Homocysteine Plasma Concentration Is Related to Severity of Lung Impairment in Scleroderma

PAOLA CARAMASCHI, NICOLA MARTINELLI, DOMENICO BIASI, ANTONIO CARLETTO, GIOVANNI FACCINI, ALESSANDRO VOLPE, MARCELLO FERRARI, CINZIA SCAMBI, and LISA MARIA BAMBARA

ABSTRACT.

Objective. To investigate the correlation between plasma concentration of total homocysteine and pulmonary involvement in patients with limited or diffuse scleroderma (systemic sclerosis, SSc).

Methods. Seventy-one patients with scleroderma were divided into 3 groups based on pulmonary involvement: Group A comprised patients without lung involvement (9 cases); Group B patients with lung involvement of mild and moderate stages (44 cases); and Group C patients with lung involvement of severe stage and endstage (18 cases). At the time of evaluation of lung involvement all patients underwent determination of plasma homocysteine concentration. Homocysteine concentration was also measured in 30 healthy controls homogeneous for sex and age.

Results. In patients with scleroderma the homocysteine concentration was significantly higher than in controls (11.1 and 6.9 µmol/l, respectively; p < 0.001). We found a significant association between plasma homocysteine concentration and severity of lung involvement that was not modified by correction for age, time from the diagnosis, type of scleroderma pattern, and serum creatinine and folate levels. Homocysteine concentration progressively increases in scleroderma patients with more severe pulmonary involvement. Subjects with high homocysteine concentration (i.e., ³ 75th percentile of homocysteine concentration in patients with scleroderma without lung involvement) were mostly present in the group with the greatest lung involvement.

Conclusion. High level of homocysteinemia is associated with an increased risk of pulmonary disease in patients with scleroderma. We hypothesize that hyperhomocysteinemia may worsen injury of the endothelium, a key lesion in scleroderma disease, favoring the development of lung involvement. Our data support the hypothesis that homocysteine could be involved in the pathogenetic process of scleroderma pulmonary involvement. (J Rheumatol 2003;30:298-304)

Key Indexing Terms:

SCLERODERMA
HOMOCYSTEINE
LUNG INVOLVEMENT

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From the Dipartimento di Medicina Clinica e Sperimentale, Istituto di Chimica Clinica, and Dipartimento di Scienze Biomediche e Chirurgiche, Policlinico GB Rossi, Verona, Italy.

Supported by a grant from Progetto Sanità, Fondazione Cassa di Risparmio di Verona, Vicenza, Belluno ed Ancona.

P. Caramaschi, MD; N. Martinelli, MD; D. Biasi, MD; A. Carletto, MD; A. Volpe, MD; C. Scambi, MD; L.M. Bambara, MD, Professor of Rheumatology, Dipartimento di Medicina Clinica e Sperimentale; G. Faccini, Biologist, Istituto di Chimica Clinica; M. Ferrari, MD, Dipartimento di Scienze Biomediche e Chirurgiche.

Address reprint requests to Dr. P. Caramaschi, Dipartimento di Medicina Clinica e Sperimentale, Policlinico GB Rossi, P. le Scuro, 37134 Verona, Italy. E-mail: caramaschi@cmib.univr.it

Submitted January 11, 2002; revision accepted July 30, 2002.

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