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Inducible nitric oxide synthase (iNOS) is required in immune response against infections and is involved in granuloma formation in animals; in murine macrophages , iNOS is induced by lipopolysaccharide and interferon-␥.In contrast , the role of iNOS in human immune response against infections is still questioned , and its expression in granulomas is poorly investigated. Using Western blotting and immunohistochemistry , we investigated iNOS expression in human lymph nodes with nonspecific reactions and in tissues containing granulomas caused by mycobacteria , Toxoplasma , Cryptococcus neoformans , Leishmania , Bartonella , noninfectious granulomas (sarcoidosis , foreign body) , and other hystiocitic reactions (Kikuchi's disease , Omenn syndrome). iNOS was undetectable in nonspecific reactive lymphadenitis , foreign-body granulomas , and Omenn syndrome , whereas it was strongly expressed in infectious granulomas , sarcoidosis , and Kikuchi's diseases. Immunohistochemistry demonstrated that iNOS was selectively expressed by the epithelioid and multinucleated giant cells within the granulomas. Use of an antinitrotyrosine antibody , recognizing nitrosilated amino acid residues derived from nitric oxide production , revealed a consistent positivity within the cells expressing iNOS , thus suggesting that iNOS is functionally active. Detection of cytokines by reverse transcriptase-polymerase chain reaction demonstrated that tissues that were positive for iNOS , also expressed the Th1-type cytokine interferon-␥ mRNA , but not the Th2-type cytokine interleukin-4. 1 At least three distinct isoforms of NOS, encoded by separate genes, are expressed in mammalian cells. Two of them are constitutively expressed in brain neurons (NOS1 or nNOS) or in endothelial cells (NOS3 or eNOS).2,3 The third isoform, termed inducible NOS (iNOS or NOS2) is expressed only on stimulation in macrophages and hepatocytes. In vitro, expression of the enzyme is associated with NO production and thereby extracellular release of NO metabolites (eg, nitrites, nitrates, peroxynitrites).4,5 NO release results into tyrosine residues nitrosation, and nitrotyrosine detection has been used as an indicator of iNOS expression and NO function. 6 -9

The aim of this guidance is to provide recommendations to clinicians and other interested parties on chronic urticaria in children. The Italian Society for Pediatrics (SIP), the Italian Society for Allergy and Immunology (SIAIP), the Italian Society for Pediatric dermatology (SIDerP) convened a multidisciplinary panel that prepared clinical guidelines for diagnosis and management of chronic urticaria in childhood. Key questions on epidemiology, natural history, diagnosis, and management were developed. The literature was systematically searched and evaluated, recommendations were rated and algorithms for diagnosis and treatment were developed. The recommendations focus on identification of diseases and comorbidities, strategies to recognize triggering factors, improvement of treatment by individualized care.