An inflammatory polyarthritis has been previously described in leprosy but accounts of the clinical characteristics have varied. All patients with joint symptoms admitted to a leprosy centre over 5 months were examined by a rheumatologist. Of 48 acute admissions, 20 (42%) had a symmetrical polyarthritis affecting the wrists and fingers. This was strikingly similar to RA in appearance. The arthritis occurred exclusively in patients with reactions mainly during anti-mycobacterial treatment. The clinical features of the joint disorder were identical in Type I (associated with alterations in immune status) and Type II (erythema nodosum leprosum) reactions. Synovial tissue from one patient revealed no mycobacteria. Four of five hand X-rays suggested small erosions of the finger joints

Ahsan, Q

Gibson, T

Hussein, K

English

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eCommons@AKUSection of Internal Medicine Department of MedicineOctober 1994Arthritis of leprosyT GibsonQ AhsanAga Khan UniversityK HusseinAga Khan UniversityFollow this and additional works at: https://ecommons.aku.edu/pakistan_fhs_mc_med_intern_medPart of the Internal Medicine CommonsRecommended CitationGibson, T., Ahsan, Q., Hussein, K. (1994). Arthritis of leprosy. British Journal of Rheumatology, 33(10), 963-966.Available at: https://ecommons.aku.edu/pakistan_fhs_mc_med_intern_med/45British Journal of Rheumatology 1994;33^63-966CLINICAL REVIEWARTHRITIS OF LEPROSYT. GIBSON, Q. AHSAN and K. HUSSEINDepartment of Medicine, Aga Khan University Hospital and Mane Adelaide Leprosy Centre, Karachi,PakistanSUMMARYAn inflammatory polyarthritis has been previously described in leprosy but accounts of the clinical characteristics havevaried. All patients with joint symptoms admitted to a leprosy centre over 5 months were examined by a rheumatologist.Of 48 acute admissions, 20 (42%) had a symmetrical polyarthritis affecting the wrists and fingers. This was strikingly similarto RA in appearance. The arthritis occurred exclusively in patients with reactions mainly during anti-mycobacterial treat-ment. The clinical features of the joint disorder were identical in Type I (associated with alterations in immune status) andType II (erythema nodosum leprosum) reactions. Synovial tissue from one patient revealed no mycobacteria. Four of fivehand X-rays suggested small erosions of the finger joints.KEY WORDS: Mycobacterium leprae, Symmetrical polyarthritis. Leprosy reactions.ONE by one the old infectious scourges of mankindhave been contained or eliminated. At least one excep-tion is leprosy. Its insidious onset makes early recogni-tion and isolation difficult and its social stigma ensuresthat treatment may not be sought until late. In thedeveloping countries of South Asia the prevalence isestimated to be 2/1000 [1]. The notorious deformityand disability of the disease are mainly due to destruc-tive tissue invasion by Mycobacterium leprae and toperipheral neuropathy. Arthritis is a recognized fea-ture, but its frequency and contribution to morbiditymay be underestimated [2]. Arthritis occurring in Type2 reactions (erythema nodosum leprosum) is described[3]. Both Type 1 and 2 reactions are associated withinflammation at sites of mycobacterial infection such asthe skin and peripheral nerves and are often precip-itated by treatment. The former is linked to down-grading or upgrading of cell-mediated immunity and ashift toward one or other clinical poles of the diseasespectrum [4]. It tends to occur in borderline diseasealthough not exclusively. The better known Type 2reaction is characterized by the additional feature ofpainful red nodules over the face and limbs and is moreoften seen in lepromatous and borderline lepromatousdisease. This study describes the pattern of arthritisamongst new admissions to a leprosy centre in Pakis-tan. The arthritis was invariably associated with eitherType 1 or 2 reactions.SUBJECTS AND METHODSThe Marie Adelaide Leprosy Centre in Karachi is acharity aided unit which has an inpatient facility forboth acute admissions and elective procedures. It is theorganizational focus for a network of leprosy controlcentres throughout Pakistan. Most of the in-patientsSubmitted 14 March; revised version accepted 15 July 1994.Correspondence to: T. Gibson, Guy's Hospital, LondonSE1 9RT.0263-7103/94/100963 + 04 $08.00/0are admitted from poor areas of Karachi, rural Sindand Baluchistan.During a 5-month period in 1992, a rheumatologist(TG) visited the unit