Sonia Mínguez

Transverse Myelitis Affecting More Than 4 Spinal Segments Associated with Systemic Lupus Erythematosus: Clinical, Immunological, and Radiological Characteristics of 22 Patients

OBJECTIVE To analyze the clinical and laboratory characteristics and outcomes of patients with transverse myelitis affecting more than 4 spinal segments secondary to systemic lupus erythematosus (SLE). METHODS A computer-assisted (PubMed) search of the literature was performed to identify all cases of transverse myelitis affecting more than 4 spinal segments secondary to SLE from 1966 to April 2008. In addition, we present 2 previously unreported cases of SLE patients with transverse myelitis affecting more than 4 spinal segments. RESULTS Twenty-two SLE patients with transverse myelitis affecting more than 4 spinal segments were finally reviewed. There were 17 (77%) females and the mean age at the diagnosis of myelitis was 29.3 +/- 9.4 years (range, 12-53 years). It was the first manifestation of SLE in 5 (23%) patients. The most frequent clinical manifestations were sensory deficit in 20 (91%) patients, variable motor deficit in 19 (86%), and urinary sphincter dysfunction in 15 (83%) patients. On magnetic resonance imaging, all patients showed increased T2 signal intensity of the spinal cord, most frequently in the cervical to mid-lower thoracic spinal segments. Most patients received a combination of therapies; corticosteroids and cyclophosphamide was the most common (45%). Three patients (14%) had complete resolution of symptoms and 14 (59%) had partial recovery. CONCLUSIONS Transverse myelitis affecting more than 4 spinal segments is a rare complication in patients with SLE but may be the first clinical manifestation of the disease in some patients. A high proportion of affected patients have variable degrees of disability after treatment.

Interferon-gamma release assays in the detection of latent tuberculosis infection in patients with inflammatory arthritis scheduled for anti-tumour necrosis factor treatment

Biological agents, particularly anti-Tumour Necrosis Factor (TNF)-α agents, have emerged as an effective treatment in patients with chronic inflammatory diseases. An association between anti-TNF-α antibodies and reactivation of latent tuberculosis infection (LTBI) has been established. Appropriate screening for TB infection has become mandatory before starting a treatment based on TNF-α inhibition. The objective was to determine the usefulness of IFN-γ release assays in diagnosing LTBI in patients with inflammatory rheumatic diseases scheduled for anti-TNF-α treatment. The study included 53 individuals with inflammatory rheumatism. All patients had a TST, a chest radiograph, QuantiFERON Gold In-Tube (QFN-G-IT) and T-SPOT.TB. To investigate the influence of non-tuberculous mycobacteria (NTM) infections on non-BCG-vaccinated patients, with a positive TST result and both negative IFN-γ assays, we performed an ex vivo ELISPOT, stimulating the cells separately with NTM sensitins. TST was positive in 7 cases, T-SPOT.TB in 11 and QFN-G-IT in 9 cases. Agreement between TST and T-SPOT.TB and QFN-G-IT was 77.35% (κ = 0.33 and κ = 0.40, respectively), and between both in vitro tests, it was 83.01% (κ = 0.57). Of the three patients with positive TST and negative T-SPOT.TB and QFN-G-IT, one positive ELISPOT result was obtained after stimulation with NTM sensitins. Positive TST, T-SPOT.TB and QFN-G-IT results were not affected by the immunosuppressive therapies. IFN-γ release assays are useful methods for avoiding TST false-positive results, but in those patients with a high risk of developing active TB and in the absence of predictive value studies in this specific kind of population for knowing how safe is the use of IGRAs alone, the combined use of TST and IFN-γ tests should be recommended in order to increase the overall number of LTBI diagnoses.

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.

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.

Artritis séptica por Staphylococcus aureus resistente a la meticilina en adultos

INTRODUCTION Septic arthritis due to methylcyllin resistant Staphylococcus aureus (MRSA) is a serious infection that has increased in incidence in the past 10years. METHODS We conducted a retrospective study (1984-2011) in which a description of the clinical and epidemiological characteristics of MRSA arthritis in adults was performed and then compared to native joint infections caused by MRSA vs. methylcyllin sensitive Staphylococcus aureus (MSSA). RESULTS Fourteen MRSA infections were included (7 native joint, 5 prosthetic and 2 bursae). No case was polyarticular. There was significant comorbidity, although none was associated to rheumatoid arthritis. Seven patients had bacteremia. Four required surgical treatment. Six died. When comparing the 7 patients with native joint MRSA infection with the 17 cases caused by MSSA, no significant differences in risk factors were seen, except more malignancies in the MRSA group. The infection was polyarticular in 7 cases (41%) of the MSSA group. Bacteremia was more frequent in the MRSA group (71.4 vs 58.8%). Empirical antibiotic was useful in 28.6% of MRSA cases versus 100% of MSSA cases. There was a greater tendency to associated mortality in MRSA arthritis (57.1% vs 17.6%, P=.07). CONCLUSIONS MRSA septic arthritis is a serious condition that occurs in the elderly and patients with high comorbidity. It is usually monoarticular, with positive blood cultures and higher mortality than MSSA arthritis. In patients at risk, vancomycin empiric antibiotic therapy is indicated.

