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.

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.

Investigating the link between disease activity and infliximab serum levels in rheumatoid arthritis patients.

OBJECTIVES: The aim of this study was to examine the extent to which infliximab (IFX) serum levels impact disease activity in rheumatoid arthritis (RA) patients. METHODS: In this cross sectional study, serum samples were taken prior to drug infusion from 60 RA patients who had been undergoing IFX therapy > 12 months as a first line of biological treatment. Patient IFX levels were tested and then associated with clinical disease activity. Three DAS28 cut-off points, <2.6, <3.2 and <5.1 were used to determine whether detectable IFX levels were any predictor of clinical disease activity. Logistic regression analysis was run to check other possible factors associated with RA clinical outcomes such as MTX concomitant use, CRP and ESR. RESULTS: Sixteen (27%) out of the 60 patients tested negative; 28 (46%) presented subtherapeutic and 16 (27%) therapeutic IFX levels. Median IFX levels were higher in patients either in remission or showing low disease activity than in those with moderate and high disease activity (p=0.014). Significant association was found between IFX levels and clinical disease activity (p=0.001). Detectable levels of IFX shows better sensitivity and specificity to identify patients with DAS28<3.2 than to identify patients with DAS28<2.6 or DAS28<5.1. Conversely, the best DAS28 cut-off to identify detectable/undetectable IFX was 3.19, with AUC under ROC curve 0.804 (Sd.E 0.070), 76% specificity and 83% sensitivity (p<0.001). MTX use, CRP and ESR did not interfere with this association. Seven out of the 8 patients with anti-IFX antibodies presented DAS28>3.2 (p=0.005). CONCLUSIONS: DAS28 and IFX serum levels were shown to have an inverse correlation. Undetectable IFX serum levels were associated to RA patients presenting DAS28>3.2 meaning that DAS28 <3.2 may be useful to clinicians to evaluate patient response to drug therapy.

[Recurrent vascular access trombosis associated with the prothrombin mutation G20210A in a adult patient in haemodialysis]. / Trombosis recurrente del acceso vascular asociada a la mutación G202 10A del gen de la protrombina en un paciente adulto en hemodiálisis.

Vascular access-related complications are a frequent cause of morbidity in haemodialysis patients and generate high costs. We present the case of an adult patient with end-stage renal disease and recurrent vascular access thrombosis associated with the prothrombin mutation G20210A and renal graft intolerance. The clinical expression of this heterozygous gene mutation may have been favoured by inflammatory state, frequent in dialysis patients. In this patient, the inflammatory response associated with the renal graft intolerance would have favored the development of recurrent vascular access thrombosis in a adult heterozygous for prothrombin mutation G20210A. In the case of early dysfunction of haemodialysis vascular access and after ruling out technical problems, it is convenient to carry out a screening for thrombophilia.

Comparison of bone and gallium-67 imaging in heroin users' arthritis.

Nine cases of primary septic arthritis in heroin addicts are reported. Fibrous and cartilaginous joint localizations are prominent (four sternoarticular, three sacroiliac, one sacroccocygeal, and one knee). In all patients but one, conventional roentgenographic studies were negative. In six cases the causative agent was Staphylococcus aureus and in two cases, Candida albicans. In one case, it could not be determined. Our clinical observations, correlating the radioisotopic studies, suggest that in the first week of evolution the diagnostic procedure of choice is the [67Ga]citrate scintigram. Indeed, during this period the [99Tc]MDP bone scan is usually negative. The early demonstration and localization of the disease, together with the rapid bacteriologic diagnosis, allows for an early and more appropriate antibiotic treatment and better results.

Antiribonucleoprotein antibodies in children with HIV infection: a comparative study with childhood-onset systemic lupus erythematosus.