weekly and examined any newpatient with joint symptoms. The history and distri-bution of joint pain, tenderness and swelling wererecorded. Patterns of leprosy (lepromatous to tubercu-loid) were identified clinically and by skin biopsy bytwo leprologists (QA, KH). Types of reaction werecategorized clinically depending on the presence orabsence of erythema nodosum leprosum and thesystemic features of a Type 2 response (e.g. orchitis).Haemoglobin, ESR, RF (latex slide test, LaboratoriesKnickerbocker, Barcelona) and X-rays of hands wereperformed where the cost could be justified clinically.Joint aspiration and needle synovial biopsy of anaffected knee were performed on two patients but syn-ovium was obtained in only one. This was stained byhaematoxylin and eosin and by Wade-Site stain forMycobacterium leprae.RESULTSThere were 48 acute admission of which 31 (64%)were for reactional states. Of these, 20 (60%) had jointsymptoms. Apart from three other patients with inci-dential OA of the knee or spine, no other patient hadjoint pain. Amongst the long-standing inpatients andelective admissions were some with peripheral neu-ropathy exhibiting digital atrophy, autoamputation,foot ulcers and Charcot joints. These were easily distin-guished and were not part of this study.Peripheral arthritis was seen in both types of reac-tion and details of the patients and the distribution ofthe joint disease are summarized in the tables accord-ing to their reaction patterns Histories were not alwayseasy to obtain because of cultural and linguistic diffi-culties. At least nine (75%) of those with Type 1 andthree (40%) with Type 2 reactions recalled joint pain orswelling before or at the time that other clinical mani-© 1994 British Society for Rheumatology963Downloaded from https://academic.oup.com/rheumatology/article-abstract/33/10/963/1782332 by Francesca Farr on 10 October 2018964 BRITISH JOURNAL OF RHEUMATOLOGY VOL. 33 NO. 10TABLE IClinical features of leprosy in patients experiencing reactionalstates with arthritisSexMean age (yr)(range)Class of leprosy:LepromatousBorderline lepromatousBorderlineBorderline tuberculoidIndeterminateOther manifestations:Ear swellingNose swellingIritis/conjunctivitisOrchitisTreatment at time of reaction:•MDRDapsoneClofazimineNoneMean (range) duration oftreatment (months)Typel8 M 4F37(16-68)3521154—433210(1-24)Type 26M 2F30(20-41)44—556216149(7-132)*MDR, multiple drug regimen: dapsone, clofazimine, rifampicin.festations of leprosy first appeared. In these cases, jointpain and swelling had worsened at the onset of thereaction. By the time of examination the associatedacute arthritis had been evident for variable periods ofdays, weeks or months. Three patients claimed thatacute joint swelling had been recurrent for severalyears. Similarly, of 10 patients with reactional swellingof nose, ears or both, seven had experienced milderswelling of these sites weeks or months beforehand.Other features of the Type 2 reaction were conjunctiv-itis or iritis in six and orchitis in two patients. Themajority of those in reaction had been receiving treat-ment although two with Type 1 had not received anyantimycobacterial therapy (Table I). It is noteworthythat the majority of patients with Type 1 reactions andarthritis were borderline cases whereas those with Type2 reactions were toward the lepromatous end of theclinical and immunological spectrum. Males wererepresented more than twice as often as females.The clinical picture of arthritis was strikingly similarto RA. Finger joints were the most commonly affectedsites (Table II). The pattern of disease was the same inboth Type 1 and 2 reactions. Swelling of the wrists,MCPs and PIPs in a symmetrical distribution wascharacteristic (Fig. 1).SF examination in one case revealed white cell count4.0 x 109/l (90% lymphocytes). No acid-fast bacilliwere seen and none was cultured. Synovial biopsyobtained from the knee of another patient revealed amodest perivascular lymphocyte infiltration but a care-ful search failed to reveal any mycobacteria.Anaemia and elevation of ESR were common(Table II). The rheumatoid latex test was negative in allpatients tested. X-rays of the hands were obtained infive patients. The quality of the films was poor but fourof the five sets of hand films showed small erosions ofPIP or MCP joints (Fig. 2).DISCUSSIONThe association of arthritis with leprosy does notreceive emphasis in standard accounts of the illness [5].Nevertheless, descriptions of joint involvement