04 Rheumatology Pasat Present

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JAPI JAnuAry 2012 VOL. 60 21

*Diecto reseach, Cosltat Phsicia & rhematologist, P.D.Hidja natioal Hospital & MrC, Vee Savaka Mag, Mahim,Mmbai 400 016

Medical histoias do eed to emembe that the cotet ofmedical kowledge oght ot to be bied beside the geat me.

C. Boyce. Lancet 2011; 378 : 655-56

. the kowledge which is o pivilege todato acqie so eal has cost othes. We ae, all of s, debtos too pofessio

William Osler1

Mscloskeletal disodes (MSD) ae likel as old as thehomosapiens. The rst recorded evidence of MSD appearsin Ebers Papyrus wrien around 1500 BC. It describes whatappeas to be athitis defomas (pobabl hematoid athitis- rA). Paleopathological stdies of Egptia mmmies sggest

existece of rA i Egptias. G. Elliot based o his stdies,coclded that rA was pa excellece the disease of Egptias.2Ma athoities, howeve, do ot agee ad coside rA to bea mode disease.

In the Indian literature, Charak Samhita (approx 300 200 BC)*descibes pai, joit swellig ad loss of fctio.3 I a eceteappaisal Aceves-Avila et al claim that rA is a old disease.4

Hippocrates described arthritis 2400 years back (400 BC). Fora log time the tem athitis was sed loosel withot efeeceto any specic form of arthritis.

Gale (129-216 AD) itodced the tem hematisms.Camoe (1940) coied the tem hematologist while the wodrheumatology appears for the rst time in the text book by

Hollade (1949).5

Rheumatic disorders were aributed to humors (rheuma).It was postulated that a substance i.e. humor, ows, seles injoints, and causes arthritis. Paracelsus (1493-1511) postulatedthat sbstaces that cold ot be passed i ie accmated, gotpecipitated i joits, ad cased athitis. Aveda cosideedathitis as oe of the Vata.

Sice the, hematolog has come a log-logwa. It is omoe a also bach of medicie. no moe is a hematologistqestioed bt what ca o do ? Thee is toda vitallo bach of iteal medicie that pobabl does ot iteactwith rheumatology. The present article aempts a brief reviewof evoltio (histo) of hematolog pto the peset time

ad peeps ito (ead deams) the fte.

The Rheumatic DiseasesA disease is born when named

Slowl bt sel fom the all pevasive diagosis of athitisidividal disease etities have bee ecogized. Pesetl moethan 100 specic rheumatic diseases are known. There surelyare more to be dened.

Amogst the fist to be defied wee got, hematoidathitis, osteoathitis, ad hematic feve.

Rheumatoid arthritis2,5,6

Thomas Sdeham had ecogized a cipplig fom ofchoic athitis, (most likel hematoid athitis). Lode Beauvais (1880) most likely also described it. Brodie pointed outits choic pogessive cose ad oted that tedo sheaths adbursae can be aected. Further, he recognized that the diseasebegins as synovitis and cartilage damage may follow. A B Garrod(1858) coined the term rheumatoid arthritis (RA) replacing theold tems athitis defomas ad hematic got. To himgoes the cedit of cleal sepaatig hematoid athitis fomosteoarthritis and gout. The radiologic features of RA were rstdescribed by Bannatyne (1896).

Gout5

The credit of much that we know of gout goes to Alfred BGarrod. Before him, Leeuwenhock (the father of microbiology)had descibed micoscopic appeaace of ate cstals (1634)and Sydenham had vividly described acute aack of gout, himselfbeing a suerer. The contributions of Garrod are i) quantitativeassay (gravimetric) to detect hyperuricaemia (1847) ii) threadtest to demonstrate urate crystals (1854) iii) demonstrationof ate cstals i joit ad soft tisses iv) postlatig thathpeicaemia ma be the eslt of ovepodctio o deexcretion (by the kidneys) v) wrote a monogram on gout (1859).

Osteoarthritis5

Osteoathitis is a disease of atiqit. The tem osteoathitiswas introduced by Spender in 1886. The credit for its modernconnotation goes to Archibald E Garrod (1907). Much earlier(1802) Heberden had noted the nodes, (Heberden nodes)ad diffeetiated them fom tophi. Gaod idetified theconnection between the nodes and the joint disease. Bouchard(1884) described the nodes at proximal interphalangeal joints(Bouchards nodes).

