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Post burn pruritus in pediatric burn patients
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Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/burns
Post burn pruritus in pediatric burn patients Sophie Maria Pierrette Nieuwendijk a,b, Iris Johanne de Korte a,b, Mereille Marren Pursad b , Monique van Dijk a,b, * , Heinz Rode b a b
Department of Pediatric Surgery, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands Department of Pediatric Surgery, Red Cross War Memorial Children’s Hospital, Cape Town, South Africa
article info
abstract
Article history:
Background: Pruritus is a common problem seen in the healing process of a burn wound and
Accepted 22 February 2018
gives great discomfort for the patient. Most research in this field has been done in the adult
Available online xxx
population, so evidence in the pediatric population is still lacking Purpose: The aims of this study were to assess the incidence and severity of post-burn
Keywords: Pediatrics Burns
pruritus, identify predictors for pruritus and evaluate the pharmacological treatments in a pediatric setting. Methods: Pruritus was assessed in this prospective observational study using a numeric rating scale and the Itch Man Scale applied by the patients’ caregiver. The predictive values of
Pruritus
candidate predictors for pruritus were compared using Fisher exact tests and Kruskal–Wallis
Itching Predictors
tests. Results: 413 patients were included in this study. Pruritus was reported in 71.7% of the patients. Complete symptom relief was only achieved in 29.8% of the patients who used medication. Time since burn (p<0.001), depth of the injury (p=0.017), TBSA burned (p=0.001) and skin grafting (p=0.001) were found to be significant predictors for post-burn pruritus. Conclusion: Post-burn pruritus is still a highly prevalent problem in pediatric burn care. Its intensity and frequency are higher especially in the first three months or with a deeper wound or a higher TBSA. © 2018 Elsevier Ltd and ISBI. All rights reserved.
1.
Introduction
1.1.
Background
Burns are a major public health concern, in particular in the developing world. Over 95% of fatal burn injuries occur in lowand middle-income countries [1]. While flame injuries are the main cause of burns in the adult population, children and especially toddlers are at higher risk of hot water burns. These burns account for approximately 5% of all burn deaths but account for a much higher proportion of non-fatal burns [2,3].The
survivors have to cope with problems such as disfigurements and pruritus (itch). Previous studies have reported that 87–93% of adult patients suffered from pruritus at 3 months post burn [4,5]. Histamine plays a main role in one of the known mechanisms of post-burn pruritus. Especially in the hypertrophic phase of the healing process a large amount of mast cells are attracted and result in an increased level of histamine [6–8]. Pruritic stimuli, like histamine, activate a specialized subpopulation of C-fibers [9]. These C-fibers convey the impulses to the dorsal horn of the spinal cord and from here on to the different areas in the cortex [10,11].
* Corresponding author at: Department of Pediatric Surgery, Erasmus University Medical Center-Sophia Children’s Hospital, Room SK 1276, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands. E-mail address: [email protected] (M. van Dijk). https://doi.org/10.1016/j.burns.2018.02.022 0305-4179/© 2018 Elsevier Ltd and ISBI. All rights reserved.
Please cite this article in press as: S.M.P. Nieuwendijk, et al., Post burn pruritus in pediatric burn patients, Burns (2018), https://doi.org/ 10.1016/j.burns.2018.02.022
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Several therapeutic strategies are used to treat the itching sensation. Some, such as antihistamines or compression garments, intervene in the peripheral aspects of the pruritic pathway. Others, such as gabapentin or massage therapy, intervene in the central aspects of the pruritic pathway [11]. The current mainstay of treatment are antihistamines, although a combined approach using centrally and peripherally acting agents has been found most effective in the treatment of acute post burn pruritus [12]. Known predictors for post burn pruritus are number of surgical procedures, i.e. a measure of deep dermal injury, posttraumatic stress symptoms, total body surface area (TBSA), female gender [4], younger age, post burn dry skin and raised/ thick scars [5]. Heat, sweating, fatigue and pain in the burned area can trigger or exacerbate the itching sensation. On the other hand, cold temperatures, cold water and rest may help alleviate the itch [13]. Like the majority of burns research conducted so far, the above-mentioned studies concerned adult populations. One pediatric study demonstrated decrease of the intensity and frequency of itch over time [14]. Evidence of possibly other predictors and triggers of post burn pruritus in the pediatric population is still lacking. We performed a study aimed at assessing the incidence and severity of post-burn pruritus, identifying risk factors for pruritus and evaluating the pharmacological treatments in a pediatric setting.
departments patients were seen at, data could be collected at different points in time after the burn incident and a part of the patients could be seen for follow up. Children who were not accompanied by a caregiver were excluded, as well as accompanied children for whom the caregiver would not give consent.
2.
Materials and methods
2.5.
2.1.
Study design
Gabapentin, 5mg per kg bodyweight, and/or an antihistaminic (chlorpheniramine (Allergex)), 1mg till 10kg and then 0.1mg per kg bodyweight, were prescribed in the wards and outpatient clinics to treat the itch.
This was a prospective observational study approved by the University of Cape Town Human Research Ethics Committee under HREC REF: 473/2015. Data were collected from April 2016 to August 2016.
2.2.
Subjects
This study was conducted at Red Cross War Memorial Children’s Hospital in Cape Town, South Africa and included children till the age of 13 with burn injuries. They were recruited either at the ward upon admission (just after the burn injury had taken place), or at one of the two outpatient clinics during a first or repeat visit. Because of the different
2.3.
Consent
One of the researchers explained the purpose of the study and presented an information sheet for further reading. Children of the age of 6 years or older were also informed and asked to provide consent. The caregiver, and the patient, if 6 years or older, signed the informed consent form if they agreed to participate in the study.
2.4.
Data collection
For the study either only the caregiver, in case the patient was younger than 6 years, or both the caregiver and patient were asked questions regarding the itch and medication in the past week and were administered several assessment scales (described below). If no itch was experienced in the past week, they were asked if there was itch at any point in time after the burn. Information about the burn injury (TBSA, depth of the wound, injury etiology, surgery, scars) and prescribed medication was retrieved from the patient’s medical file.
