Alex Magno Coelho Horimoto

[Overlap between systemic sclerosis and rheumatoid arthritis: a distinct clinical entity?]

INTRODUCTION Systemic sclerosis (SSc) is an autoimmune disease of the connective tissue characterized by the triad of vascular injury, autoimmunity (cellular and humoral) and tissue fibrosis. It is estimated that musculoskeletal pain is a common complaint of patients with SSc, ranging from 40 to 80%, and mainly in patients with early diffuse disease. Arthritis, clinically observed, may be a feature seen in the presentation of SSc, often leading to early diagnostic errors with rheumatoid arthritis (RA). In the course of the disease, arthritis is observed in 24-97% of patients with SSc. OBJECTIVES To correlate the occurrence or nonoccurrence of arthritis in patients with SSc of the Midwest region of Brazil with possible distinct clinical and laboratory manifestations observed in three groups of patients. To report the frequency of true association between systemic sclerosis and rheumatoid arthritis in patients with clinically and radiologically observed synovitis. METHODS Sixty-one SSc patients were subsequently assessed every 3 months within 1 year, in order to clinically observe the occurrence of synovitis and its patterns of progression. Patients were divided into 3 groups: 41 patients with SSc without arthritis, 16 SSc patients with arthritis and 4 patients with overlap of SSc and RA. All patients underwent a radiological examination of the hands at the end of the study. RESULTS Among all patients evaluated, we found a female predominance (98.7%), mean age of 50.94 years, white color (49.2%), limited form of the disease (47.6%), time of diagnosis between 5 and 10 years (47.6%) and duration of the disease of 8.30 years. Among all patients, 14 (22.9%) had positive rheumatoid factor (RF), while among those with positive RF, only 10 patients had arthritis during one-year follow-up. The antibody anticitrulline (anti-CCP) test was performed in 24 patients, being positive in 4 of them (16.7%), with positivity being observed only in patients with SSc/RA overlap. Comparing the clinical manifestations among the groups of patients, there was a higher incidence of gastritis and cardiac valvulopathy in patients with SSc and arthritis, but not in the others. In the group of patients with SSc/RA overlap and in patients with SSc and arthritis a significant reduction in quality of life was observed, measured by HAQ index, especially in patients with arthritis present during clinical evaluation. We found radiographic changes in 42.6% of patients with SSc. However, in patients with synovitis, radiological changes consistent with rheumatoid arthritis were found in 50% of patients. CONCLUSIONS While the frequency of clinical arthritis observed in patients with systemic sclerosis was 32.8%, the true overlap between of SSc and RA was 6.6% in this study. We also observed the frequency of positive anti-CCP in 20% of patients with arthritis versus no patients with SSc without arthritis.

Anti-Collagen Type V Antibody in Systemic Sclerosis: A Possible Useful Tool to Asses Disease Activity

Introduction: Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular injury, autoimmunity and tissue fibrosis. Usually collagen type V (V Col) is found hidden between the heterotypical fibers. It was discovered in the rheumatology department at the University of Sao Paulo (FMUSP) that deposition of this collagen occurs, however with anomalous morphology in SSc patient’s tissue, suggesting that V Col is an important molecule in fibrosis and autoimmunity process. The V Col molecule, which has atypical morphology aspect, exposed after a nonspecific inflammatory damage could result in formation of immune complexes (V Col - anti-V Col), whose deposition on the vascular endothelium, would cause a vascular damage, allowing the influx of cells of innate immunity into the extracellular matrix, resulting in an enzymatic degradation of the heterotypical fibers, with exposure of more V Col and perpetuation of the disease. Objectives: Assess whether there is a correlation between anti-V Cols presence in the serum of patients with SSc and indexes of activity, severity and quality of life measured by sHAQ. Methods: Were evaluated 60 patients with SSc diagnostic during the period of January to December 2014. Were applied Medsger severity criteria, Valentini activity criteria and health assessment questionnaire in SSc (sHAQ) in the patients, at initial assessment (baseline) and after 6 months, correlating the presence of anti-V Col with the clinical and laboratory manifestations found. Results: Most patients were female (98.3%) and had the limited form of the disease (43.3%), average age 51 years, white, average duration of nine years of disease and modified Rodnan Skin Score of 13.08. The main clinical manifestations observed in each organic system of patients were: skin thickening in the hands (78.3%), Raynauds phenomenon (100%), arthritis (33.3%), esophageal involvement (71.7%), interstitial lung disease (45%), pulmonary arterial hypertension (PAH) (19.4%) and scleroderma renal crisis (SRC) (1.7%). The most significant laboratory abnormalities were elevation of inflammatory markers in 41.7% of patients (ESR and CRP), CPK elevation (15%), low complement (C3 and C4) (3.3%), antinuclear antibody (95%), anti-centromere (41.7%), anti-DNA topoisomerase I antibody (26.7%), anti-RNA polymerase III (11.7%), anti-U1-RNP (16.7%) and anti-Ro (SSA) in 11.7% of patients. The anti-V Col was detected in 5 cases (8.3%) and showed statistical correlation with disease activity and scleroderma renal crisis, besides tendency to association with PAH; however, did not correlate with the severity index of disease or any other clinical manifestation, or with specific SSc antibodies. Conclusions: We suggest that disease activity in SSc patients could be determined by serological analysis, to detect the presence of V Col antibodies in the serum of patients with SSc, facilitating the approach of this serious disease. We suggest further studies with larger number of patients in order to confirm the usefulness of this new marker of disease activity in systemic sclerosis.

