Persistent lichen planus pigmentosus inversus in a 45-year-old woman: a decade-long clinical journey and therapeutic challenges in an uncommon dermatological variant

Abstract

Introduction and significance:

Lichen planus pigmentosus inversus (LPPI), a rare variant primarily affecting non-sun-exposed areas in Caucasians, is resistant to standard treatments. This case highlights its clinical challenges and persistence.

Case presentation:

A 45-year-old woman with a decade-long history of light to dark brown macules and patches, initially in the axillary and inguinal regions, experienced progressive spread to her forearms, upper arms, and inframammary areas. Despite normal lab results and no significant family history or trauma, histopathology confirmed LPPI. Treatment with topical steroids, pimecrolimus, tretinoin, and oral prednisolone led to partial resolution, though irritation from pimecrolimus required reduced application.

Clinical discussion:

LPPI is a chronic inflammatory condition, first described by Pock et al. in 2001, affecting primarily intertriginous areas in lighter-skinned individuals. Characterized by hyperpigmented macules with minimal pruritus, LPPI often involves the axillae, groin, and inframammary regions. Histopathological features include atrophic epidermis, pigmentary incontinence, and a lichenoid inflammatory infiltrate. Differential diagnosis includes ashy dermatosis and post-inflammatory hyperpigmentation. LPPI’s clinical course is variable, with treatments like tacrolimus and corticosteroids yielding inconsistent results.

Conclusion:

This case report documents a rare instance of pigmented inverse lichen planus in a 45-year-old woman, highlighting its chronic nature, treatment resistance, and ongoing challenges in managing pigmentation.

Introduction

In 2001, Pock et al. were the first to identify lichen planus pigmentosus inversus (LPPI), a rare variant of lichen planus pigmentosus (LPP), with only a limited number of cases documented in the medical literature thus far^[1^]. This condition shows a higher prevalence among individuals with Fitzpatrick skin types III and IV, commonly seen in regions such as Asia, the Middle East, and South America, particularly in areas of skin exposed to sunlight, like the neck^[2^]. Unlike other forms of lichen planus, pigmented inverse lichen planus is more frequently observed in Caucasians and tends to occur in areas not exposed to the sun. While most cases exhibit bilateral lesions, there have been instances of unilateral presentations. The condition primarily affects regions like the axillae, submammary area, abdomen, groin, popliteal fossa, and lumbar spine^[2^]. Unlike traditional lichen planus, the lesions associated with this subtype usually cause minimal or no itching, and there have been no reports of involvement of hair, nails, or mucous membranes. The exact cause of pigmented inverse lichen planus remains unknown, although mechanical stress from tight clothing, possibly leading to the Koebner phenomenon, is considered a potential trigger. Spontaneous remission has been reported in some cases^[3^]. However, skin lesions associated with this condition have proven to be particularly resistant to treatment, with both potent topical steroids and oral corticosteroids showing limited effectiveness^[4^]. In our report, we present a rare case of pigmented inverse lichen planus in a 45-year-old woman.

Methods

This work has been reported in line with the SCARE criteria^[5^].

Case presentation

A 45-year-old married woman presented with a decade-long history of light to dark brown macules and patches. Initially, these lesions manifested in the axillary and inguinal regions, but over the past year, they had progressively spread to her forearms, upper arms, and inframammary areas. The macules were described as less than 1 cm in diameter, while the patches exceeded this size. Some of the macules were approximately half a centimeter, and a few patches measured up to 1 cm, with their size remaining consistent over time. The patient reported occasional mild itching associated with the lesions. On physical examination, the lesions appeared as well-defined, flat, oval dark macules (Fig. 1). There were no additional abnormalities noted in the skin, nails, scalp, or mucous membranes, and no lymphadenopathy was detected. Direct skin examinations and cultures for fungi and bacteria from the affected areas returned negative results. A KOH preparation was performed to rule out dermatophyte infections, such as tinea. A gram-stained smear was also obtained to exclude erythrasma. Blood tests, including a complete blood count and liver function tests, were normal. Axillary freckling was ruled out due to the absence of other Neurofibromatosis type 1 (NF1)-related abnormalities, such as café-au-lait spots and Lisch nodules. Post-inflammatory hyperpigmentation was ruled out due to its symmetric distribution. Histopathology determined the diagnosis of LPP. The patient had no family history of pigmentary disorders and reported no history of trauma. She had been on oral contraceptives for over 18 years and denied any significant sun exposure. A biopsy of one of the pigmented patches on her arm was performed (Fig. 2). Histopathological examination revealed a slightly thinned epidermis with hyperkeratosis, a band-like lymphohistiocytic inflammatory infiltrate at the dermoepidermal junction, vacuolar degeneration of the basal layer, and pigment incontinence with melanophages in the superficial dermis, findings consistent with LPPI (Fig. 3). Treatment involved a pimecrolimus 1% cream twice a day and tretinoin 0.025% gel once a day for 6 weeks on the lesions only, but the patient had applied large amounts of the cream to even the intact skin surrounding the lesions. The patient came to us 2 weeks later with a complaint of redness and irritation where the cream was applied (Fig. 4). Therefore, we decided to recommend applying the cream to the lesions only once a day for another 4 weeks. Follow-up was every 2 weeks. We noticed that after a month of treatment, some of the lesions paled, some disappeared completely, and no new lesions appeared in the area (Fig. 5). In addition to topical treatment, the patient was given oral prednisolone 0.5 mg/kg for 6 weeks, then it was gradually withdrawn.

