Cold sensitivity, described as "an exaggerated or abnormal reaction to cold exposure of the injured part, causing discomfort or the avoidance of cold", is a common complaint following hand injuries [1, 2]. A variety of symptoms, such as pain, aching, numbness, weakness, stiffness and change in skin colour may be elicited by exposure to cold [3] but individual variations limit a symptom-based definition [4]. Post-traumatic cold sensitivity develops within the first few months and does not generally improve over time [2, 5]. The pathophysiology behind the complex phenomenon of cold sensitivity remains unclear, thus a multifactor aetiology, including bony, vascular and neural components is suggested [6]. Cold sensitivity can occur in connection with a variety of injuries and conditions. It is frequently reported after traumatic hand injuries [7–12], after surgically treated Dupuytren's contracture [13] and in patients with hand-arm vibration syndrome (HAVS) [14, 15].

Cold sensitivity may have a profound effect on health-related quality of life as well as upper extremity disability, as described in patients with specific hand injuries [16, 17] and as indicated in a group of patients with digital replantation or amputation where 65% considered cold intolerance the main reason for their disability [18]. However, the impact on disability and health-related quality of life in patients with HAVS compared to patients with a traumatic hand injury and to normal subjects has not previously been considered. For a proper comparison of patient groups, validated self-report questionnaires, such as the Cold Intolerance Symptom Severity (CISS) questionnaire [3, 19], are important for defining the individual patient's symptoms and signs and clarifying the impact cold sensitivity may have on daily life. Our aim, therefore was to describe the self-reported consequences of cold sensitivity and its association with self-reported disability and health-related quality of life in patients with hand injuries or HAVS and in normal subjects.

There was an internal dropout for the CISS questionnaire (normal population, n = 13, traumatic hand injury, n = 2, HAVS, n = 2), in that not everyone answered all included questions.

Self-reported cold sensitivity (CISS questionnaire, VAS question and PWES)

Based on a recently defined cut-off value [6] (CISS score > 50 = abnormality), abnormal cold sensitivity was seen in 4/81 (5%) of the normal population, in 39/86 (45%) of patients with traumatic hand injury [amputation injury = 26/51 (51%), nerve injury = 13/35 (37%), p = 0.208] and in 21/28 (75%) of patients with HAVS (Fig 1). Patients with HAVS had significantly higher CISS scores than patients with traumatic hand injury (p = 0.004).

The predominant problems on exposure to cold among the patients were weakness, stiffness, numbness, skin colour change, pain and aching in their injured hands (Question no 1 in the CISS questionnaire, Fig 2). Patients with HAVS had significantly more difficult problems in their hands with weakness (p = 0.022), numbness (p = 0.016), aching and pain (p = 0.001) on exposure to cold than patients with a traumatic injury (Fig 2). Accordingly, these patients had greater problems on exposure to cold in the majority of the situations highlighted in the CISS questionnaire (Table 2). Fifty-four of the 86 patients (62%) with a traumatic injury and 24/28 patients (86%) with HAVS experienced cold-induced symptoms several times daily or continuously/all the time. The relief of symptoms on return to a warm environment varied significantly between both patient groups and the normal population (p = 0.001). It took more than 30 minutes before symptom relief was experienced in 3 of 93 subjects (3%) in the normal population, in 20/86 (23%) of patients with a traumatic hand injury and in 10/28 (36%) of patients with HAVS (Table 2).

	Cold Intolerance Symptom Severity questionnaire (CISS).	Score	Normal population n = 93a	Traumatic hand injury n = 87b	HAVS n = 28
	Total CISS score (4-100)	4-100	16 (4-62)2	45 (4-96)3	59 (23-94)3
1.	Not scored1	-	-	-	-
2.	How often do you experience these symptoms?		2 (2-10)2	8 (2-10)	8 (2-10)
	-continuously/all the time	10
	-several times a day	8
	-once a day	6
	-once a week	4
	-once a month or less	2
3.	When you develop cold-induced symptoms, on your return to a warm environment are the symptoms relieved		2 (2-10)2	6 (2-10)3	6 (2-10)3
	-within a few minutes	2
	-within 30 minutes	6
	-after more than 30 minutes	10
4.	What do you do to ease or prevent your symptoms occurring? (please tick)		4 (0-10)2	4 (0-10)3	4 (0-10)3
	-take no special action	0
	-keep hand in pocket	2
	-wear gloves in cold weather	4
	-wear gloves all the time	6
	-avoid cold weather/stay indoors	8
	-other	10
5.	How much does cold bother your injured hand in the following situations? Please score (0-10)
	- holding a glass of ice water	0-10	0 (0-8)2	3 (0-10)	5 (0-10)
	- holding a frozen package from the freezer	0-10	1 (0-9)2	5 (0-10)3	7 (0-10)3
	- washing in cold water	0-10	0 (0-10)2	4 (0-10)3	7 (0-10)3
	- when you get out of a hot bath/shower with the air at room temperature	0-10	0 (0-6)2	0 (0-8)3	3 (0-10)3
	- during cold wintry weather	0-10	2 (0-10)2	8 (0-10)3	8 (4-10)3
6.	Please state how each of the following activities have been affected as a consequence of cold-induced symptoms in your injured hand and score each (0-4).
	- domestic chores	0-4	0 (0-3)2	1 (0-4)3	2 (0-3)3
	- hobbies and interests	0-4	0 (0-4)2	2 (0-4)3	3 (0-4)3
	- dressing and undressing	0-4	0 (0-2)2	0 (0-4)	1 (0-4)
	- tying your shoe laces	0-4	0 (0-3)2	1 (0-4)	2 (0-4)
	- your job	0-4	0 (0-4)2	2 (0-4)3	3 (0-4)3

