The calcium content of the blood serum in some cases of leprosy

253

TRANSACTIONSOFTHEROYALSOCIETY OF TROPICAL MEDICINE AND HYGIENE.

Vol. XXVI. No.3. November,1932.

THE

CALCIUM

C O N T E N T OF T H E B L O O D CASES OF L E P R O S Y

SERUM

IN

SOME

BY

ALEXANDER GUTHRIE BADENOCH, M.A., M.B., CH.B.* Acth,g Medical Superintendent, Federal Leper Settlement, Sungei Buloh, Federated Malay States. AND

FRANCIS ERIC BYRON, B.Sc., PH.D., A.I.C. Chemist, Institute for Medical Research, Kuala Lumpur, Federated Malay States.

This paper is intended as a preliminary note to a more detailed investigation of the serum calcium in leprosy. Estimation of the total calcium in the blood serum of eighty-one cases of leprosy was made, using the Clarke-Collip modification of the Kramer-Tisdall method. Figures indicate milligrams of calcium per 100 cubic centimetres. In thirty-six cases the estimations were repeated a varying number of times, to correlate, if possible, the findings with the clinical condition. The usual interval between estimations was one week. Special attention was paid to cases showing lepra reaction (lepra fever). The subject has been explored by a number of workers. UNBERmLL, HONEIJ and BOGERT(1920), CONCEPCION and SALCEDO(1926), LEMAN, LILES and JOHANSEN(1927), RAJEWSKI(1930), WOOLLYand Ross (1931), and others, have reported findings of considerable interest. We have been unable to find many references to lepra reaction in this connection. LEMAN, LILES and JOHANSEN,for instance, report only four cases, with inconclusive findings. Table I shows fifty-four cases from the acute wards of the Federal Leper Settlement, Sungei Buloh, arranged in ascending order of the serum calcium (first estimation). Repeated estimations are given in their chronological order. The classification of cases from the point of view of leprosy, thus N I C 1, N 2 C 3, &c., follows the lines laid down in the report of the Leonard Wood Conference, 1931. N and C indicate Neural and Cutaneous manifestations respectively, and the numbers indicate the degree of involvement. * We are indebted to Dr. R. D. FITZGERALD, Acting Adviser, Medical and Health Services, Malay States, for permission to publish this paper.

0~54

THE

CALCIUM

CONTENT

OF THE

BLOOD

SERUM

IN SOME CASES O F L E P R O S Y .

TABLE i . CALCIUM ESTIMATION IN SERUM OF SICK LEPERS. ~Case No. 1667

Race, Tamil

Sex. M

Age. 28

Leprosy.# Complications. N1 C2 Capillary bronchitis. clearing up

Reaction, Very severe. Had lasted weeks when investigation began

Reaction subsided ~04

Chinese

M

26

N2 C3

Recovery Severe. Subsiding Relapse Subsiding Relapse

Nil

Slight improvement Relapse :

124

Chinese

F

17

N1 C2

Syphilis

1014

Tamil

M

45

N3 el

1977

Chinese

M

40

N2 C2

2273

Chinese

M

50

N1 C3

Trophiculcer. Anaemia Improvement Syphilis. Chronic gonorrhma Ulcer

1187

Chinese

M

23

N1 C1

Nil

1267

Tamil

M

30

N3 C3

Chinese

M

45'

N3 C2

Multiple abscesses Chronic malaria Syphilis Syphilis. Chronic gonorrhcea. Ulcer

820

1028

Chinese

M

31

N1 C3

Syphilis. Healed pulmonary lesion N.B. Domiciliary treatment

2184

Tamil

M

48

N1 C1

2213

Chinese

F

35

N2 C2

Syphilis. Anmmia Beri-beri. Great improvement Syphilis. Ulcer

2130

Chinese

M

23

N2 C2

Syphilis

2171

Chinese

M

33

N1 C2

AnEmia

2102

Chinese

M

39

N3 C2

1271

1825 1901 1873

Chinese Chinese Chlnase Chinese

M M M M

43 40 18 23

N2 N1 N1 N1

Pulraonary tubercle Syphilis Pulmonary tubercle Chronic gonorrhma Nil Nil

2414

ChineSe

M

41

N1 C1

Syphilis.

