Analysis of 87 patients with Löfgren's syndrome and the pattern of seasonality of subacute sarcoidosis

Background and objective: Sarcoidosis is a multisystem disease of unknown aetiology. The seasonality of sarcoidosis in symptomatic, recently diagnosed patients with Löfgren’s syndrome was evaluated to help better understand the possible causative factor(s) in the pathogenesis of sarcoidosis. Methods: Four hundred and ninety‐two consecutive patients with sarcoidosis were investigated. The demographic and clinical features, course of the disease, initial diagnostic methods and both the month and age at initial diagnosis for each patient were analysed. Roger’s test for cyclic variation was used to determine the significance of any seasonal variation of incidence. Results: Löfgren’s syndrome was diagnosed in 87 patients (18%). The diagnosis of sarcoidosis was delayed in 45% of subjects (mean: 11.2 weeks). The distribution of cumulative monthly presentations peaked in May (spring) and was the lowest in January (winter) and November (autumn) (P < 0.001). The seasonal pattern was also influenced by age and gender (P < 0.05). At the onset, arthralgia was present in 46%, cough or dyspnoea in 37%, constitutional symptoms in 32% and skin lesions in 30% of the patients. Conclusions: In this study, there were differences in the amplitude of the seasonal variation by age and by gender. Well‐designed prospective studies are required to better understand the importance of the findings we respect to the pathogenesis of the disease.     

Sarcoidosis with multiple organ involvement emerging as Löfgren's syndrome

A 52-year-old woman was admitted because of high-grade remittent fever, erythema nodosum, and arthritis which had been lasting two months. Antibiotics did not improve her condition. A chest CT scan examination revealed bilateral hilar and mediastinal adenopathy and multiple nodular opacities in the bilateral lungs. The wedge biopsy of the right lower lobe using video-assisted thoracoscopy presented the histological findings of sarcoidosis. Finally, this case fulfilled the criteria of L?fgren's syndrome. Due to the uncovered cardiac involvement, the systemic glucocorticoid therapy had to be initiated. This case suggests that atypical forms of sarcoidosis should be kept in mind as well, when facing cases with unknown fever.     

Hematologic manifestations of primary Sjögren's syndrome

Sj?gren's syndrome (SS) is a chronic autoimmune disorder, primarily characterized by the mononuclear cell infiltration of exocrine glands exiting in parenchymal damage and secretory impairment. The spectrum of the disease extends from an autoimmune exocrinopathy to a systemic process with extraglandular manifestations. SS is defined as primary (pSS) when isolated, or secondary when associated with another autoimmune disease. Patients with pSS may present hematologic abnormalities, such as anemia, hemocytopenias, monoclonal gammopathies and lymphoprolipherative disorders, predominantly non-Hodgkin's lymphoma of B-cell origin. The increased prevalence of B-cell malignancies suggests that SS may be a boundary disease between autoimmunity and lymphoproliferation. In this paper, the hematologic manifestations of pSS are reviewed.     

Pulmonary manifestations of primary Sjögren's syndrome

Sj?gren's syndrome (SS) is a systemic disease with a predilection for the exocrine glands. It also is considered to be an autoimmune epitheliitis, and, as the respiratory system is lined throughout with epithelial cells, it should not be surprising that patients who have SS may develop pulmonary disease. This article describes these manifestations.     

Management of the extraglandular manifestations of primary Sjögrens syndrome

Primary Sj?gren's syndrome (pSS) is a chronic systemic autoimmune disease, of slow progression, characterized by lymphocytic infiltration of the exocrine glands, that leads to sicca symptoms, mainly xerophtalmia and xerostomia. It may involve any organ and lead to extraglandular manifestations, which also can precede typical glandular manifestations and delay the diagnosis of pSS. In the past years, better knowledge of the disease has led to improvement in treatment management.     

Cutaneous manifestations of primary Sjögren's syndrome are underestimated

The association of kerato-conjunctivitis sicca and xerostomia has been termed Sjogren's syndrome (SS). Although this disease is referred to as a non-organ-specific autoimmune condition, the vast majority of the deleterious effects of primary SS are restricted to the exocrine glands. Among them, the lacrymal and salivary glands are at the foreground, owing to the severity of the objective consequences and the importance of the subjective manifestations. As a result, cutaneous manifestations are minimized, albeit relatively common. We have carefully analyzed the literature to draw up an inventory of the possible skin complications of this syndrome. In addition to xerosis and epidermal IgG deposits, they include vasculitis and cutaneous B cell lymphoma. Alopecia, vitiligo and papular lesions have also been reported to be associated with primary SS.     

