Clinical and serologic characteristics of patients with overlap syndrome: is mixed connective tissue disease a distinct clinical entity?

We discuss the clinical and serologic features of 27 patients with overlap syndrome followed prospectively by our group. The findings are similar to those of other reports, but we have drawn attention to the presence of peritendinous nodules in these patients and mentioned some peculiar neurologic manifestations. Rheumatoid arthritis was the most common diagnosis in our patients. The presence of high-titer antibodies against the nuclear ribonucleoprotein fraction of extractable nuclear antigen (nRNP) did not allow the identification of a particular subgroup. However, patients with this antibody tended to fulfill more criteria of more diseases than those without it. The findings lead us to conclude that antibodies to nRNP do not identify a particular subgroup within the overlap syndromes and that mixed connective tissue disease does not appear to be a distinct entity.

Idiopathic familial chondrocalcinosis due to apatite crystal deposition.

Idiopathic familial chondrocalcinosis was found in five members of a family. The clinical features of the disease were morning stiffness, pain and limitation of motion of the dorsolumbar spine in four of the five members, associated with arthritis of the small joints of the hands in three, shoulder periarthritis in two and costal cartilage pain in one. Radiologically, four of the five patients had multiple intervertebral disk calcifications, mainly located at the nucleus pulposus area. Three of them also had periarticular calcific deposits, associated with costal cartilage calcifications and degenerative changes in the small joints of the hands in two. None of these cases showed cartilage calcification in the knees, public symphysis or triangular ligament of carpus. In the propositus, optical microscopy of a specimen of the second proximal interphalangeal joint obtained by open biopsy showed the presence of multiple calcified areas in the intercellular matrix and chondroid metaplasia with calcification of the matrix in the synovial membrane and capsule. X-ray diffraction studies, energy dispersive analysis, and infrared spectrophotometry of a costal cartilage sample obtained by open biopsy demonstrated the presence of carbonate calcium hydroxyapatite. In this study, no relation was found between HLA antigens, loci A, B and C, and this syndrome due to calcium hydroxyapatite crystal deposition.

Prospective study of the early course of rheumatoid arthritis in young adults: comparison of patients with and without rheumatoid factor positivity at entry and identification of variables correlating with outcome.

The early course of newly diagnosed RA among young adult patients (16-44 yr) is described from results of an ongoing study with a mean follow-up of 3.4 yr. Study diagnosis was based on the judgement of experienced rheumatologists, and data on several hundred variables were obtained on entry and annually for the purpose of defining patterns of onset and course of disease. Race and sex factors, as well as certain entry manifestations, e.g., RF, were found to correlate with onset and course patterns. Females, and especially white females, had significantly greater numbers of swollen upper extremity joints than males at entry and at last observation, with increased likelihood of developing bone erosions. At entry, RF positive patients differed only on few articular manifestations from RF negative patients, but had a higher frequency of positive ANA at entry and more subcutaneous nodules and bone erosions during follow-up. Seropositive white females at entry had significantly more swollen upper joints than their seronegative counterparts, but with no difference found at last follow-up. White females of each serogroup had more joint involvement at last examination than patients of other race-sex groups. Males had more acute onset, especially under age 30, with significantly greater improvement in arthritis and in ESR than did females. The majority (55%) of patients entered as seropositive, converted to seronegative during follow-up, and no correlation of either joint swelling or erosions was noted with this phenomenon. At last visit, RF positively did not correlate with bone erosions, but patients developing bone erosions had higher frequency of ANA and higher mean serum complement levels at last examination. The following entry factors were found to correlate significantly with a better outcome: maleness, acute onset under age 30, less swollen upper joints, and negative RF. Type of drug therapy tended to reflect severity of arthritis, rather than vice versa, and functional capacity improved significantly from entry to last evaluation in both males and females, even though the latter had stable or progressive arthritis. Further study is necessary over long intervals and in wider age range to more adequately interpret the biologic implications of findings of this ongoing study. A better understanding of the pathogenesis of RA may be derived from critical studies of the contribution of host factors, e.g., sex, and other variables predisposing to the development of RF positivity (and ANA), subcutaneous nodules, and bone erosions, particularly in systematic ongoing studies of patients with early diagnosed disease.

Radiologic review: the cervical spine in juvenile rheumatoid arthritis.

