Systematic review on antipruritic therapies for patients with Epidermolysis bullosa

Figures & data

Figure 1. PRISMA flowchart with the number of records identified and considered for inclusion.

Table 1. Study characteristics.

	n = 21
	n	%
EB type
EBS	3	14.3%
DEB	11	52.4%
RDEB only	9	42.9%
JEB	1	4.8%
KEB	0
Mixed subtypes (n = 408; RDEB 251, DDEB 22, DEB undefined 6, EBS 69, JEB 56, unknown 4)	6	28.6%
(Sub-) Type distribution
EBS	90	16.8%
JEB	61	11.4%
DDEB	26	4.9%
RDEB	353	65.9%
DEB undefined	6	1.1%
Focus on itch
Primary endpoint	3	14.3%
Secondary endpoint	16	76.2%
Exploratory endpoint	1	4.8%
Not specified	1	4.8%
Level of evidence
OCEBM level 1	0
OCEBM level 2	9	42.9%
OCEBM level 3	10	47.6%
OCEBM level 4	2	9.5%
OCEBM level 5	0
Age group
Adult	2	9.5%
Pediatric	5	23.8%
Any age	13	61.9%
Not specified	1	4.8&
Geographical location
Africa	0
Asia	3	14.3%
Australia	1	4.8%
Europe	7	33.3%
Middle East	0
North America	6	28.6%
South America	0
Multiple continents	4	19.0%
Not specified	0
Center
Monocentre	12	57.1%
Multicentre	9	42.9%
Phase
Phase I	0
Phase I/II	5	23.8%
Phase II	4	19.0%
Phase II/III	1	4.8%
Phase III	3	14.3%
Phase IV	0
Pilot trial	1	4.8%
Not specified	7	33.3%
Randomization
Randomized	9	42.9%
Non-randomized	9	42.9%
Not specified	3	14.3%
Assignment
Single group assignment	9	42.9%
Parallel group assignment	3	14.3%
Cross-over assignment	3	14.3%
Intra-patient controlled	4	19.0%
Not specified	2	9.5%
Blinding
Open label	12	57.1%
Single blind	0
Double blind	7	33.3%
Not specified	2	9.5%
Comparator
Baseline	14	66.7%
Placebo	7	33.3%

Figure 2. Summary of risk of bias assessment for included studies using the Cochrane Collaboration tool.

Figure 3. Number of outcome measurement instruments applied to assess itch, QoL or disease severity.

BEBSS: Birmingham Epidermolysis Bullosa Severity Score; DLQI: Dermatology Life Quality Index; EBDASI: Epidermolysis Bullosa Disease Activity and Scarring Index; GSS: global severity score; iscorEB: instrument for scoring clinical outcomes of research for epidermolysis bullosa; NRS: numerical rating scale; PedsQL: Pediatric Quality of Life Inventory; QOLEB: quality of life evaluation in epidermolysis bullosa; TBSA: total body surface area; VAS: visual analogue scale.

Table 2. Measurement instruments used to measure itch, QoL and disease severity.

