Hematologic Involvement Research Articles

Hand ultrasound: Comparative study between “no rhupus” lupus erythematosus and rheumatoid arthritis

Objective. To compare hand US between systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients.Methods. Hands (1st–5th metacarpophalangeal [MCP] and 1st–5th proximal interphalangeal [PIP] joints) and wrists (radiocarpal and distal radioulnar joints) of 62 “no rhupus” SLE and 60 RA patients were compared through US (linear probe, 6–18 MHz). The findings were compared to clinical, functional, serological outcomes, and disease activity indices.Results. 2108 and 2040 joint recesses were evaluated in SLE and AR patients, respectively. Synovitis was found in 46.8% and 75% of wrists, 83.9% and 86.7% of MCPs and 58.1% and 70% of PIPs in the SLE and RA groups, respectively. More significant US findings were found in RA group. Greater values of synovitis (mm) in RA group were only found in the joint recesses of wrist (p < 0.001–0.002). In SLE group, US findings were associated with “puffy hands,” Health Assessment Questionnaire score and dynamometry. Twenty-two SLE patients (35.5%) had erosion in any of joints studied. SLE patient subgroup with US erosion was associated with hematological involvement and Jaccoud's arthropathy.Conclusions. US of “no rhupus” SLE and RA patients is different, especially in wrists. In SLE patients the clinical variable most associated with US findings was “puffy hands.”

New targets for old diseases: lessons from mucolipidosis type II

Lysosomal storage disorders (LSDs) are inherited diseases characterized by progressive intracellular accumulation of undigested macromolecules within the cell due to specific lysosomal defects. Lysosomal storage results in a global impairment of many lysosome‐dependent pathways ( e.g . autophagy and endocytosis), leading to cellular dysfunction and death (Ballabio & Gieselmann, 2009). LSD patients often have a complex phenotype, with visceral, skeletal, haematological and neurological involvement. Several mechanisms underlie the etiopathogenesis of the LSDs and their relative contribution may vary, depending on the tissue and cell type. For instance, a generalized inflammatory process affecting multiple tissues has been observed in several mouse models of LSDs, although its role in disease pathogenesis remains still largely unclear (Ballabio & Gieselmann, 2009). Over 50 different LSDs have been described to date, which are due to mutations in genes that encode soluble hydrolases, membrane proteins and lysosomal accessory proteins, resulting in the block of a specific catabolic pathway. Among the lysosomal accessory proteins, one notable example is that of the α and β subunits of the N ‐acetylglucosamine phosphotransferase complex, which are encoded by the GNPTAB gene. This complex catalyses the post‐translational incorporation of a mannose 6‐phosphate (M6P) residue on newly synthesized lysosomal enzymes (Bao et al, 1996). This glycosylation event is crucial for the correct M6P receptor‐dependent targeting of lysosomal enzymes to lysosomes (Braulke & Bonifacino, 2009). In patients affected by mucolipidosis type II (MLII), a LSD due to mutations of the GNPTAB gene, lysosomal enzymes are missorted to the extracellular space. This results in intra‐lysosomal deficiency of multiple enzymes and consequent accumulation of undigested substrates in several organs and tissues, particularly the skeletal system. The pathological mechanisms leading from cellular storage defects to skeletal abnormalities in MLII patients (Schweizer et al, 2013) are poorly understood; it is therefore crucial to improve our understanding …

Thymus and mediastinal node involvement in childhood langerhans cell histiocytosis: Long‐term follow‐up from the French national cohort

BackgroundMediastinal involvement (MI) in Langerhans cell histiocytosis (LCH) has been rarely reported. Here, we describe the clinical, radiological, and biological presentation, and the outcome of childhood LCH with MI.MethodFrom the French LCH register, which includes 1,423 patients aged less than 18 years, we retrieved the medical charts of patients with mediastinal enlargement detected on chest X-rays.ResultsThirty-seven patients were retrieved, including 18 males; median age of diagnosis was 0.7 years, and median follow-up time was 6.2 years. The prevalence of MI varied with the age at diagnosis, ranging from 7% below 1 year old to less than 1% at >5 years. Thirteen cases (35%) were diagnosed because of MI-related symptoms, including respiratory distress (N = 4), superior venous cava syndrome (N = 2), and/or cough and polypnea (N = 10). CT scans performed in 32 cases at diagnosis showed tracheal compression (N = 5), cava thrombosis (N = 2), and/or calcification (N = 16). All patients presented multi-system disease at LCH diagnosis, and 35/37 were initially treated with vinblastine and corticosteroids. Death occurred in five cases, due to MI (N = 1) or hematological refractory involvement (N = 4). The overall 5-year survival was 87.1%, and immunodeficiency was not detected as a sequel.ConclusionsMI in LCH mainly occurs in young children, and diagnosis was based on CT showing thymus enlargement and calcifications. Pediatr Blood Cancer 2013;60:1759–1765. © 2013 Wiley Periodicals, Inc.

