Skin denervation and cutaneous vasculitis in systemic lupus erythematosus

Abstract

To understand the clinical significance and mechanisms of cutaneous denervation in systemic lupus erythematosus (SLE), we assessed intraepidermal nerve fibre (IENF) density of the distal leg in 45 SLE patients (4 males and 41 females, aged 38.4 +/- 13.6 years) and analysed its correlations with pathology, lupus activity, sensory thresholds and electrophysiological parameters. Compared with age- and gender-matched control subjects, SLE patients had lower IENF densities (3.08 +/- 2.17 versus 11.27 +/- 3.96 fibres/mm, P < 0.0001); IENF densities were reduced in 38 patients (82.2%). Pathologically, 11 patients (24.4%) were found to have definite cutaneous vasculitis; the severity and extent of cutaneous vasculitis were correlated with IENF densities. Patients with active lupus had even lower IENF densities than those with quiescent lupus (1.86 +/- 1.37 versus 4.15 +/- 2.20 fibres/mm, P = 0.0002). By linear regression analysis, IENF densities were negatively correlated with the SLE disease activity index (r = 0.527, P = 0.0002) and cumulative episodes of lupus flare-up within 2 years before the skin biopsy (r = 0.616, P = 0.0014). Clinically, skin denervation was present not only in the patients with sensory neuropathy but also in the patients with neuropsychiatric syndrome involving the CNS. SLE patients had significantly elevated warm threshold temperatures (P = 0.003) and reduced cold threshold temperatures (P = 0.048); elevated warm threshold temperatures were associated with the reduced IENF densities (P = 0.032). In conclusion, cutaneous vasculitis and lupus activities underlie skin denervation with associated elevation of thermal thresholds as a major manifestation of sensory nerve injury in SLE.

Imaging signatures of altered brain responses in small-fiber neuropathy

“…Procedures of the skin biopsy, immunohistochemical staining of IENFs, and quantification of IENF density are detailed in Ref. 77. Briefly, the skin surface was anaesthetized with 2% lidocaine before a punch of 3 mm in diameter was taken from the right lateral side of the distal leg, 10 cm above the lateral malleolus.…”

Evaluation of distal symmetric polyneuropathy: The role of autonomic testing, nerve biopsy, and skin biopsy (an evidence‐based review)

“…22 Other studies have employed skin biopsy for detection or monitoring of leprosy, hereditary amyloidosis, vasculitic neuropathy, and Fabry's disease. 49,53 Additional studies are required to determine the usefulness of skin biopsy in the diagnosis and monitoring of these and other varieties of neuropathy.…”

Skin biopsy: an emerging method for small nerve fiber evaluation

“…5,10,[16][17][18][19][20][21] Several studies recently applied IENFD quantification in axonal neuropathy, vasculitic neuropathy, and hereditary neuropathy. [22][23][24] Comparison the IENFD of symptomatic side with that of symmetric healthy side is a useful way to diagnose asymmetric or focal neuropathy. 25 Skin biopsy is a minimally invasive method and repeated biopsy causes no complication.…”