A number of clinical and laboratory features of HIV infection are found in systemic lupus erythematosus (SLE). The objective of this study was to analyze the presence of circulating antibodies to small nuclear ribonucleoproteins (snRNP) in both diseases. Sera from 44 HIV-infected children, from 22 patients with childhood-onset SLE, and from 50 healthy children were studied. Anti-snRNP antibodies were detected by ELISA using recombinant and affinity-purified nuclear antigens, by counterimmunoelectrophoresis (CIE), and by immunoblotting using extractable nuclear antigens. Results included the detection of anti-snRNP antibodies by ELISA in 30 HIV-infected patients (68.1%) and 19 SLE patients (86.3%). These antibodies were directed against U1-RNP (61.3% and 77.2%, respectively), Sm (29.5% and 54.5%, respectively), 60 kDa Ro/SS-A (47.7% and 50%, respectively), and La/SS-B proteins (18.1% and 9%, respectively). None of the HIV-infected children and 11 SLE patients (50%) showed anti-snRNP antibodies by CIE. None of the HIV-infected patients showed anti-70 kDa U1-RNP or anti-D-Sm antibodies by immunoblotting. No differences between the two groups were noted on the presence of nonprecipitating anti-snRNP antibodies. No such reactivities were observed among the normal sera tested. The authors concluded that nonprecipitating anti-snRNP antibodies in HIV-infected children are as frequent as in childhood-onset SLE. The significance of these antibodies is not clear at present. Although polyreactive and low-affinity antibodies and a mechanism of molecular mimicry may explain these results, a specific stimulation of B cells by nuclear antigens could not be excluded.

Costal chondritis in heroin addicts: a comparative study with postsurgical chondritis.

Infection of the chondrocostal junction occurs infrequently nowadays. However, with the increasing incidence in the last years of intravenous drug addiction, more cases have been reported recently. The authors studied two groups of patients with costal chondritis, one of heroin addicts and the other of patients who had undergone thoracic surgery previously. While in the postsurgical group the patients need some kind of resection for their treatment, in the heroin addicts an early drainage is usually enough.

AIDS and rheumatic manifestations in patients addicted to drugs. An analysis of 106 cases.

We evaluated the rheumatic manifestations in 106 patients with AIDS whose risk factor is intravenous drug addiction. All were intravenous drug addicts and carriers of the human immunodeficiency virus (HIV). Their average age was 28.36 years; 83 were men and 23 were women; 73 were in stage IV of the HIV infection; 12 were in stage III and 21 in stage II. Rheumatic manifestations were found in 21 patients (20%). Specifically, 13 had arthralgias/myalgias, 2 demonstrated oligoarthritis, 1 had tuberculous arthritis of the knee, and 1 patient showed systemic necrotizing vasculitis. Finally, 6 patients had a history of septic arthritis. There was an absence of the Reiter syndrome/reactive arthritis, a low frequency of symptoms of articular swelling, and the marked presence of histories of septic arthritis. The practices that lead to HIV infection may play a decisive role in the appearance of rheumatic manifestations in patients with AIDS, even more than the presence of the virus itself or the immunological alterations thereby produced.

Septic arthritis in patients with acquired immunodeficiency syndrome with human immunodeficiency virus infection.

We have evaluated the presence and characteristics of septic arthritis in intravenous (iv) drug users with human immunodeficiency virus (HIV) infection. Sixteen patients with both HIV infection and septic arthritis were studied and compared with 5 patients with septic arthritis but no HIV infection. Clinical profile, laboratory findings at the time of onset, localization, causative organisms, mean hospitalization time and presence of complications were the same in HIV positive and HIV negative patients. Staphylococcus aureus was the most commonly isolated organism in both groups. We conclude that septic arthritis in HIV infected iv drug users is not uncommon, it is produced by the same organisms and presents similar characteristics to the ones found in iv drug users without HIV infection. Therefore, the presence of HIV infection does not appear to modify the characteristics of septic arthritis.

[Neonatal lupus erythematosus: complete atrioventricular block and SSA/Ro antibodies]. / Lupus eritematoso neonatal: bloqueo A-V completo y anticuerpos SSA/Ro.

A newborn boy with complete A-V block and positive anti-SSA/Ro antibodies is reported. Authors comment on pathological findings of neonatal lupus erythematosus. They also review prognosis and clinical course and point out management of these patients before and after birth.

Systemic lupus erythematosus: clinical expression and anti-Ro/SS--a response in patients with and without lesions of subacute cutaneous lupus erythematosus.