Frequency of autoantibodies and serum complement levels in patients with visceral or cutaneous leishmaniasis

INTRODUCAO: A leishmaniose e uma doenca infecciosa cronica que pode variar de um espectro que inclui o acometimento cutâneo isolado com manifestacao oligossintomatica ate o acometimento sistemico com manifestacoes clinicas importantes. O desenvolvimento de infeccao em cada tipo de leishmaniose (visceral ou tegumentar) depende da interacao complexa e intrigante entre os fatores de virulencia do patogeno e a resposta imunologica do hospedeiro. Analises de soros de pacientes infectados por Leishmania demonstraram a existencia de autoanticorpos contra componentes celulares e humorais, alem de imunocomplexos circulantes e anticorpos contra a imunoglobulina G (fator reumatoide). Pacientes com leishmaniose visceral podem apresentar sintomas que mimetizam o quadro clinico encontrado em pacientes com diagnostico de Lupus Eritematoso Sistemico (LES), dificultando o diagnostico precoce e tratamento. OBJETIVOS: Identificar o perfil de autoanticorpos e a dosagem de complemento em pacientes com diagnostico de leishmaniose visceral ou tegumentar e correlacionar o quadro clinico destes pacientes com o de pacientes com diagnostico de LES. METODOS: Pesquisou-se a ocorrencia de autoanticorpos e dosagem de complemento no soro de 90 pacientes, sendo 45 deles com leishmaniose visceral e 45 com a forma tegumentar. RESULTADOS: Os autoanticorpos estatisticamente significativos presentes nos pacientes com leishmaniose visceral foram: Fator Antinuclear (FAN) positivo (4,4%) ou em baixa titulacao (8,9%) e anticorpo anticardiolipina do tipo IgG positivo (17,8%) ou indeterminado (8,9%). Encontrou-se, ainda, diminuicao do complemento serico C3 em 17,8% dos pacientes e anticorpo anti-Leishmania positivo > 1/80 em todos os pacientes com leishmaniose visceral. CONCLUSOES: A forma visceral da leishmaniose pode correlacionar-se positivamente com a presenca de autoanticorpos, possivelmente pelo desencadeamento de uma resposta sistemica predominantemente humoral do tipo Th2, constituindo-se em diagnostico diferencial obrigatorio com LES, principalmente nas areas endemicas.

Autoanticorpos em esclerose sistêmica e sua correlação com as manifestações clínicas da doença em pacientes do Centro-Oeste do Brasil

