An Unusual Presentation of Lichen Planus Pigmentosus Inversus Responsive to Topical Tacrolimus: A Case Report

Abstract

Background

Lichen planus pigmentosus inversus (LPPI) is a rare variant of lichen planus pigmentosus (LPP), characterized by sharply defined violaceous-brown to gray macules, papules, patches, or plaques primarily affecting the intertriginous and flexural areas. Unlike LPP, which predominantly affects Fitzpatrick skin types III to IV in sun-exposed areas, LPPI spares these regions and has been predominantly reported in White and Asian patients.

Case Presentation

We discuss a 66-year-old man with Fitzpatrick skin type III who presented with a year-long history of mildly itchy, hyperpigmented plaques on the inframammary folds. These plaques developed after being hospitalized for a chronic urinary tract infection that was treated with antibiotics. He felt self-conscious and anxious due to the changes in skin, which affected his quality of life. His medical history included controlled diabetes and dyslipidemia, and he reported no systemic symptoms or prior topical medication use. A physical examination revealed well-demarcated, violaceous-brown plaques without scaling. Tests for fungal organisms, antinuclear antibodies, thyroid function, and hepatitis C were negative, and routine blood work was normal. A biopsy confirmed LPPI. Initial treatments with triamcinolone were ineffective, and hydroquinone was discontinued after 2 weeks due to irritation. The patient improved with tacrolimus 0.1% ointment twice daily, showing significant reduction in hyperpigmentation and improvement in skin texture at 4 and 8 weeks, with no side effects noted.

Conclusion

This case report highlights the diagnostic and therapeutic challenges associated with LPPI and discusses its potential response to topical tacrolimus. Our findings indicate that tacrolimus 0.1% ointment provides a safe and effective nonsteroidal treatment alternative for LPPI. Given the possible impact of LPPI on quality of life, timely diagnosis and appropriate management are crucial. Due to the absence of established treatment protocols for LPPI, further studies are necessary to better understand treatment responses and guide therapeutic strategies, particularly for individuals with darker skin tones.

Introduction

Lichen planus pigmentosus inversus (LPPI) is a rare variant of lichen planus pigmentosus (LPP), characterized by asymptomatic or mildly pruritic, unilateral or bilateral hyperpigmented lesions in non-sun-exposed, intertriginous areas, such as the axillae, inguinal creases, gluteal cleft, limb flexures, and inframammary regions.¹ This condition is chronic and progressive, with periods of remission and exacerbation.¹ While LPPI primarily manifests as skin pigmentation, recent reports have noted nail involvement, adding to its cosmetic impact.² Lichen planus pigmentosus inversus affects individuals across all age groups and ethnicities but is more commonly reported in middle-aged White and Asian women.^3–5

The etiology of LPPI is unclear, though it may be linked to lichen planus and involve an autoimmune response in which the immune system attacks epidermal keratinocytes.¹ External triggers, such as friction, tight clothing, over-the-counter creams or oils, nickel exposure, and associated conditions, like hepatitis C, hypothyroidism, diabetes mellitus, dyslipidemia, and hormonal factors are implicated.^1–20 Radiotherapy, paraneoplastic processes, and COVID-19 vaccination have been proposed as potential triggers.^2,5,6

Currently, there is limited data regarding the efficacy of treatments for LPP, with therapies including topical and oral corticosteroids, tacrolimus, keratolytic agents, lightening agents, hydroxychloroquine, dapsone, and oral retinoids, yielding limited success.⁷ Spontaneous resolution has been reported in some cases.^3,5 Treatment for LPPI often proves more challenging due to its location. To date, 62 cases of LPPI have been documented, most with poor outcomes.^2–20 This report highlights an unusual presentation of LPPI, demonstrating significant improvement in hyperpigmentation and texture after just 4 weeks of treatment with tacrolimus 0.1% ointment twice daily.

Case Presentation

A 66-year-old man with Fitzpatrick skin type III presented with a 1-year history of mildly pruritic, hyperpigmented plaques on the inframammary folds bilaterally. These plaques appeared 1 week after hospitalization for a chronic urinary tract infection, which was treated with broad-spectrum antibiotics. The appearance of the plaques caused the patient significant distress, as he became increasingly concerned about their darkening over time. This change led to feelings of self-consciousness and anxiety, greatly impacting his quality of life. He denied systemic symptoms, a history of malignancy, and prior use of topical over-the-counter medications. His medical history included well-controlled diabetes mellitus and dyslipidemia.

Physical examination revealed well-demarcated, symmetrical, reticular violaceous-brown plaques localized on the inframammary folds with no associated erythema, scaling, mucosal, hair, or nail involvement (Figures 1A and 1B). Skin scrapings for fungal organisms and blood work (including complete blood count, liver function tests, and electrolytes) were normal. Tests for antinuclear antibodies, thyroid function, and hepatitis C were negative. Bilateral skin biopsies showed a dense, band-like interface lymphocytic infiltrate, vacuolar degeneration of the basal cell layer, scattered apoptotic keratinocytes, and pigmentary incontinence in the superficial dermis, confirming a diagnosis of LPPI (Figure 2). No eosinophils, plasma cells, or deep perivascular or perifollicular infiltrates were observed. Periodic acid–Schiff and Alcian blue stains were negative for fungal elements and increased dermal mucin.

