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Background: Neuro-ophthalmologic manifestations are uncommon in sarcoidosis. We aim to assess the prognostic factors and outcome of neuro-ophthalmic sarcoidosis., Methods: We conducted a multicenter retrospective study on patients with neuro-ophthalmic sarcoidosis. Response to therapy was based on visual acuity, visual field, and orbital MRI exam. Factors associated with remission and relapse were analyzed., Results: Thirty-five patients [median (IQR) age of 37 years (26.5-53), 63% of women] were included. The diagnosis of sarcoidosis was concomitant of neuro-ophthalmologic symptoms in 63% of cases. Optic neuritis was the most common manifestation. All patients received corticosteroids and 34% had immunosuppressants. At 6 months, 61% improved, 30% were stable, and 9% worsened. Twenty percent of patients had severe visual deficiency at the end of follow-up. Nonresponders patients had significantly worse visual acuity at baseline ( p = 0.01). Relapses were less frequent in patients with retro-bulbar optic neuropathy ( p = 0.03)., Conclusion: Prognosis of neuro-ophthalmic sarcoidosis is poor.

Background and Objectives: Spinal cord sarcoidosis is a rare manifestation of sarcoidosis with a consequent risk of neurologic sequelae for the patient. We investigated prognostic factors and efficacy of immunosuppressive treatments in a longitudinal cohort., Methods: We retrospectively studied patients with spinal cord sarcoidosis followed between 1995 and 2021 in 7 centers in France. Patients with definite, probable, or possible spinal cord sarcoidosis according to the Neurosarcoidosis Consortium Consensus Group criteria and with spinal cord involvement confirmed by MRI were included. We analyzed relapse or progression rate with a Poisson model, initial Rankin score with a linear model, and change in the Rankin score during follow-up with a logistic model., Results: A total of 97 patients were followed for a median of 7.8 years. Overall mean relapse or progression rate was 0.17 per person-year and decreased over time. At last visit, 46 (47.4%) patients had a loss of autonomy (Rankin score ≥2). The main prognostic factors significantly associated with relapse or progression rate were gadolinium enhancement (relative rate [95% CI] 0.61 [0.4, 0.95]) or meningeal involvement (relative rate [95% CI] 2.05 [1.31, 3.19]) on spinal cord MRI and cell count (relative rate [95% CI] per 1 log increase 1.16 [1.01, 1.33]) on CSF analysis. Relapse or progression rate was not significantly associated with initial Rankin score or Expanded Disability Status Scale. Tumor necrosis factor-α (TNF-α) antagonists significantly decreased relapse or progression rate compared with corticosteroids alone (relative rate [95% CI] 0.33 [0.11, 0.98]). Azathioprine was significantly less effective than methotrexate on relapse or progression rate (relative rate [95% CI] 2.83 [1.04, 7.75]) and change in Rankin score (mean difference [95% CI] 0.65 [0.23, 1.08])., Discussion: Regarding the relapse or progression rate, meningeal localization of sarcoidosis was associated with a worse prognosis, TNF-α antagonists resulted in a significant decrease compared to corticosteroids alone, and methotrexate was more effective than azathioprine., Classification of Evidence: This study provides Class IV evidence that in individuals with spinal cord neurosarcoidosis, TNF-α antagonists were associated with decreased relapse or progression rate compared to corticosteroids alone, but other therapies showed no significant benefit., (© 2022 American Academy of Neurology.)

Inorganic antigens may contribute to paediatric sarcoidosis. Thirty-six patients matched with 36 healthy controls as well as a group of 21 sickle-cell disease (SCD) controls answered an environmental questionnaire. Patients' indirect exposure to inorganic particles, through coresidents' occupations, was higher than in healthy and SCD controls (median score: 2.5 (0.5-7) vs 0.5 (0-2), p=0.003 and 1 (0-2), p=0.012, respectively), especially for construction, exposures to metal dust, talc, abrasive reagents and scouring products. Wood or fossil energies heating were also linked to paediatric sarcoidosis. This study supports a link between mineral environmental exposure due to adult coresident occupations and paediatric sarcoidosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Prognostic factors are lacking in cardiac sarcoidosis (CS), and the effects of immunosuppressive treatments are unclear., Objectives: To identify prognostic factors and to assess the effects of immunosuppressive drugs on relapse risk in patients presenting with CS., Methods: From a cohort of 157 patients with CS with a median follow-up of 7 years, we analysed all cardiac and extra-cardiac data and treatments, and assessed relapse-free and overall survival., Results: The 10-year survival rate was 90% (95% CI, 84-96). Baseline factors associated with mortality were the presence of high degree atrioventricular block (HR, 5.56, 95% CI 1.7-18.2, p = 0.005), left ventricular ejection fraction below 40% (HR, 4.88, 95% CI 1.26-18.9, p = 0.022), hypertension (HR, 4.79, 95% CI 1.06-21.7, p = 0.042), abnormal pulmonary function test (HR, 3.27, 95% CI 1.07-10.0, p = 0.038), areas of late gadolinium enhancement on cardiac magnetic resonance (HR, 2.26, 95% CI 0.25-20.4, p = 0.003), and older age (HR per 10 years 1.69, 95% CI 1.13-2.52, p = 0.01). The 10-year relapse-free survival rate for cardiac relapses was 53% (95% CI, 44-63). Baseline factors that were independently associated with cardiac relapse were kidney involvement (HR, 3.35, 95% CI 1.39-8.07, p = 0.007), wall motion abnormalities (HR, 2.30, 95% CI 1.22-4.32, p = 0.010), and left heart failure (HR 2.23, 95% CI 1.12-4.45, p = 0.023). After adjustment for cardiac involvement severity, treatment with intravenous cyclophosphamide was associated with a lower risk of cardiac relapse (HR 0.16, 95% CI 0.033-0.78, p = 0.024)., Conclusions: Our study identifies putative factors affecting morbidity and mortality in cardiac sarcoidosis patients. Intravenous cyclophosphamide is associated with lower relapse rates., Competing Interests: The authors have declared that no competing interests exist.

Objective: Takayasu arteritis (TAK) is a large vessel vasculitis affecting young women of childbearing age. The outcome of pregnancies in TAK patients, factors associated with maternal and foetal complications and adverse outcomes were analysed., Methods: All pregnancies in women with a TAK diagnosis were retrospectively included from 20 French hospitals providing care for TAK, until August 2015., Results: The study consisted of 43 pregnancies in 33 women, including 29 with a pre-existing TAK diagnosis and 4 diagnosed during pregnancy. Complications were observed in 20 pregnancies (47%), including 35% with arterial hypertension (n = 15), 9% with pre-eclampsia (n = 4), 2% with HELLP syndrome (n = 1) and 14% with intrauterine growth restriction (IUGR, n = 6, leading in one case to a medically indicated termination of pregnancy). There were 42 live births (98%) at a median term of 38 [27-42] weeks gestation including 9 before 37 weeks (21%). The median birth weight was 2940 [610-4310] grams. Five children (12%) required transfer to a neonatal intensive care unit. One premature boy (27 weeks gestation) died after 2 days. Treatment during pregnancy included steroids (n = 25/43; 58%), azathioprine (n = 9/43; 21%) and infliximab (n = 1/43; 2%). The risk of developing arterial hypertension during pregnancy was associated with previous chronic arterial hypertension and with an infra-diaphragmatic vasculitis injury (P = 0.01 and P = 0.04, respectively). No correlation was reported between TAK activity and any of the obstetrical complications described in the study., Conclusion: This study showed a high rate of adverse obstetrical complications without significant impact on live birth rates. Pregnancy did not appear to influence TAK disease activity. Key Points • We observed a high rate of adverse obstetrical complications in women with Takayasu arteritis; however, the rate of live births was high. Pregnancy did not appear to influence TA disease activity.