N2 C2

Rapid extension of lesions to N2, C1 Syphi|is. Av~mia

~075

Chinese

M

20

C1 C1 C1 C1

Anvemia

Leprotie eaehexia

Moderate Subsiding Nil Moderate Subsiding Moderate Subsiding Moderate Subsiding Nil Moderate Subsiding Severe, now subsiding

.,

Serum Calcium. 7"8 7"8 8 "4 8"0 8"2 8"2 8'2 8'7 7"9 0'1 8"0 9.8 8"2 9"2 9'8 9"8 9-8 8"7 0~0 8"8 9-3 10"0 8-2 8'6 9.1 8.1 8"2 8-2 9.6 8-2 8"8 8-2 8-0 8.2 9"4 8"2 8"0 8-3 8.8 8.3 8"5

Subsided

8.4 8.1 8.4 9'0

Nil

8-6 8"9 8"4 "8.4

Moderate S_u_bsiding Moderate Subsiding Relapse Subsiding Moderate Subsiding Moderate

9-0 8"5 8-5 8.6 8.2 9.3 9 .I 8.6 8"9 8-6

Nil _ _ Moderate Moderate Mild Subsided Mild TWO months later

8.6 8-8 8.8 8-8 10.2 8.8 14.2

Muderate Subsiding

15.6 8.9 9 .S

* N = N e u r a l ; C=Cutaneous; Nurnber indicates degree of involvement.

! I

A.

G.

BADENOCII

TABLE

CsAle No. Race. Sex. 1185 - c h i n e s e - - ~ d

A~ e. 17

I

AND

F.

E.

BYRON.

~55

(continued).

Lep.rosy.y _ Complications. N I C3 Ana:mia

Reactton. S~,.cr~ '

Serum Calcium. b.9 9"2

Leprotic cachexia

• 2269 " C h i n e a e - M - -

" 4~ -

g==l~ont÷: ~

J

1

"~p.III~

481

M

42

N I C3

Extensive ulceration

N1 C1 N1-C1

Nil g~f~ilis

Chinese

I450 Chinese 2--281--Cffinese

M 45 M - - - , ~ 5 ....

22-.r;2-- Chinese

M

43

1476

Chinese

3I

45

11~ 1~-

Chinese q'arnil

M M

41 3(1

-158 -Chinese M . . . . 25 "21~t7 Chi--n~e M - 36 2262 - Tarsal - - M -- 30 19~7"--Chineze -1-427 " Chin-e~e 1477

Tamil

157 Malay "T95"~CgTneae 2185 Chinese . . 1989 -~6"/'

M M

26 41

M

22

M M M

32 53 35 .

Chinese M Chines--e /V~I

"~-,i4-- ~in~e-~l---57

674 -~I,T-

Chinese M C-hinese-~M

2409 898 9,.311 2 , ~ 1 --

Chinese Tamil Chln~e ~i-n~'s-e

M 3'1 M -M

44 31

N 2 C2

-Syphilii

N2 C2

Syphilis. Debility Condition improved Syphilis. Ulcer Abscesses --.N/-[ C I My~a~tis ......... ..... N 3 C I T r o p h i c ulcer Bronchitis Pulmonary tubercle diagnosed one m o n t h later N1 el N i l - N!. C~1 " - S ~ h q l i ~ ...... N1 C 1 SyPhilis." Debility Improvement - Ni-Ci ~ -~h]lis N3 T r o p h i c ulcers " Improvement N I C1 Syphilis. A m e m i a . lmprove.m_ent ._ N1 C3 Nil N1 C1 Myocardi_tis NI-C2 Syphilis . . N 2 C2

Syl~hilis. - P h a ~ n g i t i s Ulcers. Condition improving " - N I C3 Chronic malaria 'Amcebiasis Haematemesis from gastric ulcer Improvement 23 . N ~ C I - P u l m o n a r y tubercle 'T~.'¢ N2 L~ l)ebilit~-and b e c o ~ i n ~ worse 22 40 40 ....55

N 1--(~1 N1 C3

3 1 C2 N2 CI N I C2 N-2- C 2

N e r v e pains Syphilis. A n e m i a Syphilis Nil

~'2 8"0 8.4 8'8 9.0 9"4 9.0 9.2 9:09.6 9-I 9.1 9.6 9.2 10.2 9"2 0"6 9-2 9-2

Moderate Subsiding Moderate Subsidin¢ Severe Subsided Mild Mild Subsided Nil Mild Subsidin~ Mild ..... rqh

9'0 9"2 9"3 9:3 9'8 9-3 9"4 9-0 9.4 10'0

Moderate Mild- ....... Nil Moderate Nil . . . . . . . . . . . . Nil . . . . . . Moderate Nil - Iqil Mild reaction Subsided Nil Nil Nil

......