2.6.
Medicament prescription policy
Itch Man Scale and numeric rating scale
Severity of the itch was measured with the Itch Man Scale (Fig. 1), which was specifically developed for pediatric burn patients and found valid and reliable in a population till the age of 18 years [15]. Permission to reprint this scale was granted by Shriners hospital for children. The score ranges from 0 to 4 and is supported by 5 illustrations showing an itching man. 0 is a happy man with no itch and 4 a man with the most terrible itch, impossible to sit still and concentrate. First the participants
Fig. 1 – Itch Man Scale (©2000, Blakeney and Marvin). Permission was granted by the copyright owner Shriners Hospitals for 1 Children . Ref. [16]. Please cite this article in press as: S.M.P. Nieuwendijk, et al., Post burn pruritus in pediatric burn patients, Burns (2018), https://doi.org/ 10.1016/j.burns.2018.02.022
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(only the caregiver or both the caregiver and child) were asked to score the itch on this scale. Second, they were asked to score it on a numeric rating scale (NRS) from 0 to 10, so as to validate their understanding of the Itch Man Scale.
2.7.
Vancouver Scar Scale
The Vancouver Scar Scale (VSS) is a widely used scar rating scale. The overall scale has intermediate evidence of construct validity, reliability and responsiveness in a population with
Table 1 – Patient and burn characteristics. N=413 a
Age at injury in years , median (IQR) Age at first contact (research) in yearsb , median (IQR)
1.73 (1.17–3.47) 2.19 (1.39– 4.11)
3
burn scars [17]. The VSS consist of 4 items: pigmentation, vascularity, pliability and height. In this study the scale was used to indicate if a scar was hypertrophic or not. Therefore only the item height was used, with 0 being a normal flat scar and 1 a hypertrophic scar [18]. The occupational therapists would score this scale, as they were more experienced in assessing scars.
2.8.
Analysis
IBM SPSS Statistics version 23 was used to analyze the data. A univariate analysis was done to compare the possible predictors with the Itch Man scores, scored by the caregiver. The categorical variables gender, complexion, injury etiology, surgery, scar type and medication were compared between the Itch Man scores with Fisher exact tests. Time since burn and deepest depth of injury were compared using the Monte Carlo exact test. TBSA burned was compared between the itch groups using a Kruskal–Wallis test. A logistic regression between the significant predictors (dependent variable: TBSA, independent variables: deepest depth, time since burn and skin grafting) was used to check multicollinearity, which should not exceed 5.
Gender, n (%) Boy Girl
227 (55.0) 186 (45.0)
Complexion, n (%) Black Mixed race White
242 (58.6) 166 (40.2) 5 (1.2)
3.
Results
3.1.
Patient and burn characteristics
First Language, n (%) Xhosa Afrikaans English Other
186 (45.0) 101 (24.5) 72 (17.4) 54 (13.1)
Socioeconomic statusc Low Middle High Unknown
284 (68.8) 36 (8.7) 5 (1.2) 88 (21.2)
A total of 413 patients were included, of which 55% were boys. Most children (71.2%) were under the age of 3 and at least 68.8% of the patients were from a low socioeconomic environment. Hot water burns were most frequent (80.4%). In 61.4% of cases the depth of the wound was classified as superficial partial thickness and 28.6% of the patients needed a skin graft or Meek micro graft (Table 1). Skin grafts were performed within 2 weeks after the incident in 48.2% of the cases.
3.2.
Department, n (%) Inpatient Outpatient
85 (20.6) 328 (79.4)
Injury etiology, n (%) Hot water Flame Other % TBSA burnd , median (IQR)
332 (80.4) 40 (9.7) 41 (9.9) 6.0 (4.0–12.0)
Depth injurye , n (%) Superficial partial thickness Deep partial thickness Full thickness
250 (61.4) 124 (30.5) 33 (8.1)
Surgery n (%) Skin graft Meek micro graft
113 (27) 5 (1.2)
a b c d e
n =406. n =408. Based on neighborhood. n =405. n =407.
Incidence of pruritus
Itch at any point in time after the burn was reported for 296 patients (71.7%), which was mild (Itch Man score 1 or 2) in 83.5% of the patients. More than half (54.7%) of the 117 patients without itch were seen within a week after the burn. Follow up was done in 83 patients ranging from one week to 3 months after first contact. Itch was reported in 55 patients (66.3%) of whom 12 (21.8%) scored lower on the Itch Man scale compared to the first assessment, 22 (40.0%) stayed the same and 21 (38.2%) had gotten worse or had started itching. The caregivers’ NRS and Itch Man scores correlated well, as shown by a large correlation coefficient of 0.896 (95% CI 0.87– 0.91). A correlation coefficient of 0.74 (95% CI 0.69–0.79) was found between the Itch Man scores of the caregivers and the children who were older than 6 years.
3.3.
Most itching areas
Most often the arms and legs itched, followed by the chest, abdomen and face as shown in Fig. 2. Over half of the patients (58.5%) itched on the burn wound and 23.5% of all patients
Please cite this article in press as: S.M.P. Nieuwendijk, et al., Post burn pruritus in pediatric burn patients, Burns (2018), https://doi.org/ 10.1016/j.burns.2018.02.022
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itched on the skin graft. Out of the patients who received a skin graft, 75.4% experienced itch. Some patients (16.2%) did not itch on the wound itself but on the surrounding. A small part of all patients (1.8%) reported itch on the donor site (Fig. 3).
3.4.
