ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Manifestations of systemic lupus erythematosus affecting the peripheral nervous system

Manifestations of systemic lupus erythematosus affecting the peripheral nervous system
Literature review current through: Jan 2024.
This topic last updated: Nov 02, 2022.

INTRODUCTION AND GENERAL PRINCIPLES — Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect virtually any organ, including the nervous system. Estimates of the incidence and prevalence of neurologic symptoms among patients with SLE vary greatly, due in large part to heterogeneity in definitions and methodology. In the aggregate, studies report that approximately one-third to one-half of SLE patients report neurologic or neuropsychiatric symptomatology [1-5]. Most studies do not clearly distinguish between symptoms that are causally associated with SLE versus those that are due to comorbid conditions or the effects of therapy.

The presentation of neurologic symptoms in SLE presents a distinct clinical challenge. Some but not all neurologic problems in people with SLE are caused by SLE, some will be comorbid, and some will be related to complications of treatment. Thus, the differential diagnosis is often extensive and will include entities that are severe, disabling, and life-threatening as well as those that are self-limited. While the attribution of neurologic symptoms to SLE may influence decisions about disease-modifying treatments, timely recognition of neurologic problems in SLE patients is also important to provide appropriate symptomatic management.

For most phenotypic manifestations of neuropsychiatric SLE (NPSLE), including peripheral nervous system manifestations, no biomarkers or diagnostic tests are specific enough to attribute neurologic diagnosis to SLE. Diagnosis of NPSLE almost always requires rigorous exclusion of other causes. Clinicians should take a detailed history, perform a comprehensive physical examination including neurologic and mental status examinations as appropriate, and localize the lesion or lesions neuroanatomically. Localization of neurologic findings and the nature of the clinical syndrome should guide differential diagnosis and strategies for testing rather than just possible associations with SLE.

Neurologic manifestations may precede, occur concomitantly with, or follow the diagnosis of SLE. However, most events are accompanied by other SLE disease activity and occur close to the time of diagnosis [6]. Because of the inherent complexities in regard to diagnosis and management, these patients are most appropriately managed by both rheumatologists and neurologists.

This topic will review the neurologic manifestations of SLE that affect the peripheral nervous system. Neuropsychiatric symptoms and other manifestations affecting the central nervous system (CNS) are discussed separately. (See "Neurologic and neuropsychiatric manifestations of systemic lupus erythematosus".)

Other aspects of the clinical presentation, diagnosis, and management of SLE are discussed separately.

(See "Clinical manifestations and diagnosis of systemic lupus erythematosus in adults".)

(See "Overview of the management and prognosis of systemic lupus erythematosus in adults".)

TERMINOLOGY — The term "neuropsychiatric SLE" (NPSLE) refers to primary, direct, pathological involvement of affected neuroanatomy by the disease process of SLE, such as from inflammation or thrombosis [7]. In the literature, this is sometimes referred to as "primary NPSLE." Patients with SLE can also experience secondary neuropsychiatric complications related to having SLE, such as central nervous system (CNS) infection associated with immunosuppression or neuropsychiatric symptoms secondary to medication; such complications are sometimes referred to as "secondary NPSLE."

Revisions to the American College of Rheumatology (ACR) nomenclature and case definitions for 19 NPSLE syndromes in 2001 narrowed the original definitions, increasing the specificity for causally associated syndromes (table 1) [7,8]. These include peripheral nervous system disorders as well as those that affect the CNS.

From a clinical practice standpoint, we find it most useful to consider each syndrome individually rather than NPSLE as a monolithic entity, as each clinical syndrome has a different potential causal relationship with SLE, differential diagnosis, and treatment plan. The occurrence of a particular neurologic or psychiatric syndrome in someone with SLE does not necessarily imply SLE is the underlying cause, particularly with relatively common syndromes.

EPIDEMIOLOGY AND PATHOGENESIS — Peripheral nervous system involvement in SLE is uncommon. In a retrospective cohort of 1224 patients, the overall prevalence of peripheral nervous system involvement was 6.9 percent, with 68 percent of syndromes directly attributable to SLE [9]. Polyneuropathy was most common (39.2 percent), followed by cranial neuropathies (30.9 percent) and mononeuropathy or multiple mononeuropathies (20.6 percent).

