Lupus

The objective of this paper is to identify predictors for the response to treatment of acute lupus hemophagocytic syndrome (ALHS).

We reviewed seven cases with ALHS admitted to our hospital and published ALHS cases identified in the 2001–2014 Medline database, and then conducted univariate and multivariate analyses to identify predictors for the response to treatment.

Review of our cases showed a significant and negative correlation between serum ferritin and anti-DNA antibody (p = 0.0025). All three patients treated with cyclosporine A (CsA) were considered responders despite high serum ferritin and corticosteroid resistance. We also reviewed 93 patients with ALHS identified in 46 articles. Multiple logistic regression analysis identified C-reactive protein (CRP) (OR 0.83, p = 0.042) and hemoglobin (OR 1.53, p = 0.026) measured at diagnosis of ALHS as significant predictors of the response to corticosteroid monotherapy. Moreover, among 32 patients treated with CsA, serum ferritin was significantly higher in CsA responders (12163 ± 16864 µg/l, n = 22) than in non-responders (3456 ± 6267/µg/l, p = 0.020, n = 10). Leukocyte count was significantly lower in the CsA responders (1940.0 ± 972.3/µl) than in the non-responders (3253 ± 2198/µl, p = 0.034).

Low CRP and high hemoglobin can predict a positive response to corticosteroid monotherapy while high serum ferritin and low leukocyte count can predict a positive response to CsA in patients with ALHS and therefore, when corticosteroid monotherapy is not effective in such cases, CsA could be the first choice of an additional immunosuppressive agent.

Environmental factors appear to play a role in the pathogenesis of lupus erythematosus (LE).

To determine the association between cigarette smoking and various types of cutaneous LE.

Retrospective descriptive study at a dermatology clinic of a tertiary referral hospital.

All patients diagnosed with cutaneous and/or systemic LE from January 2000 to December 2012 at the outpatient clinic for dermatological autoimmune diseases were analyzed.

405 patients were diagnosed with LE. Smokers were more common among patients with cutaneous LE, especially those with LE tumidus or discoid LE. The frequency of cigarette smokers was not significantly higher among patients with other LE-specific skin lesions and patients with systemic LE compared to the general population. Smoking at the onset of disease was associated with LE tumidus (odds ratio OR 4.5), discoid LE (OR 2.05), the male gender (OR 3.31), age < 50 years (OR 1.03), and photosensitivity (OR 2.07).

A retrospective descriptive study at a tertiary referral hospital.

Smoking is highly associated with cutaneous LE, but not systemic LE. Various risk factors appear to be involved in the pathogenesis of cutaneous and systemic LE.

The objective of this paper is to investigate the prevalence of reactivation of the human polyomavirus John Cunningham virus (JCV) in patients with systemic lupus erythematosus (SLE) and its associated clinical manifestations.

Sixty-one patients with SLE and 22 controls were enrolled. Urine JCV viral load was quantified by real-time polymerase chain reaction (PCR). Length variants of the VP1 gene were analyzed using capillary electrophoresis.

The prevalence of JCV viruria (63.9% vs. 18.2%, p < 0.001) and urine JCV viral load (2.92 ± 2.76 vs. 0.81 ± 1.85 copies/ml by log₁₀ scale, p < 0.001) were significantly higher in patients with SLE compared with controls. JCV viruria (+) SLE patients had a higher occurrence of arthritis/arthralgia compared with JCV viruria (−) SLE patients (64.1% vs. 22.7%, p = 0.003). In SLE patients, the urine JCV viral load was significantly associated with the occurrence of arthritis/arthralgia. SLE patients with urine JCV viral load >10,000 copies/ml exhibited a 12.75-fold (95% confidence interval 2.88–56.40) risk in clinical arthritis/arthralgia, 18.90-fold (95% confidence interval 2.10–170.39) risk in persistent arthritis, and significantly greater number of length variants in the VP1 gene of JCV compared with JCV viruria (−) SLE patients.

Reactivation of JCV in the urinary tract of SLE patients was very common. Both JCV viruria and urine JCV viral load were associated with the occurrence of arthritis/arthralgia in patients with SLE. High urine JCV viral load also was associated with the genetic variant in the VP1 gene.

Activation of B cells is a hallmark of systemic lupus erythematosus (SLE). Syk and TRAF6 are key signaling molecules in B-cell activation through BCR and CD40/TLR, respectively. Nevertheless, whether expression of Syk and TRAF6 is altered in SLE B cells remains unknown.

Phosphorylation and/or expression of Syk and TRAF6 were analyzed by flow cytometry in peripheral blood mononuclear cells isolated from SLE patients.

Pronounced phosphorylation and expression of Syk were noted in B cells from SLE patients compared with healthy donors. Levels of Syk phosphorylation correlated with the disease activity score. TRAF6 was significantly over-expressed in B cells of SLE patients as compared with healthy donors, and significant correlation of levels of TRAF6 expression and Syk phosphorylation was observed in SLE patients. Levels of TRAF6 expression were more pronounced in CD27+ memory B cells than in CD27-naïve B cells. In vitro treatment of SLE B cells with a Syk inhibitor (BAY61-3606) reduced Syk phosphorylation as well as TRAF6 expression.