Predictors for pruritus
As shown in Fig. 4, itch only occurs in 42.1% in the first week, which increases to 81.9% in the first three months. Severe itch (Itch Man score 3 and 4) decreases in time with 17.5%, 12.1% and 7.1% for 8–90 days, 3 months to 1year and >1year after the burn respectively. Mild itch (Itch Man score 1 and 2) occurs in 64.4%, 60.6% and 70.1% for 8–90 days, 3 months to 1year and >1year after the burn respectively. Besides the time since the burn, also the TBSA (p<0.001), depth of the injury (p=0.017) and whether a skin graft was performed (p=0.001) influenced the existence and severity of the itching sensation (Table 2). The collinearity for all these predictors was below 2. Hypertrophic scarring was seen in 19.6% of all included patients and in 69.8% of the patients with a scar. Although this was not a significant predictor for post-burn pruritus (p=0.084), a trend is seen showing that 60.0% of the normal scars itch versus 77.8% of the hypertrophic scars (Table 2).
3.5.
Anti-itch treatment
In total 218 patients (52.8%) received anti-itch medication: gabapentin (17.9%), Allergex (39.0%) or both gabapentin and Allergex (43.1%). Sixty-five of those (29.8%) achieved complete symptom relief (Itch Man Score=0) (Table 3). Table 4 shows that all patients seen at the ward (inpatients) received the prescribed dose, except for one patient who did not get the prescribed dose gabapentin, as the caregiver took
care of the medication instead of the nurse. In some cases patients seen at the clinics (outpatients) did not receive the right dose of their prescribed medication. For gabapentin 70.5% of 88 patients received the prescribed dose. For Allergex this was 58.5% of 130 patients. At follow up (n=83) anti-itch medication was used in 67.5% of the patients. Out of the patients who used anti-itch medication, 14 patients (25.0%) scored lower on the Itch Man scale, 23 (41.1%) still had the same amount of itch and 19 (33.9%) reported worse itch. For the patients who did not use anti-itch medication 10 (37.0%) experienced less itch, 15 (55.6%) had the same itch as before and 2 (7.4%) reported worse itch. Pressure garments were used in 20 patients and only 6 were seen at follow up. Most of them itched the same (n=4) and 2 itched less. Another 4 patients had started pressure garments at follow up. In 2 of them itch reduced, in 1 itch did not improve and 1 deteriorated.
4.
Discussion
This study aimed to determine the incidence of and possible predictors for post-burn pruritus and the effect of antipruritic therapy in a pediatric setting. We found that 71.7% of included patients suffered from itch at some time after the burn incident. Most itching areas are the limbs, chest and face, but this could also be due to the fact that those areas burn most often. With medication, complete symptom relief was only achieved in 29.8% of all the patients. Predictors for pruritus were time since burn, TBSA, depth of injury and having received a skin graft. This confirms what was found in adult populations in previous studies [4,5]. Prominent, though, is that we found a slight increase of pruritus at >1year post burn. Fewer people
Fig. 2 – Most itching body parts. Please cite this article in press as: S.M.P. Nieuwendijk, et al., Post burn pruritus in pediatric burn patients, Burns (2018), https://doi.org/ 10.1016/j.burns.2018.02.022
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Fig. 3 – Place of itching.
Fig. 4 – Severity of itch over time.
attending check-ups due to decreasing burn complaints, resulting in loss of follow-up, might have caused this. Female gender was not found to be a significant predictor, even though results in the adult population suggested that [4,5], but it confirms the outcomes of a study done in a pediatric setting by Schneider et al. They found female gender not to be a significant predictor of itch and showed a decrease of frequency and intensity over time [14]. Hypertrophic scarring was not a significant predictor in our study, in contrast to Carrougher et al. who found pruritus to be
highly prevalent in adult patients with hypertrophic scars [5]. We found a trend, however, towards hypertrophic scars itching more often. The exact mechanism is still unknown, but extensive deposition of collagen, in case of hypertrophy, results in more mast cells and thereby increases release of histamine leading to more itch [19]. Our study also demonstrated that complete symptom relief was only achieved in one third of all cases, even though some patients received medication to treat it. They may have been given a lower dose than prescribed or had severe itch, which
Please cite this article in press as: S.M.P. Nieuwendijk, et al., Post burn pruritus in pediatric burn patients, Burns (2018), https://doi.org/ 10.1016/j.burns.2018.02.022
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Table 2 – Univariate analysis possible predictors and pruritus. Itch Man Score
0 (n=134) n (%)
1 (n=126) n (%)
2 (n=107) n (%)
3 (n=34) n (%)
4 (n=12) n (%)
P-value
Gender Male Female
76 (56.7) 58 (43.3)
69 (54.8) 57 (45.2)
58 (54.2) 49 (45.8)
18 (52.9) 16 (47.1)
6 (50.0) 6 (50.0)
Age at first contact in years Median (IQR) Range
2.0 (1.1–3.9) 0.25–12.93
2.1 (1.5–3.6) 0.12–13.96
2.5 (1.5–4.7) 0.18–12.72
2.2 (1.4–4.5) 0.76–13.0
4.4 (2.0–7.8) 0.95–9.57
Time since burn 0–7 days 8–90 days 3 months-1year >1 year
73 29 18 13
28 58 20 19
(22.4) (46.4) (16) (15.2)
20 (18.9) 45 (42.5) 20 (18.9) 21 (19.8)
4 (12.1) 21 (63.6) 5 (15.2) 3 (9.1)
1 (8.3) 7 (58.3) 3 (25.0) 1 (8.3)
Complexion Black Mixed race White
77 (57.5) 55 (41.0) 2 (1.5)
67 (53.2) 58 (46.0) 1 (0.8)
71 (66.4) 34 (31.8) 2 (1.9)
16 (47.1) 18 (52.9) –
11 (91.7) 1 (8.3) –
Injury etiology HWB Flame Other
109 (81.3) 14 (10.4) 11 (8.2)
104 (82.5) 9 (7.1) 13 (10.3)
83 (77.6) 10 (9.3) 14 (13.1)
27 (79.4) 5 (14.7) 2 (5.9)
9 (75.0) 2 (16.7) 1 (8.3)
TBSA Median (IQR) Range
5.0 (3.0–10.0) 0.5–2.0
6.0 (4.0–11.0) 1.0–85.0
6.5 (4.0–12.0) 1.0–45.0
9.5 (4.8–9.5) 1.0–55.0
11.0 (7.0–18.0) 5.0–56
Depth injury Superficial PTa Deep PTa Full Thickness
88 (66.7) 36 (27.3) 8 (6.1)
78 (62.4) 38 (30.4) 9 (7.2)
56 (53.8) 42 (40.4) 6 (5.8)
20 (58.8) 6 (17.6) 8 (23.5)
8 (66.7) 2 (16.7) 2 (16.7)
Surgery Skin graft
23 (17.2)
37 (29.4)
39 (36.4)
12 (35.3)
7 (58.3)
Scar type None Normal Hypertrophic
102 (76.1) 14 (10.4) 18 (13.4)
88 (69.8) 13 (10.3) 25 (19.8)
69 (64.5) 7 (6.5) 31 (29.0)
29 (85.3) 1 (2.9) 4 (11.8)
9 (75.0) – 3 (25.0)
a
0.983
0.074
<0.001 (54.9) (21.8) (13.5) (9.8)
0.057
0.727
0.001
0.017
0.001
0.084
PT: partial thickness.