Author/year	Treatment approach	Definition of outcome	Measurement instrument	Items	Focus	Creation
Itch
Local
Fivenson et al. 2003	Graftskin therapy	Pruritus at the graftskin treatment site	Not reported	N/A	N/A	N/A
Venugopal et al. 2013	Allogeneic fibroblasts in 2% albumin suspension	Local itch	VAS (0–10)	Single item	Generic	Complete validated questionnaire
Gorell et al. 2015	Helicoll Collagen I Wound Dressing	Level of wound pruritus	VAS 0–4	Single item	Generic	Complete validated questionnaire
Schwieger-Briel et al. 2017	Oleogel-S10 and non-adhesive wound dressing	Wound itch	VAS (1–10)	Single item	Generic	Complete validated questionnaire
Wally et al. 2018	Diacereine 1%	Local pruritus	VAS (0–10)	Single item	Generic	Complete validated questionnaire
Murrell et al. 2020	Allantoin 0% (SD-101–0.0)	Change from baseline in patient-reported itching	Itch Man Pruritus Assessment Tool	Single item	Generic	Complete validated questionnaire
Paller et al. 2020	Allantoin 6% (SD-101–6.0)	Change from baseline in patient-reported itching	Itch Man Pruritus Assessment Tool	Single item	Generic	Complete validated questionnaire
Chiou et al. 2020	Serlopitant	Change in NRS during dressing changes	11- point NRS	Single item	Generic	Complete validated questionnaire
Guttmann-Gruber et al. 2021	Low-dose calcipotriol ointment	Pruritus score	VAS (0–10)	Single item	Generic	Complete validated questionnaire
Systemic
Neufeld-Kaiser et al. 1997	Cyproheptadine	Levels of itching	Not reported	N/A	N/A	N/A
Danial et al. 2015	Mixed	Pruritus relief	5-point Likert scale (–2 = relieves itch a lot, −1 = relieves itch a little, 0 = no change, 1 = increases itch a little, 2 = increases itch a lot)	Singel item	Generic	Complete validated questionnaire
Petrof et al. 2015	Allogeneic bone marrow–derived mesenchymal stromal cells	Pruritus	Pruritus score child version (0–10)	Multiple item	Generic	Complete validated questionnaire
Chiaverini et al. 2015	Erythromycin	Itch severity	VAS	Single item	Generic	Complete validated questionnaire
Chiaverini et al. 2016	Epigallocatechin-3-gallate	Itch	VAS	Single item	Generic	Complete validated questionnaire
Chiou et al. 2020	Serlopitant	Weekly change in the NRS itch score	11- point NRS	Single item	Generic	Complete validated questionnaire
Rashidghamat et al. 2020	Allogeneic bone marrow–derived mesenchymal stromal cells	Itch	Leuven itch scale	Single item	Generic	Complete validated questionnaire
Fujita et al. 2021	Multilineage-differentiating stress-enduring (Muse) cells	Change in VAS for itch	VAS (–100 to 100)	Single item	Generic	Complete validated questionnaire
Kiritsi et al. 2021	Allogeneic ABCB5-positive mesenchymal stem cells (allo-APZ2-EB)	Median itch score	NRS (0–10)	Single item	Generic	Complete validated questionnaire
Lee et al. 2021	Allogeneic umbilical cord blood–derived mesenchymal stem cells	Pruritus	VAS (0–10)	Single item	Generic	Complete validated questionnaire
Chen et al. 2021	Omalizumab	Pruritus score	VAS (0–10)	Single item	Generic	Complete validated questionnaire
Schräder et al. 2021	Cannabinoid-based medicines (CBM) – THC only, THC/CBD, CBD ony	Overall average daily itch	NRS (0–10)	Singel item	Generic	Complete validated questionnaire
