A novel case of eruptive vellus hair cysts arising during radiation therapy and a brief review of the literature

Introduction

In 1977, Esterly et al. coined the term ‘eruptive vellus hair cysts’ (EVHC) to describe an idiopathic, persistent, hyperpigmented, monomorphous, papular eruption observed in two children. On pathology, cysts in the mid-dermis were noted to contain multiple fragmented vellus hair shafts. There have since been nearly 130 cases of EVHC reported in the literature [1].

EVHC typically presents as a 1–7 mm symmetrical, monomorphous, skin-colored, and dome-shaped eruption of papules that can be grouped or diffuse. The eruption can present anywhere on the body but has a predilection for the anterior chest, abdomen, upper limbs, and face and may be congenital or acquired [2–4]. Most cases are idiopathic, persistent, and asymptomatic [4]. While the exact mechanism underlying EVHC pathogenesis is unknown, it is thought that a developmental issue in vellus hair follicles causes infundibular occlusion, leading to cystic dilation, hair retention, and hair bulb atrophy [1]. Histologically, the cysts are lined by a stratified squamous epithelium in the top or middle dermis, may contain keratin, and are characterized by the presence of obliquely cut vellus hair shafts. Patients with EVHC tend to seek treatment for cosmetic concerns, and most therapies rely on trials of retinoic acid, surgical removal, or laser with varying results [4]. Here, with consent obtained from the patient, we report a case of a patient who developed EVHC during radiation therapy (RT) for breast cancer. Based on a comprehensive literature review, only eight cases of EVHC have presented after a potential trigger, with the rest considered idiopathic or familial. To our knowledge, this is the first case of EVHC arising after any type of cancer treatment, making it an important cutaneous side effect for dermatologists and oncologists to consider when encountering a similar cutaneous eruption during RT.

Case report

A 39-year-old woman presented to the oncodermatology clinic for a pruritic, diffuse rash during RT for left breast cancer. During week four of RT (after a cumulative dose of 42 Gy), she developed a new, generalized, cutaneous eruption that appeared similar to ‘insect bites’, per her radiation oncologist. The lesions did not resolve after her RT course was completed. She presented to the oncodermatology clinic two weeks after completion of her RT course. Other than her recent diagnosis of breast cancer treated with lumpectomy, sentinel node biopsy, and RT, her medical history was notable only for Breast Cancer Gene-2 (BRCA-2) positivity. The patient denied any previous dermatologic history, use of new medications, or use of over-the-counter topicals. She did not receive chemotherapy or hormonal therapy. Physical exam at that time showed dozens of subcutaneous nodules with overlying excoriations and hyperpigmentation over the irradiated field (left breast) and extending to the trunk and thighs (Figure 1(A–B)). The differential diagnosis included eruptive lipomas, steatocystomas, vellus hair cysts, and cutaneous metastases. A punch biopsy of a lesion on the patient’s right buttock revealed a cyst lined by infundibular epithelium and filled with orthokeratotic cornified cells. Fragments of small hair shafts found within the dermis led to a conclusive diagnosis of eruptive vellus hair cysts (Figure 2). The patient considered surgical excision of lesions but did not return for follow-up. The eruption persisted for at least nine months after the initial presentation.

Figure 1. (A-B) Clinical Photographs of Eruptive Vellus Hair Cysts Subcutaneous nodules with overlying excoriations and hyperpigmentation on the trunk (A) and thighs (B).

Figure 2. Histology of Eruptive Vellus Hair Cyst Cyst within the dermis with numerous vellus hair cysts in the lumen (Hematoxylin & Eosin, 100x).

To our knowledge, this is the first case of EVHC arising in the setting of cancer therapy, and specifically as a sequela to RT. In fact, in most of the described cases published in the literature, EVHC appeared without a triggering event, and rarely were any cases described in the setting of medical treatment. While EVHC are benign, they can be symptomatic and cosmetically distressing. Due to their rarity, lack of a clear triggering event, and absence of standardized treatment, they may present a clinical challenge. Below we will review the literature describing the clinical presentations of EVHC to highlight their variability and treatment challenges in the hopes of promoting further research into their pathogenesis and management.

