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LETTERS

Elkon I(B. Skellr S. Parnassa A, Moller W, Danho W, Weisshach H, et al. Identification and chemical synthesis of a ribosomal protein antigenic determinant in systemic lupus erythematosus. Proc Natl Acad Sci U S A 1986;83:7419~-23. ,4vramcas S. Coupling of enzynics to protcins with glutaraldehydc: use of the conjugates for the detection of antigens and antibodieh. lnimunochemisti y lYhY;6:43-52. Derksen RHWM, van Dam AP. Gmelig Meyling FHJ, Rijlsma JWJ, Smeenk RJT. A prospective study on antiribosomal P protein in two cases of familial lupus and recurrent psychosis. Ann Kheum Dis 1990;49:779-82. Van Dam AP. Nossent 1-1. de Jong J, Meilof J. ter Rorg E-J. Swaak T, et al. Diagnostic values of antibodies against ribosomal phospho- proteins: a cross sectional and longitudinal study. J Rheuniatol 1991;18:1 U26 ~ 34.

Reply To t k Editor:

The carboxyl-terminal 22-amino acid (C-22) synthetic peptide that was used in our study was chemically synthesized by the solid-phase method developed by Merrifield (l), using a 430A automated peptide synthesizer (Applied Biosystems, Foster City, CA) as described by Elkoii et al (2). The purity of the peptide was confirmed as >99% hy analytic HPLC, amino acid analysis, and microsequelicing. We therefore have no conccrns about thc purity of the (2-22 peptide that was used in our study.

Binding of the C-22 peptide without a carrier protein to the wells of microtiter platcs (Nunc-imniuno module Maxi- sorp; Nunc, Roskilde. Denmark) was reexamined. The use of buffered solutions (e.g., c ~ h o n i ~ t e buffer, pH 9.6) was recom- mended by the manufacturer to immobilize hydrophilic pep- tides such its the C-22 peptide 10 Ihe wells of microtitcr platcs (Nunc-immuno modulc Maxisorp). Wc uscd 0.lM carbonate buffcr. pH 9.0. to immobilize the (1-22 peptide to the wells of microtitcr plates (Nunc-inimuno module F8 Maisorp). hlicro- titcr plates were coated overnight at 4°C with 100 pl of various concentrations (0 pg/nil> 1 pglml, 5 pgiml, 10 pginil. or 15 pgiml) o f thc C-22 peptide in 0.1M carhonate buffer. pH 9.0. One hundred microliters of reaction buffer containing serially diluted antirihosornal P protein antibocly-positive serum or antibody-negative seruni from patients with systemic lupus erythematosus (SLL) was added to each well in triplicate. The ELlSA sequential procedure was performed as described in our previous sludy.

As shown in Figurc 1, optical dcnsity (OD) values in antiribosomal P protein antibody-positive serum increased when increased concentrations of the C-22 pcptidc were added to the wells of microtiter plateb, but OD valucs did not increase in antibody-negative serum. OD valucs in positive serum did not increase in microliter plates that wcrc not coated with the C-22 peptide (data not shown). Purificd human IgG antiribo- sotnal PO protein antibodics from patients with SLE (3) also reacted with C-22 peptide that was inimobilized to wells (data not shown).

These results suggest that binding of the C-22 peptide increased when increased concentrations of the C-22 peptide wcrc added to the wells of microtiter platcs. We therefore have no concerns about this binding of highly purified C-22 peptide in 0.1M carbonate bufl’er, pH 9.0, to thc wells o€ microtiter plates (Nunc-inimuno module Mitxisurp).

Serum dilution

Figure 1. Keactivity or serially diluled antiribosomal P protein antibody--positive serum from a patient with systemic lupus erythem- atows (SLE) in wells coated with 1 pgirnl (3). 5 &ml (a), 10 Ggiml (A), and 15 &ml (+) of highly purified carboxyl-terminal 22-amino acid (C-22) synthctic pcptidc, comparcd with reactivity of serially diluted antiribosomal 1’ protein antibody--negative serum from anothcr patient with SLE in wells coated with 1 ~ g i m l (a). 5 p g h l (l), 10 pglrnl (A). arid 15 ~gml (.’,.) of highly purified C-25 syiithetic peptide.