Rheumatic fever5

Hippocates most pobabl had descibed hematic feve.Sydenham recognized it as a separate form of arthritis (1665).Involvement of heart was described by Dundas in 1808. He used

the term rheumatic fever. Money (1883) described myocardialgranulomas which Ascho described in detail (1904) (Aschoodles). Choea (Sdehams choea) was descibed bSdeham. Its associatio with hematic feve was oted bBright (1831) and See (1850). Its relation with streptococcalsore throat was postulated by Swift in 1928. Collis and Coburnindependently identied beta-haemolytic streptococcus as thecasative bacteim (1931). The discove of atisteptolsisb Todd completed the loop (1932).

Spondyloarthropathies(s)7

Before the concept of spondyloarthropathy (SpA) wasdeveloped by Moll and Wright (1974) diseases like ankylosingspodlitis, psoiatic athitis wee descibed as vaiats ofhematoid athitis o its atpical foms. SpA is ow ecogized

Rheumatology, Past, Present and Future

VR Joshi*

*The exact period is disputed with some claiming it to be 2000 BC oreve ealie

From the Desk of Former Editor


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as a famil of diseases that icldes aklosig spodlitis,psoiatic athitis, eactive athitis (reites sdome), athitisassociated with inammatory bowel disease and unclassiableSpA. The most chaacteistic feate of SpAs is stog associatiowith HLA B 27 and seronegativity.

Systemic lupus erythematosus (SLE)8

Historically SLE dates back to middle ages. For quitesome time the tem lps was applied to vaios ctaeoslesions. Kaposi (1872) described the systemic nature of thedisease and Osler (1900) rmly established the same. SLE istoda the pototpe coective tisse disode. The cocept

itodced of coective tisse disodes was developed bKlemprer in 1942. Cozenove (1851) introduced the term systemiclps ethematoss. Libma Sacks descibed mital valveedocaditis (1924).

Space costait does ot pemit to iclde the histo ofothe hematic disodes. A lage mbe of ca a epom.(Box 1), after the discoverer.

Diagnostic, and ClassifcationCriteria10

Most of the hematic diseases ae sdomic. The lackdenite diagnostic features, (clinical and investigative). It is

theefoe essetial to have citeia that ese ifomit ofdiagnosis, classication and epidemiological studies. Diseasespecic criteria have been developed for most of the rheumaticdisodes, majoit dig the last 3-4 decades. These havecotibted sigificatl to the pactice ad pogess ofhematolog. Citeia beig a evolvig pheomeo aepdated peiodicall.

Assessment Scales and Indices11

For similar reasons criteria have been developed to assessdisease activity e.g. DAS-28, (RA); SLEDAI (SLE); damage(vasculitis damage index); remission, cure (RA); function(HAQ, SF-36) and pain (visual analogue scale -VAS). Thesend their place not only in the research seing but also in daily

cliical pactice. Disease activit idices have empoweedhematologists to tailo/modif teatmet(s) to achievemaximm disease cotol i a objective wa ad ot based omee impessios.

These activities have bee fomlated b atioal aditeatioal associatios icldig Idia rhematologAssociatio. With all these ipts the pactice of hematologhas become more scientic and objective.

GuidelinesGidelies of maagemet have also bee developed fo most

of the hematic diseases. These too ae pdated peiodicall.

International initiativesOgoig COPCOrD (Commit Oieted Pogamme fo

Cotol of rhematic Diseases) ad the jst completed, boe adjoit decade (2000-2010) have bee two ecet majo iteatioal

initiatives. COPCORD was launched in late 1980s by WHO andIteatioal Leage Agaist rhematism (ILAr) to collectepidemiologic data (of pai ad disabilit), to impat healthedcatio ad cotol the isk factos with impoved healthcae i developig coties (gass oot developig ecoomies).Wold-wide, seveal coties have paticipated i thisprogramme. These studies have highlighted the very signicantbde of mscloskeletal disodes (MSD), emphasizig MSDsas mease of pblic health poblems.12

Bone and Joint Decade (2000-2010) was supported by WHOad uited natios. Its ageda iclded tama, athitisad osteopoosis as taget coditios. The aim was to ceateawaeess ad empowe patiets. Idia has bee a active

paticipat i both the iitiatives.

