Raynaud's Phenomenon: Infrared Functional Imaging Applied to Diagnosis and Drugs Effects

A non-invasive, innovative approach to the study of Raynaud's Phenomenon is proposed. A group of patients, with respect of a control group, underwent a simultaneous assessment of thermal properties of all ten fingers using infrared functional imaging (IRFI). The assessment highlighted a quite different behaviour between patients with Primary- (PRP) and those with scleroderma - Raynaud's Phenomenon (SSc) and, compared with other existing techniques, seems to be an objective and effective tool to discriminate between PRP and RP secondary to SSc. 18 healthy volunteers (Norm), 20 Primary Raynaud's Phenomenon (PRP) and 20 Secondary Scleroderma (SSc) patients were studied subsequently to clinical evaluation and nail fold capillaroscopy. High-resolution infrared imaging of finger re-warming processes, immediately after a 2 min cold stress, allowed to identify objective parameters. Temperature integral Q (the temperature evaluation of the area under the time-temperature curve along the re-warming period) provided particularly effective figures in describing thermal properties of the fingers. Grand average Q values were (383.4 ± 12.5) °C/min, (502.9 ± 88.1) °C/min and (1022.0 ± 110.2) ±C/min for the PRP, SSc and Normal groups, respectively. Separate evaluation of the temperature integral for each finger leads to very similar results for the fingers of all the PRP patients; a different thermoregulatory response was observed in SSc patients. The sensitivity of the method in order to distinguish healthy from ill fingers was 100 %. The specificity in distinguishing SSc from PRP was 95%. In addition, IRFI parameters provided a better understanding of the impaired control of the finger's temperature in PRP and SSc with respect to the Normal group. This pilot study also applied IRFI for the measurement of drug effects in patients with Raynaud's Phenomenon. Sixteen out of twenty SSc patients were tested in a single 1-hour session of N-acetylcysteine infusion. IRFI clearly documented a significant increase of face and hands temperature during the drug administration. The grand average value of the finger's temperature after the 1 hour NAC administration was (29.6 ± 3.7) °C, while its value before was (27.9 ± 3.7) °C (p<0.001). N-acetylcysteine seems to act as a vasodilator in patients with Raynaud's phenomenon secondary to systemic sclerosis (scleroderma).

[1]  J. Block,et al.  Raynaud's phenomenon , 2001, The Lancet.

[2]  A. Detsky,et al.  Nifedipine in the treatment of idiopathic Raynaud's syndrome. , 1986, The Journal of rheumatology.

[3]  H. Bounameaux,et al.  Effects of low-dose nifedipine on a cold provocation test in patients with Raynaud's disease. , 1990, Journal of Cardiovascular Pharmacology.

[4]  C.D. Smith,et al.  CONTROLLED TRIAL OF NIFEDIPINE IN THE TREATMENT OF RAYNAUD'S PHENOMENON , 1982, The Lancet.

[5]  A. Blann,et al.  Losartan therapy for Raynaud's phenomenon and scleroderma: clinical and biochemical findings in a fifteen-week, randomized, parallel-group, controlled trial. , 1999, Arthritis and rheumatism.

[6]  K B Pandolf,et al.  Quantification of conservative endurance times in thermally insulated cold-stressed digits. , 1991, Journal of applied physiology.

[7]  V. Fialka-Moser,et al.  Thermographic parameters in the diagnosis of secondary Raynaud's phenomenon. , 2000, Archives of physical medicine and rehabilitation.

[8]  J Werner,et al.  Efficiency function: improvement of classical bioheat approach. , 1994, Journal of applied physiology.

[9]  A. Shitzer.  On the Thermal Efficiency of Cold‐Stressed Fingers , 1998, Annals of the New York Academy of Sciences.

[10]  S D Livingstone,et al.  Changes in cold-induced vasodilation during Arctic exercises. , 1976, Journal of applied physiology.

[11]  I. Ringqvist,et al.  The effect of the calcium-entry blocker nifedipine on cold-induced digital vasospasm. A double-blind crossover study versus placebo. , 2009, Acta medica Scandinavica.

[12]  S. Marshall,et al.  Treatment of Raynaud's phenomenon with the selective serotonin reuptake inhibitor fluoxetine. , 2001, Rheumatology.

[13]  T. Medsger,et al.  Raynaud's phenomenon: a proposal for classification. , 1992, Clinical and experimental rheumatology.

[14]  F. Wigley.  When is scleroderma really scleroderma? , 2001, The Journal of rheumatology.

[15]  R. Scorza,et al.  Effects of long-term cyclic iloprost therapy in systemic sclerosis with Raynaud's phenomenon. A randomized, controlled study. , 2001, Clinical and experimental rheumatology.

[16]  M. Jayson,et al.  Measurement of cold challenge responses in primary Raynaud's phenomenon and Raynaud's phenomenon associated with systemic sclerosis. , 1992, Annals of the rheumatic diseases.

[17]  K B Pandolf,et al.  Lumped-parameter tissue temperature-blood perfusion model of a cold-stressed fingertip. , 1996, Journal of applied physiology.

[18]  T. Medsger,et al.  Criteria for the classification of early systemic sclerosis. , 2001, The Journal of rheumatology.

