Long-term results of kidney transplantation in patients with familial mediterranean fever.

INTRODUCTION: Long-term kidney transplantation (KT) results in patients with familial Mediterranean fever (FMF)-related amyloidosis are not well studied. This study reviewed the long-term survival outcomes of FMF patients who underwent KT. METHODS: We compared the outcomes of 31 patients who underwent (KT) for biopsy-proven amyloidosis secondary to FMF with 31 control patients (five with diabetes mellitus and 26 with nondiabetic kidney disease) undergoing KT between 1994 and 2021 at Baskent University Hospital. All data were recorded retrospectively from patients' files. RESULTS: THE MEDIAN AGE (QUARTILE DEVIATION: QD) at the time of KT in the FMF and control group were 31 (6.7) and 33 (11), respectively. The median follow-up period (QD) after KT was 108 (57) months in the FMF and 132 (72) months in the control group. In the FMF group, graft and patient survivals were 71% and 84% at 5 years and 45% and 48% at 10 years, respectively. In the control group, graft and patient survivals were 79% and 100% at 5 years and 63% and 71% at 10 years, respectively. Patient survival in the FMF group at 5 years was significantly lower than in the control group (p = .045). There was no statistically significant difference between the FMF and control groups in terms of graft and patient survival, and serum creatinine levels at 10 years. All patients were given triple immunosuppressive treatment with cyclosporine, mycophenolate mofetil, and prednisolone. Three patients received anakinra and one received canakinumab in addition to colchicine treatment. One FMF patient also underwent heart transplantation due to AA amyloidosis. Of the FMF patients, 11 died during follow-up. CONCLUSION: We have found that the long-term outcome of KT in patients with FMF amyloidosis is numerically worse but not statistically different from the control group. However, short- and long-term complications still need to be resolved.

S-allylcysteine inhibits chondrocyte inflammation to reduce human osteoarthritis via targeting RAGE, TLR4, JNK, and Nrf2 signaling: comparison with colchicine.

The discovery of new pharmacological agents is needed to control the progression of osteoarthritis (OA), characterized by joint cartilage damage. Human OA chondrocyte (OAC) cultures were either applied to S-allylcysteine (SAC), a sulfur-containing amino acid derivative, or colchicine, an ancient anti-inflammatory therapeutic, for 24 h. SAC or colchicine did not change viability at 1 nM-10 µM but inhibited p-JNK/pan-JNK. While SAC seems to be more effective, both agents inhibited reactive oxygen species (ROS), 3-nitrotyrosine (3-NT), lipid hydroperoxides (LPO), advanced lipoxidation end-products (ALEs as 4-hydroxy-2-nonenal, HNE), advanced glycation end-products (AGEs), and increased glutathione peroxidase (GPx) and type-II-collagen (COL2). IL-1ß, IL-6, and osteopontin (OPN) were more strongly inhibited by SAC than by colchicine. In contrast, TNF-α was inhibited only by SAC, and COX2 was only inhibited by colchicine. Casp-1/ICE, GM-CSF, receptor for advanced glycation end-products (RAGE), and toll-like receptors (TLR4) were inhibited by both agents, but bone morphogenetic protein 7 (BMP7) was partially inhibited by SAC and induced by colchicine. Nuclear factor erythroid 2-related factor 2 (Nrf2) was induced by SAC; in contrast, it was inhibited by colchicine. Although they exert opposite effects on TNF-α, COX2, BMP7, and Nrf2, SAC and colchicine exhibit anti-osteoarthritic properties in OAC by modulating redox-sensitive inflammatory signaling.

TLR4, RAGE, and p-JNK/JNK mediated inflammatory aggression in osteoathritic human chondrocytes are counteracted by redox-sensitive phenolic olive compounds: Comparison with ibuprofen.

