Sarcoid Arthritis Research Articles

Joint involvement in sarcoidosis: systematic review and meta-analysis of prevalence, clinical pattern and outcome.

To characterize joint involvement (JI) in sarcoidosis, a systematic search of MEDLINE, EMBASE and Cochrane Library was conducted from inception to July 2022 for publications reporting its prevalence, pattern, treatment and outcome. The pooled prevalence estimates (PPE) with 95% CI were calculated using binomial distribution and random effects. Meta-regression method was used to examine factors affecting heterogeneity between studies. Forty-nine articles were identified comprising a total of 8574 sarcoidosis patients, where 12% presented with JI (95% CI 10, 14; I2 = 0%). The PPE for sarcoid arthritis (SA) was 19% (95% CI 14, 24; I2 = 95%), and 32% (95% CI 13, 51; I2 = 99%) for arthralgia. Heterogeneity was due to higher JI prevalence reported in Western Asia and the Middle East, in rheumatology clinics and via surveys. Sample size of SA varied from 12 to 117 cases. Ankles were most frequently affected (PPE 80%) followed by knees and wrists. Monoarthritis was uncommon (PPE 1%; 95% CI 0, 2; I2 = 55%). Acute SA prevailed (PPE 79%; 95% CI 72, 88; I2 = 69%) with an equal proportion of oligo and polyarthritis and was frequently accompanied by erythema nodosum (PPE 62%; 95% CI 52, 71; I2 = 16%). Chronic SA was predominantly polyarticular with a higher frequency of the upper extremity joints affected. Most common non-articular manifestations with SA included fever (52%), erythema nodosum (41%), hilar adenopathy (86%) and interstitial lung disease (23%) of which one-third required corticosteroids and/or immunosuppressants. SA occurred early in the disease with a PPE of 19% and most frequent pattern of acute oligo- or polyarthritis predominantly affecting the lower extremity large joints.

Systemic Associations of Sarcoid Uveitis: Correlation With Uveitis Phenotype and Ethnicity

To examine systemic associations of sarcoid uveitis and association with uveitis clinical phenotype and ethnicity. Retrospective cross-sectional study. A total of 362 subjects with definite or presumed sarcoid uveitis from Moorfields Eye Hospital, Royal Victorian Eye and Ear, and Auckland District Health Board. Data were collected from the review of clinical notes, imaging, and investigations. Sarcoidosis was diagnosed in accordance with the International Workshop on Ocular Sarcoidosis guidelines. Diagnosis of associated systemic disease secondary to sarcoidosis. A total of 362 subjects with sarcoid uveitis were identified. Median age was 46 years, and 226 (62.4%) were female. Granulomatous anterior uveitis (47.8%), intermediate uveitis with snowballs (46.4%), and multifocal choroiditis (43.1%) were the most frequent clinical presentations, and disease was bilateral in 313 (86.5%). Periphlebitis was observed in 21.0%, and solitary optic nerve or choroidal granuloma in 11.3%. Lung parenchymal disease was diagnosed in 200 subjects (55.2%), cutaneous sarcoid in 98 (27.1%), sarcoid arthritis in 57 (15.7%), liver involvement in 21 (5.8%), neurosarcoid in 49 (13.5%), and cardiac sarcoid in 16 subjects (4.4%). Subjects with cardiac sarcoid were less likely to have granulomatous anterior uveitis (P=.017). Caucasian subjects were older at presentation (48 vs 41 years; P=.009), had less granulomatous anterior uveitis (26.4% vs 51.7%; P < .001), and were less likely to present with cutaneous involvement (23.1% vs 35.4%; P=.040). Ophthalmologists need to be aware of the systemic associations of sarcoid uveitis, in particular potentially life-threatening complications such as cardiac sarcoidosis. Differences observed in uveitis phenotype and between ethnicities require further investigation.

Musculoskeletal sarcoidosis: A single center experience over 15 years.