Clinical manifestations and early diagnosis of Sjögren syndrome

Sj?gren syndrome (SS) is a common autoimmune disease evidenced by broad organ-specific and systemic manifestations, the most prevalent being diminished lacrimal and salivary gland function, xerostomia, keratoconjunctivitis sicca, and parotid gland enlargement. Primary SS presents alone, and secondary SS occurs in connection with autoimmune rheumatic diseases. In addition, symptoms do not always present concurrently. This diversity of symptomatic expression adds to the difficulty in initial diagnosis. Armed with the recently refined criteria for diagnosis, specialists, such as rheumatologists, primary care physicians, ophthalmologists, and dentists, who would otherwise focus only on those symptoms that encompass their areas of expertise, can get a comprehensive image of the presenting patient, leading to earlier identification and treatment of SS.     

Neurological manifestations in Sjögren syndrome

PURPOSE: To describe clinical and physiopathological aspects of neurological involvement in neurological Sj?gren syndrome (SS) and to overview biological markers and therapeutical aspects. CURRENT KNOWLEDGE AND KEY POINTS: Neurological complications during SS may occur between 8.5 and 70%. Peripheral nervous system (PNS) involvement is well none but data concerning central nervous system (CNS) symptoms have been rarely described. In the present study we detail more precisely the heterogeneity of the neurological manifestation in SS. Recently new biological of SS such as alpha-fodrin antibodies have been described but there interest remain controversial. Furthermore, therapeutical data are scarce and there is to date no consensual guidelines for the therapeutical approach. PERSPECTIVE: Recent data concerning neurological involvement in SS confirm the heterogeneity of clinical presentations that may mimic stroke or multiple sclerosis. They underline the need for new biological markers. Furthermore, multicentric, randomized trials should be assessed in order to give us some therapeutical guidelines.     

Neuroendocrine manifestations in Sjögren's syndrome

Molecular biology has had a major impact on our concepts of the immune system and its relation to neuroendocrine axes, in particular, the adrenal, gonadal, and thyroid axes. It is now well established that not only are the biosynthetic and catabolic pathways of glucocorticoids and sex hormones (estrogen, progesterone, and testosterone) closely related but that the receptors for these hormones are part of a supergene family of receptors which include (in addition to these hormone receptors) the mineralocorticoid receptor, thyroid hormone receptor, retinoic acid receptors, and vitamin D receptors. This suggests a complex network of steroid hormones and receptors for the control and integration of a multitude of physiologic functions at a systemic level. The immune system seems to be tightly integrated into this homeostatic neuroendocrine regulatory network. The neurophysiologic and biochemical events that promote successful adaptation during stressful situations are now identified for illnesses that seem to occur as a result of or are associated with dysregulation of the stress response. One difficulty in interpreting the mechanisms of HPA axis dysfunction in autoimmune-inflammatory syndromes arises from the plasticity of the hormonal systems involved. Levels of hormones produced and receptors reset rapidly with changes in the hormonal milieu (deficiency or excess) and have likely changed during the course of the chronic immune disorder. This, in turn, is further confounded by the pleomorphic natural history of most autoimmune-inflammatory diseases such as SS. The levels of sex hormones and their receptors are tightly linked to HPA axis function. It may be that significant changes in the estrogen-to-androgen ratio or the ratio of their receptors alter the activity of steroid-sensitive cells such as the individual immune cells or epithelial cells, thus providing a means for endocrine regulation of the immune response in SS. Studies in the closely related disorder RA support this hypothesis. Taken together, adrenal and gonadal steroid hormone deficiency plus elevated PRL levels probably greatly facilitate cellular immunity in SS patients. This hypothesis in SS is supported by a growing body of data indicating that RA develops as a consequence of a deficiency in adrenal and gonadal steroid hormone production. It is noteworthy that the findings in female SS patients indicated a central deficiency in all three neuroendocrine axes: adrenal, gonadal, and thyroid. At present, it is not clear if any one system plays a primary role in the expression of the disease. Rather, it is likely that the net effect involves the synergistic and antagonistic effects of multiple hormones, making the specific effects of individual hormones difficult to discern.     

