Diagnostic yield of the Kveim test in sarcoidosis patients.

BACKGROUND AND AIM: Sarcoidosis is a granulomatous disorder of unknown etiology characterized by the existence of non-caseating granulomatous inflammation. Diagnosis can be challenging due to the presence of comprehensive clinical, laboratory, and radiologic manifestations. We have evaluated the diagnostic yield of the Kveim test and compared this test with the other conventional laboratory modalities. Our aim was to reach the highest level of diagnostic confidence acknowledging the absolute uncertainty in diagnosis with the current diagnostic enterprises. METHODS: Medical records of 300 sarcoidosis patients were reviewed. Patients were classified into two categories as the conventional laboratory and the Kveim test group to compare the diagnostic yield. RESULTS: Sensitivity of the Kveim test was 76.4% while the conventional laboratory tests provided a 64% diagnostic yield.  The conventional tests had a low diagnostic rate in the early disease stages. Kveim test revealed a high yield diagnosis for all stages of sarcoidosis. Integrated assessment of the two modalities reached a 96.8% sensitivity and a 94,6% specificity. CONCLUSIONS: Conventional laboratory modalities were useful for the assessment of disease activity and identification of organ involvement. Kveim test revealed a significant diagnostic yield for all stages of sarcoidosis. The lowest output was achieved in stage IV patients due to the waning of active granulomatous inflammation.  The highest diagnostic sensitivity was obtained by an integrated analysis of the conventional laboratory and the Kveim test results for all aspects of sarcoidosis.

Diagnostic utility of 68Ga-citrate and 18FDG PET/CT in sarcoidosis patients.

Sarcoidosis is a chronic granulomatous disease of unknown etiology. The disease  most commonly involves the lungs and the mediastinal lymph nodes while extrapulmonary organs such as the skin, eye, liver or spleen may also be comprised. Many imaging modalities have been used for the clinical evaluation of sarcoidosis patients but all have been found to have certain drawbacks for a reliable identification assessment due to the equivocal diagnostic results.  This case series was designed to determine the clinical trenchancy of simultaneous 68Ga citrate PET/CT [Positron emission tomography with 68Ga citrate (68Ga citrate PET/CT)] and 18F-FDG PET/CT [Positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose integrated with computed tomography (18F-FDG PET/CT)] imaging in sarcoidosis patients. The main goal of the study was to evaluate sarcoidosis with respect to disease activity and organ involvement. A total of eight sarcoidosis patients with a comorbid disease suspicion were included in the study. Conventional clinical parameters used for  the diagnosis and the activity of sarcoidosis including CT [Computed tomography (CT)] were compared with the 68Ga-citrate PET/CT findings. Concurrent 18F-FDG PET/CT was performed to verify the granulomatous inflammation of sarcoidosis and to determine coexisting malignant or other inflammatory diseases. Our study results revealed that 68Ga citrate PET/CT imaging appears to be highly useful for the diagnosis, activity assessment and extrapulmonary organ involvement in sarcoidosis. Another crucial finding was the detection of extrapulmonary organ disease that are exceptionally involved, almost inaccessible by biopsy and that could not be otherwise displayed by other conventional imaging modalities. The third hallmark was the identification of a clinically asymptomatic and occult malignancy accompanying sarcoidosis that would not be revealed in any way if synchronous 18FDG PET/CT had not been performed. Simultaneous application of 68Ga citrate and 18FDG PET/CT may provide extremely useful data for the clinical evaluation of sarcoidosis patients in terms of the primary disease diagnosis, activity state, extrapulmonary organ involvement unachievable for biopsy and the clinically occult malignant disorders.

Finger clubbing and cirrhosis in a sarcoidosis patient.

Sarcoidosis is a multisystem granulomatous inflammatory disorder frequently affecting the lungs, but also the liver, along with cirrhosis and portal hypertension occurring in less than 1% of the patients. A 56-year-old female presented with dyspnea, abdominal and leg swelling. Physical examination revealed finger clubbing, ascites and pretibial edema. Chest CT revealed diffuse micronodular opacities in both lungs without any enlarged thoracic lymph nodes. PFTs and DLCO/VA were moderately decreased. Transbronchial biopsy revealed non-caseified granulomas compatible with sarcoidosis. Serologic markers for infectious and autoimmune hepatitis were negative. Liver biopsy showed non-caseating granulomas, severe hepatitis and fibrosis. Stool, urinary analysis and antibodies for Schistosoma infection were negative. Final diagnosis was cirrhosis associated with stage III sarcoidosis. We report a case of sarcoidosis complicated by cirrhosis and portal hypertension with finger clubbing. Clinicians should bear in mind that cirrhosis, portal hypertension and clubbing may arise as the initial manifestations of sarcoidosis.