AB0662 Flares in systemic lupus erythematosus: Etiology, outcome and prognostic factors

BackgroundLupus is a chronic, remitting and relapsing autoimmune disorder characterized by unpredictable disease flares and remissions. The rate and the severity of flares during course of treatment are important predictors...

AB0667 Clinical and immunological features in a monocentric cohort of 305 italian patients affected with systemic lupus erythematosus

ObjectivesTo analyze the clinical and immunological features of an Italian cohort of systemic lupus erythematosus (SLE) patients referring to a unique center, and to evaluate their association with specific pattern...

SAT0565 Medical Costs and their Predictors in Korean Patients with Systemic Lupus Erythematosus

BackgroundSystemic lupus erythematosus (SLE) has very high economic burdens on society and healthcare system.ObjectivesThe aim of this study was to estimate the annual direct costs and predictors of cost in...

AB0378 Rituximab use in systemic lupus erythematosus patients: the experience of two central hospitals in lisbon

BackgroundSystemic lupus erythematosus (SLE) is a systemic autoimmune disease, in which severe organ damage can occur. B cells play an important role in SLE pathogenesis. Rituximab (RTX) has been used...

AB0671 Cardiovascular risk in systemic lupus erythematosus: Do renal risk factors play a part?

BackgroundSystemic lupus erythematosus (SLE) is associated with a high risk of cardiovascular disease (CVD). In addition to traditional risk factors, SLE disease related factors such as renal dysfunction are postulated...

AB0418 Differences between clinical and laboratory findings in patients with recent diagnosis of sle according to the presence or absence of anti-dna antibodies by crithidia luciliae

ObjectivesTo evaluate if the existence of anti-dsDNA antibodies detected by Crithidia luciliae indirect immunofluorescence (CLIF) method is associated with clinical and laboratory differences in patients with recent diagnosis of SLE.MethodsRetrospective...

AB1138 Vitamin D levels and disease activity in children with systemic lupus erythematosus

Background25 (OH) D3 (vitamin D) has an important role in preserving immune homoeostasis. Several surveys of rheumatology populations found reduced levels of vitamin D and association between vitamin D deficiency...

OP0066 Efficacy of rituximab in systemic manifestations of patients with primary sjÖgren’s syndrome: Results from the air registry

ObjectivesTo evaluate the efficacy and safety of rituximab (RTX) in patients with primary Sjogren’s syndrome (pSS).MethodsThe AutoImmune and Rituximab registry (AIR), an independent registry of the French Society of Rheumatology,...

FRI0340 Prevalence and significance of thrombocytopenia in juvenile-onset systemic lupus erythematosus at presentation and one year follow-up

BackgroundThrombocytopenia is both common in adult-onset Systemic Lupus Erythematosus (SLE), prevalence ranging up to 40% and associated with increased disease activity, damage accrual and mortality (1). In juvenile-onset SLE (JSLE)...

Clinical and immunological features of 888 Brazilian systemic lupus patients from a monocentric cohort: comparison with other populations

Epidemiological studies with systemic lupus erythematosus (SLE) patients have been reported worldwide but, until now, a large evaluation had not been performed in Brazil. Therefore, we determined the clinical and immunological features of 888 SLE patients followed at our service from 2008 to 2012. The mean age at SLE onset and the mean disease duration were 29.9 ± 9.5 years old and 14.5 ± 8.4 years, respectively. A predominance of female gender (91.9%) and Caucasian ethnicity (69.9%) were observed. Cumulative mucocutaneous manifestations (90.7%) were most commonly identified (malar rash (83.2%), photosensitivity (76.9%)) followed by articular (87.4%), hematological (44.0%) and renal (36.9%) involvements. Antinuclear antibody was detected in all patients, followed by anti-dsDNA (35.1%), anti-Sm (21.8%) and anti-ribosomal P protein antibodies (19.8%). Additional comparison of clinical and laboratory features between genders revealed that malar rash was observed more in female SLE patients (84.5% vs. 69.4%, p = 0.001). Male lupus patients presented a higher frequency of anti-dsDNA (45.8% vs. 34.2%, p = 0.047) and a trend of more nephritis (47.2% vs. 36.0%, p = 0.059). In conclusion, we identified a high prevalence of mucocutaneous manifestations in this Brazilian SLE cohort compared to other countries, mainly malar rash that was most commonly observed in female patients. Anti-dsDNA and other specific SLE autoantibodies were also identified in a higher frequency, predominantly in the male gender.

