Lourdes Mateo

The SAPHO syndrome: a clinical and imaging study

The purpose of this study is to describe the clinical and radiological manifestations of patients with the synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. Retrospective study (1984–2007) was performed in a single center. All patients with the SAPHO syndrome were included. Fifty-two patients were included: 26 male, mean age at diagnosis is 42±12 years. Ostearticular involvement was present before cutaneous involvement in 59.6% of patients and concomitantly in 23.5%. Anterior chest pain was the commonest clinical manifestation, it was present in 38 patients (73%), followed by peripheral arthritis in 17 patients (32%), and sacroliliac pain in 14 patients (26.9%). Cutaneous involvement was present in 33 patients (63.5%). HLA B27 antigen was present in eight patients (17.7%). Bone scintigraphy showed an increased uptake in 42 patients (93.3%). The location of the uptake was mainly in sternoclavicular and manubriosternal joints. CT scan was performed in all “hot joints” showing sclerosis, erosions, hyperostosis, and soft tissue involvement. Refractory patients were treated mainly with pamidronate. Although SAPHO syndrome is an entity that share features that fit into a variety of established disease categories, the present study has a homogenous clinical and radiological pattern that gives support to believe that the SAPHO syndrome is an isolated clinical entity.

Visceral leishmaniasis and macrophagic activation syndrome in a patient with rheumatoid arthritis under treatment with adalimumab.

BACKGROUND Visceral leishmaniasis is a protozoan infection usually asymptomatic, but can progress to fatal disease in immunocompromised hosts, especially in HIV patients. Visceral leishmaniasis is rare among patients under immunosuppressive therapies, and even more among patients under anti-TNF-alpha treatment, where only four cases have been described. OBJECTIVE 1) To describe a patient with rheumatoid arthritis receiving adalimumab who developed fever, pancytopenia, splenomegaly, and extreme hyperferritinemia. 2) To perform a review of the published cases of visceral leishmaniasis and anti-TNF-alpha therapy, and cases of coexisting leishmaniasis and macrophagic activation syndrome by search in PubMed (period 1991-2008). RESULTS Visceral leishmaniasis was established by bone marrow aspiration, and although there was no histological confirmation, according to HLH-2004 criteria, a secondary macrophagic activation syndrome was established. The patient had a favourable outcome. CONCLUSION We report herein the fifth case of visceral leishmaniasis in a patient under TNF-alpha therapy, and the first one, to our knowledge, presenting a consequent secondary macrophagic activation syndrome.

Brown tumor of the cervical spine: a case report and review of the literature.

Brown tumors (BT) are benign focal bone lesions that may appear in the context of primary and secondary hyperparathyroidism (HPT). Involvement of the spine is exceedingly rare. We present a case of brown tumor involving the cervical spine, the third reported in the literature. In the literature review (until August 2010), we found nine cases of spinal BT in primary HPT and 14 cases in secondary HPT. Fifteen patients (65%) had evidence of spinal cord compression. A 34-year-old woman on long-term hemodialysis, with secondary HPT, presented with a 9-month history of persistent neck pain. Radiographs of the cervical spine revealed an expansive osteolytic lesion in the posterior arch of the second cervical vertebra. MR imaging revealed an expansive mass on C2 affecting the vertebral body, odontoid process, right pedicle, laminas, and spinous process; there were no signs of spinal edema. A CT-guided needle biopsy of the lesion showed destruction of trabecular bone, infiltration of the fibroblastic cells, and abundant osteoclast-like multinucleated giant cells with hemorrhage and hemosiderin pigment, and the diagnosis of brown tumor was made. Cervical pain disappeared within a few days of parathyroidectomy, and rapid remineralization of C2 was evident within a few months. BT must always be considered in the context of hyperparathyroidism and osteolytic lesions. Vertebral BT can be particularly devastating due to medullar compression symptoms. Regression or complete disappearance of these lesions after parathyroidectomy is common, but prompt surgical decompression is necessary in case of medullar compression symptoms.

Tuberculosis osteoarticular: estudio de 53 casos

BACKGROUND AND OBJECTIVE: To analyze the characteristics of bone and joint tuberculosis in a Spanish university hospital. PATIENTS AND METHOD: Retrospective study (1984-2006) in a university hospital. All patients had microbiologically and/or histologically proved osteoarticular tuberculosis. Patients with clinical and radiological criteriae, positive tuberculin test responding to antituberculous treatment were not excluded despite negative cultures. RESULTS: We attended 53 patients with osteoarticular tuberculosis (35 males/18 females; mean age: 52 years). Bone tuberculosis involved axial skeleton in 37 patients (71%), peripheral distribution in 12 (21%) and both locations in 4 (8%). Mean time to diagnosis was 8 months. Most common involved joints were knee and ankle. An extraarticular involvement was found in 12 patients (22%) and multifocal bone infection in 6 (11%). Risk factors were present in 22 patients (42%), and 15% were immigrants. The diagnosis was established by a positive culture in 40 cases (75%), and 33 (62%) had suggestive histology. Complications of tuberculosis included medullar compression (9.4%), abscess (12%) and fistulae (9.4%). Spine involvement required surgical intervention in 27% and peripheral involvement in 56%. Curation was achieved in 33 patients (62.3%), curation with secuelae in 19 cases (35.9%) and no consolidation of arthrodesis in one case. CONCLUSIONS: Bone and joint tuberculosis is still common in our area and should be particularly considered in immigrants. Diagnosis delay is remarkable. Complications are present in one third of patients. Surgical treatment is often required.

