LLLT for the management of patients with ankylosing spondylitis.

This study aimed to compare the effectiveness of the combined low-level laser therapy (LLLT) and passive stretching with combined placebo LLLT laser and the same passive stretching exercises in patients suffering from Αnkylosing spondylitis. Forty-eight patients suffering from Αnkylosing spondylitis participated in the study and were randomized into two groups. Group A (n = 24) was treated with a λ = 820 Ga-Al-As laser CW, with power intensity = 60 mW/cm(2), energy per point in each session = 4.5 J, total energy per session = 27.0 J, in contact with specific points technique, plus passive stretching exercises. Group B (n = 24), received placebo laser plus the same passive stretching exercises. Both groups received 12 sessions of laser or placebo within 8 weeks; two sessions per week (weeks 1-4) and one session per week (weeks 5-8). Pain and function scales were completed before the treatment, at the end of the fourth and eighth week of treatment, and 8 weeks after the end of treatment (follow-up). Group A revealed a significant improvement after 8 weeks of treatment in all pain and function scales. At 8-week follow-up, the improvement remained only for the pain, while for all other function outcomes the differences were not statistically significant. The results suggested that after an 8-week treatment and after a follow-up, the combination of LLLT and passive stretching exercises decreased pain more effectively than placebo LLLT along with the same passive stretching exercises in patients with Αnkylosing spondylitis. Future studies are needed to establish the relative and absolute effectiveness of the above protocol.

Administration of lower doses of radium-224 to ankylosing spondylitis patients results in no evidence of significant overall detriment.

The use of low doses of radium-224 (224Ra) chloride for the treatment of ankylosing spondylitis was stopped following the discovery that patients treated with it had a higher than control incidence of leukaemia and other cancers. This was so even though the treatment resulted in decreased pain and increased mobility-both of which are associated with decreased mortality. It was decided to re-analyze the epidemiological data looking at all causes of death. The risk of leukaemia, solid cancer, death from non-cancer causes and from all causes in a study populations of men that received either the typical dose of 5.6 to 11.1 MBq of 224Ra, any dose of 224Ra or no radium were compared using the Cox proportional hazard model. For patients that received the typical dose of 224Ra agreed with the excess cancer was similar to that reported in previous studies. In contrast, these patients were less likely to die from non-cancer diseases and from all causes of death than the control patients. No excess mortality was also found in the population of all males that received the radionuclide. It is concluded that 224Ra treatment administered at low doses to patients with ankylosing spondylitis did not impact mortality from all causes. The study demonstrates the need to consider all causes of death and longevity when assessing health impacts following irradiation.

[Long-term investigation of the risk of malignant diseases following intravenous radium-224 treatment for ankylosing spondylitis]. / Langzeituntersuchung zum Risiko maligner Erkrankungen nach intravenöser Behandlung des Morbus Bechterew mit Radium-224.

BACKGROUND AND PURPOSE: In German-speaking countries, the intravenous treatment of ankylosing spondylitis (AS) with radium-224 ((224)Ra) was common between the late 1940s and 2005. In this long-term investigation, the risk of malignant diseases following intravenous (224)Ra treatment for AS was assessed. PATIENTS AND METHODS: In a prospective long-term study, 1,471 patients with AS who were treated with (224)Ra between 1948 and 1975 have been followed together with a control group of 1,324 AS patients treated neither with radioactive drugs nor with X-rays. Standardized questionnaires to evaluate the patients' health status were used. Observed numbers of malignant diseases were compared with those of the control group as well as with expected numbers for a normal population. RESULTS: After 26 years of follow-up, causes of death have been certified for 1,006 patients of the exposure group (control group: 1,072 patients). Significantly increased rates of myeloid leukemia (12 cases observed vs. 2.9 expected; p < 0.001), kidney cancer (18 vs. 9.1; p < 0.01), thyroid cancer (4 vs. 1.2; p = 0.03) and borderline significantly increased rates of cancer of female genital organs (10 vs. 5.6; p = 0.06) were found in the exposure group in contrast to no significant increases of these diseases in the control group. Rates of pulmonary and gastrointestinal malignancies were not increased. Lymphatic leukemia (exposure group: 8 vs. 2.7; p < 0.01; control group: 7 vs. 3; p = 0.03) was significantly elevated due to a high rate of chronic lymphatic leukemia in both, the exposure as well as the control group. CONCLUSION: Treatment of AS with (224)Ra led to increased incidences of myeloid leukemia and malignancies of kidneys, thyroid and female genital organs. Although this kind of therapy is now abandoned, there is a need for close follow-up of patients who received it.