Figure 1.

A view showing multiple well-defined, oval-shaped hyperchromic macules with smooth surface in the inguinal skin fold on both sides and small-brown macules in the left and right axillae.

Figure 2.

View showing the biopsy site and the lesion taken.

Figure 3.

The histological study, showing a slightly thinned epidermis with hyperkeratosis dermo-epidermal band-like lymphohistiocytic inflammatory infiltrate vacuolar degeneration of basal layer pigment incontinence with melanophages in the superficial dermis.

Figure 4.

View showing redness and irritation in the areas where the patient applied pimecrolimus cream.

Figure 5.

The following pictures are where some of the lesions have become lighter in color, and some have completely disappeared. This happened after 6 weeks of treatment.

Discussion

In 2001, Pock et al. introduced the term “lichen planus pigmentosus inversus” to describe a variant of LPP that predominantly affects intertriginous areas, based on their report of seven cases. By 2012, Gaertner and Elstein had further characterized LPPI, highlighting its unique clinical and histopathological features that set it apart from conditions like LPP and persistent dyschromic erythema, also referred to as ashy or gray dermatosis^[1,6^]. LPPI is recognized as a chronic inflammatory condition that primarily affects the skin folds, particularly in individuals with lighter skin tones. The condition is more frequently reported among Asian populations, though it has yet to appear in the indexed national medical database. A recent case series involving 18 patients revealed a slight female predominance (56%), with the average age of affected individuals being 58.8 years, ranging from 25 to 84 years. The majority of the patients (61%) were White, with the remainder being of Asian descent. The axillae, groin, and inframammary areas emerged as the most common sites of involvement. Among these cases, 39% reported mild pruritus without any other associated symptoms. Notably, no involvement of the scalp, mucous membranes, or nails was observed^[1,6,7^]. Clinically, LPPI typically presents as hyperpigmented macules, often small and lenticular, with minimal to no itching. These macules exhibit a strong preference for intertriginous regions, with the axillae being involved in 90% of reported cases, and other common sites include the neck, groin, and the area behind the knees. Larger lesions frequently display a linear or angular configuration, aligning with the skin’s natural tension lines. Wickham striae are also frequently seen^[1,6,7^]. In a minority of cases, additional lichen planus or LPP lesions may develop outside of flexural areas, though this is rare, constituting about 10% of the total affected area. The paraneoplastic features of LPP have been reported already^]8]. However, the relationship between LPPI and malignant tumors remains ambiguous^[1^]. The differential diagnosis of LPPI primarily includes persistent dyschromia with erythema, post-inflammatory hyperpigmentation, annular erythema, fixed drug eruption, and pigmented lichen planus. However, pigmented lichen planus typically arises after sun exposure and affects photo-exposed areas, unlike LPPI, which is concentrated in intertriginous zones. The most challenging differential diagnosis is ashy dermatosis, a condition that predominantly affects individuals with darker skin tones, with a preference for the trunk and limbs, sparing intertriginous areas, and is characterized by erythematous borders around active lesions^[6,7^]. Histopathological analysis of LPPI shows features consistent with regressing lichen planus. The epidermis exhibits atrophy with irregular hydropic degeneration of the basal layer, and unlike classic lichen planus, there is no epidermal hyperplasia. The superficial dermis reveals significant pigmentary incontinence, with pigment-laden macrophages and a lichenoid inflammatory infiltrate composed of lymphocytes and histiocytes, varying according to the stage of regression. Additionally, marked pigment loss and a mild lichenoid infiltrate are typically observed^[1,6,7^]. In their 2001 study, Pock and colleagues noted that the lichenoid reaction in LPPI tends to develop swiftly, accompanied by pronounced hydropic changes in the epidermal basal layer. Similar to classic lichen planus, there is compensatory keratinocyte proliferation in non-macerated areas. The clinical course of LPPI is variable; hyperpigmented macules usually appear rapidly and are more common than traditional papules. While some cases may resolve spontaneously within weeks, others can persist for years^[9-11^]. The treatment for LPP inversus is unclear. Some authors discovered that the lesions slowly disappeared without treatment throughout a few months^[10^]. Although topical and oral corticosteroids may be taken for therapy, many research studies have found them unsuccessful^[12^]. Topical tacrolimus is a preferred treatment option because of its minimal side effects and better clinical results^[12,13^]. Topical applications of tacrolimus and high-potency corticosteroids have shown inconsistent outcomes across individual cases, with some instances reporting a decrease in pigmentation^[9,11^].