was nevertheless reduced to mild itch. Alternatively, current treatment strategies are not effective because other receptors or pathways may be involved in pruritus [20,21]. Pressure garments are known to have an anti-pruritic effect [11], which our results also suggest. However, our population was small (n=24) and we had an even smaller follow up (n=10). Pressure garments were hardly used in our population, because of the discomfort in a hot climate and low socioeconomic environment. Another possible treatment for pruritus is laser therapy. Depending on scar type and thickness different types of lasers and light sources can be used in the treatment of burn scars [22]. Among other benefits, it improves scar appearance and patients reported a 49% decrease in pruritus [23]. Studies have shown laser treatment to be safe and effective in both adults and
pediatric patients. A minimum of 3–4 procedures is recommended, with the use of an ablative fractional laser [22,24].
Table 3 – Reported itch scores by caregiver and percentage of anti-itch medication given. Itch Man Score
0 1 2 3 4 (n=134) (n=126) (n=107) (n=34) (n=12) n (%) n (%) n (%) n (%) n (%)
None Allergex Gabapentin Both
69 (51.5) 19 (14.2) 17 (12.7) 29 (21.6)
58 27 12 29
(46.0) (21.4) (9.5) (23.0)
50 (46.7) 26 (24.3) 8 (7.5) 23 (21.5)
14 (41.2) 7 (20.6) 1 (2.9) 12 (35.3)
4 (33.3) 6 (50.0) 1 (8.3) 1 (8.3)
Please cite this article in press as: S.M.P. Nieuwendijk, et al., Post burn pruritus in pediatric burn patients, Burns (2018), https://doi.org/ 10.1016/j.burns.2018.02.022
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Table 4 – Given and prescribed doses gabapentin and Allergex. No itch, score 0 n (%)
Mild itch, score 1–2 n (%)
Severe itch, score 3–4 n (%)
Gabapentin, n =88 Less than prescribed dose Prescribed dose More than prescribed dose
2 (6.7) 28 (93.3) –
9 (18.4) 28 (57.1) 12 (24.5)
– 6 (66.7) 3 (33.3)
Allergex, n =130 Less than prescribed dose Prescribed dose More than prescribed dose
1 (2.7) 27 (73.0) 9 (24.3)
17 (21.2) 43 (53.8) 20 (25.0)
3 (23.1) 6 (46.1) 4 (30.8)
Medication
4.1.
0.006
0.048
Limitations
Several limiting factors may have influenced the results, such as a language barrier. The Dutch researchers did not speak the native languages(s) and communicated in English. Most of the caregivers and patients included in this study did not speak English as their first language. However, eventually almost all the information needed was obtained and understanding of the Itch Man Scale was assessed with the use of the NRS (correlation coefficient of 0.896). Also, for patients younger than 6 years the caregiver scored the Itch Man Scale, which may have been a source of bias. The correlation coefficient of 0.744 between the score of the caregiver and the child, older than six, showed that they agreed with each other in most of the cases, but still does not guarantee a score given by the caregiver consistent with the child younger than six.
4.2.
Recommendations
For further studies it is important to do a follow up on all the patients at different points in time after the burn, so the effect of treatment can be tracked without the risk of bias caused by drop-out from follow-up. For post-burn pruritus we recommend immediate anti itch treatment, as it starts within the first week after the incident. It is important to ensure complete compliance with the treatment program to get the best result. This study shows the compliance was not very high and could therefore have affected the results. Regular follow-up would be recommendable to ensure the best possible treatment is given.
5.
P-value
Conclusion
The current mainstay of pruritus treatment, antihistamines, does not seem as effective as it should be, as many children in this study still suffered from pruritus. Other treatment options, for example laser therapy, need to be further tested. The time since burn, TBSA, depth of injury and whether a skin graft was performed are predictors for pruritus, but these are factors that cannot be influenced. So still more research is needed to determine the exact mechanism of itch and find
treatment targets. This way an accurate treatment can be given that helps improve the quality of life for burn survivors.
Declaration of interest No conflict of interest to be disclosed.
Acknowledgements We would like to thank all the participants for their collaboration to this research. Also we wish to thank the employees at Red Cross War Memorial Hospital for their help during the data collection and J. Hagoort for his editorial review.
