Search

Background. Some studies with inconclusive results have reported a link between sarcoidosis and an increased risk of pulmonary embolism (PE). This study aimed at assessing a possible correlation between potential risk factors and PE in sarcoidosis patients. Methods. A total of 256 sarcoidosis patients (84 males and 172 females, mean age at diagnosis 49 ± 13) were enrolled after giving written informed consent. Clinical evaluations, laboratory and radiology tests were performed to evaluate the presence of pulmonary embolism. Results. Fifteen sarcoidosis patients with PE (4 males and 11 females, mean age at diagnosis 50 ± 11), diagnosed by lung scintigraphy and 241 sarcoidosis patients without PE (80 males and 161 females, mean age at diagnosis 47 ± 13), were observed. There was a statistically significant increase of the presence of antiphospholipid antibodies in the sarcoidosis group with pulmonary embolism. There was no statistically significant difference between the two groups as to smoking habit, obesity or hereditary thrombophilia frequency (p &gt, 0.05, respectively). Conclusions. This study demonstrates a significant correlation between the presence of antiphospholipid antibody positivity and the pulmonary embolism events in our sarcoidosis patients. Furthermore, we propose screening for these antibodies and monitoring, aimed at timely treatment.

Objectius: Determinar l'epidemiologia de la Sarcoïdosi a Osona. I descriure'n les característiques clíniques. Material i mètodes: Identificació i selecció de casos de Sarcoïdosi al nostre centre, entre 1983-2011. Revisió retrospectiva, recollida i anàlisi. Resultats: Incidència 2.12 casos/105habitants/any. n = 55. Predomini femení (69%), edat mitjana 47.8 anys. Clínica més freqüent: simptomatologia general. Patrons radiològics més freqüents: Estadi I-II. Biòpsia transbronquial: tècnica més utilitzada. Retard diagnòstic 5.9 mesos i mortalitat relacionada 7.6%. Conclusions: Incidència superior a la publicada a Catalunya. Predomini femení, amb diagnòstic més tardà que en homes. Presentació clínica predominant: síndrome Löfgren. Notable retard diagnòstic i baixa mortalitat.

Sarcoidosis is a multisystemic disease histologically characterized by non-caseating epithelioid granulomas and multinucleated giant cells; the etiology is still uncertain, and likely related to a complex interplay between environmental and genetic factors. The genitourinary system is affected in fewer than 0.2% of all clinically diagnosed cases of sarcoidosis and in 5% of those identified in autopsy studies. In this report, we describe a case of a 42–year-old male with one hypoechoic lesion per testis on B-mode evaluation; contrast-enhanced ultrasound (CEUS) on both lesions was carried out. During the early phase, the masses showed a hypovascular appearance as compared to the surrounding testicular tissue, maintaining the hypo-enhancement in the late phase. Tissue biopsy for pathological evaluation confirmed testicular sarcoid involvement, showing non-caseating granulomas. Allowing visualization of testicular microvascularisation, CEUS may play an important role in excluding malignancy, avoiding unnecessary aggressive treatment for benign conditions, such as sarcoidosis. A review of the literature of reported cases since 2004 of sarcoidosis involving the testis is also included.

Background and Aim: The prevalence and clinical significance of extrahepatic autoimmune diseases (EHAIDs) have not been evaluated in a large cohort of primary biliary cholangitis (PBC). Methods: The medical records of 1554 patients with PBC from 20 international centers were retrospectively reviewed. Development of decompensated cirrhosis (ascites, variceal bleeding, and/or hepatic encephalopathy) and hepatocellular carcinoma were considered clinical endpoints. Results: A total of 35 different EHAIDs were diagnosed in 440 (28.3%) patients with PBC. Patients with EHAIDs were more often female (92.5% vs 86.1%, P&nbsp

Background The aim of the present investigation was to evaluate the literature recurrence of peripheral giant cell granuloma and pyogenic granuloma associated with dental implants. It’s important to know the characteristics present in these lesions and possible effects on the prognosis of dental implants. Methods An electronic search without time restrictions was done in the databases: PubMed/Medline. With the keywords "Granuloma" OR "Granuloma, Giant Cell" OR "peripheral giant cell" OR "Granuloma, Pyogenic” AND "Dental implants" OR "Oral implants”. Results After applying the inclusion and exclusion criteria, a total of 20 articles were included, which reported 32 lesions (10 pyogenic granulomas, 21 peripheral giant cell granulomas and one peripheral giant cell granuloma combined with peripheral ossifying fibroma, all associated with implants). According to our review, these lesions are more frequent in males and in the posterior region of the mandible. Both excision and curettage of the lesion, compared to only excision, presented similar recurrences (40%). Explantation of the implant was performed in 41% of cases without additional recurrences. The results are not statistically significant when comparing one lesion to the other in terms of explantation (p = 0.97), recurrence (p = 0.57) or bone loss (p = 0.67). Conclusions The main therapeutic approach is tissue excision. The lesions show a high recurrence rate (34.4%), which often requires explantation of the associated implant. This recurrence rate is not affected by curettage after excision.

