Complete heart block in lupus.

Conduction abnormalities are uncommon in adult patients with lupus. We present a young woman with recurrent syncope caused by third-degree atrio-ventricular block as the initial manifestation of lupus and review 31 additional cases of systemic lupus erythematosus patients that have been described previously with complete heart block. Heart blocks occurred almost exclusively in females. The median age was 37 years. In 24 cases heart blocks were diagnosed in patients with established lupus. In only five patients, including the patient presented here, heart blocks were diagnosed before the lupus diagnosis. Syncope was the most common presenting symptom of heart block. Electrocardiographic findings prior to heart block episodes were reported in 17 cases: eight had normal findings, but nine had already variant forms of atrioventricular or intraventricular conduction defects. Anti-nuclear antibody tests were reported in 25 cases and were all positive. Anti-DNA antibodies were also common and were positive in 16 of 19 cases (84%). Anti-La and anti-Ro antibodies were less common (13% and 35%, respectively). Three patients died, all prior to 1975. Heart block resolved in 10 cases. Follow-up was reported in four of these cases and heart block recurred in three of them. A permanent pacemaker was the eventual treatment in 22 cases. The etiology of lupus-associated complete heart block is not clear. It is probably variable, possibly related to effects of autoantibodies reacting with the conduction system, myocardial disease and adverse effects of antimalarials. Insertion of a permanent pacemaker seems to be the preferable method of treatment.

Severe ASIA syndrome associated with lymph node, thoracic, and pulmonary silicone infiltration following breast implant rupture: experience with four cases.

Silicone has been considered biologically inert; thus it has been employed in many medical devices and nowadays is commonly used in plastic surgery for mammary prosthesis. It is well tolerated in most cases. However, autoimmune disorders and siliconomas with granulomatous reactions after silicone implant rupture have been described. We report cases of four women who developed systemic disorders following rupture of silicone breast implants resulting in lymph node and thoracic silicone infiltration. The symptoms in these cases, including arthralgia, myalgia, generalized weakness, severe fatigue, sleeping disturbances, cognitive impairment, memory loss, irritable bowel syndrome, and weight loss, clearly match the criteria of the recently defined autoimmune/inflammatory syndrome induced by adjuvants (ASIA).

Hyponatraemia in older people as a sign of adrenal insufficiency: a case-control study.

BACKGROUND: Hyponatraemia is a common cause of hospitalisation in older adults. Adrenal insufficiency (AI) can result in hyponatraemia. AIM: The aim of our study was to determine the frequency and characteristics of AI in elderly patients with hyponatraemia. METHODS: Thirty patients ≥65 years with Na(+) ≤130 mmol/L and 30 age-matched control subjects, all hospitalised, were included in the study. Plasma cortisol levels were determined before and after intravenous administration of 1 µg synthetic adrenocorticotropin hormone. A peak cortisol >550 nmol/L was considered to exclude AI. RESULTS: Sodium levels were 125 ± 5 and 139.8 ± 2 mmol/L in the hyponatremic and control groups respectively. Baseline cortisol <550 nmol/L was found in a half of hyponatremic patients. However, stimulated cortisol levels were compatible with AI in only one case (3%) and none of the controls. The mean cortisol levels were significantly higher in hyponatremic compared with control subjects, both in the basal state (585 ± 215 and 381 ± 135 nmol/L, respectively, P < 0.001) and after stimulation (933 ± 254 and 781 ± 160 nmol/L, P < 0.05). However, the incremental increase in cortisol levels after stimulation was similar in the two groups (361 ± 196 and 403 ± 155 nmol/L) CONCLUSIONS: AI is an uncommon cause of hyponatraemia in older age. Based on this small cohort, AI may be present in 3% of elderly patients with hyponatraemia. AI cannot be excluded by baseline cortisol in a significant minority of hyponatremic patients and further testing with adrenocorticotropin hormone stimulation is needed.

Effect of biopsy length on the rate of positive temporal artery biopsies.