The pathogenesis of primary neurologic complications in SLE is heterogeneous depending on the specific syndrome and is not well understood in many cases. Some neurologic syndromes are believed to develop as a direct consequence of the disease (eg, vasculitic neuropathy), while others are more likely to reflect a co-occurring autoimmune disorder (eg, myasthenia gravis [MG]). For those more directly attributable to SLE, both inflammatory and noninflammatory mechanisms are proposed. These are discussed separately. (See "Neurologic and neuropsychiatric manifestations of systemic lupus erythematosus", section on 'Epidemiology and pathogenesis'.)

PERIPHERAL NEUROPATHIES — The frequency of peripheral neuropathy in patients with SLE is variably reported but is typically less than 10 to 15 percent of patients with SLE [5,9-12]. In many cases, the peripheral neuropathy is attributed to a cause other than SLE [1,13].

Peripheral neuropathy may occur early in the course of the illness or after several years [13]. Peripheral neuropathy due to SLE is usually asymmetric, mild, affecting more than one nerve (polyneuropathy or multiple mononeuropathy [mononeuritis multiplex]), and affecting sensory nerves more than motor nerves. Acute neuropathies attributable to SLE are usually associated with other signs or symptoms of SLE disease activity [11].

While patients may have more than one syndrome, usually one predominates. Most patients with signs and symptoms suggesting a neuropathy will require electrodiagnostic studies to confirm that a neuropathy is present and to characterize the syndrome.

The treatment approach to peripheral neuropathy is in most cases specific to the clinical syndrome, and also depends on the severity of symptoms and whether the symptoms are attributed to active SLE as discussed below.

Sensorimotor polyneuropathy — While sensorimotor neuropathy is the most common syndrome observed in patients with SLE, it is not always directly attributable to SLE. Among patients with neuropathy attributed to SLE, the mechanisms are not well understood and are likely heterogeneous, including vasculitis or an alternative form of inflammatory infiltrate, among others [14,15].

Clinical and electrodiagnostic features – The most common type of peripheral neuropathy in patients with SLE, sensorimotor polyneuropathy typically manifests with a gradual onset of symmetric sensory symptoms that is length dependent (ie, it begins in the distal lower extremities before affecting the more proximal legs and distal upper extremities) [12,13,16]. Weakness occurs later in the course of disease.

Electrophysiologic testing (electromyography and nerve conduction studies) most commonly reveals an axonal-predominant pattern of injury affecting sensory and motor nerves bilaterally; less commonly, a demyelinating pattern is observed [12,17].

Evaluation and diagnosis – This form of peripheral neuropathy has a broad differential diagnosis even with electrophysiologic confirmation; rigorous evaluation for other potential causes in addition to SLE, including laboratory studies, is recommended. In a Johns Hopkins SLE cohort of 123 patients with peripheral neuropathies, 41 (33 percent) had causes identified that were other than SLE [18]; in the Systemic Lupus International Collaborating Clinics (SLICC) cohort, 55 percent of polyneuropathies were attributed to non-SLE causes [5]. This evaluation is described separately. (See "Overview of polyneuropathy", section on 'EMG with axonal physiology'.)

Nerve biopsy is not performed in most cases but may be considered in select cases that are severe or rapidly progressive, or that are associated with other inflammatory features or evidence of worsening SLE disease activity.

Other potential causes of polyneuropathy should be excluded. As an example, polyneuropathy can also occur as an adverse effect from specific treatments, notably including thalidomide, which is sometimes used for refractory cutaneous involvement in SLE. In a one-year prospective study, 12 of 20 patients with cutaneous SLE and baseline normal nerve conduction studies developed thalidomide-induced peripheral neuropathy [19]. (See "Overview of neurologic complications of conventional non-platinum cancer chemotherapy", section on 'Thalidomide'.)

The attribution of sensorimotor neuropathy to SLE is supported by the presence of clinical and laboratory evidence of disease activity [11,13]. The evaluation for SLE disease activity is discussed separately. (See "Neurologic and neuropsychiatric manifestations of systemic lupus erythematosus", section on 'Attribution of a clinical syndrome to SLE'.)

