Potential role of Anitschkow cells in cardiovascular disease in human and veterinary medicine: A review of the literature.

Anitschkow cells (AC) are a peculiar type of stromal cells observed in myocardium, cardiac valves and coronary vessels wall whose origin, characterization and role remain controversial. In human heart, they represent a histological hallmark of Aschoff nodules in rheumatic fever, but they have also been observed in other myocardial pathologies. Firstly, they have been considered a myocyte-derived cells, but light microscopy, immunohistochemical and ultrastructural studies pointed out that a macrophagic/histiocytic origin cannot be excluded. Many authors also reported extracardiac AC or an Anitschkow nuclear pattern, thus suggesting that these cells may represent a chromatin pattern rather than a specific cell type. In veterinary medicine, AC were described in myocarditis, myocardial necrosis, degenerative and inflammatory endocardial diseases of several species. Recently, AC have been observed in intramural coronary arteries of different animals (including cattle and fish) affected by arteriosclerotic processes. Stress related to the intensive livestock farming could represent a mechanotransduction promoting factor of arteriosclerotic changes allowing the development of Anitschkow chromatin pattern. Further studies both in human and veterinary medicine are needed to confirm the origin and role of these peculiar cells.

Brief Report: Association of Quantitative and Topographic Assessment of Heberden's Nodes With Knee Osteoarthritis: Data From the Osteoarthritis Initiative.

OBJECTIVE: To determine whether the presence, number, and topography (digit location and symmetry) of Heberden's nodes are associated with the incidence and progression of radiographic osteoarthritis (OA) of the knee. METHODS: We analyzed 8,023 knees (with 8 years of follow-up) from the Osteoarthritis Initiative. Cox regression was performed on Heberden's node presence, total number, location, and symmetry (using 2 symmetry index models) obtained at baseline physical examination as well as self-report of Heberden's node presence for evaluation of association with radiographic knee OA incidence (development of a Kellgren/Lawrence grade of ≥2) and progression (worsening in the medial joint space narrowing score of ≥1). Covariate adjustments relevant to OA outcomes were performed. RESULTS: The presence of Heberden's nodes (in 64% of the subjects) at baseline physical examinations, but not subjective self-report of Heberden's nodes, was associated with radiographic knee OA incidence (hazard ratio [HR] 1.19 and 95% confidence interval [95% CI] 1.001-1.402 [approached statistical significance]). Each additional Heberden's node found on physical examination was associated with knee OA incidence (HR 1.03 [95% CI 1.000-1.054] [approached statistical significance]) and progression (HR 1.04 [95% CI 1.016-1.063]). Knee OA incidence and progression were associated with Heberden's nodes located on the third digit (HR 1.26 [95% CI 1.068-1.487] and 1.18 [95% CI 1.019-1.361], respectively) and first digit (HR 1.186 [95% CI 0.992-1.418] [approached statistical significance] and HR 1.26 [95% CI 1.084-1.453], respectively). Heberden's node symmetry was associated with knee OA incidence (model 1 HR 1.09 [95% CI 0.997-1.185] [approached statistical significance]) and progression (model 2 HR 1.13 [95% CI 1.035-1.234]). CONCLUSION: The number of Heberden's nodes, their locations, and symmetry were associated with knee OA incidence and progression over 8 years.

Conjunctival nodule in rheumatoid arthritis.

Conjunctival nodule is very rarely seen in patients with rheumatoid arthritis. Previously reported cases were associated with the use of methotrexate. Here, we report a conjunctival rheumatoid nodule without such prior treatment. A 49-year-old woman with seropositive rheumatoid arthritis, who was being treated only with oral steroids and hydroxychloroquine, developed diffuse anterior scleritis in the right eye. In addition, examination showed a focal raised yellow/tan conjunctival nodule. The nodule was within the bulbar conjunctiva with no attachments to the underlying tissue, which is different from nodular scleritis. The nodule was not tender on palpation. The patient underwent excisional biopsy of the nodule. Intraoperatively, the lesion was noted to be a firm nodule within substantia propria of the conjunctiva. Hematoxylin-eosin staining of the specimen revealed a central area of necrosis surrounded by palisades of histiocytes. Increased dosage of oral steroid after the biopsy resulted in resolution of the ocular symptoms and signs. In conclusion, rheumatoid nodules may be seen in the conjunctiva even without prior treatment with methotrexate. These nodules may show the severity of the underlying disease and the need for more aggressive treatment.

