Role of rheumatoid factor isotypes and anti-citrullinated peptide antibodies in the differential diagnosis of non-selected patients with inflammatory arthralgia / Rol de los isotipos del factor reumatoide y los anticuerpos anti-péptido cíclico citrulinado en el diagnóstico diferencial de pacientes no seleccionados con artralgia inflamatoria

Background/ObjectivesRheumatoid arthritis (RA) is a chronic inflammatory disease characterized by swelling, tenderness and destruction of synovial joints, leading to severe disability and premature mortality. The aim of the study was to determine the diagnostic accuracy of the 3 isotypes of rheumatoid factor (RF), anti-citrullinated peptide antibodies (ACPA) and the combination of both, for the diagnosis of rheumatoid arthritis (RA) in non-selected patients with inflammatory arthralgia.MethodsWe include 129 patients with inflammatory Arthalgia from a third level reference Center of rheumatic diseases in Monterrey, México. Their samples were analyzed for RF isotypes (IgA, IgG, and IgM) by ELISA (EUROINMUN), using a cut-off of 20IU/ml, and for ACPA's 5IU/ml; a medical examination was performed to obtain the definitive diagnoses of the patients. Data analysis was carried out using ROC curves for the measurement of sensitivity, specificity, for diagnostic accuracy to verify if the use of 3 RF isotypes and ACPA had a better prediction for the diagnosis of RA than use only one isotype and the ACPA alone.ResultsThe ROC showed a sensitivity and specificity of the different antibodies with different cut-off points, being the best for the IgM with 0.802 followed by ACPA, IgA and IgG with 0.771, 0.63, and 0.728 respectively without statistical difference, the sensitivity and specificity of the combination of the 4 antibodies were 81.4 and 73.66%.ConclusionIn non-selected patients with inflammatory arthralgia, the combination of ACPA and isotypes of RF did not demonstrate more sensibility and specificity than IgM isoform of rheumatoid factor measurement only. We recommend that in the clinical scenario of arthralgia, where the diagnoses are Lupus, Sjogren syndrome and Osteoarthritis, RF IgM isoform is used followed by ACPA.(AU)

Introduccion/objetivosLa artrtitis reumatoide (AR) es una enfermedad inflamatoria crónica caracterizada por inflamación, sensibilidad y destrucción de la membrana sinovial de las articulaciones, dando lugar a una discapacidad grave y mortalidad prematura. El objetivo del estudio fue determinar la precisión diagnóstica de los 3 isotipos del factor reumatoide (RF), los anticuerpos peptídicos anti citrulinados (ACPA) y la combinación de ambos, para el diagnóstico de AR en pacientes no seleccionados con artralgia inflamatoria.MétodosFueron incluidos 129 pacientes con artralgia inflamatoria de un centro de referencia de enfermedades reumáticas de tercer nivel en Monterrey, México. Sus muestras se analizaron para determinar los isotipos de RF (IgA, IgG e IgM) mediante ELISA (Euroinmun), usando un límite de 20UI/ml, y de 5UI/ml de ACPA. Se realizó un examen médico para obtener los diagnósticos definitivos de los pacientes. El análisis de los datos se realizó mediante las curvas ROC para la medición de la sensibilidad, la especificidad y la precisión diagnóstica para verificar si el uso de 3 isotipos de RF y ACPA tenía una mejor predicción para el diagnóstico de la AR que el uso de un solo isotipo y el ACPA solo.ResultadosLa curva ROC mostró una sensibilidad y especificidad de los diferentes anticuerpos con diferentes puntos de corte, siendo el mejor para el IgM con 0,802 seguido de ACPA, IgA e IgG con 0,771, 0,63 y 0,728, respectivamente, sin diferencia estadística; la sensibilidad y la especificidad de la combinación de los 4 anticuerpos fueron 81,4 y 73,66%.ConclusiónEn pacientes no seleccionados con artralgia inflamatoria, la combinación de ACPA e isotipos de RF no demostró más sensibilidad y especificidad que la isoforma IgM de la medición del RF solamente. Recomendamos que, en el escenario clínico de artralgia, donde los diagnósticos son lupus, síndrome de Sjögren y osteoartritis, se use la isoforma RF IgM seguida de los ACPA.(AU)

Role of rheumatoid factor isotypes and anti-citrullinated peptide antibodies in the differential diagnosis of non-selected patients with inflammatory arthralgia.

