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The Efficacy of Low-Dose Enoxaparin in Psoriasis

Year 2022, Volume 13, Issue 3, 352 - 359, 01.07.2022
https://doi.org/10.31067/acusaglik.1038133

Abstract

Psoriasis is a frequently encountered inflammatory skin disease with unclear etiology and no curative therapy. Enoxaparin is a low-molecular weight heparin analogue. Heparin and its analogues in low doses have antiproliferative and immunomodulatory effects. Low-dose enoxaparin has inhibitory effects on T cell-mediated immune reactions. T lymphocytes play a key role in the immunpathogenesis of psoriasis. The aim of this study was to evaluate the efficacy of low-dose enoxaparin in the treatment of psoriasis. Twenty-three patients with chronic plaque and guttate psoriasis were enrolled in an open study. Patients were given subcutaneous injections of 5 mg enoxaparin once weekly for a total of 6 weeks. There was a statistically significant difference between the PASI (Psoriasis Area and Severity Index) scores at the beginning and at the 6th week follow up (p=0.008). Four out of 23 patients (17%) showed marked improvement (≥50% reduction in the PASI score), eight patients (35%) showed moderate improvement (25-49% reduction), five (22%) were unchanged (<25% reduction). Six patients (26%) experienced worsening with a corresponding increase in the PASI scores. According to these findings, 52% of patients were considered to get benefit from enoxaparin treatment. No systemic side-effects due to enoxaparin were observed. The only local side-effect recorded in seven patients (30%) was ecchymosis at the injection site. Low-dose enoxaparin, which appears to be safe, is a candidate to become a future alternative in the treatment of psoriasis. Further studies assessing the optimum dose and duration of treatment, as well as patient subgroups that will benefit most from enoxaparin treatment are required. In addition, efficacy of enoxaparin in psoriasis should be compared to those of standard therapeutic modalities.

References

  • 1. Nickoloff BJ. The immunologic and genetic basis of psoriasis. Arch Dermatol 1999; 135: 1104-10.
  • 2. Prinz JC. Psoriasis vulgaris - a sterile antibacterial reaction mediated by cross-reactive T cells? An immunological view of the pathophysiology of psoriasis. Clin Exp Dermatol 2001; 26: 326-32.
  • 3. Mrowietz U. Advances in systemic therapy for psoriasis. Clin Exp Dermatol 2001; 26: 362-7.
  • 4. Lider O, Baharav E, Mekori YA, et al. Suppression of experimental autoimmune diseases and prolongation of allograft survival by treatment of animals with low doses of heparins. J Clin Invest 1989; 83: 752-6.
  • 5. Lider O, Mekori YA, Miller T, et al. Inhibition of T lymphocyte heparanase by heparin prevents T cell migration and T cell-mediated immunity. Eur J Immunol 1990; 20: 493-9.
  • 6. Cahalon L, Lider O, Schor H, et al. Heparin disaccharides inhibit tumor necrosis factor-alpha production by macrophages and arrest immune inflammation in rodents. Int Immunol 1997; 9: 1517-22.
  • 7. Pillai S, Gilliam L, Conrad HE, et al. Heparin and its non-anticoagulant analogues inhibit human keratinocyte growth without inducing differentiation. J Invest Dermatol 1994; 103: 647-50.
  • 8. Hodak E, Yosipovitch G, David M, et al. Low-dose low-molecular-weight heparin (enoxaparin) is beneficial in lichen planus: a preliminary report. J Am Acad Dermatol 1998; 38: 564-8.