OBJECTIVE: To investigate the relationship between temporal artery biopsy (TAB) length and the diagnostic sensitivity for giant cell arteritis (GCA). METHODS: TAB pathology reports were reviewed for histological findings and formalin-fixed TAB lengths. The patient's charts were reviewed for clinical data. TAB was considered positive if there was a mononuclear cell infiltrate in the vessel wall. Biopsy-negative GCA was diagnosed when patients fulfilled the American College of Rheumatology classification criteria, in addition to favorable rapid response to steroid therapy. Patients were divided into 3 groups according to the clinical and histological features: Biopsy-positive GCA, biopsy-negative GCA, and no GCA. RESULTS: 305 TAB reports of 173 individuals were reviewed. When only GCA patients TAB-positive and TAB-negative were considered, TAB in the biopsy-positive patients was significantly longer than in biopsy-negative cases (p=0.008). The rate of positive biopsies was only 19% with TAB length of 5 mm or less, but increased to 71-79% with TAB lengths of 6-20 mm, and to 89% when TAB length was longer than 20 mm. Only 3% of positive biopsies were 5 mm or shorter, compared to 27% of TAB in biopsy-negative GCA cases (p<0.001). CONCLUSION: TAB with post-fixation length shorter than 5 mm carries an increased biopsy-negative rate therefore longer TAB length is required for accurate diagnosis. Increasing post-fixation TAB length beyond 20 mm may further increase the rate of positive biopsies, although data were insufficient in that regard.

Negative temporal artery biopsies: eventual diagnoses and features of patients with biopsy-negative giant cell arteritis compared to patients without arteritis.

OBJECTIVE: Characterize patients with negative temporal artery biopsies in regard to their eventual diagnoses, and to find features that would differentiate biopsy-negative GCA from non-GCA patients. METHODS: 58 patients with negative biopsies were included. Patients' data and final diagnoses were obtained from medical records. Biopsy-negative GCA was diagnosed when the American College of Rheumatology classification criteria were met, symptoms improved within 3 days of corticosteroid therapy, and no other condition relevant to the patient's symptoms diagnosed during a follow up of 6 months. RESULTS: Biopsy negative GCA was diagnosed in 11 cases (19%). "Isolated" polymyalgia rheumatica was eventually diagnosed in 5 patients (9%). Altogether, rheumatologic conditions were diagnosed in 23 cases (40%). Other patients (60%) had various hematologic, neurologic-ophthalmic, infectious and malignant disorders. Patients with biopsy-negative GCA were older than non-GCA cases, 81.7+/-6.2 and 74.8+/-8 years, respectively (p=0.05). Headaches were more common in biopsy-negative GCA patients: 91% of them presented with headaches, compared to only 40% of non-GCA patients (p=0.005). Thrombo-cytosis was more common in patients with biopsy-negative GCA compared to non-GCA patients (73% and 19%, respectively, p=0.001). Other clinical and laboratory parameters did not differ significantly between the two groups. CONCLUSIONS: 19% of patients with negative temporal artery biopsies were eventually diagnosed as GCA. Older age, headache and thrombocytosis were more common in that group. These features may help in the diagnostic approach in cases with negative biopsies.

Giant cell arteritis: intensity of the initial systemic inflammatory response and the course of the disease.