Discussion

We present the first case of a persistent EVHC eruption triggered by RT. This eruption was generalized, as it was not limited to the irradiated field. The phenomenon of a new skin eruption due to RT, extending beyond or not involving the irradiated field at all, has been well described in other cutaneous conditions, such as post-irradiation morphea [5,6], eosinophilic polymorphic and pruritic eruption associated with radiotherapy [7], generalized bullous pemphigoid [8], radiotherapy-induced pemphigus [9], erythema multiforme or erythema-multiforme-like rash [10], and RT-induced polymorphous light eruption [10]. No particular time frame or radiation dose has been implicated in these eruptions. Like the present case, breast cancer was the most common cancer associated with these generalized eruptions, portending a potential common hormonal pathogenic link between breast cancer and resulting radiation-induced generalized cutaneous reactions, as suggested by some authors [7]. Furthermore, some theorize that EVHC arise due to a defect in keratinization or vellus hair follicle formation, both of which can be heavily influenced by sex-hormone alterations [11–14]. Another hypothesis for radiation-induced generalized cutaneous reactions is that localized RT may induce a systemic release of autoantibodies, antigens, immune complexes, or cytokines, which could trigger widespread cutaneous reactions [5,15]. As the pathogenesis of EVHC itself is poorly understood, it is difficult to clearly explicate how RT might induce this eruption, but the current literature supports and provides significant evidence for generalized radiation-induced dermatologic conditions with varying known etiologies. Additionally, the time frame of this patient’s eruption (during RT and persisting afterward), along with a lack of comorbidities associated with EVHC (such as steatocystoma), or a contributory family history, supports our hypothesis.

As EVHC are rare, we performed a review of the literature to better clarify their typical presentation to aid in diagnosis. We reviewed all the English articles (n = 76) describing EVHC cases in the PubMed database. From the 76 reports, 121 individual cases of EVHC were described. Epidemiologically, EVHC were slightly more frequent in females than males (50.4% versus 44.6%) and most commonly appeared between the ages of 1–20 years old (54.5%) with a mean age of 18.4 years old at onset. Most of the reported cases (62.0%) did not disclose the race/ethnicity of the patients with EVHC, but of those reported, the highest frequency of cases occurred in Caucasians (13.2%) [16–24], followed by Blacks/African Americans (6.6%) [25–30] and Japanese (6.6%) [31–37]. Although EVHC is traditionally considered to occur more frequently in patients with a family history, 80.2% of cases had no known genetic predisposition or family history, while 19.8% of cases presented with a family history of EVHC [2,3,17,18,23,38–46].

Regarding the clinical course of EVHC, 86% of cases presented asymptomatically, while 14% reported associated symptoms, primarily pruritus [2,18,22,25,26,30,31,40,41,45,47–50]. Upon physical exam, EVHC most commonly appeared as multiple, discrete, dome-shaped, hyper-pigmented or flesh-colored, soft, or cystic papules. The most commonly considered differential diagnoses reported were keratosis pilaris (11.6%) [24,45,51–53], acneiform eruptions (10.7%) [45,52,53], perforating dermatoses (10.7%) [45,52,53], folliculitis (9.1%) [45], and acne vulgaris (5.0%) [2,25,34,54,55]. 6.6% of cases reported a potential trigger for EVHC. The proposed triggers included scratching/mechanical trauma (n = 4) [55–58], dialysis (n = 2) [34], molluscum contagiosum treated with imiquimod [19], and 3% minoxidil application [59]. In 15.4% of cases, other conditions were associated with the presentation of EVHC, most frequently steatocystoma (5.8%) [35,36,40,44,60–62], chronic kidney disease (1.7%) [34], ectodermal dysplasia (1.7%) [16,27], milia (1.7%) [19,44], and trichostasis spinulosa (1.7%) [11,24].

Clinicians most frequently treated EVHC with a retinol-derived topical (9.1%) [11,16,21,24–26,38,63–67], surgical excision/extraction with or without electrocauterization (5.8%) [19,38,47,59,68,69], carbon dioxide (CO2) laser (4.1%) [46,70–72], erbium-doped yttrium aluminum garnet (Er:YAG) laser (3.3%) [22,50,67,73], oral vitamin A or vitamin A derivatives (2.5%) [17,23,27], or topical lactic acid (1.7%) [23,30]. Most cases did not report subsequent treatment or spontaneous resolution (68.7%). However, some patients underwent spontaneous resolution without treatment (3.31%) [12,45,74,75]. 19 cases (15.7%) resolved upon treatment [1,11,19,21–23,30,46,50,55,59,66,68–71,76], while 9 treated cases (7.4%) resulted in no improvement [16,17,25–27,38,47,63,64]. The most effective treatments were topical lactic acid (2/2, 100%) [23,30], CO2 laser (4/5, 80%) [46,70,71], Er:YAG laser (3/4, 75%) [22,50], surgical extraction (5/7, 71.4%) [19,59,68,69,76], and retinol-derived topicals (3/11, 27.3%) [11,21,66].

A comprehensive review of the literature demonstrates that EVHC can present in an epidemiologically heterogeneous population with variable family histories, triggers, disease courses, disease associations, and responses to treatment. This non-uniform presentation can make it difficult for clinicians to recognize or consider when encountering an unknown cutaneous eruption. Our goal in presenting this case is to expose RT as a newly recognized trigger for the development of EVHC. Additionally, while EVHC may be cosmetically concerning, it is benign and therefore likely does not necessitate ceasing or reducing RT. This case is valuable as it broadens the collection of known cutaneous effects of RT, as well as widens the differential for dermatologists and oncologists encountering a similar eruption after RT.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data pertaining to the results of this report are available as part of the report and no additional sources of data are required.