Vitamin D deficiency in a patient with systemic lupus erythematosus

T. C. Barnes and R. C. Bucknall

Department of Rheumatology, Royal Liverpool University Hospital, Prescott Street, Liverpool L7 8XP, UK

Correspondence to: Theresa C. Barnes. E-mail: tbarnes{at}doctors.org.uk

SIR, You would not imagine that the patient illustrated opposite was vitamin D-deficient. However, she is a 21-yr-old Caucasian with systemic lupus erythematosus (SLE). Because of the nature of her condition she has to wear sunblock factor 30 all year round. Her tanned appearance is not derived from UVB exposure but from self-tanning agents.

She was diagnosed with SLE in 1997. Initially she presented with a widespread photosensitive rash. She was found to be positive for antinuclear antibodies and double-stranded DNA antibodies. A skin biopsy was consistent with cutaneous lupus. Photosensitivity tests demonstrated sensitivity to UVB light.

Soon after the diagnosis was established she was admitted to hospital with features of alveolitis, cerebral vasculitis and lupus nephritis. She was treated initially with steroids and intravenous cyclophosphamide. She is now maintained on prednisolone (11 mg once per day) and azathioprine (75 mg once per day).

The patient approached us concerned that she might be vitamin D-deficient because she was avoiding all sunlight exposure. Measurements revealed that she was vitamin D-deficient (25-OH vitamin D3 10.0 ng/ml, normal range 15–60 ng/ml). Other parameters were normal, including parathyroid hormone, alkaline phosphatase, calcium corrected for albumin and 25-OH vitamin D2 (which reflects preceding dietary intake). Her food diary confirmed a normal dietary intake of vitamin D. She was initiated on Calcichew D3 Forte (Shire, Basingstoke, UK) which contains 400 IU of cholecalciferol (vitamin D3). However, 25-OH vitamin D3 levels remained below the normal range despite normal hepatic function. The patient was felt to be compliant. Previous reports have suggested that high-dose steroids can lead to low serum concentrations of vitamin D3 [1]. This might explain the resistance in our patient. However, there is contradictory evidence, especially in patients taking low or moderate doses of prednisolone, such as our patient [2, 3]. It was felt more likely that the use of sunblock would necessitate doses greater than 400 IU, as reported in Moslem women [4]. She was started on alfacalcidol 1 mg in order to increase the dose of vitamin D without increasing the calcium intake. Her renal function tests were normal at this time, though she did have persistent, stable proteinuria (0.25 g/l). Renal dysfunction would not explain her inability to convert vitamin D3 to 25-OH-vitamin D3. Alfacalcidol led to hypercalcaemia, and at the present time efforts are being made to balance her requirements. The patient has never had any symptoms suggestive of vitamin D deficiency and has not appreciated any difference since correcting her vitamin D status.



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FIG. 1. Patient with SLE.

 
The main source of vitamin D is de novo synthesis in the skin in response to exposure to UVB sunlight. Although vitamin D is consumed in food, dietary intake alone is often insufficient, supplying only 20% of the body's requirements. A recent study has demonstrated vitamin D deficiency even in the light of large dietary doses of vitamin D (13.53 µg per day) taken by ethnic Danish Moslems who sought to avoid sun exposure [4].

Some literature suggests that chronic steroid use may result in altered metabolism of vitamin D, although there is contradictory evidence [1, 2]. In rat models, steroids have been demonstrated to alter vitamin D metabolism, leading to the formation of more polar, biologically inactive metabolites that result in decreased intestinal calcium transport [5]. Dihydroxy-vitamin D3 has been demonstrated to be reduced in corticosteroid-treated patients with a variety of collagen vascular diseases and rheumatoid arthritis [1].

Patients with lupus may have renal involvement. 1-Hydroxyl-ation is essential to make 25-OH vitamin D active. This can be disrupted in significant renal disease.

