Paroxysmal nocturnal haemoglobinuria from the first case to the current complement inhibition therapies

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare clonal disorder that affects about 1-1.5 cases per million individuals, characterised by haemolysis, peripheral blood cytopenia, bone marrow dysfunction, thrombosis, renal impairment and arterial and pulmonary hypertension. The first case of PNH was described probably in 1793 by a surgeon, Dr Charles Stewart, in the medical commentaries “Account of a singular periodical discharge of blood from the urethra”. In the following decades the most eminent physicians and scientists of the time reported several cases. In 1882, Paul Strübing was the first to identify PNH as a new disease entity. Hijmans in 1911 considered the possibility that the complement system mediated the haemolysis of PNH erythrocytes and, in the same year, Italian scientists Ettore Marchiafava and Alessio Nazari scrupulously described the pathogenesis of the condition. In 1925, Enneking introduced the name “paroxysmal nocturnal haemoglobinuria”, to define this pathology. Despite increased knowledge about this syndrome, therapies for PNH were still only experimental and symptomatic, with the use of antimicrobial agents, corticosteroids and blood transfusions. The natural history of PNH changed remarkably only in 2007, with the introduction of the Eculizumab complement blockade agent. Ravulizumab, a long-acting C5 complement inhibitor, approved in December 2018 by the US Food and Drug Administration (FDA), and on July 2019 by the European Commission, represents a new promising instrument for PNH treatment. A second generation of anti-complement agents is currently under investigation, representing future promising instruments for the treatment of PNH.