Osteoarthritic chondrocytes show an over-activity of inflammatory catabolic mediators, and olive products have attracted attention because they were discovered to have some benefits on osteoarthritis patients. We investigated the mechanisms of action of olive leaf polyphenolic compounds in osteoarthritic chondrocytes (OACs) using a standardized leaf extract, ZeyEX, and its main phenolic component, oleuropein, also compared with anti-inflammatory drug ibuprofen. OACs, isolated from joint-cartilages of Grade 4 OA patients, were found to express COMP and MMP-9 throughout their culture period. ZeyEX, oleuropein, and ibuprofen increased cell viability at concentrations of 1-100 nM, did not change at 500 nM-50 µM, but inhibited at ≥100 µM. The adherence profile of OACs increased with 1 µM of ibuprofen or ZeyEX and 10 nM-1 µM oleuropein. Although the markers for oxidative and nitrosative stresses (ROS and 3-NT) generally inhibited by three agents, the inhibitory effect of ZeyEX on 3-NT emerged dramatically (1 nM-10 µM). Lipid-hydroperoxides and HNE-adducts were also inhibited by each agent, but AGE-adducts unchanged by oleuropein while reduced by ZeyEX and ibuprofen. Inflammatory biomarkers, IL-1ß, IL-6, Casp-1/ICE, and TNF-α, were inhibited by three agents, however osteopontin and GM-CSF by only ZeyEX and ibuprofen. A decreased COMP, TLR4, and RAGE expression levels were observed by three agents, but only the effects of ZeyEX was concentration-dependent. In particular, ZeyEX and oleuropein improved COL2, inhibited p-JNK/JNK, and increased GPx. COX2 was only inhibited by ibuprofen. The results indicate that polyphenolic-olive compounds counteract redox-sensitive inflammatory aggressions in osteoarthritic chondrocytes that may stop the progression of pathology and allow regeneration.

Comparison of clinical courses and mortality of connective tissue disease-associated interstitial pneumonias and chronic fibrosing idiopathic interstitial pneumonias.

Interstitial lung disease (ILD) is a common pulmonary manifestation of connective tissue diseases (CTD). Prognostic effect of radiological usual interstitial pneumonia (UIP) pattern in CTD-associated interstitial lung disease (CTD-ILD) is unknown. This study aimed to investigate the disease progression and mortality of patients with CTD-ILD and idiopathic interstitial pneumonias (IIP) including idiopathic pulmonary fibrosis (IPF) and idiopathic nonspecific interstitial pneumonia and the prognostic impact of the radiological UIP pattern on both disease groups. The medical records of 91 patients (55 with CTD-ILD and 36 with IIP) diagnosed with ILD at pulmonary medicine department, Faculty of Medicine, Gazi University from 2004 to 2014 were retrospectively reviewed. Patients included whose baseline high-resolution computed tomography (HRCT) scans showed either a UIP or non-UIP pattern. While 67.3% (n = 37) of CTD-ILD patients possessed UIP pattern, 38.9% (n = 14) of IIP patients had UIP pattern in HRCT. Respiratory functions including the forced expiratory volume in the first second (FEV1 ), functional vital capacity (FVC), and transfer coefficient for carbon monoxide (diffusing capacity of the lung for carbon monoxide [DLCO]) of IIP group at the time of diagnosis were significantly lower than CTD-ILD group (P = .007, P = .002, and P = .019, respectively). There was no significant survival difference between CTD-ILD and IIP by using the log-rank test (P = .76). Multivariate analysis revealed that UIP pattern in HRCT (Hazard ratio: 1.85; 95% Confidence interval = 1.14-3; P = .013), annual FVC (Hazard ratio: 0.521; 95% Confidence interval = 0.32-0.84; P = .007), and annual DLCO declines (Hazard ratio: 0.943; 95% Confidence interval = 0.897-0.991; P = .02) were independent risk factors for mortality in both CTD-ILD and IIP groups. We found that UIP pattern in HRCT and annual losses in respiratory functions were the main determinants of prognosis of ILDs either idiopathic or CTD-associated.

Clinical characteristics of avascular necrosis in patients with Behçet disease: a case series and literature review.

Avascular necrosis (AVN), also known as osteonecrosis, is characterized by death of the osteocytes due to inadequate blood supply caused by various mechanisms. The hip is the most common affected joint followed by knee. Incidence of AVN in rheumatic diseases is variable and high corticosteroid (CS) therapy is a known major risk factor for development of AVN. Data on the AVN in Behçet disease (BD) are limited. The purpose of this study is to examine the clinical and treatment characteristics of BD patients with diagnosis of AVN. Retrospective medical records of 337 BD patients were reviewed. Nine BD patients with AVN were detected. The clinical data of these patients with AVN have been reviewed. All patients had MRI of the symptomatic joints compatible with AVN. All of the nine patients who were diagnosed with AVN were male. Median duration of BD was 7 years. Median time between diagnosis of BD and detection of AVN was 3 years (1-16 years). Multiple joints were involved in seven patients. Six patients had bilateral knee AVN. Six patients had vascular BD. The median time interval between initial CS dose and AVN development was 24 months (range = 2-100). The median highest daily CS dose was 64 mg/day (range = 32-80) and median cumulative CS dose prior to AVN was 18 g. All of patients had intravenous pulse steroids. CS treatment, smoking and vascular involvement may predispose to AVN in patients with BD. According to this cohort, AVN in BD frequently tended to be in the knee joint and bilateral.