Usefulness of bone densitometry in postmenopausal women with clinically diagnosed vertebral fractures.

Objective: To analyse whether bone mineral density (BMD) assessment is required in postmenopausal women presenting with low trauma vertebral fracture. Methods: Women with vertebral fracture diagnosed over a 10 year period were recruited from our database. The following were excluded: (a) patients with high energy trauma; (b) patients with malignancies; (c) patients with a metabolic bone disease other than osteoporosis. All postmenopausal women were included in whom BMD had been evaluated at both the lumbar spine and femoral neck by dual energy x ray absorptiometry during the six months after the diagnosis. Patients with a potential cause of osteoporosis other than age and menopause were not considered. A total of 215 patients were identified. Results: The mean (SD) age of the patients was 65.9 (6.9) years. BMD at the lumbar spine was 0.725 (0.128) g/cm2 and the T score was −2.94 (1.22); BMD at the femoral neck was 0.598 (0.095) g/cm2 and the T score was −2.22 (0.89). The BMD of the patients was significantly lower than that of the general population at both the lumbar spine and femoral neck. When the lowest value of the two analysed zones was considered, six patients (3%) showed a normal BMD, 51 (23.5%) osteopenia, and 158 (73.5%) osteoporosis. The prevalence of osteoporosis at the femoral neck increased with age; it was 25% in patients under 60, 35% in patients aged 60–70, and 60% in patients over 70. Conclusion: These results indicate that bone densitometry is not required in postmenopausal women with clinically diagnosed vertebral fractures if it is performed only to confirm the existence of a low BMD.

Estudio densitométrico en mujeres posmenopáusicas con artritis reumatoide tratadas con dosis bajas de glucocorticoides

Fundamento : Evaluar el estado de la densidadmineral osea (DMO) en un grupo demujeres posmenopausicas afectadas de artritisreumatoide (AR) tratadas con dosisbajas de glucocorticoides. Pacientes Y Metodo : Se incluyeron 111 pacientes.La edad media (DE) fue de 63,8(8,8) anos, la duracion media del periodoposmenopausico de 16,4 (10,1) anos y laduracion media de la enfermedad de 12,5(8,2) anos. Resultados : Se observo una reduccion significativade la DMO, respecto de la poblaciongeneral, tanto en la columna lumbar(p Conclusiones : El estudio confirma, en poblacionespanola, que las mujeres posmenopausicascon AR tratadas con dosis bajasde glucocorticoides presentan una menorDMO que la poblacion general. La prevalenciade la osteoporosis se considera elevada. Background : To study bone mineral density(BMD) in a group of postmenopausal womenwith rheumatoid arthritis (RA) treatedwith low doses of corticosteroids. Patients and Methods : One hundred and elevenpatients were included. Mean age (SD)was 63.8 (8.8) years, mean duration ofpostmenopausal period was 16.4 (10.1) yearsand the mean disease duration was12.5 (8.2) years. Results : A significant reduction of lumbarBMD (p Conclusions : The study supports, in theSpanish population, that postmenopausalwomen with RA treated with low doses ofcorticosteroids, have low BMD. We considerthat the prevalence of osteoporosis in these patients is high.

Prevalencia de los criterios de indicación de densitometría ósea y de los factores de riesgo de baja masa ósea y fractura en unidades extrahospitalarias de reumatología

Many organisms have proposed criteria to identify individuals with low bone mass or increased risk for osteoporotic fracture in order to provide them with the available diagnostic and therapeutic resources. Among these organisms are the WHO, the Catalan Agency for Health Technology Assessment (CAHTA) and the International Committee for Osteoporosis Clinical Guidelines (ICOCG). We designed a prospective multicenter study to determine the prevalence of indications for bone densitometry in rheumatology outpatient clinics by applying the criteria of these three organisms. Two hundred sixty-two women and 98 men aged 18 years or older who attended five rheumatology outpatient clinics were interviewed and their medical records were reviewed. The mean age was 58.3±13.4 years. Bone densitometry was indicated in 45% of the patients interviewed according to the CAHTA criteria, in 77% according to the WHO criteria and in 62% according to the ICOCG criteria (applicable only to women). The proportion of patients with indications for bone densitometry increased with age, and was higher in women. The concordance among criteria was low.

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.

