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IgM monoclonal gammopathy and oral lupus erythematosus — A case report
British Journal of Oral Surgery (1981) 19, 218-222
@ The British Association
0007-117X/81/00310218$02.00
of Oral Surgeons
IgM MONOCLONAL GAMMOPATHY AND ORAL LUPUS ERYTHEMATOSUS - A CASE REPORT P. WARD-BOOTH,M.B., CH.B., F.D.s.(ENG.)~and J. S. RENNIE,PH.D., F.D.s.R.c.P.s., M.R.C.PATH.** 1 Department of Oral Surgery, Canniesburn Hospital, Bearsden, Glasgow, G61 I QL; 2 Department of Oral Medicine and Pathology, Glasgow Dental Hospital and School, 211 Renfrew St., Glasgow, G2 3JZ Summary. A case of an IgM monoclonal gammopathy associated with oral lesions of lupus erythematosus is described and the possible interrelationship of the lesions discussed.
Introduction The importance of B-cell dyscrasias in oral surgery has been emphasised (Henderson & Rowe, 1969; James, 1974) and the wider use of haematological and biochemical investigations has led to an increasing number of patients in whom a paraproteinaemia can be demonstrated (Hobbs, 1980). Isolated oral manifestations of lupus erythematosus are an uncommon but well documented entity (Andreasen, 1964; Schicdt & Pindborg, 1976). This paper reports the unusual occurrence of oral lupus erythematosus associated with an IgM monoclonal gammopathy. Case report A 69-year-old male was referred for investigation of bilateral white lesions on the buccal mucosa. A provisional diagnosis of lichen planus was made and symptomatic treatment prescribed. A biopsy taken at this time showed only non-specific chronic inflammatory changes and histology did not support the clinical diagnosis of lichen planus. Little change was noted over a period of 18 months until the patient returned complaining of pain and ulceration of both cheeks. On examination the mucosa appeared atrophic and had several erosions surrounded by keratotic margins on both buccal mucosae (Fig. 1) and extending onto the lower alveolus. Routine haematological and biochemical investigations were carried out and a second biopsy performed. The haematological values were within the normal limits with the exception of the E.S.R. which was raised at 86 mm/hour (Table I). Repeated measurements confirmed a consistently elevated E.S.R. (45, 61 and 57 mm/hour). Biochemical analysis (Table II) revealed an abnormal band in the midfast gamma region and immunoelectrophoresis revealed a monoclonal IgM (K). Twenty-four hour urine collection for Bence-Jones protein estimation proved negative (Bradshaw’s test) but urine immunoelectrophoresis showed the presence of small amounts of paraprotein with characteristics identical to the serum IgM. (Received
18 December
1979; accepted 23 July 1980)
* For offprints.
218
IGM MONOCLONAL
GAMMOPATHY
AND ORAL LUPUS ERYTHEMATOSUS
FIG. 1. Erosion with keratotic margin on the left buccal mucosa.
Table I Haematological
Investigations
Hb WBC Corrected whole blood folate Serum Vitamin Blz Serum iron Serum T.I.B.C. E.S.R.
14.3 g/d1 6.3 x 109 138 ng/ml 340 pg/ml 20 pmol/l 51 pmol/l 86 mm in the first hour (sedimat)
Table II Biochemical
Investigations
S.G.O.T. S.G.P.T. Alk. Phos. Calcium Phosphate Total protein Albumin Protein electrophoresis
21 u/l 71 u/l 12 pmol/l 2.2 pmol/l 1.84 ~mol/l 70 g/l 38 g/1 abnormal band in mid gamma zone (IgM)
219
220
BRITISH
JOURNAL
OF
ORAL
SURGERY
Table III Immunoglobulin
Investigations
kG
800 mg/lOO ml 177 mg/lOO ml 1720 mg/lOO ml 711 pg/ml 32 rg/mt 294 pg/ml negative 0%
IgA IgM c3 c4 Cl inhibitor A.N.F. D.N.A. binding
(normal (normal (normal (normal (normal (normal
value value value value value value
5Wl500) 33-370) 3 l-49) 7261800) 199-574) 150-250)
The patient was referred for further investigation and a full clinical examination revealed no significant abnormality. Bone marrow biopsy was within normal limits and with the exception of the IgM all other immunoglobulin levels were unremarkable (Table III). Histological examination of the buccal biopsy showed a hyperkeratotic, mainly atrophic epithelium with prominent drop-shaped rete ridges. There was marked basal cell liquefaction and considerable basement membrane thickening (Fig. 2). A superficial mixed chronic inflammatory cell infiltrate consisting principally of lymphocytes and histiocytes was noted. Occasional lymphoid follicles were present and the features were considered highly suggestive of lupus erythematosus (Figs. 2 & 3).
