Whole-body gallium 67 scans. Role in diagnosis of sarcoidosis

Early studies of 67gallium (67Ga) scanning in sarcoidosis focused on the lungs as a measure of disease activity, likelihood of progression, and the advisability of corticosteroid therapy. The predictive value of pulmonary uptake proved to be limited, but there has been renewed interest in 67Ga scanning as a diagnostic aid with special attention to characteristic extrapulmonary uptake patterns. Review of whole-body 67Ga scans in 172 patients with sarcoidosis, 21 with lymphoma, and 51 with other disorders demonstrated distinctive cranial, mediastinal, and hilar uptake patterns in sarcoidosis patients. Bilateral hilar uptake occurred in 81 sarcoidosis patients (47%) but in no lymphoma cases. Increased lacrimal and/or salivary gland uptake was observed in 47.5% but lacked specificity. Uptake in peripheral lymph nodes was infrequent in sarcoidosis (5%) but common in lymphoma (57%). 67Ga scans are especially valuable in patients with uveitis and liver granulomas whose chest radiographs are normal or equivocal. 67Ga scans, unnecessary in typical cases of sarcoidosis, have an important diagnostic role by reducing the need for invasive biopsy procedures in asymptomatic patients.     

Sarcoïdose cardiaque : stratégies diagnostiques et thérapeutiques actuelles

Sarcoidosis is a systemic granulomatous disease characterized by pulmonary involvement in most patients and more rarely by extrapulmonary involvement such as ocular, skin, salivary, lymph nodes and joints damages. Neurological and cardiac involvements are uncommon but are associated with increased morbidity and mortality. Cardiac sarcoidosis affects 5 to 20% of patients depending on the studies and autopsy studies even report cardiac involvement in 25% of sarcoidosis patients. This review aims to summarise main data on the diagnostic value of the different imaging techniques in cardiac sarcoidosis and to also detail the management of these patients who require a multidisciplinary approach.     

结节病肺内、外影像学特征及肺外累及预测因素的初探

目的 总结结节病肺内、外影像学特征,结合患者临床资料探究结节病肺外累及的预测因素.方法 回顾性分析2012～2020年四川大学华西医院病理学明确诊断为结节病的103例住院患者临床、实验室及影像数据,观察及分析结节病肺内结节分布、纵隔淋巴结增大及肺外器官累及的影像表现,运用最小绝对收缩选择算子法(LASSO法)寻找其肺外...     

Sarcoid uveitis: Diagnostic and therapeutic update

Uveitis is a common (20-50%) and early manifestation of sarcoidosis. Typical sarcoid uveitis presents with bilateral mutton fat keratic precipitates, iris nodules, and anterior and posterior synechia. Posterior involvement includes vitreitis, vasculitis and choroidal lesions. Long-term complications are common, and cystoid macular edema is the most important and sight-threatening consequence. Diagnostic work-up of sarcoidosis usually includes chest radiography or computed tomography scan, bronchoscopy with bronchoalveolar lavage, angiotensin converting enzyme, lysozyme, gallium scintigraphy and biopsy. The gold standard for the diagnosis of sarcoidosis should be obtained with histologic examination. However, an international workshop has recently established diagnostic criteria of “intraocular sarcoidosis” (sarcoidosis uveitis) on the basis of a combination of suggestive ophthamological findings and laboratory tests, when biopsy is not performed or is negative. More recent techniques such as PET-scan and endoscopic ultrasound-guided fine-needle biopsy of intrathoracic nodes should be assessed in future prospective studies. Corticosteroids are the mainstay of treatment. Anterior and unilateral intermediate or posterior uveitis are usually treated with topical corticosteroids. Systemic corticosteroids are indicated in uveitis not responding to topical corticosteroids or in the presence of bilateral posterior involvement, especially with macular edema and occlusive vasculitis. In 5 to 20% of the patients who are corticosteroids resistant or require an unacceptable dose to maintain remission, additional immunosuppression is used, including methotrexate, leflunomide and mycophenolate mofetil. As in systemic sarcoidosis, infliximab has been recently suggested for refractory or sight threatening disease.     

Multi-organ Involvement in Non-pulmonary Sarcoidosis

Isolated extrapulmonary involvement in sarcoidosis is uncommon and reported in 5–9% of systemic sarcoidosis, this constitutes a clinical challenge due to its extensive differential diagnosis. Extrapulmonary sarcoidosis affecting more than three organs is rarely reported and there are scarce literature data published on diagnosis, clinical course and management in those cases.We hereby discuss a case of a 41-year-old female with systemic non-pulmonary sarcoidosis affecting lacrimal gland, peripheral lymph nodes, parotid gland and the liver.     