Treatment and prognosis – For acute, severe, or rapidly progressive polyneuropathy attributable to SLE, treatment typically includes glucocorticoids, usually with the addition of cyclophosphamide, azathioprine, or mycophenolate mofetil [13]. For chronic, more indolent axonal polyneuropathy presentations, long-term immunosuppression can be considered if symptoms are clearly progressive and attributed to SLE. (See "General principles of the use of cyclophosphamide in rheumatic diseases", section on 'Drug dose for intermittent CYC' and "Mycophenolate: Overview of use and adverse effects in the treatment of rheumatic diseases", section on 'Drug dose' and "Pharmacology and side effects of azathioprine when used in rheumatic diseases", section on 'Dose titration and monitoring'.)

However, symptomatic therapy with clinical monitoring is usually favored over immunotherapy, particularly if there is not clear evidence of progression [12], since many patients may have relatively mild, nonfunctionally impairing symptoms. Symptomatic treatment for polyneuropathy should also be offered as indicated, including treatment for neuropathic pain. (See "Management of diabetic neuropathy", section on 'Pain management'.)

Data regarding prognosis are limited and somewhat variable; many patients appear to improve fully or partially with treatment [5,12].

Single and multiple mononeuropathy — In one series, single and multiple mononeuropathy composed 11 and 9 percent, respectively, of patients with SLE and neuropathy [11].

Pathogenesis This pattern of neuropathy includes compressive and noncompressive etiologies. It is unlikely that a typical single compressive mononeuropathy, such as median neuropathy from carpal tunnel syndrome or foot drop from compression of the peroneal nerve at the fibular head, will be SLE related, although metabolic risks due to renal or other organ involvement could contribute secondarily.

Noncompressive single mononeuropathies and especially multiple mononeuropathies (mononeuritis multiplex) raise concern for possible vasculitic, ischemic, or infiltrative pathologies that can be associated with SLE [20]. Vasculitic mono- and multiple neuropathies (from vasculitis affecting arterioles and small- and medium-sized arteries in SLE) tend to present acutely or subacutely with painful sensory and motor dysfunction localizable to specific large-fiber nerves [14,15].

Clinical features and diagnosis – Vasculitic mono- and multiple neuropathies tend to present acutely or subacutely with painful sensory and motor dysfunction localizable to specific large-fiber nerves. Multiple mononeuropathy presents with the rapid accumulation of nerve injury and may even mimic an acute inflammatory demyelinating polyneuropathy (AIDP) [17].

Nerve biopsy of multiple mononeuropathy attributable to SLE may reveal vasculitis or sometimes a nonvasculitic lymphocytic infiltrate [21]. Electrophysiologic testing and evaluation by a neurologic specialist are valuable in such cases, and nerve biopsy may be indicated to clarify the cause and guide immunosuppressive treatment.

The attribution of sensorimotor neuropathy to SLE is supported by the presence of clinical and laboratory evidence of disease activity [11,13]. The evaluation for disease activity is discussed separately. (See "Neurologic and neuropsychiatric manifestations of systemic lupus erythematosus", section on 'Attribution of a clinical syndrome to SLE'.)

Treatment – Treatment for functionally impairing, noncompressive single mononeuropathy attributable to SLE without evidence to suggest a more likely alternate cause includes empiric glucocorticoids; addition of other immunosuppressive therapies such as cyclophosphamide or mycophenolate mofetil may be required if other nerves become involved or if there is evidence of additional significant SLE activity.

Treatment of vasculitic neuropathy attributable to SLE or a nonvasculitic but inflammatory multiple mononeuropathy attributable to SLE includes urgent administration of high-dose ("pulse") glucocorticoids, typically followed by cyclophosphamide; rituximab, mycophenolate mofetil, methotrexate, and intravenous immune globulin (IVIG) have also been tried [17,20-22]. (See "Treatment and prognosis of nonsystemic vasculitic neuropathy", section on 'Systemic glucocorticoids plus glucocorticoid-sparing agent' and "General principles of the use of cyclophosphamide in rheumatic diseases", section on 'Intermittent (pulse) cyclophosphamide' and "Rituximab: Principles of use and adverse effects in rheumatoid arthritis", section on 'Initial dose' and "Mycophenolate: Overview of use and adverse effects in the treatment of rheumatic diseases", section on 'Drug dose' and "Use of methotrexate in the treatment of rheumatoid arthritis", section on 'Dosing and administration' and "Overview of intravenous immune globulin (IVIG) therapy", section on 'Dosing in different disorders'.)

Few data on the long-term prognosis of such patients exist. In the SLICC cohort, the probability of a mononeuropathy not resolving after 10 years was 29 percent, although interpretation of these data is limited by lack of treatment information [5].

