Dermoscopy of acute radiation-induced dermatitis in patients with head and neck cancers treated with radiotherapy – Scientific Reports

There were oral cavity carcinoma, oropharyngeal carcinoma, hypopharyngeal carcinoma, laryngeal carcinoma nasopharyngeal carcinoma and neck lymph nodes tumor as a metastatic cancer from unknown primary in 1, 8, 3, 10, 3 and 1 patients, respectively. There were five women and 21 men with the mean age of 60.5 years (range 34–74) in this group.

All patients (26) observed during the course of RT developed ARD. The highest noted grade according to RTOG/EORTC, at the end of the RT treatment, was grade II in 14 patients, grade III in 10 patients, and the remaining two developed grade IV ARD. Grade I was observed in the first week (on average on Day 4.69) (Fig. 1A), grade II in the third week of the follow-up (Day 20.69) (Fig. 1C), grade III in the 6th week of the follow-up (Day 37.81) (Fig. 1E), and grade IV in the 5th week of the follow-up (Day 34.66) (Fig. 1G). The percentage occurrence of dermoscopic features depending on the grade of radiation-induced dermatitis per RTOG/EORTC¹³ is presented in Table 2 and Fig. 1B,D,F,H (Table 2).

Summary of dermoscopic findings: vessels in each grade of ARD were polymorphic. The arrangement of the vessels was also heterogeneous, and there was no typical arrangement for a particular grade of ARD. In healthy skin, we did not observe vessels in reticular distribution, but their presence was detected in every degree of ARD. Unspecific distribution was more common in healthy skin than in ARD. In each grade of ARD, a patchy scale was observed and the frequency of scale occurrence increased with the grade of development according to RTOG without characteristic color was observed. However, the incidence of scale increases with the degree of development in RTOG (Fig. 1H). Moreover, a feature present in all grades but not observed in healthy skin was follicular plugs arranged in rosettes.

Statistically significant results are underlined in bold in Table 3. A relationship between the observed dermoscopic and clinical features was checked using κ coefficient (Table 3).

The agreement between dermoscopic and clinical features was 0.03–0.54 and bright erythema, epilation, dry and moist desquamation, moderate edema, and dermoscopic features such as vessels in reticular distribution, white, yellow, brown scale and patchy scale distribution, follicular plugs arranged in rosettes and perifollicular pigmentation. Negative results mean incompatibility: when a given macroscopic feature is present, the dermoscopic feature is not present. In the next step, dermoscopic and clinical features were analyzed in terms of the influence of time, age, gender, induction chemotherapy, concurrent chemotherapy, total radiation dose, fractional dose, tumor location, as well as the histopathological diagnosis during the whole RT treatment on the skin diagnostic outcomes using logistic regression. The statistically significant relationships between clinical features and possible ARD risk factors—time, age, gender, indCHT, concurrent CHT, and fractional dose—are expressed by odds ratios reported in Table 4 whereas OR is a measure of association between radiation exposure and a clinical outcome; OR > 1 indicates the increased occurrence of any event, while OR < 1 a protective exposure) (Table 3).