Extrapulmonary sarcoidosis with chronic renal failure

We present a young woman with extrapulmonary sarcoidosis who had been treated for tuberculosis 15 years earlier. The initial diagnosis had been made on the basis of liver biopsy. The patient later developed bilateral visual loss secondary to uveitis. We identified noncaseating granulomatous lesions in the kidney, intra-abdominal lymph node, and previous liver biopsy specimens. Although rare, renal sarcoidosis can manifest itself as hypercalcemic nephropathy, granulomatous interstitial nephritis, renal tubular dysfunction, or glomerulonephritis. Corticosteroids are the treatment of choice.     

Subcutaneous sarcoidosis: report of two cases and review of the literature

Sarcoidosis is a multisystemic disease with cutaneous lesions present in about one fourth of patients. Cutaneous lesions may be specific or nonspecific based on the presence or the absence of sarcoidal granulomas. Subcutaneos sarcoidosis is the less frequent of the specific cutaneous lesions of sarcoidosis. We report here 2 new cases and review 83 cases reported in literature of subcutaneous sarcoidosis. Subcutaneous sarcoidosis present usually with asymptomatic firm nodules covered by normal-appearing skin, mostly on the forearms and legs. Diagnosis may require a high index of suspicion. In the vast majority of patients, subcutaneous nodules were the manifestation that allowed the diagnosis of systemic sarcoidosis. There is a strong association between subcutaneous sarcoidosis and bilateral hilar lymphadenopathy (72.7%). About 15% of patients have in order of frequency uveitis, parotitis, arthritis, mucositis, dactylitis, neurological and renal involvement, hepatosplenomegaly.     

Sarcoidosis: a review for the internist

Sarcoidosis is a systemic granulomatous lung disease of unknown origin affecting people of any age, mainly young adults. The disease is extremely heterogeneous with an unpredictable clinical course. Different phenotypes have been identified: an acute syndrome can be distinguished from subacute and chronic variants. About 20% of patients are chronically progressive and may develop lung fibrosis. Sarcoidosis usually involves the lungs and thoracic lymph nodes, although the skin, eyes, bones, liver, spleen, heart, upper respiratory tract and nervous system can also be affected. No reliable indicators of clinical outcome are available, and there is no single serological biomarker with demonstrated unequivocal diagnostic and prognostic value. Diagnosis requires histological confirmation although a presumptive diagnosis may be acceptable in special conditions. This review examines the diagnostic approach to sarcoidosis involving a multidisciplinary team of specialists in which the internist has the task of identifying all pulmonary and extrapulmonary localizations of the disease and of managing complications and comorbidities.     

An eye on inflammatory eye disease

The purpose of this article is to outline the interaction between ophthalmologists and internists in the management of uveitis. Two issues will be addressed: 1) which strategies should the internist follow when asked to investigate a case of uveitis; and 2) in which systemic diseases should the internist order an ocular examination to rule out intraocular inflammation. The modern approach to the diagnosis of uveitis is based on the naming-meshing system popularized by Smith and Nozik. After a short history (ocular complaints, general health) an ophthalmic examination is carried out to determine the anatomic structures involved. Based on the results a uveitis is classified as anterior uveitis, intermediate uveitis, posterior uveitis, or panuveitis. Associated factors (eg, unilateral versus bilateral, acute versus chronic, granulomatous versus nongranulomatous, etc.) are also assessed. Based on this information the type of uveitis will be named (eg, acute, nongranulomatous, unilateral, anterior uveitis) and matched (meshing) to a potential list of etiologies (eg, viral iritis, HLA-B 27 associated iritis). Targeted questioning and selected medical and laboratory investigations based on the shortlist will then identify a possible cause for a particular patient's uveitis. In other words the ophthalmologist should never ask the internist to run the full battery of tests in a patient with uveitis. He rather should indicate which type of uveitis is present and what are the most likely diagnoses to be excluded. Many systemic diseases cause diffuse inflammation and are associated with uveitis. These include tuberculosis, spirochaetal diseases such as Lyme disease and syphilis, sarcoidosis, Beh?et syndrome, juvenile idiopathic arthritis, and HIV infection amongst many others. Routine ophthalmic examination in patients with systemic disease may be indicated for diverse reasons: to prevent profound damage due to asymptomatic uveitis in JIA; to detect diagnostic clues in patients with febris e causa ignota; or to rule out opportunistic infections in HIV positive patients. It is clear that the information gained from routine examination in systemic disease will be greatly dependent on the prevalence of ocular involvement in a particular disease.     

