Hydrogen helps with psoriasis and parapsoriasisScientific Research

псориазис
Authors:

Qinyuan Zhu, Yueshen Wu, Yongmei Li, Zihua Chen, Lanting Wang, Hao Xiong, Erhong Dai, Jianhua Wu, Bin Fan, Li Ping & Xiaoqun Luo

DOI: 10.1038

Published on: 23/05/2018

Positive effects of hydrogen-water bathing in patients of psoriasis and parapsoriasis en plaques

https://doi.org/10.1038/s41598-018-26388-3

Qinyuan Zhu, Yueshen Wu, Yongmei Li, Zihua Chen, Lanting Wang, Hao Xiong, Erhong Dai, Jianhua Wu, Bin Fan, Li Ping &  Xiaoqun Luo

Abstract

Psoriasis and plaque psoriasis are chronic inflammatory skin diseases, both of which represent treatment challenges and compromise quality of life in daily practice. Reactive oxygen species (ROS) have been shown to be involved in the pathogenesis of chronic inflammatory diseases. We now report that hydrogen water is an effective ROS scavenger that significantly and rapidly improves disease severity and quality of life in patients with psoriasis and plaque psoriasis. At week 8, our parallel-controlled study showed that 24.4% (10/41) of patients who received the hydrogen water bath had at least an improvement in the Psoriasis Area Severity Index (PASI) compared to 2.9% of patients 75% (1/34). Control group (Pc = 0.022, OR = 0.094, 95% CI = [0.011, 0.777]). In the bathing patients, 56.1% (23/41) had at least a 50% improvement in the PASI score compared to 17.7% (6/34) in the control group (P=0.001, OR = 0.168, 95%) CI = [ 0.057, 0.492]). Significant improvement in itching was also observed (P = 3.94 × 10-4). In addition, at week 8, 33.3% (2/6) of patients with plaque parapsoriasis had a complete response to these chronic inflammatory skin conditions and 66.7% (4/6) had a partial response.

Results

Improve psoriasis
A total of 41 patients with psoriasis were assigned to the hydrogen water bath treatment group and 34 patients were assigned to the control group. Treatment groups were well balanced with respect to demographics and baseline characteristics (Table 1). Only one patient in the control group was discontinued due to lack of improvement during the week 2 study period and was counted as a non-responder in the control group. After 8 weeks of bath treatment, the reaction was obvious. At week 8, the mean Psoriasis Area Severity Index (PASI) score and mean Visual Analogue Score (VAS) score in the hydrogen water bath group were 5.8 and 0, respectively, significantly lower than the baseline scores (P=7.08 × 10-6 ; P = 2.42 × 10−5).

Table 1 Characteristics of the psoriasis patients.

From: Positive effects of hydrogen-water bathing in patients of psoriasis and parapsoriasis en plaques

The Hydrogen-water bathing groupThe control group
BaselineWeek 8BaselineWeek 8
No41413433
Sex(male/female)24/1724/1718/1618/15
Age40 ± 15 (18–78)40 ± 15 (18–78)39 ± 12 (18–72)39 ± 13 (18–72)
BMI23.8 ± 3.8 (17.5–35.5)23.7 ± 3.9 (17.2–35.6)23.1 ± 4.2 (15.5–31.4)23.0 ± 4.6 (15.3–31.4)
Waistline (cm)82.7 ± 10.3 (63.3–103.3)82.8 ± 9.8 (63.3–103.3)76.8 ± 8.7 (58.2–95.4)76.8 ± 8.9 (58.2–95.4)
PASI score9.8 ± 5.9 (1.4–25.2)5.8 ± 5.5 (0.2–25.2)8.5 ± 4.1 (2.8–23.8)7.9 ± 6.8 (0.8–34.5)
VAS score (median, range)2 (0–8)0 (0–4)0 (0–7)0 (0–9)
  1. PASI: Psoriasis Area Severity Index; VAS: the visual analog scale; BMI: Body Mass Index.