UNLABELLED: Patients with subacute cutaneous lupus erythematosus (SCLE) have recurrent annular and/or psoriasiphorm skin lesions, with or without systemic disease. OBJECTIVE: To analyse the clinical expression and the Ro/SS-A response associated with SCLE in patients with systemic lupus erythematosus (SLE). METHODS: 128 consecutive patients with SLE were studied. Anti-Ro/SS-A antibodies were detected by ELISA, (anti-60 kD Ro/SSA antibodies), immunoblotting (anti-60 kD and anti-52 kD Ro/SS-A antibodies) and counterimmunoelectrophoresis (CIE). RESULTS: Seventeen patients (13.2%) showed SCLE lesions. Photosensitivity was more frequent in patients with SCLE (82%) than in patients without these cutaneous lesions (45%) (OR: 5.6). Arthritis (OR: 6.3), Raynaud's phenomenon (OR: 4.9), pleuritis (OR: 7.6), central nervous system disorder (OR: 6.4), renal disease (OR: 6.3), anemia (OR: 7.9), hypocomplementemia (OR: 6.1) and anti-dsDNA antibodies (OR: 12.7) were significantly more frequent in patients without SCLE. Anti-Ro/SS-A antibodies were detected in 15 (88.2%) patients with SCLE and 62 (55.8%) patients without SCLE by ELISA, in 10 (58.8%) and 34 (30.6%) patients by immunoblotting, and in 13 (76.4%) and 34 (30.6%) by CIE, respectively. Anti-60 kD-Ro/SS-A and anti-La antibodies, but not anti-52 kD-Ro/SS-A, were significantly more frequent in patients with SCLE than in patients without SCLE. CONCLUSIONS: The presence of SCLE lesions in patients with SLE is associated with a more favourable prognosis. The major anti-Ro/SS-A response is directed against the native 60 kD Ro/SS-A protein.

Primary septic arthritis of the manubriosternal joint in a heroin user.

A 20-year-old heroin user developed staphylococcus septic arthritis of the manubrium joint. The diagnosis was established by a culture of the infected tissue and blood culture. The clinical impression was aided by 99mTc radionuclide scintimetry. Early diagnosis localized the infection. Immediate antibiotic therapy solved a problem in the sternum that seems not to have been reported in the English literature.

Primary septic arthritis in heroin users: early diagnosis by radioisotopic imaging and geographic variations in the causative agents.

We reviewed 37 cases of septic arthritis in heroin users. Our data confirm the predominance of the fibrocartilaginous joint infections in this group (sacroiliac joint 39%, chondrosternocostal unions 37%). In Spain, Staphylococcus aureus is the most commonly isolated organism (73%). This emphasizes the geographic variations in the causative germs since, in contrast to other reports, we have not identified any gram negative bacillary arthritis in our population of heroin users. Our data show that the 67gallium citrate scintigraphy is positive earlier than the 99mTc-MDP bone scan in the poorly vascularized joints (p less than 0.0005). The early localization of the infectious focus by 67gallium citrate scintigraphy followed by a prompt bacteriologic diagnosis (blood, synovial fluid or tissue cultures) allowed good therapeutic results.

Simultaneous identification of various antinuclear antibodies using an automated multiparameter line immunoassay system.

The objective was to determine the sensitivity and specificity of an automated multiparameter line immunoassay system compared with other techniques for the identification of autoantibodies in rheumatic diseases. We studied sera from 90 patients. Anti-U1RNP, anti-Sm, anti-Ro/SS-A, anti-La/SS-B, anti-Jo 1 and anti-Scl 70 antibodies were identified by counterimmunoelectrophoresis (CIE) techniques, enzyme-linked immunosorbent assay (ELISA), immunoblotting (IB) using extracts of rabbit thymus and human placenta, and an automated multiparameter line immunoassay system (INNO-LIA ANA UPDATE K-1090) that detects nine different antibodies simultaneously (anti-U1RNP, anti-Sm, anti-Ro/SS-A, anti-La/SS-B, anti-Scl 70, anti-Jo 1, anticentromere, antihistone, and antiribosomal P protein). The line immunoassay system equaled or surpassed the other techniques in the identification of anti-Sm, anti-La/SS-B, anti-Jo 1 and anti-Scl 70 antibodies (sensitivity 100%, specificity 94-100%) and was similarly effective in the case of anti-U1RNP (sensitivity 87.5%, specificity 93.9%) and anti-Ro/SS-A (sensitivity 91.4%, specificity 87.2%) antibodies. In addition, this technique detected more 52 and 60 kD anti-Ro/SS-A sera than IB. Nine antibodies can be detected with this method at a cost of 25.38 Euros per serum sample. In five hours, 19 sera can be studied. The approximate cost of detecting these nine antibodies with an automated ELISA system would be 28.93 Euros, which allows 10 sera to be studied in four hours. In conclusion, the automated multiparameter line immunoassay system is a valid method for the detection of autoantibodies in rheumatic diseases. Its most notable advantages are automated simultaneous detection of several autoantibodies in the same serum and its lower cost compared with ELISA techniques.

