Treatment of SAPHO with pamidronate

P. A. Courtney, D. J. Hosking, K. J. Fairbairn and C. M. Deighton

Department of Rheumatology, City Hospital, Hucknall Road, Nottingham NG5 1PB, UK

SIR, SAPHO is a syndrome of synovitis, acne, pustulosis, hyperostosis and osteitis [1, 2]. We report the resolution of symptoms following intravenous pamidronate in a SAPHO patient with pain which was refractory to conventional treatment.

A 42-yr-old male presented with severe anterior chest pain over the sternum. The pain occurred spontaneously but was exacerbated by movement and the application of pressure. On examination he was tender over the sternum and the sternoclavicular joints. There was pustulosis of the palms and soles, in keeping with psoriasis. The remainder of the physical examination was unremarkable.

Investigations showed that the erythrocyte sedimentation rate (ESR) was elevated at 50 mm/h but C-reactive protein was normal at <5 mg/ml. The bone profile, including alkaline phosphatase, was normal. Chest radiography showed prominent calcification of the chondral cartilages with osseous fusion of the first rib costal cartilages and hypertrophic new bone anteriorly. Isotope bone scan (Fig. 1AGo) showed intensely increased activity in the manubrium sterni, particularly on the right side and in the first segment of the body of the sternum. Radiographs of the sacroiliac joints were normal.



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FIG. 1. Isotope bone scans (A) before and (B) after treatment with intravenous pamidronate. The scans show intensely increased activity in the manubrium sterni and the first segment of the body of the sternum. When allowance is made for the scanning technique, there is no significant difference between the two scans.

 
The clinical features and investigations resulted in a diagnosis of SAPHO. Treatment with non-steroidal anti-inflammatory drugs and analgesics failed to control his symptoms. Salazopyrin (sulphasalazine) and methotrexate were ineffective, as were oral and intramuscular corticosteroid. The painful area was diffuse and considered unsuitable for local injection. For 5 yr, during these treatments, the patient continued to have severe pain and difficulty with his work as an air-traffic controller.

A trial of intravenous pamidronate was commenced (60 mg given at intervals of 3 months). The urinary hydroxyproline:creatinine ratio was measured prior to each infusion as an assessment of osteoclast function and bone turnover. The ratio was 21.8 (normally <20) prior to treatment and subsequent values decreased with pamidronate therapy, as shown in Fig. 2Go. Following the third infusion (6 months after starting treatment) the patient reported a marked improvement in the chest pain to the extent that he was asymptomatic. The treatment continued for seven infusions and he remains asymptomatic 6 months after the treatment stopped. The ESR after pamidronate treatment was 28 mm/h. However, repeat isotope bone scan at this time (Fig. 1BGo) was not significantly different from the baseline study, given the difference in scanning technique.



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FIG. 2. Urinary hydroxyproline:creatinine ratio. Intravenous pamidronate was given at time 0 and at intervals of 3 months.

 
Aseptic hyperostosis of the clavicles associated with pustulosis of the palms and soles may be linked to spondyloarthropathy, approximately one-third of SAPHO patients fulfilling the criteria for spondyloarthropathy [3], but there is no association with HLA B27. Two open studies in ankylosing spondylitis and seronegative spondarthropathy have reported significant beneficial effects with intravenous pamidronate therapy [4, 5]. There is increasing interest in the use of pamidronate for SAPHO. Sayag-Boukis et al. [6] performed an open trial of intravenous pamidronate (60 mg daily for 3 days) in six SAPHO patients, which has been presented in abstract form. All six patients achieved at least a 50% improvement in pain within 2 weeks of the infusion. Van Doornum et al. [7] reported the resolution of symptoms in one SAPHO patient and a 50% reduction in another with intravenous pamidronate treatment. These patients had a single infusion of 30 mg of pamidronate. Previous studies have not reported bone turnover markers or bone scan appearances after treatment.

Bisphosphonates are synthetic analogues of pyrophosphate and are potent inhibitors of bone resorption. They have a major therapeutic role in the management of Paget's disease, hypercalcaemia of malignancy and osteoporosis [8]. Bisphosphonates and the nitrogen-containing bisphosphonates, such as pamidronate, bind to mineral bone surfaces and inhibit osteoclast activity by reacting with the mevalonate pathway, which is critical in the synthesis of the ruffled border needed for resorption [9]. The histopathology of the sternoclavicular joints in SAPHO patients shows accelerated bone turnover characterized by an increase in the number of osteoblasts and osteoclasts [10]. Despite the marked radiological changes, alkaline phosphatase levels are often normal, as in this case. The fall in urinary hydroxyproline:creatinine ratio after pamidronate therapy (Fig. 2Go) may reflect a decrease in osteoclast activity and thus bone turnover with treatment. There is also some evidence that bisphosphonates may have an effect on the chronic inflammatory response by suppressing interleukin 1, tumour necrosis factor {alpha} and interleukin 6 [11]. The unchanged appearance of the sites of increased uptake on the bone scan after treatment in this case suggests that the pamidronate may only partially suppress the disease process, despite the improvement in symptoms. Quantitative bone scans before and after treatment, as now used in Paget's disease [12], may provide a more precise indication of changes in bone turnover in future studies of treatment interventions in SAPHO.

The pain relief in this case may have been coincidental but the response occurring after 6 months of pamidronate therapy is in line with the findings for spondyloarthritis. The overall prognosis in SAPHO is good [13], but some patients continue to have disabling pain. Bisphosphonates have been shown to be relatively well tolerated, and we suggest that intravenous pamidronate may be a useful alternative in these circumstances when conventional treatment has been ineffective.

Notes

Correspondence to: P. A. Courtney. Back

References

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Accepted 25 March 2002