Успешное лечение трифаротена типичной болезни Кирла с обзором тематической терапии.

Case Description

Kyrle's disease (KD), also referred to as hyperkeratosis follicularis et parafollicularis in cutem penetrans, is a rare perforating dermatosis marked by transepidermal elimination of keratotic material. Clinically, it presents as pruritic, hyperkeratotic papules with central plugs, typically on the extensor surfaces of the lower limbs. KD is frequently associated with systemic conditions such as chronic renal failure, particularly in patients undergoing hemodialysis, as well as poorly controlled diabetes mellitus or hepatic dysfunction. It is classified within the spectrum of acquired perforating dermatoses (APD), alongside entities such as perforating folliculitis and elastosis perforans serpiginosa. Accurate diagnosis is essential, as KD may indicate underlying metabolic or systemic disturbances requiring multidisciplinary management. Though its exact pathogenesis remains unclear, KD is believed to result from abnormal responses to epidermal trauma and faulty keratinization, leading to impaired epithelial repair and elimination of necrotic dermal debris through the epidermis [ 1 ]. Histologically, it features epidermal invaginations filled with keratin and basophilic debris, accompanied by dermal inflammation and transepidermal elimination [ 2 ]. The condition can be exacerbated by scratching or trauma, consistent with the Koebner phenomenon.

We report a rare case of KD in a 26‐year‐old man with no systemic comorbidities—an atypical presentation diverging from the classical phenotype. The patient had a six‐month history of pruritic, violaceous macules on the right thigh and wrist. Laboratory and serological investigations were unremarkable; previous medical history was irrelevant. Treatments, including topical corticosteroids and antifungals, were ineffective. In line with the dermoscopic spectrum of acquired perforating dermatosis described by Papadopoulou et al. [ 3 ], lesions showed partial expression of the characteristic concentric pattern, namely a central brown‐to‐gray structureless area with subtle whitish foci and mild peripheral pigmentation, while the white halo and peripheral vascular erythematous zone were not prominently developed. This likely reflects lesion‐stage variation rather than discordance with the diagnosis. Skin biopsy revealed keratotic plug under atrophic epidermis with an accompanying foreign body granulomatous reaction composed of dermal granulocytic, histiocytic and lymphocytic infiltrates. Conducted CD15 and CD68 immunohistochemical stainings were consistent with KD. Figure  1 illustrates the clinical presentation and high‐resolution dermoscopic features. Histopathological findings of KD, providing valuable visual support for accurate diagnosis are visible in Figures  2 , 3 , 4 .

(A–C) Dermoscopy image of Kyrle's disease lesions before treatment. (D) Pre‐treatment clinical image of Kyrle's disease affecting the right knee and thigh. (E) Clinical outcome after 8 weeks of topical trifarotene 0.005% therapy, demonstrating full lesion clearance.

Keratotic plug under atrophic epidermis with an accompanying foreign body granulomatous reaction. inset: magnification of foreign body cell (arrows), staining: hematoxylin‐eosin, Pannoramic 480 Digital Scanner (3DHistech, Hungary).

CD15 immunohistochemical staining revealing granulocyte infiltrates, anti‐CD15 Mouse Monoclonal Primary Antibody, clone MMA, BenchMark ULTRA (Roche Diagnostics International AG, Switzerland), Pannoramic 480 Digital Scanner (3DHistech, Hungary).

CD68 immunohistochemical staining showing dermal histiocytic infiltration, anti‐CD68 Mouse Primary Antibody, clone KP‐1, BenchMark ULTRA (Roche Diagnostics International AG, Switzerland), Pannoramic 480 Digital Scanner (3DHistech, Hungary).

Remarkably, complete remission without residual scarring or post‐inflammatory hyperpigmentation was achieved using topical trifarotene 0.005%, applied once daily for eight weeks. To our knowledge, this is the first reported case of KD successfully treated with trifarotene, a fourth‐generation RAR‐γ‐selective topical retinoid.