Small-fiber neuropathy — In one cohort study, a small-fiber neuropathy was identified in 0.6 percent of SLE patients (14 of 2097), accounting for 11.4 percent of all peripheral neuropathies and 17 percent of neuropathies attributable to SLE [18]. In a cross-sectional Norwegian study, small-fiber neuropathy was detected in 13 percent of SLE patients who underwent skin biopsy (not all had accompanying symptoms or signs) [23].

Clinical features Patients with small-fiber neuropathy typically have neuropathic pain in the distal hands and feet typical of "stocking-glove" distribution of length-dependent neuropathies; there can sometimes be loss of pain and temperature sensation. Small-fiber neuropathy can also present in a non-length-dependent manner, with patchy or focal involvement, including of the face, torso, and hands more than the feet; in the Johns Hopkins SLE cohort, such non-length-dependent patterns of small-fiber neuropathy were more common than length-dependent presentations [18]. Electrophysiologic testing is often normal, unless there is an associated large-fiber neuropathy.

Evaluation and diagnosis Diagnosis of small-fiber neuropathy is usually made on the basis of history and examination but can be supported by sudomotor testing or skin biopsy (which can show loss of small-fiber nerves on special stains if in an affected area) [23,24]. (See "Skin biopsy for the evaluation of peripheral nerve disease".)

Rigorous evaluation for other potential causes of small-fiber neuropathy, such as comorbid diabetes (the risk of which may be increased in the context of chronic glucocorticoid therapy in SLE), alcohol toxicity, vitamin deficiencies, monoclonal gammopathies, and hereditary causes, should also be performed before concluding a likely SLE association.

Treatment Treatment is generally symptomatic, including pharmacotherapy options that target neuropathic pain. (See "Pharmacologic management of chronic non-cancer pain in adults".)

IVIG has been attempted for refractory cases of small-fiber neuropathy of presumed autoimmune pathogenesis [25,26], but there are insufficient data to inform treatment in the context of SLE.

Inflammatory demyelinating polyradiculoneuropathy

Acute inflammatory demyelinating polyneuropathy — AIDP, also called Guillain-Barré syndrome, and the axonal variant are both described in patients with SLE (and included as 1 of the 19 phenotypic syndromes of neuropsychiatric SLE [NPSLE] by the American College of Rheumatology [ACR]), but are rare [11,18]. In one meta-analysis, the prevalence was <0.1 percent [23], and only two cases of acute inflammatory neuropathy were reported in the international SLICC cohort of 1206 patients [1]. In other series, AIDP accounted for only 1.1 percent of peripheral nervous system manifestations in SLE [12]. Thus, evidence is scarce to inform pathophysiology and potential associations [24].

Patients with AIDP typically present with acute, progressive, fairly symmetric muscle weakness and absent or depressed deep tendon reflexes.

Although high-dose glucocorticoids are commonly used in SLE flares, they are not typically first-line therapy for AIDP; their use should only be considered if there are additional active manifestations of SLE. The evaluation and management of AIDP are discussed separately. (See "Guillain-Barré syndrome in adults: Pathogenesis, clinical features, and diagnosis" and "Guillain-Barré syndrome in adults: Treatment and prognosis".)

Chronic inflammatory demyelinating polyneuropathy — Chronic inflammatory demyelinating polyneuropathy (CIDP) phenotypes have also been reported in association with SLE, but whether this is a true SLE organ system manifestation or comorbid autoimmune disease remains unclear [27,28].

CIDP is uncommon. In one series, 0.2 percent of patients (3 of 1349) with SLE had a concurrent diagnosis of CIDP [29]. In another series, CIDP accounted for 5 percent of patients with peripheral neuropathy and SLE [11].

Patients with CIDP typically present with a gradual-onset, progressive, fairly symmetric muscle weakness with absent or depressed deep tendon reflexes, as well as sensory loss in affected distributions, with weakness being most prominent.

The evaluation and management of CIDP are discussed separately. (See "Chronic inflammatory demyelinating polyneuropathy: Etiology, clinical features, and diagnosis" and "Chronic inflammatory demyelinating polyneuropathy: Treatment and prognosis".)

Autonomic neuropathy — Autonomic neuropathy is listed as a standalone NPSLE syndrome, although in clinical practice autonomic neuropathy is rare and, if present, typically coexists with other large- or small-fiber neuropathies [30].