Based on the results in Table 4, we observed the relationship between the presence of vessels in reticular distribution and time, age, gender, induction chemotherapy, and concurrent CHT (Table 4). The statistical interpretation of the OR (univariate regression) may be as follows: 1 day of observation generates an increased risk of vessels in reticular distribution by 8%, and 5 days of observation (1.08⁵ = 1.47), so by almost one and a half. A 10-year difference in the age of patients generates a (1–0.97¹⁰) × 100% = 26% reduction in the occurrence of vessels in reticular distribution. The risk of vessels in reticular distribution is 64% lower in men than in women. Induction chemotherapy reduces the risk of vessels in reticular distribution almost three times (OR = 2.94). Concurrent CHT reduces the risk of vessels in reticular distribution by 1.83 (OR = 1.83). The results regarding the effect of collected risk factors on skin reaction in a multivariate model showed that the effect of gender and induction chemotherapy increased. Moreover, in the multivariate model, the lack of concurrent CHT reduces the risk of vessels in reticular distribution by 53% (see the right panel of Table 4). Other results in the table should be interpreted analogously. Considering individual factors affecting clinical response, each day of observation during RT treatment statistically generates a higher chance of occurrence of vessels in reticular distribution (Figs. 1D,F,H, 2A,E), white scale and yellow scale (Fig. 2B), and brown scale (Fig. 2C) with patchy distribution (Figs. 1B,H, 2C), perifollicular pigmentation (Fig. 2D), follicular plugs arranged in rosettes (Fig. 2E), while the chance of unspecific distribution of vessels decreases (Fig. 2D). In the context of a macroscopic response, each day of observation during RT treatment statistically generates a higher chance of occurrence of bright erythema (Fig. 1C,E), epilation (Fig. 1C,E), dry and moist desquamation (Fig. 1C,E), moderate (Fig. 1C) and pitting edema (Fig. 1E), and ulceration (Fig. 1G) while the chance of follicular and faint erythema decreases (Fig. 1A). The results regarding the effect of collected risk factors on skin reaction in a multivariate model were comparable. In a univariate analysis, age was a significant factor for vessels in reticular distribution, vessels in unspecific distribution, follicular plugs arranged in rosettes, and perifollicular pigmentation as well as in the group of macroscopic features for follicular erythema. However, multivariate analysis did not show this relationship for the unspecific distribution of vessels, follicular plugs arranged in rosettes, or perifollicular pigmentation (the association is on the border of statistical significance, i.e., p < 0.1). Gender is important for the occurrence of vessels in reticular distribution, vessels in unspecific distribution, white, yellow, patchy scale, follicular plugs arranged in rosettes, and for macroscopic features for faint and bright erythema and dry desquamation. Multivariate analysis showed that the gender effect was stronger in each case. The risk of vessels in reticular distribution, white scale, yellow scale, patchy scale, and follicular plugs arranged in rosettes is 85%, 89%, 80%, 95%, and 69% lower in men than in women, respectively. The risk of faint erythema is 118% higher for men than women, while the chance of bright erythema and dry desquamation is 88% and 74% lower in men than in women, respectively. Induction chemotherapy increases the risk of yellow scale and reduces the risk of vessels in reticular distribution. In the multivariate model, these dependencies increase, and we observe that induction chemotherapy increases the risk of yellow scale occurrence by two-thirds (OR = 0.34) and reduces the risk of vessels in reticular distribution almost six times (OR = 5.90). Concurrent chemotherapy is important for the occurrence of vessels in reticular distribution, follicular plugs arranged in rosettes, perifollicular pigmentation and macroscopic features such as follicular erythema, tender erythema, and moist desquamation. In turn, multivariate analysis did not show this relationship for follicular plugs arranged in rosettes, follicular erythema and moist desquamation (the association is on the border of the statistical significance, i.e., p < 0.1). Non-concurrent chemotherapy reduces the risk of vessels in reticular distribution, perifollicular pigmentation and tender erythema by 53%, 51% and 94%, respectively.

Dermoscopic images of ARD described in line with the consensus of experts in non-neoplastic dermatoses on behalf of the International Dermoscopy Society by Errichetti et al.¹⁷. (A) Dermoscopic image of ARD reveals linear branched, linear curved vessels with reticular distribution and perifollicular white color; (B) dermoscopic image of acute radiodermatitis reveals white and yellow, patchy scale; (C) dermoscopic image reveals linear branched and linear curved vessels with clustered distribution, brown, patchy scale; (D) dermoscopic image reveals linear branched and linear curved vessels with unspecific distribution, and perifollicular pigmentation; (E) linear branched and linear curved vessels with reticular distribution and follicular plugs arranged in rosettes.