Carpal tunnel syndrome associated with sarcoidosis in identical twin patients.

Sarcoidosis is a multisystemic disease that may lead to neurologic complications in 10% of the patients. Carpal tunnel syndrome is very rare in sarcoidosis. We present two identical twin sarcoidosis patients with carpal tunnel syndrome. A number of factors may cause carpal tunnel syndrome like wrist anatomy, occupation, diabetes, rheumatoid arthritis, pregnancy and renal failure. Although the above factors do not directly cause carpal tunnel syndrome, they may increase your chances of developing or aggravate median nerve damage as it is in sarcoidosis. Sarcoidosis relevant neuropathy and granulomas may be the primary mechanism of sarcoidosis associated carpal tunnel syndrome. Although rare, carpal tunnel syndrome may be a feature of sarcoidosis that may lead to irreversible damage in cases of delayed diagnosis. The presence of this syndrome in identical twin patients may shed light into the pathogenesis and the genetic transmission of sarcoidosis with the associated carpal tunnel syndrome.

Clinical and prognostic significance of muscle biopsy in sarcoidosis.

The main objective of this study was to evaluate the influence of muscle involvement on the clinical features, prognostic outcome, extrapulmonary organ, and endobronchial involvement in sarcoidosis patients. The second aim was to assess the diagnostic yield of muscle biopsy for the histopathologic identification of sarcoidosis.  Fifty sarcoidosis patients participated in the study. The patients were classified into two groups according to the histopathologic presence of non-caseating granulomatous inflammatory pattern of the muscle biopsy samples and were evaluated retrospectively in regard to clinical features, prognosis, extrapulmonary, and endobronchial disease involvement. Pathologic examination of the muscle biopsy samples revealed non-caseating granulomas in eighteen and myositis in seven patients compatible with sarcoidosis. The diagnostic yield of muscle biopsy for demonstrating non-caseating granulomatous inflammation was fifty percent. Patients with muscle sarcoidosis showed a worse prognosis and a more severe extrapulmonary organ involvement than the patients without muscle disease. Muscle biopsy was not statistically significant to delineate diffuse endobronchial involvement while it was suggestive for endobronchial disease clinically. The results of our study reveal that muscle biopsy appears to be a useful diagnostic tool along with its safety and easy clinical applicability. It is a rewarding utility to predict the prognostic outcome and extrapulmonary involvement in sarcoidosis patients. Positive biopsy on the other hand confirms the identification of sarcoidosis in patients with single organ involvement carrying an equivocal diagnostic clinical pattern. Muscle biopsy may be considered as the initial step for the final diagnosis of sarcoidosis in such cases.

Association of HLA antigens with the clinical course of sarcoidosis and familial disease.

Patients with sarcoidosis usually have a benign course and a favourable prognosis. Although spontaneous remission is common, a progressive disease with a severe prognosis occurs in a small but significant number of patients. The aim of this study was to evaluate the potential significance of HLA antigens as a clinical marker on the outcome of sarcoidosis patients. We conducted a retrospective cohort study for HLA class I and II allels in 74 sarcoidosis patients and 72 healthy transplant donors. Bronchoscopy and bronchial biopsies were performed in each patient. Two or more positive bronchial biopsy samples revealing granulomatous inflammation was defined as diffuse while one positive biopsy sample was considered as limited endobronchial disease. Three or more extrapulmonary organ involvement was denoted as severe extrapulmonary disease. The patients were followed-up at least for eight years.  Incidence of progressive disease was significantly high in patients with positive HLA-DRB1*07, DRB1*14 (p<0.05) and DRB1*15 (p <0.001) allels. HLA-DRB1*14 and DRB1*15 were associated with severe extrapulmonary organ involvement (p<0.001). HLA-DRB1 *14 (p<0.05) and DRB1*15 (p<0.001) were significantly more frequent in patients with diffuse endobronchial involvement. Incidence of familial disease was 14.8% with a 6.7% identical HLA typing. Presence of HLA class I and II allels may influence the severity and prognosis of sarcoidosis significantly. Apart from defining genetic susceptibility, HLA class I and class II allels appear to be relevant and crucial markers for the to predict the clinical outcome of sarcoidosis. Distinct heterogenity of sarcoidosis may arise from the particular presence of different allels in invidual patients.