Formatting of funding sources This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. REFERENCES
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[16] Blakeney P, Marvin J. In: Children SHF, editor. Itch Man Scale. . [17] Tyack Z, Simons M, Spinks A, Wasiak J. A systematic review of the quality of burn scar rating scales for clinical and research use. Burns 2012;38:6–18. [18] Thompson CM, Sood RF, Honari S, Carrougher GJ, Gibran NS. What score on the Vancouver Scar Scale constitutes a hypertrophic scar? Results from a survey of North American burn-care providers. Burns 2015;41:1442–8. [19] Rajeev B, Ahuja PC. Postburn pruritus: a practical review. Indian J Burns 2014;22:13–21. [20] Schmelz M, Schmidt R, Weidner C, Hilliges M, Torebjork HE, Handwerker HO. Chemical response pattern of different classes of C-nociceptors to pruritogens and algogens. J Neurophysiol 2003;89:2441–8. [21] Davidson S, Giesler GJ. The multiple pathways for itch and their interactions with pain. Trends Neurosci. 2010;33:550–8. [22] Willows BM, Ilyas M, Sharma A. Laser in the management of burn scars. Burns 2017;43:1379–89. [23] Levi B, Ibrahim A, Mathews K, Wojcik B, Gomez J, Fagan S, et al. The use of CO2 fractional photothermolysis for the treatment of burn scars. J Burn Care Res 2016;37:106–14. [24] Khandelwal A, Yelvington M, Tang X, Brown S. Ablative fractional photothermolysis for the treatment of hypertrophic burn scars in adult and pediatric patients: a single surgeon’s experience. J Burn Care Res 2014;35:455–63.
Please cite this article in press as: S.M.P. Nieuwendijk, et al., Post burn pruritus in pediatric burn patients, Burns (2018), https://doi.org/ 10.1016/j.burns.2018.02.022
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Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/burns
Post burn pruritus in pediatric burn patients Sophie Maria Pierrette Nieuwendijk a,b, Iris Johanne de Korte a,b, Mereille Marren Pursad b , Monique van Dijk a,b, * , Heinz Rode b a b
Department of Pediatric Surgery, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands Department of Pediatric Surgery, Red Cross War Memorial Children’s Hospital, Cape Town, South Africa
article info
abstract
Article history:
Background: Pruritus is a common problem seen in the healing process of a burn wound and
Accepted 22 February 2018
gives great discomfort for the patient. Most research in this field has been done in the adult
Available online xxx
population, so evidence in the pediatric population is still lacking Purpose: The aims of this study were to assess the incidence and severity of post-burn
Keywords: Pediatrics Burns
pruritus, identify predictors for pruritus and evaluate the pharmacological treatments in a pediatric setting. Methods: Pruritus was assessed in this prospective observational study using a numeric rating scale and the Itch Man Scale applied by the patients’ caregiver. The predictive values of
Pruritus
candidate predictors for pruritus were compared using Fisher exact tests and Kruskal–Wallis
Itching Predictors
tests. Results: 413 patients were included in this study. Pruritus was reported in 71.7% of the patients. Complete symptom relief was only achieved in 29.8% of the patients who used medication. Time since burn (p<0.001), depth of the injury (p=0.017), TBSA burned (p=0.001) and skin grafting (p=0.001) were found to be significant predictors for post-burn pruritus. Conclusion: Post-burn pruritus is still a highly prevalent problem in pediatric burn care. Its intensity and frequency are higher especially in the first three months or with a deeper wound or a higher TBSA. © 2018 Elsevier Ltd and ISBI. All rights reserved.
1.
Introduction
1.1.
Background
Burns are a major public health concern, in particular in the developing world. Over 95% of fatal burn injuries occur in lowand middle-income countries [1]. While flame injuries are the main cause of burns in the adult population, children and especially toddlers are at higher risk of hot water burns. These burns account for approximately 5% of all burn deaths but account for a much higher proportion of non-fatal burns [2,3].The
survivors have to cope with problems such as disfigurements and pruritus (itch). Previous studies have reported that 87–93% of adult patients suffered from pruritus at 3 months post burn [4,5]. Histamine plays a main role in one of the known mechanisms of post-burn pruritus. Especially in the hypertrophic phase of the healing process a large amount of mast cells are attracted and result in an increased level of histamine [6–8]. Pruritic stimuli, like histamine, activate a specialized subpopulation of C-fibers [9]. These C-fibers convey the impulses to the dorsal horn of the spinal cord and from here on to the different areas in the cortex [10,11].
* Corresponding author at: Department of Pediatric Surgery, Erasmus University Medical Center-Sophia Children’s Hospital, Room SK 1276, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands. E-mail address: [email protected] (M. van Dijk). https://doi.org/10.1016/j.burns.2018.02.022 0305-4179/© 2018 Elsevier Ltd and ISBI. All rights reserved.
Please cite this article in press as: S.M.P. Nieuwendijk, et al., Post burn pruritus in pediatric burn patients, Burns (2018), https://doi.org/ 10.1016/j.burns.2018.02.022
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Several therapeutic strategies are used to treat the itching sensation. Some, such as antihistamines or compression garments, intervene in the peripheral aspects of the pruritic pathway. Others, such as gabapentin or massage therapy, intervene in the central aspects of the pruritic pathway [11]. The current mainstay of treatment are antihistamines, although a combined approach using centrally and peripherally acting agents has been found most effective in the treatment of acute post burn pruritus [12]. Known predictors for post burn pruritus are number of surgical procedures, i.e. a measure of deep dermal injury, posttraumatic stress symptoms, total body surface area (TBSA), female gender [4], younger age, post burn dry skin and raised/ thick scars [5]. Heat, sweating, fatigue and pain in the burned area can trigger or exacerbate the itching sensation. On the other hand, cold temperatures, cold water and rest may help alleviate the itch [13]. Like the majority of burns research conducted so far, the above-mentioned studies concerned adult populations. One pediatric study demonstrated decrease of the intensity and frequency of itch over time [14]. Evidence of possibly other predictors and triggers of post burn pruritus in the pediatric population is still lacking. We performed a study aimed at assessing the incidence and severity of post-burn pruritus, identifying risk factors for pruritus and evaluating the pharmacological treatments in a pediatric setting.
departments patients were seen at, data could be collected at different points in time after the burn incident and a part of the patients could be seen for follow up. Children who were not accompanied by a caregiver were excluded, as well as accompanied children for whom the caregiver would not give consent.
2.
Materials and methods
2.5.
2.1.
Study design
Gabapentin, 5mg per kg bodyweight, and/or an antihistaminic (chlorpheniramine (Allergex)), 1mg till 10kg and then 0.1mg per kg bodyweight, were prescribed in the wards and outpatient clinics to treat the itch.
