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Background: Tumour necrosis factor-alpha (TNF-α) plays a crucial role in sarcoidosis. In severe disease, treatment with TNF-α inhibitors may be effective. Objectives: Changes in sarcoid disease activity were assessed by fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with recalcitrant sarcoidosis treated with adalimumab. Methods: Prospective 24-week observational study. Patients continued medication with steroids and antimetabolites and received adalimumab 40 mg subcutaneously every other week. Ten patients with biopsy-proven sarcoidosis (two men) were included with a median age of 47 years (range 35-73). An FDG-PET showing uptake indicating sarcoid activity was required at inclusion and repeated at the end of the study. FDG-PET uptake was assessed by calculated standardised uptake value (SUV). Blood samples and lung function tests were performed regularly. Quality of life was assessed by the short-form health survey (SF-36) questionnaire. Results: Following treatment with adalimumab, FDG-PET uptake decreased in nine patients ( P = 0.011) and increased in one patient. Maximum SUV fell from median 14.1 to 7.0 ( P < 0.03), and mean SUV fell from median 6.5 to 2.9 ( P < 0.02). Six patients had uptake in the lungs, which decreased after treatment ( P = 0.035). Six patients had uptake in the lymph nodes, which decreased after treatment in five patients ( P = 0.035). Four patients had non-lymphatic extrathoracic uptake, which decreased after treatment ( P = 0.05). There was no effect of adalimumab on pulmonary function tests, serum angiotensin I converting enzyme and blood lymphocyte (CD3+, CD4+, CD8+) concentrations. Physical component summary score (SF-36) increased during treatment, mental component summary score was unchanged. Conclusion: In sarcoidosis, treatment with adalimumab can reduce disease activity, as assessed by FDG-PET. Please cite this paper as: Milman N, Graudal N, Loft A, Mortensen J, Larsen J and Baslund B. Effect of the TNF-α inhibitor adalimumab in patients with recalcitrant sarcoidosis: a prospective observational study using FDG-PET. Clin Respir J 2012; DOI:10.1111/j.1752-699X.2011.00276.x. [ABSTRACT FROM AUTHOR]

We report the usage of the TNF-alpha antagonist Adalimumab in patients with progressive multisystem sarcoidosis. Three patients with multisystem sarcoidosis (MSS) were treated with Adalimumab for 12 months. All three patients were quickly responded to Adalimumab and experienced a nearly complete regression of the symptoms that lead to an intensive immunosuppression. However, some accompanying symptoms of sarcoidosis, such as splenomegalia, did not respond. One patient suffered 18 months later a new unspecified abdominal lymphadenopathy. TNF-alpha antagonists can be helpful agents in the treatment for MSS. However, the experience with TNF-alpha antagonists in patients with sarcoidosis is still limited. Multicenter trials and a comparison of the different agents are needed to validate the safety and efficacy in these patients. Optimal dosage, duration of therapy and long-term toxicity of anti-TNF therapy in patients with refractory sarcoidosis are yet to be determined in prospective trials. [ABSTRACT FROM AUTHOR]

Objectives: The clinical characteristics and treatment results of patients diagnosed with sarcoidosis was investigated in Dicle University Medical Faculty Hospital. Materials and methods: A total of 39 patients were included diagnosed with sarcoidosis between 01 January 2008 and 31 December 2011.Demographic data, laboratory findings, spirometric test data, diagnostic methods and treatment regimens for the study were recorded form. According to pulmonary function test results of patients, 61.5% were normal pattern, 30.8% were restrictive pattern and 7.7% were obstructive pattern. Results: Of the 39 patients 15.4% male, 84.6% were female. The mean age was 39.5±13.1 years for males, females 44.8±14.0 years. All patients of was 17.9% stage 1, 66.7% stage 2, 10.3% stage 3 and 5.1% stage 4. 61.5% were symptomatic, 38.5% were asymptomatic. Methods of diagnosis of the patients examined, 25.6% of patients bronchoscopic biopsy procedures, 74.4% of patients surgical biopsy procedures. Of the 56.4% patients had received corticosteroid treatment, 5.1% patients had received corticosteroid + methotrexate treatment, 38.5% were followed up without the pharmacological treatment. Pharmacological treatment in the group complete at the time of the study 20.5% concluded the treatment of the person. Patients who treatment ending 8.4 months had used pharmacological treatment. Conclusions: Interstitial lung diseases which are prevalent among patients with sarcoidosis diagnosed by examining the clinical features, differential diagnosis and treatment may be possible detection of potential problems. [ABSTRACT FROM AUTHOR]

Abstract: Background: Limited data report thalidomide improves cutaneous sarcoidosis; no benefit has been reported for pulmonary localization. Objectives: To evaluate feasibility and efficacy of prolonged treatment with thalidomide for cutaneous sarcoidosis associated to pulmonary involvement in patients with resistance or contraindications to steroids. Methods: Nineteen patients were treated with thalidomide for 24months starting with 200mg/d for first 2weeks, followed by 100mg/d for 11weeks and a maintenance dose of 100mg on alternate days for 35weeks, and a gradual scaling down until therapy interruption. Criteria of efficacy were: skin score, serum ACE levels (s-ACE), chest X-ray (CXR), lung function tests (LFTs), and diffusing lung capacity for CO (DLCO). The skin score was computed as arithmetic sum of seven score parameters (min: 0, max: 28). Results: Skin score significantly decreased (P <0.001). Lower skin scores occurred after 3 and 6months (P <0.05). s-ACE levels decreased over time at the third month (P <0.001). CXR assessed by radiological stage significantly improved during the first 6months (P <0.001). DLCO showed a continuous trend of improvement. Minor side effects that have forced the suspension of the drug were drowsiness/sedation (74%), constipation (68%), and weight gain (53%). Deep vein thrombosis of the lower limbs occurred in one patient (who did not drop out the study). Eight patients (42%) abandoned thalidomide for axonal sensitive peripheral neuropathy (PN) between the ninth and the 24th month of treatment. Conclusions: Thalidomide, long-term at mid-low doses, can be considered as an effective therapeutic alternative in chronic sarcoidosis with resistance or contraindications to steroids. [Copyright &y& Elsevier]

