Diffuse Large B Cell Lymphoma Mimicking Granulomatosis with Polyangiitis.

In a patient with systemic multiorgan disease with overlapping features, the differential diagnosis included infectious diseases, malignancies, and systemic autoimmune or inflammatory diseases. We present an unusual case of a young male with B cell lymphoma who presented with symptoms mimicking systemic vasculitis and review the existing literature.

Long-term follow-up of patients with scleroderma interstitial lung disease treated with intravenous cyclophosphamide pulse therapy: a single-center experience.

BACKGROUND: Scleroderma lung disease (ILD-SSc) is treated mainly with cyclophosphamide (CYC). The effectiveness of CYC was judged after 12-24 months in most reports. OBJECTIVES: To analyze the effect of monthly intravenous CYC on pulmonary function tests including forced vital capacity (FVC) and diffusing lung capacity (DLCO), as well as Rodnan skin score (mRSS), during long-term follow-up. METHODS: We retrospectively collected the data on 26 ILD-SSc patients who began CYC treatments before 2007. Changes in FVC, DLCO and mRSS before treatment, and at 1,4 and 7 years after completion of at least six monthly intravenous CYC treatments for ILD-SSc were analyzed. RESULTS: Mean cumulative CYC dose was 8.91 ± 3.25 G. More than 30% reduction in FVC (0%, 8%, and 31% of patients), DLCO (15%, 23%, 31%), and mRSS (31%, 54%, 62%) at years 1, 4 and 7 was registered. During the years 0-4 and 4-7, annual changes in FVC, DLCO and mRSS were 3.2 vs. 0.42% (P < 0.040), 4.6 vs. 0.89% (P < 0.001), and 1.8 vs. 0.2 (P = 0.002). The greatest annual FVC and DLCO reduction over the first 4 years correlated with mortality (P = 0.022). There were no differences in the main variables regarding doses of CYC (< 6 G and > 6 G). CONCLUSIONS: In patients with ILD-SSc, CYC stabilized the reduction of FVC during treatment, but this effect was not persistent. The vascular characteristic of ILD-SSc (DLCO) was not affected by CYC treatment. CYC rapidly improved the mRSS. This effect could be achieved with at least 6 G of CYC. Higher rates of annual reduction in FVC and DLCO in the first 4 years indicate the narrow window of opportunity and raise the question regarding ongoing immunosuppression following CYC infusions.

Ultrasound investigation of the glenohumeral joint by anterior access in patients with rheumatoid arthritis and healthy controls.

BACKGROUND: The aim of this study was to measure glenohumeral joint (GHJ) parameters via the anterior access through ultrasound and to compare to data from posterior and inferior accesses. MATERIAL AND METHODS: Twenty healthy controls (M: F=15: 5, aged 45.1±11.2 years) and 16 patients (M: F=5: 11, aged 54.6±14.7 years) with active rheumatoid arthritis (RA) (DAS 28 4.6±1.2) were investigated (SonoSite-Titan). To make the GHJ visible on the anterior access, we used the original GHJ opening maneuver. The GHJ width was measured for every transducer position at 2 points. The positions were: posterior transversal, inferior longitudinal, anterior longitudinal along the articular line, anterior transversal upper, middle and lower. The joint width included thickness of cartilage plus synovial fluid/pannus. Rotator interval (RI) width and height (upper biceps channel) were measured. RESULTS: Our normal GHJ values by posterior and inferior accesses were within previously estimated values (<2 mm and <3 mm, respectively). We acquired the first values of GHJ width from the anterior access. The last were within a range of 0.7-1.7 mm for healthy controls. Patients with RA showed significantly enlarged joint cavities. RI was not inflamed. Posterior and inferior data of GHJ width were significantly correlated (p=0.01). The data did not correlate with anterior values (p=+0.44, p=-0.56). Synovitis was much more prominent in posterior, upper anterior transversal, and anterior longitudinal accesses. CONCLUSIONS: The GHJ may be visualized by anterior access using a special maneuver. Synovitis in the anterior region of the GHJ may develop at an independent rate. Anterior GHJ sonography may be complementary to the classic access.

Early repolarization: innocent or dangerous?