  • 9. Stefanidou MP, Ioannidou DJ, Panayiotides JG, et al. Low molecular weight heparin; a novel alternative therapeutic approach for lichen planus. Br J Dermatol 1999; 141: 1040-5.
  • 10. Fredriksson T, Pettersson U. Severe psoriasis--oral therapy with a new retinoid. Dermatologica 1978; 157: 238-44.
  • 11. Prinz JC, Gross B, Vollmer S, et al. T cell clones from psoriasis skin lesions can promote keratinocyte proliferation in vitro via secreted products. Eur J Immunol 1994; 24: 593-8.
  • 12. Bata-Csorgo Z, Hammerberg C, Voorhees JJ, et al. Kinetics and regulation of human keratinocyte stem cell growth in short-term primary ex vivo culture. Cooperative growth factors from psoriatic lesional T lymphocytes stimulate proliferation among psoriatic uninvolved, but not normal, stem keratinocytes. J Clin Invest 1995; 95: 317-27.
  • 13. Naparstek Y, Cohen IR, Fuks Z, et al. Activated T lymphocytes produce a matrix-degrading heparan sulphate endoglycosidase. Nature 1984; 310: 241-4.
  • 14. Fridman R, Lider O, Naparstek Y, et al. Soluble antigen induces T lymphocytes to secrete an endoglycosidase that degrades the heparan sulfate moiety of subendothelial extracellular matrix. J Cell Physiol 1987; 130: 85-92.
  • 15. Savion N, Vlodavsky I, Fuks Z. Interaction of T lymphocytes and macrophages with cultured vascular endothelial cells: attachment, invasion, and subsequent degradation of the subendothelial extracellular matrix. J Cell Physiol 1984; 118: 169-78.
  • 16. Lider O, Cahalon L, Gilat D, et al. A disaccharide that inhibits tumor necrosis factor alpha is formed from the extracellular matrix by the enzyme heparanase. Proc Natl Acad Sci U S A 1995; 92: 5037-41.
  • 17. Ingber A, Trattner A, Cohen IR, et al. Low doses of low molecular weight heparin in vivo inhibits the elicitation of contact hypersensitivity. Acta Derm Venereol 1994; 74: 454-6.
  • 18. Patel RP, Shastri MD, Ming LC, et al. Therapeutic Potential of Enoxaparin in Lichen Planus: Exploring Reasons for Inconsistent Reports. Front Pharmacol 2018; 9: 586.
  • 19. Pacheco H, Kerdel F. Successful treatment of lichen planus with low-molecular-weight heparin: a case series of seven patients. J Dermatolog Treat 2001; 12: 123-6.
  • 20. Akdeniz S, Harman M, Atmaca S, et al. The management of lichen planus with low-molecular-weight heparin (enoxaparin). Int J Clin Pract 2005; 59: 1268-71.
  • 21. Ameen WA, Alphadhily ZS. Treatment of recaltritrant lichen planus with low molecular weight heparin (Enoxaparin). Med J Babylon 2011; 8: 93-103.
  • 22. Yasar S, Serdar ZA, Goktay F, et al. The successful treatment of palmoplantar hyperkeratotic lichen planus with enoxaparin. Indian J Dermatol Venereol Leprol 2011; 77: 64-6.
  • 23. Iraji F, Asilian A, Saeidi A, et al. Comparison of therapeutic effect of low-dose low-molecular-weight heparin (enoxaparin) vs. oral prednisone in treatment of patients with lichen planus; A clinical trial. Adv Biomed Res 2013; 2: 76.
  • 24. Porter SR, Kirby A, Olsen I, et al. Immunologic aspects of dermal and oral lichen planus: a review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997; 83: 358-66.
  • 25. Craven NM, Jackson CW, Kirby B, et al. Cytokine gene polymorphisms in psoriasis. Br J Dermatol 2001; 144: 849-53.
  • 26. Piepkorn M, Pittelkow MR, Cook PW. Autocrine regulation of keratinocytes: the emerging role of heparin-binding, epidermal growth factor-related growth factors. J Invest Dermatol 1998; 111: 715-21.

