Haematological and immunological features of patients with fissured tongue syndrome

British Journal of Oral and Maxillofacial Surgery (1987) 2.5, 481-487 0 1987 The British Association of Oral and Maxillofacial Surgeons

HAEMATOLOGICAL

AND IMMUNOLOGICAL

FEATURES

OF PATIENTS

WITH FISSURED TONGUE SYNDROME

A. KULLAA-MIKKONEN,I. PENTTILL”,R. KOTILAINENand E. PUHAKAINEN” Department of Oral Surgery, University of Kuopio; *Department of Clinical Chemistry, Kuopio University Central Hospital, Kuopio, Finland Summary. Blood samples from 40 patients with fissured tongue syndrome (FTS) were examined, and the results were compared with those of 20 healthy control subjects. FTS was diagnosed when a) the patient had a fissured tongue with smooth-surfaced papillae (n=25) or b) the patient had geographic tongue and some relatives had fissured tongue (n=15). These tongue forms were verified also histologically. To evaluate the possibility of systemic disorders in patients with FTS we determined the whole blood (IgA, IgG, IgM, picture and levels of vitamin B,z, serum folate, serum ferritin, and immunoglobulins IgE). None of the patients with FTS nor any of the controls were found to be anaemic. The mean levels of serum vitamin B12, ferritin and folate were, however, slightly lower in the patient group than in the controls. These findings suggest that anaemia does not play a primary role in the aetiology of fissured tongue syndrome. The most striking haematological findings were the decreased thrombocyte and leucocyte counts in patients with fissured tongue syndrome compared with the control subjects. Furthermore, the lymphocyte count and serum IgG were low in the patient group. When the two patient groups were compared no differences were found. These observations are discussed from the standpoint of deficiency in the immunological defence mechanism of patients with fissured tongue syndrome.

Introduction

Many haematological disorders are reported to involve the tongue. Anaemias may be associated with atrophic glossitis (Hjorting-Hansen & Bertram. 1970; Jacobs, 1970; Burket, 1977; Dayal & Mani, 1979), and the tongue may become fissured or lobulated (Jones, 1973). Anaemia and gastro-intestinal disturbances (Prinz, 1927) are cited as possible causes of geographic tongue, which is often associated with fissured tongue (Redman et al., 1972; Chosack et al., 1974; Eidelman et al., 1976). There are, however, no recent haematological studies of patients with these tongue forms. The aim of this study was to examine possible changes in the whole blood picture of patients with fissured tongue or geographic tongue in order to find whether there are any systemic disorders in these patients. A histological study of fissured tongue had shown that this lesion is characterised by densely aggregated polymorphonuclear leucocytes in the epithelium and lymphoid cells in the subepithelial connective tissue (Kullaa-Mikkonen & Sorvari, 1986b; Kullaa-Mikkonen, 1986a). Geographic tongue is also a chronic inflammation that affects the dorsum of the tongue (Kullaa-Mikkonen et al., 1985a). In this study, patients with fissured tongue or with geographic tongue were studied together, because these tongue types seemed to be different forms of the same disease as described recently (Kullaa-Mikkonen, 1987). The patients with both these tongue types are said to have the ‘fissured tongue syndrome’ (FTS). The observed inflammation of these tongue types could indicate that the defence mechanism of the oral mucosa is ineffective or that an immunological process is (Received

23 December

1985; accepted 11 July

481

1986)

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taking place. Therefore, in this study the lymphocyte count in the blood and the serum levels of immunoglobulins were determined in order to evaluate some of the immunological characteristics of patients with FTS. Patients and methods