This was a prospective observational study approved by the University of Cape Town Human Research Ethics Committee under HREC REF: 473/2015. Data were collected from April 2016 to August 2016.
2.2.
Subjects
This study was conducted at Red Cross War Memorial Children’s Hospital in Cape Town, South Africa and included children till the age of 13 with burn injuries. They were recruited either at the ward upon admission (just after the burn injury had taken place), or at one of the two outpatient clinics during a first or repeat visit. Because of the different
2.3.
Consent
One of the researchers explained the purpose of the study and presented an information sheet for further reading. Children of the age of 6 years or older were also informed and asked to provide consent. The caregiver, and the patient, if 6 years or older, signed the informed consent form if they agreed to participate in the study.
2.4.
Data collection
For the study either only the caregiver, in case the patient was younger than 6 years, or both the caregiver and patient were asked questions regarding the itch and medication in the past week and were administered several assessment scales (described below). If no itch was experienced in the past week, they were asked if there was itch at any point in time after the burn. Information about the burn injury (TBSA, depth of the wound, injury etiology, surgery, scars) and prescribed medication was retrieved from the patient’s medical file.
2.6.
Medicament prescription policy
Itch Man Scale and numeric rating scale
Severity of the itch was measured with the Itch Man Scale (Fig. 1), which was specifically developed for pediatric burn patients and found valid and reliable in a population till the age of 18 years [15]. Permission to reprint this scale was granted by Shriners hospital for children. The score ranges from 0 to 4 and is supported by 5 illustrations showing an itching man. 0 is a happy man with no itch and 4 a man with the most terrible itch, impossible to sit still and concentrate. First the participants
Fig. 1 – Itch Man Scale (©2000, Blakeney and Marvin). Permission was granted by the copyright owner Shriners Hospitals for 1 Children . Ref. [16]. Please cite this article in press as: S.M.P. Nieuwendijk, et al., Post burn pruritus in pediatric burn patients, Burns (2018), https://doi.org/ 10.1016/j.burns.2018.02.022
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(only the caregiver or both the caregiver and child) were asked to score the itch on this scale. Second, they were asked to score it on a numeric rating scale (NRS) from 0 to 10, so as to validate their understanding of the Itch Man Scale.
2.7.
Vancouver Scar Scale
The Vancouver Scar Scale (VSS) is a widely used scar rating scale. The overall scale has intermediate evidence of construct validity, reliability and responsiveness in a population with
Table 1 – Patient and burn characteristics. N=413 a
Age at injury in years , median (IQR) Age at first contact (research) in yearsb , median (IQR)
1.73 (1.17–3.47) 2.19 (1.39– 4.11)
3
burn scars [17]. The VSS consist of 4 items: pigmentation, vascularity, pliability and height. In this study the scale was used to indicate if a scar was hypertrophic or not. Therefore only the item height was used, with 0 being a normal flat scar and 1 a hypertrophic scar [18]. The occupational therapists would score this scale, as they were more experienced in assessing scars.
2.8.
Analysis
IBM SPSS Statistics version 23 was used to analyze the data. A univariate analysis was done to compare the possible predictors with the Itch Man scores, scored by the caregiver. The categorical variables gender, complexion, injury etiology, surgery, scar type and medication were compared between the Itch Man scores with Fisher exact tests. Time since burn and deepest depth of injury were compared using the Monte Carlo exact test. TBSA burned was compared between the itch groups using a Kruskal–Wallis test. A logistic regression between the significant predictors (dependent variable: TBSA, independent variables: deepest depth, time since burn and skin grafting) was used to check multicollinearity, which should not exceed 5.
Gender, n (%) Boy Girl
227 (55.0) 186 (45.0)
Complexion, n (%) Black Mixed race White
242 (58.6) 166 (40.2) 5 (1.2)
3.
Results
3.1.
Patient and burn characteristics
First Language, n (%) Xhosa Afrikaans English Other
186 (45.0) 101 (24.5) 72 (17.4) 54 (13.1)
Socioeconomic statusc Low Middle High Unknown
284 (68.8) 36 (8.7) 5 (1.2) 88 (21.2)
A total of 413 patients were included, of which 55% were boys. Most children (71.2%) were under the age of 3 and at least 68.8% of the patients were from a low socioeconomic environment. Hot water burns were most frequent (80.4%). In 61.4% of cases the depth of the wound was classified as superficial partial thickness and 28.6% of the patients needed a skin graft or Meek micro graft (Table 1). Skin grafts were performed within 2 weeks after the incident in 48.2% of the cases.
3.2.
Department, n (%) Inpatient Outpatient
85 (20.6) 328 (79.4)
Injury etiology, n (%) Hot water Flame Other % TBSA burnd , median (IQR)
332 (80.4) 40 (9.7) 41 (9.9) 6.0 (4.0–12.0)
Depth injurye , n (%) Superficial partial thickness Deep partial thickness Full thickness
250 (61.4) 124 (30.5) 33 (8.1)
Surgery n (%) Skin graft Meek micro graft
113 (27) 5 (1.2)
a b c d e
n =406. n =408. Based on neighborhood. n =405. n =407.
Incidence of pruritus
Itch at any point in time after the burn was reported for 296 patients (71.7%), which was mild (Itch Man score 1 or 2) in 83.5% of the patients. More than half (54.7%) of the 117 patients without itch were seen within a week after the burn. Follow up was done in 83 patients ranging from one week to 3 months after first contact. Itch was reported in 55 patients (66.3%) of whom 12 (21.8%) scored lower on the Itch Man scale compared to the first assessment, 22 (40.0%) stayed the same and 21 (38.2%) had gotten worse or had started itching. The caregivers’ NRS and Itch Man scores correlated well, as shown by a large correlation coefficient of 0.896 (95% CI 0.87– 0.91). A correlation coefficient of 0.74 (95% CI 0.69–0.79) was found between the Itch Man scores of the caregivers and the children who were older than 6 years.
