Distal radius and tibia bone microarchitecture impairment in female patients with diffuse systemic sclerosis.

Radius and tibia bone microarchitecture, analyzed through a high-resolution peripheral quantitative computed tomography, were significantly impaired in female patients with diffuse systemic sclerosis compared with healthy controls. Acroosteolysis, quality of life-grip strength, hand disability, and disease duration were significantly associated with this bone deterioration. INTRODUCTION: The effect of diffuse systemic sclerosis (dSSc) on the bone is not completely understood. The objective of this study was to analyze the volumetric bone mineral density (vBMD), microarchitecture, and biomechanical parameters at the distal radius and tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT, XtremeCT) in female patients with dSSc and identify clinical and laboratory variables associated with these parameters. METHODS: Thirty-eight women with dSSc and 76 healthy controls were submitted to HR-pQCT at the distal radius and tibia. Clinical and laboratory findings, bone mineral density(BMD), nailfold capillaroscopy (NC), total passive range of motion(ROM), and quality of life (health assessment questionnaire-HAQ) were associated with HR-pQCT (Scanco Medical AG, Brüttisellen, Switzerland) parameters. Multiple linear regression models adjusted for clinical and laboratory variables, ROM and HAQ, were performed. RESULTS: Density, microarchitecture, and biomechanical parameters at the distal radius and tibia were significantly impaired in dSSc patients compared with healthy controls (p < 0.001). Multiple linear regression models showed that lower trabecular density (Tb.vBMD) (radius R2 = 0.561, p = 0.002; and tibia R2 = 0.533, p = 0.005), and lower trabecular number (Tb.N) (tibia R2 = 0.533, p = 0.005) were significantly associated with acroosteolysis. Higher trabecular separation (Tb.Sp) was associated with disease duration and higher HAQ-grip strength (radius R2 = 0.489, p = 0.013), while cortical density (Ct.vBMD) was associated with ROM (radius R2 = 0.294, p = 0.002). CONCLUSION: Bone microarchitecture in patients with dSSc, analyzed through HR-pQCT, showed impairment of trabecular and cortical bone at distal radius and tibia. Variables associated with hand involvement (acroosteolysis, quality of life-grip strength, and ROM) and disease duration may be considered prognostic factors of this bone impairment.

Hypomagnesaemia and hypocalcaemia in a patient with systemic sclerosis: role of proton pump inhibitors.

Proton pump inhibitors (PPI) are widely used in patients with systemic sclerosis (SSc) due to the chronic gastroesophageal reflux. The authors report a female patient with a 9-year history of SSc and long-term use of omeprazole, who complained of paresthesia and asthenia for 12 months. Physical examination revealed clinical signs of hypocalcaemia confirmed by laboratory tests that also showed hypomagnesaemia. After exclusion of possible causes, hypomagnesaemia secondary to PPI was diagnosed and omeprazole was replaced by a histamine H2-receptor antagonist: ranitidine. Despite continuous magnesium supplementation, the reintroduction of PPI at a lower dose due to worsening of dyspeptic symptoms led to recurrence of hypomagnesaemia. After definitive suspension of PPI, reintroduction of ranitidine and optimisation of anti-reflux environmental measures, the patient stabilised. In conclusion, SSc patients using PPIs should have their magnesium and calcium serum levels measured periodically, and non-specific symptoms such as asthenia, generalised paresthesia or life-threatening manifestations (seizures, arrhythmias) should not be neglected.

Hypertension and diabetes significantly enhance the risk of cardiovascular disease in patients with psoriatic arthritis.