SAT0206 Tocilizumab Serum Levels and Antidrug Antibodies and Its Relationship with Disease Activity in Rheumatic Diseases

Background Tocilizumab (TCZ) is a humanized anti-IL-6 receptor-blocking monoclonal antibody used for the treatment of rheumatoid arthritis (RA), idiopathic juvenile arthritis (IJA) and off-label in Adult Onset Still Disease (AOSD). The development of anti-TCZ antibodies could reduce treatment efficacy or induce treatment failure. Objectives To analyse TCZ serum levels and antidrug antibodies (ADA) in a cohort of RA, IJA and AOSD patients treated with TCZ, and to evaluate its relationship with Disease Activity Score using a 28-joint count (DAS28), C-reactive protein (CRP) levels and the presence of combined treatment with glucocorticoids or DMARDs. Methods Cross-section study including all patients undergoing chronic treatment with TCZ in a tertiary academic hospital. Referral area: 850,000 inhabitants. Twenty-two patients were included. TCZ serum and ADA levels were measured by ELISA (Theradiag) at baseline (before infusion), 15 days and 30 days after infusion. Results Twenty-two patients were studied: 18 RA, 3 IJA and 1 AOSD, 81.8% female; mean age and mean disease duration: 54.2 (±13) and 15.5 (±12) years respectively; 73% of the RA patients were positive for anti-CCP and 70% for rheumatoid factor, mean DAS28-CRP at day 0 and 30: 2.9 and 2.6 respectively. Fifteen patients were treated with TCZ for more than 1 year (range 12-58 months), 19 were treated with TCZ at 8 mg/kg, 2 at 6mg/kg, and one at 5mg/kg every 4 weeks due to low disease activity. Thirteen patients received TCZ in monotherapy, 9 received DMARDs combined treatment, 10 with glucocorticoids (mean dose 4mg/day, range 2-10mg). TCZ serum levels were at baseline: 1.2- 61.7 μg/ml, 15 days: <1-130.1 μg/ml and 30 days: <1-97.1 μg/ml. No patient showed presence of ADA. No correlation was found with DAS28-CRP, but there was inversely relation between CRP and TCZ serum levels (p=ns). The mean CRP levels were 14.4, 64.2 and 17.6 mg/dL at day 0, 15 and 30. TCZ Serum levels were higher in patients with combined therapy with DMARDs than those with monotherapy at day 15 and 30 (p=ns, 71 vs 55 μg/mL/23 vs 12 μg/mL, respectively). Patients treated without glucocorticoids had high levels of TCZ (68.62 vs 59.96 μg/mL at day 15 and 20.2 vs 13.68 μg/mL at day 30, p=ns) Conclusions Levels of TZC were heterogeneous. Our patients showed no presence of ADA, this data suggest that TCZ has a low immunogenic potential. No correlation was found in disease activity and TCZ serum levels, but we found a relation with CRP levels. Patients with DAMRDs or without glucocorticoids showed higher levels of TCZ. We did not find correlation between combined treatment with DMARDs or glucocorticoids and levels of TCZ. Our study was limited due to a low sample size; we cannot exclude the correlation between TCZ and DAS28-CRP in a higher sample of patients. References Dougados M, Kissel K, Conaghan PG et al. Clinical, radiographic and immunogenic effects after 1 year of tocilizumab-based treatment strategies in rheumatoid arthritis: the ACT-RAY study. Ann Rheum Dis. 2014;73(5):803-9 Van Herwaarden N, Herfkens-Hol S, van der Maas A, et al. Dose reduction of tocilizumab in rheumatoid arthritis patients with low disease activity. Clin Exp Rheumatol. 2014;32(3):390-4 Disclosure of Interest None declared

Immune-mediated inflammatory diseases differently affect IGRAs’ accuracy for latent tuberculosis infection diagnosis in clinical practice

Background Clinical accuracy of IGRAs remains unclear on patients with immune-mediated inflammatory diseases (IMIDs). Here, we assess the impact of immunosuppressants and IMIDs on QuantiFERON-TB Gold In-Tube (QFN-G-IT) and T-SPOT.TB accuracy. Methods Patients with IMIDs who required latent tuberculosis infection (LTBI) screening were enrolled and classified into: (i) 50 patients with inflammatory rheumatic diseases, (ii) 50 patients with psoriasis and (iii) 30 patients with Crohn’s disease. A total of 44 healthy individuals without immunosuppression were also included as controls. Tuberculin skin test (TST), T-SPOT.TB and QFN-G-IT assays were performed. IGRAs were performed following manufacturer’s instructions. Results Immunosuppressant’s intake was more frequent on patients with Crohn’s disease and psoriasis. Positive IGRAs and TST results were reduced in Crohn’s disease patients, whereas rate of indeterminate T-SPOT.TB results was increased in this group with respect to the other IMIDs analysed and controls. When IFN-γ response was studied, the levels of this cytokine after mitogen stimulation were significantly lower in Crohn’s and inflammatory rheumatic diseases than in psoriasis. Interestingly, psoriatic patients were the only ones not receiving corticosteroids. Furthermore, a negative correlation was observed between the IFN-γ secreted after mitogen stimulation and corticosteroids dose. Conclusions IMIDs seem to negatively affect the clinical accuracy of IGRAs, being Crohn’s disease patients the most affected individuals due to their concomitant drug-profile and impaired immune response.