以肺外表现为首发症状的结节病临床分析

目的提高对首发于肺外表现的结节病的认识。方法回顾性分析了２２例肺外结节病的临床资料，所有病例均有病理检查资料。结果６例患者的首发肺外表现为周围淋巴结肿大，５例为皮肤改变，２例为眼部症状，３例为腮腺结节病，３例为骨关节炎，１例为心脏结节病，１例为肝脾肿大，１例为神经精神症状。部分肺外结节病的胸部Ｘ线检查正常，血管紧张素转化酶亦在正常范围内。结论某些以肺外表现为首发症状的结节病可能尚处于疾病的早期阶段，故早期诊断和治疗有助于缓解肺外症状，提高治愈率     

Extrapulmonary involvement in patients with sarcoidosis in Turkey

Background and objective: Extrapulmonary sarcoidosis is common, and is almost always associated with concomitant thoracic involvement. Extrapulmonary manifestations vary on the basis of gender, age at presentation and ethnicity. The aim of this study was to investigate extrapulmonary involvement in patients with sarcoidosis in Turkey. Methods: This study was conducted by Turkish Thoracic Society Clinical Problems Study Group. New cases of sarcoidosis between 1 June 2004 and 31 May 2006 were recorded on electronic case record forms sent to all potential investigators and information about extrapulmonary involvement was collected. Results: One hundred and nineteen of 293 patients (83 female, 36 male, mean age = 45 ± 12 years) had extrapulmonary involvement in this study (40.6%). The median time to diagnosis was 6 months and this was longer than patients with just thoracic sarcoidosis (P = 0.001). Extrapulmonary symptoms were present in 181 (61.8%) patients, and skin lesions, arthralgia and back pain were the commonest (33.4%, 20.8% and 16.4%, respectively). Incidence of organ involvement was independent of age with the exception of ocular involvement, which was higher in those under the age of 40 years (P = 0.007). Conclusions: Skin and peripheral lymph node involvement were the most common sites of extrapulmonary involvement and ocular involvement was more common in those under the age of 40 years in patients with sarcoidosis in a Turkish population.     

Computed tomographic scanning in sarcoidosis

Sarcoidosis is a granulomatous disease of unknown etiology that involves the lungs or intrathoracic lymph nodes in more than 90% of patients. The clinical spectrum of sarcoidosis is protean, but pulmonary manifestations often dominate. Chest radiographs are abnormal in 90 to 95% of patients with sarcoidosis; the most characteristic feature is bilateral hilar lymphadenopathy (BHL), present in 50 to 80% of patients. Pulmonary parenchymal infiltrates are present in 25 to 50% of patients. In this article, we review the radiographic features of sarcoidosis (both typical and atypical), and the impact of chest radiographic stage on long-term prognosis. Computed tomographic (CT) scans are more sensitive than chest radiographs in delineating parenchymal, mediastinal, and hilar structures, and distinctive CT patterns may be virtually pathognomonic for sarcoidosis in some patients. Routine CT scan is not appropriate to diagnose or manage sarcoidosis, but CT may be invaluable in patients with atypical clinical or chest radiographic findings or specific complications of sarcoidosis (pulmonary or extrapulmonary), or to assess prognosis. High-resolution thin-section CT scans (HRCT) may be helpful in selected patients with stage II or III sarcoidosis to discriminate active inflammation from irreversible fibrosis. This article discusses the salient HRCT features of sarcoidosis, accuracy of CT in the differential diagnosis, and correlations of HRCT with disease extent and activity, pulmonary function, and lesion reversibility.     

Uveitis. An internist's view

The utility of an evaluation for systemic disease in a patient with uveitis is controversial. To address this issue, we reviewed the records of 236 consecutive patients with uveitis who were referred primarily by ophthalmologists to an internist in a university-based clinic. Patients were referred for a variety of purposes, including differential diagnosis, treatment recommendations, and desire for a second opinion. The study population included 121 male patients and 115 female patients. In 40% of all patients, a systemic disease thought to be causally related to the eye inflammation was diagnosed or its diagnosis was confirmed. While 53% of patients with anterior uveitis had a causally related systemic illness, only 17% of patients with posterior uveitis and 22% of patients with chorioretinitis had an associated systemic disease. The most frequently diagnosed systemic diseases were Reiter's syndrome, ankylosing spondylitis, Sj?gren's syndrome, and sarcoidosis. These diagnoses were usually not known prior to referral. An internist can make a significant contribution to the evaluation of many patients with uveitis. Furthermore, most diagnoses can be established by a thorough history and physical examination, without extensive laboratory testing.     

