A case of regional migratory osteoporosis.

We present the case of a middle-aged man with three episodes of regional migratory osteoporosis of the lower extremities occurring over a period of 8 years. Symptoms included a sudden onset of unilateral bone and joint pain. After initiation of pamidronate treatment, symptoms improved significantly. Regional migratory osteoporosis is a rare, but probably underdiagnosed condition with an unclear etiology. This case illustrates the importance of recognition of the disease in order to inform the patient, start treatment, and prevent unnecessary invasive procedures. Although in literature, not much is reported about treatment strategies, our patient was successfully treated with pamidronate after failure of oral bisphosphonates.

[Two patients with joint pain as initial presentation of a haematological malignancy]. / Twee patiënten met gewrichtsklachten als initiële presentatie van een hematologische maligniteit.

A 75-year-old man and a 53-year-old woman had longstanding joint pain, for which they had been treated with NSAIDs. When the symptoms worsened, a thorough diagnostic investigation was conducted that revealed myeloproliferative bone-marrow disorders in both patients. The man, who had polyarticular gout secondary to chronic myelomonocytic leukaemia, was able to maintain control of his joint pain with medical treatment. In the woman, with a history of stable joint pain due to polyarthritis, deterioration of the symptoms and the development of pancytopaenia led to a diagnosis of acute lymphocytic leukaemia; she died after receiving multiple courses of chemotherapy. The possibility of an underlying malignancy should be considered in patients with atypical symptoms in the locomotor system, an unexpected course or anomalous secondary symptoms.

Pustular skin lesions in patients treated with infliximab: report of two cases.

Two cases are presented in which repeated use of the TNF-alpha blocker infliximab may have led to development of pustular skin lesions. These findings might result in an improved understanding regarding the safety of infliximab with long-term usage.

[Persistent infiltrative pulmonary disease]. / Persisterende infiltratieve longafwijkingen.

Two patients, a woman aged 63 and a man aged 64 years, were admitted with pulmonary complaints and persistent infiltrative lung abnormalities as revealed in chest X-rays. Routine diagnostic analysis did not lead to a diagnosis. However, a pathological examination of biopsies acquired by means of video-assisted thoracoscopic surgery (VATS), revealed bronchiolitis obliterans organising pneumonia (BOOP). In the first patient the BOOP manifested itself as a rapidly progressive disease with fever, pulmonary complaints and X-ray abnormalities. There was no response to standard antibiotic treatment. The other patient had suffered from rheumatoid arthritis for a considerable time and gradually developed BOOP. Both patients recovered following adequate therapy with high doses of oral corticosteroids. BOOP is a pathological-anatomical entity. It is a nonspecific excessive repair response to a variety of stimuli, such as infection, drugs, collagen vascular diseases, inflammatory disorders, transplantation, intoxication and irradiation. BOOP can also occur idiopathically. A high-resolution CT-scan is useful in distinguishing BOOP from interstitial pulmonary fibrosis and other interstitial lung diseases. An open lung biopsy is necessary for the diagnosis BOOP and is best performed by means of VATS. The treatment of BOOP consists of administering high doses of corticosteroids (prednisone 1 mg/kg/day) and if treated adequately, the prognosis is fairly good. Due to the extensive variety in aetiology, the specific diagnostic procedures and the good response to necessary treatment, BOOP should be considered in the differential diagnosis of patients with persistent infiltrative lung disease.

Recombinant human erythropoietin improves health-related quality of life in patients with rheumatoid arthritis and anaemia of chronic disease; utility measures correlate strongly with disease activity measures.

Treatment with recombinant human erythropoietin (r-hu-Epo) in patients with rheumatoid arthritis (RA) and anaemia of chronic disease (ACD) resulted in improvement of both anaemia and disease activity. Utilities represent a generic and comprehensive quality of life measure, capable of integrating domain-specific information into one overall value which a patient assigns to his state of health. Therefore, the effect of r-hu-Epo on quality of life was studied by measuring utilities, derived from the rating scale and standard gamble, in a 52-week placebo-controlled randomised double-blind study with r-hu-Epo in 70 patients with active RA and ACD. Furthermore, the relation between anaemia as assessed by haemoglobin levels (Hb), disease activity as assessed with the Disease Activity Score (DAS), and utilities was investigated. Compared to the placebo group, significant improvement of Hb (P < 0.001), DAS (P = 0.01) and rating scale utilities (P = 0.002), but not of standard gamble utilities, was observed in the Epo group. Rating scale utilities correlated strongly with DAS (r = -0.47, P < 0.01), Hb (r = 0.37, P < 0.01) and changes in both DAS (r = -0.74, P < 0.01) and Hb (r = 0.44, P < 0.01). Both DAS and Hb contributed significantly to the variance in rating scale utilities (21% and 3% respectively) and to changes in rating scale utilities (43% and 3% respectively). Standard gamble utilities correlated less well with clinical disease variables than rating scale utilities did. These results indicate, that r-hu-Epo improves utility-derived health-related quality of life, most probably by improving both disease activity and anaemia. Utilities, particularly rating scale utilities, correlated well with conventional disease activity variables and proved sensitive to change. Utilities may be a useful tool for investigating quality of life in RA-patients.