Adhesion molecule expression and ventricular remodeling in chronic rheumatic heart disease: a cause or effect in the disease progression--a pilot study.

BACKGROUND: Rheumatic fever and chronic rheumatic heart disease (RHD) remains one of the most important causes of cardiovascular morbidity leading to a major public health problem, especially in developing countries. This was a pilot study to assess the presence of inflammation and expression of adhesion molecules by immunohistochemistry (IHC) in endomyocardial biopsy specimens of patients with chronic RHD. METHODS: Endomyocardial biopsy was obtained from 14 patients of chronic RHD with no features of activity clinically. Biopsies were processed for histology and IHC. IHC was carried using monoclonal antibodies against CD3, CD4, CD8, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1. RESULTS: Histomorphologically, varying degree of interstitial and perivascular fibrosis was seen in all the 13 patients (100%). Mild fibrosis (1+) was seen in five patients (38.5%); moderate interstitial fibrosis (2+) was present in four patients (30.8%).There was no Aschoff nodule or evidence of active myocarditis in any of the biopsy specimens. IMMUNOHISTOCHEMISTRY: Moderate positivity of (2+) and intense positivity of (3+) for intercellular adhesion molecule-1 was seen in 11 and 2 patients, respectively. With vascular cell adhesion molecule-1, four showed mild positivity (1+), and three showed intense positivity (3+). The phenotypic analysis of the inflammatory cells in our study revealed CD8(+) cells in 77%, CD4(+) in 23.1%, and CD3(+) in 38.5% of total patients, which suggests chronicity. CONCLUSION: The nonspecific histomorphological changes and increased adhesion molecules expression could be a part of the ventricular remodeling due to the hemodynamic stress by the stenotic or regurgitant lesions of RHD itself.

An animal model of chronic rheumatic valvulitis induced by formalin-killed streptococci.

Rheumatic heart disease is the most severe complication of rheumatic fever. Till date, very few successful animal models of rheumatic valvular disease have been reported. This study aimed at developing a suitable animal model of chronic rheumatic valvulitis for further investigation and prevention of rheumatic heart disease. Lewis rats were immunized with one administration of formalin-killed and sonicated group A streptococci together with Complete Freund's Adjuvant every 7 days for three cycles followed by group A streptococci alone till killing. Control rats were administered adjuvants and saline. Rats in group 1 were killed 12 weeks after the initial injection. Rats in group 2 and control group were killed 24 weeks after the initial injection. Results 62.5% (5/8) of rats in group 1 developed myocarditis and 50% (4/8) developed valvulitis. Histological examination of cardiac sections showed only cellular infiltrates. In contrast, 75% (6/8) of rats in group 2 developed rheumatic-like myocarditis and 62.5% (5/8) developed chronic valvulitis. Histological manifestations of the hearts in group 2 animals involved not only acute damage such as cellular infiltrates, Aschoff-like cells, verrucous vegetation, but also chronic lesions such as fibrosis, vascular neogenesis. None of the rats (0/8) in control group presented myocarditis or valvulitis. Lewis rat repeatedly immunized with formalin-killed GAS may be a suitable animal model of chronic rheumatic valvulitis. It may be useful for future investigation of the pathogenesis and possible preventive strategies of human rheumatic heart disease.

What is that nodule? A diagnostic approach to evaluating subcutaneous and cutaneous nodules.

The evaluation of patients with subcutaneous nodules remains a diagnostic challenge. The presence of nodules can be a clue to an underlying systemic disease; however, the varied presentations of nodules and numerous disease associations make the assessment of patients with nodules far from simple. With further investigation into the appearance, location, and symptoms associated with nodules, the clinical significance of these lesions can become clearer and aid in logical diagnostic evaluation. We have reviewed the causes of nodules with emphasis on those associated with rheumatic disease and provide guidelines for nodule evaluation to better characterize disease association and lead to directed diagnostic assessment.