From the histopathological studies (Kullaa-Mikkonen et al., 1985a; KullaaMikkonen & Sorvari, 1986b) 25 patients (10 men, 15 women) with fissured tongue and 15 patients (5 men, 10 women) with geographic tongue were selected for the present study. These patients ranged in age from 20 to 31 years, the mean age being 25 years. The controls consisted of 20 healthy subjects matched to the experimental group with respect to age, sex and oral health. Venous blood samples were collected between 11-11.30 a.m. to decrease the effect of diurnal variation. The following tests were performed: blood haemoglobin, mean corpuscular volume of erythrocytes (MCV), erythrocyte count, leucocyte count, platelet count and differential leucocyte count, serum vitamin B,,, serum folate, serum ferritin and serum immunoglobulins (IgA, IgG, IgM, IgE). Blood haemoglobin, MCV, erythrocyte count, leucocyte count and platelet count were performed by a Coulter Counter S Plus@ analyser (Coulter Counter Ltd, Harpenden, England), which calculates the other indices MCH (mean corpuscular haemoglobin) and MCHC (mean corpuscular haemoglobin concentration) as well as the haematocrit value on the basis of MCV and haemoglobin on erythrocyte count. The differential count of blood leucocytes was analysed by a Hematraka automated differential counter (Geometric Data, Waune, U.S.A.). Serum folate and serum vitamin Bi2 estimations were carried out by the commercial kits of Bio-Rad (Bio-Rad Laboratories, Richmond, U.S.A.). Serum ferritin concentrations were measured by a radio-immunoassay. Serum immunoglobulins IgA, IgG and IgM were determined with immunoturbidimetric methods using an IL Multistat III@ microanalyser (Instrumentation Laboratory Inc., Lexington, U.S.A.) and specific antisera of Orion Diagnostica (Espoo, Finland). Serum IgE was determined by the commercial Tandem IgE immunoassay kit of Hybritech (Liege, Belgium). Some reagins against milk, fish, wheat and moulds (cladosporium and aspergillus) were tested by the RASTtechnique of Pharmacia (Uppsala, Sweden). For the statistical evaluation of the results Student’s t-test for the differences of the means was used. Results

Whole blood picture Anaemia was defined as a haemoglobin concentration of less than 125 g/l for females and less than 135 g/l for males (Penttila et al., 1973). No significant change from the normal range of haemoglobin was found in either group (Table I). Changes in the erythrocytes were reflected in MCV, which was slightly raised above 96 fl in one control subject (5%) and in eight patients with fissured tongue syndrome (20%). Of these eight patients with MCV values above normal limits, none showed changes in serum folate and vitamin Bi2 levels. The thrombocyte count was slightly lower in patients with fissured tongue syndrome (257*47x 10’11;p
(X 10iz/l)

Erythrocytes

“‘p
MCV (tl) MCH (pg) MCHC (g/l) THROMB (x IO%) Leucocytes (X lO”/l)

Haematocrit

(g/l)

Haemoglobin

Table I Haematological values for patients tested with a t-test

125-160 135-180 4.cs.3 4.5-6.1 0.37-0.47 0.4go.54 8k96 27-32 315-360 150-400 4-10

Normal

laboratory

with fissured

range

tongue

(11x20)

131~10 159f6 4.5+0.4 4.9so.5 0.40+0.03 0.46+0.06 91.8k3.1 29.9kl.l 329+8 298+56 6.521.3

Mean&SD

(FTS) and controls.

115-147 15&167 3.8-4.7 4.6-5.6 0.3GO.44 0.44-0.52 84.497.1 28.3-31.6 3 1 l-344 191-422 4.5-8.6

Range

Controls

syndrome

with

between

122-146 142-164 4.0-4.9 4.4-5.4 0.38-0.44 0.42-0.50 86.3-102.2 26.5-32.7 298-348 158-346 2.9-X.6

Range

Patients

Differences

were

~~ 139t9 158f9 4.6kO.3 5.1+_0.3 0.41+0.02 0.46+0.02 92.8k4.5 30.3+ I .4 3302 12 2571-47” 5.4f1.31;“;

MeantSD

FTS (n=40)

the groups

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Table II

White blood cell counts and differentials (mean&SD) in patients with fissured tongue syndrome (FTS) and controls. Differences between the groups were tested with a t-test Normal range Leucocytes (X lO”11) Neutrophils (X lo”/]) Lymphocytes (x lO’/l)

4-10 2.2-6 1.5-3.5

laboratory

Controls

(n=20)

6.511.3 3.8il.l 2.1f0.5

Patients (n=40)

with FTS

5.3f1.3’“” 3.2f 1.0 1.5fO.6””

‘““p
(5.3~ lo”/1 and 6.5~10”/1, respectively; ~~0.01; Table II). In seven Jatients (17.5%) the leucocyte count was slightly below the normal range (4-10x10 /l). The distribution of lymphocytes was below normal in 19 patients with FTS (4X%), whereas 19 of the 20 controls were within the normal range (1.5-3.5 x 109/l; Table II). This difference was significant (~~0.01). In six patients the neutrophil level was below the normal range (15%). Serum vitamin B,,, serum folate and serum ferritirz Two patients with FTS had serum levels of vitamin Bi2 below the normal range. Serum folate levels were within normal limits for all patients and controls. However, the mean serum levels of both vitamin Br2 and folate were slightly lower in patients with fissured tongue than in the controls (Table III). The serum ferritin levels in control subjects ranged from 27-231 yg/l (mean 155.4 ug/l). The ferritin levels in the patient group were only slightly lower than in the controls (13-189 ug/l [mean 150.4 ug/l]). Serum immunoglobulins

