vasculitis and Henoch Schönlein purpura: a comparison between the two
`disorders. J Rheum 1992; 19: 721–28.
`2 Mills JA, Michel BA, Bloch DA, et al.The American College of
`Rheumatology 1990 criterial for classification of Henoch-Schönlein
`purpura. Arthr Rheum 1990; 33: 1114–21.
`3 Tancrede-Bohin E, Ochonisky S,Vignon-Pennamen M, Flaheul B,
`Morel P, Rybojad M. Henoch-Schönlein purpura in adult patients. Arch
`Dermatology 1997; 133: 438–42.
`4 Blanco R, Martinez-Taboada VM, Rodriguez-Valverde V,
`Garcia-Fuentes M, Gonzalez-Gay MA. Henoch-Schönlein purpura in
`adulthood and childhood. Arthr Rheum 1997; 40: 859–64.
`5 Merrill J, Lahita RG. Henoch-Schönlein purpura remitting in pregnancy
`and during sex steroid therapy. Br J Rheumatol 1994; 33: 586–88.
`6 Escudero A, Lucas E,Vidal JB, et al. Drug related Henoch Schönlein
`purpura. Allegol Immunopathol (Madr) 1996; 24: 22–24.
`7 Berthoux FC, Gagne A, Sabatier JC. HLA-Bw35 and mesangial IgA
`glomerulonephritis. N Engl J Med 1978; 298: 1034–35.
`
`Bisphosphonates for pain relief in reflex
`sympathetic dystrophy?
`is a poorly
`(RSD)
`Reflex
`sympathetic dystrophy
`characterised condition whose various and unpredictable
`features include pain, tenderness, swelling, vasomotor, and
`sudomotor changes, involuntary movements, and trophic
`phenomena.1 Also known by terms such as algodystrophy,
`Sudeck’s atrophy, and complex regional pain syndrome
`(CRPS) type I, RSD most commonly follows trauma and is
`distinguished from causalgia (CRPS type II), which is
`associated with major nerve injury.
`The pain of RSD may have various qualities but is
`typically burning, spreads outside the area that has been
`damaged, and is often accompanied by sensory features,
`including allodynia and hyperalgesia. Osteoporosis is one of
`its diverse trophic features. It characteristically spares the
`articular surfaces and may be spotty,
`focal, or more
`widespread than at the site of the causative lesion.1 First
`recognised
`radiographically
`in 1900 by Sudeck,2
`abnormalities of bone have subsequently been assessed by
`isotope, computed tomographic, and magnetic resonance
`bone scanning, and by bone densitometry. Evidence for a
`blood-flow-independent inflammatory component in RSD
`has been accruing3 to support Sudeck’s suggestion of a
`pseudo-inflammatory cause
`for
`the osteoporosis he
`described. Do Sudeck’s osteoporosis (atrophy) and these
`inflammatory changes provide clues to the cause of the
`pain of RSD and suggest new approaches to its treatment?
`Although in RSD the presence and extent of the pain
`and the osteoporosis are variable and seemingly unrelated,
`treatments
`that affect
`the musculoskeletal
`system,
`sometimes also improve pain.1 It naturally followed that
`bisphosphonates, which alleviate pain in bony disorders
`such as Paget’s and malignant bone disease, should be tried
`in other painful conditions associated with abnormal bone,
`including diabetic neuro-arthropathy4 and RSD.
`Striking relief of pain in RSD following intravenous
`pamidronate was described in 1988,5 and at least three
`further open studies of intravenous pamidronate6–8 and a
`single report of a partly double-blind study of intravenous
`alendronate9 have since confirmed that pain relief occurs in
`some but not all patients. Clodronate too is said to improve
`pain.9 Pain relief can occur within 3 days of starting
`treatment5 and last for months.8,9 Improvements within a
`few weeks in the function of the affected limb and in bone
`density have also been reported.5,9 Typical side-effects of
`bisphosphonates may occur and have led to reduction of
`the planned treatment protocol.8 Pain can recur, but the
`effects of repeated courses of treatment are not known.
