Arteritis de células gigantes: ¿Cómo debutan pacientes chilenos? Análisis de casos y revisión de la literatura / Giant cell arteritis. Experience in 32 patients

BACKGROUND: Giant cell Arteritis (GCA) is the most common systemic vasculitis in patients over 50 years. Diagnosis is based on clinical, laboratory, imaging and biopsy. Temporal artery biopsy (TAB) may be inconclusive in up to 40% of patients. AIM: To describe disease features of patients diagnosed with GCA. MATERIAL AND METHODS: Review of pathology reports of giant cell arteritis and clinical records of patients seen with the diagnosis between 2000 and 2019. Demographic, clinical, laboratory, histopathology, imaging, treatment and follow-up variables were analyzed. RESULTS: We fetched 32 patients with a median age at diagnosis of 70.5 years (range 57-90), 81% women. Twenty eight percent had polymyalgia. 72% had only cranial symptoms, 12% had extracranial involvement and 13% exclusive extracranial involvement. The median time from onset of symptoms to diagnosis was two months (range 0.5-8). All had elevated erythrocyte sedimentation rate and c reactive protein. A TAB was performed in 27 patients and in 17 (65.4%) it confirmed the diagnosis. Transmural inflam- mation was the most frequent finding. All patients received steroids. Follow-up information was available from 25 patients and 92% received a steroid-spa- ring agent, usually methotrexate (74%). Ninety two percent achieved clinical remission in the first year and 59% had minor relapses during steroid tapering. CONCLUSIONS: Our patients showed frequent extracranial involvement and TAB was a useful diagnostic tool.

[Giant cell arteritis. Experience in 32 patients]. / Arteritis de células gigantes: ¿Cómo debutan pacientes chilenos? Análisis de casos y revisión de la literatura.

BACKGROUND: Giant cell Arteritis (GCA) is the most common systemic vasculitis in patients over 50 years. Diagnosis is based on clinical, laboratory, imaging and biopsy. Temporal artery biopsy (TAB) may be inconclusive in up to 40% of patients. AIM: To describe disease features of patients diagnosed with GCA. MATERIAL AND METHODS: Review of pathology reports of giant cell arteritis and clinical records of patients seen with the diagnosis between 2000 and 2019. Demographic, clinical, laboratory, histopathology, imaging, treatment and follow-up variables were analyzed. RESULTS: We fetched 32 patients with a median age at diagnosis of 70.5 years (range 57-90), 81% women. Twenty eight percent had polymyalgia. 72% had only cranial symptoms, 12% had extracranial involvement and 13% exclusive extracranial involvement. The median time from onset of symptoms to diagnosis was two months (range 0.5-8). All had elevated erythrocyte sedimentation rate and c reactive protein. A TAB was performed in 27 patients and in 17 (65.4%) it confirmed the diagnosis. Transmural inflam- mation was the most frequent finding. All patients received steroids. Follow-up information was available from 25 patients and 92% received a steroid-spa- ring agent, usually methotrexate (74%). Ninety two percent achieved clinical remission in the first year and 59% had minor relapses during steroid tapering. CONCLUSIONS: Our patients showed frequent extracranial involvement and TAB was a useful diagnostic tool.

Interstitial lung disease and microscopic polyangiitis in chilean patients.

OBJECTIVE: To describe the clinical and serological patients characteristics with Microscopic Polyangiitis (MPA) and Interstitial lung disease (ILD). METHODS: Of all the patients with AAV diagnosed between 2007-2017 at the Hospital Clinico Universidad de Chile, those with MPA and ILD were selected and studied retrospectively. RESULTS: All patients were Hispanic; median age at diagnosis 65 years (32-84). 59% were female. All were positive for p-ANCA, 16 patients for MPO. Most common manifestations were constitutional symptoms, weight loss and fever. CT-Scans patterns were Usual Interstitial Pneumonia (UIP) in 10 patients, Nonspecific Interstitial Pneumonia (NSIP) in 6 and fibrosis not UIP or NSIP pattern in 1. In 6 cases, ILD was diagnosed 0.5-14 years before MPA and concomitantly in 11. CONCLUSIONS: Although infrequent, Microscopic Polyangiitis should be suspected in patients with ILD particularly if extra-pulmonary manifestations that rise the possibility of a systemic illness are present, regardless of the time elapsed between the latter and the diagnosis of this type of lung involvement. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (1): 37-42).

Illness Experiences in Women with Oral Dryness as a Result of Sjögren's Syndrome: The Patient Point of View.

