Coexistent minocycline-induced systemic lupus erythematosus and autoimmune hepatitis

BACKGROUND AND OBJECTIVES: The K-ras gene is one of the most extensively investigated oncogenes in a wide variety of human tumors, but has rarely been studied in distal bile duct carcinoma (DBDC). We sought to investigate the diagnostic and prognostic value of K-ras codon 12 mutations in this type of tumor. METHODS: Forty-seven patients who had undergone resection for DBDC were analyzed to reveal the incidence of K-ras codon 12 mutations, the locus most frequently involved. A rapid and simple two-step, semi-nested polymerase chain reaction (PCR) technique was used to detect mutations in paraffin-embedded tumor samples. RESULTS: The PCR mismatch amplification technique demonstrated that 35 (75%) of the 47 tumors harbored a point mutation in codon 12 of the K-ras oncogene. Patients with mutated tumors had no statistically different survival time compared to those patients without a mutation in the tumor. In contrast, negative microscopic margins proved to be a significant prognosticator. CONCLUSIONS: K-ras codon 12 mutations are common in DBDC and may be useful in the diagnosis and early detection of these tumors. However, no prognostic value of these mutations could be identified in this analysis. The results of this study also suggest that negative surgical margins remain the mainstay of prognostication in resectable DBDC. However, due to the small number of patients included in this study, the results obtained should be interpreted with care.     

Methotrexate therapy in refractory pediatric onset systemic lupus erythematosus

OBJECTIVE: To evaluate the efficacy, safety, and corticosteroid sparing potential of methotrexate (MTX) in patients with pediatric onset systemic lupus erythematosus (SLE). METHODS: The medical records of 11 patients with SLE with onset before age 16 years were reviewed. Details of clinical features, previous therapy, indications for MTX, efficacy, toxicity, and corticosteroid reduction during MTX therapy were recorded. RESULTS: At the start of MTX treatment, 7 patients had nephritis, 3 malar rash, 3 arthritis, 2 skin vasculitis, and 2 thrombocytopenia. All patients were given MTX (12.5-17.0 mg/m2/week) as the sole drug therapy along with prednisone. Although many patients showed initial improvement and/or were able to reduce the prednisone dose, after 7 to 23 months 8 patients had a flare of SLE requiring increased doses of prednisone, one patient had unchanged SLE activity, and 2 patients were permanently discontinued from MTX because of toxicity. Side effects were observed in 8 (73%) patients, but only 2 (18%) discontinued MTX due to toxicity. CONCLUSION: MTX given as the sole drug therapy along with prednisone did not show a major corticosteroid sparing potential in our patients with pediatric onset SLE.     

How to diagnose autoimmune hepatitis in systemic lupus erythematosus?

In a patient with systemic lupus erythematosus (SLE), we considered the diagnosis of autoimmune hepatitis (AIH) in view of raised serum aminotransferases, hypergammaglobulinaemia, antinuclear antibodies (titre 1:10,240), seronegativity of markers for viral hepatitis and absence of recent hepatotoxic drug usage. The diagnosis of AIH was supported by using the scoring system, recently developed by the International Autoimmune Hepatitis Group and the excellent response to treatment with prednisone. Liver histology, however, showed no characteristic features of AIH. The relevance of liver histology and scoring for AIH in SLE with hepatic involvement is discussed.     

Formalin treatment of refractory hemorrhagic cystitis in systemic lupus erythematosus

Hemorrhagic cystitis is a potentially life-threatening complication in systemic lupus erythematosus (SLE). No safe, effective and conservative treatment exists for patients who fail to respond to standard therapy. We report a 17-year-old girl with SLE who suffered from severe hemorrhagic cystitis. Initially, she received frequent red blood cell and platelet transfusions, continuous bladder irrigation, and blood clots were evacuated. Numerous kinds of treatment were tried, including electrocoagulation of bleeding foci, prostaglandin E1 bladder instillation, and hyperbaric oxygen. However, she remained severely anemic and thrombocytopenic necessitating daily transfusions of blood products. After intravesical formalin instillation was performed twice, the hematuria ceased completely.     