DiagnosticsMicobiolog, icldig seolog, biochemist, imagig

modalities, adioimmo ad othe assas, geetics have beea itegal pat of hematolog. Some of the impotat/ladmark developments are listed in (Box 2)

Molecular BiologyThe edice of modern rheumatology is based on advances

i molecla biolog. It is beod the scope of this aticle toelaboate the immese cotibtios of molecla biolog torheumatology. Briey, molecular biology has revealed that

Box 1 : Rheumatic diseases with eponyms 9

Schonlein; 1874 Henoch (1837)(Heoch Scholei ppa)

Feltys syndrome (1934)

Charcoats joints (1868) Weges gatomalosis(ow eamed galomatospolagiitis) (1936)

Jaccouds arthropathy (1869) Behcets disease/syndrome (1937)

Pagets disease of bone (1877) Chg-Stass sdome (1939)

Pos disease (spine) (1882) Cogans syndrome (1945)Weber Christian disease (1892) Takaass disease

(arteritis) (1945)

DeQevais teosovitis(1895)

Caplan syndrome (1951)

Poncets disease (1897) Lofgren syndrome (1953)

Stills disease (1897) Kawasaki disease (1961)

reites sdome (ow calledeactive athitis) (1916)

Sweet sdome (1964)

Tiees syndrome (1921) Lyme disease (1976)

Libma Sachs edocaditis (1923) Ati-phospholipid sdomeHughes syndrome) (1986)

Sjoges sdome (1933)

(It is a tavest of fate that ma of these e.g. reites sdome,Wegners granulomatosis were described rst by others).

Box 2 : Landmark developments

Leewehoek micoscopic appeaace of ate cstals i a tophs(1634)

X-rays of rheumatoid joints Bannatyne (1896)

Calorimetric measurement of uric acid - Folin Wu (1912)

Atisteptolsi atibodies Todd (1932)

rhematoid facto - rose ad Waale (1940)

LE cell-Hargraves (an interesting story of serendipity) (1948)

Lupus anticoagulant Conley (1952)

Antinuclear antibodies - Friou (1958)

Bone densitometry Cameron (1960)

Radioimmunoassay for 25 (OH) D3

Haddad (1971)

Association of HLA B 27 with AS - Schlosstein and Brewerton (1973)

ANCA Davis (1982)

(Despite the iceasig availabilit ad se of diagostics,hematolog emais a cliical specialit pa excellece)


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i. Molecla ad geetic evets shape diseases, theipogessio, ad espose to theap.

ii. Imme dsfctio (atoimmit) foms the basis ofma hematic diseases.

iii. HLA ad othe gee polmophisms pla a ole iatoimme diseases

iv. Imme cells, ctokies, sigallig pathwas ad mediatosof inammation are important therapeutic targets.

Therapeutic Milestonesrhematolog has diectl o idiectl cotibted to the

developmet of some of the most impotat theapetic agets,sch as nSAIDs, cotisoe, slfasalazie, ad biologics.

NSAID 2,3,13

The ealie theapies ivolved se of plat extacts of Willowbark and leaves; most contained salicin. Hippocrates, Galen,ad othes sed Willow extacts to teat pai of hematicdisorders. Madhav nidan (7 century AD) subclassiedarthritic disorders. Chakradaa in the 11th century neted phamacologic ad ophamacologic Avedic

theap. It iclded diet, local teatmets, bowel cleasigad medicated eemas, depedig po the tpe of athitisSalicylic acid was identied as the active substance byLeroux in 1929. In 1853, acetyl salicylic acid (aspirin) wassynthesized by Gerhardt. The rst nonaspirin, nonsteroidalanti-inammatory drug, phenylbutazone became availablei 1949 ad was followed b a host of nSAIDs. Thogheective, NSAIDs have signicant toxicity prole, especiallygastoitestial lces ad bleedig, eal toxicit,hypertension and oedema. Vane (1971) demonstratedthat nSAIDs ihibit postagladi sthesis b actig othe ezme cclooxgease (COX). I 1991 COX-2 (theidcible fom) was discoveed b Simmos ad the extgeeatio of nSAIDS (selective COX-2 ihibitos) wee

developed. Colchicine2

Extacted fom Atm cocs, colchicie was sed toteat acte got as fa back as 6 th century AD. A B Garrodestablished its se fo the diagosis ad theap of got.