		Overall prutius	5-point Likert scale	Singel item	Generic	Complete validated questionnaire
Mosallaei et al. 2022	Gentamicin	Improvement of pruritus	5-D pruritus scale	Multiple item	Generic	Complete validated questionnaire
Quality of life
Fivenson et al. 2003	Graftskin therapy	Quality of life	N/A	N/A	N/A	N/A
Venugopal et al. 2013	Allogeneic fibroblasts in 2% albumin suspension	Quality of life	QOLEB	Multiple item	EB-specific	Complete validated questionnaire
Petrof et al. 2015	Allogeneic bone marrow–derived mesenchymal stromal cells	Quality of life assessed by children	PedsQL score (child version)	Multiple item	Generic	Complete validated questionnaire
		Quality of life assessed by parents	PedsQL score (parent version)	Multiple item	Generic	Complete validated questionnaire
Wally et al. 2018	1% Diacereine	Quality of life	Questionnaire (8 questions)	Multiple item	EB-specific	Self-assembled questionnaire
Rashidghamat et al. 2020	Allogeneic bone marrow–derived mesenchymal stromal cells	Quality of life	QOLEB	Multiple item	EB-specific	Complete validated questionnaire
Fujita et al. 2021	Multilineage-differentiating stress-enduring (Muse) cells	Quality of life	N/A	N/A	N/A	N/A
Kiritsi et al. 2021	Allogeneic ABCB5-positive mesenchymal stem cells (allo-APZ2-EB)	Quality of life	QOLEB	Multiple item	EB-specific	Complete validated questionnaire
Lee et al. 2021	Allogeneic umbilical cord blood–derived mesenchymal stem cells	Quality of life	QOLEB	Multiple item	EB-specific	Complete validated questionnaire
Chen et al. 2021	Omalizumab	Quality of life	DLQI	Multiple item	Generic	Complete validated questionnaire
Mosallaei et al. 2022	Gentamicin	Quality of life	Skindex-16	Multiple item	Generic	Complete validated questionnaire
Disease severity
Petrof et al. 2015	Allogeneic bone marrow–derived mesenchymal stromal cells	Efficacy measure	BEBSS	Multiple item	EB-specific	Complete validated questionnaire
		Efficacy measure	GSS score (0–12)	N/A	N/A	N/A
Rashidghamat et al. 2020	Allogeneic bone marrow–derived mesenchymal stromal cells	Disease severity	BEBSS	Multiple item	EB-specific	Complete validated questionnaire
		Disease severity	EBDASI	Multiple item	EB-specific	Complete validated questionnaire
Kiritsi et al. 2021	Allogeneic ABCB5-positive mesenchymal stem cells (allo-APZ2-EB)	Disease severity	EBDASI	Multiple item	EB-specific	Complete validated questionnaire
		Disease severity	IscorEB	Multiple item	EB-specific	Complete validated questionnaire
Lee et al. 2021	Allogeneic umbilical cord blood–derived mesenchymal stem cells	Disease severity	BEBSS	Multiple item	EB-specific	Complete validated questionnaire
		Body surface affected by EB	TBSA (%)	N/A	N/A	N/A
Chen et al. 2021	Omalizumab	Disease severity	BEBSS	Multiple item	EB-specific	Complete validated questionnaire
Schräder et al. 2021	Cannabinoid-based medicines (CBM) – THC only, THC/CBD, CBD only	Overall EB symptoms	5-point Likert scale	Singel item	Generic	Complete validated questionnaire
Mosallaei et al. 2022	Gentamicin	Disease severity	EBDASI	Multiple item	EB-specific	Complete validated questionnaire

