A study on parasites in Mexican rheumatic disease patients.

Blastocystis hominis is a common human parasite with infection rates up to 50% in developing countries, and giardiasis is the commonest intestinal one in Mexico. No doubt, various parasites as Giardia lamblia and Entamoeba histolytica can cause rheumatic diseases. This study coproparasitoscopic analysis evaluated the cysts by B. hominis, G. lamblia, E. hartmani, E. coli and E. histolytica in Mexican rheumatic disease patients. Also, ELISA was used to detect E. histolytica, Ascaris lumbricoides, Toxocara canis, and Trichinella spiralis in Mexican patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Thirty-six patients (24 with AS and 12 with RA) and 77 healthy control individuals were enrolled in this study. The frequencies of protozoan cysts were comparable in rheumatic disease patients (AS and RA) and healthy control donors (33 and 25 vs. 26%, respectively; p > 0.05). The frequency of antibodies to T. canis was significantly higher in AS patients than in healthy control donors (16 vs. 2.6%, respectively; p = 0.027), whereas no differences were observed for the prevalence of antibodies for the other parasites (E. histolytica, A. lumbricoides and T. spiralis) (p > 0.05). This information indicates the need to intensify educational efforts for the prevention of parasite infections associated with AS disease that cannot be controlled only by drugs.

Disease activity, damage and survival in Mexican patients with acute severe systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a clinical syndrome of varying severity. Although the survival and prognosis of SLE have steadily improved, there is a group of patients who present an acute fatal outcome despite aggressive therapy. We designed this study to evaluate the factors associated with mortality in patients with acute severe SLE. During 2004-06, 41 Mexican SLE patients that could not be managed in the out-patient clinic and with acute severe major organ system involvement [nephritis, severe thrombocytopenia (platelet count below 20 000 per microL) acute neuropsychiatric pulmonary, gastrointestinal or cardiac disease and generalized vasculitis] were studied. During the first admission, disease activity (SLE Disease Activity Index (SLEDAI), SLE Activity Measured), damage [SLE International Collaborating Clinics (SLICC)], and therapy were assessed. Survival using Kaplan-Meier curves, odd ratios with 95% confidence interval and logistic regression analysis were used to determine risk factors for mortality. Ninety percent were female with a mean age of 29 +/- 19 years and mean disease duration of 21 +/- 9 months. The principal causes of first admission were renal (27%), SNC (22%) and cardiopulmonary (15%). After a mean follow-up of 9.7 +/- 6 months, 16 (39%) patients died. Deceased patients had significantly higher SLEDAI (P = 0.004), and SLICC (P = 0.03) scores. The manifestations associated with mortality were renal disease activity (odds ratio, OR 4.6, confidence interval, CI 95% 1.0-20.6), infections (OR 3.2 CI 95% 2.0-5.3) and thrombocytopenia (OR 4.0, CI 95% 1.0-15.9). The survival at 9.7 months was 72, 62 and 50% in patients with an SLEDAI score of 3-10, 11-20 and > or =21, respectively. The SLEDAI score, the presence of damage and infection were associated with death in patients with acute severe SLE.

High frequency of association of rheumatic/autoimmune diseases and untreated male hypogonadism with severe testicular dysfunction.

Our goal in the present work was to determine whether male patients with untreated hypogonadism have an increased risk of developing rheumatic/autoimmune disease (RAD), and, if so, whether there is a relation to the type of hypogonadism. We carried out neuroendocrine, genetic, and rheumatologic investigations in 13 such patients and 10 healthy male 46,XY normogonadic control subjects. Age and body mass index were similar in the two groups. Nine of the 13 patients had hypergonadotropic hypogonadism (five of whom had Klinefelter's syndrome [karyotype 47,XXY]) and 4 of the 13 had hypogonadotropic hypogonadism (46,XY). Of these last four, two had Kallmann's syndrome and two had idiopathic cryptorchidism. Eight (61%) of the 13 patients studied had RADs unrelated to the etiology of their hypogonadism. Of these, four had ankylosing spondylitis and histocompatibility B27 antigen, two had systemic lupus erythematosus (in one case associated with antiphospholipids), one had juvenile rheumatoid arthritis, and one had juvenile dermatomyositis. In comparison with the low frequencies of RADs in the general population (about 0.83%, including systemic lupus erythematosus, 0.03%; dermatomyositis, 0.04%; juvenile rheumatoid arthritis, 0.03%; ankylosing spondylitis, 0.01%; rheumatoid arthritis, 0.62%; and other RAD, 0.1%), there were surprisingly high frequencies of such disorders in this small group of patients with untreated hypogonadism (P < 0.001) and very low serum testosterone levels (P = 0.0005). The presence of RADs in these patients was independent of the etiology of their hypogonadism and was associated with marked gonadal failure with very low testosterone levels.

