INTERNATIONAL JOURNAL OF 1.11 . 1tOSY^ volume (6, Number IPrinted in the U.S.A.

(ISSN 01,18-916X)

Leprosy Reactions^Complications of Steroid Therapy'D. Samuel Thomson Sugumaran"

Leprosy is a chronic granulomatous dis-ease caused by Mycobacterium leprae.Some patients develop acute inflammatoryepisodes due to an adverse immune re-sponse to bacterial antigens, and theseepisodes are called leprosy reactions. Manyclassifications have been proposed for thesereactions, hut the classification proposed byJopling is commonly followed in manyplaces and is used here.

ReactionsType 1 reaction. Type 1 reaction occurs

in borderline tuberculoid (BT), borderlineborderline (BB) and borderline lepromatous(BL) patients (synonyms: reversal reaction,upgrading reaction, borderline reaction). Itoccurs as a cell-mediated, delayed-type hy-persensitivity (DTH) response.

Type 2 reaction. Type 2 reaction occursin BL and lepromatous (LL) patients [syn-onym: erythema nodosum leprosum (ENL)].It occurs as an immune-complex mediatedresponse. This reaction can last from 3months to 6 years.

The detailed clinical descriptions of thesereactions, their immunopathological se-quences and complications are beyond thescope of this article, but excellent publica-tions are available ( -L

Leprosy reactions can occur in patientsbefore treatment, during treatment, andeven after treatment (`.'. 23 ). Reactionsfrequently cause nerve damage which leadsto disability and deformity. Corticosteroidsare frequently used to control reactions(2.

3, 19, 20, 30 , .) Corticosteroids are effective in

the management of reactions in the follow-ing ways ( 2"): They suppress immune re-sponses (both DTH and immune complex),reduce inflammation, and prevent fibrosis.

' Received for publication on 5 February 1997.Accepted for publication in revised form on 31October 1997.

= D. S. T. Sumnaran, B.Sc., M.B.B.S., D.P.M..Specialist, Department of Medicine, SchieffelinLeprosy & Research Training Centre, Karigiri 632106 N.A.A. District. Tamil Nadu, South India: fax:91-416-74274.

Although caution about the adverse ef-fects of steroid therapy has been given bymany, to our knowledge the exact incidenceof adverse effects relating to steroid therapyhas not been described in detail in the liter-ature ( 7"). We present here our observationsof adverse effects of steroid therapy.

PATIENTS AND METHODSPatients with reactions who came to the

author between January 1991 and Decem-ber 1996 were included in the study, andwere suffering from the following reac-tions: type 1, 581; type 2, 249; total 830.

Prednisolone was the usual corticosteroidused for therapy along with an appropriateregimen of multidrug therapy (MDT). Ad-verse effects were carefully looked for andrecorded. The usual starting dose of pred-nisolone was 40-60 mg/day, given as a sin-gle dose in the morning. If symptoms suchas fever, neuritis and arthritis did not sub-side within 2 days the daily dosage was in-creased. Occasionally patients needed up to120 mg of prednisolone/day for 2 or 3 daysafter which the dosage could be reduced.The adverse effects are shown in Tables Iand 2.

Adverse effectsMoon face. Cushingoid features are

common in patients under chronic cortico-steroid therapy and "moon face" was thecommonest feature seen in all of our pa-tients after receiving corticosteroids evenfor 2 weeks ("). Patients and their relativesfelt very anxious and even suspected "kid-ney problems." We had to reassure the pa-tients about the temporary nature of thisphenomenon and that everything wouldsubside after the steroid course was over.

Steroid acne. Steroid acne was a cos-metically disturbing problem which oc-curred quite commonly after about I monthof steroid therapy. The common sites of dis-tribution of these eruptions were the face,chest, arms and scapula. This, like "moonface," also was temporary and disappearedafter steroid therapy was completed.

10

66, 1^S'agumaran: Complications of Steroids^ 11

TABLE 1. Adverse effects of steroid therapy.

ReactionsTotal

Adverse^Type 1^ Type 2effect No.^ No.^ No.

patients'^ patients''^ patients'

Moon face 581 100 249 100 830 100Steroid acne 76 13 84 34 160 19.2Gastritis 29 4.9 37 14.9 66 7.9Peptic ulcer I 0.17 I 0.40 2 0.24Skin fungus 114 19.6 76 30.5 190 22.9Cataract 24 4 57 12.9 81 9.7Diabetes 13 2.2-- 17 6.8 30 3.6Tuberculosis 3 0.5 7 2.8 10 I./Osteoporosis 2_ 0.34 11 4.4 13 1.5

Number of patients = 581.'' Number of patients = 249.`Number of patients = 830.