BACKGROUND/OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by swelling, tenderness and destruction of synovial joints, leading to severe disability and premature mortality. The aim of the study was to determine the diagnostic accuracy of the 3 isotypes of rheumatoid factor (RF), anti-citrullinated peptide antibodies (ACPA) and the combination of both, for the diagnosis of rheumatoid arthritis (RA) in non-selected patients with inflammatory arthralgia. METHODS: We include 129 patients with inflammatory Arthalgia from a third level reference Center of rheumatic diseases in Monterrey, México. Their samples were analyzed for RF isotypes (IgA, IgG, and IgM) by ELISA (EUROINMUN), using a cut-off of 20IU/ml, and for ACPA's 5IU/ml; a medical examination was performed to obtain the definitive diagnoses of the patients. Data analysis was carried out using ROC curves for the measurement of sensitivity, specificity, for diagnostic accuracy to verify if the use of 3 RF isotypes and ACPA had a better prediction for the diagnosis of RA than use only one isotype and the ACPA alone. RESULTS: The ROC showed a sensitivity and specificity of the different antibodies with different cut-off points, being the best for the IgM with 0.802 followed by ACPA, IgA and IgG with 0.771, 0.63, and 0.728 respectively without statistical difference, the sensitivity and specificity of the combination of the 4 antibodies were 81.4 and 73.66%. CONCLUSION: In non-selected patients with inflammatory arthralgia, the combination of ACPA and isotypes of RF did not demonstrate more sensibility and specificity than IgM isoform of rheumatoid factor measurement only. We recommend that in the clinical scenario of arthralgia, where the diagnoses are Lupus, Sjogren syndrome and Osteoarthritis, RF IgM isoform is used followed by ACPA.

Löfgren Syndrome with Hypercalcemia and Neuroendocrinological Involvement: A Case Report.

BACKGROUND: Sarcoidosis is a systemic inflammatory disease of unknown etiology that can affect virtually any organ. Löfgren syndrome, characterized by erythema nodosum, hilar lymphadenopathy, fever and polyarthritis, represents only 20-30% of the cases of sarcoidosis. Only 2- 10% of the cases feature hypercalcemia. CASE: The case of a 42-year-old Hispanic woman with a history of erythema nodosum and three weeks of nausea, emesis, constipation, asthenia, adynamia, polydipsia, and somnolence, concomitant with hypercalcemia, but normal parathyroid hormone (PTH) and 25-hydroxyvitamin D has been presented. The initial diagnostic approach was based upon the suspicion of multiple myeloma or bone metastases; however, further findings of bilateral hilar lymphadenopathy, elevated serum angiotensin-converting enzyme (ACE) and a right inguinal lymphadenomegaly suggested an alternate diagnosis. Biopsy of the latter supported sarcoidosis as the diagnosis. She was successfully treated in the hospital with zoledronic acid and as an outpatient with immunosuppressive therapy. Persistence of a previously undisclosed symptom of oligomenorrhea led to the detection of hyperprolactinemia secondary to hypophyseal infiltration, refractory to immunosuppressive therapy but with an adequate response to cabergoline. CONCLUSION: This case strays from Löfgren Syndrome's expected behavior, presenting a more progressive, multisystemic disease. This case report was written in adherence to the CARE guidelines of 2013 to include information in it.

Athetoid Movements as Initial Manifestation of Primary Sjögren Syndrome.

Background: Primary Sjögren syndrome (pSS) is an autoimmune disorder characterized by exocrine gland and extraglandular symptoms. We present a case report of pSS with an initial presentation of athetoid movements. Case Report: A 74-year-old female presented with a 2-month history of slow undulating movements in her trunk and thighs that eventually spread to her neck and lower extremities. She also reported dry eyes, dry mouth, as well as pain in her shoulders and thighs. Her proinflammatory markers and rheumatologic profile were positive. Her salivary gland biopsy revealed a Focus score > 2. Brain magnetic resonance imaging was normal. A diagnosis of pSS was made. The patient's symptoms improved with hydroxychloroquine, pilocarpine, gabapentin, and clonazepam. Discussion: Clinicians should consider and screen for primary autoimmune disorders as a cause of subacute athetoid movements in elderly patients. Although aggressive treatment has been recommended, treatment should be tailored to each patient's specific needs.