Year 2022, Volume 13, Issue 3, 352 - 359, 01.07.2022
https://doi.org/10.31067/acusaglik.1038133

Abstract

References

  • 1. Nickoloff BJ. The immunologic and genetic basis of psoriasis. Arch Dermatol 1999; 135: 1104-10.
  • 2. Prinz JC. Psoriasis vulgaris - a sterile antibacterial reaction mediated by cross-reactive T cells? An immunological view of the pathophysiology of psoriasis. Clin Exp Dermatol 2001; 26: 326-32.
  • 3. Mrowietz U. Advances in systemic therapy for psoriasis. Clin Exp Dermatol 2001; 26: 362-7.
  • 4. Lider O, Baharav E, Mekori YA, et al. Suppression of experimental autoimmune diseases and prolongation of allograft survival by treatment of animals with low doses of heparins. J Clin Invest 1989; 83: 752-6.
  • 5. Lider O, Mekori YA, Miller T, et al. Inhibition of T lymphocyte heparanase by heparin prevents T cell migration and T cell-mediated immunity. Eur J Immunol 1990; 20: 493-9.
  • 6. Cahalon L, Lider O, Schor H, et al. Heparin disaccharides inhibit tumor necrosis factor-alpha production by macrophages and arrest immune inflammation in rodents. Int Immunol 1997; 9: 1517-22.
  • 7. Pillai S, Gilliam L, Conrad HE, et al. Heparin and its non-anticoagulant analogues inhibit human keratinocyte growth without inducing differentiation. J Invest Dermatol 1994; 103: 647-50.
  • 8. Hodak E, Yosipovitch G, David M, et al. Low-dose low-molecular-weight heparin (enoxaparin) is beneficial in lichen planus: a preliminary report. J Am Acad Dermatol 1998; 38: 564-8.
  • 9. Stefanidou MP, Ioannidou DJ, Panayiotides JG, et al. Low molecular weight heparin; a novel alternative therapeutic approach for lichen planus. Br J Dermatol 1999; 141: 1040-5.
  • 10. Fredriksson T, Pettersson U. Severe psoriasis--oral therapy with a new retinoid. Dermatologica 1978; 157: 238-44.
  • 11. Prinz JC, Gross B, Vollmer S, et al. T cell clones from psoriasis skin lesions can promote keratinocyte proliferation in vitro via secreted products. Eur J Immunol 1994; 24: 593-8.
  • 12. Bata-Csorgo Z, Hammerberg C, Voorhees JJ, et al. Kinetics and regulation of human keratinocyte stem cell growth in short-term primary ex vivo culture. Cooperative growth factors from psoriatic lesional T lymphocytes stimulate proliferation among psoriatic uninvolved, but not normal, stem keratinocytes. J Clin Invest 1995; 95: 317-27.
  • 13. Naparstek Y, Cohen IR, Fuks Z, et al. Activated T lymphocytes produce a matrix-degrading heparan sulphate endoglycosidase. Nature 1984; 310: 241-4.
  • 14. Fridman R, Lider O, Naparstek Y, et al. Soluble antigen induces T lymphocytes to secrete an endoglycosidase that degrades the heparan sulfate moiety of subendothelial extracellular matrix. J Cell Physiol 1987; 130: 85-92.
  • 15. Savion N, Vlodavsky I, Fuks Z. Interaction of T lymphocytes and macrophages with cultured vascular endothelial cells: attachment, invasion, and subsequent degradation of the subendothelial extracellular matrix. J Cell Physiol 1984; 118: 169-78.
  • 16. Lider O, Cahalon L, Gilat D, et al. A disaccharide that inhibits tumor necrosis factor alpha is formed from the extracellular matrix by the enzyme heparanase. Proc Natl Acad Sci U S A 1995; 92: 5037-41.
  • 17. Ingber A, Trattner A, Cohen IR, et al. Low doses of low molecular weight heparin in vivo inhibits the elicitation of contact hypersensitivity. Acta Derm Venereol 1994; 74: 454-6.
  • 18. Patel RP, Shastri MD, Ming LC, et al. Therapeutic Potential of Enoxaparin in Lichen Planus: Exploring Reasons for Inconsistent Reports. Front Pharmacol 2018; 9: 586.
  • 19. Pacheco H, Kerdel F. Successful treatment of lichen planus with low-molecular-weight heparin: a case series of seven patients. J Dermatolog Treat 2001; 12: 123-6.
  • 20. Akdeniz S, Harman M, Atmaca S, et al. The management of lichen planus with low-molecular-weight heparin (enoxaparin). Int J Clin Pract 2005; 59: 1268-71.
  • 21. Ameen WA, Alphadhily ZS. Treatment of recaltritrant lichen planus with low molecular weight heparin (Enoxaparin). Med J Babylon 2011; 8: 93-103.
  • 22. Yasar S, Serdar ZA, Goktay F, et al. The successful treatment of palmoplantar hyperkeratotic lichen planus with enoxaparin. Indian J Dermatol Venereol Leprol 2011; 77: 64-6.
  • 23. Iraji F, Asilian A, Saeidi A, et al. Comparison of therapeutic effect of low-dose low-molecular-weight heparin (enoxaparin) vs. oral prednisone in treatment of patients with lichen planus; A clinical trial. Adv Biomed Res 2013; 2: 76.
  • 24. Porter SR, Kirby A, Olsen I, et al. Immunologic aspects of dermal and oral lichen planus: a review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997; 83: 358-66.
  • 25. Craven NM, Jackson CW, Kirby B, et al. Cytokine gene polymorphisms in psoriasis. Br J Dermatol 2001; 144: 849-53.
  • 26. Piepkorn M, Pittelkow MR, Cook PW. Autocrine regulation of keratinocytes: the emerging role of heparin-binding, epidermal growth factor-related growth factors. J Invest Dermatol 1998; 111: 715-21.

Details

Primary Language English
Subjects Dermatology
Journal Section Research Article
Authors

Deniz DEMİRCİOĞLU> (Primary Author)
ACIBADEM UNIVERSITY, SCHOOL OF MEDICINE
0000-0001-8290-3075
Türkiye


Nilgün ATAKAN This is me
Hacettepe University School of Medicine
0000-0003-3700-541X
Türkiye

Publication Date July 1, 2022
Application Date December 20, 2021
Acceptance Date January 20, 2022
Published in Issue Year 2022, Volume 13, Issue 3

Cite

EndNote %0 Acıbadem Üniversitesi Sağlık Bilimleri Dergisi The Efficacy of Low-Dose Enoxaparin in Psoriasis %A Deniz Demircioğlu , Nilgün Atakan %T The Efficacy of Low-Dose Enoxaparin in Psoriasis %D 2022 %J Acıbadem Üniversitesi Sağlık Bilimleri Dergisi %P 1309-470X-1309-5994 %V 13 %N 3 %R doi: 10.31067/acusaglik.1038133 %U 10.31067/acusaglik.1038133