Abnormal warm and cold sensation thresholds suggestive of small-fibre neuropathy in sarcoidosis
Introduction
Sarcoidosis is a multi-organ disorder of unknown origin, characterized by granuloma formation, which is probably antigen driven. The disease occurs throughout the world, although prevalence varies among ethnic and racial groups. Prevalence ranges from 10 to 40 per 100 000 population, mostly young adults of either gender (Newman et al., 1997). The clinical manifestation of sarcoidosis is highly variable, depending on the intensity of the inflammation and the organ systems affected. Sarcoidosis occurs most frequently in the lungs or lymph nodes, although it can appear in other organs. Spontaneous recovery may occur, but the disease can also become chronic or have a progressive course. Apart from pulmonary symptoms such as dyspnea and coughing, patients often complain of symptoms such as fatigue, pain and sweating (James, 1993; Wirnsberger et al., 1998; Sharma, 1999; Hoitsma et al., 2003). So far, no organic substrate has been found for these symptoms. Treatment of sarcoidosis consists largely of immunosuppressive drugs such as steroids, methotrexate, cyclosporin and, more recently, infliximab (Baughman and Lower, 2001). When features of disease activity, for example radiological abnormalities and lung function impairment, resolve during treatment, fatigue and pain may persist. Therefore, objective test results such as chest X-ray and laboratory parameters do not always correlate with the well-being of the patient (Wirnsberger et al., 1998). Consequently, the question arises whether these symptoms are psychogenic or manifestations of the underlying organic disease.
Recently, we observed a pattern of symptoms suggestive of small-fibre neuropathy with autonomic involvement in a subset of sarcoidosis patients (Hoitsma et al., 2002).
Small-fibre neuropathy is a generalized peripheral neuropathy selectively involving Ad and C fibres. When the somatic small afferent fibres are affected, symptoms typically consist of pain, dysaesthesias and disturbed temperature sensitivity. Furthermore, autonomic fibres may be involved, causing autonomic dysfunction. Standard nerve conduction tests evaluate only large nerve fibre function. Quantitative techniques for the assessment of small nerve fibres are not routinely applied. Therefore, the diagnosis of small-fibre neuropathy can easily be missed.
Quantitative sensory testing has become an important tool in assessing small and large sensory fibre functions. Small-calibre sensory fibres are assessed by temperature threshold testing (TTT) and large-calibre fibres by vibratory threshold testing. TTT quantifies thresholds for warm and cold perception (Fruhstorfer et al., 1976; Jamal et al., 1987; Yarnitsky and Sprecher, 1994; Reulen et al., 2003). It is a non-invasive method, easy to perform, and mostly not painful. Furthermore, the testing does not require highly trained personnel.
Autonomic neuropathy can be assessed by cardiovascular autonomic reflex testing on the basis of heart rate variability and blood pressure investigations (Ewing and Clarke, 1982). Small-fibre sudomotor function can be assessed, among other functions, by the sympathetic skin response (SSR). Although the diagnostic value of SSR is limited, it is widely available and inexpensive. Quantitative sudomotor axon reflex testing (QSART) is a more sensitive technique for sudomotor assessment, but it requires special equipment which is available in only a few centres.
The aim of the present study was to investigate small fibre sensory function by determining TTT, EMG, SSR and cardiovascular autonomic tests in a subset of sarcoidosis patients.
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Patients
From August 2000 to July 2002, 125 patients with sarcoidosis, confirmed according to international guidelines (Hunninghake et al., 1999) were referred to the Maastricht Sarcoidosis Management Center, which serves as a tertiary referral centre for sarcoidosis patients in the Netherlands. A group of 74 patients (41 men, 33 women) were included in the present study. To be included, patients had to recall symptoms suggestive of small-fibre neuropathy (a combination of two or more of the following
Temperature threshold testing
TTT results at any measured site were considered abnormal only if both MLE and MLI were abnormal. This was the case in 51 of the 74 patients with symptoms suggestive of small-fibre neuropathy (69%). Of these 51 patients 28, 7 and 16 showed only WS, only CS, and both WS and CS abnormalities, respectively (Table 2). TTT findings were more often abnormal in the feet than the hands (54 vs. 38%). However, a combination of abnormal temperature sensation in the hands and normal temperature sensation
Discussion
To the best of our knowledge we are the first to report TTT abnormalities suggestive of small-fibre neuropathy in sarcoidosis, possibly explaining symptoms which so far have often been considered to be ‘non-specific.’ Fifty-one out of 74 patients with symptoms suggestive of small-fibre neuropathy had abnormal TTT results.
WS was more often affected than CS (59 vs. 31%). CS abnormalities in combination with normal WS were present in 7 of the 74 cases. Thus, unmyelinated C fibres seemed to be more
References (51)
- et al.
Small fiber neuropathy in sarcoidosis
Lancet
(2002) - et al.
Thermal thresholds in complex regional pain syndrome type I: sensitivity and repeatability of the methods of limits and levels
Clin Neurophysiol
(2000) - et al.
Epidermal innervation: changes with aging, topographic location, and in sensory neuropathy
J Neurol Sci
(1999) - et al.
Comparison of thermal threshold tests to assess small nerve fiber function: limits vs. levels
Clin Neurophysiol
(2003) - et al.
Sarcoidosis with a Landry-Guillain-Barre syndrome and clinical response to corticosteroids
Am J Med
(1967) - et al.
Normal Hoffmann reflex latencies (H-M interval) in relation to age and body length
Clin Neurol Neurosurg
(1983) - et al.
Evaluation of quality of life in sarcoidosis patients
Respir Med
(1998) - et al.
Thermal testing: normative data and repeatability for various test algorithms
J Neurol Sci
(1994) American Academy of Neurology: Report and recommendations of the San Antonio Conference on Diabetic Neuropathy (consensus statement)
Diabetes Care
(1988)- et al.
CT features of sarcoid infiltration of a lumbosacral nerve root
J Comput Assist Tomogr
(1989)