Specific Cutaneous Lesions in Patients With Neurosarcoidosis. / Lesiones cutáneas específicas en pacientes con neurosarcoidosis.

Neurosarcoidosis is an uncommon but potentially serious disease of the central nervous system that can cause major sequelae. We analyzed the presence and diagnostic usefulness of specific cutaneous lesions in 58 patients with neurosarcoidosis. Sixteen patients (27.6%) had specific cutaneous lesions (14 men and 2 women; mean age, 50 years [range, 20-84 years]). Twenty-four types of neurological lesions were observed: cranial neuropathy (n=7), parenchymal lesions (n=4), meningeal lesions (n=3), myelopathy (n=3), pituitary lesions (n=1), hydrocephalus (n=2), and peripheral neuropathy (n=4). Twenty types of specific cutaneous lesions were observed: maculopapular lesions (n=6), plaques (n=9), lupus pernio (n=1), and scar sarcoidosis (n=4). These last lesions coexisted with maculopapular lesions in 2 patients and plaques in another 2. Specific cutaneous lesions were present at diagnosis of neurosarcoidosis in 13 patients. Recognition of specific cutaneous lesions in a patient with suspected neurosarcoidosis is important as biopsy can accelerate diagnosis.

Endpoints for clinical trials of sarcoidosis.

Over the past few years an increasing number of prospective controlled sarcoidosis treatment trials have been completed. Unfortunately, these studies utilize different endpoints making comparisons between studies difficult. At the recent World Association of Sarcoidosis and other Granulomatous disease (WASOG) meeting, a session was dedicated to the evaluation of clinical endpoints for various disease manifestations. These included pulmonary, pulmonary hypertension, fatigue, cutaneous, and a classification of clinical disease phenotypes. Based on the available literature and our current understanding of the disease, recommendations for clinical evaluation were proposed for each disease category. For example, it was recommended that pulmonary studies should include changes in the forced vital capacity. Additionally, it was recommended that all trials should incorporate measurement of quality of life.

Specific cutaneous lesions in patients with systemic sarcoidosis: relationship to severity and chronicity of disease.

BACKGROUND: Specific (granulomatous) cutaneous lesions are seen in 9-37% of cases of systemic sarcoidosis, and are usually classified into maculopapules, plaques, lupus pernio (LP), scar sarcoidosis, and subcutaneous sarcoidosis. Their prognostic significance has not been fully established. AIM: To analyse the relationship between the clinical type of granulomatous cutaneous lesions and the systemic features and prognosis of systemic sarcoidosis. METHODS: The clinical charts of 86 patients (19 men, 67 women, mean age 46.82 years) with systemic sarcoidosis and granulomatous cutaneous involvement followed up for > 2 years at Bellvitge University Hospital were reviewed. RESULTS: Cutaneous lesions developed before or at the time of diagnosis of systemic sarcoidosis in 80.23% of patients. The main cutaneous lesions were classified as maculopapules (28 patients), plaques (31), LP (6), scar sarcoidosis (7) and subcutaneous sarcoidosis (14). Erythema nodosum (EN) was seen in 30 patients. Radiological stage was 0 for 8 patients, I for 48, II for 24, III for 5 and IV for 1. Systemic sarcoidosis activity persisted for > 2 years in 47 patients, and 42 received systemic corticosteroid treatment for their disease. Maculopapular and subcutaneous sarcoidosis were mainly seen in patients with EN and radiological stage I. Plaques and LP were associated with chronic disease and requirement for systemic corticosteroids. CONCLUSIONS: Cutaneous granulomatous lesions are usually present at the diagnosis of systemic sarcoidosis, and the type of cutaneous involvement may have prognostic significance.

Subcutaneous sarcoidosis--clinicopathological study of 10 cases.

BACKGROUND: Subcutaneous sarcoidosis is a specific cutaneous lesion of sarcoidosis that is rarely reported. OBJECTIVE: Our purpose was to analyse the clinicopathological features of 10 patients with subcutaneous sarcoidosis and its relationship with the systemic features of the disease. PATIENTS AND METHODS: The patients with systemic sarcoidosis, diagnosed from 1974 to 2002 at a university hospital in Barcelona, Spain, who developed subcutaneous involvement, were included in the study. The diagnosis of systemic sarcoidosis was made according to conventional criteria. All the patients were monitored prospectively at the sarcoidosis clinic of the hospital. Skin biopsies were performed when granulomatous cutaneous involvement was suspected clinically. RESULTS: Granulomatous cutaneous involvement was demonstrated in 85 of 480 patients with systemic sarcoidosis. In 10 of these 85 patients subcutaneous sarcoidosis was diagnosed (11.8%). The lesions were most frequently located in the extremities, involving the forearms in nine patients. Indurated linear bands from the elbow to the hand were observed in five patients. In all of our patients the subcutaneous nodules appeared at the beginning of the disease. In six patients, the nodules remitted spontaneously in less than 2 years. In two cases foreign particles were detected under polarized light. CONCLUSIONS: Subcutaneous sarcoidosis is a quite uniform clinicopathological entity usually appearing at the beginning of the disease. It usually heralds forms of sarcoidosis with nonsevere systemic involvement and is not associated with chronic fibrotic disease.