BACKGROUND: Sjögren's syndrome and the associated dryness can have multiple consequences. The aim of the present qualitative study was to give an in-depth account of the life experiences of women with primary Sjögren's syndrome (pSS) and health-related behaviours, and to summarize these experiences in an integrated model. METHODS: Twelve women diagnosed with pSS who regularly attended the Hospital of the University of Chile participated in detailed interviews. The data were analysed using qualitative methods based on the principles of grounded theory. RESULTS: Selective coding identified three categories: illness experience, social interaction and psychological response. An integrated model was developed connecting these dynamic aspects and suggesting how they could lead to a life cycle crisis in cases of maladjustment. We found that problem-solving strategies, reconstruction of identity, acceptance and a social support may prevent this life cycle crisis. DISCUSSION: Xerostomia and other consequences of pSS can have a profound influence on daily life. However, the severity of the consequences depends on individual experiences with the illness, social influences and the psychological responses of the patient. Physicians, dentists and other healthcare professionals can help the patient by listening to their problems and exploring solutions based on a psychological approach.

[Aortitis: report of three cases]. / Aortitis, causas infrecuentes en Reumatología: presentación de casos.

Aortitis is a nonspecific term that describes an inflammation of the aortic wall caused by inflammatory, infectious, paraneoplastic and idiopathic diseases. The symptoms are variable and nonspecific; therefore a high level of clinical suspicion is required to diagnose it. It is often an incidental finding while looking for other diagnoses and it is confirmed mainly through imaging studies. We report three cases of aortitis: A 29-year-old woman presenting with alopecia, oral and nasal ulcers and positive antinuclear antibodies. A CAT scan showed a segmental thickening of thoracic aorta, with dilated and stenotic areas. She was successfully treated with steroids, hydroxychloroquine, cyclophosphamide and azathioprine. A 41-year-old male presenting with dorsal pain and cough. The CAT scan showed an extra-intimal thickening of the descending aorta and stenosis of the celiac artery. The final diagnosis was a polyangiitis and was treated with steroids, cyclophosphamide and azathioprine. A 28-year-old woman presenting with pain in the left upper abdomen. Imaging studies showed a thickening of the aortic arch and subclavian artery. The final diagnosis was sarcoidosis and the patient was treated with prednisone.

Aortitis, causas infrecuentes en Reumatología: presentación de casos / Aortitis: Report of three cases

Aortitis is a nonspecific term that describes an inflammation of the aortic wall caused by inflammatory, infectious, paraneoplastic and idiopathic diseases. The symptoms are variable and nonspecific; therefore a high level of clinical suspicion is required to diagnose it. It is often an incidental finding while looking for other diagnoses and it is confirmed mainly through imaging studies. We report three cases of aortitis: A 29-year-old woman presenting with alopecia, oral and nasal ulcers and positive antinuclear antibodies. A CAT scan showed a segmental thickening of thoracic aorta, with dilated and stenotic areas. She was successfully treated with steroids, hydroxychloroquine, cyclophosphamide and azathioprine. A 41-year-old male presenting with dorsal pain and cough. The CAT scan showed an extra-intimal thickening of the descending aorta and stenosis of the celiac artery. The final diagnosis was a polyangiitis and was treated with steroids, cyclophosphamide and azathioprine. A 28-year-old woman presenting with pain in the left upper abdomen. Imaging studies showed a thickening of the aortic arch and subclavian artery. The final diagnosis was sarcoidosis and the patient was treated with prednisone.

Acute herpes simplex virus 1 pneumonitis in a patient with systemic lupus erythematosus.

A woman with severe and longstanding systemic lupus erythematosus presented with a 1-week history of fever up to 38°C and pain in her right flank. Computed tomography scan of the chest revealed interstitial infiltrates and multiple nodules. Bronchoalveolar lavage did not show any inflammatory cells. Gram stain and cultures for aerobic and anaerobic bacteria, fungi, and Nocardia; acid-fast staining; polymerase chain reaction for tuberculosis, cytomegalovirus, herpesvirus 6, and parvovirus B19; and IF staining for pneumocystic and Legionella antigen were all negative. Transbronchial biopsy was nondiagnostic. Open lung biopsy with polymerase chain reaction and immunohistochemistry analyses revealed herpes simplex virus 1 infection. Acyclovir therapy was initiated and was followed by significant improvement. Herpes simplex virus 1 infection (although unusual) should be considered in patients with systemic lupus erythematosus with an atypical clinical presentation.

Weak CD4+ T-cell responses to citrullinated vimentin in rheumatoid arthritis patients carrying HLA-DR9 alleles.