Musculoskeletal (MSK) sarcoidosis presents with a variety of clinical phenotypes. Four subtypes of MSK sarcoidosis have been identified to date: Lofgren syndrome, chronic sarcoid arthritis, osseous sarcoidosis, sarcoid myopathy. Each subtype has been reported with varying incidence mainly due to lack of universal classification criteria. We performed a retrospective chart review of patients with MSK sarcoidosis at a single academic center between January 2000 and December 2014. Descriptive statistics were used to describe the proportion of patients with sarcoidosis who had the 4 MSK syndromes of interest, demographic characteristics and therapeutic agents used. A cohort of 58 patients with MSK manifestations were identified among 1016 patients with sarcoidosis. Frequency of subtypes include: Lofgren syndrome 46.6%, osseous sarcoidosis 25.9%, chronic sarcoid arthritis 24.1% and sarcoid myopathy 6.9%. The cohort was predominantly female (43/58 patients, 74%) and Caucasian (48/58 patients, 82.8%). Mean age was 47.2years. One patient had overlap of osseous sarcoidosis and chronic sarcoid arthritis, another patient initially had Lofgren syndrome and later developed chronic sarcoid arthritis. Sarcoid myopathy patients presented with myalgia more often than muscle weakness. We identified a large cohort of MSK sarcoidosis and determined the prevalence of all 4 subtypes. In patients who do develop MSK manifestations of sarcoidosis, they are commonly a part of the initial presentation of sarcoidosis. There is an unmet need to establish standardized classification criteria for the 4 MSK sarcoidosis syndromes.

EP21 Tumour necrosis factor inhibitor for the treatment of refractory extra-pulmonary disease including sarcoid arthritis and myositis

EP21 Tumour necrosis factor inhibitor for the treatment of refractory extra-pulmonary disease including sarcoid arthritis and myositis

EP17 Finding the road to sarcoidosis

Case report - IntroductionSarcoidosis is an autoimmune, multi-system condition in which the formation of non-caseating, granulomas is a key histological feature. Clinical presentation can be variable and may lead to a delay in recognition. Most cases will resolve with minimal or no intervention. Awareness of the condition and features helps guide long-term management and as illustrated in cases below, rheumatologists may often be involved in helping diagnose and coordinate the patient pathway.Case report - Case descriptionA 51- year old female ex-smoker experienced 6 months of fatigue, dry cough, mild exertional dyspnoea, sweats, mild weight loss and arthralgia after a cholecystectomy. She described lesions typical of erythema nodosum coinciding with a raised CRP (58g/L) which later normalised. Other than an elevated serum ACE (71 U/L), rest of tests were normal.Plain chest radiograph was normal but a co-incidental CT abdomen for non-specific abdominal discomfort showed small volume abdominal lymphadenopathy. Further imaging showed bilateral mediastinal and hilar lymphadenopathy. Pulmonary function tests and joint ultrasound were normal. EBUS sampling (August 2014) excluded malignancy but confirmed sarcoid granulomas. She briefly required non-steroidals for arthralgia. Four years later, she is still well with resolution of lymphadenopathy.A 41-year old male non-smoker presented with 6 weeks of bilateral heel pain followed by myalgia, weight loss, headaches, sweats, intermittent blurred vision, and a non-specific neck rash. He was afebrile with normal urinalysis, CRPs 24-39 mg/L, CCP, ANCA, ANA negative, (Serum ACE sample insufficient). Infection screening (including TB) was negative. Slit lamp examination was normal.Trans-bronchial sampling of hilar lymphadenopathy seen on imaging excluded lymphoma but showed granulomas typical of sarcoidosis. The patient fully recovered within a few months without medication or recurrence.A 63-year-old female was referred with ankle pain and swelling after 5 months of erythematous leg swelling treated initially as cellulitis. She also had bilateral, intermittent leg cramps and recent intermediate uveitis. She was positive for HLA B27 and ANA (homogenous speckled pattern) with a raised serum ACE (98 U). ANCA was negative, creatinine kinase normal. Background included treated squamous cell carcinoma and degenerative disc disease.Ankle problems had resolved when seen possibly due to prednisolone for uveitis. EBUS sampling of bilateral hilar lymphadenopathy confirmed sarcoid histology. Since commencing azathioprine (50mg) for recurrent uveitis, she stays well.Case report - DiscussionSarcoidosis is a granulomatous systemic disease thought to be Th-1 mediated but pathogenesis remains unclear. Heterogeneity in presentation and organ involvement may lead to delays or missed diagnoses. Like these cases, patients may have one or more presentations to various medical specialities before a link is made.Careful note of antecedent history, current symptoms and examination findings can point towards a differential of sarcoid particularly if bilateral ankle involvement or typical skin lesions are present. Erythema nodosum can occur which the first case had described. Given the smoking and weight loss history, the differential of malignancy had to be excluded first. Sarcoid arthropathy, as seen in these cases, typically presents as arthralgia, myalgia, or arthritis in either acute or chronic form. Sometimes myopathy and bone involvement are seen though erosive disease is uncommon.Cases often have minimal or no respiratory symptoms but chest imaging can pick up features including bilateral hilar lymphadenopathy (more than 75% of cases) and less commonly pulmonary parenchymal changes (nodules, ground glass changes, fibrosis) or pleural effusions.Most cases will resolve over time with minimal intervention as in the first two cases. Some require non-steroidal anti-inflammatories. Steroids may be required if there are more inflammatory features affecting joints or other organs. Disease modifying therapies (biologic and non-biologic) have been used in more chronic or resistant cases.Sarcoid may co-exist with or mimic other conditions. In the last case, the unifying diagnosis of uveitis, skin changes and joint involvement seems to be sarcoid. However, it was interesting that the patient had mixed serology and showed some features of a seronegative arthritis profile as spondyloarthritis and sacroiliitis have been reported with sarcoidosis.Rheumatologists are often familiar with features of the condition. Thus, they can help link symptoms to guide appropriate investigations and further management with good outcomes. Case report - Key learning points Sarcoidosis can have a heterogeneous presentation so may take a while for diagnosis to be made Respiratory symptoms may not be present despite findings on chest imagingRheumatologists are often involved in diagnosis and treatment when patients with sarcoid related arthralgia or arthritis type symptoms get referredMost cases will resolve with minimal interventionEarly recognition can streamline investigations and management subsequently improving the patient journeyIn cases with a mixed autoantibody profile, there may be a discussion on whether one or more conditions are present to explain all the features