In addition, patients with SLE often take hydroxychloroquine, which is known to lower the conversion of vitamin D2 to the more biologically active vitamin D3. It is because of this action that it is used to treat hypercalcaemia in sarcoidosis.[6]

Despite these apparent reasons for patients with SLE to be vitamin D-deficient, the literature is sparse. One study showed that in 21 patients with SLE vitamin D levels were lower than in healthy controls [7]. In another study of 12 prednisolone-treated adolescents with SLE, seven were found to be vitamin D-deficient [8]. Another study of bone parameters in patients with SLE showed that vitamin D levels were not significantly different from those of healthy controls [9]. A recent study of vitamin D levels in patients with SLE and fibromyalgia showed that vitamin D deficiency was common in both groups of patients. There was, however, no difference between vitamin D levels in patients with fibromyalgia and those with SLE [6].

Recent studies into the non-calcaemic effects of vitamin D suggest that vitamin D may have important immunomodulatory effects. In animal models, vitamin D has been shown to be an effective treatment for SLE, though its use is limited by hypercalcaemia. In similar animal models, vitamin D deficiency has been shown to worsen other autoimmune conditions [10].

In summary, patients with SLE have multiple risk factors for vitamin deficiency. The symptoms of vitamin D deficiency are non-specific, and include musculoskeletal pains, paraesthesias and cramps. These are also commonly experienced by patients with SLE and therefore may be overlooked. Treatment of vitamin D deficiency is particularly important in patients with SLE due to other concomitant insults on their bones and in view of the possible immunomodulatory effects of vitamin D. Therefore it is important to consider the possibility of vitamin D deficiency.

The patient has given written consent for publication of this paper and to the publication of her photograph.

References

  1. Klein RG, Arnaud SB, Gallagher JC, Deluca HF, Riggs BL. Intestinal calcium absorption in exogenous hypercortisolism. Role of 25-hydroxy vitamin D and corticosteroid dose. J Clin Invest 1977;60:253–9.[ISI][Medline]
  2. Hahn TJ, Halstead LR, Haddad JG Jr. Serum 25-hydroxy vitamin D concentrations in patients receiving chronic corticosteroid therapy. J Lab Clin Med 1977; 90:399–404.[ISI][Medline]
  3. Zerwekh J, Ronald D, Harris E. Low dose prednisolone therapy in rheumatoid arthritis: effect on vitamin D metabolism. Arthritis Rheum 1984;27:1050–2.[ISI][Medline]
  4. Glerup H, Mikkelsen K, Poulsen L et al. Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited. J Intern Med 2000;247:260–8.[CrossRef][ISI][Medline]
  5. Carre M, Ayigbebe O, Miravet L, Rasmussen H. The effect of prednisolone on the metabolism and action of 25-hydroxy and 1,25-dihydroxyvitamin D. Proc Natl Acad Sci USA 1974;71:2996–3000.[Abstract]
  6. Huisman AM, White KP, Algra A et al. Vitamin D levels in women with systemic lupus erythematosus and fibromyalgia. J Rheumatol 2001;28:2535–9.[ISI][Medline]
  7. Muller K, Kriegbaum NJ, Baslund B, Sorensen OH, Thyman M, Bentzen K. Vitamin D3 metabolism in patients with rheumatic diseases: low serum levels of 25-hydroxyvitamin D3 in patients with systemic lupus erythematosus. Clin Rheumatol 1995;14:397–400.[ISI][Medline]
  8. O’Regan S, Chesney RW, Hamstra A, Eisman JA, O’Gorman AM, Deluca HF. Reduced serum 1,25-(OH)2 vitamin D3 levels in prednisolone-treated adolescents with systemic lupus erythematosus. Acta Paediatr Scand 1979;68:109–11.[ISI][Medline]
  9. Redlich K, Ziegler S, Kiener HP et al. Bone mineral density and biochemical parameters of bone metabolism in female patients with systemic lupus erythematosus. Ann Rheum Dis 2000;59:308–10.[Abstract/Free Full Text]
  10. Deluca HF, Cantorna MT. Vitamin D: its role and uses in immunology. FASEB J 2001;15:2579–85.[Abstract/Free Full Text]
Accepted 3 September 2003





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