Clinical features and prognostic significance of splenic involvement in sarcoidosis.

Sarcoidosis is a systemic disease characterized by noncasefied granulomas in various organs. Incidence of splenic disease is variable and is reported to occur in 6.7 to 77 percent of the patients. Firm data establishing the clinical features and the association of splenic involvement with prognosis in sarcoidosis is scant. The aim of our study was to investigate the clinical features and the consequence of splenic involvement on the prognostic outcome of sarcoidosis patients. We evaluated the clinical and laboratory findings in 82 sarcoidosis patients. Forty-two patients with splenic involvement were compared to 48 sarcoidosis patients without splenic disease in regard to laboratory findings, endobronchial disease, extrapulmonary organ involvement, and prognosis. Lung biopsy sample was considered positive if it demonstrated noncaseating granulomas with negative fungal and mycobacterial cultures. Splenic sarcoidosis was identified by ultrasound or computed tomography and was designated as limited, diffuse or without splenic involvement. Extrapulmonary organ sarcoidosis was classified as extensive and limited. Endobronchial disease was categorized as limited or diffuse involvement. The most commonly comprised organ was lung in 95% of the cases followed by lymph nodes, skin, eye, spleen and liver in the order of frequency. Splenic disease was diffuse in 22 patients. Of these patients, 14 had extensive extrapulmonary organ involvement while 16 had diffuse endobronchial disease. There was no significant difference between the three groups for FEV1, FVC, TLC, DLCO/VA, serum and 24h urinary calcium levels. Serum ACE was higher in patients with diffuse splenic involvement (p<0.001). Incidence of persistent chronic disease was significantly higher (p<0.001) in patients with diffuse splenic sarcoidosis. Extensive extrapulmonary organ involvement and diffuse endobronchial disease were more common (p<0.001) in this group. Extensive extrapulmonary organ involvement and diffuse endobronchial disease were more frequent in patients with diffuse splenic sarcoidosis. Patients with diffuse splenic granulomas had a worse prognosis than the patients without splenic involvement or patients with limited splenic disease. Diffuse splenic involvement emerges to be a significant risk factor for persistent chronic sarcoidosis. Extensive granuloma burden in an organ may be the decisive clinical marker for the prognostic outcome of sarcoidosis patients.

Diagnosis of cutaneous sarcoidosis; clinical and the prognostic significance of skin lesions.

BACKGROUND: Sarcoidosis is a systemic disease characterized by the formation of noncaseating granulomas in various tissues. Cutaneous involvement occurs in 20 to 35 percent of the patients and may be the initial manifestation of the disease. Our study was performed to discriminate the clinical, laboratory, and prognostic differences between patients with specific and nonspecific cutaneous involvement. The second aim was to asses the diagnostic usefulness of punch biopsy in sarcoidosis. METHODS: The clinical, laboratory, pathological features, and skin biopsy results of 120 patients with cutaneous sarcoidosis were evaluated. The patients fulfilled clinical, radiologic or both features of sarcoidosis supported by the histopathologic evidence of noncaseating granulomas.Skin involvement was the initial finding in 30% of the patients. Erythema nodosum and lupus pernio were the most common skin lesions. Almost all of the patients with LP were either stage 0 or 1. Respiratory symptoms occurred in 72.2% of the patients with specific skin involvement. BronchoalveolarLavage (BAL) lymphocytosis, high ratio of CD4/CD8 and elevated serum Angiotensin Converting Enzyme (ACE) were more frequent in patients with specific cutaneous lesions. The frequency of progressive disease was significantly higher in this group. Punch skin biopsy was diagnostic in 81.6% of the patients with a complication rate of 4%. CONCLUSIONS: Specific cutaneous lesions along with BAL lymphocytosis, high CD4/CD8 ratio and elevated serum ACE levels may be predictors of progressive disease in sarcoidosis. Punch biopsy is a simple technique with a high diagnostic yield and a low complication rate for cutaneous sarcoidosis.

Analysis of HLA antigens in Turkish sarcoidosis patients.