After 8 weeks of treatment, patients treated with the hydrogen water bath showed significantly greater improvement than those in the control group, as assessed by PASI and VAS (Table 2 and Figure 1). Compared with 2.9% of control patients, 24.4% of patients who received the hydrogen water bath achieved the endpoint of at least a 75% improvement in PASI score (Pc=0.022, OR=0.094, 95% CI = [0.011, 0.777]). In PASI was improved by at least 50% in 56.1% of the patients who received the bath, compared with only 17.7% in the control group (P=0.001, OR=0.168, 95% CI=[0.057, 0.492]). Hydrogen water bath treatment also resulted in a significant improvement in itching as measured by VAS. The median change from baseline to week 8 in the bathing group was -2, while the median change in the control group was 0 (P = 3.94 × 10-4).

Table 2 Summary of the improvement of Psoriasis Area and Severity Index (PASI) and visual analog scale (VAS) at week 8.

From: Positive effects of hydrogen-water bathing in patients of psoriasis and parapsoriasis en plaques

The Hydrogen-water bathing groupThe control groupP value
Baseline PASI scoreBaseline PASI score
MildModerateSevereTotalMildModerateSevereTotal
(N = 26)(N = 11)(N = 4)(N = 41)(N = 24)(N = 9)(N = 1)(N = 34)
PASI (%)>PASI901 (2.4)1 (2.4)02 (4.8)0000>0.05
>PASI755 (12.2)3 (7.3)2 (4.9)10 (24.4)1 (2.9)001 (2.9)0.022*
>PASI5013 (31.7)8 (19.5)2 (4.9)23 (56.1)4 (11.8)2 (5.9)06 (17.6)0.001
VAS improvement (%)≤−53 (7.3)0 (0)0.31*
≤−39 (22.0)1 (2.9)0.04*
<021 (51.2)7 (20.6)0.006
≥020 (48.8)27 (79.4)0.006
  1. *The corrected P (Pc) values were adjusted by using Yate’s correction for continuity.

figure 1

Clinical improvement in psoriasis after 8 weeks of hydrogen water bath treatment. Case 1: A 64-year-old patient with psoriasis at baseline (PASI 16.4, a, b) and after bath therapy (PASI 1.8, c, d). Despite treatment with 30 mg Acitretin capsules daily for more than 4 months, psoriatic lesions did not improve except for partially reduced scaling on the plaques. Due to unbearable dryness and ruptured mucous membranes, he refused to increase the dose of the drug. Case 2: A 40-year-old patient with psoriasis at baseline (PASI 21.1, a, b) and after last bath treatment (PASI 4.1, c, d). He complained of severe itching and treatment-resistant lesions (acitretin capsules 40 mg daily for 6+ months) and was able to reduce the dose after bath therapy. Case 3: A 43-year-old patient with psoriasis at baseline (PASI 20.2, a, b) and after last hydrotherapy (PASI 4.8, c, d). The man had been receiving 5 mg of methotrexate weekly for more than 10 months and was able to successfully reduce the dose after balneotherapy. Note that patients experienced similar responses in areas not shown.

Improvement in parapsoriasis in plaques
Six patients were included: 1 male and 5 females, with a mean age of 32.8 ± 4.9 (range: 25-40) years and a mean treatment duration of 34.4 ± 31.1 (range: 12-96) months. Four patients were classified as LPP and two were classified as SPP. The characteristics of the patients are shown in Table 3. Lesion morphology or distribution improved in all patients (Figure 2). Complete responses were observed in 33.3% (2/6) of patients and partial responses were observed in 66.7% (4/6).

Table 3 Characteristics and the clinical outcomes of patients with parapsoriasis en plaques.

From: Positive effects of hydrogen-water bathing in patients of psoriasis and parapsoriasis en plaques

PatientsSex/AgeType of parasporiasisDistribution at initial presentationMorphology at initial presentationDuration of disease (month)Clinical response at week 8
1F/40LPPtrunk and extremitiespatch, plaque25PR
2F/31LPPtrunkpapule, patch12PR
3F/33SPPtrunk and extremitiespapule, patch, plaque28PR
4F/33SPPtrunkpapule, patch15PR
5M/35LPPtrunk and extremitiespatch, plaque30CR
6F/25LPPtrunk and extremitiespatch, plaque96CR
  1. SPP: small plaque parapsoriasis; LPP: large plaque parapsoriasis; PR: partial response; CR: complete response.