FIG.
2. Buccal mucosa showing drop-shaped rete pegs, chronic inflammatory follicle (Haematoxylin and eosin x 125).
infiltrate and lymphoid
IGM
FIG.
MONOCLONAL
3.
GAMMOPATHY
AND
ORAL
LUPUS
ERYTHEMATOSUS
221
Buccal mucosa showing marked basal cell liquefaction, prominent basement membrane material and a mixed chronic inflammatory infiltrate (Haematoxylin and eosin x 180).
Tmmunoperoxidase studies of the buccal mucosa revealed an essentially polyclonal infiltrate with greatly increased numbers of cells staining positively for IgM. Due to the nature of the infiltrate it was not possible to be certain of the relative proportion of kappa and lambda containing cells. The patient remains under careful follow-up and the oral lesions improved with topical steroid therapy. Discussion It is interesting to speculate upon the possible relationship between this patient’s oral lesions and the JgM gammopathy. It is known that lupus erythematosus produces raised immunoglobulins but these a monoclonal IgM are usually polyclonal IgG. Jamison et al. (1978) demonstrated band in a patient with discoid lupus erythematosus but the levels were much lower than in the present case. Further, this patient had no evidence of systemic disease and the diagnosis of lupus erythematosus rests upon the histological interpretation of the second mucosal biopsy. The oral lesions could be manifestations of a developing B-cell dyscrasia and similar oral lesions have been described in Waldenstrom’s macroglobulinaemia (Gorlin & Goldman, 1970). It is not possible to positively link the oral lesions to the monoclonal IgM, but the demonstation by the immunoperoxidase technique, of an infiltrate consisting predominantly of IgM containing cells, strongly suggests a direct role in the pathogenesis of the oral lesions. 1913-E
222
BRITISH
JOURNAL
OF ORAL
SURGERY
The significance of the paraproteinaemia is not clear. It has been suggested (Hobbs, 1980) that if none of the diseases known to cause a paraproteinaemia emerge within five years then the paraprotein is benign. However, with an abnormal IgM the followup should be extended to ten years as there may be a slow evolution of the underlying disease. Furthermore, Hobbs (1980) stresses that although not all paraproteins result from malignant neoplasms the majority (82 per cent) eventually manifest as malignancy and that symptoms may occur long before the underlying neoplasm declares its presence. It is suggested that oral lesions both clinically and histologically resembling lupus erythematosus can be added to the list of clinical effects of paraproteins. Acknowledgements We would like to thank Drs M. M. Ferguson, J. H. Dagg and D. G. MacDonald for permission to present this case. We are also grateful to the departments of Pathology and Biochemistry, Glasgow Western Infirmary for their assistance in the immunoperoxidase and immunoelectrophoresis studies. References Andreasen,
J. 0. (1964). Oral manifestations
Odontologica Scandinavica,
in discoid and systemic lupus erythematosus.
Acra
22, 295.
Gorlin, R. J. & Goldman, H. M. (1970). Thoma’s OralPathology, pp. 928-929. St. Louis: Mosby. Henderson, D. & Rowe, N. L. (1969). Myelomatosis affecting the jaws. British Journal of Oral Surgery,
6, 161.
Hobbs, J. R. (1980). Myeloma. Medicine, 29, 1507. James, D. R. (1974). The hyperviscosity syndrome. British Journal of Oral Surgery, 12, 56. Jamison, T. H., Cooper, N. M. & Epstein, W. V. (1978). Lichen planus and discoid lupus erythematosus. Archives of Dermatology, 114, 1039. Schiodt, M. & Pindborg, J. J. (1976). Histologic differential diagnostic problems for oral discoid lupus erythematosus. International Journal of Oral Surgery, 5, 250.