Infections in outpatients with systemic lupus erythematosus: a prospective study.

The objective of this study was to assess the incidence and risk factors of infections in 200 SLE outpatients. All outpatients with active or inactive SLE without infections in the previous month were included. They were assessed every 3 months. Major infections were those requiring hospitalization and parental antibiotic therapy; minor infections required oral or topical therapy. Sociodemographic, disease activity using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), therapy and laboratory variables were evaluated. After a follow-up of 22+/-7 months, 65 (32%) patients had infections; 35% of those were major. The most common sites for infection were urinary (26%), skin (23%), systemic (12%), and vaginal (9%). At infection onset, 50 of 65 patients (77%) had disease activity, with a mean SLEDAI score of 6.1. The variables significantly associated with infection in the univariate analyses were the presence of disease activity, SLEDAI score, renal activity, prednisone dose, and IV cyclophosphamide. The only variable associated with infection in the multivariate analyses was a SLEDAI score of 4 or higher. Most infections in SLE outpatients were single, minor, non-life threatening, and associated with disease activity independently of sociodemographic and therapeutic factors.

Two-dimensional echo Doppler findings in juvenile and adult onset ankylosing spondylitis with long-term disease.

The authors' objective was to determine by 2-dimensional echo Doppler (2DECHO) the cardiac abnormalities in juvenile onset ankylosing spondylitis (JOAS) and adult onset ankylosing spondylitis (AOAS) in male patients with long-term disease. Twenty patients with JOAS, 31 with AOAS, and 20 healthy controls of the same age and gender without cardiopulmonary symptoms were studied. Using 2DECHO, the heart dimensions were determined according to American Society of Echocardiography guidelines. The left ventricle ejection fraction (LVEF) was calculated by Teichholz's formula. Cardiomyopathy was established when 2DECHO had diminished LVEF. Statistics used were the Student t and Fisher test, chi2, and ANOVA. Ninety percent of JOAS and 51% of AOAS patients were B27+ (p=0.005). The disease duration was 19.3 +/- 8.8 years in JOAS and 14.8 +/- 12.8 years in AOAS (p=NS). Age at the time of the study was 30.7 +/- 9.9 years in JOAS vs 40.3 +/- 12.7 in AOAS (p=0.003), and vs 40.2 +/- 17 years in controls (p=NS). There was a higher frequency of cardiomyopathy in AOAS (32.2%) than in JOAS (25%) and the controls (0%) (p=0.01). Patients with JOAS had a higher mitral valve gradient (25%) than AOAS patients (19%, p=NS) and controls (0%, p=0.04). Abnormal aortic ring reflectance was shown in 19% of AOAS vs 0% abnormalities in JOAS and controls (p=0.01). The aortic root diameter was increased in 58% of AOAS, 30% of JOAS, and 0% of controls (p=0.001). The frequency of 2DECHO abnormalities was increased in cardiopulmonary asymptomatic spondylitis patients. Despite the high frequency of B27+, JOAS had a lower frequency of aortic abnormalities than AOAS. Mitral valve gradient was found in JOAS and in AOAS that could contribute to a decreased ejection fraction and to left ventricular dysfunction.

Tamale foot: deposit of acid mucopolysaccharides in the synovial sheaths of extensor tendons of the foot, resembling tendinitis, in a patient with juvenile ankylosing spondylitis.

We describe a clinical case of juvenile ankylosing spondylitis (AS) that developed "pseudo-chronic tendinitis" of the foot. A 20-year-old male patient had HLA-B27 positive juvenile AS since he was 13 years old. At the age of 19 he presented chronic pain in the dorsum of the left foot. Examination disclosed an increased volume of the tarsal dorsum, with rubbery consistency, with no evidence of venous or lymphatic insufficiency, godette, or inflammation in laboratory tests, giving the foot the appearance of a tamale. Synovectomy of the foot extensor tendon sheath was followed by relief of pain and swelling. Histopathological study showed a deposit of acid mucopolysaccharides (MPS) with no inflammatory cell infiltrate. Tamale foot in juvenile AS may develop as a consequence of acid MPS deposit with no evidence of synovial inflammation. The good response to synovectomy suggests this is the preferred treatment for tamale foot.