Systemic autoimmune diseases co-existing with chronic hepatitis C virus infection (the HISPAMEC Registry): patterns of clinical and immunological expression in 180 cases.

OBJECTIVES: To describe the clinical and immunologic characteristics of a large series of patients with systemic autoimmune diseases (SAD) associated with chronic hepatitis C virus (HCV) infection. METHODS: We analysed 180 patients diagnosed with SAD and chronic HCV infection seen consecutively at our centres during the last 10 years. The clinical and immunological patterns of disease expression were compared with 180 SAD-matched patients without chronic HCV infection. RESULTS: A total of 180 HCV patients fulfilled the classification criteria for the following SAD: Sjogren's syndrome (n = 77), systemic lupus erythematosus (n = 43), rheumatoid arthritis (n = 14), antiphospholipid syndrome (n = 14), polyarteritis nodosa (n = 8) and other SAD (n = 24). One hundred and thirty (72%) patients were female and 50 (28%) male, with a mean age at SAD diagnosis of 50 years. The main immunologic features were antinuclear antibodies in 69% of patients, cryoglobulinaemia in 62%, hypocomplementaemia in 56% and rheumatoid factor (RF) in 56%. Compared with the SAD-matched HCV-negative group, SAD-HCV patients presented a lower prevalence of females (P = 0.016), an older age at SAD diagnosis (P = 0.039) and a higher prevalence of vasculitis (P < 0.001) and neoplasia (P < 0.001). Immunologically, SAD-HCV patients presented a lower prevalence of antinuclear (P = 0.036), anti-extractable nuclear antigen (P = 0.038) and anti-DNA (P = 0.005) antibodies, and a higher frequency of RF (P = 0.003), hypocomplementaemia (P < 0.001) and cryoglobulins (P < 0.001). CONCLUSIONS: In comparison with an SAD-matched HCV-negative population, SAD-HCV patients were older and more likely to be male, with a higher frequency of vasculitis, cryoglobulinaemia and neoplasia. This complex pattern of disease expression is generated by a chronic viral infection that induces both liver and autoimmune disease.

Foreign bodies in granulomatous cutaneous lesions of patients with systemic sarcoidosis.

OBJECTIVE: To assess the presence of foreign material in the granulomatous cutaneous lesions of patients with systemic sarcoidosis. DESIGN AND SETTING: Observational study reevaluating histological specimens at a university referral hospital. PATIENTS: Sixty-five patients diagnosed as having sarcoidosis who developed granulomatous cutaneous involvement. MAIN OUTCOME MEASURES: To detect the presence of polarizable foreign particles in cutaneous biopsy specimens and to evaluate the association with clinical features of the patients. RESULTS: Granulomatous cutaneous involvement was demonstrated in 65 (15.3%) of 425 patients with systemic sarcoidosis. In 14 (22%) of the 65 patients, the cutaneous biopsy specimen showed foreign particles in polarized light. The skin lesions corresponded to 3 different clinical patterns: an admixture of papules and infiltration of previously undetected minute scars (n = 6); scar sarcoidosis (n = 4); and subcutaneous nodules (n = 4). The lesions were located most frequently in the extremities, involving the knees in 10 patients. CONCLUSIONS: The presence of polarizable foreign body material in granulomatous cutaneous lesions is not infrequent in patients with systemic sarcoidosis. Inoculation of foreign matter from a previous inapparent minor trauma may induce granuloma formation in individuals with sarcoidosis.

Serum amyloid A and high-density lipoprotein cholesterol: serum markers of inflammation in sarcoidosis and other systemic disorders.

Hypocholesterolemia has been observed in several inflammatory diseases such as rheumatoid arthritis, myeloproliferative disorders, systemic lupus erythematosus and sarcoidosis. Serum amyloid A is an acute-phase reactant that is related to the high-density lipoprotein cholesterol. This review discusses the relationship between the activation of the cells of the monocyte-macrophage system, determined by the serum amyloid A levels, and the lipid metabolism, measured as alterations in plasma lipoprotein concentrations. The mechanisms of this association during acute inflammation are also discussed in this review.