Introduction: Adalimumab, a humanized monoclonal antibody targeted against TNF-α, has proved to be successful in the treatment of uveitis. Another anti-TNF-α agent, i.e., infliximab, has been reported of benefit in the treatment of refractory sarcoidosis. The aim of this prospective case series was to evaluate the effect of adalimumab on intraocular inflammatory signs and other relevant clinical manifestations (lung function, serological inflammatory parameters, and fatigue) of sarcoidosis. Methods: Sarcoidosis patients with refractory posterior uveitis ( n = 26, 17 females, 41 eyes in total) were systematically followed for 12 months after initiation of adalimumab 40 mg sc once a week. Inclusion criteria were non-responsiveness to prednisone and methotrexate (MTX) or intolerance to these drugs. Adjunctive therapy with prednisone and MTX was tapered during treatment with adalimumab. Localization and improvement, stabilization or deterioration of intraocular inflammatory signs was scored. Pulmonary function- and laboratory testing were performed and Fatigue Assessment Scale was completed. Results at baseline, 6 months, and 12 months were compared. Results: Choroidal involvement resolved in 10/15 patients, five had partial improvement; vasculitis resolved in 1/1 patient; papillitis resolved in 7/8 patients, one had partial response; macular edema resolved in 5/8 patients, three had partial response; vitreous cleared completely in 5/5 patients. Overall outcome regarding intraocular inflammatory signs showed improvement in 22 patients (85%) and stabilization in four patients (15%). At 12 months, no recurrences were reported in those successfully treated. Laboratory parameters of inflammatory activity (C-reactive protein; serum angiotensin-converting enzyme and soluble interleukin-2 Receptor) improved ( p < 0.01). Moreover, fatigue improved in 14/21 (67%) of the patients suffering from fatigue and the diffusion capacity for carbon monoxide (DLCO) improved in 7/8 (88%) of patients with a decreased DLCO ( p < 0.01). The dosage of both prednisone and MTX could be tapered down significantly ( p < 0.01 and p < 0.05, respectively). Conclusions: Adalimumab appeared successful in sarcoidosis patients with refractory chronic non-infectious uveitis showing improvement in intraocular inflammatory signs as well as in other relevant clinical indicators of disease activity. Future randomized studies are needed to determine the optimal dosage, dose interval and duration of therapy in refractory multisystemic sarcoidosis. [ABSTRACT FROM AUTHOR]

The article discusses the clinicopathology in five case studies of patients with sarcoidosis of the spine. The cases include a 48-year-old man with numbness in his hand and neck pain, a 51-year-old woman with pulmonary sarcoidosis and thoracic back pain, and a 57-year-old man with lytic lesions in the thoracic spine. The article concludes surgery should only be performed when there is spinal cord compression or when there is instability secondary to a fracture.

ABSTRACT Background and objective: Invariant natural killer T (iNKT) cells may play an important role in regulating the innate and acquired immune systems in chronic obstructive pulmonary disease (COPD). However, there is little information regarding the potential role of iNKT cells in the pathogenesis of COPD. To investigate whether iNKT cells have an important role in COPD, the frequency of iNKT cells in peripheral blood of patients with COPD was analysed. Methods: This was a comparative study of 28 patients with COPD and 19 age-matched healthy control subjects. Blood iNKT cells were stained with 6B11 mAb, anti-T cell receptor Vα24 mAb, anti-T cell receptor Vβ11 mAb or α-galactosylceramide-loaded CD1d-tetramer, and analysed by flow cytometry. Results: The frequency of CD4+ 6B11+ iNKT, CD4+ Vα24+ iNKT, CD4+ Vβ11+ iNKT and CD3+ 6B11+ iNKT cells was significantly lower in peripheral blood of patients with COPD than in that of healthy control subjects. The frequency of CD4+ 6B11+ iNKT cells was significantly lower in patients with exacerbations of COPD compared with those with stable COPD. Conclusions: The frequency of iNKT was decreased in peripheral blood of patients with COPD. These results strongly suggest that iNKT cells may play an important role in the pathogenesis of COPD. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a multisystemic, granulomatous disease with an unknown etiology. Although granulomas suggest an etiology related to infectious, and organic agents, their etiologies are still unknown. A 16 year-old girl referred with complaints of cough, malaise, and painful lesions on legs lasting for 4 months. On physical examination, no pathological sign was observed, except an erythema nodosum-like purple lesion, the largest one being 5 cm in diameter was detected on the tibial region. Erythrocyte sedimentation rate was 60/1 hour and CRP 15.66 mg/L. Angiotension converting enzyme level was elevated. High resolution thoracal CT results were reported as multiple mediastinal lymphadenopaties and micronodular parenchymal infiltrations at right middle and lower lobes. In biopsy, taken during bronchoscopy, granulamatous lesions were observed. Patient was suggestively diagnosed as sarcoidosis with these findings and followed up without treatment because of relatively lesser severity of these findings. Sarcoidosis is a rare disease of childhood, and can spontaneously resolve or become chronic. Follow-up of the patients with physical examination and respiratory function tests are necessary. Steroids or methotrexate can be used for the treatment according to the clinical severity of the disease, but results are controversial. Since it a rarely seen condition, we want to emphasize the importance of sarcoidosis and review the literature. [ABSTRACT FROM AUTHOR]