Electrocardiographic (ECG) findings of wide QRS complexes in right precordial leads with saddle ST elevation in patients with polyarthritis, palpitations and family history of syncope urged us to review early repolarization syndrome (ERS). ERS is commonly seen in young men. The main ECG features are as follows: wide spread concave ST-segment elevation, more in the precordial leads (usually V2-V4); notching or irregular contour of J point and prominent concordant T waves with large amplitude. ERS was historically considered as a benign ECG variant. In recent years, it has emerged as a marker for increased risk of sudden cardiac death. The purpose of this review was to describe the ECG manifestations of this syndrome and to review the literature concerning its arrhythmogenic potential. The authors found it important not only discussing the rate of ERS life threatening but also to reemphasize its differences from other syndromes. Some of the last are much more dangerous: acute myocardial infarction and Brugada syndrome. The tables will be helpful for physicians to distinguish ERS from other syndromes in patients with chest pain and ST elevation.

Trends of SAPHO therapy: should we be content?

The interventional studies with bone biopsy of the SAPHO lesions and microbiological investigation are a significant addition to a long range of publications showing an association of SAPHO with Propionibacterium acnes. Infectious agents isolated from SAPHO patients have merited special attention for many years. Their possible etiological role is supported by the pathogen isolation from different sites: anterior chest wall, spine, synovial fluid, bone tissue, and skin pustules. A range of pathogens have been found, including Staphylococcus aureus, Hemophilusparainfluenzae, actinomyces, and even Treponemapallidum. P. acnes is a much more frequent pathogen and plays a particular role. The article focus is to emphasize limited use of interventional method to verify infection ethology of SAPHO in publications last two years. Successful therapy may be really effective and eradicative on a basis of the pathogen identification.Randomized control studies are needed to confirm the effects of antibiotic therapy.

Large leg ulcers due to autoimmune diseases.

BACKGROUND: Large leg ulcers (LLU) may complicate autoimmune diseases. They pose a therapeutic challenge and are often resistant to treatment. To report three cases of autoimmune diseases complicated with LLU. CASE REPORT: Case 1. A 55-year old woman presented with long-standing painful LLU due to mixed connective tissue disease (MCTD). Biopsy from the ulcer edge showed small vessel vasculitis. IV methylprednisolone (MethP) 1 G/day, prednisolone (PR) 1mg/kg, monthly IV cyclophosphamide (CYC), cyclosporine (CyA) 100mg/day, IVIG 125G, ciprofloxacin+IV Iloprost+enoxaparin+aspirin (AAVAA), hyperbaric oxygen therapy (HO), maggot debridement and autologous skin transplantation were performed and the LLU healed. Case 2. A 45-year old women with MCTD developed multiple LLU's with non-specific inflammation by biopsy. MethP, PR, hydroxychloroquine (HCQ), azathioprine (AZA), CYC, IVIG, AAVAA failed. Treatment for underlying the LLU tibial osteomyelitis and addition of CyA was followed by the LLU healing. Case 3. A 20-year-old man with history of polyarteritis nodosa (PAN) developed painful LLU's due to small vessel vasculitis (biopsy). MethP, PR 1 mg/kg, CYC, CyA 100 mg/d, AAVAA failed. MRSA sepsis and relapse of systemic PAN developed. IV vancomycin, followed by ciprofloxacin, monthly IVIG (150 g/for 5 days) and infliximab (5 mg/kg) were instituted and the LLU's healed. CONCLUSIONS: LLU are extremely resistant to therapy. Combined use of multiple medications and services are needed for healing of LLU due to autoimmune diseases.

Sacroiliitis and severe disability due to isotretinoin therapy.

We report a case of acute sacroiliitis with severe disability after only 3 weeks of isotretinoin therapy with graduate reduction of pain, limitation and muscle incompetence after discontinuation of the drug and ACTH-depo injection and Ethodolac therapy. Naranjo probability scale indicated a probable relationship between isotretinoin therapy and bilateral sacroiliitis. We discussed possible mechanisms of sacroiliitis and disability due to isotretinoin treatment.

Arterio-venous shunts or low oxygen utilization?

An idea of arteriovenous shunts (AVS) was proposed for explanation of dynamic regulation of oxygenation and venous hyperoxia. A formula enabling calculation of AVS and real CO2 production has recently been derived by comparing data of arterial and venous blood gases. Regarding venous hyperoxia, there is a need to differentiate capillary to tissue transport defect (low oxygen utilisation-LOU) from AVS, which may exist simultaneously. The AVS may be associated with normal or relatively high oxygen utilization from the capillary vessels and increased CO2 production. AVS is proposed to carry protective and 'stealing' properties including renal, cardiac, and pulmonary hemodynamic. Calculations of the AVS may be important for dynamic assessment of vascular and metabolic status and in emergency medicine.

