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. 2019 Jul 16;7(7):CD005027.
doi: 10.1002/14651858.CD005027.pub5.

Interventions for morphea

Julia V de Albuquerque  1 , Brenda Ng Andriolo, Monica Ra Vasconcellos, Vinicius T Civile, Anne Lyddiatt, Virginia Fm Trevisani
Affiliations

Interventions for morphea

Julia V de Albuquerque et al. Cochrane Database Syst Rev. .

Abstract

Background: Morphea (morphoea) is an immune-mediated disease in which excess synthesis and deposition of collagen in the skin and underlying connective tissues results in hardened cutaneous areas. Morphea has different clinical features according to the subtype and stage of evolution of the disease. There is currently no consensus on optimal interventions for morphea.

Objectives: To assess the effects of treatments for people with any form of morphea.

Search methods: We searched the following databases up to July 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, and five trial registers. We checked the reference lists of included studies for further references to relevant randomised controlled trials.

Selection criteria: Randomised controlled trials of topical, intralesional, or systemic treatments (isolated or combined) in anyone who has been clinically diagnosed by a medical practitioner with any form of morphea. Eligible controls were placebo, no intervention, any other treatment, or different doses or duration of a treatment.

Data collection and analysis: We used standard methodological procedures expected by Cochrane. The primary outcomes were global improvement of disease activity or damage assessed by a medical practitioner or by participants, and adverse effects. Secondary outcomes were improvement of disease activity and improvement of disease damage. We used GRADE to assess the quality of the evidence for each outcome.

Main results: We included 14 trials, with a total of 429 randomised participants, aged between 3 and 76 years. There were juvenile and adult participants; over half were female, and the majority had circumscribed morphea, followed by linear scleroderma. The settings of the studies (where described) included a dermatologic centre, a national laboratory centre, paediatric rheumatology and dermatology centres, and a university hospital or medical centre.The studies evaluated heterogenous therapies for different types of morphea, covering a wide range of comparisons. We were unable to conduct any meta-analyses. Seven studies investigated topical medications, two evaluated intralesional medications, and five investigated systemic medications. The study duration ranged from seven weeks to 15 months from baseline.We present here results for our primary outcomes for our four key comparisons. All of these results are based on low-quality evidence.The included studies were at high risk of performance, detection, attrition, and reporting bias.Global improvement of disease activity or damage after treatment may be higher with oral methotrexate (15 mg/m², maximum 20 mg, once a week, for 12 months or until disease flare) plus oral prednisone (1 mg/kg a day, maximum of 50 mg, in a single morning dose, for three months, and one month with gradually decreased dose until discontinuation) than with placebo plus oral prednisone in children and adolescents with active morphea (linear scleroderma, generalised morphea or mixed morphea: linear and circumscribed) (risk ratio (RR) 2.31, 95% confidence interval (CI) 1.20 to 4.45; number needed to treat for an additional beneficial outcome (NNTB) 3; 1 randomised controlled trial (RCT); 70 participants, all juvenile). This outcome was measured 12 months from the start of treatment or until flare of the disease. Data were not available separately for each morphea type. There may be little or no difference in the number of participants experiencing at least one adverse event with oral methotrexate (26/46) or placebo (11/24) (RR 1.23, 95% CI 0.75 to 2.04; 1 RCT; 70 participants assessed during the 12-month follow-up). Adverse events related to methotrexate included alopecia, nausea, headache, fatigue and hepatotoxicity, whilst adverse events related to prednisone (given in both groups) included weight gain (more than 5% of body weight) and striae rubrae.One three-armed RCT compared the following treatments: medium-dose (50 J/cm²) UVA-1; low-dose (20 J/cm²) UVA-1; and narrowband UVB phototherapy. There may be little or no difference between treatments in global improvement of disease activity or damage, as assessed through the modified skin score (where high values represent a worse outcome): medium-dose UVA-1 phototherapy versus low-dose UVA-1 group: MD 1.60, 95% CI -1.70 to 4.90 (44 participants); narrowband UVB phototherapy versus medium-dose UVA-1 group: MD -1.70, 95% CI -5.27 to 1.87 (35 participants); and narrowband UVB versus low-dose UVA-1 group: MD -0.10, 95% CI -2.49 to 2.29 (45 participants). This RCT included children and adults with active morphea (circumscribed morphea, linear scleroderma (with trunk/limb variant and head variant), generalised morphea, or mixed morphea), who received phototherapy five times a week, for eight weeks. Outcomes were measured at eight weeks from the start of treatment.Safety data, measured throughout treatment, from the same RCT (62 participants) showed that treatment with UVA-1 phototherapy may cause mild tanning compared to narrowband UVB: narrowband UVB versus medium-dose UVA-1: RR 0.03, 95% CI 0.00 to 0.42; 35 participants; narrowband UVB versus low-dose UVA-1: RR 0.03, 95% CI 0.00 to 0.41; 45 participants. However, there may be no difference in the number of participants reporting mild tanning when comparing medium and low dose UVA-1 phototherapy (RR 1.00, 95% CI 0.91 to 1.10; 44 participants). Transient erythema was reported in three participants with narrowband UVB and no participants in the low- or medium-dose UVA-1 groups.

