Clinical and Experimental Dermatology (1979) 4, 31.

Original Articles

Granuloma annulare and diabetes mellitus

B.L.ANDERSEN AND J.VERDICH Department of Dermatology and Ve'nerology, University Hospital, Odense, Denmark

Accepted for publication' '^ Jtme 1978

Summary Thirty-eight patients with granuloma annulare were investigated with special reference to excluding diabetes mellitus by performing oral glucose tolerance tests and tissue typing. The patients had similar sex and age distributions to those in previous series. The results suggest that a relationship between granuloma annulare and diabetes meUitus does exist.

Several groups of investigators in recent years have tried to demonstrate a relationship between granuloma annulare and diabetes mellitus (Rhodes et al., 1966; Dickeu, Carrington & Winkelmann, 1969; Romaine, Rudner & Altmau, 1969; Mobacken, Gisslen & Johannisson, 1970; Haim, Friedmann-Birnbaum & Shafrir, 1970; Hammond, Dyess & Castro, 1972; Williamson & Dykes, 1972; Haim et al., 1973). Such a relationship is suggested by the histological similarity between granuloma annulare and necrobiosis lipoidica, a disorder in which diabetes mellitus is present in about 65",, of cases (Muller & Winkelmann, 1966). Ttie results published so far are conflicting. Rhodes et al. (1966) and Romaine et al. (1969) suggested a relationship between diabetes mellitus and granuloma annulare, especially the generalized type. Mobacken et al. (1970), Dicken el al. (1969) and Williamson & Dykes (1972) were not able to demonstrate such a relationship. An association between certain HL-A tissue types and juvenile diabetes mellitus has recently been demonstrated (Svejgaard et aL, 1975; Thomsen et aL, 1975)The present study demonstrates a possible relationship between grauuloma annulare and diabetes mellitus by means of HL-A typing and standard laboratory procedures. Reprint requests: Dr B.L.Ari,dersen, Department of Dermatology and Veneroiogy, University Hospital, D K 5000 Odense, Denmark. 0307-6938,79/0300-0031 S02.00

(; 1979 Blackwell Scientific Publications

3^

B.L.Andersen and jf.Verdich

Table 1. Clinical data of patients

No,

Age

Sex

(years) I 2

3 4 5 6 7 8 9

64 55 25

53 66 14 27

9 II

IO

28

11

44

12

14

-3

s

T4

13

15 i6

20

17 i8

IT

14

2O

64 7 55

19 21

29

22

14

23

31

24

11

25

61

26

12

27

II

28

29

29

28

30

31 28

31 32

33 34 35 36 37 38

31 20

28 30 16

5 9

F ¥ F F F M F M F F IF M M M F M M M M F M F F M F 1F F F M F F ¥ F p IF

Duration of disease (months) 20

30

4 60

48 30 70 12

48 30 22

30

5 6 4 7 36 50

6 25

6 18

3 60

6 5 2

6 36 48 85 180 30

6 36 I 10

26

1-ocalization Dorsum man. et ped., crura, femora Fingers, hands, elbow, knee Elbow Fingers, eibow Knee, elbow Dorsum ped., crura Finger Dorsum ped. Dorsum ped., wrist Fingers Elbow Forearms, crura, dorsum ped. Fingers Lower extremities Lower and upper extremities Fingers Finger Finger, elbow, foot Foot Upper extremities Fingers Lov/cr and upper extremities, trunk Upper extremities Elbows Fingers Hands Hand Fingers Finger Feet Hands Fingers Fingers Hand filbow Dorsum ped. Upper extremities, trunk, lower extremities Feet

Single; multiple Multiple MultipleSingle Multiple Multiple Multiple Single Multiple A/lultiple Single Single Multiple Single .Multipe Multiple Multiple Single Multiple Single Multiple Multiple Generalized Multiple Multiple Multiple Multiple Multiple Multiple Single Multiple Multiple Multiple Multiple Single Single Single Multiple Multiple

Granuloma annulare and diabetes meUitus

witb granuloma annulare

Other diseases

Family history of diabetes

Biopsy

Hypertension Astbma

Abnormal glucoseparameters

Tissue type (HLA-system) W44 ; B12) Al, 2; B7, 8 A3, 9; B15 (SL): W44 ( B12); C\V4 A I ; W32;B8, 15 (SL) AI, 2 ; B 8 ;

; (old-age) Mvxoedema

A I ; W I 9 ; B 8 , 13

(insulin)



• (old-age)



(old-age)

Diabetes mellitus —

f (old-age)

Diabetes mellitus

; (old-age)

Hypertension (insulin)