Incidence of leukaemia and other malignant diseases following injections of the short-lived alpha-emitter 224Ra into man.

We performed an epidemiological study on 1,471 ankylosing spondylitis patients treated with repeated intravenous injections of the short lived alpha-emitter (224)Ra (excluding radiation therapy with X-rays) between 1948 and 1975. These patients have been followed together with a control group of 1,324 ankylosing spondylitis patients treated neither with radioactive drugs nor with X-rays. The mean follow-up time was 26.3 years in the exposed and 24.6 years in the control group. To date, causes of death have been ascertained for 1,006 exposed patients and 1,072 controls. Special emphasis was placed on the reporting of malignant diseases. Expected numbers of cases were computed for the age, sex and calendar year distribution of both groups using cancer registry incidence rates. In the exposed group 18 cases of kidney cancer (vs. 9.1 cases expected, P < 0.01) and 4 malignant thyroid tumours (vs. 1.2 cases expected, P = 0.03) were observed. In the control group the observed cases for these tumours were not significantly elevated. The most striking observation, however, were the 21 cases of leukaemia in the exposed group (vs. 6.8 cases expected, P < 0.001) compared to 12 cases of leukaemia in the control group (vs. 7.5 cases expected). Further sub-classification of the leukaemias demonstrated a high increase of myeloid leukaemia in the exposed group (12 cases observed vs. 2.9 cases expected, P < 0.001), and out of these, especially a high excess of acute myeloid leukaemias (7 cases observed vs. 1.8 expected, P = 0.003). In the controls the observed cases are within the expected range (4 myeloid leukaemias vs. 3.1 cases). This increase in total leukaemias as well as particularly in myeloid leukaemias is significant in direct comparison between the exposed and control groups too (P < 0.05). The enhanced leukaemia incidence in the exposed group is in line with the observation of increased leukaemia incidence in mice injected with (224)Ra.

Efficacy of wIRA in the treatment of sacroiliitis in male patients with ankylosing spondylitis and its effect on serum VEGF levels.

BACKGROUND: This study aimed to assess the efficacy of water-filtered infrared A (wIRA) in sacroiliitis in male patients with ankylosing spondylitis (AS) and the effect of wIRA therapy on serum vascular endothelial growth factor (VEGF). METHODS: One hundred twenty male AS patients with active sacroiliitis were randomly divided into wIRA group and control group. wIRA treatment was performed twice daily for 5 consecutive days with 24-h interval before switching the treatment (crossover design). Bath ankylosing spondylitis disease activity index (BASDAI) scores, pain visual analogue scale (VAS), and morning stiffness VAS were recorded prior to and after each treatment period. Additionally, C-reactive protein (CRP), serum VEGF, and resistance index (RI) of sacroiliac joints detected by ultrasonography were recorded at baseline and after the first and second treatment period, respectively. The efficacy was examined by using repeated measures analysis of variance (ANOVA). RESULTS: BASDAI, pain VAS, and morning stiffness VAS scores decreased significantly (P < 0.001) after wIRA treatment and no-wIRA treatment (control group), and the difference between the two groups was significant (P < 0.001). CRP declined and RI increased during the wIRA treatment as compared with the no-wIRA treatment (P < 0.001). The increase in RI was associated with improvement of pain VAS scores (P = 0.018), while serum VEGF was unaffected by the treatment. CONCLUSIONS: wIRA treatment achieved symptom and pain relief for AS patients with active sacroiliitis. wIRA treatment also improved RI revealed by ultrasonography, and this effect was associated with improved pain VAS scores.

Increased risk of myeloid leukaemia in patients with ankylosing spondylitis following treatment with radium-224.

