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. 2025 Apr;15(4):869-887.
doi: 10.1007/s13555-025-01378-2. Epub 2025 Mar 10.

Defining Predictive Factors for Permanent Chemotherapy-Induced Alopecia: Trichoscopy, Reflectance Confocal Microscopy and Histopathology Study on 77 Patients

Michela Starace #  1   2 , Victor Desmond Mandel #  3   4 , Marco Ardigo  5 , Miriam Anna Carpanese  6 , Federico Quadrelli  1   2 , Francesca Pampaloni  7   8 , Kaleci Shaniko  3 , Aurora Alessandrini  1   2 , Francesca Bruni  1   2 , Alfredo Rossi  9 , Maria Caterina Fortuna  9 , Gemma Caro  9 , Norma Cameli  10 , Martina Silvestri  10 , Gabriella Fabbrocini  11 , Maria Carmela Annunziata  11 , Mariateresa Cantelli  11 , Maria Vastarella  11 , Daniela Rubino  12 , Claudio Zamagni  12 , Giovanni Pellacani  3   9 , Bianca Maria Piraccini  1   2
Affiliations

Defining Predictive Factors for Permanent Chemotherapy-Induced Alopecia: Trichoscopy, Reflectance Confocal Microscopy and Histopathology Study on 77 Patients

Michela Starace et al. Dermatol Ther (Heidelb). 2025 Apr.

Abstract

Introduction: Literature about trichoscopy of permanent chemotherapy-induced alopecia (pCIA) is still scarce, while no data were published regarding reflectance confocal microscopy (RCM). The aim of our study is to monitor the different phases of chemotherapy-induced alopecia development with trichoscopy and RCM, in order to identify predictor factors for permanent alopecia.

Methods: This multicentre, prospective, observational study evaluated patients with cancer who were candidates for chemotherapy with a drug implicated in pCIA development. Patients were followed for the next 2 years after recruitment.

Results: A total of 77 patients were enrolled. Six months after the discontinuation of chemotherapy in all patients with pCIA, trichoscopic examination revealed a diffuse presence of multiple yellow dots, the persistence of regrowing hairs, and an increase degree of miniaturization in comparison to baseline. RCM detected the permanence of inflammatory cells over time, especially around the adnexal structures, which led to the appearance of fibrosis and alteration of the normal rimming.

Conclusions: Trichoscopy and RCM allowed one to detect the different phases of chemotherapy-induced alopecia development. The following predictor factors for pCIA were identified: a positive history of cyclophosphamide- and taxane-based chemotherapy; a diffuse presence of multiple yellow dots at trichoscopy; onset and persistence of a diffuse inflammatory infiltrate at RCM.

Keywords: Alopecia; Chemotherapy; Confocal; Hair diseases; Microscopy; Neoplasms.

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Conflict of interest statement

Declarations. Conflict of Interest: Victor Desmond Mandel, Marco Ardigo’, Miriam Anna Carpanese, Federico Quadrelli, Francesca Pampaloni, Kaleci Shaniko, Aurora Alessandrini, Francesca Bruni, Alfredo Rossi, Maria Caterina Fortuna, Gemma Caro, Norma Cameli, Martina Silvestri, Gabriella Fabbrocini, Maria Carmela Annunziata, Mariateresa Cantelli, Maria Vastarella, Daniela Rubino, Claudio Zamagni, Giovanni Pellacani, Bianca Maria Piraccini have nothing to disclose. Honorarium, grant or other forms of payment were not given to anyone of the authors to produce the manuscript. Michela Starace is an Editorial Board member of Dermatology and Therapy. Michela Starace was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Ethical Approval: The protocol was approved by the local ethics committee and institutional review boards (366/17; protocol number 4643/C.E, Comitato Etico Provinciale, Azienda Ospedaliero Universitaria Modena). The study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments. All patients provided written informed consent for participation in the study.

