The Institute for the History of Rheumatology, an offspring of the Italian Society of Rheumatology, is born in Venice.

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Impact of COVID-19 pandemic in the activity of a Therapeutic Apheresis unit in Italy.

INTRODUCTION: The recent Coronavirus Disease 2019 (COVID-19) outbreak has led to profound and rapid changes in the Italian and Veneto Region Healthcare System. This context also includes the quick reorganization which the Apheresis Unit (AU) of the Padova University Hospital, i.e. the Regional Reference Center for Therapeutic Apheresis (TA), had to face. MATERIAL AND METHODS: The study retrospectively evaluated the TA activity (procedures performed, patients treated and consultations) during the COVID-19 pandemic, from March to April 2020, comparing the activity in the same time period in 2018 and 2019. RESULTS: In the period analyzed, a significant reduction in both the total number of procedures performed and of patients treated, respectively by 17 % and 16 % for the procedures and by 19 % and 20 % for patients treated compared to the same period of 2018 and 2019, respectively, was observed. A concomitant reduction in requests for TA consultation for new patients (both outpatients and inpatients) was observed, equal to 32 % and 21 % compared to 2018 and 2019, respectively. CONCLUSION: Many reasons determined the observed reduction in the TA activity during the recent COVID-19 outbreak. The AU itself was quickly reorganized in terms of location and supplies to allow for the appropriate COVID-19 patients care. Many non urgent cases, after multidisciplinary discussion between Clinicians and Apheresis Specialists, were deferred, maintaining close phone and e-mail contact with patients.

Multiloci identification of Diaporthe fungi isolated from the medicinal plant Costus spiralis (Jacq.) Roscoe (Costaceae).

AIMS: The purpose of this study is to identify species from genus Diaporthe associated with a medicinal plant Costus spiralis by ITS, EF 1-α, TUB and CAL gens. METHODS AND RESULTS: The 30 isolates from the genus Diaporthe associated with the medicinal plant Costus spiralis were characterized based on morphological characters and the microculture technique and grouped by DNA fingerprinting with the ISSP gene. Afterwards, a total of 12 isolates were selected for the identification of the species based on the comparative research on the blast through the sequences of the ITS gene. Phylogenetic Tree of Maximum Likelihood were generated with the ITS gene individually and with the genes ITS, TUB, CAL and EF1-α combined with the Diaporthe species recognized and with the additional sequences obtained from GenBank for these species. CONCLUSIONS: It was not possible to characterize the 30 isolates microscopically and macromorphologically through the microculture technique and the macromorphological characteristics. The 12 isolates selected based on the DNA fingerprinting profile identified phylogenetically, revealed five distinct species of Diaporthe which are present in C. spiralis. SIGNIFICANCE AND IMPACT OF THE STUDY: The molecular analyses used in this study are excellent alternatives for species-level identification of Diaporthe associated with medicinal plants.

Apheresis treatment of cryoglobulinemic vasculitis: A multicentre cohort study of 159 patients.

OBJECTIVE: To assess the effectiveness of apheresis therapy (AT) in treating the clinical manifestations of patients with complicated cryoglobulinemic vasculitis (CV). METHODS: A retrospective cohort study of 159 CV patients attending 22 Italian Centers who underwent at least one AT session between 2005 and 2015. The response to AT was evaluated on the basis of a defined grading system. RESULTS: Peripheral neuropathy was the most frequent clinical condition leading to AT. Therapeutic plasma exchange was used in 70.4% of cases. The outcome of AT was rated very good in 19 cases, good in 64, partial/transient in 40, and absent/not assessable in 36. Life-threatening CV-related emergencies and renal impairment independently correlated with failure to respond to AT. The independent variables associated with an increased risk of death were age at the time of the first AT session, multi-organ life-threatening CV, the presence of renal impairment and failure to respond to AT. The time-dependent probability of surviving until CV-related death in the second year was 84%, with an AHR in patients with absent/not assessable response to AT of 11.25. CONCLUSION: In this study AT is confirmed to be a safe procedure in patients with CV. Early AT should be considered in patients with severe CV, especially in cases with impending renal involvement, in order to prevent irreversible kidney damage. Although its efficacy in patients with multi-organ failure is limited, AT is the only treatment that can rapidly remove circulating cryoglobulins, and should be considered an emergency treatment.

A short story of anti-rheumatic therapy. VIII. The immunodepressants.