OBJECTIVE: Giant cell arteritis (GCA) has a variable course. We assessed whether intensity of initial systemic inflammatory response (ISIR) can predict the course of GCA. METHODS: Charts of 130 GCA patients were reviewed. ISIR intensity at presentation was determined by 5 parameters of inflammation: sedimentation rate >100 mm/h, thrombocytosis >400,000/microl, hemoglobin <11 g/dl, leukocytosis >11000/microl, and fever >37.5 degrees C. Patients were divided into 3 groups according to ISIR intensity: strong (4-5 parameters present, n=24), moderate (2-3 parameters, n=55) and weak ISIR (0-1 parameter, n=51). RESULTS: There were no significant differences between these groups regarding mean age, female:male ratio and the initial prednisone dose. At 1 year, 75% of patients in the strong ISIR group required >5 mg/d of prednisone, compared to 54% and 37% of patients with moderate or weak ISIR, respectively (p=0.015). Disease flares were more common in patients with strong ISIR during a 3-year period, compared to patients with moderate or weak ISIR (77%, 67% and 43%, respectively, p=0.013). Only 33% of patients with strong ISIR were able to discontinue steroids after 3 years, compared to 49% and 77% of patients with moderate and weak ISIR, respectively (p=0.003). CONCLUSION: GCA Patients with strong ISIR have prolonged disease course with more flares, requiring higher steroid doses. ISIR intensity should be taken into consideration when planning studies evaluating potential steroid-sparing agents, as response to treatment may vary in patients with different ISIR intensities.

Gallium-67 scintigraphy in polymyalgia rheumatica.

A patient with atypical presentation of polymyalgia rheumatica is presented. Her major symptoms were mild weakness, pain on passive movement of the shoulder and hip girdles, with mild tenderness but no joint stiffness. Muscle enzymes were within the normal range. The diagnostic work-up included gallium-67 scintigraphy, which showed intense uptake in both shoulders, with remarkable improvement following steroid treatment. A prospective study may delineate the possible role of this imaging modality in establishing a diagnosis of polymyalgia rheumatica.

The incidence of giant cell arteritis in Jerusalem over a 25-year period: annual and seasonal fluctuations.

OBJECTIVE: Giant-cell arteritis (GCA) incidence is reported to be rising. A cyclic pattern of annual incidence rates and seasonal variations were reported by several groups. However, such fluctuations were not observed by others. We examined both annual and seasonal rates of GCA over a period of 25 years in Jerusalem. METHODS: Charts of all patients diagnosed as GCA between 1980-2004 were reviewed. In 170 cases GCA was biopsy-proven. Thirty-six additional cases were included as they met the American College of Rheumatology GCA classification criteria. Data on the Jerusalem population throughout the study period was collected from the annual publications of the Israel Bureau of Statistics. Age- and sex-specific incidence rates per 100000 population aged>or=50 were calculated. RESULTS: For the whole period, the average age-adjusted incidence rate was 11.3 per 100000, and 9.5 for the biopsy-positive cases. The female: male ratio was 1.4:1. Cyclic fluctuations of GCA incidence with 3 distinctive peaks, 8-10 years apart, were observed. Altogether, there was no apparent increase in GCA incidence during this period. Seasonal variations were observed: in 192 patients we were able to estimate the time of onset of GCA symptoms. It showed a peak in the months of May and June, with the number of patients being twice as expected for this period (p<0.001). CONCLUSION: GCA onset was more common in late spring and early summer, and fluctuations in GCA annual incidence with 3 distinctive peaks were observed during a 25-year period. These suggest infectious or other environmental etiology, however thus far no such agents were proven.

Perceived efficacy among patients of various methods of complementary alternative medicine for rheumatologic diseases.

OBJECTIVE: The purpose of this cross-sectional survey was to obtain and analyze data on self-perceived efficacy of different types of complementary alternative medicine (CAM) by patients with various rheumatologic conditions. METHODS: Patients followed in rheumatology outpatient clinics were screened for the use of CAM. Patients reporting the use of CAM were asked to participate in face-to-face structured interviews, specifying the various CAM types they used, and grading their subjective impression of efficacy of each CAM type on a scale of 1-10. RESULTS: 350 consecutive patients were screened and 148 reported using CAM. In general, homeopathy and acupuncture were the most commonly used CAM types (44% and 41% of the CAM users, respectively). The mean number of different CAM methods used by a CAM user was 1.9 +/- 1.1. Patients with fibromyalgia used significantly more CAM methods (2.7 +/- 1.4, p = 0.005). On patients' self-perceived efficacy scale of 1-10, the mean score of the whole group was 5.3 +/- 3.2. Acupuncture and homeopathy achieved significantly higher self-perceived efficacy scores in CAM users with spondylo-arthropathies and osteoarthritis, respectively, when compared to some of the other disease groups. Satisfaction was lowest among CAM users with rheumatoid arthritis, vasculitis and connective tissue diseases. CONCLUSION: In general, CAM users were less than moderately satisfied with self-perceived-efficacy of CAM therapies. However efficacy of specific CAM methods differed significantly among patients in different disease groups.