Evidence of autonomic dysfunction can also exist in SLE without other evidence of large-fiber neuropathy, but causation from SLE and association with inflammatory disease activity is unclear [31].

Patients with symptoms potentially attributable to autonomic dysfunction (eg, gastroparesis, urinary retention, orthostatic hypotension) should be evaluated for other potential causes before attributing them to SLE. (See "Mechanisms, causes, and evaluation of orthostatic hypotension" and "Acute urinary retention" and "Diabetic autonomic neuropathy".)

Plexopathy — Despite inclusion of plexopathy as an NPSLE-defining syndrome by ACR nomenclature, reports of associations of this condition with SLE in the literature are limited to only a few case reports [18,32]; there were no cases of plexopathy in a meta-analysis [33] or the SLICC cohort [1].

Plexopathies involve the brachial plexus or lumbar plexus and have a broad differential diagnosis. The diagnosis and evaluation are described separately. (See "Brachial plexus syndromes" and "Lumbosacral plexus syndromes".)

CRANIAL NEUROPATHIES — Cranial neuropathies (excluding optic neuropathy) occurred in 15 of 1206 patients (1.2 percent) in the Systemic Lupus International Collaborating Clinics (SLICC) cohort; however, four of these were not attributed to SLE on final analysis [1].

Clinical features — In SLE, cranial neuropathies can reportedly affect any cranial nerve. Depending upon the location of the neuropathy, symptoms and signs may include diplopia, nystagmus, ptosis, facial pain or sensory loss, dysarthria, facial weakness, and hearing loss and vertigo [14,34,35]. (See "Third cranial nerve (oculomotor nerve) palsy in adults" and "Fourth cranial nerve (trochlear nerve) palsy" and "Sixth cranial nerve (abducens nerve) palsy" and "Bell's palsy: Pathogenesis, clinical features, and diagnosis in adults" and "Bell's palsy: Treatment and prognosis in adults" and "Trigeminal neuralgia".)

Optic neuritis in SLE is discussed separately. (See "Neurologic and neuropsychiatric manifestations of systemic lupus erythematosus", section on 'Optic neuritis'.)

Evaluation and differential diagnosis — Symptoms and signs of cranial neuropathy must be distinguished from other SLE-related and non-SLE-related pathologies, such as brainstem demyelination, stroke, and meningitis. Careful evaluation for other neurologic deficits and consideration of a central nervous system (CNS) localization, such as from a stroke, are important in the context of a patient with SLE. (See "Neurologic and neuropsychiatric manifestations of systemic lupus erythematosus", section on 'Stroke'.)

The following tests should be ordered in most patients:

Contrast-enhanced brain magnetic resonance imaging (MRI)

Antiphospholipid antibody (aPL) testing (see "Diagnosis of antiphospholipid syndrome", section on 'Antiphospholipid antibody testing')

In most cases, an isolated cranial neuropathy (particularly a pupil-sparing cranial nerve III, IV, or VI palsy), especially if in association with comorbid hypertension or diabetes in a patient with SLE, will be attributed to microvascular disease when physical examination and MRI do not identify another etiology.

An otherwise idiopathic unilateral seventh nerve (facial) palsy will often be considered as Bell's palsy unless there are other atypical features to suggest an SLE-associated process. (See "Bell's palsy: Pathogenesis, clinical features, and diagnosis in adults" and "Bell's palsy: Treatment and prognosis in adults".)

Further evaluation is indicated if the cranial neuropathy is not isolated:

Cerebrospinal fluid analysis should be obtained in patients with accompanying meningeal signs (headache, stiff neck, fever) when multiple cranial neuropathies are present, or if there are other focal neurologic signs or symptoms not readily explained by neuroimaging.

One case report described a patient with SLE and multiple cranial neuropathies that were attributed to idiopathic intracranial hypertension (IIH) [36]; an association between SLE and IIH is reported in other studies as well. (See "Idiopathic intracranial hypertension (pseudotumor cerebri): Epidemiology and pathogenesis", section on 'Systemic illnesses'.)

An evaluation for possible myasthenia gravis (MG) should be pursued for patients who present with bilateral ocular-motor symptoms and/or ptosis that cannot be attributed to a single cranial nerve, particularly if there is fatigability of the findings by history or on examination [37]. (See 'Myasthenia gravis' below.)