A 36-year-old man visited our hospital because of blurred vision and redness of the conjunctiva. Slit-lamp examination showed panuveitis. Two days later, he suddenly experienced dizziness, speech disturbance, paralysis of his right extremities, and gait disturbances. Neurological examinations suggested that his symptoms were caused by a left lateral medullary lesion. He also had erythema mainly on his trunk. Magnetic resonance imaging (MRI) of his brain demonstrated a small infarct on the left side of the medulla oblongata. Clinical presentation and MRI findings were consistent with the diagnosis of a Wallenberg's syndrome. He also had bilateral hilar lymphadenopathy. A skin biopsy showed granulomatous nodular dermatitis compatible with sarcoidosis. He was treated with steroid pulse therapy and his neurological and ocular symptoms immediately improved. Only seven similar cases of intracranical sarcoidosis have been reported, but none had been treated with steroid pulse therapy. We recommend that steroid pulse therapy be considered to treat patients with sarcoidosis with signs of lesions in the central nervous system. [ABSTRACT FROM AUTHOR]

The article discusses a modified Delphi study aimed at investigating whether a consensus could be reached on the best approaches for screening for and management of cardiac sarcoidosis. For this study, several sarcoid experts in the U.S. were identified based on their national reputation and their active involvement in sarcoidosis clinics at their institutions. According to the study results, the lack of agreement among experts on key aspects of diagnosis and management was noted.

A case of painless isolated extraocularmuscle sarcoid and a literature review are presented. The atypical features in our case include a lack of overt inflammatory symptoms and signs, such as pain, ptosis, and diplopia. The presentation of minimal symptoms without improvement warrant a biopsy to establish the diagnosis and to administer appropriate treatment in order to prevent potential long-term complications from sarcoidosis. [ABSTRACT FROM AUTHOR]

Tumour necrosis factor (TNF) is an important cytokine involved in the pathology of a number of inflammatory conditions, and thus blockade with anti-TNF therapies is becoming the cornerstone in managing such diseases. With increasing use, evidence is collected for the association of sarcoid-like granulomatous disease developing after the initiation of anti-TNF-α therapy, with disease reversal after discontinuation. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Sinonasal sarcoidosis is difficult to treat. Infliximab seems to be useful in the treatment of sarcoidosis of the upper respiratory tract. Case series: We report three cases of sinonasal sarcoidosis in two women of 36 and 42-year-old and in a 64-year-old man. Resistance or dependence to corticosteroids and absence of efficacy of methotrexate therapy in one patient led to administer anti-TNFα therapy with infliximab. Outcome was favourable on sarcoid lesions but treatment was discontinued because of infectious complications and worsening of sarcoid chest involvement. Conclusion: This case series suggests that infliximab might be useful for the treatment of sarcoidosis with sinonasal involvement. [Copyright &y& Elsevier]

Giant cell myocarditis, but not cardiac sarcoidosis, is known to cause fulminant myocarditis resulting in severe heart failure. However, giant cell myocarditis and cardiac sarcoidosis are pathologically similar, and attempts at pathological differentiation between the two remain difficult. We are presenting a case of fulminant myocarditis that has pathological features suggestive of cardiac sarcoidosis, but clinically mimicking giant cell myocarditis. This patient was treated with cyclosporine and prednisone and recovered well. This case we believe challenges our current understanding of these intertwined conditions. By obtaining a sense of severity of cardiac involvement via delayed hyperenhancement of cardiac magnetic resonance imaging, we were more inclined to treat this patient as giant cell myocarditis with cyclosporine. This resulted in excellent improvement of patient's cardiac function as shown by delayed hyperenhancement images, early perfusion images, and SSFP videos. [ABSTRACT FROM AUTHOR]

The options for treatment of sarcoidosis have expanded. In this article, we outline a stepwise approach to treatment. Recommendations for treatment are based on available evidence. While corticosteroids remain the treatment of choice for initial systemic therapy, other agents have been shown to be steroid sparing, and therefore useful for long-term management. In addition, new agents have proved to be useful for patients with refractory disease. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a granulomatous lung disease in which several cytokines play a pivotal pathogenetic role. Steroid-resistant disease can be treated with immunosuppressive drugs, antimalarial therapies and recently with anti-TNFα agents. The use of biological agents for the treatment of sarcoidosis springs from research into the pathogenesis of the disease and also from the experience of rheumatologists with other chronic inflammatory diseases. Rituximab, golimumab and ustekinumab are cytokine modulators, useful in the treatment of immunoinflammatory disorders, for which randomized trials to evaluate safety and efficacy in sarcoidosis are not yet available. Novel anticytokine drugs administered alone or in association may offer a new approach to treatment of the disease. This review focuses on recent advances in anti-TNFα agents and cytokine modulators for the treatment of sarcoidosis and their therapeutic prospects. [ABSTRACT FROM AUTHOR]

Copyright of Journal of the Child / Çocuk Dergisi is the property of Journal of Child and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

L.R. Minces, J.K. Bhama, R. Abdel-Massih, E.J. Kwak, S.S. Haider, M.H. Nguyen, Y. Toyoda, F.P. Silveira. Successful double lung transplantation in a patient with bilateral pulmonary and sinus aspergillomas. Transpl Infect Dis 2011: 13: 485-488. All rights reserved Abstract: The outcome of patients with aspergilloma undergoing lung transplantation is not completely known, but anecdotal reports of poor outcome after transplant have discouraged this practice. We present a 45-year-old female with pulmonary sarcoidosis complicated by bilateral pulmonary and sinus aspergillomas who underwent successful double lung transplantation. Patients with aspergillomas can receive lung transplantation, provided that there is sufficient technical expertise to explant the infected lungs with minimal chance of chest wall contamination, and aggressive antifungal therapy is used post transplantation. [ABSTRACT FROM AUTHOR]

