Acquired Reactive Perforating Collagenosis Complicated by Diabetes Mellitus and Hypertension: A Case Report

Reactive perforating collagenosis (RPC), first described by Mehregan et al. [1] in 1967, is a rare perforating dermatosis characterized by transepidermal elimination of degenerated collagen. While hereditary RPC manifests in childhood, acquired RPC (ARPC) typically occurs in adults and is strongly linked to systemic diseases such as diabetes mellitus, chronic kidney disease, and hypertension [2, 3]. The pathogenesis remains elusive, though microvascular damage, hyperglycemia-induced collagen degeneration, and epidermal trauma from scratching are implicated [4, 5]. ARPC is frequently misdiagnosed due to its resemblance to other pruritic or perforating disorders, necessitating histopathological confirmation. Despite its rarity, ARPC’s association with prevalent metabolic conditions like diabetes and hypertension underscores its clinical significance. This case report elucidates the diagnostic pitfalls, multidisciplinary management, and therapeutic outcomes of ARPC in a patient with long-standing diabetes and hypertension, thereby enriching the literature on this underrecognized entity.

A 55-year-old male presented with a 2-month history of pruritic papules and nodules on both lower limbs, worsening over the preceding 2 weeks. Initial self-treatment with unspecified anti-inflammatory ointments and subsequent antifungal therapy at a local hospital yielded no improvement. This case report follows the CARE Guidelines for case reports. The CARE Checklist is included as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000545693).

The patient had a 15-year history of type 2 diabetes mellitus managed with oral hypoglycemics (fair glycemic control) and a 5-year history of hypertension treated with nifedipine (blood pressure well-controlled). No family history of similar dermatoses was reported.

Scattered dark-red, round papules and nodules (soybean-to-peanut-sized) were observed on the extensor surfaces of both lower legs. Lesions exhibited elevated margins, central umbilication with tan keratotic plugs, and surrounding erythema. Texture was firm, tender on palpation, and resistant to extraction. Depressed scars were noted, with greater lesion density on the right calf (Fig. 1a, b).

Lesions displayed a well-demarcated central brown structureless area with crater-like changes, encircled by a white homogeneous zone and peripheral pale-red halo. Additional features included punctate globular vessels, scaling, thin crusts, and the rose petal sign (Fig. 2a, b).

Biopsy revealed cup-shaped epidermal necrosis filled with keratin plugs, degenerated collagen fibers, and inflammatory cells. Masson staining confirmed transepidermal collagen penetration (Fig. 3, 4a, b).

A diagnosis of ARPC complicated by diabetes and hypertension was established. Topical retinoic acid cream (thrice daily) was prescribed. At 1-month follow-up, lesions regressed significantly, leaving depressed scars and shallower central pits (Fig. 1c, d).

The pathogenesis of this disease is still unclear. The possible mechanism of ARPC involves the repair process of extracellular matrix changes related to superficial trauma such as scratches and an imbalance in oxygen supply [4]. It is generally believed that concomitant systemic diseases are an important factor in its occurrence [5]. In addition, it includes epidermal defects caused by scratching trauma [6], genetic susceptibility (the disease is presumed to be autosomal dominant or recessive inheritance), and microvascular lesions caused by systemic diseases [7] (such as diabetes, chronic kidney disease, liver disease, thyroid dysfunction, AIDS, malignant tumors, etc.), which exacerbate the glycosylation of proteins and other compounds, thereby leading to collagen structural degeneration. It is also considered a paraneoplastic phenomenon [8].

ARPC typically presents clinically as lesions occurring on the limbs and trunk, often accompanied by itching; initially as one or several red papules, which gradually enlarge into firm nodules with central depression containing brownish keratin plugs, accompanied by itching, and Koebner phenomenon may be observed; some lesions may resolve spontaneously, leaving behind hyperpigmentation, hypopigmentation, and atrophic scars. Its histopathological characteristics include epidermal cup-shaped depressions filled with a large number of keratin plugs, inflammatory cells, and collagen fibers [9], with collagen fibers vertically passing through the epidermis, thickening of the surrounding epidermal spinous layer, and infiltration of lymphocytes and neutrophils around dermal blood vessels. Special staining shows red staining in Van Gieson and PAS stains, or blue-stained degenerated collagen passing through the epidermis in Masson staining. Typical dermatoscopic features include a central brownish structureless keratinous area in the lesion, surrounded by a white structure, with ring-shaped and dot-like blood vessels at the periphery [9, 10].