(ISA, IgG, IgM, IgE) and reagins

The IgA values of controls were within the normal range, whereas in three out of 40 patients with FTS (8%) IgA values were below normal (Table III). In patients with fissured tongue we observed a tendency towards decreased IgG levels compared to the controls (p
Although fissured tongue has long been recognised, its diagnosis and clinical appearance are extremely variable. This may explain why no clinical significance has been shown for fissured tongue. In this study, a tongue biopsy was taken from each patient, and as described previously for fissured tongue (Kullaa-Mikkonen & Sorvari, 1986a; b; Kullaa-Mikkonen et al., 1985a), signs of chronic inflammation and smooth-surfaced papillae were seen. Therefore the patients examined

*p
Strum vitamin BL2 (pmol/l) Serum folate (nmol/l) Serum ferritin (pg/l) IgA (g/l) IgG (g/l) IgM (g/l) IgE (kU/l)

Table III Serum levels of vltamm (FTS) and in controls

150-650 4.5-32 lo-260 0.9-4.5 8.0-18.0 0.62.8 O-150

laboratory

range

and immunoglobulins

Normal

B,2, folate

211-595 9.5-25.7 27-23 l 1.3-3.1 9.3-16.6 0.9-2.3 5.0-82.0

Range

(n=20)

IgM, IgG,

Controls

(IgA,

366? 109 16.2k5.0 155.4k32.0 2.1+0.x 12.6i 1.8 1.4kU.5 58.5f 104.1

MeanLSD

TgE) in patients

with

127-495 8.G20.0 13-189 0.7-3.X 7.9-13.7 0.G2.3 6.G-821 .O

Range

Patients

with fissured

syndrome

345+ 100 14.X-+3.6 150.4+29.5 1.9+0.7 10.9+ I .‘)-I1.4+0.4 82.2f 195.7

MeanfSD

FTS (n=40)

tongue

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represent fissured tongue with pathological significance rather than normal tongue fissuring (Kullaa-Mikkonen, 1986a; b). The patients with geographic tongue were selected from the families where fissured tongue was diagnosed in some relatives (Kullaa-Mikkonen, 1986b). The term ‘fissured tongue syndrome’ (FTS) was used because fissured tongue and geographic tongue had some morphological similarities and they were common in the same families. Therefore, these two tongue types seemed to be different entities of the same inflammatory disease of the tongue. In addition, the subjects of this study included only young people within a narrow age range. It was demonstrated recently that inflammation is an essential feature of fissured tongue (Kullaa-Mikkonen & Sorvari, 1986a). Anaemia and deficiencies of vitamin B-complex have long been known to cause glossitis (Beck, 1977). Our results indicate that anaemia does not play a primary role in the pathogenesis of fissured tongue, an observation that agrees with findings in a group of elderly Finns (Makila, 1971). Absence of anaemia in the patients with FTS does not, however, preclude the possibility that a slight deficiency of vitamin Bi2 or folate might play a part. Two patients (5%) with fissured tongue had vitamin Bi2 deficiency and taken together, the patients with FTS had a significantly decreased mean level of serum IgG. Deficiency of vitamin B i2 results rarely from dietary lack but commonly from disease, or malabsorption secondary to gastrectomy, severe gastrointestinal impaired synthesis of intrinsic factor. The most frequent cause of vitamin Bi2 deficiency is due to atrophy of the gastric mucosa causing a deficiency of intrinsic factor, which is produced by gastric parietal cells. These findings imply that FTS might indicate an inability of the gastrointestinal mucosa to absorb vitamins, as was also suggested by Witkop & Barros (1963). The most striking haematological findings for FTS were the decreased thrombocyte and leucocyte counts. Furthermore, we observed a decreased level of lymphocytes in the blood of the patients compared to the controls. These observations may reflect some deficiency in the defence mechanisms of such patients. These findings and the cause of the inflammatory infiltrate of lymphoid cells in the fissured and geographic tongue could be an important subject for future investigation. Patients with FTS are often examined for a variety of allergic disorders. The normal serum levels of IgE and the negative reagin-findings, however, indicate that an allergic mechanism could hardly cause FTS. The decreased serum levels of IgG in patients with fissured tongue may reflect a disturbance in the synthesis or metabolism of this immunoglobulin. Salivary IgG, on the other hand was increased, reflecting local production of this antibody in the epithelium of fissured tongue (Kullaa-Mikkonen et al., 1986b). It is tempting to speculate that patients with FTS may have an immunological disorder, which could be augmented by the relatively small amount of vitamin B i2 in serum. The gastrointestinal diseases often present in patients with fissured tongue, such as achlorhydria, chronic gastritis and irritable colon (Kullaa-Mikkonen, 1986a), are known to be associated with impaired immunological defence. Further studies, however, are needed to clarify the role of immunological mechanisms and that of gastrointestinal disease in fissured tongue syndrome. References Beck, W. S. (1977). Vitamin B,? deficiency. In Hematology, Eds. W. J. Williams, E. Beutler. A. J. Erslev & R. W. Rundles, 2nd Ed., McGraw-Hill & Co., N.Y., pp. 307. Burket, L. W. (1977). The Tongue: In: Lynch M. A. (ed.) Burket’s Oral Medicine. Diagnosis and Trearment. J. B. Lippincott Co.