Citrullinated vimentin (cVIM) is one of the antigens specifically targeted by anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients. The association between ACPA and certain HLA-DRB1 alleles, those coding for the shared epitope (SE), suggests that this response could be T-cell mediated. HLA-DR9 alleles, which do not code for the SE, have recently been associated with ACPA (+) RA. The objective of this work was to study CD4+ T cell responses to cVIM in RA patients and healthy controls carrying HLA-DR9 alleles. Fourteen RA patients and ten healthy controls previously genotyped for HLA-DRB1 were studied for the presence of serum anti-cVIM antibodies by Western blot and ELISA. Peripheral blood mononuclear cells were stimulated with native vimentin and cVIM, and CD4+ T cells proliferation was assessed by flow cytometry. Citrulline-specific CD4+ T cells proliferation was found not only in RA patients but also in healthy controls. Although most patients carrying HLA-DR9 alleles present anti-cVIM antibodies, HLA-DR9 alleles were associated with weaker cVIM-driven CD4+ T-cell responses among RA patients. These results suggest that HLA-DR9 alleles could exert a protective effect on the recognition of cVIM epitopes by CD4+ T cells. In this context, other citrullinated proteins may break T and B cell tolerance, with cVIM only acting as a cross-reactive target for ACPA.

Anti-TNF therapy in patients with rheumatoid arthritis decreases Th1 and Th17 cell populations and expands IFN-γ-producing NK cell and regulatory T cell subsets.

The aim of this work was to study the effect of anti-TNF treatment on CD4+ Th1, Th17 and regulatory T cells (Tregs), together with CD8+ T cells and NK cells from rheumatoid arthritis (RA) patients. For this purpose, 18 RA patients received adalimumab during 16weeks and their peripheral blood lymphocytes were assessed by flow cytometry at the beginning and at the end of the study. We found that the proportion of Th17 cells was directly correlated with Th1 cells, but inversely correlated with IFN-γ-producing NK cells. A decrease was observed in Th1, Th17 cells and IFN-γ-producing CD8+ T cells by anti-TNF therapy. Conversely, the proportion of Tregs increased, as did the percentage of IFN-γ-producing NK cells. We postulate that a rise in IFN-γ production due to recovery of NK cells' function, together with expanded Tregs, contribute to decrease the Th17 response in anti-TNF-treated RA patients.

The presence of anti-citrullinated protein antibodies (ACPA) does not affect the clinical response to adalimumab in a group of RA patients with the tumor necrosis factor (TNF) α-308 G/G promoter polymorphism.

The introduction of antitumor necrosis factor (TNF) agents has improved the outcome for many patients with rheumatoid arthritis (RA). To date, the only replicated genetic predictor of anti-TNF response is the -308 G > A single-nucleotide polymorphism in the TNF promoter region. The presence of the -308 TNF G/G genotype appears to be a marker of good response to anti-TNF treatment. Anti-citrullinated protein antibodies (ACPA) have been linked with erosive disease, and have been established as the single most reliable prognostic factor in clinical practice. To test the hypothesis that the ACPA status may affect the -308 G/G patients rate of response to TNF blockade, we prospectively investigated a group of 52 RA patients with the -308 G/G genotype who were ACPA (+) or ACPA (-). All patients were treated with adalimumab, and the clinical response was studied using the Disease Activity Score in 28 joints (DAS28) at 24 weeks of treatment. Over 85% of patients were DAS28 responders in both groups. No significant differences were found between patients from both groups, according to the DAS28 criteria of response at week 24 (p = 0.79). In conclusion, our findings suggest that the ACPA status does not affect the clinical response to anti-TNF therapy in -308 TNF G/G patients.

Comparison of the clinical efficacy of two different immunosuppressive regimens in patients with chronic vogt-koyanagi-harada disease.

PURPOSE: To prospectively compare 2 immunosupressive regimens in patients with active Vogt-Koyanagi-Harada disease in spite of systemic glucocorticoid treatment. METHODS: Forty-four patients were diagnosed between 1998 and 2005. Twenty-one developed chronic intraocular inflammation in spite of glucocorticoid treatment and were randomized to receive either prednisone and azathioprine (AZA) (n = 12) or prednisone and cyclosporine (CyA) (n = 9). RESULTS: In the AZA group Tyndall score decreased from 1.21 +/- 1.10 to 0.29 +/- 0.62 (p < .01), and visual acuity (LogMAR) improved from 0.32 +/- 0.35 to 0.09 +/- 0.16 (p < .001). In the CyA group Tyndall score decreased from 1.67 +/- 1.08 to 0.16 +/- 0.51 (p < .001), and visual acuity improved from 0.41 +/- 0.40 to 0.25 +/- 0.42 (p < .001). Patients in the AZA group needed a significantly higher average prednisone dose and total cumulative dose than those in the CyA group, p < .01 for each comparison. CONCLUSIONS: Both regimens showed a good clinical efficacy, but CyA seems to be a better glucocorticoid-sparing agent than AZA.