The use of immunosuppressive drugs in rheumatology is fairly recent, starting just after the Second World War with the introduction of the first alkylating agents in oncohematology. When it became clear that some rheumatic diseases, particularly rheumatoid arthritis and systemic lupus erythematosus, showed an immune-mediated pathogenesis, including proliferation of immunocompetent cells, an application was soon found for immunosuppressive drugs in their treatment. This review outlines the historical milestones that led to the current use of drugs belonging to the major groups of immunosuppressants, i.e. alkylating agents (cyclophosphamide), folic acid (methotrexate) and purine (azathioprine) antagonists. We will also talk about the history of cyclosporin A, the first "selective" immunosuppressive agent, and that of some immunoactive drugs used more recently in rheumatology, such as mycophenolate mofetil, dapson and thalidomide, is briefly described.

Some historical remarks on microcrystalline arthritis (gout and chondrocalcinosis).

The history of microcrystalline arthritis only began in 1961 when Daniel McCarty and Joseph Lee Hollander demonstrated the presence of sodium monourate crystals in the synovial fluid of gouty patients. However, gout is a historical disease, thanks to the descriptions of Hippocrates, Caelius Aurelianus, Soranus of Ephesus and Araeteus of Cappadocia. The relationship between hyperuricemia and gout was first documented in the nineteenth century by Alfred Baring Garrod, who demonstrated deposits of uric acid crystals on a linen thread held dipped in acidified blood (the so-called "thread method"). Gout has always been considered a prerogative of the moneyed classes (arthritis divitum), and history is full of famous gouty personalities, including kings, emperors, popes, commanders, politicians, artists, writers, philosophers and scientists. Another form of microcrystalline arthritis, chondrocalcinosis, was identified as being a rheumatic disorder different from gout in the 1960s. As a specific clinical entity, it was first identified in 1958 by Dusan Zitnˇan and Stefan Sit'aj in a few Slovak families.

[A short history of anti-rheumatic therapy - VI. Rheumatoid arthritis drugs]. / Piccola storia della terapia antireumatica - VI. I farmaci dell'artrite reumatoide.

The treatment of rheumatoid arthritis traditionally includes symptomatic drugs, showing a prompt action on pain and inflammation, but without any influence on disease progression, and other drugs that could modify the disease course and occasionally induce clinical remission (DMARDs or disease modifying anti-rheumatic drugs). This review describes the historical steps that led to the use of the main DMARDs in rheumatoid arthritis, such as gold salts, sulphasalazine, chloroquine and hydroxychloroquine, D-penicillamine, and other immunoactive drugs, including methotrexate, azathioprine, cyclosporin and leflunomide. The historical evolution of use of these drugs is then discussed, including the strategy of progressive ("therapeutic pyramid") or of more aggressive treatment, through the simultaneous use of two or more DMARDs ("combination therapy").

[A short history of anti-rheumatic therapy--V. analgesics]. / Piccola storia della terapia antireumatica--V. Gli analgesici.

The pharmacological treatment of pain has very ancient origins, when plant-derived products were used, including mandrake extracts and opium, a dried latex obtained from Papaver somniferum. In the XVI and XVII centuries opium came into the preparation of two compounds widely used for pain relief: laudanum and Dover's powder. The analgesic properties of extracts of willow bark were then recognized and later, in the second half of the XIX century, experimental studies on chemically synthesized analgesics were planned, thus promoting the marketing of some derivatives of para-amino-phenol and pyrazole, the predecessors of paracetamol and metamizol. In the XX century, nonsteroidal anti-inflammatory drugs were synthesized, such as phenylbutazone, which was initially considered primarily a pain medication. The introduction on the market of centrally acting analgesics, such as tramadol, sometimes used in the treatment of rheumatic pain, is quite recent.

[A short history of anti-rheumatic therapy--VII. Biological agents]. / Piccola storia della terapia antireumatica--VII. I farmaci "biologici".

The introduction of biological agents has been a major turning-point in the treatment of rheumatic diseases, particularly in rheumatoid arthritis. This review describes the principle milestones that have led, through the knowledge of the structure and functions of nucleic acids, to the development of production techniques of the three major families of biological agents: proteins, monoclonal antibodies and fusion proteins. A brief history has also been traced of the cytokines most involved in the pathogenesis of inflammatory rheumatic diseases (IL-1 and TNF) and the steps which have led to the use of the main biological drugs in rheumatology: anakinra, infliximab, adalimumab, etanercept and rituximab.