A3,9;B7 A I , 2; B8; W39 A2;BW22, 27; CWi; W2 A2; W19; B13; W44( B12) A2, 29;Bi7; W44( B12) A2, 11; B27; W44( B12); CW2 A i , 2 ; B8, 15; CW3 A I , 2; B8; W44 ; B12) Al, 2; B7, 8 A2; W3o;Bi3, 40; CW3 A26, 29; BW44( B12), 37 A I ; W19?; B8; W45 A I , 9; B8; \V35; CW4 Ar,3;BS, i5 A I , 3;B8, I5 A9, 29; BW44 ( BE2); CW4 Al, 3; B18; W38 A3; W19; H7, 27; C W I A2; BW39, 40; CW3 A3;Wi9;B7, 13 A I , 2; B8, 15; CW3 A2, 26; BW35, 40; GW3; W4 A I , 2; B8; W44 A2; B15; CW3 A2 ; B7; W44 A2; W19?; B14, 18 A3, 29;Bi5;W44;CW3 A2, n ; B7; W44 A I , 28; BW35; W44; CW2; W4 A2; B15; W22; C W I ; V!'3 A I , 28; B5, 17 A9, 26; B5, 7 A I ; B8

33

34

B.L.Andersen and J. Verdich

Material and methods Thirty-eight patients with granuloma annulare were examined in the Dermatological Department from April 1971 to December 1977. Diagnosis was based on typical clinical appearance ofthe lesions and/or biopsy. The sex and age ofthe patients, duration ofthe cutaneous lesions and the number of biopsies performed is shown in Table i. Two patients also had hypertension requiring treatment, one patient had myxoedema, one patient bronchial asthma and two patients had diabetes mellitus treated with insulin. Three patients with no previous history of diabetes mellitus showed a diabetic glucose tolerance test; one of these had a family history of maturity onset diabetes. In all, eight patients had a family history of diabetes mellitus. The patients were all called up for a new examination in the Dermatological Department in December 1977. If a biopsy had not been performed on an earlier occasion and clinical signs of granuloma annulare were still present, a biopsy was taken. A total of 24 patients were biopsied. The remaining 14 patients had the diagnosis of granuloma annulare made on the clinical appearance of the lesions alone. HL-A tissue typing was performed in all cases. In patients with a known history of diabetes mellitus, no further laboratory investigations were made. In the remainder an oral glucose tolerance test was performed. In addition, the fasting values of serum triglycerides, serum glycerol (free) and serum insulin were determined. The oral glucose tolerance test was performed in accordance with WHO conditions (after 12 h of fasting and no smoking, a dose of 50 g D-glucose (adults) or i g per kg body weight (children) was given orally). Fasting plasma glucose and urine glucose were determined. Two hours after glucose ingestion, plasma glucose and urine glucose were determined again. The normal value of plasma glucose 2 h after glucose ingestion is < 8 o mmol/1. Borderline values are 8-O-9-5 mmol/1. Diabetic values are >9-5 mmol/1. Plasma glucose was determined by Trinder's method (1969). HL-A tissue typing was done by the method of Kissmeyer-Nielsen and Kjerbye (1967) at the Tissue Typing Laboratory, Municipal Hospital, Arhus, Denmark. Results The relation between the patients' age, site of lesions, glucose tolerance and HL-A tissue type is shown in Table i. The sex and age distribution shows a male female ratio of i :2 2, with granuloma annulare occurring more frequently in the first three decades of life (79**0). Twenty-five patients (66'VO had no signs of granuloma annulare at the time of re-examination. These patients had skin lesions lasting an average of 245 months (range 1-85 months). The patients were treated either with intralesional triamcinolone 5 mg/ml, CO2 freezing or grenz rays. Twenty-six patients (68';o) had multiple lesions of granuloma annulare. Eleven patients (29",,) only had single lesions. Three patients were found to have abnormal glucose tolerance (Table 2). Two patients had insulin-treated diabetes mellitus before granuloma annulare

Granuloma annulare and diabetes meUitus

II ra D

ffi

3 CO .£! 6 £ ID

3

1-1

u

O

•S

V

hies

en

£

C•^ 2c CL,

,.

H

5J C

p3

(J •—

M

LJ .—

ii "o 3

^ -5 -S ffi c^ cS

5J

O

•/"!

35

36

B.L.Andersen and J. Verdich

developed. One patient with abnormal glucose tolerance had been treated witb thiazide diuretics for some years because of hj'pertension. HL-A tissue typing showed the type B 8 in 15 patients (39"..). This frequency is significantly (P < 0-05) higher than in the normal Danish population (237" „) (Svejgaard et al., 1975).