Idiopathic granulomatous vulvitis and subsequent oral granulomatosis: a diagnostic and therapeutic challenge

Sarcoidosis is a multisystem inflammatory disease characterized by non-caseating granulomas which mainly affect the pulmonary lymphatic system and lungs; although any organs can be interested. The association between sarcoidosis and cancer is still controversial, but many studies demonstrated an increased risk of cancer in patients with sarcoidosis, whereas few cases of sarcoidosis occurring after cancer have been reported. This report outlines and describes clinical, biologic and radiologic features of 3 patients with a history of surgical treatment and adjuvant chemotherapy for colon cancer, followed by a diagnosis of sarcoidosis some years later. The history of cancer and the lymph nodes positivity found through PET scan induced us to hypothesize a relapsing cancer disease. However, this hypothesis was not confirmed by the lymph nodes biopsy, which is the core method of diagnosis of sarcoidosis.

FASE 1 DE LA TESIS DOCTORAL Objetivo: Describir los principales hallazgos clínicos e histopatológicos asociados con sarcoidosis cutánea y investigar la relación de estas lesiones cutáneas con afectación sistémica. Métodos: Se realizó un estudio retrospectivo de 41 pacientes que fueron diagnosticados de sarcoidosis cutánea. Resultados: El estudio incluyó a 34 mujeres y 7 hombres. La afectación sistémica ocurrió con frecuencia en pacientes con lesiones cutáneas de tipo nodular o placas y en pacientes con lupus pernio. Los síntomas sistémicos fueron observados más comúnmente en pacientes con niveles séricos elevados de ECA (84.6% vs 40%; p < 0.05). Nuestro estudio también indica que los pacientes con afectación cutánea y sistémica tenían una forma más crónica de la enfermedad que los pacientes con solamente lesiones cutáneas (91,6% vs 29,4%; p < 0.001). Además, la resolución completa de las lesiones cutáneas se observó más frecuentemente en pacientes sin sintomatología sistémica asociada (66.6% vs 23.5%; p < 0.05). Curiosamente, los pacientes con un infiltrado granulomatoso moderado/severo en sus biopsias, tenían una presentación clínica más severa durante el curso de la enfermedad, con una afectación cutánea más generalizada (65,6% vs. 30%), así como una forma más crónica de la enfermedad (56.3% vs 30%). Otro interesante hallazgo histopatológico observado fue la presencia de una zona de Grenz en 20 casos (47,6%). Conclusión: Una correlación clínico-patológica correcta y metódica es importante para nuestra práctica clínica ya que puede darnos pistas útiles para el diagnóstico y el pronóstico de esta enfermedad. FASE 2 DE LA TESIS DOCTORAL Objetivo: Durante los últimos años, los investigadores han debatido el papel que los agentes infecciosos pueden tener en la patogénesis de la sarcoidosis. Por lo tanto, se realizó una meta-análisis para explicar mejor esta posible asociación. Métodos: Se utilizaron cuatro bases de datos diferentes (Medline, Scopus, Web of Science y Cochrane) para seleccionar todos los artículos originales publicados entre 1980 y 2015. Resultados: Cincuenta y ocho estudios fueron seleccionados para esta meta-análisis. Nuestros resultados sugieren un correlación etiológica entre Propionibacterium acnes y sarcoidosis, con un OR de 18,80 (12,62, 28,01). También se encontró una asociación significativa entre sarcoidosis y micobacterias, con un OR de 6,8 (3,73, 12,39); Borrelia (OR 4,82; IC 0,98, 23,81) y HHV-8 (OR 1,47; IC 0,02, 110,06), aunque sugerido por investigaciones anteriores, no se asociaron con sarcoidosis. Conclusión: Esta meta-análisis sugiere que algunos casos de sarcoidosis puedan ser causados por agentes infecciosos. FASE 3 DE LA TESIS DOCTORAL Objetivo: Utilizando técnicas de biología molecular, el estudio tuvo como objetivo evaluar el papel potencial de las micobacterias, bacterias y Leishmania como factor etiológico de lesiones cutáneas que demuestran histológicamente una dermatitis granulomatosa sarcoidea, con tinciones especiales y cultivos negativos para microorganismos. Métodos: Cuarenta y ocho biopsias cutáneas diagnosticadas como dermatitis granulomatosas sarcoideas se incluyeron retrospectivamente en el estudio. Se realizó análisis de PCR para bacterias (16S rRNA), micobacterias (hsp65, 16S-23S rRNA y FluoroType® Kit) y Leishmania spp ADN. Resultados: Doce de las 48 muestras histológicas (25%) mostraron resultados positivos por PCR para la detección de ADN de microorganismos. Mycobacterium tuberculosis se identificó en 6 muestras, Mycobacterium xenopi en 2 muestras, ADN específico de Leishmania en 3 casos y una muestra reveló la presencia de ADN de Pseudomonas aeruginosa. Todos los casos fueron diagnosticados clínica y histológicamente como sarcoidosis cutánea. La correlación de los resultados moleculares con los resultados clínicos y histológicos nos permitió identificar importantes pistas sutiles que podrían ayudar a los médicos a obtener un diagnóstico correcto en estos casos difíciles. Conclusión: Las actuales técnicas de diagnóstico molecular en microbiología sugieren que algunas dermatitis granulomatosas sarcoideas pueden estar relacionadas con microorganismos., PHASE 1 OF DOCTORAL THESIS Objectives: Describe the main clinical and histopathological findings associated with cutaneous sarcoidosis and to investigate the relationship of these skin lesions with systemic involvement. Methods: A retrospective review of 41 patients who were diagnosed with cutaneous sarcoidosis was done. Results: The study included 34 females and 7 males. Systemic disease occurred frequently in patients with lupus pernio and nodulo-plaques type lesions. Systemic symptoms were observed more commonly in patients with raised serum ACE levels (84.6% vs. 40%; p