[Pain in the hip area accompanied by a fever]. / Pijn in de heupregio met koorts.

In 3 patients, 2 women aged 16 and 64 years and 1 man aged 64 years, with pain in the left hip region and fever, the diagnosis psoas abscess was made. After antibiotic treatment and drainage they recovered well. The primary from of psoas abscess is presumably caused by haematogenous spread of bacteria, mostly Staphylococcus aureus. The secondary form is caused by spread of infection from surrounding tissue, mostly gastrointestinal micro-organisms with Crohn's disease and diverticulitis. Painful passive extension and endorotation as well as a painful flexion stress-test of the hip joint can indicate a psoas abscess. Echography and blood cultures should be performed if a psoas abscess is suspected. If echography is inconclusive, CT-scan can establish the diagnosis. The psoas abscess should be treated by percutaneous or surgical drainage combined with antibiotic therapy. The underlying cause of a secondary psoas abscess should be treated separately.

Elevated levels of inflammatory cytokines in bone marrow of patients with rheumatoid arthritis and anemia of chronic disease.

OBJECTIVE: Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) play an important role in decreased erythropoiesis in patients with anemia of chronic disease (ACD) and rheumatoid arthritis (RA). Modulation of quantities of bone marrow erythroid progenitors during chronic inflammation may be one of the pathogenetic mechanisms leading to ACD. We studied bone marrow from patients with ACD with RA by investigating, first, local production of inflammatory cytokines in the bone marrow, and second, the relative fraction of late erythroid progenitors (erythropoietin and transferrin receptor positive cells; EpoR+ TrfR+) in bone marrow. In addition, the effects of TNF-alpha on EpoR+ TrfR+ cells were studied in vitro. METHODS: Levels of IL-6 and TNF-alpha were measured by EL ELISA in supernatant of bone marrow and peripheral blood cultures from 14 patients with RA and ACD and 14 patients with RA without anemia. The numbers of EpoR+ TrfR+ cells in bone marrow samples of both groups were assessed by 2 color fluorescence flow cytometry. RESULTS: Levels of IL-6 and TNF-alpha were significantly higher in the supernatant of bone marrow cultures of patients with ACD compared to controls. No significant differences in the fraction of EpoR+ TrfR+ cells in samples was observed between the 2 groups of patients. Incubation of the samples with TNF-alpha did not result in modulation of the number of EpoR+ TrfR+ cells. CONCLUSION: Local production of proinflammatory cytokines in the bone marrow may be associated with the development of ACD in RA.

Effect of recombinant human erythropoietin on anaemia and disease activity in patients with rheumatoid arthritis and anaemia of chronic disease: a randomised placebo controlled double blind 52 weeks clinical trial.

OBJECTIVE: To study whether recombinant human erythropoietin (r-hu-Epo) improves anaemia and reduces disease activity in patients with rheumatoid arthritis and anaemia of chronic disease (ACD). METHODS: A 52 week placebo controlled randomised double blind trial with r-hu-Epo was performed in 70 patients with active rheumatoid arthritis and ACD. Thirty four patients were treated with 240 U kg-1 r-hu-Epo subcutaneously, initially three doses weekly, while 36 patients received placebo. RESULTS: A significant increase of haemoglobin from a median of 112 to 135 g litre-1 occurred in the Epo group within six weeks and could be sustained with reduced doses (median 240 U kg-1 once weekly). Sustained benefit compared to placebo was also apparent by six weeks for disease activity, as indicated by the Paulus 20% response rate. Of patients in the Epo group, 32% eventually showed a Paulus 20% response, compared to 8% of the placebo group (P = 0.016). Significant differences in favour of the Epo group were also observed in the secondary disease activity measures Ritchie index, number of swollen joints, pain score, ESR, and patients' global assessment of disease activity. C reactive protein concentrations did not change significantly. CONCLUSIONS: Treatment of ACD in rheumatoid arthritis with r-hu-Epo is effective in restoring normal haemoglobin levels and also exerts a beneficial effect on disease activity.

Course and characteristics of anaemia in patients with rheumatoid arthritis of recent onset.