Rheumatologic complications of vitamin A and retinoids.

Retinoids are synthetic derivatives of vitamin A. They are administered primarily for dermatological conditions, such as psoriasis, acne, and disorders of keratinization. Toxicity has proven a significant problem with long-term administration of the retinoids. Bone abnormalities mimicking seronegative spondyloarthropathy or diffuse idiopathic skeletal hyperostosis have been described in many cases, as well as other rheumatologic manifestations such as arthritis, myopathy, and vasculitis. These retinoid-related adverse effects are reviewed.

Alpha-interferon-induced arthritis: clinical presentation treatment, and prevention.

OBJECTIVE: The therapeutic applications of alpha-interferon (IFN) have expanded greatly to include chronic viral hepatitis and malignant disorders. Autoimmune phenomena occur frequently with IFN therapy, but arthritis is uncommon. We describe the clinical features and treatment of IFN-induced arthritis. METHODS: A patient with chronic myelogenous leukemia who developed arthritis secondary to IFN therapy is presented. The clinical features and treatment of this condition in 37 additional cases are reviewed. RESULTS: The most common clinical presentation was symmetric polyarthritis. This was associated with antinuclear antibodies in 72% of patients and rheumatoid factor in 34%. Cessation of IFN, with or without the addition of antiinflammatory or remittive agents, resulted in remission of arthritis in 89% and 71% of the cases, respectively. Restarting IFN therapy resulted in recurrence of arthritis in 63%. In the patient described in this report, recurrence of arthritis was prevented by coadministration of hydroxychloroquine (HCQ) and prednisone. CONCLUSION: Arthritis is an uncommon complication of IFN therapy; but it may lead to cessation of this treatment modality. In such cases, coadministration of a remittive agent such as HCQ may enable reinstitution of IFN therapy without recurrence of arthritis.

Parvovirus infection mimicking systemic lupus erythematosus.

There are striking similarities between human parvovirus B19 (HPV-B19) infection and systemic lupus erythematosus (SLE): both may present with malar rash, fever, arthropathy, myalgia, cytopenia, hypocomplementemia, anti-DNA, and antinuclear antibodies (ANA). Therefore, it is difficult at times to differentiate HPV-B19 infection from SLE presentation or exacerbation. We report 4 cases of HPV-B19 infection mimicking SLE and review 10 other reported cases, all of whom were women. The similarity to a typical SLE presentation was indeed striking: most patients presented with rash, arthropathy, myalgia, fever, and positive ANA. In some cases, HPV-B19 infection seemed to exacerbate SLE rather then resemble it, and differentiation was difficult. Nearly all patients improved within several weeks. However, a few patients had symptoms and laboratory abnormalities lasting more than 6 months. The possibility of HPV-B19 infection should be entertained in patients presenting with SLE-like features.

Anti-nuclear envelope antibodies: Clinical associations.