[A short history of anti-rheumatic therapy. IV. Corticosteroids]. / Piccola storia della terapia antireumatica. IV. I cortisonici.

In 1948 a corticosteroid compound was administered for the first time to a patient affected by rheumatoid arthritis by Philip Showalter Hench, a rheumatologist at the Mayo Clinic in Rochester, Minnesota (USA). He was investigating since 1929 the role of adrenal gland-derived substances in rheumatoid arthritis. For the discovery of cortisone and its applications in anti-rheumatic therapy, Hench, along with Edward Calvin Kendall and Tadeusz Reichstein, won the 1950 Nobel Prize for Medicine. In this review we summarize the main stages that led to the identification of the so-called compound E, which was used by Hench. We also consider the subsequent development of steroid therapy in rheumatic diseases, through the introduction of new molecules with less mineralocorticoid effects, such as prednisone, and more recently, deflazacort.

[A short history of anti-rheumatic therapy. III. Non steroidal anti-inflammatory drugs]. / Piccola storia della terapia antireumatica. III. I farmaci antiflogistici non steroidei.

The chemical advances of the 20th century led to the synthesis of non steroidal anti-inflammatory drugs (NSAIDs), beginning from phenylbutazone and indomethacin and continuing with other new drugs, including ibuprofen, diclofenac, naproxen, piroxicam and, more recently, the highly selective COX-2 inhibitors (coxibs). This progress derived from the discovery of the mechanism of action of these drugs: the inhibition of synthesis of prostaglandins due to the cycloxigenase enzyme system, according to the experimental contributions of John R. Vane.

[A short history of anti-rheumatic therapy. II. Aspirin]. / Piccola storia della terapia antireumatica. II. L'aspirina.

The discovery of aspirin, an antipyretic, anti-inflammatory and analgesic drug, undoubtedly represents a milestone in the history of medical therapy. Since ancient times the derivatives of willow (Salix alba) were used to treat a variety of fevers and pain syndromes, although the first report dates back to 1763 when the English Reverend Edward Stone described the effect of an extract of the bark willow in treating malaria. In the XIX century many apothecaries and chemists, including the Italian Raffaele Piria and Cesare Bertagnini, developed the biological processes of extraction and chemical synthesis of salicylates, and then analyzed their therapeutic properties and pharmacokinetic and pharmacodynamic characteristics. In 1899 the Bayer Company, where Felix Hoffmann, Heinrich Dreser and Arthur Eichengrün worked, recorded acetyl-salicylic acid under the name "Aspirin". In the XX century, besides the definition of the correct applications of aspirin in the anti-rheumatic therapy being defined, Lawrence L. Crawen identified the property of this drug as an anti-platelet agent, thus opening the way for more widespread uses in cardiovascular diseases.

[A short history of anti-rheumatic therapy. I. An introduction on traditional and drug treatments]. / Piccola storia della terapia antireumatica. I. Una premessa sulle terapie tradizionali e farmacologiche.

The origins of anti-rheumatic therapy are very old and mainly related to the use of traditional, sometimes extravagant, treatments, as a part of folk medicine. Spa therapy has long been used for the treatment of rheumatic diseases, as well as, in later times, physical treatments, including electrotherapy. Drug treatment has developed beginning from substances of vegetable origin, such as willow and colchicum extracts. Then it has been spread out through the chemical synthesis of compounds with specific action and therefore more effective, owing to the great development of pharmaceutical industry.

[The main stages in the history of systemic lupus erythematosus]. / Le principali tappe nella storia del lupus eritematoso sistemico.

Systemic lupus erythematosus can be considered the most characteristic and important among the connective tissue diseases. In this short review the main stages of its history are sketched, from the introduction of the term "lupus", traditionally attributed to Roger Frugardi, in 1230 (but in fact already documented in the 10th century) to the actual knowledge of its clinical and laboratory aspects. Initially considered exclusively of dermatological interest, the first to describe a systemic form with visceral involvement were Moriz Kohn Kaposi and William Osler. Significant contribution was also given by serological diagnosis, and in particular, by the identification of specific markers of disease, such as anti-native DNA and anti-Sm antibodies, allowing early diagnosis and the establishment of an adequate therapy.

The Italian SIdEM registry for apheresis: an overview of the 2005 statistics.

