IN11..RNAI I(^\I. 1(^()I. I.1^ Volume 67, Number 4

Printed in the USA(ISSN 0148-916X)

CORRESPONDENCE

This department is,fOr the publication of informal communication.s. that are of interestbecouse they are infOrmative and stimulating, and for the discussion of controversialmotters. The mandate of 1/lis Jetin,YYt. is to disseminai,' information relating to leprosyparticular and also other mycobacterial diseases. Dis.s.ident cominem or interpretation 011published research is of course valid, but personalitv attacks on individuais would seco:111111eCeSSar.V. Political comments, valW or not, ol.so ore unwelcome. Thev might result iaintelf erence with the distribution of the fouRNALalul thus intedère with its prime purpose.

Leprosy at the Age of 141 Years: a Case Report

To THE EDITOR:

A 141-year old male, the oldest livinghuman being in Nepal, presented withasymptomatic, rnultiple, erythematousplaques ali over bis body for the last 2months. The lesions appeared suddenly onbis face and progressed to involve the upperand lower limbs and trunk. There was a bis-tory of redness of the eyes and lacrimationfor the previous 20 clays. Fever, arthralgia,epistaxis, testicular swelling and pain ineyes were absent. The patient had neversuffered from any major illness in bis entirelife. He was the documented oldest citizenof Nepal, according to the records of theNepal [and Survey. He was a much reveredfigure and a lot of people used to visa bishome to have audience with him daily. Thepatient had been living a simple life. Hewas married and had tive children and threegreat-grandchildren. There was no historyof leprosy in the family.

Examination revealed a frail old manalert and conscious but unable to respond toqueries because of impaired hearing. 1-lisconjunctivae were congested and there wasa scanty purulent discharge. There was nopallor, icterus, lymphadenopathy, pedaledema, trophic ulceration or plantar fissur-ing. There was an atrophic, 2 cm x 1 cm,depigmented scar on the depressed bridgeof the nose. The systemic examination waswithin normal limits. Cutaneous examina-tion showed well-defined, erythematous, in-durated plaques ou both eyebrows without

any madarosis. Multiple, erythematous,to well-defined plaques varying in size from1 cm to I() cm were present bilaterally in anasymmetrical panem over bald arcas of thescalp, the nape of the neck, the chin,cheeks, nose, trunk, buttocks and upper andlower extremities (Figs. 1 and 2). Multiple,nontender, erythematous nodules N,verepresent over the cheeks and chin. The leftulnar nerve was thickened and mildly ten-der. There were no deformities. Sensationover the lesions, hands and feet could notbe tested because of bis advanced age andinability to communicate.

A clinicai diagnosis of borderline lepro-matous (BL) Hansen's disease was made.Slit-skin smears for acid-fast bacilli (AFB)were positive from the lesions and earlobes(BI 1+). A skin biopsy from a lesion on theleft forcam] showed atrophy of the epider-mis and multiple epithelioid cell granulo-mas in the upper and deep defluis. Thegranulomas were composed of epithelioidcells, lymphocytes, and a few giant cells.Nerve destruction was seen in places. Thebiopsy was negative for AFB. The histolog-ical diagnosis of borderline tuberculoid(BT) Hansen's disease was made. Alihematological and biochemical investiga-tions were normal. The patient was startedou the World Health Organization multi-bacillary multidrug therapy (WHO/MDT)regime)]. The patient expired 2 weeks laterof an unknown cause at home.

Leprosy is a chronic infectious disease,caused by Mveobacterium /eprae, affecting

471

472^ International Journal of Leprosv^ 1999

Fio. 2. Erythematous plaques and nodules over thechia and right eheek.

FiG. 1. Erythematous plaques ou right lower limb.

the peripheral nerves, skin and certain othertissues (2). It is transmitted from one personto another, probably by contact with un-treated patients hosting contagious forms ofthe disease. In highly endemic regions, avery large percentage of the population isexposed to the infection but only 5% de-velop the disease, depending ou the cell-mediated immunity of the individual. Theprevalence of leprosy is highest amongyoung adults ('). It has been reported in aliage groups but the prevalence is only0.09% for those over 80 years of age. In anarticle by Monteiro, et al. from Brazil onocular changes in leprosy patients, it ismentioned that their oldest patient was aged89 years ("). There were no reports of anypatient older than this, to the best of ourknowledge.

We report here a case of borderline lep-romatous Hansen's disease in a 141-year-old person. Our patient was unique not be-cause of his advanced age alone but be-cause the onset of disease was at the age of141 years. This case highlights the long in-

cubation period of leprosy. We believe thatthe patient must have acquired the infectionat an early age, as is true for most of thepeople living in endemic areas. The late on-set of the disease in our patient may be be-cause of decreased immunity in old age (4).However, the possibility of his acquiring in-fection even later in life from the peoplewho had started visiting him from far andwide, after recognition as the oldest livingperson of Nepal, cannot be discounted.

