Anti-carbamylated proteins antibody repertoire in rheumatoid arthritis: evidence of a new autoantibody linked to interstitial lung disease.

OBJECTIVE: To analyse the association between anti-carbamylated protein antibodies (Anti-CarP) and interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. METHODS: Cross-sectional study including RA patients fulfilling the 2010 ACR/EULAR criteria. The main population comprised two groups: (1) RA patients diagnosed with RA-ILD (RA-ILD group); (2) RA patients without ILD (non-ILD RA group). Non-ILD RA patients in whom ILD was suspected underwent a diagnostic work-up and, if ILD was diagnosed, were switched to the RA-ILD group. ILD was diagnosed by high-resolution computed tomography and confirmed by a multidisciplinary committee. An independent replication sample was also obtained. Three Anti-CarP IgG autoantibodies against fetal calf serum (Anti-FCS), fibrinogen (Anti-Fib) and chimeric fibrine/filagrine homocitrullinated peptide (Anti-CFFHP) and one Anti-CarP IgA against FCS (Anti-FCS-IgA) were determined by home-made ELISA. Associations between Anti-CarP and ILD were analysed using multivariable logistic regression adjusted by smoking, sex, age, RA disease duration, rheumatoid factor and anticitrullinated protein antibodies. RESULTS: We enrolled 179 patients: 37 (21%) were finally diagnosed with RA-ILD. Anti-CarP specificities were more frequent in RA-ILD patients (Anti-FCS 70% vs 43%; Anti-Fib 73% vs 51%; Anti-CFFHP 38% vs 19%; Anti-CarP-IgA 51% vs 20%, p<0.05 for all comparisons). Serum titers of Anti-CarP were significantly higher in RA-ILD patients. Anti-CarP specificities showed a robust effect towards increasing the odds of ILD in the multivariate analysis (Anti-FCS (OR: 3.42; 95% CI: 1.13 to 10.40), Anti-Fib (OR: 2.85; 95% CI: 0.83 to 9.70), Anti-CFFHP (OR: 3.11; 95% CI: 1.06 to 9.14) and Anti-FCS-IgA (OR: 4.30; 95% CI: 1.41 to 13.04)). Similar findings were observed in the replication sample. CONCLUSIONS: Anti-CarP were strongly associated with ILD. The role of homocitrullination in RA-ILD merits further investigation.

Heart⁻Lung⁻Muscle Anti-SAE Syndrome: An Atypical Severe Combination.

A 78-year-old man with 3 months of progressive dyspnea, dysphony, dysgeusia, and proximal muscle weakness was diagnosed of probably idiopathic inflammatory myopathy with nonspecific interstitial pneumonia. Variable degrees of atrioventricular block and persistently elevated cardiac enzymes indicated a diagnosis of myocarditis, confirmed with cardiac magnetic resonance imaging and endomyocardial biopsy. A comprehensive immune work-up revealed anti-small ubiquitin-like modifier-1 activating enzyme (anti-SAE) antibody, a novel myositis-specific antibody, previously described mainly with overt cutaneous dermatomyositis and late skeletal muscle manifestations. Here, heart⁻lung⁻muscle involvement combined with anti-SAE antibodies was a severe combination.

Hypophosphatemic osteomalacia induced by tenofovir in HIV-infected patients.