Authors' conclusions: Compared to placebo plus oral prednisone, oral methotrexate plus oral prednisone may improve disease activity or damage in juvenile active morphea (linear scleroderma, generalised morphea or mixed morphea: linear and circumscribed), but there may be a slightly increased chance of experiencing at least one adverse event.When medium-dose UVA-1 (50 J/cm²), low-dose UVA-1 (20 J/cm²), and narrowband UVB were compared against each other in treating children and adults with active morphea (circumscribed morphea, linear scleroderma, generalised morphea and mixed morphea), there may be little or no difference between these treatments on global improvement of disease activity or damage. UVA-1 phototherapy may cause more mild tanning than narrowband UVB, but there may be no difference between medium- and low-dose UVA-1 phototherapy. These results are based on low-quality evidence.Limitations of data and analyses include risk of bias and imprecision (small number of participants or events and wide confidence intervals). We encourage multicentre RCTs to increase sample size and evaluate, with validated tools, different treatment responses according to the subtypes of morphea and age groups.

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Conflict of interest statement

Julia V de Albuquerque: nothing to declare. Brenda NG Andriolo: nothing to declare. Monica RA Vasconcellos: nothing to declare. Anne Lyddiatt: nothing to declare. Vinicius T Civile: nothing to declare. Virginia FM Trevisani: nothing to declare.