Figure 1.

Well-demarcated reticular violaceous-brown plaque on the right inframammary fold (A) and on the left inframammary fold are seen (B).

Figure 2.

Histopathological findings showed orthohyperkeratosis, hypergranulosis, saw-tooth rete ridges, interface dermatitis with vacuolar changes, and a lichenoid infiltrate of lymphocytes in the upper dermis, moderately pigmentary incontinence and scattered Civatte bodies on the papillary dermis (Hematoxylin and eosin, 40× magnification).

Initial treatment, with triamcinolone 0.1% ointment twice daily for 4 weeks, failed to produce improvement in symptoms or clinical appearance. The patient was then given 4% hydroquinone to apply daily but discontinued it after 2 weeks due to irritation and burning. Following this, tacrolimus was introduced. After just 4 weeks of using tacrolimus 0.1% ointment twice daily, the patient noticed a lighter and more even skin tone. By week 8, there was a significant smoothing of the texture and a further reduction in hyperpigmentation (Figures 3A and 3B). No side effects were reported, and the patient was instructed to continue treatment until skin pigmentation was significantly reduced, alleviating the patient’s distress.

Figure 3.

By week 8, significant smoothing of the texture and a further reduction in hyperpigmentation were observed after using tacrolimus 0.1% ointment twice daily on the right inframammary fold (A) and on the left inframammary fold (B).

Discussion

Lichen planus pigmentosus inversus is an unusual variant of LPP first described by Pock et al in Caucasians from Central Europe.³ It has been described mainly in Asian and White patients, with a predominance in women and a predilection for axillae and groin.^3,5,8,9 Our case adds to the limited number of LPPI cases reported in individuals with darker skin tones.^3,6,9,11,12 To our knowledge, it is the only case involving the inframammary region that improved clinically with tacrolimus ointment. Benassar et al described a case with a similar presentation involving the inframammary region.¹³ In that case, however, tacrolimus treatment was discontinued after 3 weeks due to a lack of clinical response.¹³ Ghorbel et al reported a case limited to the submammary folds, treated with betamethasone for 8 weeks with no improvement.⁹ External mechanical stimuli, such as friction and tight clothing, have been proposed as the most common triggers,¹ with spontaneous resolution after discontinuation of the trigger.³ However, our patient denied wearing any tight clothing.

Lichen planus pigmentosus inversus is generally resistant to treatment, including topical and oral steroids.⁷ However, Dizen et al and Oshima et al reported moderate improvement using mometasone furoate in intertriginous areas, including the submammary region, for 12 to 36 weeks.⁷ Also, within 6 months, Nakazato et al reported marked improvement using betamethasone lactate propionate.¹⁴ In addition, common side effects from long-term use of steroids in intertriginous areas were not reported in these cases.^7,14

Guertler et al describe a case of bilateral pigmented axillary and inguinal lesions treated with tacrolimus 0.1% cream daily, showing improvement over 8 to 16 weeks.¹⁵ Patel et al documented a reduction in lesion size by week 3 in a case of unilateral exclusive axillae involvement treated initially with clobetasol for 2 weeks, followed by daily tacrolimus 0.1%.¹⁶ This response may be due to the smaller area of involvement and use of a class I topical steroid.

Our case demonstrates that topical tacrolimus effectively reduced hyperpigmentation in the inframammary folds by week 4, with no observed side effects. In contrast, treatment with triamcinolone acetonide and hydroquinone showed no clinical response in our patient. Tacrolimus ointment, used for at least 4 weeks, appears beneficial for managing LPPI limited to the inframammary region due to its minimal side-effect profile and good therapeutic response applied in small areas. In contrast to our case, Kim et al reported an insignificant response to a regimen of topical tacrolimus for 4 weeks and clobetasol propionate for 2 weeks, applied to newly developing lesions in the right groin.¹⁰ The lack of clinical response in this case may have been due to an ongoing trigger during the time of treatment.

Although spontaneous resolution has been documented,^3,13 our findings suggest that tacrolimus may be a potential treatment option to this challenging condition. Given the chronic nature of LPPI and its impact on quality of life, our case highlights tacrolimus as a treatment worth further exploration, particularly in intertriginous areas, such as the inframammary folds.

Conclusion

This case report highlights the diagnostic and therapeutic challenges associated with LPPI and discusses its potential response to topical tacrolimus. Our findings indicate that tacrolimus 0.1% ointment is a safe and effective nonsteroidal alternative for managing LPPI. Given the significant impact of LPPI on quality of life, timely diagnosis and management are crucial. Given the rarity of LPPI, collaborative case series and retrospective studies may help elucidate treatment responses and guide therapeutic strategies, particularly in individuals with darker skin tones.

Funding Statement

This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare-affiliated entity.