Arthritis in sarcoidosis: A multicentric study from India.

Ten to 15% of patients with sarcoidosis have associated arthritis. Chronic arthritis is fairly uncommon. There is a paucity of data on articular manifestations of the disease from India. Case records of adult patients with sarcoidosis presenting to 11 rheumatology centers from 2005 to 2017 were retrospectively reviewed. Joint involvement was assessed clinically, classified as acute or chronic depending on duration of symptoms less or greater than 6months, respectively. A total of 117 patients with sarcoid arthritis were reviewed. Forty-five patients were classified as having Lofgren's syndrome. The pattern of joint involvement revealed the ankle to be most commonly affected in both the groups. Shoulder, wrist, metacarpophalangeal, proximal interphalangeal joints of hands and knee joint involvement were significantly more common in chronic sarcoid arthritis. Peripheral lymphadenopathy and uveitis were significantly more frequent in chronic sarcoid arthritis. Forty out of 49 patients with acute arthritis followed up over a median of 1.8years had achieved complete remission. Twelve out of 16 chronic sarcoid arthritis (median follow up 2.5years) had achieved complete remission with 15, 12 and five patients on steroids, methotrexate and hydroxychloroquine, respectively. One patient with acute sarcoid arthritis with concomitant interstitial lung disease had died due to lung infection. Acute oligoarthritis was the commonest presentation with the ankle being the most commonly affected joint. Upper limb joint (predominantly distal) and knee involvement were more common as reported in our largest series worldwide of chronic sarcoid arthritis in adults. Hilar adenopathy and erythema nodosum were common extra-articular features in both acute and chronic sarcoid arthritis. A limitation of the study was the retrospective nature of the analysis.

113 Skewing of T Helper axis towards Th1 and Th17 cells in sarcoid arthritis compared to non-articular sarcoidosis

113 Skewing of T Helper axis towards Th1 and Th17 cells in sarcoid arthritis compared to non-articular sarcoidosis

The clinical characteristics of sarcoid arthropathy based on a prospective cohort study.