Measurement of damage in 210 Mexican patients with systemic lupus erythematosus: relationship with disease duration.

The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index is a validated instrument specifically designed to ascertain damage in SLE; this instrument has been applied mainly to Caucasians and African-American SLE patients. The objective of this study was to assess damage using the SLICC/ACR Damage Index in Mexican SLE patients. The SLICC/ACR Damage Index was applied to 210 consecutive SLE patients with disease of variable duration. The SLICC/ACR Damage Index was assessed by review of hospital clinical records, interview and physical examination. One hundred and seventeen (55.5%) patients had some damage. The proportion of patients with damage increased significantly with disease duration (33% at 1-60 months, 66% at 61-120 months and 70% at > or = 121 months, P < 0.001). The main organ systems involved were musculoskeletal (osteonecrosis), neuropsychiatric (neuropathy, seizures), gonadal (amenorrhea prior to age 40 years), ocular (cataracts), renal (glomerular filtration < 50%) and peripheral vascular (permanent damage by venous thrombosis). Damage was frequent, increased over time, particularly for ocular, renal, musculoskeletal and gonadal. Patients who experienced damage were older, had a longer disease duration, a greater number of ACR criteria at diagnosis, and were more likely to have renal involvement and antibodies to dsDNA. The damage occurred in many different domains and started to develop early after disease onset. Mexican patients had more peripheral vascular and gonadal involvement compared with published data from non-Hispanic SLE populations.

Does serum rheumatoid factor have an influence on the clinical picture of ankylosing spondylitis?

OBJECTIVE: To describe the influence of serum rheumatoid factor (RF) on the clinical and radiological picture of definite ankylosing spondylitis (AS). METHODS: In a retrospective chart review of 281 AS patients typed for RF, the clinical picture of RF positive patients (Group 1) was compared with RF negative patients (Group 2); mode of onset, disease duration, and treatment were recorded. All patients were examined to determine their clinical status; the blood cell count. HLA-B27, serum IgG, IgM, IgA, and erythrocyte sedimentation rate (ESR) were determined, and radiological studies of the entire spine, pelvis and affected peripheral joints were carried out. In patients from Group 1 the HLA-DR was also determined. RESULTS: Fifteen of 281 patients (8 men, 7 women) with AS were RF+ (1:64 to 1:1024) (5.3%) and 11 were HLA-B27+. Seven patients in Group 1 had spine involvement and chronic arthritis of the knees. Four out of these 7 were tested for DR, and none was positive; in 6, AS and rheumatoid arthritis (RA) coexisted, 2 were DR1 and 2 were DR4 (test not carried out in 2). In two others we found spinal involvement only, and one of them had both DR1 and DR4. The onset of AS was similar in both groups. Group 1 was characterized by a chronic disease of moderate intensity with chronic arthritis of the metacarpophalangeal and proximal interphalangeal joints (p = 0.0008 and p = 0.04, respectively), no valvulopathy (p = 0.04) and fewer uveitis sequelae (p = 0.007) than Group 2. The ESR (p = 0.01), IgG (p = 0.008) and IgM (p = 0.0001) were higher in Group 1 than in Group 2. CONCLUSIONS: The presence of RF in AS is associated with a chronic disease of moderate intensity with chronic peripheral arthritis and fewer extra-articular manifestations. The presence of RF, not always associated with HLA-DR, seems to affect the course of AS and does not necessarily indicate an association with RA.

Storage histiocytes and hemophagocytosis: a common finding in the bone marrow of patients with active systemic lupus erythematosus.

