The treatment for acquired reactive perforating collagenosis with abrocitinib: A case report

Introduction

Reactive perforating collagenosis is a dermatological condition characterized by the transepidermal elimination of collagen. Clinically, it presents as papules with umbilicated hyperkeratosis or dome-shaped lesions featuring a central crater.¹ Etiologically, reactive perforating collagenosis can be classified into hereditary and acquired forms. The acquired form, known as acquired reactive perforating collagenosis (ARPC), predominantly affects adults and is frequently associated with intense pruritus and various systemic diseases. Currently, there is no established treatment for ARPC. Abrocitinib, a highly selective Janus kinase 1 inhibitor, received approval for the treatment of atopic dermatitis (AD) in China in April 2022. This article presents a case of ARPC successfully managed with abrocitinib, suggesting a novel therapeutic option for this condition.

Case report

A 54-year-old male patient presented with a 5-year history of recurrent erythema, papules, and nodules accompanied by pruritus on the trunk and extremities. Initially, 5 years prior, the patient developed scattered erythematous patches and umbilicated papules of varying sizes, some of which progressed to nodules or ulcers, accompanied by severe pruritus (Fig 1).

Fig 1.

In July 2023, clinical examination revealed erythema, papules, nodules, and ulcers on both lower limbs. A-C, The skin rashes and localized magnifications on the anterior and lateral aspects of the lower limbs prior to treatment; (D and E) cup-shaped depressions of the epidermis containing keratotic plugs, parakeratotic cells, and basophilic collagen fibers, observed under low and medium magnification; (F) denatured collagen fibers at the base of the keratotic plugs, penetrating the epidermis in a vertical orientation.

The patient had sought medical attention at multiple hospitals. There was no personal or familial history of atopic diseases. Comprehensive diagnostic evaluations, including blood routine, liver and kidney function tests, coagulation function assessment, a complete set of immune tests, tumor markers, purified protein derivative, hepatitis screening, antinuclear antibody test, HIV screening, and chest computed tomography, revealed no abnormalities. However, the total IgE level was elevated at 706.1 IU/ml. The patient was diagnosed with “pruritus nodosum” or “atopic dermatitis.” Despite treatment with antihistamines, immunosuppressants, and topical glucocorticoid ointment, the disease was poorly controlled and recurred. The patient was admitted to our department in July 2023. Pathological examination revealed a cup-shaped depression of the epidermis, containing keratotic plugs, parakeratotic cells, and basophilic collagen fibers. Masson trichrome staining demonstrated that degenerated collagen fibers at the base of the keratotic plugs extended vertically through the epidermis (Fig 1). Based on the clinical manifestations, a diagnosis of ARPC was established. Following the exclusion of contraindications, the patient was administered abrocitinib at a dosage of 100 mg daily, which resulted in a significant improvement in pruritus. At the 3-month follow-up, the patient continued to administer abrocitinib, demonstrating significant control over rash and pruritus (Fig 2).

Fig 2.

In October 2023, there was a marked reduction in the primary erythema, papules, and nodules on both lower limbs, and the ulcerated surface exhibited complete healing. A, The frontal view of the lower limb rash post-treatment; (B) the lateral view of the rash post-treatment; (C) a localized magnified image post-treatment.

Discussion

The patient's medical history spanned 5 years, with no documented history of atopic diseases or relevant familial predispositions. Multiple examinations revealed normal peripheral blood eosinophil levels, although the total IgE levels were elevated. Consequently, the patient had previously been diagnosed with AD or prurigo nodosum at other medical facilities. Upon admission to our hospital, following comprehensive pathological evaluation and Masson staining, the patient was diagnosed with ARPC.

ARPC, along with Kyrle's disease, perforating folliculitis, and elastosis perforans serpiginosa, is regarded as 1 of the 4 canonical forms of primary perforating dermatoses. In 1994, Faver et al proposed the diagnostic criteria for this condition: (1) Histopathological findings demonstrate the disappearance of necrotic basophilic collagen tissue and the formation of cup-shaped epidermal depressions; (2) Clinical manifestations include umbilicated papules or nodules with adherent keratinized plugs at the center; (3) Skin lesions typically appear after the age of 18.² There are limited reports on the prevalence and incidence of this disease.

ARPC presents significant treatment challenges due to the absence of a standardized therapeutic approach. The majority of documented treatments are based on case reports, which include the use of allopurinol, itraconazole, retinoic acid, doxycycline, topical glucocorticoids, phototherapy, and traditional Chinese medicine.^1,3,4 Recently, dupilumab has emerged in the literature as a potential treatment option aimed at alleviating pruritus and managing inflammation.⁵

The pathogenesis of ARPC remains incompletely understood, involving complex interactions among abnormal collagen metabolism, immune dysfunction, genetic predisposition, and environmental factors.⁴ Kawakami et al reported an association between the over-expression of the μ-receptor and interleukin (IL)-31 in the pathogenesis of ARPC.⁶ In a related study, Liu et al conducted an immunological analysis of skin lesions from patients with AD and ARPC. Their findings indicated that the density of dermal T cells in ARPC was comparable to that observed in AD. Furthermore, Th2 cells were more prevalent than Th1 cells, and the expression levels of IL-4 and IL-13 were significantly elevated compared to healthy controls.⁷

Abrocitinib is a highly selective inhibitor of Janus kinase 1, an intracellular enzyme that facilitates signal transduction initiated by the interaction of cytokines or growth factor receptors with the cell membrane. This process subsequently influences hematopoietic and immune cell functions.⁸ Abrocitinib is instrumental in the signal transduction of interferon-γ, IL-4, IL-13, IL-9, IL-22, IL-31, and thymic stromal lymphopoietin, thereby exerting multitarget inhibition on molecular signaling pathways associated with type 2 inflammation and pruritus. Abrocitinib may mitigate rash and pruritus in ARPC by modulating the transmission of inflammatory cytokines such as IL-4, IL-13, and IL-31. With the patient's informed consent and after ruling out contraindications, abrocitinib was administered, resulting in significant therapeutic efficacy.

ARPC is frequently associated with systemic conditions, with diabetes, chronic kidney failure, and hypertension being the most prevalent.² Additionally, several researchers have identified associations with various systemic diseases, including renal, cardiovascular, respiratory, gastrointestinal, and hematological disorders; autoimmune diseases; vascular diseases; dermatological conditions; and malignancies.^2,9 In this particular case, the patient underwent comprehensive screening for diabetes, chronic renal failure, active infections, thromboembolism, adverse cardiovascular events, malignancies, and other potential conditions prior to the administration of abrocitinib. No adverse events or systemic diseases were observed during the follow-up period.

Currently, there are no documented studies on the application of abrocitinib in the treatment of ARPC or its underlying mechanism of action. This article presents a case of ARPC demonstrating significant efficacy with abrocitinib, thereby suggesting a novel therapeutic option for this condition.

Conflicts of interest

None disclosed.