Pharmacotherapeutic management of pulmonary sarcoidosis

Corticosteroids are the mainstay of treatment for sarcoidosis. Although the indications for medical therapy of sarcoidosis are controversial, standard therapy for symptomatic, progressive disease consists of corticosteroids. The British Thoracic Society concluded, with respect to systemic corticosteroids for the treatment of sarcoidosis, that some patients required no treatment, some required prednisone for control of symptoms, and others, with persistent disease, appeared to benefit from long-term corticosteroid therapy. Inhaled budesonide can be an effective treatment for lung sarcoidosis, with few adverse effects, when used in combination with oral systemic corticosteroids such as deflazacort administered in a tapered regimen for 6 months. A randomized controlled trial has also demonstrated the efficacy of 3 months of treatment with oral prednisolone in a tapered regimen followed by inhaled budesonide for 15 months in patients with early stage pulmonary sarcoidosis.Alternative drugs are required in chronic resistant sarcoidosis and/or in conditions where systemic corticosteroids are contraindicated. Immunosuppressive agents (chlorambucil, cyclophosphamide, methotrexate, cyclosporine, azathioprine), anticytokine agents (thalidomide, pentoxifylline), antimalarials (chloroquine, hydroxychloroquine), melatonin and monoclonal antibody (infliximab) have been used in such situations. Chlorambucil and cyclophosphamide have been used in anecdotal cases of pulmonary sarcoidosis as corticosteroid-sparing agents. However, their toxicity and neoplastic potential recommend prudence in patient selection. A comparison between combination therapy with cyclosporine and prednisone and prednisone alone has shown an increased prevalence of serious adverse effects with combined therapy with no between-group differences in treatment efficacy. The cost and toxicity of cyclosporine limit its use to patients in whom its efficacy has been proven. In patients with chronic or refractory disease, methotrexate, usually administered once a week as a single oral dose for at least 2 years, has resulted in a significant improvement in respiratory function, chest radiographs and extrapulmonary manifestations. In most patients, this treatment enabled discontinuation of corticosteroids. Azathioprine may be effective as a corticosteroid-sparing agent in the long-term treatment of sarcoidosis. The combination of prednisolone and azathioprine over a period of 2 years has induced long-lasting remission in patients with resistant sarcoidosis. Thalidomide at low doses is effective in selected cases of sarcoidosis with cutaneous and mild pulmonary involvement. Pentoxifylline alone or combined with low doses of corticosteroids has achieved significant improvement in respiratory function in patients with pulmonary sarcoidosis. Chloroquine and hydroxychloroquine have been shown to have a specific effect in cutaneous manifestations, neurological involvement and hypercalcemia associated with sarcoidosis. Infliximab has yielded good results in patients with chronic resistant pulmonary and extrapulmonary sarcoidosis resistant to corticosteroid and cytotoxic therapy. The effectiveness of melatonin in cutaneous and pulmonary sarcoidosis has also been confirmed in a single center.     

Overlap of granulomatous vasculitis and sarcoidosis: presentation with uveitis, eosinophilia, leg ulcers, sinusitis, and past foot drop

A 24-year-old black woman with a history of pulmonary and hepatic sarcoidosis followed by foot drop presented with uveitis, eosinophilia, leg ulcers, and sinus opacification. Biopsy of the leg ulcer and review of the past lung biopsy revealed numerous epithelioid noncaseating granulomas and granulomatous vasculitis. Although her clinical presentation raised the possibility of Wegener's granulomatosis, the many discrete granulomas and lack of necrosis on her biopsies were more in favor of sarcoidosis. Although granulomatous vasculitis has been reported as part of necrotizing sarcoid granulomatosis, our patient was unique in the extent and type of her extrapulmonary symptomatology.     