3.3.
Most itching areas
Most often the arms and legs itched, followed by the chest, abdomen and face as shown in Fig. 2. Over half of the patients (58.5%) itched on the burn wound and 23.5% of all patients
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itched on the skin graft. Out of the patients who received a skin graft, 75.4% experienced itch. Some patients (16.2%) did not itch on the wound itself but on the surrounding. A small part of all patients (1.8%) reported itch on the donor site (Fig. 3).
3.4.
Predictors for pruritus
As shown in Fig. 4, itch only occurs in 42.1% in the first week, which increases to 81.9% in the first three months. Severe itch (Itch Man score 3 and 4) decreases in time with 17.5%, 12.1% and 7.1% for 8–90 days, 3 months to 1year and >1year after the burn respectively. Mild itch (Itch Man score 1 and 2) occurs in 64.4%, 60.6% and 70.1% for 8–90 days, 3 months to 1year and >1year after the burn respectively. Besides the time since the burn, also the TBSA (p<0.001), depth of the injury (p=0.017) and whether a skin graft was performed (p=0.001) influenced the existence and severity of the itching sensation (Table 2). The collinearity for all these predictors was below 2. Hypertrophic scarring was seen in 19.6% of all included patients and in 69.8% of the patients with a scar. Although this was not a significant predictor for post-burn pruritus (p=0.084), a trend is seen showing that 60.0% of the normal scars itch versus 77.8% of the hypertrophic scars (Table 2).
3.5.
Anti-itch treatment
In total 218 patients (52.8%) received anti-itch medication: gabapentin (17.9%), Allergex (39.0%) or both gabapentin and Allergex (43.1%). Sixty-five of those (29.8%) achieved complete symptom relief (Itch Man Score=0) (Table 3). Table 4 shows that all patients seen at the ward (inpatients) received the prescribed dose, except for one patient who did not get the prescribed dose gabapentin, as the caregiver took
care of the medication instead of the nurse. In some cases patients seen at the clinics (outpatients) did not receive the right dose of their prescribed medication. For gabapentin 70.5% of 88 patients received the prescribed dose. For Allergex this was 58.5% of 130 patients. At follow up (n=83) anti-itch medication was used in 67.5% of the patients. Out of the patients who used anti-itch medication, 14 patients (25.0%) scored lower on the Itch Man scale, 23 (41.1%) still had the same amount of itch and 19 (33.9%) reported worse itch. For the patients who did not use anti-itch medication 10 (37.0%) experienced less itch, 15 (55.6%) had the same itch as before and 2 (7.4%) reported worse itch. Pressure garments were used in 20 patients and only 6 were seen at follow up. Most of them itched the same (n=4) and 2 itched less. Another 4 patients had started pressure garments at follow up. In 2 of them itch reduced, in 1 itch did not improve and 1 deteriorated.
4.
Discussion
This study aimed to determine the incidence of and possible predictors for post-burn pruritus and the effect of antipruritic therapy in a pediatric setting. We found that 71.7% of included patients suffered from itch at some time after the burn incident. Most itching areas are the limbs, chest and face, but this could also be due to the fact that those areas burn most often. With medication, complete symptom relief was only achieved in 29.8% of all the patients. Predictors for pruritus were time since burn, TBSA, depth of injury and having received a skin graft. This confirms what was found in adult populations in previous studies [4,5]. Prominent, though, is that we found a slight increase of pruritus at >1year post burn. Fewer people
Fig. 2 – Most itching body parts. Please cite this article in press as: S.M.P. Nieuwendijk, et al., Post burn pruritus in pediatric burn patients, Burns (2018), https://doi.org/ 10.1016/j.burns.2018.02.022
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Fig. 3 – Place of itching.
Fig. 4 – Severity of itch over time.
attending check-ups due to decreasing burn complaints, resulting in loss of follow-up, might have caused this. Female gender was not found to be a significant predictor, even though results in the adult population suggested that [4,5], but it confirms the outcomes of a study done in a pediatric setting by Schneider et al. They found female gender not to be a significant predictor of itch and showed a decrease of frequency and intensity over time [14]. Hypertrophic scarring was not a significant predictor in our study, in contrast to Carrougher et al. who found pruritus to be
highly prevalent in adult patients with hypertrophic scars [5]. We found a trend, however, towards hypertrophic scars itching more often. The exact mechanism is still unknown, but extensive deposition of collagen, in case of hypertrophy, results in more mast cells and thereby increases release of histamine leading to more itch [19]. Our study also demonstrated that complete symptom relief was only achieved in one third of all cases, even though some patients received medication to treat it. They may have been given a lower dose than prescribed or had severe itch, which
Please cite this article in press as: S.M.P. Nieuwendijk, et al., Post burn pruritus in pediatric burn patients, Burns (2018), https://doi.org/ 10.1016/j.burns.2018.02.022
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Table 2 – Univariate analysis possible predictors and pruritus. Itch Man Score
0 (n=134) n (%)
1 (n=126) n (%)
2 (n=107) n (%)
3 (n=34) n (%)
4 (n=12) n (%)
P-value
Gender Male Female
76 (56.7) 58 (43.3)
69 (54.8) 57 (45.2)
58 (54.2) 49 (45.8)
18 (52.9) 16 (47.1)
6 (50.0) 6 (50.0)
Age at first contact in years Median (IQR) Range
2.0 (1.1–3.9) 0.25–12.93
2.1 (1.5–3.6) 0.12–13.96
2.5 (1.5–4.7) 0.18–12.72