(1) Background: Pediatric sarcoidosis is a rare and mostly severe disease. Very few pediatric series with a prolonged follow-up are reported. We aimed to evaluate the evolution of pediatric sarcoidosis in adulthood. (2) Material and methods: Patients over 18-years-old with a pediatric-onset sarcoidosis (≤15-year-old) who completed at least a three-year follow-up in French expert centers were included. Clinical information at presentation and outcome in adulthood were studied. (3) Results: A total of 52 patients were included (34 prospectively in childhood and 18 retrospectively in adulthood), with a mean age of 12 (±2.7) at diagnosis. The median duration time of follow-up was 11.5 years (range 3-44.5). Relapses mostly occurred during treatment decrease (84.5%), others within the three years after treatment interruption (9.1%), and rarely when the disease was stable for more than three years (6.4%). Sarcoidosis was severe in 11 (21.2%) in adulthood. Patients received a high corticosteroid cumulative dose (median 17,900 mg) for a median duration of five years (range 0-32), resulting in mostly mild (18; 35.3%) and rarely severe (2; 3.8%) adverse events. (4) Conclusions: Pediatric-onset sarcoidosis needed a long-term treatment in almost half of the patients. Around one fifth of pediatric-onset sarcoidosis patients had severe sarcoidosis consequences in adulthood., Competing Interests: F.C.-A. is the PI of an academic study of the efficacy of infliximab in extrapulmonary sarcoidosis. T.A. reports personal fees from Chiesi, other from Vital Aire, other from Astrazeneca, other from Boehringer Ingelheim, outside the submitted work. D.V. reports personal fees from Roche, personal fees from Boehringer Ingelheim, outside the submitted work. N.N. reports grants from Société de pneumologie pédiatrique et d’allergologie (France), outside the submitted work. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. All others authors declared no direct conflict of interest related to the present work.

Objective: To describe the clinical presentation, distribution of lesions, treatment, and outcomes of osseous sarcoidosis., Methods: A French retrospective multicenter study of patients with biopsy-proven sarcoidosis analyzed patients with 1) a biopsy-proven granuloma without caseous necrosis, and either 2) osseous clinical manifestations, or 3) abnormal osseous imaging. Sarcoidosis patients with osseous involvement (cases) were compared with 264 age- and sex-matched sarcoidosis patients with no osseous manifestations (controls)., Results: In the osseous sarcoidosis group (n=88), forty-two (48%) patients had osseous-related symptoms involving the axial (69%) and/or appendicular (58%) skeleton. On imaging, the most commonly affected bones were in the spine (52%), pelvis (42%), hands (22%) and femur (19%). Compared with controls, cases had higher rates of mediastinal (93% vs. 47%) and extra-thoracic lymph node involvement (66% vs. 21%), pulmonary (90% vs. 65%) and cutaneous involvement (44% vs. 23%) (all P<0.0001), and hypercalcemia (8.5% vs. 2%, P=0.014). Spleen/liver and gastrointestinal involvement were less frequent in the osseous sarcoidosis group (29% vs. 45%, and 1% vs. 17%, respectively, P<0.0001). Response rates to with glucocorticoids alone, glucocorticoids plus methotrexate or glucocorticoids plus hydroxychloroquine were 23/44 (52%), 9/13 (69%) and 4/6 (67%), respectively., Conclusion: In patients with osseous sarcoidosis the spine and pelvis were the most commonly affected bones. Compared with controls, cases with osseous sarcoidosis have higher rates of thoracic and extra-thoracic lymph node involvement, pulmonary and cutaneous involvement, and hypercalcemia. Most patients with osseous sarcoidosis had a good response to glucocorticoids in combination with methotrexate or hydroxychloroquine., (Copyright © 2019 Société française de rhumatologie. All rights reserved.)

Background: Sarcoidosis is a systemic disease characterized by the formation of immune granulomas in various organs, mainly the lungs and the lymphatic system. Exaggerated granulomatous reaction might be triggered in response to unidentified antigens in individuals with genetic susceptibility. The present study aimed to determine the genetic variants implicated in a familial case of sarcoidosis., Methods: Sarcoidosis presentation and history, NOD2 profile, NF-κB and cytokine production in blood monocytes/macrophages were evaluated in individuals from a family with late appearance of sarcoidosis., Results: In the present study, we report a case of familial sarcoidosis with typical thoracic sarcoidosis and carrying the NOD2 2722G > C variant. This variant is associated with the presence of three additional SNPs for the IL17RA, KALRN and EPHA2 genes, which discriminate patients expressing the disease from others. Despite a decrease in NF-κB activity, IL-8 and TNF-A mRNA levels were increased at baseline and in stimulated conditions., Conclusions: Combination of polymorphisms in the NOD2, IL17RA, EPHA2 and KALRN genes could play a significant role in the development of sarcoidosis by maintaining a chronic pro-inflammatory status in macrophages.

