Hemophagocytic lymphohistiocytosis in a patient with Sjögren's syndrome: case report and review.

Hemophagocytic lymphohistiocytosis (HLH) is a very rare syndrome with a mortality up to 95% of cases if not treated. It is characterised by an excessive activation of the immune system that leads to a disproportionate and destructive inflammatory response. The high mortality rates are in part due to a delay in the diagnosis, and therefore clinicians must maintain a high index of suspicion. When the treatment is started early, the survival rate reaches around 55% of cases. HLH usually presents with persistent fever, pancytopenia, and organomegaly and is associated with very high levels of serum ferritin. In this manuscript, we present the case of a patient with primary Sjögren's syndrome who developed HLH after an acute infection by Cytomegalovirus. We will describe and discuss the pathogenesis, differential diagnosis and a pragmatic approach to the treatment for this critically important and, when diagnosed early, potentially curable syndrome.

Atlas-based knee osteophyte assessment with ultrasonography and radiography: relationship to arthroscopic degeneration of articular cartilage.

OBJECTIVES: To investigate intra- and inter-reader agreement of ultrasonography (US) and conventional radiography (CR) for the evaluation of osteophyte presence and size within the tibiofemoral joint. In addition, to correlate these findings with arthroscopic degeneration of the articular cartilage. METHOD: Forty adult patients with knee pain were enrolled in this study. Knee CR and US scanning of the medial and lateral bone margins were performed on all patients. A novel atlas for the US grading of knee osteophytes was used in the evaluation. The number and size of the osteophytes were evaluated semi-quantitatively in two rounds from both the CR images (four readers) and the US images (14 readers). The Noyes grading system was used for the evaluation of arthroscopic degeneration of the articular cartilage in 26 patients. RESULTS: On average, intra- and inter-reader US and CR agreement was substantial and comparable to each other (κ = 0.60-0.72). US detected more osteophytes than CR at both the medial (65% vs. 48%) and lateral (70% vs. 60%) compartments. A statistically significant correlation between CR- or US-based osteophyte and arthroscopy grades was observed only for US at the medial compartment (rs = 0.747, p < 0.001). CONCLUSIONS: The detection of knee osteophytes using the novel US atlas is as reproducible as reading conventional radiographs. US is more sensitive to detect knee osteophytes than CR. Furthermore, osteophytes detected with US correlate significantly with arthroscopic cartilage changes at the medial knee compartment whereas those detected by CR do not.

Juvenile, adult and late-onset systemic lupus erythematosus: a long term follow-up study from a geographic and ethnically homogeneous population.

OBJECTIVES: This paper aims to identify clinical and serological differences, damage accrual and mortality, in juvenile, adult and late-onset SLE. METHODS: We conducted our study with patients fulfilling SLE classification criteria taken from the Hospital Gregorio Marañon Autoimmune Systemic Rheumatic Diseases' Registry (1986 to 2012). Clinical characteristics, laboratory data and therapies used during the course of the disease were analysed with patients divided into 3 groups: juvenile-onset (≤ 18 years), adult-onset (19-50) and late onset (>50 years). RESULTS: Four hundred and forty-five patients were included. Renal disease and cutaneous manifestations were more frequent in the juvenile-onset group at disease onset. During follow-up, juvenile-onset group presented a higher incidence of renal disease, malar rash, Raynaud's phenomenon, cutaneous vasculitis, and neuropsychiatric manifestations than the other two groups. Arthritis and lymphopoenia were more frequent in the adult-onset group. Arterial hypertension and neoplasm were more frequent in the late-onset group. Low serum complement, anti-dsDNA, anti-U1RNP and anti-Sm antibodies were more common in the juvenile-onset group. Patients with late-onset SLE had more damage accrual. Thirty-seven patients (8.3%) died during the study. All-cause mortality was significantly higher in the late-onset group. Age at disease onset >50 years was an independent risk factor for damage accrual (OR, 2.2; 95%CI, 1.1-4.6; p=0.029) and mortality (OR, 2.6; 95%CI, 1.1-6.3; p=0.03). CONCLUSIONS: We found significant differences in clinical and serological profiles between juvenile, adult and late-onset SLE. The most significant of which was a higher prevalence of neuropsychiatric and renal complications as well as different autoantibody signatures for the juvenile-onset group.

The reliability of musculoskeletal ultrasound in the detection of cartilage abnormalities at the metacarpo-phalangeal joints.

OBJECTIVE: To assess the reliability of ultrasound (US) in detecting cartilage abnormalities at the metacarpo-phalangeal (MCP) joints in people with cartilage pathology. METHODS: Nine expert ultrasonographers initially achieved consensus on definitions and scanning protocols. They then examined the second to fifth MCP joints of the dominant hand of eight people with hand osteoarthritis (OA). US examinations were conducted in two rounds, with independent blinded evaluations of cartilage lesions. Global cartilage abnormalities were assessed by applying a dichotomous (presence/absence) score; in addition, the following lesions were evaluated using the same scoring system: loss of anechoic structure and/or thinning of the cartilage layer, and irregularities and/or loss of sharpness of at least one cartilage margin. Reliability was assessed using kappa (k) coefficients. RESULTS: Thirty-two joints were examined. Intra-observer k values ranged from 0.52 to 1 for global cartilage abnormalities; k values ranged from 0.54 to 0.94 for loss of anechoic structure and/or thinning of cartilage layer and from 0.59 to 1 for irregularities and/or loss of sharpness of at least one cartilage margin. Values of k for inter-observer reliability were 0.80 for global cartilage abnormalities, 0.62 for loss of anechoic structure and/or thinning of cartilage layer, and 0.39 for irregularities and/or loss of sharpness of at least one cartilage margin. CONCLUSION: US is a reliable imaging modality for the detection of cartilage abnormalities in patients with cartilage pathology in the MCP joints. The analysis of specific cartilage measures showed more variable results that may be improved by modifying definitions and further standardization of US techniques.