Treatment — In general, an isolated cranial nerve palsy (excluding optic neuritis) does not usually provide an indication for immunosuppressive therapy. Those that are attributed to microvascular disease should prompt attention to risk factor modification, and if antiphospholipid syndrome (APS) is a plausible etiology on the basis of laboratory testing, antiplatelet or anticoagulation therapy should be considered. (See "Management of antiphospholipid syndrome", section on 'Secondary thrombosis prevention' and "Management of antiphospholipid syndrome", section on 'Long-term anticoagulation'.)

OTHER NEUROMUSCULAR DISORDERS

Myasthenia gravis — While myasthenia gravis (MG) is formally considered a neuropsychiatric SLE (NPSLE) syndrome, in most cases, it is believed that the MG represents a co-occurring autoimmune disorder rather than a direct manifestation of SLE. This association is rare; in one cohort of 1206 patients with SLE, there were none with MG [1]. In another series of 524 SLE patients, MG was reported in 7 (1.3 percent) [12]. SLE may manifest in patients with previously diagnosed MG and vice versa [38].

Myasthenia presents with fluctuating muscle weakness typically involving the limbs, which is often accompanied by ocular muscle weakness (manifested by ptosis and/or diplopia) and/or bulbar symptoms such as dysarthria and dysphagia. Some patients present with isolated ocular muscle symptoms, so-called ocular MG. (See "Clinical manifestations of myasthenia gravis".)

The evaluation includes antibody testing and electrophysiologic testing. Reported cases of MG in SLE are typically acetylcholine receptor antibody positive; other test findings are typical of MG in other settings [38-42]. The diagnosis and management of MG are discussed separately. (See "Diagnosis of myasthenia gravis" and "Overview of the treatment of myasthenia gravis".)

Muscle disease — Myalgias, muscle tenderness, or muscle weakness are common complaints in patients with SLE. However, significant myopathy or myositis are relatively less common in SLE. Muscle weakness can also occur as a complication of SLE treatment, particularly from glucocorticoids and sometimes from antimalarial drugs such as hydroxychloroquine.

Muscle disease in patients with SLE is discussed separately. (See "Arthritis and other musculoskeletal manifestations of systemic lupus erythematosus", section on 'Muscle involvement'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Systemic lupus erythematosus".)

SUMMARY AND RECOMMENDATIONS

Peripheral neuropathies – Approximately 10 to 15 percent of patients with systemic lupus erythematosus (SLE) develop a peripheral neuropathy; the most common syndromes are sensorimotor polyneuropathy, single and multiple mononeuropathy, and small-fiber neuropathy.

Most patients with signs and symptoms suggesting a neuropathy will require electrodiagnostic studies to confirm that a neuropathy is present and to characterize the syndrome. The presence of a small-fiber neuropathy can often be determined on the basis of history and examination.

For any of these syndromes, attribution to SLE should not be assumed. Other causes should be excluded, and patients should be evaluated for SLE disease activity, as this will direct the most appropriate therapy. (See 'Peripheral neuropathies' above.)

Cranial neuropathies – Cranial neuropathies are a rare complication of SLE. In most cases, a central nervous system (CNS) cause should be excluded with a contrast-enhanced magnetic resonance imaging (MRI) study. (See 'Cranial neuropathies' above.)

For patients with multiple cranial neuropathies in whom an MRI does not reveal a cause, further evaluation is likely indicated and should include a lumbar puncture; it is also important to consider myasthenia gravis (MG) in the appropriate clinical context.

Most cases of isolated cranial neuropathy are likely to be attributed to microvascular disease.

Myasthenia gravis – MG likely represents a co-occurring autoimmune disorder rather than a direct manifestation of SLE. The association of MG in SLE is rare; the clinical features, diagnosis, and treatment of MG are discussed separately. (See "Clinical manifestations of myasthenia gravis" and "Diagnosis of myasthenia gravis" and "Overview of the treatment of myasthenia gravis".)

Muscle disease – While muscle complaints (pain and weakness) are common in patients with SLE, myopathy and myositis are unusual. (See "Arthritis and other musculoskeletal manifestations of systemic lupus erythematosus", section on 'Muscle involvement'.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Shahram Khoshbin, MD, and Peter H Schur, MD, who contributed to earlier versions of this topic review.