OBJECTIVE: To investigate long-term health effects in AS patients treated with (224)Ra. METHODS: A prospective epidemiological study has been carried out on 1471 AS patients treated with repeated intravenous injections of (224)Ra between 1948 and 1975. These patients have been followed together with a control group of 1324 AS patients not treated with radioactive drugs and/or X-rays. Numbers of malignancies expected in a normal population were computed from German and Danish cancer registry data. RESULTS: After a mean follow-up time of 26 yrs in the exposed group or 25 yrs in the control group, causes of death have been ascertained for 1006 exposed patients and 1072 controls. In particular, 19 cases of leukaemia were observed in the exposure group (vs 6.8 cases expected, P < 0.001) compared to 12 cases of leukaemia in the control group (vs 7.5 cases expected). Further subclassification of the leukaemia cases demonstrated a high increase of myeloid leukaemia in the exposure group (11 cases observed vs 2.9 cases expected, P < 0.001), especially a high excess of acute myeloid leukaemias (7 cases observed vs 1.8 cases expected, P = 0.003), whereas in the controls the observed cases are within the expected range (4 myeloid leukaemias vs 3.1 cases expected). CONCLUSIONS: The enhanced leukaemia incidence in the exposed group is in line with results from experiments in mice injected with varying amounts of the bone-seeking alpha-emitter (224)Ra. In these studies, in animals exposed to lower doses of (224)Ra, i.e. at doses lower than those found to induce osteosarcomas, an increased risk of leukaemia was observed.

[Cost-benefit analysis of [224Ra] radium chloride therapy for ankylosing spondylitis (Bekhterev's disease)]. / Kosten-Nutzen-Analyse einer Therapie der ankylosierenden Spondylitis (Morbus Bechterew) mit Radiumchlorid [224Ra].

BACKGROUND AND PURPOSE: Cost-benefit analyses are helpful in setting priorities for funding health-care programs. The authors studied the cost/benefit of treatment with radium-224 compared to the treatment without radium-224 in patients with ankylosing spondylitis (AS). MATERIAL AND METHODS: The data of a 2-year retrospective observational study were used to estimate cost/benefit of [224Ra] therapy. Twelve patients treated with [224Ra], complete recruit in AOK Saxony, matched (age, gender, employment status) with twelve patients receiving conservative treatment without [224Ra], were compared for lost productivity and direct medical costs, such as doctor visits, medication and hospitalization, 1 year before and after treatment. RESULTS: 1 year after the first i.v. injection of [224Ra], all cost factors in the case group were reduced compared to 1 year before treatment with [224Ra] (hospitalization 29.4%, doctor visits 23.5%, medication 9.4%, and lost productivity even 82.3%). The total costs decreased by an average of 3,870 Euros. Because of the small sample the differences showed a trend but were not significant. CONCLUSION: The use of [224Ra] in patients with AS seems to reduce lost productivity and direct medical costs, but additional studies based on more patients and long-term data are needed.

A parallel analysis of cancer mortality among atomic bomb survivors and patients with ankylosing spondylitis given X-ray therapy.

Radiation-induced cancer mortality rates among atomic bomb survivors with doses of at least 100 rad and patients with ankylosing spondylitis given X-ray therapy have been compared for the first time. The estimated average mean bone marrow dose for the spondylitics is more than twice that for atomic bomb survivors, and yet spondylitics experienced only half the risk of radiation-induced leukemia of atomic bomb survivors. For sites that were heavily irradiated in the spondylitics, provisional estimates indicate comparable doses in the two studies, and similar levels of cancer risk were observed. For these sites, when information from the studies was combined, there were statistically significant excesses for cancers of the esophagus, stomach, lung, and ovaries, multiple myeloma, other lymphomas, and tumors of the spinal cord and nerves. Very high relative risks (RR's) for tumors of the spinal cord and nerves were observed in both studies. For sites that were lightly irradiated in the spondylitics, in addition to previously documented sites, there was a statistically significant excess of cancers of the liver and gallbladder among atomic bomb survivors. A previous subdivision of cancer sites into radiosensitive and other tissues was not supported by the atomic bomb survivor data. Changes in the rates of radiation-induced cancers with age at exposure and time since exposure were studied and compared with the use of generalized linear modeling of the RR's and also by examination of the excess mortality rates. The level of agreement between the two studies was high; provided it is accepted that the reduced level of leukemia risk in the spondylitics is due to cell sterilization, no inconsistencies were found. For a group of solid tumors selected from heavily irradiated sites in the spondylitics, excess risk increased with both age at exposure and time since exposure and RR decreased with age at exposure, but it did not vary with time since exposure between about 5 and at least 30 years following exposure. The finding of a constant RR with time since exposure did not extend to all remaining neoplasms other than leukemia, because the RR for these neoplasms increased with time since exposure in atomic bomb survivors.

Samarium-153-EDTMP for palliation of ankylosing spondylitis, Paget's disease and rheumatoid arthritis.