Avaliação laríngea em pacientes reumatológicos / Laryngeal assessment in reumatic disease patients

As doenças reumáticas produzem alterações sistêmicas e podem, por isso, comprometer os vasos sangüíneos, as serosas e as mucosas de todo o trato aerodigestivo. Casos esporádicos de acometimento laríngeo por doenças reumáticas têm sido descritos. Esse estudo tem por objetivo avaliar e descrever as alterações laríngeas encontradas em pacientes reumatológicos. FORMA DE ESTUDO: coorte transversal. MATERIAL E MÉTODO: Estudo transversal com pacientes portadores de lúpus eritematoso sistêmico, esclerodermia e doença mista do tecido conjuntivo. Os pacientes submeteram-se a exame clínico otorrinolaringológico e à videolaringoestroboscopia. RESULTADOS: Foram incluídos no estudo 27 pacientes sendo que 26 conseguiram realizar a videolaringoestroboscopia. Alterações laríngeas foram observadas em 11 dos 12 pacientes portadores de lúpus, nos 11 pacientes portadores de esclerodermia e nos 3 pacientes portadores de doença mista do tecido conjuntivo. Lesões sugestivas de nódulo em bambu foram identificados em 5 pacientes e 92,3 por cento dos pacientes apresentaram sinais laríngeos de síndrome faringolaríngea do refluxo. CONCLUSÃO: Neste estudo identificamos 5 lesões sugestivas de nódulos em bambu e sinais laríngeos de refluxo em quase todos os pacientes.

Aspectos anatomopatológicos da febre reumática / Pathological aspects of the heart in rheumatic fever

A febre reumática é uma doença inflamatória, sistêmica e recorrente, que se manifesta cerca de uma a seis semanas após a infecção aguda da orofaringe por estreptococos beta-hemolíticos do grupo A. Presume-se que seja uma resposta imunológica a antígenos estreptocócicos ou uma reação auto-imune induzida pelos estreptococos, em indivíduos geneticamente suscetíveis. Acomete crianças de 5 a 15 anos, mas 20 por cento dos surtos iniciais ocorrem em indivíduos de meia idade ou idosos. No coração há comprometimento dos tecidos conjuntivos pericárdico, miocárdico e endocárdico. A pericardite é exuberante e predominantemente fibrinosa, com aspecto macroscópico de "pão com manteiga". A miocardite causa aumento cardíaco, principalmente por dilatação ventricular. No tecido conjuntivo cardíaco encontram-se nódulos de Aschoff, que retratam histologicamente as fases evolutivas da doença: exsudativa, proliferativa e cicatricial. O nódulo de Aschoff, na fase proliferativa, é patognomônico de atividade reumática, apresentando degeneração fibrinóide do colágeno e acúmulo de células inflamatórias, dentre elas as células de Anitsch-kow. Pequenas vegetações são encontradas nas linhas de fechamento valvar, mais comumente mitro-aórticas. Histologicamente são elevações da superfície valvar, decorrentes da deposição de fibrina e plaquetas ou da degeneração fibrinóide do colágeno local. O dano cardíaco é cumulativo, aumentando a cada episódio de atividade. As alterações reumáticas crônicas mais importantes resultam da cicatrização das lesões agudas valvares e podem ocorrer em todas as valvas. A estenose mitral é a seqüela reumática mais freqüente, seguida pela estenose mitro-aórtica e pela estenose aórtica isolada. Pode haver associação de estenose e insuficiência valvar, que é mais comum nas lesões aórticas.

Laryngeal assessment in rheumatic disease patients.