Oral and ocular manifestations in Sjögren's syndrome

OBJECTIVE: Little is known about the relationship between lachrymal and salivary gland involvement in Sj?gren's syndrome (SS). It is also of interest to know which eye test contributes most to the diagnosis of SS. We investigated the performance of different tear tests and how these tests relate to common serologic and salivary tests in SS. METHODS: In patients suspected of SS, the tear breakup time and the tear mucus score were evaluated in addition to the routine tests. Eighty consecutive patients were included, categorized into primary SS (pSS), secondary SS (sSS), and negative for SS. RESULTS: The tear breakup time and mucus score both performed insufficiently in diagnosing SS, in contrast to the Rose Bengal score. In pSS and sSS patients, a clear correlation was noted between tear and saliva quality and secretion rate, and between the Rose Bengal score and parotid sialography. Increased Rose Bengal scores also correlated significantly with hyperglobulinemia and presence of SSB antibodies in serum, with duration of subjective eye dryness, and with decreased tear gland function. CONCLUSION: The Rose Bengal score remains the eye test of choice having the highest specificity for SS. Hyperglobulinemia and especially positive SSB serology may warrant close monitoring of the eyes, since these serum findings appear to relate to the severity of ocular surface damage. Theoretically, a positive evaluation of either the ocular or oral component, in addition to positive serology or histopathology, could be sufficient to diagnose the syndrome for clinical purposes.     

Diagnosis of acute sarcoid arthritis (Löfgren's syndrome) in India,a country with high burden of tuberculosis

ObjectiveThe present study was carried out to test if Visser et al's 2002 diagnostic criteria for acute sarcoid arthritis (Löfgren syndrome) are applicable in India, a country with high burden of tuberculosis.Methods30 consecutive patients classified as acute sarcoid arthritis according to Visser et al's criteria were included. They were screened for TB with standard Mantoux test, radiograph of chest and if found normal, contrast enhanced computerized tomography (CE-CT) of thorax.Results24 of 30 patients showed a negative Mantoux test as well as normal chest radiograph and CE-CT. These patients were labeled as acute sarcoid arthritis. There were, 6 (20%) patients who had one or more features of TB by way of a positive Mantoux test and/or mediastinal lymphadenopathy with central necrosis, or asymmetrical hilar lymphadenopathy. The latter patients were diagnosed as having Poncet's disease, a parainfectious arthritis associated with the presence of tuberculosis at a distant site way from musculoskeletal system. Therapeutic response to low-dose glucocorticoid, hydroxychloroquine and low-dose methotrexate produced dramatic results among those diagnosed with acute sarcoid arthritis. On the other hand, those diagnosed as having Poncet's disease were given standard anti-TB drugs with excellent response.ConclusionIn a country with high burden of TB like India Visser et al's clinical criteria for the diagnosis of acute sarcoid arthritis (Löfgren syndrome) may not be very specific; TB must be ruled out before diagnosing acute sarcoid arthritis (Löfgren syndrome).     

Clinical manifestations of neurological involvement in primary Sjögren’s syndrome

The aim of this study was to evaluate neurological manifestations of primary Sjögren’s syndrome (pSS) and investigate the etiology and pathogenesis of peripheral and central nervous complications in pSS. Thirty-two patients with pSS were enrolled in the present study, 20 of whom had neurological involvement plus sicca symptoms. The clinical features were evaluated by neurological examinations including nerve conduction study, magnetic resonance imaging, cerebrospinal fluid, and electroencephalogram. The frequency of fever was significantly higher (P?=?0.006) in pSS with neurological involvement than in pSS without neurological involvement. There was no statistical significance in other factors between the two groups. Peripheral nervous system (PNS), central nervous system (CNS), and both PNS and CNS involvements were revealed in 14, 3, and 3 patients, respectively. Optic neuritis and trigeminal neuralgia were revealed frequently in cranial neuropathy. Anti-aquaporin 4 antibody was detected in one patient with optic neuritis. Of the nine patients with polyneuropathy, eight patients presented pure sensory neuropathy including small fiber neuropathy (SFN). pSS with SFN appeared to have no clinically abnormal features, including muscle weakness and decreasing deep tendon reflex. Skin biopsy revealed epidermal nerve fiber degenerated in one pSS patient with pure sensory neuropathy who was diagnosed as having SFN. Our observations suggest that a number of mechanisms can be attributed to neurological involvements in pSS rather than just the mechanisms previously described (i.e., vasculitis and ganglioneuronitis). Presumably, specific autoantibodies may directly induce injury of the nervous system.     