Samarium-153-EDTMP is an effective agent for palliation of widespread skeletal metastases because it concentrates in bone metastases which have an osteoblastic component. Similar concentration in areas of osteoblastic activity in ankylosing spondylitis, Paget's disease and rheumatoid arthritis suggests a possible new treatment approach. Three patients with ankylosing spondylitis, one patient with Paget's disease and one patient with rheumatoid arthritis were treated with 153Sm-EDTMP. Objective and subjective improvement was noted, especially in ankylosing spondylitis patients. Samarium-153-EDTMP has disease-modifying potential in ankylosing spondylitis and Paget's disease and has palliative value in resistant rheumatoid arthritis. Further trials to determine optimal dose, treatment scheduling, long-term disease-modifying potential and toxicity are needed.

Myeloid leukaemia frequency after protracted exposure to ionizing radiation: experimental confirmation of the flat dose-response found in ankylosing spondylitis after a single treatment course with X-rays.

The dose-response for leukaemia induction by exposure to ionizing radiation protracted over several weeks was largely independent of dose not only in X-rayed patients with ankylosing spondylitis but also in experimentally gamma-rayed CBA/H mice. In the experiment the induced leukaemia frequency of acute myeloid leukaemia was independent of a several thousand-fold variation in physical dose rate. Any difference in leukaemia induction between brief and protracted exposures must therefore depend on specifically biological consequences of protracted exposures. Experimental analysis is required to provide the guides for inference about risks of low level exposure from observations on relatively heavily irradiated populations.

Leukemia mortality after X-ray treatment for ankylosing spondylitis.

Leukemia mortality has been studied in 14,767 adult ankylosing spondylitis patients diagnosed between 1935 and 1957 in the United Kingdom, of whom 13,914 patients received X-ray treatment. By 1 January 1992, there were 60 leukemia deaths among the irradiated patients, almost treble that expected from national rates. Leukemia mortality was not increased among unirradiated patients. Among those irradiated, the ratio of observed to expected deaths for leukemia other than chronic lymphocytic leukemia was greatest in the period 1-5 years after the first treatment (ratio = 11.01, 95% confidence interval 5.26-20.98) and decreased to 1.87 (95% confidence interval 0.94-3.36) in the 25+ year period. There was no significant variation in this ratio with sex or age at first treatment. The ratio for chronic lymphocytic leukemia was slightly but not significantly raised (ratio = 1.44, 95% confidence interval 0.62-2.79). Most irradiated patients received all their exposure within a year. Based on a 1 in 15 random sample, the mean total marrow dose was 4.38 Gy. Doses were nonuniform, with heaviest doses to the lower spine. The risk for nonchronic lymphocytic leukemia was adequately described by a linear-exponential model that allowed for cell sterilization in heavily exposed parts of the marrow and time since exposure. Ten years after first exposure, the linear component of excess relative risk was 12.37 per Gy (95% confidence interval 2.25-52.07), and it was estimated that cell sterilization reduced the excess relative risk by 47% at 1 Gy (95% confidence interval 17%-79%). The average predicted relative risk in the period 1-25 years after exposure to a uniform dose of 1 Gy was 7.00.

Late effects in ankylosing spondylitis patients treated with 224Ra.

This study is comprised of 1577 ankylosing spondylitis patients from 9 German hospitals who have been treated with multiple injections of (224)Ra. The majority of the patients, most of them treated in the years 1948-1975, received one series of 10 weekly intravenous injections of about 1 MBq of (224)Ra each. This dose leads to a mean absorbed dose due to alpha-particle radiation of 0.56 Gy to the marrow-free skeleton of a 70- kg man (mean bone surface dose of about 5 Gy). To provide comparative information on causes of death and on health effects possibly related to the basic disease itself, a control group of 1462 ankylosing spondylitis patients with roughly the same age distribution has been established. By the end of 1998, 649 patients in the exposed group and 762 control patients had died. Among other observations, it is of particular interest that 13 cases of leukemia in the exposed group have been observed. This is a highly significant excess (P < 0.001) compared to a standard population, but only a marginally significant excess in comparison to the seven cases observed in the control group. Subclassification of the leukemias shows a clear preponderance of the myeloid leukemias in the exposed group (8 cases observed compared to 1.7 cases expected, P < 0.001), whereas in the control group the observed cases are within the expected range for myeloid leukemia (3 cases observed compared to 2.2 cases expected, P = 0.3). The (224)Ra cohort of the earlier study (higher-dose group) has provided a risk coefficient that predicts about 8 excess malignant bone tumors for the irradiated cohort in this study. In actuality, 4 cases of malignant tumors in the skeleton have been observed so far. However, excess of breast cancer has not been observed in either the irradiated or the control group, which is in contrast to the findings in the earlier (224)Ra cohort of Study I.