Objective: To describe the features of exceptional coexisting Takayasu arteritis (TA) and sarcoidosis, two conditions of unknown cause associated with a common immunologic pattern., Methods: We report seven cases of concomitant sarcoidosis-Takayasu or Takayasu-like vasculitis, observed in two referral centers between 1995 and 2015., Results: All patients were female. The mean age at sarcoidosis diagnosis and TA diagnosis was 36 and 37 years, respectively. Sarcoidosis occurred in 86% of cases before or together with TA. Sarcoidosis always had a classic expression except for one renal localization. Sarcoidosis was not severe and mostly non-treated (86%). In all cases of TA, supra-aortic arteries were involved; in only two TA cases a more diffuse inflammatory arterial involvement was noted. In one case, Takayasu arteritis occurred despite immunosuppressive therapy given for sarcoidosis. All patients received for TA a treatment with corticosteroids associated with methotrexate (four cases), infliximab (one case) or tocilizumab (one case). After a mean follow-up of 89 months, TA always improved and no death was observed., Conclusions: TA stands as pathology associated with sarcoidosis. TA occurred in three cases among 50. When sarcoidosis preceded TA, a recovery of sarcoidosis was achieved mostly without treatment. TA is a prognostic and therapeutic factor. Immunosuppressive treatment, including steroids, led to a good prognosis for TA as well as for sarcoidosis., (© 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Sarcoidosis is associated with cell-mediated immunodeficiency and treatment of symptomatic sarcoidosis usually includes systemic immunosuppressants. Data relative to incidence, prognosis factors, and outcome of infections are scarce.Retrospective cohort study of 585 patients with biopsy proven sarcoidosis in a tertiary referral specialist clinic, with a nested case-control analysis. Twenty nine patients (4.9%) with severe infections were compared to 116 controls subjects with sarcoidosis, matched according to their gender, ethnicity, age at diagnosis, and treatment with corticosteroids.After a median follow-up of 8 years [range; 1-46], 38 severe infections [mycobacterial infections (n = 14), fungal infections (n = 10), bacterial (n = 8), viral (n = 3) and parasitic (n = 1)] were observed in 30 patients. The incidence of severe infections was 0.71% persons-year (CI 95% 0.5-0.98) and 0.43% persons-year (CI 95% 0.27-0.66). Patients with severe infection were more frequently of male gender (60% vs 46%) and were more likely treated by ≥ 3 immunosuppressive agents (OR = 3.8, IC 95% [1.5-9.64], P = .005) and by cyclophosphamide (OR = 5.55, IC 95% [1.9-16.1], P = .002), and with neurological (OR = 3.36 CI 95% [1.37-8.25], P = .008), or cardiac (OR = 2.65 CI 95% [1.09-6.43], P = .031) involvement of the sarcoidosis, compared to the controls. Two patients died within the 6 months following infection, due to progressive multifocal leucoencephalopathy (n = 1), and of peritonitis (n = 1).Severe infections are observed in 5.1% of our patients with sarcoidosis after a median follow-up of 8 years. Risk factors for severe infections included neurological or cardiac involvement of sarcoidosis, the use of immunosuppressive agents and mainly cyclophosphamide.

Importance: Prognostic factors are lacking in neurosarcoidosis (NS), and the association of immunosuppressive treatments with outcomes are unclear., Objectives: To identify prognostic factors of and analyze the association of immunosuppressive treatment with relapse of NS., Design, Setting, and Participants: In this retrospective study, a cohort of 234 patients fulfilled the diagnostic criteria for NS in a tertiary referral center in Paris, France, from January 1, 1990, through December 31, 2015. The median follow-up was 8 years (range, 2 months to 23 years)., Main Outcomes and Measures: All neurologic and extraneurologic data and treatments were analyzed. Functional outcomes measured by the absolute value and the variation from baseline of the Expanded Disability Status Scale (EDSS) score at 60 months after the diagnosis, overall survival, and relapse-free survival (RFS) were assessed. Analyses were stratified by the period of NS diagnosis (1990-1999 vs 2000-2015)., Results: The 234 patients undergoing assessment included 117 women (50.0%) and 117 men (50.0%); median age was 42 years (interquartile range, 32-53 years). The probable 10-year survival rate was 89% (95% CI, 84%-94%). Older age (hazard ratio [HR] per 10 years, 1.64; 95% CI, 1.19-2.27; P = .003), peripheral nervous system involvement (HR, 6.75; 95% CI, 2.31-19.7; P < .001), and higher baseline EDSS score (HR per point, 1.21; 95% CI, 1.06-1.39; P = .005) were associated with mortality. The estimated 10-year RFS rate was 14% (95% CI, 9%-22%) for all relapses and 28% (95% CI, 20%-38%) for neurologic relapses. Encephalic involvement was associated with shorter neurologic RFS (HR, 2.35; 95% CI, 1.44-3.83; P < .001). A lower risk for relapse was associated with cyclophosphamide (HR, 0.26; 95% CI, 0.11-0.59; P = .001), methotrexate sodium (HR, 0.47; 95% CI, 0.25-0.87; P = .02), and infliximab (HR, 0.16; 95% CI, 0.02-1.24; P = .08) treatments. Follow-up was greater than 60 months in 160 patients (68.4%). An elevated baseline EDSS score (odds ratio [OR] per point, 1.92; 95% CI, 1.55-2.37; P < .001), tobacco use (OR, 3.64; 95% CI, 1.36-9.73; P = .01), encephalic symptoms (OR, 3.04; 95% CI, 1.11-8.38; P = .03), and less than 4 extraneurologic sarcoidosis localizations (OR, 3.06; 95% CI, 1.04-8.98; P = .04) were associated with an EDSS value of at least 2.5 at 60 months. Encephalic involvement (16 of 17 patients [94.1%]; P = .008) and peripheral nervous system involvement (5 of 17 patients [29.4%]; P = .03) were associated with worsening of the EDSS score at 60 months., Conclusions and Relevance: This study identifies putative factors affecting morbidity and mortality in patients with NS. Immunosuppressive therapies (ie, intravenous cyclophosphamide, methotrexate, and infliximab) in these patients may be associated with lower relapse rates.

Introduction: The off-label use of TNF antagonists in refractory sarcoidosis is increasingly reported but data on their efficacy and safety are still insufficient., Objective: To report on efficacy and safety of TNF antagonists in severe and refractory sarcoidosis., Methods: Examination of retrospective demographic, clinical, therapeutic, and adverse event data on 132 sarcoidosis patients (58% women; mean (min-max) age = 45.5 (14-78) years) given TNF antagonists (mainly infliximab, 91%) and investigation of response-linked factors., Results: The overall clinical response (complete and partial) rate was 64%. TNF-antagonist efficacy (i.e., significant decrease of the ePOST score) was noted in cases with neurologic, heart, skin, and upper respiratory tract involvements. No significant difference in efficacy was found between anti-TNF used alone and TNF with immunosuppressant. The use of anti-TNF allowed reducing prednisone dosage at end of follow-up (p < 0.001). Adverse events were observed in 52% of the patients; they included infections (36%) and allergic reactions (8%) and required treatment interruption in 31 cases (23%). When TNF antagonists were interrupted, 13 patients experienced relapses within 14 months on average (median follow-up: 20.5 months)., Conclusion: TNF antagonists were efficacious in about two-thirds of patients with severe/refractory sarcoidosis but their use led to a high rate of adverse events., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Cardiac sarcoidosis (CS) is a severe localization, observed mostly in cardiology departments. Despite appropriate cardiological treatment, CS is a potentially life-threatening condition, and accounts for 13-85% of sarcoidosis-related deaths., Aims: This retrospective study aimed to give an overview of CS in a non-cardiac unit, to analyse the effect of first-line immunosuppressive treatment on outcome and survival and to evaluate factors associated with relapses., Methods: From 534 cases of sarcoidosis, we selected 59 patients with CS according to "2006 international criteria". We performed an in-depth analysis regarding symptoms, physical signs and cardiac investigation results. Patients were followed for a median period of 60 months., Results: The median age at cardiac signs was 42 years. Echocardiography abnormalities, isotopic defects and abnormal magnetic resonance imaging findings were observed in 81%, 84% and 92% of patients, respectively. First-line treatment included steroids alone in 24 patients and steroids plus immunosuppressive therapy in 35 patients. Forty-seven (80%) patients recovered; 12 stabilized or worsened. The recovery rate was 75% in the steroids alone group versus 83% in the steroids plus immunosuppressive therapy group. Five (9%) patients died during follow-up, with two deaths attributed to CS. The overall 1- and 5-year survival rates were 98% and 92%, respectively., Conclusion: Our series of patients with CS who received steroids alone or combined with immunosuppressive therapy had a good prognosis, with an overall 5-year survival rate of 92%. The recovery rate was 85%, with no significant difference between patients treated with steroids alone or plus immunosuppressive therapy., (Copyright © 2017. Published by Elsevier Masson SAS.)