Cohort studies of large series of patients with sarcoidosis over a long period of time are scarce. The aim of this study is to report a 40-year clinical experience of a large series of patients at Bellvitge University Hospital, a tertiary university hospital in Barcelona, Spain. Diagnosis of sarcoidosis required histological confirmation except in certain specific situations. All patients underwent a prospective study protocol. Clinical assessment and follow-up of patients were performed by a multidisciplinary team. From 1976 to 2015, 640 patients were diagnosed with sarcoidosis, 438 of them (68.4%) were female (sex ratio F/M 2:1). The mean age at diagnosis was 43.3±13.8 years (range, 14–86 years), and 613 patients (95.8%) were Caucasian. At diagnosis, 584 patients (91.2%) showed intrathoracic involvement at chest radiograph, and most of the patients had normal pulmonary function. Erythema nodosum (39.8%) and specific cutaneous lesions (20.8%) were the most frequent extrapulmonary manifestations, but there was a wide range of organ involvement. A total of 492 patients (76.8%) had positive histology. Follow-up was carried out in 587 patients (91.7%), over a mean of 112.4±98.3 months (range, 6.4–475 months). Corticosteroid treatment was administered in 255 patients (43.4%), and steroid-sparing agents in 49 patients (7.7%). Outcomes were as follows: 111 patients (18.9%) showed active disease at the time of closing this study, 250 (42.6%) presented spontaneous remission, 61 (10.4%) had remission under treatment, and 165 (28.1%) evolved to chronic sarcoidosis; among them, 115 (19.6%) with mild disease and 50 (8.5%) with moderate to severe organ damage. A multivariate analysis showed that at diagnosis, age more than 40 years, the presence of pulmonary involvement on chest radiograph, splenic involvement, and the need of treatment, was associated with chronic sarcoidosis, whereas Löfgren syndrome and mediastinal lymphadenopathy on chest radiograph were indicators of good outcome. Sarcoidosis is a multisystem disease with protean clinical-radiographic manifestations. Although almost half of patients follow a spontaneous resolution or under treatment, a significant number of them may have several degrees of organ damage. This study emphasizes the value of a multidisciplinary approach and long-term follow-up by specialized teams in sarcoidosis. info:eu-repo/semantics/acceptedVersion