Circulating levels of soluble MER in lupus reflect M2c activation of monocytes/macrophages, autoantibody specificities and disease activity.

IntroductionSystemic lupus erythematosus (SLE) is characterized by impaired efferocytosis and aberrant activation of innate immunity. We asked if shedding of MER receptor tyrosine kinase (MerTK) and AXL into soluble (s) ectodomains was related to immunological and clinical aspects of SLE.MethodsLevels of sMER and sAXL in the plasma of 107 SLE patients and 45 matched controls were measured by ELISA. In 40 consecutive SLE patients, we examined potential correlations between either sMER or sAXL and plasma levels of sCD163, a marker of M2 activation. All three soluble receptors were measured in supernatants of monocytes/macrophages cultured in various immunological conditions. Membrane expression of MerTK, AXL and CD163 was assessed by flow cytometry.ResultsBoth sMER and sAXL were associated with anti-chromatin and anti-phospholipid autoantibodies, and with hematological and renal involvement. However, sMER and sAXL did not significantly correlate with each other; sAXL correlated with growth arrest-specific 6 (Gas6), whereas sMER correlated with reduced free protein S (PROS) levels. Only sMER showed significant associations with lupus-specific anti-dsDNA, anti-Sm, anti-ribonucleoprotein (anti-RNP) and anti-Ro60 autoantibodies. Strong correlations with disease activity indices (Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), complement reduction, titer of circulating anti-dsDNA) were found for sMER, not for sAXL. Patients with active SLEDAI, nephritis, anti-dsDNA and anti-Ro60 positivity showed higher levels of sMER compared to controls. Levels of sMER, not sAXL, correlated with sCD163 levels, and these correlated with SLEDAI. Production of sMER and sCD163 occurred under “M2c” polarizing conditions, whereas sAXL was released upon type-I IFN exposure.ConclusionsAlterations in homeostasis of anti-inflammatory and efferocytic “M2c” monocytes/macrophages may have a role in immunopathogenesis of SLE.

Progressive Multifocal Leukoencephalopathy as the First Manifestation of Occult Sarcoidosis

Progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the central nervous system, is caused by reactivation of the JC virus. This disease is typically seen in individuals with known immune suppression. It has also been associated with other inflammatory conditions, such as sarcoidosis. A 68-year-old woman without known immune suppression presented with mental status changes over several weeks. Brain biopsy and cerebrospinal fluid analysis led to the diagnosis of PML. On autopsy, she was found to have previously undiagnosed sarcoidosis. To our knowledge, this is the first published case of PML as the first manifestation of sarcoidosis in the absence of inflammatory hematologic involvement.

Mycosis Fungoides and Head and Neck Malignancies

Mycosis fungoides is a cutaneous T-cell lymphoma characterized by cutaneous patches and plaques that may progress to hematologic involvement and Sezary syndrome. Second primary tumors have been described in the literature without emphasis on head and neck neoplasms. We report two cases of head and neck malignancies in patients with a history of mycosis fungoides. A PubMed literature search was performed and results were reviewed. Second primary tumors in the head and neck have been reported in the nose and nasal cavity, sinuses, oral cavity, pharynx, hypopharynx, larynx, tracheobronchial tree, thymus, and skin. We present cases of submandibular mucoepidermoid carcinoma and papillary thyroid carcinoma in patients with a history of mycosis fungoides. Mycosis fungoides may confer increased risk of developing a second primary neoplasm of the head and neck. Possible mechanisms may include immunosuppression inherent in treatment modalities, the disease course of mycosis fungoides, or related genetic mutations.