INTRODUCTION Systemic sclerosis (SSc) is a connective tissue disease of autoimmune nature characterized by the triad of vascular injury, autoimmunity (cellular and humoral) and tissue fibrosis. Autoantibodies do not seem to be simply epiphenomena, but are involved in disease pathogenesis. It is believed that the SSc-specific autoantibodies are responsible both for amplifying immune response and targeting cell types that are relevant in the pathophysiology of SSc. OBJECTIVES To correlate the profile of the following specific autoantibodies: anti-centromere (ACA), anti-topoisomerase I (topo I) and anti-RNA polymerase III (RNAP III) with clinical and laboratory manifestations observed in 46 patients with SSc in the Midwest region of Brazil. METHODS The occurrence of specific autoantibodies in 46 patients with SSc was investigated, correlating the type of autoantibody with clinical and laboratory manifestations found. RESULTS Among all patients evaluated, we found a predominance of females (97.8%), mean age 50.21 years old, Caucasian (50%), limited cutaneous SSc (47.8%), time of diagnosis between 5-10 years (50%), and disease duration of 9.38 years. According to the specific autoantibody profile, 24 patients were ACA-positive (52.2%), 15 were positive for anti-topo I (32.6%), and 7 showed positive anti-RNAP III (15.2%). The anti-topo I autoantibody correlated with diffuse scleroderma, with greater disease severity and activity, with worse quality of life measured by the SHAQ index, with a higher prevalence of objective Raynauds phenomenon and digital pitting scars of fingertips. The ACA correlated with limited scleroderma, with earlier onset of disease, as well as higher prevalence of telangiectasias. The anti- RNAP III correlated with diffuse scleroderma, with a higher occurrence of subjective Raynauds phenomenon and muscle atrophy. There was no association between the positivity for anti-topo I, ACA and anti-RNAP III antibodies and other variables related to laboratory abnormalities, as well as Rodnan skin score and skin, vascular, musculoskeletal, gastrointestinal, cardiopulmonary and renal manifestations. CONCLUSIONS The clinical subtype of the disease and some clinical manifestations in SSc may correlate positively with the presence of specific autoantibodies.

Sjogrens Syndrome and Sicca Symptoms in Patients with Systemic Sclerosis

Introduction: Several autoimmune diseases can be accompanied by dysfunction of the salivary glands, regardless of the presence or absence of association with Sjogrens syndrome (SS). A recent study by Maeshima and colleagues found salivary hyposecretion in 58.3% of patients with various connective tissue diseases, particularly systemic sclerosis (SSc). Objective: To determine the prevalence of SS and sicca symptoms in patients with SSc. Assess whether the presence of SS in patients with SSc causes worsening of the disease. Methods: 69 SSc patients periodically monitored in the rheumatology clinic at NHU / UFMS composed the study. All patients were questioned about sicca symptoms and clinical features. We evaluated the RF levels, ANA, anti-Ro / La. Results and Discussion: 69 SSc patients were enrolled in the study, with average age of 51.2 years, women at 98.3% and white by 50%. Sicca symptoms were present in 48 patients (69,5%) with SSc; 43/69 patients (62,3%) with dry mouth and 46/69 patients (66,7%) with dry eye. Sicca symptoms observed predominantly in patients with diffuse disease (75%). The antinuclear antibody positivity was 95% and the rheumatoid factor (RF) was observed in 14 patients (23.3%). Anti-Ro (SSA) were detected in 11 patients (15,9%) antibodies and anti-La (SSB) in 6 patients (8,7%) in this study. Only 16 patients (23.2%) had true SS, according to the American-European Consensus Group on Classification Criteria for Sjogrens syndrome. The findings in the study corroborate data found in literature. Koback and colleagues found similar data, 68% of patients with the limited form presented sicca symptoms, RF was present in 19.2% and anti-Ro in 10.3%. Hyposecretion salivary study in patients without SS found significant differences between groups, being much higher in the SSc group compared to patients with SLE, RA, MCTD and myopathies. Conclusion: This study confirms that sicca symptoms are found in large numbers of patients with SSc. SS prevalence was observed in 23.2% of the SSc patients, mainly in patients of diffuse form of the disease. We conclude that the presence of SS did not change positively or negatively the severity or the clinical manifestations observed in patients with SSc.

Associação entre poliarterite nodosa e síndrome antifosfolípide: relato de caso e revisão de literatura

We describe here the case of a 37 years old man with polyarteritis nodosa (PAN) associated to antiphospholipid syndrome (APS), that developed intense endothelial dysfunction, several aneurisms and arterial occlusions, including pseudo-aneurism of the gastric-duodenal artery. We performed a literature review this rare association between PAN and APS.

Reumatismo pós-quimioterapia: uma disfunção da tolerância imunológica?

Post-chemotherapy rheumatism is a rare syndrome characterised by polyarthralgia that develops following a period of 1 to 4 months of various forms of chemotherapy for cancer treatment. There is very little representation of post-chemotherapy rheumatism (PCR) in literature. Here we report the case of a 21 years old girl with Hodgkin lymphoma who was not treated with cyclophosphamide, the drug considered as an etiological factor in PCR. Rather, we suggest the possibility of a transitory dysfunction in immunological tolerance mechanisms.