figure 2

Clinical evaluation of a patient with plaque parapsoriasis who rapidly achieved complete remission after 4 weeks of hydrogen water bathing. A 35-year-old man with large plaque parapsoriasis was followed for 30 months, during which two biopsies were performed, neither showing progression. He had flare-ups after 10 months of narrow-band UVB therapy, and despite an increase in power, there was no significant improvement in the subsequent 6 months of phototherapy. Even after only 4 weeks, his lesions rapidly improved significantly without concomitant therapy (a). Hematoxylin-eosin staining showed mildly hyperkeratotic and partially parakeratotic epidermis with moderate density of superficial perivascular infiltrates. Lymphoid cells are mostly cytologically normal small lymphocytes, and there is focal unicellular epidermotropism (b).side effect. Two psoriasis patients complained about the temperature of hydrogen water. After adjusting the actual temperature based on patient satisfaction, the discomfort was alleviated. No other side effects were found during the study.

References

  1. Nestle, F. O., Kaplan, D. H. & Barker, J. Psoriasis. N Engl J Med. 361, 496–509 (2009).

    Article PubMed CAS Google Scholar

  2. Sehgal, V. N., Srivastava, G. & Aggarwal, A. K. Parapsoriasis: a complex issue. Skinmed 6, 280–286 (2007).

    Article PubMed Google Scholar

  3. Lowes, M. A., Bowcock, A. M. & Krueger, J. G. Pathogenesis and therapy of psoriasis. Nature 445, 866–873 (2007).

    ADS Article PubMed CAS Google Scholar

  4. Mansouri, Y. & Goldenberg, G. New systemic therapies for psoriasis. Cutis 95, 155–160 (2015).

    PubMed Google Scholar

  5. Johnson-Huang, L. M., Lowes, M. A. & Krueger, J. G. Putting together the psoriasis puzzle: an update on developing targeted therapies. Dis. Model. Mech. 5, 423–433 (2012).

    Article PubMed CAS PubMed Central Google Scholar

  6. Aydogan, K. et al. Efficacy of low-dose ultraviolet a-1 phototherapy for parapsoriasis/early-stage mycosis fungoides. Photochem. Photobiol. 90, 873–877 (2014).

    PubMed CAS Google Scholar

  7. Christophers, E. Psoriasis–epidemiology and clinical spectrum. Clin. Exp. Dermatol. 26, 314–320 (2001).

    Article PubMed CAS Google Scholar

  8. Rapp, S. R., Feldman, S. R., Exum, M. L., Fleischer, A. B. & Reboussin, D. M. Psoriasis causes as much disability as other major medical diseases. J. Am. Acad. Dermatol. 41, 401–407 (1999).

    Article PubMed CAS Google Scholar

  9. Weiss, S. C. et al. Quantifying the harmful effect of psoriasis on health-related quality of life. J. Am. Acad. Dermatol. 47, 512–518 (2002).

    Article PubMed Google Scholar

  10. Haeffner, A. C., Smoller, B. R., Zepter, K. & Wood, G. S. Differentiation and clonality of lesional lymphocytes in small plaque parapsoriasis. Arch. Dermatol. 131, 321–324 (1995).

    Article PubMed CAS Google Scholar

  11. Kikuchi, A. et al. Parapsoriasis en plaques: its potential for progression to malignant lymphoma. J. Am. Acad. Dermatol. 29, 419–422 (1993).

    Article PubMed CAS Google Scholar

  12. Ackerman, A. B. If small plaque (digitate) parapsoriasis is a cutaneous T-cell lymphoma, even an ‘abortive’ one, it must be mycosis fungoides! Arch. Dermatol. 132, 562–566 (1996).

    Article PubMed CAS Google Scholar

  13. Raskin, C. A. Small plaque parapsoriasis and mycosis fungoides. Arch. Dermatol. 132, 1388 (1996).

    Article PubMed CAS Google Scholar

  14. Weinberg, J. M. & Tutrone, W. D. Biologic therapy for psoriasis: the T-cell-targeted therapies efalizumab and alefacept. Cutis. 71, 41–45 (2003).

    PubMed Google Scholar

  15. Kadam, D. P., Suryakar, A. N., Ankush, R. D., Kadam, C. Y. & Deshpande, K. H. Role of oxidative stress in various stages of psoriasis. Indian J. Clin. Biochem. 25, 388–392 (2010).

    Article PubMed CAS PubMed Central Google Scholar

  16. Ichihara, M., Sobue, S., Ito, M., Hirayama, M. & Ohno, K. Beneficial biological effects and the underlying mechanisms of molecular hydrogen – comprehensive review of 321 original articles. Med. Gas. Res. 5, 12 (2015).