Sarcoidosis is known as a Th1-mediated disease, which can mimic many primary rheumatologic diseases or sometimes co-exist with them. Clinical characteristics of sarcoid arthropathy are not well described and the studies reported in the literature so far are mostly based on data from referrals. The aim of this study was to evaluate the incidence and clinical characteristics of sarcoid arthropathy. All our patients were prospectively evaluated in our rheumatology outpatient center from 2011 to 2015. A total of 114 (32 male) patients with sarcoidosis who were admitted to our clinic were included in the study. Clinical, demographical, laboratory, radiological and histological data of these patients obtained during 4-year follow-up and treatment period were compiled and analyzed. The mean patient age was 48.1 years (range, 20-82 years), and the mean disease duration was 40.5 months (range, 1-300 months). Sarcoid arthritis was observed in 71 (62.3%), and arthralgia in 106 (92.9%) patients. Out of the 71 patients with arthritis, 61 (85.9%) had involvement of ankle, 7 (9.8%) knee, 2 (2.8%) wrist, MCP and PIP joints, and 1 (1.4%) had shoulder periarthritis. Oligoarthritis (two to four joints) was the most common pattern followed by monoarthritis and polyarthritis. Arthritis and erytjhema nodosum and arthritis and female sex was found to be correlated (p = 0.03 and p = 0.001). Again, in patients with arthritis, even higher levels of CRP/ESR as well as ANA and RF positivity were observed (p = 0.03, p = 0.01, p = 0.01, and p = 0.02, respectively). A total of 11 patients had another rheumatic pathology concurrent with sarcoidosis. Inflammatory arthritis occurs in a majority of patients with sarcoidosis. Acute arthritis with bilateral ankle involvement is the most common pattern of sarcoid arthropathy. Sarcoidosis can mimic many primary rheumatic diseases or may coexist with them. Sarcoidosis should be considered not only as a mimicker but also as a Th1-mediated primary rheumatologic pathology.

Sarcoidosis: a rheumatologist's perspective.

Sarcoidosis is a systemic disorder of unknown etiology, which may involve various tissues and organs and is characterized by a noncaseating granuloma reaction. While pathogenesis is not yet clear, cellular immune system activation and nonspecific inflammatory response occur secondarily to several genetic and environmental factors. T helper 1-cells and macrophage-derived pro-inflammatory cytokines stimulate the inflammatory cascade and formation of granuloma occurs as a result of tissue permeability, cell influx, and local cell proliferation. The different prevalence, clinical results, and disease course observed in different races and ethnic groups, is an indicator of the heterogeneous nature of the disease. Sarcoidosis may mimic and/or may occur concomitantly with numerous primary rheumatic diseases. This disease most commonly presents with bilateral hilar lymphadenopathy, pulmonary infiltrations, and skin and eye lesions. Locomotor system involvement is observed at a range of 15% and 25%. Two major joint involvements have been described: acute and chronic form. The most common form, the acute form, may be the first sign of sarcoidosis and present with arthralgia, arthritis, or periarthritis. Chronic sarcoid arthritis is usually associated with pulmonary parenchymal disease or other organ involvement and occurs rarely. While asymptomatic muscular involvement is reported between 25% and 75%, symptomatic muscular involvement is very rare. Symptomatic myopathy may present as three different types: chronic myopathy, palpable nodular myositis, or acute myositis. Even if rare, 2-5% of cases may exhibit osseous involvement and it is frequently associated with lupus pernio, chronic uveitis, and multisystemic disease. Sarcoidosis was reported together with different rheumatologic diseases. There are studies showing that sarcoidosis may mimic the clinical and laboratory findings of these disorders. Nonsteroidal anti-inflammatory drugs and corticosteroids are used for treating the symptoms of rheumatologic findings. In patients who are unresponsive to corticosteroids, immunosuppressive and anti-tumor necrosis factor alpha drugs may be used. In this review, the incidence of rheumatologic symptoms, the clinical findings, and the treatment of rheumatologic manifestations of sarcoidosis are discussed.

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).

THU0387 Refractory Sarcoid Arthritis in World Trade Center- Exposed New York City Firefighters Necessitating Anti-TNF Alpha Therapy

BackgroundSarcoidosis is characterized by multisystem granulomatous inflammation, predominantly of the lungs. Acute joint manifestations occur in 25–40% of cases and are usually self-limited with only 1–4% developing chronic arthritis. We...

SAT0080 Ankle synovitis and its prognostic implications in a very early arthritis cohort

BackgroundAnkle synovitis occurs in over a third of early inflammatory arthritis patients and may be present in isolation. However, the clinical outcomes associated with ankle involvement in this population are...

THU0508 Incidence of Inflammatory Joint Diseases in Northern Savo Area in Finland in 2010

BackgroundMonitoring of the incidence of inflammatory joint diseases may provide new insight into the etiology of these diseases.ObjectivesAll rheumatologists practising in the Northern Savo rheumatological outpatient departments collected data on...