Table 3. Overview of local and systemic treatment modalities reporting on itch outcomes for EB patients.

Author/year	Treatment approach	Dosage and frequency	EB type	Number of patients	Child/adult	Comperator	Primary purpose	Endpoint assessment	Treatment efficacy itch	Treatment efficacy QoL	Treatment efficacy disease severity	Level of evidence
Cell therapy
Local therapies
Venugopal et al. 2013	Allogeneic fibroblasts in 2% albumin suspension	Intralesional injection into wound base (0.25 mL/cm^2 containing 5 × 10^6 fibroblasts or suspension solution alone)	RDEB	5	Adult	Placebo	Wound healing	Month 12	No change VAS local itch between the treatment groups (p > 0.40)	QOLEB improvement not significant (greater improvement in the psychosocial than the functional dimension)	N/A	2
Fivenson et al. 2003	Graftskin therapy	Single transplantation per site (96 sites in total)	EBS (3), JEB (1), RDEB (5)	9	Child	Baseline	Wound healing	Weeks 4 and 12, and between weeks 20 and 28	Decreased pruritus at the graftskin treatment sites in 5 of 9 patients	Improved quality of life	N/A	3
Systemic therapies
Petrof et al. 2015	Allogeneic bone marrow derived mesenchymal stromal cells	Three i.v. infusions (each dose 1–3 × 10^6 cells/kg) on day 0, 7 and 28	RDEB	10	Child	Baseline	Safety	Days 60, 180	Mean difference pruritus score (0–10) from baseline −1.3 (95% CI −4.2, 1.5), −1.3 (95% CI −4.2, 1.5); n = 3	Mean difference PedsQL (child version, lower is improvement) from baseline −5.2 (95% CI −25.6, 15.2), −2.8 (95% CI −18.6, 13.0); n = 5	Mean difference BEBSS from baseline −5.2 (95% CI −10.7, 0.3), −6.9 (95% CI −12.7, −1.1)	3
										Mean difference PedsQL (parent version, lower is improvement) from baseline −4.4 (95% CI −8.1, −0.7), −2.9 (95% CI −7.5, 1.8); n = 8	Mean difference GSS from baseline −2.4 (95% CI −3.4, −1.4), −1.6 (95% CI −2.96, −0.24)
Rashidghamat et al. 2020	Allogeneic bone marrow–derived mesenchymal stromal cells	Two i.v. infusions 2–4 × 10^6 cells/kg on day 0 and 14	RDEB	10	Adult	Baseline	Safety, wound healing	Days 28 and 60	Leuven Itch Scale – Frequency mean reduction 13.89 (95% CI, 3.76–24.02, significant), 18.75 (95% CI, 9.07–28.43, significant) – Severity mean reduction 15.44 (95% CI, 4.47–26.42, significant), 15.16 (95% CI, −1.74 to 32.05, significant) – Consequences of itch mean reduction 12.64 (95% CI, 0.40–24.88, significant), 17.21 (95% CI, 6.40–28.01, significant)	Mean improvement QOLEB at days 28 and 60 of 1.89 (95% CI, –0.87 to 4.65) and 3.13 (95% CI, –0.26 to 6.51)	Mean reduction BEBSS 0.33 (95% CI, −0.3 to 0.97) and 1.61 (95% CI, −0.05 to 3.27)	3
											Minimal change EBDASI
Fujita et al. 2021	Multilineage-differentiating stress-enduring (Muse) cells	Single infusion 1.5 × 10^7 cells (2.98 ± 0.61 × 10^5 cells/kg)	RDEB (2), DDEB (3)	5	Both	Baseline	Wound healing	Week 4	No change on VAS itch; temporary worsening at weeks 12 and 20 throughout a 52 weeks surveillance time	No change	N/A	3
Kiritsi et al. 2021	Allogeneic ABCB5-positive dermal mesenchymal stem cells (allo-APZ2-EB)	Three i.v. infusions 2 × 10^6 cells/kg on day 0, 17 and 35	RDEB	16	Both	Baseline	Disease severity	Week 12	Median reduction NRS itch from baseline by 14.3% (0%–42.9%, not significant); greatest reduction observed at day 35 from baseline by 14.3% (0%–42.9%, p = 0.033)	QOLEB median change from baseline (higher is worsening) 6.5% (–18.8% to 15.4%; not significant)	EBDASI median reduction 3.4% (0.0%–9.4%, not significant) – EBDASI activity score median reduction 13.0% (2.9%–30%, p = 0.049)	3
											IscorEB median reduction 8.1% (–2.7% to 23.8%, not significant) – IscorEB-c median reduction 18.2% (1.9%–39.8%, p = 0.037)
Lee et al. 2021	Allogeneic umbilical cord blood–derived mesenchymal stem cells	Three i.v. injections (1 × 10^6 to 3 × 10^6 cells/kg) day 0, 14, 28	RDEB	6	Both	Baseline	Safety, disease severity	Day 56	Significant reduction in mean itch VAS by −2 points (95% CI, −3.76 to −0.24)	Significant improvement of QOLEB by 6.2 (CI 95%, –8.69, –3.65)	Significant decrease in mean BEBSS by 5.6 points (95% CI, −7.39 to −3.86)	3
											Significant decrease in mean TBSA by 5.4 points (95% CI, −8.14 to −2.61)
Protein therapy
Local therapies
