Successful Treatment of Systemic Lupus Erythematosus Cerebritis with Intravenous Immunoglobulin

Neuropsychiatric lupus includes extremely diverse clinical manifestations, ranging from mild cognitive dysfunction to a severe, life-threatening presentation. We report a 28-year-old patient with systemic lupus erythematosus who had persistent fever for 3 months, and developed within a few hours motor and sensory aphasia, rotator nystagmus with deviation of the eyes, and severe nuchal rigitidy. An extensive series of imaging and laboratory tests were interpreted as normal, except for an elevated opening pressure at lumbar puncture, cerebrospinal fluid inflammatory findings, and asymmetrical cortical perfusion on single-photon emission computed tomography. The patient received one course of high-dose intravenous immunoglobulin (IVIg) and within 5 days her condition returned to that of 3 months before admission. The mechanisms of injury, along with the management of cerebral lupus and the mechanisms of action of IVIg, are discussed. Received: 13 July 1998 / Accepted: 29 October 1998     

The Urinary Excretion of Glycosaminoglycans and Heparan Sulphate in Lupus Nephritis

Renal involvement in systemic lupus erythematosus (SLE) affects the disease outcome. In order to advance the diagnosis and the initiation of therapy, non-invasive diagnostic techniques are required. In this study, urinary glycosaminoglycans (GAG) and heparan sulphate (HS) were measured in 26 patients with biopsy-proven lupus nephritis and compared to 16 healthy controls. Uronic acid as a representative of GAGs in urine was determined spectrophotometrically with the meta-hydroxydiphenyl, following acid treatment. HS was determined as hexosamine by the method of Smith and Gilkerson. The median values of GAG (3.99 mg/g crea./day) and HS (2.41 mg/g crea./day) in patients were significantly (P= 0.001) higher than in the control group (1.98 and 0.87, respectively). There was a positive correlation between GAG and HS values (P= 0.000, r= 0.924) in SLE patients. There were no differences in HS excretion, microalbuminuria and SLE-DAI scores between different classes of lupus nephritis. However, GAG values in class 3 nephritis were significantly (P= 0.033) higher than from both class 2 and class 4 lupus nephritis. There were no differences in all the measured parameters between normoalbuminuric, microalbuminuric and macroproteinuric patients. Furthermore, there were no correlations between GAG, HS excretions and SLE-DAI scores or microalbuminuria. These results suggest that urinary GAG and HS may serve as useful, independent and non-invasive markers of lupus nephritis. Received: 26 September 2001 / Accepted: 5 February 2002     

Clinico-Laboratory Characteristics of Patients with Dermatomyositis Accompanied by Rapidly Progressive Interstitial Lung Disease

The clinico-laboratory features of 16 patients with dermatomyositis (DM) were compared between patients with accompanying rapidly progressive interstitial lung disease (RP-ILD, n= 7) and those with chronic interstitial lung disease (C-ILD, n= 9), and also between deceased (seven RP-ILD and three C-ILD) and living patients (six C-ILD). The extent of muscle weakness of the extremities and frequency of autoantibody positivity were significantly lower in DM patients with RP-ILD than in DM patients with C-ILD. Furthermore, significantly lower serum ceatine kinase/lactate dehydrogenase levels (0.26 ± 0.27) were found in the 10 patients who died than in the six living patients (1.21 ± 1.09). A higher CD4+/CD8+ T-lymphocyte ratio in the peripheral blood (3.51 ± 2.65) was detected in the four DM patients with RP-ILD who died than in the six living DM patients with C-ILD (1.22 ± 0.49). Received: 8 September 1998 / Accepted: 16 February 1999     

Therapeutic Plasma Exchange for the Treatment of Rapidly Progressive Glomerulonephritis

Abstract: Therapeutic plasma exchange (TPE) has been widely accepted as a successful means of removing the antiglomerular basement membrane (anti-GBM) antibodies that result in the rapidly progressive glomerulonephritis (RPGN) of Goodpasture's syndrome. TPE has also been investigated as a means of removing the immune complexes associated with the glomerulonephritides of systemic lupus erythematosus, IgA nephropathy, Henoch Schönlein purpura, and cryoglobulinemia. Recently, an antineutrophil cytoplasmic antibody (ANCA) has been implicated in the pathogenesis of RPGN associated with such diseases such as Wegener's granulomatosis and periarteritis nodosa. ANCA has also been found in many cases of RPGN formally considered to be idiopathic. The identification of this autoantibody has given new credence to the possibility that TPE may be beneficial in the treatment of these diseases. This article reviews the data regarding the use of TPE for RPGN.     