  1. Hanly JG, Urowitz MB, Su L, et al. Prospective analysis of neuropsychiatric events in an international disease inception cohort of patients with systemic lupus erythematosus. Ann Rheum Dis 2010; 69:529.
  2. Ahn GY, Kim D, Won S, et al. Prevalence, risk factors, and impact on mortality of neuropsychiatric lupus: a prospective, single-center study. Lupus 2018; 27:1338.
  3. Muhammed H, Goyal M, Lal V, et al. Neuropsychiatric manifestations are not uncommon in Indian lupus patients and negatively affect quality of life. Lupus 2018; 27:688.
  4. El Hadidi KT, Medhat BM, Abdel Baki NM, et al. Characteristics of systemic lupus erythematosus in a sample of the Egyptian population: a retrospective cohort of 1109 patients from a single center. Lupus 2018; 27:1030.
  5. Hanly JG, Li Q, Su L, et al. Peripheral Nervous System Disease in Systemic Lupus Erythematosus: Results From an International Inception Cohort Study. Arthritis Rheumatol 2020; 72:67.
  6. Hanly JG, Urowitz MB, Gordon C, et al. Neuropsychiatric events in systemic lupus erythematosus: a longitudinal analysis of outcomes in an international inception cohort using a multistate model approach. Ann Rheum Dis 2020; 79:356.
  7. The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum 1999; 42:599.
  8. Ainiala H, Hietaharju A, Loukkola J, et al. Validity of the new American College of Rheumatology criteria for neuropsychiatric lupus syndromes: a population-based evaluation. Arthritis Rheum 2001; 45:419.
  9. Bortoluzzi A, Piga M, Silvagni E, et al. Peripheral nervous system involvement in systemic lupus erythematosus: a retrospective study on prevalence, associated factors and outcome. Lupus 2019; 28:465.
  10. Bluestein HG. Neuropsychiatric disorders in systemic lupus erythematosus. In: Systemic Lupus Erythematosus, Lahita RG (Ed), John Wiley and Sons, New York 1987.
  11. Florica B, Aghdassi E, Su J, et al. Peripheral neuropathy in patients with systemic lupus erythematosus. Semin Arthritis Rheum 2011; 41:203.
  12. Toledano P, Orueta R, Rodríguez-Pintó I, et al. Peripheral nervous system involvement in systemic lupus erythematosus: Prevalence, clinical and immunological characteristics, treatment and outcome of a large cohort from a single centre. Autoimmun Rev 2017; 16:750.
  13. Fargetti S, Ugolini-Lopes MR, Pasoto SG, et al. Short- and Long-Term Outcome of Systemic Lupus Erythematosus Peripheral Neuropathy: Bimodal Pattern of Onset and Treatment Response. J Clin Rheumatol 2021; 27:S212.
  14. Bertsias GK, Ioannidis JP, Aringer M, et al. EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs. Ann Rheum Dis 2010; 69:2074.
  15. Omdal R, Henriksen OA, Mellgren SI, Husby G. Peripheral neuropathy in systemic lupus erythematosus. Neurology 1991; 41:808.
  16. Jasmin R, Sockalingam S, Ramanaidu LP, Goh KJ. Clinical and electrophysiological characteristics of symmetric polyneuropathy in a cohort of systemic lupus erythematosus patients. Lupus 2015; 24:248.
  17. Gwathmey KG, Burns TM, Collins MP, Dyck PJ. Vasculitic neuropathies. Lancet Neurol 2014; 13:67.
  18. Oomatia A, Fang H, Petri M, Birnbaum J. Peripheral neuropathies in systemic lupus erythematosus: clinical features, disease associations, and immunologic characteristics evaluated over a twenty-five-year study period. Arthritis Rheumatol 2014; 66:1000.
  19. Yuki EFN, Soares R, Kupa LVK, et al. One-year prospective nerve conduction study of thalidomide neuropathy in lupus erythematosus: Incidence, coasting effect and drug plasma levels. Lupus 2021; 30:956.
  20. Martinez-Taboada VM, Alonso RB, Armona J, et al. Mononeuritis multiplex in systemic lupus erythematosus: response to pulse intravenous cyclophosphamide. Lupus 1996; 5:74.
  21. Rivière E, Cohen Aubart F, Maisonobe T, et al. Clinicopathological features of multiple mononeuropathy associated with systemic lupus erythematosus: a multicenter study. J Neurol 2017; 264:1218.
