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To report three cases of bullous pemphigoid in patients treated with vildagliptin. Case 1: An 86-year-old woman presented with bullous pemphigoid after 1 month of treatment with vildagliptin and metformin. After introduction of clobetasol, the symptoms resolved although vildagliptin was continued. However, the skin lesions reappeared 3 months later. Sustained remission was achieved only after definitive withdrawal of vildagliptin. Case 2: A 79-year-old man presented with bullous pemphigoid after 37-month treatment with gliclazide, vildagliptin and metformin. The disease at first responded to clobetasol but 3 months later the lesions reappeared. They finally regressed when the gliptin was discontinued. Case 3: A 77-year-old woman, treated with gliclazide and vildagliptin for 26 months, presented with bullous pemphigoid, which responded well to discontinuation of the gliptin and topical clobetasol. Gliptins are new molecules for treatment of type 2 diabetes mellitus, which have been suspected of implication in bullous pemphigoid. Such cases have been described in the literature (seven with vildagliptin and three with sitagliptin). In nine of these cases, the gliptin was associated with metformin, but the latter had never been considered responsible. The mechanism implicated in the development of bullous pemphigoid has not yet been clearly identified, but may involve a modified immune response or alteration of the antigenic properties of the epidermal basement membrane. These reports support the risk of bullous pemphigoid in patients exposed to gliptins., (© 2014 Société Française de Pharmacologie et de Thérapeutique.)

Background: Specific cutaneous infiltrates of chronic lymphocytic leukaemia (CLL) are rare. They occur after a mean disease duration of 3 years. CLL skin infiltrates as the primary manifestation of the disease have been reported, but a normal lymphocyte count at diagnosis is rare. We present two cases of CLL initially presenting in the skin, without lymphocytosis., Patients and Methods: A 53-year-old man developed papulonodular lesions of the face and infiltrated plaques of the scalp, and an 85-year-old woman presented erythematous nodules of the face and neck. Histopathology revealed a lymphocytic infiltrate, consisting of small mature B-cells CD20+, CD79+, with an aberrant phenotype CD5+. CD23 was positive in one case. The two patients had no lymphocytosis, but immunophenotyping was characteristic of CLL. In the second case, there was a sub-mental adenopathy, histologic analysis of which was consistent with CLL. The CLL was classified as Binet stage A in the two cases. No disease progression was noted at follow-up., Discussion: The unusual feature of these cases is the lack of lymphocytosis at diagnosis. Thus, the skin lesions resulted in further evaluations for CLL, although the diagnosis was not suggested by the blood count., Conclusion: Skin involvement in CLL does not appear to be a poor prognostic indicator, arguing in favour of recruitment of circulating monoclonal B-cells rather than an additional tumour mass., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

The reaction catalyzed by IMP dehydrogenase (IMP: NAD+ oxidoreductase EC 1.2.1.14) from Aerobacter aerogenes has been investigated kinetically at pH 8.1 as a three reactant system by means of steady-state velocity studies in the absence of products, as well as by inhibition studies using products and substrate analogues. The mechanism appears to be a partially random one in which IMP and K+ can bind randomly to the free enzyme while NAD does not react unless K+ or both K+ and IMP are present on the enzyme. While the steady-state velocity data can be analysed adequately on the basis that rapid equilibrium conditions apply, this is only an approximate description of the mechanism since product inhibition studies indicate that there is a significant concentration of an enzyme-XMP (enzyme-K-XMP) complex in the steady-state.