Relationship between autoantibody clustering and clinical subsets in SLE: cluster and association analyses in Hong Kong Chinese

This study aims to identify the existence of, and relationship between autoantibody clusters and clinical subsets in Chinese SLE patients. Data from 1928 SLE patients from Hong Kong were analysed. Using cluster analysis, patients were grouped by autoantibodies into clusters. The frequencies of various clinical manifestations were then compared between each cluster. Separate association analyses between individual autoantibodies and clinical manifestations as well as between clinical manifestations were also performed without any prior clustering. Three separate autoantibody clusters were identified, each with significantly different clinical manifestations. Cluster 1 was characterized by anti-dsDNA and the greatest prevalence of renal disorder but the lowest frequencies of other clinical manifestations. Cluster 2 was represented by the predominance of anti-Smith, anti-RNP and aPL, with greater prevalence of malar rash, oral ulcers, arthritis and serositis. Cluster 3 was characterized by anti-Ro and anti-La with greater prevalence of discoid rash, photosensitivity and haematological involvement. Individual association analysis also revealed similar findings. Patients of clusters 2 and 3 were more closely related, while cluster 1 was more distinct, associated with renal disorder only and negatively associated or not associated with other manifestations. We conclude that autoantibody clustering and clinical subsets exist in SLE patients of our locality. These clusters may be viewed as a bipolar spectrum of related autoantibody and clinical manifestations. At one end are patients with over-representation of anti-dsDNA and renal disorder, while at the other end are two distinct autoantibody clusters (anti-Sm/anti-RNP/aPL and anti-Ro/anti-La) with overlapping of other clinical manifestations.

Clinical Profile of Patients with Systemic Lupus Erythematosus

Clinical features of systemic lupus erythematosus vary between different parts of the World; however, this information on Nepalese systemic lupus erythematosus does not exist. Patients with systemic lupus erythematosus fulfilling the American College of Rheumatology criteria treated in Patan Hospital were studied by means of retrospective review of their case records. The results were compared with various regional and international studies. The female to male ratio was 36:1 with a mean age at diagnosis 28.67 years. Cutaneous manifestations were the most common 72 (96%) presentations followed by musculoskeletal involvement 70 (93%). Haematological and renal involvements each were present in 33 (44%) of patients. Pulmonary and neuropsychiatric involvements were present in 15 (20%) and 8 (11%) patients respectively. Antinuclear antibody and anti-double stranded deoxyribonucleic acid antibodies were positive in 70 (93%) and 66 (88%) of patients respectively. A quarter of patients had some form of co-morbid conditions. At the time of last follow up, 70 (93%), 66 (90%), and 6 (9%) of patients were taking antimalarials, steroids and immunosuppressive agents respectively, mostly in combinations. Eighty seven percent of patients had their disease activity under control at the time of last follow up whereas four percent still had an active disease. In another four percent died during the course of therapy and the outcome was unknown in another four percent of patients who lost to follow up. Clinical characteristics and antinuclear antibody pattern of Nepalese lupus patients is more or less similar to those with patients from other countries in the region and in the World.

Idiopathic hypereosinophilic syndrome revealed by encephalopathy

Idiopathic hypereosinophilic syndrome (HES) is characterized by persistent hypereosinophilia (⩾1500/mm3) with evidence of end-organ damage without a definite underlying cause. Hypereosinophilia-induced encephalopathy is a rare clinical syndrome. We present a male patient with idiopathic HES with distinctive encephalopathy who had hypereosinophilia for more than 6months. Eosinophils in repeated blood tests were more than 1500/mm3. He had hematological, brain, bone-marrow, and possible cardiac involvement. Although numerous efforts were made to identify the underlying cause of hypereosinophilia, specific causes could not be found in this patient. Bone-marrow analysis confirmed the diagnosis. The unique features were the prominent involvement of the cerebral cortex and the dramatic response to steroids with marked improvement of eosinophilia and brain function. The mechanisms of hypereosinophilia-induced encephalopathy are discussed.

Middle cerebral artery involvement in systemic lupus erythematosus presenting as a stroke – an unusual initial presentation of the disease

Systemic lupus erythematosus (SLE) disproportionately affects the African American population and usually presents with a constellation of symptoms. Along with hematologic, musculoskeletal, serous and skin involvement, the most common causes of morbidity are attributed to altered blood rheology causing accelerated atherosclerotic vascular disease (ASVD). ASVD occurs in predominantly premenopausal women at an age where ASVD is rare or uncommon. Classical central nervous system manifestations are very rare from the outset of the disease. Here we present a 44-year old African American woman with newly diagnosed SLE and no significant atherosclerotic risk factors, who presented initially with symptoms of subacute stroke.