Abstract: A 55-year-old woman with chronic hepatitis C presented with acute painless, unilateral, granulomatous uveitis without other systemic symptoms. Ocular symptoms began 20 weeks after starting pegylated interferon alpha (IFN-α)-2a and ribavirin. The anterior granulomatous uveitis quickly improved after application of topical steroid. However, the vision of the right eye worsened 4 weeks later because of a new episode of vitritis with multiple snowballs along and in retinal vessels. These were nodular and/or segmental periphlebitis with candlewax drippings in appearance. Multiple granulomas persisted for 4 weeks and spontaneously disappeared after immediate discontinuation of IFN-α therapy. We reviewed eight additional granulomatous uveitis of presumed ocular sarcoidosis during IFN-α therapy in previous articles and all of these patients suffered from bilateral uveitis. However, our case was treated with IFN-α and resulted in unilateral granulomatous panuveitis. Sixteen weeks after discontinuation of IFN-α therapy, the patient recovered well with regards to vision and no recurrence occurred. [Copyright &y& Elsevier]

Equine sarcoids are fibroblastic wart-like skin lesions that can locally invade subcutaneous and muscular tissues and result in cosmetic defects and interference with normal activities. Sarcoids can also be difficult to treat. Eighteen horses with sarcoids were presented to the author for treatment from 1995-2009. Based on the Ke cycle of Five Element theory, a single acupuncture needle was placed in the Ting point (Jing-well point, the first or last acupoint of a Channel located at the oronary band of the hoof) of the Channel that controls the Channel on which the sarcoid resided. The needle was left in place un-manipulated for 20 minutes. Acupuncture was repeated three times, 3-4 weeks apart. The diameter of the sarcoid for each horse was measured in centimeters at each visit and 5-7 weeks after the final treatment. The sarcoids significantly reduced in size following acupuncture treatment in 77.7% (14/18) of horses. The mean±standard deviations of the tumor size for all 18 tumors before and after treatment were 12.17±13.19 cm and 7.01±16.08 cm respectively and were significantly different at p=0.01 using a paired student t-test. For the 14 horses that responded to acupuncture, the mean±standard deviations of the tumor size before treatment and after treatment were 9.07±6.30 cm and 1.51±1.50 cm, which was significantly different at p=0.001 using a paired student t-test. Since Ting point acupuncture is simple, relatively inexpensive and has no adverse side effects compared to conventional sarcoid treatments, it may be useful for equine sarcoid treatment and further studies are warranted. [ABSTRACT FROM AUTHOR]

Copyright of Brazilian Journal of Pulmonology / Jornal Brasileiro de Pneumologia is the property of Sociedade Brasileira de Pneumologia e Tisiologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Sarcoidosis is a multisystemic granulomatous disease of unknown origin. Bilateral hilar lymphadenopathy, pulmonary infiltrates, and skin and ocular lesions are the most frequently detected manifestations. Although involvement of the spleen is frequent, it is quite rare to experience massive splenomegaly and its clinical symptoms. Since this condition is uncommon, we report here a patient admitted to our clinic with abdominal pain due to massive splenomegaly, together with typical clinical findings. [ABSTRACT FROM AUTHOR]

Chronic pain is one of the most commonly reported symptoms among sarcoidosis patients. Not only does it significantly affect quality of life, but it also is a source of frustration for both the patient and physician because the etiology for pain often is unknown. Although patients typically complain of neuropathic-type pain, nerve conduction studies and other conventional diagnostic procedures frequently fail to reveal objective evidence of neurologic disease. However, in recent years, the growing use of specialized tests such as skin biopsy and sudomotor testing has helped to establish the diagnosis of small-fiber neuropathy as the cause of pain in these patients via objective and quantifiable means. Management of sarcoidosis small-fiber neuropathy should consist of target-directed treatment of the underlying disease and appropriate symptomatic therapy. [ABSTRACT FROM AUTHOR]

Purpose: To compare the evidence base and systemic treatment strategies for sarcoidosis. Methods: Medline and EMBASE literature search on ''sarcoidosis AND treatment'', ''sarcoidosis AND uveitis AND treatment'', and ''sarcoidosis AND eye AND treatment''. The search was limited to randomized controlled trials (RCTs) and meta-analyses. Results: A total of 19 RCTs for the systemic treatment of extraocular sarcoidosis were identified. The majority were on corticosteroid--oral and inhaled. There were two meta-analyses on corticosteroid, including a Cochrane review. Only two RCTs were indentified for the treatment of intraocular sarcoidosis, one on etanercept, and the other from 1967 on prednisolone or oxyphenbutazone vs. placebo. There were no meta-analyses. Due to the paucity of RCTs other treatment studies were included but these were limited to only a few immunosuppressive agents and on small numbers of patients. Conclusion: Limited high-quality evidence exists for the systemic treatment of sarcoidosis, in particular intraocular disease. [ABSTRACT FROM AUTHOR]

Copyright of Archivos de Bronconeumología (English Edition) is the property of Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Sarcoidosis is a common disorder with heterogeneous severity. Corticosteroids are the cornerstone of its treatment and allow a disease remission but only with a suspensive effect. Immunosuppressive drugs, hydroxychloroquine and infliximab may be useful in some patients. Half of the patients recover spontaneously without any treatment. In the remaining patients, a treatment is necessary either at presentation or during the follow-up in the presence of a disease flare. Treatment duration should be of at least 12 months. The main indications of a systemic treatment include ophthalmologic, neurologic, cardiovascular, renal, laryngeal involvements, severe pulmonary manifestations, lupus pernio and marked hypercalcaemia. Initially, patients should receive prednisone or prednisolone at 0.5 to 1 mg/kg daily for 6 to 12 weeks to obtain a complete remission, and then followed by a gradual dose reduction every 6 to 12 weeks. After treatment completion, a 36-month duration monitoring is warranted to confirm recovery. Low-dose methotrexate and azathioprine are the most useful immunosuppressive drugs and are indicated in patients with of failure or contra-indication of corticosteroids or in those patients who needs a long term prednisone dose higher than 10 mg daily to control the sarcoidosis. Cyclophosphamide used is severe neurologic or heart involvement that is resistant to corticosteroids and other immunosuppressive drugs. Hydroxychloroquine and chloroquine are indicated in extensive skin lesions or as corticosteroids sparing agents. Infliximab can be useful in some severe sarcoidosis patients refractory to classical treatment, except for cardiac involvement. Topical corticosteroids can be used for limited skin involvement, anterior uveitis or cough. In the future, a more individualized treatment could be drawn from pharmacogenetic studies. The key point remains the availability of etiologic or innovative drugs for sarcoidosis refractory to currently available therapy. [Copyright &y& Elsevier]