Heterogeneity of the anti-Ro(SSA) response in rheumatic diseases.

OBJECTIVE: The immune response to the Ro(SSA) antigen is heterogeneous. Anti-Ro(SSA) positive sera may contain antibodies recognizing either a 60 or a 52 kDa polypeptide component of the Ro(SSA) particle. Thus we sought to determine the profile of anti-Ro(SSA) antibodies defined by immunoblotting in patients with rheumatic diseases. METHODS: Immunoblotting against human placenta extract and ELISA against recombinant Ro(SSA) antigen as confirmatory tests were done to detect anti-Ro(SSA) antibodies in 563 sera from patients with systemic lupus erythematosus (SLE). Sjögren's syndrome (SS), rheumatoid arthritis (RA) and other connective tissue diseases. RESULTS: Anti-52 kDa antibodies were more common in primary patients with SS (9/22; 40.9%) than in patients with SLE (29/135; 21.4%) or patients with RA (7/315; 2.2%). Anti-60 kDa antibodies were more frequent in patients with SLE (26/135; 19.2%) than in patients with primary SS (2/22; 9%) or RA (17/315; 5.3%). None of the 22 patients with primary SS had only antibodies to the 60 kDa polypeptide. Among the 153 patients whose sera were positive by ELISA, 73 (47.7%) were negative by immunoblotting. The most frequent diagnoses in these sera were RA and SLE. The anti-52 kDa sera had higher optical density values compared to anti-60 kDa sera. CONCLUSIONS: Our observations indicate the existence of qualitatively and quantitatively different anti-Ro(SSA) responses in the rheumatic diseases. The major responses are anti-52 kDa antibodies in primary SS, both anti-52 and anti-60 kDa antibodies in SLE, and anti-60 kDa antibodies in RA and other connective tissue diseases.

Anticardiolipin antibodies in pediatric patients with human immunodeficiency virus.

OBJECTIVE: To study the presence of IgG and IgM anticardiolipin antibodies (aCL) in children with human immunodeficiency virus (HIV) infection and to determine their prevalence and clinical significance. METHODS: We studied 34 children with HIV infection: 26 patients were classified P-2, and 8 were P-1 according to the Centers for Disease Control classification. HIV transmission was from mother to child in 33 cases. aCL were measured by ELISA: RESULTS: IgG aCL were found in 28 (82%) and IgM aCL in 7 (20%). No difference in frequency and levels was found between class P-2 (85%, mean 54.5 PL units) and class P-1 (75%, mean 50.3 PL units). aCL were not related to the duration of the infection, clinical stage of disease, or with events like opportunistic infections. Children from sexually infected or intravenous drug user mothers showed no differences. CONCLUSION: As in adults, aCL are commonly found in children with HIV infection. The significance of this finding is still unclear.

Antiribonucleoprotein antibodies in children with human immunodeficiency virus infection: comparative study with childhood-onset systemic lupus erythematosus.

UNLABELLED: A number of clinical and laboratory features of human immunodeficiency virus (HIV) infection are found in systemic lupus erythematosus (SLE). OBJECTIVE: To analyze the presence of circulating antibodies to small nuclear ribonucleoproteins (snRNP) in both diseases. METHODS: We studied sera from 44 HIV-infected children, from 22 patients with childhood-onset SLE, and from 50 healthy children. Anti-snRNP antibodies were detected by (ELISA) using recombinant and affinity-purified nuclear antigens, by counterimmunoelectrophoresis (CIE), and by immunoblotting using extractable nuclear antigens. RESULTS: Anti-snRNP antibodies were detected by ELISA in 30 HIV-infected patients (68.1%) and 19 SLE patients (86.3%). These antibodies were directed against U1-RNP (61.3% and 77.2%), Sm (29.5% and 54.5%), 60kD-Ro/SS-A (47.7% and 50%), and La/SS-B proteins (18.1% and 9%), respectively. None of the HIV-infected children and 11 SLE patients (50%) showed anti-snRNP antibodies by CIE. None of the HIV-infected patients showed anti-70 kD U1-RNP or anti-D-Sm antibodies by immunoblotting. No differences between the two groups were noted relative to the presence of nonprecipitating anti-snRNP antibodies. No such reactivities were observed among the normal sera tested. CONCLUSIONS: Nonprecipitating anti-snRNP antibodies in HIV-infected children are as frequent as in childhood-onset SLE. The significance of these antibodies is not clear at present. Perhaps they are polyreactive and low-affinity antibodies and a mechanism of molecular mimicry may explain these results; however, we cannot exclude a specific stimulation of B-cells by nuclear antigens.