In their study, Isshi and Ilirohata did not identify the source of their 06-well microliter plates (4). We suppose that the discrepancy between the results obtained and our own results may be due t u the d microtiter platcs uscd and differences in the pH ol’ the buffcrcd solutions uscd to dissolve the (‘-22 pcptidc.

Tali~i Yoshio, ML) Jun-Ichi Masuyama, MD Masahiro Iwanioto. MD Akio Miriiori, hlD Akira l’akeda, MD Hitoaki Okazaki, MD Sliogo Kano, MU Seiji Minota, MU Jichi Mrdical School Toch igi- ken. J ~ p i i ~ i

1. Merrifield PB. Solid-phase peptide synthesis. J .4m Chem Soc

S. Parnassa A, Moller W, Dilnho W. Weissbach H, ct al. ldcntification and chemical synthesis of a ribosomal protein antigenic determinant i n systemic lupus crythcmatosus. Proc Nat l Acad Sci U S A l986;83:7419--23,

3. Ywhic) T. Masuyarua J - I . Kauo S. Antiribosomal PO protein anlibodies react with the surface of human umbilical vein cndothe- lial cells. J Rheumatol 1996;23:131 1-2.

3. lsshi K, Hirohata S. Association of anti-ribosornal P prolein antibodies with ncuropsychiatric systemic lupus eiytlirinato~us. Arlhrilis Rheum 199h;39:14X3-9O.

Fibromyalgia: more questions and implications

To the Editor: Rcccnt multicenter studies indicate that conventional

medical carc docs not reduce costs or alter the prognosis or

LETTERS 1139

outcome of fibromyalgia (1.1). This is sad ncws considering the rising incidence of this disorder. These fiiidings raise addi- tional questions about fibromyalgia and its diagnosis and treatment: 1) Could the high incidcnce of anxiety and depres- sion, perhaps not optimally controlled, in fibromyalgia he rclatcd to these reported findings that prognosis is not im- proved with convcntioiial mcdical care? 2) Are many patients led to believe they have an intractable disease for which treatment options are limited, instead of taught that pain ran be controlled by techniques that involve active patient partic-

3) What constitutes conventional medical care? Since ciplinary treatment has been shown to be promising

(3) but was not utilixd in these reported studies (1,2), were f'ewrr patients seen by mental health professionals and re- ferred lor seK-help and long-term exercise programs? 4) Have patients with predominantly psychological conditions been included in thc fibromyalgia group because o f the presence o f tcnder points?

Thc rclationship of anxicty and depression to fihroiiiy- algia is well recognized, but needs to be determined for each patient. As noted by Winfield (5) and others (6,7), tender points as described in the American College o f Rhcumatology (ACR) criteria for fibroinyalgia (4) caii also occur in psycho- logical distress a iid sornatization disorder, thus decreasing the specificity for fibromyalgia. These patients need psychological therapy, which could be overlooked if their disorder is labeled as simple fibromyalgia. Pcrhaps the prcscncc of diffuse tender points. hotli within and outside o f the anatomic ACR criteria locations: is suggestive of a psychogenic ctiology. We need better diagnostic categories to describe these patients.

It has hcen suggested that fibromyalgia may not be a distinct entity, but "one end of a continuous spectrum," including psychological distress and somatization disorder (5).

ociated features of fibromyalgia, such as fatigue, restless sleep, headache, numbncsa, and irritable bowel syndronic, may occur from activation or down-regulation of specific neural circuits in the context of a central pain sensiti- zation state ( X ) . Psychological syndromes, such a s anxiety and depression, also fit into this neurophysiologic picture, expand- ing the spectrum of clinical manifestations.

As suggested by Winfield ( 5 ) , a d d i h n a l studies are indicated. These should include further evaluation of factors known to amplify pain, such a s depressive emotiorial states. Temperament. belief systems, and cultural factors tnay a l so play pivotal roles in certain patients. 'l'hose who believe they have serious disease and that pain always requires medication for relief' (a belief' not inti-cqucntly promoted by hcalth care providers) may he resistant to accepting nonpharmacologic therapies involving active patient participation, such as educa- tion and exercise. Cultural factors can iniluence patients' attitudes toward psychological comorbidities and their willing- ness to involve mental health professionals in thcir trcatnicnt when indicated. In my cxpcricnce, thcsc difficulties are partic- ularly prevalent in the rural South.