Blau syndrome (BS) and early onset sarcoidosis (EOS) are, respectively, the familial and sporadic forms of the pediatric granulomatous autoinflammatory disease, which belong to the group of monogenic autoinflammatory syndromes. Both of these conditions are caused by mutations in the NOD2 gene, which encodes the cytosolic NOD2 protein, one of the pivotal molecules in the regulation of innate immunity, primarily expressed in the antigen-presenting cells. Clinical onset of BS and EOS is usually in the first years of life with noncaseating epithelioid granulomas mainly affecting joints, skin, and uveal tract, variably associated with heterogeneous systemic features. The dividing line between autoinflammatory and autoimmune mechanisms is probably not so clear-cut, and the relationship existing between BS or EOS and autoimmune phenomena remains unclear. There is no established therapy for the management of BS and EOS, and the main treatment aim is to prevent ocular manifestations entailing the risk of potential blindness and to avoid joint deformities. Nonsteroidal anti-inflammatory drugs, corticosteroids and immunosuppressive drugs, such as methotrexate or azathioprine, may be helpful; when patients are unresponsive to the combination of corticosteroids and immunosuppressant agents, the tumor necrosis factor-α inhibitor infliximab should be considered. Data on anti-interleukin-1 inhibition with anakinra and canakinumab is still limited and further corroboration is required. The aim of this paper is to describe BS and EOS, focusing on their genetic, clinical, and therapeutic issues, with the ultimate goal of increasing clinicians' awareness of both of these rare but serious disorders.

Orofacial granulomatosis (OFG) is an uncommon disease characterized by persistent or recurrent soft tissue enlargement, oral ulceration and a variety of other orofacial features. It could be an oral manifestation of a systemic disease. For a correct differential diagnosis, local and systemic conditions characterized by granulomatous inflammation should be excluded using appropriate clinical and laboratory investigations. In fact, the diagnosis of OFG may be confirmed only by histopathological identification of noncaseating granulomas. The literature from 1943 to 2014 was reviewed with emphasis on the etiology of OFG and on clinical manifestations of systemic pathologies associated with OFG. The precise cause of OFG is still unknown, although several theories have been suggested, such as infection, hereditary factors and allergy. OFG is a disease that has a wide spectrum of presentation, which may include the oral manifestation of a systemic condition such as Crohn's disease, sarcoidosis, granulomatosis with polyangiitis and Melkersson-Rosenthal syndrome.

Objectius: Determinar l’epidemiologia de la Sarcoïdosi a Osona. I descriure’n les característiques clíniques. Material i mètodes: Identificació i selecció de casos de Sarcoïdosi al nostre centre, entre 1983-2011. Revisió retrospectiva, recollida i anàlisi. Resultats: Incidència 2.12 casos/105habitants/any. n = 55. Predomini femení (69%), edat mitjana 47.8 anys. Clínica més freqüent: simptomatologia general. Patrons radiològics més freqüents: Estadi I-II. Biòpsia transbronquial: tècnica més utilitzada. Retard diagnòstic 5.9 mesos i mortalitat relacionada 7.6%. Conclusions: Incidència superior a la publicada a Catalunya. Predomini femení, amb diagnòstic més tardà que en homes. Presentació clínica predominant: síndrome Löfgren. Notable retard diagnòstic i baixa mortalitat.

Background: Lung diffusion for carbon monoxide (DLCO) has been shown to associate with the risk of pulmonary arterial hypertension development and, most likely, with right ventricular (RV) myocardial dysfunction in sarcoidosis patients. Besides its known role as a marker of left ventricular dysfunction, experimental evidence suggests a role of NT-proAtrial Natriuretic Peptide (NT-proANP) also in modulating pulmonary circulation. We therefore investigated possible relationships between NT-proANP, lung diffusion impairment and RV dysfunction. Methods: Thirty-two pulmonary sarcoidosis outpatients and eighteen volunteers underwent full clinical assessment, including full lung function tests and Doppler echocardiography integrated with tissue Doppler imaging (TDI) study. Resting circulating NT-proBNP and NT-proANP plasma levels were also determined. Results: NT-proANP and RV-myocardial performance index (RV-MPI) were significantly higher in those patients with the greatest DL CO impairment, whereas no differences were found for NT-proBNP values. At multivariable analysis, only DLCO (β: - 0.496; standard error: 3.38; p = 0.000) and RV-MPI (β: 0.373; standard error: 6.56; p = 0.031) remained significantly associated with NT-proANP levels. Conclusions: Our finding may support a key role of NT-proANP in the complex mechanisms underlying modulation of lung function. An early increase in pulmonary vascular resistance may stimulate NT-proANP increase, thus explaining its association with signs of early RV myocardial dysfunction. This hypothesis warrants further confirmation. © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Granulomatosis with polyangiitis (Wegener's, GPA) is an uncommon disease of unknown etiology classically involves the ELK triad of the ear, nose, throat (E), lungs (L) and kidneys (K) with necrotizing granulomatous inflammation and vasculitis. Most of the initial symptoms begin in the head and neck region with a wide spectrum of involvement of any site ranging from the nasal septum, paranasal sinuses, oral mucosa, larynx and even the external, middle and internal ear. Diagnosis may be delayed because the onset is heterogeneous and sometimes limited to one organ. The pathologic findings of a characteristic inflammatory reaction pattern, and the serum findings of elevated antineutrophil cytoplasmic antibodies can help to establish the diagnosis. The differentiation from other conditions that mimic GPA such as lymphoma and infections is of critical importance to initiate appropriate treatment. Treatment of the underlying disease is medical with the use of immunosuppressive agents and will not be reviewed here. This review focuses on the otorhinolaryngologic manifestation and complication of GPA as well as their surgical management and specifies the role of the otorhinolaryngologist as an integral member of the multidisciplinary care team for patients with GPA. © 2012 Elsevier B.V.