LPP is identified by the gradual appearance of brown-violet-colored macules or hyperpigmented plaques. Lesions are asymptomatic or slightly irritating and have various sizes, well-defined borders, and a smooth surface^[6,14^]. LPP is a disorder defined by persistent and asymptomatic slaty-gray pigmentation, especially on the face^[15^]. Ashy dermatosis is a pigmentary disorder that causes many hyperpigmented macular lesions on the trunk and proximal extremities^[16^]. Riehl’s melanosis is defined by brown-gray reticulated-to-diffuse hyperpigmented macules or patches over the face, neck, and upper chest^[17^]. Toxic melanoderma is characterized by significant darkening of the skin and mucosa, often accompanied by anemia^[18^]. Erythema dyschromicum perstans is a pigmentation condition characterized by gray or blue-brown macules or patches in humans with Fitzpatrick skin types III–V^[19^]. Individuals with NF1 present with dermatologic features such as café-au-lait macules, skinfold freckling, neurofibromas, plexiform neurofibromas, nevus anemicus, glomus tumors, and hypopigmentation^[20^]. Tinea versicolor usually manifests as asymptomatic, hypopigmented or hyperpigmented, finely scaled, round or oval macules/patches on the trunk and upper arms^[21^]. Erythrasma is defined by asymptomatic lesions that occur in skin folds and wet places. Red or brown hyperpigmented areas of skin with scaling and vital hypopigmentation are frequent^[22^]. Post-inflammatory pigmentation is marked by frequent pruritic patches and plaques with exudation, crusting, scaling, fissures, and lichenification in the following phases^[23^].

Conclusion

This case report highlights a rare presentation of pigmented inverse lichen planus in a 45-year-old woman, contributing to the limited literature on this uncommon dermatological condition. The patient’s clinical course aligns with previously documented cases, emphasizing the chronic nature of the disease and its resistance to standard treatment modalities. Although the treatment regimen, including topical steroids and oral corticosteroids, provided some relief and halted the progression of new lesions, the persistence of pigmentation underscores the challenges in managing this condition effectively. The irritation caused by pimecrolimus, despite its benefits, further complicates the therapeutic approach. This case underscores the importance of continued research and case documentation to better understand pigmented inverse lichen planus, optimize treatment strategies, and improve patient outcomes.

Ethical approval

Not applicable.

Consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Sources of funding

No funding.

Author contributions

A.A.: resources, conceptualization, writing: original draft of manuscript, review, and editing. Z.A. and I.F.: writing: original draft of manuscript, review, and editing. M.M.A.: writing: review and editing.

Conflicts of interest disclosure

The authors declare that they have no conflict of interest.

Research registration unique identifying number (UIN)

This case report is not a first time of reporting, new device or surgical technique. So I would not need a Research Registry Unique Identifying Number (UIN).

Guarantor

Ahmad Alkheder.

Provenance and peer review

Not commissioned, externally peer reviewed.

Data availability statement

Not applicable.