Importance: Evidence for the long-term efficacy and safety of anti-tumor necrosis factor α agents (anti-TNF) in treating cutaneous sarcoidosis is lacking., Objective: To determine the efficacy and safety of anti-TNF in treating cutaneous sarcoidosis in a large observational study., Design, Setting, and Participants: STAT (Sarcoidosis Treated with Anti-TNF) is a French retrospective and prospective multicenter observational database that receives data from teaching hospitals and referral centers, as well as several pneumology, dermatology, and internal medicine departments. Included patients had histologically proven sarcoidosis and received anti-TNF between January 2004 and January 2016. We extracted data for patients with skin involvement at anti-TNF initiation., Main Outcomes and Measures: Response to treatment was evaluated for skin and visceral involvement using the ePOST (extra-pulmonary Physician Organ Severity Tool) severity score (from 0 [not affected] to 6 [very severe involvement]). Epidemiological and cutaneous features at baseline, efficacy, steroid-sparing, safety, and relapses were recorded. The overall cutaneous response rate (OCRR) was defined as complete (final cutaneous ePOST score of 0 or 1) or partial response (ePOST drop ≥2 points from baseline but >1 at last follow-up)., Results: Among 140 patients in the STAT database, 46 had skin involvement. The most frequent lesions were lupus pernio (n = 21 [46%]) and nodules (n = 20 [43%]). The median cutaneous severity score was 5 and/or 6 at baseline. Twenty-one patients were treated for skin involvement and 25 patients for visceral involvement. Reasons for initiating anti-TNF were failure or adverse effects of previous therapy in 42 patients (93%). Most patients received infliximab (n = 40 [87%]), with systemic steroids in 28 cases (61%) and immunosuppressants in 32 cases (69.5%). The median (range) follow-up was 45 (3-103) months. Of the 46 patients with sarcoidosis and skin involvement who were treated with anti-TNF were included, median (range) age was 50 (14-78) years, and 33 patients (72%) were women. The OCRR was 24% after 3 months, 46% after 6 months, and 79% after 12 months. Steroid sparing was significant. Treatment was discontinued because of adverse events in 11 patients (24%), and 21 infectious events occurred in 14 patients (30%). Infections were more frequent in patients treated for visceral involvement than in those treated for skin involvement (n = 12 of 25 [48%] vs n = 2 of 21 [9.5%], respectively; P = .02). The relapse rate was 44% 18 months after discontinuation of treatment. Relapses during treatment occurred in 35% of cases, mostly during anti-TNF or concomitant treatment tapering., Conclusions and Relevance: Anti-TNF agents are effective but suspensive in cutaneous sarcoidosis. The risk of infectious events must be considered.

Backgroung: This study investigated the efficacy and safety of TNF antagonists in sarcoid uveitis in unselected cases. Design: This is a multicentre study on patients with sarcoidosis who received TNF antagonists in pneumology and internal medicine departments in France. We present here the subgroup of patients with biopsy-proven sarcoid uveitis included in the nationwide registry STAT (Sarcoidosis treated with TNF AnTagonists). Results: Among the 132 patients included in this multicenter study, 18 patients with refractory uveitis were treated as a first-line TNF antagonist with infliximab (n=14), adalimumab (n=3) and certolizumab (n=1). Before anti-TNF initiation, the median duration of sarcoidosis was 42 months and 83% of the patients have been treated with at least one immunosuppressive drug. Six patients switched for a second-line TNF antagonist. After a mean time under treatment of 29 months, the treatment resulted in a significant decrease of the ophthalmic extrapulmonary Physician Organ Severity Tool (ePOST) (mean score: 4.2 vs. 2.6) scores and a steroid sparing effect (29.4±20.7 vs. 6.2±5.2 mg/d). Overall, the ophthalmic response, either complete or partial, was 67%. Nine patients (50%) presented adverse events, including severe infectious complications in 5 patients, which required anti-TNF treatment interruption in 6 cases (33%). Among the 7 responder patients who discontinued anti-TNF therapy, 71% relapsed. Finally, 12 patients (67%) could continue TNF antagonist treatment. Conclusions: TNF antagonists were efficient in 67% of biopsy-proven refractory sarcoid uveitis. Severe adverse events, mainly infectious complications, were frequent. The high frequency of relapses after anti-TNF-α discontinuation requires a close patient follow-up thereafter. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 74-80) ., (Copyright: © 2017.)

Digestive tract sarcoidosis (DTS) is rare and case-series are lacking. In this retrospective case-control study, we aimed to compare the characteristics, outcome, and treatment of patients with DTS, nondigestive tract sarcoidosis (NDTS), and Crohn disease.We included cases of confirmed sarcoidosis, symptomatic digestive tract involvement, and noncaseating granuloma in any digestive tract. Each case was compared with 2 controls with sarcoidoisis without digestive tract involvement and 4 with Crohn disease.We compared 25 cases of DTS to 50 controls with NDTS and 100 controls with Crohn disease. The major digestive clinical features were abdominal pain (56%), weight loss (52%), nausea/vomiting (48%), diarrhea (32%), and digestive bleeding (28%). On endoscopy of DTS, macroscopic lesions were observed in the esophagus (9%), stomach (78%), duodenum (9%), colon, (25%) and rectum (19%). As compared with NDTS, DTS was associated with weight loss (odds ratio [OR] 5.8; 95% confidence interval [CI] 1.44-23.3) and the absence of thoracic adenopathy (OR 5.0; 95% CI 1.03-25). As compared with Crohn disease, DTS was associated with Afro-Caribbean origin (OR 27; 95% CI 3.6-204) and the absence of ileum or colon macroscopic lesions (OR 62.5; 95% CI 10.3-500). On the last follow-up, patients with DTS showed no need for surgery (versus 31% for patients with Crohn disease; P = 0.0013), and clinical digestive remission was frequent (76% vs. 35% for patients with Crohn disease; P = 0.0002).The differential diagnosis with Crohn disease could be an issue with DTS. Nevertheless, the 2 diseases often have different clinical presentation and outcome., Competing Interests: The authors report no conflicts of interest.