We report the frequency of the finding of storage and hemophagocytic histiocytes in the bone marrow of patients with systemic lupus erythematosus with one or more hemocytopenias. The study was performed on bone marrows of ten patients with systemic lupus erythematosus during an episode of hemocytopenia. Four patients were not receiving any treatment and six had been taking oral prednisone (3.5 +/- 1.5 mg/day) for the previous 6 months. Hemocytopenias found were lymphocytopenia in five, thrombocytopenia in three, and neutropenia and anemia in two each. The bone marrow had variable cell content; megakaryocytes, the myeloid:erythroid ratio, as well as lymphocyte, plasma cell, and reticular cell contents were usually increased. Seven bone marrow samples showed storage histiocytes (sea-blue histiocytes and other histiocytes that contained unidentified intracytoplasmic material). These same samples revealed histiocytes phagocytosing erythoblasts, erythrocytes, polymorphonuclear neutrophils, lymphocytes or platelets. The presence of these histiocytes in all seven patients was related to a decrease in serum complement and with lupus disease activity as measured with the SLEDAI index (mean +/- SD = 2.1 +/- 1.5). The SLEDAI score of the remaining three patients, who had no histiocytes in their bone marrow, was 0, 0, and 1, respectively. The present study reveals that the bone marrow in patients with systemic lupus erythematosus and peripheral hemocytopenia contains storage and hemophagocytic histiocytes and the significance of these cells is discussed.

Intravenous cyclophosphamide pulses in the treatment of pyoderma gangrenosum associated with rheumatoid arthritis: report of 2 cases and review of the literature.

Pyoderma gangrenosum is a chronic ulceronecrotic inflammatory cutaneous disorder that can be associated with diseases such as rheumatoid arthritis (RA). No definitive treatment exists for this condition; steroids have been the mainstay of therapy, and the addition of immunosuppressives has been advocated. We describe 2 patients with pyoderma gangrenosum occurring in the setting of RA who, in addition to steroids, received pulse intravenous cyclophosphamide and had a remarkably good and lasting response. This is the first report of such a therapeutic approach. The pertinent literature is discussed. We conclude that pulse cyclophosphamide is another possible therapy for pyoderma gangrenosum.

Acute sideroblastic anemia in active systemic lupus erythematosus.

This work describes the development of sideroblastic anemia (SA) during the clinical activity of systemic lupus erythematosus (SLE) in two patients. The cases refer to two women with SLE who developed SA during a relapse of the illness. Both patients fulfilled at least four criteria of the American Association of Rheumatology for SLE. In one patient, the treatment with prednisone was followed by the resolution of the SLE activity and the disappearance of the SA. Several years later there was no evidence of ringed sideroblasts or malignancy in the bone marrow. In the other patient, the clinical activity of the SLE and SA developed during the beginning of a septicemic event which finally led to her death. Our clinical cases allow us to show that the transitory development of SA can occur during a period of clinical activity of SLE and that its association, although infrequent, is due to a common physiopathogenic mechanism.

Ankylosing spondylitis: clinical course in women and men.

OBJECTIVE: To compare the clinical course; laboratory and radiological features of women and men with ankylosing spondylitis (AS). METHODS: Retrospective review of charts of 41 women and 41 men with AS (25 B27+ and 16 B27- in each group) individually matched for age at onset and disease duration. RESULTS: No differences were observed in the clinical picture in either sex, but the disease was less severe in women than in men with lesser duration of uveitis attacks, lower leukocyte counts (p < 0.05), lower levels of gamma-globulins (p < 0.05), and longer asymptomatic periods. At the end of the study, women had less restriction of spinal extension (p = NS), less sequelae of uveitis without significant visual loss (p = NS), required fewer hip replacements, had less frequency of bamboo spine (p < 0.02), and better functional class (p < 0.0027) than men. CONCLUSION: There are no significant clinical or radiographic differences between women and men with AS. However, the disease was more severe in men and these features may be due to sexual dimorphism.

Testicular function in active ankylosing spondylitis. Therapeutic response to human chorionic gonadotrophin.

Testicular function was studied in 22 patients with ankylosing spondylitis (AS) with serum measurements of hormone levels, seminal fluid analysis and testicular reserve test. Results were correlated with disease activity. The abnormal findings were elevated luteinizing hormone (LH), inversion of estradiol/testosterone ratio (E2:T) and diminished testicular reserve for testosterone (T) and slightly increased for estradiol (E2). Nine patients with severe active AS received biweekly 2,500 IU of human chorionic gonadotrophin injections with a resulting increase in E2 serum levels. When the values of E2 reached 40 pg/ml or higher, there was a decrease of the sedimentation rate (p less than 0.05) and a reversal to normal of the E2:T ratio. This was accompanied by an improvement in AS at the 10th week that lasted up to 9 weeks after discontinuation of treatment. Our findings suggest a possible role of sex hormones in the physiopathogenesis of AS and offers a possible therapeutic alternative.