Neuropatía del trigémino y dermatomiositis

La enfermedad más frecuente del nervio trigémino es la neuralgia. Se caracteriza por un dolor facial grave, paroxı́stico y unilateral en el territorio de una o varias de las 3 ramas del nervio. Suele afectar más a mujeres y su incidencia aumenta con la edad. El diagnóstico es fundamentalmente clı́nico y se basa en criterios de inclusión y exclusión. La etiologı́a de la neuralgia del trigémino es idiopática en un 90% de los casos. Actualmente se considera que, en la mayorı́a de las neuropatı́as del nervio trigémino consideradas como idiopáticas, hay una compresión subyacente de la raı́z del nervio por un bucle arterial o venoso aberrante. En menos del 10% de los pacientes con neuropatı́a del trigémino se identifica una causa, como tumores, aneurismas, infarto cerebral isquémico, esclerosis múltiple o determinadas enfermedades reumáticas, como las conectivopatı́as. A continuación se presenta una neuropatı́a del trigémino asociada a dermatomiositis. Mujer de 62 años, con antecedentes personales de safenectomı́a. Acudió a consulta por hipoestesia facial bilateral de predominio izquierdo, con disestesias y dolor sordo y punzante, sin existencia de una zona gatillo ni caracterı́sticas neurálgicas tı́picas. Todo esto de 5 meses de evolución. En el estudio neurofisiológico se observó que en el blink-reflex (reflejos trigeminofaciales) se constataba un defecto aferencial en la primera rama del trigémino izquierdo, lo que confirmó la existencia de una neuropatı́a del trigémino. La resonancia magnética craneal fue normal. En las pruebas de laboratorio destacaron unos anticuerpos antinucleares positivos de 1/2.560 con patrón moteado fino. En la anamnesis dirigida, la paciente referı́a un fenómeno de Raynaud que afectaba a ambas manos y de 5 años de evolución, disfagia a sólidos y astenia sin sı́ndrome tóxico acompañante. La exploración fı́sica evidenció pápulas de Gottron en las manos, tenue heliotropo y debilidad de los músculos flexores del cuello ası́ como cutı́culas engrosadas con hemorragias en astilla. El resto de la exploración por aparatos fue normal. En las pruebas de laboratorio, el hemograma fue normal, en la bioquı́mica plasmática destacó una proteı́na C reactiva de 15,87 mg/l (valor normal o5) y creatincinasa de 354 U/l. Se confirmaron el valor y el patrón de los anticuerpos antinucleares (ANA). La radiologı́a de tórax fue normal. El electromiograma evidenció un patrón de miopatı́a inflamatoria. La biopsia del músculo deltoides fue compatible con miopatı́a inflamatoria del tipo dermatomiositis. La tomografı́a computarizada de tórax fue normal. La tomografı́a por emisión de positrones fue normal y los marcadores tumorales fueron negativos. Se inició tratamiento con glucocorticoides orales (1 mg/kg/dı́a), con el que mejoró la fuerza y se normalizaron las enzimas musculares. Un año después, la paciente está en tratamiento con dosis bajas de glucocorticoides y no hay debilidad alguna; no obstante, los sı́ntomas de la neuropatı́a prosiguen invariables. La neuropatı́a del trigémino puede ser el primer sı́ntoma de una enfermedad del tejido conectivo, especialmente aquellas neuropatı́as del trigémino que se consideran atı́picas. Las enfermedades del tejido conectivo que se asocian con mayor frecuencia son la conectivopatı́a indiferenciada, la enfermedad mixta del tejido conectivo, la esclerosis sistémica y el sı́ndrome de Sjögren primario. El curso de la conectivopatı́a, ası́ como el de la neuropatı́a del trigémino, suele ser más indolente que en aquellos casos en que se presenta de forma aislada. En el caso de las miopatı́as inflamatorias, se han comunicado 6 casos asociados a polimiositis. En la revisión efectuada mediante el buscador PubMed con las palabras clave )trigeminal neuropathy* y )myositis* , de los años 1968 a 2008, se describe un único caso asociado a dermatomiositis junto con neoplasia pancreática. Se describe la asociación de la neuropatı́a del trigémino y las conectivopatı́as, aunque es poco frecuente. La etiopatogenia de esta asociación es poco conocida, se cree que la afectación se halla en el ganglio de Gasser o en la rama sensitiva del V par craneal y se ha indicado que podrı́a tratarse de un proceso autoinmune; por el momento no se ha podido descartar una vasculitis aislada de estas estructuras. La neuralgia del trigémino, sobre todo si ésta es atı́pica, puede ser la primera manifestación de una conectivopatı́a. En este tipo de neuropatı́a podrı́a ser útil realizar un estudio de autoinmunidad con el objeto de diagnosticar una posible conectivopatı́a subyacente y administrar un tratamiento de manera precoz.