  22. Enevoldson TP, Wiles CM. Severe vasculitic neuropathy in systemic lupus erythematosus and response to cyclophosphamide. J Neurol Neurosurg Psychiatry 1991; 54:468.
  23. Gøransson LG, Tjensvoll AB, Herigstad A, et al. Small-diameter nerve fiber neuropathy in systemic lupus erythematosus. Arch Neurol 2006; 63:401.
  24. Tseng MT, Hsieh SC, Shun CT, et al. Skin denervation and cutaneous vasculitis in systemic lupus erythematosus. Brain 2006; 129:977.
  25. Schofield JR, Chemali KR. How We Treat Autoimmune Small Fiber Polyneuropathy with Immunoglobulin Therapy. Eur Neurol 2018; 80:304.
  26. Tavee JO, Karwa K, Ahmed Z, et al. Sarcoidosis-associated small fiber neuropathy in a large cohort: Clinical aspects and response to IVIG and anti-TNF alpha treatment. Respir Med 2017; 126:135.
  27. Vina ER, Fang AJ, Wallace DJ, Weisman MH. Chronic inflammatory demyelinating polyneuropathy in patients with systemic lupus erythematosus: prognosis and outcome. Semin Arthritis Rheum 2005; 35:175.
  28. Lewis M, Gibson T. Systemic lupus erythematous with recurrent Guillain-Barré-like syndrome treated with intravenous immunoglobulins. Lupus 2003; 12:857.
  29. Julio PR, Cortês MMM, Costallat LTL, et al. Chronic inflammatory demyelinating polyradiculoneuropathy associated with systemic lupus erythematosus. Semin Arthritis Rheum 2021; 51:158.
  30. McCombe PA, McLeod JG, Pollard JD, et al. Peripheral sensorimotor and autonomic neuropathy associated with systemic lupus erythematosus. Clinical, pathological and immunological features. Brain 1987; 110 ( Pt 2):533.
  31. Shalimar, Handa R, Deepak KK, et al. Autonomic dysfunction in systemic lupus erythematosus. Rheumatol Int 2006; 26:837.
  32. El-Dokla AM, Bonilla E, Ali S, Perl A. Recurrent brachial plexopathy as initial presentation of systemic lupus erythematosus: A case report and review of the literature. Lupus 2022; 31:500.
  33. Unterman A, Nolte JE, Boaz M, et al. Neuropsychiatric syndromes in systemic lupus erythematosus: a meta-analysis. Semin Arthritis Rheum 2011; 41:1.
  34. Keane JR. Eye movement abnormalities in systemic lupus erythematosus. Arch Neurol 1995; 52:1145.
  35. Andonopoulos AP, Naxakis S, Goumas P, Lygatsikas C. Sensorineural hearing disorders in systemic lupus erythematosus. A controlled study. Clin Exp Rheumatol 1995; 13:137.
  36. Shin SY, Lee JM. A case of multiple cranial nerve palsies as the initial ophthalmic presentation of antiphospholipid syndrome. Korean J Ophthalmol 2006; 20:76.
  37. Appenzeller S, Veilleux M, Clarke A. Third cranial nerve palsy or pseudo 3rd nerve palsy of myasthenia gravis? A challenging diagnosis in systemic lupus erythematosus. Lupus 2009; 18:836.
  38. Minchenberg SB, Chaparala G, Oaks Z, et al. Systemic lupus erythematosus-myasthenia gravis overlap syndrome: Presentation and treatment depend on prior thymectomy. Clin Immunol 2018; 194:100.
  39. Jallouli M, Saadoun D, Eymard B, et al. The association of systemic lupus erythematosus and myasthenia gravis: a series of 17 cases, with a special focus on hydroxychloroquine use and a review of the literature. J Neurol 2012; 259:1290.
  40. Castrejón I, Shum K, Tseng CE, Askanase A. Association between myasthaenia gravis and systemic lupus erythematosus: three case reports and review of the literature. Scand J Rheumatol 2011; 40:486.
  41. Bekircan-Kurt CE, Tuncer Kurne A, Erdem-Ozdamar S, et al. The course of myasthenia gravis with systemic lupus erythematosus. Eur Neurol 2014; 72:326.
  42. Sampath S, McCann LJ, McDonagh J, et al. Co-existence of juvenile-onset systemic lupus erythematosus and juvenile myasthenia gravis. Lupus 2015; 24:1462.
Topic 4665 Version 31.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