`
`THE LANCET
`
`COMMENTARY
`
`The use of different drugs, treatment regimens, and
`methods of assessing pain all make it difficult to reach
`definitive conclusions from these studies. Furthermore, the
`trials have each included 23 or fewer patients, patients’
`underlying conditions (although mostly post-traumatic)
`have been heterogeneous, some reports have not made
`clear how many patients had pain relief, and length of
`follow-up was unstated in some but was less than a year in
`all studies. Existing data are therefore only preliminary.
`Nevertheless the bisphosphonates, currently unlicensed for
`use in RSD, seem to be well worth further investigation in
`appropriately controlled, long-term, sufficiently studies, to
`reach conclusions on their analgesic properties and
`therapeutic benefits in this disorder.
`to
`Do
`the effects of bisphosphonates contribute
`understanding the cause of pain in RSD? These drugs bind
`to bone and inhibit bone resorption by inhibition of
`osteoclasts, but processes that affect the structure of bone
`are not necessarily those responsible for the rapid pain
`relief. Rather, pain relief may result from effects on
`prostaglandin E2 and other nociceptive substances.10
`Among the other properties of bisphosphonates is the
`ability to sensitise afferent nerve fibres, from whose endings
`various neuropeptides and neuromodulators are released
`following disease and trauma. In turn these neuropeptides,
`which produce vasodilatory and inflammatory effects that
`often resemble sympathetically mediated phenomena,11
`may contribute to pain and other sensory symptoms and
`perhaps also to trophic changes in various tissues, including
`bone.12 Further studies using bisphosphonates could prove
`valuable in elucidating the causes and treatment of both the
`pain and the osteoporosis of RSD and related disorders.
`
`GDSchott
`National Hospital for Neurology and Neurosurgery,
`London WC1N 3BG, UK
`
`1 Kozin F. Reflex sympathetic dystrophy: a review. Clin Exp Rheumatol
`1992; 10: 401–09.
`2 Sudeck P. Ueber die acute entzündliche Knochenatrophie. Arch Klin
`Chir 1900: 62: 147–57.
`3 Oyen WJM, Arntz IE, Claessens RAMJ,Van der Meer JWM, Corstens
`FHM, Goris RJA. Reflex sympathetic dystrophy of the hand: an
`excessive inflammatory response? Pain 1993; 55: 151–57.
`4 Selby PL,Young MJ, Boulton AJM. Bisphosphonates a new treatment
`for diabetic Charcot neuroarthropathy? Diab Med 1994; 11: 28–31.
`5 Devogelaer JP, Dall’Armellina S, Huaux JP, Nagant de Deuxchaisnes C.
`Dramatic improvement of intractable reflect sympathetic dystrophy
`syndrome by intravenous infusions of the second generation
`bisophosphonate APD. J Bone Miner Res 1988; 3 (suppl 1): S122 (abstr
`213).
`6 Rehman MTA, Clayson AD, Marsh D, Adams J, Cantrill J,
`Anderson DC.Treatment of reflex sympathetic dystrophy with
`intravenous pamidronate. Bone 1992; 13: 116 (abstr).
`7 Maillefert JF, Chatard C, Owen S, Peere T,Tavernier C,Tebib J.
`Treatment of refractory reflex sympathetic dystrophy with pamidronate.
`Ann Rheum Dis 1995; 54: 687.
`8 Cortet B, Flipo R-M, Coquerelle P, Duquesnoy B, Delcambre B.
`Treatment of severe, recalcitrant reflex sympathetic dystrophy:
`assessment of efficacy and safety of the second generation
`bisphosphonate pamidronate. Clin Rheumatol 1997; 16: 51–56.
`9 Adami S, Fossaluzza V, Gatti D, Fracassi E, Braga V. Bisophosphonate
`therapy of reflex sympathetic dystrophy syndrome. Ann Rheum Dis 1997;
`56: 201–04.
`10 Strang P. Analgesic effect of bisphosphonates on bone pain in breast
`cancer patients. Acta Oncol Suppl 1996; 35: 50–54.
`11 Schott GD. An unsympathetic view of pain. Lancet 1995; 345: 634–36.
`12 Dray A. Neurogenic mechanisms and neuropeptides in chronic pain.
`Prog Brain Res 1996; 110: 85–94.
`
`Vol 350 • October 18, 1997
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