B cells from rheumatoid arthritis patients show important alterations in the expression of CD86 and FcgammaRIIb, which are modulated by anti-tumor necrosis factor therapy.

INTRODUCTION: Several molecules help preserve peripheral B cell tolerance, but when altered, they may predispose to autoimmunity. This work studied the expression of the costimulatory molecule CD86 and the inhibitory receptor for IgG immune complexes FcgammaRIIb (CD32b), on B cells from rheumatoid arthritis (RA) patients, and the influence of anti-tumor necrosis factor (TNF) therapy. METHODS: Peripheral B cells from 18 RA patients and 13 healthy donors were characterized using flow cytometry. Eleven patients who underwent a six-month adalimumab therapy were further assessed for phenotypic changes on their B cells. RESULTS: RA patients exhibited a high percentage of naïve and memory B cells expressing CD86. In contrast, expression of FcgammaRIIb was significantly reduced on RA memory B cells and plasmablasts as compared to healthy donors, probably due to downregulation of this receptor when differentiating from naïve to memory cells. These alterations on FcgammaRIIb were associated with high levels of anti-citrullinated vimentin autoantibodies. In addition, treatment with adalimumab normalized the expression of CD86 on memory B cells and reduced the expression of FcgammaRIIb, mainly on naïve B cells. CONCLUSIONS: Our findings show that peripheral B cells from RA patients have an altered expression of key molecules, such as CD86 and FcgammaRIIb. Because this latter receptor is required for feedback inhibition, a deficient expression might contribute to humoral autoimmune responses. Furthermore, these molecules are likely to be influenced by inflammatory factors, since they were modulated by TNF inhibition.

[Retrospective review of 44 Chilean patients with Behçet disease]. / Enfermedad de Behçet en Chile: Análisis clínico de 44 casos.

BACKGROUND: Behçet's disease (BD) is a rare multisystemic inflammatory disease that is potentially disabling and may cause death. AIM: To describe the characteristics of BD patients from two Chilean centers. PATIENTS AND METHOD: Retrospective review of the clinical records of patients with BD attended in two rheumatology services between 1985 and 2007. The "Behçet's Disease Research Committee of Japan" (BDCJ) and the "International Study Group for Behçet's Disease" (ISG) diagnostic criteria were applied. RESULTS: We found 44 cases (25 males), diagnosed as BD. The mean age at the onset of symptoms was 26+/- 12 years. According to BDCJ criteria, 13 patients had complete BD, 24 had incomplete BD and 7 had a suspected BD. Thirty two patients fulfilled the ISG criteria. Forty two patients (95%) had oral ulcers, 33 (75%) had genital ulcers and 29 (66%) had ophthalmological involvement. Eleven and three patients had symptoms of central and peripheral nervous system involvement, respectively. No gender differences were detected. CONCLUSIONS: The clinical characteristics of these patients were similar to those described abroad, except for a higher frequency of peripheral nervous system involvement and a lower rate of arthritis.

Enfermedad de Behçet en Chile: Análisis clínico de 44 casos / Retrospective review of 44: Chilean patients with Behçet disease

Background: Behget's disease (BD) is a rare multisystemic inflammatory disease that is potentially disabling and may cause death. Aim: To describe the characteristics of BD patients from two Chilean centers. Patients and method: Retrospective review of the clinical records of patients with BD attended in two rheumatology services between 1985 and 2007. The "Behget's Disease Research Committee of Japan" (BDCJ) and the "International Study Group for Behget's Disease" (ISG) diagnostic criteria were applied. Results: We found 44 cases (25 males), diagnosed as BD. The mean age at the onset of symptoms was 26± 12 years. According to BDCJ criteria, 13 patients had complete BD, 24 had incomplete BD and 7 had a suspected BD. Thirty two patients fulfilled the ISG criteria. Forty two patients (95 percent) had oral ulcers, 33 (75 percent) had genital ulcers and 29 (66 percent) had ophthalmological involvement. Eleven and three patients had symptoms of central and peripheral nervous system involvement, respectively. No gender differences were detected. Conclusions: The clinical characteristics of these patients were similar to those described abroad, except for a higher frequency of peripheral nervous system involvement and a lower rate of arthritis.

Infliximab can induce a prolonged clinical remission and a decrease in thyroid hormonal requirements in a patient with SAPHO syndrome and hypothyroidism.