—Sudha Agrawal, M.D.Assistant Professor

—Arun Joshi, M.D.Senior Residem

—Mary Jacob, M.N.A.M.S.Professor and HeadDepartment of Dermatology

and Venereology

—Shatrughan P. Sah, M.D.Assistant ProfessorDepartnieitt of Pathology

—Arun Agarwalla, M.D.Senior Resideilt

Vijay Kumar Garg, M.D.Associate ProfessorDepartinent of Derniatology

and Venereology13. P. Koirala Institute of Health ScienceDharan, Nepal

67, 4^ Correspondence^ 473

Reprint requests to Dr. S. Agrawal at theabove address or FAX 977-25-20251;e-mail: sudha92@hotmail.com

REFERENCES• A1.1, P M. The age at onset of leprosy. Lepr. Rev.

35 (1964) 193-197.2. JOPLING, W. 11. and McDou0ALL, A. C. Delinition,

epidemiology and world distribution. In: Hand-book of Leprosy. 4th edn. Oxford: HeinemannMedical Books, 1988, pp. 1-9.

3. MONTEIRO, L. G., CAmPos, W. R., ()Rum:, F. andGRossi, M. A. F. Study of ocular changes in lep-rosy patients. Indian J. Lepr. 70 (1998) 197-202.

4. NoomaN, S. K. The epideiniology of leprosy. In:Leprosv. 2nd edn. Hastings, R. C., ed. London:Churchill Livingstone, 1992, pp. 29-45.

Apoptosis in Leprosy PatientsTo THE EDrfoR:

The protection-associated host responseto Mrcobacterium leproe infection isstrongly dependent upon subsequent cellu-lar immunity ('). Apoptosis appears as aphysiological mechanism that leads to cellelimination without inducing inflammationor damage to contiguous cells (3.5). In thisstudy, we have tested the hypothesis thatamong the various factors potentially re-sponsible for the lymphocyte alterations inleprosy, apoptosis could be implicated.Along this line, we evaluated the impact ofleprosy infection on the levei of sponta-neous apoptosis and the type of cells(CD4', CD8+, CD19+) that were likely con-cerned.

After informed consent, 19 newly de-tected leprosy patients (11 males, 8 fe-males) were included in the study before re-ceiving any treatment. Nine of them hadmultibacillary (MB) leprosy and 10 hadpaucibacillary (PB) leprosy. Seven (5males, 2 females) Senegalese healthy adultdonors were enrolled as controls.

Peripheral blood mononuclear cells wereisolated from heparinized whole blood byHistopaque®-1077 density gradient (SigmaDiagnosis, St. Louis, Missouri, U.S.A.) andcultured at 10" cells/ml in 24-well platesunder unstimulated (medium afoite) condi-tions. The plates were thereafter incubatedfor 2 clays (determined after a preliminarykinetic study) at 37°C in a water-saturatedatmosphere containing 5% CO,. Quantifica-tion of apoptosis was performed by 11ov cy-tometry as already described by stainingthe lymphocytes with 7 amino-actino-mycinD (7AAD; Sigma) which discrimi-nates live from early apoptotic cells. CD4',

CD8' and CDI9 cells were identitied usingmonoclonal antibodies (Becton DickinsonImmunocytometry Systems, San Jose, Cali-fornia, U.S.A.). The nonparametricKruskal-Wallis test was used to comparethe data between the different groups; a pvalue of <0.05 was considered as signifi-cant.

The proportions of apoptotic lympho-cytes were compared in leprosy patientsand controls. A highly sig,niticant increase(p = 0.01) in the levei of spontaneous apop-tosis in leprosy patients was found as com-pared to controls, suggesting a notable im-pact of the Al. leprae infection. Hence,apoptosis seems to be an active phenome-non in leprosy as previously found for sev-eral other intracellular infections (7.'"), in-cluding inalaria ()). However, the percent-age of 7AAD-positive cells was notsigniticantly different between the twogroups of PB and MB patients. Such obser-vation has to be contirmed with a greaternumber of patients.

The relative distribution of the lympho-cyte subset within apoptotic cells was stud-ied (ratio of the percentage of the apoptoticsubpopulation studied on the percentage oftotal apoptotic cells of the culture). Wefound that the distribution of CD4', CD8'and CD19+ cells within apoptotic cells didnot differ between patients and controls,suggesting that the infection simply in-duced an exaggeration of a naturally occur-ring mechanism.

Another type of analysis was performedin calculating the ratio of the percentage ofthe apoptotic subpopulation on the percent-age of the population concerned. This al-lowed us to determine the number of apop-totic cells within each subset separately.