Median values (range) for total score and individual questions¹ in different subgroups.

^{a and b} Some variations in response rate (internal drop out) in separate questions were noted ^a n = 81-93,

^b n = 86-87

¹Question number 1 concerns severity of different symptoms on exposure to cold and is not included in the total CISS score. See Fig 2 for detailed information.

² Patients (= traumatic hand injuries and HAVS subsumed together) had significantly worse scores/problems than the normal population. Mann-Whitney U- Test; p = 0.002 to 0.04

³ A significant difference wasnoted between subgroups (Kruskal Wallis Test; p < 0.001). Patients with HAVS had significantly worse scores/problems than patients with traumatic hand injury. Mann-Whitney U-Test = 0.001 for all items.

Cold wintry weather was very troublesome for both patient groups in contrast to the normal subjects. Cold sensitivity also affected patients' involvement in their hobbies and interests (Table 2). Twenty-one of 39 patients (54%) with a traumatic hand injury and abnormal CISS score had severe problems with cold- induced symptoms during their leisure activities, while a clear majority (32/47, 68%) of patients with a normal CISS score only experienced minor problems or no difficulties at all.

Perceived problems on exposure to cold, expressed as median (range) scores on the VAS question, were 2 (0-9.5) for the normal subjects, 6 (0-9.8) for patients with a traumatic hand injury and 8 (1-10) for patients with HAVS. Normal subjects had significantly less problems on exposure to cold than the patients groups (p = 0.001). Patients with HAVS also had significantly greater problems than patients with a traumatic hand injury (p = 0.001).

Patients in both groups were exposed to cold in their work environment to a significantly higher degree than the normal population (PWES score, Table 3) and reported, accordingly, a negative effect on their work ability (Question 6, Table 2). Twenty-seven percent of all patients (traumatic hand injury; n = 14, HAVS; n = 9) reported that they were unable to work because of problems with cold sensitivity. Patients with a traumatic hand injury who changed their work had significantly higher CISS scores (p = 0.015) than those who remained in their previous work employment, 66 (21-86) and 45 (7-85), respectively]. There was no such difference in the patient group with HAVS [68 (27-91) and 58 (23-94), p = 0.286].

Potential Work Exposure Scale	Normal population n = 49	Traumatic hand injury n = 51	HAVS n = 19
PWES: Total score (0-30)	5 (0-20.1)1	10.2 (0-25)	9.4 (0-21.6)
1. How much of your work requires manipulation of objects with your hands at temperature near or below freezing? (0-10)2	1.3 (0-6.4)1	5 (0-10)	5 (0-7.5)
2. At work, how much time are you required to be working either outside in the cold or in a refrigerated environment? (0-10)2	2.5 (0-7.5)1	5 (0-10)	5 (0-10)
3. How much do you do with the temperature at or near freezing when you are not able to wear gloves or mittens? (0-10)2	0.3 (0-7.5)	0.7 (0-9.3)	1.9 (0-8.7)

Median values (range) for total score and individual questions in different subgroups.

¹ Patients were exposed to cold in their work environment to a significantly higher degree than the normal population (p = 0.013). No significant difference was found between patients with a traumatic hand injury and HAVS.

² 0 = never, 10 = all the time

Cold sensitivity - association with disability and health-related quality of life

The CISS score correlated significantly with the DASH score (traumatic hand injury; r_S = 0.57, p = 0.002, HAVS; r_S = 0.72, p = 0.001). Significantly higher DASH scores (p = 0.001), indicating more serious disability, were seen in both patient groups with abnormal CISS score compared to those with a normal CISS score (Fig 3).

Patients with abnormal cold sensitivity (i.e. CISS score > 50) from the groups with traumatic hand injury or HAVS had a poorer health-related quality of life than the patients from these groups with normal cold sensitivity, as shown by a significantly larger mean deviation from norms in the subscales Role Physical and Bodily pain. A similar pattern of abnormality appeared for the patients with traumatic hand injury in the subscale Physical Functioning (Fig 4a) and in the subscales Vitality and Mental Health for the patients with HAVS (Fig 4b).