Figures

1
1
A ‐ Confluent sclero‐atrophic lesions, with hypochromic, achromic and brownish areas on the thighs, generalised morphea; B ‐ sclero‐atrophic oval lesion with dyschromic areas and halo erythematosus in its right and inferior portion, active circumscribed morphea; C ‐ brown macula with discretely erythematous areas and irregular borders, circumscribed morphea in involution. Copyright © 2019 Monica RA Vasconcellos: reproduced with permission.
2
2
Linear scleroderma. A ‐ Sclero‐atrophic lesion involving the back of the hand and fingers, with deviation in the fourth and fifth chirodactyls; B – Streak of atrophy in the tongue (left) and dental implant defect (right); C – segmental sclero‐atrophic lesions in the trunk and limbs interspersed by hyper pigmented maculae. Copyright © 2019 Monica RA Vasconcellos: reproduced with permission.
3
3
Study flow diagram.
4
4
Risk of bias graph: review authors' judgements about each 'Risk of bias' item represented as percentages across all included studies.
5
5
Risk of bias summary: review authors' judgements about each 'Risk of bias' item for each included study.
1.1
1.1. Analysis
Comparison 1 Medium‐dose UVA‐1 (50 J/cm²) x Low‐dose UVA‐1 (20 J/cm²) phototherapy, Outcome 1 Modified Skin Score (MSS) at the end of the eight‐week treatment.
1.2
1.2. Analysis
Comparison 1 Medium‐dose UVA‐1 (50 J/cm²) x Low‐dose UVA‐1 (20 J/cm²) phototherapy, Outcome 2 Modified Skin Score (MSS) at last follow‐up visit (week 20).
1.3
1.3. Analysis
Comparison 1 Medium‐dose UVA‐1 (50 J/cm²) x Low‐dose UVA‐1 (20 J/cm²) phototherapy, Outcome 3 Number of participants with mild tanning.
1.4
1.4. Analysis
Comparison 1 Medium‐dose UVA‐1 (50 J/cm²) x Low‐dose UVA‐1 (20 J/cm²) phototherapy, Outcome 4 Ultrasound dermal density at the end of the eight‐week treatment.
1.5
1.5. Analysis
Comparison 1 Medium‐dose UVA‐1 (50 J/cm²) x Low‐dose UVA‐1 (20 J/cm²) phototherapy, Outcome 5 Ultrasound corium thickness at the end of the eight‐week treatment.
2.1
2.1. Analysis
Comparison 2 Narrowband UVB x Medium‐dose UVA‐1 (50 J/cm²) phototherapy, Outcome 1 Modified Skin Score (MSS) at the end of the eight‐week treatment.
2.2
2.2. Analysis
Comparison 2 Narrowband UVB x Medium‐dose UVA‐1 (50 J/cm²) phototherapy, Outcome 2 Modified Skin Score (MSS) at last follow‐up visit (week 20).
2.3
2.3. Analysis
Comparison 2 Narrowband UVB x Medium‐dose UVA‐1 (50 J/cm²) phototherapy, Outcome 3 Number of participants with mild tanning.
2.4
2.4. Analysis
Comparison 2 Narrowband UVB x Medium‐dose UVA‐1 (50 J/cm²) phototherapy, Outcome 4 Number of participants with transient erythema.
2.5
2.5. Analysis
Comparison 2 Narrowband UVB x Medium‐dose UVA‐1 (50 J/cm²) phototherapy, Outcome 5 Ultrasound dermal density at the end of the eight‐week treatment.
2.6
2.6. Analysis
Comparison 2 Narrowband UVB x Medium‐dose UVA‐1 (50 J/cm²) phototherapy, Outcome 6 Ultrasound corium thickness at the end of the eight‐week treatment.
3.1
3.1. Analysis
Comparison 3 Narrowband UVB X Low‐dose UVA‐1 (20 J/cm²) phototherapy, Outcome 1 Modified Skin Score (MSS) at the end of the eight‐week treatment.
3.2
3.2. Analysis
Comparison 3 Narrowband UVB X Low‐dose UVA‐1 (20 J/cm²) phototherapy, Outcome 2 Modified Skin Score (MSS) at last follow‐up visit (week 20).
3.3
3.3. Analysis
Comparison 3 Narrowband UVB X Low‐dose UVA‐1 (20 J/cm²) phototherapy, Outcome 3 Number of participants with mild tanning.
3.4
3.4. Analysis
Comparison 3 Narrowband UVB X Low‐dose UVA‐1 (20 J/cm²) phototherapy, Outcome 4 Number of participants with transient erythema.
3.5
3.5. Analysis
Comparison 3 Narrowband UVB X Low‐dose UVA‐1 (20 J/cm²) phototherapy, Outcome 5 Ultrasound dermal density at the end of the eight‐week treatment.
3.6
3.6. Analysis
Comparison 3 Narrowband UVB X Low‐dose UVA‐1 (20 J/cm²) phototherapy, Outcome 6 Ultrasound corium thickness at the end of the eight‐week treatment.
4.1
4.1. Analysis