Löfgren syndrome in Turkey

Abstract
In the 36-year period between 1966 and 2002, 514 patients were diagnosed with sarcoidosis at Cerrahpala Medical Faculty, Gstanbul, Turkey, and of these 98 (19.1%) had Löfgren syndrome. The frequency of female patients with Löfgren was higher than the frequency among other sarcoidosis patients (female : male ratio 4.8 vs . 1.64; P  < 0.001). Erythema nodosum was diagnosed in 72.4% of the subjects and arthritis or arthralgia was diagnosed in 51%. Erythema nodosum and arthritis or arthralgia were more frequent in Löfgren; however, pulmonary parenchymal involvement was more frequent in other sarcoidosis patients (all P ‐values < 0.001). (Intern Med J 2003; 33: 535−537)     

Frequency of systemic manifestations in patients with primary Sjögren's syndrome in Argentina

Twenty to 71% of patients with Sjögren's syndrome (SS) will develop systemic manifestations. Objective: to characterize the clinical-serological presentation and the frequency of systemic manifestations in patients with primary SS. Methods: Retrospective study including patients with SS visited in “Hospital Británico de Buenos Aires” during the period from January 2000 to August 2008.Results: Forty-one patients fulfilled the 2002 American-European classification criteria for SS. All patients were women. Mean age at enrollment was 57,85±12,42 years (range 26–79). Mean duration of the disease was 9,28 years (range 0,08–24). Thirty-three (80,49%) developed systemic manifestations. The most frequent were arthritis, cutaneous vasculitis and polyneuropathy. This group featured more frequently ANA titles ≥1/640 and hypocomplementemia; although no statistical significance was found. The frequency of systemic manifestations found was greater than reported in the literature.Conclusions: A multidisciplinary approach focusing also on systemic manifestations should be the new standard for management of SS.     

Neurologic manifestations in primary Sjögren syndrome: a study of 82 patients

Neurologic involvement occurs in approximately 20% of patients with primary Sj?gren syndrome (SS). However, the diagnosis of SS with neurologic involvement is sometimes difficult, and central nervous system (CNS) manifestations have been described rarely. We conducted the current study to describe the clinical and laboratory features of SS patients with neurologic manifestations and to report their clinical outcome. We retrospectively studied 82 patients (65 women and 17 men) with neurologic manifestations associated with primary SS, as defined by the 2002 American-European criteria. The mean age at neurologic onset was 53 years. Neurologic involvement frequently preceded the diagnosis of SS (81% of patients). Fifty-six patients had CNS disorders, which were mostly focal or multifocal. Twenty-nine patients had spinal cord involvement (acute myelopathy [n = 12], chronic myelopathy [n = 16], or motor neuron disease [n = 1]). Thirty-three patients had brain involvement and 13 patients had optic neuropathy. The disease mimicked relapsing-remitting multiple sclerosis (MS) in 10 patients and primary progressive MS in 13 patients. We also recorded diffuse CNS symptoms: some of the patients presented seizures (n = 7), cognitive dysfunction (n = 9), and encephalopathy (n = 2). Fifty-one patients had peripheral nervous system involvement (PNS). Symmetric axonal sensorimotor polyneuropathy with a predominance of sensory symptoms or pure sensory neuropathy occurred most frequently (n = 28), followed by cranial nerve involvement affecting trigeminal, facial, or cochlear nerves (n = 16). Multiple mononeuropathy (n = 7), myositis (n = 2), and polyradiculoneuropathy (n = 1) were also observed. Thirty percent of patients (all with CNS involvement) had oligoclonal bands. Visual evoked potentials were abnormal in 61% of the patients tested. Fifty-eight patients had magnetic resonance imaging (MRI) of the brain. Of these, 70% presented white matter lesions and 40% met the radiologic criteria for MS. Thirty-nine patients had a spinal cord MRI. Abnormalities were observed only in patients with spinal cord involvement. Among the 29 patients with myelopathy, 75% had T2-weighted hyperintensities. Patients with PNS manifestations had frequent extraglandular complications of SS. Anti-Ro/SSA or anti-La/SSB antibodies were detected in 21% of patients at the diagnosis of SS and in 43% of patients during the follow-up (mean follow-up, 10 yr). Biologic abnormalities were more frequently observed in patients with PNS involvement than in those with CNS involvement (p < 0.01). Fifty-two percent of patients had severe disability, and were more likely to have CNS involvement than PNS involvement (p < 0.001). Treatment by cyclophosphamide allowed a partial recovery or stabilization in patients with myelopathy (92%) or multiple mononeuropathy (100%). The current study underlines the diversity of neurologic complications of SS. The frequency of neurologic manifestations revealing SS and of negative biologic features, especially in the event of CNS involvement, could explain why SS is frequently misdiagnosed. Screening for SS should be systematically performed in cases of acute or chronic myelopathy, axonal sensorimotor neuropathy, or cranial nerve involvement. The outcome is frequently severe, especially in patients with CNS involvement. Our study also underlines the efficacy of cyclophosphamide in myelopathy and multiple neuropathy occurring during SS.