Tenofovir disoproxil fumarate (TDF) is an adenine analogue reverse transcription inhibitor widely used in first-line treatment of human immunodeficiency virus (HIV) infection and also in hepatitis B virus infection. Its use has been linked to sporadic Fanconi syndrome, renal failure and bone disease. We present the clinical characteristics of tenofovir-induced osteomalacia, discuss bone biopsy findings, describe predisposing factors and compare our results with other reported cases. We describe five cases of hypophosphatemic osteomalacia induced by TDF and recorded at the rheumatology service of a university hospital between 2010 and 2014. We also report the characteristics of bone biopsies of this pathology, which have not been previously described. We include a review of published cases of proximal renal tubulopathy (PRT) and osteomalacia induced by TDF (PubMed 1995-2014; keywords: osteomalacia, tenofovir, Fanconi syndrome, hypophosphatemic osteomalacia, proximal renal tubulopathy, bone biopsy). Five HIV patients who developed hypophosphatemic osteomalacia under TDF treatment (>5 years) presented increasing bone pain and a progressive inability to walk without assistance as a result of multiple insufficiency fractures. Bone biopsy performed in three patients after tetracycline labelling showed increased osteoid thickness, confirming osteomalacia. A literature review retrieved 17 publications on this condition, including 53 cases: 26 patients developed isolated PRT, 25 presented PRT and with multiple insufficiency fractures and two presented isolated bone disease, including osteomalacia and osteoporosis. Rheumatologists should be alert to this complication in patients receiving tenofovir. The main complaint reported by these patients is diffuse pain, predominantly in the lower limbs, indicating multiple stress fractures. Serum phosphate and appropriate screening for abnormal proximal tubule function should be monitored. Bone scintigraphy should be carried out in cases of limb pain before the occurrence of more severe complications.

[Amyloidosis complicating spondyloarthropathies: Study of 15 cases]. / Amiloidosis secundaria a espondiloartritis: estudio de 15 casos.

BACKGROUND AND OBJECTIVE: Secondary amyloidosis (AA) is a rare complication of rheumatic diseases. OBJECTIVE: The aim of this study was to determine the frequency of symptomatic amyloidosis AA in patients with spondyloarthropathy. PATIENTS AND METHOD: Retrospective study (1984-2013). We reviewed the medical records of patients with spondyloarthropathy who had a histological diagnosis of amyloidosis AA (15 patients). RESULTS: We identified 1.125 patients with spondyloarthropathies. Fifteen (1.3%) patients with amyloidosis AA were recruited. It was suspected in 14 patients (93.3%) because of nephrotic syndrome in most of them: 14 were symptomatic (93.3%): 5 (33.3%) ankylosing spondylitis (AS), 5 (33.3%) spondylitis associated with inflammatory bowel diseases (IBD), 4 (26.7%) psoriatic arthritis, and one (6.7%) reactive arthritis. The mean disease duration was 23.9 years. Mortality after one and 5 years of follow-up was 30 and 50% respectively. CONCLUSIONS: The frequency of clinical amyloidosis AA in our patients was 1.3%. There was a marked male predominance, with AS or IBD. Clinical amyloidosis was diagnosed at a relatively late stage in spondyloarthropathy.

[Löfgren syndrome: a study of 80 cases]. / Síndrome de Löfgren: estudio de 80 casos.

BACKGROUND AND OBJECTIVE: Löfgren's syndrome is characterized by hiliar adenopathies, erythema nodosum and arthritis. It is a benign variant of sarcoidosis, common in the Mediterranean area. To describe the clinical characteristics, treatment and outcome of a series of patients diagnosed with Löfgren's syndrome. PATIENTS AND METHODS: Retrospective design (1984-2013). SETTING: Two university hospitals with a reference population of 1,015,000 inhabitants. RESULTS: Eighty patients were diagnosed: 29 men and 51 women (mean age 42.3 years). Forty eight patients (60%) presented with the classical triad: hiliar adenopathies, erythema nodosum and arthritis; 18 (22%) with hiliar adenopathy and arthritis; 13 (16%) hiliar adenopathies and erythema nodosum. All showed abnormalities in the chest study. According to the radiological pattern, patients were classified in stage i-ii. Biopsy was performed in 39 patients and was diagnostic in 28. Treatment was based on non-steroidal anti-inflammatory drugs (54 patients, 67%) and corticosteroids (33 patients, 41%). Fourteen patients (17%) suffered a recurrence of the disease. CONCLUSIONS: Löfgren's syndrome is a benign form of sarcoidosis with a well defined clinical pattern. Biopsy is usually not required. Recurrence is scarce. The disease has a good prognosis.