Serum ferritin as an activity marker for granulamotosis with polyangiitis.

BACKGROUND: Serum ferritin correlates well with the activities of systemic lupus erythematosus (SLE) and dermatomyositis, but it has not been previously studied in patients with vasculitis. METHODS: Medical records of granulomatosis with polyangiitis (GPA, Wegener's granulomatosis) patients with at least six months of regular follow-up were evaluated. The activity of GPA was assessed with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG). Serum ferritin and other acute phase markers were measured at initial presentation. RESULTS: Serum ferritin levels were found to be the highest in GPA patients with alveolar hemorrhage, median (IQR) 1041 (1281) µg/L. Patients with renal disease also had high levels of ferritin and it was correlated with concurrent glomerular filtration rate (r = -0.65, p < .001). Serum ferritin is also correlated well with the BVAS/WG scores (r = 0.79, p < .001). CONCLUSIONS: Measurement of serum ferritin might help in assessing disease activity of GPA.

Serum Vitamin B12, Homocysteine and Methylmalonic Acid Levels in Patients With Parenchymal Neuro-Behçet's Syndrome.

OBJECTIVES: This study aims to investigate the role of serum levels of vitamin B12 (VitB12), homocysteine (Hcy), and methylmalonic acid (MMA) in the development of parenchymal neuro-Behçet's syndrome (NBS) and to compare them with healthy controls and Behçet's syndrome (BS) patients without NBS. PATIENTS AND METHODS: Serum VitB12, Hcy, and MMA were measured using enzyme-linked immunosorbent assay in 64 patients (36 males, 28 females; mean age 36±8.3 years; range 20 to 56 years) who met the criteria of the International Study Group for Behçet's Disease and 30 matched healthy controls (17 males, 13 females; mean age 35.76±9.6 years; range 20 to 50 years). The study participants were grouped as BS patients with NBS, BS patients without NBS, and healthy controls. RESULTS: There was no significant difference between the groups regarding serum VitB12, Hcy, and MMA levels (p>0.05). Serum VitB12 levels were below the lower limit and serum Hcy levels were above the upper limit in all participants. MMA levels were normal in all participants. There was no correlation between the serum levels of VitB12, Hcy, and MMA and disease activity (p>0.05). CONCLUSION: The results of this study suggest that there is no significant association between VitB12 deficiency and parenchymal NBS. Further studies are needed to investigate the underlying mechanisms of the variable effects of VitB12 deficiency on different clinical manifestations of BS.

The association between the parenchymal neurological involvement and posterior uveitis in Behçet's syndrome.

OBJECTIVES: Behçet's syndrome (BS) is a systemic vasculitis, which may involve multiple organ systems simultaneously. Clinical findings in BS often fit into well-recognized patterns, such as the association between papulo-pustular skin lesions and arthritis. We have recently observed a distinct pattern, in which a subtype of neuro-Behçet's syndrome (NBS) is often preceded by specific ophthalmic manifestations of the disease process. The purpose of this study is to evaluate the association between the parenchymal subtype of NBS and posterior uveitis (PU). METHODS: We have retrospectively reviewed the clinical records of 295 patients with BS, who met the international classification criteria for BS, diagnosed at two major rheumatology clinics from 2010 to 2014. Patient demographics, ophthalmic examinations, clinical and radiologic patterns of neurological involvement were recorded. Manifestations of BS were classified as PU, NBS, vascular involvement, and arthritis. The association between clinical findings was analysed for statistical significance. RESULTS: Of the 295 patients, 100 had PU and 44 had NBS. 30 patients had parenchymal NBS and 14 had vascular NBS. Patients with PU were significantly more likely to have neurological involvement compared to those without PU (p<0.001; Odds Ratio: 3.924; 95% CI: 1.786-8.621). Rate of posterior uveitis was higher in patients with parenchymal NBS when compared to patients with vascular NBS, vascular BS or arthritis (63.3%, 21.4%, 22% and 4.2% respectively, p<0.001). CONCLUSIONS: Our findings suggest a clinically and statistically significant association between posterior uveitis and parenchymal type of neurologic involvement in BS. The development of posterior uveitis in a patient with previously diagnosed BS should be recognized as a "warning sign" for predisposition to neurologic involvement. These patients should be informed about the possible signs and symptoms of neurological involvement, which can cause very rapid and irreversible damage unless recognized and treated immediately.

