Roxithromycin-Associated Acute Thrombocytopenia.

BACKGROUND Recently, some case reports have been published on the macrolide antimicrobials azithromycin and clarithromycin as the cause of thrombocytopenia. The publicly accessible databases of the European Medicine Agency and the WHO drug monitoring program contain dozens of reports of roxithromycin-associated thrombocytopenia. CASE REPORT We described the case of a 78-year-old woman presenting to our unit with petechial lesions of the palate, 2 hematomas of the tongue, and purpuric macules in the abdomen and in the left lower limb 4 days after a course of roxithromycin. She presented to the Emergency Department with 3 out-of-range blood test results: neutrophils (11 960/mL; range: 1500-7000/mL), platelet count (3000/mL; range: 150 000-400 000/mL), and lactate dehydrogenase (379 IU/L; range: 135-225 IU/L). Thrombocytopenia occurred in the absence of aggregates and observed nucleolated lymphocytes. Lymphoproliferative pathologies and thrombotic microangiopathy were excluded by the hematologist. To rule out neoplastic lesions, an abdominal ultrasound examination was made. Antibody screening was performed for antinuclear antibodies, extractable nuclear antigen, antineutrophil cytoplasmic antibodies (all negative), and for Parvovirus B-19 (IgM negative, IgG positive), as well as HHV-6 and HHV-8 (both negative), to exclude an autoimmune or viral etiology. She recovered after intravenous methylprednisolone 60 mg/day and intravenous-immunoglobulin therapy 400 mg/kg/day. After 9 days, the patient was discharged with resolution of skin and buccal lesions. Her platelet count was 515 000/mL. CONCLUSIONS To the best of our knowledge, this is the first case of roxithromycin-associated acute autoimmune thrombocytopenia reported in the medical literature. We suggest that clinicians should consider this drug to be among the possible causes of drug-induced thrombocytopenia.

Searching Novel Therapeutic Targets for Scleroderma: P2X7-Receptor Is Up-regulated and Promotes a Fibrogenic Phenotype in Systemic Sclerosis Fibroblasts.

Objectives: Systemic sclerosis (SSc) is a connective tissue disorder presenting fibrosis of the skin and internal organs, for which no effective treatments are currently available. Increasing evidence indicates that the P2X7 receptor (P2X7R), a nucleotide-gated ionotropic channel primarily involved in the inflammatory response, may also have a key role in the development of tissue fibrosis in different body districts. This study was aimed at investigating P2X7R expression and function in promoting a fibrogenic phenotype in dermal fibroblasts from SSc patients, also analyzing putative underlying mechanistic pathways. Methods: Fibroblasts were isolated by skin biopsy from 9 SSc patients and 8 healthy controls. P2X7R expression, and function (cytosolic free Ca2+ fluxes, α-smooth muscle actin [α-SMA] expression, cell migration, and collagen release) were studied. Moreover, the role of cytokine (interleukin-1ß, interleukin-6) and connective tissue growth factor (CTGF) production, and extracellular signal-regulated kinases (ERK) activation in mediating P2X7R-dependent pro-fibrotic effects in SSc fibroblasts was evaluated. Results: P2X7R expression and Ca2+ permeability induced by the selective P2X7R agonist 2'-3'-O-(4-benzoylbenzoyl)ATP (BzATP) were markedly higher in SSc than control fibroblasts. Moreover, increased αSMA expression, cell migration, CTGF, and collagen release were observed in lipopolysaccharides-primed SSc fibroblasts after BzATP stimulation. While P2X7-induced cytokine changes did not affect collagen production, it was completely abrogated by inhibition of the ERK pathway. Conclusion: In SSc fibroblasts, P2X7R is overexpressed and its stimulation induces Ca2+-signaling activation and a fibrogenic phenotype characterized by increased migration and collagen production. These data point to the P2X7R as a potential, novel therapeutic target for controlling exaggerated collagen deposition and tissue fibrosis in patients with SSc.