Our results suggest that the activated Syk-mediated TRAF6 pathway leads to aberrant activation of B cells in SLE, and also highlight Syk as a potential target for B-cell-mediated processes in SLE.

Observed low prevalence of SLE among familial Mediterranean fever (FMF) patients in several large cohorts suggests a possible protective effect of the MEFV mutations from SLE. In contrast, SLE patient carriers for the common MEFV mutations had rather complex disease expression with an increased frequency of febrile episodes and pleurisy and a decreased renal complication rate. Our aim was to investigate the prevalence of MEFV gene mutations in patients with SLE and their effect on organ involvement in a well-defined group of biopsy-proven SLE nephritis patients.

The prevalence of four MEFV gene mutations (M694V, M680I, V726A and E148Q) was investigated in 114 SLE patients and effect on disease severity was analyzed in patients with biopsy-proven SLE nephritis.

None of the SLE patients fulfilled the revised Tel-Hashomer criteria. Fourteen of 114 SLE patients (12.2%) were found to carry at least one MEFV mutation. A single patient in the SLE-Nephritis group was compound heterozygous for M694V/M680I mutations and only one patient in the SLE-Mild group was homozygous for E148Q mutation. Carrier frequency was similar to controls in SLE patients (12.2 vs 18.8%, p = 0.34). After the exclusion of the less penetrant E148Q mutation, re-analysis revealed an association between exon 10 mutations and SLE nephritis (p = 0.050, odds ratio (OR) = 4.16, 95% confidence interval (CI) = 1.04–16.6). Carrier rate for the E148Q mutation decreased in the SLE group (controls vs. SLE = 20/186 vs. 3/114, p = 0.08) and E148Q mutation was absent in SLE nephritis (controls vs. SLE nephritis = 20/186 vs. 0/47, p = 0.016, OR = 11.69, 95% CI = 0.69–197.13).

Carrier rate for the studied MEFV mutations was slightly lower in the SLE group, which is in agreement with previous observations that FMF may confer some protection from SLE. Exon 10 mutations were associated with SLE nephritis after the exclusion of the E148Q mutation. The significance of the E148Q as a disease-causing mutation is controversial, and whether E148Q substitution is a polymorphism generally affecting inflammatory pathways is not addressed in the current literature.

In this regard, absence of the E148Q mutation in SLE nephritis may serve as a clue for further investigation into its role as a general modulatory polymorphism for inflammation. This clarification is necessary to conclude whether other more penetrant MEFV gene mutations confer susceptibility to nephritis in SLE.

We aimed to determine 1) ultrasound (US) abnormalities in patients with systemic lupus erythematosus (SLE) with and without hand arthralgia at the day of examination compared with clinical evaluation and healthy controls, and 2) inter-observer reliability of the US abnormalities.

Thirty-three female SLE patients were twice examined with US by three trained examiners. Using B-mode and Doppler US, unilateral wrist and metacarpophalangeal (MCP) joints were examined for synovitis and erosions as well as signs of hand tenosynovitis using a GE Logiq 9 US machine with Doppler settings for slow flow. All patients also underwent clinical joint evaluation and were compared with 11 healthy controls (HC).

Among the patients with SLE 16 (48%) had signs of wrist synovitis, which was only observed in one HC (p = 0.03). Corresponding figures for any MCP joint were 12 (36%) and 0 (p = 0.06). In SLE patients, 18% had hand tenosynovitis and 6% bone erosions. Wrist synovitis was detected by US in 16 SLE patients (81%) with arthralgia compared with 17 patients without (18%) (p = 0.0005). Any US abnormalities were observed in 44% of 25 wrists without tenderness at clinical examination and in 46% of 26 wrists without swelling. Corresponding percentages for MCP2 joints were 27% and 21%. Inter-observer reliability of the US findings was good to excellent for examination of hand joints and tendons.

A majority of SLE patients with hand arthralgia showed US signs of synovitis, erosions and tenosynovitis indicating subclinical disease. Even SLE patients without clinical signs of joint inflammation demonstrated US abnormalities. Good to excellent inter-observer reliability was found in US evaluation of hands in patients with SLE.

The objectives of this paper are to study the impact of disease activity in a large cohort of patients with systemic lupus erythematosus (SLE) and estimate the rate of response to therapies.

We conducted a nationwide, retrospective, multicenter, cross-sectional cohort study of 3658 SLE patients. Data on demographics, disease characteristics: activity (SELENA-SLEDAI), damage, severity, hospitalizations and therapies were collected. Factors associated with refractory disease were identified by logistic regression.

