Case Report: Polyvinylpyrrolidone deposition disease from repeated injection of opioid substitution drugs: report of a case with a fatal outcome.

Background: Intravenous injection of oral opioid substitution drugs (OSD) is widespread among injecting drug users. Several OSDs contain the polymer polyvinylpyrrolidone (PVP) as an excipient. Parenterally administered PVP of high molecular weight may accumulate in tissues and organs. This phenomenon was first described in the 1950s, when PVP was utilised in medication for parenteral use. We report a case of an opioid-addicted patient with extensive PVP-deposition caused by repeated injections of OSDs. Case presentation: A 30-year-old male drug addicted patient in opioid substitution therapy (OST) was repeatedly referred to his local hospital in a poor general condition. Work-up revealed severe normocytic anaemia, renal insufficiency, pancreas insufficiency and pathological fractures. Biopsies from fractured bones, bone marrow and gastric mucosa showed extensive infiltrates of histiocytes with intracytoplasmic vacuoles. Vacuole content stained slightly bluish in hematoxylin and eosin stain, red in Congo red stain and black in periodic acid methenamine silver stain. The morphological appearance and staining properties were in accordance with the diagnosis of PVP deposition. The patient had been injecting both buprenorphine tablets and a specific methadone syrup for several years. The methadone syrup contained large amounts of high molecular weight PVP, making it the most likely cause of the deposition. His health quickly deteriorated and he died, impaired by multi-organ failure and cachexia, five years after the first diagnosis of PVP-deposition. The autopsy revealed extensive PVP-deposition in all sampled organs and tissues. Conclusions: Histological investigation and the correct identification of PVP in the biopsies led to the discovery of a severe adverse effect from long-standing misuse of a drug. The disseminated PVP deposition likely contributed to multi-organ dysfunction and cachexia with a fatal outcome. The deposited PVP likely originated from repeated injections of a certain methadone syrup.

Polyvinylpyrrolidone deposition disease in patients with intravenous opioid use: a case series.

The polymer polyvinylpyrrolidone (PVP) is an excipient widely used in prescription drugs. Depending on the molecular weight (MW), parenterally administered PVP may accumulate in various tissues. Consequently, moderate and high MW PVP have only been used in oral preparations since the late 1970s. Surprisingly, starting in 2009, pathology departments in Norway received biopsies revealing PVP deposition, all from patients with a history of intravenous drug use. We identified 13 patients with PVP deposition and re-evaluated 31 biopsies and two autopsies. Common indications for biopsy were renal insufficiency, anemia, pathological fractures, and abdominal complaints. We observed PVP deposits in all biopsies (kidney, hematopoietic bone marrow, bone, gastrointestinal tract, lymph node, and skin) and all sampled tissue from the autopsies. Overall, the clinical findings could be related to PVP deposits in the biopsies. In the most seriously affected patients, PVP deposition caused severe organ dysfunction and contributed to the fatal outcomes of two patients. All patients except for one were prescribed opioid substitution drugs (OSDs), and most of the patients admitted to having injected such medications. Several OSDs contain PVP. One methadone formulation that was marketed in Norway from 2007 to 2014 contained large amounts of very high MW PVP, making it the most likely source of PVP deposition. Although the presumed source of PVP in these patients has now been withdrawn from the market, pathologists should be aware of PVP deposits when evaluating biopsies from this patient group.