Löfgren's syndrome revisited: a study of 186 patients.

PURPOSE: To evaluate the clinical features, the results of noninvasive tests and biopsies, and the outcome of patients with Löfgren's syndrome. SUBJECTS AND METHODS: Patients diagnosed as having Löfgren's syndrome at a university hospital in Barcelona, Spain, from 1974 to 1996, were prospectively followed. Löfgren's syndrome was defined as the association of erythema nodosum or periarticular ankle inflammation with unilateral or bilateral hilar or right paratracheal lymphadenopathy. RESULTS: Löfgren's syndrome was diagnosed in 186 patients. The mean age was 37 +/- 11 years, and 157 (85%) were women. In 91 patients (49%), symptoms started during the spring (P < 0.0001). Erythema nodosum, periarticular ankle inflammation, or both were present at onset in 173 patients (93%). At the time of diagnosis, 161 patients (87%) had no respiratory symptoms; 151 (81%) had stage I abnormalities on chest radiograph, 29 (16%) stage II, and 6 (3%) stage 0. Five percent of patients had decreased forced vital capacity, and 15% had decreased carbon monoxide diffusing capacity. Extrathoracic involvement was infrequent. Serum angiotensin-converting enzyme levels were increased in 50% of patients. Gallium-67 scans showed hilar uptake in all the studied patients, but it yielded useful additional diagnostic information only in those with normal chest radiographs or with unilateral hilar lymphadenopathy. The diagnosis was proven with biopsy results in 63% of patients. None of the patients without histologic confirmation were subsequently found to have a diagnosis other than sarcoidosis. In the 133 patients who were followed for a mean of almost 5 years, 11 (8%) continued to have active disease, and 8 (6%) had several recurrences between 18 months and 20 years after a complete resolution. A normal serum angiotensin-converting enzyme level at diagnosis was associated with disease resolution without recurrence. CONCLUSION: Löfgren's syndrome is usually a self-limiting form of sarcoidosis. Histologic confirmation is not necessary in typical cases. In a small number of patients, the disease may remain active or recur long after its onset, although usually with mild organ dysfunction.

Vertebral and rib sarcoidosis: long-term clinical remission with methotrexate.

We describe a patient with bilateral hilar lymphadenopathy shown on a chest radiograph and supraclavicular lymphadenopathy. Biopsy of a supraclavicular lymph node showed non-caseating granulomas. A diagnosis of sarcoidosis was made and no treatment was given. One year later she complained of cervical and lumbar pain and decreasing strength of the right hand. Magnetic resonance imaging of the spine showed multiple lesions within the vertebral bodies of six vertebrae, and thoracic computed tomography showed partial destruction of the first right rib. A biopsy of the second lumbar vertebra demonstrated non-caseating granulomas. Corticosteroid treatment was unsuccessful and long-term remission of the symptoms was achieved with a weekly low dose of methotrexate.

Low levels of high density lipoprotein cholesterol in patients with active sarcoidosis.

OBJECTIVE: To determine lipoprotein abnormalities in patients diagnosed with sarcoidosis and their relation to disease activity. METHODS: We studied 90 patients with biopsy-proven sarcoidosis who had not been treated with corticosteroids (44 with active disease and 46 with inactive disease) and 147 control subjects. Sarcoidosis activity was evaluated by means of clinical, chest X-ray, gallium-67 scan, serum angiotensin converting enzyme (peptidyl-dipeptidase A) values, and pulmonary function tests. Analysis of lipoprotein metabolism included: serum cholesterol, low density lipoprotein (LDL)-cholesterol, high density lipoprotein (HDL)-cholesterol, HDL2-cholesterol, HDL3-cholesterol, apolipoprotein A-I, apolipoprotein B, and triglyceride concentrations. RESULTS: Patients with active sarcoidosis had significantly low HDL-cholesterol concentrations (1.15 +/- 0.27 mmol/l) as compared with inactive sarcoid patients (1.40 +/- 0.34 mmol/l) and with the healthy control subjects (1.49 +/- 0.34 mmol/l) (p = 0.00001). The decrease in the HDL-cholesterol concentrations seen in patients with active disease was due mainly to the cholesterol bound to HDL2 subfraction. Apolipoprotein A-I concentrations were significantly reduced in the patients with active disease (1.18 +/- 0.32 g/l) compared to the healthy controls (1.38 +/- 0.27 g/l) (p = 0.003). There were no significant differences in cholesterol, triglyceride, LDL-cholesterol or apolipoprotein B values among the three groups. Multivariate logistic regression analysis showed that HDL-cholesterol was the only variable independently associated with disease activity (Regression Coefficient b = -0.03; S.E. = 0.008; p = 0.0005). CONCLUSION: The decrease in HDL-cholesterol that is observed in patients with sarcoidosis is limited to those with active disease.