arenumerous [6-11]. There is inconsistency in the docu-mented picture of the joint disease. In one prospectivestudy of 25 patients, arthritis was seen both with andwithout other features of Type 2 reactions [11]. Itaffected one, few or many joints; SF was non-inflamma-tory, inflammatory or purulent and acid-fast bacilliwere seen in occasional samples. These observationsimply that there may be more than one pattern ofarthritis which in some cases is due to direct infectionand in others to a different mechanism. There is con-firmatory evidence that mycobacteria can be found inthe synovium of some affected patients [12, 13]. Otheraccounts describe an inflammatory peripheral arthritisoccurring in the absence of reactional states but inthese reports there was no attempt to exclude directinfection of involved joints [14, 15].Our own description of a peripheral arthritis resem-bling RA echoes earlier studies in which examinationof SF and tissue failed to yield mycobacteria [3, 16].Successful synovial biopsy was achieved in only one ofour patients and that did not reveal acid-fast bacilli.TABLE IIDistnbution of joint inflammation and results of investigations in patients with reactional states and arthritisShoulderElbowWristMCPPIPDIPKneeAnkleMTPMean (range) haemoglobin (g/dl)Mean (range) ESR (mm/h)Rheumatoid latex positiveX-ray erosionsTypelTenderness25910926989.6570/103/3(8.2- 11.5)(25-128)Swelling36891352Type2Tenderness557511749.4730/21/2(5.2- 11.6)(15-160)Swelling1342——32Downloaded from https://academic.oup.com/rheumatology/article-abstract/33/10/963/1782332 by Francesca Farr on 10 October 2018GIBSON ETAL.: ARTHRITIS OF LEPROSY 965FIG. 1.—Symmetrical swelling of PIP, MCP and wrist joints in apatient with a leprosy reaction.Some earlier accounts of this clinical picture did notdescribe associated reactions although the onset ofarthritis was considered by Bonvoisin et al. [17] to her-ald a reactional state. The relationship of peripheralarthritis with Type 2 reactions has been noted by others[18, 19] but we are the first to describe joint inflam-mation resembling RA occurring in both Type 1 and 2reactions. The two reactional states are not alwayseasily distinguishable and painful swelling of specificsites such as the ears and nose is common to both. Theappearance of minor joint erosions in a small numberof patients made the comparison with rheumatoiddisease even more striking. Similar changes have beenobserved by others [20, 21]. None of our patients had apositive rheumatoid latex test which is surprisingbecause leprosy is reputed to be one of the chronic non-rheumatoid diseases associated with RF [22]. Theanaemia and high ESR are characteristic of reactionalstates which represent the paradox of acute inflam-mation and worsening of symptoms despite effectiveantimycobacterial infection [23].Both Type 1 and 2 reactions, especially the latter,tend to occur during treatment when it is presumed anincreased mycobacterial antigen load follows death ofthe organisms. However, as in the current series ofpatients, spontaneous reactions also occur in untreatedpatients. In both types, swelling and inflammationdevelop at sites where invasion by mycobacteria com-monly occur, such as skin, nerves, eyes, ears and nose.By analogy the acute arthritis probably also arises injoints infiltrated by the organism. This would explainthe disparities in the descriptions of arthritis in leprosyand accords with the histories of previous, but milderjoint symptoms in many of our patients. Men seem tobe more vulnerable than women to reactions and thepredominance of males amongst our patients hasalready been noted. Although the two patterns of reac-tional states share some clinical characteristics each isthought to have a different nnmunopathogenesis. InType 1 reactions, patients move toward either the lep-romatous (severe) or tuberculoid (mild) pole of thedisease. In the latter case at least, the cytokine profile inthe skin is distinctive, with amongst other features aFig. 2.