The synthesis of vitamin D is altered by the granulomatous inflammation of sarcoidosis leading to increased production of 1, 25-dihydroxyvitamin D. Mounting evidence suggests that vitamin D is an immunomodulating hormone that inhibits both antigen presentation by cells of the innate immune system, and the cytokine release and proliferation of Th1 cells. These and other extraskeletal health benefits have led to an increase in vitamin D assessment and pharmacological supplementation in the general population. This review highlights the altered synthesis and general immunomodulating properties of vitamin D with a special emphasis on known interactions with sarcoidosis. In addition, the assessment of vitamin D nutritional status, its pharmacological supplementation, and the management of bone health in patients with sarcoidosis are reviewed. [ABSTRACT FROM AUTHOR]

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, Sj?gren 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. [ABSTRACT FROM AUTHOR]

Ocular disease occurs in approximately a third of sarcoidosis patients. The rate of disease varies around the world, with Japanese sarcoidosis patients having ocular disease in more than 70% of cases. If untreated, ocular disease can lead to permanent visual impairment, including blindness. The most common manifestation is uveitis, with anterior involvement often being self-limiting, whereas posterior involvement can be chronic. The diagnosis of ocular sarcoidosis in patients with known sarcoidosis usually requires a specific examination by an ophthalmologist. For patients presenting with uveitis of unknown etiology, criteria have been proposed for diagnosing ocular sarcoidosis. The treatment of ocular disease ranges from topical therapy to systemic treatments such as methotrexate. Recent reports have demonstrated that monoclonal antibodies blocking tumor necrosis factor can be quite effective for chronic refractory ocular sarcoidosis. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a systemic disease with skin manifestations. Skin manifestations are classified as nonspecific if they are not characterized by granulomatous inflammation and specific if the lesions have granulomas histologically. Erythema nodosum is the most common nonspecific skin manifestation, and it portends a good prognosis. Specific skin lesions have a varied clinical appearance, although often they can be distinguished by their yellow translucent character. Despite the potential variable appearance, there are common clinical presentations. Lupus pernio lesions are nodular violaceous specific skin lesions found predominantly on the face associated with scarring and a poor prognosis. Treatment of cutaneous sarcoidosis is primarily done to avoid scarring and cosmetic disfigurement. Local and systemic corticosteroids are the mainstay of treatment for the disease. Corticosteroid-sparing agents used to manage the disease include antimalarials, methotrexate, and tetracycline antibiotics. Tumor necrosis factor-? (TNF-?) antagonists such as infliximab may have a role in cutaneous sarcoidosis, especially in refractory cases that are resistant to the standard regimens. [ABSTRACT FROM AUTHOR]

Cardiac involvement is undeniably one of the most challenging issues in sarcoidosis. Although autopsy studies reveal heart lesions in 20 to 30% of sarcoid patients, fewer than 5% suffer from clinical disease. Cardiac sarcoidosis (CS) has a predilection for the myocardium, but the pericardium and endocardium may also be affected. CS manifestations are various and most frequently include the following: (1) aberrations of atrioventricular or intraventricular conduction, either silent or symptomatic; (2) ventricular arrhythmias; (3) subacute congestive heart failure; and (4) sudden death. CS must be detected in all sarcoid patients by means of detailed medical history, physical examination, and resting electrocardiogram (ECG) at first evaluation and during follow-up. In patients with suspected CS, further investigations are aimed at evaluating diagnosis and cardiac consequences. Unfortunately, no gold standard exists that would allow CS diagnosis with a level of confidence. Endomyocardial biopsy is an invasive procedure that lacks sensitivity. Patients need, at a minimum, specialized cardiologic advice, echocardiography, and 24-hour ambulatory ECG. Other diagnostic tools include thallium, technetium, and gallium scintigraphy, and more recently, 18F-fluorodeoxyglucose positron emission tomography and cardiac magnetic resonance (CMR). The respective role of these new imaging tools in the diagnostic approach remains to be defined. CMR has the advantage of not exposing patients to radiation, but it is not feasible in those with cardiac devices. In Western countries, heart involvement accounts for 13 to 25% of sarcoidosis-related deaths, and it is the leading cause of mortality in Japan. The main prognostic indicators are New York Heart Association functional class, left ventricular enlargement, and sustained ventricular tachycardia. Treatment is based on systemic corticosteroids with an initial dose between 30 mg/day and 1 mg/kg/day (which is usually maintained for at least 24 months), specific cardiologic agents, and the placement of a pacemaker or implantable cardiac defibrillator in case of an atrioventricular block or severe intractable ventricular arrhythmias. Cardiac transplantation is exceptionally required. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a disease of unknown etiology, characterized pathologically by noncaseating granulomas that most commonly involve the lung, skin, lymph nodes, and eyes. Syndromes with similar pathological and immunologic features to sarcoidosis such as chronic beryllium disease, hypersensitivity pneumonitis, and tuberculosis illustrate that granulomatous diseases may or may not have an infectious etiology. Although the etiology of sarcoidosis remains unknown, recent molecular, genetic, and immunologic studies strengthen the association of sarcoidosis with infectious antigens. Currently, the strongest agents considered include PROPIONIBACTERIUM and MYCOBACTERIUM species. Independent studies report the presence of microbial nucleic acids and proteins within sarcoidosis specimens. Th-1 immune responses to mycobacterial proteins have been detected within sarcoidosis diagnostic bronchoalveolar lavage (BAL). These proteins are actively secreted by the mycobacterial SecA 2 secretion system and are important to evade the host immune system. Recent discoveries regarding MHC class II alleles provide additional insight regarding the role of microbial antigens in sarcoidosis pathogenesis. Although further investigation is warranted, the recent progress of independent laboratories, using complementary techniques, strengthens the role of microbial antigens in sarcoidosis pathogenesis. These studies lay a strong foundation toward identifying therapeutic targets. [ABSTRACT FROM AUTHOR]