Gastritis. Patients complaining of aburning sensation in the stomach or epigas-tric distress were considered as sufferingfrom gastritis. This usually occurred anytime during steroid therapy (less than 6months of therapy or beyond 6 months oftherapy) and with any dosage. Occasionallythere was also vomiting. All of these pa-tients were managed with oral antacids andranitidine without any interruption of thesteroid therapy. When the vomiting wassevere, we administered ranitidine andsteroids parenterally along with intravenousfluids for a few days until the gastritis sub-sided. We also suspect that clofaziminemight have contributed to these symptomsin some patients on multibacillary MDT ( 14 ).

Peptic ulcer. Following are two exam-ples of peptic ulcer: I) A 35-year-oldwoman with type 1 reaction developed se-

TABLE 2. Incidence of adverse effectswith reference to duration of steroid ther-apy.

Incidence of adverse effectsduring steroid therapy (in mos.)

1-3 3-6 6-12 >12

Moon face 830 Acne 160 Gastritis 6 45 11 4Peptic ulcer 2 Skinfungus 190Cataract 81Diabetes 30Tuberculosis 7Osteoporosis 12 I

vere abdominal pain 2 weeks after takingprednisolone 30 mg daily. She was found tohave a perforated peptic ulcer at laparot-omy. The steroid therapy was discontinuedin this patient. 2) a 40-year-old man withsevere type 2 reaction and a history of alco-holism developed profuse hematemesis 1week after prednisolone therapy (30mg/day). The patient died of shock before ablood transfusion could be arranged. Eventhough this is a serious complication, its in-cidence is quite rare, contrary to popularbelief C. ").

It is possible that we might have missedsome of the asymptomatic silent ulcerssince we relied only on clinical symptoms.

Fungus infection of the skin. Skin fun-gus occurred quite commonly, probably dueto immune suppression during steroid ther-apy. Itchy plaques occurred over the thighs,abdomen, chest and axillae, groin and glu-teus. This usually was controlled with topi-cal antifungal agents (clotrimazole or mi-conazole) and occasionally a patient neededoral griseofulvin as well.

Cataract. The annoying problem ofcataract occurred quite frequently in pa-tients who were on steroids for more than12 months ('". ". 3 '). Generally, in the initialstage patients suffered from "glare disabil-ity" disturbing their vision when they wereoutdoors under bright sunlight ( 7 ). The vi-sual difficulty was described as "foggy,""cloudy" and "smoky," but vision dramati-cally improved after dusk. Vision also im-proved in clarity if they wore dark sun-

Adverseeffect

International Journal of Leprosy^ 1998

glasses during bright sunlight. Because ofthis glare disability, initially there was diffi-culty in recognizing distant objects and insome patients, as the cataract formation in-tensified, there was difficulty in recognizingnear objects, greatly compromising theirday-to-day activities (difficulty in recogniz-ing friends and foe, difficulty in reading thenumber on a bus when boarding, difficultyduring manual weed removal and harvestwork and, of course, in reading fine print inthe newspaper). Those driving at night felt"blinded" by the headlights of oncomingvehicles. The experience was described as a"smoke screen" or "colorful dazzlingscreen," akin to driving on a rainy nightwithout the windshield wipers working.

In the initial stages even though the pa-tients suffered from glare disability and dif-ficulty in recognizing distant objects, visualacuity in Snellen's chart was found to benormal or near normal (6/6 or 6/9). Hence,testing for the glare disability and contrastsensitivity using Pelli-Robson's chart mayhelp to detect the magnitude of this problemmuch earlier ( 37 ).

The incidence of cataract due to steroidsis found to be variable in different diseaseconditions, sometimes the disease itself in-creasing the susceptibility to cataract for-mation ('). It is also suspected that M. lep-rae may contribute to cataract formationdue to quinone formation ("). Eleven pa-tients had severe impairment of vision andneeded cataract surgery, 7 had intraocularlens (IOL) and 2 wear spectacles. All areable to attend to their daily work. Two pa-tients could not subject themselves tosurgery due to other family problems. Vi-sion improved in 12 patients on reductionof the steroid dose. Aspirin and vitamin Care said to be helpful in preventing cataractformation. Hence, we now routinely add vi-tamin C 100 mg and aspirin 300 mg dailyto the regimens of patients requiring morethan 6 months of steroid therapy ('. 3").How far this helps, we have to wait and see.