the Divisions of Dermatology at the Dipartimento di edicina Specialistica, Diagnostica e Sperimentale, Universit a Bologna, and the Ospedale Santa Chiara, Trento, Italy. ing sources: None. licts of interest: None declared. ints not available from the authors. spondence to: Riccardo Balestri, MD, Dipartimento di edicina Specialistica, Diagnostica e Sperimentale, Universit a di Bologna, Clinica Dermatologica, Via Massarenti 1, 40138 Bologna, Italy. E-mail: ilsabo@libero.it. J Am Acad Dermatol 2013;69:e217-8. 0190-9622/$36.00 a 2013 by the American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2013.03.030

La sarcoidosis es una enfermedad sistémica, granulomatosa de etiología desconocida que afecta al adulto joven. Puede interesar a cualquier órgano aunque también existen formas asintomáticas. En este trabajo se describen las características clínicas, el tratamiento y la evolución de una serie de pacientes diagnosticados de sarcoidosis. Es un estudio retrospectivo en un hospital universitario con un área de referencia de 700.000 habitantes. La manifestación de inicio más frecuente fue el síndrome de Löfgren. La mayoría de los pacientes recibieron tratamiento con antiinflamatorios esteroideos y no esteroideos y presentaron una buena evolución, con resolución de la enfermedad. La sarcoïdosi és una malaltia sistèmica, granulomatosa d’etiologia desconeguda que afecta a l'adult jove. Pot afectar qualsevol òrgan encara que també hi ha formes asimptomàtiques. En aquest treball es descriuen les característiques clíniques, el tractament i l'evolució d'una sèrie de pacients diagnosticats de sarcoïdosi. És un estudi retrospectiu en un hospital universitari amb una àrea de referència de 700.000 habitants. La manifestació d'inici més freqüent va ser la síndrome de Löfgren. La majoria dels pacients van rebre tractament amb antiinflamatoris esteroïdals i no esteroïdals i varen evolucionar bé , cap a la curació de la malaltia.

18F-FDG-PET/CT is widely employed to evaluate lymphoma patients. False positive results are quite frequent, generally due to active phase of inflammation. We describe an unusual PET/CT presentation of a sarcoid-like reaction (SLR) in a patient monitored for Hodgkin Lymphoma characterized by an intense uptake in lymph nodes and multiple bone foci in a PET/CT study. The final diagnosis was obtained by biopsy. This study draws attention to the fact that multifocal bone marrow uptakes due to a sarcoideal reaction may be a possible cause of false positive results in 18F-FDG-PET/CT studies in oncology patients. © 2012 Elsevier España, S.L. and SEMNIM

Sarcoidosis is a multisystemic granulomatous disease of unknown etiology that usually presents with bilateral hiliar adenopathies, pulmonary infiltrations, and ocular and cutaneous lesions. The specific cutaneous lesions, or granulomatous, are produced in from 9% to 37% of patients with systemic sarcoidosis. Nevertheless, few patients have been described having specific lesions from sarcoidosis in the oral mucous membrane. We present 2 patients with systemic sarcoidosis who developed specific sarcoidosis lesions in the oral mucous membrane. The first patient presented a plaque on the tongue of a chronic nature associated with facial lupus pernio. The second patient presented a rapidly growing nodular lesion on the lower lip that was in fact the presentation sign of the disease. Although infrequent, oral lesions may constitute the first sign of systemic sarcoidosis. For this reason the oral mucous membrane needs to be explored when there is suspicion of sarcoidosis, and systemic sarcoidosis must be included in the differential diagnosis of oral granulomatous lesions.

Background: The clinical variability of cutaneous sarcoidosis (CS) often makes its correct diagnosis challenging. Although traditionally employed for the diagnosis of skin tumors, during the past years dermoscopy also gained increasing interest as an aid in the clinical diagnosis of inflammatory and infectious skin manifestations in general dermatology. Objective: Our purpose was to evaluate the usefulness of dermoscopy in the differential diagnosis of CS. Methods: This was a retrospective analysis of 7 clinical and dermoscopic images of CS that were collected at dermatology clinics in France and Italy between 2005 and 2009. Results: Retrospective dermoscopic evaluation revealed small grouped, translucent orange globular structures associated with linear vessels of variable diameter in all 7 cases. In 5 cases, additional central scar-like areas were seen. Conclusion: Lesions showing dermoscopically translucent yellow to orange globular-like or structureless areas associated with linear vessels should raise the suspicion of a granulomatous skin disease, including CS.

