The inflammatory process is controlled by the glucocorticoids’ activity, enhancing the transcription of anti-inflammatory genes and decreasing the transcription of inflammatory genes (Figure 3 ) [ 15 ].
Glucocorticoids induce the expression of annexin A1 (also known as lipocortin 1; encoded by ANXA 1) and ALXR (the annexin A1 receptor) by mechanisms still not known. Annexin A1 is a protein mainly located on basal keratinocytes of the basement membrane. Although in normal skin annexin A1 has been identified within cytoplasm, in diseased skin the intracellular localization of annexin A1 is apparently modified. In lesional psoriatic skin, annexin A1 appears only in the cell membrane, suggesting a translocation of the protein. This transition may occur to promote the binding of annexin A1 to phospholipids, therefore reducing the production of inflammatory prostanoids [ 37 ].
Annexin A1 inhibits phospholipase A 2 (PLA 2 ), thus blocking the synthesis of arachidonate-derived eicosanoids (prostaglandins, prostacyclins, leukotrienes, and thromboxanes) [ 32 ]. This blocking is furthered by the repression of glucocorticoid-mediated cyclooxygenase 2 transcription [ 38 – 41 ]. It remains unclear if the reduction of these substances levels come first and then plaque resolution, or if the normalization of prostanoid levels follows plaque clearance [ 37 ].
Exogenous and endogenous annexin A1 may regulate the innate immune cells activities controlling its levels of activation. Annexin A1 signals throw a formyl peptide receptor 2 (FPR2, ALXR in humans). Despite the activation of ALXR singnalling can occur by the annexin A1 autocrine, paracrine, and juxtacrine functions, the juxtacrine interaction seems to be the mechanism by which the anti-inflammatory process occurs. Concerning the innate response, it seems that the upregulation of the annexin A1 expression by leukocytes induced by glucocorticoids may be responsible for the inhibition of leukocytes response. Glucocorticoids also increase the secretion of annexin A1 by macrophages and the annexin A1 secreted by mast cells and monocytes, promotes the clearance of apoptotic neutrophils by macrophages. Endogenous annexin A1 is also released from apoptotic neutrophils and acts on macrophages promoting phagocytosis and removal of the apoptotic cells. The ALXR may be one mediator of this mechanism. Contrasting with the innate immunity, the adaptive immune system seems to act in a different way. Activation of T cells results in the release of annexin A1 and in the expression of ALXR. Although, glicocorticoids may reduce the annexin A1 expression within T-cell exposure as a consequence, there is an inhibition of T-cell activation and T cells differentiate into T helper 2 [ 42 , 43 ].
An example of an acute hepatitis-like syndrome arising after pulse methylprednisolone therapy. These episodes arise typically 2 to 4 weeks after a third or fourth cycle of pulse therapy, and range in severity from an asymptomatic and transient rise in serum aminotransferase levels to an acute hepatitis and even fulminant hepatic failure. In this instance, the marked and persistent rise in serum enzymes coupled with liver histology suggesting chronic hepatitis led to a diagnosis of new-onset autoimmune hepatitis, despite the absence of serum autoantibodies or hypergammaglobulinemia. Autoimmune hepatitis may initially present in this fashion, without the typical pattern of serum autoantibodies during the early, anicteric phase. The diagnosis was further supported by the prompt improvements in serum enzymes with prednisone therapy. The acute hepatitis-like syndrome that can occur after pulses of methylprednisolone is best explained as a triggering of an underlying chronic autoimmune hepatitis caused by the sudden and profound immunosuppression followed by rapid withdrawal. This syndrome can be severe, and fatal instances have been reported. Whether reinitiation of corticosteroid therapy with gradual tapering and withdrawal is effective in ameliorating the course of illness is unclear, but anecdotal reports such as this one suggest that they are beneficial and should be initiated promptly on appearance of this syndrome. Long term follow up of such cases is also necessary to document that the autoimmune hepatitis does not relapse once corticosteroids are withdrawn again.
The growth of children and adolescents receiving orally inhaled corticosteroids, including QVAR, should be monitored routinely (., via stadiometry). If a child or adolescent on any corticosteroid appears to have growth suppression, the possibility that he/she is particularly sensitive to this effect should be considered. The potential growth effects of prolonged treatment should be weighed against clinical benefits obtained and the risks associated with alternative therapies. To minimize the systemic effects of orally inhaled corticosteroids, including QVAR, each patient should be titrated to his/her lowest effective dose [see Dosage and Administration ( )] .
Betamethasone dipropionate was patented by Merck in 1987 as an augmented cream/lotion, Diprolene in the ., and Disprosone in Europe.  These patents expired in 2003 and 2007 respectively leading to generic production of betamethasone dipropionate. During this time other topical corticosteroids such as triamcinolone acetonide and clobetasol propionate also became available as generic creams. Merck filed for "pediatric exclusivity" in 2001 launching a clinical trial to prove betamethasone dipropionate's safety and efficacy for use in pediatrics. 
Betamethasone dipropionate was patented by Merck in 1987 as an augmented cream/lotion, Diprolene in the ., and Disprosone in Europe.  These patents expired in 2003 and 2007 respectively leading to generic production of betamethasone dipropionate. During this time other topical corticosteroids such as triamcinolone acetonide and clobetasol propionate also became available as generic creams. Merck filed for "pediatric exclusivity" in 2001 launching a clinical trial to prove betamethasone dipropionate's safety and efficacy for use in pediatrics.