Objectives: Infliximab (IFX) appears to be effective in refractory sarcoidosis. However, data are lacking regarding its efficacy in severe sarcoidosis (i.e. with cardiac and/or neurological involvement)., Methods: Retrospective single-centre study including 16 unselected consecutive patients with biopsy proven, severe, and resistant sarcoidosis, who were treated by infliximab (3 or 5 mg /kg at 0, 2 and 6 weeks, then every 8 weeks) between 2005 and 2013., Results: Following IFX therapy we observed an improvement in 92% of cases, with a marked decrease of the severity score [median score 6 (3-12) vs. 2 (1-8), p<0.0001] and trend toward steroid sparing effect [12.5 (0-40) vs. 8.5 mg/d (0-30), p=0.11] between baseline and the end of follow-up, respectively. Regarding the index organ response, we observed a remission of cardiac and central nervous system involvements in 4 out of 4 and 11 out 12 cases, respectively. Thirty-eight percent of patients experienced a relapse. After a median follow-up of 57 months (2 to 91), we observed 7 (44%) infectious complications, 1 paradoxical cutaneous granuloma and 1 leucoencephalopathy. Infectious complications were mostly observed in male [6/7 (86%), p=0.06], with a longer duration of steroids (108 vs. 39 months, p=0.11) and immunosuppressant use prior IFX (42 vs. 24 months, p=0.08) compared to their negative counterpart, respectively., Conclusions: IFX was efficient in severe and refractory sarcoidosis. Infectious complications were frequent and occurred mainly in male patients with longer duration of steroids and immunosuppressant use prior to IFX.

Sarcoidosis is a granulomatous disease that most frequently affects the lungs with pulmonary infiltrates and/or bilateral hilar and mediastinal lymphadenopathy. An association of sarcoidosis and lymphoproliferative disease has previously been reported as the sarcoidosis-lymphoma syndrome. Although this syndrome is characterized by sarcoidosis preceding lymphoma, very few cases of sarcoidosis following lymphoma have been reported. We describe the clinical, biological, and radiological characteristics and outcome of 39 patients presenting with sarcoidosis following lymphoproliferative disease, including 14 previously unreported cases and 25 additional patients, after performing a literature review. Hodgkin lymphoma and non-Hodgkin lymphoma were equally represented. The median delay between lymphoma and sarcoidosis was 18 months. Only 16 patients (41%) required treatment. Sarcoidosis was of mild intensity or self-healing in most cases, and overall clinical response to sarcoidosis was excellent with complete clinical response in 91% of patients. Sarcoidosis was identified after a follow-up computerized tomography scan (CT-scan) or fluorodeoxyglucose-positron emission tomography/computerized tomography (FDG-PET/CT) evaluation in 18/34 patients (53%). Sarcoidosis is therefore a differential diagnosis to consider when lymphoma relapse is suspected on a CT-scan or FDG-PET/CT, emphasizing the necessity to rely on histological confirmation of lymphoma relapse.

Objective: To describe characteristics, risk factors, and treatment outcome of progressive multifocal leukoencephalopathy (PML) complicating sarcoidosis., Methods: A retrospective chart and literature review was performed. Patients were identified through records from physicians of the Groupe Sarcoïdose Francophone. Each case was compared with 3 controls., Results: Ten cases were found (8 men). The median age at sarcoidosis diagnosis was 34.9 (±6) years. PML and sarcoidosis were diagnosed concomitantly in 2 cases, while sarcoidosis was previously known in 8 cases, including 7 cases treated with steroids (mean time between sarcoidosis diagnosis and PML was 114 [±99] months). The mean CD4 cell count was 215 (±139)/mm(3). Neurosarcoidosis was thought to be the problem in 8 cases and treatment was intensified, delaying PML diagnosis by 4.5 (±3.9) months. Eight patients received PML-specific treatment. On the whole, 6 patients died of PML within a mean time of 8 (±4.3) months. Patients with PML were significantly younger than controls. When combining our 10 patients with another 20 from the literature, we found that 17 patients (57%) died from sarcoidosis-associated PML; thus, the fatality rate was 57%., Conclusions: PML during sarcoidosis is often misdiagnosed. It is not associated with severe CD4 lymphocytopenia. Fatality rate is high in comparison with PML associated with other conditions. Interrupting immunosuppression remains the mainstay of treatment.

Purpose of Review: Heart involvement during sarcoidosis is a medical emergency. The review focuses on published data analysis of clinical management and therapy involving a multidisciplinary monitoring of cardiac sarcoidosis., Recent Findings: With the emergence of new modalities, especially MRI and FDG PET scan, cardiac sarcoidosis is most often suspected and confirmed even in atypical cases. Laboratory investigations may help to diagnose and survey. Cardiac sarcoidosis drastically changes functional and vital prognosis. Recent studies define earlier detrimental predictable criteria to underline how beneficial is the combination of immunosuppressive therapy and cardiac treatment to patients. There are no large prospective studies, but case reports and small series support an appropriate therapeutic approach, which includes corticosteroids and immunosuppressive agents., Summary: Our review illustrates the importance of looking for cardiac sarcoidosis in all sarcoidosis patients and to propose more specific and sensitive investigations when suspected on clinical and/or electrical signs. It emphasizes the need for more adapted criteria and even more prognostic criteria to choose the best therapeutic option.

Importance: Hydroxychloroquine-induced pigmentation is not a rare adverse effect. Our data support the hypothesis that hydroxychloroquine-induced pigmentation is secondary to ecchymosis or bruising., Objective: To describe the clinical features and outcome of hydroxychloroquine (HCQ)-induced pigmentation in patients with systemic lupus erythematosus (SLE)., Design, Setting, and Participants: In a case-control study conducted at a French referral center for SLE and antiphospholipid syndrome, 24 patients with SLE, with a diagnosis of HCQ-induced pigmentation, were compared with 517 SLE controls treated with HCQ., Main Outcomes and Measures: The primary outcome was the clinical features of HCQ-induced pigmentation. Skin biopsies were performed on 5 patients, both in healthy skin and in the pigmented lesions. The statistical associations of HCQ-induced pigmentation with several variables were calculated using univariate and multivariate analyses., Results: Among the 24 patients, skin pigmentation appeared after a median HCQ treatment duration of 6.1 years (range, 3 months-22 years). Twenty-two patients (92%) reported that the appearance of pigmented lesions was preceded by the occurrence of ecchymotic areas, which gave way to a localized blue-gray or brown pigmentation that persisted. Twenty-three patients (96%) had at least 1 condition predisposing them to easy bruising. Results from skin biopsies performed on 5 patients showed that the median concentration of iron was significantly higher in biopsy specimens of pigmented lesions compared with normal skin (4115 vs 413 nmol/g; P < .001). Using multivariate logistic regression, we found that HCQ-induced pigmentation was independently associated with previous treatment with oral anticoagulants and/or antiplatelet agents and with higher blood HCQ concentration., Conclusions and Relevance: Hydroxychloroquine-induced pigmentation is not a rare adverse effect of HCQ. Our data support the hypothesis that HCQ-induced pigmentation is secondary to ecchymosis or bruising.