Discussion The aetiology of granuloma annulare is still unknown (Beare & Wilson Jones, 1972). Sex and age distribution and duration ofthe disease correspond with a previously published study by Wells & Smith (1963). However, the incidence of single, multiple and generalized lesions is somewhat different to that found in other series (Mobacken ei aL, 1970; Haim et aL, 1970; Hammond et ah, 1972; Williamson & Dykes, 1972; Dicken et aL, 1969; Romaine et aL, 1969; Haim et al., 1973). The only patient with generalized granuloma annulare was an insulin-treated diabetic. A relationship between generalized granuloma annulare and diabetes mellitus has been suggested in one study (Haim et aL, 1970) but another study could not confirm this (Dicken et aL, 1969). In previously published studies, attempts have been made to demonstrate latent diabetes in patients with granuloma annulare by means of cortisone glucose tolerance tests (Rhodes et al., 1966; Mobacken et aL, 1970; Hammond et aL, 1972; Williamson & Dykes, 1972), but the number of patients with an abnormal cortisone glucose tolerance test and normal oral glucose tolerance test who later developed clinical diabetes meUitus, is unknown (Deckert, 1978). In this study, a standard oral glucose tolerance test was performed to unveil possible subclinical diabetes mellitus. In addition, serum glycerides serum glycerol (free) and serum insulin were determined (fasting). Studies dealing with HL-A tissue types and disease associations have demonstrated an association between HL-A B 8 and BW i^ 3.nd insulin dependent diabetes niellitos (Svejgaard et aL, 1975; Thomsen et aL, 1975). The frequency of clinical diabetes mellitus in this study is higher (7-9",•) than in the normal Danish population (2";,) (Deckert, 1978). The significant increase in frequency of the tissue type HL-A B 8 in our series suggests that there may be a relationship between grsnuloma annulare and diabetes mellitus.

Acknowledgments We wish to thank Professor F.Kissmsyer-Nielsen M.D. and L.Lamm, M.D., Tissue Typing Laboratory, Municipal Hospital, Arhus, Denmark, for performing the tissue typing and statistical evaluation of the results.

References BEARE, J.M. & WILSON JONES, E . (1972) Nccrobiotic disorders. In: Textbook of Dermatology, (Ed. by A.Rook, D.S.Wilkinson and F.J.G.Ebling), 2nd edn, pp. 1353-1362. Blackwell Scientific Publications, Oxford.

Granuloma annulare and diabetes mellitus

37

DECKERT, T . (1978) Niels Steensens Hospital, Copenhagen: personal communication. DiCKFN, C.H., CARRINGTON, S.G. & WINKELMANN, R.K. (1969) Generahzed granuloma annulare. .Archives of Dermatology, 99, 556-563. HAIM, S., FRIEDMANN-BIRMBAUM, R . & SHAFRIR, A. (1970) Generalized granuloma annulare: Relationship to diabetes meUitus as revealed in 8 cases. British Journal of Dermatology, 83, 302-305. HAIM, S., FRIEDMAN-BIRNHAUM, R . , HAIM, N . , SHAFRIR, A. & RAVINA, A. (1973) Carbohydrate tolerance

in patients with granv.loma annulare. British Journal of Dermatology, 88, 447-451. HAMMOND, R . , DYESS, K . & CASTRO, A. (1972) Insulin production and glucose tolerance in patients with granuloma annulare. British Journal of Dermatology, 87, 540-547KissMEYER-NlELSEN, F. ti. KjERBYE, E. (1967) Lymphocytotoxic micro-technique, purification of lymphocytes by flotatii^n. In: Histocompatibility Testing (Ed. by E.S.Curtoni, P.L.Mattiuz and R.M. Tosi), pp. 381-383. Munksgaard, Copenhagen. MOBACKEN, H . , GISSLEN, H . & JOHANNISSON, G . (1970) Granuloma annulare. Cortisone glucose tolerance test in a non-diabetic group. Acta dermato-venerologica, 50, 440-444. Mui-LER, S.A. & WINKEL;M.NN, R.K. (1966) Necrobiosis lipoidica diabeticorum. Archives of Dermatology, 93, 272-281. RHODES, F,.L., H I L L , D.M., AMES, A . C , TOURLE, C A . & TAYLOR, C.G. (1966) Granuloma annulare;

prednisone glycosuria test in a non-diabetie group. British Journal of Dermatology, 78, 532-535. ROMAINE, R . , RUDKER, E.f. & ALTMAN, J. (1969) Papular granuloma annulare and diabetes mellitus. Archives of Dermatology, 98, 152-154. SVEJGAARD, A., PLATZ, V., RYDER, L.P., STAUB-NIELSEN, L . & THOMSEN, M . C1975) HL-A and disease

associations—a survey. Transplantation Reviezvs, 22, 3-43. THOMSEN, M . , PLATZ, P., ORTVED ANDERSFN, D . , CHRISTY, M . , LYNGSOE, J., NERUP, J., RASMUSSEN, K . ,

RYDER, L.P., STAUB->[IELSEN, L . & SVEJGAARD, A. (1975) MCL typing in juvenile diabetes mellitus and idiopatic Addisor's disease. Transplantation Reviews, 22, 125-147. TRINDER, P. (1969) Determination of blood glucose using 4-amino phenazone as oxygen acceptor. Journal of Clinical Pa:hology, 22, 246. WELLS, R.S. & SMITH, M.A. (1963) The natural history of granuloma annulare. British Journal of Dermatology, 75, 199-205. WILLIAMSON, D.M. & DYKES, J.R.W. (1972) Carbohydrate metabolism in granuloma sinrwXarc. Journal of investigative Dermatology, 58, 400- 404.

Granuloma annulare and diabetes mellitus.

Clinical and Experimental Dermatology (1979) 4, 31. Original Articles Granuloma annulare and diabetes mellitus B.L.ANDERSEN AND J.VERDICH Departmen...
225KB Sizes 0 Downloads 0 Views