Nuclear imaging. 67Gallium, 201thallium, 18F-labeled fluoro-2-deoxy-D-glucose positron emission tomography.

67Gallium scan has been used for years in sarcoidosis as a marker of activity, a determiner of the extent and distribution of the disease, a diagnostic support, and an aid in therapeutic management. Because of its limited sensitivity and specificity for sarcoidosis, however, it is currently used mainly to assist in diagnosis in difficult cases, particularly in those with isolated extrathoracic sarcoidosis. The finding of the typical lambda or panda patterns supports the diagnosis and reinforces the indication to perform an appropriate biopsy or Kveim-Siltzbach test. In addition, the detection of clinically silent extrathoracic uptake may provide sites for biopsy. 67Gallium scans' routine use in the follow-up of pulmonary sarcoidosis under treatment has decreased because that is best accomplished by means of serial chest radiographs and PFT. 201Thallium scintigraphy studies the myocardial perfusion and is complementary to echocardiography and 24-hour electrocardiographic monitoring in the assessment of sarcoid cardiac involvement. It typically shows segmental areas of decreased uptake in the ventricular myocardium that disappear or decrease in size during stress or after intravenous administration of dipyridamole. That reverse distribution is not specific for cardiac sarcoidosis, however, because it may also occur in other cardiomyopathies. PET is based on the increase of glucose metabolism in inflamed tissues. It may have great potential to assess sarcoidosis activity, but it is still largely experimental and is not routinely employed.

Cutaneous involvement in sarcoidosis. Relationship to systemic disease.

Sarcoidosis is an antigen-mediated disease defined by granuloma formation in different organs. It involves mainly the mediastinal and peripheral lymph nodes, lungs, eyes, skin, liver, and spleen. Cutaneous lesions of sarcoidosis may be specific, showing histologically noncaseating granulomas, or nonspecific, most typically erythema nodosum. Frequently, both types of skin lesions are the means of presentation of the disease and may contribute to the diagnosis. A workup for systemic sarcoidosis should be undertaken in every patient with sarcoid cutaneous granulomas. Some types of cutaneous lesions have prognostic significance. Lupus pernio and plaques are associated with more severe systemic involvement and more chronic course, while erythema nodosum is the hallmark of acute and benign disease.

Periarticular ankle sarcoidosis: a variant of Löfgren's syndrome.

OBJECTIVE: To focus more attention on the syndrome characterized by periarticular ankle inflammation associated with bilateral hilar adenopathy--some authors regard it as a variant of the Löfgren syndrome, while other suggest it is a distinct clinical entity-- we present a series of 33 cases of periarticular ankle sarcoidosis. METHODS: Sarcoidosis was diagnosed in 330 patients at Bellvitge Hospital over a 20 year period. The medical charts of patients who presented with periarticular ankle inflammation (swelling of both ankles with acute inflammatory signs and preserved articular motion) were reviewed. RESULTS: 33 patients (10%) were identified. Periarticular ankle inflammation began during the spring in more than one-half (54.5%). The mean age was 33 years and patients were predominantly women (66.6%). Most cases (78.8%) were stage I on chest radiograph. All patients had thoracic gallium scans showing increased hilar/mediastinal uptake. Increased characteristic parotid, lacrimal, and/or submandibular uptake was found in 11 of 13 patients who had head scans. Four of 6 whose scans included the legs had bilateral ankle uptake. Erythema nodosum was present concomitantly in 36.3% of patients. No granulomas were found in 4 biopsies of periarticular ankle tissue. All 24 patients who were followed had inactive disease one year after diagnosis. CONCLUSION: The association of periarticular ankle inflammation with bilateral hilar adenopathy is an acute form of sarcoidosis that follows a benign course to total remission. It should be regarded as a variant of the Löfgren syndrome.

Sarcoidosis: chest radiograph screening of familial contacts.

