Rapid, progressive neuropathic arthropathy of the hip in a patient co-infected with human immunodeficiency virus, hepatitis C virus and tertiary syphilis: case report

BACKGROUND: Syphilis is a chronic infection that is classified into three stages. In its tertiary stage, syphilis spreads to the brain, heart and other organs; the lesions may involve the skin, mucous membranes and bones. Neuropathic arthropathy associated with tertiary syphilis has rarely been described in Europe and its association with HIV-HCV co-infection has not been reported so far.This article reports the case of a man with tertiary syphilis presenting with rapidly evolving neuropathic arthropathy of the hip and extensive bone destruction. CASE PRESENTATION: On initial presentation, the patient complained of progressively worsening left-sided coxalgia without localized or generalized inflammation. The patient reported to have no history of previous infections, trauma or cancer. Plain x-ray films of the left coxofemoral joint showed marked degeneration with necrosis of the proximal epiphysis of femur and morphological alterations of the acetabulum without protrusion. Primary coxarthrosis was diagnosed and hip arthroplasty was offered, but the patient declined treatment. Three months later, the patient presented a marked deterioration of his general condition. He disclosed that he was seropositive for HCV and HIV, as confirmed by serology. Syphilis serology testing was also positive. A Girdlestone's procedure was performed and samples were collected for routine cultures for bacteria and acid fast bacilli, all resulting negative.Although histological findings were inconclusive, confirmed positive serology for syphilis associated with progressive arthropathy was strongly suggestive of tertiary syphilis, probably exacerbated by HIV-HCV co-infection. The patient partially recovered the ability to walk. CONCLUSIONS: Due to the resurgence of syphilis, this disease should be considered as a possible cause of neuropathic arthropathy when other infectious causes have been ruled out, particularly in patients with HIV and/or HCV co-infection

Epigenetic polypharmacology: from combination therapy to multitargeted drugs

The modern drug discovery process has largely focused its attention in the so-called magic bullets, single chemical entities that exhibit high selectivity and potency for a particular target. This approach was based on the assumption that the deregulation of a protein was causally linked to a disease state, and the pharmacological intervention through inhibition of the deregulated target was able to restore normal cell function. However, the use of cocktails or multicomponent drugs to address several targets simultaneously is also popular to treat multifactorial diseases such as cancer and neurological disorders. We review the state of the art with such combinations that have an epigenetic target as one of their mechanisms of action. Epigenetic drug discovery is a rapidly advancing field, and drugs targeting epigenetic enzymes are in the clinic for the treatment of hematological cancers. Approved and experimental epigenetic drugs are undergoing clinical trials in combination with other therapeutic agents via fused or linked pharmacophores in order to benefit from synergistic effects of polypharmacology. In addition, ligands are being discovered which, as single chemical entities, are able to modulate multiple epigenetic targets simultaneously (multitarget epigenetic drugs). These multiple ligands should in principle have a lower risk of drug-drug interactions and drug resistance compared to cocktails or multicomponent drugs. This new generation may rival the so-called magic bullets in the treatment of diseases that arise as a consequence of the deregulation of multiple signaling pathways provided the challenge of optimization of the activities shown by the pharmacophores with the different targets is addressed