ARPC is relatively rare in clinical practice, and relying solely on clinical manifestations can easily lead to misdiagnosis or missed diagnosis. This patient was initially misdiagnosed at disease onset but was later confirmed through preliminary dermatoscopic screening and histopathological examination. Therefore, ARPC must be differentiated from the following conditions:

• Prurigo nodularis can involve the entire body but predominantly affects the extensor surfaces of limbs, presenting as firm pea-sized nodules with severe pruritus. Histopathology shows no degenerated collagen fibers traversing the epidermis, primarily manifesting as acanthosis of the epidermal spinous layer.

• Pyoderma gangrenosum typically presents as infiltrative masses with central necrosis and ulceration, accompanied by pain.

• Lymphomatoid papulosis: a polymorphic skin lesion more common in children and elderly patients.

• Papulonecrotic tuberculid associated with Mycobacterium tuberculosis infection, often showing strongly positive tuberculin skin tests.

• Acute pseudo-verrucous papulosis, frequently observed in adolescents, often leaving acne-like scars.

• Malignant atrophic papulosiscommonly affects the trunk and proximal limbs: histopathology reveals central progressive necrotic areas and occluded small arteries at the lesion base.

• Perforating folliculitis manifests as non-confluent follicular papules: dermatoscopy shows a central structureless gray area with bright white masses surrounded by reticular brown lines [11].

• Keratosis perforans: histopathology demonstrates transepidermal elimination of hyperkeratosis, with epidermal invaginations filled with keratin extending vertically into the dermis. Follicles or sweat gland ducts may be involved, accompanied by mild dermal inflammation.

• Creeping penetrating elastosis presents with central volcano-like depressions containing keratin plugs. Dermatoscopy reveals keratin plugs as dense white/gray-white structures surrounded by keratotic papules with irregular shapes and slightly blurred edges [12]. Histopathology shows transepidermal channels containing basophilic material and fragmented elastic fibers, alongside thickened degenerated elastic fibers in the superficial dermis and mild lymphocytic infiltration.

• Perforating granuloma annulare: histopathology displays palisaded granulomas in the superficial dermis, with central collagen degeneration and basophilic deposits surrounded by lymphocytes and histiocytes. Giemsa staining shows a positive reaction.

Currently, there is no specific treatment for ARPC, and the treatment principle is to actively control the primary disease and symptomatic treatment. Systemic steroids and retinoids, as well as UVB phototherapy, are recognized treatment options [13]. Avoiding scratching and reducing itching helps control the progression of ARPC. Treatment methods reported in domestic and foreign literature include oral corticosteroids, antihistamines, amitriptyline, immunosuppressants, methotrexate, allopurinol, etc.; topical use of keratolytic, moisturizers, retinoids, and corticosteroids; as well as cryotherapy with liquid nitrogen, photodynamic therapy, etc. [14] but the therapeutic effects vary greatly. There are also reports of successful treatment with NB-UVB [15] and 308-nm excimer laser [16]. At the same time, for cases of ARPC complicated by infection, it is necessary to promptly identify the infecting bacteria provide symptomatic anti-infective treatment, and be alert to the possibility of secondary infection [17]. The etiology and pathogenesis of ARPC still need further in-depth study.

ARPC is a recognized nosological entity that is often accompanied by several systemic diseases, including malignant conditions. Therefore, thorough paraclinical exploration is essential to uncover a possible underlying extracutaneous disease.

This study protocol was reviewed ethical approval was given by the Clinical Research Ethics Review Committee, Affiliated Hospital of Hebei University Number (HBDYFSYY-2021-305) (attached file titled patient IRB). Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images (attached file titled patient consent).

The authors have no conflicts of interest to declare.

This study was supported by Project of Baoding Science and Technology Bureau (No. 2241ZF311) and Foundation Project of the Affiliated Hospital of Hebei University (No. 2022QB29).

M.Z. and X.R. identified the patient’s case as a potential candidate for a case report; collected all relevant clinical data including patient history, contributed to physical examination findings and treatment course; drafted the initial manuscript; and incorporated revisions based on feedback from co-authors. Y.W. and R.C. performed essential diagnostic evaluations to characterize the underlying pathology, that included histological examination of the skin biopsy to assess tissue morphology and immunophenotyping studies to identify the type and activation state of infiltrating lymphocytes. J.S., C.L. and S.Z. supervised the management of the patient throughout the course of their care; provided mentorship and guidance to the first author during case identification, data collection, and manuscript writing; reviewed and critically revised all drafts of the manuscript, ensuring scientific accuracy and clarity; and provided final approval for submission of the manuscript.

The data that support the findings of this study are not publicly available due to their containing sensitive patient health information that could compromise participant privacy, but are available from the corresponding author, Xiangxiang Ren, upon reasonable request.