Marked Improvement of Severe Cardiac Dysfunction After One Course of Intravenous Immunoglobulin in a Patient with Systemic Lupus Erythematosus

Intravenous immunoglobulin (IVIg) is currently used with much enthusiasm for the treatment of many autoimmune diseases, including systemic lupus erythematosus (SLE). Among its various indications, IVIg has also been found to be beneficial in myocarditis, whether or not it is associated with an autoimmune disease (e.g. Kawasaki’s disease). We report a 59-year-old SLE patient who, while being treated with steroids, developed severe cardiac dysfunction with a left ventricular ejection fraction of 20%. Coronary angiography demonstrating normal coronary arteries supported the diagnosis of myocarditis. High-dose IVIg treatment was started, followed by improved cardiac function a few days later and normalisation of the ejection fraction (50%) 1 month later. This is the second report of a beneficial effect of IVIg in myocarditis secondary to SLE. Received: 27 June 1998 / Accepted: 2 November 1998     

Intravenous Cyclophosphamide Pulse Therapy for the Treatment of Lung Disease Associated with Scleroderma

Until recently, renal crisis was the most significant cause of morbidity and mortality in patients with scleroderma (SSc). Nowadays, following the introduction of angiotensin-converting enzyme inhibitors used in renovascular hypertension, pulmonary fibrosis and pulmonary hypertension have become the most common causes of death in SSc. Consequently, the early diagnosis and treatment of pulmonary fibrosis is essential to improve morbidity and mortality in SSc patients. The aim of this study was to investigate the effect of intravenous cyclophoshamide pulse therapy in patients with SSc and evidence of active alveolitis assessed on a high resolution computed tomographic (HRCT) scan, and to compare the effect of cyclophosphamide pulse therapy with oral therapy. Sixteen consecutive patients with SSc were allocated alternately to the two treatment groups. Eight patients were treated with monthly cyclophoshamide pulse therapy (750 mg/m²) for 12 months; the other eight patients were treated with oral cyclophosphamide (2–2.5 mg/kg/day) for the same period. All patients received concurrently prednisone (10 mg/day). Pulmonary function tests and HRCT scans were performed before therapy and at 6 and 12 months. In the oral cyclophosphamide group, three patients with a grade I pattern showed regression of disease extent. In the other five patients (one with grade II and four with grade III) the pattern and extent of disease remained stable during the study. No statistical differences were found in forced expiratory volume in 1 s, forced vital capacity and total lung capacity during the study period. The diffusing capacity for carbon monoxide increased significantly between baseline and 12 months (p= 0.043). In the cyclophosphamide pulse therapy group, seven patients with a grade I pattern showed regression of disease extent at 6 months (p= 0.018) and 12 months (p= 0.012). One patient with grade III remained stable during the study. In both groups the regression of the extent of disease estimated on HRCT was due to a decrease in the ground glass appearance. The extent of the reticular appearance remained stable throughout the study. Our results indicate that cyclophosphamide pulse therapy is effective in suppressing active alveolitis (ground glass appearance). Although in this study it is not possible to compare pulse therapy with oral therapy because of the different pattern seen on HRCT between the two groups, it seems that oral therapy is also effective in suppressing active alveolitis. Neither regimen improved pulmonary involvement when the reticular appearance predominated over the ground glass appearance on HRCT. It is concluded that either pulse or oral cyclophosphamide therapy may improve the outcome of SSc patients. Received: 10 November 1998 / Accepted: 4 April 1999     

Plasma Exchange Is Highly Effective for Anti‐Neutrophil Cytoplasmic Antibody‐Associated Vasculitis Patients With Rapidly Progressive Glomerulonephritis Who Have Advanced to Dialysis Dependence: A Single‐Center Case Series

Plasma exchange (PEX) can be an effective treatment in anti‐neutrophil cytoplasmic antibody‐associated vasculitis with severe renal damage; however, it is still controversial. Among cases of newly diagnosed AAV with rapidly progressive glomerulonephritis at our department from 2008 onward, 11 patients who received PEX (seven cases for severe renal damage [R‐PEX] and four cases for lung hemorrhage [L‐PEX]) were retrospectively analyzed. All cases of R‐PEX were dependent on hemodialysis at the beginning of PEX and all received seven sessions of PEX (50 mL/kg or 1.3 plasma volume per exchange) within 2 weeks. All cases became dialysis‐independent within 8 weeks, with 3‐ and 12‐month cumulative renal survival rates of 100% and 80%, respectively. All cases of L‐PEX retained their renal function. In rapidly developing, newly dialysis‐dependent antibody‐associated vasculitis with rapidly progressive glomerulonephritis patients with normal renal function before disease onset, standard PEX can be expected to induce sufficient renal recovery to establish dialysis independence.     