@ The British Association
0007-117X/81/00310218$02.00
of Oral Surgeons
IgM MONOCLONAL GAMMOPATHY AND ORAL LUPUS ERYTHEMATOSUS - A CASE REPORT P. WARD-BOOTH,M.B., CH.B., F.D.s.(ENG.)~and J. S. RENNIE,PH.D., F.D.s.R.c.P.s., M.R.C.PATH.** 1 Department of Oral Surgery, Canniesburn Hospital, Bearsden, Glasgow, G61 I QL; 2 Department of Oral Medicine and Pathology, Glasgow Dental Hospital and School, 211 Renfrew St., Glasgow, G2 3JZ Summary. A case of an IgM monoclonal gammopathy associated with oral lesions of lupus erythematosus is described and the possible interrelationship of the lesions discussed.
Introduction The importance of B-cell dyscrasias in oral surgery has been emphasised (Henderson & Rowe, 1969; James, 1974) and the wider use of haematological and biochemical investigations has led to an increasing number of patients in whom a paraproteinaemia can be demonstrated (Hobbs, 1980). Isolated oral manifestations of lupus erythematosus are an uncommon but well documented entity (Andreasen, 1964; Schicdt & Pindborg, 1976). This paper reports the unusual occurrence of oral lupus erythematosus associated with an IgM monoclonal gammopathy. Case report A 69-year-old male was referred for investigation of bilateral white lesions on the buccal mucosa. A provisional diagnosis of lichen planus was made and symptomatic treatment prescribed. A biopsy taken at this time showed only non-specific chronic inflammatory changes and histology did not support the clinical diagnosis of lichen planus. Little change was noted over a period of 18 months until the patient returned complaining of pain and ulceration of both cheeks. On examination the mucosa appeared atrophic and had several erosions surrounded by keratotic margins on both buccal mucosae (Fig. 1) and extending onto the lower alveolus. Routine haematological and biochemical investigations were carried out and a second biopsy performed. The haematological values were within the normal limits with the exception of the E.S.R. which was raised at 86 mm/hour (Table I). Repeated measurements confirmed a consistently elevated E.S.R. (45, 61 and 57 mm/hour). Biochemical analysis (Table II) revealed an abnormal band in the midfast gamma region and immunoelectrophoresis revealed a monoclonal IgM (K). Twenty-four hour urine collection for Bence-Jones protein estimation proved negative (Bradshaw’s test) but urine immunoelectrophoresis showed the presence of small amounts of paraprotein with characteristics identical to the serum IgM. (Received
18 December
1979; accepted 23 July 1980)
* For offprints.
218
IGM MONOCLONAL
GAMMOPATHY
AND ORAL LUPUS ERYTHEMATOSUS
FIG. 1. Erosion with keratotic margin on the left buccal mucosa.
Table I Haematological
Investigations
Hb WBC Corrected whole blood folate Serum Vitamin Blz Serum iron Serum T.I.B.C. E.S.R.
14.3 g/d1 6.3 x 109 138 ng/ml 340 pg/ml 20 pmol/l 51 pmol/l 86 mm in the first hour (sedimat)
Table II Biochemical
Investigations
S.G.O.T. S.G.P.T. Alk. Phos. Calcium Phosphate Total protein Albumin Protein electrophoresis
21 u/l 71 u/l 12 pmol/l 2.2 pmol/l 1.84 ~mol/l 70 g/l 38 g/1 abnormal band in mid gamma zone (IgM)
219
220
BRITISH
JOURNAL
OF
ORAL
SURGERY
Table III Immunoglobulin
Investigations
kG
800 mg/lOO ml 177 mg/lOO ml 1720 mg/lOO ml 711 pg/ml 32 rg/mt 294 pg/ml negative 0%
IgA IgM c3 c4 Cl inhibitor A.N.F. D.N.A. binding
(normal (normal (normal (normal (normal (normal
value value value value value value
5Wl500) 33-370) 3 l-49) 7261800) 199-574) 150-250)
The patient was referred for further investigation and a full clinical examination revealed no significant abnormality. Bone marrow biopsy was within normal limits and with the exception of the IgM all other immunoglobulin levels were unremarkable (Table III). Histological examination of the buccal biopsy showed a hyperkeratotic, mainly atrophic epithelium with prominent drop-shaped rete ridges. There was marked basal cell liquefaction and considerable basement membrane thickening (Fig. 2). A superficial mixed chronic inflammatory cell infiltrate consisting principally of lymphocytes and histiocytes was noted. Occasional lymphoid follicles were present and the features were considered highly suggestive of lupus erythematosus (Figs. 2 & 3).
