Pamidronate: a novel treatment for the SAPHO syndrome?

H. Marshall, J. Bromilow, A. L. Thomas and N. K. Arden1,

Department of Rheumatology, Portsmouth Hospitals' NHS Trust, Portsmouth and
1 Department of Rheumatology, Southampton General Hospital, Southampton, UK

SIR, The SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and osteitis) was first described by Chamot et al. in 1987 [1]. It can occur at any age but usually appears between childhood and middle age. The most troublesome symptom is bone pain, which most often affects the anterior chest wall. Dermatological features include pustulosis of the palms and soles, pustular psoriasis, acne conglobata or fulminans and hydradenitis suppurativa [2].

Radiological findings include osteolysis, osteitis, hyperostosis, osteosclerosis and, eventually, ankylosis [3]. Bone scintigraphy shows increased isotope uptake in the anterior chest wall in 70–90% of cases [4]. Histologically, the bone shows features suggestive of subacute or chronic sterile osteomyelitis [5], although it can appear Pagetoid [6].

The natural history of SAPHO follows a prolonged relapsing and remitting course [7]. As patient numbers have been small, evidence for treatments has been based on anecdotal evidence and small case–control studies. Treatments thought to be of benefit include tetracycline [8], azithromycin [9], colchicine and calcitonin [10]. Corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs) can produce symptomatic improvement, but are limited by their potential side-effects in long-term use.

We postulated that intravenous disodium pamidronate, a bisphosphonate that reduces bone turnover, would be beneficial in the management of this syndrome as bone biopsies often demonstrate evidence of increased bone turnover, often similar in appearance to Paget's disease, and calcitonin, which reduces the rate of bone turnover, has previously shown benefit.

A 49-yr-old female presented in 1991 with sacroiliac and anterior chest-wall pain. On examination, she was tender over the right first and second costochondral joints and had a palpable swelling over the right sternoclavicular joint. Investigations revealed a high erythrocyte sedimentation rate (ESR) of 58 mm/h and alkaline phosphatase of 127 IU/l. All other investigations, including biochemistry, routine haematology and radiographs of the joints involved, were normal. She was treated with an NSAID and her pain settled.

Two months later she developed pustulosis of her palms and soles, which was treated with topical steroids. In 1992 she had an increase in pain in her lower back, right shoulder and left hip. The palpable tender swelling over her right sternoclavicular joint was again noted on examination. X-rays at this time showed some sclerosis of the lumbar spine at L4 and L5. Technetium 99m bone scintigraphy revealed increased uptake at the right sternoclavicular joint and anterior aspect of the first rib. Computed tomography (CT) of the anterior chest showed an expanding lesion in the cartilaginous portion of the anterior aspect of the right first rib. This lesion was biopsied and reported as a low-grade osteomyelitis but labelled ‘Pagetoid’ because of the very striking irregular sclerosis of the majority of the trabeculae.

Her disease underwent a period of relative stability, with the symptoms controlled by simple analgesia. In 1998 she developed episodic, severe pain in the right anterior chest wall with marked swelling, erythema and tenderness over the right sternoclavicular joint and first rib. She also complained of less severe pain affecting the neck, shoulders and hips. The flares of her musculoskeletal symptoms coincided with flares of her palmoplantar pustulosis. Each attack lasted 1–2 weeks out of every month. She was unable to continue her normal work as a hairdresser. Investigations at the time revealed an ESR of 49 mm/h and a C-reactive protein (CRP) concentration of 20 mg/l (normal range 0–5).

Radiographs of the cervical spine and sternoclavicular joints demonstrated sclerosis of the vertebral bodies at C5 and C6, the manubrium and the medial end of the right first rib. An isotope bone scan (Fig. 1) showed increased isotope uptake at these sites in addition to the anterior end of the left second rib and the lower lumbar spine. CT of her sternoclavicular joints was consistent with a diagnosis of SAPHO.

The patient received three intravenous pulses of 30 mg of pamidronate (Aredia Dry Powder; Novartis) over a 5-month period and was followed up for 8 months. During this treatment, regular samples were taken for standard bone biochemistry, inflammatory markers, haematology, osteocalcin, bone-specific alkaline phosphatase and urine collagen cross-links.

During treatment, the palmar pustulosis continued unchanged but the associated attacks of musculoskeletal pain were dramatically reduced in terms of severity and duration such that, after the three treatments, she was completely pain-free and able to return to work. The benefit of each pulse of pamidronate appeared to last for approximately 10 weeks before mild pain began to recur and she needed a subsequent pulse. There was a gradual fall in CRP from 20 to 8 mg/l during treatment, but no significant change in the ESR or markers of bone turnover.

This case study demonstrates significant and rapid symptomatic benefit from intravenous pamidronate therapy in a woman with SAPHO. It may be that a similar response could be achieved using oral bisphosphonates; however, they were not used in this case as the patient had oesophagitis.



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FIG. 1.  Isotope bone scans of lateral neck and sternal views.

 

Notes

Correspondence to: N. K. Arden, Department of Rheumatology, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. Back

References

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Accepted 26 June 2001