OBJECTIVE: To describe the incidence, cause, and course of anaemia in rheumatoid arthritis (RA). METHODS: Medical records of 225 patients who received a diagnosis of RA between 1990 and 1992 were reviewed longitudinally for mention of anaemia. Anaemia was classified as anaemia of chronic disease if ferritin concentrations reflected adequate body iron stores. Among iron depleted anaemic patients, iron deficiency anaemia was identified using the response to iron supplementation. RESULTS: Anaemia developed in 64% of the patients, mostly within 18 months of follow up, but disappeared again in 54% of those patients. The prevalence of anaemia varied from 39% to 53% throughout follow up. Iron depletion was found in 38% of anaemic patients; 40% of them did not recover from their anaemia after iron supplementation and were classified as having anaemia of chronic disease. Anaemia of chronic disease thus caused 77% and iron deficiency anaemia 23% of observed anaemia. Recovery from anaemia occurred in 42% of the patients with anaemia of chronic disease and in 72% of iron depleted patients after iron supplementation. Anaemic patients, particularly those with anaemia of chronic disease, had a significantly greater number of the American College of Rheumatism criteria for RA, significantly more erosive joint damage, and significantly increased concentrations of serum rheumatoid factor than patients without anaemia. CONCLUSION: Anaemia appeared as a frequent and dynamic manifestation. Recovery and recurrence of anaemia was observed throughout follow up, leading to a longstanding and relatively high prevalence of the condition. Iron deficiency was diagnosed frequently and follow up revealed a considerable overlap with anaemia of chronic disease, making this the most important cause of anaemia in RA. Recovery from anaemia occurred more frequently in iron depleted anaemic patients than in those with anaemia of chronic disease. Anaemic patients, particularly those with anaemia of chronic disease, seemed to have a more serious course of their RA compared with non-anaemic patients.

IL-6-induced anaemia in rats: possible pathogenetic implications for anemia observed in chronic inflammations.

Anaemia of chronic disease (ACD) is frequently found in rheumatoid arthritis (RA). In the pathogenesis of ACD both cytokines, such as tumour necrosis factor-alpha (TNF-alpha), IL-1 and IL-6 as well as a relative deficiency of erythropoietin (EPO), are thought to play a key role. In the present study the role of IL-6 in the pathogenesis of this anaemia was investigated. IL-6 was administered intraperitoneally to rats for 14 sequential days. It appeared that IL-6 was able to induce anaemia. No evidence for suppression of bone marrow erythropoiesis or enhanced sequestration of erythrocytes in the liver was found. However, decreased plasma and bone marrow iron contents were observed in anaemic rats. Blood loss in intestinal tissue was demonstrated using erythrocyte labelling with 99mtechnetium. Histologically this was associated with inflammatory cell infiltration, oedema and bleeding in the intestinal wall. In conclusion, IL-6 induced anaemia in rats. This anaemia was caused by intestinal blood loss.

R-h-erythropoietin counteracts the inhibition of in vitro erythropoiesis by tumour necrosis factor alpha in patients with rheumatoid arthritis.

Anaemia of chronic disease (ACD) is a common extra-articular manifestation of rheumatoid arthritis (RA). Tumour necrosis factor alpha (TNF alpha) plays an important role in the development of ACD. The objective of the present study was to assess inhibition of in vitro colony-forming unit erythrocyte (CFUe) and blast-forming unit erythrocyte (BFUe) growth by TNF alpha and to examine whether this suppression could be counteracted by adding increasing concentrations of recombinant human erythropoietin (EPO) (r-h-EPO) to bone marrow cultures of RA patients with ACD and without anaemia (controls). Bone marrow cells of RA patients with ACD and control patients were cultured. The cultures were incubated with increasing concentrations of r-h-EPO (0.25; 0.5; 1; 2 U/ml), each in combination with increasing quantities of TFN alpha (0; 50; 100; 200; 400 U/ml). CFUe and BFUe were assessed after 7 and 14 days, respectively. Dose-dependent inhibition of BFUe and CFUe by increasing concentrations of TNF alpha was observed in ACD and controls. Regarding CFUe (ACD patients) incubated with 0.25 U/ml EPO, 50 U/ml TNF alpha caused 28% suppression compared to cultures without TNF alpha. Increasing the concentration of r-h-EPO from 0.25 U/ml to 2 U/ml completely restored the number of CFUe. A similar pattern was observed in BFUe growth in both groups. These data demonstrated the suppressive effects of TNF alpha on erythropoiesis in vitro and that the suppressed erythropoiesis could be partly corrected by the addition of excess r-h-EPO to the cultures. No significant differences were observed between ACD and control RA patients.(ABSTRACT TRUNCATED AT 250 WORDS)