Deforming arthropathy or lupus and rhupus hands in systemic lupus erythematosus

OBJECTIVE: Although deforming arthropathy in systemic lupus erythematosus (SLE) is characterised by a number of manifestations, definitive criteria for the different forms have not yet been established. To define deforming arthropathy and its different types a study was undertaken of 176 SLE patients. METHODS: Using as criterion any deviation from any of the metacarpus finger axes 17 patients (16 women, one man) were identified with clinical deforming arthropathy. These patients were evaluated according to a standardised protocol that covered all known characteristics of deforming arthropathy. By means of "Jaccoud's arthropathy index" three different forms were identified. RESULTS: Three patients had an erosive form of deforming arthropathy (or rhupus hand) such as those seen in frank rheumatoid arthritis (RA), eight patients were identified as having Jaccoud's arthropathy (or lupus hand), and the remaining six patients had mild deforming arthropathy. Jaccoud's arthropathy is characterised by severe deformation of the hands (ulnar deviation, swan neck deformities, and Z deformity of the thumb) and feet with multiple non-erosive subluxations, mild aching and little or no evidence of synovitis. All patients, but one, fulfilled just four criteria of the ACR classification and joint symptoms were always found to precede the diagnosis of SLE. Furthermore a remarkable association of Jaccoud's arthropathy with fetal loss, thrombosis--both venous and arterial--and the presence of antiphospholipid antibodies was found. CONCLUSIONS: These data suggest that Jaccoud's arthropathy represents a subset of SLE. Subdivision of deforming arthropathy into several clinical forms can facilitate the clinical management of this disorder.     

Down syndrome associated with systemic lupus erythematosus: a mere coincidence or a significant association?

An 8-year-old male, who had Down syndrome associated with systemic lupus erythematosus (SLE), is described. He also had a partial complement 4 deficiency. This case is a reminder that the physician should be aware of the possibility of an immune defect in a male presenting with SLE at a young age. The question of whether the association of Down syndrome with SLE is coincidental or whether there is a predilection for autoimmune disorders in Down syndrome is discussed.     

Anti-platelet antibodies in patients with systemic lupus erythematosus and the primary antiphospholipid antibody syndrome: their relationship with the observed thrombocytopenia

The role of antiphospholipid antibodies in the pathogenesis of the thrombocytopenia observed during primary antiphospholipid antibody syndrome (APAS) and systemic lupus erythematosus (SLE) remains controversial. We have used the MAIPA test to examine the frequency and specificity of anti-platelet antibodies directed against the major platelet membrane glycoproteins (GP IIb-IIIa, GP Ib-IX, GP Ia-IIa and GP IV) in patients where SLE and APAS were associated or not with thrombocytopenia. Results were compared with a series of 26 ITP patients, 46% of whom were shown to possess anti-platelet antibodies directed against one or more of the platelet surface glycoproteins. When APAS was associated with thrombocytopenia, 7/10 patients possessed antibodies against GP IIb-IIIa and/or GP Ib-IX. For SLE patients with thrombocytopenia, 6/10 patients were shown to have antiplatelet antibodies against GP IIb-IIIa, GP Ib-IX or GP IV. In contrast, for APAS (n=11) and SLE patients (n=11) without thrombocytopenia, only one patient had an antibody directed against GP IIb-IIIa and one patient had an antibody to GP IV. Our results suggest that antibodies directed against major platelet membrane glycoproteins may play a role in the thrombocytopenia that is seen during SLE and APAS.     

Celiac disease associated with systemic lupus erythematosus

Celiac disease in children has been occasionally reported to be associated with various disorders such as arthritis, cutaneous vasculitis and diabetes mellitus. We report on a 12-year-old girl with celiac disease, diagnosed at 1 year of age, who developed systemic lupus erythematosus. This association has not yet been reported in children.     