In our patients, zygapophyseal joint fusion was the most frequent and characteristic roentgenographic finding of cervical spine involvement in JRA. It was not associated with any subset of patients. Atlanto-dens interval greater than 4.5 mm was present in 20% of patients, but was not related to the development of neurologic manifestations. Mild enthesopathic-like changes around the upper cervical area were observed in some children. In patients with severe long standing disease and extensive zygapophyseal joint fusion, longitudinal ligament calcification was observed. Growth disturbances of the cervical spine were more frequently observed in patients with zygapophyseal joint fusion and earlier onset of disease.

Protrusio acetabuli in seronegative spondyloarthropathy.

Protrusio acetabuli (PA) is a complication of many disorders involving the hip joint. Its frequency and clinical features in seronegative sponyloarthropathy (SNSA) are unknown. The prevalence and characteristics of PA were studied in 50 adults and 25 children with SNSA (40 ankylosing spondylitis, 24 psoriatic arthropathy, and 11 Reiter's syndrome). PA was considered present when the acetabular line medially exceeded the ilioischial line by 3 mm or more in men, 6 mm or more in women, more than 1 mm in boys, and more than 3 mm in girls. PA prevalence was 25% in the total group (19 of 75 patients), 22% in adults, and 32% in children. There were no significant differences in seronegative disease type; PA was present with similar frequency between genders and did not correlate with disease duration, clinical severity of hip involvement, or previous medication. Radiological damage was similar in adults and children and did not differ in those with and without PA. Similarly, functional capacity did not differ between groups. It is concluded that PA is a frequent complication in SNSA; however, its presence does not seem to modify the functional prognosis of these patients.

Spinal artery steal syndrome in Paget's disease of bone.

We report a case of vertebral Paget's disease with paraplegia and no evidence of spinal cord compression, in which the neurological condition improved dramatically after treatment with calcitonin. Spinal cord vascular steal syndrome is suggested as another mechanism responsible for this neurologic complication.

Juvenile onset Reiter's syndrome. A retrospective study of 26 patients.

Clinical, laboratory and radiological findings were evaluated in 26 children with Reiter's syndrome, all of whom met the 1982 diagnostic criteria of A. Calin. Twenty-two of the patients (85%) were male and 4 were female (15%); the mean age at onset was 10.5 years (range 4-15.5 yrs). Mean follow-up time was 28.6 months. Diarrhea prior to onset was observed in 18 cases (69%), but there was no report of venereal disease. The full classic triad was initially observed in only 9 patients (35%), urethritis alone in 6 (23%) and conjunctivitis alone in 4 (15%). Arthritis was present in all patients, with the lower limb joints involved in 25 cases (96%); the pattern was pauciarticular in 18 (69%), polyarticular in 7 (27%) and monoarticular in one (4%). There was complete remission in 15 out of the 26 patients (58%), while a sustained and fluctuating course was seen in 7 (27%) and 3 (11.5%) patients, respectively; a single patient showed a remitting course. Balanitis was present in 11 out of the 22 male (50%) cases. Twelve out of 18 patients tested (67%) proved to be HLA B27 positive and there was radiological evidence of sacroiliitis in 5 out of 24 patients (21%). Reiter's syndrome should be included in the differential diagnosis of the arthritic child. As a rule, the course of joint involvement is remittent and sequelae affecting functional capacity are indeed exceptional.

Adult Still's disease and inflammatory myositis.

Although myalgias occur often in adult onset Still's disease (AOSD), inflammatory myositis is rare. We describe a 41-year-old female with AOSD, who had clinical, enzymatic, electromyographic and pathological evidence of myositis, fulfilling the diagnostic criteria for polymyositis. To our knowledge, this exceptional association has only once been reported before.

Lymphadenopathy secondary to silicone hand joint prostheses.

The occurrence of lymphadenopathies was investigated in 23 patients with diverse rheumatic conditions who had silastic prosthesis in joints of the hands, to determine whether these adenopathies were due to the presence of silicone particles. Five cases had clinically detectable lymph node enlargement and tissue samples were studied by light and scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDXA). In 3 out of the 5 cases foreign body granulomas were observed by light microscopy, SEM showing a highly irregular distribution of foreign body material with a peak for silicone by EDXA. Foreign body particle distribution closely correlated with silicone concentration. No granulomas were found in the two remaining patients with adenopathies who presented a non-specific reactive lymphadenitis. Our findings show that silicone lymphadenopathy is a more frequent complication (13%) of silastic arthroplasty than is usually recognized and therefore should be considered in the differential diagnosis of patients with lymph node enlargement who have previously received a silicone arthroplasty.

Ectopic ossification following total hip replacement in juvenile chronic arthritis.