OBJECTIVES: New evidence has lightened the linkage between psoriatic arthritis (PsA) and the development of atherosclerosis and cardiovascular disease (CVD). We aimed to describe the prevalence of cardiovascular events and associated risk factors among patients with PsA. METHODS: Retrospective evaluation of medical records from consecutive PsA patients who fulfilled the CASPAR criteria for PsA attending a specialised spondyloarthritis clinic at a single referral centre. CVD was defined based on the occurrence of coronary artery disease (CAD) or cerebrovascular ischaemic disease events. RESULTS: We evaluated 158 PsA patients, 48.7% females and 51.3% males, aged 53.7±13.9 yrs. Mean PsA duration was 13.7±8.9 yrs and polyarticular subtype affected 66 (42%) patients. According to drug therapy, 85 (54%) were using NSAIDs and 21 (13%) low-dose prednisone; 32 (20%) were on anti-TNF agents, 94 (60%) metothrexate, 18 (11%) leflunomide, 13 (8%) sulfasalazine, 5 (3%) other immunossupressors and 4 (2.5%) were on chloroquine. Over half patients (87, 55%) had arterial hypertension (AH); 51 (32%) had dyslipidaemia (DLP), 38 (29%) hypertriglyceridemia and 36 (23%) diabetes mellitus (DM). Lipid profile was similar for both genders with mean total cholesterol= 186.5±38.6mg/dl, LDL=112.3±30.6 mg/dl, HDL= 47.89±14.6 and triglycerides= 127.4± 65.6 mg/dl. Of note, 14% PsA patients have had CVD, namely cerebrovascular or coronary heart disease. Sex, age, disease duration, joint involvement subtype, disease activity, CRP and lipid levels were similar among patients with and without CVD. The prevalence of AH (95% vs. 45%, p<0.001), DLP (75% vs. 27.7%, p<0.001) and DM (60% vs. 19%, p<0.001) were significantly greater in PsA patients who have had CVD compared to those without CVD, conferring an odds ratio of 21.0 for AH and of 5.4 for DM. CONCLUSIONS: The high prevalence of CVD in PsA patients is influenced by increased AH and DM. Hence early recognition and specific treatment is mandatory in order to reduce the risk for CVD, avoiding early morbidity and mortality.

Effect of age at disease onset in the clinical profile of spondyloarthritis: a study of 1424 Brazilian patients.

OBJECTIVES: To analyse demographic and clinical variables in patients with disease onset before and after 40, 45 and 50 years in a large series of Brazilian SpA patients. METHODS: A common protocol of investigation was prospectively applied to 1424 SpA patients in 29 centres distributed through the main geographical regions in Brazil. The mean age at disease onset was 28.56 ± 12.34 years, with 259 patients (18.2%) referring disease onset after 40 years, 151 (10.6%) after 45 years and 81 (5.8%) after 50 years. Clinical and demographic variables and disease indices (BASDAI, BASFI, BASRI, MASES, ASQoL) were investigated. Ankylosing spondylitis was the most frequent disease (66.3%), followed by psoriatic arthritis (18%), undifferentiated SpA (6.7%), reactive arthritis (5.5%), and enteropathic arthritis (3.5%). RESULTS: Comparing the groups according to age of disease onset, those patients with later onset presented statistical association with female gender, peripheral arthritis, dactylitis, nail involvement and psoriasis, as well as negative statistical association with inflammatory low back pain, alternating buttock pain, radiographic sacroiliitis, hip involvement, positive familial history, HLA-B27 and uveitis. BASDAI, BASFI and quality of life, as well as physicians and patient's global assessment, were similar in all the groups. Radiographic indices showed worse results in the younger age groups. CONCLUSIONS: There are two different clinical patterns in SpA defined by age at disease onset: one with predominance of axial symptoms in the group with disease onset ≤ 40 years and another favouring the peripheral manifestations in those with later disease onset.

The challenge of early systemic sclerosis for the EULAR Scleroderma Trial and Research group (EUSTAR) community. It is time to cut the Gordian knot and develop a prevention or rescue strategy.