OBJECTIVES: Characterization of the clinical associations and clinical implications of antibodies reacting with antigens of the nuclear envelope. METHODS: Description of an illustrative case and a MEDLINE search-assisted literature review of relevant cases. RESULTS: With indirect immunofluorescence, autoantibodies directed against various antigens of the nuclear envelope stain the nucleus in a ring-like (rim) pattern. Autoantibodies against 5 antigenic components of the nuclear envelope have been described: anti-gp210, p62, lamina, lamina-associated polypeptides, and lamin B receptor. Antibodies to antigens of the nuclear pore complex, such as gp210 and p62, are highly specific (> 95%) for primary biliary cirrhosis and may aid in the serologic diagnosis of this condition, especially in cases in which antimitochondrial antibodies are not detectable. In contrast, antilamin antibodies are not disease-specific but seem to be associated with lupus anticoagulant or anticardiolipin antibodies, antiphospholipid syndrome, thrombocytopenia, autoimmune liver diseases, and arthralgia. High-titered antilamin antibodies help to define a subset of lupus patients with antiphospholipid antibodies who are at a lower risk of developing thrombotic events. In addition, preliminary data suggest that the presence of antilamin antibodies may be helpful in the diagnosis of chronic fatigue syndrome. CONCLUSIONS: Each of the antibodies reacting with nuclear membrane antigens has its own spectrum of disease associations. RELEVANCE: Determination of anti-nuclear envelope antibody pattern by indirect immunofluorescence, with subsequent determination of the specific antibody, carries important diagnostic and prognostic implications in various autoimmune conditions.

Valvular dysfunction in antiphospholipid syndrome: prevalence, clinical features, and treatment.

Valvular abnormalities develop in 36% and 35% of patients with primary antiphospholipid syndrome (PAPS) and with systemic lupus erythematosus (SLE) respectively, and in 48% of patients with SLE and antiphospholipid antibodies (aPL). Valvulopathy includes leaflet thickening, vegetations, regurgitation, and stenosis. A literature survey shows that significant morbidity from valvular dysfunction, mostly mitral regurgitation leading to congestive heart failure, occurs in 4% and 6% of SLE and PAPS patients, respectively. The pathogenesis of valvulopathy may involve interaction of aPL with antigens on the valve surface, resulting in valvulitis. Current therapy includes symptomatic measures and valve replacement. A novel approach for symptomatic antiphospholipid syndrome (APS) related valvulopathy involves treatment with systemic corticosteroid. We describe four such patients and their dramatic clinical and hemodynamic response to treatment with prednisone when symptomatic measures failed.

Parvovirus infection mimicking systemic lupus erythematosus in a pediatric population.

OBJECTIVES: To assess the striking similarities of presentation in a pediatric population between human parvovirus B19 (HPV-B19) infection and systemic lupus erythematous (SLE). METHODS: Medical records of seven patients (ages 6 to 15) with HPV-B19 infection were reviewed retrospectively. RESULTS: Six of seven cases presented with a history of malar rash, and all seven had prolonged arthralgias and fatigue. Six of seven had a positive antinuclear antibody (ANA) titer ranging from 1:40 to greater than 1:640, with two patients having antibodies to Scl-70 and others to Sm, RNP, SS-A (Ro), or SS-B (La). The erythrocyte sedimentation rate (ESR) varied from 2 to 68 mm/h. Two patients presented with elevated rheumatoid factor (RF) titers of 24 and 271 IU/mL, respectively. All had elevated IgM antibody levels to parvovirus at the onset, and markedly elevated IgG levels when evaluated throughout their disease course. Over the course of 2 to 3 months, three improved, but the other four continued to have symptomatology for 14, 40, 78, and 120 weeks, respectively. Treatment was symptomatic, and no one developed classic SLE. CONCLUSIONS: HPV-B19 infection in a pediatric patient group may present with SLE-like symptomatology and positive serology suggestive of SLE. The course of the disease is usually self-limited, though it may be prolonged in some for up to 120 weeks.

Thrombotic microangiographic hemolytic anemia in systemic lupus erythematosus.