Primary Sjögren's syndrome is associated with significant cognitive dysfunction.

AIM: Cognitive dysfunction is a neurologic manifestation in primary Sjögren syndrome (PSS). On the other hand, several antibodies are related to cognitive dysfunction. The aim of this study is to assess the cognitive dysfunction of PSS patients via detailed neurologic tests. Moreover, its associations with antibodies were also evaluated. METHOD: Twenty-eight female patients with PSS and 17 healthy controls comprised the study groups. Short-term memory, long-term memory, verbal learning, visual memory, visual spatial perception, attention, verbal frequency function, executive functions and information processing speed were evaluated with neurologic tests in both of the study groups. Furthermore, anti-N-methyl-D-aspartate (NMDA) type anti-glutamate-receptor antibody, anti-ribosomal-p and antiganglioside antibodies were assessed in the study groups. RESULTS: The attention, data processing speed, verbal learning, short-term verbal memory and visuo-spatial perception performances were lower in the patients with PSS when compared to the healthy controls. The difference reached statistical significance in Paced Auditory Serial Addition Test (P < 0.01), Serial Digit Learning Test (P < 0.01), clock drawing (P = 0.03), Auditory Verbal Learning Test immediate verbal memory (P = 0.01) and Benton Judgement of Line Orientation Test (P = 0.03). Even if antiganglioside antibodies were more likely to be present in the PSS group when compared to the healthy controls, no relationship was found between its positivity and cognitive dysfunction. CONCLUSION: Results of this study suggest that cognitive dysfunction is quite prevalent in PSS patients without being associated with studied antibodies.

The Association Between Neutrophil/Lymphocyte Ratio and Disease Activity in Rheumatoid Arthritis and Ankylosing Spondylitis.

BACKGROUND: Elevated neutrophil count is associated with poor prognosis and increased mortality in many conditions. Neutrophil to lymphocyte ratio (NLR) has emerged as a marker of inflammation in neoplastic and cardiovascular disorders. Herein, we investigated utility of this simple tool in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). METHODS: The study consisted of 136 RA and 140 AS patients, along with 117 healthy control subjects. RA and AS activities were determined with Disease Activity Score (DAS) and Bath Ankylosing Spondylitis Disease Activity indices (BASDAI), respectively. The association between NLR and disease activity was analyzed. RESULTS: Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and neutrophil counts were significantly higher in RA and AS patients compared to healthy controls. Similarly, NLR was higher compared to control subjects, both in RA (2.53 ± 1.4 vs. 2.16 ± 1.0, P = 0.019) and AS (2.43 ± 1.4 vs. 2.16 ± 1.0, P = 0.077). NLR correlated well with ESR and CRP, both in RA and AS. Moreover, NLR increased across worsening DAS28 activity groups (2.1 ± 1.0 in patients with remission, 2.5 ± 1.0 in low-moderate, 3.8 ± 2.5 in high disease activity). However, no association was found between NLR and BASDAI. CONCLUSION: NLR is a cheap and readily available marker for the assessment of disease activity in RA.

Rapid resolution of protracted febrile myalgia syndrome with anakinra: Report of two cases.

Protracted febrile myalgia syndrome (PFMS) is a very rare but severe manifestation of familial Mediterranean fever (FMF) which is characterized by severe debilitating pain in large muscle groups that may last for several weeks. Colchicine is ineffective and treatment is largely supportive. Demonstration of crucial role of interleukin-1 (IL-1) in the pathogenesis of FMF has increased the use of IL-1 blockers in colchicine resistant or intolerant patients. Herein, we reported successful use of an IL-1 inhibitor, anakinra, in treatment of two patients with PFMS.

Differential diagnosis of elevated erythrocyte sedimentation rate and C-reactive protein levels: a rheumatology perspective.