Sarcoidosis is a systemic disorder characterized by granulomatous lesions, principally affecting the lungs. There are numerous reports in the literature of an associated involvement of the thyroid, much more frequently in hypothyroid than in hyperthyroid subjects. The present case report refers to a woman presenting with thyroid nodules and normal biochemical levels and thyroid function parameters, while histology revealed sarcoid-type lesions. Subsequent investigations and a long follow-up showed no evidence of involvement of other sites, including the lungs. Consequently, after a long period of normal health associated with the negative results of the examinations, a diagnosis of sarcoidosis limited to the thyroid was proposed, which was cured by thyroidectomy.

Background: The clinical value of computed tomographic (CT) scanning of the chest in the initial assessment of sarcoidosis was investigated. Methods: One hundred consecutive patients referred to the sarcoidosis outpatient services of the Mount Sinai Medical Center, New York from 1990 to 1992 with a presumptive diagnosis of sarcoidosis were studied. The diagnosis was subsequently confirmed in all by a positive tissue biopsy sample or the Kveim-Siltzbach test. Clinical and laboratory data of each patient were reviewed. Chest radiographs were classified according to the classical stages of sarcoidosis. Thirty five of the 100 patients had a CT scan of the chest performed before presentation. The CT scans were compared with the presenting clinical data and standard chest radiographs in order to determine if they yielded useful additional information regarding diagnosis or treatment. Results: The chest CT scan revealed no additional clinically relevant information compared with conventional chest radiographs in any of the 35 studies performed. In two patients mediastinal adenopathy was detected by CT scan which was not seen on standard radiographs. Two patients thought to exhibit hilar adenopathy and pulmonary infiltrations by standard radiography had no parenchymal disease on the CT scan. Bilateral parenchymal infiltrates were seen in one patient which were interpreted as unilateral infiltrates by standard radiographs. The variance between conventional radiographs and CT scans in these five patients was not clinically valuable. Conclusions: CT scans of the chest do not add clinically useful information to the standard chest radiographs in the initial assessment of sarcoidosis in patients presenting with the typical standard radiological patterns. CT scanning of the thorax is indicated in patients with proven or suspected sarcoidosis when the standard chest radiographs are normal or not typical of sarcoidosis, when signs or symptoms of upper airway obstruction are present, when the patient has haemoptysis, if there is a suspicion of a complicating second intrathoracic disease, or the patient is a candidate for lung transplantation.

To the Editor: the February 8 Case Record involves a patient with Löfgren's syndrome. In his discussion of the case, Dr. Bates does not sufficiently emphasize the importance of the recognition of periarticular ankle inflammation as a particular presenting sign of acute sarcoidosis. In the Nordic countries and Spain, Löfgren's syndrome is the most common form of the disease and frequently starts with periarticular ankle inflammation. In our series of 186 white patients with Löfgren's syndrome, 35 (19 percent) presented with periarticular ankle inflammation alone and 46 (25 percent) had periarticular ankle inflammation in association with erythema nodosum.