On the basis of the hypothesis that sarcoidosis might be a transmissible disease, we thought a study of the familial contacts of known cases, as is done in tuberculosis, might reveal asymptomatic cases. In order to assess the efficiency of chest radiographs in detecting asymptomatic sarcoidosis in such contacts, we carried out a cross-sectional study. The population studied consisted of 66 index cases of sarcoidosis who were self-selected by their agreeing to take part in the study. Criteria were established with regard to the size of the family to be studied, along with three grades of intensity in the relationship between the index cases and their respective contacts. 976 familial contacts over 14 years of age, from grandparents to grandchildren of the index cases were identified, including nonconsanguineous contacts. 496 close contacts were asked to take part in the survey. Among these contacts there were 2 with a previous sarcoidosis, a prevalence of 4/1,000. 239 of these 496 contacts agreed to radiograph screening. Among those screened, no new cases of sarcoidosis were detected. We concluded that at present in our environment, with a low incidence and good prognosis, routine screening of relatives is not indicated. Nevertheless, longitudinal epidemiological studies designed to ascertain the pattern of transmission of the disease and including chest radiograph screening in a population with a high incidence of the disease could be of interest.

Excessive thoracic computed tomographic scanning in sarcoidosis.

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.

Interstitial nephritis in sarcoidosis: simultaneous multiorgan involvement.

Two cases of sarcoidosis with interstitial nephritis (lymphocytic and granulomatous) are described. In contrast to the majority of reported cases, patients simultaneously exhibited renal failure and multiple extrarenal manifestations, including bone marrow granulomas. Pretreatment gallium-67 gamma scan of the kidneys produced negative results. Patients were treated with steroids. Treatment resulted in a normal renal function after 1 year in the patient with lymphocytic interstitial nephritis. Renal function improved in the patient with granulomatous interstitial nephritis, and a second renal biopsy performed 13 months after diagnosis revealed granuloma disappearance and residual interstitial fibrosis. These cases provide evidence that interstitial nephritis in sarcoidosis may appear simultaneously with multiorgan involvement. The absence of gallium-67 renal intake does not guarantee that the disease is not active in the kidneys.

[The Kveim-Siltzbach test in sarcoidosis]. / La prueba de Kveim-Siltzbach en la sarcoidosis.

BACKGROUND: The Kveim-Siltzbach test has been widely used in the diagnosis of sarcoidosis. This reactive is currently available in the authors' hospitals. Previous experience with this test in the same centers was reviewed to know its diagnostic usefulness. The present is the first series described in Spain. METHODS: From 1977 to 1988 the Kveim-Siltzbach test was performed in 79 patients diagnosed or suspected of having sarcoidosis. The study was carried out as cooperation of the validation process of sarcoid spleen suspensions (lots K12, K12 1/2, K32, K41, K42, K42 1/2 and K50 of the Colindale antigen) prepared in the Standards Laboratory for Serological Reagents in the Royal Brompton Hospital in London. RESULTS: The results of test positivity were determined following the criteria established by Siltzbach. The global sensitivity of the Kveim-Siltzbach test was 78% (CI 95% = 67.8-86.9). Positivity ranged from 84% in subacute sarcoidosis to 61% in chronic sarcoidosis (p = 0.08). Likewise, it was higher in patients with radiologic stage I (84%) and II (81%) with respect to stage III (62%) or the cases with exclusive extrathoracic sarcoidosis (stage 0) (57%) (p = 0.11). No association was found between the Kveim-Siltzbach test positivity and the elevation in serum values of the angiotensin-converting enzyme (p = 0.575). CONCLUSIONS: In the present study the Kveim-Siltzbach test showed high sensitivity in the diagnosis of sarcoidosis. This fact, together with the high specificity observed in other studies, makes the test a very useful tool for the non-invasive diagnosis of sarcoidosis.

Combined portal and pulmonary hypertension in sarcoidosis.

A case is reported of a 48-year-old man previously diagnosed as having mitral valvular disease, who was admitted for evaluation of chronic cor pulmonale. Seven years before admission, an intraoperative liver biopsy had shown multiple noncaseating granulomas. The further course was characterized by progressive chronic intrahepatic cholestasis and portal hypertension. Right heart catheterization revealed a mean pulmonary artery pressure of 43 mm Hg and a normal wedge pressure (5 mm Hg). A perfusion lung scan was normal. Open lung biopsy demonstrated noncaseating granulomas and extensive pulmonary fibrosis. To our knowledge, only one case of sarcoidosis with combined portal and pulmonary hypertension has previously been described.

Multiple atypical bone involvement in sarcoidosis.

We describe a patient with right paratracheal and left hilar lymph nodes detected by chance on chest radiography that followed a spontaneous remission. However, a few months later she complained of multiple scalp nodules. Skull roentgenogram and computerized tomogram scan showed multiple osteolytic lesions with increased uptake in bone and gallium scans. Lytic lesions were also detected in her right mandibular bone and right clavicle. Noncaseating granulomas were demonstrated in skull and cervical lymph node biopsies.