OBJECTIVE: In the case of high erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, the diagnosis of the underlying disease can be challenging especially in serologically unrevealing patients who have nonspecific clinical findings. We aimed to investigate the final distribution of definitive diagnoses in patients who initially presented with nonspecific clinical findings and sustained elevations in serum ESR/CRP levels. MATERIAL AND METHODS: The medical records of patients hospitalized in a rheumatology clinic between January 2010 and January 2011 were retrospectively analyzed. The patients were classified into two main groups: those with previously diagnosed underlying rheumatic disease (RD) and those without. The groups were analyzed for the final distribution of definitive diagnoses. RESULTS: Out of 112 patients in the general study population, 47 had a previous RD and 65 had no previous history of RD. In these 65 patients, the most common etiology of nonspecific elevations in ESR/CRP levels was new onset RD (52.3%). Polymyalgia rheumatica (PMR) was the most common new onset RD (38% of all new onset RD) followed by seronegative rheumatoid arthritis. The incidences of infections and malignancies were 24.6% and 9.2%, respectively. CRP levels were significantly higher in infections when compared with new onset RD or malignancies (p<0.05). In patients with previous RD, the flare of the underlying disease was the most common etiology of nonspecific elevations in ESR/CRP levels (n=39, 83%, 20 female/19 male). CONCLUSION: Extraordinarily high levels of serum CRP in a patient with nonspecific clinical findings should raise suspicion for non-rheumatic diagnoses, such as infection and malignancy, even in the presence of a previously diagnosed RD. Advanced radiological investigation is justified in these cases to rule out malignancy.

Retro-orbital granuloma associated with granulomatosis with polyangiitis: a series of nine cases.

Retro-orbital granuloma is a rare and devastating component of granulomatosis with polyangiitis (GPA). Current medical treatment protocols are falling short, and outcomes are poor. The aim of the study was to investigate the frequency, clinical features, and treatment outcomes of retro-orbital granuloma in patients with GPA. This is a retrospective, multi-centre study, which involves GPA cohorts from five different clinics. Data were extracted from patient charts including history, physical examination, radiological-laboratory-histological findings, and treatment protocols. Major clinical outcome measures were changes in the volume of the granuloma on comparative MRI, and visual acuity on repeated ophthalmologic examinations. Among 141 GPA patients, nine (five females and four males) were diagnosed with a retro-orbital granuloma. Median duration of disease was 8 years. Proptosis and diplopia were the dominant presenting symptoms (77%), followed by orbital pain (55%). Three out of nine patients had isolated retro-orbital granulomas, without other organ involvement of GPA. Five patients received conventional pulse steroid and pulse cyclophosphamide (CYC) as the first-line remission induction therapy. Four of these patients had progressive disease, and a regression in granuloma size was observed in one patient using this regimen. Two patients were already receiving immunosuppressants when they were diagnosed with retro-orbital granuloma. Six patients had been treated with RTX as the second-line remission induction therapy. None of these patients had progression following RTX therapy. Three patients underwent orbital decompression surgery. The indication for the decision for surgery was either progressive loss of vision or intractable pain. Standard first-line chemotherapy (CYC and steroids) was ineffective against retro-orbital granuloma associated with GPA. RTX could be an alternative in these cases. Surgical intervention may help to decrease the morbidity. Further prospective studies with greater patient numbers are needed to test the clinical efficiency of RTX as a first-line remission induction chemotherapy.

Minimally invasive minor salivary gland biopsy for the diagnosis of amyloidosis in a rheumatology clinic.

Background. Systemic amyloidosis is a potentially fatal condition, unless diagnosed and treated before development of irreversible organ damage. Demonstration of amyloid deposits within tissue biopsies is only definitive diagnostic method, which makes appropriate selection of biopsy site essential. Herein, we evaluated efficacy of minimally invasive minor salivary gland biopsy (MSGB) for the diagnosis of amyloidosis. Methods. We analyzed 37 biopsies taken from 35 patients. Suggestive findings for amyloidosis were significant proteinuria, renal impairment, refractory diarrhea, neuropathy, and restrictive cardiomyopathy. Minor salivary gland was the initial biopsy site in all subjects. When MSGB was negative but there was a high suspicion for amyloidosis, a kidney, duodenum, or rectal biopsy was performed for further investigation. Results. Mean age of patients was 45.4 and 21 were female. In 11 patients amyloidosis was diagnosed with MSGB. In overall 18 patients were diagnosed with amyloidosis. Sixteen of them were identified as being of AA type and two were AL type amyloidosis. The sensitivity of minimally invasive MSGB is 61.1% for diagnosing amyloidosis in this study. Conclusion. MSGB is a safe and simple method for the diagnosis of amyloidosis which can be performed in an outpatient setting. We suggest extensive use of this minimally invasive method.