Early diagnosis of systemic sclerosis (SSc) may allow the start of treatment that could slow disease progression. For this reason early diagnosis of the disease is of pivotal importance. However, the lack of diagnostic criteria and valid predictors significantly limit patient evaluation and the use of potentially effective drugs in the earliest phase of SSc. Early SSc may be suspected on the basis of Raynaud's phenomenon, puffy fingers, autoantibodies and SSc capillaroscopic pattern. In practice, the aim is to have criteria for the diagnosis of very early SSc. The criteria that are proposed are obviously provisional and need to be validated: (a) initially through a Delphi technique; (b) thereafter perhaps using already available datasets; but (c) of critical importance, through prospective studies. Only after prospective studies can these potential criteria be considered validated. The consensus on criteria for the classification of very early SSc might be part of the evolving EULAR/ACR project of reclassification of SSc.

Sensorineural dysacusis in patients with systemic lupus erythematosus.

The objective of this study was to establish the frequency of involvement of the auditory apparatus in 45 female patients with systemic lupus erythematosus (SLE) submitted to general clinical and laboratory assessments, and tone and vocal audiometry accompanied by a questionnaire evaluating auditory symptoms. The control group consisted of 45 healthy women, matched by age. Auditory symptoms were present in 25 (55.5%) patients, with a diagnosis of sensorineural hearing loss in seven (15.6%) patients. A significant correlation with hypoacusis (P < 0.001), ear fullness (P = 0.012) and tinnitus (P = 0.017) was observed in patients with hearing loss. None of the clinical or laboratory parameters showed an association with sensorineural hearing loss. In the control group, three women (6.7%) presented audiometric alterations, including two with altered tympanometry results and one with mild sensorineural hearing loss. In conclusion, an adequate investigation of auditory symptoms is important during the follow-up of patients with SLE, since manifestations of the auditory apparatus and sensorineural hearing loss can affect a significant proportion of patients.

Prevalence of pulmonary hypertension in systemic sclerosis.

OBJECTIVE: To assess the prevalence of pulmonary arterial hypertension (PAH) in patients with the diagnosis of systemic sclerosis (SSc) followed at a tertiary university service. MATERIAL AND METHODS: Fifty-seven patients with SSc were studied by clinical assessment directed at the cardiopulmonary system, pulmonary function tests and Doppler echocardiography (ECHO). The following criteria were considered for the diagnosis of PAH: pulmonary artery systolic pressure (PASP) > or = 40 mmHg and/or the presence of other direct and indirect signs of PAH detected upon ECHO. RESULTS: Sixteen patients (28%) were diagnosed with PAH upon ECHO, 13 based on PASP > or = 40 mmHg and 3 based on direct and indirect signs of PAH; 8 patients had isolated PAH and 8 had PAH secondary to pulmonary fibrosis. Nine patients showed signs suggestive of cor pulmonale upon ECHO; among these patients, 6 had pressure recordings > or = 40 mmHg and 3 had a PSAP between 35 and 40 mmHg; one patient was asymptomatic and 8 showed signs suggestive of PAH upon clinical examination. Among the clinical and laboratory variables studied, a correlation was only observed between PAH and an elevated erythrocyte sedimentation rate (p = 0.004). CONCLUSIONS: The prevalence of PAH associated with SSc observed in this study was similar to those reported in the literature. However, the cut-off of PSAP measured by ECHO and used for the diagnosis of PAH associated with SSc needs to be revised.

Prognostic factors of low bone mineral density in systemic sclerosis.