Aim: To assess the clinical features, treatment and outcome of oral sarcoidosis and to determine whether oral involvement is associated with a particular clinical phenotype of sarcoidosis., Design: Multicentric retrospective study., Methods: Retrospective chart review. Each patient was matched with four controls., Results: Twelve patients (9 women, 3 men) were identified. Their median age at sarcoidosis diagnosis was 38 years. Oral involvement was the first clinical evidence of sarcoidosis in seven cases and was a relapse symptom in five cases. Clinical presentations were nodules (n = 7) or ulcers (n = 5) and were mostly solitary. The tongue was the commonest site affected (n = 4), followed by lips (n = 3), oral mucosa (n = 2), palate (n = 2) and gingiva (n = 1). Patients with oral sarcoidosis were significantly younger and had more frequent lacrimal or salivary glands and upper airway tract clinical involvement than the controls; increased angiotensin-converting enzyme was less frequent in oral sarcoidosis. Multiple treatments of oral sarcoidosis were used: no treatment (n = 3), surgery (n = 2), corticosteroids (n = 7), hydroxychloroquine (n = 3), methotrexate (n = 2), doxycycline (n = 1). Methotrexate was efficient in one patient, hydroxychloroquine showed benefit in only 1 out of 3 patients. Three patients presented oral relapses. After a mean follow-up of 6 years, 10 patients experienced a complete (n = 7) or partial (n = 3) remission of oral sarcoidosis; stability was observed in the remaining two cases., Conclusion: Although oral manifestations of sarcoidosis are unusual, physicians should be aware that this specific localization is frequently the first manifestation of the disease. Treatment modalities range from observation in asymptomatic patients to immunosuppressants for severe involvement.

The coexistence of systemic lupus erythematosus (SLE) and myasthenia gravis (MG) is rarely reported, and most of the published studies are case reports. Hydroxychloroquine, an antimalarial agent, is an essential treatment in patients with SLE but special caution is recommended when used in MG patients. We retrospectively analyzed the clinical features, laboratory findings, and outcome of 17 patients with both diseases with a special focus regarding hydroxychloroquine use and with a review of the literature. All patients were women. The mean age at MG onset and SLE diagnosis was 34.5 [14-64] and 37.8 [18-72] years, respectively. The presenting symptoms of MG were limb weakness (94%), ocular (88%) and bulbar involvement (53%). Autoantibodies against the acetylcholine receptor were positive in 94% of cases. The main manifestations of SLE included arthritis (88%), cytopenias (53%) and skin rash (41%). Treatment of SLE required hydroxychloroquine (94%), steroids (47%) and immunosuppressive drugs (18%). Among eight patients (47%) who developed MG after initiation of hydroxychloroquine, the question of induction of MG by hydroxychloroquine was raised in one patient. On the other hand, an exacerbation of myasthenic symptoms was only seen in one of the eight patients who received hydroxychloroquine after the diagnosis of MG. Including our cases, we reviewed a total of 70 patients with SLE and MG. Compared with a large series of 1,000 unselected SLE patients, those with associated MG were older, had lower incidence of cutaneous, renal, and neurological manifestations, and higher frequency of anticardiolipin antibodies and lupus anticoagulant. In conclusion, the clinical pattern of patients with SLE and MG seems to be characterized by a less severe course of SLE and higher frequency of antiphospholipid antibodies. Hydroxychloroquine treatment appears to be safe in this setting.

Sarcoidosis, a chronic multisystem disease, is a common cause of ocular inflammation. Even though clinical features are well-established, diagnosis requires histological confirmation, which remains difficult in patients with uveitis. Thus, the frequency of ocular sarcoidosis is overestimated. A set of criteria has been recently established in order to improve the diagnostic procedure. New imaging tools will enable the ophthalmologist to evaluate the level of ocular inflammation and to monitor its resolution after treatment initiation. Indocyanine green angiography and optical coherence tomography have dramatically improved our understanding of choroidal granulomas and macular edema. Treatment is based on topical and systemic corticosteroids in most of the cases, but immuno-suppressive agents may be necessary. The visual outcome remains favorable but severe complications, including glaucoma, cystoid macular edema and choroidal neovascularization, may need a prompt and aggressive management., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

The prognosis of sarcoidosis often considered as "benign" is significantly changed in the presence of a cardiac localization. An in-depth interview, a clinical examination together with ECG are often for most of sarcoidosis. Certain conditions (severe multisystemic sarcoidosis, rares localizations in particular neurological, renal, gastric) lead to necessary investigations: Holter ECG, echocardiography, thallium scintigraphy with dipyridamole test, PET scanner and MRI in order to identify infraclinical presentations. Diagnosis relies on guidelines of Japansese criteria, but can benefit from MRI and PET scanner even though their place is not yet clearly defined in clinical pratice. Diagnosing cardiac sarcoidosis means deciding an immunosuppressive treatment. It is highly important to gather all criteria to validate a consistent diagnosis or at least a high probability. In order to best adapt therapy, a coordinated patient care involving the cardiologist and the sarcoidosis specialist is necessary., (Copyright © 2012. Published by Elsevier Masson SAS.)

Background: To ascertain the sensitivity, specificity, and positive and negative predictive value of minor salivary gland biopsy in subsets of patients with uveitis consistent with ocular sarcoidosis., Method: Minor salivary gland biopsies performed in 230 patients with uveitis of indeterminate origin but clinically compatible with ocular sarcoidosis were reviewed. The biopsy results were analysed together with clinical features of uveitis and with the results of other relevant examinations, such as serum levels of angiotensin-I-converting enzyme and lysozyme, tuberculin skin test, chest radiography or CT scan, pulmonary function tests and bronchoalveolar lavage., Results: Only seven of the 230 patients with uveitis had sarcoid granulomas on the minor salivary gland biopsy. All seven of these patients had a granulomatous uveitis and a compatible chest x-ray with sarcoidosis. The profitability of minor salivary gland biopsy can be improved by limiting the procedure to patients having granulomatous uveitis and a compatible chest x-ray. In these conditions, the positivity rate of minor salivary gland biopsy increased from 3% to 24% without loss of sensitivity., Conclusion: Minor salivary gland biopsy is most useful for assessing the diagnosis of sarcoid uveitis in a second-line investigation for patients with granulomatous uveitis and a radiologic pattern compatible with sarcoidosis.

There are many similarities between mycobacteriosis, in particular, tuberculosis, and sarcoidosis such as predominant intrathoracic localisation (even if all organs and tissues may be concerned), great variability of phenotypic expression, and granulomatous inflammatory reaction, caseous necrosis not being an absolute criterion of tuberculosis. Moreover, microbial (or mycobacterial?) agents may play a role in the pathogenesis of sarcoidosis which remains a diagnosis of exclusion particularly in atypical cases. The authors report a case of a non-immunocompromised female patient who presented, simultaneously, isolated axillary tubercular adenitis and neuro-sarcoidosis without any other localisation. This case illustrates the difficulty to distinguish between both of these two diseases and thus to choose an adequate treatment when diagnosis is not proven. Moreover, our patient (human leucocyte antigen B27 positive) presented symptoms of spondylarthritis which also may have a nosological link with tuberculosis or sarcoidosis.

The authors report on four patients aged over 50 with chronic myopathy suggestive of sporadic inclusion body myositis. They present progressive and selective weakness of the quadriceps femoris muscles. Asymmetrical and selective atrophy of the forearm muscles were noted in all, with more severe involvement of the flexors than the extensors. Biopsy revealed granulomatous myositis. Histological features of sporadic inclusion body myositis were lacking. Evidence for systemic sarcoidosis was found in one patient. Corticosteroid treatment was associated with a partial but significant improvement in two patients. Granulomatous myositis may mimic inclusion body myositis and may be steroid-responsive.