A Complex Case of Hepatitis in a Patient with Systemic Lupus Erythematosus

Liver involvement in patients with systemic lupus erythematosus (SLE) is considered rare. Previous treatment with potentially hepatotoxic drugs or viral hepatitis have usually been implicated as the main causes of liver disease in SLE patients. On the other hand, even after careful exclusion of these aetiologies, the problem remains whether to classify the patient as having a primary liver disease with associated autoimmune clinical and laboratory features resembling SLE, such as autoimmune hepatitis, or as having liver disease as a manifestation of SLE.  We report the case of an elderly woman who presented with acute hepatitis, who had been diagnosed with SLE 14 years ago and who also had Sjo¨gren’s syndrome and anti-phospholipid’s syndrome for several years. The histology depicted chronic active hepatitis and, after drug-induced hepatitis and viral hepatitis were excluded, the serological and clinical features were shown to be typical of liver damage caused by SLE. The patient was treated with azathioprine 100mg/d and prednisone 30 mg/d. The clinical symptoms resolved in 10 days and the laboratory values were normal at the end of the first month of therapy. Prednisone was progressively reduced, during a period of 4 months, to 10 mg/d but azathioprine was kept to the same dose. One year after the diagnoses the patient is still in remission.  Although uncommon, hepatic involvement is well recognised in SLE. The interest of this case lies in the differential diagnosis and recognition of this condition, which deserves an agressive treatment. Received: 8 March 1999 / Accepted: 8 March 1999     

Sudden Sensorineural Hearing Loss as a First Manifestation of Systemic Lupus Erythematosus: Association with Anticardiolipin Antibodies

Sudden sensorineural hearing loss is a rarely reported manifestation of systemic lupus erythematosus (SLE). This condition has been most frequently seen in individuals with concomitant anticardiolipin antibody (ACL) syndrome, although a direct causal relationship remains unconfirmed. We report an unusual case of a young male with sudden unilateral hearing loss as the first manifestation of SLE. This individual was also found to be ACL positive and subsequently presented with other thrombotic manifestations compatible with this syndrome. The literature regarding this condition is reviewed and the significance of this case in fortifying the association of anticardiolipin antibodies and sensorineural hearing loss is discussed. Received: 27 September 2000 / Accepted: 4 December 2000     

Efficacy of Early Treatment of Severe Juvenile Dermatomyositis with Intravenous Methylprednisolone and Methotrexate

A pilot study was conducted to assess the efficacy of early treatment of severe juvenile dermatomyositis (JDMS) patients with intravenous methylprednisolone (IVMP) and methotrexate (MTX). Twelve children diagnosed with severe JDMS were treated with IVMP and MTX. Six patients were treated early (within 6 weeks of the diagnosis) while in the other six patients, MTX was started 5–72 months after the diagnosis was made. The clinical responses of the patients to treatment, including alterations in muscle strength, muscle enzyme levels and corticosteroid dosage as well as the development of side-effects, were recorded. The indications for starting the treatment were defined and documented. The primary measures of response were resolution of the clinical indications for treatment, decreased activity of the disease manifestations and tapering of the corticosteroids to the minimal dose or discontinuation without clinical or biochemical flare. The main indications for starting IVMP and MTX were dysphagia and severe cutaneous vasculitis. All the patients received MTX orally for at least 8 months, as well as IVMP (30 mg/kg/dose), but none of the patients was on additional second-line treatments. The six patients who were treated early with MTX showed a significant clinical improvement. In five out of the six, the corticosteroid dosage was eventually reduced to <5 mg/day. None of them developed calcinosis. In contrast, two of the six patients who were treated late with MTX developed calcinosis. This study suggests that MTX and IVMP are a useful combination in the early treatment of severe JDMS. Given the fact that our sample was small, further studies in a controlled trial are necessary to confirm these findings. Received: 8 March 1999 / Accepted: 7 September 1999     

Pachymeningitis and Optic Neuritis in Rheumatoid Arthritis: Successful Treatment with Cyclophosphamide

Pachymeningitis is a rare complication of rheumatoid arthritis. The case of a 52-year-old male rheumatoid arthritis patient with pachymeningitis and optic neuritis who was successfully treated with intravenous cyclophosphamide is described. Received: 3 April 2000 / Accepted: 25 September 2000     