9'4 10.6 9'6 10.7 9"6 9"6 9'8 9.8 10-6

"

10.8 9.8 13.2 12.6 10.11 I 1 "6 10-1

Nil Nil Mild reaction Subsided Nil Nil Nil Mild Subsiding

-1o.2

Leprosy stationary ~ J 9 0 - - T ~ m i l - - - IVl ...... 2219J.4 ~hinea--~ _1_~/_4-1---"r~m.i [ - 1644 Chinese

2347

Chinese

-,~- C l

Ner~v-epainS . . . . .

Nil

............

1~1- - 45 -- N I C1 Syphilis Nil M - - - 1 8 - . - - _ N _ I Cl___S_yph!lia. ~- N_e~_.e_pain__s__N_!! ...... M 53 N1 C3 Ulcers. Bed. sores Severe with eye involvement

M

73

N1 C2 to N1 C8

Senili W. plegna Bedmrea

Old

hemi-

9:4--

Afebrile extension of leprotic lesions

* N - : Neoral ; C = Cutaneous ; N u m b e r indicates degree of involvement.

10-2 10'2 15.0 14.11 12-2 16-(} 15.2 11-8 9.6 9.9 10.2 10.4 1~:4 10:4 10'6 14 "2 14 "4 13-4 15'0 15"1

....

-

256

THE CALCIUM CONTENT

O F T H E B L O O D S E R U M I N S O M E CASES O F L E P R O S Y .

TAaLE II. CALCIUM ESTIMATION IN SERUM OF HEALTHY LEPERS (CONTROL).

Case No.

Race,

Sex.

Age.

Leprosy.*

Complication,

1994

Chinese

M

20

N1 C3

Nil

548

Chinese

M

31

N1 C2

Ulcer.

883

Chinese

M

29

N 2 C3

724

Syphilis

Reaction,

Serum Calcium.

Nil

9,3

Nil

9.4

Ulcer

Nil

10.0

Chinese

M

32

N 2 C1

Nil

Nil

10"2

2292

Arab

M

22

N1 C2

Nil

Nil

10'2

2200

Malay

M

18

N1 - -

Nil

Nil

10"3

1741

Tamil

M

18

N1 C1

Syphilis

Nil

10.4

1461

Chinese

M

28

N 1 C3

Ulcer

Nil

10-6

981

Chinese

M

29

N1 C2

Syphilis.

Nil

10.8

722

Chinese

M

20

N 2 C3

Ulcer

Nil

10,8

1759

Chinese

M

18

N1 - -

Nil

Nil

10"8

1672

Eurasian

M

31

N2 ~

Nil

Nil

10"2

2299

Chinese

M

22

N1 C1

Nil

Nil

10"2

2139

Chinese

M

28

N t C2

Syphilis

Nil

9"8

1361

Chinese

F

24

N1 C1

Nil

Nil

9"8

Tamil

M

31

N 2 C1

Nil

Nil

I0"3 10"0

335

Ulcer

21

Eurasian

M

43

N 2 C2

Nil

Nil

929

Chinese

M

39

N1 C1

Nil

Nil

9"9

1320

Chinese

M

46

N1 C I

Nil

Nil

10'6

1453

Javanese

M

36

N 2 C1

T r o p h i c ulcer

Nil

9'4

1765

Chinese

M

36

N1 C1

Syphilis

Nil

10"0

1843

Chinese

M

33

N1 C1

Nil

Nil

10.4

1890

Chinese

M

19

N1 C1

Nil

Nil

9"9

1990

Tamil

F

24

N1 C1

Nil

Nil

9'5

2105

Chinese

M

39

N2 CI

T r o p h i c ulcer

Nil

10"5

2250

Chinese

M

26

N1 C2

Ulcer

Nil

10"5

2472

Tamil

M

23

N 2 C1

T r o p h i c ulcer

Nil

10"5

* N = Neural ; C = Cutaneous ; N u m b e r indicates degree o f involvement;

In the Summary of the figures, Table I is divided into two groups, viz., thirty-three" reaction " cases and twenty-one " non-reaction "cases. Minimum and maximum figures are shown for each group, taking all the estimation into account. Averages are also shown, based on first estimation only, except in Cases 2,185 and 2,418 where the lepra reaction occurred after the first estimation had been made : t h e s e cases are i n c l u d e d i n t h e " r e a c t i o n " group only.