Gorell et al. 2015	Helicoll Collagen I Wound Dressing	Weekly application to wound	RDEB	10	Both	Baseline	Wound healing	Weekly until week 8 after application	Average wound pruritus VAS (0–4) decrease 0.89, p = 0.004	N/A	N/A	2
Small molecules
Local therapies
Schwieger-Briel et al. 2017	Oleogel-S10 and non-adhesive wound dressing	1 cm or 125 µL or 115 mg Oleogel-S10 per cm2 wound area (corresponds to thickness of approximately 1 mm) and covered with a non-adhesive wound dressing (Mepilex^®) on Day 0. Oleogel-S10 was administered at wound dressing changes about every 24 to 48 hours	RDEB (9), DDEB (1)	10	Both	Placebo	Wound healing	Day 14 or 28	No change on wound itch VAS	N/A	N/A	2
Wally et al. 2018	Diacereine 1%	2.0 g of cream (i.e., 20.0 mg of diacerein) daily to defined skin area	EBS	15	Child	Placebo	Blister formation	Week 4	Localized itch VAS: No change (over time or between groups)	No significant change	N/A	2
Murrell et al. 2020	Allantoin 0% (SD-101-0.0)	Once a day to the entire body	EBS (8), RDEB (40), JEB (17)	87	Both	Baseline	Wound healing	Month 3	Itch Man Pruritus Assessment Tool mean improvement −0.7 (SE 0.2) n = 80	N/A	N/A	2
Paller et al. 2020	Allantoin 6% (SD-101-6.0)	Once a day to the entire body	EBS (18), RDEB (119), JEB (32)	Verum: 82 Placebo: 87	Both	Placebo	Wound healing	Day 7 (month 3 data not shown)	Itch Man Pruritus Assessment Tool mean improvement (p = 0.262) Verum −0.5 (SE 0.15) n = 77 Placebo −0.3 (SE 0.14) n = 79	N/A	N/A	2
Guttmann-Gruber et al. 2021	Low-dose calcipotriol ointment	Daily application 0.05 µg/g calcipotriol in ultraphil ointment	RDEB	6	Both	Placebo	Wound healing	Day 28	Improvement of local itch VAS verum to 1.83 vs placebo 5.52 (p < 0.0001)	N/A	N/A	2
Systemic therapies
Chiaverini et al. 2016	Epigallocatechin-3-gallate	Depend on the patient’s weight (from 400 to 800 mg a day)	RDEB	17	Both	Placebo	Blister formation	Month 4	Evolution of VAS itch (end of the period – beginning of the period) non significant improvement p = 0.38 Verum − 1.17 ± 3.53 (n = 12) Placebo 0 ± 2.16 (n = 14)	N/A	N/A	2
Chiou et al. 2020	Serlopitant	Loading dose of 3 tablets (15 mg), followed by 8 weeks of treatment with 5 mg	RDEB (13), JEB (1)	Verum: 7 Placebo: 7	Both	Placebo	Pruritus	Week 8	0.64-point reduction in itch NRS relative to placebo (p = 0.11)	N/A	N/A	2
									No change in itch NRS during dressing changes (p = 0.85)
Neufeld-Kaiser et al. 1997	Cyproheptadine	Standard dosage daily (Physician’s Desk Reference. 48th ed. Montvale, NJ: Medical Economics Data Production Co; 1994:1513)	EBS	10	N/A	Baseline	Blister formation (number of blisters lanced each day)	Week 6	3 patients reported improvement of itch	N/A	N/A	3
Chiaverini et al. 2015	Erythromycin	<10 kg: 250 mg per day; 10–15 kg: 500 mg per day; 15–25 kg: 750 mg per day; 25–35 kg: 1000 mg per day	EBS	6	Child	Baseline	Blister formation	Month 5	No change on VAS itch	N/A	N/A	3
Chen et al. 2021	Omalizumab	150 mg s.c. every 4 weeks for at least 3 cycles	RDEB	11	Both	Baseline	Clinical improvement	At the last treatment cycle (individual)	Reduction VAS pruritus by 42% (p < 0.0001) at last cycle in ten out of eleven patients (one patient terminated the treatment because of poor response)	Decreased DLQI values (lower is improvement) at last cycle, p < 0.0001	Reduced by 15%, p < 0.0005 at last cycle	3
Mosallaei et al. 2022	Gentamicin	Three patients daily i.v. gentamicinsulfate at a dosage of 7.5 mg/kg daily for 14 days Two patients with the high dosage of 10mg/kg daily for 28 days	JEB	5	Child	Baseline	Change in expression of laminin 332	3 months after last dose	Improvement (3), no change (1), worsening (1) on 5-D pruritus scale	Skindex-16 survey (2): Symptom scores stable, downward trends in emotions and functioning components	EBDASI (2): Data incomplete	3
Survey studies
Schräder et al. 2021	Cannabinoid-based medicines (CBM) – THC only, THC/CBD, CBD only	Predominantly inhaled, topical and oral, and sublingual; mostly at least once a day	RDEB (37), DDEB (8), EBS (17), JEB (8)	71	Both	Baseline	Effects on symptoms	N/A	Median pruritus change-score: − 3, IQR: − 1.25 to − 5 [p < 0.001, 95% CI 2.59–3.10])	N/A	46/48 (95.8%) improvement, 1/48 (2.1%) no change, 1/48 (2.1%) worsening of overall EB symptoms on 5-point likert scale	4
									40/44 (90.9) improvement, 3/44 (6.8%) no change, 1/44 (2.3%) worsening on overall pruritus 5-point Likert scale

