Autoinflammatory diseases in childhood,part 1: monogenic syndromes

Autoinflammatory diseases constitute a family of disorders defined by aberrant stimulation of inflammatory pathways without involving antigen-directed autoimmunity. They may be divided into monogenic and polygenic types. Monogenic autoinflammatory syndromes are those with identified genetic mutations, such as familial Mediterranean fever, tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS), mevalonate kinase deficiency or hyperimmunoglobulin D syndrome, cryopyrin-associated periodic fever syndromes (CAPS), pyogenic arthritis pyoderma gangrenosum and acne (PAPA) syndrome, interleukin-10 and interleukin-10 receptor deficiencies, adenosine deaminase 2 deficiency and pediatric sarcoidosis. Those without an identified genetic mutation are known as polygenic and include systemic-onset juvenile idiopathic arthritis, idiopathic recurrent acute pericarditis, Behçet syndrome, chronic recurrent multifocal osteomyelitis and inflammatory bowel disease among others. Autoinflammatory disorders are defined by repeating episodes or persistent fever, rash, serositis, lymphadenopathy, arthritis and increased acute phase reactants, and thus may mimic infections clinically. Most monogenic autoinflammatory syndromes present in childhood. However, because of their infrequency, diverse and nonspecific presentation, and the relatively new genetic recognition, diagnosis is usually delayed. In this article, which is Part 1 of a two-part series, the authors update monogenic autoinflammatory diseases in children with special emphasis on imaging features that may help establish the correct diagnosis.

     

Quantitative cytochemistry of lysosomal structures in rat incisor maturation enamel organ

Trimetaphosphatase was used as a lysosomal marker in the ruffle-ended maturation ameloblasts and associated papillary cells. Morphometric analysis was carried out of the percentage area of these cells (density) occupied by the various enzyme-reactive lysosomal structures. The density of total TMPase-positive lysosomal structures, tubular lysosomes and multivesicular bodies in ruffle-ended ameloblasts were all significantly greater (p less than or equal to 0.05) in early than in late maturation enamel formation. In papillary cells the same was true of tubular lysosomes, whereas the greater density of enzyme-positive total structures in early maturation was not statistically significant when compared to late maturation. These findings demonstrate a corresponding pattern between enamel-organ lysosomal activity and the period of early enamel maturation when most enamel protein is lost. They support the likely involvement by ruffle-ended ameloblasts and papillary cells in absorption and degradation of exogenous enamel proteins.     

Immunohistochemical localization of alphavbeta3 integrin receptor during experimental tooth movement.

During orthodontic treatment, multinucleated clast cells carry out the resorption of mineralized tissues. Adhesion of clast cells to the mineralized tissues is mediated by transmembrane cell-surface glycoproteins called integrins, specifically by the alphavbeta3 integrin, which plays an important role in the process of bone resorption. The role of the alphavbeta3 integrin in bone resorption leading to osteoporosis has been demonstrated, but its role in alveolar bone and root resorption during orthodontic tooth movement is unknown. This study examined the expression of the alphavbeta3 integrin during experimental tooth movement. Tooth movement was achieved in 16 male Sprague-Dawley rats (each weighing 120-200 g) with elastic bands between their maxillary first and second molars. The molar-bearing segments were dissected and processed for histologic and immunohistochemical examination. The expression of alphavbeta3 integrin was examined with 2 primary antibodies: a polyclonal anti-alphav integrin subunit antibody and a polyclonal anti-beta3 integrin subunit antibody. Negative controls were similarly processed but without incubation with primary antibodies. The alphavbeta3 integrin was expressed both by osteoclasts associated with alveolar bone resorption and by odontoclasts associated with root resorption during experimental tooth movement. Furthermore, the beta3 integrin subunit was expressed by the epithelial rests of Malassez in the periodontal ligament. Negative controls did not show immunolabeling. The alphavbeta3 integrin adhesion receptor is expressed during experimental tooth movement and might be involved in the process of mineralized tissue resorption and the functions of the epithelial rests of Malassez.     

A comparison of the sealing properties of different retrograde techniques: an autoradiographic study

Single-rooted teeth were instrumented and filled in vitro with a lateral condensation of gutta-percha with sealer. Following obturation, the tooth apices were treated by various retrograde procedures. The teeth were then coated with ethyl acetate, immersed in 45Ca solution, washed, and sectioned, and autoradiographs were used to compare the leakage of the various techniques. Statistical analysis indicated that lateral condensation produced a significantly better seal than any retrograde technique tested except retrofilling with Super EBA cement and that a significantly worse seal was obtained with amalgam retrofill when compared to all retrograde techniques except cold-burnished gutta-percha following apicoectomy. No significant difference existed between other group combinations.     

Scanning and transmission electron microscopy of tubular structures presumed to be human odontoblast processes

Tubular structures interpreted as being odontoblast processes can be observed with the scanning electron microscope (SEM) on fractured dentin surfaces which have been demineralized and treated with collagenase. To confirm the nature of these structures, SEM preparations exhibiting similar tubular structures were subsequently examined with the transmission electron microscope (TEM). Newly-erupted human third molars were fractured buccolingually with heavy-gauge industrial nippers or sectioned mesiodistally with a Leitz saw microtome and fixed in glutaraldehyde. The exposed dentin surfaces were decalcified to a depth of approximately 500 microns and then treated with bacterial collagenase. Half of the specimens were critical-point-dried and coated for SEM. The other half were post-fixed and processed for TEM. After examination by SEM, the specimens were embedded and thin-sectioned for TEM. SEM observations of both the fractured and cut surfaces of dentin showed tubular structures running from the surface of the pulp to the dentino-enamel junction. When the SEM preparations were examined with TEM, the tubular structures were seen to be the inner sheath of the peritubular matrix, not odontoblast processes. In the specimens directly processed for TEM, the structures lying inside the sheath could be visualized clearly. In the outer two-thirds of the dentin, the tubules were essentially empty. Well-defined odontoblast processes were seen lying inside the sheath only in the inner dentin.