2.2 (1.4–4.5) 0.76–13.0
4.4 (2.0–7.8) 0.95–9.57
Time since burn 0–7 days 8–90 days 3 months-1year >1 year
73 29 18 13
28 58 20 19
(22.4) (46.4) (16) (15.2)
20 (18.9) 45 (42.5) 20 (18.9) 21 (19.8)
4 (12.1) 21 (63.6) 5 (15.2) 3 (9.1)
1 (8.3) 7 (58.3) 3 (25.0) 1 (8.3)
Complexion Black Mixed race White
77 (57.5) 55 (41.0) 2 (1.5)
67 (53.2) 58 (46.0) 1 (0.8)
71 (66.4) 34 (31.8) 2 (1.9)
16 (47.1) 18 (52.9) –
11 (91.7) 1 (8.3) –
Injury etiology HWB Flame Other
109 (81.3) 14 (10.4) 11 (8.2)
104 (82.5) 9 (7.1) 13 (10.3)
83 (77.6) 10 (9.3) 14 (13.1)
27 (79.4) 5 (14.7) 2 (5.9)
9 (75.0) 2 (16.7) 1 (8.3)
TBSA Median (IQR) Range
5.0 (3.0–10.0) 0.5–2.0
6.0 (4.0–11.0) 1.0–85.0
6.5 (4.0–12.0) 1.0–45.0
9.5 (4.8–9.5) 1.0–55.0
11.0 (7.0–18.0) 5.0–56
Depth injury Superficial PTa Deep PTa Full Thickness
88 (66.7) 36 (27.3) 8 (6.1)
78 (62.4) 38 (30.4) 9 (7.2)
56 (53.8) 42 (40.4) 6 (5.8)
20 (58.8) 6 (17.6) 8 (23.5)
8 (66.7) 2 (16.7) 2 (16.7)
Surgery Skin graft
23 (17.2)
37 (29.4)
39 (36.4)
12 (35.3)
7 (58.3)
Scar type None Normal Hypertrophic
102 (76.1) 14 (10.4) 18 (13.4)
88 (69.8) 13 (10.3) 25 (19.8)
69 (64.5) 7 (6.5) 31 (29.0)
29 (85.3) 1 (2.9) 4 (11.8)
9 (75.0) – 3 (25.0)
a
0.983
0.074
<0.001 (54.9) (21.8) (13.5) (9.8)
0.057
0.727
0.001
0.017
0.001
0.084
PT: partial thickness.
was nevertheless reduced to mild itch. Alternatively, current treatment strategies are not effective because other receptors or pathways may be involved in pruritus [20,21]. Pressure garments are known to have an anti-pruritic effect [11], which our results also suggest. However, our population was small (n=24) and we had an even smaller follow up (n=10). Pressure garments were hardly used in our population, because of the discomfort in a hot climate and low socioeconomic environment. Another possible treatment for pruritus is laser therapy. Depending on scar type and thickness different types of lasers and light sources can be used in the treatment of burn scars [22]. Among other benefits, it improves scar appearance and patients reported a 49% decrease in pruritus [23]. Studies have shown laser treatment to be safe and effective in both adults and
pediatric patients. A minimum of 3–4 procedures is recommended, with the use of an ablative fractional laser [22,24].
Table 3 – Reported itch scores by caregiver and percentage of anti-itch medication given. Itch Man Score
0 1 2 3 4 (n=134) (n=126) (n=107) (n=34) (n=12) n (%) n (%) n (%) n (%) n (%)
None Allergex Gabapentin Both
69 (51.5) 19 (14.2) 17 (12.7) 29 (21.6)
58 27 12 29
(46.0) (21.4) (9.5) (23.0)
50 (46.7) 26 (24.3) 8 (7.5) 23 (21.5)
14 (41.2) 7 (20.6) 1 (2.9) 12 (35.3)
4 (33.3) 6 (50.0) 1 (8.3) 1 (8.3)
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Table 4 – Given and prescribed doses gabapentin and Allergex. No itch, score 0 n (%)
Mild itch, score 1–2 n (%)
Severe itch, score 3–4 n (%)
Gabapentin, n =88 Less than prescribed dose Prescribed dose More than prescribed dose
2 (6.7) 28 (93.3) –
9 (18.4) 28 (57.1) 12 (24.5)
– 6 (66.7) 3 (33.3)
Allergex, n =130 Less than prescribed dose Prescribed dose More than prescribed dose
1 (2.7) 27 (73.0) 9 (24.3)
17 (21.2) 43 (53.8) 20 (25.0)
3 (23.1) 6 (46.1) 4 (30.8)
Medication
4.1.
0.006
0.048
Limitations
Several limiting factors may have influenced the results, such as a language barrier. The Dutch researchers did not speak the native languages(s) and communicated in English. Most of the caregivers and patients included in this study did not speak English as their first language. However, eventually almost all the information needed was obtained and understanding of the Itch Man Scale was assessed with the use of the NRS (correlation coefficient of 0.896). Also, for patients younger than 6 years the caregiver scored the Itch Man Scale, which may have been a source of bias. The correlation coefficient of 0.744 between the score of the caregiver and the child, older than six, showed that they agreed with each other in most of the cases, but still does not guarantee a score given by the caregiver consistent with the child younger than six.
4.2.
Recommendations
For further studies it is important to do a follow up on all the patients at different points in time after the burn, so the effect of treatment can be tracked without the risk of bias caused by drop-out from follow-up. For post-burn pruritus we recommend immediate anti itch treatment, as it starts within the first week after the incident. It is important to ensure complete compliance with the treatment program to get the best result. This study shows the compliance was not very high and could therefore have affected the results. Regular follow-up would be recommendable to ensure the best possible treatment is given.
5.
P-value
Conclusion
The current mainstay of pruritus treatment, antihistamines, does not seem as effective as it should be, as many children in this study still suffered from pruritus. Other treatment options, for example laser therapy, need to be further tested. The time since burn, TBSA, depth of injury and whether a skin graft was performed are predictors for pruritus, but these are factors that cannot be influenced. So still more research is needed to determine the exact mechanism of itch and find
treatment targets. This way an accurate treatment can be given that helps improve the quality of life for burn survivors.
Declaration of interest No conflict of interest to be disclosed.
Acknowledgements We would like to thank all the participants for their collaboration to this research. Also we wish to thank the employees at Red Cross War Memorial Hospital for their help during the data collection and J. Hagoort for his editorial review.
Formatting of funding sources This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. REFERENCES
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