Immunological and clinical differences between juvenile and adult onset of systemic lupus erythematosus.

INTRODUCTION: Systemic lupus erythematosus (SLE) in children usually follows a more severe course than in adults, but sometimes in the previous studies reported there are many confounding factors. OBJECTIVE: To analyse the immunological and clinical characteristics of SLE juvenile onset and SLE adult onset. METHODS: We studied 179 patients with SLE, 49 patients were aged 6-18 yrs at onset of disease. Anti-dsDNA antibodies were detected by radioimmunoassay and antibodies to extractable nuclear antigens (ENA): anti-nRNP, anti-Sm, anti-Ro/SS-A and anti-La/SS-B antibodies by ELISA, counterimmuno-electrophoresis and immunoblotting. RESULTS: Juvenile-onset SLE shows a higher frequency of cutaneous vasculitis (44.8% vs 27.6%; P < 0.05), seizures (18.3% vs 7.6%; P < 0.05) nephropathy (67.3% vs 48.4%; P < 0.025), and discoid lupus erythematosus (26.5% vs 13.8%; P < 0.05). The incidence of articular manifestations is lower than in adults (85.7% vs 96.1%; P < 0.025). No significant differences were found between the two groups in relation with the prevalence of antinuclear antibodies. CONCLUSIONS: Juvenile-onset SLE has more frequent neurological and renal manifestations than adult-onset SLE, but immunological markers are similar in both groups. These features suggest the most severe clinical manifestations in the juvenile-onset SLE group are not related with the presence of studied antibodies by different methods.

Anti-BB'-Sm antibodies, anticardiolipin antibodies, and thrombosis in systemic lupus erythematosus.

OBJECTIVE: Anticardiolipin antibodies (aCL) are associated with thrombosis in patients with systemic lupus erythematosus (SLE). Our aim was to determine whether there is an association between aCL, anti-Sm antibodies, and thrombosis in patients with SLE. METHODS: Sera from 153 patients with SLE were studied by ELISA, immunoblotting, and counter-immunoelectrophoresis (CIE) for anti-Sm antibodies, aCL and anti-dsDNA antibodies were detected by ELISA and radioimmunoassay, respectively. RESULTS: Anti-Sm antibodies were detected in 62 patients (40.5%) by ELISA and in 16 (10.4%) by CIE; IgG-anti-BB'-Sm in 44 (28.7%) by immunoblotting; IgG-aCL in 82 (53.5%), IgM-aCL in 44 (28.7%), and anti-dsDNA antibodies in 128 (83.6%). Anti-Sm and anti-dsDNA antibodies were significantly more frequent in patients with than in patients without aCL. Of the 89 patients with aCL, 36 (40.4%) showed IgG-anti-BB'-Sm antibodies (OR: 4.7; 95% CI: 2-10.5). Thrombosis was present in 20 (22.4%) SLE patients with aCL and in two (3.1 %) SLE patients without aCL (OR: 8.9; 95% CI: 2.4-31.8). Of the 22 patients with thrombosis, five (22.7%) had precipitating anti-Sm antibodies (OR: 3.2; 95% CI: 1.04-9.8) and 14 (63.6%) showed IgG-anti-BB'-Sm antibodies (OR: 5.8; 95% CI: 2.3-14). Anti-BB'-Sm and aCL were significantly more frequent in patients with anti-dsDNA antibodies (32 and 62%) than in patients without these antibodies (12 and 36%) (OR: 3.4 and 2.9; 95% CI: 1.03-11.1 and 1.2-6.7, respectively). CONCLUSION: IgG-anti-BB'-Sm antibodies are associated with aCL, anti-dsDNA, and thrombosis in patients with SLE. Our findings suggest a possible association between anti-Sm, anti-dsDNA, and aCL responses in these patients.