Spondyloepiphyseal Dysplasia Tarda with Progressive Arthropathy

Spondyloepiphyseal dysplasia tarda with progressive arthropathy, described by Wynne-Davies et al., is a rare autosomal recessive disorder. It is characterised by generalised platyspondyly and epiphyseal involvement, with enlargement of both ends of the short tubular bones of the hands. Clinical features include onset in childhood, a disproportionately short stature and premature osteoarthritis. We describe the clinical and radiographic findings of a young woman suffering from spondyloepiphyseal dysplasia tarda with progressive arthropathy. Received: 31 May 1999 / Accepted: 2 December 1999     

Effects of Cisapride on Oesophageal Transit of Solids in Patients with Progressive Systemic Sclerosis

In most patients with progressive systemic sclerosis (PSS) the oesophagus is affected. Reflux symptoms are most frequent, whilst dysphagia also occurs. Cisapride, a prokinetic agent, may enhance motility along the gastrointestinal tract. The effects of cisapride on oesophageal transit were evaluated in 12 PSS patient using a solid-phase radionuclide oesophageal transit study. Each PSS patient was given cisapride 10 mg or placebo orally three times a day in a random, double-blind, crossover fashion. The results show that cisapride does not seem to have any impact on oesophageal transit in patients with PSS. Received: 1 August 2000 / Accepted: 6 August 2001     

Successful treatment with low-dose weekly methotrexate in a case of undifferentiated spondyloarthropathy coexisting with cutaneous polyarteritis nodosa

A case of a 56-year-old woman diagnosed with HLA-B27-positive undifferentiated spondyloarthropathy who developed cutaneous lesions consistent with cutaneous polyarteritis nodosa is presented. The rarity of this association and the dramatic response of both conditions to low-dose weekly methotrexate are emphasised. Received: 15 May 2001 / Accepted: 11 January 2002     

A case of polymyositis with anti-histidyl-t-RNA synthetase (Jo-1) antibody syndrome following extensive vinyl chloride exposure

Occupational exposure to vinyl chloride monomers is known to induce Raynaud’s phenomenon, periportal fibrosis, liver angiosarcoma and scleroderma-like syndrome. We report the first case of occupational polymyositis in a 58-year-old man exposed to vinyl chloride. A dysimmune process was strongly suspected as having induced vinyl chloride disease. Our patient had an anti-histidyl-t-RNA-synthetase (Jo1) antibody, which has never to our knowledge been reported in this occupational disease. Received: 18 July 2000 / Accepted: 25 April 2001     

Mixed Connective Tissue Disease Associated with Skin Defects of Livedoid Vasculitis

A 21-year-old woman who had a 2-year history of mixed connective tissue disease (MCTD) developed rapidly evolving ulcers consistent with livedoid vasculitis (LV) in all distal extremities. She presented clinically with Raynaud’s phenomenon, polyarthritis and swollen hands; serologically with high titres of ANA and anti-nRNP; and immunogenetically with HLA-DR4 and HLA-DR53. Although there was initial success in treatment except for the skin defects over the ankles, the patient died from disseminated intravascular coagulation. We suggest that LV may be a poor prognostic manifestation in MCTD. Received: 9 August 1999 / Accepted: 25 January 2000     

Adult Onset of Multifocal Eosinophilic Granuloma of Bone: A Long-term Follow-up with Evaluation of Various Treatment Options and Spontaneous Healing

We report a case of multifocal–monosystemic Langherhans cell histiocytosis (LCH), formerly usually referred to as eosinophilic granuloma (EG) of bone. The condition developed in a 36-year-old man. A notable infrequent thoracic spine location and two successive distinct costal lesions were observed. Both the first costal site and the vertebral location healed spontaneously; the second costal lesion underwent biopsy resection. The patient’s disease course with an 8-year follow-up is discussed with reference to various treatment options, emphasising in selected cases a watchful conservative approach, in view of the widely documented potential for spontaneous healing. Received: 7 November 1997 / Accepted: 13 July 1998     

Unsuccessful Treatment with Fludarabine in Four Cases of Refractory Rheumatoid Arthritis

The aim of this study was to evaluate the efficacy of fludarabine treatment in patients suffering from refractory rheumatoid arthritis. Four patients affected by refractory seropositive rheumatoid arthritis underwent treatment with fludarabine for 6 months. The drug was administered intravenously at a dose of 25 mg the first month in a single infusion, and then monthly for 5 months at a dose of 25 mg for 3 consecutive days. All four patients obtained no clinical benefit from the treatment; moreover, inflammation indices worsened and the prednisone dosage was increased during the trial, in spite of a significant fall in CD4+ T cells. In our experience low-dose fludarabine is not useful in the treatment of refractory rheumatoid arthritis. Received: 1 September 1999 / Accepted: 2 March 2000