Open Access Austin Journal of Clinical Neurology Original Article Severe Peripheral Neuropathy in a Young Female with Primary Sjogren’s Syndrome Mirica R1* and Soare I2 1Faculty of Medicine, Carol Davila University of Medicine Abstract and Pharmacy, Romania Neurological disorders represent one of the most common extraglandular 2Faculty of Medicine, Titu Maiorescu University, Romania manifestations may be found in patients with Sjogren’s syndrome. In this *Corresponding author: Roxana Mirica, Faculty paper we will present the case of a 43-year-old patient with symptomatic onset of Medicine, Carol Davila University of Medicine and characterized by paresthesia with “stocking-glove” distribution, evolving with Pharmacy, 60, Grigore Alexandrescu Street, District 1, zip severe ataxia. Clinical examination revealed disturbances of proprioceptive code 010626, Bucharest, Romania sensitivity in both thoracic and pelvic limbs. The titer of antinuclear antibodies was 1/320, Anti-Ro (SS-A) antibodies were positive, and the biopsy of minor Received: April 29, 2020; Accepted: May 19, 2020; salivary glands showed histopathological changes. The patient underwent Published: May 26, 2020 repeated electromyography examinations that revealed sensory axonal polyneuropathy. SICCA symptoms started several years after the onset of the first neurological manifestations, and the Schirmer’s test was ‘borderline’. Corroboration of clinical and paraclinical data led to the diagnosis of primary Sjogren’s syndrome with sensory axonal polyneuropathy. The administration of Plaquenil (Hidroxychloroquine sulfate), intravenous immunoglobulin, glucocorticoids, plasmapheresis, Mycophenolate mofetil, Belimumab and Rituximab did not improve neurological complaints, the peripheral neuropathy being refractory to treatment. Keywords: Primary sjogren’s syndrome; Sensory axonal polyneuropathy; Severe ataxia Introduction such as unsteady gait, intense vertigo accompanied by nausea without vomiting, balance and coordination disorders, dysarthria, decreased Sjogren’s syndrome is an autoimmune disorder affecting the concentration, important physical asthenia, right ear tinnitus exocrine glands [1], associated with peripheral nervous system associated with bilateral hearing loss and visual impairment with manifestations, with sensory neuropathy as one of the most common ‘blurred vision’ in the right eye. It also associates muscle twitching neurological forms [2]. and atrophies at the level of the pelvic limbs and hypotonia. To Sjögren’s syndrome, in both primary and secondary forms, investigate these signs and symptoms, several electromyography is defined as a chronic [3], multisystemic disease of unspecified examinations were performed in April, June and December 2011, etiology, and is more common in middle-aged women (aged 40-50) and the diagnosis was axonal sensitive polyneuropathy. The patient [1]. The primary type is characterized by the involvement of exocrine also states the presence of Raynaud’s phenomenon, urinary urgency glands with or without systemic complications, and the secondary and chronic constipation, symptoms with an onset of approx. 2 years. form is associated with other autoimmune diseases [1]. Peripheral In 2012, the suspicion of an antiphospholipid syndrome was nervous system involvement is the consequence of neuronal damage raised, with positive anti-beta-2 glycoprotein antibodies and by immunological mechanism [2], such as apoptosis, antibody neuroborreliosis (based on dark field microscopy), but without expression, B and T cell changes, and cytokine levels [4,5]. We increased serum antibody titer, disproved by the cerebrospinal fluid present a clinical case of primary Sjogren’s syndrome with severe result (cellularity, proteinorrachia, glycorrhachia–within normal sensory axonal polyneuropathy. limits), for which she received repeated courses of antibiotics that Methods and Materials suddenly worsened the symptoms, with significant weight loss, so that the patient was able to move only with the help of another person. 43-year-old M.I. patient with significant family history (mother- rheumatoid arthritis and mixed connective tissue disease, aunt- In 2014, the diagnosis of primary Sjogren’s syndrome was rheumatoid arthritis), with dyslipidemia, tenosynovitis in both established based on the presence of anti-Ro antibodies and antinuclear radiocarpal joints operated in 2005 and 2006, is admitted to a clinical antibodies and on the performed biopsies (of minor salivary gland hospital in Bucharest for symptoms started in December 2010, and sural nerve and gastrocnemius muscle). The histopathological consisting of paresthesia with distal onset, predominantly in the left appearance of the salivary gland fragment examined revealed focal hemibody, both