Clinical images: Infliximab therapy of polyarticular small joint sarcoid arthritis

Nespeco, J. Whiteford, and M. Margaret; at the University of Buenos Aires and German Hospital, Buenos Aires, Argentina, A. M. Heidenreich, C. Vollenweider, I. Adler, A. C. Smith, S. Daverio, and V. Kambo; at Peking Union Medical College Hospital, Beijing, China, W. Zheng, Y. Jiang, D. Xu, J. Su, S. Zhang, J. Zhao, D. Du, H. Wang, Z. Li, J. Xiao, Q. Wu, C. Zhang, W. Meng, J. Zhang, and Y. Dong; at Copenhagen University Hospital, Glostrup, Denmark, S. Johansen, S. Hamann, P. Helin, J. Lindegaard, A. M. Manniche, and S. P. Kreutzmann; at Kanazawa Medical University, Ishikawa, Japan, Y. Masaki, T. Sakai, K. Kitagawa, N. Shibata, M. Honjo, T. Kawanami, K. Fujimoto, and S. Sugai; at King’s College, London, UK, P. Shirlaw, B. Kirkham, P. Morgan, L. Fernandes-Naglik; at Aravind Eye Hospital, Madurai, India, M. Srinivasan, S. Avinash, M. Das, A. Kumar, R. Banushree, B. Babu, R. Shanthi, A. Ram, R. Saravanan, K. N. Kannappan, J. Mascarenhas, and N. Kalyani; at the University of Pennsylvania, Philadelphia, F. Vivino, S. Seghal, V. Bunya, M. Massaro-Giordano, S. K. Abboud, A. Pinto, and L. Fisher; and at Johns Hopkins University, Baltimore, Maryland, A. Baer, E. Akpek, W. Henderson, C. Gourin, and A. Keyes.

The non-antibiotic properties of tetracyclines: Clinical potential in ophthalmic disease

IntroductionBeyond their decades of long use as broad-spectrum antibiotics, tetracyclines and their derivatives have been shown to exhibit non-antimicrobial properties including their ability to interact with matrix metalloproteinases (MMP), tissue inhibitors of MMPs, growth factors and cytokines. As such, they are capable of affecting inflammation, immunomodulation, cell proliferation, and angiogenesis. Although they have been used to treat a variety of conditions including acne, cutaneous sarcoid, and rheumatoid arthritis, amongst others, their use in treating ophthalmologic disease is in its infancy. Materials and methodsA literature review on the role of non-antimicrobial properties of tetracyclines, semisynthetic tetracyclines, and chemically modified non-antibacterial tetracyclines (CMTs) and their clinical properties was performed. The effects of these compounds in relation to ophthalmic disease are presented. ResultsDue to their non-antimicrobial properties, tetracyclines and their derivatives are capable of influencing a wide variety of ocular diseases in animal models. By affecting expression of MMP-9 and tumor necrosis factor (TNF)-α, these compounds decrease corneal permeability, improve corneal smoothness, and reduce meibomian gland dysfunction; this improves the tear film which in turn restores the optical quality of the tear film and cornea. Sterile corneal ulceration may be inhibited via anticollagenase activity; this has been demonstrated in both animal models and case reports. CMTs suppress cataractogenesis in a diabetic rat model, possibly by affecting MMPs. With respect to retinal disease, tetracyclines can inhibit both microglial-mediated cell death and retinal cell apoptosis as well as prevent retinal capillary damage via caspase inhibition thus preventing retinal neovascularization. Experimental choroidal neovascularization is reduced by inhibition of MMP-2 and MMP-9, elevation of pigment epithelial derived growth factor (PEDF), and reduction of vascular endothelial growth factor (VEGF) expression via Fas ligand. DiscussionDue to their non-antimicrobial properties, tetracyclines and their derivatives are capable of influencing a wide variety of ocular disease in animal models. Research suggests that they are able to reduce inflammation in the eyelid meibomian glands, improve optical clarity of the cornea, retard cataract formation, and limit ocular angiogenesis. They may have a role in treating the leading causes of vision loss: cataract, age-related macular degeneration, and diabetic retinopathy, all of which are anticipated to increase in incidence due to the aging population. ConclusionsTetracyclines, semisynthetic tetracyclines, and CMTs may have a role in the treatment of several important ophthalmologic diseases; however, further research is required, including prospective multicenter clinical trials.