Sarcoidosis is a granulomatous disorder of unknown cause that affects the spinal cord in fewer than 1% of patients who suffer from it. We conducted a retrospective case-control study of 31 patients with spinal cord sarcoidosis and compared them to 30 patients with myelopathies of other causes to analyze their clinical, laboratory, and magnetic resonance imaging (MRI) profiles and to assess their long-term prognoses. Thirty-one patients presented with clinical signs of myelopathy and were diagnosed with sarcoidosis. Twenty-two of these patients had biopsy-proven noncaseating granulomas. In 9 patients, sarcoidosis involved only a neurologic localization. Patients in the control group were mainly diagnosed with multiple sclerosis or optic neuromyelitis. Patients with sarcoidosis were more likely to have elevated levels of C-reactive protein (CRP), elevated lactate dehydrogenase (LDH), and hypergammaglobulinemia in serum, as well as a higher protein content and white blood cell count in cerebrospinal fluid. Spinal cord MRIs performed in 26 patients with spinal cord sarcoidosis revealed T2-hyperintensities that were extensive and heterogeneous with a central distribution in axial slides. Twenty-six patients with spinal cord sarcoidosis presented neurologic sequelae after follow-up (mean, 64 +/- 8 mo), although 2 patients completely recovered. Neurologic sequelae correlated with cerebrospinal fluid white blood cell counts. One-third of the patients had a monophasic course of the disease, another third had a relapsing-remitting course, and the remaining third had a progressive course. Four patients had pulmonary embolism during follow-up. Spinal cord sarcoidosis remains a diagnostic dilemma since neurologic localization is frequently the only manifestation. Because treatment for spinal cord sarcoidosis is far different from treatment for other myelopathies, such as multiple sclerosis and optic neuromyelitis, diagnosis of sarcoidosis remains an important challenge. Here, we show that spinal cord MRI and blood and cerebrospinal markers may be useful tools in the diagnosis of spinal cord sarcoidosis. We suggest that accessory salivary gland biopsies, chest X-rays, protein electrophoresis, and blood levels of CRP and LDH should be obtained for each patient with subacute myelopathy. We also recommend paying careful attention to thromboembolism in patients with spinal cord sarcoidosis because of systemic disease and their decreased mobility.

We conducted the current study to investigate the clinical, laboratory, and histologic features at presentation and the outcome of renal sarcoidosis (RS). Exhaustive retrospective data were collected by the French Sarcoidosis Group. Forty-seven adult patients were assessed (30 male/17 female, M/F ratio: 1.76). Median estimated glomerular filtration rate (eGFR) was 20.5 mL/min per 1.73 m(2) (range, 4-93 mL/min per 1.73 m(2)). Moderate proteinuria was found in 31 (66%) patients (median, 0.7 g/24 h; range, 0-2.7 g/24 h), microscopic hematuria in 11 (21.7%) patients, aseptic leukocyturia in 13 (28.7%) patients. Fifteen of 47 (32%) patients had hypercalcemia (>2.75 mmol/L). Eleven of the 22 (50%) patients diagnosed between June and September had hypercalcemia compared with only 4 of the 25 (16%) cases diagnosed during the other months (p < 0.001). Thirty-seven patients presented with noncaseating granulomatous interstitial nephritis (GIN), and 10 with interstitial nephritis without granulomas. Apart from hypercalcemia, the clinical phenotype was also remarkable for the high frequency of fever at presentation. All patients initially received prednisone (median duration, 18 mo), 10 received intravenous pulse methylprednisolone. eGFR increased from 20 +/- 19 to 44 +/- 24.7 mL/min per 1.73 m(2) at 1 month (p < 0.001, n = 38), to 47 +/- 19.9 mL/min per 1.73 m(2) at 1 year (p < 0.001, n = 46), to 49.13 +/- 25 mL/min per 1.73 m(2) at last follow-up (p < 0.001, n = 47). A complete response to therapy at 1 year and at last follow-up was strongly correlated with complete response at 1 month (p < 0.01). Renal function improvement was inversely related to initial histologic fibrosis score. A complete response to therapy at 1 year was strongly correlated with hypercalcemia at presentation (p = 0.003). Relapses were purely renal (n = 3) and purely extrarenal (n = 10) or both (n = 4), often a long time after presentation, with in some cases severe cardiac or central nervous system involvement. We conclude that hypercalcemia and fever at presentation are often associated with RS; RS is most often and permanently responsive to corticosteroid treatment, but some degree of persistent renal failure is highly frequent and its degree of severity in the long run is well predicted from both histologic fibrotic renal score and response obtained at 1 month.

We describe the case of a 69-year-old man with systemic granulomatosis who presented with left-sided hemiplegia. Initial diagnosis concerning the neurological troubles was cerebral vasculitis. Corticosteroids associated with antituberculosis therapy showed a rapid but transient amelioration followed by neurological aggravation. Two weeks later, JC virus was detected in cerebrospinal fluid by PCR and the diagnosis of progressive multifocal leukoencephalopathy (PML) was made. Treatment with cytarabine and cidofovir was initiated but the patient died three months after the first neurological signs. In the presence of central neurological symptoms occurring during systemic granulomatosis before specific therapy, PML should be evoked.

Sarcoidosis is characterized by extensive local inflammation (granuloma, cytokine secretion) associated with anergy (poor response to antigens in vitro and in vivo). We postulated that this paradoxical situation would correspond to a disequilibrium between effector and regulatory T lymphocytes (T reg cells). We show that CD4+CD25(bright)FoxP3+ cells accumulate at the periphery of sarcoid granulomas, in bronchoalveolar lavage fluid, and in peripheral blood of patients with active disease. These cells exhibited powerful antiproliferative activity, yet did not completely inhibit TNF-alpha production. Sarcoidosis is therefore associated with a global T reg cell subset amplification whose activity would be insufficient to control local inflammation. At the same time, peripheral T reg cells exert powerful antiproliferative activity that may account for the state of anergy. Altogether, these findings advance our conceptual understanding of immune regulation in a way that resolves the immune paradox of sarcoidosis and permit us to envisage a profound clinical impact of T reg cell manipulation on immunity.

This retrospective study concerned 18 female and 23 male patients with cardiac sarcoidosis (CS). The average age at CS diagnosis was 38 years. CS was observed in white (73% of cases) and in black or Caribbean patients (27% of cases). All patients had extracardiac histologic proof of sarcoid tissue. In 63% of cases, the CS arose during the follow-up of systemic sarcoidosis. Systemic sarcoidosis was not specific except for a high frequency of neurosarcoidosis. Revealing cardiac signs were clinical in 63% of cases and electrical in 22%. In most patients these signs were associated with an abnormal echocardiography (77%) and/or a defect on thallium-201 or sestamibi imaging (75%). Thirty-nine patients received steroid therapy (initial dose mostly equal to 1 mg/kg per day), associated in 13 cases with another immunosuppressive treatment. In 26% of cases the immunosuppressive treatment was associated with a specific cardiac treatment. In the long-term follow-up (average follow-up, 58 mo), 87% of the cases showed an improvement, and 54% were cured from a clinical and laboratory point of view (electrocardiogram, 24-hour monitoring, echocardiography, radionuclide imaging). There was no sudden death. Two patients worsened, which can be explained in 1 case by very late treatment and in the other case by lack of treatment, except for a pacemaker. Our experience leads us to treat CS with corticosteroids as soon as possible and to use another immunosuppressive treatment where there is an insufficient therapeutic response or where there are contraindications to corticosteroids.

