SMALL FIBRE SENSORY INVOLVEMENT IN PATIENTS WITH PRIMARY SJÖGREN SYNDROME: HISTOLOGICAL AND NEUROPHISIOLOGIC STUDY

Objectives: To evaluate the impairment of small fibre nerve in patients with primary Sjögren Syndrome (pSS) either asymptomatic or with symptom of small fibre sensory neuropathy (SFSN). Methods: All pSS patients fulfilled the revised American-European Consensus Group criteria for the diagnosis of definitive SS (2002). Other causes known to be associated with SFSN were excluded. All patients underwent neurologic and laboratory examination, Neuropathy Pain Questionary (VAS) designed to assess distinct pain qualities (Bradley 1997) and conventional neurophysiological examination. Involvement of small fibres was investigated by quantitative sensory thresholds (QST) in the foot, distal leg and proximal thigh; cutaneus blood flow (CBF) by laser Doppler Flowmetry (LDF) at foot, distal leg and proximal thigh, with different modalities: basal CBF (bCBF) and temperature, vasoconstrictor reflexes induced by deep breathing (DB) and postural variation (veno-arteriolar reflex, VAR), vasodilatation induced by local heating (LH). Skin biopsy was performed at proximal thigh and distal leg to evaluate epidermal nerve fiber density and morphology. Results: We studied 20 patients with pSS (15 F/5 M, mean age 53.8 yrs, range 27-66, mean duration of disease 9.3 yrs). All patients complained of sicca symptoms. 70% of pts had concomitant joint involvement; 15% had Raynaud phenomenon, 5% cutaneous vasculitis. One patient had a concomitant biopsy proven celiac disease. Autoimmune thyroiditis was present in 40% of pts. The main immunologic features were ANA in 90%, anti-Ro/SSA antibodies in 55%, anti-La/SSB in 45%, rheumatoid factor in 45%, cryoglobulinemia in 5%. Concerning the neurologic examination, 10 pts presented typical symptoms of SFSN while 10 were asymptomatic; pain and burning were the most prominent features. Conventional Neurophysiology was normal. QST was abnormal in 90% of symptomatics, and 80% of asymptomatics, with particular deficit of cold sensation. LDF bCBF and LDF DB were abnormal in 30% of patients; LDF LH in 50%; LDF VAR in 25%. Intraepidermal nerve fibre (INEF) density and morphology were abnormal in 80% of patients. In 16 patients (8 asymptomatics and 8 symptomatic) IENF density was significantly lower at the proximal thigh than at the distal leg. Only in two patients (both symptomatics) IENF density was lower at distal site, with the length-dependent loss of cutaneous innervation. Conclusion: Our findings suggest an early impairment of small nerve fibres in pSS patients, despite of the presence or absence not of sensory symptoms, suggesting that pSS may cause a functional impairment of peripheral axons. In pSS IENF loss and functional tests impairment were frequently non length-dependent, suggesting the presence of small fiber sensory neuronopathy, probably localized at the level of dorsal root ganglia.