Table 4. Adverse events reported in clinical studies.

Author/year	Treatment approach	Number of patients	Adverse events	Type of adverse event	Treatment related adverse events
Cell therapy
Local therapies
Venugopal et al. 2013	Allogeneic fibroblasts in 2% albumin suspension	5	N/A	N/A	0
Fivenson et al. 2003	Graftskin therapy	9	1	N/A	Postoperative wound infection (1)
Systemic therapies
Petrof et al. 2015	Allogeneic bone marrow derived mesenchymal stromal cells	10	163	Most frequent: DMSO odor (28), skin/mucosal blsiters/wounds (18), respiratory tract infections (10), diarrhea (9), skin infections (7), vomiting (6), pruritus (4)	40 – DMSO odor (28), Skin/mucosal blisters/wounds (2), pruritus (2), nausea (2), fine hair growth (1), milia (1), rash (1), abdominal pain (1), increased appetite (1), bradycardia (1)
Rashidghamat et al. 2020	Allogeneic bone marrow–derived mesenchymal stromal cells	10	9	N/A	0
Fujita et al. 2021	Multilineage-differentiating stress-enduring (Muse) cells	5	N/A	Stomach pain (grade 3), acquired lacrimal stricture (grade 2), fever (grade 1), gastroenteritis (grade 1), upper respiratory tract infection (grade 1), paraesthesia of the upper arms (grade 1)	Paresthesia 24h after infusion resolved within 14 days (1)
Kiritsi et al. 2021	Allogeneic ABCB5-positive mesenchymal stem cells (allo-APZ2-EB)	16	72	Most frequent: Infection or infestation (8), gastrointestinal disorders (6), blood and lymphatic disorders (4), eye disorders (2), hypersesnitivity (2)	Hypersensitivity reactions (2, serious but resolved without sequelae shortly after withdrawal of treatment), mild lymphadenopathy (1)
Lee et al. 2021	Allogeneic umbilical cord blood–derived mesenchymal stem cells	6	13	Wound infection (4), general condition deterioration (1), dizziness (1), acute gastritis (1), nausea (1), fever (1), H. zoster (1), upper resp tract infection (1), lacrimal duct obstruction (1), epistaxis (1)	2
Protein therapy
Local therapies
Gorell et al. 2015	Helicoll Collagen I Wound Dressing	10	N/A	Most frequent: Pain during dressing changes (5), pruritus at a target wound (4), and foul-smelling exudate (2)	N/A
Small molecules
Local therapies
Schwieger-Briel et al. 2017	Oleogel-S10 and non-adhesive wound dressing	10	The substance was tolerated very well without any complaints of stinging or burning	N/A	N/A
Wally et al. 2018	Diacereine 1%	15	Verum 5 (none in the treatment area) Placebo 8 (none in the treatment area)	Most frequently: Pruritus (verum 1, placebo 0), Fever (verum 1, placebo 3)	0
Murrell et al. 2020	Allantoin 0% (SD-101-0.0)	87	N/A	N/A	N/A
Paller et al. 2020	Allantoin 6% (SD-101-6.0)	Verum: 82 Placebo: 87	Verum 71 Placebo 61	AEs Occurring in ≥ 5% of Patients, most frequent: worsening of pruritus (verum 9, placebo 8), nasopharyngitis (verum 11, placebo 3)	Verum 15 (TrAEs occurring in ≥2% of Patients, most frequent: generalized or localized pruritus 6, generalized pruritus 2, wound 2, blister 2) Placebo 19 (TrAEs occurring in ≥2% of Patients, most frequent: generalized or localized pruritus 5, generalized pruritus 0, wound 2, blister 2)
Guttmann-Gruber et al. 2021	Low-dose calcipotriol ointment	6	N/A	N/A	0
Systemic therapies
Chiaverini et al. 2016	Epigallocatechin-3-gallate	17	Verum: 26 Placebo: 16 p = 0.256	Most frequent: Upper respiratory tract infection (verum 5, placebo 3), diarrhea (2), esophageal pain (verum 2, placebo 0), epidermoid carcinoma (verum 2, placebo 1)	Verum: 5 Placebo: 3
Chiou et al. 2020	Serlopitant	Verum: 7 Placebo: 7	N/A	N/A	Most frequent: nausea (verum 2, placebo 1), diarrhea (verum 1, placebo 0), headache (1)
Neufeld-Kaiser et al. 1997	Cyproheptadine	10	N/A	Drowsiness, increased appetite, irritability	N/A
Chiaverini et al. 2015	Erythromycin	6	5	N/A	0
Chen et al. 2021	Omalizumab	12	N/A	N/A	N/A
Mosallaei et al. 2022	Gentamicin	5	0	N/A	N/A
Survey studies
Schräder et al. 2021	Cannabinoid-based medicines (CBM) – THC only, THC/CBD, CBD only	71	45	Dry mouth (20), cough/wheezing (13), dry/red eyes (12), fatigue (10), dizziness/lightheadedness (7), paranoia (3), problems with memory/attention (3), problems with coordination (3)	N/A
Danial et al. 2015	Bathing products	146	N/A	N/A	N/A
	Moisturizers
	Topical products
	Oral medication taken for pruritus
	Oral medication taken for pain
	Oral medication taken for sleep
	Dressings
	Complementary/alternative methods

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Data availability statement

The data that support the findings of this review are available from the corresponding authors upon reasonable request.