Data collection on apheresis activities in Italy throughout 2005 including techniques, types of blood cell separators, clinical indications and adverse effects was performed by means of a standardized questionnaire. These data provided by 83 Apheresis Units from 16 Italian regions, albeit rough, are sufficiently informative, mainly in comparison with previous surveys on these statistics (1997 and 2000). In 2005 a total number of 204,746 apheresis procedures were carried out, with a clear-cut prevalence of apheresis production (87.7%), performed by 66 out of 83 Apheresis Units (79.5). Lombardy, Veneto and Tuscany were the most active regions for therapeutic apheresis (51.1% of the total national procedures). An increasing number in extracorporeal photochemotherapy as compared to the 2000 national survey (3,386 vs. 704 procedures) is the most striking observation to emerge from the 2005 data collection on therapeutic apheresis in Italy. Adverse effects, predominantly mild ones (i.e., paresthesia due to citrate-induced hypocalcemia), occurred in 0.12% of apheresis production and 6.04 of therapeutic sessions, particularly in the course of peripheral blood stem cell collection (20.79%), as already reported in the 2000 national survey.

[Historical evolution of the concept of fibromyalgia: the main stages]. / Evoluzione storica del concetto di fibromialgia: le tappe principali.

The concept of fibromyalgia is fairly recent, by evolving from previous notions such as muscular rheumatism and fibrositis. In this concise report the main stages leading to the development of the concept of fibromyalgia are sketched out, beginning from the notions of fibrositis nodules, trigger points and myofascial pain, up to the most recent knowledge including this clinical condition in the cluster of central sensitivity syndromes.

Thrombocytopenia in high-risk patients with antiphospholipid syndrome.

Essentials The prevalence of thrombocytopenia in patients with antiphospholipid syndrome is not well defined. We studied triple positive patients with antiphospholipid syndrome and its catastrophic variant. Prevalence of thrombocytopenia was 6% and 100% in patients who developed the catastrophic form. In triple positive patients thrombocytopenia is low and platelets drop during the catastrophic form. SUMMARY: Background Thrombocytopenia is the most common non-criteria hematological feature in patients with antiphospholipid syndrome (APS). This condition is more common in patients with catastrophic APS (CAPS). Objectives To evaluate the prevalence of thrombocytopenia in a large series of high-risk patients with APS, and to assess the behavior of the platelet count during CAPS. Methods/Patients This was a cross-sectional study in which we analyzed the platelet counts of a homogeneous group of high-risk APS patients (triple-positive). Six of these patients developed a catastrophic phase of the disease, and the platelet count was recorded before the acute phase, during the acute phase, and at recovery. Results The mean platelet count in 119 high-risk triple-positive patients was 210 × 109 L-1 . With a cut-off value for thrombocytopenia of 100 × 109 L-1 , the prevalence of thrombocytopenia was 6% (seven patients). No difference between primary APS and secondary APS was found. In patients who suffered from CAPS, a significant decrease from the basal count (212 ± 51 × 109 L-1 ) to that at the time of diagnosis (60 ± 33 × 109 L-1 ) was observed. The platelet count became normal again at the time of complete remission (220 ± 57 × 109 L-1 ). A decrease in platelet count always preceded the full clinical picture. Conclusions This study shows that, in high-risk APS patients, the prevalence of thrombocytopenia is low. A decrease in platelet count was observed in all of the patients who developed the catastrophic form of the disease. A decrease in platelet count in high-risk APS patients should be considered a warning signal for disease progression to CAPS.

[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.

[On the main stages of the history of intra-articular therapy]. / Sulla storia delle terapie intra-articolari. Le tappe principali.

In this review the main stages in the history of intra-articular therapy of the rheumatic diseases are summarized. The first approach to such a local treatment has been likely performed in 1792 by the French physician Jean Gay, who injected in a swelling knee the "eau du Goulard" (Goulard's water), namely a mixture based on lead compounds. In the XIX century iodine derivatives have been mainly applied as an intra-articular treatment. In the XX century, before the wide use of intra-articular corticosteroids, chiefly due to the Joseph Lee Hollander's experiences, a variety of drugs has been employed, including cytostatics and sclerosing substances. A further important stage has been synoviorthesis, by using specific radionuclides, that would actually represent an anti-synovial treatment. In the last years a spread use of intra-articular hyaluronic acid, particularly in osteoarthritis, has been recorded, with the aim to warrant articular viscosupplementation. Future of intra-articular treatment should be represented by the biological drugs, i.e., anti-TNF, but it is still untimely to define the exact role of such a local treatment of arthritis.