FIG.
2. Buccal mucosa showing drop-shaped rete pegs, chronic inflammatory follicle (Haematoxylin and eosin x 125).
infiltrate and lymphoid
IGM
FIG.
MONOCLONAL
3.
GAMMOPATHY
AND
ORAL
LUPUS
ERYTHEMATOSUS
221
Buccal mucosa showing marked basal cell liquefaction, prominent basement membrane material and a mixed chronic inflammatory infiltrate (Haematoxylin and eosin x 180).
Tmmunoperoxidase studies of the buccal mucosa revealed an essentially polyclonal infiltrate with greatly increased numbers of cells staining positively for IgM. Due to the nature of the infiltrate it was not possible to be certain of the relative proportion of kappa and lambda containing cells. The patient remains under careful follow-up and the oral lesions improved with topical steroid therapy. Discussion It is interesting to speculate upon the possible relationship between this patient’s oral lesions and the JgM gammopathy. It is known that lupus erythematosus produces raised immunoglobulins but these a monoclonal IgM are usually polyclonal IgG. Jamison et al. (1978) demonstrated band in a patient with discoid lupus erythematosus but the levels were much lower than in the present case. Further, this patient had no evidence of systemic disease and the diagnosis of lupus erythematosus rests upon the histological interpretation of the second mucosal biopsy. The oral lesions could be manifestations of a developing B-cell dyscrasia and similar oral lesions have been described in Waldenstrom’s macroglobulinaemia (Gorlin & Goldman, 1970). It is not possible to positively link the oral lesions to the monoclonal IgM, but the demonstation by the immunoperoxidase technique, of an infiltrate consisting predominantly of IgM containing cells, strongly suggests a direct role in the pathogenesis of the oral lesions. 1913-E
222
BRITISH
JOURNAL
OF ORAL
SURGERY
The significance of the paraproteinaemia is not clear. It has been suggested (Hobbs, 1980) that if none of the diseases known to cause a paraproteinaemia emerge within five years then the paraprotein is benign. However, with an abnormal IgM the followup should be extended to ten years as there may be a slow evolution of the underlying disease. Furthermore, Hobbs (1980) stresses that although not all paraproteins result from malignant neoplasms the majority (82 per cent) eventually manifest as malignancy and that symptoms may occur long before the underlying neoplasm declares its presence. It is suggested that oral lesions both clinically and histologically resembling lupus erythematosus can be added to the list of clinical effects of paraproteins. Acknowledgements We would like to thank Drs M. M. Ferguson, J. H. Dagg and D. G. MacDonald for permission to present this case. We are also grateful to the departments of Pathology and Biochemistry, Glasgow Western Infirmary for their assistance in the immunoperoxidase and immunoelectrophoresis studies. References Andreasen,
J. 0. (1964). Oral manifestations
Odontologica Scandinavica,
in discoid and systemic lupus erythematosus.
Acra
22, 295.
Gorlin, R. J. & Goldman, H. M. (1970). Thoma’s OralPathology, pp. 928-929. St. Louis: Mosby. Henderson, D. & Rowe, N. L. (1969). Myelomatosis affecting the jaws. British Journal of Oral Surgery,
6, 161.
Hobbs, J. R. (1980). Myeloma. Medicine, 29, 1507. James, D. R. (1974). The hyperviscosity syndrome. British Journal of Oral Surgery, 12, 56. Jamison, T. H., Cooper, N. M. & Epstein, W. V. (1978). Lichen planus and discoid lupus erythematosus. Archives of Dermatology, 114, 1039. Schiodt, M. & Pindborg, J. J. (1976). Histologic differential diagnostic problems for oral discoid lupus erythematosus. International Journal of Oral Surgery, 5, 250.