Hyperprolactinemia in males with systemic lupus erythematosus

Alanine dehydrogenase [EC 1. 4. 1. 1] was purified to homogeneity from a crude extract of Enterobacter aerogenes ICR 0220. The enzyme had a molecular mass of about 245 kDa and consisted of six identical subunits. The enzyme showed maximal activity at about pH 10.9 for the deamination of L-alanine and at about pH 8.7 for the amination of pyruvate. The enzyme required NAD+ as a coenzyme. Analogs of NAD+, deamino-NAD+ and nicotinamide guanine dinucleotide served as coenzymes. Initial-velocity and product inhibition studies suggested that the deamination of L-alanine proceeded through a sequential ordered binary-ternary mechanism. NAD+ bound first to the enzyme, followed by L-alanine, and the products were released in the order of ammonia, pyruvate, and NADH. The Km were 0.47 mM for L-alanine, 0.16 mM for NAD+, 0.22 mM for pyruvate, 0.067 mM for NADH, and 66.7 mM for ammonia. The Km for L-alanine was the smallest in the alanine dehydrogenases studied so far. The enzyme gene was cloned into Escherichia coli JM109 cells and the nucleotides were sequenced. The deduced amino acid sequence was very similar to that of the alanine dehydrogenase from Bacillus subtilis. However, the Enterobacter enzyme has no cysteine residue. In this respect, the Enterobacter enzyme is different from other alanine dehydrogenases.     

Neuropsychiatric systemic lupus erythematosus and the syndrome of inappropriate secretion of antidiuretic hormone: a case report with very late onset systemic lupus erythematosus

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with neuropsychiatric lupus (NP-SLE) is rare. We report a case of SIADH associated with the new onset of SLE in an 88-yr-old female. The unique features of this case include the extreme age of onset of SLE presenting with neuropsychiatric manifestations and positive antiribosomal P antibody titres. Both the NP manifestations of SLE and SIADH were highly correlated with the SLE disease activity. This case illustrates a novel presentation of NP-SLE with SIADH which may develop due to antibody-mediated hypothalamic dysfunction.     

Elevated anticardiolipin antibodies in autoimmune haemolytic anaemia irrespective of underlying systemic lupus erythematosus

In patients with systemic lupus erythematosus (SLE) and concomitant Coombs positive autoimmune haemolytic anaemia (AIHA) anticardiolipin antibodies (aCL) are found more frequently and at higher titres than in SLE patients without AIHA. In order to assess if aCL elevation is primarily associated with the underlying SLE, or with AIHA itself, we examined AIHA patients with and without underlying SLE for the presence of aCL. aCL (IgG and IgM) were determined by ELISA in 74 SLE patients without AIHA, 22 SLE patients with AIHA, 50 patients with idiopathic AIHA (warm-reactive autoantibodies), 52 patients with idiopathic AIHA (cold-reactive autoantibodies) and 50 healthy controls. The mean IgG and IgM aCL titres in SLE patients without AIHA (IgG 37.0 U/ml, IgM 8.9 U/ml) were significantly elevated compared with the values in healthy controls (IgG 9.1 U/ml, IgM 3.2 U/ml; P < 0.005). The mean aCL levels in SLE patients with AIHA (IgG 53.2 U/ml, IgM 28.2 U/ml) were higher than in SLE patients without AIHA (P = 0.09 for IgG, P < 0.005 for IgM). Interestingly, the mean aCL levels of patients with idiopathic AIHA (warm-reactive autoantibody type: IgG 29.2 U/ml, IgM 19.3 U/ml; cold-reactive autoantibody type: IgG 27.4 U/ml, IgM 18.9 U/ml) were also significantly elevated compared with healthy controls P < 0.001). As aCL are elevated not only in SLE (with and without concomitant AIHA) but also in idiopathic AIHA it can be speculated that aCL are involved in the pathomechanism of autoantibody-induced erythrocyte destruction per se irrespective of an underlying SLE.