Rheumatologic Manifestations of Sarcoidosis

Sarcoidosis is a systemic, clinically heterogeneous disease characterized by the development of granulomas. Any organ system can be involved, and patients may present with any number of rheumatologic symptoms. There are no U.S. Food and Drug Administration-approved therapies for the treatment of sarcoidosis. Diagnosing sarcoidosis becomes challenging, particularly when its complications cause patients' symptoms to mimic other conditions, including polymyositis, Sjögren syndrome, or vasculitis. This review presents an overview of the etiology of and biomarkers associated with sarcoidosis. We then provide a detailed description of the rheumatologic manifestations of sarcoidosis and present a treatment algorithm based on current clinical evidence for patients with sarcoid arthritis. The discussion will focus on characteristic findings in patients with sarcoid arthritis, osseous involvement in sarcoidosis, and sarcoid myopathy. Arthritic conditions that sometimes coexist with sarcoidosis are described as well. We present two cases of sarcoidosis with rheumatologic manifestations. Our intent is to encourage a multidisciplinary, translational approach to meet the challenges and difficulties in understanding and treating sarcoidosis.

Chronic Sarcoid Arthritis Presenting as an Intra-Articular Knee Mass

Patients may present with a primary complaint of intra-articular knee masses causing mechanical symptoms of snapping or locking. If the history, physical examination, laboratory tests, and imaging studies point to a benign process, acceptable treatment consists of arthroscopic excision and postoperative pathology analysis. As reported in several case series, the final diagnosis can be pigmented villonodular synovitis, localized nodular synovitis, hemangioma, lipoma, or rheumatoid nodules. In this case presentation, a 39-year-old man with no previous medical conditions and a negative preoperative chest radiograph underwent arthroscopic surgery for a single intra-articular knee mass. The unexpected diagnosis, after pathology review and further medical work-up, was arthritis secondary to chronic sarcoidosis.

Local expression of the serum amyloid A and formyl peptide receptor-like 1 genes in synovial tissue is associated with matrix metalloproteinase production in patients with inflammatory arthritis.

To evaluate the regulation of acute-phase serum amyloid A (A-SAA) production in inflamed synovial tissue, and to elucidate a possible pathophysiologic role in the induction of matrix metalloproteinase (MMP) release by fibroblast-like synoviocytes (FLS). Synovial tissue samples were obtained by arthroscopic biopsy from the knee joints of patients with inflammatory arthritis. Primary cultures of FLS from patients with rheumatoid arthritis (RA), psoriatic arthritis, sarcoid arthritis, and undifferentiated arthritis were established. Total RNA was extracted from FLS and analyzed by reverse transcription-polymerase chain reaction (PCR) using specific primers for A-SAA and formyl peptide receptor-like 1 (FPRL1), an A-SAA receptor. Southern blot analysis confirmed the PCR products generated. Immunohistochemical analysis demonstrated the expression of A-SAA protein production by several synovial cell populations, and immunofluorescence analysis confirmed A-SAA colocalization with the macrophage marker CD68. Primary FLS cultures stimulated with recombinant human A-SAA resulted in dose-dependent MMP-1 and MMP-3 production, as measured by an enzyme-linked immunosorbent assay. A-SAA messenger RNA (mRNA) and FPRL1 mRNA were present in FLS, macrophages, and endothelial cells isolated from the synovial tissue of patients with RA and other categories of inflammatory arthritis. A-SAA expression was regulated by proinflammatory cytokines and occurred in association with FPRL1 expression in FLS and endothelial cells, which is consistent with a biologic role at the sites of inflammation. Recombinant human A-SAA induced both MMP-1 and MMP-3 secretion by FLS. The mean fold increases in A-SAA-induced MMP-1 and MMP-3 production were 2.6 and 10.6, respectively, compared with 7.6-fold and 41.9-fold increases in interleukin-1 beta-induced MMP-1 and MMP-3 production. The up-regulation of the A-SAA and FPRL1 genes in inflamed synovial tissue suggests an important role in the pathophysiology of inflammatory arthritis. A-SAA induces the production of MMPs. Therapeutic targeting of A-SAA, or FPRL1, may modulate pathophysiologic pathways that are associated with matrix degradation in patients with RA and other forms of progressive inflammatory arthritis.