[19]  Satish S. Nair,et al.  Parametric studies of human thermal mechanisms and measurements , 2000, IEEE Transactions on Biomedical Engineering.

[20]  H. Paulus,et al.  Measurement of clinical change in progressive systemic sclerosis: a 1 year double-blind placebo-controlled trial of N-acetylcysteine. , 1979, Annals of the rheumatic diseases.

[21]  T. Moore,et al.  The "distal-dorsal difference" as a possible predictor of secondary Raynaud's phenomenon. , 1999, The Journal of rheumatology.

[22]  H. Maricq,et al.  Patterns of finger capillary abnormalities in connective tissue disease by "wide-field" microscopy. , 1973, Arthritis and rheumatism.

[23]  J D Coffman,et al.  Total and capillary fingertip blood flow in Raynaud's phenomenon. , 1971, The New England journal of medicine.

[24]  M. Cacchio,et al.  Effects of 50 Hz sinusoidal electromagnetic fields on MCP-1 and RANTES generated from activated human macrophages. , 2001, International journal of immunopathology and pharmacology.

[25]  J. Belch,et al.  Raynaud's phenomenon: its relevance to scleroderma. , 1991, Annals of the rheumatic diseases.

[26]  R. Madhok,et al.  Oral iloprost as a treatment for Raynaud's syndrome: a double blind multicentre placebo controlled study. , 1995, Annals of the rheumatic diseases.

[27]  V. Welch,et al.  Calcium-channel blockers for Raynaud's phenomenon in systemic sclerosis. , 2001, Arthritis and rheumatism.

[28]  G. Burnstock,et al.  Raynaud's phenomenon , 1995 .

[29]  A. Herrick,et al.  Quantifying digital vascular disease in patients with primary Raynaud’s phenomenon and systemic sclerosis , 1998, Annals of the rheumatic diseases.

[30]  A. Masi.  Preliminary criteria for the classification of systemic sclerosis (scleroderma). , 1980, Bulletin on the rheumatic diseases.

[31]  T. Moore,et al.  Thermography and nailfold capillaroscopy as noninvasive measures of circulation in children with Raynaud's phenomenon. , 1998, The Journal of rheumatology.

[32]  R. Ferrari,et al.  The role of glutathione status in the protection against ischaemic and reperfusion damage: effects of N-acetyl cysteine. , 1988, Journal of molecular and cellular cardiology.

[33]  T. Lewis,et al.  Observations upon the reactions of the vessels of the human skin to cold , 1930 .

[34]  J. F. Wolfe,et al.  Diagnostic potential of in vivo capillary microscopy in scleroderma and related disorders. , 1980, Arthritis and rheumatism.

[35]  A. Adami,et al.  CD23 and CD69 expression on human neutrophils of healthy subjects and patients with peripheral arterial occlusive disease. , 2001, International Journal of Immunopathology and Pharmacology.

[36]  O. Hartling,et al.  Controlled double-blind trial of the clinical effect of nifedipine in the treatment of idiopathic Raynaud's phenomenon. , 1986, American Heart Journal.

[37]  P. Dieppe,et al.  Treatment of Raynaud's phenomenon by intravenous infusion of prostacyclin (PGI2) , 1982, The British journal of dermatology.

[38]  O. Alfieri,et al.  Oxygen free radicals and myocardial damage: protective role of thiol-containing agents. , 1991, The American journal of medicine.

[39]  J. Kirby,et al.  Comparison of intravenous infusions of iloprost and oral nifedipine in treatment of Raynaud's phenomenon in patients with systemic sclerosis: a double blind randomised study. , 1989, BMJ.

[40]  M. Pozzi,et al.  Treatment of Raynaud's phenomenon with intravenous prostaglandin E1alpha-cyclodextrin improves endothelial cell injury in systemic sclerosis. , 2001, The Journal of rheumatology.

[41]  Leroy Ec,et al.  Raynaud's phenomenon: a proposal for classification. , 1992, Clinical and experimental rheumatology.

[42]  G. Rodnan,et al.  Morphologic changes in the digital arteries of patients with progressive systemic sclerosis (scleroderma) and Raynaud phenomenon. , 1980, Medicine.

[43]  B. Olsson,et al.  Pharmacokinetics and bioavailability of reduced and oxidized N-acetylcysteine , 2004, European Journal of Clinical Pharmacology.

[44]  K. Darton,et al.  Pyroelectric vidicon thermography and cold challenge quantify the severity of Raynaud's phenomenon. , 1991, British journal of rheumatology.

[45]  M. Weinrich,et al.  Geographic variation in the prevalence of Raynaud's phenomenon: Charleston, SC, USA, vs Tarentaise, Savoie, France. , 1993, The Journal of rheumatology.

[46]  A. Gabrielli,et al.  Intravenous N-acetylcysteine for treatment of Raynaud's phenomenon secondary to systemic sclerosis: a pilot study. , 2001, The Journal of rheumatology.

[47]  C. Kallenberg,et al.  Nifedipine in Raynaud's phenomenon: relationship between immediate, short term and longterm effects. , 1987, The Journal of rheumatology.

[48]  J. Stamler,et al.  N-acetylcysteine potentiates platelet inhibition by endothelium-derived relaxing factor. , 1989, Circulation research.