OBJECTIVE: To analyse the results of bone densitometry in patients with systemic sclerosis (SSc), evaluating the prognostic factors of low bone mineral density (BMD) in fertile and postmenopausal patients, and comparing to a control healthy group. METHODS: Cross-sectional study analysing 61 female SSc patients, aged 25 to 51 years, who performed a bone densitometry using dual x-ray absorptiometry. BMD values (lumbar spine, femoral neck, Ward and trochanter) infertile and postmenopausal patients were compared according to SSc clinical variant (limited and diffuse), race, previous use of drugs (corticosteroids and cyclophosphamide) and bone mass index (BMI). These results were compared with 47 fertile and 60 postmenopausal healthy women; multivariate linear regression analysis was used to study the influence of the variables of interest in the BMD results. RESULTS: Twenty-seven SSc patients presented osteopenia and 14 densitometric osteoporosis. No statistical association was found between BMD values and SSc clinical variants, race and previous use of corticosteroids and cyclophosphamide, in the fertile and in the postmenopausal groups. Fertile SSc patients were paired by age and race with the control group, but BMI (p = 0.035) was significantly lower in the SSc group. BMD values of lumbar spine (p = 0.070, statistical trend), femoral neck (p = 0.003), Ward (p < 0.001) and trochanter (p = 0.003) were significantly lower in the SSc group. Postmenopausal SSc patients were paired by age and race with the control group, but BMI (p < 0.001) was also significantly lower in the SSc group. Age at menopause (p = 0.006) was also significantly lower and time from menopause (p < 0.001) was significantly higher in the SSc group. BMD values of femoral neck (p < 0.001), Ward (p < 0.001) and trochanter (p = 0.001) were significantly lower in the SSc group. Multivariate linear regression analysis showed that BMI was the main variable influencing BMD in the fertile and postmenopausal groups. CONCLUSION: In the present study, BMD results in fertile and postmenopausal SSc patients were independent of the SSc clinical variants, race and previous use of corticosteroids and cyclophosphamide. A low BMD in appendicular sites was observed infertile and postmenopausal SSc patients when compared to a control healthy group, associated to a low BMI.

Neuroimaging findings in scleroderma en coup de sabre.

OBJECTIVES: To describe the neuroimaging and clinical findings in patients with localized scleroderma en coup de sabre (LScs). METHODS: Patients with LScs were evaluated by high-resolution MRI and CT. The authors performed three-dimensional reconstructions of MRI and CT scans to evaluate brain and bone structures. RESULTS: Nine patients with LScs were evaluated (five women), with ages ranging from 6 to 53 years (mean, 30.7 years). Brain CT showed bone deformities with thinning of the skull under the skin lesions in six patients. MRI scans showed focal atrophy and blurring of the gray-white matter interface localized under the skin lesion in all patients. In three patients it was associated with hyperintense signal on fluid-attenuated inversion recovery (FLAIR) and T2-weighted images. Follow-up MRI showed extension of the brain lesion in one patient; in the remaining patients, the lesion did not progress. Four of the nine patients had partial epilepsy. One had surgery for management of refractory seizures, and pathologic findings indicated a focal inflammatory process. CONCLUSION: Localized scleroderma en coup de sabre is associated with focal, and in some progressive, brain lesions underlying the skin atrophy. Epilepsy, when present, is related to these brain lesions. Imaging findings and histopathology indicated that the process, most likely focal inflammatory, may be progressive.

Undifferentiated spondyloarthropathies: a 2-year follow-up study.

The aim of the study was to analyse the 2-year follow-up of a series of patients with the diagnosis of undifferentiated spondyloarthropathy (uSpA). A prospective study was carried out analysing 68 patients with symptomatic uSpA who fulfilled the European Spondylarthropathy Study Group (ESSG) criteria for seronegative spondyloarthropathies (SpA) and were aged between 18 and 50 years. Inclusion criteria included inflammatory low back pain (ILBP) (without radiographic sacroiliitis), asymmetric oligoarthritis (predominantly affecting large joints in the lower limbs) and heel enthesopathies (Achilles tendinitis and/or plantar fasciitis). Imaging methods included pelvic radiography (at study entry and after 2 years) and calcaneal radiography (at study entry). There was a predominance of male gender (78%), caucasoid race (72%) and positive HLA-B27 (54%), with a mean age of 31 years and mean disease duration of 5 years. The first disease manifestations were ILBP (49%), asymmetric oligoarthritis (35%) and heel enthesopathies (16%). A positive family history of a definite SpA was mentioned by 9% of the patients. Seventeen patients (25%) scored 5 points in the Amor set of SpA criteria; logistic regression analysis showed that HLA-B27, heel enthesopathy and asymmetric oligoarthritis were significantly associated with Amor criteria > or = 6, whereas ILBP was associated with Amor criteria <6. Male sex was associated with heel enthesopathies (p = 0.041) and ankle involvement (p = 0.015). Caucasoid race was associated with ILBP (p=0.015) and buttock pain (p = 0.047). Positive HLA-B27 was associated with wrist involvement (p=0.019) and Amor criteria > or = 6 (p=0.001). After a 2-year follow-up the following outcomes were observed: uSpA 75%; disease remission 13%; ankylosing spondylitis 10%; psoriatic arthritis 2%. Logistic regression analysis showed that buttock pain and positive HLA-B27 (trend) were statistically associated with progression to a definite SpA. In conclusion, uSpA can represent a provisional diagnosis in the group of SpA and a systematic follow-up is necessary in order to better establish the different patterns of the disease.