Turkish lupusPRO: cross-cultural validation study for lupus.

LupusPRO is a disease-targeted patient-reported outcome measure that was developed and validated from and among US patients with systemic lupus erythematosus (SLE). We herein report the results of the cross-cultural adaptation and validation study of the Turkish translated version of the LupusPRO. Turkish LupusPRO and the Medical Outcomes Study Short Form (SF-36) (Turkish) were administered to the Turkish lupus patients. Disease activity was ascertained using the physician global assessment (PGA), Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI), and flare (defined by LFA-Lupus Foundation of America). Disease damage was assessed with Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SDI). Also, second Turkish LupusPRO tests were given to the patients to be completed within 2-3 days and sent back to us. Internal consistency reliability, test-retest reliability, and convergent and criterion validity (against disease activity or health status) were tested. All reported p values are two-tailed. The conceptual framework of the LupusPRO was evaluated using confirmatory factor analysis appropriate for categorical data. One hundred two SLE subjects (94 % women) were enrolled. The median (IQR) age and mean disease duration (±SD) were 38.5 (18) years and 60.3 (±56.3) months, respectively. The mean ± SD, SLEDAI, and SDI scores were 3.1 ± 3.7 and 0.52 ± 0.75, respectively. There were 25 patients who had flares at the time of study. Forty-two patients with no change in their health status completed and sent back the second LupusPRO test and were included in the test-retest analysis. Test-retest reliability of LupusPRO domains ranged from 0.87 to 0.97, while internal consistency reliability of the domains ranged from 0.63 to 0.94. Convergent validity with corresponding domains of SF-36 was present. Health-related quality-of-life domains performed well against disease activity measures (PGA, total SLEDAI, LFA flare, and SF-6D-overall health status), establishing its criterion validity. Item-to-factor loadings representing the hypothesized item-to-scale relationships were satisfactory. The model fit for the hypothesized item-to-scale relationships was also satisfactory. The Turkish version of the LupusPRO is valid and appears to perform comparably to the English and Spanish language versions. It can be used as a patient-reported outcome parameter in clinical trials, as well as longitudinal studies for testing responsiveness to change.

An old disease with new insights: Update on diagnosis and treatment of gout.

Gout is an acute and chronic inflammatory disorder associated with high morbidity and impaired quality of life. There has been a substantial increase in the prevalence and incidence of gout in recent years. Novel diagnostic and therapeutic options have provided new insights into the pathogenesis and management of hyperuricemia and gout in the last decade. This clinical review aims to summarize the diagnostic process and management of acute and chronic gout.

Real-time sonoelastography of Achilles tendon in patients with ankylosing spondylitis.

OBJECTIVE: Real-time sonoelastography (SE) is a new ultrasound-based imaging technique that provides information on tissue elasticity and stiffness. We determined the efficacy of SE for assessing Achilles tendon abnormalities in patients with ankylosing spondylitis (AS). MATERIALS AND METHODS: Forty-one consecutive AS patients and 32 asymptomatic healthy subjects were enrolled. Achillodynia was scored on a 0- to 100-mm visual analog scale. A high-resolution ultrasound machine equipped with an elastography-compatible linear probe was used to perform bilateral B-mode ultrasound, Doppler ultrasound, and SE examinations of Achilles tendons. Tendons were divided into proximal, middle, and distal segments. B-mode examinations included tendon thicknesses, echotextures, and enthesopathic findings. SE using color-coded images was performed in the same areas. Normal consistent tendon structures were coded as blue or green, and moderately (yellow) or severely (red) softened areas were considered pathological. RESULTS: The distal third of the Achilles tendons was the most commonly affected part in the AS patients compared with healthy subjects (p = 0.001), whose middle third was more commonly affected. Achillodynia intensity tended to be higher in patients with pathological B-mode or SE examination findings (p = 0.09 and p = 0.07 respectively). Softening detected by SE in the distal third was associated with enthesopathy findings such as calcaneal bone erosions (Fisher's X (2), p = 0.07) and tendinous enlargement (Fisher's X (2), p = 0.001). B-mode and SE findings had moderate to good correlation in the assessment of Achilles tendon abnormalities. CONCLUSIONS: Sonoelastography may be useful for the evaluation of tendon abnormalities in patients with AS; in addition; it may be useful for the evaluation of other inflammatory rheumatic conditions.