BACKGROUND: Sarcoidosis is a systemic granulomatous disorder associated with high CD4+cell activity, without any detectable pathogen. Clustering in families occurs, and the existence of a genetic predisposition to sarcoidosis is widely accepted. There are differences among different ethnic groups. METHODS: We studied HLA polymorphisms in 64 Turkish patients with biopsy proven sarcoidosis. The control group was taken of 160 donor candidates of kidney transplantation within the same period. RESULTS: Fifty-one patients were female, and 13 were male. The mean age was 39 +/- 6.1 years. Frequency of HLA A2, A9, A24 (9), A25, A69 (28), B12, B22, B38, B49 (21), DR4, and DR14 antigens were significantly higher, and frequencies of HLA B7 and DR7 were significantly less in sarcoidosis patients. Clustering in some families were also noted in our study. CONCLUSIONS: This study implies a genetic predisposition to sarcoidosis in the Turkish population. Clustering in some families should be kept in mind.

Mediterranean spotted fever: a review of fifteen cases.

We aimed to determine the following things: the frequency of patients with Mediterranean spotted fever (MSF) during the last 10 years among those patients admitted with fever and rash, their clinical features, and the factors predicting the diagnosis of MSF among patients admitted with fever and rash. Between 1993-2002, the files of all patients admitted to our hospital with fever and rash were collected. The clinical features and serologic results of the patients diagnosed with MSF were further investigated. The diagnosis of MSF was established by epidemiological and clinical features and also by the clinical response within 2 days after doxycycline treatment. During the previous 10 years, 140 patients were admitted with fever and rash, and 15 (10%; four females, 11 males; mean age: 41 years; range: 17-70) of them were diagnosed with MSF. Clinical features were as follows: fever (100%), rash (100%), myalgia and/or arthralgia (93%), headache (87%), petechiae (27%), tache noire (13%), leucocytosis (74%), thrombocytopenia (33%), and accelerated erythrocyte sedimentation rate (100%). In nine of these patients, the diagnosis of MSF was established by epidemiological and clinical features and was confirmed by serologic studies. As a complication, one patient developed facial paralysis. Six (40%) were given several antibiotics. In conclusion, MSF should be considered in the differential diagnosis when a patient is admitted with fever, maculopapular rash, headache, myalgia and/or arthralgia, especially in spring, summer, or autumn.

Reactive hypoglycemia in lean young women with PCOS and correlations with insulin sensitivity and with beta cell function.

Reactive hypoglycemia (RH), which is a postprandial hypoglycemic state, occurs within 2-5 h after food intake. It is classified as idiopathic, alimentary, or diabetic reactive hypoglycemia. We studied the incidence of reactive hypoglycemia and looked for any correlations between it and the presence of insulin sensitivity and/or beta cell function in young lean polycystic ovary syndrome (PCOS) patients. This study was designed as a cross-sectional study in 64 lean young women with PCOS (BMI < or = 25 kg/m2). Various indices of insulin sensitivity and beta cell function derived from the oral glucose tolerance test (OGTT) results were used. We found the rate of RH to be 50% in lean young women with PCOS. DHEA-S and PRL levels were found to be lower in subjects with RH (P < 0.05 and P > 0.05, respectively). Beta cell function indices such as the insulinogenic index (at 120 min), CIR (at 120 min) and HOMA beta cell index were found to be insignificantly higher in the RH group than the nonreactive hypoglycemia (NRH) group. The 4 h glucose level, but not the 3 h glucose level, was significantly correlated with insulin resistance indices, such as fasting insulin level, HOMA-IR, Quicky index, and FIRI in the RH group. Significantly decreased DHEA-S levels were an interesting finding. In conclusion, there is an urgent need to investigate RH in lean young women with PCOS. Our results indicate that more definite insulin resistance occurs in subjects with RH in the fourth hour of the OGTT than those with RH in the third hour. In addition, RH in the fourth hour together with a low DHEA-S level may be predictive of future diabetes in young women with PCOS even when they are not obese.

The sensitivity and specificity of Brucella agglutination tests.