—Minor erosions of MCP joints (arrows) in a patient withType 1 reaction and associated arthritis.relatively reduced IL-4 [24]. It has been reported thatin Type 2 reactions, there is immune complex deposi-tion and IL-4 remains strongly expressed [24]. It thusseems that two different immune mechanisms may beoperating. As in our patients, Type 2 reactions tend tobe confined to lepromatous or borderline lepromatouspatients, that is to those with the greater concentrationof organisms and the least cell-mediated immunityagainst the mycobacterial antigen. Our observationssuggest that the arthritis which accompanies these dif-ferent reactions are identical. Much has yet to belearned about the immunological events which influ-ence the clinical spectrum of leprosy and its complica-tions. Whether or not the reactional states are asdistinct as claimed, requires confirmation. The strikingsimilarity of the associated arthritis with rheumatoiddisease warrants emphasis especially since some auto-immune diseases may be induced by infection [25].Closer examination of the immunological sequenceand its relationship to the presence of Mycobacteriumleprae within the joints could carry implications for themechanism of other joint disorders.ACKNOWLEDGEMENTSThe authors thank Dr Thomas Chiang and the staff atthe Marie Adelaide Leprosy Centre for their assistance,and Dr Rabia Hussein for her help and encouragement.Dr Gibson was partly supported by the Arthritis andRheumatism Council and the Special Trustees of Guy'sHospital.REFERENCES1. Cossermelli-Messina W. Leprosy: Statistics in theAmericas. J Rheumatol 1993;2(h893-6.2. Chandrasekaran A. Infection and arthritis, our experi-ences, a retrospective and prospective study. J IndRheum Ass 1993,1:7-20.3. Karat A, Karat S, Job C, Furness M. Acute exudativearthritis in leprosy—rheumatoid arthntis like syn-drome in association with erythema nodosum lep-rosum. BMJ 1967;3:770-2.4. Naafs B. Reactions in leprosy. Biol Mycobacteria19893:359-94.5. Bryceson A, Pflatzgraff R. Leprosy. Edinburgh:Churchill Livingston, 1990.Downloaded from https://academic.oup.com/rheumatology/article-abstract/33/10/963/1782332 by Francesca Farr on 10 October 2018966 BRITISH JOURNAL OF RHEUMATOLOGY VOL. 33 NO. 106. Iveson J, McDougall A, Leatham A, Harris H. Lep-romatous leprosy presenting with polyarthritis, myo-sitis and immune complex glomerulonephritis. BMJ1975;3:619-21.7. Berman L. Exudative arthritis in leprosy. ArthritisRheum 1979^593.8. Albert D, Weisman M, Kaplan R. The rheumaticmanifestations of leprosy. Medicine 1980:59:442-8.9. Markusse H, Smelt A, Teepe R. Unusual arthritis: beon the alert after leprosy. Clinic Rheumatol 1989;8:266-8.10. Atkin S, El-Ghorbarey A, Kamel M, Owen J, Dick W.Clinical and laboratory studies of arthritis in leprosy.BMJ 1989398:1423-5.11. Pernambuco J, Opromolla D, Tolentino M, Fleury R.Arthritis in lepromatous Hansen's disease. IntJ Lep-rosy 1979 47 (Suppl. 2):353-4.12. Modi T, Lele R. Acute joint manifestations in leprosy.J Ass Phys India 1969;17:247-54.13. Holla V, Kenetkar M, Kolhatkar M, Kulkarin C. Lep-rous synovitis. A study of 50 cases. Int J Leprosy1983:51:29-32.14. Bank I. Arthritis in leprosy. Arch Int Med 1984;144:421.15. Atkin S, Welbury R, Stanfield E, Beavis D, Iwais B,Dick W. Qinical and laboratory studies of inflamma-tory polyarthritis in patients with leprosy in PapuaNew Guinea. Ann Rheum Dis 1987;4fc688-90.16. Lele R, Sainani G, Sharma K. Leprosy presenting asrheumatoid arthritis. / Ass Phys India 1965:13:275-7.17. Bonvoisin B, Martin J, Bouvier M, Bocquet B, Bouil-liat J, Duivon J. Les manifestations articulaires de lalepre. Sent Hop Paris 1983^<h302-5.18. Alcocer J, Herrera R, Lavalle C, Gudino J, Fraga A.Inflammatory arthropathies in leprosy. ArthritisRheum 1979^587.19. Chavez-Legaspi M, Gomez-Vazquez A, Garcia de laTorre I. Study of rheumatic manifestation and ser-ologic abnormalities in patients in leprosy. J Rheum1985;12:738-41.20. Enna C, Jacobson R, Rausch R. Bone changes in lep-rosy: a correlation of clinical and radiographic fea-tures Radiology 1971;l(Mh295-306.21. Morley K, Vickers H, Hughes G. An unusual cause ofarthritis. Postgrad MedJ 1983^9-^22-4.22. Garcia de la Torre I. Autoimmune phenomena in lep-rosy, particularly anti-nuclear antibodies and rheu-matoid factor. J Rheumatol 1993;2<h900-3.23. Malin A, Waters M, Shehade S, Roberts M. Leprosy inreaction: a medical emergency. BMJ 1991^02:1324.24. Yamamura M, Wang X, Ohmen J et al. Cytokine pat-terns of immunological mediated tissue damage. JImmunol 1992;149:1470-5.25. Ehrenstein M, Isenberg D. Autoimmunity associatedwith infection: leprosy, acute rheumatic fever andLyme disease. Curr Opin Immunol 1991;3:930-5.Downloaded from https://academic.oup.com/rheumatology/article-abstract/33/10/963/1782332 by Francesca Farr on 10 October 2018

Arthritis of leprosy

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Arthritis of leprosy

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