Primary ankylosing spondylitis: patterns of disease in a Brazilian population of 147 patients.

OBJECTIVE: To analyze patterns of disease in a population of Brazilian patients with primary ankylosing spondylitis (AS). METHODS: Retrospective study (1988-98) analyzing 147 patients with a diagnosis of primary AS according to the modified New York criteria. Selected patients had complete clinical (initial symptom, axial and peripheral involvement, heel enthesitis, extraarticular manifestations) and radiological (sacroiliac, lumbar, thoracic, and cervical spine) investigations, and these data were compared with sex, race, age at onset, and HLA-B27. RESULTS: There was a predominance of men (84.4%), Caucasian race (75.5%), adult onset (> 16 years, 85%), and positive HLA-B27 (78.2%). Family history of AS was noted in 14.3% of the patients. Pure axial AS was observed in 37 patients (25.2%). The predominant initial symptoms were inflammatory low back pain (61.9%) and peripheral arthritis (22.4%). Thoracic and cervical spine involvement was noted in 70.1% of the patients; radiological findings included syndesmophytes in 46.9% and "bamboo spine" in 20.4% of patients. The extraaxial joints most frequently involved were: ankles (39.5%), hips (36.1%), knees (29.3%), shoulders (19%), and sternoclaviculars (14.3%); heel enthesitis was present in 22.4%. Acute anterior uveitis was noted in 14.3% of patients. Male sex was associated with involvement of thoracic spine (p = 0.002), cervical spine (p = 0.002), and hips (p = 0.042), whereas female sex was associated with sternoclavicular (p = 0.024) involvement. Caucasian race presented higher frequency of positive family history (p = 0.023); there was no statistical significance of clinical and radiological variables compared with African-Brazilians. Juvenile onset AS presented higher frequency of ankle (p = 0.012) and knee (p = 0.001) involvement, heel enthesitis (p = 0.001), and total hip replacement (p = 0.038), whereas adult onset was associated with thoracic (p = 0.026) and cervical spine (p = 0.026) involvement and positive family history (p = 0.044). Positive HLA-B27 was associated with ankle involvement (p = 0.007) and heel enthesitis (p = 0.013). CONCLUSION: In this population women showed a milder axial involvement, Caucasian race presented axial and peripheral involvement similar to African-Brazilians, juvenile onset AS was associated with articular involvement of the lower limbs, and positive HLA-B27 was associated with ankle involvement.

Methotrexate in the treatment of ankylosing spondylitis.

The authors carried out an open prospective study analyzing methotrexate (MTX) efficacy and toxicity in 34 patients with ankylosing spondylitis (AS) for a period of one year. All the patients presented with active axial disease, characterized by inflammatory spinal pain, prolonged morning stiffness, erythrocyte sedimentation rate (ESR) > or = 25 mm, and failure on treatment with non-steroidal anti-inflammatory drugs for a period of more than two years. MTX was taken at a single weekly intramuscular dose of 12.5 mg. Thirty-one patients (91%) concluded treatment. Eighteen patients (53%) were considered responders to MTX; most of them presented peripheral arthritis. Despite clinical improvement, axial measures were unaltered at the end of the study. The mean value of ESR decreased significantly at the end of the treatment (p=0.0001), predominantly in the responders group. Side effects were observed in 23 patients (68%) and included dyspeptic syndrome, transient elevation of liver enzymes, and dizziness. The results of this one year open study suggest that MTX can be an efficient drug in the treatment of AS.