Our results show that abnormal self-reported cold sensitivity was not only observed in patients with a traumatic hand injury, but was particularly common among patients with hand-arm vibration syndrome (HAVS) as compared to normal subjects. In addition, the severity and occurrence of symptoms and the relief of cold-induced symptoms after returning to a warm environment, the influence on daily life, disability and health-related quality of life were most apparent in patients with a diagnosis of HAVS. Among our patients this diagnosis was based on a history of regular exposure to hand-held vibrating tools with white fingers on exposure to cold and/or sensorineural symptoms, an impaired vibrotactile sense and neurophysiological findings supporting HAVS but excluding other causes of neuropathy.

A novel finding in this study was the significant relationship between abnormal self-reported cold sensitivity and health-related quality of life in our patients, indicating the severe impact of cold sensitivity for the individual patient. The association was particularly apparent for subscales in the SF-36 focusing on how the magnitude and interference of bodily pain affects work performance or questions concerning satisfaction and performance at work or during other daily activities (Role Physical). In addition, abnormal cold sensitivity was also associated with greater disability, as measured using the DASH questionnaire. A more severe cold sensitivity, associated with more functional limitations and reduced health-related quality of life, has previously been reported in patients with upper extremity injuries [16]. Consequences and adaptations in daily life may also result in changed life roles and a struggle to maintain self-image [24]. A majority of vibration-exposed patients consider cold sensitivity as severe or as a problem that hinders their functioning [15]. Furthermore, they report a poorer quality of life and difficulties in the activities of daily living [25]. It is important to include an assessment of cold sensitivity for vibration-exposed patients since it may be an early neurological symptom of vibration-induced injury [14, 26].

Both groups of patients had an underlying nerve injury or neuropathy. Structural changes in nerve trunks occur after a traumatic hand injury, but may also be present in HAVS [14] although possibly differing in character [27, 28]. Complex structural alterations occur in nerve trunks in HAVS with demyelination, degeneration of nerve fibres of different diameter, receptor dysfunction and even a central component has recently been suggested [29, 30]. Thus, the structural changes in HAVS may be even more complex, located at multiple levels, but profound changes also take place after a traumatic hand injury with nerve involvement. However, several non-neuronal factors may be predictors of cold sensitivity [6]. A difference between the two groups of patients were that patients with HAVS were older and had a history of long-time vibration exposure compared to the patients with traumatic hand injuries who were relatively recently injured. Even a short exposure time to vibrating tools may induce cold sensitivity and reduce sensitivity to temperature [31]. However, we have previously described that age peer se has no impact on cold sensitivity in neither normal's nor hand injured patients; thus, ruling out the possibility that age may explain the difference in symptoms between the groups [6]. The complex pathophysiology in HAVS may contribute to the severe self-reported cold sensitivity in this group. In addition, there was no significant difference in CISS scores between our patients with an amputation and those with a pure nerve lesion, which may indicate that nerve regeneration per se has no impact on cold sensitivity.

All patients ranked weakness, stiffness, numbness and skin-colour change as the most troublesome symptoms on exposure to cold, while pain and aching were only ranked as equally troublesome in patients with HAVS. There are some inconsistencies in previous studies concerning exactly what symptoms patients experience when exposed to cold [4, 5, 32]. Such inconsistencies may be explained by variations in the study population or whether the severity or presence of symptoms was evaluated. Our patients experienced cold-induced symptoms frequently with a significant difference in the time it took for patients, compared to the normal subjects, to experience relief of symptoms on return to a warm environment. Activities, such as holding a package from the freezer or washing in cold water, are problematic and cold sensitivity has a clear impact on leisure activities in a majority of patients with abnormal self-reported cold sensitivity. This is in keeping with earlier findings [24, 33]. Cold, wintry weather was, as expected, very troublesome for the majority of patients. Not only temperature, but also rain, high humidity and windy weather trigger cold-induced symptoms. Patients with severe cold sensitivity may therefore also have problems during other seasons. Interestingly, seasonal variation is not included as a variable in the CISS questionnaire. One strength of our study is that we investigated the patients at a defined time-point during the cold season.

The frequent exposure to cold, as shown by high scores on the PWES, put hand-injured patients in an exposed position and forced them to change their work. Patients who had changed employment had significantly higher CISS scores than those who remained in their jobs, indicating the impact cold sensitivity may have.

In conclusion, abnormal cold sensitivity is seen in 75% of patients with HAVS and in 45% of patients with a traumatic hand injury. The predominant problems are weakness, numbness, stiffness, skin colour change and pain/aching, on exposure to cold. One important finding was a significant difference in time taken for symptoms to be relieved on return to a warm environment between both patient groups and compared to the normal population. Cold sensitivity among patients with traumatic hand injuries, such as nerveinjuries and amputations, and HAVS may have a profound impact on performance at work, in leisure pursuits and in other activities in daily life. It is apparent that there is an association between self-reported cold sensitivity and disability and health-related quality of life.