a) INTRODUCCIÓN.La sarcoidosis es una enfermedad cuya evolución puede oscilar desde formas asintomáticas o con eritema nudoso con remisión espontánea, hasta cuadros progresivamente incapacitantes a pesar de un tratamiento con corticoides. La dificultad fundamental se plantea en poder identificar, en la presentación inicial de la enfermedad, aquellos datos que ayuden a establecer un pronóstico y, en consecuencia, a indicar un tratamiento. En la literatura médica sobre el pronóstico se han analizado sólo aspectos parciales de la enfermedad y no se ha utilizado una metodología estadística adecuada. En el Hospital de Bellvitge de Barcelona se dispone de una amplia casuística de pacientes con sarcoidosis y el establecimiento del pronóstico y la indicación de tratamiento son especialmente problemáticos. Por dicho motivo se inició un estudio con los siguientesb) OBJETIVOS1) Estudiar la casuística de sarcoidosis del hospital.2) Estudiar los factores pronósticos de persistencia de actividad de la enfermedad en el tiempo, mediante técnicas estadísticas univariantes y multivariantes.c) MATERIAL Y METODOS1) Casuística general: El estudio abarcó un periodo de 14 años y se efectuó en el Servicio de Medicina Interna del Hospital de Bellvitge, en colaboraci6n con otros servicios. A todos los pacientes incluidos en el estudio se les exigió confirmación anatomopatológica, excepto si se trataba de un síndrome de Lofgren.y fueron sometidos a un protocolo de estudio prospectivo que incluía datos referidos a formas clínicas, estadios radiológicos, marcadores de actividad, evolución y tratamiento.2) Estudio de los factores pronósticos: El pronóstico se definió como "la persistencia de actividad de la enfermedad en el transcurso del tiempo". La actividad se definió como "la presencia de datos clínicos y/o de alteraciones radiológicas y/o de alteraciones en los marcadores de actividad, persistentes o cambiantes en el tiempo. A partir del protocolo de estudio se definieron las variables que se estudiaron como factores pronósticos.3) Metodología estadística: se efectuaron dos tipos de análisis estadísticos:1º) Análisis de la persistencia de actividad a los 2 años del diagnóstico, mediante el test de chi-cuadrado y el test de regresión logística múltiple.2º) Análisis de la persistencia de actividad en el transcurso del tiempo, mediante Curvas actuariales (Kaplan-Meier) y el test de Mantel-Cox, y el test de Cox para Curvas actuariales ("Cox proportional hazards regression models"). Con esta metodología se realizaron dos análisis: uno con variables clínicas y otro que incluía además a los marcadores de actividad.d) RESULTADOS1) Casuística general: Se estudiaron 209 pacientes, con una edad media de 40 años y una relación mujer/varón de 3: 1. Destacó el elevado número de formas clínicas con eritema nudoso (62.7%) y la mayor frecuencia de estadio 1 en la radiografía de tórax (59.3%). Los niveles séricos de la enzima de conversión de la angiotensina fueron superiores a 2 DE en el 44% de los pacientes con eritema nudoso y en el 65% de los pacientes sin eritema nudoso. La captación endotorácica de galio-67 fue predominantemente en forma de estadio 1 (67.3%). Un 16% de los casos presentaron disminución de la capacidad vital y un 17% del test de difusión del monóxido de carbono. El 64% de los pacientes a los que se practicó lavado broncoalveolar presentó alveolitis de alta intensidad (linfocitosis superior al 28%).2) Estudio de los factores pronósticos: El estudio clínico de persistencia de actividad a los 2 años incluyó a 155 pacientes y las variables que se asociaron con independencia de las demás a un mal pronóstico fueron: ausencia de eritema nudoso, edad superior a 40 años, esplenomegalia y afectación del parénquima en la radiografía de tórax. El estudio clínico de persistencia de actividad en el transcurso del tiempo incluyó 193 casos y las variables que con independencia de las demás se asociaron a un mal pronóstico fueron: ausencia de eritema nudoso, afectación del parénquima en la radiografía de tórax, esplenomegalia, edad avanzada y ausencia de adenopatías en la radiografía de tórax. El estudio clínico y de los marcadores de actividad, de persistencia de actividad en el tiempo, incluyó 116 casos y las variables que con independencia de 1as demás se asociaron a un mal pronóstico fueron: ausencia de eritema nudoso, edad avanzada, elevación del nivel sérico de la enzima de conversión de la angiotensina, hipergammaglobulinemia, disminución de la capacidad vital y sexo varón.e) DISCUSIONLa sarcoidosis no es infrecuente en nuestro medio. La elevada frecuencia del síndrome de Löfgren destaca sobre el 17% de la media mundial, mientras que la distribución por estadios radiológicos es similar a la del resto de las series. Para el estudio de los factores pronósticos es necesario definir el concepto de pronóstico y el de actividad. La metodología estadística empleada muestra que para el estudio del pronóstico el test de Cox para curvas actuariales es superior al test de regresión logística múltiple. Las variables asociadas a un mal pronóstico tienen todas ellas un sentido clínico. Los marcadores de actividad son útiles en el seguimiento de la enfermedad, así como en el establecimiento del pronóstico.f) CONCLUSIONESLas conclusiones más importantes de la presente tesis son las siguientes:1) En nuestro medio, la sarcoidosis no es infrecuente y el síndrome de Lofgren es la forma clínica más común.2) El test de Cox para curvas actuariales es la metodología estadística multivariante más apropiada para estudiar el pronóstico de la enfermedad.3) En el estudio clínico, las variables asociadas a un mal pronóstico fueron: ausencia de eritema nudoso, afectación del parénquima en la radiografía de tórax, esplenomegalia, edad avanzada y ausencia de adenopatías en la radiografía de tórax.4) En el estudio conjunto clínico y de los marcadores de actividad las variables asociadas a un mal pronóstico fueron: ausencia de eritema nudoso, edad avanzada, elevación del nivel sérico de la ECA. hipergammaglobulinemia, disminución de la capacidad vital y sexo varón. En consecuencia, los marcadores de actividad son útiles para establecer el pronóstico de la sarcoidosis.5) El problema del pronóstico en la sarcoidosis se plantea fundamentalmente en las formas sin eritema nudoso. En consecuencia, un estudio del pronóstico realizado en una serie amplia de pacientes sin eritema nudoso podía proporcionar información más especifica para esta forma clínica de la enfermedad., The aim of this study was to define the prognostic factors in sarcoidosis using univariate and multivariate statistical methods (Cox proportional hazards regression model).We studied prospectively 209 patients suffering from sarcoidosis, during a 14 year period (1974-1987) in Bellvitge Hospital (Barcelona). The prognosis was defined as "persistence of activity of the disease by means of clinical, radiological and other markers".Main results:1) Our population with sarcoidosis had a high incidence of erythema nooosum (62.7%) and a predominance of stage 1 on x-ray. The activity markers (serum angiotensin converting enzyme, pulmonary gallium scan, pulmonary function test, and broncoalveolar lavage) showed to be a useful follow-up parameter.2) Prognostic factors: A Cox proportional-hazards regression model picked the following variables: absence of erythema nodosum (Risk Ratio=2'78), greater than 40 years (Risk Ratio=1'67), elevation of serum angiotensin converting enzyme (Risk Ratio=1'45), immunoglobulin level elevation (Risk Ratio=2'47), vital capacity decrease (Risk Ratio=2'17), and male sex (Risk Ratio=1'8) as independent predictors of bad prognosis. We suggest that accurate definition of prognostic factors in sarcoidosis may provide a better treatment approach for the disease.