A. G. BADENOCH AND F. E. BYRON.

O~57

Table II is intended to provide a control, not from normal individuals but from otherwise healthy lepers. T h e twenty-seven cases selected have no record of reaction or, with one exception*, other acute illness during the past six months. Nearly all of t h e m are on the staff of the Institution doing a full day's work, and of none of t h e m can it be said that the leprotic process is definitely advancing. Figures are summarised and compared with those in Table I. It is recalled that the calcium content of the blood serum in normal Europeans usually lies between 9.6 and 10.6 mg. per 100 c.cm. (DE WESSELOW 1924), t h o u g h many tropical inhabitants may be considered as abnormal in this respect (BYRON, 1930 ; KELLY • HENDERSON, 1930, and ORR & GILKS, 1931). In connection with diet, two points are to be noted : - (1) In hospital cases clinical improvement, usually accompanied by a rise in serum calcium, is associated with the transition from a calcium-poor diet to hospital milk diet which ensures a full calcium intake. (2) Of 27 controls, 16 for one reason or another were receiving our No. 7 or No. 8 diet, both of which probably provide enough calcium for the needs of the adult. T h e remaining eleven were in receipt of a daily wage and were able to supplement their ordinary diet, with eggs, fowls, fresh vegetables, etc.

SUMMARY OF SERUM CALCIUM FIGURES IN MILLIGRAMS PER

100 C.CM.

Table I. (Sick cases). A. Group of lepra reaction cases. Minimum . . . . . . Average . . . . . . Maximum . . . . . . B. Group of non-reaction cases. Minimum Average 9-7 (omitting Case "2347 . . . . . . Maximum Table H. (Controls,) . . . . . . Minimum . . . . . . Average Maximum . . . . . .

7.9 8.9 10.6 8.2 9"5) 16"0 9-3 10.2 10.8

Comparison of Group Averages. Sick Cases. Controls. Reaction.

Non-reaction.

8"9

9.5t

10.2

* Case 2,347, a case of rapidly advancing leprosy with abnormally high blood calcium. t Arsenical dermatitis, some time after the estimation was made.

258

THE CALCIUM CONTENT OF THE BLOOD SERUM IN SOME CASES OF LEPROSY.

CONCLUSIONS. 1. L e p r a reaction is nearly always associated with a serum calcium figure that is definitely below normal. 2. O t h e r sick cases have a higher blood calcium but are still below normal as a rule. 3. Sick cases of both groups, in which the estimation was repeated usually showed a rise in serum calcium concomitant with clinical i m p r o v e m e n t . This is true o f " non-reaction " as well as o f " reaction " cases. 4. Certain cases (viz., Cases 1,644, 2,347, 2,361, 2,418 and 2,414) showed an abnormally high serum calcium, which appeared to be correlated with more or l e s s rapid advance of the, leprotic process. In one such case the leprosy i m p r o v e d and the serum calcium fell. In four eases an attack of lepra reaction coincided with a relative low reading of the serum calcium. 5. Otherwise healthy cases of leprosy usually have a serum calcium figure that approaches to or falls within normal limits. 6. Observations are offered bearing on the relation of diet to serum calcium concentration and the incidence and clinical course of attacks of lepra reaction. REFERENCES. BYRON, F. E. (1930). The calcium and phosphorus content of the blood and the creafinine coefficient of the urine of some inhabitants of Malaya. Bulletin, Institute for NIedical Research, Kuala Lumpur, F.M.S. No. 4. CONCEPCION, I., & SALCEDO, JUAN (Junior). (1926). The calcium content of the blood in leprosy. Jl. Philippine Islands. IVied. Assoc. vi, No. 5. DE WESSELOW, O. L . V . (1924). Chemistry of the blood in clinical medicine. Ernest Ben_n, Ltd., London. KELLY, F. C., & HENDERSON,J.M. (1930). Calcium requirements in the human subject. Collected papers of the Rowett Research Institute, ii. LEMAN, I. I., LILES, R.T., & JOHANSEN,F.A. (1927). Blood serum calcium in leprosy. Amer. Jl. Trop. Med., vii, No. 1. ORR, J. B., & GILKS, J. L. (1931). The physique and health of two African tribes. Special Report Series, Med. Res. Council. No. 155. RAJEWSKI. (1930). Zur bioehemisehen Charakteristik der Lepra. Arch. f. Schiffs-u. Trop.-Hyg. xxxiv (12), December, 651-657. Review (L.R.) in Trop. Dis. Bull,, 1931. xxviii, No. 4. April. UNDERHILL, E. P., HONEIJ, J. A., & BOGERT, L. J. (1920). Studies on calcium and magnesium metabolism in disease. I. Calcium and magnesium metabolism in leprosy. Jl. Exper. Med., xxxii, No. 1. WOOLEY, J. G., with the technical assistance of Ross, HILARY. (1931) Phosphorus, total calcium and diffusible calcium content of the blood sera of lepers and their relation to bone changes. Pub. Health Reports, U.S. Pub. Health Service, xlvi, No. 12. WOOLEY,J. G., & Ross, H. (1931). Calcium phosphorus and protein metabolism in leprosy. Ibid. xlvii, No. 7.