Transverse myelitis in Behçet's disease: a series of four cases and review of the literature.

OBJECTIVES: Transverse myelitis (TM) is an uncommon neurologic condition characterised by the segmental involvement of the spinal cord. Although its etiology is unknown, a well established list of associations have been described, many items of which point towards an autoimmune and vasculitic process. TM is also a rare complication of Behçet's disease (BD), an autoimmune process. Herein we present 4 cases of TM associated with BD. METHODS: Retrospective chart reviews of 104 patients were done. Diagnosis of BD was established in each case according to the diagnostic criteria established by the International Study Group for Behçet's Disease. Demographic data, clinical and radiologic presentations of TM, treatment strategies and outcomes were obtained from hospital records. RESULTS: Among the 15 patients with neurological involvement, four cases (3 male, 1 female) of acute TM associated with BD were confirmed. TM associated with BD affected cervical and thoracic levels of the spinal cord. Myelitis involved multiple segments (4 cases). TM developed at any stage of the disease, even as a dramatic initial presentation, leading to the diagnosis of BD (1 case). The longest time elapsed since the diagnosis of BD prior to the development of TM was 10 years. A major association was the history of panuveitis in all four cases. Cyclophosphamide and steroid therapy were the mainstay of the treatment once the TM had developed. Treatment outcomes were variable, depending mostly on the severity of the neurologic involvement at presentation, timing of the initiation of the therapy and patients adherence with the treatment. Two of 4 cases recovered without major sequela. CONCLUSIONS: Although rare, the presented association and its detailed clinical discussions would serve to enhance our understanding of both TM and the spectrum of neurologic complications that BD may harbour. Early recognition and initiation of therapy are crucial for successful outcome.

Enthesopathy in patients with familial Mediterranean fever: increased prevalence in M694 V variant.

Enthesopathy is pathology of bony insertions of tendons, ligaments or joint capsules. It is a frequent finding in rheumatic diseases, like ankylosing spondylitis (AS) and Behçet's disease. Musculoskeletal complaints are common in patients with familial Mediterranean fever (FMF), and these could be a clinical manifestation of enthesopathy. Hence, we investigated the possible association between FMF and enthesopathy. Fifty-six patients with FMF and 11 patients with FMF-associated spondyloarthropathy (FMFS) were enrolled. Forty-seven healthy individuals and 36 patients with AS formed the healthy and diseased control groups. Musculoskeletal complaints were meticulously questioned, and all patients underwent a detailed physical and ultrasonographic (US) examination of the lower limbs. US scorings of enthesopathy was performed according to the Glasgow Ultrasound Enthesitis Scoring System (GUESS). Demographic data, disease characteristics, MEFV genotypes and HLA B27 results were retrieved from the medical records. Patient-reported pain and physical examination findings consistent with enthesopathy were frequent in all groups with the highest prevalence in the FMFS group. Heel was the most common region affected in all patient groups. FMF patients harboring M694 V variant had higher GUESS scores compared to patients with other variants (2.78 ± 2.43 vs. 1.37 ± 1.67, p = 0.026). There was no statistically significant difference in the mean ± SD GUESS scores between healthy subjects and those FMF patients with genetic variants other than M694 V (1.38 ± 1.42 vs. 1.37 ± 1.67, p > 0.05). Enthesopathy may not be a feature of general FMF population; rather, it might be specifically associated with the presence of M694 V variant. Our results further support the previous evidence regarding M694 V mutation and spondyloarthropathy association.

An Unusual Case of Madelung's Disease with Multiple Atypical Fractures.

Madelung's disease is a rare acquired disorder of fat metabolism characterized by multiple symmetric lipomas with typical distribution mainly around the upper trunk, neck, and shoulders. The condition is strongly associated with chronic alcohol use and has various systemic manifestations like polyneuropathy, muscle weakness, and small bone fractures. Herein, we report a 56-year-old male patient with Madelung's disease and multiple fractures and discuss possible underlying factors leading to multiple fractures.