SAPHO syndrome is a rare entity that compromises the skeletal system (arthritis-osteitis) and is associated with various dermatological conditions such as palmoplantaris pustulosis (PPP) and acne. We present the case of a 39-year-old man with invalidating arthritis derived from a SAPHO syndrome and hypothyroidism (after radioiodine treatment for a Graves' disease). Due to the severity and refractoriness of his disease, we decided to use infliximab. He showed a prompt and prolonged response of his joint and cutaneous manifestations after three doses of a tumor necrosis factor alpha (TNF-alpha) blocker. Interestingly, he also decreased his levothyroxine requirements after TNF-alpha blockade therapy.

[The influence of -238 and -308 TNF alpha polymorphisms on the pathogenesis and response to treatment in rheumatoid arthritis]. / Papel de los polimorfismos -238 y -308 del promotor del factor de necrosis tumoral alfa en la patogenia y respuesta al tratamiento anti-factor de necrosis tumoral alfa en artritis reumatoide.

Rheumatoid arthritis (RA) is a systemic autoimmune disease that affects 0.8% of the world population, it affects the synovial membrane of joints and the clinical presentation encompasses a wide spectrum, ranging from a mild to a severe and erosive disease that causes joint and cartilage destruction which finally provokes irreversible structural damage and patient disability. In the last years, there have been important advances in the pathogenesis of this disease, the efforts have been concentrated on pro-inflammatory cytokines such as tumor necrosis factor alpha (TNFalpha). This protein guides numerous events in the synovial and systemic inflammatory process and is encoded in the Major Histocompatibility Complex (MHC), one of the most polymorphic of the genome. Polymorphisms affecting the TNFalpha gene and its regulatory regions are associated with RA prevalence and course. There is a possible association between these polymorphisms and the clinical response to the use of monoclonal antibodies anti-TNFalpha. The possibility that the determination of genotypes -238 and -308 may have prognostic and therapeutic consequences is debated nowadays.

[Rituximab (anti-CD20 monoclonal antibody) for refractory systemic lupus erythematosus: report of one case]. / Uso del rituximab(anticuerpo monoclonal anti-CD20) en lupus eritematoso sistémico refractario a tratamiento: Caso clínico.

New therapeutic approaches that include depletion of B cells using rituximab, a chimeric monoclonal antibody directed against the B cell specific antigen CD-20 have been developed for the treatment of systemic lupus erythematosus (SLE). We report the case of a 18 years old girl with SLE that did not respond and experienced adverse effects with the use of hydroxycloroquine, methotrexate, mycophenolate mofetil, azathioprine and high-dose steroids. Rituximab was given weekly at 375 mg/m(2) for four doses. The drug was well tolerated and the patient had no adverse reactions. She remains asymptomatic three months later.

[Unwanted children after birth: frequency measurement and trends analysis]. / Hijo no deseado después del parto: medición de frecuencia y análisis de tendencia.

BACKGROUND: A significant proportion of pregnancies occurring in Metropolitan Santiago are unplanned and unwanted. It is reasonable to postulate that the frequency of unwanted children must be high. AIM: To measure the frequency of unwanted children in newborns of a public hospital of Santiago. MATERIAL AND METHODS: In a period of fourteen months a score assigning survey to detect unwanted children was applied, after birth, to 741 women delivering at San Juan de Dios Hospital in Metropolitan Santiago. Women whose newborns were hospitalized or had congenital malformations were excluded from the survey. RESULTS: Forty children (5.4%) scored as unwanted while 52 (7%) qualified as being in a doubtful situation. When compared to desired children, unwanted infants had a lower frequency of suitable pregnancy controls (p < 0.0002) and a higher incidence of mothers declaring bad relations with children's father (p < 0.0002). A trend towards higher frequency of single mothers (p: 0.044) was observed. A lower frequency of first born children (p: 0.017) and a higher frequency of children born in the fourth place, was observed among unwanted newborns (p < 0.002). CONCLUSIONS: In the last 15 years, previous studies, carried out with similar methodologies, have showed a comparable frequency of unwanted children. These condition seems to be associated with poor pregnancy control, high birth order and bad relations with the child's father.

Síndrome de Sweet: presentación de un caso / Sweet's syndrome: case review

Se presenta un caso clínico de síndrome de Sweet diagnosticado en una paciente de 31 años. El diagnóstico se estableció sobre las bases clínicas e histológicas. El tratamiento consistió en corticoides sistémicos, con buena respuesta. Se aprovecha para revisar parte de la bibliografía existente en relación con la etiopatogenia, clínica, asociación a otras enfermedades y tratamiento