Trifarotene offers a targeted mechanism of action aligned with KD pathophysiology. It modulates keratinocyte differentiation through selective RAR‐γ activation, reducing hyperkeratosis and inflammation while restoring epidermal homeostasis. Retinoids regulate gene expression involved in keratinocyte proliferation and differentiation, normalize keratinization, reduce inflammatory mediators such as IL‐31—key contributors to KD pathogenesis [ 4 ]. Trifarotene's high selectivity for RAR‐γ, the dominant isoform in the epidermis, enhances local efficacy while minimizing systemic absorption and irritation seen with broader‐acting retinoids, particularly those targeting RAR‐β [ 4 ]. Moreover, limited RAR‐γ expression in placental tissue suggests lower teratogenic risk compared to older retinoids [ 5 ]. Trifarotene also affects newer therapeutic pathways, such as proteolysis, skin hydration, and cellular adhesion. Its combined antiproliferative and anti‐inflammatory properties render it especially suitable for follicular‐based perforating dermatoses like KD. Unlike tretinoin, which in Poland is only available in fixed‐dose antibiotic combinations, trifarotene is accessible as a monotherapy, increasing its clinical utility. Importantly, for patients with renal or metabolic comorbidities who may not tolerate systemic agents, topical trifarotene provides a safer, localized alternative. Its follicular penetration may further enhance efficacy in disorders involving follicular keratin extrusion. Although our patient had no systemic comorbidities, this does not preclude a potential role for trifarotene in patients with systemic disease‐associated KD. In APD, especially in cases linked to diabetes mellitus or chronic kidney disease, optimization of the underlying systemic condition and control of pruritus remain central therapeutic principles. However, because trifarotene acts locally by normalizing keratinocyte differentiation and reducing cutaneous inflammation, its clinical benefit would be expected to target the epidermal hyperkeratotic/perforating component regardless of whether a systemic trigger is present. Therefore, in patients with diabetes, renal failure, or other comorbidities, topical trifarotene should be regarded not as a substitute for systemic disease control, but as a potentially useful adjunctive topical option, particularly when systemic retinoids or other systemic therapies are contraindicated or poorly tolerated. Further reports are needed to determine whether response rates in comorbid patients are comparable to those observed in isolated cases such as ours.

Table  1 provides a comprehensive overview of all topical treatment modalities for KD described in the literature, accompanied by key clinical and histopathological features. This compilation serves as a valuable reference, particularly in patients with significant comorbidities where systemic therapy may be contraindicated or challenging to implement.

TABLE 1 Overview of topical treatment options for Kyrle's disease with corresponding clinical and histopathological features reported in the literature. Author and year Sex and age Localization of Kyrle disease Description Dermatoscopy Hist‐pat Underlying systemic association Topical treatment Outcome
Retinoids
Present study 26‐year‐old man Only right thigh and skin on the right wrist Macular lesions with a brown to violaceous discoloration
Brown macular lesions with a central keratin plug within a crateriform depression, peripheral erythema, and surrounding pigmentation
Keratotic plug under atrophic epidermis with an accompanying foreign body granulomatous reaction composed of dermal granulocytic, histiocytic and lymphocytic infiltrates None