Of twenty-one patients with juvenile chronic arthritis (seventeen with juvenile rheumatoid arthritis and four with juvenile ankylosing spondylitis) who had total hip replacement before the age of thirty years, thirteen patients (62 per cent) showed different degrees of ectopic ossification: nine (53 per cent) of the seventeen with juvenile rheumatoid arthritis and all four of those with juvenile ankylosing spondylitis. Human leukocyte antigen B5 was found with an increased frequency in the patients with ectopic ossification. Functional capacity was not impaired regardless of the severity of the ectopic ossification. As in patients with adult-onset disease, ectopic ossification after total hip replacement occurred with a higher frequency in the patients with juvenile-onset ankylosing spondylitis than in those with juvenile-onset rheumatoid arthritis.

Carcinomatous arthritis of the elbow caused by metastatic breast carcinoma.

We report a case of persisting chronic monoarthritis of the elbow in a 54-year-old woman with previous breast surgery for carcinoma. An open biopsy of the elbow showed a chronic nonspecific synovitis and a poorly differentiated metastatic adenocarcinoma on the radial head. This is the first report of elbow arthritis due to metastatic breast carcinoma.

Auranofin in juvenile rheumatoid arthritis. An open label, non-controlled study.

An open label, non-controlled trial of six-month duration was designed to determine the safety and efficacy of auranofin in the treatment of 13 children with polyarticular JRA. Adverse reactions were observed in 5 of the 13 patients (38%) but only in one was it serious enough to discontinue treatment. None of the patients developed diarrhea or hematologic abnormalities. Therapeutic response was evaluated in the 11 patients who completed the six-month treatment. According to the final overall assessment 9 of the 11 children had improved, one remained unchanged and one worsened. After four months of treatment serum gold levels in 11 patients ranged between 28 and 59 micrograms/dl, with a mean value of 34 micrograms/dl. There was no correlation between serum gold levels and the frequency and severity of side effects.

Rheumatoid nodulosis: a puzzling variant of rheumatoid arthritis.

Four patients with rheumatoid nodulosis are here described, together with a review of cases reported to date in the literature. This particular variant of rheumatoid arthritis (RA) is characterized by the presence of subcutaneous rheumatoid nodules, scanty or absent systemic manifestations and a clinically benign course. Joint involvement appears more commonly as palindromic rheumatism, although patients with arthralgia episodes alone and others with chronic polyarthritis have been described. Seldom reported up to now, a consideration of this entity may help to avoid diagnostic pitfalls and the use of aggressive therapy.

Joint involvement in polymyositis/dermatomyositis.

The frequency and features of joint involvement were evaluated in 29 patients with polymyositis/dermatomyositis (PM/DM); eight of them (27.5%) presented arthritis. Mean age was 30 years, and mean disease duration was 5.3 years. Oligoarthritis was observed in 5 cases, while 3 presented polyarthritis; in most cases arthritis was concurrent with the musculocutaneous picture. On comparing the 8 arthritis patients with the remaining 21, no significant clinical or serological differences were found. However, males predominated in the arthritis group, 75% vs 19% (p < 0.05). Arthritis responded favourably to underlying disease treatment and articular sequelae were not observed.

Neurological features in overlap syndrome.

We report the frequency of neurological findings in 33 patients with overlap syndrome and describe 2 patients presenting unusual neurological involvement. Five of the 33 patients (15%) had one or more neurological findings. Unilateral trigeminal sensory neuropathy was presents, in 4 patients, in 3 of whom this was the only neurological feature. In the other patient it was associated with other manifestations of central as well as peripheral nervous system involvement, with an overall clinical pattern highly suggestive of a demyelinating disorder. The fifth patient, after an aseptic meningitis-like illness, developed a slowly progressive paraparesis, likewise pointing to a demyelinating disease. Our findings suggest that neurological manifestations, mainly trigeminal neuropathy, are frequent features in overlap syndrome; occasionally, central nervous system involvement mimicking a demyelinating disease may also be observed.

Site-dependent bone mineral density response to oral pamidronate and calcium in postmenopausal osteoporosis: a preliminary report.