An epidemiological assessment of lens opacifications that impaired vision in patients injected with radium-224.

The incidence of lens opacifications that impaired vision (cataract) was analyzed among 831 patients who were injected with known dosages of 224Ra in Germany shortly after World War II. The dependence of the incidence on dosage, i.e., injected activity per unit body weight, and on time after treatment was determined. The observations are equally consistent with proportionality of the incidence of cataract to the square of dosage or with a linear dependence beyond a threshold of 0.5 MBq/kg. The possibility of a linear dependence without threshold was strongly rejected (P less than 0.001). The analysis of temporal dependences yielded a component that was correlated with the injected amount of 224Ra and a component that was uncorrelated. The former was inferred by a maximum likelihood analysis to increase approximately as the square of the time after treatment. The component unrelated to the treatment was found to increase steeply with age and to become dominant within the collective of patients between age 50 and 60. The relative magnitudes of the two components were such that a fraction of 55 to 60% of the total of 58 cataracts had to be ascribed to the dose-related incidence. Impaired vision due to cataract was diagnosed before age 54 in 25 cases. In terms of injected activity per unit body weight no dependence of the sensitivity on age was found; specifically there was no indication of a faster occurrence of the treatment-related cataracts in patients treated at older ages.

The reverse protraction factor in the induction of bone sarcomas in radium-224 patients.

More than 50 bone sarcomas have occurred among a collective of about 800 patients who had been injected in Germany after World War II with large activities of radium-224 for the intended treatment of bone tuberculosis and ankylosing spondylitis. In an earlier analysis [H. Spiess and C. W. Mays, in Radiation Carcinogenesis. (C. L. Sanders et al., Eds.) pp. 437-450. USAEC Symposium Series 29, CONF-720505, 1973] it was concluded that, at equal mean absorbed doses in the skeleton, patients with longer exposure time had a higher incidence of bone sarcomas. The previous analysis was based on approximations; in particular, it did not account for the varying times at risk of the individual patients. In view of the implications of a reverse protraction factor for basic considerations in radiation protection, the need was therefore felt to reevaluate the data from the continued follow-up by more rigorous statistical methods. A first step of the analysis demonstrates the existence of the reverse dose-rate effect in terms of a suitably constructed rank-order test. In a second step of the analysis it is concluded that the data are consistent with a linear no-threshold dose dependence under the condition of constant exposure time, while there is a steeper than linear dependence on dose when the exposure times increase proportionally to dose. A maximum likelihood fit of the data is then performed in terms of a proportional hazards model that includes the individual parameters, dose, treatment duration, and age at treatment. The fit indicates proportionality of the tumor rates to mean skeletal dose with an added factor (1 + 0.18.tau), where tau is the treatment time in months. This indicates that a protraction of the injections over 15 months instead of 5 months doubles the risk of bone sarcoma.

Risks of leukemia in Japanese atomic bomb survivors, in women treated for cervical cancer, and in patients treated for ankylosing spondylitis.

The dose-response relationship for radiation-induced leukemia was examined in a pooled analysis of three exposed populations: Japanese atomic bomb survivors, women treated for cervical cancer, and patients irradiated for ankylosing spondylitis. A total of 383 leukemias were observed among 283,139 study subjects. Considering all leukemias apart from chronic lymphocytic leukemia, the optimal relative risk model had a dose response with a purely quadratic term representing induction and an exponential term consistent with cell sterilization at high doses; the addition of a linear induction term did not improve the fit of the model. The relative risk decreased with increasing time since exposure and increasing attained age, and there were significant (P < 0.00001) differences in the parameters of the model between datasets. These differences were related in part to the significant differences (P = 0.003) between the models fitted to the three main radiogenic leukemia subtypes (acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia). When the three datasets were considered together but the analysis was repeated separately for the three leukemia subtypes, for each subtype the optimal model included quadratic and exponential terms in dose. For acute myeloid leukemia and chronic myeloid leukemia, there were reductions of relative risk with increasing time after exposure, whereas for acute lymphocytic leukemia the relative risk decreased with increasing attained age. For each leukemia subtype considered separately, there was no indication of a difference between the studies in the relative risk and its distribution as a function of dose, age and time (P > 0.10 for all three subtypes). The nonsignificant indications of differences between the three datasets when leukemia subtypes were considered separately may be explained by random variation, although a contribution from differences in exposure dose-rate regimens, inhomogeneous dose distribution within the bone marrow, inadequate adjustment forcell sterilization effects, or errors in dosimetry could have played a role.