Comparison 4 Medium‐dose (70 J/cm²) or Low‐dose (20 J/cm²) UVA‐1 phototherapy x No treatment, Outcome 1 Number of plaques with moderate to significant tanning.
4.2
4.2. Analysis
Comparison 4 Medium‐dose (70 J/cm²) or Low‐dose (20 J/cm²) UVA‐1 phototherapy x No treatment, Outcome 2 Number of plaques with painless erythema.
4.3
4.3. Analysis
Comparison 4 Medium‐dose (70 J/cm²) or Low‐dose (20 J/cm²) UVA‐1 phototherapy x No treatment, Outcome 3 Number of plaques with pruritus.
5.1
5.1. Analysis
Comparison 5 20 J/cm2 UVA x 10 J/cm² UVA phototherapy, Outcome 1 Number of participants with generalised tanning.
5.2
5.2. Analysis
Comparison 5 20 J/cm2 UVA x 10 J/cm² UVA phototherapy, Outcome 2 Number of participants with temporary pruritus.
5.3
5.3. Analysis
Comparison 5 20 J/cm2 UVA x 10 J/cm² UVA phototherapy, Outcome 3 Number of participants with increased erythema and exacerbated pain.
5.4
5.4. Analysis
Comparison 5 20 J/cm2 UVA x 10 J/cm² UVA phototherapy, Outcome 4 Number of participants with skin softening at the end of the seven‐week treatment.
6.1
6.1. Analysis
Comparison 6 20 J/cm2 UVA x 5 J/cm² UVA phototherapy, Outcome 1 Number of participants with generalised tanning.
6.2
6.2. Analysis
Comparison 6 20 J/cm2 UVA x 5 J/cm² UVA phototherapy, Outcome 2 Number of participants with temporary pruritus.
6.3
6.3. Analysis
Comparison 6 20 J/cm2 UVA x 5 J/cm² UVA phototherapy, Outcome 3 Number of participants with increased erythema and exacerbated pain.
6.4
6.4. Analysis
Comparison 6 20 J/cm2 UVA x 5 J/cm² UVA phototherapy, Outcome 4 Number of participants with skin softening at the end of the seven‐week treatment.
7.1
7.1. Analysis
Comparison 7 10 J/cm2 UVA x 5 J/cm² UVA phototherapy, Outcome 1 Number of participants with generalised tanning.
7.2
7.2. Analysis
Comparison 7 10 J/cm2 UVA x 5 J/cm² UVA phototherapy, Outcome 2 Number of participants with temporary pruritus.
7.3
7.3. Analysis
Comparison 7 10 J/cm2 UVA x 5 J/cm² UVA phototherapy, Outcome 3 Number of participants with skin softening at the end of the seven‐week treatment.
8.1
8.1. Analysis
Comparison 8 Photodynamic therapy × No Treatment, Outcome 1 Number of plaques with pigmentation.
8.2
8.2. Analysis
Comparison 8 Photodynamic therapy × No Treatment, Outcome 2 Number of plaques with burning sensation during phototherapy.
8.3
8.3. Analysis
Comparison 8 Photodynamic therapy × No Treatment, Outcome 3 Number of plaques with dryness.
8.4
8.4. Analysis
Comparison 8 Photodynamic therapy × No Treatment, Outcome 4 Number of plaques with erythema.
8.5
8.5. Analysis
Comparison 8 Photodynamic therapy × No Treatment, Outcome 5 Number of plaques with pruritus.
8.6
8.6. Analysis
Comparison 8 Photodynamic therapy × No Treatment, Outcome 6 Number of plaques with reduction in the skin score at the 12‐week follow‐up.
9.1
9.1. Analysis
Comparison 9 Fractional carbon dioxide laser × Low‐dose UVA‐1 (30 J/cm²) phototherapy, Outcome 1 Number of lesions with mild to moderate pain during therapy.
9.2
9.2. Analysis
Comparison 9 Fractional carbon dioxide laser × Low‐dose UVA‐1 (30 J/cm²) phototherapy, Outcome 2 Number of lesions with marked pain during therapy.
9.3
9.3. Analysis
Comparison 9 Fractional carbon dioxide laser × Low‐dose UVA‐1 (30 J/cm²) phototherapy, Outcome 3 Number of lesions with pruritus in first 24h.
9.4
9.4. Analysis
Comparison 9 Fractional carbon dioxide laser × Low‐dose UVA‐1 (30 J/cm²) phototherapy, Outcome 4 Number of lesions with hyperpigmentation.
9.5
9.5. Analysis
Comparison 9 Fractional carbon dioxide laser × Low‐dose UVA‐1 (30 J/cm²) phototherapy, Outcome 5 Number of lesions with persistent erythema.
9.6
9.6. Analysis
Comparison 9 Fractional carbon dioxide laser × Low‐dose UVA‐1 (30 J/cm²) phototherapy, Outcome 6 Ultrasound biomicroscopy dermal thickness at the 10‐week follow‐up.
9.7
9.7. Analysis
Comparison 9 Fractional carbon dioxide laser × Low‐dose UVA‐1 (30 J/cm²) phototherapy, Outcome 7 Clinical score at the 10‐week follow‐up.
9.8
9.8. Analysis