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TONGUE

SYNDROME

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Chosack, A., Zadick, D. & Eidelman, E. (1974). The prevalence of scrotal tongue and geographic tongue in 70,359 Israeli schoolchildren. Comrnuniry Denfistry and Oral Epidemiology, 2, 253. Dayal, P. K. & Mani, N. .I. (1979). Clinical aspects of the tongue in anaemia. Annales Denfale, 38, 21. Eidelman, E., Chosack, A. & Cohen, T. (1976). Scrotal tongue and geographic tongue: Polygenic and associated trains. Oral Surgery, Oral Medicine, Oral Pathology, 42, 591. Hjeirting-Hansen, E. & Bertram, U. (1970). Oral aspects of pernicious anaemia. British Dental Journal, 81, 861. Hume, W. .I. (1975). Geographic stomatitis: a critical review. Journal qf Dentistry, 3, 25. Jacobs, A. (1970). Iron deficiency anaemia and oral mucous membrane. Brifish Journal of Dermatology, 81, 861. Jones, J. H. (1973). The oral mucous membrane markers of internal disease. British Dental Journal, 134, 81. Kullaa-Mikkonen, A. (1986a). Studies on lingua fissurata. Thesis. Proceedings of the Finnish Dental Society, 82, Suppl. IV. Scandinavian Journal of Dental Kullaa-Mikkonen, A. (1987). Familial study of fissured tongue. Research. In press. Kullaa-Mikkonen, A. & Sorvari, T. E. (1986b). Lingua fissurata. A clinical, stereomicroscopic and histopathological study. International Journal of Oral and Manillofacial Surgery 15, 525. Kullaa-Mikkonen, A. & Sorvari, T. E. (1986a). A scanning electron microscopic study of fissured tongue. Journal of Oral Pathology, 15, 93. Kullaa-Mikkonen, A., Sorvari, T. E. & Kotilainen, R. (1985a). Morphological variations on the dorsal Proceedings of the Finnish Den& Society, 81, 104. surface of the human tongue. Kullaa-Mikkonen, A., Tenovuo, J. & Sorvari, T. E. (1985b). Changes in composition of whole saliva in patients with fissured tongue. Scandinavian Journal of Dental Research, 93, 522. MBkil& E. (1971). Changes in tongue topography in relation to iron and vitamin B status. Proceedings of the Finnish Dental Society, 67, 286. Prinz, H. (1927). Wandering rash of the tongue. Dental Cosmos, 69, 272, (cited by Hume, 1975). PenttilL, I. M., Jokela, H., Nummi, S., Saastamoinen, J. & Viitala, A. J. (1973). Pienen verenkuvan Suomen Liiiikiirilehti, 28, 2173. vertailuarvot. Redman, R. S., Shapiro, B. L. & Gorlin, R. J. (1972). Hereditary component in the etiology of benign migratory glossitis. American Journal of Genetics, 24, 124. Witkop, C. J. & Barros, L. (1963). Oral and genetic studies of Chileans 1960. I-Oral anomalies. American Journal of Physical Anthropology, 21, 15.