A 43-year-old woman reports that her fingers turn blue and tingly when they are exposed to cold temperatures. She also has had recent complaints of fatigue and joint pain (arthralgia).
The clinical problem
In 1862, Maurice Raynaud recognized that some people who were exposed to cold temperatures had transient digital ischemia, temporary lack of blood flow to the fingers, that he had described as an exaggerated response of the central nervous system. The term “Raynaud’s phenomenon” (RP) is now used to describe these episodic events that represent constriction of the blood vessels supplying the arteries, precapillary arterioles, and cutaneous arteriovenous shunts in the fingers.
The ischemic phase of the attack is evidenced by the appearance of a demarcated pale or cyanotic skin, limited to the digits. It typically starts in one or several digits after exposure to the cold, such as getting something out of the freezer or walking outside in the winter, or during a stressful situation. The involvement of several fingers typically spreads to all fingers of both hands. The attack usually ends with a rapid reflow of blood into the digit(s), which is manifested by erythematous skin (reactive hyperemia). In general, the prevalence of RP is less than 5%. Geographic variations in the prevalence reflect differences in climate with the frequency and severity of the attacks proportionately related to the daily ambient temperature. Clear exacerbations occur during the winter season. Approximately 80% of patients with RP who are seen by an internist are found simply to have an exaggerated physiologic response to cold temperatures. In a community-based survey that we distributed, more than 10% of participants responded affirmatively to the question: “Are either your fingertips or toes unusually sensitive to cold temperatures?” Cool skin and nondemarcated mottling of the skin of the digits, hands, and limbs are considered a normal response to exposure to the cold. RP should be distinguished from acrocyanosis, a condition characterized by continuous cyanosis of the hands or feet that is aggravated by cold temperatures, but is not pathologic. However, there is a small percentage of patients with RP that indicates a clinical manifestation of a serious underlying autoimmune disease such as scleroderma that may lead to critical ischemia of a digit or limb. This depends on the severity of the insult and the size of the blood vessel, and can result in just a superficial ulceration or a more problematic deep-tissue necrosis with gangrene, resulting in amputation.
The diagnosis of RP is made through a history of cold sensitivity with episodic pallor or cyanosis of the distal portions of the digits (or both). Photographs of the hands taken during an attack can be used to confirm the history (as seen in figures 1 and 2). Laboratory-based techniques to measure digital and cutaneous blood flow after a cold challenge can be used to distinguish patients with RP from cold-sensitive persons. These tests are complex and are generally not used clinically since they require a carefully controlled ambient temperature to provide meaningful data. Clinical criteria are used to distinguish patients with uncomplicated or primary RP from those with secondary RP – associated with various autoimmune disorders. The suggested criteria for primary RP are: symmetric attacks; the absence of tissue necrosis, ulceration, or gangrene; the absence of a secondary cause on the basis of a patient’s history and general physical examination; normal nail-fold capillaries; a negative test for antinuclear antibody; and a normal erythrocyte sedimentation rate.
The median age at the onset of primary RP is 14 years, and only 27% begin at 40 years or later. If a patient meets the criteria for primary RP and is followed for a two-year period without the development of clinical or laboratory signs, then secondary disease is highly unlikely (less than 15%).
The NIH Raynaud’s Treatment Trial that was led by Dr. Bielory and conducted at various sites throughout the United states including the New Jersey Medical School, Wayne State University, University of Pittsburgh, and Medical University of South Carolina in patients with primary Raynaud’s phenomenon (history of two or more attacks per day during the previous cold season) involved a randomized, controlled clinical trial, double-masked for drug and placebo but not masked for temperature and control biofeedback. Participants were randomized to one of four treatment groups: (1) sustained-release nifedipine; (2) pill placebo; (3) temperature biofeedback; or (4) control (electromyographic) biofeedback. Nifedipine is produced by Pfizer, Inc. The primary outcome measure – color chart-verified primary RP attacks during one winter month approximately one year after initiation of treatment – was self-reported. Secondary outcome measures included verified attacks at two months, all attacks at two months and one year, and quality of life.
The eight-year study concluded that temperature biofeedback is not better than its control treatment and is inferior to sustained-release nifedipine for treating primary RP. Sustained-release nifedipine (30 to 60 mg once daily) showed a 66 percent reduction in attacks and was a safe and effective treatment for this disease. Side effects resulted in the discontinuation of nifedipine in 15 percent of participants, and those who continued vasodilator therapy reported sustained benefit during the one-year follow-up. In addition, the study showed that stress was not a significant predictor of RP attack characteristics. Higher anxiety was related to more frequent attacks above 60º F and to greater attack severity at all temperatures, but no greater pain above 60º F, and between 40º and 49.9º F, was noted. A more detailed evaluation of specific cooling temperature effects showed that at the 15º C and 10º C local cooling temperatures, the patients in the nifedipine group had a higher mean digital systolic blood pressure, a higher relative digital systolic blood pressure (RDSP), a smaller proportion of subjects with RDSP < 70% and a smaller proportion of subjects with a zero reopening pressure than the patients in the three other treatment groups. These results were statistically significant at 10º C. The nifedipine group was significantly different from all others (p < 0.05). No significant difference was found between the three other treatment groups, suggesting that the use of the calcium channel blocker was able to maintain arterial pressure in the digital arteries to keep them open at lower temperatures. The ability to learn the desired physiological response was seen in only 35% of the temperature biofeedback group, and 55% of the EMG biofeedback group while 67% of a normal temperature biofeedback group were capable of learning hand warming, suggesting that the ability to warm hands decreased the incidence of RP.
The patient described at the beginning of this article most likely has primary RP and would probably do quite well using a chronic treatment plan with a long acting calcium channel blocker. She may develop a secondary autoimmune disease process associated with Raynaud’s phenomenon.