Comparison 9 Fractional carbon dioxide laser × Low‐dose UVA‐1 (30 J/cm²) phototherapy, Outcome 8 Participant satisfaction score at the 10‐week follow‐up.
9.9
9.9. Analysis
Comparison 9 Fractional carbon dioxide laser × Low‐dose UVA‐1 (30 J/cm²) phototherapy, Outcome 9 Number of lesions with good or very good improvement in the clinical score at the 10‐week follow‐up.
10.1
10.1. Analysis
Comparison 10 Polymerized collagen intralesional injection (0.2 to 1.0 mL / 1.66 to 8.3 mg weekly) × Methylprednisolone subcutaneous injection (maximum dose of 20 mg or 5.0 mL monthly) plus placebo intralesional injection, Outcome 1 Number of participants with short‐duration pain at injection site.
10.2
10.2. Analysis
Comparison 10 Polymerized collagen intralesional injection (0.2 to 1.0 mL / 1.66 to 8.3 mg weekly) × Methylprednisolone subcutaneous injection (maximum dose of 20 mg or 5.0 mL monthly) plus placebo intralesional injection, Outcome 2 Number of participants with pruritus.
10.3
10.3. Analysis
Comparison 10 Polymerized collagen intralesional injection (0.2 to 1.0 mL / 1.66 to 8.3 mg weekly) × Methylprednisolone subcutaneous injection (maximum dose of 20 mg or 5.0 mL monthly) plus placebo intralesional injection, Outcome 3 Number of participants with sclerosis.
10.4
10.4. Analysis
Comparison 10 Polymerized collagen intralesional injection (0.2 to 1.0 mL / 1.66 to 8.3 mg weekly) × Methylprednisolone subcutaneous injection (maximum dose of 20 mg or 5.0 mL monthly) plus placebo intralesional injection, Outcome 4 Skin score at the end of the three‐month treatment.
10.5
10.5. Analysis
Comparison 10 Polymerized collagen intralesional injection (0.2 to 1.0 mL / 1.66 to 8.3 mg weekly) × Methylprednisolone subcutaneous injection (maximum dose of 20 mg or 5.0 mL monthly) plus placebo intralesional injection, Outcome 5 Skin score at last follow‐up visit (month nine).
10.6
10.6. Analysis
Comparison 10 Polymerized collagen intralesional injection (0.2 to 1.0 mL / 1.66 to 8.3 mg weekly) × Methylprednisolone subcutaneous injection (maximum dose of 20 mg or 5.0 mL monthly) plus placebo intralesional injection, Outcome 6 Number of morphea lesions at the end of the three‐month treatment.
11.1
11.1. Analysis
Comparison 11 Oral methotrexate (15 mg/m², maximum 20 mg a week) plus oral prednisone × Placebo plus oral prednisone, Outcome 1 Clinical response at the end of the 12‐month treatment.
11.2
11.2. Analysis
Comparison 11 Oral methotrexate (15 mg/m², maximum 20 mg a week) plus oral prednisone × Placebo plus oral prednisone, Outcome 2 Number of participants with at least one adverse event.
11.3
11.3. Analysis
Comparison 11 Oral methotrexate (15 mg/m², maximum 20 mg a week) plus oral prednisone × Placebo plus oral prednisone, Outcome 3 Skin Score Rate (SSR) at the end of the 12‐month treatment.
11.4
11.4. Analysis
Comparison 11 Oral methotrexate (15 mg/m², maximum 20 mg a week) plus oral prednisone × Placebo plus oral prednisone, Outcome 4 Percentage thermal change at the end of the 12‐month treatment.
11.5
11.5. Analysis
Comparison 11 Oral methotrexate (15 mg/m², maximum 20 mg a week) plus oral prednisone × Placebo plus oral prednisone, Outcome 5 Number of participants with new lesions at the end of the 12‐month treatment.
12.1
12.1. Analysis
Comparison 12 Oral hydroxychloroquine (200 mg twice a day) plus topical corticosteroid x Oral methotrexate (15 mg a week) plus topical corticosteroid, Outcome 1 Modified Skin Score (MSS) at the end of the three‐month treatment.
12.2
12.2. Analysis
Comparison 12 Oral hydroxychloroquine (200 mg twice a day) plus topical corticosteroid x Oral methotrexate (15 mg a week) plus topical corticosteroid, Outcome 2 Number of participants with liver enzymes rise more than three times during the three‐month treatment.
12.3
12.3. Analysis
Comparison 12 Oral hydroxychloroquine (200 mg twice a day) plus topical corticosteroid x Oral methotrexate (15 mg a week) plus topical corticosteroid, Outcome 3 VAS for participants' estimate of skin tightness at the end of the three‐month treatment.
