ABSTRACT
OBJECTIVE: Erythema dyschromicum perstans (EDP) can be difficult to diagnose and treat; therefore, we reviewed the literature to assess whether histology can be used to differentiate lichen planus pigmentosus (LPP) from EDP and determine which treatments are the most effective for EDP. We also present a case of a patient who was treated successfully with narrow-band ultraviolet B (NB-UVB). METHODS: A systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was conducted up to July 2017 using four databases. RESULTS: Histologic analyses from the literature reveal a significant percentage of melanophages, lymphocytic infiltrates, and basal vacuolar degeneration in EDP, and a significant histologic overlap with LPP. The review of the literature on treatment outcomes showed that NB-UVB and tacrolimus were effective with minimal side effects. Clofazimine was effective, but demonstrated significant-to-intolerable side effects. Griseofulvin, isotretinoin, and dapsone provided unsatisfactory results as lesions recurred after discontinuation. Lasers were largely ineffective and may cause postinflammatory hyperpigmentation and fibrosis. CONCLUSION: A diagnosis of EDP should not be based on histologic findings alone. Clinical history, morphology, and distribution should be used to differentiate EDP and LPP. NB-UVB and tacrolimus are promising treatments for EDP with minimal side effects. This is the first report to our knowledge of sustained resolution of EDP after treatment with NB-UVB at long-term follow-up of 4 years. Larger studies are needed to confirm these findings.
ABSTRACT
BACKGROUND: Factor (F)Xa has 11 gamma-carboxylated glutamic acid (Gla) residues that are involved in calcium-dependent membrane binding. The serpin antithrombin (AT) is an important physiological regulator of FXa activity in an inhibition reaction that is enhanced by heparin. Recently, Rezaie showed that calcium further enhanced the heparin-catalyzed AT inhibition of FXa by promoting 'ternary complex' formation, and these results showed a role for the gamma-carboxyl-glutamate (Gla)-domain of FXa. OBJECTIVES: In this study, we used recombinant FXa mutants to assess the role of individual Gla residues in augmenting or antagonizing the AT-heparin inhibition reaction in the presence of calcium. RESULTS AND CONCLUSIONS: In the absence of heparin, AT inhibition of plasma and the recombinant FXas were essentially equivalent. Similar to plasma-derived FXa, calcium increased about 3-fold the inhibition rate of wild-type recombinant FXa by AT-heparin over that in the presence of EDTA. Interestingly, three different effects were found with the recombinant FXa Gla-mutants for AT-heparin inhibition: (i) Gla-->Asp 14 and 29 were enhanced without calcium; (ii) Gla-->Asp 16 and 26 were not enhanced by calcium; and (iii) Gla-->Asp 19 was essentially the same as wild-type recombinant FXa. These results support a theory that mutating individual Gla residues in FXa alters the calcium-induced conformational changes in the Gla region and affects the antithrombin-heparin inhibition reaction.