Fluorodeoxyglucose PET scan in pulmonary sarcoidosis during treatment with inhaled and oral corticosteroids

The objective was to investigate longitudinal changes in fluorodeoxyglucose PET scan (FDG-PET) in a patient with pulmonary sarcoidosis prior to and during treatment with inhaled corticosteroids followed by systemic corticosteroids. The patient was a 41-year-old man presenting with stage I pulmonary sarcoidosis (hilar adenopathy), which had progressed to stage II (pulmonary infiltrates) 19 months later. FDG-PET was performed at 19, 29 and 33 months after presentation. No treatment was given prior to the 1st PET. Subsequently, before the 2nd PET, the patient was treated with inhaled beclomethasone (QVAR Autohaler) 0.8 mg/day for 8 months. Finally, prior to the 3rd PET, the patient was treated with oral prednisolone 30 mg/day for 3 months. The 1st PET showed a high FDG uptake in the hilar and mediastinal lymph nodes and a high focal uptake in the peripheral parts of the lungs. The 2nd PET showed a slight uptake in a few mediastinal lymph nodes and an unchanged high focal uptake in the peripheral parts of the lungs and the pleura. The 3rd PET showed no abnormal uptake at all. In conclusion, as assessed by FDG-PET, inhaled beclomethasone had no recognizable influence on sarcoid inflammatory activity. Treatment with oral prednisolone depressed the inflammatory activity to such a degree that it was undetectable by PET. The results are in accordance with clinical studies on pulmonary sarcoidosis, showing a marginal effect of inhaled corticosteroids and a marked effect of systemic corticosteroids.     

Clinical phenotypes and prediction of chronicity in sarcoidosis using cluster analysis in a prospective cohort of 694 patients

BackgroundSarcoidosis is a heterogeneous disease with high variability in natural history and clinical spectrum. The study aimed to reveal different clinical phenotypes of patients with similar characteristics and prognosis.MethodsCluster analysis including 26 phenotypic variables was performed in a large cohort of 694 sarcoidosis patients, collected and followed-up from 1976 to 2018 at Bellvitge University Hospital, Barcelona, Spain.ResultsSix homogeneous groups were identified after cluster analysis: C1 (n=47; 6.8%), C2 (n=85; 12.2%), C3 (n=153; 22%), C4 (n=29; 4.2%), C5 (n=168; 24.2%), and C6 (n=212; 30.5%). Presence of bilateral hilar lymphadenopathy (BHL) ranged from 65.5% (C4) to 97.9% (C1). Patients with Löfgren syndrome (LS) were distributed across 3 phenotypes (C1, C2, and C3). In contrast, phenotypes with pulmonary (PS) and/or extrapulmonary sarcoidosis (EPS) were represented by groups C4 (PS 100% with no EPS), C5 (PS 88.7% plus EPS), and C6 (EPS). EPS was concentrated in groups C5 (skin lesions, peripheral and abdominal lymph nodes, and hepatosplenic involvement) and C6 (skin lesions, peripheral lymph nodes, and neurological and ocular involvement). Unlike patients from LS groups, most patients with PS and/or EPS were treated with immunosuppressive therapy, and evolved to chronicity in higher proportion. Finally, the cluster model worked moderately well as a predictive model of chronicity (AUC=0.705).ConclusionCluster analysis identified 6 different clinical patterns with similar phenotypic variables and predicted chronicity in our large cohort of patients with sarcoidosis. Classification of sarcoidosis into phenotypes with prognostic value may help physicians to improve the efficacy of clinical decisions.     

What is the future of methotrexate in sarcoidosis? A study and review

The decision for treating patients with chronic systemic sarcoidosis is often difficult and controversial. Methotrexate (MTX) has been used to treat patients with chronic forms of the disease for years, although prospective, randomized studies assessing the efficacy and toxicity of this agent are lacking. This is the follow-up study of 91 patients with the chronic form of pulmonary and extrapulmonary sarcoidosis who were treated with MTX. All patients experienced treatment with corticosteroids before they were administered MTX. Most of the patients treated with MTX showed improvement on chest radiographs, lung function tests, and extrapulmonary signs of the disease 6 months after the treatment began. No side effects that would cause the patients to discontinue the treatment were observed.     

Membranous nephropathy with epithelial crescents in a patient with pulmonary sarcoidosis.

Renal failure in patients with pulmonary or extrapulmonary sarcoidosis has been attributed to interstitial disease. Reports of cases of primary glomerular abnormality with renal failure in patients with sarcoidosis are rare. We describe a patient with pulmonary sarcoidosis and renal failure due to membranous nephropathy with epithelial crescents. A review of primary glomerular involvement in patients with sarcoidosis and the association of immune complexes in the pathogenesis of the two diseases is discussed.