Cortisone2

- 1930 - Kendall isolated 6 dierent compounds (A-F)fom adeal glad

- 1948 - Compound E was found to have anti-rheumaticpopeties (Kedall)

- 1948 - Hench treated the first case of rheumatoidathitis with compod E

Toda cotisoe is a itegal pat of teatmet of maiflammato hematic ad o hematic disodes(despite the love ad hate elatioship it geeates).

Methotrexate 14

- Methotrexate (MTX) was synthesized in 1950s as a folateatogoist to teat lekaemia.

- Doble-blid placebo cotolled tials wee caied otin 1980s. These established its role in the treatment ofhematoid athitis

- I 1990s the ole of folic acid spplemetatio to edcemethotexate toxicit was ealized

- Pesetl MTX is the sheetacho of teatmet of rA

eithe as mootheap o i combiatio with otheagets (DMArDs ad biologics)

Biologics 15

1975 Monocyte derived tumour necrosis (TNF) factor wasidentied its role in orchestrating inammation appreciated(1988)

1993 Anti-TNF antibodies were shown to be eective inthe teatmet of patiets with rA (1993). Pesetl thee isa explosio of biologic agets that act agaist the macompoets of imme espose sch as cells, ctokies,and signaling pathways. While highly eective, dangerof ifectio especiall tbeclosis soo became appaetleading to the (modied) concept of diagnosis and treatmentof latet tbeclosis.

Cost emais a impotat cosideatio while cosideigtheir use. Most biologics work beer in combination withmethotexate.

Antimalarials2,16

Payne (1895), rst suggested the use of quinine to treatlupus erythematosus and rheumatic diseases. In 1951 Page

demostated efficac of qiacie (mepacie) i lpsethematoss. This was followed b the se of chlooqie(Baguall 1957) and now hydroxychloroquine (HCQ). HCQ todayis sed extesivel i ma hematic diseases becase of itsmultiple benets, low toxicity, and low cost.

Gold2,17

As far as back 2000 BC, Egyptians and Chinese used gold formedicinal purposes. In 1927 Landre had recommended its useto teat hematic feve.

Gold salts were rst used to treat rheumatoid arthritis byForestier (1925) on the wrong assumption of tuberculosis as itsaetiological facto ad gold was the sed to teat tbeclosis. Ithe 1970s and 80s gold was the most commonly used DMARD.

Pesetl gold salts ae ael sed to teat rA becase of theavailability of beer and safer drugs.

Steoids, methotexate, chlooqie/hdoxchlooqie,leunomide, sulfasalazine, mycofenolate, biologics and others(cclospoie, azathiopie etc.) have evoltioized theotcome of hematic diseases.

Change in Therapeutic PerceptionEal actio ad aggessio is the ew Mata of

hematolog, especiall i case of r.A. The chage is -

RA is not a benign disease

Joint damage starts early

The best chance to control the disease eectively is as nearthe disease oset as possible. The pevios go slow, go lowpaadigm is ot acceptable.

Combination therapy is eective and not more toxic

Complete remission is possible, (albeit at present in a smallpopotio of patiets)

Pulse therapy

Some examples ae -

Methotrexate in weekly pulse doses (eective and less toxic)

Pulse cyclophosphamide treatment (Austin 1986). It has hada signicant impact on the management of SLE, systemicvasclitidis, ad othe sstemic hematic diseases.

Steroid pulse therapy for rheumatic emergencies


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Surgery 2

Before the advent of joint replacement therapy surgicalitevetios cosisted mail of sovectom ad athodesisfo sovitis ad osteotomies fo osteoathitis of kee ad hip.

Hip joit eplacemet, developed b Chale, (1961)chaged it all. Joit eplacemet has pove to be a boo topatiets with advaced joit disease, beaable pai, addisabilit. newe models have iceased the age of joit

motion, improved function (squaing and negotiating stairs ispossible with mode posthesis) ad logevit of the posthesis.