Immunoreactive insulin levels in ankylosing spondylitis.

Serum glucose, serum immunoreactive insulin and sedimentation rate (ESR) were measured in eighteen male patients with ankylosing spondylitis (AS) and seven male healthy controls. The findings were correlated with the presence or absence of inflammatory activity of the disease. Fourteen patients had active AS with ESR of 47.0 +/- 27.7 mm; they had increased insulin levels measured as area under curve (AUC) of a glucose tolerance test 107.4 +/- 44.1 cm2 vs controls 40.8 +/- 12.6 cm2 (p less than 0.03). In 4 patients with clinically inactive AS and with ESR of 17.0 +/- 4.0 mm the insulin levels as the AUC were 83.2 +/- 38.0 cm2 vs controls (p = ns). In the whole group there was a direct correlation between ESR and serum immunoreactive insulin levels (r = 0.47 p less than 0.05). Our study suggests that AS may be associated with hyperinsulinism, whose role in the physiopathogenesis of the disease remains unknown.

Ovarian function studies in active ankylosing spondylitis in women. Clinical response to estrogen therapy.

Ovarian function was studied in 17 women with active ankylosing spondylitis (AS). Levels of FSH, LH, prolactin and androstenedione were normal in menstruating patients and FSH and LH were elevated in menopausal patients. In menstruating patients with active AS the estradiol levels were lower than in patients with inactive AS and significantly (p less than 0.05) lower than controls. Progesterone levels in menstruating patients were lower (P = NS) than controls. In menopausal patients estrogen levels were lower than their controls (P = NS). There was a significant (p less than 0.05) inverse correlation between the sedimentation rate and the estrogen level. Seven patients accepted oral estrogen therapy (average duration 4 months) and peripheral arthritis subsided within one month, all variables of clinical activity of AS improved and at the end of the study all patients were in functional class I.

[Purine metabolism in ankylosing spondylitis: clinical study]. / Metabolismo de las purinas en la espondilitis anquilosante: estudio clínico.

We undertook a prospective study of 23 male patients with Ankylosing Spondylitis (AS) (New York Criteria), 18 HLA-B27 positive and 5 HLA-B27 negative, five of them had hyperuricemia. The following data of evolution were taken into consideration: age at onset of disease, time course of the disease, presence of urolithiasis, heart disease, flares of uveitis. Clinical activity and degree of disability were evaluated every one to 3 months; on each visit, every patient had determinations of serum and urinary uric acid levels, serum and phosphorus, erythrocyte sedimentation rate (ESR), serum protein electrophoresis, as well as X-ray films of the vertebral spine and pelvis. Three groups of patients were detected, all of them with equal age at onset, duration of disease, frequency of B27, peripheral arthritis, and leukocytosis. One group had hyperuricemia (5 of 23 patients, 80% of them HLA-B27 positive) and a lesser degree of clinical activity of the disease (p less than .001, a higher frequency of uveitis (40%, lower levels of serum gammaglobulins (p less than 0.05) and ESR (p less than 0.05), a lesser degree of ankylosis of the spine, and a better functional prognosis than the other groups. Another group (8 of 23 patients, 75% of them were HLA-B27 positive) had normouricemia and hyperuricosuria, and showed a higher frequency of fever (50%), an abnormal urinalysis, and urolithiasis (25%).

[Functional abnormalities of complement in familial and sporadic ankylosing spondylitis]. / Anormalidades funcionales del complemento en la espondilitis anquilosante familiar y esporádica.

Levels of complement fractions of 12 patients with sporadic ankylosing Spondylitis and 6 patients with familial Ankylosing Spondylitis (N. Y. Criteria) were studied by an hemolytic and functional method (microhemolysis in plate. Cordis Lab. Miami, Fla. USA). Abnormal levels were found in 94% of them high levels of C1 and C2 (p 0.002), and C3 (p 0.05) C8 and C9 (p 0.001) deficiencies, mixed or isolated, correlated with the severity of the diseases. C9 deficiency belongs to familial Ankylosing Spondylitis. These functional deficiencies of serum complement can favor the colonization and persistence of germs, which could mediate in the genesis of Ankylosing Spondylitis.