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Cutaneous vasculitis associated with granulocyte colony-stimulating factor.

Abstract

BACKGROUND: Several cases of cutaneous vasculitis have been reported in patients treated with granulocyte colony-stimulating factor (G-CSF). OBJECTIVE: The purpose of this study was to determine the prevalence of cutaneous vasculitis in patients receiving G-CSF therapy, causal relation to the drug, and possible pathomechanisms. METHODS: Review of the literature, retrieval of cases from the safety database of the manufacturer of G-CSF, and global assessment of the causal relation of the drug to adverse drug reactions were done. RESULTS: Eighteen cases of cutaneous vasculitis were found, of which only three have been published. A skin biopsy was done in 12 and showed leukocytoclastic vasculitis. Although cutaneous vasculitis was rare in patients treated for neutropenia associated with malignant disease and chemotherapy, it occurred in 6% of the patients with chronic benign neutropenias. Cutaneous vasculitis usually followed the increase of absolute neutrophil count (ANC) and subsided after the decrease of ANC. There was no recurrence if ANC was kept below 800/mm3. The course of G-CSF was completed in most patients. CONCLUSION: Cutaneous vasculitis should be recognized as an adverse reaction to G-CSF with low morbidity. It can be managed by reduction of dose or discontinuation of G-CSF therapy and use of topical steroids.

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BibTeXRIS

K K Jain. 1994. Cutaneous vasculitis associated with granulocyte colony-stimulating factor.. https://doi.org/10.1016/s0190-9622(94)70149-0

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Comparative oxidation studies of methionine residues reflect a structural effect on chemical kinetics in rhG-CSF.

The effect of protein conformation on the rate of chemical degradation is poorly understood. To address the role of structure on chemical degradation kinetics, comparative oxidation studies of methionine residues in recombinant human granulocyte colony-stimulating factor (rhG-CSF) were performed. The kinetics of oxidation of methionine residues by hydrogen peroxide (H2O2) in rhG-CSF and corresponding chemically synthesized peptides thereof was measured at different temperatures. To assess structural effects, equilibrium denaturation experiments also were conducted on rhG-CSF, yielding the free energy of unfolding as a function of temperature. A comparison of the relative rates of oxidation of methionine residues in short peptides with those of corresponding methionine residues in rhG-CSF yields an understanding of how protein tertiary structure affects oxidation reactions. For the temperature range that was studied, 4-45 degrees C, the oxidation rate constants followed an Arrhenius equation quite well, suggesting the lack of temperature-induced local structural perturbations that affect chemical degradation rates. One of the four methionine residues, Met 122, exhibited an activation energy significantly different from that of the corresponding peptide. Extrapolation of kinetic data predicts non-Arrhenius behavior around the melting temperature. Three phenomenological models based on different mechanisms are discussed, and an application to shelf life prediction of pharmaceuticals is presented.

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