Beware of the biologicals--hospitals may die: the Rheumatism Foundation Hospital, Heinola, Finland (1951-2010).

The first patient entered the Rheumatism Foundation Hospital, Heinola, Finland in July 1951. From that point on, the hospital helped patients suffering from rheumatic disorders. Specialists in the hospital actively developed treatments and published a large number of scientific articles in international journals. The hospital was well known internationally among people working in the field. Progress in the development of disease-modifying medication (biological agents in particular) has dramatically improved the life of patients with rheumatic diseases, but all effective treatments may also have adverse effects. In this article, we briefly review the history of the Rheumatism Foundation Hospital, which was closed permanently in March 2010 due to bankruptcy. The economical difficulties were caused primarily by the progress made in disease-modifying therapy, which decreased the need of rehabilitation and operative treatment of patients with rheumatic diseases. It seems that a great success in biological agents can carry "serious adverse effects", which may kill hospitals. This is an important primary observation, which should be noticed when the future of specialised institutes is planned.

[From the plant to chemistry--the early history of "rheumatic medication"]. / Von der Pflanze zur Chemie--die Frühgeschichte der "Rheumamittel".

The empirical administration of medication of plant, animal and even mineral origin goes back thousands of years. It was only in the 19th century that such therapy gained a scientific basis by means of the possibility to extract the active substances and analyze them chemically, and ultimately create them synthetically and modify them chemically.Meadow saffron was used from the 2nd century BC for the treatment of joint disease and gout; the active ingredient colchicine was discovered in 1819. For 4000 years willow bark has also been considered a remedy against fever, pain and gout. The active ingredient salicin was isolated in 1829, followed by salicyl acid in 1838, while the better tolerated acetylsalicylic acid was synthesized in 1897. Although the antipyretic agent cinchona was never a rheumatic remedy, it was initially considered an important antiinflammatory medication. In 1844, during the search for an alternative to quinin, antipyrin was developed, from which many antiphlogistic, antipyretic and analgetic active substances were later derived. Following the Second World War, the strongest antiinflammatory drug, cortisone, was discovered, derivates of which are still indispensable today for the treatment of inflammatory rheumatic diseases. At about the same time, there was a new wave of research which lead to the development of a large number of so-called non-steroidal antiinflammatory drugs. Following the discovery of proinflammatory cytokines in the 1970s, it became possible in the 1990s to produce antibodies against these substances, which gave rheumatic therapy new perspectives in the form of "biologicals". The sap from poppy seed capsules was already considered to have analgesic properties in the time of Hippocrates. The active ingredient morphine was isolated at the beginning of the 19th century. Today, only synthetically produced"opioids" are used, if at all, for the treatment of rheumatic disease.

[Wars in the history of rheumatology]. / Le guerre nella storia della reumatologia.

Some important discoveries in the history of rheumatology happened during war periods. It is well known that arthritis associated with conjunctivitis and urethritis, following dysenteric episodes, has been described during the First World War from the German Hans Reiter and, nearly contemporarily, from the French Nöel Fiessinger and Edgar Leroy. Less known is instead the fact that the first cases of sympathetic algoneurodystrophy have been reported by the American Silas Weir Mitchell in soldiers wounded by fire-arms, during the Civil War of Secession. Other war episodes have been crucial for the development of some drugs now abundantly applied to the care of rheumatic diseases. The discovery of therapeutic effects of immunosuppressive agents, in fact, happened as an indirect consequence of the use of poison gas, already during the First World War (mustard gas), but above all after an episode in the port of Bari in 1943, where an American cargo boat was sunk. It had been loaded with a quantity of cylinders containing a nitrogenous mustard, whose diffusion in the environment provoked more than 80 deaths owing to bone marrow aplasia.Moreover, the history of the cortisone shows a strict link to the Second World War, when Germany imported large quantities of bovine adrenal glands from Argentina, with the purpose of producing some gland extracts for the Luftwaffe aviators, in order to increase their performance ability.