Sarcoidosis is an immune-mediated systemic syndrome of unknown etiology. The treatment of the granulomatous inflammation in sarcoidosis is thus dependent on nonspecific suppression of the immune response. Although steroid-sparing approaches have moved to front-line therapy for many other immune-mediated inflammatory diseases, corticosteroids remain the initial treatment of choice for most patients with sarcoidosis due in large part to the clinical variability and high rates of spontaneous remission. Given the heterogeneity of clinical phenotypes between patients, treatment approaches must be individualized. For patients with persistent disease, or for patients who are intolerant of systemic steroids, there are several steroid-sparing immune-modulating medications that have been effective for treating sarcoidosis. Besides immunosuppressives, we will also overview several sarcoidosis-related issues that contribute to patient-reported symptoms, a "sarcoidosis penumbra." Recognition and judicious therapy for these related issues are often key to optimizing outcomes and quality of life. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a systemic disease characterized by noncaseating granulomas in the involved organs. Neurologic manifestations involving the central and/or peripheral nervous system occur in about 5% of patients. Neurosarcoidosis is often refractory to conventional treatment and therefore more effective treatment options are needed. While the etiology of the disease is still unknown, there is now a better understanding of its pathogenesis on a molecular level. It is clear that tumor necrosis factor-α (TNFα) plays a pivotal role in the development of the granulomas and it is believed to be a key cytokine involved in the pathogenesis of the disease. Taking advantage of this better understanding of disease pathogenesis, anti-TNFα agents are being increasingly used to treat refractory sarcoidosis. We report a patient with refractory neurosarcoidosis who showed dramatic improvement in the clinical and radiological manifestations following treatment with infliximab; he suffered a relapse upon discontinuation of the medication. [ABSTRACT FROM AUTHOR]

The article focuses on a study which examined the efficacy of thalidomide in patients with severe early-onset sarcoidosis (EOS). Study authors gave thalidomide to two patients with EOS, whose peripheral blood monocytes were analyzed to understand the mechanism of the drug. They concluded that thalidomide has the capacity to improve clinical symptoms and laboratory findings in patients with EOS.

Studies of seasonal patterns of incidence of sarcoidosis may provide a better understanding of potential environmental triggers of the disease. In this study, Olmsted County, Minnesota residents who were diagnosed with sarcoidosis between 1976 and 2013 were identified based on individual medical record review. The seasonal variation of incident sarcoidosis was then calculated. The age-adjusted and sex-adjusted incidence rate of sarcoidosis was lower in autumn (2.0/100 000; 95% CI 1.5 to 2.5) compared with winter (3.2/100 000; 95% CI 2.6 to 3.8), spring (2.8/100 000; 95% CI 2.2 to 3.4) and summer (2.9/100 000; 95% CI 2.2 to 3.5, p=0.024). Subgroup analysis per decade consistently showed lower incidence of sarcoidosis in autumn. [ABSTRACT FROM AUTHOR]

Background: A major gap in the management of sarcoidosis is the lack of accessible and objective methods to measure disease activity. Since 90% of patients have pulmonary involvement, we explored if a disease activity score based on thoracic CT scans could address this clinical issue.Methods: High-resolution CT scans from 100 consecutive patients with sarcoidosis at a regional sarcoidosis service were scored for extent of CT abnormalities known to relate to granuloma or lymphocytic infiltration from published CT-pathological studies. These individual abnormality scores were then correlated against serum ACE, sIL-2R and change in FVC to identify CT abnormalities that reflect contemporaneous disease activity. The sum of these scores, or CT Activity Score (CTAS), was then validated against FVC response to treatment.Findings: CT extent scores for nodularity, ground-glass opacification, interlobular septal thickening and consolidation correlated significantly with at least one of the disease activity parameters and were used to form CTAS. CTAS was found to predict FVC response to treatment at 1 year and was highly reproducible between radiologists. An abbreviated CTAS (aCTAS), constructed from presence or absence of the four CT abnormalities, also showed significant correlation with FVC response to treatment. CTAS and aCTAS also correlated with response to treatment in the fibrotic subgroup.Interpretation: CTAS provides a concept for an objective and reproducible CT scoring method to quantify disease activity in sarcoidosis. The score can potentially be used to stratify patients according to disease activity, determine response to treatment and establish if fibrotic sarcoidosis is active. [ABSTRACT FROM AUTHOR]

The article discusses the prevalence of cardiac sarcoidosis among middle-aged individuals presenting with high-grade atrioventricular block, ventricular tachyarrhythmias or left ventricular dysfunction and heart failure. It states that the diagnosis of cardiac sarcoidosis requires either myocardial histology showing noncaseating granulomatous inflammation in the absence of other explanations or similar extracardiac histology.

We describe the first case of mediolateral episiotomic sarcoidosis of the deep vaginal tissue, without involvement of the pulmonary parenchyma or pulmonary symptoms. A 68-year-old female was admitted with a vaginal mass that had developed about 1 month prior. On bimanual examination, we found a painful solid mass approximately 4 cm in diameter on the episiotomy line of the deep vaginal tissue. The patient underwent pelvic magnetic resonance imaging on suspicion of a malignancy, and a vaginal true-cut biopsy was performed. The biopsy specimen exhibited non-caseating, granulomatous inflammation and many multinucleated giant cells, strongly suggesting sarcoidosis. We had excluded other granulomatous diseases; a final diagnosis was made of stage-1 sarcoidosis in the deep vaginal mass. A 3-month course of methotrexate (2.5 mg/week) was commenced to treat a flare-up of rheumatoid arthritis. The vaginal mass resolved. To the best of our knowledge, this is the first case of sarcoidosis in a deep vaginal mass without pulmonary parenchymal or other solid-organ involvement. [ABSTRACT FROM PUBLISHER]

The article focuses on the most common therapies for sarcoidosis. It mentions that corticosteroids is used for sarcoidosis which stimulates gene transcription. It states that various studies examined the effects of inhaled corticosteroids on pulmonary sarcoidosis in which a study detected an undetermined evidence to affirm the utilization of inhaled corticosteroids. It mentions medication alternatives for sarcoidosis such as Methotrexate (MTX), antimalarial agents and TNF-α inhibitors.