    Article PubMed CAS PubMed Central Google Scholar

  17. Ohsawa, I. et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat. Med. 13, 688–694 (2007).

    Article PubMed CAS Google Scholar

  18. Ohta, S. Molecular hydrogen as a novel antioxidant: overview of the advantages of hydrogen for medical applications. Methods Enzymol. 555, 289–317 (2015).

    Article PubMed CAS Google Scholar

  19. Ohta, S. Recent progress toward hydrogen medicine: potential of molecular hydrogen for preventive and therapeutic applications. Curr. Pharm. Des. 17, 2241–2252 (2011).

    Article PubMed CAS PubMed Central Google Scholar

  20. Huang, C. S., Kawamura, T., Toyoda, Y. & Nakao, A. Recent advances in hydrogen research as a therapeutic medical gas. Free Radic. Res. 44, 971–982 (2010).

    Article PubMed CAS Google Scholar

  21. Ishibashi, T. et al. Improvement of psoriasis-associated arthritis and skin lesions by treatment with molecular hydrogen: A report of three cases. Mol. Med. Rep. 12, 2757–2764 (2015).

    Article PubMed CAS Google Scholar

  22. Brimhall, A. K., King, L. N., Licciardone, J. C., Jacobe, H. & Menter, A. Safety and efficacy of alefacept, efalizumab, etanercept and infliximab in treating moderate to severe plaque psoriasis: a meta-analysis of randomized controlled trials. Br. J. Dermatol. 159, 274–285 (2008).

    Article PubMed CAS Google Scholar

  23. Dubertret, L. et al. CLinical experience acquired with the efalizumab (Raptiva) (CLEAR) trial in patients with moderate-to-severe plaque psoriasis: results from a phase III international randomized, placebo-controlled trial. Br. J. Dermatol. 155, 170–181 (2006).

    Article PubMed CAS Google Scholar

  24. Ellis, C. N., Krueger, G. G. & Group, A. C. S. Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes. N. Engl. J. Med. 345, 248–255 (2001).

    Article PubMed CAS Google Scholar

  25. Schmitt, J. et al. Efficacy and safety of systemic treatments for moderate-to-severe psoriasis: meta-analysis of randomized controlled trials. Br. J. Dermatol. 170, 274–303 (2014).

    Article PubMed CAS Google Scholar

  26. Fallah, A. S., Neumann, H., Hop, W. C. & Thio, H. B. Fumarates vs. methotrexate in moderate to severe chronic plaque psoriasis: a multicentre prospective randomized controlled clinical trial. Br. J. Dermatol. 164, 855–861 (2011).

    Article CAS Google Scholar

  27. Mease, P. J. et al. Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial. Lancet. 356, 385–390 (2000).

    Article PubMed CAS Google Scholar

  28. Aydogan, K., Karadogan, S. K., Tunali, S., Adim, S. B. & Ozcelik, T. Narrowband UVB phototherapy for small plaque parapsoriasis. J. Eur. Acad. Dermatol. Venereol. 20, 573–577 (2006).

    Article PubMed CAS Google Scholar

  29. El-Mofty, M. et al. Narrow band UVB (311 nm), psoralen UVB (311 nm) and PUVA therapy in the treatment of early-stage mycosis fungoides: a right-left comparative study. Photodermatol. Photoimmunol. Photomed. 21, 281–286 (2005).

    Article PubMed CAS Google Scholar

  30. Niki, E. Lipid peroxidation: physiological levels and dual biological effects. Free Radic. Biol. Med. 47, 469–484 (2009).

    Article PubMed CAS Google Scholar

  31. Ishibashi, T. Molecular hydrogen: new antioxidant and anti-inflammatory therapy for rheumatoid arthritis and related diseases. Curr. Pharm. Des. 19, 6375–6381 (2013).

    Article PubMed CAS PubMed Central Google Scholar

  32. Niki, E. Biomarkers of lipid peroxidation in clinical material. Biochim. Biophys. Acta. 1840, 809–817 (2014).

    Article PubMed CAS Google Scholar

  33. Briganti, S. & Picardo, M. Antioxidant activity, lipid peroxidation and skin diseases. What’s new. J. Eur. Acad. Dermatol. Venereol. 17, 663–669 (2003).