Childhood sarcoidosis in Denmark 1979-1994: incidence, clinical features and laboratory results at presentation in 48 children

Aim: To describe the incidence, clinical presentation and paraclinical findings in childhood sarcoidosis in Denmark, 1979–1994. Methods: Patients (n= 5536) with a diagnosis of sarcoidosis were drawn from the nationwide Patient Registry; 81 patients were ±15 y of age. The diagnosis of sarcoidosis was reconfirmed in 48/81 (59%) patients. In 35/48 (73%) patients, diagnosis was verified by histology, and in 13 it was substantiated by paraclinical/clinical findings. Results: The series comprised 26 boys and 22 girls (male/female ratio 1.18). Median age at diagnosis was 13 y (range 0.7–15). In 1979–1994 the incidence was 0.29 per 100 000 person-years ±15 y of age. The incidence was 0.06 in children ±4 y of age and increased gradually with age to 1.02 in children aged 14–15 y. General malaise, fever, weight loss, abdominal discomfort, respiratory symptoms, lymphadenopathy and central nervous system symptoms were common; 31% of patients had erythema nodosum, 12.5% sarcoid skin lesions, 25% uveitis/iridocyclitis and 4.2% sarcoid arthritis. Chest X-rays were normal (stage 0) in 10% of patients, and showed pulmonary infiltrates stage I in 71%, stage II in 8.3% and stage III in 8.3%. Lung function tests were examined in 13 patients: 50% had decreased FEV1 and vital capacity, 80% decreased DLCO. Haemoglobin values were normal. Some patients had mild leukopenia, some moderate leukocytosis and a few had moderate eosinophilia. Erythrocyte sedimentation rate was elevated in 40% of the patients. Plasma calcium was elevated in 30% of the patients; 4 patients had severe hypercalcaemia and elevated plasma creatinine, and 1 patient had nephrocalcinosis. Serum angiotensin-converting enzyme was elevated in 55% of the patients. Liver function tests were normal with no sarcoid hepatitis. Urinary examination (glucose, albumin, haemoglobin) was normal in 96% of the patients; the patient with nephrocalcinosis had albuminuria and haematuria. Conclusion: The incidence of sarcoidosis in Danish children is low and increases with age. Sarcoidosis in young children may present clinical features that are different from the appearance of those in older children and often constitute a diagnostic challenge. In older children, the clinical appearance has many features in common with the presentation in adults.

Childhood sarcoidosis in Denmark 1979–1994: incidence, clinical features and laboratory results at presentation in 48 children

To describe the incidence, clinical presentation and paraclinical findings in childhood sarcoidosis in Denmark, 1979-1994. Patients (n = 5536) with a diagnosis of sarcoidosis were drawn from the nationwide Patient Registry; 81 patients were < or = 15 y of age. The diagnosis of sarcoidosis was reconfirmed in 48/81 (59%) patients. In 35/48 (73%) patients, diagnosis was verified by histology, and in 13 it was substantiated by paraclinical/clinical findings. The series comprised 26 boys and 22 girls (male/female ratio 1.18). Median age at diagnosis was 13 y (range 0.7-15). In 1979-1994 the incidence was 0.29 per 100000 person-years < or = 15 y of age. The incidence was 0.06 in children < or = 4 y of age and increased gradually with age to 1.02 in children aged 14-15 y. General malaise, fever, weight loss, abdominal discomfort, respiratory symptoms, lymphadenopathy and central nervous system symptoms were common; 31% of patients had erythema nodosum, 12.5% sarcoid skin lesions, 25% uveitis/iridocyclitis and 4.2% sarcoid arthritis. Chest X-rays were normal (stage 0) in 10% of patients, and showed pulmonary infiltrates stage I in 71%, stage II in 8.3% and stage III in 8.3%. Lung function tests were examined in 13 patients: 50% had decreased FEV1 and vital capacity, 80% decreased DLCO. Haemoglobin values were normal. Some patients had mild leukopenia, some moderate leukocytosis and a few had moderate eosinophilia. Erythrocyte sedimentation rate was elevated in 40% of the patients. Plasma calcium was elevated in 30% of the patients; 4 patients had severe hypercalcaemia and elevated plasma creatinine, and 1 patient had nephrocalcinosis. Serum angiotensin-converting enzyme was elevated in 55% of the patients. Liver function tests were normal with no sarcoid hepatitis. Urinary examination (glucose, albumin, haemoglobin) was normal in 96% of the patients; the patient with nephrocalcinosis had albuminuria and haematuria. The incidence of sarcoidosis in Danish children is low and increases with age. Sarcoidosis in young children may present clinical features that are different from the appearance of those in older children and often constitute a diagnostic challenge. In older children, the clinical appearance has many features in common with the presentation in adults.