Purpose: To evaluate the diagnosis, treatment, and visual outcome in patients with retinal vasculitis (RV). Materials and Methods: The clinical records of 71 patients diagnosed with RV between 1997 and 2007 were reviewed retrospectively. The diagnosis was made by slit-lamp examination and fundus fluorescein angiography. Results: Forty-one patients were diagnosed with Behçet's disease (57.7%), 7 patients with sarcoidosis (9.8%), 7 patients with primary RV (9.8%), 4 patients with pars planitis (5.6%), 4 patients with multiple sclerosis (5.6%), 3 patients with Eales' disease (4.2%), 2 patients with ocular toxoplasmosis (2.8%), 1 patient with Lyme disease (1.4%), 1 patient with idiopathic retinal vasculitis, aneurysm, and neuroretinitis (IRVAN) syndrome (1.4%), and 1 patient with tuberculosis (1.4%). Fluorescein angiography of these patients showed optic disc leakage in 60 patients (84.5%), diffuse vascular leakage in 59 patients (83.09%), cystoid macular edema in 21 patients (29.5%), peripheral segmentary vascular leakage in 12 patients (16.9%), peripheral retinal ischemia in 10 patients (14.08%), and macular ischemia in 5 patients (7.04%). Occlusive vasculitis was determined in 11 patients (15.4%). Visual acuity improved in 43 patients (60.5%), stayed at the same level in 19 patients (26.7%), and worsened in 9 patients (12.6%) after the treatment given according to the diagnosis. Conclusion: Retinal vasculitis may occur in isolated form or in association with other ocular and systemic inflammatory diseases. We can expect better visual outcomes with a multidisciplinary diagnostic and therapeutic approach. [ABSTRACT FROM AUTHOR]

Abstract Purpose  We aimed at investigating whether early metabolic response to corticosteroid therapy may be used as a diagnostic tool to discriminate between cancer and sarcoidosis, a well-known cause of false-positive 2-deoxy-2-[F-18]fluoro-d-glucose-positron emission tomography (FDG-PET) findings in oncology. Procedure  Two cancer patients with biopsy-proven sarcoidosis or sarcoid-like reaction had multiple thoracic FDG foci. After infectious disease had been excluded, patients received oral corticosteroids for 16 and 14 days, respectively, and underwent posttherapeutic FDG-PET examination. Results  Posttreatment PET revealed a complete metabolic response in both patients, and clinical and imaging follow-up showed no sign of cancer progression. Conclusion  Early metabolic response to systemic corticosteroid treatment may be used as a tool in the establishment of final diagnosis when sarcoidosis is suspected in a cancer patient and could be capable of differentiating cancer from sarcoidosis in the case of coexisting diseases. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 37 year old woman with a history of seizures who presented to the emergency room of a hospital with complaints of vertigo, facial weakness and seizures. A discussion of the woman's medical history prior to the emergency room visit is presented. Diagnostic testing which was conducted on the woman and resulted in a diagnosis of neurosarcoidosis is discussed. The woman's recovery after treatment with prednisone is examined.

We report the case of a 38-year-old, female patient with neurosarcoidosis involving the pituitary gland and hypothalamus, who was treated with stereotactic radiotherapy (24 Gy in 12 fractions) with an excellent result. The purpose of this case report was to illustrate and discuss the diagnostic and therapeutic challenges faced in the management of neurosarcoidosis, as well as document our experience with the use of stereotactic radiotherapy in the treatment of neurosarcoidosis. [ABSTRACT FROM AUTHOR]

Although healthcare providers have arrived at a relatively comfortable zone of accepted clinical practice in the management of cutaneous sarcoidosis, virtually every treatment is based on minimal evidence-based data and relies almost exclusively on anecdotal information. Although it would be convenient to blame this state of affairs on the lack of certainty about disease aetiology, the unavoidable fact is that little has been executed, even in the realm of well designed comparative trials. Nonetheless, worldwide accepted standard therapies for sarcoidosis include the administration of corticosteroids, antimalarials and methotrexate. A stepwise approach to patient care is appropriate, and potent topical corticosteroids (e.g. clobetasol) or repeated intralesional injections of triamcinolone (3–10 mg/mL) may be all that is needed in mild skin-limited disease. In patients requiring systemic therapy for recalcitrant or deforming skin lesions (or for widespread disease), corticosteroids (e.g. prednisone 40–80 mg/day, tapered accordingly) used alone or in combination with antimalarials or methotrexate may be indicated. Antimalarials and methotrexate are considered second-line interventions and may be used as monotherapy for steroid-resistant sarcoidosis or in patients unable to tolerate steroids. Given the concern regarding ocular toxicity, the maximum dosages of chloroquine and hydroxychloroquine should not exceed 3.5 and 6.5 mg/kg/day, respectively. Methotrexate is given in weekly doses of 10–30 mg, with the caveat that haematological, gastrointestinal, pulmonary and hepatic toxicities are possible.Despite universal acceptance as standard care, the aforementioned treatments often result in an incomplete clinical response or unacceptable adverse events. In such situations, more innovative treatment options may be used. Treatments that may well gain widespread future use include the tumour necrosis factor-α inhibitors infliximab and adalimumab. Experience is limited, but early reports are promising. Infliximab is administered via intravenous infusion at doses of 3–10 mg/kg at 0, 2 and 6 weeks and as indicated thereafter, whereas adalimumab is injected subcutaneously at doses of 40 mg either weekly or every 2 weeks. Because adalimumab is not approved for the management of sarcoidosis, the optimum dose administration interval is uncertain. However, it has been given in both weekly and every other week regimens. Isotretinoin, 0.5–2 mg/kg/day, has been used successfully in a handful of reported cases. However, the teratogenic potential of isotretinoin is often prohibitive considering that the primary demographic group likely to develop sarcoidosis is women of childbearing potential. Thalidomide at dosages of 50 to >400 mg/day has limited, albeit promising, supporting data. However, access is restricted in many countries because of a deserved pregnancy category X rating. Melatonin (20 mg/day) and allopurinol (100–300 mg/day) are not well studied in cutaneous sarcoidosis, and the clinical experience with tetracycline derivatives has been mixed. That said, there are compelling reports of therapeutic benefit with both doxycycline and minocycline. Because neither of these agents is associated with the severe toxicity of cytotoxic drugs, they may serve as effective therapy in some patients. Pentoxifylline (400 mg three times daily) has been of use in a small number of reported cases of pulmonary sarcoidosis, but there are no reports on its use in patients with primarily cutaneous disease. Both ciclosporin and chlorambucil have been largely abandoned given their associated toxicity and disappointingly unreliable efficacy. Finally, laser therapy is a newer modality that may provide patients with a quick and non-invasive treatment option for cutaneous sarcoidosis. [ABSTRACT FROM AUTHOR]