[Granulomatosis with polyangiitis (Wegener). Description of 15 cases]. / Granulomatosis con poliangeítis (Wegener). Descripción de 15 casos.

BACKGROUND: Granulomatosis with polyangiitis (GP) is a necrotizing vasculitis of unknown etiology that involves small and medium caliber vessels. It is associated with anti neutrophil cytoplasm antibodies (ANCA). It most often affects the respiratory tract and the kidneys and its most important pathologic feature is the presence of necrotizing granulomas. OBJECTIVES: To detail the features of 15 patients with GP diagnosed in a university referral center. PATIENTS AND METHODS: Retrospective study: between 1984 and 2009, 15 patients with GP were diagnosed in our center. Epidemiological, clinical, laboratory test as well as pathologic studies and treatment were retrospectively analyzed. Biopsy diagnosis of GP was considered as an inclusion criterion. RESULTS: Fifteen patients were diagnosed: 12 men and 3 women. Mean age at diagnosis: 52.2 years (14-78). 12 patients had a history of smoking. A biopsy was diagnostic in all patients. ANCA were positive in 11 cases, 6 had a cytoplasmic c-ANCA pattern. All patients had pulmonary involvement and seven (40%) had renal involvement. All patients received intravenous glucocorticoids and cyclophosphamide as induction therapy. During the disease progression 5 patients died. CONCLUSIONS: The clinical features of this series do not differ from those described by other authors. However, a history of smoking is more common than expected. Frequently used drugs were glucocorticoids and cyclophosphamide (oral and pulse therapy). The course was usually unfavorable, with outbreaks or complications due to immunosuppression, except for those with limited forms. Immunosuppressive therapy should be maintained indefinitely in most cases.

Value of bone SPECT-CT to predict chronic pain relief after percutaneous vertebroplasty in vertebral fractures.

BACKGROUND CONTEXT: Longer life span has resulted in increased risk of vertebral osteoporotic fractures. Among minimally invasive procedures, percutaneous vertebroplasty (PV) has shown excellent results in the treatment of chronic vertebral pain. The role of preintervention bone single photon emission computed tomography-computed tomography (SPECT-CT) has not been clearly established for the management of these patients. PURPOSE: To determine the value of bone SPECT-CT in patient selection, treatment planning, and prediction of response to PV. A comparison with magnetic resonance imaging (MRI) was also aimed. STUDY DESIGN: Prospective consecutive series. PATIENT SAMPLE: We studied the performance of bone SPECT-CT on 33 consecutive patients with chronic pain because of vertebral fracture intended for PV. OUTCOME MEASURES: Improvement of clinical status was based on comparison of preprocedure and postprocedure outcome measurements of pain, mobility, and analgesic use. METHODS: Bone SPECT was done using a dual-detector variable-angle gamma camera coupled with a two-slice CT scanner (Symbia T2 System; Siemens, Munich, Germany). Magnetic resonance imaging was done using a magnet of 1.5 T (Giroscan System ACS NT Intera; Philips, Amsterdam, The Netherlands). RESULTS: Of the 33 patients, 24 finally underwent PV. Positive SPECT-CT images predicted clinical improvement in 91% (21 of 23) of them. Agreement between SPECT-CT and MRI was 80% (20 of 25). Single photon emission computed tomography-computed tomography images showed an alternative cause of pain in some cases, such as new fractures or multiple coexisting fractures, persisting bone remodeling in a previous cemented vertebra, and facet or discal degenerative disease. Single photon emission computed tomography-computed tomography was mandatory in eight patients that could no receive MRI, all of whom improved after PV. CONCLUSIONS: Positive bone SPECT-CT seems a good predictor of postprocedural response. It also adds valuable information as to the cause of back pain and facilitates complete patient evaluation in patients that can not receive MRI.

Bone mineral density and bone fracture in male patients receiving long-term suppressive levothyroxine treatment for differentiated thyroid carcinoma.

