Rheumaderm pp 299-304 | Cite as

Treatment of Generalized Morphea with Oral 1.25-Dihydroxyvitamin D3

  • Nina G. Caca-Biljanovska
  • M. T. Vlckova-Laskoska
  • D. V. Dervendi
  • N. P. Pesic
  • D. S. Laskoski
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 455)


Scleroderma is a chronic connective tissue disease characterized by excessive collagen synthesis and its deposition in the skin and various internal organs. Immune system abnormalities and disturbances of connective tissue metabolism have been suggested to play a central role in the pathogenesis of scleroderma. 1.25-Dihydroxyvitamin D3 (1.25(OH)2 D3 causes inhibition of fibroblast growth, has a role in controlling collagen synthesis and deposition and has numerous immunoregulatory activities. We assessed the effects of oral 1,25 (OH)2 D3 in the treatment of patients with generalized morphea. Three patients with generalized morphea, entered an open prospective study. They were treated with oral calcitriol (1,25 dyhidroxyvitamin D3) in an oral daily dose of 0.50-0.75 μg. After the treatment period of 4–6 months, a significant clinical improvement was observed. The mobility of the joints improved, the skin extensibility increased and a substantial improvement of the skin induration. No serious side effects were observed. The improvement persisted after discontinuation of therapy during a follow-up period of one year. The evolution of the patients’ condition during the 6 months therapy with calcitriol, suggests that it can be used as a beneficial agent in the treatment of generalized morphea. Double- blind, placebo-controlled trials are needed to assess its therapeutic value and a larger number of patients is desirable.

Scleroderma is a chronic connective tissue disease in which, after an inflammatory phase, sclerosis of circumscribed or generalized areas of skin develops with or without the involvement of internal organs. Morphea is a form of scleroderma that is limited to the skin.

The etiology and pathogenesis of scleroderma remains unknown, hereditary tendency is sometimes present and an autoimmune basis is widely suspected, but actual mechanisms have not been precisely identified. Various therapeutic modalities have been used or proposed for the treatment of scleroderma, but their efficacy has not been proven in most cases.

Recently, Hulshof et al. [4] and Humbert et al. [3] reported a beneficial effect of oral 1 ,25-dihydroxyvitamin D3 (calcitriol) in patients with morphea. Calcitriol is the biologically active metabolite of Vitamin D3 and acts on target tissues (fibroblasts and lymphocytes), passing cellular easily and bind with high affinity to a nuclear receptor [6].

1,25 (OH)2 D3 causes dose-dependent inhibition of fibroblast growth and collagen synthesis, and has numerous immunoregulatory activities [3]. Therefore, encouraged by the promising results in the literature, we decided to begin treatment with calcitriol in three patients with generalized morphea (disseminated localized scleroderma).


Oral Daily Dose Localize Scleroderma Skin Induration Skin Biopsy Specimen Glycosaminoglycan Synthesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Humbert PG. Dupond JL. Rochefort A. et al. Localized scleroderma: response to 1.25-dihydroxyvitamin D3. Clin Exp Dermatol 15: 396–398 (1990).PubMedCrossRefGoogle Scholar
  2. 2.
    Humbert PG. Dupond JL. Agache P. et al. Treatment of scleroderma with oral 1.25-dihydroxyvitamin D3: Evaluation of skin involvement using non-invasive techniques. Acta Derm Venereol (Stockh) 73: 449–451 (1993).Google Scholar
  3. 3.
    Humbert PG. Delaporte E. Dupond JL. et al. Treatment of localized scleroderma with oral 1.25-dihydroxyvitamin D3. Eur J Dermatol 4: 21–3 (1994).Google Scholar
  4. 4.
    Hulshof MM. Pavel S. Ferdinand C. et al. Oral calcitriol as a new therapeutic modality for generalized morphea. Arch Dermatol. 130: 1290–1293 (1994).PubMedCrossRefGoogle Scholar
  5. 5.
    Boelsma E. Pavel S. Ponec M. Effects of calcitriol on fibroblasts derived from skin of scleroderma patients. Dermatology 191: 226–233 (1995).PubMedCrossRefGoogle Scholar
  6. 6.
    Calberg C. The antiproliferative effect of vitamin D3 analogues. Dermatology 192:195–197 (1996).CrossRefGoogle Scholar
  7. 7.
    Holic MF. Smith E. Pincus S. Skin as the site of vitamin D synthesis and target tissue for 1 25-dihydroxyvitamin D3. Arch Dermatol 123: 1677–1683 (1987).CrossRefGoogle Scholar
  8. 8.
    McCarthy DM. Hibbin JA. Holmand JM. A role for 1.25-dihydroxyvitamin d3 in control of bone marrow colagen deposition? Lancet i: 78–80 (1984).CrossRefGoogle Scholar
  9. 9.
    Falanga aV. Alstadt SP. Effect of a plateled release fraction on glycosaminoglycan synthesis by cultured dermal fibroblasts from patients with progressive systemic sclerosis. British Journal of Dermatology 118: 339–345(1988).PubMedCrossRefGoogle Scholar
  10. 10.
    Rigby WFC. Stacy T. Fariger MW. Inhibition of T lymphocyte mitogenesis by 1.25-dihydroxyvitamin D3 (calcitriol). J Clin Invest 74: 1451–5 (1984).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Nina G. Caca-Biljanovska
    • 1
  • M. T. Vlckova-Laskoska
    • 1
  • D. V. Dervendi
    • 1
  • N. P. Pesic
    • 1
  • D. S. Laskoski
    • 2
  1. 1.Department of DermatologyUniversity Hospital SkopjeRepublic of Macedonia
  2. 2.University of WisconsinMadisonUSA

Personalised recommendations