12.4
12.4. Analysis
Comparison 12 Oral hydroxychloroquine (200 mg twice a day) plus topical corticosteroid x Oral methotrexate (15 mg a week) plus topical corticosteroid, Outcome 4 VAS for participants' estimate of pruritus at the end of the three‐month treatment.
13.1
13.1. Analysis
Comparison 13 Topical tacrolimus 0.1% × Placebo, Outcome 1 Number of plaques with pruritus.
13.2
13.2. Analysis
Comparison 13 Topical tacrolimus 0.1% × Placebo, Outcome 2 Durometer score at the end of the 12‐week treatment.
13.3
13.3. Analysis
Comparison 13 Topical tacrolimus 0.1% × Placebo, Outcome 3 Plaque surface area at the end of the 12‐week treatment.
13.4
13.4. Analysis
Comparison 13 Topical tacrolimus 0.1% × Placebo, Outcome 4 Number of plaques with a reduced modified DIET score at the end of the 12‐week treatment.
13.5
13.5. Analysis
Comparison 13 Topical tacrolimus 0.1% × Placebo, Outcome 5 Modified DIET score at the end of the 12‐week treatment.
14.1
14.1. Analysis
Comparison 14 Oral calcitriol (0.75 μg increased to 1.25 μg/day) × Placebo, Outcome 1 Number of participants with transient hypercalciuria.
14.2
14.2. Analysis
Comparison 14 Oral calcitriol (0.75 μg increased to 1.25 μg/day) × Placebo, Outcome 2 Skin score at the end of the 9‐month treatment.
14.3
14.3. Analysis
Comparison 14 Oral calcitriol (0.75 μg increased to 1.25 μg/day) × Placebo, Outcome 3 Skin score at the end of the 15‐month follow‐up.
15.1
15.1. Analysis
Comparison 15 Tranilast plus topical betamethasone valerate 0.1% versus topical betamethasone valerate 0.1%, Outcome 1 Clinical score at the end of the three‐month treatment.
15.2
15.2. Analysis
Comparison 15 Tranilast plus topical betamethasone valerate 0.1% versus topical betamethasone valerate 0.1%, Outcome 2 Physician Global Assessment of Activity at the end of the three‐month treatment.
15.3
15.3. Analysis
Comparison 15 Tranilast plus topical betamethasone valerate 0.1% versus topical betamethasone valerate 0.1%, Outcome 3 Number of lesions with disease progression at the end of the three‐month treatment.
15.4
15.4. Analysis
Comparison 15 Tranilast plus topical betamethasone valerate 0.1% versus topical betamethasone valerate 0.1%, Outcome 4 Physician Global Assessment of Damage at the end of the three‐month treatment.
16.1
16.1. Analysis
Comparison 16 Traditional Chinese Medicine herbal tea plus herbal oil and vitamin B6 x Phenoxymethylpenicillin plus DAC base cream, Outcome 1 Number of participants with adverse events.
17.1
17.1. Analysis
Comparison 17 Acupuncture, hot herbal compress, and moxibustion plus Centella triterpenes tablets and vitamin E × Heparin sodium cream plus Centella triterpenes tablets and vitamin E, Outcome 1 Number of participants with significant clinical response at the end of the six‐month treatment.
17.2
17.2. Analysis
Comparison 17 Acupuncture, hot herbal compress, and moxibustion plus Centella triterpenes tablets and vitamin E × Heparin sodium cream plus Centella triterpenes tablets and vitamin E, Outcome 2 Number of participants with pain during treatment.
17.3
17.3. Analysis
Comparison 17 Acupuncture, hot herbal compress, and moxibustion plus Centella triterpenes tablets and vitamin E × Heparin sodium cream plus Centella triterpenes tablets and vitamin E, Outcome 3 Skin sclerosis score at the end of the six‐month treatment.
17.4
17.4. Analysis
Comparison 17 Acupuncture, hot herbal compress, and moxibustion plus Centella triterpenes tablets and vitamin E × Heparin sodium cream plus Centella triterpenes tablets and vitamin E, Outcome 4 Joint function score at the end of the six‐month treatment period.
17.5
17.5. Analysis
Comparison 17 Acupuncture, hot herbal compress, and moxibustion plus Centella triterpenes tablets and vitamin E × Heparin sodium cream plus Centella triterpenes tablets and vitamin E, Outcome 5 Joint pain score at the end of the six‐month treatment.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD005027.pub4