A total of 3658 patients (90% female; median SLE duration (interquartile range): 10.4 years (5.3–17.1)) were included. At the time of their last evaluation, 14.7% of the patients had moderate-severe SLE (SELENA-SLEDAI score ≥6). There were 1954 (53.4%) patients who were hospitalized for activity at least once over the course of the disease. At some stage, 84.6% and 78.8% of the patients received glucocorticoids and antimalarials, respectively, and 51.3% of the patients received at least one immunosuppressant. Owing to either toxicity or ineffectiveness, cyclophosphamide was withdrawn in 21.5% of the cases, mycophenolate mofetil in 24.9%, azathioprine in 40.2% and methotrexate in 46.8%. At some stage, 7.3% of the patients received at least one biologic. A total of 898 (24.5%) patients had refractory SLE at some stage. Renal, neuropsychiatric, vasculitic, hematological and musculoskeletal involvement, a younger age at diagnosis and male gender were associated with refractory disease.

A significant percentage of patients have moderately-to-severely active SLE at some stage. Disease activity has a big impact in terms of need for treatment and cause of hospitalization. The effectiveness of the standard therapies for reducing disease activity is clearly insufficient. Some clinical features are associated with refractory SLE.

Our objectives were: 1) to determine the prevalence of CMV infection at the time of SLE diagnosis, and 2) to determine the risk factors for CMV infection.

A database review of 670 patients with pediatric SLE (pSLE) seen over a 20-year period identified seven patients with a CMV infection detected at the time of diagnosis of SLE. CMV was diagnosed by serology, urine and bronchoalveolar lavage. Clinical manifestations, laboratory findings, virology studies and treatments were reviewed.

CMV infection was detected in seven patients at the time of SLE diagnosis (1.04% of total cohort): six were female: mean age was 13 years. Predominant features included non-Caucasian ethnicity (p < 0.01 as compared to total SLE cohort), persistent fevers on prednisone in seven and nephrotic syndrome in four. Laboratory findings included: anemia in seven, lymphopenia in five, elevated liver enzymes in four, with anti-dsDNA and anti-RNP antibodies present in six and five, respectively. Six patients received ganciclovir and CMV hyperimmune globulin (Cytogam®) with the continuation of prednisone during CMV treatment. Six of seven fully recovered without sequelae (one without treatment) but one patient died with active CMV infection.

There were 1.04% of patients with pSLE who developed CMV infection. All were of non-Caucasian ethnicity. Persistent fever despite prednisone, with concomitant anemia, may be additional clues to CMV infection in pSLE. We suggest all patients have routine testing for CMV immunity at initial presentation of pSLE.

Eltrombopag activates the thrombopoietin (TPO) surface receptor on the megakaryocyte, which increases the production of platelets, and rapidly improves circulating platelet numbers in patients with immune thrombocytopenic purpura (ITP). This allows for rapid tapering and/or cessation of corticosteroid therapy. Less is known about the platelet response to this drug in ITP associated with systemic lupus erythematosus (SLE).

A retrospective review was performed of the clinical course of three consecutive patients, each with SLE-associated ITP who were initially treated with corticosteroids or other immunomodulatory therapy. These patients were treated with eltrombopag at the DMC Center for Bleeding Disorders and Thrombosis. Eltrombopag was administered according the package insert, with an initial dose of 50 mg daily, with weekly, then monthly monitoring of platelet counts and dose adjustments. Some immunomodulatory agents (e.g. hydroxychloroquine) were continued to control non hematologic SLE manifestations.

All three patients maintained acceptable platelet counts (>50,000/mm³ for >3 years) following tapering and cessation of corticosteroids. The drug was well-tolerated and there were no adverse events, and specifically no thrombotic events.

Eltrombopag is effective as a rapidly acting corticosteroid sparing therapy for patients with ITP associated with SLE. This is important in reducing corticosteroid related side effects and morbidities in treating SLE patients with ITP. Larger studies are needed to ascertain safety and efficacy of eltrombopag in SLE patients with ITP, particularly those with coexisting antiphospholipid antibodies.

Lupus erythematosus tumidus (LET) is a subtype of cutaneous lupus erythematosus (CLE) that has been well characterized in recent years. However, some controversy still remains concerning the histological features of epidermal involvement.

The objective of this report is to describe the clinical and microscopic features of LET in patients diagnosed at Hospital Universitari Germans Trias i Pujol, Spain.

We conducted a retrospective study of 25 patients with a diagnosis of LET.

All patients presented with typical LET lesions (smooth, erythematous plaques without macroscopic epidermal changes, such as follicular plugs or scale, that resolved without residual scarring or hypopigmentation). None of the patients fulfilled the criteria for systemic lupus erythematosus during follow-up. Test results for antinuclear antibodies were positive in five patients (20%), with titres below one of 320 in all cases. Twenty-two patients (88%) required antimalarial therapy; response was good in 70% and moderate response in 30%. Minor epidermal alterations were observed in 52% of biopsy specimens, with focal basal vacuolization being the most frequent.

LET is a variant of CLE that has distinctive clinical, histologic and prognostic features. Unlike the patients in the case series previously described in the literature, most of our patients required treatment with antimalarials. Histology revealed mild epidermal alterations in a significant percentage of patients. Thus, in our opinion, the absence of microscopic epidermal alterations is not constant in LET.