SAPHO syndrome: is a range of pathogen-associated rheumatic diseases extended?

SAPHO syndrome, representing a constellation of synovitis, acne, palmo-plantar pustulosis, hyperostosis, and osteitis, is now recognized as a distinct medical entity: a reactive infectious osteitis. Genetic, immunological, and bacterial mechanisms are implicated in the development of the disease. Diagnostic problems may arise due to non-complete manifestations of SAPHO: either acne and arthritis or acne and anterior wall osteitis with an unclear pustulosis history. The interventional study of Assmann et al. is a significant addition to a long range of publications showing an association of SAPHO with Propionibacterium acnes. Randomized control studies are needed to confirm the effects of antibiotic therapy.

Glucosamine sulfate--environmental antibacterial activity.

We have recently showed antibacterial activity against E. coli in vitro of a trademark Mega-Gluflex-containing glucosamine sulfate (GS) and chondroitin sulfate (CS). The purpose of this study was to examine the antibacterial activity of GS as a new trademark Arthryl (Manufacturer Rottapharm Ltd, Ireland; Distributor in Israel Rafa Laboratories Ltd) in vitro. We used cabbage and chicken broths and milk (every media of 20 ml) left opened for 1 week with and without Arthryl supplements 1,500 mg, the content of one package of the medication. A similar volume (20 ml) is ingested in taking the medication. Experiments with three repeatable results were taken for consideration. Arthryl inhibited environmental bacterial colonies' growth in every media but fungi growth was not impaired. Milk stayed liquid for the whole week with supplement of the Arthryl compared with sour milk transformation without Arthryl. Sample B showed inhibitory properties of the bacterial colonies on the fungi growth. The sample with Arthryl showed progressive growth of fungi without bacterial growth after 10 days of follow up compared with bacterial growth on media without Arthryl. Glucosamine sulfate as a new trademark Arthryl has environmental antibacterial properties but does not inhibit growth of fungal colonies.

Differentiating subscapular tendon and glenohumeral joint on anterior shoulder sonography.

BACKGROUND: Anterior sonography of the glenohumeral joint has been suggested as a useful method of assessing inflammatory joint disease. The proximity of the subscapular tendon (SSC) to the glenohumeral joint (GHJ) in the shoulder might require differentiating between these two structures. CASE REPORTS: Anterior shoulder sonographic evaluation (Sonosite-Titan) was carried out on four patients: active rheumatoid arthritis (1), osteoarthritis (1), healthy young man (1), silent crystal induced joint disease (1). The shoulder was in a position of supination and external rotation. SSC and GHJ were compared with the transducer located just medial to the biceps tendon (for SSC) and just lateral to the coracoid process (for GHJ). The structural and location differences between the subscapular tendon and the glenohumeral joint on anterior shoulder sonography were discerned. A transverse view of SSC with the transducer located just medial to the biceps tendon (BT) shows the following distinguishing features of the SSC: minor tuberositas, concave surface of the lower surgical neck, fibrillar structure of SSC, continuation of the lower bone margin without demonstration of the thickness of the labrum. A longitudinal view of GHJ with the transducer located just lateral to the coracoid process indicates a rate of GHJ synovial distension, convex, round humeral head with termination of its lower margin and labrum thickening, lack of fibrillar structure of GHJ, and convex round shape of the GHJ capsule. CONCLUSIONS: Differentiating SSC and GHJ on anterior shoulder sonography with above mentioned sonographic features misinterpretation of US data might be minimized.

Ultrasound imaging of fasciitis due to body-building supplement.