Correspondence: SIR, We were interested to read the case report by Melsom and coworkers.' We have been followinl up a patient who presented a similar difficult diagnosis.

To determine whether bronchoalveolar lavage reflects the histologic aspects of the lung histology in patients with sarcoidosis and hypersensitivity pneumonitis, cells recovered from lavage fluid were compared with tissue sections from transbronchial lung biopsies in 33 patients. The evaluation of cellular types and their topographic distribution in situ was determined by using monoclonal antibodies in combination with immunohistochemical techniques. Cell counts in bronchoalveolar lavage and lung biopsies were significantly correlated both in sarcoidosis and hypersensitivity pneumonitis. In fact, the relative proportions of inflammatory and immunocompetent cells recovered from lavage fluid accurately overlapped those observed in lung tissue sections. However, in patients with more pronounced alveolitis, the frequency of macrophages in tissue sections was higher than that observed in the bronchoalveolar lavage, and the degree of lymphocytes in the lavage was higher than that observed in the corresponding biopsy. Specifically, in these patients the lavage underestimated the amount of macrophages in the lung biopsies and overestimated the number of lymphocytes that were present in the lung parenchyma. This was more evident in patients with hypersensitivity pneumonitis, where the intensity of alveolitis was higher than in sarcoidosis. Our data support the idea that, at least in patients with sarcoidosis and hypersensitivity pneumonitis, bronchoalveolar lavage correctly samples the alveolitis. Discrepancies in patients with very high intensity alveolitis could be due to a more pronounced recirculation of lymphocytes from the parenchyma to the alveolar spaces.

Diffuse parenchymal lung diseases (DPLD) represent a diverse group of disorders affecting the distal lung parenchyma, specifically the tissue and spaces surrounding the alveoli, which may be filled with inflammatory cells, proliferating fibroblasts or established fibrosis, often leading to architectural distortion and impaired gas exchange. While the underlying pathogenetic mechanisms are known or inferred for some DPLD (such as sarcoidosis, silicosis, drug reactions and collagen vascular diseases), the pathogenesis of the majority of these entities - particularly those characterized by progressive fibrosis - is poorly understood. Several lines of evidence indicate that the development of pulmonary fibrosis is genetically determined. They include: 1. familial clustering; 2. the occurrence of pulmonary fibrosis in the context of rare inherited disorders; 3. substantial variability in the development of pulmonary fibrosis amongst individuals exposed to organic or inorganic dusts; 4. difference in susceptibility to fibrogenic stimuli amongst inbred strains of mice. This review focuses on idiopathic pulmonary fibrosis (IPF) and sarcoidosis, the two most common DPLD and the two entities for which there is stronger evidence of a genetic predisposition, although how aberrant genes interact with each other and with environmental factors, such as smoking in IPF and infectious agents in sarcoidosis, in determining disease susceptibility and clinical phenotypes is largely unknown. Finally, we discuss practical issues and implications for both patients and physicians of recent advances in the genetics of sarcoidosis and IPF.