Thrombotic microangiopathic hemolytic anemia (TMHA) is characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological symptoms, and kidney involvement. It presents as thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS). TMHA has been considered to occur only rarely in systemic lupus erythematosus (SLE). However, there has been an increase in the reporting of this association in recent years, and autopsy studies have suggested that TMHA may be underdiagnosed in SLE because of the similarity in symptoms. We report four patients with SLE-related TMHA and describe 24 more patients from a literature review. All patients were women, 50% had active SLE, 89% presented as TTP, and 11% presented as HUS. Those patients with active SLE had low complement levels. Antiphospholipid antibodies or lupus anticoagulant were positive in 5 of 8 cases. Patients treated with plasma infusions or plasmapheresis had a lower mortality rate at 25% compared with 57% mortality in patients who were not treated with plasma infusions or plasmapheresis. It is suggested that TMHA should be considered in any SLE patient presenting with neurological symptoms or renal failure associated with fever, hemolytic anemia, and thrombocytopenia. Early recognition and appropriate therapy with plasmapheresis may improve prognosis.

Autoantibody studies in juvenile rheumatoid arthritis.

Early studies showed few immunologic abnormalities in juvenile rheumatoid arthritis (JRA) patients. There were no specific laboratory markers useful for diagnosis and assessment of the course of disease in JRA. Previous work showed an association of antinuclear antibodies (ANA) with early-onset pauciarticular disease and iridocyclitis. Similarly, the presence of 19S immunoglobulin (Ig) M rheumatoid factors (RF) was associated with late-onset polyarticular disease in girls. More recent studies have detected many unique autoantibodies. Newer assays show 19S IgM RF in up to 35% of JRA patients, although still mainly in girls with late-onset polyarticular disease. Hidden 19S IgM RF can be shown in up to 75% of JRA patients using different procedures, primarily in those with active polyarticular-or pauciarticular-onset disease. Immune complexes have been detected in JRA patients by means of different techniques; their presence usually correlates with active disease. Studies on a specific ANA in JRA have shown no common extractable nuclear antigen, but antihistone antibodies have been found in up to 75% of cases, again mainly in those with pauciarticular onset and iritis. Finally, a variety of unusual immunologic proteins have also been detected, including anti-ocular, anti-cellular, anti-cardiolipin, anti-perinuclear factor, and anti-collagen antibodies. This review evaluates the significance of these antibodies that can now be found in JRA.

Decreased salivary output in patients with Gaucher disease.

BACKGROUND: Gaucher disease, the most common sphingolipid storage disease, results in accumulation of glucocerebroside in macrophages or "Gaucher cells". In a preliminary screening of 109 patients with type I disease, when asked specifically about dry mouth, approximately one quarter claimed to suffer from this symptom. AIM: To ascertain whether decreased salivary output is a feature of Gaucher disease. DESIGN: Prospective case-control study. METHODS: Salivary output was measured in 65 adult patients and 65 healthy controls using the Saxon test with Hochberg's modification. RESULTS: Mean salivary output was 1.91+/-1.19 g/min in the patient group vs. 2.74+/-1.17 g/min in the control group (p<0.001). This difference was greater among males. These results were not improved in the patients receiving enzyme replacement therapy, which is effective in ameliorating most Gaucher-related signs and symptoms. DISCUSSION: Recent studies have implicated an association between sicca syndrome and viral hepatitis C infection, which may imply an immunological trigger for these findings, but in this specific cohort, only three patients were reactive for hepatitis C. Follow-up of patients, both untreated and receiving enzyme therapy, is needed to delineate the association with salivary hypofunction, and ascertain whether enzyme therapy may induce sicca symptoms.

Diflunisal versus naproxen in the management of rheumatoid arthritis.

Diflunisal (500 mg orally, twice daily) and naproxen (375 mg orally, twice daily) were compared for efficacy and tolerability in a 12-week open-label study in 33 patients with active rheumatoid arthritis (RA). Both drugs resulted in marked reduction in the number of swollen, tender, and painful joints and comparable improvement in patients' assessment of disease activity and pain. There were no significant differences between the two medications in the measured indices of disease activity. No adverse experiences were reported by patients in either treatment group. The results indicate that both diflunisal and naproxen were equally effective and that both agents are generally well tolerated in this group of patients with RA.