Evaluation by dual-photon absorptiometry of bone mineral loss in rheumatic children on long-term treatment with corticosteroids.

The introduction of reliable and non-invasive methods of measuring bone mass has allowed investigators to study the bone mass loss (ostopenia) related to rheumatic diseases and corticosteroid therapy. Serial measurements of lumbar bone mineral density (BMD) by dual-photon absorptiometry (DPA) is an effective method of checking bone mineralisation. In children, however, the bone mass is not constant over time, so bone densitometric measurements must take into account not only the net loss but also the missing increase in BMD. In order to study the effects of both chronic rheumatic disease and the long-term administration of corticosteroids in children, as a first step the reference curves of bone mineralisation (mean BMD values and annual % BMD growth rates) were calculated from a control population of 79 children (32 males and 47 females) aged 3 to 20 years. All the subjects involved in the study underwent DPA utilising a Norland Bonestar instrument provided with a 153 Gadolinium source and the average BMD (g/cm2) of the lumbar spine was calculated. As a second step, a transverse study was carried out on a series of 157 children and young adults affected by chronic rheumatic diseases with juvenile onset. As a third step, a longitudinal study on the adverse effect of the chronic administration of corticosteroids on bone mineralisation was carried out on a series of 58 patients affected by chronic rheumatic diseases with juvenile onset who were being treated with long-term corticosteroids. Serial measurements of bone mass should help us to improve our strategies in preventing and counteracting osteopenia due to the chronic administration of corticosteroids also in children.

[Rheumatic fever]. / La febbre reumatica.

While rheumatic fever (RF) remains a major problem in underdeveloped countries, in continental United States and Western Europe the incidence of this disease declined markedly in the sixties and reached a nadir during the seventies. However in the last eighties a resurgence of RF has been documented in some areas of the United States with an eightfold increase of incidence over the prior 15 year average. Although a true outbreak of RF has not been documented in Italy, a trend towards an increased number of new cases per year has been observed at the Centre for Rheumatic Children at the Gaetano Pini Institute in Milan. Most of these children presented a mild disease with clinical features rather different from those described in classical textbooks. Most of them satisfied the revised Jones' criteria, in some cases the objective signs of arthritis could not be noticed, but the joint involvement presented as marked arthralgia while other features supported the diagnosis of RF. Rheumatic carditis was observed in more than 1/3 of cases with a high rate of residual valvular heart disease of a mild degree of severity in most cases. In conclusion RF has not completely disappeared in Italy and remains as a possible cause of permanent valvular heart damage in children. It is possible that the increasing morbidity observed in the last eighties may be related to the reduced primary prophylaxis against streptococcal infections due to the wrong conviction that RF is no more a risk in developed countries.

Changes of immunological parameters during auranofin treatment in children affected with juvenile chronic arthritis.

Auranofin [S-triethylphosphine gold-2,3,4,6 tetra-O-acetyl-l-thio-beta-D-glucopyranoside) SK&F 39162) has been administered at 0.1-0.25 mg/kg/day as the sole remission-inducing drug to 46 children affected with juvenile chronic arthritis (JCA). There were 22 males and 24 females; 12 children were affected with pauciarticular onset JCA, 26 with polyarticular onset JCA and 8 with systemic onset JCA. Three sets of efficacy criteria were evaluated quarterly: eight clinical, (Ritchie Index, number of affected, swollen and limited joints, number of joint with increased temperature, morning stiffness, Steinbrocker functional class, physician's disease evaluation), three hematochemical and one therapeutical. In most patients a panel of immunological parameters was routinely performed inclusive of peripheral blood lymphocyte subsets, serum immunoglobulins and C3c-C4 complement components. Patients who showed a definite improvement of at least two out of the three orders of efficacy criteria were classified as responders to auranofin. Out of the 35 patients evaluable after at least six months of treatment there were 24 (68%) responders. Nonresponders had a basal higher level of serum IgA and a basal lower level of serum C4. Both responders and nonresponders presented a reduction of the T4/T8 ratio during auranofin treatment, while only in responders did the basal high levels of IgG and C3c show a definite decrease.

Injectable gold dermatitis and proteinuria: retreatment with auranofin.

Seven female patients with classical rheumatoid arthritis (RA), treated successfully with injectable gold salts (Fosfocrisolo ICI, 0.10 g/week, with a serum gold concentration of 200-400 mcg/dl), experienced severe gold side-effects after 3 to 20 months of therapy, requiring their withdrawal from gold despite the good results in both clinical and laboratory findings. Four patients showed mucocutaneous side-effects (2 dermatitis and 2 stomatitis) and three a moderate or severe proteinuria. Renal biopsy was performed in these patients, with a histological picture of membranous glomerulonephritis referable to gold therapy. Remission inducing drug (R.I.D.) therapy being mandatory in patients with a chronic progressive disease, and in view of the previous efficacy of gold salts, the patients were put on oral gold, Auranofin being administered 3 mg b.i.d. Both the mucocutaneous side-effects and the proteinuria ameliorated within 2 to 6 months, and the remission of the disease was maintained. The chemical and pharmacokinetic differences between the above two gold compounds are discussed.

[Tolerance and efficacy of proglumetacine in patients with rheumatoid arthritis]. / Tollerabilità ed efficacia della proglumetacina in pazienti affetti da artrite reumatoide.

The efficacy of proglumetacin , a new non-steroidal antiinflammatory drug, was assessed in 32 patients with rheumatoid arthritis. During treatment with 400-650 mg daily of proglumetacin over a period of 7-14 days, morning stiffness and side-effects were checked weekly or in severely ill patients daily. All patients but one completed the period of treatment. In spite of the short period of observation, a significant improvement was seen in the majority of cases (55%), while in 39% proglumetacin was not more effective than treatments before the admission to the study. In the group of patients treated for 14 days, morning stiffness parameters showed a significant improvement after 7 days and at the end of the period of study. Overall , only 3 patients referred side-effects: 1 case of transient headache and 2 cases of severe gastric pain. In our preliminary study, proglumetacin results to be effective as an antiinflammatory drug also in severe rheumatoid arthritis and safe for its low incidence of side-effects.