Gynaecologic history in systemic sclerosis.

The aim of the study was to analyse the gynaecologic history of 150 Brazilian patients with systemic sclerosis (SSc) by comparing the outcome of the pregnancies before and after disease onset and in the two clinical variants of SSc, as well as to assess the effects of the pregnancy on the progress of the disease. A retrospective analysis was carried out of 150 female SSc patients, more than 18 years old, who attended the outpatient clinic of the Unit of Rheumatology of the State University of Campinas. The patients were questioned about the number of pregnancies, deliveries (full-term infants, premature births and twins) and fetal deaths (spontaneous abortions and perinatal deaths). These data were subdivided into pregnancies before and after SSc onset. In those gestations started after disease onset the patients were questioned about the evolution of SSc during the pregnancy. The patients were also asked about dyspareunia and the age at menopause. Thirty-two patients (21 %) had never been pregnant, and only five of them were considered infertile. One hundred and eighteen patients (79%) had a total of 406 pregnancies, with an average of 3.4 per patient; there were 364 pregnancies before and 42 after SSc onset. There were 58 fetal deaths (14% of the pregnancies), 50 of these occurring before and eight after disease onset; 55 were spontaneous abortions and the other three were perinatal deaths. The fertility rate was higher in the limited SSc (3.6) than in the diffuse SSc patients (3.1), although the percentage of fetal deaths and the evolution of SSc during the pregnancy were similar in the two clinical variants. In the pregnancies that occurred after the onset of SSc, the clinical course remained stable in 72% of the cases, worsened in 14% and improved in 14%. Dyspareunia was mentioned by 49 patients (37% of those with an active sexual life). Menopause was reported by 72 patients, predominantly with limited SSc (61 patients). The fertility rate in the postmenopausal SSc patients was 3.9, similar to that observed in general postmenopausal population in Brazil. The analysis of the gynaecologic history in this series of SSc patients showed no increased risk in infertility or spontaneous abortions. The fertility rate in the two SSc clinical variants was higher than that observed in the local global population. Most of the patients who became pregnant after the onset of SSc showed no signs of worsening during the course of the disease.

Rhythmic external compression of the limbs: a method for healing cutaneous ulcers in systemic sclerosis.

OBJECTIVE: To evaluate the usefulness of rhythmic external compression (REC) of the limbs on the healing of ischemic cutaneous ulcers in systemic sclerosis (SSc). METHODS: A prospective study analyzing 17 patients with SSc with symptomatic ischemic cutaneous ulcers in the limbs of more than 4 weeks' duration, who submitted to 20 sessions of REC, each session of one hour duration, 3 times a week. Patients were assessed at study entry, at the end of REC sessions, and at 30, 60, and 90 days after treatment. We also conducted a retrospective analysis of the outcome of ischemic vascular ulcers in a group of 20 patients with SSc who did not undergo REC. RESULTS: Twenty-eight ischemic vascular ulcers were submitted to REC. There was complete healing of 20 ulcers (71%) at the end of REC sessions. The healing was statistically more frequent in the distal ulcers (fingers and toes) (p = 0.0289), independent of SSc variant. There was a statistically significant correlation between pain resolution until the 15th session of REC and future ulcer healing (p < 0.0001). At followup, there were relapses in 2 ulcers 30 days after treatment. In the 20 patients with SSc who did not undergo REC, at followup, after 90 days of conventional treatment, there was healing of 7 ulcers (35%). CONCLUSION: REC could represent a therapeutic option in the treatment of ischemic cutaneous ulcers in SSc.