UNLABELLED: Rheumatic diseases usually promote several systemic disorders, which can affect blood vessels, mucosa and serosa of the aerodigestive tract. Scarce laryngeal involvement has been described in these patients and this study aims at investigating laryngeal alterations found in patients with rheumatic diseases. STUDY DESIGN: Transversal cohort. MATERIAL AND METHOD: A transversal study was developed with systemic lupus erythematous, systemic sclerosis and mixed connective tissue disease's patients. They were evaluated by means of clinical examinations and videolaryngoestroboscopy. RESULTS: Twenty-seven patients were included in the study, 26 succeeded in completing the videolaryngoestroboscopy. Laryngeal abnormalities were seen in 11 of 12 patients with lupus, in all 11 patients with sclerodermia and in 3 patients with mixed connective tissue disease. Vocal fold bamboo node was observed in 5 patients and 92.3% of all patients presented laryngeal signs of gastroesophageal reflux disease. CONCLUSION: We noticed 5 vocal fold bamboo nodes and gastroesophageal reflux disease in almost all patients.

Anitschkow myocytes or cardiac histiocytes in human hearts.

The caterpillar chromatin pattern of the nucleus in longitudinal section and owl-eye appearance in transverse section characterize the Anitschkow cell of Aschoff bodies in rheumatic heart disease. Determining whether it is of muscle origin or cardiac histiocyte has been a source of controversy for many years. In a study of fetal and neonatal hearts from humans, vesicular nuclei often displaying the Anitschkow chromatin pattern were the predominant cell type in the myocardium. Because a similar pattern was also observed in two cell types related to laryngeal cartilage and the neighbouring fibrous tissue in a six week old neonate, it was concluded that the Anitschkow chromatin pattern probably indicates cellular immaturity rather than any specific cell type.

Rheumatic Aschoff nodules revisited. II: Cytokine expression corroborates recently proposed sequential stages.

AIMS: A recent immunohistochemical analysis of the Aschoff lesions in rheumatic fever, combining immunohistochemical analysis with comparative morphology, permitted the division of the Aschoff nodules into three stages: (1) Aschoff nodule without admixed lymphocytes, (2) Aschoff nodules with a few T lymphocytes, and (3) Aschoff nodules containing many admixed lymphocytes of both B- and T-cell phenotype. It was postulated that the order of progression was from stage 1 with macrophages only, to accumulation of first T lymphocytes (stage 2) and then B lymphocytes (stage 3). This study was undertaken to determine the role and distribution of interleukin 1 (IL-1), interleukin 2 (IL-2) and tumour necrosis factor alpha (TNF alpha) in the various stages of the rheumatic Aschoff nodule to investigate our hypothesis on the progression of these nodules. METHODS AND RESULTS: Sixteen fresh valve specimens from patients with acute rheumatic fever undergoing valve surgery were obtained. Tissue sections from 14 specimens identified as containing Aschoff nodules were subjected to immunohistochemistry for (1) T and B lymphocytes, to stage the lesions according to our previously proposed criteria; (2) IL-1, IL-2 and TNF alpha; and (3) CD4 and CD8 to phenotype the T lymphocytes. The stage 1 and 2 lesions expressed IL-1 and TNF alpha in the macrophages. The stage 3 lesions showed more variable expression of all three cytokines including IL-2 within T lymphocytes. CONCLUSION: TNF alpha and IL-1 secretion in macrophages is required for T and B lymphocytes activation and aggregation; suggesting that macrophages arrive at the scene of rheumatic injury prior to the lymphocytes. IL-2 is usually expressed later in the inflammatory process and was found only in the lymphoid aggregates. This study therefore produces corroborative evidence for our previously proposed developmental stages of the Aschoff nodule.

[Rheumatic heart disease and infective endocarditis in a patient with acquired immunodeficiency syndrome]. / Cardiopatia reumática e endocardite infecciosa em paciente com síndrome de imunodeficiência adquirida.

A 36-old-woman was admitted with an infectious syndrome, respiratory insufficiency and vasculitis. There was a history of chronic intravenous drug abuse, sexual promiscuity and rheumatic heart disease. She had HIV positive tests. The vasculitis and heart failure worsened and the patient died of stroke. At autopsy it was found histologic evidence of AIDS, rheumatic heart disease with Aschoff nodes, infective endocarditis with cerebral abscesses and thalamic infarction.