Studies on the effect of exogenous subclinical thyrotoxicosis on bone mineral density (BMD) in male patients treated with suppressive doses of levothyroxine for differentiated thyroid carcinoma (DTC) are not conclusive. In order to evaluate BMD (in femoral neck, lumbar spine, and distal radius) and bone fractures in men under long-term suppressive treatment with levothyroxine for DTC, we conducted a cross-sectional, retrospective study in 33 Caucasian men (mean ± SD age: 56 ± 14 years) under treatment for DTC. The control group comprised 33 healthy age- and body mass index-matched male volunteers. BMD was assessed by dual-energy X-ray absorptiometry (DXA). Bone turnover biomarkers (calcium, phosphate, alkaline phosphatase, PTH, vitamin D, urinary calcium, and N-Telopeptide/creatinine index) and testosterone were determined. Previous bone fractures were evaluated with a questionnaire and X-ray images of thoracic and lumbar vertebrae. Patients were treated for a mean duration of 15 ± 5 years. No differences were found between patients and controls in bone turnover biomarkers or areal BMD, T-scores or Z-scores in all sites evaluated. No earlier fractures or pain episodes were registered in either group and the incidence of asymptomatic vertebral fractures did not differ significantly between patient (18.8%) and control groups (16.7%), (P = 0.9). In conclusion, long-term suppressive treatment with levothyroxine in men with DTC does not appear to exert deleterious effects on bone mineral density or increase the prevalence of fracture.

[Osteoporosis as a first manifestation of systemic mastocytosis. Study of 6 cases]. / Osteoporosis como primera manifestación de una mastocitosis sistémica. Estudio de 6 casos.

BACKGROUND AND OBJECTIVE: We describe 6 cases of secondary osteoporosis due to systemic mastocytosis diagnosed in the last 6 years. RESULTS: Three females and 3 males, age range: 47-66 years, diagnosed with osteoporosis were subsequently diagnosed with systemic mastocytosis. Diagnosis delay: 0.5-17 years. Cutaneous involvement was present in 3 patients, hematologic involvement in 2 patients and gastrointestinal involvement in 2 patients. Histamine levels in urine were elevated in all cases. Four patients had fractures. Treatment with bisphosphonates was started. After 3 years the values of bone mineral density (BMD) improved in the 5 patients evaluated. Two patients had new vertebral fractures and started teriparatide. CONCLUSIONS: Osteoporosis is an unfrequent initial manifestation of systemic mastocytosis. These patients have a high risk of fractures. Our results suggest that although bisphosphonates improve the bone mineral density the risk of fractures persists.

[Paget's disease of bone: study of 314 patients]. / Enfermedad ósea de Paget: estudio de 314 pacientes.

BACKGROUND: To describe the clinical and laboratory features of Paget's disease of bone at the time of diagnosis. PATIENTS AND METHOD: This multicenter and retrospective study included 314 patients. Diagnosis was performed by means of characteristic radiological findings and typical bone scintigraphy. The variables analyzed included: epidemiological variables, cause of diagnosis, bone involvement, disease extension (Coutris index), complications, alkaline phosphate (AP) levels and disease activity (Renier index). RESULTS: There were 159 (50.5%) males and the mean age was 64.9 years (SD 12.6). Diagnosis was casual in 228 (72.6%) patients. Polyostotic involvement was detected in 201 (63.9%) patients. More common locations were pelvis, skull and lumbar spine. Sacrum was more frequently involved in men than in women (p < 0.05), whereas skull involvement was more common in women (p < 0.05). The number of bones involved was 3.1 SD 3 and the percentage of skeletal involvement was 8.7 % (SD 6.5). One hundred ninety eigth (63%) patients had complications. The disease was active in 242 (77%) patients with a mean AP value of 377 IU/L (SD 493); the activity of the disease measured by the Renier index was 34 (SD 46); the activity was greater in the skull and the humerus. CONCLUSIONS: Paget's disease of bone is usually asymptomatic. Polyostotic involvement and activity are common at the time of diagnosis. Knowledge of the extension and activity by means of a mathematical model may aid to make therapeutical decisions.