Diabetes. Steroid-induced diabetes is awell-recognized complication, and we en-countered this within 3 months of startingsteroid therapy. There was a wide range ofpostprandial blood sugar levels in these pa-tients (from 230 mg/100 ml and 700mg/100 ml). We were able to control dia-betes with oral sulfonyl areas (gliben-

TABLF. 3. Drugs used in treatment ofleprosy reactions.

Type I reaction^Type 2 reaction

Corticostcroids^CorticosteroidsClorazimine?^Clofatimine (higher dosages)

ThalidomideChloroquineColchieincPotassium antimony tartrate

(PAT)Aspirin

clamide). To our great relief, the diabeteswas always temporary and we could alwaysstop antidiabetic therapy after the pred-nisolone dosage was reduced to

66, 1^Sugumaran: Complications of Steroids^ 13

DISCUSSIONMany drugs have been used in the treat-

ment Of leprosy reactions in addition to spe-cific anti leprosy chemotherapy (Table 3).Corticosteroids are effective in both typesof reactions (`. ' 3 2"). Even though thalido-mide gives excellent relief in type 2 reac-tion, it is not easily available, cannot begiven to women of child-bearing age, andfor men it has to be given under supervisionafter hospitalization, hence its continuedadministration over a long period is notpracticable (24. 34 ) . Other drugs for type 2 re-action are slow in action and not very effec-tive in severe degrees of prolonged reactions(". 12 . 15 . 21 . 23 .-"). Hence, using corticosteroidswith other drugs in various combinationsand dosages becomes mandatory with theattendant adverse effects inevitable. Also,corticosteroids are the only drugs availableat all places at a reasonable cost. At thesame time, the awareness of the problemslikely to arise because of steroid therapyand the magnitude of the problem will helpthe physician and other field workers en-gaged in leprosy therapy to approach theproblem of reactions with caution and with-out undue prejudice toward steroids, be-cause proper treatment of reactions willdefinitely prevent the majority of disabili-ties ( 27 . 3 ').

CONCLUSIONWe have described the adverse effects we

came across during treatment of patientssufferimz, from leprosy reactions (type 1 andtype 2) with corticosteroids with a view topresent the entire problem in the proper per-spective. The incidence of adverse effects isfound to be more among patients sufferingfrom type 2 reaction. This is because thetype 2 reactions occurred frequently andlasted for a longer duration than did thetype 1 reactions. Hence, a higher percent-age of patients with type 2 reaction (230 outof 249, 92%) required steroids for 6 ormore months than did the patients with typeI reaction (266 out of 581, 45%). Cortico-steroids are available easily at a reasonablecost, but we feel that efforts must be takento identify alternative drugs of equal orhigher efficacy without the side effects.Some workers have claimed the usefulnessof cyclosporin, azathioprine and methotrex-ate hut they are very costly, need more su-

pervision, and may not be very suitable forfield use. Feedback and comments from thereaders on this important problem will helpthe leprosy workers as well as benefit lep-rosy patients.

SUMMARYThe adverse effects of corticosteroid ther-

apy while treating 830 patients sufferingfrom leprosy reaction (type I = 581; type 2= 249) are presented. Some of the adverseeffects were cosmetically distressing, whileothers were disabling. Patients sufferingfrom type 2 reactionbecause of the ten-dency of the reaction to recur over a longtimeneeded steroids for a longer dura-tion; hence, adverse effects were more fre-quent. Measures to counter some of the ad-verse effects are suggested and the need toidentify drugs with potentially less adverseeffects is emphasized.

RESUMENSe analizaron los etectos adversos de los corticoes-teroides en el tratzuniento de la reaccion tipo 2) reci-bieron la terapia esteroidal. Algunos de los efectos ad-versos fueron solo de tipo estetico mientras que otrosfueron descapacitantes. Los pacientes con reaccionleprosy tip 2, debido al comportamiento recurrente deIa reaccion, necesitaron un tratamiento esteroidal Indsprolongado y por esta razn los efectos adversosfuern inds frecuentes. Se sugieren algunas medidaspara contrarrestar algunos de los efectos adversos y seenfatita la necesidad de huscar drogas con menos efec-tos indeseables.

