1198 LETTERS

Therapeutic and direct neurotoxic effects of gold therapy

To the Editor: We were interested in the paper by Levine et al that

described their study of the neurotoxic effects of gold therapy in rats (Levine JD, Goldstine J , Mayes M, Moskowitz MA, Basbaum AI: The neurotoxic effects of gold sodium thiomalate on the peripheral nerves of the rat: insights into the antiinflammatory actions of gold therapy. Arthritis Rheum 29:897-901, 1986). The authors’ main finding, that gold has direct neurotoxic effects, is in keeping with the results of a study that we published in 1980 (Katrack SM, Pollock M, O’Brien CP, Nukada H, Allpress S, Calder C, Palmer DG, Grennan DM, McCormack PL, Laurent MR: Clinical and morphological features of gold neuropathy. Brain 103:671-693, 1980). Since our study seems to have escaped attention, we will briefly describe our main findings.

Our interest in this problem was stimulated by 3 patients who developed peripheral neuropathies while re- ceiving gold therapy. Two of them had the unusual clinical features of myokymia. Their cumulative doses of gold were 490 mg, 1,310 mg, and 1,350 mg, respectively. In parallel experimental studies in hens, we found that gold produced a dose-related neuropathy , with histologic findings of axonal degeneration and segmental demyelination. Similar path- ologic findings were noted in the sural nerve biopsy speci- mens from our 3 patients. We concluded that the neuropathic effects of gold were probably the result of a direct toxic effect.

Unlike Levine and coworkers, we did not find a selective loss of unmyelinated nerve fibers, and we drew no parallel between neurotoxicity and therapeutic effects of gold.

D. M. Grennan, MD, FRCP University of Manchester Salford, UK D. G. Palmer, MD, FRACP M. Pollock, FRACP University of Otago Dunedin, NZ

To the Editor: We appreciate the comments of Dr. Grennan and

colleagues. We were aware of their important light micros- copy study of the neurotoxic effect of gold on myelinated fibers in the hen. Our electron microscopy study, however, was directed at the effects of gold on unmyelinated fibers that contain neuropeptides. That we did not observe a statistically significant effect of gold on myelinated afferents may reflect the number of animals studied. Given the known toxic effect of heavy metals on the peripheral nervous system, it is likely that gold will exert some of its effects on myelinated, as well as unmyelinated, fibers.

Jon Levine, MD, PhD Allan Basbaum, PhD University of California San Francisco, CA

Reply to letter by Casey et a1

To the Editor: We read with interest the letter by Casey and co-

workers regarding the beta-2-microglobulin (P2M) origin of dialysis-related amyloid (1). When we published a report on our first case of amyloid arthropathy in March 1985 ( 2 ) , we suggested that when the potassium permanganate method was used ( 3 ) , the amyloid deposits were of the AA type. Admittedly, this is not specific enough to ascertain the type of the protein subclass.

At that time, specific antibodies were not available to further characterize these amyloid deposits. Since then, we have tested the amyloid deposits in our 2 previously de- scribed patients (4), with specific antibodies directed against P2M (Dakopatts, Copenhagen, Denmark). Positive results were obtained in both cases, using an immunoperoxidase (peroxidase-antiperoxidase) technique. This amyloid mate- rial has been shown to be related to P2M, and indeed, confirms the findings of other investigators (5-7).

J. P. Huaux, MD H. Noel, MD J. M. Vandenbroucke, MD C. van Ypersele de Strihou, MD C. Nagant de Deuxchaisnes, MD St-Luc University Hospital Brussels, Belgium

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Casey TT, Stone WJ, DiRaimondo CR, Page DL, Gorevic PD: Dialysis-related amyloid is amyloid of beta-2-microglobulin

origin (letter). Arthritis Rheum 29:1170, 1986 Huaux JP, Noel H, Bastien P, Malghem J , Maldague B, Devogelaer JP, Nagant de Deuxchaisnes C: Amylose articulaire, fracture du col fkmoral et hemodialyse periodique chronique. Rev Rhum Ma1 Osteoartic 52:179-182, 1985 Wright JR, Calkins E, Humphrey RL: Potassium permanganate reaction in amyloidosis. Lab Invest 36:274-281, 1977 Huaux JP, Noel H, Malghem J, Maldague B, Devogelaer JP, Nagant de Deuxchaisnes C: Erosive azotemic osteoarthropathy: possible role of amyloidosis (letter). Arthritis Rheum 28:

Gorevic PD, Casey TT, Stone WJ, DiRaimondo CR, Prelli FC, Frangione B: Beta-2-microglobulin is an amyloidogenic protein in man. J Clin Invest 76:2425-2429, 1985 Gejyo F, Yamada T, Odani S, Nakagawa Y, Arakawa M, Kunitomo T, Kataoka H, Suzuki M, Hirasawa Y, Shirahama T, Cohen AS, Schmid K: A new form of amyloid protein associated with chronic hemodialysis was identified as beta 2-microglobulin. Biochem Biophys Res Commun 129:701-706, 1985 Shirahama T, Skinner M, Cohen AS, Gejyo F, Arakawa M, Suzuki M, Hirasawa Y: Histochemical and immunohistochemi- cal characterization of amyloid associated with chronic hemo- dialysis as beta-2-microglobulin. Lab Invest 53:705-709, 1985

1075-1076, 1985

Eosinophilic synovitis and urticaria: an association with symptomatic dermatographism or urticaria1 vasculitis?

To the Editor: Brown and associates (1) have recently described an

interesting new subset of patients who have dermatographism associated with eosinophilic synovitis and, in some cases, elevated IgE levels. Warin and Champion (2) have identified