Brucellosis is a systemic infectious disease caused by Gram-negative bacilli, the genus Brucella, and clinical features are diverse. Therefore, several infectious and non-infectious diseases are considered in its differential diagnosis. In this study, we aimed to determine the positivity rate of Brucella agglutination tests in the culture-positive brucellosis and in diseases mimicking brucellosis clinically.Thirty patients with culture-positive brucellosis, and 280 patients with the diseases mimicking brucellosis clinically (20 with miliary tuberculosis, 33 with malaria, 20 with typhoid fever, 20 with adult-onset Still's disease, 47 with systemic lupus erythematosus, 50 with rheumatoid arthritis, 27 with sarcoidosis, and 63 with active lymphoma) were included in the study. Brucella agglutination tests (Rose-Bengal and Wright) were studied in serum samples of these 310 patients. Both Rose-Bengal and Wright tests (the latter in a titer of 1/160 or higher) were positive in all patients with brucellosis. For the other diseases, the test was slightly positive (1/40) in one patient with malaria and another with non-Hodgkin's lymphoma, and weakly positive (1/20) in a patient with typhoid fever. It remained negative in the remaining. In conclusion, agglutination tests currently used in the diagnosis of brucellosis are very sensitive and specific. Brucellosis can be effectively excluded from the diseases having similar clinical features by the use of agglutination tests.

Comparison of various simple insulin sensitivity and beta-cell function indices in lean hyperandrogenemic and normoandrogenemic young hirsute women.

OBJECTIVE: To assess and compare various simple insulin sensitivity and beta-cell function indices in lean, hirsute, young women. DESIGN: Prospective study. SETTING: Departments of endocrinology and metabolism at a university and a state hospital. PATIENT(S): Seventy-one hirsute young women were classified as hyperandrogenemic or normoandrogenemic. MAIN OUTCOME MEASURE(S): Insulin sensitivity and beta-cell function indices derived from a single sample and an oral glucose tolerance test (OGTT). RESULT(S): Lean hyperandrogenemic hirsute women have insulin resistance and increased beta-cell function. The most sensitive indices of insulin resistance were total and 1-hour and 2-hour post-challenge insulin levels during OGTT. When a cut-off value of 3.2 or greater for homeostasis model assessment of insulin resistance (HOMA-IR) was accepted, 46% of hyperandrogenemic women and 30% of normoandrogenemic women were insulin resistant. Fasting insulin level was best correlated with the fasting insulin resistance index, HOMA-IR, and Quicky index. The HOMA-IR was best correlated with fasting insulin level and the hepatic insulin sensitivity index (ISI(HOMA)). CONCLUSION(S): Insulin levels based on OGTT are the most useful index of insulin resistance and beta-cell function index in hirsute women. The HOMA-IR may be a proposed global test for insulin resistance; it correlated well with both OGTT-derived insulin resistance and beta-cell function indices and with global insulin resistance indices derived from a single sample (such as ISI (HOMA), Quicky index, FIRI(-1), fasting Belfiore index, and glucose/insulin ratio).

Acute viral cholecystitis due to hepatitis A virus infection.

Acute hepatitis A virus (HAV) infection is frequent in developing countries. Although some gallbladder abnormalities are defined during the course, an acute cholecystitis is extremely rare. We here report 2 additional cases of cholecystitis due to acute HAV infection and review the previously reported 2 cases. One of our patients was admitted with jaundice and a suspicious portal mass with a presumed diagnosis of cholagiocarcinoma. The other presented with jaundice, abdominal pain, and constitutional symptoms. Both patients were planned to be operated on. During the follow-up, absence of fever, leukocytosis, acute-phase protein response, and calculus in biliary system were against the diagnosis of a bacterial cholecystitis. Moreover the course of cholecystitis was closely parallel to that of the HAV infection. Both patients were managed conservatively. It was concluded that rare, acute viral cholecystitis can develop during the course of acute HAV infection.

Primary antiphospholipid syndrome: a cause of fever of unknown origin.

Antiphospholipid syndrome (APS) is defined as the occurrence of thrombosis, recurrent miscarriage, or both in association with laboratory evidence of persistent antiphospholipid antibodies. Owing to protean manifestations and laboratory studies, the diagnosis may be difficult. Because the other signs and symptoms of thrombosis are predominant, prolonged fever is not usually the main clinical finding. We describe a patient who presented with fever of unknown origin (FUO) and was found to have thromboses of the splenic vein, the superior mesenteric vein, and the portal vein due to the primary antiphospholipid syndrome. We also reviewed the medical literature (Medline 1966-2001), including the main FUO series of the previous 40 years, and laparotomy series for FUO. We conclude that although very rare, primary APS and thrombosis may present with FUO. APS should be considered in the differential diagnosis of prolonged fever associated with thrombosis.