Radiologically diagnosed postmenopausal osteoporotic patients with at least one nontraumatic vertebral flattening were treated for one year with either oral pamidronate (APD), 300 mg/day plus calcium 1 g/day (n=39) or with calcium alone (n=21). Bone mineral density (BMD) was assessed in lumbar spine, femoral neck, trochanter and Ward's triangle by dual X-ray absorptiometry in order to determine the number of responders at each site. As no densitometric inclusion criteria were stipulated, wide inter- and intra-individual variations in both regional basal BMD and response to therapy were found. However, the APD-treated group showed significant mean BMD increases in spine (+3.1%; p < 0.001) and femoral neck (+3.2%; p < 0.002) versus basal level, whereas the calcium only group failed to exhibit significant differences. The entire 60-strong population was then split into two groups, according to whether individual BMD content was greater or less than the mean basal value for each skeletal site evaluated. For either treatment, subpopulations with lower basal BMD tended to achieve greater bone gain, though statistically significant differences were only disclosed at trochanter (p < 0.004) with APD and at femoral neck (p < 0.002) in the calcium only group. Globally speaking, increases in BMD were observed in 60-80% of patients receiving either treatment - who were thus defined as responders - at each particular skeletal area assessed. However, when only skeletal areas with low basal BMD were considered, the number of responders reached 60-100%. Responsive sites varied among patients: out of 56 cases, 9 (24%) on APD and 6 (32%) on calcium alone responded in all 4 areas evaluated, while a single case on the latter treatment failed to show BMD response at any site. Overall, the mean number of responsive sites was 2.7. Odds ratios were calculated considering treatment modality and high or low basal BMD as parameters, but no significant differences were found in the number of responders. It may be concluded that APD induces moderate lumbar and femoral neck bone mass gain in severe postmenopausal osteoporosis, whereas calcium alone leads to non significant variations, both findings being in agreement with reported data. Therefore, evaluated APD doses enhance mineralization in responsive sites alone, but fail to increase the total number of responders. Interestingly, responsive sites seem to be those relitively spared by the course of the disease.

Jaccoud's arthropathy of the hands in overlap syndrome.

The objective of this work was to evaluate the frequency and features of Jaccoud's syndrome of the hands in patients with overlap syndrome. Twenty-three patients with overlap syndrome were prospectively evaluated by means of a complete physical examination, serological assessment, and hand X-rays. The presence of Jaccoud's syndrome was defined by Kahn's criteria. Patients with or without Jaccoud's arthropathy were compared in their clinical, serological and radiological features. Five out of 23 patients (21.7%) presented Jaccoud's syndrome. Clinical and serological features of patients with or without the syndrome proved similar except for alignment abnormalities, which by definition were more frequent in the group with Jaccoud. A significantly greater number of patients meeting diagnostic criteria for SLE were observed in the Jaccoud group (80% versus 21%; p = 0.03). There was no other disease or associated condition such as chronic renal failure or high-dose steroid treatment concomitant with the development of Jaccoud's syndrome. It may be concluded that in patients with overlap syndrome, Jaccoud' arthropathy seems to be more frequent in patients who meet criteria for SLE.

Protrusio acetabuli in juvenile rheumatoid arthritis.

Acetabular protrusion (PA) as measured by a line crossing method was studied in 73 patients with juvenile rheumatoid arthritis (JRA) and its frequency found to be 12% (9/73), presenting bilaterally in 5 cases and unilaterally in 4. All patients had some other forms of radiological damage and the presence of PA was predominantly observed in the JRA group with greater age at onset (8 vs 4.2 years; p < 0.001) and lower frequency of extraarticular manifestations (22% vs 72%; p < 0.01). There was no correlation with type of JRA onset, course of disease, sex, disease duration, seropositivity for rheumatoid factor, and prior steroid intake.

Idiopathic osteoporosis during pregnancy.

Among the idiopathic forms of osteoporosis, the one developing during pregnancy is the least common and scarcely studied. Poorly understood, it seems to stem from transient failure of calcitropic hormones and decreased osteoblast activity. A 25-year-old patient presented with coxofemoral pain during the last three months of pregnancy, followed by multiple vertebral compression fractures at postpartum. Laboratory, radiological, densitometric and histological examinations led to a diagnosis of idiopathic osteoporosis in pregnancy, once other causes of osteopenia had been ruled out. Bone densitometries performed 12 and 24 months later showed an increase in mineral density, thus demonstrating the self-limited nature of this entity.

Holter monitoring in ankylosing spondylitis patients during methylprednisolone pulse therapy.

Sudden death following steroid pulse therapy has been recently reported. Continuous electrocardiographic recording was performed 24 hours before, during, and 24 hours after each one to three high dose intravenous methyl prednisolone pulses administered of five patients with severe ankylosing spondylitis unresponsive to conventional therapy. No increase in supraventricular or ventricular arrhythmias was observed. Bradyarrhythmias, conduction disturbances or ischemic changes were not found. Cardiovascular symptoms did not occur in any case; there were no significative changes in any of the clinical controls. Transient elevations of serum glucose were observed in all patients. Although a transient increase in potassium and decrease in sodium urinary excretion was noted, serum levels remained within normal values.