RESUMELes diets secondaires du traitement par cortico-steroides de 830 !naiades souffrant (rune reactionlepreuse (type I = 581: type 2 = 249) sont presents.Certains effets secondaires taient de nature cosine-tique, d'autres de type incapacitant. Les patients souf-mint d'une reaction de type 2, it cause d'une tendance la recidive stir tine longue priode, ncessitaient ontraitement par steroides plus long: it s'ensuivail des ef-lets secondaires plus frequents. Des mesures pour con-trer certains diets secondaires sont suggeres et Ia n-cessit ('identifier des medicaments avec potentielle-ment moans d'effels secondaires est soulignee.

Acknowledgment. I thank the administration ofthe Sacred Heart Leprosy Centre for permission toconduct this study. My thanks also go to all the med-ical officers who extended their kind cooperation. Igratefully acknowledge the cooperation of the MedicalRecords Department staff and the laboratory techni-cians while collecting this data. I thank Mr. S. Mullin-s:tiny for secretarial assistance. Special thanks go to

14^ haernationa/ Journal of Leprosy^ 1998

Mr. S. Seshadri for typing the ma n uscript patiently andovercoming all difficulties in spite of repeated alter-ations.

REFERENCESI. ALLEN, M. B., RAY, S. G., LErrcii, A. G., Dfin.LoN,

B. and CULLEN, B. Steroid aerosols and cataractformation. BMJ 299 (1989) 432-433.

2. BECX-BLEUMINK, M. The management of nervedamage in the Leprosy Control Services. Lepr.Rev. 61 (1990) 1-11.

3. BECN-BLEUNIINK, M. and BERDE, D. Occurrenceof reactions: their diagnosis and management inleprosy patients treated with multidrug therapy;experience in the Leprosy Control Programme ofthe All Africa Leprosy and Rehabilitation Train-ing Centre (ALERT) in Ethiopia. Int. J. Lepr. 60(1992) 173-184.

4. MUNI:, G. Reactions in leprosy. Lepr. Rev. Spe-cial Issue (1983) 61S-67S.

5. CIIENG, H. Aspirin and cataract. Br. J. Ophthal-mol. 76 (1992) 257-258.

6. DANIEL, E., ALENANDER, R. and ClIACK0 S. Ocu-lar leprosy: do steroids complicate matters? (Let-ter) Int. J. Lepr. 63 (1995) 115-117.

7. GRoENEN, G., JANSSENS, L., KAyEmnE, T., NoLLET,E., CoussoNs, L. and RVITYN, S. R. Prospectivestudy on the relationship between intensive bacte-ricidal therapy and leprosy reactions. Int. J. Lepr.54 (1986) 236-244.

8. GuPLANDL NI. and TurromoTo, A. Steroid ulcers:a myth revisited. BMJ 304 (1992) 655-656.

9. HARDING, J. J. and VAN HENINGEN, R. Drugs, in-cluding alcohol, that act as risk factors for cataractand possible protection against cataract by aspirin-like analgesics and cyclopenthiazide. Br. J. Oph-thalmol. 72 (1988) 809-814.

10. HASTINGS, R. C. and TRAUTNIAN, J. R. B.633 inlepromatous leprosy; effect in erythema nodosumleprosum. Lepr. Rev. 39 (1968) 3-7.

11. HAYNES, R. C., Jr. Adrenocorticotropic hormone;adrenocortical steroids and their synthetic analogs;inhibitors of the synthesis and actions of adreno-cortical hormones. In: Goodman and Gilman'sThe Pharmacological Basis of Therapeutics. 8thedn. Gilman, A. G., Roll, T. W., Nies, A. S. andTaylor, I'., eds. New York: Pergamon Press, 1990,PP. 1431-1462.

12. INIKANIP, F. NI. J. 11. Clofazimine (l.amprene orB633) in lepra reactions. Lepr. Rev. 52 (1981)135-140.

13. JACOBSON, R. R. Treatment of leprosy. In: Lep-rosy. Hastings, R. C., ed. Edinburgh: ChurchillLivingstone, 1985, pp. 211-217.

14. JONANG, W. II. Side effects of antileprosy drugsin common use. Lepr. Rev. 54 (1983) 261-270.

15. KARAT, A. B. A., JEEVARATNANI, A., KARAT, S. andRAO,^S. S. Efficacy of clofazimine in the pro-phylaxis and suppression of reactive phases of

lepromatous leprosy. Int. J. Lepr. 39 (1971)838-841.