Historically Gluck (1853-1942) had suggested kneeeplacemet with implats made of ivo ad metal ad caiedot joit eplacemet i joit tbeclosis ad tmos (of hip,kee, sholde, elbow ad wist) !

Support serviceEve impovig othotics, phsiotheap, titio ad

fomatio of sppot gops have i o small measecotibted to impoved patiet cae (especiall i the moeadvaced coties).

Future Crystal-ball GazingThe wish list is lage. A few expectatios ae

Eective preventive measures

Vaccination

Preclinical diagnosis of rheumatic diseases

Magic bullets

Thee is geat hope that most if ot all ca be achieved i thepeset cet itself

Specically for India one hopes

Availability of rheumatologist (at least one) in each district

Availability of cheap and effective therapeutic agents

icldig sgical implats Scientific evaluation of systems of medicine especially

Aveda

Public education and awareness. Today there is unfortunatelya plethoa of miscoceptios ad blid faith

References1. W. W. Buchanan, J. Daqueker, History of Rheumatic Diseases, In

M. C. Hochberg, A. J. Silman, J. S. Smolen, M. Weinbla, M. H.Weisma (Eds), Rheumatology, 3d Ed. Edinburgh, Mosby 2003;1-8.

2. Milestoes i rhematolog. The Patheo pblishig Gop. Icnew yok. 1999. repited b special aagemet i Idia 2001by Panther Publishers private Limited, Bangalore.

3. D. Ashwikma rat (pesoal commicatio)

4. F. J. Aceves Avila, F. Medina, A. Fraga. The antiquity ofhematoid athitis : a eappaisal.J Rheumatol 2001;28:751757

5. T G Benedek History of Rheumatic Diseases. In J. H. Klippel (Ed).Primer on the Rheumatic diseases. Atlanta, Arthritis Foundation,1997;11:15.

6. T. Appelboom, P. Halbeg. Histo (rhematoid Athitis) I M. C.Hochberg A. J. Silman, J. S. Smolen, M. Weinbla, M. H. Weisman(Eds), rhematolog, 3d Ed. Edinburgh, Mosby 2003;753 756.

7. A. S. Russel. History (Spondyloarthropathy) In M. C. HochbergA. J. Silman, J. S. Smolen, M. Weinbla, M. H. Weisman (Eds),rhematolog, 3d Ed. Edinburgh, Mosby 2003;1145-1147

8. V. Rus. History (Connective Tissue Diseases) In M. C. HochberA. J. In Silman, J. S. Smolen, M. Weinbla, M. H. Weisman (Eds),rhematolog, 3d Ed. Edinburgh, Mosby 2003;1285 1289.

9. E. L. Maerson. Notes on history of eponymic idiopathic vasculitis.The diseases of Heoch Scholei, Wege, Chg-Stass, Hoto,Takayasum, Behcet and Kawasaki.Arth Care Res 2000;13:237-245

10. S. E. Gobiel. Classificatio of rhematic Diseases. I M. C.

Hochberg, A. J. Silman, J. S. Smolen, M. Weinbla, M. H. Weisman(Eds), rhematolog, 3d Ed. Edinburgh, Mosby 2003;912.

11. R. N. Bellamy. Principles of Outcome Assessment, In M. C.Hochberg A. J. Silman, J. S. Smolen, M. Weinbla, M. H. Weisman(Eds), rhematolog, 3d Ed. Edinburgh, Mosby 2003;21 30.

12. A. Chopa. A abdel-n asse. Epidemiolog of hemat icmusculoskeletal disorders in the developing world. Best Practiceand Research Clinical Rheumatology 2008;22:553-604

13. L. R. Ballous, B. W E Wong. Nonsteroidal anti-inammatory drugsIn G.S. Firestain, R. C. Budd, E D Harris, (Jr ), I. B. McInnes, S.Ruddy,J.S. Sergent Eds. Text Book of Rheumatology. Sounders-Elsevier.Philadelphia 2009;8:833-861

14. R. Was, G. Clunie, F. Hall, T. Marshall. Methotrexate in OxfordDesk refeece rhematolog. Oxfod uivesit Pess, Oxfod2009;1:532-536



17. R. Was, G. Clunie, F. Hall, T. Marshall. Methotrexate in OxfordDesk refeece rhematolog. Oxfod uivesit Pess, Oxfod2009;1:546-548.

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