Extramedullary relapses in children with acute lymphoblastic leukemia occur most frequently in the central nervous system and in the testis. In this report, the authors describe a 16-year-old girl with an isolated renal relapse of acute lymphoblastic leukemia after a disease-free interval of 2 years and 8 months. This clinically inconspicuous renal relapse was suggested by a routine follow-up renal sonography. No evidence of disease was found in bone marrow or peripheral blood. Renal biopsy was required to establish the diagnosis. Treatment consisted of intensive chemotherapy and autologous bone marrow transplantation. The patient has been in second complete continuous remission for 7 years. The authors recommend the use of an intensive multidrug salvage regimen.

Purpose: To document the changes observed at sequential magnetic resonance (MR) imaging of sarcoidosis lesions of the central nervous system (CNS) during treatment with corticosteroids., Materials and Methods: The abnormalities detected in 24 patients (mean follow-up, 36 months) were compared before and after therapeutic periods (n = 75) that were divided into attack (high-dose), upkeep (decreased-dose), and minimal (low-dose) periods. Parenchymal lesions were classified as type 1 (enhanced with gadolinium), type 2 (demyelinating), or type 3 (lacunar) and were assessed as regressing, stable, or progressing., Results: Seven of the 24 patients had several types of lesions. Isolated type 3 lesions (six patients) were the only lesions not associated with neurologic deficit. Type 1 lesions (13 patients) regressed in 22 of 22 attack periods and progressed in nine of 27 upkeep and minimal periods. MR imaging depicted relapses in patients with multifocal CNS involvement or long-standing CNS impairment or in those who had previously received steroid therapy. Type 2 (seven patients) and type 3 (13 patients) lesions remained stable in 68 of 68 therapeutic periods. Type 1 lesions appeared in three patients with type 2 and type 3 lesions during two upkeep and three minimal periods. Findings at follow-up MR imaging contributed to the reintroduction of high-dose corticosteroid therapy in eight patients., Conclusion: MR imaging can be used to differentiate between reversible and irreversible lesions in CNS sarcoidosis. MR imaging can be a useful tool for adjusting treatment to prevent irreversible CNS damage.

The members of the actinomycete genus Frankia are nitrogen-fixing symbionts of may species of woody dicotyledonous plants belonging to eight families. Several strains isolated from diverse actinorhizal plants growing in different geographical areas were used in this study. The phylogenetic relationships of these organisms and uncharacterized microsymbionts that are recalcitrant to isolation in pure culture were determined by comparing complete 16S ribosomal DNA sequences. The resulting phylogenetic tree revealed that there was greater diversity among the Alnus-infective strains than among the strains that infect other host plants. The four main subdivisions of the genus Frankia revealed by this phylogenetic analysis are (i) a very large group comprising Frankia alni and related organisms (including Alnus rugosa Sp+ microsymbionts that are seldom isolated in pure culture), to which Casuarina-infective strains, a Myrica nagi microsymbiont, and other effective Alnus-infective strains are related; (ii) unisolated microsymbionts of Dryas, Coriaria, and Datisca species; (iii) Elaeagnus-infective strains; and (iv) "atypical" strains (a group which includes an Alnus-infective, non-nitrogen-fixing strain). Taxa that are related to this well-defined, coherent Frankia cluster are the genera Geodermatophilus, "Blastococcus," Sporichthya, Acidothermus, and Actinoplanes. However, the two genera whose members have multilocular sporangia (the genera Frankia and Geodermatophilus) did not form a coherent group. For this reason, we propose that the family Frankiaceae should be emended so that the genera Geodermatophilus and "Blastococcus" are excluded and only the genus Frankia is retained.

We present a case of sclerosing hemangioma of the lung, revealed as a solitary round mass on routine chest radiography in a 14-year-old patient. CT and MRI findings were consistent with a solid neoplasm but no specific characteristics were identified. Analysis of the surgical biopsy material led to a cytological diagnosis of adenocarcinoma. Definitive diagnosis of sclerosing hemangioma of the lung was established on pathological examination of the whole surgical specimen.

Among the Frankia strains capable of establishing a nitrogen-fixing symbiosis with actinorrhizal plants, in planta sporangial formation is not universal and has led to the distinction between spore-positive (Sp+) and spore-negative (Sp-) nodules. Numerous Frankia strains have been isolated in pure culture from Sp+ nodules of different host plants, but, although they were able to reinfect their respective host plant, none of them was able to differentiate endophytic sporangia under laboratory conditions. The first step of this study was to demonstrate, at the molecular level, the existence of specific Sp+ strain genotypes differing from Sp- strain genotypes in a single alder stand. In a second step, by way of PCR amplification and sequencing of the PCR products, we have characterized oligonucleotide primers specific for the genus Frankia and for each of the two types of Frankia microsymbionts able, or not, to differentiate sporangia inside natural green alder nodules. These primers applied in PCRs with DNA extracted from nodules confirmed the morphological identification and revealed the presence of nodules colonized by both types of actinomycetes. Finally, a preliminary PCR study was conducted with DNA extracted directly from soil samples which permitted checking the rhizosphere of Sp+ and Sp- nodules for the presence of the corresponding strains.

Nodules collected from Alnus nepalensis growing in mixed forest stands at three different sites around Shillong, were crushed in various culture media to obtain isolates of Frankia. The isolates were found to have typical Frankia morphology as revealed by the scanning electron microscope. Seedlings inoculated with isolates or crushed nodules formed nitrogen fixing nodules. Frankia specific DNA probes amplified the DNA of the tested isolate AnpUS4. Partial nucleotide sequence of the 16S rRNA gene indicated that AnpUS4 was phylogenetically distinct from all other Frankia strains characterized so far.

Thirty-five cases of biopsy-proven sarcoidosis with neurologic manifestations are reported. Neurosarcoidosis was the presenting symptom in 31% of cases and the only clinical manifestation in 17%. Mean follow-up time was 48 months. Central nervous system involvement was observed in 37% and meningitis in 40% of patients. Other manifestations were cranial nerve palsies (37%), peripheral neuropathy (40%), and myopathy (26%). Multiple neurologic manifestations were present in 51% of cases. All but 4 were treated with corticosteroids. Another immunosuppressive agent or cerebral irradiation was added in 6 and 2 patients, respectively. Complete recovery was observed in 46%, improvement in 46%, 4% remained stable, and 4% worsened. There were no deaths. We advocate treating neurosarcoidosis with corticosteroids as early as possible. If the patient's condition worsens, additional immunosuppressive agents or cerebral irradiation is warranted.