in the thoracic limbs, “glove”-like (with progression sialadenitis with predominantly B lymphocytes. The biopsy of up to 2/3 left arm and right elbow), and in the pelvic limbs, “stocking”- the left sural nerve showed signs of severe axonal polyneuropathy like (with progressive evolution up to the knee), as well as on the face. manifested morphologically by decreased density of myelin fibers, 2 2 In 2011, the patient complains of the occurrence of related symptoms at 1,987 fb/mm (N=7,000-11,000 fb/m ), 34% fibers with myelinic Austin J Clin Neurol - Volume 7 Issue 1 - 2020 Citation: Mirica R and Soare I. Severe Peripheral Neuropathy in a Young Female with Primary Sjogren’s ISSN : 2381-9154 | www.austinpublishinggroup.com Syndrome. Austin J Clin Neurol 2020; 7(1): 1138. Mirica et al. © All rights are reserved Mirica R Austin Publishing Group ovoids and bullae and 15% fibers with segmental demyelination Since 2014, several regimens have been tried: Plaquenil 200 lesions of the total dissociated myeloid fibers. The microscopy of mgx2/day (stopped in 2017 for ineffectiveness), 9 courses of IVIg (2g/ the left gastrocnemius muscle showed muscle lesions of neurogenic kg body weight) between 2014 to 2018, 4 plasmapheresis sessions in origin with the presence of fibers in necrobiosis.Laboratory tests and December 2017 (without clinical-biological improvement), and in investigations for disseminated lupus erythematosus, rheumatoid 2016 a 4-month period of experimental medication–Belimumab- arthritis, Wegener’s granulomatosis, scleroderma, dermatomyositis, without efficacy. In 2018, Prednisone 25 mg/day and Mycophenolate polymyositis did not confirm all these diagnoses. Serum protein mofetil 500 mg-2 capsules/day combination therapy was administered electrophoresis, immunogram, thyroid hormones, HBs Ag, anti-HVC for 5 months; the dose of Prednisone was reduced to 15 g/day due to a antibodies, HIV, anti-neuronal antibodies, anti-MAG antibodies, myasthenic syndrome and cortisone-induced myopathy. In the early anti-ganglioside antibodies, anti-cardiolipin antibodies Ig M and Ig part of 2019, the patient is undergoing treatment with Rituximab 500 G, anti-β2 glycoprotein antibodies Ig G, anti-Sm antibodies, anti-La mg-2g/week (given as off-label medication under the conditions of antibodies, anti-p ANCA antibodies, anti-centromere antibodies, Sjogren’s syndrome with treatment-refractory polyneuropathy). The anti-SCL 70 antibodies, ndc DNA, C-reactive protein, rheumatoid first course was performed in July 2018, with the patient reporting factor, serum complement C3, C4 were within normal limits with an improvement in xerostomia and xerophthalmia, normalization positive result for ribosomal P protein. At the same time, Schirmer’s of ATPO (Autoantibodies Thyroid Peroxidase) value, decrease of test was ‘borderline’ and cryoglobulinemia and lupus cells–absent. anti-Ro antibodies titer, the rest of the complaints (especially the neurological ones) remaining unchanged. Since October 2019, the The patient also performed visual and auditory evoked potentials patient has been recommended the following regimen: intravenous that revealed long-latency potentials. Cerebral and cervical-dorsal- immunoglobulin, Mycophenolate mofetil, Arlevert (Cinnarizine and lumbar spine MRI with contrast agent excluded other presumptive dimenhydrinate)–3 capsules/day, Thiossen (Thioctic acid)-1 capsule/ diagnoses, such as multiple sclerosis, with no evidence of central day and vitamin B and D supplements, also without success. nervous system demyelination. In April 2018, the patient is diagnosed with chronic autoimmune thyroiditis-subclinical hypothyroidism, The patient is monitored every 3 months for clinical reassessment, for which Euthyrox treatment is administered, 25 µg/day. During for IV Ig administration and for dosage adjustment of the other the same period, manifestations of SICCA syndrome-xerostomia drugs from the therapeutic scheme as well. The last readmission in and xerophthalmia (approximately 7 years after the onset of the first hospital was in January 2020, when the patient described a worsening neurological complaints) occurred. of neurological symptoms (paresthesia), but cortisone-induced myopathy, myasthenic syndrome, xerophthalmia and xerostomia The objective examination upon re-admission in September were remitted. 2019 revealed pale skin, livedo reticularis at the distal extremities, underweight, no joint swelling, no rash, pulmonary auscultation Disscusion and Results without added crackles, cardiac without added murmurs, no Sjogren’s syndrome is an autoimmune, slowly progressive orthostatic hypotension phenomena, supple abdomen, mobile with disorder [7] of unknown cause, involving genetic and environmental respiration, spontaneous