyperkeratosis, and patchy hair loss. To our knowledge, there are only five other reported cases of anti-TNF-α-induced LPP, with only one resulting from infliximab.^9–13

The pathophysiology of anti-TNF-α-induced lichenoid eruption is yet to be elucidated; ² however, a number of mechanisms have been proposed using models of psoriasis, lupus-like eruptions, and dermatomyositis. Some authors have suggested that the inhibition of TNF-α leads to upregulation of opposing cytokines, such as interferon-alpha (IFN-α), which may activate T cells and dendritic cells, resulting in an inflammatory reaction. ¹⁴ Similarly, it has also been proposed that in select genotypes the effect of TNF-α inhibition might disrupt the delicate immune milieu, thereby accelerating IFN-α production and triggering pathological activation of T cells and dendritic cells.^3,15 Plasmacytoid dendritic cells are the primary source of IFN-α and have been found in great abundance in cutaneous and oral lichen planus lesions.^16,17 Furthermore, there is evidence that type 1 IFNs (IFN-α and IFN-β) play an important role in the pathogenesis of lichen planus through activation of cytotoxic CD8⁺ T cells, which have the ability to autoactivate against keratinocytes. ¹⁸

Recent research on LPP has demonstrated decreased expression of peroxisome proliferator-activated receptor gamma (PPARγ), a transcription factor that regulates the expression of genes involved in inflammation and lipid homeostasis. PPARγ is important for healthy pilosebaceous units, and loss of function has been implicated in the pathogenesis of LPP. ¹⁹ INF and TNF can reduce PPARγ expression; therefore, it is thought that unopposed IFN may result in the downregulation of PPARγ, thereby leading to the development of LPP in patients on TNF-α inhibitors.^9,19

Lichenoid eruptions represent a rare adverse effect of TNF-α inhibitors. We describe a case of a patient who presented with lichenoid dermatitis and LPP from infliximab. Clinicians managing patients with immune conditions should be aware of this adverse reaction to biologics. It is uncertain whether a lichenoid eruption warrants discontinuation of TNF-α therapy; however, the decision should be made on an individual basis. ¹¹