Orbital sarcoid has a diverse clinical presentation varying from lacrimal gland infiltration, soft tissue orbital mass and intra- and extraorbital optic nerve involvement, to extraocular muscle involvement. Whether orbital disease precedes other systemic manifestations or not, systemic treatment is considered necessary. Even though systemically administered corticosteroids have been the mainstay for a long time, methotrexate proves to be an effective and well-tolerated steroid-sparing drug, especially for refractive disease. Furthermore, modern drugs have emerged with promising results; and ongoing studies are expected to evaluate and compare them. [ABSTRACT FROM AUTHOR]

Background: Distinct mutations of the caspase activating recruitment domain 15 ( CARD15) gene (also known as nucleotide-binding oligomerisation domain protein 2) on chromosome 16q are associated with the chronic granulomatous disease called Blau syndrome. Sarcoidosis is a systemic granulomatous disease, which has features in common with Blau syndrome. Aim: The aim of this study was to evaluate whether ethnic Danes with sarcoidosis have CARD15 mutations associated with Blau syndrome. Methods: Analysis of exon 4 of the CARD15 gene containing mutations associated with Blau syndrome was performed by polymerase chain reaction and sequencing of genomic DNA from 52 patients with histologically verified sarcoidosis. Results: None of the patients had mutations in CARD15 associated with Blau syndrome. Eight other variations were found in exon 4: single nucleotide polymorphism (SNP)6 in 40% of the 104 alleles examined, SNP7 in 26%, c. 1833 C > T and SNP8 in 4%, c. 2107 C > T in 2%, and c. 931 C > T, c. 1292 C > T and c. 2377 G > A in 1%. One variation was found in intron 4 (IVS4 + 10 A > C) in 3% of the alleles. The frequencies of the variations in sarcoidosis patients were not statistically significant compared with frequencies in a control group of 103 healthy subjects. The course of disease was not significantly different in patients with or without variations in CARD15 or in the 46 patients with SNP6 and/or SNP7. Conclusions: Danish sarcoidosis patients have frequent variations in CARD15 exon 4, but do not present any mutation associated with Blau syndrome. The variations found had no influence on the course of disease. Please cite this paper as: Milman N, Nielsen FC, Hviid TVF and van Overeem Hansen T. Blau syndrome-associated mutations in exon 4 of the caspase activating recruitment domain 15 ( CARD15) gene are not found in ethnic Danes with sarcoidosis. The Clinical Respiratory Journal 2007; 1: 74–79. [ABSTRACT FROM AUTHOR]

Steroid-resistant sarcoidosis has conventionally been treated with various drugs, including methotrexate, azathioprine, cyclophosphamide, cyclosporine, antimalarial drugs and thalidomide, with variable success. There is a compelling need for more efficient and safer alternatives to these agents. Several lines of evidence suggest a critical role of TNF-α (tumour necrosis factor-α) in the initiation and organization of sarcoid granulomas. Inhibition of TNF-α with monoclonal antibodies has therefore received attention as a potential treatment option in therapy-resistant sarcoidosis. A number of case reports and small case series describe successful treatment of refractory disease with infliximab. Preliminary evidence from an RCT (randomized controlled trial) with infliximab in pulmonary sarcoidosis suggests a modest improvement in functional and radiological parameters. In contrast, the results with etanercept have been disappointing, perhaps related to differences in the mechanism of TNF-α blockade. The experience with adalimumab in sarcoidosis is too limited to draw conclusions. An open-label study and an RCT evaluating the efficacy of adalimumab in sarcoidosis with pulmonary and cutaneous involvement respectively, have been initiated. Although TNF-α antagonists appear relatively safe, especially when compared with conventional agents, caution is warranted in view of the increased incidence of tuberculosis, which may be a particular diagnostic challenge in patients with sarcoidosis. Pending publication of the RCTs, the use of TNF-α blockade in sarcoidosis should remain in the realm of experimental treatment. [ABSTRACT FROM AUTHOR]

Lymphadenopathy refers to any disease process involving lymph nodes that are abnormal in size and consistency. Lymphadenitis specifically refers to lymphadenopathies that are caused by inflammatory processes. Cervical lymphadenopathy is a common problem in the pediatric age group and is largely inflammatory and infectious in etiology. Although most patients are treated successfully by their primary care physician, surgical consultation is frequently required for patients who fail to respond to initial therapy or for those in whom there is an index of suspicion for a neoplastic process. This article addresses current approaches to the diagnosis and management of cervical lymphadenitis in children. [ABSTRACT FROM AUTHOR]