    Article PubMed CAS Google Scholar

  34. Yu, X. J. et al. Expression and localization of the activated mitogen-activated protein kinase in lesional psoriatic skin. Exp. Mol. Pathol. 83, 413–418 (2007).

    Article PubMed CAS Google Scholar

  35. Kawamura, T. et al. Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo. Am. J. Physiol. Lung Cell Mol. Physiol. 304, L646–656 (2013).

    Article PubMed CAS PubMed Central Google Scholar

  36. Zhai, X. et al. Lactulose ameliorates cerebral ischemia-reperfusion injury in rats by inducing hydrogen by activating Nrf2 expression. Free Radic. Biol. Med. 65, 731–741 (2013).

    Article PubMed CAS Google Scholar

  37. Itoh, T. et al. Molecular hydrogen suppresses FcepsilonRI-mediated signal transduction and prevents degranulation of mast cells. Biochem. Biophys. Res. Commun. 389, 651–656 (2009).

    Article PubMed CAS Google Scholar

  38. Itoh, T. et al. Molecular hydrogen inhibits lipopolysaccharide/interferon γ-induced nitric oxide production through modulation of signal transduction in macrophages. Biochem. Biophys. Res. Commun. 411, 143–149 (2011).

    Article PubMed CAS Google Scholar

  39. Arbiser, J. L. Fumarate esters as angiogenesis inhibitors: key to action in psoriasis? J. Invest. Dermatol. 131, 1189–1191 (2011).

    Article PubMed CAS Google Scholar

  40. Liu, H., Colavitti, R., Rovira, I. I. & Finkel, T. Redox-dependent transcriptional regulation. Circ. Res. 97, 967–974 (2005).

    Article PubMed CAS Google Scholar

  41. Bell, E. L., Klimova, T. A., Eisenbart, J., Schumacker, P. T. & Chandel, N. S. Mitochondrial reactive oxygen species trigger hypoxia-inducible factor-dependent extension of the replicative life span during hypoxia. Mol. Cell Biol. 27, 5737–5745 (2007).

    Article PubMed CAS PubMed Central Google Scholar

  42. Ohno, K., Ito, M. & Ichihara, M. Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases. Oxid. Med. Cell Longev. 35, 31–52 (2012).

    Google Scholar

  43. Ishibashi, T. et al. Therapeutic efficacy of infused molecular hydrogen in saline on rheumatoid arthritis: a randomized, double-blind, placebo-controlled pilot study. Int. Immunopharmacol. 21, 468–473 (2014).

    Article PubMed CAS Google Scholar

  44. Bacchetti, T. et al. Oxidative stress and psoriasis: the effect of antitumour necrosis factor-α inhibitor treatment. Br. J. Dermatol. 168, 984–989 (2013).

    Article PubMed CAS Google Scholar

  45. Yu, J. J. et al. Compound glycyrrhizin plus conventional therapy for psoriasis vulgaris: a systematic review and meta-analysis of randomized controlled trials. Curr. Med. Res. Opin. 33, 279–387 (2017).

    Article PubMed CAS Google Scholar

  46. van-de-Kerkhof, P. C. The Psoriasis Area and Severity Index and alternative approaches for the assessment of severity: persisting areas of confusion. Br. J. Dermatol. 137, 661–662 (1997).

    Article PubMed CAS Google Scholar

  47. Carlin, C. S., Feldman, S. R., Krueger, J. G., Menter, A. & Krueger, G. G. A 50% reduction in the Psoriasis Area and Severity Index (PASI 50) is a clinically significant endpoint in the assessment of psoriasis. J. Am. Acad. Dermatol. 50, 859–866 (2004).

    Article PubMed Google Scholar

  48. Szepietowski, J. C., Reich, A. & Wiśnicka, B. Itching in patients suffering from psoriasis. Acta. Dermatovenerol. Croat. 10, 221–226 (2002).

    PubMed Google Scholar

  49. Haldane, J. B. The estimation and significance of the logarithm of a ratio of frequencies. Ann. Hum. Genet. 20, 309–311 (1956).

    Article PubMed MATH CAS Google Schola

 

References
Contact Us

Използваме бисквитки (cookies). В случай че продължите да разглеждате и ползвате този сайт, Вие се съгласявате с нашата Политика за поверителност