Malignancies in patients treated with high doses of radium-224.

Predominantly from 1945 to 1955, a group of patients in Germany was treated with multiple injections of the short-lived alpha-particle emitter (224)Ra. The patients suffered from ankylosing spondylitis, tuberculosis and in a few cases from other diseases. The "Spiess study" (study I) follows up the health of 899 of these patients; it includes most of the patients who were treated with high doses (mean bone surface dose: 30 Gy, mean specific activity: 0.66 MBq/kg), and nearly all of those treated under the age of 21 years. The most striking consequence of the (224)Ra injections was the occurrence of 56 malignant bone tumors. They appeared in a temporal wave that peaked around 8 years after exposure. A new analysis was recently performed, because a reassessment of the dosimetry resulted in changed bone surface doses, especially for the patients treated at younger ages. Averaged over all ages at exposure, the estimated risk coefficient is in general agreement with earlier analyses. However, there is now an increase in bone tumor risk that is significantly greater for younger ages at exposure. The earlier finding of an inverse protraction factor is confirmed. During the most recent years of follow-up, a significant excess of nonskeletal solid malignancies has become manifest. In 1998, a significant increase of breast cancer incidence, of soft tissue malignancies, of thyroid carcinomas, and of liver, kidney and bladder cancer was found. An eightfold increased risk of mammary cancers in those treated at a young age is particularly striking. Equally notable are two cases of breast cancer in male patients. To identify potential confounders, a control group of tuberculosis patients not treated with (224)Ra was established. The comparison confirms that the (224)Ra treatment is responsible for most of the excess of mammary cancer.

Management of refractory ankylosing spondylitis and related spondyloarthropathies.

Ankylosing spondylitis is the prototype of an interrelated group of disorders termed spondyloarthropathies, which include reactive arthritis, psoriatic arthritis, and rheumatic disorders associated with inflammatory bowel disease. It can be difficult to differentiate between these disorders because they may occur simultaneously or sequentially. In addition, some of the clinical characteristics of these diseases, such as enthesiopathy and eye involvement, are similar no matter what the diagnosis. The monitoring, diagnosis, and treatment of these diseases are related more to their clinical presentation than to the precise diagnosis.

Chronic myelogenous leukemia following repeated radiation therapy for histiocytosis X.

Low dose radiotherapy has been used to treat a variety of benign disorders including Histiocytosis X. Ionizing radiation may be leukemogenic with leukemia developing between 3.5 to 11 years after exposure. Twenty to 30% of these leukemias are chronic myelogenous leukemia (CML). In this report the rare development of PH1 + CML 11 years after radiation therapy for Histiocytosis X is recorded.

Mortality, course of disease and prognosis of patients with ankylosing spondylitis.

Patients with ankylosing spondylitis (AS) have about a 50% increased risk of mortality on the basis of the limited amount of data available. There is some evidence that the progression of disease is strongest in the first 10 years of disease but it is also clear that the disease keeps on being active for further decades. The overall burden of disease is similar to rheumatoid arthritis but the overall disease duration of AS is longer. Prognostic factors have also not been studied extensively in AS but it seems clear that early hip involvement indicates a worse outcome. The same is true for early limitation of spinal mobility, laboratory evidence of ongoing disease activity (ESR, hypergammaglobulinemia), peripheral arthritis and dactylitis. The significance of organ involvement for the prognosis, especially in the kidney in the form of amyloidosis, and in the heart and lungs, is less clear. Radiation therapy of the spine, which had been performed quite extensively in former decades, has been associated with a mean radiation dose of about double that of atomic bomb survivors and an increased risk of leukemia and mortality. This therapy has been largely abandoned nowadays. Elder rheumatologists report however that the clinical improvement of irradiated patients has been partly impressive.

Ankylosing spondylitis--the history of medical therapies.

This is a concise overview of the history of medical therapies for patients suffering from ankylosing spondylitis. Recent therapeutic advances are also summarised.