16. KELLY, P. J., SANIBROOK, P. N. and EISNIAN, J. A.Potential protection by cyclosporin against gluco-corticoid effects on bone. (Letter) Lancet 2 (1989)1388.

17. MSIIANA, R. N. Erythema nodosum leprosum isprecipitated by an imbalance of T lymphocytes.Lepr. Rev. 53 (1982) 1-7.

18. NAAI.s, B.. PEARsoN, J. NI. II. and WDEATE, II. W.Reversal reaction: the prevention of nerve dam-age; comparison of short- and long-term steroidtreatment. Int. J. Lepr. 47 (1979) 7-12.

19. NAAEs, B. and WDEATE, II. W. The time intervalbetween the start of antileprosy treatment and thedevelopment of reactions in borderline patients.Lepr. Rev. 49 (1978) 153-157.

20. PLARtioN, J. M. II. The use of corticosteroids inleprosy. Lepr. Rev. 52 (1981) 293-298.

21. PEALTzGRAi I. R.^The control of neuritis in lep-rosy with clofaziinine. Int. J. Lepr. 40 (1972)392-398.

22. PRABDAKARAN, K. Cataract in leprosy: a bio-chemical approach. Lepr. Rev. 42 (1971) 11-13.

23. RAMANUJANI, K. and Di LARNIENDRA. Managementof reactions in leprosy. In: Leprosy. Vol. I. Dhar-mendra, ed. Bombay: Kothari Medical Publishing!louse, 1978, pp. 512-534.

24. RAmt), G. and GiRialAR, A. Treatment of steroiddependent cases of recurrent lepra reaction with acombination of thalidomide and clolatimine.Lepr. India 51 (1979) 497-504.

25. REID, D. NI., Nicoll., J. J., SNIII II, M. A., HIG-GiNGs, B.,^P. and NUKI, G. Cortico-steroids and hone in asthma: comparison withrheumatoid arthritis and polymyalgia rheumatica.BMJ 293 (1985) 1463-1466.

26. RIAD, I. R., HEAP, S. W., KING, A. R. and InitERT-soN, II. K. "Iwo year follow-up of biphosphonate(API)) treatment in steroid osteoporosis. (Letter)Lancet 2 (1988) 1144.

27. Rici(ARDus, J. 11. and SNIITII, W. C. The risk ofstandardised regimens of corticosteroids for thetreatment of leprosy reactions in the field. Lepr.Rev. 66 (1995) 328-329.

28. RIDLEY, D. S. and RADiA, K. B. The histologicalcourse of reactions in borderline leprosy and theiroutcome. Int. J. Lepr. 49 (1981) 383-392.

29. RIDLEY, NI. J. and RiDLEY, D. S. The immuno-pathology of erythema nodosum leprosum: therole of extravascular complexes. Lepr. Rev. 54(1983) 95-107.

30. Rose. P. and Wm Fits, M. F. R. Reversal reactionsin leprosy and their management. Lepr. Rev. 62(1991) 113-121.

31. ST. CLAIRE RonERTN, D. Steroids, the eye andgeneral practitioner. BMJ 292 (1986) 1414-1415.

32. SAROJINI, P. S. and NIsilANA, R. N. Use of colchi-eine in the management of erythema nodostun lep-rosum (ENL). Lepr. Rev. 54 (1983) 151-153.

66, I^ Sugumaran: Complications of Steroids^ 15

33. SAm., A. and SiJimn, N. Lepra reaction: its rela-tion with fragmentation of Mycobacterium leprueunder sullone therapy. Int. J. Lepr. 34 (1966)17-22.

34. SIITSKIN, J.. MAGoit..\ , A. and SAGitot, F. Motorconduction velocity studies in patients with lep-rosy reaction treated with thalidomide and otherdrugs. Int. J. Lepr. 37 ( I969) 359-364.

35. SRINIVASAN, H. Prevention of disabilities in lep-rosya practical guide. Geneva: World I lealthOrganization, 1993.

36. VAN iENINGEN, R. and HARDING, J. J. Do aspirin-like analgesics protect against cataract'? A case-control study. Lancet 1 (1956) 1111-1113.

37. WILLIAMSON, T. II., STRONG, N. P., SARRow J.,AGGAuwAt., R. K. and I IARRAD, R. Contrast sensi-tivity and glare in cataract using the Pelli-Robsonchart. Br. J. Ophthalinol. 76 (1992) 719-722.

Page 1Page 2Page 3Page 4Page 5Page 6