Trifaroten

once daily
Complete remission after 8 weeks of treatment Lokesh V. et al. (2017) [ 6 ] 52‐year‐old woman Neck, trunk, abdomen, lower limbs and gluteal region Hyperpigmented hyperkeratotic papules with central keratotic plugs N/A Basophilic epidermis material with neutrophils and refractile eosinophilic, superficial dermis with perivascular lymphocyte infiltrate Diabetes mellitus type 2, Tretinoin 0.1% gel, urea and propylene glycol After 2 months—moderate flattening of the lesions, no signs of new lesions Nair P. et al. (2015) [ 7 ] 64‐year‐old man Limbs, back, hands, face and scalp Hyperpigmented hyperkeratotic papules with central crusted keratotic plugs N/A  Irregular epithelial hyperplasia with follicular cornified plug and focal parakeratosis Diabetes and hypertension, chronic renal failure Topical retinoids and emollients Regression after 1 month
Ataseven A. et al. (2014) [ 8 ]
Case
number 1
38‐year‐old woman Extensor surfaces of knees and shins Multiple, keratotic papules Erythematous papules exhibiting a central depression with keratotic plugging Epidermal invagination into the dermis, epidermal hyperplasia, compact hyperkeratosis, basal vacuolization, degenerative basophilic material and plug formation Chronic renal failure, total blindness of the left eye Retinoic acid 0.1% for 6 weeks Unspecified but described treatment is recommended
Ataseven A. et al. (2014) [ 8 ]
Case
number 2
62‐year‐old woman Extensor surfaces of shins Keratotic papules Erythematous papules with central depression and keratotic plug Epidermal invagination into the dermis, compact hyperkeratosis parakeratosis and plug formation, vacuolar degeneration in the basal layer, dermal vascular proliferation and chronic inflammatory cell infiltration Diabetes mellitus, hypertension, asthma, hypertri‐glyceridemia Retinoic acid 0.1% for 6 weeks Unspecified but described treatment is recommended Morton CA et al. (1996) [ 9 ] 34‐year‐old man Scalp, extensor limb surfaces Dome‐shaped papules/nodules with central crust‐filled craters N/A Epidermal ulceration with inflammatory debris/ narrower ulcer crater containing hair shafts within the inflammatory debris Insulin‐dependent diabetes, chronic renal failure, peritoneal dialysis Tretinoin 0,01% gel, capsaicin cream 0,075% Improved on tretinoin, but new lesions still appear
Immunosuppressants
Kinoshita M. et al. (2017) [ 10 ] 49‐year‐old man Trunk and limbs Persistent keratotic papules N/A  Epidermal invagination into the dermis and thickened parakeratotic plugs Diabetes‐induced chronic renal failure, dialysis for 6 years Tacrolimus 0,1% Rash resolved with pigmentation
Bodman M. et al. (2015) [ 11 ]
Case number 1
57‐year‐old man Left ankle, both elbows hyperkeratotic, well‐circumscribed nodule and hyperpigmented papules Brown and deeper gray amorphous hyper‐pigmentation surrounding multiple horny plugs Hyperkeratotic plug embedded in an epidermal invagination associated with adjacent epidermal hyperplasia Diabetes mellitus, chronic renal failure, peritoneal dialysis for 10 years, peripheral arterial disease, obesity and gout Triamcinolone, 0.5% ointment Complete clearance after 1‐month treatment
Bodman M. et al. (2015) [ 11 ]
Case number 2
44‐year‐old woman Both lower extremities Multiple hyperpigmented, hyperkeratotic plaques without erythema or blanching N/A Acanthotic epidermis with thinned rete ridge pattern, a broad zone of superficial dermal fibrosis with interstitial lymphocytic inflammatory infiltrates. Endophytic epithelial invaginations and focal epithelial necrosis Insulin dependent diabetes mellitus, multiple sclerosis, depression, hypertension and asthma Triamcinolone, 0.5% ointment, 40% urea cream under occlusion Improvement Kumar H. et al. (2010) [ 12 ] 52‐year‐old man Extensor surfaces of the legs and both arms Hyperkeratotic papules N/A Transepithelial elimination of subepithelial material with epidermal invagination, Van Gieson staining—negative Type 2 diabetes, chronic kidney disease, dialysis Clobetasol propionate 0.05%, salicylic acid 12.5%  Complete remission with local hypo‐pigmentation and scar formation
Others
Nogueira F. et al. (2018) [ 13 ] 51‐year‐old man Trunk, back and upper limbs hyperchromic, pruritic macules, and papules N/A follicle with parakeratosis, vascular and conjunctive neoformation, multinucleated foreign‐body giant cells around the follicle Hypertension, diabetes mellitus, chronic kidney disease stage G4 and HIV Keratolytic soap Skin lesion improvement

Overview of topical treatment options for Kyrle's disease with corresponding clinical and histopathological features reported in the literature.

Brown macular lesions with a central keratin plug within a crateriform depression, peripheral erythema, and surrounding pigmentation

Trifaroten

once daily

Ataseven A. et al. (2014) [ 8 ]

Case

number 1

Ataseven A. et al. (2014) [ 8 ]

Case

number 2

Bodman M. et al. (2015) [ 11 ]

Case number 1

Bodman M. et al. (2015) [ 11 ]

Case number 2

This case, involving both an uncommon host profile and a novel treatment modality, underscores the potential for trifarotene as an effective therapeutic option. Further controlled studies are warranted to validate these findings and explore the broader applicability of this approach.

Funding

The authors have nothing to report.

Consent

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

Conflicts of Interest

The authors declare no conflicts of interest.

Acknowledgments

Open Access funding enabled and organized by $BLENDED_DEAL.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

Associated Data

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.