Figures

Fig. 1
Fig. 1
Chemotherapy-induced alopecia (CIA) in a patient affected by breast cancer. Clinical (a and b) and trichoscopic (c and d) images of the patient before starting chemotherapy. Reflectance confocal microscopy (RCM) (e and f) allows one to observe the normal hair follicles and hair shafts without structure abnormalities. Hair shaft thickness as well as the thickness of the medulla, cortex and cuticle can be evaluated in most of the terminal hair. Clinical (a′ and b′) and trichoscopic (c′and d′) images of the patient 2 weeks after starting chemotherapy. Trichoscopy shows the presence of CIA dots (red circles) that appear as dilated follicular infundibula containing yellowish, amorphous material, surrounded by a thin, white collaret (red circles). At RCM (e′ and f′) CIA dots appear as mashed, malted, non-homogeneous material inside the lumina (red circles). When a hair follicle becomes a CIA dot it is possible to detect a transverse black line (white arrows) in the proximal part of the hair shaft, representing an area of damage that will lead to hair breakage. Moreover, in this phase terminal hairs are still present. Clinical (a″ and b″) and trichoscopic (c″ and d″) images of the patient 2 weeks after the end of chemotherapy. In this phase, trichoscopy shows the onset of regrowing hairs and the persistence of black dots (black circle), yellow dots (yellow circles), and dysmorphic hair (blue arrow), while CIA dots are infrequently detectable (red circle). RCM (e″– i″) allows one to observe in detail the altered morphology of the regrowing hairs and the hair with shaft abnormalities (blue arrow). Black dots (black circle) look as homogeneous and reflective material filling follicular ostia normal in size, while yellow dots (yellow circle) appear as empty adnexal lumina filled by material highly refractile in the corneal layer that progressively diminishes as it gradually reaches the dermis. Clinical (a″′ and b″′), trichoscopic (c″′ and d″′), and RCM images (e″′ and f″′) of the patient 6 months after the end of the chemotherapy display total regrowth with normal hair and follicle
Fig. 2
Fig. 2
Permanent chemotherapy-induced alopecia (pCIA) in a patient affected by follicular non-Hodgkin’s lymphoma. Clinical (a and b) and trichoscopic (c and d) images of the patient before starting chemotherapy. RCM (e and f) reveals a certain grade of hair miniaturization in androgen-sensitive areas of the scalp. Clinical (a′ and b′) and trichoscopic (c′ and d′) images of the patient 2 weeks after starting chemotherapy. Trichoscopy shows the onset of dilated follicular infundibula containing yellowish, amorphous material, surrounded by a thin, white collaret that corresponds to CIA dots (red circles). At reflectance confocal microscopy (RCM) (e′ and f′) CIA dots appear as dilated follicular ostia with mashed, malted, non-homogeneous material, containing normal or fragmented hair (red circles). A transverse black line (white arrow) is detectable in the proximal part of the hair shaft and corresponds to an area of damage that will lead to hair breakage. Furthermore, during this phase an inflammatory infiltrate (red circles) can be unveiled by RCM. Clinical (a″ and b″) and trichoscopic (c″ and d″) images of the patient 2 weeks after the end of chemotherapy. Trichoscopy shows the onset of regrowing hairs and the persistence of black dots (black circles), yellow dots (yellow circles), dysmorphic hair (blue arrows), and CIA dots (red circle). RCM (e″–g″) allows one to observe in detail the hair with shaft abnormalities (blue arrow), black dots (black circle), yellow dots (yellow circle) and the amorphous necrotic-like material (red circle) that involves all the follicular ostia in CIA dots. During this phase, RCM reveals the presence of an inflammatory infiltrate with involvement of the dermo-epidermal junction and focal obscuration of the dermal papillae (f″). Clinical (a″′ and b″′), trichoscopic (c″′ and d″′), and RCM images (e″′ and f″′) of the patient 6 months after the end of the chemotherapy display partial hair regrowth. Trichoscopy shows the diffuse presence of multiple yellow dots (yellow circles), the persistence of regrowing hairs (green arrows), and an increase degree of miniaturization in comparison to baseline. RCM reveals the altered morphology of the regrowing hairs (green arrows), multiple yellow dots (yellow square), and permanence of inflammatory cells over time, especially around the adnexal structures (red square), leading to the appearance of fibrosis and alteration of the normal rimming
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