We need to improvc our understanding of the many variables aJfecting chronic musculoskeletal pain (9). broaden our clinical concepts, and individualize therapies. Psychosocial factors relating to symptoms should be considered in these patients who h a w no characteristic physical and laboratory lindings other than tender points. Our goal shocild be to decrease thc number of patients with intractable symptoms

who lead poorer-quality lives nnd who h,ne high levch ut health care utilizdtion. with aawudted high ~ 0 ~ 1 5 Kheum,itolcr- gists and piimar) care phyiicians may hnve niore t o oifei theia patients by coordinating rathcr than providing, direct cnre

Stephen C; <;elfrind, MU Bel(1rii. MS

I. Wolfe F, Anderson J, Harkriess D, Bennett RM, ('aro XJ. C;oltl- enberg DI., et al. A pvoyxctive, longitudiiial. niulticenter study of service utilization and costs in fibromyalgia. ht l i r i t ib Khcum 1997;4(3:1500-70.

2. Wolfe F, Anderson J, Harkness D, Bennett RM, Car(> SJ, CL;olcl- enlierg UL. et al. Health status and disease scvcr results of a six-centcr loiigitiidinal study. Arthrit 157 1-9.

3. nenriett RM. Campliell S, Burclihardt C, Clark SK. O'llcilly C'~ Wieiis A. A multi-disciplinary approach to fibioiiiyalgia ti zatmcnt. J hilusculoskclctal Mcd IYOl;X:21-32.

1. Wolfe F. Smyihe HA, Yunus MB, Bennett RM, Horn1)ard~er I:. Cioldenberg DL, et a1 e Amcrican Collcgc of l ~ l l ~ l l n l a t o l o ~ ~ IUWJ critcria f o r thc fication of fihromyalgin: repori 0 1 the multicenter criteria committee. Arthritis Rheum 1990;33: 160-72.

5. Wiiificld JB. Fibromyalgia: what's next'? Arthritis <:are Res 1'197: 10:210-21.

6. Croft P, Scholluin J. Silman A. I'opulation study of tciidci point counts and pain as evidence of fihromyalgia. RMJ IY94:3i)Y:h9h-0.

7. Wolfe F. Ros\ K. Anderson J, Russell TJ. Heticrt L. The prevaleiicc and characteristics of fibromyalgia in i h e gericral ~~opulatiori. A - t h r i h Rheum 1995;3,4:19-28.

S. Bennett RM. Fibiornyalgia arid tlic disability dilcmma: a ncn era in understanding a complex. niultidimeiisiorial pain syiidromc. Arthri- tis Khcuiii lYY6:39:1h17-34.

9. Goldenherg DL, Mosey CJ. Schniid CIT. A model to assess severiiy and impact of fibromyalgia. J Rheumatol 1995;12:23 1.3-8.

Leishmaniasis mimicking new-onset juvenile dermatomyositis: comment on the article by Pachman et a1

70 tlw Ldifvr I read with interest the artide by €"~chni,iii et '11

comparing Llinical nncl Liborntot y featureq in children with new-onset juvenile derm~itoniyositis (juvenile DM) verw5 health? controls and children with juvenile J lieumatoid nithi I -

tis ( I ) As Pachman and colleagucq pointed out, iever,il line5 ol evidence suggest that jiicenik I>M m q hdve ,in infectmu\ trigger, such d5 KNA picornaviruses, group A B-hemolytic strcptocoui, Toxophvnci gondii, coxsdckievi~ u i 13 (C'Vl3), or hepatitii B viiu5 infection However, theii itudy rzbealed no significant differences in titers of 'intibodies to ionic intectiou\ agent5 previously implicated in the etiology of thc diwd4e ( I e Tgondii, hcrpei simplcx viru\, dnd CVB [types 1-61), ai th the cxcsption of increased entcrovual titci i in juwnile DM pa- tients and healthy contiols under 7 yean ot <ige, which suggeyted to the authors n common local enviioniiiental eupo- sure to this virus A l s o . no drffeieiiccs hetween t h c jwcnile DM and control groups were found with regaid to insect h i k c

One of the chief stdement\ m d e in tl-rc article In Pachmdn and coworkers was that, even though an inlectious agent seemed not to play a role in di5eaie pathi)genc\i\ h i e d on thc findings in their ytudy, i t may he that the relevant ,tgcnt ha5 not yct bccn identified Thi5 prompts me to call attention