BACKGROUND: Fascia and soft tissues, rich in collagen, receptors of pain and capable of significant distention, may be targets of autoimmune inflammatory diseases. We observed fasciitis due to the protein supplement Pure Whey, which has not been reported previously. METHODS: Sonography (Sonosite-Titan, 5 to 10 MHz, L-38) was performed on a patient (age, 26 years; body mass index, 38 kg/m2) with protein fasciitis. He had developed compact swelling of his forearms, hands, and legs, with skin irregularity and severe disability (without peripheral eosinophilia, normal Ig and ESR 18/hr) after taking Pure Whey, containing L-tryptophan (1.4 g per 100 g of protein). A deep skin biopsy was performed. The thickness of the brachioradial fascia (BRF) was measured and compared with 10 healthy control subjects (men ages 36.7 +/- 8.3 years; body mass index, 26.4 +/- 6.5 kg/m2). RESULTS: The deep skin biopsy showed severe fat interlobular and fascial thickening with mononuclear (noneosinophilic) infiltrate and fibrosis associated with fasciitis. BRF of the 10 healthy men had a thickness of 0.75 +/- 0.19 mm, compared with the patient's 2.4 mm thickened and cleaved BRF. After 2.5 months of corticosteroid therapy (30 mg/d with tapering) and discontinuation of the protein supplement, the patient's BRF returned to a monolayer appearance. Its thickness reduced to normal (0.8 mm), with significant clinical improvement. CONCLUSIONS: This case of noneosinophilic fasciitis associated with ingestion of L-tryptophan-containing protein supplement responded favorably to corticosteroid therapy. Sonography proved to be an effective method to visualize and confirm the fasciitis and to follow the course and therapy.

Alcohol poisoning and venous hyperoxia.

ABSTRACT Venous PCO(2) and PO(2) in the presence of normal arterial PCO(2) and PO(2) in patients with alcoholic intoxication have not been previously evaluated. The objective of this study was to compare arterial and venous blood gases in patients with alcoholic intoxication and healthy controls. Sixteen patients with alcoholic intoxication and 20 controls underwent simultaneous blood sampling from a radial artery and an antecubital vein for acid-base analysis. Osmolality and ethanol blood concentration was estimated. Elevated venous pO(2) were found in 56% of patients with alcoholic poisoning compared with 15% of controls. A formula was found describing possible arterio-venous shunt accounting for elevated venous pO(2) and enabling calculation of the relevant venous carbon dioxide content and CO(2) product. The values of the venous pO(2) and arterio-venous shunt were more significant in the alcohol group than in controls (p = 0.002, p = 0.001, respectively). Percentage of patients with a-v shunts was significantly higher in the alcohol group (81%) than in controls (25%) (p = 0.002, OR 2.6, 95% CI 0.13-6.52). The relevant venous CO(2) and CO(2) product had the non-significant trend to be higher in the alcohol group. In conclusion, this study reports ethanol-induced venous pO(2) and pCO(2) elevation. This may be associated with the effects of tissue perfusion stealing and high oxygen consumption. On the other hand, possible beneficial consequences may occur: acceleration of alcohol elimination and reduction of alcohol-induced tissue damage.

From molecular mimicry to cross-reactivity or pathogen expansion? A hypothesis.

Very recently, several studies have convincingly demonstrated the role of infection in the development of the antiphospholipid syndrome. Cross antibody-mediated reactivity due to molecular mimicry between endothelial glycoproteins and microbial products was considered as an important pathogenic mechanism. However, another consequence of the molecular mimicry may be proposed. Similar tissues have less likelihood of being rejected and have a greater chance of being accepted by the host. According to this principle, pathogens with common-to-host antigens may attach readily and not be eliminated. A direct expansion of such pathogens may involve new territories. The targets of the approach 1, "from molecular mimicry to cross-reactivity," are T-B cells system inhibition-modulation. The targets of approach 2, "from molecular mimicry to pathogen expansion," are pathogens, enforcement of barriers, elimination techniques, and preventive strategy.

Fever due to aortitis.

We report a case of vasculitis with predominant aortic involvement. Vasculitis of large vessels has a limited number of tools for diagnosis and follow-up. A 78-year-old woman was referred to the internal medicine department with a 2-month history of fever of unknown origin (FUO), night sweats, weight loss and markedly elevated ESR and CRP. The results of an extended routine investigation found no infection, malignancy, hypersensitivity or autoimmune disorder. The patient did not suffer from claudication; systolic blood pressure difference between arms was 20 mm Hg. Temporal artery biopsies were negative. 2-18F-Fluorine-2-deoxy-D -glucose positron emission tomography (FDG PET) scan imaging demonstrated intense FDG uptake along the aorta and in the brachio-cephalic and carotid arteries consistent with arteritis. A high dose of corticosteroid therapy (1 mg/kg) was instituted with further tapering. The therapy was followed by complete resolution of the symptoms and pathological FDG uptake on repeated FDG PET. Second-line therapy was not added because of positive conversion of Mantaux test followed by rifampicin prophylaxis. FDG PET should be a part of the work-up of FUO when routine investigation fails to determine its etiology. FDG PET is useful both for diagnosis and assessment of response to therapy for large-vessel vasculitis.