Assessing the intra- and inter-reader reliability of dynamic ultrasound images in power Doppler ultrasonography.

OBJECTIVE: To assess the intra-reader and inter-reader reliabilities of interpreting ultrasonography by several experts using video clips. METHOD: 99 video clips of healthy and rheumatic joints were recorded and delivered to 17 physician sonographers in two rounds. The intra-reader and inter-reader reliabilities of interpreting the ultrasound results were calculated using a dichotomous system (normal/abnormal) and a graded semiquantitative scoring system. RESULTS: The video reading method worked well. 70% of the readers could classify at least 70% of the cases correctly as normal or abnormal. The distribution of readers answering correctly was wide. The most difficult joints to assess were the elbow, wrist, metacarpophalangeal (MCP) and knee joints. The intra-reader and inter-reader agreements on interpreting dynamic ultrasound images as normal or abnormal, as well as detecting and scoring a Doppler signal were moderate to good (kappa = 0.52-0.82). CONCLUSIONS: Dynamic image assessment (video clips) can be used as an alternative method in ultrasonography reliability studies. The intra-reader and inter-reader reliabilities of ultrasonography in dynamic image reading are acceptable, but more definitions and training are needed to improve sonographic reproducibility.

Ultrasonographic findings in knee osteoarthritis: a comparative study with clinical and radiographic assessment.

OBJECTIVE: To compare ultrasonographic (US) findings with clinical and radiographic assessment in knee osteoarthritis (OA). METHODS: Fifty patients with primary knee OA were studied. Clinical assessment of both knees was performed by the same rheumatologist who recorded a visual analogue scale (VAS) for pain (VASP). All patients underwent a US examination of their knees by a second blinded rheumatologist. Weight-bearing anteroposterior and lateral knee radiographs were read by a third blinded rheumatologist who assessed the Kellgren and Lawrence (K-L) grade, the femorotibial (FT) space width and the presence of patello-femoral degenerative signs. RESULTS: Forty patients had bilateral symptomatic knee OA and 10 unilateral symptomatic OA. All knees showed radiographic FT degenerative signs. US findings in symptomatic knees were effusion (47%), protrusion of the medial meniscus (MMP) with displacement of the medial collateral ligament (MCLD) (61%) and Baker's cyst (22%). US effusion, MMP and MCLD were associated with a significantly higher VAS score for pain (P<0.05). MMP was associated with medial FT space width (P<0.05). Patients who had a difference between VAS score for pain in each knee greater than 30 (28 patients) showed significantly more unilateral effusion, MMP, MCLD and worse K-L grade in the more symptomatic knee than those with a difference lesser than 30 (22 patients). CONCLUSION: Knee effusion and MMP with MCLD are associated with pain in knee OA. In addition, MMP may contribute to the radiographic medial FT space narrowing. We propose US for assessing periarticular and intraarticular abnormalities involved in the pathophysiology of knee OA.

LH receptor in testosterone-producing ovarian tumor. In vivo and in vitro HCG-stimulated testosterone production.

The aim of the present work is to report in vivo and in vitro hormonal studies performed on a 71 year old virilized woman due to a Leydig cell tumor of the ovary. Testosterone (T), Cortisol, DHEA(s) and ACTH concentrations were determined in blood samples taken every 4 h throughout 24 h previous to surgery. T average concentration from the 6 samples was 3.3 ng/ml (range: 2.5-4.2 ng/ml). DHEA(s) was normal; Cortisol and ACTH levels were normal and their circadian rhythms were present. T value obtained during Dexamethasone administration (2 mg daily/3 days) was 2.4 ng/ml. This value was significantly higher than those obtained from postcorticoid normal women (0.3 +/- 0.1 ng/ml), suggesting an extraadrenal source. T concentration was 5.4, 6.0 and 6.6 ng/ml at 24, 48 and 72 h after hCG injection (5000 IU). After tumor removal, T values decreased progressively up to 6.0 ng/ml values, 5 days later, and remained steady on the following days. The studies performed in vitro were: determination of T in the tumor cytosol, specific binding of LH to ovarian tumor cell membrane fraction and T production in tissue culture in both with and without added hCG conditions. Normal ovarian tissue from the same patient under similar experimental conditions was used as control. The T concentration expressed as ng/mg of protein in the tumor and normal ovarian cytosol was 9.1 and 1.1, respectively. Scatchard analysis of specific 125I-hCG binding to tumor and normal ovarian cells indicated 53 pg and 28 pg of labeled hCG bound/mg of membrane protein, respectively, suggesting that this Leydig cell tumor of the ovary contained LH (hCG) receptors. The amounts of T, expressed as ng/mg of tissue/6 days, generated by tumoral and normal tissue ere 4.1 and 0.3, respectively. The addition of hCG elicited a response of 6.3 and 0.6 ng/mg protein/6 days in both preparation, respectively. These results demonstrate in vivo and in vitro hCG-stimulated T production in this particularly masculinizing ovarian tumor and suggest tumoral LH dependence.