References

References to studies included in this review

Azimi 2013 {published data only}
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    1. Yan XN, Zhang JR, Zhang CQ, Tian Q, Chen L, Chen L. Efficacy observation on acupuncture and moxibustion combined with hot compress of TCM herbs for scleroderma. Zhongguo Zhen Jiu [Chinese Acupuncture & Moxibustion] 2013;33(5):403‐6. [CENTRAL: CN‐00918725] - PubMed
Zulian 2011 {published data only}
    1. Zulian F, Martini G, Vallongo C, Vittadello F, Falcini F, Patrizi A, et al. Methotrexate treatment in juvenile localized scleroderma: a randomized, double‐blind, placebo‐controlled trial. Arthritis and Rheumatism 2011;63(7):1998‐2006. [CENTRAL: CN‐00801715] - PubMed

References to studies excluded from this review

Bodemer 1999 {published data only}
    1. Bodemer C, et al. Localized scleroderma in childhood and therapeutic trial with calcitriol: A therapeutic option to define [[French] Sclerodermies localisees de l'enfant et tentative therapeutique par calcitriol: Une possibilite therapeutique a definir]. Annales de Dermatologie et de Venereologie 1999;126(10):725‐726. - PubMed
Didenko 1978 {published data only}
    1. Didenko IG. Therapeutic effectiveness of ultrasonics and lidase phonophoresis in various forms of scleroderma. Vestnik Dermatologii i Venerologii 1978;6:76‐79. [CENTRAL: CN‐01131746] - PubMed
Dortu 1974 {published data only}
    1. Dortu J. Evaluation of Elarzone‐Dausse phlebology. Phlebologie 1974;27(3):381‐384. [PUBMED: 4614284] - PubMed
Dytoc 2014 {published data only}
    1. Dytoc M, Wat H, Cheung‐Lee M, Sawyer D, Ackerman T, Fiorillo L. Evaluation of the efficacy and safety of topical imiquimod 5% for plaque‐type morphea: a multicenter, prospective, vehicle‐controlled trial. Journal of Cutaneous Medicine & Surgery 2015;19(2):132‐139. [CENTRAL: CN‐01097258] - PubMed
Hu 1996 {published data only}
    1. Hu G, Zhu Y, Ran LH, Wang ZY. Clinical observation on the efficacy of Prostaglandin E1 and Propylene glycol alginate sodium in the treatment of scleroderma. Chinese journal of dermatology 1996;29(4):284‐285. [CENTRAL: CN‐00843757]
Smirnov 1998 {published data only}
    1. Smirnov A. Gonadotherapy as a treatment of patients with localized scleroderma. Journal of the European Academy of Dermatology & Venereology 7‐11 Ocober 1998;11(Suppl 2):S273.
Wang 2008 {published data only}
    1. UVA1 Light for Treatment of Scleroderma and Similar Conditions. clinicaltrials.gov/ct2/show/NCT00476801 (first received 22 May 2007).
    1. Wang F, Garza LA, Cho S, Kafi R, Hammerberg C, Quan T, et al. Effect of increased pigmentation on the antifibrotic response of human skin to UV‐A1 phototherapy. Archives of dermatology 2008;144(7):851‐58. [CENTRAL: CN‐00649884] - PMC - PubMed

References to studies awaiting assessment

NCT00812188 {unpublished data only}
    1. NCT00812188. A prospective, open label trial of high dose UVA‐1, 3x/week or medium dose UVA‐1, 3x/week vs. fluocinonide 0.05% cream treatment of morphea. clinicaltrials.gov/ct2/show/record/NCT00812188 (first received 18 December 2008).
NCT01799174 {unpublished data only}
    1. NCT01799174. Treatment study comparing UVA‐1 phototherapy versus placebo treatment for morphea. clinicaltrials.gov/ct2/show/NCT01799174 (first received 26 February 2013).

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Publication types